Nephrology

Exome sequencing clarifies CKD etiology and refines living donor risk assessment

Among 231 kidney transplant recipients, exome sequencing of 409 CKD genes identified pathogenic or likely pathogenic variants in 23%. Genetic diagnoses most often involved cystic kidney disease and glomerulopathy genes and reclassified clinical CKD phenotype in 37% of these cases. Pathogenic variants were found in 4% of 46 prospective living donors, suggesting limited yield of universal testing in asymptomatic donors. In 122 prior donors with adverse post-donation kidney outcomes, 19% carried pathogenic variants, supporting targeted testing of high-risk donors. These findings favor routine genetic workup for recipients with unclear etiology and selective, risk-based testing in donor evaluation and follow-up. 1

Hemoadsorption plus HD modestly lowers mortality and cardiovascular events in ESKD

In 1,362 maintenance hemodialysis patients, hemoadsorption plus HD reduced all-cause mortality versus HD alone over 39.5 months (HR 0.78, 95% CI 0.61-0.99). Cardiovascular mortality and major cardiovascular events were also lower with hemoadsorption (HRs 0.66 and 0.77, respectively). Important adverse events, mainly infections and blood pressure abnormalities, were similar between groups. The control arm predominantly used low-flux HD with intermittent HDF, which may limit extrapolation to centers using high-flux or intensive modalities. These data support incorporating hemoadsorption into chronic HD protocols, where available, to improve long-term cardiovascular outcomes. 2

Preemptive immunosuppression escalation prevents flares in serologic lupus nephritis relapse

Forty-nine lupus nephritis patients in clinical remission but with asymptomatic serologic reactivation were randomized to preemptive treatment or observation for 24 months. Preemptive therapy increased prednisolone to 0.4-0.5 mg/kg/day and optimized mycophenolate or azathioprine, then tapered steroids to baseline by 12 weeks. No kidney flares occurred in the preemptive arm versus five renal flares in controls at a median of 6 months. Preemptive treatment improved anti-dsDNA and C3, and significantly increased flare-free survival for renal, extra-renal, and overall flares. Adverse events and kidney function were similar, supporting this strategy for serologic flares in otherwise stable lupus nephritis. 3

Substantial, frequently missed CKD burden among multinational CAD patients

Among 4,548 coronary artery disease patients from 14 countries, 32% met KDIGO criteria for CKD 6 to 24 months after diagnosis. Of those with CKD, 19.7% were low-moderate, 6.9% high, and 5.6% very high KDIGO risk. Without urinary albumin-creatinine ratio measurement, 51.3% of CKD cases would have been missed. Primary cardiovascular events occurred in 7.9%, with highest incidence in KDIGO high-risk groups, independent of other risk factors. Cardio-renal protective therapy use was low, underscoring missed opportunities for RAAS blockade and SGLT2 inhibitors in this high-risk population. 4