Is fetuin-A a biomarker of dialysis access dysfunction?

BACKGROUND: The arteriovenous (AV) access function of hemodialysis (HD) patients can be impaired by afferent artery stiffness due to preexisting microcalcification and by venous stenosis secondary to neointimal hyperplasia in whose development participates an upregulated local inflammatory process. Fetuin-A is a circulating potent inhibitor of vascular calcification and plays an important anti-inflammatory role. The aims of this prospective study were to investigate the relationship between baseline serum fetuin-A levels and: blood flow (QA) values at baseline, AV access failure (thrombosis or intervention for stenosis) during follow-up and primary unassisted AV access patency. METHODS: We measured baseline serum fetuin-A levels and QA values of the AV access in 64 HD patients under routine QA surveillance for stenosis. Patients were classified into tertiles according to their baseline fetuin-A levels (g/L): <0.5 (tertile-1), 0.5-1.20 (tertile-2), and >1.20 (tertile-3). RESULTS: Fetuin-A was positively correlated with QA (Spearman coefficient = 0.311, p = 0.012). Fourteen patients (21.9%) underwent AV access failure and they had lower fetuin-A (0.59 ± 0.32 g/L) and lower QA (739.4 ± 438.8 mL/min) values at baseline compared with the remaining patients (1.05 ± 0.65 g/L and 1273.0 ± 596.3 mL/min, respectively) (p = 0.027 and p < 0.001, respectively). The AV access failure rate was highest (34.8%) in tertile-1 (lowest fetuin-A level). Unadjusted Cox regression analysis showed a decrease in the risk of AV access patency loss by increasing fetuin-A concentration (hazard ratio 0.395 (95% confidence interval: 1.42-1.69), p = 0.044) but it was not confirmed in the adjusted model, although the hazard ratio was low (0.523). Kaplan-Meier analysis showed that patients in tertile-3 (highest fetuin-A concentration) had the highest primary unassisted AV access patency (λ2 = 4.68, p = 0.030, log-rank test). CONCLUSION: If our results are confirmed in further studies, fetuin-A could be used as a circulating biomarker to identify HD patients at greater risk for AV access dysfunction, who would benefit from much closer dialysis access surveillance.

The Density of Renal Lymphatics Correlates With Clinical Outcomes in IgA Nephropathy.

Introduction: IgA nephropathy (IgAN) is the most common primary glomerulonephritis (GN) worldwide. The disease course fluctuates, and the most important challenge is the considerable variation in the time lag between diagnosis and the development of a hard clinical end point, such as end-stage kidney disease (ESKD). The reaction of renal tissue to damage resembles the common wound-healing response. One part of this repair in IgAN is the expansion of lymphatic vessels known as lymphangiogenesis. The aim of this work was to establish the prognostic value of the density of lymphatic vessels in the renal biopsy at the time of diagnosis, for predicting the risk of ESKD in a Spanish cohort of patients with IgAN. Methods: We performed a retrospective multicenter study of 76 patients with IgAN. The end point of the study was progression to ESKD. The morphometric analysis of lymphatic vessels was performed on tissue sections stained with antipodoplanin antibody. Results: Density of lymphatic vessels was significantly higher in patients with IgAN with mesangial hypercellularity >50%, segmental sclerosis, higher degrees of interstitial fibrosis, and tubular atrophy. Patients with more lymphatic vessels had significantly higher values of proteinuria and lower estimated glomerular filtration rate (eGFR). A density of lymphatic vessels ≥8 per mm2 was associated with a significantly higher rate of progression to ESKD at 3 years from biopsy. After adjustment for the International IgAN prediction score, at the multivariate logistic regression, high density of lymphatic vessels (≥8 per mm2) remained significantly associated with a higher rate of early progression to ESKD. Conclusion: This study contributes to the understanding of the natural history of the progression to ESKD in patients with IgAN revealing the density of lymphatics vessels may optimize the prognostic value of the International IgA predicting tool to calculate the risk of ESKD, favoring the evaluation of new targeted therapies.

The impact of pre-existing radial artery pathology by histological assessment on the maturation, function and patency of the radiocephalic fistula for hemodialysis.

BACKGROUND: We prospectively analyzed the effect of preexisting structural changes of the radial artery (RA) wall by histological examination on the wrist radiocephalic fistula (RCF) outcomes. METHODS: During RCF creation, one segment of the RA wall was collected and its histomorphometric analysis was performed. The RCF function was evaluated by measuring blood flow rate. RESULTS: At the end of follow-up, 75.7% of the thirty-seven patients enrolled were performing hemodialysis by using their successful RCF and 24.3% of them showed early RCF failure. Compared to patients with a healthy RA, the RCF of those with medial RA microcalcification reached up a lower flow and a shorter primary patency (P=0.005 and P=0.040, respectively). The RA microcalcification was predictive of the RCF function (coefficient -614.9, 95% CI: -994.7 to -235.1, P=0.003). Compared to patients with successful RCF, those with failed RCF had a greater frequency of weak RCF thrill after releasing the clamps (P=0.045). Dependence on hemodialysis during RCF placement was predictive of its early failure (OR: 23.2, 95% CI: 1.76 to 306.9, P=0.017). Both having at least one cardiovascular comorbidity (HR 4.30, 95% CI: 1.29 to 14.39, P=0.018) and a thicker media layer of the RA (HR 1.60, 95% CI: 1.87 to 2.15, P=0.002) were predictive of primary RCF patency. CONCLUSIONS: The function and survival of the successful RCF were related to preoperative RA abnormalities such as microcalcification and media layer thickness. Both dependence on hemodialysis during RCF placement and an attenuated RCF thrill were associated with early RCF failure.

Beneficial dose conversion after switching from higher doses of shorter-acting erythropoiesis-stimulating agents to C.E.R.A in CKD patients in clinical practice: MINERVA Study.

PURPOSE: To assess whether the correction dose recommended by the summary of product characteristics was adequate and to confirm the adequacy of the recommended conversion dosing strategies from shorter-acting erythropoiesis-stimulating agents (ESAs) to continuous erythropoietin receptor activator (C.E.R.A) in anaemic chronic kidney disease (CKD) patients in the clinical setting. METHODS: This was a 12-month, multicenter, prospective, observational study in anaemic CKD patients on haemodialysis and not on dialysis receiving C.E.R.A (at least one dose). RESULTS: A total of 227 patients were included (not on dialysis; n = 142; haemodialysis: n = 85). The present analysis was conducted on ESA-naïve patients (not on dialysis: n = 31) and patients switched from other ESA (not on dialysis: n = 63; haemodialysis: n = 57). Both on and not on dialysis patients switched from other ESA received lower starting C.E.R.A doses than those recommended, and remained stable during the 12-month period. The higher the previous ESA dose was, the more beneficial the C.E.R.A dose conversion factor was. The proportion of patients with stable haemoglobin within the target range (11-13 g/dL) did not vary during the 12-month period both in nondialysis CKD patients and in those undergoing dialysis [baseline: 42 (66.7 %) and 34 (59.6 %); month 6: 21 (55.3 %) and 26 (50.0 %); month 12: 20 (64.5 %) and 25 (69.4 %), respectively]. In naïve patients, the mean weight-adjusted C.E.R.A dose during the study (1.19 ± 0.49 µg/kg/month) was similar to the recommended one. C.E.R.A was well tolerated. CONCLUSIONS: Conversion from shorter-acting ESAs to C.E.R.A doses lower than those recommended can efficiently maintain target haemoglobin levels both in nondialysis and haemodialysis CKD patients, particularly when switching from higher ESA doses. A monthly C.E.R.A dose of 1.2 µg/Kg seems adequate for anaemia correction.