Diagnostic utility of C4d immunohistochemistry in membranous nephropathy.

OBJECTIVES: Membranous nephropathy (MN), also called membranous glomerulopathy, is one of the leading causes of nephrotic syndrome in adults which is defined by the presence of subepithelial immune complex deposits with a spectrum of changes in the glomerular basement membrane (GBM). It is known that C4d is a byproduct of the classic and lectin pathway. There is deposition of C4d noted in the cases of immune complex-mediated glomerulonephritis involving the classical/lectin pathway including MN. The main objective of this study is to assess the utility C4d as an immunohistochemical (IHC) stain in MN. MATERIALS: A total of 43 cases of MN (primary & secondary) were taken, and 39 cases of minimal change disease (MCD)/focal segmental glomerulosclerosis (FSGS) were used as the control group. All the relevant data were retrieved from the hospital database. C4d immunohistochemistry was performed in the cases as well as the control group. RESULTS: A diffuse continuous staining pattern in the glomeruli was observed in cases of primary MN whereas a discontinuous staining in the glomerulI favors a secondary MN. 26/29 cases of MCD showed positivity in the podocytes. Among the cases of FSGS, 7/10 cases showed positivity in the podocytes with 3 cases showing an associated mesangial blush pattern of staining. CONCLUSION: Very few studies are available demonstrating the importance of C4d IHC in MN. C4d IHC can be a useful adjunct for immunofluorescence, especially in cases of early MN.

Revisit of Polyomavirus Nephropathy Grading in Renal Allograft Recipients According to the Banff 2019 Working Group Classification: A Study From a Large Transplant Center in South India.

Background In renal transplant patients, the biopsy-proven incidence of polyomavirus nephropathy (PVN) is approximately 5%. There is no consensus in the morphologic classification of definitive PVN, which is attempted in the Banff 2019 Working Group classification, which groups histologic changes, reflects clinical presentation, and facilitates comparative outcome analyses. This study aims to analyze the clinical and histopathological findings and outcomes among the three classes in the recent classification. Materials and methods The study was conducted in the department of pathology and nephrology over a period of six years. All cases diagnosed as PVN on renal allograft biopsies were included. The clinical and biochemical findings were obtained from hospital records. Histopathology slides were reviewed and classified according to Banff 2019 criteria and were analyzed with clinical, laboratory, histopathological parameters along with the clinical outcome. Results Out of 205 renal transplants performed during the study period, 14 patients (6.8%) were diagnosed with PVN. The mean age of diagnosis was 38 years, with a Male: Female ratio of 1.8:1. The median period of diagnosis of the viral infection after transplant was 10 months. Histomorphology grading according to Banff 2019 revealed four cases (28.5%) in PVN class 1, eight cases (57.2%) in PVN class 2, and two cases (14.3%) in PVN class 3. Cases in PVN class 1 presented early. PVN class 1 was associated with a single type of inclusion, and multiple type inclusions were observed in higher classes. Associated diseases were thrombotic microangiopathy (TMA), borderline cellular rejection, antibody-mediated rejection (ABMR), and concomitant infections. PVN class 1 had a better outcome compared to PVN class 2 and class 3. Conclusion PVN1 was observed to have better clinical presentation and outcomes than PVN2 and 3; however, this could not be statistically concluded due to the low sample size and other associated diseases.

Clinicopathological Profile of Paraprotein-Associated Kidney Disease in Monoclonal Gammopathies: An Observational Study.

Background Renal involvement in monoclonal gammopathies presents with different clinico-morphological patterns and can manifest at the onset or the late phase of hematological disease, or after chemotherapy. The spectrum is ever-expanding with advancements in diagnostic methods. Renal biopsy is needed for accurate diagnosis, as each of these patterns carries therapeutic and prognostic implications. Methods A total of 41 cases of monoclonal gammopathies were included in the study. Clinical, biochemical, and hematological details were obtained, and pathological variables were observed. Patients were followed till the maximum possible period, and treatment history and follow-up creatinine details were collected. Results The spectrum of renal biopsy lesions observed included light chain cast nephropathy (LCCN) n=19, amyloidosis n=11, monoclonal immunoglobulin deposition disease (MIDD) n=6, and proliferative glomerulonephritis with monoclonal immunoglobulin deposition (PGNMID) n=5; 10 of these cases can be categorized as monoclonal gammopathy of renal significance (MGRS). Acute kidney injury (AKI) (41%) is the predominant clinical presentation in general whereas the majority of amyloidosis cases presented with nephrotic and sub-nephrotic proteinuria. LCCN cases had high serum creatinine and calcium, positivity for M-spike, as well as a high FLC ratio, compared to the other types. Around 100% of LCCN and MIDD patients had myeloma and 100% of PGNMID cases had normal marrow. Conclusion More than three-fourths of patients were diagnosed with monoclonal gammopathies with biochemical and hematological workups after an initial kidney biopsy. The clinicopathological profile of these patients had a broad spectrum but there were still some consistent findings within the different types. A subgroup of patients (MGRS) had undetectable serum paraproteins but had monoclonal immunoglobulin deposition in the kidney.

Prevalence and determinants of sarcopenia in Indian patients with chronic kidney disease stage 3 & 4.

OBJECTIVES: There is limited literature on the prevalence and determinants of sarcopenia in the Indian predialysis chronic kidney disease (CKD) population. The current study attempts to characterize sarcopenia in CKD stages 3 & 4 using 3-compartment model dual-energy X-ray absorptiometry (DXA). METHODS: This is secondary data from a randomized trial on bicarbonate supplementation for preserving muscle mass. A 3-compartment DXA was done to assess body composition in 188 subjects aged 18 to 65, with stable kidney function. Sarcopenia was defined by Asian Working Group criteria - appendicular skeletal mass index < 5.4 kg/m2 in women and < 7 kg/m2 in men. RESULTS: Sarcopenia was present in 69.1% (n = 130). There was no difference in the prevalence of sarcopenia in CKD stage 3 (n = 62; 72.1%) vs CKD stage 4 (n = 68, 66.7%); P = 0.434. A lower body mass index (BMI) (OR 1.69; 95% CI 1.43, 2.01) and lower bicarbonate levels (OR 1.22; 95% CI 1.02, 1.47), and age (OR 0.95; 95% CI 0.91, 0.98) was independently associated with the muscle mass. A BMI cut-off of 18 failed to identify sarcopenia in 78.4% (n = 102) subjects (Kappa statistic 0.396). The receiver operating characteristic curve for mid-arm muscle circumference for identifying sarcopenia was 0.651 (95% CI 0.561, 0.740). CONCLUSIONS: Sarcopenia is highly prevalent in CKD 3 and 4. Sarcopenic individuals are older, with a low BMI and lower bicarbonate levels. The anthropometric parameters and biochemical parameters did not help identify sarcopenia in the predialysis population.