Disparities in Risk Factors for Progression of CKD

Many patients with CKD invariably experience progression, slow or fast, to later CKD stages and require renal replacement therapy at some point. Controlling the primary risk factors for CKD has been shown to slow progression of CKD but does not prevent the development of ESRD. The mechanisms underlying slow or fast progression of CKD are complex but are generally attributable to nephron loss from the primary disease, which sets a vicious circle of further nephron loss, characterized by hypertrophy and hyperfiltration of the remaining nephrons, intraglomerular hypertension, proteinuria, and toxicity of filtered proteins on tubular epithelial cells (13). Although these forces have been attributed to pertain to many glomerular diseases, the processes are particularly described in diabetic nephropathy, in which podocyte loss may be a downstream effect (4).

/kidneynews/11_1/11/graphic/11f1.jpgIn addition, activation of the renin-angiotensinogen aldosterone system, development of metabolic acidosis, and, to a lesser extent, dyslipidemia and anemia further contribute to a progressive decline in renal function (5). Higher rates of CKD progression in African Americans than in other racial and ethnic groups may be accounted for by other progression-specific factors, such as the renin-angiotensinogen aldosterone system, BP (salt sensitivity), and response to injury. These factors have demonstrated marked racial disparities in physiology and in responses to treatment (6).

African Americans demonstrate lower plasma renin levels than do other racial groups (7, 8), which suggests that non–renin-mediated mechanisms play a major role in the pathogenesis of hypertension in this population. African Americans are more salt sensitive than are other racial groups (5), which results in greater amounts of salt and water retention, ultimately leading to plasma volume expansion and hypertension. This picture is further exacerbated by sympathetic overdrive in African Americans, largely resulting from socioeconomic stressors, which further drive hypertension (9).

Response to injury is also exacerbated in African Americans, as evidenced by overexpression of TGF-β1 in patients with hypertension and kidney disease (10). TGF-β induces fibrosis during the process of tissue repair and is a major mediator of glomerulosclerosis (11). It is also postulated that TGF-β1 modulates the expression of angiotensin II (12) and endothelin (13), further resulting in ischemia and injury to tissues. Taken together, TGF-β1 is overly expressed in African American patients with CKD and accelerates the progression of CKD in this patient population.

Differences in other risk factors for CKD and for CKD progression play important roles in the disparities associated with CKD. These risk factors may be divided into traditional and nontraditional risk factors. The traditional risk factors, such as diabetes, hypertension, history of acute kidney injury, malignancy, advancing age, cardiovascular disease, obesity, metabolic syndrome, and long-term use of nephrotoxic agents like nonsteroidal inflammatory drugs, are all well known and may be influential in any individual.

Nontraditional risk factors, such as poverty, lack of access to optimal healthcare, lack of health insurance, environmental factors, cultural beliefs, language and literacy barriers, and genetics, also described as social determinants of health, have been shown to play a greater role in ethnic minorities (14). In several instances, social conditions may have a direct effect on kidney disease and kidney disease progression. For example, it has been shown that reduced annual household income is associated with greater odds of both microalbuminuria and macroalbuminuria (15). Further, uninsured compared with insured individuals may be less likely to receive clinical care for optimal BP control (16), which may have a direct impact in CKD progression, particularly in African Americans.

Indeed, African Americans are susceptible to CKD progression not only from molecular and environmental factors but also from genetic factors. In one prospective study, Salifu et al. (17) showed that between African Americans and whites under equivalent glycemic control, there was no significant difference in diabetic CKD progression from one stage to the next, which suggests that other factors may explain the previously observed differences. APOL1 high-risk variants are associated with greater risk of incident proteinuria and CKD in African Americans (18). In fact, the APOL1 risk variants and interplay with environmental factors may account for up to 70% of the differences in the prevalence of kidney failure in African Americans compared with whites and individuals with nondiabetic kidney disease (19).

In this brief description of disparities in risk factors for progression in CKD, we have described some of the primary mechanisms that have been shown to generally lead to CKD and CKD progression. However, it is important to note the host of other risk factors that are typically not routinely considered when certain groups of patients are being evaluated for optimal care. This especially pertains to patients of racial and ethnic minorities, who are affected by many nontraditional risk factors that may directly or indirectly influence CKD and CKD progression. In addition to these nontraditional risk factors, there is a high prevalence of late referrals (30% to 40%) of patients in these minorities from primary care physicians to nephrologists (20). It is clear that early referral would optimize renal care before CKD begins and would potentially reduce CKD progression and prevent the need for dialysis. This practice should be encouraged.

January 2019 (Vol. 11, Number 1)


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