News & Views

A new study describes the development of proteomics-based ageing clocks that calculate the biological age of specific organs and define features of extreme ageing associated with age-related diseases. Their findings support the notion that plasma proteins can be used to monitor the ageing rates of specific organs and disease progression.

Improved understanding of the interrelated nature of cardiovascular, kidney and metabolic (CKM) health, the development of novel risk prediction equations, and the availability of powerful new therapies provide an opportunity to change the course of CKM health. Achieving such change at a population level will require additional advances to deliver equitable interdisciplinary care.

The demand for kidney transplants is far from met by human donors — a problem that may be solved by the clinical translation of porcine kidney xenotransplantation. A new paper describes the development of genetically ‘humanized’ pigs, the kidneys of which kept nephrectomized cynomolgus macaques alive for up to 2 years.

New clinical studies suggest that mesenchymal stem cell (MSC) therapy can have positive clinical effects, potentially via immunomodulation, in patients with diabetic nephropathy or nephrotic syndrome. These trials suggest that the therapy is safe, but adverse reactions highlight the need to examine the source and functional attributes of MSCs closely.

A recent study reports that adenosine A2A receptor-mediated lymphangiogenesis increases lymphatic clearance of excess Na⁺ from the skin and reduces blood pressure, whereas impairment of this process leads to salt-sensitive hypertension. These findings raise intriguing physiological questions regarding the relationships among sodium, water and blood pressure.

Racial and ethnic minoritized populations are underrepresented in clinical trials in nephrology, but overrepresented in adverse kidney disease outcomes. Targeted enrolment, revision of problematic policies, inclusion of minoritized populations in trial planning, and language-, race- and ethnicity-concordant investigative teams can improve representation in clinical trials.

In a ground-breaking development, rat kidneys have been cryopreserved for an unprecedented duration of 100 days and subsequently transplanted successfully after nano-rewarming. This extraordinary achievement opens new possibilities for the field of organ banking.

Kidney failure is a serious but rare consequence of progressive chronic kidney disease. A meta-analysis of individual participant-level trial data, across heterogeneous treatments and disease groups, has shown glomerular filtration rate (GFR) slope to be a valid, fit-for-purpose and robust surrogate marker of kidney failure.

Human ageing trajectories are highly individual and dependent on genetic and non-genetic factors. An analysis of the interconnectivity of distinct age-related chronic diseases shows that organ-specific chronic diseases accelerate the ageing of other organ systems, which has important implications for mortality. Notably, chronic kidney disease was identified a highly important risk factor for the ageing of other organ systems.

APOL1 risk variants are associated with an increased risk of chronic kidney disease. Findings from a new study demonstrate that a small molecule, inaxaplin, inhibits APOL1 channel function; furthermore, inaxaplin reduced proteinuria in patients with focal segmental glomerulosclerosis and two APOL1 risk variants.

Two studies have applied a mechanical stimulus directly to a cilium, independent of a chemical signal, and demonstrated that force-based bending of a single nodal axoneme is sufficient to induce intraciliary Ca²⁺ flux in a PKD2-dependent manner, which propagates to drive asymmetric gene expression.

An estimated 10–15% of individuals with hypertension are resistant to available antihypertensive therapies. Findings from two new clinical trials — BrigHTN and PRECISION — that assessed the blood pressure-lowering effects of the aldosterone synthase inhibitor baxdrostat and the dual endothelin receptor antagonist aprocitentan, respectively, suggest these approaches hold promise for patients with treatment-resistant hypertension.

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.