Reviews & Analysis

Artificial intelligence is increasingly being used to improve diagnosis and prognostication for acute and chronic kidney diseases. Studies with this objective published in 2019 relied on a variety of available data sources, including electronic health records, intraoperative physiological signals, kidney ultrasound imaging, and digitized biopsy specimens.

Applying single-cell RNA sequencing (scRNA-seq) to human tissues can reveal the phenotypic diversity of resident and infiltrating cells at high resolution. In this Review, the authors examine important design considerations for applying this technology to kidney cells and discuss current findings from scRNA-seq studies of lupus nephritis.

Acute kidney injury (AKI) is an important clinical problem that is associated with adverse short- and long-term outcomes. Studies published in 2019 provide new insights into the staging, risk stratification and subphenotyping of AKI as well as the adverse effects of AKI on the heart.

A new study links pathogenic cubilin gene (CUBN) variants to proteinuria without progressive renal impairment, providing reassurance for a subset of patients, calling into question the accepted pathogenesis of glomerulosclerosis and suggesting future therapeutic options.

After nearly two decades, a new therapeutic agent, canagliflozin, received regulatory approval to prevent loss of kidney function, end-stage kidney disease, hospitalization for heart failure and cardiovascular death in patients with diabetic kidney disease. Nonetheless, the residual risk of kidney disease progression and complications remains high, underlining the importance of ongoing therapeutic development.

In this Review, Stewart and colleagues describe how single-cell technologies, in particular single-cell RNA sequencing, can be used to map the complex immune landscape within organs, and how such technologies might provide insights into the role of the immune system in kidney health and disease pathogenesis.

Single-cell genomics provide a powerful approach to investigate the intrinsic complexity of the kidney and understand the diverse cell types and states that exist during kidney development, homeostasis and disease. Several advances were made in 2019 that enhance our understanding of kidney immune cell states in health and disease and the quality of current kidney organoid model systems for studying human diseases.

2019 saw advances in the generation of induced pluripotent stem cell (iPSC)-derived nephron progenitors and in our understanding of how nephrons form in a kidney organoid. Fundamental studies of regeneration in zebrafish continue to provide vital clues as to how we might use iPSC-derived cells to regenerate a human nephron in vivo.

In recent years, the molecular view of clear cell renal cell carcinoma (ccRCC) has been based primarily on gene transcription data with limited information on protein features. A new study led by the Clinical Proteomic Tumor Analysis Consortium now offers a comprehensive view of the ccRCC proteome.

A new genome-wide association study of patients with type 1 diabetes mellitus reveals novel loci that are associated with the development of diabetic kidney disease. The most significant of these loci encodes the α3 chain of type IV collagen, which is an important component of the glomerular basement membrane.

Hepatorenal syndrome type 1 (HRS-1) is a specific type of acute kidney injury (AKI) that is largely considered a functional derangement that ultimately affects renal vasculature tone. This Review describes new insights that suggest that non-haemodynamic tubulo-toxic factors, such as endotoxins and bile acids, might mediate parenchymal renal injury in patients with cirrhosis, suggesting that concurrent mechanisms might contribute to the development of AKI in patients with cirrhosis.

The field of nephrology has conducted fewer trials than other medical specialties. Here, the authors discuss how innovations in trial design and conduct could help achieve the goal of conducting a greater number of larger renal trials.

Here, the authors discuss evidence for a role of NAD⁺ imbalance in the pathogenesis of acute kidney injury (AKI) and chronic kidney disease (CKD). They suggest that disruption of NAD⁺ metabolism may contribute to mechanistic links among AKI, CKD and ageing.

Greater understanding of podocyte biology has improved our understanding of the mechanisms that contribute to the development of nephrotic syndrome. Here, Saleem outlines how our understanding of disease mechanisms that contribute to nephrotic syndrome could transform the classification and treatment of this disease.

Oncometabolites — conventional metabolites that, when aberrantly accumulated, have pro-oncogenic capabilities — have been implicated in renal cell carcinoma (RCC). Here, the authors review the role of oncometabolites in RCC, their origins and downstream effects and their potential applications as novel therapeutic targets and biomarkers.

Once confined to the world of science fiction, advances in information technology, particularly in computational and storage resources, have enabled use of artificial intelligence in medicine to become a reality. Two new studies report the use of deep learning — currently the most promising algorithmic artificial intelligence approach — in kidney pathology.

This Perspectives article, written on behalf of the participants of the NIDDK Workshop on ‘Sex and the Kidneys’, considers opportunities for clinical, basic and translational research into sex differences in renal disease as well as the potential tools and resources needed to conduct this research.

Iron is essential for life but must be strictly regulated to avoid harmful effects. The authors discuss new insights into systemic and cellular iron handling with respect to renal physiology and pathology, current treatment practices and novel therapies for kidney disease.

The authors of this Perspectives article describe the physiological and statistical principles underlying measured glomerular filtration rate (mGFR) and estimated glomerular filtration rate (eGFR). They discuss their limitations, the circumstances under which mGFR and eGFR should be used, and approaches to improve these methodologies.

Fibroblast growth factor 23 (FGF23) is crucial to phosphate and calcium homeostasis. In this Review, the authors discuss how levels of biologically active FGF23 are controlled by balanced FGF23 transcription and protein cleavage, and how serum iron levels, inflammation and erythropoietin affect that balance.