OTHER REASONS FOR THE DISPARITIES
“There are no unnatural or supernatural phenomena, only a very large gap in our knowledge of what is natural.”
—Edgar Mitchell, Apollo 14 astronaut
Proteinuria is another key cardiorenal risk factor prevalent in African Americans.
Knight et al,13 analyzing data from the Third National Health and Nutrition Examination Survey, found that people with high-normal blood pressure (systolic pressure 130–139 mm Hg or diastolic pressure 85–89 mm Hg) were twice as likely to have microalbuminuria (odds ratio 2.13, 95% confidence interval [CI] 1.51–3.01) compared with people with optimal blood pressure (systolic pressure < 120 mm Hg and diastolic pressure < 80 mm Hg). Compared with whites as the reference group, Mexican Americans had slightly but not statistically significantly higher odds of microalbuminuria (odds ratio 1.16; 95% CI 0.90–1.51), and African Americans had significantly higher odds (odds ratio 1.30; 95% CI 1.04–1.64).
The incidence of hypertension-related end-stage renal disease is nearly five times higher in African Americans than in whites, and the rate of hypertension-related end-stage renal disease is 15 times higher in African American men ages 24 to 44 than in whites of the same ages.3 The greater risk of proteinuria in African Americans at any given level of higher blood pressure is thought to contribute in part to these disparate rates.
The renin-angiotensin system
The renin-angiotensin system plays a role in modulating hypertension and mediating hypertension-related complications. Hypertensive African Americans are more likely than hypertensive whites to have low-renin, salt-sensitive hypertension. Therein lies a paradox.
Since the renin-angiotensin system promotes the progression of CKD, we would expect patients with low-renin hypertension to have a lower risk of hypertension-related endorgan damage than patients with high-renin hypertension. However, many African Americans (who as a group have high rates of sodium sensitivity and low plasma renin levels) experience more severe hypertension-related end-organ complications such as proteinuria and cardiorenal disease.14
A reason for this paradox may be that the circulating renin-angiotensin system is separate from the intrarenal one. Supporting this theory is the observation that up-regulation of the intrarenal renin-angiotensin system accompanies renal interstitial inflammation and oxidative stress in the kidneys and cardiovascular tissues of salt-sensitive rats fed a high-salt diet.15 In other experiments in salt-sensitive rats, renin-angiotensin system blockade reversed endothelial dysfunction, attenuated proteinuria, and reduced renal injury independent of blood pressure changes even though the animals had low circulating renin levels.16
These findings imply that drugs that block the renin-angiotensin system, ie, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, could still be a rational therapy for CKD patients with low-renin hypertension, particularly African Americans, in whom local up-regulation of the renin-angiotensin system in the kidney could exacerbate both diabetic and hypertensive CKD.17 Although these drugs may not lower blood pressure as much in low-renin hypertension as in high-renin hypertension, they may still afford the same cardiorenal protection.
Variations in the MYH9 and APOL1 genes on chromosome 22 have recently been found in genome-wide admixture mapping studies and may explain as much as 70% of the differences in the rates of nondiabetic end-stage renal disease between white and black Americans.7,18,19 In addition, genetic variations may modulate differences in blood-pressure response to antihypertensive medications across racial and ethnic groups,20 complicating treatment recommendations and clinical outcomes in our increasingly diverse nation.
Comment. The pathophysiologic basis for the variability in the course of CKD is probably multifactorial and is still poorly understood. Nevertheless, we may be able to delay the progression of CKD and prevent its complications with specific therapeutic and life-style interventions.
Race and ethnicity are associated with sociocultural and biologic variations that influence the risk and progression of CKD. Understanding these factors for minority populations can help in targeting interventions to attenuate the disproportionately high rates of CKD progression and complications.
The pathophysiologic reason African Americans have a greater prevalence of end-stage renal disease and a more rapid progression of CKD is complex and probably involves the interplay of biological, behavioral, and environmental factors such as salt intake, stress levels, and exposure to heavy metals.21