Journal Article

A randomized controlled trial of different serum phosphate ranges in subjects on hemodialysis

Bhargava, Ramya, Hann, Mark, Hurst, Helen, Hutchison, Alastair J., Kalra, Philip A., Brenchley, Paul

2019

Overview

Background Hyperphosphataemia in dialysis subjects is associated with increased mortality. However cause and effect has not been proven, and the ideal phosphate target range is unknown despite KDOQI’s call for studies over 12 years ago. The design and conduct of a randomized controlled trial is challenging because maintaining two groups within differing target ranges of serum phosphate has not been achieved over a long follow-up of 1 year, in a trial setting, before. The SPIRiT study examines the subject acceptance, recruitment and retention rates for such a study in which subjects were randomised to two distinct serum phosphate concentrations, then titrated and maintained over 12 months. Methods A two center trial of 104 hemodialysis subjects randomized to lower range LRG 0.8–1.4 mmol/L or 2.5–4.3 mg/dL) and higher range (HRG 1.8–2.4 mmol/L or 5.6–7.4 mg/dL) serum phosphate groups. Two months’ titration and ten months’ maintenance phase. Interventions were non-calcium phosphate binders, self-help questionnaires, with blood tests at specified time intervals. Results Thirteen percent of the eligible dialysis population were successfully recruited. A mean separation by serum phosphate of 1.1 mg/dL was achieved and maintained between the groups over 10 months. Drop-out rate was 27% with mortality 10%. Nine subjects in the HRG (17.6%) and two subjects in the LRG (3.8%) died during the study, however the study was not powered to detect significant differences in outcomes. Conclusion Randomizing dialysis subjects to separate treatment targets for serum phosphate can achieve a clinically significant sustained separation over 12 months. A large scale longer term study is required to examine outcomes including mortality. Trial registration The trial registration number is ISRCTN24741445 – Date of registration 16th January, retrospectively registered.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Aged / Calcium phosphates / Cardiovascular disease / Cardiovascular Diseases - epidemiology / Care and treatment / Chelating Agents - pharmacology / Chelating Agents - therapeutic use / Chronic Kidney Disease-Mineral and Bone Disorder - drug therapy / Chronic Kidney Disease-Mineral and Bone Disorder - etiology / Cinacalcet - therapeutic use / Clinical outcomes / Clinical Research / Clinical trial / Clinical trials / Demographic aspects / Dialysis / Female / Follow-Up Studies / Hemodialysis / Hemodialysis patients / Humans / Hydroxycholecalciferols - therapeutic use / Hyperphosphatemia / Hyperphosphatemia - blood / Hyperphosphatemia - drug therapy / Hyperphosphatemia - etiology / Hyperphosphatemia - prevention & control / Internal Medicine / Kidney diseases / Kidney Failure, Chronic - blood / Kidney Failure, Chronic - complications / Kidney Failure, Chronic - mortality / Kidney Failure, Chronic - therapy / Lanthanum - pharmacology / Lanthanum - therapeutic use / Male / Measurement / Medicine / Medicine & Public Health / Middle Aged / Mortality / Nephrology / Oral phosphate binders / Parathyroid Hormone - blood / Patient Acceptance of Health Care / Patient Dropouts / Patient outcomes / Patients / Phosphate / Phosphate binders / Phosphates / Phosphates - blood / Phosphorus imbalance / Phosphorus, Dietary / Registration / Renal Dialysis - adverse effects / Renal replacement therapy / Research Article / Sepsis - epidemiology / Sevelamer - pharmacology / Sevelamer - therapeutic use / Sodium / Studies / Systematic review / Titration