154 results on '"Pankaj Hari"'
Search Results
2. Feasibility and Efficacy of Sustained Low-Efficiency Dialysis in Critically Ill Children with Severe Acute Kidney Injury
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Menka Yadav, Anand N. Tiwari, Rakesh Lodha, Jhuma Sankar, Priyanka Khandelwal, Pankaj Hari, Aditi Sinha, and Arvind Bagga
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Pediatrics, Perinatology and Child Health - Abstract
To examine the feasibility, efficacy, and safety of sustained low-efficiency dialysis (SLED) in hemodynamically unstable, critically ill children.Critically ill patients, 1-18 y old with hemodynamic instability (≥ 1 vasoactive drugs) and severe acute kidney injury (AKI) requiring kidney replacement therapy (KRT) in a tertiary care pediatric intensive care unit were prospectively enrolled. Patients weighing ≤ 8 kg or with mean arterial pressure 5Between November 2018 and March 2020, 18 patients with median age 8.6 y and vasopressor dependency index of 83.2, underwent 41 sessions of SLED. In 16 patients, SLED was feasible within 12 h of indication. No session was terminated prematurely. Ultrafiltration achieved was 4.0 ± 2.2 mL/kg/h, while URR was 57.7 ± 16.2% and eKt/V 1.17 ± 0.56. Hemodynamic scores did not change significantly. Asymptomatic hypokalemia was the chief adverse effect. Sessions were associated with a significant improvement in indices on ultrasound and left ventricular function. Fourteen patients died.SLED is feasible, safe, and effective in enabling KRT in hemodynamically unstable children with severe AKI.
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- 2022
3. Clinical features and outcomes of patients with diacylglycerol kinase epsilon nephropathy: a nationwide experience
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Priyanka Khandelwal, Sharan Thangaraju, Sriram Krishnamurthy, Alpana Ohri, Priya Pais, Georgie Mathew, Jyoti Sharma, Aditi Sharma, Pankaj Hari, Aditi Sinha, Geetika Singh, and Arvind Bagga
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Nephrology ,Pediatrics, Perinatology and Child Health - Published
- 2023
4. Short-term safety and efficacy of escalating doses of atorvastatin for dyslipidemia in children with predialysis chronic kidney disease stage 2–5
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Punitha Lakxmi Ramesh, Priyanka Khandelwal, R. Lakshmy, Aditi Sinha, Arvind Bagga, and Pankaj Hari
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Nephrology ,Pediatrics, Perinatology and Child Health - Published
- 2023
5. Anti-factor H antibody associated hemolytic uremic syndrome following SARS-CoV-2 infection
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Priyanka Khandelwal, Sudarsan Krishnasamy, Srinivasavaradan Govindarajan, Manish Kumar, Binata Marik, Aditi Sinha, Pankaj Hari, and Arvind Bagga
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Adolescent ,SARS-CoV-2 ,Coronavirus 19 ,Factor H ,COVID-19 ,Recurrence ,Renal Dialysis ,Nephrology ,Child, Preschool ,Complement Factor H ,Pediatrics, Perinatology and Child Health ,Humans ,Original Article ,Complement factor H related protein ,Thrombotic microangiopathy ,Child ,Alternative complement pathway ,Atypical Hemolytic Uremic Syndrome ,Autoantibodies - Abstract
Background The pathogenesis of autoantibody generation in anti-factor H (FH) antibody associated atypical hemolytic uremic syndrome (aHUS) is unknown and is perhaps triggered by an infectious or environmental agent. We observed an unusual increase of patients with anti-FH antibody associated aHUS coinciding with the second pandemic wave in New Delhi and suspected that SARS-CoV-2 infection might be a potential trigger. Methods We screened for SARS-CoV-2 infection using reverse transcriptase polymerase chain reaction (RT-PCR) and serology in 13 consecutive patients with anti-FH antibody associated aHUS during the past year in New Delhi. Results We report 5 patients, 4–13 years old, who presented with a febrile illness without respiratory symptoms during the second pandemic wave. Of these, 3 patients presented with a relapse 25–85 months following the initial episode of aHUS. SARS-CoV-2 was detected by RT-PCR in 1 patient and by serology in 4 patients (median titer 47.1 cut-off index). Patients had high titers of anti-FH antibodies (median 2,300 AU/ml). Genetic studies, done in 3 of the 5 patients, showed homozygous CFHR1 deletion without other significant genetic abnormalities. Specific management comprised plasma exchanges and oral prednisolone, combined with either cyclophosphamide or mycophenolate mofetil. At median follow-up of 3.3 months, the estimated glomerular filtration rate in 4 patients ranged from 62 to 110 ml/min/1.73 m2; one patient was dialysis-dependent. Conclusion Increased vigilance is required during the pandemic, especially in patients with anti-FH associated aHUS, who might relapse despite quiescent disease for a prolonged period. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information. Supplementary Information The online version contains supplementary material available at 10.1007/s00467-021-05390-4.
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- 2022
6. Variants in complement genes are uncommon in patients with anti-factor H autoantibody-associated atypical hemolytic uremic syndrome
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Priyanka Khandelwal, Aditi Joshi, Aradhana Mathur, Mamta Puraswani, Bahadur Singh Gurjar, Aditi Sinha, Pankaj Hari, Mohammed Faruq, and Arvind Bagga
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Nephrology ,Pediatrics, Perinatology and Child Health - Abstract
Coexisting genetic variants in patients with anti-factor H (FH)-associated atypical hemolytic uremic syndrome (aHUS) have implications for therapy. We estimated the prevalence of complement genetic variants in children with anti-FH aHUS from a prospective nationwide cohort and determined if significant genetic variants impact long-term kidney outcomes.Of 436 patients in the database, 77 consecutive patients, 21 with a relapse and 9 with kidney failure and/or death were included. Targeted sequencing, using a 27-gene panel including CFH, CFI, CFB, C3, CD46, PLG, DGKE, and THBD and multiplex ligation-dependent probe amplification of CFH-CFHR region, was performed. The adverse outcome was eGFR 30 ml/min/1.73 mPatients had high anti-FH titers 5670 (2177-13,545) AU/ml, relapsing course (42.1%), and adverse outcomes (19.6%). Variants, chiefly of unknown significance, were found in 7 (6.5%; 95% CI 3.1-13.2%); a pathogenic variant was found in one patient. Homozygous deletion of CFHR1 was present in 91.6% compared to 9.8% in 184 healthy controls. Plasma exchanges and immunosuppression showed a trend of improving outcomes, independent of genetic defects (HR 0.32; P = 0.070). Meta-analysis of 18 studies (384 patients) showed that the pooled prevalence of pathogenic and likely pathogenic variants was 3% (95% CI 0-8%). Of 37 total variants in the meta-analysis, 7 (18.9%) each were pathogenic and likely pathogenic; others were variants of unknown significance.Significant variants in complement regulatory genes are rare in patients with anti-FH-associated aHUS. Irrespective of genetic defects, plasma exchanges and immunosuppression showed a statistical trend to improved outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.
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- 2023
7. SARS-CoV-2 infection in children with chronic kidney disease
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Sudarsan Krishnasamy, Rajni Gaind, Swarnim Swarnim, Kanika Kapoor, Megha Brijwal, Shobha Sharma, Mukta Mantan, Pankaj Hari, Kirtisudha Mishra, Arvind Bagga, Manish Kumar, Priyanka Khandelwal, and Aditi Sinha
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Nephrology ,medicine.medical_specialty ,Nephrotic Syndrome - Relapse ,medicine.medical_treatment ,Nephrotic syndrome ,urologic and male genital diseases ,Letter to the Editors ,Renal Dialysis ,Risk Factors ,Interquartile range ,Internal medicine ,Humans ,Medicine ,Hospital Mortality ,Renal Insufficiency, Chronic ,Child ,Children ,Dialysis ,Retrospective Studies ,SARS-CoV-2 ,business.industry ,Acute kidney injury ,COVID-19 ,Odds ratio ,medicine.disease ,Pediatrics, Perinatology and Child Health ,Original Article ,Kidney replacement therapy ,business ,Kidney disease - Abstract
Background Information on the course of SARS-CoV-2 infection in children with chronic kidney disease (CKD) is limited. Methods We retrospectively reviewed the presentation and outcomes of SARS-CoV-2 infection in patients with CKD followed at any of the four pediatric nephrology centers in New Delhi from April 2020 to June 2021. Outcomes, including cardiopulmonary and renal complications, were reported in relation to underlying disease category and illness severity at presentation. Results Underlying illness in 88 patients included nephrotic syndrome (50%), other CKD stages 1–4 (18.2%), CKD 5D (17%), and CKD 5T (14.8%). Thirty-two of 61 patients with symptomatic COVID-19 and 9/27 asymptomatic patients were admitted for median 10 (interquartile range 7–15) days. Seventeen (19.3%) patients developed moderate or severe COVID-19. Systemic complications, observed in 30 (34.1%), included acute kidney injury (AKI, 34.2%), COVID-19 pneumonia (15.9%), unrelated pulmonary disease (2.3%), and shock (4.5%). Nineteen (21.6%) had severe complications (AKI stage 2–3, encephalopathy, respiratory failure, shock). Eight (11%) of twelve (16.4%) patients with severe AKI required dialysis. Three (3.4%) patients, two with steroid-resistant nephrotic syndrome in relapse and one with CKD 1–4, died due to respiratory failure. Univariate logistic regression indicated that patients presenting with nephrotic syndrome in relapse or moderate to severe COVID-19 were at risk of AKI (respective odds ratio, 95%CI: 3.62, 1.01–12.99; 4.58, 1.06–19.86) and/or severe complications (respective odds ratio, 95%CI: 5.92, 1.99–17.66; 61.2, 6.99–536.01). Conclusions Children with CKD presenting with moderate-to-severe COVID-19 or in nephrotic syndrome relapse are at risk of severe complications, including severe AKI and mortality. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information Supplementary Information The online version contains supplementary material available at 10.1007/s00467-021-05218-1.
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- 2021
8. Importance of clinical practice guidelines to practicing pediatric nephrologists and IPNA survey
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Pankaj Hari, Koichi Nakanishi, Dieter Haffner, Paula A. Coccia, Olivia Boyer, Arvind Bagga, Melvin Bonilla-Felix, Hong Xu, Khalid Alhasan, Giovanni Montini, Susan Samuel, Ali Duzova, and Ill So Ha
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medicine.medical_specialty ,Attitude of Health Personnel ,business.industry ,030232 urology & nephrology ,Guideline ,030204 cardiovascular system & hematology ,Pediatrics ,Scientific evidence ,Nephrologists ,Clinical Practice ,03 medical and health sciences ,Cross-Sectional Studies ,0302 clinical medicine ,Trustworthiness ,Nephrology ,Surveys and Questionnaires ,Family medicine ,Practice Guidelines as Topic ,Pediatrics, Perinatology and Child Health ,Humans ,Medicine ,business ,Regional differences ,Pediatric population - Abstract
Clinical practice guidelines (CPGs) are systematically developed statements backed by scientific evidence to assist practitioners in management in clinical practice. An international cross-sectional survey was conducted by the IPNA to examine the perceptions of pediatric nephrologists on guidelines and their usage and to identify important diseases for future clinical practice guidelines (CPGs). The survey found that the majority of pediatric nephrologists find CPGs useful in clinical practice and admitted to using them most of the time. Developing CPGs is challenging and there are standards available to develop trustworthy guidelines. While evidence-based global guidelines are ideal, pediatric nephrologists expressed the desire that they address regional differences. Most respondents (89.2%) to the survey agreed that adult guidelines did not cover the pediatric perspective adequately and 71.4% opined that consensus-based pediatric guidelines can be developed when evidence for the pediatric population is lacking. The development of high-quality practice guidelines requires substantial resources and may not be feasible in resource-poor countries. Adaptation of an existing guideline has been suggested as an alternative and the ADAPTE collaboration provides a systematic approach to adapting guidelines. Several diseases where pediatric guidelines are needed as a priority including IgA and C3 glomerulopathy were identified in the survey. Implementation of guideline-based care is challenging and the survey found that lack of availability of guidelines (43%) and resources (22.8%) are important reasons for poor implementation in lower-middle and low-income countries. Perceived complexity of guidelines, physician attitudes, and lack of training also contribute to non-adherence to guidelines.
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- 2021
9. Sequential rituximab therapy sustains remission of nephrotic syndrome but carries high risk of adverse effects
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Aditi Sinha, Georgie Mathew, Arushi Arushi, Srinivasavaradan Govindarajan, Kshetrimayum Ghanapriya, Neetu Grewal, Khushboo Rai, Megha Brijwal, Sree Laya Kalluru, Prachi Tewari, Angeli Misra, Priyanka Khandelwal, Pankaj Hari, and Arvind Bagga
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Transplantation ,Nephrology - Abstract
Background Sequential rituximab (RTX) administration has emerged as an important strategy to sustain remission of disease in patients with difficult-to-treat nephrotic syndrome. Methods We report the efficacy and safety of sequential therapy with two or more courses of intravenous RTX in 250 patients with difficult-to-treat steroid dependence (n = 127) and calcineurin inhibitor (CNI)-dependent or CNI-refractory steroid resistance (n = 123) managed at one center during 2015–2021. Subsets of patients were cross-sectionally tested for hypogammaglobulinemia, seroprotection against and hyporesponsiveness to vaccines for hepatitis B and tetanus, BK/JC viruria and human antichimeric antibodies (HACAs). Results Sequential RTX therapy, initiated at a median of 10 years [interquartile range (IQR) 7.3–14.4], was administered for 1.8 courses/person-year [95% confidence interval (CI) 1.7–2.0] over 2.0 years (95% CI 1.2–3.0). Therapy was associated with postponement of relapses by a median of 3 years in patients with steroid-sensitive disease and 2 years in those with steroid resistance. Relapses were reduced by a mean of 2.0 relapses/person-year (95% CI 1.8–2.2), enabling a reduction in prednisolone dose to 0.04 mg/kg/day (95% CI 0.01–0.11) and withdrawal of additional immunosuppression in 154 (62%) patients. RTX-associated adverse events, occurring at 0.20 events/person-year (95% CI 0.17–0.23), were chiefly comprised of infusion reactions (n = 108) and infections (n = 46); serious adverse events were observed in 10.8% patients, at 0.03 events/person-year (95% CI 0.02–0.05). Hypogammaglobulinemia was observed in 35% of 177 patients and was moderate to severe in 8.5% of cases. Rates of seroprotection at baseline and response following vaccination were lower for hepatitis B [1.9% and 29.4% (n = 52)] than tetanus [65.5% and 34.5% (n = 58)]. BK/JC viruria, without viremia, was observed in 7.3% of 109 cases. A total of 19 of 107 patients (17.8%) had HACAs, which were associated with B cell nondepletion and serum sickness. Age at therapy of Conclusions Sequential therapy with RTX effectively reduces relapses in patients with difficult-to-treat steroid- and/or CNI-dependent or CNI-refractory nephrotic syndrome. Therapy is associated with high rates of hypogammaglobulinemia and infusion reactions.
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- 2022
10. Clinical Features and Genetic Sequencing of Children with Fanconi-Bickel Syndrome
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Srinivasavaradan, Govindarajan, Priyanka, Khandelwal, Shally, Sharma, Anuja, Agarwala, Aditi, Sinha, Pankaj, Hari, and Arvind, Bagga
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The present paper reports 10 patients (9 families) with Fanconi-Bickel syndrome managed during 2010-2021. Patients presented with polyuria, polydipsia, hepatomegaly, rickets, and stunting at a median of 5 (3, 7.3) mo; one had transient neonatal diabetes. Glucosuria, generalized aminoaciduria, β
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- 2022
11. Short-Duration Prednisolone in Children with Nephrotic Syndrome Relapse
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Pankaj Hari, Aditi Sinha, Deepika Kainth, Shivam Pandey, and Arvind Bagga
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Male ,medicine.medical_specialty ,Nephrotic Syndrome ,Time Factors ,Epidemiology ,Prednisolone ,Nephrotic Syndrome - Relapse ,Population ,Anti-Inflammatory Agents ,030232 urology & nephrology ,Critical Care and Intensive Care Medicine ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Recurrence ,law ,Internal medicine ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,Child ,education ,Transplantation ,education.field_of_study ,business.industry ,Hazard ratio ,Editorials ,medicine.disease ,Confidence interval ,Regimen ,Nephrology ,Child, Preschool ,Female ,business ,Nephrotic syndrome ,medicine.drug - Abstract
Background and objectives In children with nephrotic syndrome, steroids are the cornerstone of therapy for relapse. The adequate duration and dosage of steroids, however, have not been an active area of research, especially in children with infrequently relapsing nephrotic syndrome. This study investigated the efficacy of an abbreviated regimen for treatment of a relapse in this population. Design, setting, participants, & measurements In a single-center, open-label, randomized controlled trial, we evaluated the efficacy of prednisolone as a “short regimen” (40 mg/m2 on alternate days for 2 weeks) compared with “standard regimen” (40 mg/m2 on alternate days for 4 weeks) for children aged 1–16 years who achieved remission of a relapse. The primary outcome was the proportion of children developing frequent relapses or steroid dependence at 12 months. Results A total of 117 patients were enrolled and randomized to short (55) or standard (62) regimen. Fourteen (24%) patients in standard regimen and 12 (23%) in short regimen developed frequent relapses or steroid dependence over a period of 1 year (risk difference, −1%; 95% confidence interval, −15 to 16; P=0.90). A large 95% confidence interval crossed the proposed noninferiority margin. In a time to event analysis, there was no significant difference in the proportion of children developing frequent relapses or steroid dependence and time to outcome between the two groups (hazard ratio, 1.01; 95% confidence interval, 0.83 to 1.23; P=0.98). Time to relapse, relapse rate, and steroid-related adverse events were similar in both groups. Cumulative steroid exposure was significantly lower in the short regimen (risk difference, −541 mg/m2; 95% confidence interval, −917 to −164 mg/m2; P Conclusions In children with infrequently relapsing nephrotic syndrome, a short steroid treatment for relapse resulted in a similar proportion of patients developing frequent relapses or steroid dependence; however, noninferiority of a short regimen was not established. Clinical Trial registry name and registration number: CTRI/2015/11/006345
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- 2021
12. Consensus Guidelines on Management of Steroid-Resistant Nephrotic Syndrome
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Jyoti Sharma, Pankaj Hari, Mukta Mantan, Aditi Sinha, Anil Vasudevan, Priyanka Khandelwal, Ranjeet Thergaonkar, and Arvind Bagga
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medicine.medical_specialty ,Proteinuria ,business.industry ,MEDLINE ,Guideline ,medicine.disease ,Steroid-resistant nephrotic syndrome ,Calcineurin ,Pediatrics, Perinatology and Child Health ,Pediatric surgery ,medicine ,Pediatric nephrology ,medicine.symptom ,business ,Intensive care medicine ,Congenital nephrotic syndrome - Abstract
Justification The management of steroid resistant nephrotic syndrome (SRNS) is challenging. These guidelines update existing 2009 Indian Society of Pediatric Nephrology recommendations on its management. Objective To frame revised guidelines on diagnosis and evaluation, treatment and follow up, and supportive care of patients with the illness. Process The guidelines combine evidence-based recommendations and expert opinion. Formulation of key questions was followed by systematic review of literature, evaluation of evidence by experts and two face-to-face meetings. Recommendations Fourteen statements provide updated advice for managing steroid resistance, and underscore the importance of estimating proteinuria and baseline kidney function, and the need for kidney biopsy and genetic screening. Calcineurin inhibitors are recommended as most effective in inducing remission of proteinuria, the chief factor associated with long-term renal survival. Advice on managing allograft recurrence, congenital nephrotic syndrome, and monitoring and supportive care, including transition of care, are described. This revised practice guideline is intended to improve management and patient outcomes, and provide direction for future research.
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- 2021
13. Multiple opportunistic infection-associated hemophagocytic lymphohistiocytosis in nephrotic syndrome: A case report
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Pankaj Hari, Priyanka Khandelwal, Sireesh Varadaraju, and Jhuma Sankar
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Pediatrics ,medicine.medical_specialty ,corticosteroid ,Tuberculosis ,Opportunistic infection ,media_common.quotation_subject ,medicine.medical_treatment ,Congenital cytomegalovirus infection ,RJ1-570 ,intravenous immunoglobulin ,Medicine ,Pneumocystis jirovecii ,cytomegalovirus ,media_common ,Hemophagocytic lymphohistiocytosis ,biology ,business.industry ,Convalescence ,Immunosuppression ,biology.organism_classification ,medicine.disease ,pneumocystis jirovecii ,tuberculosis ,business ,Nephrotic syndrome - Abstract
Multiple opportunistic coinfections during corticosteroid therapy for the nephrotic syndrome are uncommon. Infection-associated hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal multisystem disorder, manifesting as a state of hypercytokinemia in response to an infectious trigger. We describe a 4½-year-old boy with steroid-dependent nephrotic syndrome receiving high-dose steroids, who developed respiratory failure due to pulmonary tuberculosis, Cytomegalovirus, and Pneumocystis jirovecii coinfections; HLH complicated the course. Aggressive management of the underlying infections with antitubercular, antiviral, and antifungal therapy, prompt recognition of HLH, and immunomodulation with intravenous (IV) immunoglobulin and IV methylprednisolone enabled convalescence. This report emphasizes the serious risks of immunosuppression and the need for strict vigilance for rare opportunistic infections with multiple pathogens in patients receiving oral steroids for nephrotic syndrome. Clinical distinctions between severe sepsis and HLH may be ambiguous; a high level of suspicion is required for timely recognition and management.
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- 2021
14. Virulence gene mutations as a differentiator of clinical phenotypes: insights from community-acquired uropathogenic
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Manisha, Yadav, Swati, Pundir, Rajesh, Kumari, Arvind, Kumar, Shwetha J, Venugopal, Rajashree, Panigrahy, Vibhor, Tak, Sneha K, Chunchanur, Hitender, Gautam, Arti, Kapil, Bimal, Das, Seema, Sood, Harshal Ramesh, Salve, Sumit, Malhotra, Shashi, Kant, Pankaj, Hari, Susmita, Chaudhuri, and Sarita, Mohapatra
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Phenotype ,Virulence ,Pregnancy ,Virulence Factors ,Escherichia coli Proteins ,Mutation ,Urinary Tract Infections ,Humans ,Uropathogenic Escherichia coli ,Female ,Escherichia coli Infections - Abstract
Uropathogenic
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- 2022
15. Antibiotic resistance of uropathogens among the community-dwelling pregnant and nonpregnant female: a step towards antibiotic stewardship
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Sarita, Mohapatra, Shwetha J, Venugopal, Mani, Kalaivani, Shashi, Kant, Vibhor, Tak, Rajashree, Panigrahy, Sneha K, Chunchanur, Deepak, Kocher, Birasen, Behera, Swati, Pundir, Susmita, Chaudhuri, Hitender, Gautam, Seema, Sood, Bimal Kumar, Das, Arti, Kapil, Arvind, Kumar, Rajesh, Kumari, R, Ambica, Pankaj, Hari, Sumit, Malhotra, and Harsal Ramesh, Salve
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Bacteriuria ,Drug Resistance, Microbial ,Microbial Sensitivity Tests ,Amoxicillin-Potassium Clavulanate Combination ,Anti-Bacterial Agents ,Antimicrobial Stewardship ,Cross-Sectional Studies ,Pregnancy ,Cefixime ,Urinary Tract Infections ,Escherichia coli ,Humans ,Female ,Prospective Studies ,Independent Living - Abstract
Indiscriminate and widespread use of antibiotics has resulted in emergence of many antibiotic-resistant organisms. Antibiotic administration during pregnancy is mostly avoided, unless there is compelling medical condition. We hypothesized that the uropathogens isolated from pregnant women would be more susceptible to antibiotics compared to those isolated from nonpregnant women, thus will be helpful in formulating separate empiric guideline for pregnant women based on the resistance pattern.This was a prospective cross-sectional study conducted over a period of 2 years in which females with the clinical diagnosis of either cystitis or asymptomatic bacteriuria during pregnancy were included from the community settings. Uropathogen species and their antimicrobial resistance pattern were compared between the pregnant and nonpregnant groups. After accounting for centre-to-centre variation and adjusting for age and socio-economic status, the adjusted odds ratio for antibiotic resistance was calculated and compared between pregnant and nonpregnant women using logistic regression analysis.A total of 1758 women (pregnant: 43.3%; nonpregnant: 56.6%) were screened in the study over a period of 2 years, out of which 9.3% (163/1758) were having significant bacteriuria. Escherichia coli and Klebsiella pneumoniae were the two commonest uropathogen in both the groups; their prevalence being 83.6% in pregnant women and 85.2% in nonpregnant women, respectively. Resistance against ampicillin, cefixime, cefoxitin, ceftazidime, ceftriaxone and amoxicillin-clavulanic acid were found significantly lower in the pregnant women compared to nonpregnant. After adjusting the age and socio-economic status accounting for centre-to-centre variation, the odds of resistance for cefixime, amoxicillin-clavulanic acid and co-trimoxazole were found lower and statistically significant among the pregnant women group.The antimicrobial resistance was significantly higher among the community-dwelling nonpregnant women compared to pregnant women in case of few antibiotics. The study highlighted the need of building local antibiogram that could help to initiate the empirical treatment and thus prevent emergence of antimicrobial resistance.
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- 2022
16. Prevalence and resistance pattern of uropathogens from community settings of different regions: an experience from India
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Sarita Mohapatra, Rajashree Panigrahy, Vibhor Tak, Shwetha J. V., Sneha K. C., Susmita Chaudhuri, Swati Pundir, Deepak Kocher, Hitender Gautam, Seema Sood, Bimal Kumar Das, Arti Kapil, Pankaj Hari, Arvind Kumar, Rajesh Kumari, Mani Kalaivani, Ambica R., Harshal Ramesh Salve, Sumit Malhotra, and Shashi Kant
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General Materials Science - Abstract
Introduction. Urinary tract infection (UTI) is one of the most common infections in clinical practice worldwide in both healthcare and community settings causing significant morbidity and mortality. It is one of the major conditions at the community level treated empirically and regarded as a potential cause of emergence of antimicrobial resistance (AMR). Limited information is available regarding community-acquired UTI (CA-UTI) from India. Methodology. This is a first of its kind, multicentric-cross-sectional study at the community level targeting patients attending the out-patient department (OPD) of the community health centre (CHC) from four geographical regions (North, South, West and East) of India. The study had been designed to determine the epidemiology, antibiogram profile and identification of extended-spectrum beta-lactamase (ESBL) producer and carbapenem resistant (CR) uropathogens. Samples were collected prospectively from UTI suspected patients coming at CHC and processed at the tertiary healthcare centres using a common standard operating procedure. Clinical history of all the patients exhibiting significant bacteriuria was collected and data was analysed. Result. Overall, 250 out of a total of 2459 (10.1 %) urine samples were positive for bacteria with significant bacteriuria (adult: paediatrics, 6.7 : 1). Females were predominantly affected (male: female, 1 : 2.9). History of recent episode of UTI was observed as the commonest risk factor followed by diabetes mellitus. Altogether, 86 % of total cases were caused by Escherichia coli (68 %) and Klebsiella pneumoniae (17.6 %) together. Among the commonly used oral antibiotics for the Gram-negative bacilli (GNB), the highest resistance was observed against beta-lactams, first- and second-generation cephalosporins, fluoroquinolones and co-trimoxazole. Overall, the prevalence of ESBL producer and CR isolates were 44.8, and 4.3 %, respectively. However, the ESBL production, CR and nitrofurantoin resistance among the uropathogenic E. coli (UPEC) isolates was 52.8, 5.1 and 14 %, respectively. No resistance was found against fosfomycin among the UPEC isolates. Conclusion. The current study highlights the increasing incidence of AMR among uropathogens at the community-settings of India. A significant percentage of ESBL producers among the isolated UPEC and K. pneumoniae were observed. The currently available evidence supports the clinical recommendation of fosfomycin and nitrofurantoin for empiric therapy in CA-UTI in India.
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- 2022
17. Phenotypic variability in distal acidification defects associated with WDR72 mutations
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Pankaj Hari, Priyanka Khandelwal, Vijay Prakash Mathur, Arvind Bagga, Aditi Sinha, Thenral S Geetha, Mahesh, Sandhya Nair, and Sumantra Raut
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Vacuolar Proton-Translocating ATPases ,medicine.medical_specialty ,030232 urology & nephrology ,030204 cardiovascular system & hematology ,Gastroenterology ,Renal tubular acidosis ,03 medical and health sciences ,0302 clinical medicine ,Distal renal tubular acidosis ,Polyuria ,Furosemide ,Internal medicine ,medicine ,Humans ,Amelogenesis imperfecta ,Hypercalciuria ,business.industry ,Proteins ,Fanconi syndrome ,Forkhead Transcription Factors ,Metabolic acidosis ,Acidosis, Renal Tubular ,Hydrogen-Ion Concentration ,medicine.disease ,Bicarbonates ,Biological Variation, Population ,Nephrology ,Fludrocortisone ,Mutation ,Pediatrics, Perinatology and Child Health ,Nephrocalcinosis ,medicine.symptom ,Acidosis ,business - Abstract
Distal renal tubular acidosis (RTA) is typically caused by defects in ATP6V0A4, ATP6V1B1, and SLC4A1, accounting for 60–80% of patients. Genes recently implicated include FOXI1, ATP6V1C2, and WDR72, of which WDR72 is associated with dental enamel defects. We describe 4 patients, from three unrelated consanguineous families, with RTA and amelogenesis imperfecta. Distal tubular acidification was evaluated by furosemide-fludrocortisone test, urine-to-blood PCO2 gradient and fractional excretion of bicarbonate. Exome sequencing was performed using a panel of genes implicated in human disease. Patients had polyuria, hypokalemia, hypercalciuria, and nephrocalcinosis, but metabolic acidosis varied in severity. Although all patients acidified urine to pH
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- 2020
18. Therapy and outcomes of C3 glomerulopathy and immune-complex membranoproliferative glomerulonephritis
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Geetika Singh, Pankaj Hari, S. P. Bhardwaj, Priyanka Khandelwal, Aditi Sinha, and Arvind Bagga
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Nephrology ,medicine.medical_specialty ,Cyclophosphamide ,Glomerulonephritis, Membranoproliferative ,C3 Glomerulonephritis ,030232 urology & nephrology ,030204 cardiovascular system & hematology ,Kidney ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Glomerulopathy ,Internal medicine ,Membranoproliferative glomerulonephritis ,Humans ,Medicine ,Dense Deposit Disease ,Rapidly progressive glomerulonephritis ,Child ,Retrospective Studies ,business.industry ,medicine.disease ,Calcineurin ,Pediatrics, Perinatology and Child Health ,business ,medicine.drug - Abstract
Data on therapy and outcome of dense deposit disease (DDD), C3 glomerulonephritis (C3GN), and immune-complex MPGN (IC-MPGN) in children are limited.In this retrospective single-center study from 2007 to 2019, kidney biopsies were reviewed to include patients aged18-years with C3 glomerulopathy and IC-MPGN. Initial immunosuppression comprised prednisolone, mycophenolate mofetil (n = 51), tacrolimus (n = 11), and/or IV cyclophosphamide (n = 20). Clinicopathological features, response to therapy, and adverse outcome (eGFRA total of 92 patients were classified as DDD (n = 48, 52.2%), C3GN (n = 26, 28.3%), and IC-MPGN (n = 18, 19.6%) by immunohistochemistry and electron microscopy; 8 patients with DDD were misclassified as IC-MPGN on immunofluorescence. At last follow-up (median 4.3 years), complete or partial remission occurred in 28.5, 36.1, and 16.7% patients with DDD, C3GN, and IC-MPGN, respectively. Serum albumin at onset 2.5 g/dL (HR = 0.29, P = 0.005) and persistently low serum C3 (HR = 0.34, P = 0.02) were associated with lack of remission. The 5-year kidney survival was 62.6, 85.5, and 88.5% in patients with DDD, C3GN, and IC-MPGN, respectively (log-rank, P = 0.006). Presentation as rapidly progressive GN (HR = 11.2, P 0.001), age 10 years at onset (HR = 4.0, P = 0.004), and DDD (HR = 4.2, P = 0.02) were independently associated with adverse outcome; achieving remission was protective (HR = 0.04; P 0.001).Outcome in patients with C3 glomerulopathy and IC-MPGN was unsatisfactory, and only a small proportion of patients achieved complete or partial remission. Patients with DDD were more likely to present with rapidly progressive GN and were at higher risk of adverse outcomes, including kidney failure.
- Published
- 2020
19. Managing Children With Renal Diseases During the COVID-19 Pandemic
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Om Prakash Mishra, Pankaj Hari, Arvind Bagga, Madhuri Kanitkar, Anil Vasudevan, Priya Pais, Mukta Mantan, Sriram Krishnamurthy, Georgie Mathew, and Sanjeev Gulati
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Pneumonia, Viral ,Nephrotic syndrome ,Recommendations ,Transplant ,Betacoronavirus ,03 medical and health sciences ,0302 clinical medicine ,Renal Dialysis ,Chronic kidney disease ,030225 pediatrics ,Pediatric surgery ,Health care ,Pandemic ,medicine ,Humans ,030212 general & internal medicine ,Child ,Intensive care medicine ,Pandemics ,Dialysis ,Kidney transplantation ,Immunosuppression Therapy ,SARS-CoV-2 ,business.industry ,Acute kidney injury ,COVID-19 ,medicine.disease ,Kidney Transplantation ,Hemodialysis ,Preparedness ,Pediatrics, Perinatology and Child Health ,Kidney Diseases ,Coronavirus Infections ,business ,Kidney disease - Abstract
The Coronavirus outbreak is a rapidly evolving pandemic, placing unprecedented strain on health-care systems. COVID-19 presents challenges for management of children with renal diseases, especially those receiving long-term immunosuppressive medications, including renal transplant recipients and those with chronic kidney disease and acute kidney injury requiring dialysis. Our preparedness for managing this vulnerable group of children is the need of the hour. The purpose of this article is to provide guidance to caregivers and health care personnel involved in management of children with renal diseases and to ensure patient well-being, while protecting staff from infection.
- Published
- 2020
20. Isolated nephrocalcinosis due to compound heterozygous mutations in renal outer medullary potassium channel
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Arvind Bagga, Aditi Sinha, Pankaj Hari, Jasintha Sabanadesan, and Priyanka Khandelwal
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Adult ,Male ,Heterozygote ,medicine.medical_specialty ,Adolescent ,endocrine system diseases ,Hypercalciuria ,030232 urology & nephrology ,Metabolic alkalosis ,Case Report ,030204 cardiovascular system & hematology ,Kidney ,urologic and male genital diseases ,Compound heterozygosity ,Bartter syndrome ,03 medical and health sciences ,0302 clinical medicine ,Tubulopathy ,Polyuria ,Internal medicine ,medicine ,Humans ,Potassium Channels, Inwardly Rectifying ,Child ,Ultrasonography ,business.industry ,Bartter Syndrome ,Exons ,General Medicine ,medicine.disease ,Hypokalemia ,Nephrocalcinosis ,Endocrinology ,Mutation ,Female ,medicine.symptom ,business - Abstract
Identification of a monogenic etiology is possible in a proportion of patients with childhood-onset nephrolithiasis or nephrocalcinosis. Bartter syndrome (BS), a hereditary tubulopathy characterized by polyuria, hypokalemic alkalosis and growth retardation that rarely presents with isolated nephrocalcinosis. Patients with defect in renal outer medullary potassium channel, encoded by the KCNJ1 gene causing BS type 2, typically present during the neonatal period. We describe a 14-year-old girl with mild late-onset BS type 2 with reported pathogenic compound heterozygous variations in exon 2 of KCNJ1 (c.146G > A and c.657C > G). This patient presented with isolated medullary nephrocalcinosis due to hypercalciuria; absence of hypokalemia and metabolic alkalosis was unique. This case highlights the importance of screening the KCNJ1 gene in patients with hypercalciuria and nephrocalcinosis, even in older children.
- Published
- 2020
21. Metabolic and Genetic Evaluation in Children with Nephrolithiasis
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Anita Mandal, Priyanka Khandelwal, Thenral S. Geetha, Sakthivel Murugan, Jitendra Meena, Manisha Jana, Aditi Sinha, Rajeev Kumar, Amlesh Seth, Pankaj Hari, and Arvind Bagga
- Subjects
Hyperoxaluria ,Phenotype ,Sulfurtransferases ,Pediatrics, Perinatology and Child Health ,Hypercalciuria ,Humans ,India ,Nephrolithiasis ,Child - Abstract
To evaluate metabolic and genetic abnormalities in children with nephrolithiasis attending a referral center in North India.The patients aged 1-18 y old with nephrolithiasis underwent biochemical evaluation and whole-exome sequencing. The authors evaluated for monogenic variants in 56 genes and compared allele frequency of 39 reported polymorphisms between patients and 1739 controls from the GenomeAsia 100 K database.Fifty-four patients, aged 9.1 ± 3.7 y were included. Stones were bilateral in 42.6%, familial in 33.3%, and recurrent in 25.9%. The most common metabolic abnormalities were hypercalciuria (35.2%), hyperoxaluria (24.1%), or both (11.1%), while xanthinuria (n = 3), cystinuria (n = 1), and hyperuricosuria (n = 1) were rare. Exome sequencing identified an etiology in 6 (11.1%) patients with pathogenic/likely pathogenic causative variants. Three variants in MOCOS and one in ATP7B were pathogenic; likely pathogenic variants included MOCOS (n = 2), AGXT, and SLC7A9 (n = 1, each). Causality was not attributed to two SLC34A1 likely pathogenic variants, due to lack of matching phenotype and dominant family history. Compared to controls, allele frequency of the polymorphism TRPV5 rs4252402 was significantly higher in familial stone disease (allele frequency 0.47 versus 0.53; OR 3.2, p = 0.0001).The chief metabolic abnormalities were hypercalciuria and hyperoxaluria. A monogenic etiology was identified in 11% with pathogenic or likely pathogenic variants using a gene panel for nephrolithiasis. Heterozygous missense variants in the sodium-phosphate cotransporter SLC34A1 were common and required evaluation for attributing pathogenicity. Rare polymorphisms in TRPV5 might increase the risk of familial stones. These findings suggest that a combination of metabolic and genetic evaluation is useful for determining the etiology of nephrolithiasis.
- Published
- 2022
22. Genetic and clinical profile of patients with hypophosphatemic rickets
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Binata Marik, Arvind Bagga, Aditi Sinha, Priyanka Khandelwal, Pankaj Hari, and Arundhati Sharma
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Fibroblast Growth Factors ,Vacuolar Proton-Translocating ATPases ,Genetics ,Humans ,General Medicine ,Acidosis, Renal Tubular ,Familial Hypophosphatemic Rickets ,Vitamin D ,PHEX Phosphate Regulating Neutral Endopeptidase ,Genetics (clinical) ,Rickets, Hypophosphatemic - Abstract
Nutritional vitamin D deficiency is the most frequent cause of rickets followed by genetic causes, that include entities like classic hypophosphatemic rickets (FGF23 related), Dent disease, Fanconi syndrome, renal tubular acidosis, and vitamin D dependent rickets. Hypophosphatemia is a feature in all these forms. The diagnosis relies on a combination of clinical, biochemical and radiological features, but genetic testing is required to confirm the diagnosis. We screened 66 patients with hypophosphatemic rickets referred to this center between May 2015 and July 2019 using whole exome sequencing (WES) in addition to the measurement of their intact serum fibroblast growth factor 23 (FGF23) levels. WES revealed 36 pathogenic and 28 likely pathogenic variants in 16 different genes (PHEX, FGF23, DMP1, ENPP1, CLCN5, CTNS, SLC2A2, GATM, SLC34A1, EHHADH, SLC4A1, ATP6V1B1, ATP6V0A4, CYP27B1, VDR and FGFR1) in 63 patients which helped differentiate between the various forms of hypophosphatemic rickets. Intact serum FGF23 levels were significantly higher in patients with variations in PHEX, FGF23, DMP1 or ENPP1 genes. The major genetic causes of rickets were classic hypophosphatemic rickets with elevated FGF23 levels, distal renal tubular acidosis, and vitamin D dependent rickets. Based on the present results, we propose a customized gene panel for targeted exome sequencing, which will be useful for confirming the diagnosis in most patients with hypophosphatemic rickets.
- Published
- 2021
23. Efficacy of rituximab versus tacrolimus in difficult-to-treat steroid-sensitive nephrotic syndrome: an open-label pilot randomized controlled trial
- Author
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Georgie Mathew, Aditi Sinha, Aijaz Ahmed, Neetu Grewal, Priyanka Khandelwal, Pankaj Hari, and Arvind Bagga
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Nephrotic Syndrome ,Treatment Outcome ,Nephrology ,Recurrence ,Prednisolone ,Pediatrics, Perinatology and Child Health ,Humans ,Pilot Projects ,Steroids ,Rituximab ,Tacrolimus ,Immunosuppressive Agents - Abstract
Rituximab and tacrolimus are therapies reserved for patients with frequently relapsing or steroid-dependent nephrotic syndrome who have failed conventional steroid-sparing agents. Given their toxicities, demonstrating non-inferiority of rituximab to tacrolimus may enable choice between these medications.This investigator-initiated, single-center, open-label, pilot randomized controlled trial examined the non-inferiority of two doses of intravenous (IV) rituximab given one-week apart to oral therapy with tacrolimus (1:1 allocation), in maintaining sustained remission over 12 months follow-up, in patients with difficult-to-treat steroid-sensitive nephrotic syndrome, defined as frequently relapsing or steroid-dependent disease that had failed ≥ 2 steroid-sparing strategies. Secondary outcomes included frequency of relapses, proportion with frequent relapses, time to relapse and frequent relapses, and adverse events (CTRI/2018/11/016342).Baseline characteristics were comparable for 41 patients randomized to receive rituximab (n = 21) or tacrolimus (n = 20). While 55% of patients in each limb were in sustained remission at 1 year, non-inferiority of rituximab to tacrolimus was not demonstrated (mean difference 0%; 95% CI - 30.8%, 30.8%; non-inferiority limit - 20%; P = 0.50). Frequent relapses were more common in patients administered rituximab compared to tacrolimus (risk difference 30%, 95% CI 7.0, 53.0, P = 0.023). Both groups showed similar reductions in relapse rates and prednisolone use. Common adverse events were infusion-related with rituximab and gastrointestinal symptoms with tacrolimus.Therapy with rituximab was not shown to be non-inferior to 12-months treatment with tacrolimus in maintaining remission in patients with difficult-to-treat steroid-sensitive nephrotic syndrome. Frequent relapses were more common with rituximab. While effective, both agents require close monitoring for adverse events. A higher resolution version of the Graphical abstract is available as Supplementary information.
- Published
- 2021
24. Short-Term Effects of Cholecalciferol Supplementation on cFGF23 Levels in Children with Chronic Kidney Disease and Vitamin D Insufficiency
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Abraar Sheriff, Georgie Mathew, Aditi Sinha, Smriti Hari, Nandita Gupta, Lakshmy Ramakrishnan, Pankaj Hari, and Arvind Bagga
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Vitamins ,Alkaline Phosphatase ,Vitamin D Deficiency ,Phosphates ,Fibroblast Growth Factors ,Parathyroid Hormone ,Pediatrics, Perinatology and Child Health ,Dietary Supplements ,Humans ,Calcium ,Prospective Studies ,Renal Insufficiency, Chronic ,Vitamin D ,Child ,Cholecalciferol - Abstract
Data on the effect of vitamin D supplementation on fibroblast growth factor 23 (FGF23), in chronic kidney disease (CKD) are scarce. In a prospective interventional study, the effect of vitamin D supplementation on cFGF23 (C-terminal FGF23) levels in children with CKD stages 2-4 was examined. Forty-one children with CKD and vitamin D insufficiency were administered 600,000 units of cholecalciferol over 3 d; 88% of patients achieved sufficiency at 8 wk. Significant increase in serum cFGF23 and phosphate levels was observed in CKD stage 2 after supplementation, but not in CKD stages 3 and 4. There was no correlation of the change in cFGF23 level with baseline or change in bone health parameters (calcium, phosphate, parathormone or alkaline phosphatase) or with change in flow-mediated dilatation (FMD) of the brachial artery. It is concluded that cholecalciferol supplementation increases serum calcium and reduces PTH, but does not adversely affect FGF23 levels in CKD.
- Published
- 2021
25. Survey of Telemedicine by Pediatric Nephrologists During the COVID-19 Pandemic
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Mignon McCulloch, Hui-Kim Yap, Pankaj Hari, Arvind Bagga, Maria Díaz-González de Ferris, Guido Filler, Timothy E. Bunchman, Bradley A. Warady, Nikhil Nair, Sidharth Kumar Sethi, Katherine Twombley, Sharon M. Bartosh, Rupesh Raina, Gaurav Kapur, and Sarah Rush
- Subjects
pediatric nephrology online services ,Telemedicine ,Coronavirus disease 2019 (COVID-19) ,patient satisfaction ,business.industry ,patient experience ,Health Insurance Portability and Accountability Act ,COVID-19 pandemic ,providerexperience ,medicine.disease ,Patient satisfaction ,Clinical Research ,Nephrology ,Patient experience ,Pandemic ,Health care ,medicine ,Medical emergency ,telemedicine ,business ,Reimbursement - Abstract
Introduction The slow increase in use of telemedicine began to expand rapidly, along with reimbursement changes, during the coronavirus disease-2019 (COVID-19) pandemic. Standardized protocols for these services are lacking but are needed for effective and equitable health care. In this study, we queried pediatric nephrologists and their patients about their telemedicine experiences during the pandemic. Methods Surveys that were in compliance with the Health Insurance Portability and Accountability Act were deployed online to patients and physicians. Results We collected survey responses from 400 patients and 197 pediatric nephrologists. Patients reported positive experiences with telemedicine visits as it was logistically easier than in-person visits. Patients also felt that the quality of their visits were equivalent to what they would receive in person. Physicians used a wide variety of online systems to conduct synchronous telemedicine with Zoom (23%), EPIC (9%), Doxy.me (7%), services not specified (37%), or a mix of local or smaller services (24%). Most physicians' concerns were related to technological issues and the ability to procure physical exams and/or laboratory results. Conclusions There is a paucity of published trials on telemedicine services in pediatric nephrology. Virtual care was feasible and acceptable for patients, caregivers, and providers during the COVID-19 pandemic., Graphical abstract
- Published
- 2021
26. Efficacy and Safety of Combination Therapy with Tolvaptan and Furosemide in Children with Nephrotic Syndrome and Refractory Edema: A Prospective Interventional Study
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Jitendra Meena, Pankaj Hari, Aditi Sinha, and Arvind Bagga
- Subjects
Heart Failure ,Male ,Nephrotic Syndrome ,Furosemide ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Tolvaptan ,Edema ,Humans ,Drug Therapy, Combination ,Prospective Studies ,Child ,Diuretics - Abstract
Severe edema in children with nephrotic syndrome is often refractory to conventional diuretics. Tolvaptan has been used satisfactorily for managing edema in patients with heart failure and cirrhosis. The safety and efficacy of combination therapy with oral tolvaptan and intravenous (IV) furosemide was assessed in patients with furosemide refractory edema.Patients, aged 5-18 y with nephrotic syndrome and severe edema, were screened for eligibility. After excluding hypovolemia, patients received IV furosemide (3-4 mg/kg/d) for 48 h. Those refractory to IV furosemide (weight loss 3%) received tolvaptan (0.5-1 mg/kg once daily) and IV furosemide for the next 48 h. Parameters were compared between 48 h of furosemide alone and combination therapy.A total of 24 patients (18 boys) with mean age of 8.0 ± 3.0 y were enrolled. Urine volume significantly increased with combination therapy as compared to furosemide therapy (mean difference: 1.2 mL/kg/h; 95% CI: 0.8-1.65 mL/kg/h) (p 0.001). Compared to therapy with furosemide alone, combination therapy resulted in significant reduction in body weight from 26.9 ± 10.3 kg to 24.8 ± 9.7 kg (p 0.001). Estimated glomerular filtration rate did not change (p = 0.81) but serum sodium increased from 135.7 ± 3.3 mEq/L to 140.4 ± 4.8 mEq/L (p 0.001) with combination therapy; 2 patients showed asymptomatic hypernatremia.The combination of oral tolvaptan and IV furosemide is effective in augmenting diuresis and reducing weight in patients with furosemide refractory edema but requires monitoring of electrolytes and volume status.
- Published
- 2021
27. Therapy with the combination of tolvaptan and furosemide for refractory edema in nephrotic syndrome
- Author
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Pankaj Hari, Aditi Sinha, Arvind Bagga, and Jitendra Kumar Meena
- Subjects
medicine.medical_specialty ,business.industry ,Urology ,Tolvaptan ,Furosemide ,medicine.disease ,lcsh:Diseases of the genitourinary system. Urology ,lcsh:RC870-923 ,Refractory ,Nephrology ,Edema ,Medicine ,medicine.symptom ,Letters to Editor ,business ,Nephrotic syndrome ,medicine.drug - Published
- 2020
28. Successful use of tocilizumab in amyloidosis secondary to systemic juvenile idiopathic arthritis
- Author
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Pankaj Hari, Narendra Kumar Bagri, Adarsh Barwad, Saroj Kumar Tripathy, Ravi Hari Phulware, and Ayush Gupta
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Male ,medicine.medical_specialty ,Immunology ,Arthritis ,Antibodies, Monoclonal, Humanized ,chemistry.chemical_compound ,Tocilizumab ,Enalapril ,Rheumatology ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Juvenile ,Child ,Cyclophosphamide ,Antihypertensive Agents ,Proteinuria ,Adult patients ,business.industry ,Amyloidosis ,medicine.disease ,Dermatology ,Arthritis, Juvenile ,chemistry ,Antirheumatic Agents ,Hypertension ,Kidney Diseases ,medicine.symptom ,Complication ,business - Abstract
Amyloidosis secondary to juvenile idiopathic arthritis is a known complication of poorly controlled systemic juvenile idiopathic arthritis (SJIA), occurring in 1-2% of the patients. The IL-6 inhibitor tocilizumab is effective in controlling systemic signs and symptoms of sJIA and may be of therapeutic benefit in secondary amyloidosis. Herein, we report the clinical timeline of a 10-year boy with sJIA and secondary amyloidosis, who showed a sustained improvement of systemic symptoms and a reduction in proteinuria with tocilizumab. Compared to the data on adult patients affected with the secondary amyloidosis, there are very few reports on therapeutic options for the children affected with SJIA and secondary amyloidosis in the paediatric population. While doing a systematic literature search for writing this review, we could only retrieve nine case reports and one case series of the children affected with SJIA and secondary amyloidosis, including five cases which were treated with tocilizumab. We also looked into the clinical and biochemical response to various agents that have been used in the previous cases, including tocilizumab. The available literature and the present case report suggest that tocilizumab may be considered as a safe and effective option to treat SJIA-related secondary amyloidosis.
- Published
- 2019
29. Glomerular C4d Staining Does Not Exclude a C3 Glomerulopathy
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Geetika Singh, Immanuel Pradeep, Arvind Bagga, Amit K. Dinda, Aasma Nalwa, Adarsh Barwad, Shamresh Kumar Singh, Lavleen Singh, Aditi Sinha, Pankaj Hari, Sanjay K. Agarwal, and Soumita Bagchi
- Subjects
Pathology ,medicine.medical_specialty ,C3 Glomerulonephritis ,030232 urology & nephrology ,lectin pathway ,030204 cardiovascular system & hematology ,lcsh:RC870-923 ,Immunofluorescence ,03 medical and health sciences ,0302 clinical medicine ,C3 glomerulonephritis ,Glomerulopathy ,Translational Research ,Medicine ,Dense Deposit Disease ,C3 glomerulopathy ,dense deposit disease ,medicine.diagnostic_test ,business.industry ,lcsh:Diseases of the genitourinary system. Urology ,medicine.disease ,C4d ,Staining ,Complement system ,Nephrology ,Lectin pathway ,Alternative complement pathway ,business - Abstract
Introduction: C4d, an early product in the classical/lectin complement pathway has shown potential in the evaluation of C3 glomerulopathy where its absence would support an alternative pathway abnormality. As autoimmune/genetic complement testing is not readily available to most parts of the world, glomerular C4d staining may serve as a useful additional step toward the diagnosis. Methods: To test this hypothesis, C4d staining was performed on a large cohort of C3 glomerulopathy. Archival cases from 2011 to 2017 were reviewed and immunohistochemistry for C4d was performed, scored (scale of 0 to 3+), and correlated with the immunofluorescence and ultrastructural findings. Paraffin immunofluorescence was performed in cases of “discordant C4d” to unmask Igs. Results: Twenty-seven cases of dense deposit disease (DDD) and 14 cases of C3 glomerulonephritis (C3GN) were retrieved. C4d demonstrated a range of staining intensities with negative/traces in only 22% of DDD and 64% of C3GN. Lower-intensity C4d staining (1 to 2+) was mostly concordant with similar amounts of Igs/C1q. Discordant 3+ staining was noted in approximately 50% of cases of DDD and 20% of cases of C3GN. Among them, paraffin immunofluorescence unmasked polyclonal Igs in 2 of 5 cases of DDD and 1 of 3 cases of C3GN. Conclusion: This observational study suggests that the presence of glomerular C4d should not exclude a C3 glomerulopathy. In lower intensities, it appears to represent overlying classical/lectin pathway activation with concordant Ig/C1q deposits. A subset of cases, however, displays intense and discordant C4d staining, which raises the possibility of an associated lectin pathway abnormality, a potential future area of study. Keywords: C3 glomerulonephritis, C3 glomerulopathy, C4d, dense deposit disease, lectin pathway
- Published
- 2019
30. Hemolytic uremic syndrome in a developing country: Consensus guidelines
- Author
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Ranjeet Thergaonkar, Anil Vasudevan, Sidharth Kumar Sethi, Marie-Agnès Dragon-Durey, Arvind Bagga, Kirtisudha Mishra, Saroj Kumar Patnaik, Aditi Sinha, Pankaj Hari, Jyoti Sharma, and Priyanka Khandelwal
- Subjects
Nephrology ,medicine.medical_specialty ,Consensus ,Thrombotic microangiopathy ,Consensus Development Conferences as Topic ,030232 urology & nephrology ,India ,Developing country ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Plasma therapy ,Intensive care medicine ,Developing Countries ,Plasma Exchange ,Shiga-Toxigenic Escherichia coli ,business.industry ,Acute kidney injury ,Eculizumab ,medicine.disease ,Hemolytic-Uremic Syndrome ,Practice Guidelines as Topic ,Pediatrics, Perinatology and Child Health ,Research studies ,Differential diagnosis ,business ,medicine.drug - Abstract
Hemolytic uremic syndrome (HUS) is a leading cause of acute kidney injury in children. Although international guidelines emphasize comprehensive evaluation and treatment with eculizumab, access to diagnostic and therapeutic facilities is limited in most developing countries. The burden of Shiga toxin-associated HUS in India is unclear; school-going children show high prevalence of anti-factor H (FH) antibodies. The aim of the consensus meeting was to formulate guidelines for the diagnosis and management of HUS in children, specific to the needs of the country. Four workgroups performed literature review and graded research studies addressing (i) investigations, biopsy, genetics, and differential diagnosis; (ii) Shiga toxin, pneumococcal, and infection-associated HUS; (iii) atypical HUS; and (iv) complement blockade. Consensus statements developed by the workgroups were discussed during a consensus meeting in March 2017. An algorithm for classification and evaluation was developed. The management of Shiga toxin-associated HUS is supportive; prompt plasma exchanges (PEX) is the chief therapy in patients with atypical HUS. Experts recommend that patients with anti-FH-associated HUS be managed with a combination of PEX and immunosuppressive medications. Indications for eculizumab include incomplete remission with plasma therapy, life-threatening features, complications of PEX or vascular access, inherited defects in complement regulation, and recurrence of HUS in allografts. Priorities for capacity building in regional and national laboratories are highlighted. Limited diagnostic capabilities and lack of access to eculizumab prevent the implementation of international guidelines for HUS in most developing countries. We propose practice guidelines for India, which will perhaps be applicable to other developing countries.
- Published
- 2019
31. Telemedicine for Pediatric Nephrology: Perspectives on COVID-19, Future Practices, and Workflow Changes
- Author
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Rupesh Raina, Nikhil Nair, Aditya Sharma, Ronith Chakraborty, Sarah Rush, Hui Kim Yap, Sidharth K. Sethi, Arvind Bagga, Pankaj Hari, Timothy Bunchman, Sharon Bartosh, Katherine Twombley, Gaurav Kapur, Mignon McCulloch, Guido Filler, Bradley A. Warady, and Maria Díaz-González de Ferris
- Subjects
Telemedicine ,Coronavirus disease 2019 (COVID-19) ,business.industry ,education ,Delphi method ,MEDLINE ,medicine.disease ,Pediatrics ,Article ,Work (electrical) ,Nephrology ,health services administration ,Hypertension ,Internal Medicine ,medicine ,Pediatric nephrology ,Work flow ,Medical emergency ,Acute Kidney Injury [Index Words] ,Rural area ,business ,Dialysis - Abstract
Although the use of telemedicine in rural areas has increased steadily over the years, its use was rapidly implemented during the onset of the coronavirus disease 2019 (COVID-19) crisis. Due to this rapid implementation, there is a lack of standardized work flows to assess and treat for various nephrotic conditions, symptoms, treatment modalities, and transition processes in the pediatric population. To provide a foundation/suggestion for future standardized work flows, the authors of this report have developed standardized work flows using the Delphi method. These work flows were informed based on results from cross-sectional surveys directed to patients and providers. Most patients and providers were satisfied, 87% and 71%, respectively, with their telemedicine visits. Common issues that were raised with the use of telemedicine included difficulty procuring physical laboratory results and a lack of personal warmth during telemedicine visits. The work flows created based on these suggestions will both enhance safety in treating patients and allow for the best possible care.
- Published
- 2021
32. Consensus Guidelines on Management of Steroid-Resistant Nephrotic Syndrome
- Author
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Anil, Vasudevan, Ranjeet, Thergaonkar, Mukta, Mantan, Jyoti, Sharma, Priyanka, Khandelwal, Pankaj, Hari, Aditi, Sinha, Arvind, Bagga, and R N, Srivastava
- Subjects
Proteinuria ,Nephrotic Syndrome ,Recurrence ,Humans ,Steroids ,Child ,Kidney - Abstract
The management of steroid resistant nephrotic syndrome (SRNS) is challenging. These guidelines update existing 2009 Indian Society of Pediatric Nephrology recommendations on its management.To frame revised guidelines on diagnosis and evaluation, treatment and follow up, and supportive care of patients with the illness.The guidelines combine evidence-based recommendations and expert opinion. Formulation of key questions was followed by systematic review of literature, evaluation of evidence by experts and two face-to-face meetings.Fourteen statements provide updated advice for managing steroid resistance, and underscore the importance of estimating proteinuria and baseline kidney function, and the need for kidney biopsy and genetic screening. Calcineurin inhibitors are recommended as most effective in inducing remission of proteinuria, the chief factor associated with long-term renal survival. Advice on managing allograft recurrence, congenital nephrotic syndrome, and monitoring and supportive care, including transition of care, are described. This revised practice guideline is intended to improve management and patient outcomes, and provide direction for future research.
- Published
- 2021
33. Non-antibiotic interventions for prevention of urinary tract infections in children: a systematic review and meta-analysis of randomized controlled trials
- Author
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Pankaj Hari, Jitendra Meena, Jogender Kumar, Christy C. Thomas, and Sumantra Raut
- Subjects
Adult ,medicine.medical_specialty ,medicine.drug_class ,Antibiotics ,urologic and male genital diseases ,Placebo ,Lower risk ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Antibiotic resistance ,Randomized controlled trial ,law ,030225 pediatrics ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Antibiotic prophylaxis ,Child ,Randomized Controlled Trials as Topic ,First episode ,business.industry ,Probiotics ,Antibiotic Prophylaxis ,Anti-Bacterial Agents ,Meta-analysis ,Pediatrics, Perinatology and Child Health ,Urinary Tract Infections ,business - Abstract
A considerable proportion of children experience a recurrence of urinary tract infection (UTI) following the first episode. While low-dose antibiotic prophylaxis has been the mainstay for the prevention of UTI, recent evidence raised concerns over their efficacy and safety. Hence, we aim to systematically synthesize evidence on the efficacy and safety of non-antibiotic prophylactic interventions for UTI. Using keywords related to study population (children) and intervention (non-antibiotic), we searched CENTRAL, Embase, PubMed, and Web of Science for randomized controlled trials (RCTs) published until August 2020. RCTs comparing any non-antibiotic interventions with placebo/antibiotics for prevention of UTIs in children were considered eligible. We used a random-effect model to provide pooled estimates. Sixteen trials evaluating 1426 participants were included. Cranberry was as effective as antibiotic prophylaxis (RR: 0.92; 95% CI: 0.56-1.50) but better than placebo/no therapy (RR: 0.48; 95% CI: 0.28-0.80) in reducing UTI recurrence. Probiotic therapy was more effective in reducing UTI recurrence (RR: 0.52; 95% CI: 0.29-0.94) when compared with placebo. While probiotic therapy was not better than antibiotics prophylaxis in preventing UTI (RR: 0.82; 95% CI: 0.56-1.21), they have a lower risk of antibiotic resistance (RR: 0.38; 95% CI: 0.21-0.69).Conclusion: Cranberry products and probiotics are the two non-antibiotic interventions that have been chiefly evaluated, reduce the risk of UTI recurrence when compared with placebo in children with a normal urinary tract. The findings from this systematic review suggest that while cranberry and probiotics may be used, there is a definite need to identify better and more acceptable non-antibiotic interventions. What is Known: • Efficacy of the low-dose antibiotic is controversial in preventing UTI and it is associated with increase in the risk of antimicrobial resistance. • Non-antibiotic interventions such as cranberry products are effective in preventing UTI recurrence in adults. What is New: • Cranberry products are effective in reducing the recurrence of UTI in children with normal urinary tract. • Low-quality evidence suggests that probiotics can be a potential prophylactic measure to reduce recurrence of UTI in the pediatric population.
- Published
- 2020
34. Managing Children with Renal Diseases during COVID-19 Pandemic
- Author
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Anil, Vasudevan, Mukta, Mantan, Sriram, Krishnamurthy, Priya, Pais, Georgie, Mathew, Pankaj, Hari, Madhuri, Kanitkar, Sanjeev, Gulati, Arvind, Bagga, and Om P, Mishra
- Abstract
The coronavirus outbreak is a rapidly evolving pandemic, placing unprecedented strain on health-care systems. COVID-19 presents challenges for management of children with renal diseases especially those receiving long-term immunosuppressive medications, including renal transplant recipients and those with chronic kidney disease and acute kidney injury requiring dialysis. Our preparedness for managing this vulnerable group of children is the need of the hour. The purpose of this article is to provide guidance to caregivers and health care personnel involved in management of children with renal diseases and to ensure patient well-being, while protecting staff from infection.
- Published
- 2020
35. Impaired Distal Tubular Acidification, Renal Cysts and Nephrocalcinosis in Monogenic Hypertension
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Menka Yadav, Aditi Sinha, Pankaj Hari, and Arvind Bagga
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Adult ,medicine.medical_specialty ,Hypokalemia ,urologic and male genital diseases ,Gastroenterology ,Asymptomatic ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Polyuria ,030225 pediatrics ,Internal medicine ,medicine ,Humans ,Exome ,business.industry ,Cysts ,Infant, Newborn ,Hydrogen-Ion Concentration ,Kidney Diseases, Cystic ,medicine.disease ,Nephrocalcinosis ,Blood pressure ,chemistry ,Pediatrics, Perinatology and Child Health ,Hypertension ,Spironolactone ,Female ,medicine.symptom ,business ,Polydipsia ,030217 neurology & neurosurgery - Abstract
Monogenic defects in tubular sodium handling contribute a small proportion to hypertension in childhood. Presentation varies from severe hypertension manifesting at birth to asymptomatic hypertension and hypokalemic metabolic alkalosis detected incidentally in adulthood. A 12-y-old girl presenting with polyuria, polydipsia, severe hypertension and seizures, was found to have hypokalemia, renal medullary cysts and nephrocalcinosis. Clinical exome revealed a homozygous variation of unknown significance in exon 5 of the HSD11B2 gene, indicating the diagnosis of apparent mineralocorticoid excess. Therapy with spironolactone was associated with resolution of hypokalemia and normal blood pressure during two-year follow up.
- Published
- 2020
36. Prevalence of Bladder and Bowel Dysfunction in Toilet-Trained Children With Urinary Tract Infection and/or Primary Vesicoureteral Reflux: A Systematic Review and Meta-Analysis
- Author
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Pankaj Hari, Arvind Bagga, Georgie Mathew, Jitendra Kumar Meena, and Aditi Sinha
- Subjects
dysfunctional elimination syndrome ,medicine.medical_specialty ,Constipation ,Urinary system ,MEDLINE ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,Pediatrics ,Vesicoureteral reflux ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,Internal medicine ,medicine ,In patient ,skin and connective tissue diseases ,business.industry ,lcsh:RJ1-570 ,lcsh:Pediatrics ,vesicoureteral reflux ,constipation ,medicine.disease ,female genital diseases and pregnancy complications ,Bowel dysfunction ,Meta-analysis ,Relative risk ,Pediatrics, Perinatology and Child Health ,Systematic Review ,voiding dysfunction ,medicine.symptom ,urinary tract infection ,business - Abstract
Introduction: Urinary tract infection (UTI) in children leads to renal scarring in 10-15% of patients. Urinary tract anomalies and bladder and bowel dysfunction (BBD) are documented risk factors for recurrent UTIs. Estimates of baseline prevalence of BBD in children with UTI will help the clinician in the management strategy. Hence, a systematic review and meta-analysis was conducted to estimate the pooled prevalence of BBD. Methods: MEDLINE, EMBASE, and CENTRAL (Cochrane Central Register of Controlled Trials) databases were searched for articles related to UTI, primary vesicoureteral reflux (VUR), and BBD. We included studies that provided prevalence of BBD in toilet-trained patients aged 1-18 years with UTI and/or VUR. BBD was defined based on clinical history or questionnaire or urodynamic studies. Two authors independently reviewed, assessed, and abstracted data from studies. Pooled prevalence was calculated based on a random effects model. Results: Forty-three studies fulfilling the eligibility criteria were selected from a total of 1,731 studies. Among patients presenting with UTI without primary VUR, pooled prevalence of BBD was 41% (95% CI: 26-55; nine studies, 920 patients, I 2 = 96.0%), whereas its prevalence in patients with primary VUR was 49% (43-56; 30 studies, 5,060 patients, I 2 = 96.0%). Weighting by the study design and quality did not affect the prevalence. In patients with primary VUR, prevalence of BBD was higher in females (53%; 42-65) than in males (44%; 15-73). In studies where urodynamic study was used for the diagnosis of BBD, prevalence was 63%. The presence of BBD in patients with primary VUR increased risk of recurrent UTIs [relative risk (RR): 2.1; 1.7-2.5]. In five studies that reported separate data on constipation, pooled prevalence of constipation was 27% (16-37). Conclusion: Almost half of the patients with primary VUR have BBD, and its presence increases the risk of recurrent UTIs. Trends of high BBD prevalence were also observed in patients presenting with UTI without VUR. These prevalence estimates suggest that all toilet-trained children presenting with UTI with or without VUR should be assessed for BBD, which will help in their further management.
- Published
- 2020
37. Effect of atorvastatin on dyslipidemia and carotid intima-media thickness in children with refractory nephrotic syndrome: a randomized controlled trial
- Author
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Pankaj Hari, Amit Kumar Satpathy, Ramakrishnan Lakshmy, Ranjeet Thergaonkar, Priyanka Khandelwal, Arvind Bagga, Aditi Sinha, and Smriti Hari
- Subjects
Male ,medicine.medical_specialty ,Nephrotic Syndrome ,Adolescent ,Atorvastatin ,030232 urology & nephrology ,Serum albumin ,Serum Albumin, Human ,030204 cardiovascular system & hematology ,Placebo ,Carotid Intima-Media Thickness ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Double-Blind Method ,Internal medicine ,Hyperlipidemia ,Humans ,Medicine ,Prospective Studies ,cardiovascular diseases ,Child ,Dyslipidemias ,Creatinine ,biology ,business.industry ,Cholesterol, LDL ,Atherosclerosis ,medicine.disease ,Carotid Arteries ,Treatment Outcome ,Intima-media thickness ,chemistry ,Nephrology ,Pediatrics, Perinatology and Child Health ,biology.protein ,Female ,lipids (amino acids, peptides, and proteins) ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,Nephrotic syndrome ,Dyslipidemia ,medicine.drug - Abstract
Dyslipidemia is an important cardiovascular risk factor in steroid-resistant nephrotic syndrome (SRNS). Efficacy of statins for treatment of hyperlipidemia in children with SRNS is unclear. This prospective, randomized, double-blind, placebo-controlled, parallel-group clinical trial enrolled 30 patients with SRNS, aged 5–18 years, with serum low-density lipoprotein cholesterol (LDL-C) levels between 130 and 300 mg/dl, to receive a fixed dose of atorvastatin (n = 15, 10 mg/d) or placebo (n = 15) by block randomization in a 1:1 ratio. Primary outcome was change in serum LDL-C at 12 months. Change in levels of other lipid fractions, carotid intima-media thickness (cIMT), flow-mediated dilation (FMD) of the brachial artery, and adverse events were also evaluated. At the end of 12 months, atorvastatin was not superior to placebo in reducing plasma LDL-C levels, median percentage reduction 15.8% and 9.5% respectively, in atorvastatin and placebo arms (n = 14 in each; P = 0.40). Apolipoprotein B levels significantly declined with atorvastatin in modified intention-to-treat analysis (P = 0.01) but not in the per-protocol analysis. There was no significant effect on other lipid fractions, cIMT and FMD. Adverse events were similar between groups. Change in serum albumin was negatively associated with change in serum LDL-C, very low-density lipoprotein cholesterol, total cholesterol, triglyceride, and apolipoprotein B (P
- Published
- 2018
38. Lupus Nephritis in Indian Children: Flares and Refractory Illness
- Author
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Kesavan Sankaramangalam, Jaiben George, Pankaj Hari, Aditi Sinha, Arvind Bagga, and Amit K. Dinda
- Subjects
Male ,medicine.medical_specialty ,Adolescent ,Refractory period ,030232 urology & nephrology ,Lupus nephritis ,India ,urologic and male genital diseases ,Single Center ,End stage renal disease ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,Internal medicine ,Pediatric surgery ,Humans ,Medicine ,Child ,skin and connective tissue diseases ,Retrospective Studies ,030203 arthritis & rheumatology ,business.industry ,Incidence ,Incidence (epidemiology) ,Infant, Newborn ,Infant ,Retrospective cohort study ,medicine.disease ,Lupus Nephritis ,Treatment Outcome ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Disease Progression ,Female ,business ,Follow-Up Studies - Abstract
To evaluate the incidence of flares and treatment resistance in children with lupus nephritis and their association with renal outcomes. We retrospectively reviewed the case records of 34 children treated for lupus nephritis (Class II-IV) at a single center. Patients were followed for a minimum of five years to evaluate treatment response, onset of flares, and renal survival. Regression analyses were performed to identify the factors associated with treatment refractoriness, incidence of flares and renal survival. The incidence of flares was 0.16 episodes/person/year. Eight patients (23.5%) were refractory to treatment. The five-year renal survival was 79%. Multiple episodes of flares (P=0.028) and therapy refractoriness (P=0.003) were associated with poor renal survival. Prevention and aggressive management of renal flares is expected to prevent progression to end stage renal disease in lupus nephritis.
- Published
- 2018
39. Characterization of genetic predisposition and autoantibody profile in atypical haemolytic-uraemic syndrome
- Author
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Pankaj Hari, Himanshi Saini, Priyadarshini Chatterjee, Aditi Sinha, Vineeta Bal, Prasenjit Guchhait, Priyanka Khandelwal, Angika Bhasym, Bahadur Singh Gurjar, Anna George, Savit Prabhu, Tholu Manikanta Sriharsha, Mamta Puraswani, Arvind Sahu, Savita Saini, Amita Sharma, Anita Kamra Verma, Arvind Bagga, and Satyajit Rath
- Subjects
0301 basic medicine ,biology ,business.industry ,Immunology ,Autoantibody ,Original Articles ,Epitope ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Genotype ,Genetic predisposition ,biology.protein ,Immunology and Allergy ,Medicine ,Haemolytic-uraemic syndrome ,Antibody ,business ,Gene ,030215 immunology ,Paediatric patients - Abstract
We previously reported that Indian paediatric patients with atypical haemolytic–uraemic syndrome (aHUS) showed high frequencies of anti‐complement factor H (FH) autoantibodies that are correlated with homozygous deletion of the genes for FH‐related proteins 1 and 3 (FHR1 and FHR3) (FHR1/3 (–/–)). We now report that Indian paediatric aHUS patients without anti‐FH autoantibodies also showed modestly higher frequencies of the FHR1/3 (–/–) genotype. Further, when we characterized epitope specificities and binding avidities of anti‐FH autoantibodies in aHUS patients, most anti‐FH autoantibodies were directed towards the FH cell‐surface anchoring polyanionic binding site‐containing C‐terminal short conservative regions (SCRs) 17–20 with higher binding avidities than for native FH. FH SCR17–20‐binding anti‐FH autoantibodies also bound the other cell‐surface anchoring polyanionic binding site‐containing region FH SCR5–8, at lower binding avidities. Anti‐FH autoantibody avidities correlated with antibody titres. These anti‐FH autoantibody characteristics did not differ between aHUS patients with or without the FHR1/3 (–/–) genotype. Our data suggest a complex matrix of interactions between FHR1‐FHR3 deletion, immunomodulation and anti‐FH autoantibodies in the aetiopathogenesis of aHUS.
- Published
- 2018
40. Prevalence and predictors of peripheral neuropathy in nondiabetic children with chronic kidney disease
- Author
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G S Toteja, Pankaj Hari, Ravindra Mohan Pandey, Aditi Sinha, Arvind Bagga, Sangeetha Yoganathan, Sheffali Gulati, and Mohammad Irshad
- Subjects
Axonal neuropathy ,medicine.medical_specialty ,Physiology ,business.industry ,030232 urology & nephrology ,medicine.disease ,Micronutrient ,Confidence interval ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Peripheral neuropathy ,Physiology (medical) ,Internal medicine ,Cohort ,Etiology ,medicine ,Demyelinating neuropathy ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Kidney disease - Abstract
Introduction This study sought to determine the prevalence and predictors of peripheral neuropathy in nondiabetic children with chronic kidney disease (CKD). Methods Fifty-one consecutive normally nourished children, 3-18 years of age, with CKD stages IV and V of nondiabetic etiology were enrolled from May to December 2012. Nerve conduction studies were performed in 50 children. Blood samples were analyzed for the biochemical parameters, trace elements, and micronutrients. Results The prevalence of peripheral neuropathy in our cohort was 52% (95% confidence interval 37.65, 66.34). The majority (80.8%) of the children had axonal neuropathy, and 11.5% had demyelinating neuropathy. Isolated motor neuropathy was identified in 92.3% of the children, and sensorimotor neuropathy was identified in 7.6%. The significant risk factors associated with peripheral neuropathy were older age, low serum copper, and dialysis therapy. Discussion Electrodiagnostic studies should be performed in children with CKD to assess for peripheral neuropathy for the purpose of optimizing medical care. Muscle Nerve 57: 792-798, 2018.
- Published
- 2018
41. Genetics of Refractory Rickets: Identification of Novel PHEX Mutations in Indian Patients and a Literature Update
- Author
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Arundhati Sharma, Aditi Sinha, Arvind Bagga, Pankaj Hari, and Binata Marik
- Subjects
0301 basic medicine ,Genetics ,Mutation ,medicine.diagnostic_test ,business.industry ,PHEX ,Genetic disorder ,030209 endocrinology & metabolism ,Rickets ,medicine.disease_cause ,medicine.disease ,DMP1 ,03 medical and health sciences ,Hypophosphatemic Rickets ,030104 developmental biology ,0302 clinical medicine ,Pediatrics, Perinatology and Child Health ,Medicine ,Missense mutation ,business ,Genetics (clinical) ,Genetic testing - Abstract
Refractory rickets is a genetic disorder that cannot be treated by vitamin D supplementation and adequate dietary calcium and phosphorus. Hereditary hypophosphatemic rickets is one of the major forms of refractory rickets in Indian children and caused due to mutations in the PHEX, FGF23, DMP1, ENPP1, and SLC34A3 genes. This is the first study in India on a large number of patients reporting on mutational screening of the PHEX gene. Direct sequencing in 37 patients with refractory rickets revealed eight mutations in 13 patients of which 1 was nonsense, 2 were deletions, 1 was a deletion–insertion, and 4 were missense mutations. Of these mutations, four (c.566_567 delAG, c.651_654delACAT, c.1337delinsAATAA, and c.2048T > A) were novel mutations. This article discusses the mutations in Indian patients, collates information on the genetic causes of refractory rickets, and emphasizes the significance of genetic testing for precise diagnosis, timely treatment, and management of the condition, especially in developing countries.
- Published
- 2018
42. POS-462 EFFICACY AND SAFETY OF PREDNISOLONE ON ALTERNATE DAYS MADE DAILY WITH INFECTIONS VERSUS LEVAMISOLE IN FREQUENTLY RELAPSING NEPHROTIC SYNDROME: AN OPEN LABEL RANDOMIZED CONTROLLED TRIAL
- Author
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Pankaj Hari, Ashish C. Sinha, Arvind Bagga, and K. Ghanapriya
- Subjects
medicine.medical_specialty ,Frequently Relapsing Nephrotic Syndrome ,business.industry ,Levamisole ,Diseases of the genitourinary system. Urology ,law.invention ,Randomized controlled trial ,Nephrology ,law ,Internal medicine ,medicine ,Prednisolone ,RC870-923 ,Open label ,business ,medicine.drug - Published
- 2021
43. POS-457 EFFICACY AND SAFETY OF RITUXIMAB VERSUS TACROLIMUS IN FREQUENTLY RELAPSING NEPHROTIC SYNDROME: AN OPEN LABEL RANDOMIZED CONTROLLED TRIAL
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Pankaj Hari, A. Ahmad, N. Grewal, Ashish C. Sinha, Arvind Bagga, and G. Mathew
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medicine.medical_specialty ,Frequently Relapsing Nephrotic Syndrome ,business.industry ,Diseases of the genitourinary system. Urology ,Tacrolimus ,law.invention ,Randomized controlled trial ,Nephrology ,law ,Internal medicine ,Medicine ,Rituximab ,RC870-923 ,Open label ,business ,medicine.drug - Published
- 2021
44. Mutations in membrane cofactor protein (CD46) gene in Indian children with hemolytic uremic syndrome
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Mamta Puraswani, Himanshi Saini, Aditi Sinha, Priyanka Khandelwal, Pankaj Hari, Shweta Birla, Divya Bhatia, Arvind Bagga, and Arundhati Sharma
- Subjects
0301 basic medicine ,Transplantation ,medicine.diagnostic_test ,biology ,business.industry ,CD46 ,viruses ,In silico ,030232 urology & nephrology ,Intron ,medicine.disease ,Molecular biology ,female genital diseases and pregnancy complications ,Flow cytometry ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Nephrology ,Atypical hemolytic uremic syndrome ,RNA splicing ,medicine ,biology.protein ,Antibody ,business ,Gene - Abstract
Background Mutations in the CD46 gene account for an important proportion of patients with atypical hemolytic uremic syndrome (aHUS) who characteristically show multiple relapses, no response to plasma exchange and low recurrence risk in allograft. We screened for mutations in CD46 in patients with and without circulating anti-factor H (FH) antibodies-associated aHUS. Methods We estimated CD46 surface expression by flow cytometry and sequenced the CD46 gene in 23 and 56 patients with and without circulating anti-FH antibodies, respectively. Human Splicing Finder and PolyPhen2 were used for in silico prediction of pathogenicity. Results Two novel and three known (c.286 +2T > G, c.104G > A and c.565T > G) mutations in CD46 were found in nine (11.4%) patients; one patient had a variant of unknown significance and two patients presented during the first year of life. Novel intronic (c.1127 + 46C > G) and exonic (c.911C > T) mutations are proposed to activate cryptic splicing sites or alter protein conformation. Markedly reduced CD46 surface expression was found in homozygous states in five patients. Conclusion Patients with mutations in CD46 present at all ages, including the first year of life. Mutations in intron 2, (c.286 +2T > G) may be a potential hot spot in Indian children. Flow cytometry for CD46 expression is a satisfactory screening tool enabling early diagnosis.
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- 2017
45. Mycophenolate mofetil is inferior to tacrolimus in sustaining remission in children with idiopathic steroid-resistant nephrotic syndrome
- Author
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Pankaj Hari, Arvind Bagga, Mani Kalaivani, Aditi Sinha, Aarti Gupta, and Amit K. Dinda
- Subjects
Male ,medicine.medical_specialty ,Nephrotic Syndrome ,Time Factors ,Adolescent ,Prednisolone ,030232 urology & nephrology ,India ,chemical and pharmacologic phenomena ,Kaplan-Meier Estimate ,Gastroenterology ,Tacrolimus ,03 medical and health sciences ,0302 clinical medicine ,Focal segmental glomerulosclerosis ,Recurrence ,Internal medicine ,medicine ,Humans ,Minimal change disease ,Prospective Studies ,030212 general & internal medicine ,Child ,Adverse effect ,Glucocorticoids ,Drug Substitution ,business.industry ,Remission Induction ,Age Factors ,Infant ,Mycophenolic Acid ,medicine.disease ,Steroid-resistant nephrotic syndrome ,Calcineurin ,Treatment Outcome ,surgical procedures, operative ,Nephrology ,Child, Preschool ,Immunology ,Drug Therapy, Combination ,Female ,business ,Nephrotic syndrome ,Immunosuppressive Agents ,medicine.drug - Abstract
Studies of nephrotic syndrome show that substitution of calcineurin inhibitors by mycophenolate mofetil (MMF) enables sustained remission and corticosteroid sparing and avoids therapy associated adverse effects. However, controlled studies in patients with steroid resistance are lacking. Here we examined the effect of switching from therapy with tacrolimus to MMF on disease course in an open-label, one-to-one randomized, controlled trial on children (one to 18 years old), recently diagnosed with steroid-resistant nephrotic syndrome, at a referral center in India. Following six months of therapy with tacrolimus, patients with complete or partial remission were randomly assigned such that 29 received MMF while 31 received tacrolimus along with tapering prednisolone on alternate days for 12 months. On intention-to-treat analyses, the proportion of patients with a favorable outcome (sustained remission, infrequent relapses) at one year was significantly lower (44.8%) in the MMF group than in the tacrolimus group (90.3%). The incidence of relapses was significantly higher for patients treated with MMF than tacrolimus (mean difference: 1.05 relapses per person-year). While there was no difference in the proportion of patients with sustained remission, the risk of recurrence of steroid resistance was significantly higher for patients receiving MMF compared to tacrolimus (mean difference: 20.7%). Compared to tacrolimus, patients receiving MMF had a significantly (71%) lower likelihood of a favorable outcome and significantly increased risk of treatment failure (frequent relapses, steroid resistance). Thus, replacing tacrolimus with MMF after six months of tacrolimus therapy for steroid-resistant nephrotic syndrome in children is associated with significant risk of frequent relapses or recurrence of resistance. These findings have implications for guiding the duration of therapy with tacrolimus for steroid-resistant nephrotic syndrome.
- Published
- 2017
46. Phenotype of dent disease in a cohort of Indian children
- Author
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Pankaj Hari, Ranjeet Thergaonkar, S. P. Bhardwaj, Arvind Bagga, Aditi Sinha, and Cheong Hi
- Subjects
0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Adolescent ,030232 urology & nephrology ,Dent Disease ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Polyuria ,Chloride Channels ,Night Blindness ,medicine ,Humans ,Hypercalciuria ,Renal Insufficiency ,Child ,Retrospective Studies ,biology ,business.industry ,CLCN5 ,Infant ,Fanconi syndrome ,Retrospective cohort study ,medicine.disease ,Hypophosphatemic Rickets ,Phenotype ,030104 developmental biology ,Child, Preschool ,Mutation ,Pediatrics, Perinatology and Child Health ,biology.protein ,Nephrocalcinosis ,medicine.symptom ,business - Abstract
To describe the clinical and genotypic features of Dent disease in children diagnosed at our center over a period of 10 years. Case series. Pediatric Nephrology Clinic at a referral center in Northern India. The medical records of patients with Dent disease diagnosed and followed up at this hospital from June 2005 to April 2015 were reviewed. The diagnosis of Dent disease was based on presence of all three of the following: (i) low molecular weight proteinuria, (ii) hypercalciuria and (iii) one of the following: nephrolithiasis, hematuria, hypophosphatemia or renal insufficiency, with or without mutation in CLCN5 or OCRL1 genes. The phenotype in 18 patients diagnosed with Dent disease during this period was characterized by early age at onset (median 1.8 y), and polyuria, polydipsia, salt craving, hypophosphatemic rickets and night blindness. Rickets was associated with severe deformities, fractures or loss of ambulation in six patients. Nephrocalcinosis was present in three patients, while none had nephrolithiasis. Generalized aminoaciduria was seen in 13 patients, two had glucosuria alone, and one had features of Fanconi syndrome. Over a median follow up of 2.7 years, one patient developed renal failure. Genetic testing (n=15) revealed 5 missense mutations and 3 nonsense mutations in CLCN5 in 13 patients. Five of these variations (p.Met504Lys, p.Trp58Cys, p.Leu729X, p.Glu527Gln and p.Gly57Arg) have not been reported outside the Indian subcontinent. Our findings suggest a severe phenotype in a cohort of Indian patients with Dent disease.
- Published
- 2016
47. Current Management of Urinary Tract Infection and Vesicoureteral Reflux
- Author
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Ranjeet Thergaonkar and Pankaj Hari
- Subjects
medicine.medical_specialty ,Urinalysis ,Adolescent ,Fever ,Urinary system ,Urology ,urologic and male genital diseases ,Vesicoureteral reflux ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,030225 pediatrics ,medicine ,Dysuria ,Humans ,Antibiotic prophylaxis ,Child ,Reflux nephropathy ,Vesico-Ureteral Reflux ,Proteinuria ,medicine.diagnostic_test ,Pyelonephritis ,business.industry ,Infant ,medicine.disease ,female genital diseases and pregnancy complications ,Leukocyte esterase ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Urinary Tract Infections ,Female ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Urinary tract infection (UTI) is defined as the growth of a significant number of microorganisms of a single species in the urine, in the presence of symptoms. Symptoms in young children are non-specific such as fever without focus; young infants may manifest with irritability, failure to thrive, jaundice, vomiting and diarrhea. Older children usually have symptoms of cystitis or pyelonephritis. Symptoms of cystitis are dysuria, frequency, new onset incontinence and malodorous urine while symptoms of pyelonephritis are high grade fever, flank pain and vomiting. Rapid urine testing by microscopy for pus cells, dipstick testing for leukocyte esterase and nitrite, and enhanced urinalysis are supportive tests. Urine culture samples should be collected with proper technique and results interpreted for significant growth accordingly. Antibiotic therapy for 7–14 d for complicated UTI and 3–4 d for uncomplicated UTI is adequate. Further evaluation is recommended clinically for bladder-bowel dysfunction and obvious anatomical defects and by imaging for vesicoureteral reflux (VUR), usually by micturating cystourethrography (MCU). Since MCU involves exposure to radiation and urethral catheterization, it is now reserved for children with parenchymal involvement or recurrent UTI. VUR is the backward flow of urine into one or both ureters. Clinical manifestations other than UTI include incidental diagnosis on antenatal ultrasonography. Reflux nephropathy, the renal scarring associated with VUR may manifest clinically as hypertension, proteinuria and renal failure. The management of VUR is primarily with antibiotic prophylaxis. Anatomical correction is indicated in case of breakthrough febrile UTI. No intervention has been shown to reduce renal scarring.
- Published
- 2019
48. Clinical and Immunological Profile of Anti-factor H Antibody Associated Atypical Hemolytic Uremic Syndrome: A Nationwide Database
- Author
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Mamta Puraswani, Priyanka Khandelwal, Himanshi Saini, Savita Saini, Bahadur Singh Gurjar, Aditi Sinha, Rajashri Pramod Shende, Tushar Kanti Maiti, Abhishek Kumar Singh, Uma Kanga, Uma Ali, Indira Agarwal, Kanav Anand, Narayan Prasad, Padmaraj Rajendran, Rajiv Sinha, Anil Vasudevan, Anita Saxena, Sanjay Agarwal, Pankaj Hari, Arvind Sahu, Satyajit Rath, and Arvind Bagga
- Subjects
lcsh:Immunologic diseases. Allergy ,0301 basic medicine ,Male ,medicine.medical_specialty ,Thrombotic microangiopathy ,Adolescent ,Databases, Factual ,medicine.medical_treatment ,Immunology ,Left ventricular hypertrophy ,Gastroenterology ,Autoantigens ,03 medical and health sciences ,0302 clinical medicine ,Maintenance therapy ,Internal medicine ,plasma exchange ,Atypical hemolytic uremic syndrome ,medicine ,renal reserve ,Humans ,Immunology and Allergy ,Child ,Autoantibodies ,Original Research ,Proteinuria ,business.industry ,atypical hemolytic uremic syndrome ,Antibody titer ,Acute kidney injury ,Infant ,Immunosuppression ,medicine.disease ,factor H ,thrombotic microangiopathy ,030104 developmental biology ,Child, Preschool ,Complement Factor H ,Female ,medicine.symptom ,lcsh:RC581-607 ,business ,Immunosuppressive Agents ,030215 immunology - Abstract
Background: Atypical hemolytic uremic syndrome (aHUS), an important cause of acute kidney injury (AKI), is characterized by dysregulation of the alternative complement pathway. Autoantibodies to factor H (FH), a chief regulator of this pathway, account for a distinct subgroup. While high anti-FH titers predict relapse, they do not correlate well with disease activity and their functional characterization is required.Methods: Of 781 patients
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- 2019
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49. Dyslipidemia and cardiovascular health in childhood nephrotic syndrome
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Pankaj Hari, Priyanka Khandelwal, and William E. Smoyer
- Subjects
Adult ,Nephrotic Syndrome ,Adolescent ,Lipoproteins ,030232 urology & nephrology ,030204 cardiovascular system & hematology ,Bioinformatics ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Ezetimibe ,Risk Factors ,medicine ,Humans ,Risk factor ,Child ,Dyslipidemias ,business.industry ,PCSK9 ,Hypertriglyceridemia ,medicine.disease ,Atherosclerosis ,Steroid-resistant nephrotic syndrome ,Nephrology ,LDL apheresis ,Pediatrics, Perinatology and Child Health ,lipids (amino acids, peptides, and proteins) ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,Dyslipidemia ,medicine.drug ,Lipoprotein - Abstract
Children with steroid-resistant nephrotic syndrome (SRNS) are exposed to multiple cardiovascular risk factors predisposing them to accelerated atherosclerosis. This risk is negligible in steroid-sensitive nephrotic syndrome, but a substantial proportion of children with SRNS progress to chronic kidney disease, exacerbating the already existing cardiovascular risk. While dyslipidemia is an established modifiable risk factor for cardiovascular disease in adults with NS, it is uncertain to what extent analogous risks exist for children. There is increasing evidence of accelerated atherosclerosis in children with persistently high lipid levels, especially in refractory NS. Abnormalities of lipid metabolism in NS include hypertriglyceridemia and hypercholesterolemia due to elevated apolipoprotein B-containing lipoproteins, decreased lipoprotein lipase and hepatic lipase activity, increased hepatic PCSK9 levels, and reduced hepatic uptake of high-density lipoprotein. Existing guidelines for the management of dyslipidemia in children may be adapted to target lower lipid levels in children with NS, but they will most likely require both lifestyle modifications and pharmacological therapy. While there is a lack of data from randomized controlled trials in children with NS demonstrating the benefit of lipid-lowering drugs, therapies including statins, bile acid sequestrants, fibrates, ezetimibe, and LDL apheresis have all been suggested and/or utilized. However, concerns with the use of lipid-lowering drugs in children include unclear side effect profiles and unknown long-term impacts on neurological development and puberty. The recent introduction of anti-PCSK9 monoclonal antibodies and other therapies targeted to the molecular mechanisms of lipid transport disrupted in NS holds promise for the future treatment of dyslipidemia in NS.
- Published
- 2019
50. Membrane-filtration based plasma exchanges for atypical hemolytic uremic syndrome: Audit of efficacy and safety
- Author
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Christy C. Thomas, Bhim Singh Rathi, Aditi Sinha, Arvind Bagga, Anand Narain Tiwari, Priyanka Khandelwal, and Pankaj Hari
- Subjects
Male ,medicine.medical_specialty ,Abdominal pain ,Adolescent ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,Gastroenterology ,Tertiary Care Centers ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Atypical hemolytic uremic syndrome ,medicine ,Humans ,Adverse effect ,Child ,Atypical Hemolytic Uremic Syndrome ,Medical Audit ,Plasma Exchange ,business.industry ,Infant ,Membranes, Artificial ,Hematology ,General Medicine ,Eculizumab ,medicine.disease ,Treatment Outcome ,Child, Preschool ,Vomiting ,Plasmapheresis ,Chills ,Female ,medicine.symptom ,business ,Central venous catheter ,Filtration ,030215 immunology ,medicine.drug - Abstract
While complement blockade with eculizumab is recommended as first-line therapy of atypical hemolytic uremic syndrome (aHUS), plasma exchanges (PEX) remain the chief option for anti-factor H (FH) antibody associated disease and when access to eculizumab is limited.We reviewed adverse events (AEs) and adverse outcomes (eGFR30 mL/min/1.73 mDuring January 2013 to June 2018, 109 patients with aHUS (74 with antibodies to FH), aged median (range) 7.6 (0.5-18) year weighing 22.1 (6-90) kg, underwent 2024 sessions of PEX. AE, in 12.1% patients, were usually self-limiting and included chills (5.5%), vomiting/abdominal pain (3.3%), hypotension (1.6%), urticaria (1.5%), seizures (0.2%), hypocalcemia (0.2%), and hemorrhage (0.1%); plasma hypersensitivity and severe reactions were rare. Rate of catheter-related infections was 1.45/1000 catheter-days. Filter reuse (OR 1.69; 95% CI 1.26-2.26; P .001) and20 sessions of PEX/patient (OR 1.99; 95% CI 1.27-3.10; P = .002) were independently associated with adverse events; infusion of IV calcium gluconate during PEX was protective (OR 0.26; 95% CI 0.16-0.43; P .001). Hematological remission was achieved in 96.3% patients after 6 (5-8) PEX sessions; 80.8% and 89.6% patients were dialysis independent by one and 3 months, respectively.PEX is safe and associated with satisfactory short-term outcomes in children with aHUS. Prolonged PEX and filter-reuse are associated with complications.
- Published
- 2019
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