News & Views

Although direct kidney infection by SARS-CoV-2 remains controversial, a study based largely on autopsies shows increased tubulointerstitial fibrosis in patients with COVID-19 and suggests direct kidney infection. Moreover, in human kidney organoids, SARS-CoV-2 infection upregulates several pro-fibrotic and pro-inflammatory pathways.

Cockayne syndrome is a genetic disease characterized by impairment of DNA repair mechanisms, premature ageing, cachexia and kidney dysfunction. New research in a mouse model of Cockayne syndrome demonstrates that injury induces a subset of kidney proximal tubule cells to express the anorexigenic peptide GDF15. These findings link kidney injury to cachexia and highlight the role of the kidney in mediating inter-organ homeostasis.

Dapagliflozin reduces the risk of new-onset diabetes mellitus, according to results from a pre-specified pooled analysis of the DAPA-CKD and DAPA-HF trials. The study adds to the growing list of sodium–glucose co-transporter 2 inhibitor benefits and raises the possibility of an expanded target patient population.

A recent clinical trial reports promising efficacy and safety data for belzutifan in patients with von Hippel–Lindau (VHL) disease–associated renal cell carcinoma. On the basis of these results, belzutifan became the first therapeutic agent to be approved for the systemic treatment of cancer associated with VHL disease.

Concerns regarding the incorrect use of race as a biological construct and the resulting negative effect on health equity have led to reconsideration of the inclusion of race in equations for estimating glomerular filtration rate. Now, two studies report that cystatin-C-based equations can accurately estimate glomerular filtration rate independent of race.

Four new reports uncover the lineage relationships between cells throughout the body using mutations in the genome as cellular barcodes. The mutational composition of different tissues provides insights into both developmental processes and organ homeostasis, and may have important implications for our understanding of hereditary diseases such as polycystic kidney disease.

A new study reports that common mitochondrial DNA variants in specific haplogroups induce metabolic alterations that affect the onset of common age-related diseases. Unravelling the role of this subtle, long-lasting burden of mitochondrial DNA variants on kidney homeostasis could provide novel insights into the pathophysiology of chronic kidney disease.

Building on previous cardiovascular outcome trials with glucagon-like peptide 1 receptor agonists, the AMPLITUDE-O trial reported significant improvements in major adverse cardiovascular and kidney outcomes with efpeglenatide in type 2 diabetes. A longer-term trial with dose-dependent analysis on kidney outcome components will better define the effects of efpeglenatide in the diabetic kidney.

The AURORA 1 study reports that low-dose voclosporin added to standard immunosuppressive treatment improved rate of remission in patients with lupus nephritis. Further studies are needed to investigate the long-term efficacy and tolerability of voclosporin and to compare the effects of this treatment with those of low doses of tacrolimus or ciclosporin.

Proper glomerular basement membrane (GBM) structure and function are required for appropriate glomerular filtration and abnormalities in the α3α4α5 (α345) network of collagen IV — a GBM component — can lead to disease. New insights into the mechanisms underlying α345 hexamer assembly and function from genetic and structural data identify possible targets for therapeutic modulation.

New data from the ILLUMINATE-A trial of lumasiran demonstrate the safety and efficacy of this RNA interference therapeutic in patients with primary hyperoxaluria type 1. Further studies are required to investigate the potential long-term benefits of this promising therapy.

Glucocorticoids have, for decades, been an enduring component of treatment regimens for anti-neutrophil cytoplasm autoantibody (ANCA)-associated vasculitis. However, a growing number of studies have encouraged a move towards reduced glucocorticoid usage. Findings of the ADVOCATE trial suggest that complement blockade may pave the way for complete glucocorticoid avoidance.

A new study reports the seroprevalence of SARS-CoV-2 antibodies among a cross-section of patients on haemodialysis and uses these data to estimate seroprevalence in the general US population. Although this study demonstrates the potential of monitoring infectious disease prevalence in dialysis populations, the findings should be interpreted with caution.

Recent clinical trials demonstrated that sodium–glucose co-transporter 2 inhibitors can reduce hospitalization for heart failure and improve hard kidney end points in patients with and without type 2 diabetes mellitus. These observations consolidate the view that organ protection is independent of blood glucose control and mitigation of traditional risk factors.

A new study examined post-mortem kidney tissue from 63 patients with COVID-19. The results suggest that SARS-CoV-2 has kidney tropism, including the ability to replicate in kidney cells, and that kidney transduction by SARS-CoV-2 is associated with shorter survival time and increased incidence of acute kidney injury.

Timing of dialysis initiation in critically ill patients is controversial. The STARRT-AKI trial reports that an accelerated initiation strategy did not improve 90-day survival and increased dialysis dependency compared with a standard approach in which patients had greater fluid accumulation and metabolic complications at initiation but 38% avoided dialysis.

A new study uses the OpenSAFELY health analytics platform to identify risk factors for COVID-19 mortality. This analysis, which includes data for more than 17 million people in the UK, suggests that patients with chronic kidney disease are at higher risk than those with other known risk factors, including chronic heart and lung disease.

The generation of local immune responses in organs requires a coordinated effort, not just from immune cells, but also from ‘structural’ cells such as epithelial cells, endothelial cells and fibroblasts. New insights gained from profiling these cells across organs in the mouse emphasizes the important contribution of this structural cell network to organ immunity.

Long-term immunosuppression in transplant recipients is associated with important adverse effects including increased risk of infection and malignancy. New data from the ONE Study suggests that use of cell-based medicinal products containing regulatory immune cells is a potentially useful therapeutic strategy to enable minimization of immunosuppression in these patients.

The mechanism underlying glomerular filtration barrier selectivity has not been resolved. A new study that reports an inverse correlation between slit diaphragm density and proteinuria in a genetic mouse model of focal segmental glomerulosclerosis suggests that podocytes function to compress the glomerular basement membrane (GBM) and that failure of this process results in GBM stretching and increased permeability.