Complementary and Alternative Medicine Use and Glomerular Disease: A Contemporary Case Series.

Rationale & Objective: Complementary and alternative medicine (CAM) intake is widely prevalent in many parts of India. Heavy metals are known ingredients in some of these formulations. We studied the spectrum of glomerular diseases in patients using CAM. Study Design: Case series. Setting & Participants: Patients with proteinuria or unexplained acute kidney injury, who underwent a kidney biopsy between May 2021 and September 2022, and who provided a history of recent CAM intake were included in the study. For patients enrolled prospectively, blood and urine samples were analyzed using mass spectrometry for the presence of mercury, lead, arsenic and cadmium. The CAM formulation, when available, was analyzed using inductively coupled plasma-optical emission spectroscopy. Results: Twenty-eight patients were enrolled in the study, with a median duration of CAM intake of 4 months (interquartile range, 2-6 months). Heavy metal screening was performed in 17 patients, of whom 15 had elevated urine mercury levels, 10 had elevated blood mercury levels, and 1 had elevated blood and urine arsenic levels. Of the 6 CAM formulations that were analyzed, all had high levels of mercury. Kidney biopsy findings were membranous nephropathy (n = 19), minimal change disease (n = 8), and mesangial proliferative glomerulonephritis (n = 1). Of the 19 patients with membranous nephropathy, 14 were associated with neural epidermal growth factor-like protein 1 (NELL-1). With conservative management alone, 17 patients achieved complete remission. Limitations: Not all patients underwent blood and urine mercury testing, and only 6 patients provided the CAM samples for analysis. Furthermore, occupational and residential exposure to mercury could not be excluded. Conclusions: The most common kidney pathology noted in our study was membranous nephropathy, which was predominantly associated with neural epidermal growth factor-like protein 1. A significant proportion of the patients recovered completely after withdrawal of the offending agent and initiation of renin-angiotensin system blockade.

Complementary and alternative medicine (CAM) intake is widely prevalent in many parts of India, and heavy metals are known ingredients in some of these formulations. We describe the clinical spectrum of kidney disease, among patients who had recently ingested CAM. All patients underwent a kidney biopsy, and the most common finding was an entity called "NELL-1-associated membranous nephropathy," which is known to be associated with heavy metal toxicity and CAM intake. Of 17 patients screened for such heavy metals, 15 had greater-than-permissible levels of mercury. Furthermore, 6 patients provided the CAM formulations that they had consumed for analysis: all contained high levels of mercury. Most such patients recovered following withdrawal of the offending CAM agent.

Efficacy of Corticosteroids in Infection-Related Glomerulonephritis-A Randomized Controlled Trial.

Introduction: Infection-related glomerulonephritis (IRGN) is associated with glomerular immune complex deposition along with complement activation. Steroids may attenuate glomerular injury and thereby improve renal outcomes. Methods: We randomly assigned patients who had biopsy-proven IRGN and serum creatinine greater than 1.5 mg/dl to receive corticosteroids plus supportive care (intervention arm), or supportive care alone (control arm). Patients were followed up for 6 months. The primary outcome was complete renal recovery at 6 months. Safety of steroid therapy was also assessed. Results: A total of 52 patients underwent randomization. At 6 months, 17 of 26 patients (65.4%) in the intervention arm and 14 of 26 patients (53.8%) in the control arm had complete renal recovery (odds ratio 1.6; 95% confidence interval, 0.5-4.9; P = 0.397). There was no statistically significant difference in any of the secondary outcomes. Adverse events occurred in 12 patients (46.2%) in the intervention arm and 2 patients (7.7%) in the control arm (P = 0.002). Conclusion: In this single-center trial, corticosteroids did not result in a statistically significant increase in rates of complete renal recovery at 6 months. There was a significantly increased risk of adverse events associated with the use of corticosteroids.

Clinical Profile, Histopathology, and Outcomes in Infection-Related Glomerulonephritis - Single-Center Experience.

Background: Infection-related glomerulonephritis (IRGN) is an important source of renal morbidity with adverse outcomes in adults. Data from large centers in India is lacking on this common, yet poorly understood entity. Materials and Methods: We performed a prospective observational study of all patients diagnosed with IRGN at our center over a 3-year period between 2017 and 2019. "Typical IRGN" patients were diagnosed based on clinical and laboratory assessment; others underwent renal biopsy. Renal and patient survival outcomes were assessed in addition to factors that help predict outcomes. Results: One hundred and twenty-five patients with a diagnosis of IRGN were included in the study, including 86 patients who underwent renal biopsy. This represented 24% of all biopsies during this time period, and IRGN was the most common nondiabetic kidney disease identified in diabetic biopsies at our center. Female preponderance and a seasonal variation were striking. Atypical sources of infection like otomycosis, tooth abscess, and dengue virus infection were noted. Male gender and diabetes were important risk factors for severe disease. Rapidly progressive glomerulonephritis (RPGN), atypical serum complement profiles, and comorbid illnesses were common in adults. Though children had more benign disease and outcomes, life-threatening complications were also noted. C3 dominance was the most striking immunofluorescence (IF) finding and was associated with poorer outcomes. Crescentic IRGN was rare, and four cases of IgA-dominant IRGN were noted. Also, 24% of the cohort required renal replacement therapy. RPGN presentation of IRGN portended worst prognosis with end-stage renal disease (ESRD) in 31% and death in 22% of patients. Conclusion: IRGN is a common clinical entity in adults with the potential for adverse renal and survival outcomes. We have identified clinical and biopsy characteristics that are associated with ESRD and death.

Adenovirus-Associated Thrombotic Microangiopathy and Necrotizing Interstitial Nephritis in a Renal Transplant Recipient: A Case Report and Review.

Adenoviral infections, though rare, may be a source of significant morbidity and mortality in the early post renal transplant period. We present a case of fever and graft dysfunction in a deceased donor renal transplant recipient whose initial post-operative period was complicated by vascular thrombosis and ureteric necrosis. He had received induction immunosuppression with Rabbit-Anti Thymocyte Globulin. Graft biopsy was suggestive of Thrombotic Microangiopathy (TMA) accompanied by intense interstitial inflammation, hemorrhage, necrosis, WBC casts and tubular injury. Viral cytopathic changes were discernible on light microscopy, leading to suspicion of adenoviral infection. This was confirmed with immunohistochemical demonstration of adenoviral antigens in the graft biopsy. He was treated with a step down of immunosuppression and intravenous Immunoglobulin. However, the patient's general condition deteriorated rapidly, and he succumbed to his illness. We highlight this association of TMA and necrotizing tubulo-interstitial nephritis with adenoviral infection of the renal allograft.

Etiological Spectrum and Histopathological Diagnosis of Rhabdomyolysis Associated Myoglobin Cast Nephropathy in South India.

BACKGROUND AND AIMS: Rhabdomyolysis occurs due to injury to skeletal muscle fibers and the release of muscle constituents into the circulation. Myoglobin cast nephropathy leading to acute kidney injury is one of the most severe complications of rhabdomyolysis. This is a retrospective study which aims to analyse the clinicopathological features of myoglobin cast nephropathy. METHODS: A total of 57 cases of myoglobin cast nephropathy were identified after performing immunohistochemical staining for myoglobin on all renal biopsies with pigment casts. The clinical, laboratory data, histopathological findings and clinical outcome of these cases were evaluated. RESULTS: The mean patient age was 34.47 years (range 17-77) and the male to female ratio was 6.1:1. All patients presented with acute kidney injury with mean serum creatinine of 8.4 mg/dl (range: 1.7 to 20.8 mg/dl). Rhabdomyolysis was clinically suspected only in 31 patients. Along with myoglobin casts, acute tubular injury was present in all the biopsies. The most frequent conditions associated with myoglobin cast nephropathy in our study were snake envenomation and unaccustomed physical activities. A few activities that caused rhabdomyolysis in our patients were unique to India. CONCLUSION: Clinicians should be aware of the wide spectrum of causes for rhabdomyolysis. The classical clinical and laboratory findings of rhabdomyolysis may not be present in many of the patients. The pathologist must have a high index of suspicion, and immunohistochemical stain should be used to confirm the diagnosis.

An Emergent Cause of Renal Allograft Dysfunction.

Infection-related glomerulonephritis (IRGN) results from an immune-mediated process in the occurrence of non-renal infection. Despite increased incidence of infections post-transplant, which is attributed to the immunosuppression, IRGN serves to be a rare cause of de novo GN. Here, we present a 43-year old male, a deceased donor renal transplant recipient, who presented with acute decline in allograft function that developed in association with IRGN five years after transplant. He continued to have renal allograft dysfunction despite treatment with antibiotics. We infer that IRGN must be thought of as a possible entity, although rare, in the diagnosis of de novo GN post-transplant. Furthermore, the absence of definitive treatment protocol makes this emerging cause of renal allograft dysfunction be associated with the poor prognosis.

'Snapshot' of an annual data from a large South Indian Renal Biopsy Registry.

Results from biopsy registries are important to know about the prevalence of renal diseases. In large studies done over several years, significant interobserver variability could have existed. Single-year biopsy registry data are analyzed in this study. The study included 481 renal biopsy specimens including 65 from allografts. Primary glomerulonephritis constituted 37.74% and secondary glomerular diseases constituted 32.21% of native kidney biopsies. Minimal change disease was the most common primary glomerular disease, followed by membranous nephropathy (MN). Lupus nephritis was the most common secondary glomerular disease. This study included specimens from 34 geriatric patients and MN was the most common lesion in that age group. Acute cellular rejection was the most common diagnosis in renal allograft biopsies.