Search

Introduction: Clinical use of tacrolimus has been challenging due to its narrow therapeutic index and highly variable pharmacokinetics. In this study, we compared patients who received body weight-based tacrolimus dosing pre-transplant (transplanted from 2016 to 2018) with those who received CYP3A5 genotype-based dosing (2018 to 2020). Methods: Eighty-two renal transplant recipients were non-randomly assigned to genotype-adapted or bodyweight-based tacrolimus dosing groups. The primary end point was to study the proportion of subjects who achieved the target tacrolimus C0 on post-op day 4. Secondary end points included clinical outcomes and safety. Results: The proportion of subjects who achieved the target tacrolimus C0 on postoperative days 4 and 10 were significantly higher in the adapted group, 53.6% and 47.5%, compared to 24.3% and 17% in controls, respectively (P = 0.01). Adapted group subjects achieved their first target tacrolimus C0 significantly earlier (4 days) compared to 25 days in controls (P = 0.01). The total number of tacrolimus dose modifications required in the first postop month were lower in the adapted group; 47 compared to 68 in the controls (P = 0.05). The proportion of subjects with sub-therapeutic tacrolimus exposure on postoperative day 4 was significantly higher in the controls, 56% versus 10% in the adapted group (P < 0.001). There were no significant differences between the groups in the rate of biopsy proven acute rejections, adverse events, and graft function at the end of 3 months follow up. Conclusion: Genotype-based tacrolimus dosing leads to more subjects achieving the target tacrolimus C0 earlier. However, there may be a higher risk of tacrolimus nephrotoxicity. [ABSTRACT FROM AUTHOR]

Acute porphyrias are metabolic disorders resulting from deficiency of a specific enzyme involved in heme biosynthetic pathway. These deficiencies also affect normal renal physiology, as kidneys are also involved in heme synthesis. Sometimes, this could even lead to end stage renal disease. Acute Intermittent Porphyria, an autosomal dominant disorder arising from half-normal activity of hydroxymethylbilane synthase, is characterized by occurrence of vague neurovisceral attacks (abdominal pain, nausea, vomiting, constipation and neuropsychiatric symptoms), with urinary excretion of porphyrin precursors, such as 5-Amino-levulinic acid (ALA) and Porphobilinogen (PBG). Acute attacks are triggered by dehydration, diarrhea, steroids, low calorie diets. Treatment includes avoidance of precipitating factors, adequate hydration, high carbohydrate diet and heme replacement. Here, we present an adolescent female who had presented with recurrent abdominal pain, dyselectrolyemia with associated seizures, was diagnosed with Acute Intermittent Porphyria and recovered well with symptomatic management. [ABSTRACT FROM AUTHOR]

Introduction: Tacrolimus blood levels are influenced by polymorphisms involving Cytochrome 3A subfamily (CYP3A5) and P-Glycoprotein (ABCB-1) genes. However, their role in transplant outcomes was less studied in South Indian population. We studied the prevalence and impact of these polymorphisms in renal transplant recipients from South India. Methods: An analysis of CYP3A5, ABCB1 genotype done in 101 renal transplant recipients by polymerase chain reaction was correlated with blood tacrolimus trough levels (CLIA method), weight, concentration/dose (L/D) ratio, incidence of biopsy proven early acute rejections, and tacrolimus toxicity. Results: Prevalence of CYP3A5*1/*1, *1/*3 and *3/*3 and ABCB1 (3435C>T) TT, CT, CC genotypes were 12 (11.9%), 48 (47.5%), 41 (40.6%) and 16 (15.8%), 45 (44.6%), 40 (39.6%), respectively. Mean tacrolimus level, median concentration/dose (L/D) ratio were significantly lower in homozygous (CYP3A5*1/*1-6.01 ng/mL; 48.99 ng/mL/mg/kg/day) and heterozygous expresser group (CYP3A5*1/*3-5.84 ng/mL; 68.93 ng/mL/mg/kg/day) when compared with nonexpresser group [CYP3A5*3/*3-7.46 ng/mL (P < 0.001);181.3 ng/mL/mg/kg/day (P < 0.05]. No significant differences observed between the ABCB1 genotypic groups. Incidence of early acute rejections (30% vs. 9.76%; P 0.016) and tacrolimus-related toxicity (14.6% vs. 5%; P 0.039) were significantly higher in CYP3A5 expressers and nonexpressers, respectively. No correlation observed between the ABCB1 polymorphisms between rejection episodes or tacrolimus renal toxicity. Among 101 patients, 40.6% were non-expressers (poor metabolizers) (*3/*3). Conclusions: CYP3A5 polymorphisms correlated with tacrolimus dose requirements and blood levels, incidence of early acute rejection, and tacrolimus nephrotoxicity. CYP3A5 polymorphism analysis prior to renal transplant will aid more precise early tacrolimus dose calculation to balance between rejection and toxicity. [ABSTRACT FROM AUTHOR]

Despite kidney transplantation (KT) being considered as the best treatment modality for end-stage renal disease (ESRD), patient and graft survival in the elderly population is poorer than younger individuals. Many authors argue that prolonged life expectancy outweighs the risk of remaining on dialysis, but few studies had compared the treatment modalities, especially with peritoneal dialysis (PD). A retrospective study was conducted at a tertiary care institute to compare outcome of elderly ESRD patients, who received KT with those continued on PD; and to evaluate the predictors of patient survival. Patient survival at 1 year was (76.2% vs. 91.1%); 5 years (53.7% vs. 21.8%); and 10 years (35.6% vs. 0.00%) among KT and PD population, respectively. Infection was the most common cause of death among KT group (35 [41.2%] vs. 34 [28.2%]) while cardiovascular mortality in PD group (55 [46.2%] vs. 7 [8.2%]). Technique survival at 1, 5, and 10 years in PD group was 92.8%, 58.5%, and 0%, respectively. Similarly, graft survival at 1, 5, and 10 years in KT group was 98.7%, 90.2%, and 90.2%, respectively. Multivariate analysis showed body mass index (BMI) (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.82-0.93, p < 0.001), and albumin (HR 0.55, 95% CI 0.37-0.80, p = 0.002) were significant predictors of survival. In the 1st year, patient survival was better in PD than KT, but after adjustment for BMI and albumin, both short-term and long-term survival in elderly KT group was better than that of PD. Hence, elderly ESRD patients should not be barred from KT just because of age. [ABSTRACT FROM AUTHOR]

Posttransplant lymphoproliferative disease (PTLD) is an uncommon complication of immunosuppression after solid organ transplantation. Early PTLD (<1 year after transplantation) is frequently found around the allograft, whereas late PTLD (>1 year after transplantation) does not have such a preference. 18-Fluorodeoxyglucose positron emission tomography-computed tomography (18FDG PET-CT) has clinical significance in the evaluation of PTLD. 18FDG PET-CT scan allows precise anatomic localization of FDG-avid lesions, hence helpful in staging of disease and evaluation of response to therapy. It can better characterize persistent lesions and differentiate residual tumor from fibrosis or necrosis. We present a rare case report of a perigraft PTLD developing 12 years after renal transplantation sparing the graft, in an Epstein--Barr virus-negative patient. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are known to suppress gene expression by binding to messenger RNAs and in turn regulate different pathophysiological processes. Transforming growth factor-β, mitogen-activated protein kinase signaling, and Wnt signaling-like major pathways associated with miRNAs are involved with kidney diseases. The discovery of miRNAs has provided new insights into kidney pathologies and may provide effective therapeutic strategies. Research has demonstrated the role of miRNAs in a variety of kidney diseases including diabetic nephropathy, lupus nephritis, hypertension, nephritic syndrome, acute kidney injury, renal cell carcinoma, and renal fibrosis. miRNAs are implicated as playing a role in these diseases due to their role in apoptosis, cell proliferation, differentiation, and development. As miRNAs have been detected in a stable condition in different biological fluids, they have the potential to be tools to study the pathogenesis of human diseases with a great potential to be used in disease diagnosis and prognosis. The purpose of this review is to examine the role of miRNA in kidney disease. [ABSTRACT FROM AUTHOR]

Deceased donor renal transplantation (DDRT) constitutes less than 5% of all kidney transplantais in India. A retrospective analysis of 173 deceased donor renal transplants performed in a public funded government hospital was done. Mean age of the recipients was 36 years (male:female ratio 2.4:1), and that of the donors was 32.3 years (male:female ratio 6:1). The cold ischemic time was 340 ±170 minutes. Mean follow-up period was 36 months. Forty one patients died, 75% of them in the first post-transplant year. Sepsis and cardiovascular disease were the most common causes of death. Twenty two percent had acute rejection. There was no significant difference in the incidence in the rate of acute rejection, bacterial, fungal infections and death rate between the cohorts of induction and non induction immunosuppression. The patient and death censored graft survival at 1 year were 80 and 82.6% and at 5 years were 76 and 80% respectively. [ABSTRACT FROM AUTHOR]

In renal allograft recipients, cytomegalovirus (CMV) typically causes tubulointerstitial nephritis. Only rarely glomeruli are involved. We present a rare case of CMV with collapsing glomerulopathy, necrotizing glomerulonephritis, and crescent formation in a renal allograft recipient. Immunohistochemistry confirmed CMV infection. The patient was started on valganciclovir and his renal function remained stable. A repeat renal biopsy performed three months later showed morphologically normal glomeruli and CMV immunostaining was also negative. Nephropathologists have to carefully screen for CMV in cases with crescentic or collapsing glomerulopathy as the later lesions resolve after treating the underlying viral infection. This study will add on to the various glomerular changes associated with CMV infection. [ABSTRACT FROM AUTHOR]

Chronic kidney diseases (CKD) adversely affects fetal and maternal outcomes during pregnancy. We retrospectively reviewed the renal, maternal and fetal outcomes of 51 pregnancies in women with CKD between July 2009 and January 2012. Of the 51 subjects (mean age 27.8 ± 7.04), 32 had 19 had estimated glomerular filtration rate (eGFR) <60 ml/min. There was significantly greater decline in eGFR at 6 weeks (55.8 ± 32.7 ml/min) after delivery as compared to values at conception (71.7 ± 27.6 [P < 0.001]). The average decline of GFR after 6 weeks of delivery was faster in patients with GFR < 60 ml/min/1.73 m2 at −18.8 ml/min (stage 3, n = 13, −20.2 ml/min; stage 4, n = 6, −15.8 ml/min) as compared to −15.1 ml/min in patients with GFR ≥ 60 ml/min/1.73 m2. Three of the six patients (50%) in stage 4 CKD were started on dialysis as compared to none in earlier stages of CKD (P = 0.002). At the end of 1 year, all patients in stage 4 were dialysis dependent, while only 2/13 in stage 3 were dialysis dependent (Odds ratio 59.8, 95% confidence interval 2.8-302, P = 0.001). Preeclampsia (PE) was seen in 17.6%. Only 2/32 (6.25%) patients with GFR ≥ 60 ml/min/1.73 m2 developed PE while 7/19 (36.84%) patients with GFR < 60 ml/min developed PE. Of the 51 pregnancies, 15 ended in stillbirth and 36 delivered live births. Eleven (21.56%) live‑born infants were delivered preterm and 7 (13.72%) weighed < 2,500 g. The full‑term normal delivery was significantly high (50%) in patients with GFR ≥ 60 ml/min/1.73 m2 (P = 0.006) and stillbirth was significantly high ‑ 9/19 (47.36%) patients with GFR < 60 ml/min/1.73 m2. To conclude, women with CKD stage 3 and 4 are at greater risk of decline in GFR, PE and adverse maternal and fetal outcomes as compared to women with earlier stages of CKD. [ABSTRACT FROM AUTHOR]

Pregnancy-associated acute kidney injury (PAKI) is encountered frequently in developing countries. We evaluated the maternal, fetal and renal outcomes in women with PAKI who needed at least one session of dialysis. Of the total of 98 cases (mean age 28.85 ± 5.13 years; mean parity 2.65 ± 1.28) of PAKI, the most common cause of PAKI was postabortal sepsis. Eighteen patients died; those with oligoanuria, sepsis and central nervous system (CNS) involvement were at greater risk of mortality. The relative risk (RR) of neonatal mortality was lower after with full‑term delivery (RR: 0.17, 95% confidence interval (CI): 0.03-0.96, P = 0.02) compared to preterm delivery. Of the 80 surviving patients, 60 (75%) patients achieved complete recovery of renal function at the end of 3 months; and of the remaining 14 had presumed (n = 4) or, biopsy-proven (n = 10) acute patchy cortical necrosis. The RR of non-recovery of renal function was high (RR: 24.7, 95% CI: 3.4- 179.5) in patients who did not recover at 6 weeks. Of the 14 patients with cortical necrosis, 3 (21.42%) became independent of dialysis at 6 months. PAKI patients should be watched for dialysis independency for 6 months. [ABSTRACT FROM AUTHOR]

We evaluated whether polymorphisms in interleukin (IL‑1) gene cluster (IL‑1 alpha [IL‑1A], IL‑1 beta [IL‑1B], and IL‑1 receptor antagonist [IL‑1RN]) are associated with end stage renal disease (ESRD). A total of 258 ESRD patients and 569 ethnicity matched controls were examined for IL‑1 gene cluster. These were genotyped for five single‑nucleotide gene polymorphisms in the IL‑1A, IL‑1B and IL‑1RN genes and a variable number of tandem repeats (VNTR) in the IL‑1RN. The IL‑1B − 3953 and IL‑1RN + 8006 polymorphism frequencies were significantly different between the two groups. At IL‑1B, the T allele of − 3953C/T was increased among ESRD (P = 0.0001). A logistic regression model demonstrated that two repeat (240 base pair [bp]) of the IL‑1Ra VNTR polymorphism was associated with ESRD (P = 0.0001). The C/C/C/C/C/1 haplotype was more prevalent in ESRD = 0.007). No linkage disequilibrium (LD) was observed between six loci of IL‑1 gene. We further conducted a meta‑analysis of existing studies and found that there is a strong association of IL‑1 RN VNTR 86 bp repeat polymorphism with susceptibility to ESRD (odds ratio = 2.04, 95% confidence interval = 1.48-2.82; P = 0.000). IL‑1B − 5887, +8006 and the IL‑1RN VNTR polymorphisms have been implicated as potential risk factors for ESRD. The meta‑analysis showed a strong association of IL‑1RN 86 bp VNTR polymorphism with susceptibility to ESRD. [ABSTRACT FROM AUTHOR]

Idiopathic minimal change disease is a disorder of T‑cell dysfunction. The relative predominance of regulatory T cells (Tregs), Th1, and Th2 cells in nephrotic syndrome (NS) remains controversial. Imbalance in peripheral blood regulatory and effector T cells (Teff) are linked to cell mediated immune response and may be associated with steroid response in NS. Peripheral blood CD4 + CD25 + FoxP3 + (Tregs), CD4 + IFN‑γ+ (Th1), and CD4 + IL‑4 + (Th2) lymphocytes were analyzed in 22 steroid‑sensitive NS (SSNS) patients in sustained remission, 21 steroid‑resistant NS (SRNS) and 14 healthy controls. The absolute percentage values and ratio of Th1/Tregs, Th2/Tregs, and Th1/Th2 were compared between SSNS, SRNS and control subjects. The percentage of Tregs was lower in SRNS patients (P = 0.001) compared with that of SSNS and healthy control. The percentage of Th1 cells was higher in SRNS (P = 0.001) compared to that of SSNS patients; however, it was similar to healthy controls (P = 1.00). The percentage of Th2 cells in SRNS (P = 0.001) was higher as compared to SSNS and controls. The ratio of Th1/Treg cells in SRNS (P = 0.001) was higher as compared to SSNS patients and controls. The ratio of Th2/Treg was also higher in SRNS as compared to SSNS and controls. The ratio of Th1/Th2 cells in SSNS, SRNS, and healthy controls were similar. The cytokines secretion complemented the change in different T‑cell subtypes in SSNS, SRNS and healthy controls. However, the IFN-γ secretion in healthy controles was low inspite of similar percentage of Th1 cells among SRNS cases. We conclude that greater ratio of Tregs compared to that Th1 and Th2 favor steroid sensitivity and reverse ratio results in to SRNS. The difference in ratio is related to pathogenesis or it can be used as marker to predict steroid responsiveness needs further evaluation. [ABSTRACT FROM AUTHOR]

IgG4 interstitial nephritis is a recently described entity. A middle-aged gentleman with bilateral parotid enlargement, hepatosplenomegaly and generalized lymphadenopathy was referred to us for evaluation of renal failure. He had trace proteinuria and large kidneys. Kidney biopsy revealed interstitial nephritis with characteristic storiform fibrosis. Immunohistochemistry demonstrated intense staining for IgG4-secreting plasma cells in the interstitium. [ABSTRACT FROM AUTHOR]

Glomerular filtration rate (GFR) prediction equations are widely used in clinical practice for quick assessment of kidney function. Gates method using radionuclide technique is an alternative to prediction equations for quick assessment of GFR. Aim of the study was to compare Gates method and modification of diet in renal disease (MDRD) equation in a sizeable patient population with wide range of renal function to evaluate their clinical utility. GFR was estimated in 897 subjects with wide range of renal function by gates method, and MDRD equation and results were compared against measured GFR. Subjects were divided in to 4 groups (0.30 ml, 31.60 ml, 61.90 ml, >90 ml) on the basis of measured GFR and comparison between two methods done through linear regression analysis. Analysis of R2 indicated that 56% of the interindividual variability for Gates GFR was in accordance to variation in measured GFR, in the GFR range of (0.30 ml), this value dropped to 39% in the GFR range of 31.60 ml, 40% in the GFR range of 61.90 ml, 26.4% in the GFR range of >90 ml, the corresponding figure for MDRD GFR were 47.9%, 31.1%, 17.6% and 16.1%, respectively. Gates method is more precise for GFR estimation at all levels of renal function. [ABSTRACT FROM AUTHOR]

The aim of the study was to study the distribution of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism, and its association with steroid responsiveness in children with idiopathic nephrotic syndrome (INS). One hundred twenty-five children with INS were classified into two groups: steroid-sensitive nephrotic syndrome (SSNS: n = 90) and steroid-resistant nephrotic syndrome (SRNS: n=35). The control group consisted of 150 unrelated healthy children. Genomic DNA was extracted from peripheral leucocytes by the standard salting-out method. ACE genotyping was performed and ACE genotypes DD, ID, and II were compared between different groups. The frequency distribution of the DD genotype was significantly increased in children with INS compared to control subjects (P = 0.0012) while the difference was not significant (P = 0.071) between SSNS and control subjects. The frequency distribution of the DD genotype was significantly high in the SRNS group compared to control subjects (P < 0.0001). The distribution of the DD genotype was high in SRNS compared to SSNS group patients (P = 0.016). In conclusion, the presence of the DD genotype may predict risk for steroid resistance in childhood INS. [ABSTRACT FROM AUTHOR]

To evaluate graft function and its effect on body composition and nutritional status of renal transplant patients using Bioelectrical Impedance Analysis. 100 patients {male 82; female 18) who underwent renal transplant between year 1997 and 2006. Their mean age was 39±10.3 years, mean height 164.2±7.6 cm and weight 58.9±9.0 kg, mean serum creatinine 1.48±.0.59 rag% and mean GFR 43.8±15.3 mljmin. GFR and body composition was assessed using multi frequency bioelectrical impedance analyzer BIOSCAN. All the patients were on 2 or 3 immunosuppressive drugs. All the patients had normal SGA scores. Data were analyzed in two steps. First analysis included comparison of patients with well matched 61 healthy controls (male 45 female 16) for age (41.7±11.3 years), sex and height (163.5±9.7 cm), with weight 63.7±12.0 kg) and serum creatinine 0.97±0.19 rag%. Patients were then divided into two groups based on GFR as calculated by Bioscan (group 1: borderline graft function GFR <40 ml]min: n= 33, X 27.8±10.2 ml/min and group 2: good graft function GFR 340 ml/minute, n =67, X 51.7±10.4 ml/min). Both groups were compared with each other. The results show that there was significant difference (p 0.000 for all variables unless specifically mentioned otherwise) between controls and PTP in weight (P.0 08), creatinine, body mass index (BMI, phase angle (PA) fat free mass (FFM, FFM% fat mass (PM) FM%, total body water (TBW %, extracellular water (ECW), ECW%, Intracellular water (ICW), ICW%, ECW/ICW, body cell mass (BCM P=0.002), GFR, extracellular solids (ECS 0.32) ECfiuid (ECF) plasma, interstitial fluid (ITSF), target fat rain (TFM P=0.021), target water min (TWM) systolic BP and diastolic BP. When groups 1 and 2 were compared, significant differences (P=0.000) were observed. Group 1 patients had low weight, PA (P=0.017), BMI (P=0.003), resting metabolic rate (RMR), FFM, TBW, ICW, ICW% (0.001), BCM, ECM (P=0.026). GFR, Protein (P=0.020), Mineral (P=0.050), Calcium, glycogen, dry weight, ECS, TFmax (P=0.046). Group 1 patients had higher ECW%, ECW/ICW compared to group 2. Though clinically all patients had normal SGA scores and were non-edematous, their intravascular compartments were expanded as depicted by high absolute values of ECW, ECW/ICW, ECF, plasma INSTFL compared to controls. Significant differences between Group 1 and Group 2 patients indicate that transplant patients with borderline graft function were more nutritionally depleted as compared to those with better GFR. Transplant patients as a group had higher systolic and diastolic blood pressure which may be related to their volume expanded status. Both nutritional deficit and volume expansion were detected objectively by BIA which is a non-invasive tool for out patient monitoring. [ABSTRACT FROM AUTHOR]

Background: chronic liver disease and its complication are major problem in renal transplant patients. Our aim was to elucidate the influence of hepatitis B(B+C), C(C+B) virus infection on the long term outcome of renal transplantation. Methods: The data of 889 of renal transplant patients who underwent renal transplant at our centre between 1989-2005, and had adequate virological data were analyzed retrospectively Qualitative differences between groups were assessed by means of the Chi-square test. Patient and graft: survival were estimated by means of the Kaplan-Meier product limit method and compared by means of the log-rank test; Proportional hazard Cox's model, was used for multivariate analysis. Results: Prevalence were 4.4% for B+C-, 4.9% for C+B-, 0.9% for hepatitis B and C both positive (B+C+) and 89.8% for hepatitis B and C both negative (B-C-) patients. Because of very low prevalence of B+C+ patients, this group was removed from the analysis. The 10-year death censored graft survival was not significantly different between the B+, C+ and B-C- patients, it was 81%, 81%, 85%, in B-C-, B+C- and C+B- patients respectively (P=0.639). The patient survival at 10 years was inferior (85%) among the infected patients as compared to 93% in non-infected patients (P=0.04). In patients with C+B- group patient survival was significantly inferior as compared to C-B- (non infected) patients. (P=0.015). Odd's risk ratio: 5.9;95% CI 91.7-115.2. For B+C- group patient survival was not statistically significantly inferior as compared to B-C- patients (88% v/s 93%; P=0.58). There were more deaths in infected groups because of liver disease. In infected patients, the causes of death was sepsis in 66.6% (4/6) and related to liver failure in the remaining 33.3% (2/6). Whereas 83.3% of deaths in non infected group were because of sepsis, 33.3% because of cardiovascular disease and 4.2 % died of malignancy (P=0.002). At multivariate analysis Hum/ infective status (RR, 3.4; 95% CI, 1.19-9.9; P=0.042) was independently associated with a worse patient survival. Among the infected patients 27.8% patients developed Chronic liver disease (CLD) [persistent deranged LFT >6 months] as compared to 0.8% in non infected group (P<0.0001). 21.6%, 33.3% of patients in groups B + and C + respectively developed CLD. Significantly more no of infected patients developed post transplant diabetes (PTDM); C+ 37.5%, B+C- 12.1%, as compared to 8.4 % in non infected group. (P<0.0001). Conclusion: In the long term B+ and C+ patients had a higher risk of poor patient survival and death related to liver disease, but the graft survival is not significantly affected. [ABSTRACT FROM AUTHOR]

Drugs currently used to treat membranous nephropathy vary in their effectiveness among patients and can cause severe side effects. FDA has approved sirolimus for suppressing immune system of patients who have kidney transplant to reduce the risk of organ rejection. The drug does not have any certain side effects that have caused problems for patients treated with other immunosuppressants. To evaluate the safety and efficacy of a new immunosuppressive drug, sirolimus in reducing the proteinuria of patients with idiopathic membranous nephropathy resistant to previous therapy. We prospectively studied ten patients of idiopathic membranous nephropathy, who were resistant to previous therapy with ponticelli regimen (I. V. MP f/b prednisolone and cyclophosphamide every alternate month x 6 months) and of these, five were also non responsive to CsA for six months. All of them screened for the evidence of active infection before starting with sirolimus. All of them had nephrotic range proteinuria at the time of starting the therapy. Sirolimus was started with 3 mg on day 1 followed by 2 mg once a day and adjusted the dosage to achieve the target blood level (4-12 ng/ml) for a period of six months. Oral prednisolone in a dose of 1 mg/kg/day was also given along with sirolimus and tapered off slowly once remission achieved or after 8 weeks of therapy. During treatment, patients were follow up monthly for reduction of proteinuria, GFR and other clinical and laboratory parameters for the safety and effectiveness of the drug. All patients were male, age group of 20 -40 yrs, mean age of onset was 27.2 year, mean duration of illness 36 months, and all of them completed ponticelli regimen, 05 patients (50%) received CsA after they did not respond to ponticelli regimen. 7 patients (70%) received ACEI for 12 months before starting the sirolimus. Eight patients (80%) were reponders [four patients (50%) achieved complete remission (nil proteinuria), and four had partial remission (50% reduction in proteinuria)] and two (20%) were non responders. The mean time to achieve remission was 94±34 days and the mean dose of sirolimus was 2 mg per day. The mean trough levels of sirolimus were 4.7±1.8 ng/ml. The mean 24 hrs proteinuria were significantly lower from baseline of 6.25±1.63 gm/day to 0.825±0.967 gm/day (P= 0.010) and the mean serum albumin levels were increased from baseline 2.67±0.479 gm/dl to 3.28±0.538 gm/dl (P=0.108) after 94±34 days of therapy. The mean GFR values at the end of the study were similar to those prior to the starting of sirolimus 52.5±4.6 ml/mt/1.73 m² vs 49.2±2.3 ml/mt/1.73 m².The mean duration of follow up was 310±188 days. Five patients required statins for control of dyslipidemia on sirolimus therapy. Three patients had cutaneous infection (2 had fungal, 1 had scabies) which responded to antifungal and antiscabies treatment, one had developed diabetes mellitus which was controlled with oral hypoglycemic agent and diarrhea due to entamoeba histolytica. One had urinary tract infection during therapy. None of them relapsed after stopping sirolimus (mean period of 162±112 days). This is the only study so far on the safety and effectiveness of sirolimus in resistant cases of idiopathic membranous nephrotic syndrome. Our results shows that sirolimus is effective in controllong proteinuria without nephrotoxicity and serious adverse events in patients with resistant idiopathic membranous nephropathy. A prospective controlled study on large number of patients needs to be done to compare the safety and efficacy of sirolimus in idiopathic membranous nephropathy cases who are resistant to ponticelli and CsA based immunosupression regimen. [ABSTRACT FROM AUTHOR]

Anti-IL-2 receptor has been proved to be effective in reducing the rate of acute rejection in kidney transplantation and also improving both the rate of graft and patient survival. In this study, we retrospectively reviewed the role of anti-IL-2 receptor (basiliximab) as induction immunosuppression. Methods: Sixty five kidney transplant recipients from living donors who received IL-2 blocker basiliximab (group 1) as induction therapy in combination with CsA, Steroid and MMF or Azathioprine, were compared with similarly matched renal transplant recipients (N=555) who did not receive induction therapy {group 2). Survival analysis was done using Kaplan- Meir analysis. Chi --square test was used to compare the outcome difference of various parameters between the two groups. Result: Both the groups were similar in terms of male to female ratio, basic disease, mean age of recipient as well as of donors. Group 1 has more no of immunologically high risk patients {2nd transplants 4.6% v/s 1.5%, P>.05}, More spousal donors {35.4% v/s 20.8 % P<0.009). Significantly more no of patients in group1 (47.7%) received MMF based immunosuppression as compared to group2 (22.6%) (P=0.016). Total no of rejections were significantly less in Group1 (15.4%) v/s 29.4% in group 2 (P=0.023, Odds ratio=0.44). More number of patients in Group 2 suffered steroid resistant rejections however the difference was not statistically significant. (11.1% in group 2 v/s 4.6% in group 1). Three percent patients suffered late acute rejections in group 1 v/s 3.9% in group 2. (P=NS). Death censored graft survival was significantly better hi group 1 at 5 yr as compared to group 2. (86% v/s 77% P<0.02). It was 100% at 1yr (group1) v/s 96%, in group 2. Actuarial patient survival at one and 5 yr was 100% and 92% in group 1 v/s 99% and 95% in group2 (P= >.05). On multivariate analysis for association with graft survival only the late acute rejections and steroid resistant rejection were independently associated with poor graft survival, whereas type of maintenance immunosuppression (MMF v/s non MMF), use of induction therapy and total no of acute rejection episodes had no association. Conclusions: The use of anti-IL-2 receptor antibodies (basiliximab) as induction immunosuppression in immunologically high-risk patients results in the significantly better prevention of acute rejection, and 5yr graft survival. It also results in reduced severity of acute rejection. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate the safety and efficacy of sirolimus (SRL) in patients with SRNS. This study comprises 19 pts (both children and adults) with SRNS of biopsy proven idiopathic (NS) (6 Minimal change, 13 FSGS). Sirolimus was initiated in a dose of 2 mg once daily increased to attain a trough sirolimus level of 5-15 ngm/ml. All previous immunosuppressant agents (except Prednisolone) were discontinued 2 months prior to start of sirolimus. The primary outcome variable was complete or partial remission. The mean age of onset was 13.3±11.8 yrs (12 male and 7 female), 6 pt had MCD and 13 had FSGS. Two pts did not respond after 6 months of SRL therapy. 16 pts who received adequate therapy (6 months) and were able to achieve target level. Of these 13 pts (81.25%) responded to sirolimus: complete remission in 10 pts (62.5%), 3 pts (18.75%) attained partial remission and 3 (18.75) were non responsive. The mean time to achieve remission was 96.92±35.91 days and the mean dose of sirolimus was 2.32±0.47. The mean trough levels were 3.93±1.75 ng/ml. Of 14 cyclophosphamide resistant pts, 9 attained complete remission and 2 partial remission. Of the 10 cyclosporine resistant pts 9 attained complete remission and 1 partial remission. Of 4 Mycophenolate mofetyl non responder pt, 3 attained complete remission and 1 partial remission. 4 pts relapsed after stopping siroloimus but achieved remission on restart of SRL. The mean urine spot protein/creatinine ratio was significantly lower (7.25±7.50 vs 0.42±0.59, P= 0.0004) and the mean serum albumin levels increased at the end of treatment (2.35±0.70 vs. 4.07±0.35 P= 0.0001). The mean GFR value at the end of study was higher (92.6±27.8 ml/mt/m² vs 86.9±37.4) in pts who achieved complete remission. The mean duration of follow up was 240±126 days. Our results suggest that sirolimus is effective in pts with SRNS including those who are resistant to current therapeutic measures and has no nephrotoxicity. [ABSTRACT FROM AUTHOR]

Microfilarial parasites can obstruct the lymphatic tree giving rise to varying lymphatic and extra-lymphatic symptoms. Renal manifestations can range from asymptomatic proteinuria, chyluria, and nephrotic syndrome, to acute glomerulonephritis. The diagnosis of filariasis is usually made by the demonstration of the parasite in the peripheral blood smear, with or without eosinophilia. The renal involvement by this parasite has been sparsely reported in the literature. We hereby report five cases of filariasis detected on histopathological examination of renal biopsies, performed for other indications, along with a brief report of the additional histological findings. Three native and two graft biopsies were included. All our patients were male, with a mean age of 47 years (range 37 to 66 years). The serum creatinine ranged from 1.2 to 12.9 mg/dL. The mean 24-hour urinary protein was 3.6 gm/day. Peripheral blood eosinophilia was not recorded in any case, however, ESR was raised in all cases. Urine examination revealed varying proteinuria, with hematuria in two cases. Histological examination revealed microfilaria in all five biopsies, along with focal segmental glomerulosclerosis in two cases, combined cellular and humoral rejection, minimal change disease and acute tubular necrosis in one case each respectively. All patients were treated with diethylcarbamazine 6mg/kg/day or 12 days, in addition to the renal medications. Diagnosing the parasite is crucial as the patient is likely to benefit due to the timely treatment of the disease. Reporting this case series highlights an interesting finding in nephropathology., Competing Interests: There are no conflicts of interest., (© 2024 Indian Journal of Nephrology | Published by Scientific Scholar.)

Dichlorvos, an organophosphate compound, has the potential to cause acute kidney injury (AKI) besides its well-known neuromuscular complications. We report a case of severe-recurrent AKI that progressed to end-stage-renal-disease (ESRD) following accidental exposure to Dichlorvos. A 52-year-old male farmer presented with breathlessness after accidental exposure while spraying in the field. He required mechanical ventilation due to allergic pneumonitis and developed anuric AKI, requiring renal replacement therapy (RRT). Biopsy revealed severe acute tubulointerstitial nephritis (ATIN), which responded to steroids, and the patient became dialysis-independent by 4 weeks. Two weeks later, the patient had recurrent AKI requiring RRT. A repeat biopsy revealed severe ATIN. However, despite steroid treatment, he progressed to ESRD. Organophosphate compounds can cause renal injury with a wide spectrum of presentations, ranging from subclinical AKI to severe dialysis-dependent renal failure, which may eventually progress to end-stage renal disease., Competing Interests: There are no conflicts of interest., (© 2024 Indian Journal of Nephrology | Published by Scientific Scholar.)

Competing Interests: There are no conflicts of interest.

Introduction: Subclinical hypothyroidism (SCH) is highly prevalent and associated with chronic kidney disease (CKD). However, it is still unanswered whether the restoration of euthyroid status in these patients will be beneficial in retarding a decline in glomerular filtration rate in early CKD patients. We aim to evaluate the efficacy of levothyroxine therapy versus placebo in slowing estimated glomerular filtration rate (eGFR) decline among CKD patients (stage 2-4) with SCH., Methods: This study will be a multicentric, double-blind, randomized, parallel-group, placebo-controlled study. A total of 500 CKD patients, 250 patients in the treatment group and 250 patients in the placebo group, will be randomized. The randomization between the treatment arm and placebo arm will be performed as per the computer-generated random number table in a 1:1 ratio. The sample size was calculated based on the assumed reduction in eGFR after 1-year follow-up in the treatment and placebo groups of 10% and 25%, respectively, at a minimum two-sided 99% confidence interval and 90% power of the study and considering 20% loss on follow-up. Each patient will be followed every 3 months for at least 1 year after randomization. Individuals completing 1-year follow-up visits will be considered for analysis. The baseline and follow-up data will be compared between the treatment and placebo groups. The study will evaluate the efficacy and safety of levothyroxine therapy versus placebo in slowing eGFR decline among CKD patients (stage 2-4) with SCH. The primary endpoint will be the end of follow-up of the patients, reduction of eGFR by ≥50% from a baseline of that patient, or development of ESKD or death of the patients. The secondary endpoint will be any cardiovascular event or arrhythmia after the institution of the drug., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Nephrology.)

Background and Aim: Primary glomerular disease accounts for one-sixth of all chronic kidney diseases (CKDs) in India. We remain limited in our ability to effectively treat these conditions because of lack of understanding of the disease mechanisms and lack of predictors to identify the clinical course and therapeutic responsiveness. We propose to develop a network of investigators in glomerular diseases, collect information in a systematic fashion to understand the clinical outcomes, answer translational research questions better, and identify and recruit patients for clinical trials., Materials and Methods: This is a prospective, observational study. The Indian TrANslational GlomerulonephrItis BioLogy nEtwork (I-TANGIBLE) cohort will enroll patients (>18 years) with biopsy-proven minimal change disease (MCD), focal segmental glomerulonephritis (FSGS), membranous nephropathy (MN), IgA nephropathy (IgAN), or membranoproliferative glomerulonephritis (MPGN) (immune complex- and complement-mediated), with first biopsy taken within 2 years of enrollment. Patients with estimated glomerular filtration (eGFR) rate <15 ml/min/1.73 m 2 for >3 months at the time of screening, kidney transplant or bone marrow transplant recipients, patients with active malignancy, and patients with active hepatitis B/C replication or human immunodeficiency virus (HIV)-I/II will be excluded. Clinical details including history, medication history and details, and family history will be obtained. Consenting patient's blood and urine samples will be collected and stored, aligned to their clinical follow-up., Expected Outcomes: The network will allow accurate ascertainment of disease burden of glomerular diseases across study sites, establishment of the treatment pattern of common glomerular diseases, investigation of medium- and long-term outcomes (remission, relapse, rate of eGFR decline), and building a suitable infrastructure to carry out clinical trials in primary glomerular disease., Competing Interests: Dr. Vivekanand Jha has received grant funding from GSK, Baxter, Astra Zeneca, Boerhringer Ingelheim, NephroPlus, and Zydus Cadilla, under the policy of all honoraria being paid to the organization. All the other authors do not have any conflict of interest to declare., (Copyright: © 2023 Indian Journal of Nephrology.)

Introduction: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide, but there is a marked geographic difference in its prevalence and prognosis. IgAN is known to have an aggressive course in Asians. However, its exact prevalence and clinicopathologic spectrum in North India are not well documented., Materials and Methods: The study included all patients aged above 12 years with primary IgAN on kidney biopsy from January 2007 to December 2018. Clinical and pathological parameters were noted. Two histopathologists independently reviewed all kidney biopsies, and MEST-C score was assigned as per the Oxford classification., Results: IgAN was diagnosed in 681 (11.85%) out of 5751 native kidney biopsies. The mean age was 32 ± 12.3 years, and the male to female ratio was 2.5:1. At presentation, 69.8% had hypertension, 68% had an estimated glomerular filtration rate (eGFR) of less than 60 ml/min, 63.2% had microscopic hematuria, and 4.6% had gross hematuria. The mean proteinuria was 3.61 ± 2.26 g/day, with 46.8% showing nephrotic range proteinuria and 15.2% showing nephrotic syndrome manifestation. Histopathologically, 34.4% of patients had diffuse global glomerulosclerosis. Oxford MEST-C scoring revealed M1 in 67%, E1 in 23.9%, S1 in 46.9%, T1/T2 in 33%, and crescents in 19.6% of biopsies. The mean serum creatinine was significantly higher in cases with E1, T1/2, and C1/2 scores ( P < 0.05). Hematuria and proteinuria were significantly higher ( P < 0.05) with E1 and C1/2 scores. Coexisting C3 was associated with higher serum creatinine at presentation ( P < 0.05)., Conclusion: IgAN patients with late presentation and advanced disease became less amenable to immunomodulation in our cohort. The implementation of point-of-care screening strategies, early diagnosis, and retarding disease progression should be prioritized in the Indian strategy., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Journal of Nephrology.)

Introduction: Antibody-mediated rejection (ABMR) is one of the major determinants of graft survival. Although diagnostic precision and treatment options have improved, response to therapy and graft survival has not improved very significantly. The phenotypes of early and late acute ABMR differ in many ways. In this study, we assessed the clinical characteristics, response to therapy, DSA positivity, and outcomes of early and late ABMR., Methods: During the study period, 69 patients with acute ABMR diagnosed on renal graft histopathology were included with a median follow-up of 10 months after rejection. Recipients were stratified into early acute ABMR (<3 months of transplant; n = 29) and late acute ABMR (>3 months of transplant; n = 40). Graft survival, patient survival, response to therapy, and doubling of serum creatinine were assessed and compared between the two groups., Results: Baseline characteristics and immunosuppression protocols were comparable between the early and late ABMR groups. Late acute ABMR had an increased risk of doubling of serum creatinine than the early ABMR group ( P = 0.002). Graft and patient survival were not statistically different between the two groups. Response to therapy was inferior in the late acute ABMR group ( P = 0.00). Pretransplant DSA was present in 27.6% in the early ABMR group. Late acute ABMR was frequently associated with nonadherence or suboptimal immunosuppression and low DSA positivity (15%). Infections such as CMV, bacterial, and fungal infections were similar in the earlier and late ABMR groups., Conclusion: Late acute ABMR group had a poor response to anti-rejection therapy and also an increased risk of doubling of serum creatinine compared to the early acute ABMR group. There was also a tendency toward increased graft loss in late acute ABMR patients. Late acute ABMR patients are more frequently associated with nonadherence/suboptimal immunosuppression. There was also a low incidence of anti-HLA DSA positivity in late ABMR., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Journal of Nephrology.)

Introduction: Recent data suggest a risk of gestational hypertension, proteinuria and pre-eclampsia among pregnancies after kidney donation., Methods: This retrospective study among females who donated kidneys (1997-2017) at a tertiary renal transplant center in Northern India assessed the maternal and fetal outcomes of their pregnancy. Data of participants were collected using pre-tested semi structured questionnaire., Results: In total, 925 female kidney donors (1332 pregnancies) in the pre-donation group and 45 females (48 pregnancies) in the post donation period were included. The mean age of first pregnancy, weight (kg) gain, proportion of history of pre-natal check-up, institutional delivery, and history of unrelated donation was statically significant among the post-donation group. The proportion of pre-eclampsia, gestational hypertension, gestational diabetes, and post-partum hemorrhage was insignificantly higher among the post-donation group with higher preterm birth with low-birth-weight babies. Proteinuria ( P < 0.05) was significantly higher among post donation pregnancies. In multivariate analysis, cesarean delivery and low birth weight (<2500 g) were common among the post-donation pregnancy group., Conclusions: The study demonstrated no significant risk to maternal outcomes butan increased risk to fetal outcomes in terms of prematurity and low birth weight among the post-donation pregnancy group., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Indian Journal of Nephrology.)