Genetic screening in kidney transplant candidates

Area of Science:

• Nephrology
• Genetics
• Transplantation

Background:

• Chronic kidney disease (CKD) etiology is unknown in approximately 16% of patients requiring renal replacement therapy.
• Identifying the cause of CKD is crucial for appropriate management and treatment.
• Monogenic kidney diseases represent a significant portion of undiagnosed CKD cases.

Purpose of the Study:

• To determine the prevalence of monogenic kidney diseases among kidney transplant candidates with an unknown cause of CKD.
• To assess the diagnostic yield of molecular investigations in this patient cohort.
• To evaluate the impact of genetic diagnosis on patient management and counseling.

Main Methods:

• Molecular investigation of kidney transplant candidates referred to a nephrogenetic outpatient clinic.
• Inclusion criteria: absence of established diagnosis, glomerular filtration rate <30 ml/min/1.73 m², and/or renal morphology abnormalities, and/or extrarenal involvement, and/or family history of CKD.
• Genetic testing was performed on 84 eligible patients.

Main Results:

• A positive genetic diagnosis was established in 36% of patients (30 out of 84).
• Among those with a genetic diagnosis, 70% had monogenic nephropathy, and 30% carried APOL1 high-risk alleles.
• Patients with a positive genetic diagnosis were more likely to have a family history of kidney disease (70% vs. 37%, P = .004).

Conclusions:

• Genetic testing is effective in diagnosing monogenic kidney diseases in a significant proportion of transplant candidates with unknown CKD.
• Establishing a genetic diagnosis facilitates genetic counseling and informs potential living donor evaluations.
• Molecular investigations are essential for uncovering the etiology of CKD in undiagnosed cases.