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Chronic kidney disease (CKD) not associated with known risk factors has been reported from parts of India and is presumed to be similar to CKD of unknown etiology (CKDu) that has been described from Central America. The reports from India have been fragmented without clear description of the disease phenotype or its determinants. This paper summarizes the current state of knowledge around CKDu in India based on a review of literature, multi-stakeholder consultation, and a survey of Indian nephrologists. We also contacted individual research groups to solicit data. Our findings suggest that that CKDu is reported from most regions in India; however, it is interpreted differently from the phenotype described from Central America and Sri Lanka. The differences include lack of a clear demographic or occupation group, older age of affected participants, and presence of mild hypertension and low-grade proteinuria. Well-designed prospective field studies with appropriate diagnostic workup are needed to establish the disease burden and identify etiologies, along with socioeconomic and health consequences, the intersection with the environment, and the public health response. Community-based research should phenotype the entire CKD population rather than be restricted to cases with presumed CKDu based on predefined criteria. Guidelines are needed for clinical evaluation, referral, management, and harmonization of clinical documentation and health records. More data are needed to support the existence of a unique CKDu phenotype in India.

Large-scale deployment of COVID-19 vaccines will seriously affect the ongoing phases 2 and 3 randomised placebo-controlled trials assessing SARS-CoV-2 vaccine candidates. The effect will be particularly acute in high-income countries where the entire adult or older population could be vaccinated by late 2021. Regrettably, only a small proportion of the population in many low-income and middle-income countries will have access to available vaccines. Sponsors of COVID-19 vaccine candidates currently in phase 2 or initiating phase 3 trials in 2021 should consider continuing the research in countries with limited affordability and availability of COVID-19 vaccines. Several ethical principles must be implemented to ensure the equitable, non-exploitative, and respectful conduct of trials in resource-poor settings. Once sufficient knowledge on the immunogenicity response to COVID-19 vaccines is acquired, non-inferiority immunogenicity trials-comparing the immune response of a vaccine candidate to that of an authorised vaccine-would probably be the most common trial design. Until then, placebo-controlled, double-blind, crossover trials will continue to play a role in the development of new vaccine candidates. WHO or the Council for International Organizations of Medical Sciences should define an ethical framework for the requirements and benefits for trial participants and host communities in resource-poor settings that should require commitment from all vaccine candidate sponsors from high-income countries.

Kidney international 100(4), 753-779 (2021). doi:10.1016/j.kint.2021.05.015, Published by Elsevier, New York, NY

The pathophysiology and the factors determining disease severity in COVID-19 are not yet clear, with current data indicating a possible role of altered iron metabolism. Previous studies of iron parameters in COVID-19 are cross-sectional and have not studied catalytic iron, the biologically most active form of iron. The study was done to determine the role of catalytic iron in the adverse outcomes in COVID-19. We enrolled adult patients hospitalized with a clinical diagnosis of COVID-19 and measured serum iron, transferrin saturation, ferritin, hepcidin and serum catalytic iron daily. Primary outcome was a composite of in-hospital mortality, need for mechanical ventilation, and kidney replacement therapy. Associations between longitudinal iron parameter measurements and time-to-event outcomes were examined using a joint model. We enrolled 120 patients (70 males) with median age 50 years. The primary composite outcome was observed in 25 (20.8%) patients—mechanical ventilation was needed in 21 (17.5%) patients and in-hospital mortality occurred in 21 (17.5%) patients. Baseline levels of ferritin and hepcidin were significantly associated with the primary composite outcome. The joint model analysis showed that ferritin levels were significantly associated with primary composite outcome [HR (95% CI) = 2.63 (1.62, 4.24) after adjusting for age and gender]. Both ferritin and serum catalytic iron levels were positively associated with in-hospital mortality [HR (95% CI) = 3.22 (2.05, 5.07) and 1.73 (1.21, 2.47), respectively], after adjusting for age and gender. The study shows an association of ferritin and catalytic iron with adverse outcomes in COVID-19. This suggests new pathophysiologic pathways in this disease, also raising the possibility of considering iron chelation therapy.

Introduction Kidney Disease: Improving Global Outcomes (KDIGO) 2012 recommends cyclical cyclophosphamide plus glucocorticoids (GC) (modified Ponticelli regimen) or calcineurin inhibitors (CNIs) such as tacrolimus (TAC) or cyclosporine as the first-line agents for the management of primary membranous nephropathy (PMN) that is resistant to antiproteinuric therapy with renin-angiotensin system blockers. However, the long-term outcome of patients treated with CNIs is not known. Methods We report the outcomes of 70 patients randomized 1:1 to receive modified Ponticelli regimen or TAC/GC for renin-angiotensin system–resistant PMN who were prospectively followed for 6 years. Patients were followed monthly for 12 months, then quarterly for 12 months, and then every 6 months through the end of 6 years. Results At the end of 6 years, 21 (61.76%) and 9 (28.12%) patients maintained relapse-free remission in modified Ponticelli regimen and TAC/GC groups, respectively (relative risk [RR]: 2.19, 95% confidence interval [CI]: 1.23 to 4.15), and 30 (88.23%) and 17 (53.12%) patients were in remission (including relapses) in modified Ponticelli regimen and TAC/GC groups (RR: 1.66; 95% CI: 1.21 to 2.45), respectively. There was no significant difference in the proportion of patients who had a 40% decline in the estimated glomerular filtration rate (eGFR), death, or end-stage kidney disease between the groups. None of the patients treated with modified Ponticelli regimen reported a solid organ or hematological malignancy. Conclusions To conclude, in the long-term, modified Ponticelli regimen is superior to TAC/GC as first-line therapy for the management of antiproteinuric-resistant PMN., Graphical abstract

The aim was to assess methods utilized in assessing mast cell involvement in functional abdominal pain disorders (FAPDs), specifically to describe variability in methods utilized to assess both mast cell density and activation and determine if a consensus exists. After a literature search identified 70 manuscripts assessing mast cell density, data were extracted including FAPD diagnosis, site of biopsy, selection of microscopic fields analyzed, selection of mucosal region analyzed, method of mast cell identification, method to assess mast cell density, and if performed, method to assess mast cell activation. There appears to be some consensus favoring inmmunohistochemical stains over histochemical stains for identifying mast cells. Otherwise, considerable variability exists in methodology for assessing mast cell density and activation. Regardless of method, approximately 80% of studies found increased mast cell density and/or activation in comparison to controls with no method being superior. A wide variety of methods have been employed to assess mast cell density and activation with no well-established consensus and inadequate data to recommend specific approaches. The current methodology providing physiologic information needs to be translated to a standard methodology providing clinical information with the development of criteria establishing abnormal density and/or activation, and more importantly, predicting treatment response.

Tuberculosis (TB) is a highly contagious airborne disease caused by Mycobacterium tuberculosis that primarily affects the lungs. TB is a significant and major public health emergency globally. According to the WHO Global Tuberculosis Report 2020, 10 million people developed TB disease in the year 2019. The main objective of the study was to assess the level of knowledge, attitude and practice in TB patients. The study also reveals the association between KAP and the demographics of the subjects. An observational study was employed to collect data from a total of 71 subjects. Both quantitative and qualitative statistical analysis were adopted. From the findings, the mean age of the study population was 45.5 ± 13.96 years. Over 15.50% of subjects appeared to have adequate knowledge, 87.33% of subjects had a fair attitude, and around 58% of subjects were reported to have good practices towards TB. A weak positive correlation between knowledge and attitude (p = 0.051), weak positive correlation between knowledge and practice (p = 0.138) whereas, a significant and moderately positive correlation between attitude and practice (p = 0.002) was observed. The mean knowledge scores of graduates and post-graduates were higher in comparison with other study subjects. The study findings showed that the majority of subjects had several misconceptions about TB and hence prioritized interventions and more awareness programs at the root levels are needed to aid TB control and eradication.

Background The non-transferrin-bound catalytic iron moiety catalyses production of toxic reactive oxygen species and is associated with adverse outcomes. We hypothesized that serum catalytic iron (SCI) is associated with progression of chronic kidney disease (CKD). Methods Baseline samples of the Indian chronic kidney disease (ICKD) Study participants with at least one follow-up visit were tested for total iron, iron-binding capacity, transferrin saturation (TSAT), SCI, ferritin and hepcidin. SCI was measured using the bleomycin-detectable iron assay that detects biologically active iron. Association with the incidence of major kidney endpoints [major adverse kidney event (MAKE), a composite of kidney death, kidney failure or >40% loss of estimated glomerular filtration rate (eGFR)] was examined using Cox proportional hazards model adjusted for sex and age. Results A total of 2002 subjects (mean ± standard deviation age 49.9 ± 11.6 years, 68.1% males, baseline eGFR 41.01 mL/min/1.73 m2) were enrolled. After a median (interquartile range) follow-up of 12.6 (12.2–16.7) months, the composite MAKE occurred in 280 (14%). After adjusting for age and sex, increase from 25th to 75th percentile in SCI, TSAT, ferritin and hepcidin were associated with 78% (43–122%), 34% (10–62%), 57% (24–100%) and 74% (35–124%) increase in hazard of MAKE, respectively. SCI was associated with MAKE and kidney failure after adjustment for occupational exposure, hypertension, diabetes, tobacco, alcohol use, history of acute kidney injury, baseline eGFR and urine albumin to creatinine ratio, and allowing baseline hazard to vary by centre. Conclusions SCI is strongly and independently associated with composite MAKE in patients with mild-to-moderate CKD. Confirmation in other studies will allow consideration of SCI as a risk marker and treatment target.

Infection with the hepatitis C virus (HCV) has adverse liver, kidney, and cardiovascular consequences in patients with chronic kidney disease (CKD), including those on dialysis therapy and in those with a kidney transplant. Since the publication of the original Kidney Disease: Improving Global Outcomes (KDIGO) HCV Guideline in 2008, major advances in HCV management, particularly with the advent of direct-acting antiviral therapies, have now made the cure of HCV possible in CKD patients. In addition, diagnostic techniques have evolved to enable the noninvasive diagnosis of liver fibrosis. Therefore, the Work Group undertook a comprehensive review and update of the KDIGO HCV in CKD Guideline. This Executive Summary highlights key aspects of the guideline recommendations.

Continuous ambulatory peritoneal dialysis (CAPD) related peritonitis is a major cause of technique failure, morbidity, and mortality in patients on CAPD. Its prevention and management is key to success of CAPD program. Due to variability in practice, microbiological trends and sensitivity towards antibiotics, there is a need for customized guidelines for management of CAPD related peritonitis (CAPDRP) in India. With this need, Peritoneal Dialysis Society of India (PDSI) organized a structured meeting to discuss various aspects of management of CAPDRP and formulated a consensus agreement which will help in management of patients with CAPDRP.

Background: Exact information about the efficacy of various medications proposed by regulatory bodies in children with COVID-19 is limited due to the lack of controlled trials in the existing literature. Methods: Different electronic databases (MEDLINE, EMBASE, Web of Science, COCHRANE CENTRAL, LitCovid, medRxiv, and bioRxiv) were searched for articles describing the management of COVID-19 cases in children with 18 shortlisted medications. Prospective/retrospective studies/case series (with at least 20 cases) reporting COVID-19 in patients aged ≤14 years were searched to collect information regarding clinical details and severity of participants, medications used, and outcome. The pooled estimate of these parameters across studies was performed using a random-effect or fixed-effect meta-analysis depending on the degree of heterogeneity. Results: From a total of 5794 records, 97 studies/case series (8243 patients) fulfilled the eligibility criteria and were included in this systematic review. A total of 21% children received at least one medication specifically used for COVID-19. While antivirals were used in 15.3% of children, remedesivir was the most commonly used antiviral drug in 6.2% of included children without many reports of serious adverse effects. There was a more prevalent use of anti-inflammatory medications including corticosteroids (27.8%, P = 0.01). Total 91% of severe cases described in literature in children received some anti-inflammatory medications. Among them, corticosteroids (17%) and Intravenous immune globulin (IVIG) (17.5%) were the most predominant followed by interferon (4.2%), tocilizumab (1.5%), and anakinra (0.8%). The most predominant therapy among multisystem inflammatory syndrome in children (MIS-C) cases were IVIG (81%), followed by aspirin (67%), corticosteroids (64%), inotropes (62%), and anticoagulation (56%, mostly low molecular weight heparin, LMWH). Overall mortality was only 1.3%, but when we analyzed separately including only cases with moderate and severe disease, the mortality rate was 4.6%. Conclusion: Among pharmacological modalities, anti-inflammatory agents like corticosteroids and antivirals like remdesivir have the most promising evidence for severe cases of pediatric COVID-19. Intravenous immunoglobulin and other anti-inflammatory/immunomodulatory agents like anakinra, aspirin, and anticoagulants have important therapeutic role in cases with MIS-C. Most of the mild cases recover with conservative treatment only.

Introduction Patients with chronic kidney disease (CKD) require multiple medications. There is no information on prescription patterns or the use of evidence-based therapies for management of CKD from low-middle-income countries. Using baseline data from the Indian CKD (ICKD) cohort, we describe the drug prescription practices in patients with mild to moderate CKD. Methods The ICKD study is a prospective, observational cohort study of mild to moderate kidney disease across 11 centers in India. We analyzed all the prescriptions captured at enrollment in the ICKD study. Drugs were categorized into 11 different groups. We provide descriptive data on prescription details and evaluate the appropriateness of medication use. Results Complete prescription data were available in 3966 out of 4056 (97.8%) subjects enrolled in the ICKD database. Most patients had stage 3 CKD, 24.9% had diabetic kidney disease, 87% had hypertension, and 25.5% had moderate to severe proteinuria. Renin-angiotensin-aldosterone system blockers were prescribed in less than half (47.9%) and in 58.8% of patients with proteinuric CKD. Metformin was prescribed in 25.7% of diabetic subjects with CKD. Only 40.4% of patients were taking statins; 31.1% and 2.8% subjects with anemia were receiving iron and erythropoiesis-stimulating agents, respectively. Conclusion This study highlights the missed opportunities for improving outcomes through appropriate prescriptions of drugs in patients with CKD. There is need for dissemination of evidence-based guidelines and institution of sustainable implementation practices for improving the overall health of patients with CKD., Graphical abstract

Background Chronic kidney disease (CKD) is an important cause of morbidity and mortality worldwide. There is a lack of information on epidemiology and progression of CKD in low–middle income countries. The Indian Chronic Kidney Disease (ICKD) study aims to identify factors that associate with CKD progression, and development of kidney failure and cardiovascular disease (CVD) in Indian patients with CKD. Methods ICKD study is prospective, multicentric cohort study enrolling patients with estimated glomerular filtration rate (eGFR) 15–60 mL/min/1.73 m2, or >60 mL/min/1.73 m2 with proteinuria. Clinical details and biological samples are collected at annual visits. We analysed the baseline characteristics including socio-demographic details, risk factors, disease characteristics and laboratory measurements. In addition, we compared characteristics between urban and rural participants. Results A total of 4056 patients have been enrolled up to 31 March 2020. The mean ± SD age was 50.3 ± 11.8 years, 67.2% were males, two-thirds of patients lived in rural areas and the median eGFR was 40 mL/min/1.73 m2. About 87% were hypertensive, 37% had diabetes, 22% had CVD, 6.7% had past history of acute kidney injury and 23% reported prior use of alternative drugs. Diabetic kidney disease, chronic interstitial nephritis (CIN) and CKD-cause unknown (CKDu) were the leading causes. Rural participants had more occupational exposure and tobacco use but lower educational status and income. CIN and unknown categories were leading causes in rural participants. Conclusions The ICKD study is the only large cohort study of patients with mild-to-moderate CKD in a lower middle income country. Baseline characteristics of study population reveal differences as compared with other cohorts from high-income countries.

Antibiotic resistance surveillance is an objective of global action plan on antimicrobial resistance endorsed by the World Health Organization. The current study reports the identification of frequently occurring Gram-negative bacterial community (GNBC) previously isolated from municipal treated wastewater and their antibiotic resistance profiles. Further, the genes responsible for extended-spectrum beta lactamases (ESBL) activity were identified in ESBL-positive organisms. The isolates were characterized using biochemical assays and identification was confirmed by VITEK®2 automated system. Antibiotic susceptibility testing against seven different classes of antibiotics was also performed on the same system using AST-N280 cards. The most dominant isolates identified were Acinetobacter baumannii, Morganella morganii, Kluyvera intermedia, Stenotrophomonas maltophilia, Escherichia coli, Aeromonas hydrophila/caviae, Klebsiella pneumoniae, Enterobacter cloacae and Citrobacter freundii. The isolates were observed to be significantly resistant against the antibiotics amoxicillin-clavulanic acid, cefuroxime, cefuroxime axetil and colistin. Two of the isolates, E. cloacae sp. dissolvens and S. maltophilia, were found to be positive for ESBL activity encoded by blaCTX-M gene. The possible intrusion of hospital wastewater in domestic sewage is also discussed. This study may help assess the risk of wastewater reuse by detecting dominant bacteria as a step towards the development of new microbiological standards. HIGHLIGHTS Stenotrophomonas maltophilia found to be most resistant and E. coli least resistant among the isolates.; Five isolates found to be resistant to the last resort antibiotic Colistin.; Molecular determinant of two extended spectrum beta lactamase producing isolates found to be blaCTX-M gene.; This report might aid in devising a suitable strategy for reducing risk to human health upon treated wastewater reuse.

Background The increasing burden of kidney failure (KF) in India necessitates provision of cost-effective kidney replacement therapy (KRT). We assessed the comparative cost-effectiveness of initiating KRT with peritoneal dialysis (PD) or haemodialysis (HD) in the Indian context. Methods The cost and clinical effectiveness of starting KRT with either PD or HD were measured in terms of life years (LYs) and quality-adjusted life years (QALYs) using a mathematical Markov model. Complications such as peritonitis, vascular access–related complications and blood-borne infections were considered. Health system costs, out-of-pocket expenditures borne by patients and indirect costs were included. Two scenarios were considered: Scenario 1 (real-world scenario)—as per the current cost and utilization patterns; Scenario 2 (public programme scenario)—use in the public sector as per Pradhan Mantri National Dialysis Programme (PMNDP) guidelines. The lifetime costs and health outcomes among KF patients were assessed. Results The mean QALYs lived per KF person with PD and HD were estimated to be 3.3 and 1.6, respectively. From a societal perspective, a PD-first policy is cost-saving as compared with an HD-first policy in both Scenarios 1 and 2. If only the costs directly attributable to patient care (direct costs) are considered, the PD-first treatment policy is estimated to be cost-effective only if the price of PD consumables can be brought down to INR70/U. Conclusions PD as initial treatment is a cost-saving option for management of KF in India as compared with HD first. The government should negotiate the price of PD consumables under the PMNDP.

Background Maintenance hemodialysis (MHD) patients face disadvantages with higher risk of acquiring SARS‐CoV‐2 infection, atypical manifestations, and associated multiple comorbidities. We describe patients' outcomes with symptomatic COVID‐19 on MHD in a large cohort of patients from India. Methods Data were collected prospectively from hemodialysis units in 11 public and private hospitals between March 15, 2020, and July 31, 2020. The survival determinants were analyzed using stepwise backward elimination cox‐regression analysis. Results Of the 263 total patients (mean age 51.76 ± 13.63 years and males 173) on MHD with symptomatic COVID‐19, 35 (13.3%) died. Those who died were older (p = 0.01), had higher frequency of diabetic kidney disease (p = 0.001), comorbidities (p = 0.04), and severe COVID‐19 (p = 0.001). Mortality was higher among patients on twice‐weekly MHD than thrice‐weekly (p = 0.001) and dialysis through central venous catheter (CVC) as compared to arteriovenous fistula (p = 0.001). On multivariate analysis, CVC use (HR 2.53, 95% CI 1.26–5.07, p = 0.009), disease severity (HR = 3.54, 95% CI 1.52–8.26, p = 0.003), and noninvasive ventilatory support (HR 0.59, 95% CI 0.25–0.99, p = 0.049) had significant effect on mortality. Conclusion The adjusted mortality risk of COVID‐19 in MHD patients is high in patients associated with severe COVID‐19 and patients having CVC as vascular access.

Purpose: The purpose of this study is to describe the demographic profile, clinical features, visual outcomes, and follow-up patterns after successful cataract surgery in children from the tribal community in Odisha, India. Methods: We retrospectively reviewed records of tribal children aged 4 months–16 years, who underwent public health financed cataract surgery at our institute from January 1, 2015, to December 31, 2019. Collected data included demographic profile, clinical features, outcomes, and follow-up. Univariate and multivariate linear regression identified factors affecting the visual outcome at a 6-week follow-up. Results: During this period, a total of 352 children [536 eyes; mean age: 9.11 ± 4.4 years, 219 boys (62%)] underwent cataract surgery. The most common etiology and presenting complaints were idiopathic congenital cataract and decreased vision, respectively. In 304 children (86%), presenting best-corrected visual acuity (BCVA) was

BACKGROUND Falls are very much common in elderly. Fall in geriatric population is one of the common reasons for hospitalization, which may put financial burden on the patient and family. Fall in geriatric population many a times causes fracture and it may lead to serious complications which can threaten life. It may lead to disability and patient may become a handicap. In our study, we identified the correlation between motor strategies of balance control and causes of fall in post-operative elderly individuals. METHODS In this observational study, a total of 100 post-operative elderly individuals who had a fall and who underwent surgery for fracture correction were included. Both males and females in age group of 60 years and above were included. Outcome measures used were balance tests, manual muscle tests and goniometry. RESULTS 28 % individuals had fall due to low level of motor control at ankle joint and 40 % individuals at hip joint. In 16 % of individuals reaching strategy was affected. Suspensory strategy was affected in 10 % of individuals while stepping strategy was affected in 6 % of elderly. Elderly had fall due to weak musculature at hip joint (35 %), knee joint (15 %), ankle joint (30 %) and spine (25 %) irrespective of the individual’s gender. CONCLUSIONS Impairment in motor strategies of balance control such as, hip strategy, stepping strategy, reaching strategy, suspensory strategy, ankle strategy leads to fall in elderly. On the basis of assessment of manual muscle testing (MMT), range of motion and motor strategies of balance control, we concluded that impairment in motor strategies of balance, and reduced joint range of motion lead to falls. KEY WORDS Motor Strategies for Balance Control, Balance Tests, Manual Muscle Testing, Range of Motion

Objective: To study the pregnancy outcome and management of ovarian cysts during pregnancy. Methods : A prospective observational study was conducted in Prathima Institute of Medical Sciences, Karimnagar from June 2018 to June 2020. A total of 32 cases with ovarian cysts 5cm with benign features as suggested by ultrasound were included in the study. The pregnancy outcome and management were studied. Results : Out of 32 pregnant women with ovarian cysts, 25(78.12%) were asymptomatic and were managed conservatively. Of the 25, spontaneous resolution was seen in 18(56.25%) patients while 7(21.87%) patients in whom ovarian cyst persisted or was incidentally detected during cesarean section were managed by cystectomy at the same time. Surgery was needed in the antenatal period in 7(21.87%) patients due to complications such as increase in size of the cyst seen in 4(12.5%) and torsion seen in 3(9.37%). All the 32 patients had good perinatal outcome. There were no miscarriages. All patients continued to term except one, who presented at 36 weeks with torsion, andunderwent emergency cesarean section with oophorectomy. Histopathological examination of the excised cysts showed 5 as simple cyst, 5 as serous cystadenomas, 3 as mucinous cystadenomas and 1 as dermoid. Conclusion: Management of the ovarian cysts during pregnancy is conservative. Most of them undergo spontaneous resolution. Surgical management is reserved for only symptomatic patients. Pregnancy outcome as such is not affected by ovarian cysts during pregnancy.

The International Society of Nephrology Global Kidney Health Atlas analyzed the current state of kidney care in Newly Independent States and Russia. Our results demonstrated that the Newly Independent States and Russia region was not an exception and showed the same effect of chronic kidney disease on health and its outcomes, facing many difficulties and challenges in terms of improving kidney care across the countries. This work summarized and presented demographics, health information systems, statistics, and national health policy of the region, as well as characteristics of the burden of chronic kidney disease and kidney failure (KF) of participating countries. Besides significant economic advancement in the region, the collected data revealed existing shortage in KF care providers, essential medications, and health product access for KF care. Moreover, there was low reporting of kidney replacement therapy (dialysis and kidney transplantation) quality indicators and low capacity for long-term hemodialysis, peritoneal dialysis, and kidney transplantation. The financial issues and funding structures for KF care across the region needs strategic support for fundamental changes and further advancement. This article emphasizes the urgent need for further effective regional and international collaborations and partnership for establishment of universal health care systems for KF management.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment modality for peritoneal surface malignancies. A variety of metabolic derangements have been reported in the perioperative period in these patients, most of which are a result of the complex interaction of peritoneal denudation, chemotherapy bath, and fluid imbalance. We report three cases of hyperammonemia-related neurological dysfunction seen in HIPEC patients. To the best of our knowledge, this is the first report of this presentation. Timely recognition of this condition needs a high degree of suspicion, and unless aggressively treated, is likely to be associated with poor outcome. How to cite this article: Sharma V, Solanki SL, Saklani AP. Hyperammonemia after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Report of Three Cases with Unusual Presentation. Indian J Crit Care Med 2021;25(5):590–593.

The International Society of Nephrology established the Global Kidney Health Atlas project to define the global capacity for kidney replacement therapy and conservative kidney care, and this second iteration was to describe the availability, accessibility, quality, and affordability of kidney failure (KF) care worldwide. This report presents results for the International Society of Nephrology North America and the Caribbean region. Relative to other regions, the North America and Caribbean region had better infrastructure and funding for health care and more health care workers relative to the population. Various essential medicines were also more available and accessible. There was substantial variation in the prevalence of treated KF in the region, ranging from 137.4 per million population (pmp) in Jamaica to 2196 pmp in the United States. A mix of public and private funding systems cover costs for nondialysis chronic kidney disease care in 60% of countries and for dialysis in 70% of countries. Although the median number of nephrologists is 18.1 (interquartile range, 15.3-29.5) pmp, which is approximately twice the global median of 9.9 (interquartile range, 1.2-22.7) pmp, some countries reported shortages of other health care workers. Dialysis was available in all countries, but peritoneal dialysis was underutilized and unavailable in Barbados, Cayman Islands, and Turks and Caicos. Kidney transplantation was primarily available in Canada and the United States. Economic factors were the major barriers to optimal KF care in the Caribbean countries, and few countries in the region have chronic kidney disease-specific national health care policies. To address regional gaps in KF care delivery, efforts should be directed toward augmenting the workforce, improving the monitoring and reporting of kidney replacement therapy indicators, and implementing noncommunicable disease and chronic kidney disease-specific policies in all countries.

Populations in the high-income countries of Western Europe are aging due to increased life expectancy. As the prevalence of diabetes and obesity has increased, so has the burden of kidney failure. To determine the global capacity for kidney replacement therapy and conservative kidney management, the International Society of Nephrology conducted multinational, cross-sectional surveys and published the findings in the International Society of Nephrology Global Kidney Health Atlas. In the second iteration of the International Society of Nephrology Global Kidney Health Atlas, we aimed to describe the availability, accessibility, quality, and affordability of kidney failure care in Western Europe. Among the 29 countries in Western Europe, 21 (72.4%) responded, representing 99% of the region's population. The burden of kidney failure prevalence varied widely, ranging from 760 per million population (pmp) in Iceland to 1612 pmp in Portugal. Coverage of kidney replacement therapy from public funding was nearly universal, with the exceptions of Germany and Liechtenstein where part of the costs was covered by mandatory insurance. Fourteen (67%) of 21 countries charged no fees at the point of care delivery, but in 5 countries (24%), patients do pay some out-of-pocket costs. Long-term dialysis services (both hemodialysis and peritoneal dialysis) were available in all countries in the region, and kidney transplantation services were available in 19 (90%) countries. The incidence of kidney transplantation varied widely between countries from 12 pmp in Luxembourg to 70.45 pmp in Spain. Conservative kidney care was available in 18 (90%) of 21 countries. The median number of nephrologists was 22.9 pmp (range: 9.47-55.75 pmp). These data highlight the uniform capacity of Western Europe to provide kidney failure care, but also the scope for improvement in disease prevention and management, as exemplified by the variability in disease burden and transplantation rates.

Kidney international 100(4, Supplement) S1-S276 (2021). doi:10.1016/j.kint.2021.05.021 special issue: "KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases", Published by Elsevier, New York, NY

Background The Anemia Studies in chronic kidney disease (CKD): Erythropoiesis via a Novel prolyl hydroxylase inhibitor Daprodustat-Dialysis (ASCEND-D) trial will test the hypothesis that daprodustat is noninferior to comparator epoetin alfa or darbepoetin alfa for two co-primary endpoints: hemoglobin (Hb) efficacy and cardiovascular (CV) safety. Methods We report the trial design, key demographic, clinical and laboratory findings, and baseline therapies of 2964 patients randomized in the open-label (sponsor-blinded) active-controlled, parallel-group, randomized ASCEND-D clinical trial. We also compare baseline characteristics of ASCEND-D patients with patients who are on dialysis (CKD G5D) enrolled in other large CV outcome trials (CVOTs) and in the most relevant registries. Results The median age of patients was 58 years, 43% were female; 67% were White and 16% were Black. The median Hb at baseline was 10.4 g/dL. Among randomized patients, 89% were receiving hemodialysis and 11% peritoneal dialysis. Among key comorbidities, 42% reported a history of diabetes mellitus and 45% a history of CV disease. Median blood pressure was 134/74 mmHg. The median weekly dose of epoetin was 5751 units. Intravenous and oral iron uses were noted in 64 and 11% of patients, respectively. Baseline demographics were similar to patients with CKD G5D enrolled in other CVOTs and renal patient registries. Conclusions ASCEND-D will evaluate the efficacy and safety of daprodustat compared with epoetin alfa or darbepoetin alfa in the treatment of patients with anemia with CKD G5D. This trial is registered with ClinicalTrials.gov: NCT02879305. EudraCT Number: 2016-000541-31; Sponsor Protocol Number: 200807.

Background Early and accurate diagnosis followed by timely treatment are the key prerequisites to fight tuberculosis (TB) and reduce its global burden. Despite scientific advances, the rapid and correct diagnosis of both pulmonary and extrapulmonary tuberculosis remains a challenge because of traditional reliance on detection of the elusive bacilli. Mycobacterium tuberculosis (Mtb)-specific host immune activation and cytokine production have shown significant promise as alternative means of detecting and distinguishing active disease from latent infection. We queried the diagnostic ability of phenotypic markers on Mtb-specific cytokine-producing immune cell subsets for identifying active TB. Methods Subjects belonging to the following groups were recruited: pulmonary and extrapulmonary TB, latent TB, cured TB, sick controls, and healthy controls. Polychromatic flow cytometry was used to identify host immune biomarkers in an exploratory cohort comprising 56 subjects using peripheral blood mononuclear cells. Clinical performance of the identified biomarker was evaluated using whole blood in a blinded validation cohort comprising 165 individuals. Results Cytokine secreting frequencies of Mtb-specific cluster of differentiation 4-positive (CD4+) T cells with CD38+CD27– phenotype clearly distinguished infected individuals with active tuberculosis from those without disease. Tumor necrosis factor-α (TNF-α) secretion from CD38+CD27–CD4+ T cells upon stimulation with ESAT6/CFP10 peptides had the best diagnostic accuracy at a cutoff of 9.91% (exploratory: 96.67% specificity, 88.46% sensitivity; validation: 96.15% specificity, 90.16% sensitivity). Additionally, this subset differentiated treatment-naive patients with TB from individuals cured of TB following completion of anti-TB therapy. Conclusions Mtb-specific CD38+CD27–TNF-α +CD4+ T-cell subset is a robust biomarker both for diagnosing TB and assessing cure.

Background and introduction: A new strain of corona virus emerged during the month of December 2019, in china particularly from theWuhan city. Majority of the patients presented with atypical pneumonia in Wuhan city, which later contributed this atypical pneumonia is due to novel coronal virus and named it as SARS-CoV-2 virus. Chinese authorities later investigated that the virus was originated from whole sale food and meat market in Wuhan. Many of the initial patients were wet market sellers, stall owners and regular visitors of the market Aims and objectives of the study: 1. To find out CO-RADS scoring of patients diagnosed as COVID-19 positive by RT-PCR. 2. To find out chest CT-scan findings in of patients diagnosed as COVID-19 positive. Methodology: The present study was an Observational cross-sectional study of patients suffering from COVID -19 infected patients affected with corona virus (COVID-19) at Katuri Medical College and Hospital, Guntur, during the period of 6 months from April 15, 2020 to October 15, 2020. Total of 567 patients included in the study based on the prevalence of COVID-19 infection in India. Inclusion criteria and exclusion criteria used to study the patients in the study. Results: Among 567 patients included in the study, CO-RADS Scoring system patients were divided into 6 categories. Among them 17 (2.9%) patients belong to CO-RAD-1 group, 188 (33.1%) patients were diagnosed with RT-PCR as COVID-19 infection belonging to the score of 2-3, 310 (54.6%) patients with CO-RADS 4-5 and 7 patients with CO-RADS. 52 (9.1%) patients were categorized to CO-RADS-6. The most common chest CT features of patients having COVID-19 infection is ground glass opacities which constitute 80.65 % (457/567), interlobular septal thickening found in 60.2% (341/567) patients. Linear opacities constitute 55.4% (314/567), consolidation which constitute 59.7 % (338/567). Crazypaving pattern is seen in 29.3% (166/567) of the patients followed by honey

Phototherapy-induced hypocalcemia has been postulated to result from a decline in serum melatonin levels. The present observational study evaluated the effects of phototherapy on serum calcium and melatonin levels, and assessed their correlation, if any. Eighty-nine neonates with a total serum bilirubin levels of 14.1 ± 2.8 mg/dL were recruited at the mean age of 51.9 ± 21.7 h. After a median interquartile range (IQR) duration of phototherapy for 24.0 (24-25.5) h, serum calcium levels decreased significantly, from 9.6 ± 0.8 to 9.4 ± 0.6 mg/dL; p = 0.02, leading to asymptomatic hypocalcemia in 2.2% of the neonates. Median (IQR) serum melatonin levels also decreased from 187.8 (133.5-227.6) to 176.3 (145.6-202.5) pg/mL after phototherapy, the difference being statistically insignificant. No significant correlation was documented between the duration of phototherapy with calcium and melatonin levels. The authors conclude that phototherapy resulted in a small but significant reduction of serum calcium levels without any significant correlation with serum melatonin.

BACKGROUND Reduced heart rate variability (HRV) is associated with an increased risk of cardiovascular morbidity and mortality. The aim of the study was to determine whether reduced HRV is predictive of angiographic coronary artery disease (CAD) METHODS This study was done among 71 clinically stable subjects who underwent elective coronary angiography for diagnosis or pre-operative evaluation. High frequency (HF; 0.15 – 0.40 Hz), low frequency (LF; 0.04 – 0.15 Hz), LF / HF ratio, total power ≤ 0.4 Hz were used as the conventional indices of HRV. Analysis of variance (ANOVA) and chi square test was used to assess the statistical analysis. Statistical significance analysis was carried out with International Business Machines Statistical Package for the Social Sciences (IBM SPSS) version 22. RESULTS Out of 71 subjects, only 58 were available for final analysis. 20 subjects had normal coronary arteries, 19 had single vessel disease and remaining 19 had multi vessel disease. The HF power of HRV showed decreasing trend as the severity of angiographic stenosis increased. The median values of LF power for single vessel disease and multi vessel disease were 148 ms2 and 160 ms2 respectively. The group without coronary artery disease has a median of 215 ms2 for LF power. The median HF power was lower in single vessel disease group (133 ms2 ) compared to group with normal coronaries (139 ms2 ) and it was very low in multi vessel disease (81 ms2 ) group compared to group with normal coronaries. CONCLUSIONS A weak association of HF and LF power of HRV with degree of angiographic stenosis was observed. KEYWORDS Heart Rate Variability, Coronary Angiogram, Angiographic Stenosis

Computational fluid dynamics (CFD) is numerical strategy developed for simulating the behavior of liquid and gas flow. CFD may be applied starting from aerospace, engine design, vehicle aerodynamics, power plants and chemical industries for analyzing and solving relevant system design and process issues. Biogas produced during anaerobic digestion (AD) is sustainable and renewable alternative to fossil fuels. AD may improve the controlled production of biogas and offers significant environmental benefits. This review focuses on research outcomes relevant for enhanced biogas production by exploring the possible applications of CFD in AD technology. CFD-related research performed in AD conditions in order to improve mixing performance, reduce power consumption, and understand the effects of total solid (TS) concentrations on flow behavior have been discussed. In addition, the use of AD for bio-hydrogen production, wastewater treatment, and sludge treatment are looked in. This review also identifies novel areas for AD technology advancement where there is potential for economic improvement in renewable energy production. Finally, future research needs have been identified, focusing on the opportunities to integrate conceptual and mathematical models for advancing CFD simulations for bioenergy.

Rhino cerebral Mucormycosis is the current life-threatening infection commonly affecting immunocompromised patients espe-cially post COVID-19 within 6 weeks having poor glycemic control, Intravenous drug users, ICU patients, post chemotherapy, iron overload, persistent neutropenia and follow-up cases of hematological malignancies. It affects the nasal and paranasal sinuses by air-borne spores producing the infection. A prospective case series conducted at the department of pathology, KAMSRC between May 1st to September 30th 2021 with a study population of 27 cases. Variables included age, gender, history of covid, duration and development of symptoms, Clinical presentation, clinical diagnosis, co-morbidities, histopathological examination and microbiological correlation. The most prevalent isolated agent is Mucor (48.1%) followed by Rhizopus (18.5%), Aspergillus (11.1%) and mixed mucor with aspergillus (11.1%). Conclusion: Understanding the mechanism of host innate immunity and specific preventive strategies are important for favorable prognosis. Histopathological examination aids in early diagnosis of Mucormycosis

Purpose: To report clinical profile, diagnostic challenges, and outcomes in cases of subacute/chronic cerebral sinus venous thrombosis (CSVT) presenting to neuro-ophthalmologists/neurologists. Methods: This was a multicentric, retrospective, observational study. Records of patients with neuroimaging proven subacute/chronic CSVT seen the from January 1, 2016 to March 31, 2020 were analyzed. Data collected included duration of symptoms, diagnosing physician, ophthalmological vs. focal/generalized neurological symptoms, optic disc examination, perimetry, and neuroimaging findings. Statistical analysis was performed using STATA software. Results: Forty-three patients with subacute (30)/chronic (13) CSVT were identified (32 males, 11 females). Median age was 37 (IQR 27–47) years. The presenting complaints were blurred vision 34 (79%), headaches in 25 (58%), vomiting 12 (28%), and diplopia 11 (26%). Eleven patients had associated sixth cranial nerve palsy. All but two patients had either disc edema/optic atrophy; four had unilateral disc edema at presentation. Ophthalmologists and neurologists diagnosed/suspected CSVT correctly in 13/29 (45%) and 11/14 (78.5%) patients, respectively. Most common initial alternate diagnosis was idiopathic intracranial hypertension in 12 (28%). Female gender, age ≤36, unilateral papilledema, not obtaining venogram at initial workup increased chances of initial alternate diagnosis. Median follow-up duration was 21 days. Average visual function remained stable in majority of patients at last follow-up. In total, 47.6% of patients had best-corrected visual acuity ≥20/30 at the final follow-up. Conclusion: In our series, subacute or chronic CSVT presented presented primarily with symptoms of intracranial hypertension. Unilateral papilledema, middle-aged patients, female gender, lack of focal/generalized neurological symptoms created diagnostic dilemma. Visual function remained stable in majority of patients.

A YPO4:Er3+–Yb3+ nanophosphor has been synthesized by a facile coprecipitation method. The photon upconversion has been carried out at 980 nm continuous-wave laser diode excitation. Optical heating...

Changes in absorptive capacity and first‐pass metabolism in the small intestine affect oral drug bioavailability. Characterization of such changes as a consequence of inflammation is important for developing physiologically‐based pharmacokinetic (PBPK) models for inflammatory bowel disease. We sought to elucidate the impact of small intestinal Crohn’s disease (CD) on villous length and CYP3A4 expression in children. Freshly frozen duodenal and terminal ileum (TI) biopsies from 107 children (1–19 years) with and without CD were evaluated for active inflammation. Villous length and CYP3A4 mRNA/protein expression were compared among regions of active and inactive inflammation in CD and controls. A twofold reduction in villous length was observed in inflamed duodena and ilia of children with CD, but in the absence of regional inflammation, villi in CD were comparable in length to controls. Expression of CYP3A4 mRNA correlated significantly with villous length in the TI (P = 0.0003), with a trend observed in the duodenum that did not reach statistical significance. In the presence of active inflammation, a significant decrease in CYP3A protein expression was confirmed in the duodenum, where protein expression also correlated significantly with villous length across diagnoses (P

Introduction Despite reports of a high prevalence of chronic kidney disease (CKD) from the coastal Uddanam region of Andhra Pradesh, India, there are no accurate data on the distribution of kidney function abnormalities and CKD risk factors in this region. Methods A total of 2419 participants were recruited through multistage cluster random sampling from 67 villages. Serum creatinine and urine protein creatinine ratio were measured using validated methodologies. All abnormal estimated glomerular filtration rate (eGFR) and urine protein creatinine ratio values were reconfirmed after 3 months. A range of sociodemographic factors were evaluated for their association with CKD using Poisson regression. Results Of 2402 eligible subjects (mean ± SD age, 45.67 ± 13.29 years; 51% female), 506 (21.07%) had CKD (mean ± SD age, 51.79 ± 13.12 years; 41.3% female). A total of 246 (10.24%) had eGFR 0.15 g/g). The poststratified estimates, adjusted for age and sex distribution of the region for CKD prevalence, are 18.7% (range, 16.4%–21.0%) overall and 21.3% (range, 18.2%–24.4% ) and 16.2% (range, 13.7%–18.8%) in men and women, respectively. Older age, male sex, tobacco use, hypertension, and family history of CKD were independently associated with CKD. Compared with those with higher eGFR, those with eGFR 0.15, except a lower frequency of males in the former. Conclusion We confirmed the high prevalence of CKD in the adult population of Uddanam. The cause was not apparent in a majority. Subjects with a low eGFR with or without elevated proteinuria were phenotypically distinct from those with proteinuria and preserved eGFR. Our data suggest the need to apply a population-based approach to screening and prevention and studies to understand the causes of CKD in this region., Graphical abstract

Context Hypothyroidism is associated with reversible decline in kidney function as measured by estimated glomerular filtration rate (eGFR). eGFR and proteinuria are the most important markers for clinical assessment of kidney function. Though hypothyroidism is associated with proteinuria in cross-sectional data, the impact of treatment on proteinuria is unknown. Objective This study explores the effect of thyroid hormone replacement therapy on eGFR and 24-hour urine protein excretion in patients with severe primary hypothyroidism. Design and Participants This study was a prospective, observational cohort study in adults with severe primary hypothyroidism (serum thyrotropin [TSH] > 50 µIU/mL). Individuals with preexisting or past kidney disease, kidney or urinary tract abnormalities, calculi or surgery, diabetes mellitus, or hypertension were excluded. The participants received thyroid hormone replacement therapy. Thyroid functions, eGFR, 24-hour urine protein excretion, and biochemical parameters were measured at baseline and 3 months. Setting This study took place at a single center, a tertiary care referral and teaching hospital. Results Of 44 enrolled participants, 43 completed 3 months of follow-up. At 3 months, serum TSH levels decreased and thyroxine levels increased (P Conclusions Thyroid hormone replacement therapy in patients with severe primary hypothyroidism improves eGFR and decreases 24-hour urine protein excretion, thereby suggesting reversible alterations.

Objective: To study the role of Indomethacin in patients with Idiopathic Polyhydramnios who were symptomatic. Methods: A prospective study was conducted in Prathima Institute of Medical Sciences, Karimnagar from September 2017 to May 2019. Eighteen patients with Idiopathic Polyhydramnios who presented with respiratory embarrassment, premature opening of os or presence of uterine activity were given Indomethacin orally at a dose of 25mg 6th hourly. The significance of changes in AFI was tested by paired t test. Results : There was significant improvement in the symptoms in all the eighteen patients. The mean age of the patients in our study was 26.4±5.5 years. The majority 14(77.7%) of women were multigravida. Mean gestational age at presentation was 30.78±1.56 weeks. Mean AFI at presentation was 31.56±3.68 cm. Indomethacin was given orally at a dose of 25mg, every 6th hourly for a mean duration of 22.5±6.38 days. Mean AFI at the end of treatment was 20.28±5.64 cm. Pregnancy was prolonged by an average of 5.5±1.89 weeks. The difference in AFI at the end of treatment was statistically significant (p

Whole-body vibration (WBV) is one of the leading risk factors for development of musculoskeletal disorders (MSDs) that develop symptoms of lower back pain, pain in the neck and shoulders, digestive problems, blood pressure and diabetes among professional dumper operators. The present study specifically aimed at assessing the WBV exposure of 79 dumper operators engaged in two Indian opencast coal mines through vibration measurements followed by questionnaire survey. From the daily frequency-weighted root mean square exposure, dumper operators have experienced vibration levels higher than the Health Guidance Caution Zone (HGCZ) of Standard No. ISO 2631-1:1997. However, on the basis of daily vibration dose values, 60.8% of operators have experienced vibration levels above the HGCZ. Finally, an attempt was also made to explore the potential of a Bayesian network to predict the risk factors for WBV of dumper operators in development of MSDs to prioritize the factors for human health risk assessment.

The high demand for synthetic hydroxyapatite for biomedical applications is on the rise day by day at the same time, there is a pressing need for producing hydroxyapatite (HA) at an economically viable cost to make the treatment affordable to everyone. In order to meet this objective, recycling of waste to value added products and cost effective methods suitable for scaling up the process are being attempted by researchers. In this report, an attempt has been made to optimize the parameters for the synthesis of nano HA from eggshell biowaste using well explored microwave method by employing a lab scale and pilot scale microwave reactors. Several parameters such as pH, organic modifier concentration and microwave power against volume of the reaction mixture has been studied from the view point of enhancing the yield of the product. The preliminary experiments done using lab scale reactor helped the optimization of pH and EDTA concentration. From the lab scale experiments, we found that the yield was directly proportional to the microwave power. The parameters optimized in the lab scale has been carried over to the pilot scale reactor. The results from pilot scale reactor revealed that although the microwave power from pilot scale reactor is considerably higher than that of the maximum power (900 W) of the lab scale reactor there is no significant difference in the yield of the product but the microwave irradiation time has reduced considerably which is almost in proportion to the power of the reactor. Parameters optimized from these batch processes will be useful for devising new scaling up process such as continuous flow methods.

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Community-acquired acute kidney injury (CA-AKI) is the dominant form of AKI encountered in developing countries in Asia. Economic disparities, variations in access to health care services, geographic conditions, environmental risk factors, and sociocultural circumstances shape the causes and outcomes of CA-AKI. Infections, drugs, plant and chemical toxins, envenomations, and obstetric complications are common causes of CA-AKI. Previously healthy young individuals who often work outdoors in fields or farms are exposed to a wide variety of work-related or environmental risk factors for CA-AKI. Improving disease definitions, better data, and evolving host-pathogen interactions have changed disease descriptions and presentations over the past 20 years. Among infections, although the incidence of malaria has decreased, the number of cases with dengue and scrub typhus have increased sharply. The recognition of AKI in relation to Plasmodium knowlesi, Plasmodium vivax, scrub typhus, and leptospirosis in areas not traditionally considered at risk, association of infections with the future development of chronic kidney disease, and the role of complement dysregulation in infection-associated AKI are important new findings. Snake-bite-related toxic envenomation continues to be an important cause of AKI in some counties and is a neglected public health problem. On the other hand, significant decreases in the incidence of AKI related to acute diarrheal illness or obstetric causes are signs of hope. Coordinated efforts between administrative stakeholders, society, and health care delivery services at all levels have the potential to propel research and improve outcomes in CA-AKI.

Introduction The coronavirus disease 2019 (COVID-19) pandemic has affected the care of patients with noncommunicable diseases, including those suffering from kidney-related ailments. Many parts of the world, including India, adopted lockdown to curb community transmission of disease. The lockdown affected transportation, access to health care facilities, and availability of medicines and consumables as well as outpatient and inpatient services. We aimed to analyze the effect of lockdown imposed due to the COVID-19 pandemic on the care of patients with kidney diseases in India. Methods We surveyed 19 major hospitals (8 in the public and 11 in the private sector) to determine the effect of lockdown on the care of patients with kidney disease, including those on dialysis after the first 3 weeks of lockdown. Results The total number of dialysis patients in these centers came down from 2517 to 2404. Approximately 710 (28.2%) patients missed 1 or more dialysis sessions, 69 (2.74%) required emergency dialysis sessions, 104 (4.13%) stopped reporting for dialysis, and 9 (0.36%) were confirmed to have died. Outpatient attendance in the surveyed hospital came down by 92.3%, and inpatient service reduced by 61%. Tele-consultation was started but was accessed by only a small number of patients. Conclusion Lack of preparedness before lockdown resulted in an interruption in health care services and posed an immediate adverse effect on the outcome of dialysis patients and patients with kidney disease in India. The long-term impact on the health of patients with less severe forms of kidney disease remains unknown.