Cum Hoc, Ergo Propter Hoc: Health Disparities Real and Imagined : Clinical Journal of the American Society of Nephrology

Journal Logo


Cum Hoc, Ergo Propter Hoc

Health Disparities Real and Imagined

Gadegbeku, Crystal A.; Chertow, Glenn M.

Author Information
Clinical Journal of the American Society of Nephrology 4(2):p 251-253, February 2009. | DOI: 10.2215/CJN.06361208
  • Free

In the November 2008 issue of CJASN, Ibrahim et al. (1) reported racial differences in metabolic characteristics of the National Health and Nutrition Examination Survey (NHANES) 2003 through 2006 population with respect the presence or absence of chronic kidney disease (CKD) defined by an estimated GFR (eGFR) > and <60 ml/min. The authors concluded that the African American population is more likely to experience metabolic consequences of CKD before reaching the eGFR <60 ml/min threshold and asserted that these observations support a need to adapt clinical practice guidelines shifting screening for CKD to a higher eGFR threshold specifically for African Americans. These same contentions were made by four of the five authors in an article published only months earlier in JASN (1,2).

The assumption that the measured clinical parameters in this representative population are physiologically linked to CKD in African Americans is simplistic and ignores the effects of a combination of genetic and physiologic adaptations superimposed on a background of social and environmental factors that account for minority health disparities (3). The observed population differences noted in the article by Ibrahim et al. (1) were previously well described and should not serve as justification for the policy changes that the authors recommend. Although we agree that clinical practice guidelines should be reviewed and refined over time, the contention that the prevalence or severity of hypertension, anemia, hyperparathyroidism, and other metabolic abnormalities that are associated with the classification of CKD somehow reflects “disadvantage” or barriers to minority communities distracts from real disparities that African American and other minority populations truly experience.

Ibrahim et al. (1) noted racial differences in hemoglobin concentrations in the NHANES population with and without CKD. Variations in hematologic parameters by race are well documented (4,5); African Americans tend to have lower hemoglobin concentrations, mean corpuscular volumes, transferrin saturations, and white blood cell counts than white individuals. In individuals of African ancestry, in part as a result of adaptations against malaria, α-thalassemia and sickle trait are common and significantly contribute to differences in hemoglobin concentrations. Epidemiologic evidence suggests that 7% of African Americans have sickle trait and 30% carry at least one α gene mutation with 9% carrying both genetic variants (4). Iron deficiency is also more common among African American women than other race and gender groups. The NHANES data reported by Ibrahim et al. (1) mirror previous observations in children (5) as well as adults and may be explained by factors other than erythropoietin deficiency related to CKD (the logical fallacy “cum hoc, ergo propter hoc” translated as “with this, because of this” [Latin]).

The authors also raised the possibility that elevations in intact parathyroid hormone (PTH) may suggest “early” development of secondary hyperparathyroidism. A substantial body of evidence elucidates physiologic differences and outcomes in bone metabolism in African Americans (6). Individuals of African descent have higher PTH and 1,25-dihydroxyvitamin D [1,25(OH)2D] associated with lower 25-hydroxyvitamin D [25(OH)D] than other race/ethnicity groups (6). Greater skin pigmentation (from multiple ethnic backgrounds) is associated with lower 25(OH)D formation; therefore, enhanced 1,25(OH)2D production in response to higher PTH may be an adaptive response. Further adaptations include intestinal resistance to 1,25(OH)2D and skeletal resistance to PTH, which together favor bone formation and may explain lower rates of osteoporosis and fractures despite higher PTH concentrations in African Americans. In addition to these physiologic characteristics, African Americans have a high prevalence of very low circulating 25(OH)D levels consistent with vitamin D deficiency, thought to be secondary to avoidance of milk products as a result of lactose intolerance as well as overall reduced dietary vitamin D intake (7,8). Concentrations of 25(OH)D and 1,25(OH)2D, which were lower in African Americans in the NHANES III population but not measured during the 2003 through 2006 surveys, are needed to interpret fully the observations by Ibrahim et al. (1) vis-a[Combining Grave Accent]-vis PTH. Nonetheless, complex physiologic and environmental factors contribute to racial differences in the PTH–vitamin D–calcium–phosphorus axis, including recent evidence supporting differences in the bone-derived circulating hormone fibroblast growth factor 23 (9). Further research characterizing normal vitamin D metabolism in African Americans is needed before disturbances of bone metabolism can be defined and understood or directly attributed to impaired kidney function (again, cum hoc, ergo propter hoc).

An increased prevalence of hyperuricemia in African Americans was previously described in NHANES I (10). Uric acid concentrations are directly correlated with systolic BP (11), obesity (11), and the metabolic syndrome (12), all of which are more prevalent in African Americans than in white individuals. African Americans with hypertension are more often treated with diuretic agents, which can also contribute to hyperuricemia (13). Furthermore, lifestyle behaviors and environmental factors such as high-fructose diets (14), alcohol intake, and lead exposure/intoxication (11,15) are more common in individuals of lower socioeconomic status, including African Americans, and are also associated with hyperuricemia. Thus, several factors other than impaired kidney function could explain the seeming racial imbalance in hyperuricemia with and without CKD.

Overall, comparisons of white to African Americans with regard to health outcomes must take into consideration the impact of social and environment differences, which include barriers to quality health care. Differences in the prevalence of poverty—8.2% for whites compared with 24.3% for African Americans (—result in numerous downstream consequences, including life expectancies an average of 5.1 yr shorter for African Americans. Reflecting these national statistics, the NHANES III African American population was much less likely to have had incomes >$20,000, to have completed high school, and to have had health insurance. These socioeconomic factors are indicators of access to health care and therefore, not surprising, have been linked to health outcomes such as glycemic and hypertension control (16). Even among Medicare beneficiaries, clinical performance measures were 7 to 14% lower for African Americans than for white individuals (17); therefore, any observations based on race/ethnicity must consider sociodemographic disparity as a determinant of observed differences. Using CKD burden in African Americans as an example, sociodemographic, lifestyle, and related clinical factors combined explained 44% of the excess ESRD burden (18). Furthermore, 80% of accelerated progression in diabetic nephropathy among African Americans was attributed to these same factors (19).

As we venture to understand the burden of CKD in the African American population, we must strive to appreciate the full scope of contributing factors to the burden of CKD. Examining health consequences outside the context of socioeconomic, cultural, behavioral, and even biologic differences may lead us down the path of misdirected policies that do not address the root causes of real health disparities.



Published online ahead of print. Publication date available at

See related article, “Screening for Chronic Kidney Disease Complications in US Adults: Racial Implications of a Single GFR Threshold,” on pages 1792–1799 of the November 2008 issue of CJASN.


1. Ibrahim HN, Wang C, Ishani A, Collins AJ, Foley RN: Screening for chronic kidney disease complications in US adults: Racial implications of a single GFR threshold. Clin J Am Soc Nephrol3 :1792– 1799,2008
2. Foley RN, Wang C, Ishani A, Collins AJ: NHANES III: Influence of race on GFR thresholds and detection of metabolic abnormalities. J Am Soc Nephrol18 :2575– 2582,2007
3. Adler NE, Rehkopf DH: U.S. disparities in health: Descriptions, causes, and mechanisms. Annu Rev Public Health29 :235– 252,2008
4. Beutler E, West C: Hematologic differences between African-Americans and whites: The roles of iron deficiency and alpha-thalassemia on hemoglobin levels and mean corpuscular volume. Blood106 :740– 745,2005
5. Rana SR, Sekhsaria S, Castro OL: Hemoglobin S and C traits: Contributing causes for decreased mean hematocrit in African-American children. Pediatrics91 :800– 802,1993
6. Harris SS: Vitamin D and African Americans. J Nutr136 :1126– 1129,2006
7. Nesby-O'Dell S, Scanlon KS, Cogswell ME, Gillespie C, Hollis BW, Looker AC, Allen C, Doughertly C, Gunter EW, Bowman BA: Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: Third National Health and Nutrition Examination Survey, 1988–1994. Am J Clin Nutr76 :187– 192,2002
8. Zadshir A, Tareen N, Pan D, Norris K, Martins D: The prevalence of hypovitaminosis D among US adults: Data from the NHANES III. Ethn Dis15 :S5-97– S5-101,2005
9. Gutierrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, Smith K, Lee H, Thadhani R, Ju[Combining Diaeresis]ppner H, Wolf M: Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med359 :584– 592,2008
10. Fang J, Alderman MH: Serum uric acid and cardiovascular mortality the NHANES I epidemiologic follow-up study, 1971–1992. National Health and Nutrition Examination Survey. JAMA283 :2404– 2410,2000
11. Johnson RJ, Kang DH, Feig D, Kivlighn S, Kanellis J, Watanabe S, Tuttle KR, Rodriguez-Iturbe B, Herrera-Acosta J, Mazzali M: Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension41 :1183– 1190,2003
12. Onat A, Uyarel H, Hergenc G, Karabulut A, Albayrak S, Sari I, Yazici M, Keles[COMBINING CEDILLA] I: Serum uric acid is a determinant of metabolic syndrome in a population-based study. Am J Hypertens19 :1055– 1062,2006
13. Singh H, Johnson ML: Prescribing patterns of diuretics in multi-drug antihypertensive regimens. J Clin Hypertens (Greenwich)7 :81– 87, quiz 88–89,2005
14. Nakagawa T, Tuttle KR, Short RA, Johnson RJ: Hypothesis: Fructose-induced hyperuricemia as a causal mechanism for the epidemic of the metabolic syndrome. Nat Clin Pract Nephrol1 :80– 86,2005
15. Den Hond E, Nawrot T, Staessen JA: The relationship between blood pressure and blood lead in NHANES III. National Health and Nutritional Examination Survey. J Hum Hypertens16 :563– 568,2002
16. Mainous AG 3rd, King DE, Garr DR, Pearson WS: Race, rural residence, and control of diabetes and hypertension. Ann Fam Med2 :563– 568,2004
17. Trivedi AN, Zaslavsky AM, Schneider EC, Ayanian JZ: Relationship between quality of care and racial disparities in Medicare health plans. JAMA296 :1998– 2004,2006
18. Tarver-Carr ME, Powe NR, Eberhardt MS, LaVeist TA, Kington RS, Coresh J, Brancati FL: Excess risk of chronic kidney disease among African-American versus white subjects in the United States: A population-based study of potential explanatory factors. J Am Soc Nephrol13 :2363– 2370,2002
19. Krop JS, Coresh J, Chambless LE, Shahar E, Watson RL, Szklo M, Brancati FL: A community-based study of explanatory factors for the excess risk for early renal function decline in blacks vs whites with diabetes: The Atherosclerosis Risk in Communities study. Arch Intern Med159 :1777– 1783,1999
Copyright © 2009 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.