Q&A on WAGR syndrome and Chronic Kidney Disease

Jeffrey Kopp, MD

Staff Clinician

National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD

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Each kidney has about 1 million glomeruli each of which is a cluster of blood capillaries; these glomeruli filter small molecules including toxins from the blood.

Focal Segmental Glomerulosclerosis (FSGS) is a set of diseases in which scarring (sclerosis) affects the glomeruli and does so in a manner that at the onset of disease affects parts (segments) of some glomeruli (focal distribution) while other glomeruli remain normal.

Q: Do all individuals with WAGR syndrome need to be screened for FSGS?

A: Yes. We recommend that all individuals with WAGR syndrome have regular screening to detect kidney disease.

Q: My child never had Wilms tumor -- does he/she need to be screened for kidney disease?

A: Yes. Even if your child never had Wilms tumor, your child is still at risk for developing kidney problems.

Q: What percent of individuals with WAGR syndrome develop kidney disease?

A: We do not know the exact incidence as this is something we are still in the process of researching. A recently published case series of 54 patients with WAGR syndrome reported that 60% of individuals older than age 12 years had decreased kidney function or kidney failure (Pediatrics 2005; 116:984-988).

Q: What is the cause of kidney disease in WAGR syndrome?

A:  When patients with WAGR develop kidney disease, they most commonly have FSGS. As noted above FSGS is a syndrome and WAGR patients may have several factors that promote this kind of kidney scarring.

  • First, the WT1 gene is critical for normal function of the podocyte (meaning “foot cell”), which is a glomerular cell type. WAGR patients have only one normal copy of the WT1 gene, located on the other copy of chromosome 11, and in many cases this appears insufficient for the podocyte to function normally.

  • Second, WAGR patients are prone to obesity, which puts a metabolic stress on the kidneys by compelling the kidneys to overfunction to cope with the increased body size. An analogy would be that a car engine that is driven at high speed, or high rpms, for a long period of time will last less long that an engine that is driven moderately.

  • Third, WAGR patients who have had a Wilms tumor will have just one remaining kidney, and that kidney then is called upon to do the work of two kidneys - again, this represents stress to the kidney. By itself it is unlikely to be problem (remember that people can donate one kidney safely to another person) but it can make other kidney diseases worse.

  • Fourth, if hypertension develops, this may cause FSGS or may accelerate the progressive scarring of FSGS that was initiated by another factor.

  • Fifth, WAGR patients who have had radiation that extended to the normal kidney may have radiation damage. WAGR patients who develop diabetes are at risk to develop diabetic kidney disease, which is a different disease from FSGS, but has in common glomerular scarring (glomerulosclerosis).

Q: At what age should the testing begin for WAGR kidney disease?

A: We recommend that testing for kidney problems begin at birth. During infancy and early childhood, individuals with WAGR syndrome are at high risk for developing Wilms tumor. During late childhood and early adolescence, the risk for kidney disease increases. Therefore, lifelong monitoring is recommended.

Q: What tests can be done to detect early kidney disease?

A: For FSGS screening, children should have annual measurement of blood pressure and measurement of urine protein. We are not sure at what age this annual testing should begin, whether it should be age 5 or 10 years or some other age.

There are three ways to measure urine protein:

  • Dipstick test, done as part of a routine urinalysis - this can be useful but is not very sensitive (in other words, it can miss small amounts of protein in the urine that can still be a sign of kidney disease).

  • Measurement of the urine protein/creatinine ratio, which is more sensitive and can detect early kidney disease.

  • Measurement of the urine albumin/creatinine ratio (albumin is plasma protein). This is a standard test to detect early diabetic kidney disease, but its role in other kidney disease is less certain.

Q: What are the early signs and symptoms of kidney disease?

A: Early kidney disease typically has no symptoms, and thus regular laboratory testing is important.

Q: How is WAGR kidney disease treated?

A: There are three therapies that slow progression of other scarring kidney diseases, and although they have not been studied specifically in WAGR patients, these therapies are likely to be effective.

  • First, control of blood pressure to the age-appropriate normal level.

  • Second, use particular blood pressure medicines, termed ACE inhibitors and ARBs (angiotension receptor blockers). These medications have three beneficial effects: lower systemic blood pressure, lower blood pressure within the glomerulus, and prevent or slow the process of glomerular scarring (glomerular sclerosis) by turning of signaling molecules that regulate production of collagen (the major scar protein).

  • Third, limit dietary sodium (salt) intake, as this lowers blood pressure and also increases the effectiveness of ACE inhibitors and ARBs to reduce kidney scarring.

Q: Is the recommended treatment different for individuals with WAGR syndrome compared to other people with kidney failure? If so, why?

A: Treatment of progressive disease due to WAGR is similar treatment of progressive kidney disease of other causes. When the kidneys fail, the options are chronic dialysis (either hemodialysis or peritoneal dialysis) or kidney transplant - and kidney transplant is the preferred treatment.

Adapted from: “Nephrology 101: What Every Parent Must Know,” an interview with Jeffrey Kopp, MD, in WINGS, the newsletter of the International WAGR Syndrome Association, Spring/Summer 2009, pp 9-10.