Clinical Profile and Outcomes of Patients with Membranous Nephropathy Resistant to Modified Ponticelli Regimen

Introduction: Membranous nephropathy is one of the most common causes of nephrotic syndrome. Among the available treatment options, the tried and tested regimen is the modified Ponticelli regimen. Despite adequate therapy, studies have shown that close to one-quarter of patients fail to attain complete remission. However, data is limited regarding patients who are resistant to this regimen. Method(s): This was an ambispective, observational study conducted in Madras Medical College, Chennai, India between April 2021 to August 2022. All patients with biopsy-proven primary membranous nephropathy resistant to modified Ponticelli regimen were included. Complete remission was defined as proteinuria < 0.5g/day combined with a stable eGFR. Partial remission was defined as reduction of proteinuria by 50% to < 3.5g/day but >0.5g/day. Resistance to therapy was defined as the failure to attain at least partial remission, 12 months after completion of modified Ponticelli regimen. Result(s): A total of 13 patients were enrolled in the study. The median age was 41 years (IQR 38-49) with a male preponderance (n=9;69%). Serum MPLA2R antibody was positive for 9 patients. All patients were negative for ANA and serology for hepatitis B, hepatitis C and HIV were negative. The most common clinical presentation was with nephrotic syndrome, seen in nine patients (69.23%). Renal failure was seen at presentation in 4 patients (30.76%), with one patient warranting initiation of hemodialysis. At 12 months, post completion of modified Ponticelli regimen, the median quantum of proteinuria was 8.7 grams per day. Due to trend towards normalisation of serum albumin and immunological remission, 3 patients were managed with optimised RAS inhibition after modified Ponticelli regimen. Currently, they are in partial remission. Four patients were treated with a second course of modified Ponticelli regimen. Of them one patient is in partial remission, while two patients had progressed to end-stage renal disease and are currently on maintenance hemodialysis. One patient who was resistant to the second course, was managed with a trial of calcineurin inhibitors (CNI) therapy followed by 4 doses of Rituximab (500mg each) due to persistent proteinuria. However, he was lost to follow up during the COVID pandemic and presented with end stage renal disease warranting hemodialysis. A trial of CNI therapy was given to 6 patients. All patients had nephrotic-range proteinuria 12 months post CNI therapy initiation. Five patients were then given Rituximab, among whom, two patients attained complete remission, while three patients have attained immunological and clinical remission. One patient was given a second trial of modified Ponticelli regimen following CNI therapy and is currently in complete remission. Two of these patients developed thrombotic complications - one patient diagnosed with coronary artery disease and one patient with renal vein thrombosis. Conclusion(s): Rituximab is a promising option for patients with primary membranous nephropathy who do not respond to modified Ponticelli regimen. No conflict of interestCopyright © 2023

COVID VACCINE ASSOCIATED GLOMERULAR DISEASES- A CASE SERIES

Introduction: Vaccination is a known trigger for the development of de-novo or flare of glomerular diseases. Here we present a case series of fourteen patients with COVID vaccine- associated glomerular diseases (CVAGD). Methods: Patients with new onset proteinuria, hematuria or renal failure after SARS- CoV2 vaccine were included in the study. Demographic and clinical details were collected and laboratory investigations including serum creatinine, albumin, urine microscopy and urine spot protein creatinine ratio were done. Renal biopsy specimens were subjected to light microscopy and immunofluorescence examination. Results: We cared for 14 patients with CVAGD. Of them, eight patients were males. The mean age was 25.7 years. Three patients had relapse of their previous disease while eleven patients had no previously detected renal diseases. Eleven patients had received COVISHIELD and three had received COVAXIN. All patients presented after the first vaccine dose. At presentation, seven patients had nephrotic syndrome, two patients had rapidly progressive renal failure and five patients had nephritic syndrome. The mean duration of symptom onset after vaccination was 18 days. Renal biopsy revealed IgA nephropathy in 3 patients, endocapillary proliferative glomerulonephritis in 2 patients, minimal change disease in 5 patients, pauci- immune glomerulonephritis (ANCA associated vasculitis) in one patient, lupus nephritis ISN/RPS class 3 in one and focal segmental glomerulosclerosis in two patients. There was no history of COVID infection in any of our patients. Three patients had renal failure at presentation but none required renal replacement therapy. The patients with MCD and FSGS were treated with steroids, patients with ANCA vasculitis and lupus nephritis were managed with the appropriate Cyclophosphamide and steroid regimens while the others were managed conservatively with anti-proteinuric medications. On follow up, five patients (One IgAN, three MCD, one endocapillary proliferative GN) achieved complete remission of proteinuria and resolution of renal failure, while the remaining eight patients achieved partial remission. One patient with MCD had a relapse of proteinuria 3 weeks after achieving partial remission, he responded well to steroid therapy. All 14 patients remain on close follow up. Conclusions: Although causality cannot be definitively established, there is a definite temporal association between the presentation of glomerular diseases and COVID vaccination, in the absence of other inciting factors. Hence, new-onset or relapse of glomerular diseases presenting post vaccination, although rare, should be observed as a possible adverse event. Intriguing questions such as how to proceed with the vaccination schedule in patients with CVAGD and would changing the vaccine type reduce the risk of relapse remain unanswered. No conflict of interest

Clinical characteristics and outcome of novel coronavirus disease in kidney transplant recipients: A single-center prospective observational study

Background: Organ transplant recipients are at increased risk of infections which may result in acute graft dysfunction and death. Coronavirus disease (COVID-19) is the ongoing global infectious challenge and little is known about the impact of this novel virus in kidney transplant recipients. We here describe the clinical presentations, laboratory profile, and outcomes of 42 such patients, from a large tertiary care center in south India. Materials and Methods: This prospective, observational study included all renal transplant recipients with confirmed COVID-19 by reverse transcription polymerase chain reaction from the start of the outbreak till August, 2020. Clinical features at presentation, laboratory and radiological data, and outcomes were analyzed. Results: Forty-two patients were included in the analysis. As many as, 86.7% patients of our cohort had symptoms at presentation, with the most common symptoms being fever (52.5%), breathlessness (50%), and cough (40.5%). Significant need for respiratory support was noted in individuals with longer duration posttransplant (P < 0.03). Acute worsening of allograft function was observed in 22 (52.4%) patients. Fourteen (65%) of them had acute on chronic graft dysfunction and acute graft dysfunction was noted in 8 (35%) patients. Six patients (14.5%) died due to the disease and none of the parameters were found to be an independent predictor of mortality in regression analytic models including acute graft dysfunction (P = 0.49) or acute on chronic graft dysfunction (P = 0.07). There was no correlation between disease severity and baseline immunosuppressive agents whether tacrolimus or cyclosporine (P = 0.57) and mycophenolate mofetil or azathioprine (P = 0.91). Conclusions: Our largest cohort of patients from India showed higher incidence of acute graft dysfunction and significant mortality in patients with COVID-19.

Outcomes of symptomatic coronavirus disease 19 in maintenance hemodialysis patient in India.

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.

Indoor air quality improvement in COVID-19 pandemic: Review.

INTRODUCTION: The advent of COVID-19 has impinged millions of people. The increased concern of the virus spread in confined spaces due to meteorological factors has sequentially fostered the need to improve indoor air quality. OBJECTIVE: This paper aims to review control measures and preventive sustainable solutions for the future that can deliberately help in bringing down the impact of declined air quality and prevent future biological attacks from affecting the occupant's health. METHODOLOGY: Anontology chart is constructed based on the set objectives and review of all the possible measures to improve the indoor air quality taking into account the affecting parameters has been done. OBSERVATIONS: An integrated approach considering non-pharmaceutical and engineering control measures together for a healthy indoor environment should be contemplated rather than discretizing the available solutions. Maintaining social distance by reducing occupant density and implementing a modified ventilation system with advance filters for decontamination of viral load can help in sustaining healthy indoor air quality. CONCLUSION: The review paper in the main, provides a brief overview of all the improvement techniques bearing in mind thermal comfort and safety of occupants and looks for a common ground for all the technologies based on literature survey and offers recommendation for a sustainable future.

Epidemiology, Genomic Structure, the Molecular Mechanism of Injury, Diagnosis and Clinical Manifestations of Coronavirus Infection: An Overview.

COVID-19 is caused by a novel beta coronavirus (SARS-CoV-2) strain that was first discovered in 2019 in the Wuhan city of China. Based on virus genome sequencing studies, the bat is suspected as the natural host of virus, and infection might be transmitted from bats via unknown intermediate hosts like reptiles and snakes etc., to infect humans. COVID-19 is transmitted from person to person contact, primarily via droplet infection within the incubation period or after clinical manifestations of fever, cough, sneezing, sputum, dyspnea, and pneumonia and through contaminated fomites. COVID-19 enters the respiratory tract through the ACE2 receptor on alveoli through binding of s-protein of the virus and causes injuries though the cytopathic effect, as well as cytokines and other mediators, released after developing sepsis. ACE 2 is almost 100-fold higher in kidneys than lung, and the virus can also involve the kidney in the same manner. Kidney involvement manifests in the form of proteinuria, hematuria, and an acute rise in serum creatinine. Kidney involvement is an independent risk factor for mortality. Diagnosis is primarly made by detecting viral RNA by reverse transcriptase polymerase chain reaction (rtPCR) in nasopharyngeal swab samples. Role of antibodies, both IgM and IgG are still evolving and at best restricted for epidemiological purpose. Though a large number of treatments, including hydroxychloroquine, anti-viral, convalescent plasma etc., are being tried, as of now treatment is symptomatic only.

The Adverse Effect of COVID Pandemic on the Care of Patients With Kidney Diseases in India.

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.