Acetate-free biofiltration to remove fibroblast growth factor 23 in hemodialysis patients: a pilot study.

AIM: Serum levels of 32 kDa-phosphaturic hormone fibroblast growth factor 23 (FGF23) rise early in renal failure in order to keep phosphatemia within the normal range; however, this compensatory mechanism itself contributes to chronic kidney disease-mineral bone disorder. High FGF23 is also associated to left ventricular hypertrophy, vascular calcifications and thus increased cardiovascular risk. The aim of this pilot pre-post study was to evaluate the effects of a single hemodiafiltration session with acetate-free biofiltration (AFB) on FGF23 serum levels. METHODS: Nine hemodialysis patients were enrolled; sessions were performed using the Integra® monitor (Hospal, Bologna, Italy) and a polyacrylonitrile membrane. Peripheral venous blood samples were taken before (pre-HD), at mid- and after treatment (post-HD); dialysate samples were collected by the Quantiscan™ monitoring system. FGF23 was measured by a human FGF-23 ELISA kit. Mid- and post-HD values were corrected for hemoconcentration. RESULTS: Pre-HD FGF23 levels positively correlated with dialysis vintage (r = 0.7192; p = 0.0443). They were significantly reduced by the hemodialysis session (from 2.38 ± 1.80 to 1.15 ± 1.21 ng/ml, p = 0.0171) with a reduction ratio of 52.55 ± 28.76%. FGF23 was detected in the dialysate samples. CONCLUSION: FGF23 underwent a significant reduction during AFB. Such removal was greater than that induced by conventional hemodialysis as reported in the literature (19%-decrease using modified cellulosic membranes). This difference may be attributed to the ability of AFB hemodiafiltration to efficiently remove middle molecules by convection. Whether a better clearance of FGF23 during hemodialysis may result in improved cardiovascular outcomes in the long term needs to be confirmed by randomized controlled trials.

Sclerostin levels in uremic patients: a link between bone and vascular disease.

Sclerostin is a marker of low-turnover bone disease in end stage renal disease patients. The aim of this study was to evaluate serum sclerostin in uremic patients, analyzing its behavior during a single hemodialysis session. Twenty-one adult patients on intermittent hemodialysis treatment were enrolled. Acetate Free Bio-filtration (AFB) was the technique employed. Uremic patients were characterized by higher levels of serum sclerostin when compared with values observed in healthy subjects. Sclerostin assessed in pre-dialysis samples was 1.4 ± 1.02 ng/mL, whereas, in post dialysis samples, a reduction of sclerostin values was observed (0.8 ± 0.6 ng/mL; p: 0.008). Sclerostin correlated with parameters of dialysis adequacy, such as creatinine levels and Kt/V values, and it was significantly associated with atherosclerotic disease. Receiver operating characteristics analysis revealed a good diagnostic profile in identifying atherosclerotic disease. Sclerostin, a full dialyzable substance during AFB dialysis, is closely associated with atherosclerotic disease. Its reduction obtained through AFB could represent a defensive mechanism, improving vascular disease and renal osteodystrophy.

Salt-water imbalance and fluid overload in hemodialysis patients: a pivotal role of corin.

Natriuretic peptides (NP) play a key role in regulation of salt and water balance. Corin, a serine protease which activates NP, plays a key role in regulation of blood pressure and cardiac function. The aim of the study was to evaluate the involvement of corin in renal physiopathology, analyze its levels in dialyzed patients and evaluate its relation with fluid overload and comorbidities such as heart failure and blood hypertension. We studied serum corin in uremic patients (n = 20) undergoing hemodialysis therapy (HD) and in healthy subjects (HS). Corin levels in uremic patients were higher than in HS (p < 0.0001). Moreover, its concentration did not change after a single HD session. Hypertensive patients and subject suffering from heart failure were characterized by high values of corin. After multivariate analysis, direct correlations were maintained between corin and dialysis vintage (ß = 0.83; p = 0.0002), heart failure (ß = 0.42; p < 0.0001), systolic blood pressure (ß = -0.70; p = 0.0002) and body weight (ß = -0.39; p < 0.0001). Corin might be implicated in the regulation of salt and water balance and the disturbances of volume homeostasis of HD patients. However, further studies are warranted to understand the role of corin in kidney diseases and to define its diagnostic and prognostic role.

Lipid disorders in patients with renal failure: Role in cardiovascular events and progression of chronic kidney disease.

The spectrum of lipid disorders in chronic kidney disease (CKD) is usually characterized by high triglycerides and reduced high dense lipoprotein (HDL), associated with normal or slightly reduced low dense lipoprotein (LDL)-cholesterol. This dyslipidemia is associated with an increased risk for atherosclerotic cardiovascular disease. Keys for the cardiovascular risk reduction in these patients are lowering the number and modifying the composition of the cholesterol-carrying atherogenic lipoprotein particles. Statins have an important role in primary prevention of cardiovascular events and mortality in non-hemodialyzed CKD patients. The benefits in terms of progression of renal failure are contradictory. Patient education regarding dietary regimen should be part of the CKD clinical management.

[DPP-4 inhibitors in nephropatics].

The use of glucose-lowering drugs in advanced stage diabetic nephropathic patients should be done very carefully. Some drugs are contraindicated or not recommended. The same insulin needs a dose reduction to avoid dangerous hypoglycemia. For some years the use of inhibitors of the DDP-4 has been approved in T2DM patients with CKD III and IV stage, proposing the use without limitations even in case of ESRD. We conducted a prospective observational study of a cohort of 60 patients with T2DM and CKD stage IV, selecting a sample of 15 patients taking an inhibitor of DPP-4 and comparing it with those who took therapy "old" drugs, despite having similar characteristics of CKD. In both groups, we found: 1) the effectiveness of therapy, through the assessment of glycated hemoglobin and glycemic profile; 2) the possible occurrence of "hypoglycemia", "side effects", accelerating the progression of CKD. No patients being treated with inhibitors of DPP-4 have experienced hypoglycemia, or adverse events, or adverse effects on the progression of CKD. The glycated hemoglobin, revealed more stability than the comparison group. Hypoglycaemic episodes were present only in the group receiving intensive insulin. Although kidneys and their dose, in case of high degree of CKD, primarily eliminate inhibitors of DPP-4, with some exceptions, should be reduced, in our experience they have proven beneficial drugs in diabetics with kidney disease, being effective and well tolerated in the case of ESRD, where the only treatment option was represented by insulin.