Kidney Disease

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Kidney Disease
Kidney disease is the ninth leading cause of death in the United States. March was declared National Kidney Month to increase awareness of kidney disease and related risk factors.

Genetic Testing
Genetic testing for renal diseases, like polycystic kidney disease (PKD), nephrolithiasis and nephrocalcinosis, congenital abnormalities of kidney and urinary tract (CAKUT), and nephrotic syndrome, is important for patients with a family history of kidney disease, even if they do not have symptoms. A genetic diagnosis can impact care and affect medical decisions for patients and their families.

Autosomal Dominant Polycystic Kidney Disease (ADPKD)
With a prevalence of 1 in 1,000 to 2,500 people worldwide, autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder. Genetic variants in the complex PKD1 gene are responsible for 85% of ADPKD cases, which makes genetic testing challenging. PKD1 has several pseudogenes that share nearly 98% sequence similarity to exons 1-33. Full coverage of this region is needed to accurately sequence PKD1.

For the PKD1 gene, including exons 1 to 33 (homologous regions), we primarily use next generation sequencing (NGS) (~96%) complemented with Sanger sequencing for low-coverage regions (~4%). For any pathogenic, likely pathogenic, and uncertain variants found in exons 1 to 33, we use long-range PCR based Sanger sequencing to confirm. Therefore, our test provides full coverage of all coding exons of the PKD1 gene plus 10 bases of flanking noncoding DNA in all available transcripts, along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. For full test information, see the Testing Strategy section within our test description.

While ADPKD is often diagnosed through ultrasounds, CT scans, and MRIs, genetic testing for autosomal dominant polycystic kidney disease is important, because there is a 50% chance of inheritance. More than 50% of people with ADPKD will develop kidney failure by age 50, and once kidney failure occurs, dialysis or a transplant are the only options (“What is ADPKD”). Genetic testing can allow for earlier diagnosis and enhanced care management to try to slow the disease.

Autosomal Recessive Polycystic Kidney Disease (ARPKD)
Affecting an estimated 1 in 20,000 children, autosomal recessive polycystic kidney disease is a rare genetic disorder. While the severity of ARPKD varies widely, the most severe cases, which account for ~30% of patients with pathogenic variants in PKHD1, are often neonatal lethal due to the underdevelopment of the lungs caused by poor prenatal kidney function. If an affected child survives the newborn period, the chances for longer term survival are good but many still progress to end stage renal disease (ESRD) and will need dialysis or a kidney transplant before their 10th birthday. While there is currently no treatment or cure for ARPKD, genetic testing can aid in better specialized care immediately after birth and affect health management to handle associated complications (“What is ARPKD”).

Kidney Stones
The formation of kidney stones (i.e. renal stones or urinary stones) is a multifactorial process involving an interaction of environmental, dietary, and genetic factors. 10-15% of adults are affected by kidney stones in their lifetime, and of those, 40% have a family history of kidney stones (University of Wisconsin Hospitals and Clinics). At least 30 genes have been linked to a monogenic form of nephrolithiasis or nephrocalcinosis in autosomal dominant, autosomal recessive, or X-linked inheritance (Braun et al. 2016; Halbritter et al. 2015; Gee et al. 2016). Genetic testing for nephrolithiasis and nephrocalcinosis aids in diagnosis for patients by analyzing multiple genes concurrently. A diagnosis of nephrolithiasis and nephrocalcinosis can influence preventative care, including lifestyle changes, to reduce the formation of kidney stones in affected individuals.

Congenital Abnormalities of Kidney and Urinary Tract (CAKUT)
Accounting for 40-50% of childhood chronic kidney disease cases worldwide, CAKUT represents a group of highly genetically and phenotypically heterogeneous diseases resulting from disturbances in normal kidney development due to exposure to environmental risk factors and/or genetics (Sanna-Cherchi et al. 2018. PubMed ID: 29293093; Vivante et al. 2014. PubMed ID: 24398540; Nicolaou et al. 2015. PubMed ID: 26281895). Despite the multifactorial nature of the CAKUT spectrum, dozens of genes to date have been found to cause monogenic CAKUT (Sanna-Cherchi et al. 2018. PubMed ID: 29293093). The known pathogenic variants in these genes include all types of variants and modes of inheritance, including autosomal recessive, autosomal dominant, and X-linked.

Nephrotic Syndrome
Nephrotic syndrome (NS) is the most common glomerular disease in children. It is a genetically heterogeneous disease defined by proteinuria, hypoalbuminemia, hyperlipidemia, and edema (Benoit et al. 2010. PubMed ID: 20333530; Santín et al. 2011. PubMed ID: 21415313; Preston et al. 2019. PubMed ID: 29181713). While treatment can include taking medications, approximately 20% of nephrotic syndrome cases in young adults and children are classified as steroid-resistant NS (SRNS) in terms of its response to a standardized steroid therapy. These patients tend to have rapid progression to end-stage renal failure. The clinical courses of nephrotic syndrome vary greatly with a wide range of age at onset from birth to adulthood. A conclusive molecular diagnosis is necessary for better personalized treatment and accurate genetic counselling.


Benoit et al. 2010. PubMed ID: 20333530
Braun D.A. et al. 2016. PubMed ID: 26787776
Cornec-Le Gall et al. 2019. PubMed ID: 30819518
Nicolaou et al. 2015. PubMed ID: 26281895
Preston et al. 2017. PubMed ID: 29181713
Rossetti et al. 2012. PubMed ID: 22383692
Sanna-Cherchi et al. 2018. PubMed ID: 29293093
Santín et al. 2011. PubMed ID: 21415313
Tan et al. 2014. PubMed ID: 24374109
University of Wisconsin Hospitals and Clinics Authority. “Genetic Heritability For Kidney Stones.” UW Health,
Vivante et al. 2014. PubMed ID: 24398540
“What Is ADPKD.” PKD Foundation, Accessed February 25, 2020.
“What Is ARPKD.” PKD Foundation, Accessed February 25, 2020.