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.

'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.

Isolated renal involvement of cytomegalovirus inclusion disease in an infant.

Cytomegalovirus (CMV) is the most common cause of congenital infections in humans occurring in 1% of all liveborns. Symptomatic congenital CMV infection involves multiple systems and causes significant morbidity and mortality in newborns. Isolated CMV infection of the kidneys in a living infant has not been reported in literature. Here, we report an infant who presented only with renomegaly and renal biopsy showed extensive CMV inclusions. Serum and urine polymerase chain reaction for CMV were positive, and CMV involvement of other organs was ruled out. The child for treated with intravenous ganciclovir and is currently on follow-up. Cytomegalic inclusion disease involving only kidneys without other systems involvement can occur. The treatment protocol is unclear and long-term follow-up is needed.

Infection-related glomerulonephritis in a renal allograft.

Infection-related glomerulonephritis (IRGN) is an immune-mediated glomerulo-nephritis, most commonly caused by bacterial infections. Although there is an increased incidence of infectious episodes in renal transplant recipients, IRGN as a cause of de novo glomerulonephritis is rarely seen probably due to impaired immunity. We hereby report a 28-year-old male renal transplant recipient, who developed IRGN following impetigenous skin lesions after six years of transplant. He developed rapid worsening of allograft function and was started on hemodialysis. Allograft renal biopsy showed diffuse exudative endocapillary proliferation with crescents. Electron microscopy revealed large subepithelial hump-like deposits. Despite pulse steroid therapy, he became dialysis dependent. Our patient is unique in the way that poststreptococcal glomerulonephritis in an adult after renal transplantation has not been reported so far. We conclude that IRGN after renal transplant, though rare is a possible etiology for allograft dysfunction. There is no definitive treatment protocol for this de novo glomerulonephritis which has an overall poor prognosis.

An overlap of granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis.

We present a case report of overlap of granulomatosis with polyangiitis (GPA; formerly known as Wegener's granulomatosis) and eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome). We report a 45-year-old female who presented with rapidly progressive renal failure associated with fever, polyarthralgia, and respiratory symptoms with cytoplasmic antineutrophilic cytoplasmic antibody (ANCA) and proteinase (PR-3) antigen positivity. Computerized tomography scan of the chest showed diffuse alveolar hemorrhage with renal biopsy revealing pauci-immune necrotizing crescentic glomerulonephritis with intense eosinophilic infiltration suggestive of eosinophilic GPA (EGPA). Our patient had ANCA-associated vasculitis (AAV) with features suggestive of both GPA and EGPA. She was treated with methylprednisolone and cyclophosphamide and attained remission after 2 weeks of therapy. This is a rare report of a patient with AAV having features of both EGPA and GPA.

Renal cell carcinoma with t(6,11): A case report and review of literature.

Renal cell carcinomas (RCCs) with t(6,11) are very rare tumours. Only a few cases have been reported so far. t(6,11) results in fusion of alpha gene and transcription factor EB (TFEB) gene resulting in the overexpression of TFEB. The specific light and immunohistochemical features help in the diagnosis of this rare type of tumor. We report a case of t(6,11) RCC in a 38-year-old female who was incidentally found to have a right renal mass. We present this case to emphasize the typical light microscopic picture of this extremely rare tumor. Two population of cells are seen: larger cells with abundant cytoplasm and smaller cells with scant cytoplasm. Smaller cells are arranged around hyaline nodules resulting in the formation of characteristic pseudorosettes. Immunohistochemically, these tumors are diffusely positive for vimentin and focally positive for HMB 45 and CD 117. Knowledge about the typical biphasic light microscopic appearance and the characteristic immunohistochemical features help in the diagnosis of this rare type of translocation associated RCC.

Lack of electron microscopy hinders correct renal biopsy diagnosis: A study from India.

Electron microscopy (EM) is performed routinely on all native kidney biopsies in the western world. However, in India, it is not regularly performed due to non-availability and financial constraints. The aim of this prospective study was to evaluate the usefulness of routinely performing EM on native kidney biopsies. In order to eliminate selection bias, all consecutive native kidney biopsies were included in this study, provided they had adequate tissue for light, immunofluorescence (IF), and EM. The biopsies were reported on the basis of light and IF microscopy. EM was performed on each case by another pathologist who also independently reviewed the light microscopic slides and IF images. The findings were then reviewed to assess how the ultrastructural features contributed to the primary diagnosis and assigned to one of the following categories: 1. Crucial for diagnosis, 2. Important contribution, or 3. Not required. Of the 115 cases evaluated, EM was crucial in 12% of the cases. In 20% of the cases, it provided important confirmatory information and in the remaining 68% cases, EM was not considered required. This study supports the use of EM as a routine diagnostic tool in the evaluation of native kidney biopsies. There is an urgent need for availability and accessibility of EM in our country.

Collagenofibrotic glomerulopathy.

BACKGROUND: Collagenofibrotic glomerulopathy is a rare renal disease of unknown etiology that is secondary to deposition of type III collagen within the glomerulus. Only rare case series exist in the literature. METHODS: Renal biopsies diagnosed with collagenofibrotic glomerulopathy were prospectively collected at the Center for Renal and Urological Pathology (AAK) (Chennai, Tamil Nadu, India) from 2012 to 2015. Eight patients were entered into the study. The average age was 38 years with five males and three females. RESULTS: All patients presented with nephrotic syndrome, and five displayed hypertension. The average serum creatinine was 146.5 µmol/L (88.4-282.9 µmol/L range). All serologic testing was negative, and complement levels were normal. No clinical evidence of nail-patella syndrome was seen. All cases showed diffuse mesangial expansion and double contour formation by peroidic acid-Schiff (PAS)-negative material. All immunofluorescence studies were negative. By electron microscopy all cases showed electron dense, banded to curvilinear collagen bundles within the mesangium and subendothelial aspect of the peripheral capillary walls. All patients appear to have sporadic disease occurrence with no family history of renal disease. No hemolytic uremic syndrome, liver fibrosis, lymphoma or co-occurrence of other renal disease were seen. CONCLUSION: Collagenofibrotic glomerulopathy is a rare disease that appears to occur more frequently in adult Indian populations in a sporadic, non-familial manner. To our knowledge, this is the largest cases series of collagenofibrotic glomerulopathy in an adult population.

Spectrum of nephrotic syndrome in adults: clinicopathological study from a single center in India.

BACKGROUND: The etiology of nephrotic syndrome (NS) in adults varies depending on the geographical location and is poorly studied in the Indian subcontinent. METHODS: Patients (≥16 years old) with NS presenting to our center and undergoing a kidney biopsy from April 2010 to September 2012 were included for this study. All biopsies were subjected to light and immunofluorescence microscopy, and electron microscopy in selected cases. The histopathological spectrum was analyzed according to the various clinical parameters. RESULTS: A total of 410 kidney biopsies were included for analysis. Two hundred and thirty seven (57.8%) patients were male and 173 (42.19%) patients were female. The average age at presentation was 33.68 ± 13.88 years. Among the patients, 88.05% (n = 361) were diagnosed with primary glomerular diseases (PGD) and 11.95% (n = 49) with secondary glomerular diseases (SGD). The most common histological lesions were focal segmental glomerulosclerosis (FSGS) (24.63%) followed by minimal change disease (MCD) (23.9%) and membranous nephropathy (MN) (22.44%). The most common form of SGD was lupus nephritis (LN) (6.58% of all cases). FSGS (28.27%) and MCD (21.96%) were the most common lesions in males and females, respectively. In the age groups of 16-29 years, 30-59 years, and ≥60 years, MCD (28.96%), MN (24%), and MN (40.74%) were the most common lesions, respectively, followed by FSGS in all groups (25.68%, 24.5%, and 18.52%, respectively). Among the patients, 27.07% had serum creatinine ≥1.5 mg/dL and 28.54% had either macroscopic or microscopic hematuria. CONCLUSIONS: FSGS is increasingly becoming the most common cause of adult NS. This trend in Asia is seen predominantly in countries of the Indian subcontinent.