Disparities in the Treatment of CKD and Efforts to Slow Progression

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The best chance to slow or reverse the progression of chronic kidney disease (CKD) is in CKD stage 1, when GFR is still preserved. The strategy in stage 1 CKD is to control comorbidities (treat to target) and to perform risk assessment and intervention for cardiovascular disease (1). Unfortunately, many patients, particularly those of minority extraction, do not get this early referral benefit, as noted in the previous section. Current evidence-based progression-specific treatment approaches in CKD include treating BP to acceptable goals, blockade of the renin-angiotensinogen aldosterone system (RAAS), and controlling metabolic acidosis. Trials of antioxidants by the use of bardoxolone, an inhibitor of oxidative stress that failed phase 3 clinical trials, was associated with worsened albuminuria and heart failure (2). Antagonists of inflammation, renal fibrosis, extracellular matrix deposition, and endothelin 1 have not yielded any meaningful clinical application. Interestingly, antagonists of the mineralocorticoid receptor have demonstrated reduced albuminuria but have been associated with high blood potassium levels, which may limit their use in patients with advanced CKD (3). Of the progression-specific treatment approaches, the RAAS system and BP control exhibit significant racial disparities, as detailed below.

There are no recommended different target BP levels based on race or ethnicity. The results from many randomized controlled trials addressing optimal BP in patients with CKD (4, 5) and observational studies (68) have yielded different results; nonetheless, guidelines issued by the Kidney Disease: Improving Global Outcomes (KDIGO), the European Society of Hypertension (ESH), and the European Society of Cardiology (ESC) and the Eighth Joint National Committee (JNC 8) cite evidence pointing to the benefit of lowering BP in individuals with CKD below the level acceptable in the general population; a BP goal below 140/90 mm Hg for those without albuminuria and 130/80 mm Hg for those with albuminuria (911). The Systolic Blood Pressure Intervention Trial (SPRINT) (12), which is the most recent of nondiabetic hypertension studies in which patients with CKD constituted 30% of the study population, provides additional evidence of the benefit of more intensive BP lowering to a systolic of pressure of 120 mm Hg or less, compared with a systolic pressure of 140 mm Hg or less, although the study was not powered to evaluate CKD per se. The benefit of BP lowering was similar between African Americans and whites.

The benefit of using inhibitors of the RAAS to achieve these optimal BP targets and to slow progression is well established in CKD (1316). However, concerns have been raised about their effectiveness in African Americans. Unfortunately, only a few clinical studies have enrolled sufficient numbers of African Americans. A subgroup analysis of black patients in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (17) found less BP reduction with lisinopril than with amlodipine. This concern was addressed in a randomized controlled trial in the African American Study on Kidney Disease and Hypertension (AASK) (18), which demonstrated that angiotensin-converting enzyme inhibitors appeared to be more effective than β-blockers or dihydropyridine calcium channel blockers in slowing GFR decline. The JNC 8 and other guidelines now recommend achieving a target BP below 140/90 mm Hg with a treatment strategy that also includes blockade of the RAAS, irrespective of race, unless not tolerated or contraindicated. Evidence suggests that angiotensin receptor blockers and angiotensin-converting enzyme inhibitors are equivalent in their effectiveness in retarding eGFR decline (19); hence, either class of drugs can be used to slow CKD progression, but the combination should be avoided because of the serious side effects, such as hyperkalemia and a greater decline in estimated GFR (20).

January 2019 (Vol. 11, Number 1)

References

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