Rituximab, Use and B Cell Depletion in Patients with Membranous Nephropathy- A Retrospective, Observational Study.

Introduction: Rituximab (Rtx), an anti-CD20 monoclonal antibody, results in selective B-cell depletion and has emerged as an important therapeutic option in idiopathic membranous nephropathy (MN). We conducted a retrospective observational study to evaluate the efficacy and tolerability of Rtx in MN with respect to the B-cell count depletion. Methods: Twenty patients with biopsy proven primary MN, both treatment naïve and treatment resistant, who received a fixed dose protocol of 500mg IV Rtx 1month apart were retrospectively observed with a minimum follow-up period of 12 months. The primary clinical outcome was complete (CR) or partial remission (PR) at 12 months in relation to B-cell depletion at 6 and 12 months. Results: All were patients (men, 90%) of PLA2R-Ab positive with MN with a mean age of 37.7 ± 12.5 years. The mean 24-h urinary protein was 7.5 ± 2.15 gm/day, serum albumin was 2.01 ± 0.6gm/dL, and eGFR was 86.5 ± 20 mL/min/1.73m2. Primary composite outcome at 12 months was 66.7%, with 5.6% CR and 61.1% PR.The mean PLA2R-Ab at 12 months was low in those with remission compared to those who did not achieve (17.8 ± 21.2 RU/mL vs 311.7 ± 356.0; P = 0.01). Sustained B cell depletion at 6 months was seen in 84.3% (OR = 2.2, 95% CI = 0.11-42.7; P = 0.53) and 32% at 12 months (OR = 2.25, 95% CI = 0.18-27.7, and P = 0.66). Conclusion: Acceptable remission rates were seen with Rtx in both treatment naïve and treatment-resistant patients with MN. There was no significant association between B-cell depletion and remission.

Impact of Fasting during Ramadan on Renal Functions in Patients with Chronic Kidney Disease.

Introduction: The impact of Ramadan fasting in patients with chronic kidney disease (CKD) remains less studied and with inconsistent results. In this study, we tried to look at the impact of Ramadan fasting on renal function in patients with CKD. Materials and Methods: In this prospective observational study, we included 28 adult CKD patients. All relevant biochemical parameters including renal function tests were done in the month before Ramadan fasting and within 3 months after Ramadan. Urine output, body weight, and blood pressure were also monitored during Ramadan and after the end of Ramadan for at least 10 days. Results: All the 28 patients (mean age: 46 ± 12 years) included in the study managed to fast for the whole month, and none displayed any new clinical symptoms or signs. The renal function worsened in four (14.28%), and it was significant in those with CKD Stages 4 and 5 (P < 0.003). Conclusion: Stable CKD patients can fast with careful monitoring; however, there is a risk of renal function deterioration in advanced CKD.

Crescentic Glomerulonephritis Associated with Polycythaemia Vera: A Rare Occurrence.

Glomerular diseases are one of the most challenging entities in terms of diagnosis and management, especially when associated with systemic illnesses such as malignant disorders. Herein, a case of crescentic glomerulonephritis (CrGN) associated with polycythaemia vera (PV) in a 50-year-old female is described. She presented with bilateral pedal oedema, splenomegaly, renal dysfunction and severe proteinuria. On evaluation, we found PV and CrGN. Renal involvement in PV is rare and generally considered as a manifestation of hypervolemia or high-viscosity-induced renal hyper-perfusion and hyper-filtration. This is a unique case of immunologically-mediated renal disease in PV.

INASL-ISN Joint Position Statements on Management of Patients with Simultaneous Liver and Kidney Disease.

Renal dysfunction is very common among patients with chronic liver disease, and concomitant liver disease can occur among patients with chronic kidney disease. The spectrum of clinical presentation and underlying etiology is wide when concomitant kidney and liver disease occur in the same patient. Management of these patients with dual onslaught is challenging and requires a team approach of hepatologists and nephrologists. No recent guidelines exist on algorithmic approach toward diagnosis and management of these challenging patients. The Indian National Association for Study of Liver (INASL) in association with Indian Society of Nephrology (ISN) endeavored to develop joint guidelines on diagnosis and management of patients who have simultaneous liver and kidney disease. For generating these guidelines, an INASL-ISN Taskforce was constituted, which had members from both the societies. The taskforce first identified contentious issues on various aspects of simultaneous liver and kidney diseases, which were allotted to individual members of the taskforce who reviewed them in detail. A round-table meeting of the Taskforce was held on 20-21 October 2018 at New Delhi to discuss, debate, and finalize the consensus statements. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications. The strength of recommendations (strong and weak) thus reflects the quality (grade) of underlying evidence (I, II, III). We present here the INASL-ISN Joint Position Statements on Management of Patients with Simultaneous Liver and Kidney Disease.

Impact of Pharmacogenetic Determinants of Tacrolimus and Mycophenolate on Adverse Events in Renal Transplant Patients.

BACKGROUND: Graft acceptance against immunity is one of the major challenges in solid organ transplant. Immunosuppressive medications have effectively improved the post-transplantation outcome however, it has its own limitations. Genetic polymorphisms in drug-metabolizing enzymes have been identified as the potential targets in developing a pharmacogenetic strategy, to individualize drug dose and also in preventing the adverse events. OBJECTIVE: The rationale of the study was to explore polymorphisms in tacrolimus and mycophenolate metabolic pathways that influence the adverse clinical outcomes in renal transplant recipients. METHODS: A total of 255 renal transplant recipients were analyzed for the pharmacogenetic determinants of tacrolimus (CYP3A5*3 ABCB1 1236 T>C ABCB1 2677 G>A/T ABCB1 3435 T>C) and mycophenolate (UGT1A8*3 UGT1A9 IMPDH I IMPDH II c.787C>T ABCC2 -24 C>T and c.3972C>T) using Sanger sequencing. RESULTS: Acute rejection (AR) was observed in 5.88% of the transplant recipients whereas acute tubular necrosis (ATNs) was observed in 7.45% of the patients within early stage of the maintenance phase. Infections such as urinary tract infection (UTI) and cytomegalovirus (CMV) infection were observed in 11.37% and 12.16% of the patients. The AUC of mycophenolate was significantly higher in patients with increased risk for infections. ABCC2 -24 C>T c.3972C>T polymorphisms and ABCB1 3435 C-allele were associated with reduced risk for infections. ABCC2 rs3740066 was associated with 2.06-fold all-cause mortality risk. CYP3A5 AG- and UGT1A9-440 CC-genotypes showed increased risk and ABCC 3972C>T CC-genotype showed protection against adverse events. CONCLUSION: Genetic variants in tacrolimus and mycophenolate metabolic pathways were found to influence the morbidity and mortality in renal transplant recipients.