Acute oxalate nephropathy: exploring the role of excess dietary oxalate intake.

Acute oxalate nephropathy is a rare but important cause of severe acute kidney injury. We report here two cases presenting as unexplained AKI which were confirmed histologically to be due to acute oxalate nephropathy. Dietary oxalate or its precursor vitamin C was the cause of oxalate exposure in both of these cases. While one patient recovered, another continued to need dialysis and succumbed to underlying metastatic cancer. This cause should be suspected in all patients presenting with unexplained AKI, and detailed history about dietary intake of oxalate or vitamin C should be inquired.

Inherited Fanconi renotubular syndromes: unveiling the intricacies of hypophosphatemic rickets/osteomalacia.

INTRODUCTION: Fanconi renotubular syndromes (FRTS) are a rare group of inherited phosphaturic disorders with limited Indian as well as global data on this condition. Here, we describe the experience of a single Endocrinology center from Western India on FRTS. MATERIALS AND METHODS: Comprehensive clinical, biochemical, radiological, management, and genetic details of FRTS patients managed between 2010 and 2023 were collected and analyzed. RESULTS: FRTS probands had mutations (eight novel) in six genes [CLCN5 (n = 4), SLC2A2 (n = 2), GATM, EHHADH, HNF4A, and OCRL (1 each)]. Among 15 FRTS patients (11 families), rickets/osteomalacia was the most common (n = 14) presentation with wide inter- and intra-familial phenotypic variability. Delayed diagnosis (median: 8.8 years), initial misdiagnosis (8/11 probands), and syndrome-specific discriminatory features (8/11 probands) were commonly seen. Hypophosphatemia, elevated alkaline phosphatase, normal parathyroid hormone (median: 36 pg/ml), high-normal/elevated 1,25(OH)2D (median: 152 pg/ml), hypercalciuria (median spot urinary calcium to creatinine ratio: 0.32), and variable proximal tubular dysfunction(s) were observed. Elevated C-terminal fibroblast growth factor 23 in two probands was misleading, till the genetic diagnosis was reached. Novel observations in our FRTS cohort were preserved renal function (till sixth decade) and enthesopathy in FRTS1 and FRTS3 families, respectively. CONCLUSION: Our findings underscore frequent under- and misdiagnosis of FRTS; hence, a high index of suspicion for FRTS in phosphopenic rickets/osteomalacia, with early consideration of genetic testing is essential to ensure timely diagnosis of FRTS. The novel variants and phenotypic manifestations described here expand the disease spectrum of FRTS.

Acquired disorders of phosphaturia: Beyond tumor-induced osteomalacia.

Phosphate is an integral part of human cellular structure and function. Though most recognised disorders of phosphaturia are genetic in origin, phosphate loss due to acquired conditions is commonly encountered in clinical practice. Acquired hypophosphatemia is most commonly due to renal phosphate wasting and can produce significant morbidity. It also heralds future kidney damage, and continued exposure can lead to progressive kidney injury and potentially renal failure. These conditions are a diverse group of disorders with common shared mechanisms causing loss of phosphate in the urine. Renal phosphate loss can occur as an isolated entity or as a part of generalised proximal tubular dysfunction, i.e., Fanconi's syndrome. An insight into the pathophysiological mechanisms of acquired phosphaturia can help clinicians monitor their patients better and avoid potential harms.

Hereditary Hypophosphatemic Rickets with Hypercalciuria Presenting with Enthesopathy, Renal Cysts, and High Serum c-Terminal FGF23: Single-Center Experience and Systematic Review.

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare disorder of phosphate homeostasis. We describe a single-center experience of genetically proven HHRH families and perform systematic review phenotype-genotype correlation in reported biallelic probands and their monoallelic relatives. Detailed clinical, biochemical, radiological, and genetic data were retrieved from our center and a systematic review of Pub-Med and Embase databases for patients and relatives who were genetically proven. Total of nine subjects (probands:5) carrying biallelic SLC34A3 mutations (novel:2) from our center had a spectrum from rickets/osteomalacia to normal BMD, with hypophosphatemia and hypercalciuria in all. We describe the first case of genetically proven HHRH with enthesopathy. Elevated FGF23 in another patient with hypophosphatemia, iron deficiency anemia, and noncirrhotic periportal fibrosis led to initial misdiagnosis as tumoral osteomalacia. On systematic review of 58 probands (with biallelic SLC34A3 mutations; 35 males), early-onset HHRH and renal calcification were present in ~ 70% and late-onset HHRH in 10%. c.575C > T p.(Ser192Leu) variant occurred in 53% of probands without skeletal involvement. Among 110 relatives harboring monoallelic SLC34A3 mutation at median age 38 years, renal calcification, hypophosphatemia, high 1,25(OH)2D, and hypercalciuria were observed in ~30%, 22.3%, 40%, and 38.8%, respectively. Renal calcifications correlated with age but were similar across truncating and non-truncating variants. Although most relatives were asymptomatic for bone involvement, 6/12(50%) had low bone mineral density. We describe the first monocentric HHRH case series from India with varied phenotypes. In a systematic review, frequent renal calcifications and low BMD in relatives with monoallelic variants (HHRH trait) merit identification.

Novel Therapeutics for Management of Lupus Nephritis: What Is Next?

Lupus nephritis is a severe, organ-threatening manifestation of systemic lupus erythematosus. The current standard of care in the treatment of lupus nephritis is limited to broad-spectrum immunosuppressants, which have significant concerns of short- and long-term toxicity. With traditional approaches, kidney survival and patient outcomes have remained suboptimal. Robust research in the therapeutics of lupus nephritis has resulted in development of many novel drugs targeting specific inflammatory response pathways. Some newer agents have shown a definitive signal of benefit when added to standard of care. With the advent of precision medicine in nephrology, lupus nephritis treatment may undergo a shift toward incorporating approaches using these newer drugs and individualizing care of our patients. This review highlights major advances in management of lupus nephritis over the last 25 years and explores the ongoing trials of emerging therapies in lupus nephritis.

Mercury-associated neural epidermal growth factor-like 1 protein (NELL-1) positive membranous nephropathy after use of skin lightening creams.

INTRODUCTION: Membranous nephropathy, one of the common causes of glomerulonephritis worldwide, is reported in association with mercury exposure. Neural epidermal growth factor-like 1 protein is a recently described target antigen in membranous nephropathy. CASE SERIES: Three woman (ages 17, 39, and 19 years old) presented sequentially for our evaluation with complaints consistent with nephrotic syndrome. All three had nephrotic range proteinuria, hypoalbuminemia, hypercholesterolemia, hypothyroidism, and inactive urinary sediments. Kidney biopsies were performed in the first two patients, which demonstrated findings consistent with membranous nephropathy and positive staining for neural epidermal growth factor-like 1 protein. On discovery that they were all using the same skin-lightening cream, samples of the cream were tested and found to contain between 2,180 parts per million and 7,698 parts per million of mercury. Elevated urine and blood mercury concentrations were also found in the first two patients. All three patients improved following cessation of use and treatment with levothyroxine (all three patients) and corticosteroids and cyclophosphamide in patients one and two. DISCUSSION: We hypothesize the role of autoimmunity triggered by mercury exposure in the pathogenesis of neural epidermal growth factor-like 1 protein membranous nephropathy. CONCLUSION: Mercury exposure should be carefully assessed as a part of the evaluation of patients with neural epidermal growth factor-like 1 protein positive membranous nephropathy.

Spectrum of renal dysfunction after curative parathyroidectomy in symptomatic primary hyperparathyroidism.

OBJECTIVE: The long-term renal consequences of curative parathyroidectomy (PTX) in symptomatic primary hyperparathyroidism (sPHPT) are not well characterized. We aimed to assess renal glomerular and tubular functions in an sPHPT cohort at ≥1 year's follow-up. DESIGN: Retrospective-prospective study. METHODS: sPHPT patients with preoperative eGFR ≥60mL/min/1.73m2 and in remission (normocalcemic) for ≥1 year after PTX underwent clinical and biochemical assessment (calcium profile, renal parameters). Ammonium chloride and bicarbonate loading tests were performed in patients with renal tubular dysfunction (RTD). RESULTS: Forty-eight patients (31 females) with median plasma PTH 1,029 (338-1604) pg/mL and mean eGFR 109.2±26.0mL/min/1.73m2 at diagnosis were evaluated at 5.62±3.66 years after curative PTX. At follow-up, eGFR was <60mL/min/m2 in 5 patients (10.4%). Patients with >10% drop in eGFR (n=31) had significantly higher pre-PTX plasma PTH (1,137 vs. 687pg/mL), and longer time to post-PTX evaluation (6.8 vs. 3.4 years). RTD was seen in 11 patients (22.9%): urinary low molecular weight proteinuria (14.6%), distal renal tubular acidosis (12.5%), hypophosphatemia (8.3%), and hypokalemia (8.3%); RTD was associated with significantly lower post-PTX eGFR (72.7 vs. 95.4mL/min/m2). Five of the 7 RTD patients undergoing loading test had impaired urinary acidification, whereas none had impaired bicarbonate resorption. CONCLUSIONS: Reduction in eGFR and subclinical RTD were prevalent at long-term follow-up in the present Asian-Indian cohort with cured sPHPT. Further studies are warranted to understand the clinical implications of these various renal abnormalities.

Clinical Course and Outcomes of COVID-19 in Kidney Transplant Recipients.

Introduction: Kidney transplant recipients (KTR) are at increased risk of morbidity and mortality due to coronavirus disease 2019 (COVID-19). This study aimed to explore the clinical characteristics and outcomes of COVID-19 in KTR. Methods: We reviewed the clinical profile, outcomes, and immunological responses of recipients admitted with COVID-19. We determined the risk factors for mortality and severe COVID-19. Results: Out of 452 recipients on follow-up, 60 were admitted with COVID-19. Prevalent comorbidities were hypertension (71%), diabetes (40%), lung disease (17%). About 27% had tuberculosis. The median Sequential Organ Failure Assessment score at presentation was 3 (interquartile range [IQR] 1-5). There was a high incidence of diarrhea (52%) and anemia (82%). Treatment strategies included antimetabolite withdrawal (85%), calcineurin inhibitor decrease or withdrawal (64%), increased steroids (53%), hydroxychloroquine (21%), remdesivir (28.3%), and tocilizumab (3.3%). Severe COVID-19 occurred in 34 (56.4%) patients. During a median follow-up of 42.5 days (IQR 21-81 days), 83% developed acute kidney injury (AKI) and eight (13%) died. Mortality was associated with the baseline graft dysfunction, hypoxia at admission, lower hemoglobin and platelets, higher transaminases, higher C reactive protein, diffuse radiological lung involvement, hypotension requiring inotropes, and Kidney Diseases Improving Global Outcomes (KDIGO) stage 3 AKI (univariate analysis). Around 57% of patients remained RT-PCR positive at the time of discharge. By the last follow-up, 66.6% of patients developed IgM (immunoglobulin M) antibodies and 82.3% of patients developed IgG antibodies. Conclusion: COVID-19 in kidney transplant recipients is associated with a high risk of AKI and significant mortality.

Cardiovascular Complications in Kidney Transplant Recipients with COVID-19: A Case Series.

Kidney transplant recipients (KTRs) are at a higher risk for developing severe COVID-19 which can be associated with cardiovascular complications. We studied five KTRs recipients infected with COVID-19 who developed severe cardiovascular complications. Two patients presented with ST segment myocardial infarction and two with clinically suspected myocarditis. One patient presented with atrial fibrillation. Two of these patients developed cardiogenic shock. Inflammatory markers were at peak during the event in four of these who had presented with severe COVID-19. Coronary angiography done in two patients with STEMI did not reveal any evidence of atherosclerotic coronary artery disease. Also, based on the cardiovascular (CV) risk estimation by Framingham score, four patients had low CV risk and one patient had intermediate CV risk. All five patients survived. Even with low CV risk, KTRs can develop myocardial injury and arrhythmias solely because of severe COVID-19.

High dependency renal unit for the management of COVID-19 in patients with severe acute or chronic kidney disease.

Coronavirus disease 2019 (COVID-19) in patients with severe impairment of kidney function is associated with high mortality. We evaluated the effect of high dependency renal unit (HDRU), with nephrologists as primary care physicians, as a quality improvement initiative for the management of these patients. This was a quasi-experimental observational study conducted at a tertiary care hospital in western India. Patients hospitalized for COVID-19 with pre-existing end-stage-renal-disease and those with severe AKI requiring dialysis (AKI-D) were included. For the first 2 months, these patients were cared for in medical wards designated for COVID-19, after which HDRU was set up for their management. With nephrologists as primary care providers, the 4 key components of care in HDRU included: care bundles focusing on key nephrology and COVID-19 related issues, checklist-based clinical monitoring, integration of multi-specialty care, and training of nurses and doctors. Primary outcome of the study was in-hospital mortality before and after institution of the HDRU care. Secondary outcomes were dialysis dependence in AKI-D and predictors of death. A total of 238 out of 4254 (5.59%) patients with COVID-19, admitted from 28th March to 30th September 2020, had severe renal impairment (116 AKI-D and 122 end-stage-renal-disease). 145 (62%) had severe COVID-19. From 28th May to 31st August 2020, these patients were managed in HDRU. Kaplan-Meier analysis showed significant improvement in survival during HDRU care [19 of 52 (36.5%) in pre-HDRU versus 35 of 160 (21.9%) in HDRU died, P ≤ .01]. 44 (67.7%) AKI-D survivors were dialysis dependent at discharge. Breathlessness and altered mental status at presentation, development of shock during hospital stay, and leukocytosis predicted mortality. HDRU managed by nephrologists is a feasible and potentially effective approach to improve the outcomes of patients with COVID-19 and severe renal impairment.

A Unified Citywide Dashboard for Allocation and Scheduling Dialysis for COVID-19 Patients on Maintenance Hemodialysis.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has caused significant global disruption, especially for chronic care like hemodialysis treatments. Approximately 10,000 end-stage kidney disease (ESKD) patients are receiving maintenance hemodialysis (MHD) at 174 dialysis centers in Greater Mumbai. Because of the fear of transmission of infection and inability to isolate patients in dialysis centers, chronic hemodialysis care was disrupted for COVID-19-infected patients. Hence, we embarked on a citywide initiative to ensure uninterrupted dialysis for these patients. Materials and Methods: The Municipal Corporation of Greater Mumbai (MCGM) designated 23 hemodialysis facilities as COVID-positive centers, two as COVID-suspect centers, and the rest continued as COVID-negative centers to avoid transmission of infection and continuation of chronic hemodialysis treatment. Nephrologists and engineers of the city developed a web-based-portal so that information about the availability of dialysis slots for COVID-infected patients was easily available in real time to all those providing care to chronic hemodialysis patients. Results: The portal became operational on May 20, 2020, and as of December 31, 2020, has enrolled 1,418 COVID-positive ESKD patients. This initiative has helped 97% of enrolled COVID-infected ESKD patients to secure a dialysis slot within 48 hours. The portal also tracked outcomes and as of December 31, 2020, 370 (27%) patients died, 960 patients recovered, and 88 patients still had an active infection. Conclusions: The portal aided the timely and smooth transfer of COVID-19-positive ESKD patients to designated facilities, thus averting mortality arising from delayed or denied dialysis. Additionally, the portal also documented the natural history of the COVID-19 pandemic in the city and provided information on the overall incidence and outcomes. This aided the city administration in the projected resource needs to handle the pandemic.

Recovery of kidney function after AKI because of COVID-19 in kidney transplant recipients.

Evidence on the evolution of graft function in kidney transplant recipients recovering from coronavirus disease-2019 (COVID-19) is lacking. This multicenter observational study evaluated the short-term clinical outcomes in recipients with acute kidney injury (AKI) secondary to COVID-19. Out of 452 recipients following up at five centers, 50 had AKI secondary to COVID-19. 42 recipients with at least 3-month follow-up were included. Median follow-up was 5.23 months [IQR 4.09-6.99]. Severe COVID-19 was seen in 21 (50%), and 12 (28.6%) had KDIGO stage 3 AKI. Complete recovery of graft function at 3 months was seen in 17 (40.5%) patients. Worsening of proteinuria was seen in 15 (37.5%) patients, and 4 (9.5%) patients had new onset proteinuria. Graft failure was seen in 6 (14.3%) patients. Kidney biopsy revealed acute tubular injury (9/11 patients), thrombotic microangiopathy (2/11), acute cellular rejection (2/11), and chronic active antibody-mediated rejection (3/11). Patients with incomplete recovery were likely to have lower eGFR and proteinuria at baseline, historical allograft rejection, higher admission SOFA score, orthostatic hypotension, and KDIGO stage 3 AKI. Baseline proteinuria and the presence of orthostatic hypotension independently predicted incomplete graft recovery. This shows that graft recovery may remain incomplete after AKI secondary to COVID-19.

Adenocarcinoma of lung masquerading as systemic auto-immune disease.

A 40-year-old previously healthy male presented with acute onset painless dimness of vision in both eyes since the past week and low-grade fever, anorexia and weight loss for the past 1 month. He had been evaluated at a local hospital and diagnosed to have a posterior cerebral artery territory infarct on the left side on the strength of cranial CT. Shortly after receiving antiplatelets and warfarin he had developed severe coagulopathy as evidenced by haematemesis, epistaxis and haematuria. Preliminary investigation revealed prolonged clotting parameters, renal failure and anaemia. Cerebral MRI showed multiple areas of cortical haemorrhage. In the course of his hospital stay, he developed further stigmata of auto-immunity including Coomb's positive haemolytic anaemia, recurrent venous thromboses and a palpable purpuric truncal rash. He was eventually diagnosed to have an adenocarcinoma of the lung, and was subsequently referred to an oncologist for further therapy.