This Week in Nephrology — May 28, 2026

Welcome to This Week in Nephrology. This week we're covering 10 notable papers spanning CKD risk and progression, new mechanisms in kidney injury, and strategies to optimize organ transplantation. Let's dive in.

Our first theme is a deep dive into chronic kidney disease, looking at a new conceptual framework, a better risk prediction tool, and a commonly overlooked medication risk.

A commentary in Kidney International frames the kidney's central role in the newly defined cardiovascular-kidney-metabolic, or CKM, syndrome [4]. This concept, formally recognized by the American Heart Association, unifies obesity, diabetes, hypertension, and cardiovascular disease with CKD, emphasizing the need for interdisciplinary care. The authors review how existing KDIGO guidelines on blood pressure, diabetes, and lipids already provide a robust framework for managing patients with or at risk for CKM syndrome, reinforcing the importance of early detection and comprehensive risk management.

Building on this theme of integrated risk, a study in CJASN evaluated the new PREVENT cardiovascular risk equation specifically in patients with CKD [6]. Researchers compared PREVENT against older models like the Pooled Cohort Equation and SCORE2 in over 4,200 patients from cohorts in South Korea and the United States.

The Study They assessed the models' ability to predict a composite cardio-kidney outcome, which included major adverse kidney events like a 50% eGFR decline or kidney failure, as well as major adverse cardiovascular events.

Results The PREVENT-CVD equation, which incorporates kidney-specific measures, was significantly better at predicting this combined outcome than the other models. Its superiority was driven by a much stronger prediction of kidney events, while also improving discrimination for cardiovascular events and mortality. The authors conclude that the PREVENT score better reflects the shared pathophysiology of cardio-kidney disease and should be a preferred tool for risk stratification in the CKD population.

Rounding out this section is an important finding from Kidney International Reports on a modifiable risk factor for CKD progression: anticholinergic medication burden [7]. Investigators analyzed data from over 3,000 patients in the French CKD-REIN cohort. They calculated each patient's anticholinergic burden at baseline using a standard scoring system. Over a 5-year follow-up, a high anticholinergic burden was independently associated with a more than 50% increased risk of progressing to kidney replacement therapy compared to no burden. A low or moderate burden showed a trend toward increased risk, but it was not statistically significant. This study suggests that disrupting cholinergic signaling may contribute to kidney function decline and underscores the critical importance of regular medication review and optimization in our CKD patients.

Our second theme turns to the mechanisms of kidney injury and the ongoing search for effective treatments.

First, from JASN, a study delves into the molecular pathways of the AKI-to-CKD transition [2]. Researchers focused on the platelet-activating factor receptor, or PTAFR, which was upregulated in renal tubular epithelial cells after ischemia-reperfusion injury in mice. They found that specific deletion of this receptor in tubules protected against kidney injury and fibrosis.

Mechanism Mechanistically, PTAFR activation promoted G2/M cell cycle arrest by preventing the degradation of p53. The team also identified a novel endogenous ligand for this receptor, a specific phosphatidylethanolamine, which was elevated in the urine of human AKI patients and correlated with kidney dysfunction. Finally, they identified a small-molecule antagonist that mitigated injury in their mouse model, pointing to PTAFR as a promising therapeutic target.

Also in JASN, another study explores a potential new role for a familiar drug class. SGLT2 inhibitors are known for their nephroprotective effects, but their impact on autoimmune diseases like ANCA-associated vasculitis has been unclear [5]. In a rat model of AAV, canagliflozin was found to alleviate kidney injury and pulmonary hemorrhage. Transcriptomic analysis showed a suppression of adaptive immunity pathways. In a series of elegant mouse experiments, including an adoptive transfer model, the researchers demonstrated that canagliflozin treatment suppressed pathogenic Th1 and Th17 T-cell responses. This effect was linked to the inhibition of the p38 signaling pathway in activated T cells. These pre-clinical findings suggest SGLT2 inhibitors may have a direct immunomodulatory effect, offering a potential new therapeutic avenue for AAV.

However, the path from promising mechanism to clinical success is not always straightforward. A study in Nephrology, Dialysis, Transplantation reports the results of the MANGROVE trial, a phase 2a study of the CFTR inhibitor GLPG2737 for autosomal dominant polycystic kidney disease [3]. The rationale was that inhibiting CFTR-mediated chloride transport could reduce cyst fluid secretion. Unfortunately, after 52 weeks of treatment, there was no difference between the GLPG2737 group and the placebo group in the primary endpoint of height-adjusted total kidney volume growth. There was also no significant difference in the rate of eGFR decline. While the drug was well-tolerated, it was not efficacious, and the study was terminated early. This serves as a sober reminder of the challenges in developing new treatments for ADPKD.

Our third theme examines system-level challenges and strategies in organ transplantation, covering both deceased and living donation.

A paper in the American Journal of Transplantation looks beyond Organ Procurement Organization performance to ask how individual donor hospital characteristics contribute to deceased donor organ recovery rates [10]. Using 2023 data from nearly 1,800 hospitals, the analysis revealed several key factors. Recovery rates were higher in government-owned and non-profit hospitals compared to private ones. As expected, Level I and Level II trauma centers had much higher recovery rates. Interestingly, higher patient experience and trust scores were associated with lower recovery rates, while higher hospital-level mortality and acuity were associated with higher rates. The OPO's operational model also mattered, with transfer agreements and freestanding donor care units linked to better recovery. The authors argue that future OPO performance metrics may need to account for these hospital-level factors, which significantly influence the donation process.

Shifting from deceased to living donation, a review in Kidney International Reports summarizes the landscape of Kidney Exchange Programs, or KEPs [8]. These programs are essential for overcoming immunological barriers for patients who have a willing but incompatible living donor. The article traces the evolution of KEPs, from simple paired exchanges to complex national and international chains. It highlights ongoing operational challenges, including managing cold ischemia time, complex logistics, and ensuring fairness in matching algorithms. The review also touches on the debates around international kidney exchange and the potential role of new technologies like machine perfusion. It concludes by outlining strategic priorities to optimize the capacity, equity, and outcomes of these life-saving programs.

Finally, we spotlight a particularly vulnerable patient group and a foundational study on the biology of aging.

A narrative review in Kidney International focuses on Neonatal Acute Kidney Injury [9]. The authors highlight the staggering incidence: AKI occurs in roughly one-third of all babies treated in a neonatal intensive care unit. While consensus definitions have improved recognition, they still rely on serum creatinine and urine output, which are insensitive and delayed markers of injury, especially in preterm infants. The review points to the promise of urinary biomarkers, like NGAL, which appear more reliable in neonates than in adults for detecting early injury. Importantly, the authors emphasize that even without novel biomarkers, multidisciplinary AKI stewardship programs that focus on risk stratification and minimizing nephrotoxic medication exposure have been shown to substantially reduce the incidence of AKI in this fragile population.

To close, a study in Nature takes a step back to look at the fundamental biology of aging itself [1]. By integrating over 11,000 transcriptomes from 25 tissues across four different mammals, researchers identified universal transcriptomic signatures of mammalian aging and mortality. These signatures were conserved across species and could predict lifespan, time to death, and chronic diseases. Network analysis revealed a modular architecture, with distinct modules for inflammation, mitochondrial function, and chromatin modification, among others. These module-specific clocks showed that different interventions target different aspects of aging; for example, caloric restriction primarily affected mitochondrial modules, while chronic diseases accelerated inflammatory-module aging. This work provides a powerful framework for quantifying and targeting the aging of specific cellular subsystems, with broad implications for age-related conditions, including CKD.

If you only have time for one paper this week, make it the study in Kidney International Reports on anticholinergic burden and CKD progression [7]. This paper is our Editor's Pick because it provides a simple, immediately actionable step for every clinician: meticulously review medication lists for anticholinergic drugs to potentially slow CKD progression in your patients.

Here are the key takeaways from this week in Nephrology...

First, embrace the new Cardiovascular-Kidney-Metabolic, or CKM, syndrome framework. When assessing risk in your CKD patients, the new PREVENT score is a superior tool for predicting integrated cardio-kidney outcomes compared to older cardiovascular risk models.

Second, be vigilant about medication lists. A high anticholinergic medication burden is independently associated with a more than 50% increased risk of progression to kidney replacement therapy. This is a modifiable risk factor we can address in clinic.

Third, the therapeutic pipeline continues to evolve. While promising preclinical data suggests SGLT2 inhibitors may have immunomodulatory effects in ANCA vasculitis, we were also reminded of the bench-to-bedside gap with a negative trial of a CFTR inhibitor in ADPKD.

Fourth, organ recovery is a system-wide effort. Beyond OPO performance, individual hospital characteristics like trauma level, ownership status, and patient demographics significantly impact deceased donor organ recovery rates, and these factors should be considered in performance evaluations.

Finally, remember our youngest patients. Neonatal AKI is common and consequential. Quality improvement programs focusing on risk stratification and avoiding nephrotoxic medications can make a significant difference in the NICU.

That's your roundup for This Week in Nephrology. The full transcript and references are available on the episode page in your AudioScholar library. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.