Genetic testing

Current evidence suggests that genetics play a role in the development of kidney disease. Common genetic disorders associated with kidney disease include polycystic kidney disease, Alport’s Syndrome and Fabry’s disease. The advances of genome-wide association studies (GWAS) helped identify several hundred other genes linked to kidney diseases. This made genetic testing a useful tool in the management of kidney disease patients. In this blog, we will detail the benefits of broad-panel genetic testing in kidney disease management.

Next Generation Sequencing

Various methods for identifying genetic variants have been used in the past. The exome is that 2% of the genome that codes for all biological proteins. Next generation sequencing is a new technology that allows DNA sequencing of the entire human exome within a single day. It also captures a broader spectrum of variations that can affect the genetic code. This revolutionary technology can identify mutations associated with CKD. It can also recognize variants associated with an increase in risk or severity of CKD. It is now available for kidney disease patients. This type of “broad-panel genetic testing” can transform care for patients with kidney disease.

Clinical benefits of genetic testing in kidney disease management

Identify diagnosis of unknown causes

While diabetic and hypertensive kidney diseases are the most common causes of kidney failure, there are others. There are instances when providers find themselves unable to identify the cause of kidney disease. Indeed, in some cases, urinalysis is actually “bland” and the workup to identify the cause of kidney disease is negative.
Even a kidney biopsy may not be helpful. It may show glomerulosclerosis and fibrosis (scarring). This does not help identify the original cause of kidney disease. Genetic testing can have a tremendous value in these cases. In fact, whole exome sequencing was able to diagnose up to one third of the patients who had unknown causes of kidney disease.

Reclassify a clinical diagnosis

It is common for providers to label kidney disease patients with unknown causes as hypertensive kidney disease or “nephrosclerosis”. This is because hypertension is common in kidney disease patients. Studies have shown that 60-90% of patients with chronic kidney diseases have high blood pressure. It is often not clear which came first, hypertension or kidney disease. It is possible that patients who were diagnosed with hypertensive kidney disease have another cause. In fact, studies have shown that up to a quarter of kidney diseases can be reclassified with a broad-panel genetic testing.

Target the therapy and workup

Broad-panel genetic testing can help providers avoid unnecessary procedures, tests, and treatments. It gives accurate and “molecular level diagnosis”. It provides a better idea of the outcome of the specific kidney disease. It also helps providers avoid the use of immunosuppressive medications in patients with genetic causes of kidney disease. Furthermore, it can guide therapy for specific genetic causes that we currently have treatment for such as Fabry’s disease. This type of testing may, indeed, eliminate the need for a kidney biopsy.

Role in kidney transplant

Genetic testing can have a tremendous impact in guiding kidney transplant and in the care of kidney transplant recipients. Kidney transplant donors can be pre-screened by broad panel genetic testing to assess if they carry any genetic kidney disease risk. While carrying the genes does not necessarily indicate that the donor will have the disease, it can play an important role in selection. This is especially true for living donor kidney transplant when the recipient has a known genetic kidney disease, and the donor is too young to have any manifestations.
In addition, many immunosuppressive medications that are used by kidney transplant patients are metabolized by well-established pathways that can be affected by genetic SNPs. 
Having this genetic information can help providers prescribe the proper dose of immunosuppressive medications which is critical in transplant patients to avoid rejection or toxicity. This evolving field is called pharmacogenomics.

Help with management of kidney patients

Broad panel genetic testing can identify patients who are at risk for kidney disease, reclassify the exact cause of kidney disease, and guide treatment. Knowing the molecular basis of some kidney diseases can guide lifestyle modification interventions, future development of drugs, and gene therapy. It can also identify early complications outside the kidneys that can be related to the specific genetic disease and prompt early interventions.

Available broad panel genetic tests

Broad panel genetic tests are now available for providers and patients, and are relatively inexpensive. Many of them are covered by insurance companies. We have utilized Natera’s Renasight broad panel genetic test for this purpose. It provides next generation sequencing for 382 genes that are associated with kidney disease. There are also other genetic testing companies that test a small panel of genes for free to identify patients for drug or gene therapy.

The Bottom Line

We are at the dawn of a new era in nephrology and kidney care. Broad panel genetic testing will revolutionize kidney disease management. Our genes are not our destiny, but we cannot change our destiny without knowing our genes.