Concomitant Case of Anti-Glomerular Basement Membrane (GBM) Antibody Disease and Membranous Nephropathy.

Anti-glomerular basement membrane (GBM) disease is a form of rapidly progressive glomerulonephritis with acute deterioration of kidney function. Atypical forms of this disease have been described which do not show positive serology for the classical anti-GBM antibody (Ab) but their presence on kidney biopsies. Furthermore, concomitantly any other separate glomerular pathology along with anti-GBM disease has been only rarely seen. A 40-year-old male patient presented with complaints of lower limb swelling and hematuria. Initial blood investigations revealed nephrotic range proteinuria and hypoalbuminemia. The patient underwent a renal biopsy. Initial reports showed the presence of "linear" deposits for immunoglobulin G (IgG) Ab and crescent formation in the majority of glomeruli. Treatment with plasmapheresis was initiated for the same. Electron microscopy, which later revealed subepithelial deposits raised suspicion of concomitant membranous nephropathy (MN). This finding was confirmed with a staining biopsy block with an anti-PLA2R Ab stain. Treatment was initiated to treat both glomerular pathologies, which very rarely present together and do not have standard guidelines for treatment. The patient responded to treatment with a reduction in serum creatinine values and did not require maintenance hemodialysis. There have been only a handful of documented cases, only in the form of a few case series that have described the presence of both anti-GBM disease and MN in the same kidney biopsy.

Study of the Urinary TGF-ß1 Profile in Diabetic Nephropathy: A Single-Center Experience From India.

Background Diabetic nephropathy is one of the important causes of end-stage kidney disease (ESKD). Of the various cytokines playing a role in the pathogenesis of diabetic nephropathy, transforming growth factor beta-1 (TGF-ß1) is an important one. Its major role is to mediate extracellular matrix deposition. Increased renal expression of TGF-ß1 is found in diabetic nephropathy and its urinary excretion can serve as a useful marker of outcomes. Material and methods A prospective observational study was conducted, which included 10 cases of diabetic nephropathy in group A with age ≥ 18 years and a urinary protein creatinine ratio (UPCR) value of > 0.5 mg/mg and 10 healthy controls in group B. Patients with active urinary tract infection, chronic kidney disease (CKD) stage Vd patients on maintenance hemodialysis, and renal transplant recipients were excluded from the study. Urinary TGF-ß1 level estimation in a 24-hour urine sample, 24-hour urine protein, and other baseline laboratory investigations were done. Results In diabetic nephropathy cases (group A), the mean value of urinary TGF-ß1 levels was 88.33± 12.44 ng/24 hours. In the control group (group B), the mean value of urinary TGF-ß1 was 29.03 ± 3.23 ng/24 hours. Urinary TGF-ß1 levels were significantly elevated in group A as compared to group B (p<0.001). There was no significant correlation between urinary TGF-ß1 levels and estimated glomerular filtration rate (eGFR) (r=0.376, p= 0.285) as well as the urinary TGF-ß1 levels and 24-hour urine protein levels (p = 0.334, r = 0.341) in diabetic nephropathy cases. Glycosylated hemoglobin (HbA1c) levels didn't correlate with the urinary TGF-ß1 levels (r = -0.265, p = 0.46). Conclusion The urinary TGF-ß1 levels were significantly elevated in diabetic nephropathy patients as compared to healthy controls. There was no significant correlation between urinary TGF-ß1 levels and proteinuria, eGFR, or HbA1c levels in diabetic nephropathy patients.

Measured Glomerular Filtration Rate in Live Related Kidney Donors Three Months Post-Kidney Donation: A Single-Center Experience From Western India.

Background Glomerular filtration rate (GFR) estimation is pivotal in the evaluation of kidney donors. There are various methods available for assessing GFR, but there has been a lack of consensus on the measurement of GFR and the frequency of renal evaluation after kidney donation. Our study aims to analyze the measured GFR (m-GFR) before and three months after kidney donation and note the compensatory abilities of the remnant kidney in live related kidney donors. Methods This prospective observational study was conducted at the Department of Nephrology, Dr. D. Y. Patil Medical College, Hospital & Research Centre, Pune, from April 2021 to December 2022. The study included 30 donors from both genders aged between 23 and 73 years. The measured GFR was calculated using a technetium-99m diethylene triamine pentaacetic acid (Tc-99m DTPA) scan. We analyzed donor characteristics and various parameters that included demography, anthropometry, blood pressure, and serum creatinine and measured GFR (m-GFR) using a Tc-99m DTPA scan, which was compared before and three months after donor nephrectomy. Results Of the 30 donors, 25 (83.3%) were females and five (16.7%) were males. The mean age of donors was 49.23 ± 12.29 years. The mean body mass index (BMI) was noted to be 24.73 ± 5.58 kg/m2, whereas the mean body surface area (BSA) was 1.59 ± 0.12 m2. In terms of the measured GFR by DTPA scan, pre-donation and post-donation, the average GFR for our population was 103.83 ± 10.07 mL/minute/1.73 m2 and 60.47±6.57 mL/minute/1.73 m2, respectively. The mean measured GFR of remnant kidney increased by 9.21 ± 4.39 mL/minute/1.73 m2 in 28 donors, while two donors had a fall in the mean measured GFR by 6.8 ± 1.69 mL/minute/1.73 m2. Conclusions To safeguard donor health, accurate measurement of GFR at various timelines after kidney donation should be considered as there are various limitations associated with the use of serum creatinine-based GFR estimating equations for solitary kidneys. However, long-term studies are required to analyze the changes in GFR after nephrectomy and determine the adequacy of compensatory changes in the remnant kidney post-kidney donation.

Metastatic methicillin-resistant Staphylococcus aureus infection with infective endocarditis, pulmonary septic emboli, axillary abscess with a subacute presentation in a patient with chronic end-stage kidney disease on maintenance haemodialysis.

A male adult patient on maintenance haemodialysis due to end-stage diabetic nephropathy presented with low-grade intermittent fever, cough and generalised weakness for 3 weeks. Initial blood investigations revealed an elevated neutrophil count with raised inflammatory markers. Chest CT revealed loculated hydropneumothorax with multiple cavitary nodules. Repeated blood cultures from the cuffed tunnelled catheter site and the right arm and sputum cultures were negative for pyogenic bacteria and yeast aetiology. The patient complained about left axillary pain on the fourth day of admission. Ultrasound-guided percutaneous aspiration from an axillary focal collection and subsequent culture revealed a methicillin-resistant Staphylococcus aureus (MRSA) infection. Echocardiography detected multiple vegetations on the tricuspid valve. The patient responded clinically to vancomycin and removal of the permanent catheter. This was a case of a tunnelled catheter-related metastatic MRSA infection with infective endocarditis, pulmonary septic embolism with a subacute presentation, and repeated blood culture negativity.

Safety and efficacy of mycophenolate in COVID-19: a nonrandomised prospective study in western India.

Background: Antivirals and immunosuppressive agents are used with variable success in the treatment of COVID-19. Mycophenolate, an inhibitor of enzyme inosine monophosphate dehydrogenase, is an immunosuppressant used to prevent allograft rejection and other autoimmune diseases. Few laboratory studies have also reported antiviral properties of mycophenolate. The current study tried to assess the safety and efficacy of mycophenolate in patients hospitalised with COVID-19. Methods: This was a prospective non-randomised open label study with the objective to assess the effect of addition of mycophenolate to the standard of care on mortality due to COVID-19 and duration of hospital stay. The target study population was comprised of patients requiring inpatient treatment for COVID-19 during the period from Jan 15-April 15, 2021. The study was registered with Clinical Trial Registry of India (CTRI/2021/01/030477, registered on date-14/01/2021). Adult patients (n = 106) requiring hospitalisation for COVID-19 received mycophenolate, 360 mg, one tablet daily for one month. Mycophenolate was initiated within 48 h of the diagnosis of SARS-CoV-2 infection by RT‒PCR. While patients who did not consent for mycophenolate (n = 106), received only standard of care, and were considered as control group. The relevant clinical data including NEWS2 scores and high-resolution computed tomography of the thorax were collected and analysed. Findings: The mortality and hospital stay were significantly lower in the study group compared to the control group. Mycophenolate significantly reduced mortality after adjustment for other predictors (adjusted odds ratio: 0.082 with 95% CI: 0.012-0.567). Mycophenolate was an independent predictor of survival in patients hospitalised due to COVID-19. There was also no evidence of secondary bacterial infections and post-COVID complications. Interpretation: Mycophenolate administration is safe in COVID-19. Mycophenolate reduces mortality and duration of hospital stay in patients with COVID-19. Funding: Shri Janai Research Foundation, India.

Role of T-lymphocytes in Kidney Disease.

Background The role of T-regulatory cells (Tregs) in inflammatory renal disease is not yet established. We attempted to study peripherally circulating T-cells expressing RORγt+Foxp3+ dynamics in acute kidney injury (AKI) and chronic kidney disease (CKD). Aim To determine the role of T-regulatory cells in AKI and CKD. Research methodology  This is a cross-sectional study conducted between January 2019 to January 2021 at a single tertiary care centre in Pune, India. Candidates enrolled in the study were either patients with CKD not on maintenance hemodialysis or newly diagnosed cases of AKI. Kidney transplant recipients, patients with autoimmune diseases like systemic lupus erythematosus (SLE), IgA nephropathy, or those receiving immuno-suppressants were excluded. T-lymphocytes were analyzed using a flow cytometer.  Results We studied 80 patients with kidney injury, 40 each belonging to the AKI and CKD study groups and 10 healthy volunteers as controls. The rationale behind having a small control group was to merely get an idea of T helper 17 (Th17):Treg ratio and different immune cell-phenotype profiles in healthy volunteers without kidney injury, diabetes, hypertension or any other risk factors. The ratio of RORγt:Foxp3 was ≤ 1 in these individuals (control group) while this ratio was significantly altered (MFI RORγt:Foxp3 ≥1) in the AKI/CKD study arm. We examined peripherally circulating T-lymphocytes in acute kidney injury and chronic kidney disease, comparing their activity to healthy volunteers. Biopsy-proven kidney injury patients (29/80) were also included in this study. We found that the ratio of RORγt:Foxp3 was altered in patients with kidney injury (acute and chronic) and was statistically significant compared to controls, indicating that injury may be attributed to T-cell dysfunction.  Conclusion Our study provides some evidence of T-cell dysfunction in the pathology of kidney injury in acute and chronic kidney disease via activity of Foxp3 and RORγt. We found that there is evidence of altered Th17/Treg activity in kidney injury, more prevalent in acute than chronic, when compared to healthy volunteers.

Angiotensin converting enzyme inhibitors maintain polytetrafluroethylene graft patency.

BACKGROUND: A patent vascular access is crucial for hemodialysis patients. Stenosis and thrombosis lead to access failure. Endothelial injury via angiotensin II may mediate a hyperplastic and prothrombotic response. Thus angiotensin II inhibition with angiotensin-converting enzyme inhibitors (ACEI) may prolong vascular access patency. This study determines the impact of ACEI use on access patency in both polytetrafluroethylene (PTFE) grafts and fistulas. METHODS: Demographics, access history and medication use were reviewed in 266 accesses from four dialysis centres. Primary patency, date of surgery to date of first access failure, was determined. Excluded accesses had incomplete history or <30 day patency. Groups divided into ACEI and non-ACEI based on patient use of ACEI during access patency. Statistical methods included: unpaired Student t to compare continuous variables, Chi-square and Fisher's Exact test to compare proportions and evaluate for risk estimation, univariate and multivariate Cox regression to investigate variables associated with duration of access patency. Cox-adjusted survival and Hazard curves were obtained for significant variables. RESULTS: Non-ACEI (PTFE) graft group included more males and older patients; however, when these covariates were adjusted during both univariate and multivariate regression, suggested, only ACEI use was associated with greater access patency duration, 671.7 days (ACEI) vs 460.0 days (non-ACEI), p=0.012. ACEI group had fewer clotting events, 55% versus 71% (non-ACEI) group, p=0.042. ACEI use had little effect on primary patency of the fistula however male gender increased time to fistula failure, p=0.002. CONCLUSIONS: Retrospective evaluation suggests ACEI use in patients with PTFE grafts may prolong and maintain patency. Fistula patency is affected by gender with longer patency noted in males. Further prospective studies are necessary to confirm the role of ACEI in maintaining vascular access patency.