Disparities in the Treatment of CKD and Efforts to Slow Progression


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)


1. Levey AS, et al. National Kidney Foundation practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Ann Intern Med 2003; 139:137–147.

2. Chin MP, et al. Risk factors for heart failure in patients with type 2 diabetes mellitus and stage 4 chronic kidney disease treated with bardoxolone methyl. J Card Fail 2014; 20:953–958.

3. Bakris GL, et al. Effect of finerenone on albuminuria in patients with diabetic nephropathy: A randomized clinical trial. JAMA 2015; 314:884–894.

4. Klahr S, et al. Modification of Diet in Renal Disease Study Group. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. N Engl J Med 1994; 330:877–884.

5. Lewis JB. Blood pressure control in chronic kidney disease: Is less really more? J Am Soc Nephrol 2010; 21:1086–1092.

6. Townsend RR. Blood pressure targets in CKD. Adv Chronic Kidney Dis 2015; 22:96–101.

7. Kovesdy CP, et al. Observational modeling of strict vs conventional blood pressure control in patients with chronic kidney disease. JAMA Intern Med 2014; 174:1442–1449.

8. Anderson AH, et al. Chronic Renal Insufficiency Cohort Study Investigators. Time-updated systolic blood pressure and the progression of chronic kidney disease: A cohort study. Ann Intern Med 2015; 162:258–265.

9. Taler SJ, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for management of blood pressure in CKD. Am J Kidney Dis 2013; 62:201–213.

10. Verbeke F, et al. A European Renal Best Practice (ERBP) position statement on the Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for the management of blood pressure in non-dialysis-dependent chronic kidney disease: an endorsement with some caveats for real-life application. Nephrol Dial Transplant 2014; 29:490–496.

11. James PA, et al. 2014 Evidence-based guideline for the management of high blood pressure in adults: Report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014; 311:507–520.

12. Wright JT Jr, et al. SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015; 373:2103–2116.

13. The Collaborative Study Group, Lewis EJ, et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 1993; 329:1456–1462.

14. Ruggenenti PI, et al. Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria. Lancet 1999; 354:359–364.

15. Brenner BM, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345:861–869.

16. Jafar TH, et al. Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease: A meta-analysis of patient-level data. Ann Intern Med 2001; 135:73–87.

17. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288:2981–2997.

18. Wright JT Jr, et al. African American Study of Kidney Disease and Hypertension Study Group. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: Results from the AASK trial. JAMA 2002; 288:2421–2431.

19. Barnett AH1, et al. Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med 2004; 351:1952–1961.

20. Mann JF, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): A multicentre, randomised, double-blind, controlled trial. Lancet 2008; 372:547–553.