Reviews & Analysis

New findings implicate sodium transport in α-cell secretory dysfunction, leading to impaired counter-regulatory responses in diabetes. However, these findings also raise important questions about the tissue-specific roles of sodium transport and suggest that inhibitors of sodium transport may have potentially divergent roles in the pancreas, kidney and heart.

Discoveries in 2018 using single-cell sequencing and gene-editing technologies have revealed their transformative potential for the investigation of kidney physiology and disease. Their promise is matched by the speed of their evolution.

Numerous exciting studies that advanced our understanding of immune-mediated kidney disease were published in 2018. Whereas most of these studies analysed the role of pro-inflammatory mediators, several novel anti-inflammatory mechanisms were discovered that involve immune cells and mediators with previously unrecognized protective roles in renal disease.

With many failures, a sense of helplessness has overshadowed the field of acute kidney injury (AKI). Publications in 2018 offer new hope: better drug targets, better end points and improved understanding of conditions that cause AKI and its complications bring promise that a drug will soon be available.

In 2018, consolidating evidence for renoprotective benefits was seen with respect to sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide 1 agonists, which are currently being incorporated into clinical practice. The focus now turns to novel therapeutic targets to optimize renoprotection as diabetic kidney disease grows to epidemic proportions worldwide.

In this Perspectives article, Porrini and colleagues appraise the results of studies that have compared the performance of formulae developed to estimate glomerular filtration rate (GFR) against measured GFR reference methods. They contend that the persistence of errors in GFR estimation formulae indicates an inadequacy of serum creatinine and cystatin C levels as markers of actual renal function.

A new study discovered thousands of expression quantitative trait loci (eQTLs) in the renal glomerular and tubulointerstitial compartments and integrated these data with other omics data sets to identify genes with roles in the pathogenesis of chronic kidney disease. This report reinforces the necessity of using compartment-derived eQTLs to advance kidney genomic discovery.

Fibroblast growth factor 23 (FGF23) regulates phosphate homeostasis by modulating renal phosphate absorption, vitamin D metabolism and parathyroid hormone secretion. In this Review, Marc Vervloet discusses the role of FGF23 on phosphate regulation as well as its additional effects in the cardiovascular and immune systems.

The IDEAL-ICU study reports no mortality benefit of early versus delayed initiation of renal replacement therapy (RRT) in patients with early septic shock and acute kidney injury. In the delayed initiation group, 17% of patients required emergency RRT but more than one-third spontaneously recovered renal function and did not require RRT.

This Expert Consensus Document from the International Kidney and Monoclonal Gammopathy Research Group includes an updated definition of monoclonal gammopathy of renal significance (MGRS) and recommendations for the use of kidney biopsy and other modalities for evaluating suspected MGRS

Klotho proteins are crucial elements of the receptor complex for the endocrine fibroblast growth factors FGF19, FGF21 and FGF23. In this Review, Makoto Kuro-o discusses the functions of the FGF–Klotho endocrine systems in health and disease, including their role in ageing-related disorders.

This Review describes the epidemiology and mechanisms underlying the reciprocal relationship between hepatitis C virus (HCV) infection and chronic kidney disease (CKD). The authors also discuss recommended treatment approaches for patients with HCV infection and CKD, and outline remaining issues in the field.

Autoimmune diseases and kidney transplantation can result in immune-mediated kidney pathology. In this Review, the authors discuss the roles of effector and regulatory B cells and the efficacy of B cell-targeting therapies in these settings.

The complement system has a key role in inflammatory reactions that occur before, during and after transplantation. Here, the authors discuss this role and highlight current and future strategies to regulate complement activation and potentially improve outcomes in kidney transplantation.

This Review focuses on the epidemiology, pathogenesis and treatment of dyslipidaemia in patients with chronic kidney disease (CKD) and end-stage renal disease. The authors discuss emerging clinical data on the use of novel lipid-lowering agents and reappraise the 2013 KDIGO Guidelines for Lipid Management in CKD.

A genetic study using a Mendelian randomization approach provides evidence that albuminuria — as well as being the result of hypertension — might also cause hypertension and cardiometabolic disease. We suggest that a mechanism behind these findings could involve sodium retention by urinary protein-induced activation of the epithelial sodium channel in the distal tubule.

Here, Johnson and Xue describe various physiological and psychosocial challenges that lead to the sensitization of hypertension. These challenges drive neuroplasticity in the brain network controlling sympathetic tone and blood pressure, and provide a new paradigm for understanding essential hypertension.

The polycystin complex structure has been solved at near-atomic resolution. Its surprising architecture provides new insights into the transient receptor potential (TRP) family of cation channels and the pathogenesis of autosomal dominant polycystic kidney disease. This discovery should have a transformative impact on the development of treatment strategies to cure the disease.

A new study reports that genome-wide polygenic risk scores can identify individuals at risk of common complex diseases, such as coronary artery disease or type 2 diabetes, with comparable performance to that of monogenic mutation screens. These findings support the potential clinical utility of genome-wide association study (GWAS)-based risk stratification; however, several issues need to be addressed before this approach can be applied to kidney disease.

Here, Lam and colleagues review advances in understanding the pathogenesis of tuberous sclerosis complex (TSC). Although rapalogues are effective cytostatic treatments for TSC, the unique metabolic vulnerabilities of cells lacking hamartin and/or tuberin might represent opportunities for developing cytocidal treatments.