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Clinical trials of sodium–glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP1) receptor agonists have shown beneficial effects of these agents on kidney outcomes in patients with type 2 diabetes mellitus. Two new cohort studies now demonstrate that these findings are generalizable to the broad range of patients seen in clinical practice.
New data suggest that plasma soluble urokinase receptor (suPAR) might be a predictive biomarker and potential therapeutic target for acute kidney injury (AKI). However, many questions remain regarding the potential of suPAR to inform clinical decision making, identify patients for enrolment in clinical trials and add to the understanding of AKI pathogenesis.
A recent metabolite genome-wide association study (mGWAS) investigated the relationship between genetic factors and the urine metabolome in kidney disease. The findings demonstrate that mGWAS hold promise for identifying novel genetic factors involved in adsorption, distribution, metabolism and excretion of metabolites and pharmaceuticals, as well as biomarkers for disease progression.
The PEXIVAS clinical trial demonstrated that, in patients with anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV), adjuvant plasma exchange did not reduce the risk of all-cause mortality or end-stage kidney disease and a reduced dose of glucocorticoids was not inferior to standard dosing. These findings might warrant a change in standard AAV therapy.
Paradoxically, elevated BMI is a recognized positive prognostic factor in renal cell carcinoma (RCC). A recent investigation of the transcriptomic signatures of RCC tumours and peritumoural tissues suggests potential biological mechanisms underlying this effect. However, the clinical utility of BMI in the context of RCC remains uncertain.
Routinely collected data from electronic health records (EHRs) could potentially be used to facilitate clinical trials. Use of computational phenotypes shows promise for detecting trial-eligible paediatric patients; however, moving from EHR identification to recruitment requires consideration of legal, ethical and logistical challenges.
The KALM-1 randomized double-blind placebo-controlled phase III trial showed that intravenous difelikefalin, a selective κ-opioid receptor agonist, significantly reduces itch intensity in haemodialysis patients with uraemic pruritus. However, 49% of difelikefalin-treated patients showed no improvement. In light of the increasing number of patients with end-stage renal disease, additional treatments are sorely needed.
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.
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.
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.
Erythropoiesis-stimulating agents (ESAs) are widely used to treat anaemia in patients with kidney disease. A potential alternative approach is to increase erythropoietin production using small-molecule inhibitors of prolyl hydroxylase domain (PHD) enzymes. Recent phase III trials of the PHD inhibitor roxadustat demonstrate similar efficacy and safety to ESAs.
A recent study reports the first high-resolution, cryo-electron microscopy-based structure of zebrafish Na+-K+-Cl− cotransporter 1 (NKCC1). This structure provides important insights into the determinants of ion translocation by NKCC1 and other cation-Cl− cotransporters such as NKCC2. It could thus facilitate the design of drugs to target these transporters individually.
A new study of deep learning based on electronic health records promises to forecast acute kidney injury up to 48 hours before it can be diagnosed clinically. However, employing data science to predict acute kidney injury might be more challenging than it seems.
A new study reports important differences between the characteristics of patients with end-stage renal disease on dialysis who are enrolled in clinical trials worldwide and the general US dialysis population. These findings highlight the importance of including older patients and those with comorbidities in clinical trials.
Haemorrhagic stroke is more common in adults with chronic kidney disease (CKD) than in the general population. A recent study reports that low concentrations of LDL significantly increase the risk of haemorrhagic stroke. This finding challenges the concept of aggressive lipid lowering in patients with high cardiovascular risk, including those with CKD.
The MENTOR trial reported that rituximab is superior to ciclosporin for remission of nephrotic syndrome in patients with membranous nephropathy. Rituximab is better tolerated than other treatments but, as up to 40% of patients did not respond to rituximab, alternative immunosuppressive therapies may still be required for a substantial minority of patients.
Understanding of the cardinal role of the kidneys in maintaining fluid and electrolyte homeostasis is deeply rooted in nephrology. However, the fact that the kidney regulates protein and energy homeostasis similarly to the liver has long been overlooked. Comprehensive whole-body metabolomics studies now shed light on this important aspect of kidney function.
The clinical relevance of minor histocompatibility antigens in transplantation is disputed. High-throughput approaches are now being used to investigate the role of genome-wide genetic incompatibility in transplant outcomes. A recent study reports that donor and recipient mismatch at the LIMS1 locus is associated with an increased risk of acute rejection.
Inhibitors of sodium–glucose cotransporter 2 (SGLT2) and dipeptidyl peptidase 4 (DPP4) are widely used in patients with type 2 diabetes to improve glycaemic control and reduce cardiovascular risks. Two recent clinical trials, CREDENCE and DELIGHT, demonstrate that these drugs can also slow down the progression of kidney disease in these patients.
