Pre-Transplant Cytokine Levels as Signatures of Microvascular Inflammation in Kidney Allograft Biopsies.

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.

Soluble Tumor Necrosis Factor Receptor 2: A Promising Predictive Biomarker for Renal Dysfunction in Membranous Glomerulonephritis.

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.

Maternal serum and fetal cord-blood ischemia-modified albumin concentrations in normal pregnancy and preeclampsia: a systematic review and meta-analysis.

BACKGROUND/AIMS: A meta-analysis of maternal serum ischemia-modified albumin (IMA) and fetal cord-blood IMA concentrations in normal pregnancy (NP) compared to non-pregnant healthy controls (HC) and in preeclampsia (PE) compared with normal pregnant controls were studied. METHODS: All major databases were searched for eligible studies. We included eight studies comparing serum IMA between NP and HC, 14 studies comparing serum IMA between PE and NP and five studies comparing cord-blood IMA between PE and NP groups. Meta-analyses on these included studies were performed using Review Manager 5.3. Pooled-overall effect size as standardized mean difference (SMD), publication bias, subgroup, and sensitivity analysis data were generated. RESULTS: Random-effects meta-analysis indicated a significant increase in serum IMA in the NP group (SMD = 0.98, p = .01) and the PE group (SMD = 0.94, p < .0001) as compared with HC and NP groups, respectively. And, the cord-blood IMA has been found to be significantly increased in PE (SMD = 6.51, p < .0001) compared with the NP group. CONCLUSIONS: This meta-analysis, the first of its kind showed that the increased serum IMA concentrations were indicative of increased oxidative stress in NP and PE. Measurement of maternal serum IMA and fetal cord-blood IMA concentrations were useful as simple, novel, and inexpensive markers of oxidative stress (OS) status in PE patients. Future large-scale studies are needed to explore IMA in relationship to the disease severity in PE.