Is genetic testing recommended for patients with Chronic Kidney Disease (CKD)?

Genetic Testing for Chronic Kidney Disease (CKD)

Genetic testing is recommended for CKD patients with specific clinical indicators suggesting hereditary disease, but not for all CKD patients routinely. 1

Indications for Genetic Testing in CKD

Genetic testing should be performed when:

1. Clinical features suggest genetic disease:

   • High prevalence of monogenic subtypes within clinical category (e.g., congenital/cystic nephropathies, steroid-resistant nephrotic syndrome)
   • Positive family history of kidney disease
   • Early age of onset (particularly pediatric CKD)
   • Syndromic/multisystem features
   • Consanguinity
   • Possibility of identifying a condition amenable to targeted treatment (e.g., enzyme replacement therapy for Fabry disease) 1

2. In at-risk relatives:

   • Especially when the individual is a potential kidney donor 1

3. As an alternative to kidney biopsy:

   • In patients at high risk of biopsy-related complications
   • When there is high pre-test probability of finding a genetic variant based on family or clinical history 1

4. When kidney biopsy would not be informative:

   • CKD or kidney failure of unknown etiology with advanced disease
   • When other features suggest hereditary disease 1

5. To guide treatment decisions:

   • Information to guide continuation of immunosuppressive therapy (e.g., in steroid-resistant or partially responsive nephrotic syndrome)
   • When genetic testing can provide prognostic information (e.g., ADPKD or Alport syndrome, age at kidney failure) 1

6. For transplant-related decisions:

   • Diagnosis of diseases with risk of recurrence in renal allografts (e.g., atypical hemolytic uremic syndrome/thrombotic microangiopathy) 1

Clinical Impact of Genetic Testing in CKD

Recent evidence demonstrates significant clinical utility:

• Genetic testing can identify monogenic disorders in approximately 10-11% of adults with CKD 2
• In the RenaCARE study, 20.8% of CKD patients had positive genetic findings, with half resulting in a new or reclassified diagnosis 3
• Genetic results altered management in 90.7% of patients with positive genetic findings, including treatment changes in 32.9% 3
• Most common genes implicated include PKD1, PKD2, COL4A3, COL4A4, COL4A5, UMOD, MUC1, and HNF1B 2

Practical Implementation

When implementing genetic testing in CKD:

• Focus on patients with "red flags" suggesting genetic disease (early onset, family history, hematuria of unknown cause) 2
• Consider cost-effectiveness by applying testing early in the diagnostic process 4
• Provide appropriate pre-test and post-test genetic counseling 4
• Use testing results to guide:
  • Prognostication
  • Personalized management including nephroprotection
  • Transplantation decisions
  • Family screening
  • Reproductive planning 4

Common Pitfalls and Caveats

• Underdiagnosis: Inherited kidney diseases account for 10-15% of cases requiring kidney replacement therapy but are frequently misdiagnosed or labeled as "unknown etiology" 5
• Interpretation challenges: Conflicting interpretation of variant pathogenicity can occur 5
• Resource limitations: Access to genetic testing varies by healthcare setting 1
• Knowledge gaps: Adult nephrologists may have limited familiarity with inherited kidney diseases 5

Quality Assurance Measures

To ensure appropriate implementation of genetic testing:

• Monitor nephrologist adoption of genetic testing and appropriate referral patterns
• Evaluate utilization of genetic results to determine if appropriate changes in diagnosis and care occur
• Define and measure disease-specific outcomes (kidney failure development, progression rates, treatment changes)
• Assess potential harmful impacts of genetic testing
• Establish audits/assessments for centers offering genetic testing in nephrology 1

By following these guidelines, genetic testing can be appropriately integrated into CKD care, improving diagnosis accuracy, treatment decisions, and patient outcomes.