Year in Review

The COVID-19 pandemic and the Movement for Black Lives have focused attention on racial disparities in kidney health outcomes. In 2020, kidney professionals highlighted threats posed by racism and other negative social drivers of kidney health, and proposed solutions to address these issues through scholarship and advocacy for social justice.

In 2020 a number of clinical trials have provided insights into therapeutic approaches for the treatment of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis and lupus nephritis. Moreover, mechanistic insights have potential to open new therapeutic strategies in the future.

Genetic research in nephrology is rapidly advancing. Key studies published in 2020 demonstrate that genetic findings can provide new tools for patient diagnosis and risk stratification as well as important insights into kidney physiology and disease mechanisms that could potentially lead to novel therapies.

The consequences of the COVID-19 pandemic have been devastating; however, evidence suggests that patients with, or at risk of, kidney disease are disproportionally affected. Patients on dialysis and kidney transplant recipients are at higher risk of adverse outcomes from COVID-19, whereas, conversely, patients with severe COVID-19 are at increased risk of acute kidney injury, with short-term and possibly long-term consequences for nephrological care.

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.

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.

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.

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.

The function of polycystin proteins and the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) are not well understood. Studies published in 2018 made important contributions to the understanding of genetic mechanisms, the structure of the polycystin complex and the roles of G-protein signalling and the immune system in ADPKD.

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.

Technical advances in genome sequencing and association studies have yielded critical insights into the genetic architecture of kidney diseases. Here, I summarize four key studies from 2017 that deciphered the genetic basis of known and novel diseases and provided insights into the mechanisms of glomerular, developmental defects and manifestations of kidney disorders.

2017 saw the emergence of a new era in renoprotective medicine for diabetic kidney disease with reports of promising renal outcomes with the sodium–glucose cotransporter 2 (SGLT2) inhibitors empagliflozin and canagliflozin from follow-up analyses of the EMPA-REG OUTCOME trial and the CANVAS Program, respectively, and with use of the glucagon-like peptide 1 (GLP1) agonist liraglutide in the LEADER trial.

New findings in 2017 enhanced our understanding of the mechanisms that regulate blood pressure. Key studies provided insights into immune mechanisms, the role of the gut microbiota, the adverse effects of perivascular fat and inflammation on the vasculature, and the contribution of rare variants in renin–angiotensin–aldosterone system genes to salt sensitivity.

In 2017, progress was made in several aspects of immune-mediated kidney disease. Mechanistic studies provided new insights into the underlying signals that confer risk to, or protection from, immune pathways, whereas new approaches to the treatment of immunological kidney disease will hopefully translate into a move away from the use of toxic corticosteroids.

Studies of cellular energetics have revealed important roles of metabolic pathways in determining cell fate and response to injury. Insights from 2017 into the mechanisms underlying these pathways might identify therapeutic targets to minimize injury and promote repair.

Approaches to effectively prevent and manage organ dysfunction in critically ill patients remain elusive. Key studies in 2016 highlighted the challenges in finding effective treatments for renal failure in sepsis and assessed the optimal timing of renal replacement therapy initiation in critically ill patients with acute kidney injury.