It is important to remember that a given individual with WAGR syndrome may or may not have or develop the condition listed below.
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| Renal Failure and WAGR Syndrome |
Renal (kidney) failure is a common feature of WAGR syndrome. Up to 60% of individuals with WAGR syndrome may develop renal failure at some point in their lives, most often during adolescence or early adulthood.
Who Is At Risk?
Currently there is no method for predicting which individuals with WAGR syndrome will develop renal failure. Anyone with WAGR syndrome is at risk for this complication, including those who have never had Wilm’s tumor.What Causes Renal Failure in People with WAGR Syndrome?
The type of renal failure associated with WAGR syndrome is called
“Focal Segmental Glomerulosclerosis,” or FSGS. This type of renal failure can occur with a number of other medical conditions, such as diabetes. It is not known why people with WAGR syndrome develop FSGS, but it is thought to be the result of the genetic defect that causes WAGR syndrome.
FSGS refers to a condition in which the glomeruli, the tiny tubes which filter the blood to make urine, become scarred. Instead of filtering properly, these damaged glomeruli allow protein to appear in the urine. Over time, the kidneys lose their ability to function properly, and kidney failure is the result.
How Is FSGS Treated?
The course and outcome of FSGS varies from one patient to another. Some patients with FSGS respond well to medication, and their kidney function may remain relatively stable for long periods of time. Other patients may go quickly from diagnosis to the need for dialysis or kidney transplant.
Many patients with FSGS respond well to treatment with a class of drugs called angiotensin converting enzyme (ACE) inhibitors. ACE inhibitors are not a cure, but they do appear to slow the progression of the disease in some patients. The same may be true for patients with WAGR Syndrome and FSGS.
Signs of renal failure may include hypertension (high blood pressure) hyperlipidemia (very high cholesterol) and/or proteinuria (protein in the urine)
Early diagnosis of renal failure is important, because appropriate treatment may help prolong the time between diagnosis of the condition, and the need for dialysis or kidney transplant. Guidelines for testing and monitoring at each stage of life are available here:
Guide for Parents:Health Supervision for Individuals with WAGR Syndrome>
To learn more about the function of the kidneys, FSGS, or living with chronic renal failure, please visit the following websites:
http://www.nephron.com
http://www.renalnet.com
http://www.kidney.org
United Kingdom
National Kidney Federation
Provides info on dialysis.
There is some info especially prepared for children and their parents.
www.kidney.org.uk
UK Transplant
Provides info on kidney transplants
www.uktransplant.org.uk
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Characteristics and outcomes of children with the Wilms tumor-Aniridia syndrome: a report from the National Wilms Tumor Study Group.
Breslow NE, Norris R, Norkool PA, Kang T, Beckwith JB, Perlman EJ, Ritchey ML, Green DM, Nichols KE; National Wilms Tumor Study Group.
Department of Biostatistics, Box 357232, University of Washington, Seattle, WA 98195-7232, USA. norm@u.washington.edu
PURPOSE: Children with the rare Wilms tumor (WT)-aniridia (WAGR) syndrome have not had systematic evaluation of their clinical and pathologic features. We compared demographics, disease characteristics, and treatment outcomes in a large cohort of WT patients who did or did not have the WAGR syndrome.
PATIENTS AND METHODS: Clinical and pathology records were reviewed for 8,533 patients enrolled between 1969 and 2002 by the National Wilms Tumor Study Group.
RESULTS: Sixty-four patients (0.75%) had the WAGR syndrome. For WAGR and non-WAGR patients, respectively, the average birth weights (2.94 and 3.45 kg), median ages at diagnosis (22 and 39 months), and the percentages with bilateral disease (17% and 6%), metastatic disease (2% and 13%), favorable histology (FH) tumors (100% and 92%), and intralobar nephrogenic rests (ILNR; 77% and 22%) all differed. Survival estimates for WAGR and non-WAGR patients were 95% +/- 3% and 92% +/- 0.3% at 4 years but 48% +/- 17% and 86% +/- 1.0%, respectively, at 27 years from diagnosis. Five late deaths in WAGR patients were from end-stage renal disease (ESRD).
CONCLUSION: The excess of bilateral disease, ILNR-associated FH tumors of mixed cell type, and early ages at diagnosis in WAGR patients all fit the known phenotypic spectrum of constitutional deletion of chromosome 11p13.
Despite a favorable response of their WT to treatment, WAGR patients have a high risk of ESRD as they approach adulthood. The renal pathology associated with this apparent late manifestation of WT1 deletion, and the explanation for the abnormally low birth weights in patients with del 11p13, have yet to be determined.
Publication Types:
· Research Support, U.S. Gov't, P.H.S.
PMID: 14673045 [PubMed - indexed for MEDLINE]
J Urol. 2005 Nov;174(5):1972-5.
Links
End stage renal disease in patients with Wilms tumor: results from the National Wilms Tumor Study Group and the United States Renal Data System.
· Breslow NE,
· Collins AJ,
· Ritchey ML,
· Grigoriev YA,
· Peterson SM,
· Green DM.
Department of Biostatistics, University of Washington, Fred Hutchinson Cancer Research Center, Seattle, Washington 98195-7232, USA. norm@u.washington.edu
PURPOSE: We sought to assess accurately the full spectrum of end stage renal disease (ESRD) in Wilms tumor survivors by combining the unique resources of the National Wilms Tumor Study Group (NWTSG) and the United States Renal Data System (USRDS), and to confirm preliminary reports of an increased incidence of ESRD in patients with the Wilms tumor-aniridia syndrome (WAGR).
MATERIALS AND METHODS: ESRD was ascertained in 5,910 patients enrolled in NWTSG studies during 1969 to 1994 by record linkage to USRDS and by direct followup. Cumulative ESRD incidence was estimated accounting for intercurrent mortality.
RESULTS: Of 115 cases of ESRD 10 (9%) were ascertained by the NWTSG alone, 13 (11%) by USRDS alone and 92 (80%) by both. Cumulative incidence of ESRD at 20 years from diagnosis of unilateral Wilms tumor was 74% for 17 patients with the Denys-Drash syndrome, 36% for 37 patients with WAGR, 7% for 125 male patients with hypospadias or cryptorchidism (genitourinary [GU] anomalies) and 0.6% for 5,347 patients with none of these conditions. The incidence of ESRD after diagnosis of bilateral Wilms tumor was 50% for the Denys-Drash syndrome (6 patients), 90% for WAGR (10), 25% for GU anomaly (25) and 12% for other (409). ESRD in patients with WAGR or GU anomalies tended to occur relatively late, often during or after adolescence.
CONCLUSIONS: The risk of ESRD is remarkably low for the majority of patients with Wilms tumor. However, those with WAGR or associated GU anomalies are at higher risk and should be screened indefinitely to facilitate prospective treatment of impaired renal function.
PMID: 16217371 [PubMed - indexed for MEDLINE]
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From Late Breaking News 2008
National Wilms Tumor Study
Considerations for Living with One Kidney
by Michael Ritchey, MD
Most patients who undergo treatment for childhood renal tumors undergo a nephrectomy. As a result, these patients are left with one kidney or half of their functioning kidney tissue. A very small percentage of patients
have tumors in both kidneys and some of these children have even less remaining renal tissue after surgical interventions. One concern for patients undergoing treatment of renal tumors is the long-term effect on kidney function.
When physicians speak of kidney function they normally refer to the glomerular
filtration rate (GFR). This is a test that can accurately measure the level
of the kidney function. In most patients who have the kidney removed,
the glomerular filtration rate by the remaining kidney will increase. This is a process of compensation in which the solitary kidney makes up for its missing mate. This adaptive response by the kidney is both beneficial and potentially harmful.
The main function of the kidneys is to filter the plasma and to eliminate waste products. A normal solitary kidney can usually handle this task very well. Another function of the kidney is to help regulate the blood pressure. The kidney helps regulate salt excretion. It also produces some hormones that can affect blood pressure.
In addition to the surgical effects of removing kidney tissue, the treatments
for childhood renal cancer can affect kidney function. Some chemotherapy
agents can injure the kidney. This can occur temporarily but can also be permanent. Radiation therapy that may be needed to treat the cancer can also affect kidney function particularly if the remaining kidney was included in the radiation field. The effect of radiation is very dependent on the dose of the radiation therapy used. Fortunately, fewer patients currently being treated for Wilms tumor receive radiation therapy;
those who are irradiated are given lower doses than in the past.
Overall, the incidence of overt renal failure where patients require active treatment for inadequate kidney function is very low, less than 1%. Patients who have treatment for a single renal tumor in one kidney rarely develop late renal failure. The rate is higher in those with tumors in both kidneys.
In addition, some particular patients are at increased risk. These include children with certain genital anomalies or rare syndromes such as aniridia or the Denys-Drash syndrome. These latter patients have an inherent risk for renal failure due to an inherited specific disorder of the kidney.
All patients who undergo treatment for Wilms tumor should have long-term follow-up including annual measurements of blood pressure and urinalysis and blood test to assess kidney function. If there is elevation of the blood pressure, then prompt referral to a nephrologist, that is a kidney specialist, is warranted. Early intervention to lower blood pressure can prevent progression of kidney disease. Likewise, measurement of protein in the urine is extremely important because this a first sign of kidney failure. Again, referral to the nephrologist and early active treatment is recommended. The nephrologist may make specific recommendations regarding diet and avoidance of other risk factors that may affect kidney function.
Additional information can be found at the Children’s Oncology Group (COG) website. The COG has developed guidelines for follow-up of children treated for childhood cancer. These are risk-based, exposure-related recommendations
for the identification and management of late effects due to therapies used for childhood cancer. They are designed for asymptomatic survivors presenting for routine medical follow-up two or more years after completion of cancer therapy. Patient education materials called “Health Links” accompany the guidelines; both the guidelines and Health Links can be downloaded from www.survivorshipguidelines.org.
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