Urine Nephrin and Podocalyxin Reflecting Podocyte Damage and Severity of Kidney Disease in Various Glomerular Diseases-A Cross-Sectional Study.

Background/Objectives: Glomerulopathy is a term used to describe a broad spectrum of renal diseases, characterized by dysfunction of glomerular filtration barrier, especially of podocytes. Several podocyte-associated proteins have been found and proved their usefulness as urine markers of podocyte dysfunction. Two of them are nephrin (NEP) and prodocalyxin (PDC). This study aims to evaluate the association of podocyte damage, as it is demonstrated via the concentrations of urinary proteins, with clinical and histological data from patients with several types of glomerulonephritis. Methods: We measured urine levels of two podocyte-specific markers, NEP and PDC (corrected for urine creatinine levels), in patients with a wide range of glomerulopathies. Serum and urine parameters as well as histological parameters from renal biopsy were recorded. Results: In total, data from 37 patients with glomerulonephritis and 5 healthy controls were analyzed. PDC and NEP concentrations correlated between them and with serum creatinine levels (p = 0.001 and p = 0.013 respectively), and with histological lesions associated with chronicity index of renal cortex, such as severe interstitial fibrosis, severe tubular atrophy and hyalinosis (for PDC/NEP, all p < 0.05). In addition, the PDC and NEP demonstrated statistically significant correlations with interstitial inflammation (p = 0.018/p = 0.028). Regarding electron microscopy evaluation, PDC levels were correlated with distinct characteristics, such as fibrils and global podocyte foot process fusion, whereas the NEP/CR ratio was uniquely significantly associated with podocyte fusion only in non-immune-complex-mediated glomerulonephritis (p = 0.02). Among the other clinical and histological parameters included in our study, a strong correlation between proteinuria >3 g/24 h and diffuse fusion of podocyte foot processes (p = 0.016) was identified. Conclusions: Podocalyxin and nephrin concentrations in urine are markers of podocyte dysfunction, and in our study, they were associated both with serum creatinine and histological chronicity indices.

Coagulation Abnormalities in Renal Pathology of Chronic Kidney Disease: The Interplay between Blood Cells and Soluble Factors.

Coagulation abnormalities in renal pathology are associated with a high thrombotic and hemorrhagic risk. This study aims to investigate the hemostatic abnormalities that are related to the interaction between soluble coagulation factors and blood cells, and the effects of hemodialysis (HD) on it, in end stage renal disease (ESRD) patients. Thirty-two ESRD patients under HD treatment and fifteen healthy controls were included in the study. Whole blood samples from the healthy and ESRD subjects were collected before and after the HD session. Evaluation of coagulation included primary and secondary hemostasis screening tests, proteins of coagulation, fibrinolytic and inhibitory system, and ADAMTS-13 activity. Phosphatidylserine (PS) exposure and intracellular reactive oxygen species (iROS) levels were also examined in red blood cells and platelets, in addition to the platelet activation marker CD62P. Platelet function analysis showed pathological values in ESRD patients despite the increased levels of activation markers (PS, CD62P, iROS). Activities of most coagulation, fibrinolytic, and inhibitory system proteins were within the normal range, but HD triggered an increase in half of them. Additionally, the increased baseline levels of ADAMTS-13 inhibitor were further augmented by the dialysis session. Finally, pathological levels of PS and iROS were measured in red blood cells in close correlation with variations in several coagulation factors and platelet characteristics. This study provides evidence for a complex coagulation phenotype in ESRD. Signs of increased bleeding risk coexisted with prothrombotic features of soluble factors and blood cells in a general hyperfibrinolytic state. Hemodialysis seems to augment the prothrombotic potential, while the persisted platelet dysfunction might counteract the increased predisposition to thrombotic events post-dialysis. The interaction of red blood cells with platelets, the thrombus, the endothelium, the soluble components of the coagulation pathways, and the contribution of extracellular vesicles on hemostasis as well as the identification of the unknown origin ADAMTS-13 inhibitor deserve further investigation in uremia.

Hypocomplementemia is associated with more severe renal disease and worse renal outcomes in patients with ANCA-associated vasculitis: a retrospective cohort study.

BACKGROUND: The complement system has been recently proposed to play an important role in the pathogenesis of ANCA-associated vasculitis (AAV). This study evaluated the value of serum and kidney deposited C3 in predicting renal outcomes in AAV. METHODS: This was a retrospective study of 47 patients with AAV, who were categorized according to their serum C3 levels as hypo- or normo-complementemic and to those with positive or negative kidney biopsy immunofluorescence (IF) for C3. Baseline characteristics as well as progression to end-stage renal disease (ESRD) between the 2 groups were compared. RESULTS: In total, 23% (11/47) were hypo-complementemic; these patients were older (74 vs. 65 years, p = 0.013), had higher creatinine levels (4.9 vs. 2.2 mg/dL, p = 0.006), were more often hemodialysis dependent (64% vs. 19%, p = 0.009) and progressed more often to ESRD (55% vs. 11%, p = 0.01) compared to normo-complementemic patients (n = 36). On multivariate analysis, serum creatinine at diagnosis (HR = 16.8, 95%CI: 1.354-208.62, p = 0.028) and low serum C3 (HR = 2.492; 95% CI: 1.537-11.567; p = 0.044) were independent predictors for ESRD. Among 25 patients with an available kidney biopsy, 56% had C3 deposition by IF and displayed more often a mixed histological pattern (72% vs. 27%, p = 0.033), low serum C3 levels (42% vs. 18%, p < 0.001) and serious infections during follow-up (57% vs. 18%, p = 0.047) compared to those with negative (n = 11) IF staining. CONCLUSION: Almost one of four patients with AAV has low C3 levels at diagnosis which is associated with more severe renal disease and worse renal outcomes (ESRD). This should be taken into account in therapeutic and monitoring strategies.

Peritoneal dialysis as a therapeutic solution in elderly patients with cardiorenal syndrome and heart failure: A case-series report.

BACKGROUND: The aim of this work was to evaluate the impact of peritoneal dialysis (PD) on venous congestion, right ventricular function, pulmonary artery systolic pressure (PASP), and clinical functional status in elderly patients with cardiorenal syndrome (CRS) and chronic heart failure (HF). METHODS: A case series of 21 (17 males, age 70 ± 11 years) consecutive patients with HF along with diuretic resistance and right ventricular dysfunction (median renal failure duration 60 months, range 13-287 months, mean ejection fraction 36 ± 11%) having been engaged in PD; 76% of the patients were under automated peritoneal dialysis (APD), whereas the rest were under continuous ambulatory PD (CAPD). Patients' PASP and central venous pressure (CVP) - through compression sonography - and body weight were evaluated before initiating the PD program and at 6 and 12 months. RESULTS: During the follow-up period, the mortality rate was 8 deaths out of 21 patients (38%) A significant reduction by 29.9% in PASP levels (p = 0.013) and by 42% in CVP levels (p < 0.001), and in right ventricular function assessed by tricuspid annulus tissue Doppler velocity (p = 0.04) was observed, whereas patients' weight increased by 3.7% (p = 0.001). New York Heart Association class improved in 12 patients, whereas in the remaining patients, it remained constant (p = 0.046). In 8 patients, complications were reported (mainly presence of Staphylococcus aureus). In conclusion, PD seems to confer a substantial benefit in clinical status, which is in line with improvement in venous congestion and right ventricular systolic pressure among elderly patients with HF along with CRS.