Should high-flux hemodialysis be replaced by online hemodiafiltration for treating end-stage renal disease patients?

Abstract

End-stage renal failure is caused by several diseases (mainly diabetic nephropathy, vascular diseases, acute or chronic glomerulonephritis, tubule-interstitial nephritis, and various inherited diseases such as autosomal dominant polycystic kidney disease) that lead to loss of renal function and require the initiation of renal replacement therapies. In developed countries, the prevalence of end-stage renal disease (ESRD) ranges from 1–2 cases per 1000 inhabitants and is associated with high morbidity, mortality and cost. Since the beginning of maintenance therapy for ESRD through dialysis or transplantation, the number of patients treated for terminal kidney failure worldwide has continued to grow at a rate far exceeding the growth rate of the general population. By 2013, more than 1 million patients were estimated worldwide to receive dialysis treatment, with the numbers growing at an annual global average rate of 7% [1]. Nowadays, renal replacement therapies are based on renal transplantation, peritoneal dialysis and various hemodialysis (HD) techniques. Obviously, the most effective treatment option for ESRD patients is renal transplantation and, in fact, approximately 50% of patients with ESRD in developed countries have a functioning graft. Unfortunately, only 25–35% of patients with ESRD will receive a living or deceased kidney allograft during their lifetime. Thus, dialysis techniques will be needed for patients waiting for a kidney transplant and for those who are not candidates for transplantation. Despite continuous improvement in HD devices, membrane biocompatibility, dialysate purification and distinct pharmacological therapies (erythropoietinstimulating agents, phosphate binders or antiparathyroid agents), mortality among these patients remains too high, at approximately 15–20% per year [2]. The kidney participates in the regulation of acid–base balance, electrolyte concentrations, extracellular fluid volume and blood pressure. These functions are accomplished by mechanisms of filtration, reabsorption, and secretion, which are done in the nephron. Filtration (convection) is the process by which small and large molecules are filtered from the blood to make an ultrafiltrate that becomes urine. The kidney generates 180 l of filtrate a day and reabsorbs a large percentage leading to the generation of only approximately 2 l of urine daily. Conversely, conventional HD techniques are based on the diffusion capacity of molecules across a semi-permeable membrane, which allows adequate clearance of low-molecular-weight particles. However, clearance of middle and large molecules is considerably less adequate. To increase the clearance of middle–large molecules, synthetic membranes with high-flux (HF) permeability (ultrafiltration coefficient higher than 20 ml/h/mmHg/m 2 ) were introduced many years ago. Comparison of HF - HD and low-flux HD (LF - HD) has yielded contradictory results: the HEMO study conducted in the USA showed no survival differences [3] while the MPO study showed that HF - HD was associated with better long-term survival in patients with hypoalbuminemia and diabetes mellitus [4]. Clearance of middle–large molecules is maximized by combining diffusive and convective transport, a hemodiafiltration modality that attempts to mimic 1