While most CKD cases in the U.S. are caused by diabetes (40%), high blood pressure (25%), or other acquired conditions, genetic disorders are increasingly recognized as a key factor, especially in children and young adults. In fact, recent genetic studies show that between 10% and 20% of CKD cases in adults have a monogenic (single-gene) origin, often missed without specialized testing. The road to identifying a genetic cause isn’t always straightforward—symptoms often overlap with other kidney diseases, and family history may not be obvious. That’s why understanding the genetic landscape of CKD can be critical to getting the right diagnosis and care.*

Polycystic Kidney Diseases (ADPKD & ARPKD)

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of CKD. Affecting 1 in every 400 to 1,000 people. ADPKD leads to fluid‑filled cysts in both kidneys, progressive kidney enlargement, and eventual failure for over half of patients, often by age 70. 

While less frequent, autosomal recessive polycystic kidney disease (ARPKD) presents much earlier in life, sometimes in childhood, with more severe manifestations. Both parents must carry the mutated gene, and children have a 25% chance of inheriting the disease. 

Alport Syndrome and Cystinosis

If you notice hematuria (blood in urine), hearing changes, or eye symptoms alongside kidney issues, Alport syndrome may be a suspect. This disorder stems from mutations in the genes (COL4A3, COL4A4, COL4A5) responsible for type IV collagen, a key structural protein in kidneys, ears, and eyes. It can follow X‑linked, autosomal recessive, or autosomal dominant inheritance. 

Another rare but serious hereditary condition is cystinosis. A rare genetic disorder that leads to the accumulation of the amino acid cystine within cells, causing crystal formations that damage various organs and tissues. This condition primarily affects the kidneys and eyes but can also impact the brain, muscles, liver, thyroid, pancreas, and testes. 

Tubulointerstitial and Other Monogenic Disorders

Beyond cystic and basement‑membrane disorders, monogenic forms of CKD are increasingly recognized. Recent studies estimate that anywhere from 10% to 20% of CKD cases in adults are due to single‑gene (monogenic) disorders. This highlights the growing importance of genetic diagnosis in managing kidney disease.

Examples of these rarer conditions include medullary cystic kidney diseases, arising from mutations in MUC1 or UMOD, which impair tubular cell function and gradually advance CKD in an autosomal dominant fashion. Similarly, nephronophthisis, often due to mutations in NPHP genes, is a common cause of CKD in children and young adults. 

Getting a Genetic Diagnosis When the Cause Is Unknown

If you’ve been told you have CKD but the underlying cause isn’t clear, you’re not alone. A growing number of people are diagnosed with “CKD of unknown origin”, especially if standard tests rule out diabetes, hypertension, or autoimmune diseases. In these cases, genetic testing may uncover inherited causes that were missed earlier. 

To get started, advocate for yourself. Ask your nephrologist or primary care doctor:

• “Could this be genetic?”
• “Would a genetic test help explain my CKD?”
• “Can I be referred to a genetic counselor or nephrologist who specializes in inherited kidney diseases?”

Bringing a detailed family history can strengthen your case. Mention any relatives with kidney failure, hearing loss, vision issues, or diagnoses like polycystic kidney disease or Alport syndrome. 

Knowing the specific genetic disorder behind your CKD can lead to earlier interventions, tailored therapies, access to clinical trial opportunities, and better long-term outcomes. It can also help you and your care team avoid unnecessary treatments and focus on what truly works for your condition. Don’t be afraid to ask questions, push for answers, and explore whether genetics might be part of the story. The right diagnosis could be the first step toward a better, more manageable future.

*Journal of Clinical Investigation (JCI). (2024) “Impact of Genetic Diagnoses on CKD Management and Prognosis” https://www.jci.org/articles/view/178573

*American Journal of Kidney Diseases (AJKD). (2024) “The Clinical Utility of Genetic Testing in the Diagnosis of CKD of Unknown Cause”. https://www.ajkd.org/article/S0272-6386(24)00871-0/abstract

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