Autosomal dominant polycystic kidney disease (ADPKD) in African Americans: Prevalence and clinical course.
ASN 30th Annual Meeting, San Antonio
J Am Soc Nephrol (Sep) 8:373A 1997
ADPKD accounts for 8% of ESRD in Caucasians, but there is little available data on the prevalence of ADPKD or on ADPKD-associated ESRD in the African American population. Animal models of cystic renal disease tell us that differing genetic backgrounds can exert profound influences on the severity of a given genetic mutation. Understanding how these genetic factors influence disease expression may provide keys to therapeutic amelioration of disease severity and/or rate of progression. Moreover, African Americans experience an increased rate of renal failure in response to such insults as hypertension and diabetes. Thus, the generic question of how differing genetic backgrounds influence ADPKD manifestations in humans is an extremely important one, as is the specific issue of how ADPKD presents in African Americans as a population.
Heifner and Guay-Woodford have examined the prevalence and clinical course of ADPKD in African Americans with ESRD in Alabama, based on patients identified in the regional Network 8 ESRD database. Adjusting for differing population sizes, the prevalence of ADPKD in ESRD patients was 4.3/100,000 African Americans, not different from the 3.2/100,000 Caucasians.
Of 38 African-American ADPKD patients examined in detail, 66% had reached ESRD at a mean age of 50.4 yrs, significantly younger than that for Caucasian ADPKD patients (see Comments). However, unlike the Caucasian ADPKD experience, there was no apparent accelerating effect of male gender on ESRD onset in African Americans. African-American ADPKD/ESRD patients were more likely to have manifested >2 episodes of gross hematuria (62 vs. 42%) but were less likely to exhibit hypertension (76 vs. 88%) as compared to Caucasian ADPKD/ESRD patients. Importantly, the high prevalence of proteinuria >300 mg/day and hypertension (100% and 76% respectively) prior to dialysis in African- American ADPKD/ESRD patients was significantly greater than that in African American/ADPKD patients without ESRD (28.6% and 61% respectively).
Authors conclude that, while ADPKD prevalence among ESRD patients is similar for African Americans and Caucasians, ESRD occurs at a younger age in African Americans with ADPKD and its course responds differently to factors such as gender, hypertension, and gross hematuria.
Comment: Given the differing genetic backgrounds of Caucasian and African American populations, it is somewhat surprising to find a similar prevalence of ADPKD. Caution is in order in interpreting/extrapolating the results on natural history of ADPKD in African Americans: numbers are small (potential sampling bias) and all derive from the same geographic region (potential bias toward an unrepresentative subset of genetic mutations). Furthermore, in the estimated % of African American ADPKD patients progressing to ESRD, the actual denominator is not certain, since data base inclusion may have been biased in favor of more severe and/or early-onset disease. Nonetheless, the findings provide interesting evidence that, as in animal models of cystic disease, the genetic background may have significant effects on the clinical course of disease in man.
These findings, if confirmed, also portend a potentially poorer renal prognosis for African Americans with ADPKD. Whether or not this reflects the same factors that increase African American susceptibility to renal damage in hypertension and diabetes, it clearly merits aggressive genetic screening for ADPKD in members of affected African American families and vigorous treatment of the known renal risk factors. (Unfortunately, ADPKD is one renal condition in which Angiotensin Converting Enzyme inhibitor treatment has not been shown to have renoprotective effect.) Although not yet available, the authors also plan to determine whether the prevalences of PKD1 and PKD2 mutations differ in these populations. This will be an important addition, since absence of the clinically milder PKD2 mutations in the African American population studied could contribute to the apparently poorer prognosis. (Susan P. Bagby, M.D., Oregon Health Sciences University and VA Portland Medical Center, Portland, OR)
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ASN 30th Annual Meeting, San Antonio
Cystic disease : Hereditary polycystic disease