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Background and objective Nephrotic syndrome is a significant worldwide health concern impacting millions of people and is marked by heavy proteinuria, edema, and decreased serum levels of albumin. Albuminuria arises from abnormal glomerular permeability and impaired tubular reabsorption, contributing to declining kidney function and a heightened risk of cardiovascular complications. The objective of this study was to investigate the prognostic role of proteinuria on the persistent decline in estimated glomerular filtration rate (eGFR) (<30 ml/minute/1.73m2) during follow-up and the dynamics of remission and relapse in various subtypes of nephrotic syndrome. Methods A total of 134 adult patients, diagnosed with various histopathological categories of nephrotic syndrome, were prospectively studied. Urine protein levels were assessed using the pyrogallol red-molybdate (PRM) method. The Kaplan-Meier analysis and log-rank test were utilized to assess the prognostic role of proteinuria at manifestation on persistent decline in estimated glomerular filtration rate (eGFR) (<30 ml/minute/1.73m2) and to evaluate remission and relapse based on proteinuria levels over an 18-month follow-up period. Results Patients with sub-nephrotic levels of proteinuria at manifestation did not progress to end-stage renal disease on follow-up. Patients with sub-nephrotic levels of albuminuria at manifestation were significantly associated with remission on follow-up. The Kaplan-Meier analysis indicated a significant probability of persistent eGFR decline (p < 0.001) in adult nephrotics with higher levels of albuminuria. Furthermore, patients with sub-nephrotic range proteinuria had earlier remission (p < 0.001) compared to those with relapse (p = 0.001) during the follow-up, as demonstrated by log-rank tests. Conclusion This study highlights that sub-nephrotic albuminuria at manifestation is linked to a reduced risk of renal progression and persistent eGFR decline compared to adult nephrotics with higher levels of albuminuria. Early detection and effective management of proteinuria, are crucial for preventing renal function decline and improving patient outcomes.
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Background and objective Membranous glomerulonephritis (MGN) is a common cause of adult nephrotic syndrome. Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine that signals by attaching to TNF receptors. TNF-α plays a pivotal role in the development and progression of different forms of glomerulonephritis. Several research findings suggest that TNF-α receptors (TNFR1 and TNFR2) are predictors of estimated glomerular filtration rate (eGFR) decline. In light of this, this study aimed to explore the relationship between TNFR2 and eGFR, as well as the predictive role of TNFR2 in eGFR decline in MGN. Methods A total of 50 consecutive patients with a diagnosis of primary MGN based on renal biopsies and clinical workups were included in the study. TNFR2 levels in serum, urine, and gene expression were evaluated at baseline and after three months of follow-up by using enzyme-linked immunosorbent assay (ELISA) kits for TNFR2 (KTE60215, Abbkine, Wuhan, China). Cox regression was employed to determine the predictive significance of TNFR2 in persistent eGFR decline. Additionally, an ROC curve analysis was conducted to assess the prognostic value of TNFR2 in predicting persistent eGFR decline among MGN patients. Results We assessed the levels of inflammatory markers TNF-α and TNFR2, examined their correlation with eGFR and renal injury, and investigated their potential in predicting persistent eGFR. Patients with MGN exhibited elevated levels of TNFR2 in their serum, urine, and gene expression compared to healthy individuals. Additionally, there was a positive correlation between serum TNFR2 and TNF-α, urine protein-creatinine ratio (UPCR), uric acid, and total cholesterol. Conversely, there was a negative correlation with eGFR, serum albumin, and calcium. Serum TNFR2 showed statistical significance in a univariate Cox regression analysis (HR: 1.010, 95% CI: 1.00-1.01, p = 0.045) for predicting a persistent decline in eGFR. However, it did not show significance concerning relapse and remission. An ROC curve was created to assess TNFR2's prognostic potential as a biomarker, demonstrating an AUC of 0.683, with a sensitivity of 68% and specificity of 64%. Conclusions Based on our findings, TNFR2 is a predictive biomarker for eGFR decline in MGN, correlating with renal inflammation and predicting deterioration in renal function. TNFR2 emerges as a promising biomarker for early identification in patients at risk of renal function decline.
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BACKGROUND: The presence of microvascular inflammation (MVI) characterized by leukocyte margination in the glomeruli (glomerulitis, Banff score 'g') and peritubular capillaries (peritubular capillaritis, Banff score 'ptc') is a hallmark histological feature of antibody-mediated rejection (AMR), even in the absence of circumferential C4d positivity. In this study, we assessed the efficacy of pre-transplant plasma cytokines as an ancillary screening tool to identify MVI in kidney allograft indication biopsies to facilitate better graft survival. METHOD: This single-center prospective analytical study comprises 38 kidney transplant recipients whose peripheral blood was collected before transplant and assessed for the plasma cytokine concentrations of FOXP3, IL-6, TGF beta, and IL-17 using enzyme-linked immunosorbent assays (ELISA). Histopathological assessment was done in post-transplant indication biopsies, and Banff scores of 'g+ ptc' were calculated to categorize recipients into three MVI groups. The correlational, regression, and ROC curve analyses were used to assess the association and predictive ability of the cytokines with respect to MVI. RESULTS: In our study cohort, 27 recipients had MVI=0, five had MVI=1, and six had MVI≥2. A significant difference in plasma cytokines was observed between these groups, and we found a strong negative correlation of FOXP3 with MVI, whereas a strong positive correlation of IL-6, TGF beta, and IL-17 was recorded with MVI. We have also assessed the predictive ability of these cytokines, FOXP3, IL-6, TGF-beta, and IL-17, through the ROC curve, which showed an AUC of 0.70, 0.76, 0.84, and 0.72, respectively. CONCLUSION: Our findings suggest that the pre-transplant levels of cytokines FOXP3, IL-6, TGF-beta, and IL-17 could be measured to identify recipients at risk of post-transplant MVI, which could further serve as an additional tool for effective management of the kidney allograft.
