Plasma p-cresol lowering effect of sevelamer in non-dialysis CKD patients: evidence from a randomized controlled trial.

BACKGROUND: The accumulation of p-cresol, a metabolic product of aromatic amino acids generated by intestinal microbiome, increases the cardiovascular risk in chronic kidney disease (CKD) patients. Therefore, therapeutic strategies to reduce plasma p-cresol levels are highly demanded. It has been reported that the phosphate binder sevelamer (SEV) sequesters p-cresol in vitro, while in vivo studies on dialysis patients showed controversial results. Aim of our study was to evaluate the effect of SEV on p-cresol levels in non-dialysis CKD patients. METHODS: This was a single-blind, randomized placebo-controlled trial (Registration number NCT02199444) carried on 69 CKD patients (stage 3-5, not on dialysis), randomly assigned (1:1) to receive either SEV or placebo for 3 months. Total p-cresol serum levels were evaluated at baseline (T0), and 1 (T1) and 3 months (T3) after treatment start. The primary end-point was to evaluate the effect of SEV on p-cresol levels. RESULTS: Compared to baseline (T0, 7.4 ± 2.7 mg/mL), p-cresol mean concentration was significantly reduced in SEV patients after one (- 2.06 mg/mL, 95% CI - 2.62 to - 1.50 mg/mL; p < 0.001) and 3 months of treatment (- 3.97 mg/mL, 95% CI - 4.53 to - 3.41 mg/mL; p < 0.001); no change of plasma p-cresol concentration was recorded in placebo-treated patients. Moreover, P and LDL values were reduced after 3 months of treatment by SEV but not placebo. CONCLUSIONS: In conclusion, our study represents the first evidence that SEV is effective in reducing p-cresol levels in CKD patients in conservative treatment, and confirms its beneficial effects on inflammation and lipid pattern.

[Renal denervation in ADPKD: an exceptional case]. / Un caso eccezionale di denervazione renale in paziente affetto da ADPKD.

Sympathetic overactivity plays a crucial role in the genesis and aggravation of arterial hypertension in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD). Renal denervation has been shown to be effective and safe in reducing blood pressure (BP) in patients with treatment-resistant hypertension, even with chronic kidney disease (CKD). However, there are no cases in hypertensive patients with ADPKD. We report the exceptional case of a woman with stage 4 CKD secondary to ADPKD and uncontrolled treatment-resistant hypertension. Because of the ineffectiveness of all pharmacological and surgical therapeutic strategies, including the uninephrectomy, renal denervation by radiofrequency ablation of the renal artery was performed. The patient decreased the requirement of antihypertensive medication and the BP showed a remarkable reduction, that resulted stable 12 months after the procedure.

[Enzyme replacement therapy in patients with Fabry disease: state of the art and review of the literature]. / Terapia enzimatica sostitutiva in pazienti con malattia di Fabry.

Anderson-Fabry disease is a hereditary X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme alpha galactosidase A. It results in the accumulation of the glycosphingolypid globotrioasoyl ceramide (Gb3 in different cells and organs, resulting in a multi-system pathology including end organ failure. Patients with Fabry disease present clinically with cardiac, renal and neurological involvement; both life expectancy and quality of life are severely compromised. The current causal treatment for Fabry disease is enzyme replacement therapy (ERT), available since 2001. The two recombinant preparations available for ERT are agalsidase alfa (Replagal) and agalsidase beta (Fabrazyme). They have both been showed to have positive effect on kidney and heart, on the symptoms of pain and quality of life. Few data to date are available on comparison of the two preparations of ERT. This article reviews evidence of the literature and shows our personal experience about the safety and efficacy of ERT.