ABSTRACT Aim Rapid decline of kidney function increases the risk of morbidity and mortality, but few studies have conducted genome‐wide association studies (GWAS) to examine the association with kidney function decline. Methods This study used over 110 000 Taiwanese adults with 28 426 follow‐ups in a community‐dwelling longitudinal cohort (Taiwan Biobank) to identify the important genetic loci of five kidney function‐related traits, and to predict the rapid decline of kidney function. Results A total of 68 genetic loci were significantly overlapped in any two of the five kidney‐related traits ( p = 5 × 10 −8 ). A genetic correlation network of 68 genetic loci showed all five kidney function‐related traits were closely related. BUN and creatinine in serum and eGFR were clustered to interconnect with bone density measurement and kidney stone, urine microalbumin was interconnected with hypertension and diabetes, and serum uric acid was positively correlated with serum lipid profiles and gout. Among the 68 significant genetic loci identified, six were significantly associated with kidney function decline among the 28 426 participants with follow‐up data. Using a cohort of 266 early CKD patients (stage I–III) with an averaged ~6 years of follow‐up prospectively, we further found the genetic locus of rs3925584, close to the MPPED2 gene, significantly predicted the slope of kidney function decline ( p = 0.0193). Conclusion These findings provide insights into the genetic determinants of kidney function and its decline in a Taiwanese population.
ABSTRACT Aim Patients undergoing haemodialysis (HD) are at high risk of developing cachexia. Early detection and implementation of interventions are essential. However, associations between cachexia and exercise capacity in patients undergoing HD remain unclear. We examined the associations between cachexia and exercise capacity in HD patients. Methods This cross‐sectional study included outpatients on maintenance HD who underwent the cardiopulmonary exercise testing (CPET) and physical function assessments. Cachexia was defined based on the Asian Working Group for Cachexia (AWGC) 2023 criteria. Pre‐cachexia was diagnosed in patients who did not meet the definition of cachexia but fulfilled at least one mandatory or optional criterion. Pre‐cachexia was operationally classified by the authors based on the AWGC 2023 criteria. Assessments of exercise capacity included peak oxygen uptake (peak VO 2 ), peak work rate (peak WR) and ventilatory equivalent for carbon dioxide (VE/VCO 2 ) slope, measured using the CPET. Exercise capacity was compared across cachexia stages. Results 109 patients (median age: 70.0 years; female: 28.4%) were included, with 21.1%, 45.9% and 33.0% classified as non‐cachexia, pre‐cachexia and cachexia, respectively. Patients with cachexia were older, had a higher VE/VCO 2 slope, and lower peak WR than those without cachexia. Patients with pre‐cachexia also showed a lower peak WR than those without cachexia. Peak VO 2 was not significantly associated with cachexia stage. Conclusion In outpatients on maintenance HD, cachexia was associated with reduced exercise capacity. Furthermore, lower muscle function was observed in the pre‐cachexia and cachexia.
ABSTRACT Donor‐specific antibodies (DSA) are associated with antibody‐mediated rejection (AMR) and graft loss in kidney transplantation. In deceased donor kidney transplantation, virtual crossmatch (VXM) using solid‐phase assays has largely replaced physical crossmatch (PXM). However, comparative data in living donor kidney transplantation (LDKT), particularly for Japanese recipients, remain limited. This study examined the correlation between VXM and PXM and evaluated the incidence of early AMR in Japanese LDKT. We retrospectively analysed 102 LDKT recipients between July 2012 and August 2020, all of whom underwent both VXM and PXM. Patients were stratified into four groups: VXM+/PXM+, VXM+/PXM−, VXM−/PXM+, and VXM−/PXM−. Discordant results were observed in 7% of cases. VXM+/PXM− cases involved low‐titre DSA undetectable by flow cytometric crossmatch (FCXM), whereas all VXM−/PXM+ cases were B‐cell FCXM‐positive in ABO‐incompatible recipients. In ABO‐compatible transplantation, AMR developed in 43% (3/7) of VXM+/PXM+ recipients, 0% (0/1) of VXM+/PXM−, and 2% (1/57) of VXM−/PXM− recipients; no VXM−/PXM+ cases were observed. The VXM+/PXM+ group demonstrated frequent severe AMR, with two cases progressing to chronic active AMR. In contrast, AMR in the VXM−/PXM− group was rare, mild, and successfully managed with steroid pulse therapy alone. These findings indicate that VXM provides reliable immunologic risk stratification in Japanese LDKT and can serve as a practical alternative to PXM without compromising clinical outcomes.
