WMJ Vol 124 Issue 1: Association of Rare Variants in Kidney Developmental Genes With Chronic Kidney Disease and Blood Pressure: A UK Biobank Study

ABSTRACT

Introduction: Chronic kidney disease (CKD) and hypertension are heritable traits. The source of this heritability remains largely unknown, and exploration has been limited principally to common genetic variants, with few studies having examined rare variants.

Methods: In this cross-sectional observational study, we evaluate whole exome sequencing data using the UK Biobank to identify the ability of rare variants in 58 kidney developmental genes to predict CKD or elevated blood pressure using logistic regression models with subgroup analysis performed by ancestry.

Results: Significant predictors of CKD included rare variants in CLCN5 (OR 1.59; 99% CI, 1.02–2.47; P = 0.007). Predictors of blood pressure included rare variants in SIX1 (OR 0.57; 99% CI, 0.35–0.94; P = 0.004) and NPHS1 (OR 0.84; 99% CI, 0.72–0.99; P = 0.005), which were protective against blood pressure elevation, and WT1 (OR 1.58; 99% CI, 1.02–2.45; P = 0.007), which was associated with elevated blood pressure. In individuals of White British ancestry, rare variants in SIX1 protected against elevated blood pressure (OR 0.58; 99% CI, 0.34–0.99; P = 0.009). Among individuals of non-White British ancestry, predictors of CKD included rare variants in SLC12A3 (OR 2.02; 99% CI, 1.08–3.78; P = 0.004) and CALB1 (OR 3.12; 99% CI, 1.15–8.47; P = 0.003). Presence of rare variants in WT1 significantly predicted elevated blood pressure (OR 2.49; 99% CI, 1.08–5.78; P = 0.005).

Conclusions: From this study, we conclude that rare variants in kidney developmental genes contribute to the risk of developing CKD and elevated blood pressure. These associations vary by ancestry.

Intended Audience

The intended audience for this continuing education activity is healthcare professionals caring for the people of Wisconsin and beyond.

Learning Objectives

As a result of participating in this journal-based activity, healthcare team members will be able to:

  1. Explain the relationship between lower nephron endowment and the risk of developing chronic kidney disease (CKD) and hypertension
  2. Summarize results of the cross-sectional observational study designed to identify genes of kidney development in which rare variants are predictive of blood pressure outcomes or chronic kidney disease.
  3. Discuss how findings on rare genetic variants in kidney developmental genes may inform future precision medicine approaches to screening and risk stratification for CKD and hypertension
Course summary
Available credit: 
  • 1.00 AAPA Category 1 CME
  • 1.00 AMA PRA Category 1 Credit™
  • 1.00 ANCC Contact Hours
  • 1.00 University of Wisconsin–Madison Continuing Education Hours
    • 1.00 Approved for AMA PRA Category 1 Credit™
Registration opens: 
03/10/2026
Course expires: 
03/09/2027
Cost:
$0.00
Part of: 
Wisconsin Medical Journal Volume 124
Rating: 
0

FACULTY DISCLOSURE

It is the policy of the University of Wisconsin–Madison Interprofessional Continuing Education Partnership (ICEP) to identify, mitigate and disclose all relevant financial relationships with ineligible companies* held by the  speakers/presenters, authors, planners, and other persons who may influence the content of this accredited continuing education (CE). In addition, speakers, presenters and authors must disclose any planned discussion of unlabeled/unapproved uses of drugs or devices during their presentation.

For this accredited continuing education activity all relevant financial relationships have been mitigated and detailed disclosures are listed below.

Name of IndividualIndividual's Role in ActivityFinancial Relationship DisclosureDiscussion of Unlabeled/Unapproved Uses of Drugs/Devices
Marianna Shershneva, MD, PhDAccreditation SpecialistNo relevant relationships with ineligible companies to discloseNo
James Eberhard, MFAAccreditation SpecialistNo relevant relationships with ineligible companies to discloseNo
Benjamin L. Spector, MDAuthorNo relevant relationships with ineligible companies to discloseNo
Byunggil Yoo, MSAuthorNo relevant relationships with ineligible companies to discloseNo
Neil Miller, PhDAuthorNo relevant relationships with ineligible companies to discloseNo
Monica Gaddis, PhDAuthorNo relevant relationships with ineligible companies to discloseNo
Isabelle Thiffault, PhDAuthorNo relevant relationships with ineligible companies to discloseNo
Laurel Willig, MD
 		AuthorNo relevant relationships with ineligible companies to discloseNo
Tripti Singh, MDReviewerNo relevant relationships with ineligible companies to discloseNo
Venkata Manchala, MDReviewerNo relevant relationships with ineligible companies to discloseNo
Fahad Aziz, MDEditorNo relevant relationships with ineligible companies to discloseNo
Roberta Pawlak, PhD, RN, NEABCReviewerNo relevant relationships with ineligible companies to discloseNo
Caitlin Weitzel, APNP, ACNP, MSNReviewerNo relevant relationships with ineligible companies to discloseNo
Kevin Wyne, PAC, MPAS, MScReviewerNo relevant relationships with ineligible companies to discloseNo

*Ineligible companies are those whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on, patients. The ACCME does not consider providers of clinical services directly to patients to be ineligible companies.

Discloser List CME Internal Report

Accreditation and Credit Designation Statements

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Accreditation Statements
In support of improving patient care, this activity has been planned and implemented by the University of Wisconsin–Madison ICEP and the Wisconsin Medical Journal.  The University of Wisconsin–Madison ICEP is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.
 

American Medical Association (AMA)

The University of Wisconsin–Madison ICEP designates this journal-based CE activity for a maximum of 1.0 AMA PRA Category 1 Credit™.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

 

American Nurses Credentialing Center (ANCC)

The University of Wisconsin–Madison ICEP designates this journal-based CE activity for a maximum of 1.0 ANCC contact hour.  

American Academy of Physician Assistants (AAPA)

The University of Wisconsin–Madison ICEP has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. This activity is designated for 1.0 AAPA Category 1 CME credits. Approval is valid until 03/09/2027. PAs should only claim credit commensurate with the extent of their participation.

 

Continuing Education Units

The University of Wisconsin–Madison ICEP, as a member of the University Professional & Continuing Education Association (UPCEA), authorizes this program for 0.1 continuing education units (CEUs) or 1 hour.

Available Credit

  • 1.00 AAPA Category 1 CME
  • 1.00 AMA PRA Category 1 Credit™
  • 1.00 ANCC Contact Hours
  • 1.00 University of Wisconsin–Madison Continuing Education Hours
    • 1.00 Approved for AMA PRA Category 1 Credit™

Cost:
$0.00
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