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Chronic kidney disease (CKD) is known to be associated with cognitive impairment, but the mechanisms that underlie this kidney–brain connection are unclear. A recent study provides evidence that CKD is an independent risk factor for cognitive decline due to cerebral small vessel disease.
Kidney donation and chronic kidney disease are associated with an increased risk of pre-eclampsia. A recent study in pregnant uninephrectomized mice provides new insights into the mechanisms that underlie these associations and potential therapeutic strategies.
A new study used metabolic tracing of the three main carbon sources (glucose, glutamine and lipids) on cultured slices of mouse kidneys to identify the dynamic metabolic changes that occur after injury in different segments of the kidney tubule at the single-cell level.
Chronic kidney disease (CKD) is often well advanced before it is detected. Although polygenic scores may enable the early stratification of patients at risk of CKD, the transferability of polygenic scores for the prediction of CKD to populations of non-European ancestry was limited. A new cross-ancestry polygenic score for CKD overcomes these issues, demonstrating good performance across ancestries.
Two recent randomized trials provide evidence to guide the management of sepsis. The CLASSIC trial reports that restrictive fluid therapy has no mortality benefit compared to a standard regimen in patients with septic shock, whereas the LOVIT trial reports that high-dose intravenous vitamin C might be harmful in patients with severe sepsis.
Necroptosis is a form of regulated necrosis in which RIPK3 is activated by binding to RIP homotypic interaction motif (RHIM)-containing proteins. Now, researchers describe a non-canonical pathway of RIPK3 activation that is triggered by osmotic stress and NHE1-mediated cytosol alkalinization. This previously undescribed mechanism of osmotic stress-induced necroptosis might have implications for treating cancer and other diseases.
A post hoc analysis of the COAPT trial suggests that transcatheter mitral valve repair for secondary mitral regurgitation is efficacious in patients with heart failure and chronic kidney disease. The intervention also reduced the risk of kidney failure, raising hypotheses regarding the mechanisms that link heart failure and loss of kidney function.
Targeting type I interferon immune responses is a potential strategy for the treatment of systemic lupus erythematosus. Although a phase 2 clinical trial of anifrolumab did not meet its primary end point, further studies are needed to assess the effects of interferon blockade on flare rates of lupus nephritis. However, the observed higher risk of herpes zoster associated with anifrolumab use suggests that caution is warranted with this strategy.
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.