Most people who make the transition to maintenance dialysis therapy are treated with a fixed dose thrice-weekly hemodialysis regimen without considering their residual kidney function (RKF). The RKF provides effective and naturally continuous clearance of both small and middle molecules, plays a major role in metabolic homeostasis, nutritional status, and cardiovascular health, and aids in fluid management. The RKF is associated with better patient survival and greater health-related quality of life, although these effects may be confounded by patient comorbidities. Preservation of the RKF requires a careful approach, including regular monitoring, avoidance of nephrotoxins, gentle control of blood pressure to avoid intradialytic hypotension, and an individualized dialysis prescription including the consideration of incremental hemodialysis. There is currently no standardized method for applying incremental hemodialysis in practice. Infrequent (once- to twice-weekly) hemodialysis regimens are often used arbitrarily, without knowing which patients would benefit the most from them or how to escalate the dialysis dose as RKF declines over time. The recently heightened interest in incremental hemodialysis has been hindered by the current limitations of the urea kinetic models (UKM) which tend to overestimate the dialysis dose required in the presence of substantial RKF. This is due to an erroneous extrapolation of the equivalence between renal urea clearance (Kru) and dialyser urea clearance (Kd), correctly assumed by the UKM, to the clinical domain. In this context, each ml/min of Kd clears the urea from the blood just as 1 ml/min of Kru does. By no means should such kinetic equivalence imply that 1 ml/min of Kd is clinically equivalent to 1 ml/min of urea clearance provided by the native kidneys. A recent paper by Casino and Basile suggested a variable target model (VTM) as opposed to the fixed model, because the VTM gives more clinical weight to the RKF and allows less frequent hemodialysis treatments at lower RKF. The potentially important clinical and financial implications of incremental hemodialysis render it highly promising and warrant randomized controlled trials.

Staging to capture kidney function and pathophysiologic processes according to severity is widely used in chronic kidney disease or acute kidney injury not requiring dialysis. Yet the diagnosis of "end-stage kidney disease" (ESKD) considers patients as a single homogeneous group, with negligible kidney function, in need of kidney replacement therapy. Herein, we review the evidence behind the heterogeneous nature of ESKD and discuss potential benefits of recasting the terminology used to describe advanced kidney dysfunction from a monolithic entity to a disease with stages of ascending severity. We consider kidney assistance therapy in lieu of kidney replacement therapy to better reconcile all available types of therapy for advanced kidney failure including dietary intervention, kidney transplantation, and dialysis therapy at varied schedules. The lexicon "kidney dysfunction requiring dialysis" (KDRD) with stages of ascending severity based on levels of residual kidney function (RKF)-that is, renal urea clearance-and manifestations related to uremia, fluid status, and other abnormalities is discussed. Subtyping KDRD by levels of RKF could advance dialysis therapy as a form of kidney assistance therapy adjusted based on RKF and clinical symptoms. We focus on intermittent hemodialysis and underscore the need to personalize dialysis treatments and improve characterization of patients included in clinical trials.

Abdominal compartment syndrome (ACS) is defined as any organ dysfunction caused by intra-abdominal hypertension (IAH), referred as intra-abdominal pressure (IAP) ≥ 12 mm Hg according to the World Society of Abdominal Compartment Syndrome. Abdominal compartment syndrome develops in most cases when IAP rises above 20 mmHg. Abdominal compartment syndrome, while being a treatable and even preventable condition if detected early in the stage of intra-abdominal hypertension, is associated with high rates of morbidity and mortality if diagnosis is delayed: therefore, early detection is essential. Acute kidney injury (AKI) is a common comorbidity, affecting approximately one in every five hospitalized patients, with a higher incidence in surgical patients. AKI in response to intra-abdominal hypertension develops as a result of a decline in cardiac output and compression of the renal vasculature and renal parenchyma. In spite of the high incidence of intra-abdominal hypertension, especially in surgical patients, its potential role in the pathophysiology of AKI has been investigated in very few clinical studies and is commonly overlooked in clinical practice despite being potentially treatable and reversible. Aim of the present review is to illustrate the current evidence on the pathophysiology, diagnosis and therapy of intra-abdominal hypertension and abdominal compartment syndrome in the context of AKI.

Some randomized controlled trials (RCTs) have sought to determine whether different dialysis techniques, dialysis doses and frequencies of treatment are able to improve clinical outcomes in end-stage kidney disease (ESKD). Virtually all of these RCTs were enacted on the premise that 'more' haemodialysis might improve clinical outcomes compared to 'conventional' haemodialysis. Aim of the present narrative review was to analyse these landmark RCTs by posing the following question: were their intervention strategies (i.e., earlier dialysis start, higher haemodialysis dose, intensive haemodialysis, increase in convective transport, starting haemodialysis with three sessions per week) able to improve clinical outcomes? The answer is no. There are at least two main reasons why many RCTs have failed to demonstrate the expected benefits thus far: (1) in general, RCTs included relatively small cohorts and short follow-ups, thus producing low event rates and limited statistical power; (2) the designs of these studies did not take into account that ESKD does not result from a single disease entity: it is a collection of different diseases and subtypes of kidney dysfunction. Patients with advanced kidney failure requiring dialysis treatment differ on a multitude of levels including residual kidney function, biochemical parameters (e.g., acid base balance, serum electrolytes, mineral and bone disorder), and volume overload. In conclusion, the different intervention strategies of the RCTs herein reviewed were not able to improve clinical outcomes of ESKD patients. Higher quality studies are needed to guide patients and clinicians in the decision-making process. Future RCTs should account for the heterogeneity of patients when considering inclusion/exclusion criteria and study design, and should a priori consider subgroup analyses to highlight specific subgroups that can benefit most from a particular intervention.

Purpose of review

Advanced kidney failure requiring dialysis, commonly labeled end-stage kidney disease or chronic kidney disease stage 5D, is a heterogeneous syndrome -a key reason that may explain why: treating advanced kidney dysfunction is challenging and many clinical trials involving patients on dialysis have failed, thus far. Treatment with dialytic techniques - of which maintenance thrice-weekly hemodialysis is most commonly used - is broadly named kidney 'replacement' therapy, a term that casts the perception of a priori abandonment of intrinsic kidney function and subsumes patients into a single, homogeneous group.

Recent findings

Patients with advanced kidney failure necessitating dialytic therapy may have ongoing endogenous kidney function, and differ in their clinical manifestations and needs. Different terminology, for example, kidney dysfunction requiring dialysis (KDRD) with stages of progressive severity could better capture the range of phenotypes of patients who require kidney 'assistance' therapy.

Summary

Classifying patients with KDRD based on objective, quantitative levels of endogenous kidney function, as well as patient-reported symptoms and quality of life, would facilitate hemodialysis prescriptions tailored to level of kidney dysfunction, clinical needs, and personal priorities. Such classification would encourage clinicians to move toward personalized, physiological, and adaptive approach to hemodialysis therapy.