Informatics Analysis of Health Indicators and Pathological Manifestations of Foot-Process in Patients with Primary IgA Nephropathy

Objective: This paper focuses on the foot-process in renal biopsies of patients with lgA, and examines their correlation with baseline clinical indicators and pathological manifestations in patients with lgA. Method: A retrospective data of patients who performed renal biopsy proven IgA nephropathy was selected. The patients who reached the agreed standard were grouped based on the degree of foot-process. There were three groups (ABC Groups) (Du, Y. and Huang, C, 2009. The value of proteinuria and foot process fusion in the onset of prognosis of acute kidney disease. Chinese Journal of Integrated Traditional and Western Medicine, 10(1), pp.44-45): group A for patients with no obvious foot-process lesion; group B for patients with segmental foot-process; group C for patients with massive foot-process. The three groups were reviewed in the aspects of baseline clinical indicators and Oxford classification, so as to discover foot-process’ effect on patients with IgA nephropathy. Results: A total of 129 patients with IgA nephropathy were included in the study. Concerning about the clinical baseline indicators related to the degree of foot-process, the 24-hour proteinuria level at admission was statistically significant and positively correlated (r = 0.324, P = 0.000). The comparison between groups showed there was statistically significant difference between group C and group A and group B (P = 0.001, P = 0.035). According to the Oxford Classification, only the differences of mesangial hypercellularity (M) and segmental sclerosis/adhesion (S) were statistically significant (r = 0.239, P = 0.006; r = 0.257, P = 0.003) and were positively correlated. In terms of mesangial hypercellularity (M), the differences between group A and B, group A and C were statistically significant (P = 0.01, P = 0.003). The comparison between group B and group C showed statistical difference (P = −0.031) in segmental sclerosis/adhesion (S). Among the 76 patients with S0 revealed by the Oxford classification, there were 55 patients of glomerulosclerosis, which was positively correlated with the degree of foot process (r = 0.211, P = 0.016). The comparison between group A and group C showed statistical difference (P = 0.014). Conclusion: The severity foot-process was positively correlated with the level of proteinuria. Foot-process is positively related with mesangial hypercellularity, segmental sclerosis and glomerulosclerosis. With more severe the foot-process, there will be more serious mesangial hypercellularity and irreversible glomerular injury. Foot-process is positively correlated with Lee’s Pathological Grading.

The association of microhematuria with mesangial hypercellularity, endocapillary hypercellularity, crescent score and renal outcomes in immunoglobulin A nephropathy

Background Microhematuria is common in immunoglobulin A nephropathy (IgAN). However, current prognostication is based on proteinuria and mesangial hypercellularity, endocapillary hypercellularity, segmental sclerosis, tubulointerstitial fibrosis and crescent (MEST-C) scores. Methods In this retrospective study, we evaluated whether MEST-C score components are associated with the presence of microhematuria at biopsy and whether the degree of microhematuria during follow-up is associated with change in estimated glomerular filtration rate (eGFR), after adjusting for clinical and histological parameters. We identified 125 patients with biopsy-proven IgAN and MEST-C scoring who were not on immunosuppressive therapy at biopsy. Microhematuria was defined as ≥3 red blood cells (RBCs)/high-power field (hpf). Results Of the 125 patients, 97 had microhematuria at baseline and were more likely to have M1, E1 and C ≥ 1 lesions (P < 0.05 for all) compared with patients without microhematuria. Of the 125 patients, 72 had follow-up data available. An increase in the degree of microhematuria was significantly associated with an eGFR decline of −0.81 mL/min/1.73 m2 [95% confidence interval (CI) −1.44 to −0.19, P = 0.01], after adjusting for follow-up time, proteinuria and T score. Severe microhematuria (≥21 RBCs/hpf) was associated with an even larger decline in eGFR (−3.99 mL/min/1.73 m2; 95% CI −6.9411 to −1.0552, P = 0.008), after similar adjustments. Conclusion Degree of microhematuria during follow-up is an independent predictor of eGFR decline after adjusting for clinical and histological parameters. Therefore, monitoring the degree of microhematuria as well as proteinuria is important when evaluating patients with IgAN. Additional studies using improvement in microhematuria as a primary surrogate outcome are needed.

RETROSPECTIVE STUDY OF HISTOLOGICAL ANALYSIS AND ITS CORRELATION WITH CLINICAL PRESENTATION AND OUTCOME OF IGA NEPHROPATHY FROM A TERTIARY CENTRE OF GUWAHATI ASSAM.

Background: IgA nephropathy (IgAN) is one of the most common glomerular diseases with varied presentations. We aimed to study clinical presentation and outcome of IgAN and correlate with histopathology at the time of presentation. Methods: This is a retrospective study in which we analyzed kidney biopsy data, clinical manifestations and outcome of 137 patients with a diagnosis of primary IgAN from 2012 to 2016. Kidney biopsies were reviewed as per Oxford classification assessing mesangial hypercellularity, endocapillary hypercellularity, segmental sclerosis/adhesion, tubular atrophy/interstitial fibrosis. Correlation analysis was done for biopsy findings and clinical presentation/outcome. P score less than 0.05 was taken as significant. Results: Mean age for presentation was 27.35 years with 83 males and 54 females. Asymptomatic urinary abnormality was the most common clinical presentation (28.5%). Mean serum creatinine was 2.23 ± 2.06mg/dl with mean proteinuria of 1.49 ± 1.43g/day. Mesangial hypercellularity (M) and Endocapillary hypercellularity (E) lesions were significantly associated with proteinuria at the time of biopsy (p=0.02& 0.04 respectively). Segmental glomerulosclerosis (S) and tubular atrophy (T) were significantly associated with eGFR and mean arterial pressure at the time of biopsy. Mean time of follow up was 1.6 years. M1, E0, S1, T0 were the most common lesions. M, S and T lesions in biopsy were significantly associated with decrease in GFR at the end of follow up. Conclusion: In our study, most common presentation of IgAN was AUA with rarity of macroscopic hematuria. M, S and T lesions were associated with decreased GFR on follow up. Key words: IgA Nephropathy, Nephrotic Syndrome, Oxford MEST classification

Plasma fractalkine levels are associated with renal inflammation and outcomes in immunoglobulin A nephropathy

Background A recognized noninvasive biomarker to improve risk stratification of immunoglobulin A nephropathy (IgAN) patients is scarce. Fractalkine has been shown to play a key role in glomerular disease as chemoattractant, adhesion and even fibrosis factor. The current study assessed the possibility of plasma fractalkine as a novel biomarker in IgAN patients. Methods Plasma fractalkine was measured in 229 patients with renal biopsy consistent IgAN from 2012 to 2014, and clinical, pathological and prognostic relationships were analyzed. Results The plasma fractalkine levels in IgAN patients were significantly correlated with the creatinine level and 24-h urine protein by both univariate and multivariate analysis. Mesangial hypercellularity was still significantly correlated with the plasma fractalkine levels even after adjustment for other potential predictor variables by multivariate analysis. In addition, the counts of CD20+ B cells or CD68+ macrophage in renal biopsies of IgAN patients were significantly correlated with the plasma fractalkine levels, but not CD4+ and CD8+ T cells. Finally, we concluded that patients with higher plasma fractalkine levels had higher risk of poor renal outcome compared with those with lower plasma fractalkine levels. No association was observed between the CX3CR1 polymorphisms and clinical parameters including plasma fractalkine levels and prognosis. Recombinant fractalkine induced mesangial cells extracellular matrix synthesis and promoted the migration of microphage cells RAW264.7. Conclusions Plasma fractalkine levels were associated with creatinine level, 24-h urine protein, mesangial hypercellularity pathological damage, the CD68+ macrophage and CD20+ B cell infiltration in renal tissue and renal outcome in IgAN patients. Plasma fractalkine might be a potential prognosis novel predictor in Chinese patients with IgAN.