Kidney Week

Abstract: FR-PO0290

Reevaluating the Albuminuria-eGFR Relationship Using Genetics: The READ-GEN Study

Session Information

• Diabetic Kidney Disease: Basic and Translational Science Advances - 1
  November 07, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 701 Diabetic Kidney Disease: Basic

Authors

• Ahluwalia, Tarunveer S., Steno Diabetes Center Copenhagen, Herlev, Capital Region of Denmark, Denmark

Tarunveer S. Ahluwalia, PhD

• Naaman, Cilia Hanna, Steno Diabetes Center Copenhagen, Herlev, Capital Region of Denmark, Denmark

Cilia Hanna Naaman

• Rossing, Peter, Steno Diabetes Center Copenhagen, Herlev, Capital Region of Denmark, Denmark

Peter Rossing, MD, DrMed

• Hansen, Tine, Steno Diabetes Center Copenhagen, Herlev, Capital Region of Denmark, Denmark

Tine Hansen, MD

Background

Chronic kidney disease (CKD) is a global health and economic burden, especially in people with type 2 diabetes (T2D). According to Kidney Disease Improving Global Outcomes (KDIGO) guidelines, early CKD is identified using markers, a) estimated glomerular filtration rate (eGFR) and b) albuminuria (ALB). Albeit many genetic loci are associated with these markers, their shared genetic basis remains unclear. The study aims to map the genetic ALB-eGFR relationship in people with and without T2D to advance CKD risk monitoring and treatment.

Methods

465,446 UK Biobank (UKB) participants (94% Europeans), with information on known ALB single nucleotide polymorphisms (SNPs), urinary albumin, and serum creatinine measures were included. 19,380 had T2D. eGFR was calculated using the 2021 CKD-EPI creatinine race-free equation. After preprocessing (outlier and missing data removal), ALB and eGFR were normalized (log transformed). Associations between 59 SNPs and continuous measures of a. ALB and b. eGFR were tested using multiple linear regression in the full UKB cohort and T2D UKB subgroup. Analyses were adjusted for sex, age, and systolic blood pressure, considering significant at p ≤ 0.05 before and after Bonferroni correction (BC).

Results

Among 59 known ALB SNPs tested, 40 replicated for ALB (p ≤ 0.05). 29 of 40 associated with eGFR before and 24 after BC. The top findings included LRMDA locus (rs67339103 A-allele) associated with higher ALB (Beta = 0.022, p<0.001) and lower eGFR (Beta = -0.001, p<0.001) and SHROOM3 locus (rs10023335 C-Allele) associated with lower ALB (Beta = -0.02, p<0.001) and lower eGFR (Beta = -0.003, p<0.001) after BC. In the T2D population, 16 loci associated with ALB. 4 of 16 loci associated with eGFR before and 3 after BC especially the TSPAN9 gene locus rs10491967 A-allele (ALB, Beta = 0.029, p = 0.003; eGFR, Beta= -0.006, p<0.001).

Conclusion

Our study reveals the complex and pleiotropic genetic relationship between ALB and eGFR, with diverse effects observed in both, general and T2D populations.
We replicate ALB loci (40 in general and 16 in T2D) and identify their pleiotropic relation with eGFR, highlighting significance for CKD risk monitoring and the influence of diabetes status. These findings support future Polygenic Risk Score-based precision studies, aimed at personalized CKD interventions.

Funding

• Private Foundation Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025fx4g7dcf