A Randomized Controlled Trial Comparing Remission Induction with Modified Multitarget Therapy with Intravenous Cyclophosphamide in Proliferative Lupus Nephritis.

Introduction: Therapy of proliferative lupus nephritis (PLN) is yet to be optimized. Standard of care for induction consists of intravenous (IV) cyclophosphamide (CYC) and steroids, which shows an improved outcome, but end-stage renal disease (ESRD) progression, increased mortality, and therapy-related adverse effects remain a major concern. The other treatment reported to induce early remission was the multitarget therapy comprising tacrolimus, mycophenolate, and steroid, but infections were high in the multitarget therapy. Considering azathioprine as a potentially safer and effective alternative anti-B-cell therapy, modified multitarget therapy (MMTT) was planned replacing mycophenolate with azathioprine. Material and Methods: A single-center, 24-week, open-label, randomized controlled trial comprising adults of age 18-65 years with biopsy-proven PLN was carried out. The intervention groups were 1) MMTT: tacrolimus 0.075 mg/kg/day and azathioprine 2 mg/kg/day and 2) IV CYC group with a starting dose of 0.75 (adjusted to 0.5-1.0) g/m2 every 4 weeks for 6 months. Both groups received 3 days of pulse methylprednisolone followed by a tapering course of oral prednisone therapy. Results: Among 100 randomized patients, 48 were in MMTT arm and 52 were in IV CYC arm. At the end of 24 weeks, overall remission (complete and partial) was comparable in both the arms: MMTT (86.36%) and IV CYC (87.75%). There was comparable proteinuria reduction and systemic lupus erythematosus disease activity index (SLEDAI) score improvement with recovery of complement level C3 in both groups. Major adverse events were numerically more in the IV CYC group, including one death from pneumonia. Conclusion: The MMTT arm is as effective as IV CYC in improving short-term outcome in PLN, with a comparable safety profile.

Utility of serum anti-phospholipase A2 receptor antibody as a biomarker in membranous nephropathy: An experience from a tertiary care center of Eastern India.

Background: Membranous nephropathy (MN) is a pattern of glomerular injury. Exact categorization into primary membranous nephropathy (PMN) or secondary membranous nephropathy (SMN) is essential for treatment. An endogenous podocyte antigen, M-type phospholipase A2 receptor (PLA2R) has been discovered to be involved in the pathogenesis of PMN. Aims and Objectives: In this article, we aimed to analyze renal tissue PLA2R and serum anti-PLA2R antibodies in MN cases and determined the diagnostic utility. Materials and Methods: The study was of prospective type carried out from March 2019 to August 2020. Analysis of cases of MN was performed with PLA2R paraffin immunoflourescence and serum anti-PLA2R antibody ELISA. Results: Overall sensitivity, specificity, PPV, and NPV of serum anti-PLA2R ELISA for PMN was 91.3%, 80%, 75%, and 93.3%, respectively, and of tissue PLA2R staining for PMN was 91.67%, 81.08%, 75.86%, and 93.75%, respectively. There was strong concordance between two methods. In the patients that were followed up, we found baseline serum anti-PLA2R antibody was less in complete remission group than that in non-remission group and the reduction in serum anti-PLA2R antibody was more in complete remission group than that in non-remission group. Conclusion: Routine light and immunofluorescence examination are incapable of giving exact categorical opinion regarding PMN and SMN. Serum anti-PLA2R antibody detection and renal tissue PLA2R analysis are sensitive and specific in detecting PMN. Baseline serum anti-PLA2R antibody and anti-PLA2R antibody quantification trends are related to prognosis of PMN. So they can be incorporated as additional biomarker.

Protocol and Methods: Role of Levothyroxine on the Progression of Chronic Kidney Disease in Subclinical Hypothyroid Populations (LP-CKD) - A Multicenter Randomized Controlled Trial.

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.

Update on Coronavirus 2019 Vaccine Guidelines for Transplant Recipients.

The coronavirus disease 2019 (COVID-19) vaccine and its utility in solid organ transplantation need to be timely revised and updated. These guidelines have been formalized by the experts-the apex technical committee members of the National Organ and Tissue Transplant Organization and the heads of transplant societies-for the guidance of transplant communities. We recommend that all personnel involved in organ transplantation should be vaccinated as early as possible and continue COVID-19-appropriate behavior despite a full course of vaccination. For specific guidelines of recipients, we suggest completing the full schedule before transplantation whenever the clinical condition permits. We also suggest a single dose, rather than proceeding unvaccinated for transplant, in case a complete course is not feasible. If vaccination is planned before surgery, we recommend a gap of at least 2 weeks between the last dose of vaccine and surgery. For those not vaccinated before transplant, we suggest waiting 4 to 12 weeks after transplant. For the potential living donors, we recommend the complete vaccination schedule before transplant. However, if this is not feasible, we suggest receiving at least a single dose of the vaccine 2 weeks before donation. We suggest that suitable transplant patients and those on the waiting list should accept a third dose of the vaccine when one is offered to them. We recommend that organs from a deceased donor with suspected/proven vaccine-induced thrombotic thrombocytopenia should be avoided and are justified only in cases of emergency situations with informed consent and counseling.

Effect of Coronavirus Disease 2019 on Transplantation and Nephrology in India: A Nationwide Report From India.

BACKGROUND: The effect of coronavirus disease 2019 (COVID-19) on a developing nation is sparsely reported and, more importantly, the discrepancies in public and private sectors are underexplored. METHODS: We retrospectively investigated the data on the effect of COVID-19 on renal transplantation between 2019 and 2020 in a nationwide analysis from 8 public and 10 private sector hospitals of India. RESULTS: On comparing the yearly data, the number of living-related transplants and deceased donor transplants declined by 48% (2610 vs 1370) and 49% (194 vs 99), respectively. The outpatient numbers and in-center admissions decreased by 40.4% (616,741 vs 367,962) and 30.8 % (73,190 vs 49,918). respectively. There was no increase in the number of renal or graft biopsies in the COVID-19 era. The number of waitlisted patients on hemodialysis was higher in public (304,898 vs 338,343) when compared with private (163,096 vs 150,292) in the last 2 years. Similarly, the number of waitlisted patients on peritoneal dialysis (4655 vs 3526) was higher in the public sector compared with private sector (932 vs 745). The decline in living transplants during the pandemic was higher in public sectors (58%) compared with the private (49%). However, the decline in deceased donation was higher in private (57.9%) relative to public (50.6%). CONCLUSIONS: COVID-19 has adversely affected the transplantation activities across the Indian transplantation centers, with a disproportionately higher impact on waitlisted patients in public sector programs. A sound prioritization of health care resources is mandated to safeguard the most deprived and high-risk waitlisted patients during the pandemic.

Is Early COVID-19 in Kidney Transplant Recipients Concerning Enough to Halt Transplantation? A Multicenter Comparative Analysis from India.

BACKGROUND: Limited data exist on the incidence and outcome of early coronavirus disease 2019 (COVID-19) in kidney transplantation recipients (KTR). METHODS: A retrospective multicenter research study was conducted across 12 centers in India. We explored the symptomatology, demographic, laboratory findings, and outcome of COVID-19 within 30 days of transplantation. The outcome was compared with the overall KTR and waitlisted patients acquiring COVID-19. RESULTS: The incidence of early COVID-19 was 2.6% (n = 22) for the cumulative 838 renal transplants performed since nationwide lockdown in March 2020 until May 2021. Overall, 1049 KTR were diagnosed with COVID-19 and 2% of those had early COVID-19. The median age of the early COVID-19 cohort was 43 (31-46) years. COVID-19 severity ranged from asymptomatic (18.2%), mild (59.1%), moderate (9.1%), and severe (13.6%). Among clinical symptoms, dyspnea and anosmia were frequent, and in laboratory parameters, neutrophil lymphocyte ratio, high-sensitivity C-reactive protein, and D-dimer were higher in patients requiring oxygen. The mortality in early COVID-19 was not higher than overall KTR (4.5% vs 8.5%; P = 1). COVID-19 severity (23.9% vs 15.7%; P = .0001) and mortality (15.5% vs 8.5%; P = .001) among waitlisted patients (n = 1703) were higher compared with overall KTR. CONCLUSIONS: We report higher burden of COVID-19 in waitlisted patients compared with KTR and a favorable outcome in early COVID-19 in KTR. Our report will help the transplant physicians in dealing with the ongoing dilemma of halting or resuming transplantation in the COVID-19 era.

Snake bite associated with acute kidney injury.

Acute kidney injury (AKI) is a well-known life-threatening systemic effect of snake envenomation which commonly happens secondary to snake bites from families of Viperidae and Elapidae. Enzymatic toxins in snake venom result in injuries to all kidney cell types including glomerular, tubulo-interstitial and kidney vasculature. Pathogenesis of kidney injury due to snake envenomation includes ischaemia secondary to decreased kidney blood flow caused by systemic bleeding and vascular leakage, proteolytic degradation of the glomerular basement membrane by snake venom metalloproteinases (SVMPs), deposition of microthrombi in the kidney microvasculature (thrombotic microangiopathy), direct cytotoxic action of venom, systemic myotoxicity (rhabdomyolysis) and accumulation of large amounts of myoglobin in kidney tubules. Clinical features of AKI include fatigue, loss of appetite, headache, nausea, vomiting, oliguria and anuria. Monitoring of blood pressure, fluid balance, serum creatinine, blood urea nitrogen and serum electrolytes is useful in managing AKI induced by snake envenomation. Early initiation of anti-snake venom and early diagnosis of AKI are always desirable. Biomarkers which will help in early prediction of AKI are being explored, and current studies suggest that urinary clusterin, urinary neutrophil gelatinase-associated lipocalin, and serum cystatin C may play an important clinical role in the future. Apart from fluid and electrolyte management, kidney support including early and prompt initiation of kidney replacement therapy when indicated forms the bedrock in managing snake bite-associated AKI. Long-term follow-up is important because of chances of progression towards CKD.

The changing face of pregnancy-related acute kidney injury from eastern part of India: A hospital-based, prospective, observational study.

This study was initiated to look into the etiologies, prevalence, and outcome of pregnancy-related acute kidney injury (PRAKI) in a tertiary care hospital. Women admitted with PRAKI from January 2015 to December 2016 were included in the study. All patients were investigated and treated and followed up for the next six months.. For statistical analysis, Chi- square test and analysis of variance were performed to analyze the data. Multivariate analysis was applied to compare the risk of nonrecovery of renal function in different etiologies of PRAKI. During the study period, 81 patients were admitted with PRAKI, of whom 68 (84%) received hemodialysis (HD). A total of 449 patients including all cases of AKI underwent HD from January 2015 to June 2016. The incidence of dialysis requiring PRAKI was 68 out of the 449 patients (15%). Sixty-eight (84%) patients required dialysis support while the most common cause was sepsis (49%), with the second being pregnancy-associated atypical hemolytic-uremic syndrome (P-aHUS) (17%) followed by obstetric hemorrhages (16%). There was a significant reduction of first-trimester AKI (8.6%) compared to a previous study published from this institute (19.3%). The maternal mortality (25%) and fetal mortality (23.5%) were high. Nearly 39% of the patients had complete recovery of renal function. This study revealed significant PRAKI burden due to a largely preventable cause, puerperal sepsis. Renal survival was poor in P- aHUS. The gaps in the obstetric care may be identified for the improvement of fetomaternal outcome.

A Cross-sectional Prospective Study of Asymptomatic Urinary Abnormalities, Blood Pressure, and Body Mass Index in Healthy School Children.

INTRODUCTION: Screening school children for urinary abnormalities is an inexpensive task but is not commonly undertaken in India. Although debated in western countries, its utility in early diagnosis of kidney disorders has been proved by studies from Asia. We examined the prevalence of asymptomatic urinary abnormalities (AUA), obesity, and hypertension in school children and analyzed data to identify potential risk factors among those detected with such abnormalities. METHODS: Children and adolescents 8 to 18 years of age of either gender, attending 14 public schools in West Bengal, were screened prospectively from July 2013 to July 2016 for detecting asymptomatic urinary abnormalities by a spot urine test using a dipstick. Sociodemographic profile, medical examination (weight, height, and blood pressure), and questionnaire-based data were recorded. RESULTS: A total of 11,000 children were screened. Of these, data from 9306 children were available for AUA, obesity, and hypertension. The prevalence rate was 7.44% (95% confidence interval [CI] = 6.91%-7.97%) for at least 1 AUA. Isolated hematuria was present in 5.2% (95% CI 4.75%-5.65%), whereas isolated proteinuria was present in 1.9% (95% CI = 1.62%-2.18%). The prevalence of prehypertension was 13.43% (95% CI = 12.74%-14.12%) and that of hypertension and abnormal body mass index was 4.05% (95% CI = 6.43%-7.47%) and 38.67 (95% CI = 37.68%-39.66%) respectively. DISCUSSION: The prevalence rates of AUA were comparable with those in some Asian countries but higher than in most developed countries. Of children and adolescents 8 to 18 years of age, those 13 to 18 years had significantly more high risk factors such as AUA, hypertension, and obesity.