BACKGROUND Among patients in the United States with chronic kidney disease, black patients are at increased risk for end-stage renal disease, as compared with white patients. METHODS In two studies, we examined the effects of variants in the gene encoding apolipoprotein L1 (APOL1) on the progression of chronic kidney disease. In the African American Study of Kidney Disease and Hypertension (AASK), we evaluated 693 black patients with chronic kidney disease attributed to hypertension. In the Chronic Renal Insufficiency Cohort (CRIC) study, we evaluated 2955 white patients and black patients with chronic kidney disease (46% of whom had diabetes) according to whether they had 2 copies of high-risk APOL1 variants (APOL1 high-risk group) or 0 or 1 copy (APOL1 low-risk group). In the AASK study, the primary outcome was a composite of end-stage renal disease or a doubling of the serum creatinine level. In the CRIC study, the primary outcomes were the slope in the estimated glomerular filtration rate (eGFR) and the composite of end-stage renal disease or a reduction of 50% in the eGFR from baseline. RESULTS In the AASK study, the primary outcome occurred in 58.1% of the patients in the APOL1 high-risk group and in 36.6% of those in the APOL1 low-risk group (hazard ratio in the high-risk group, 1.88; P<0.001). There was no interaction between APOL1 status and trial interventions or the presence of baseline proteinuria. In the CRIC study, black patients in the APOL1 high-risk group had a more rapid decline in the eGFR and a higher risk of the composite renal outcome than did white patients, among those with diabetes and those without diabetes (P<0.001 for all comparisons). CONCLUSIONS Renal risk variants in APOL1 were associated with the higher rates of end-stage renal disease and progression of chronic kidney disease that were observed in black patients as compared with white patients, regardless of diabetes status. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.)

Ramipril, compared with amlodipine, retards renal disease progression in patients with hypertensive renal disease and proteinuria and may offer benefit to patients without proteinuria.

BACKGROUND In observational studies, the relationship between blood pressure and end-stage renal disease (ESRD) is direct and progressive. The burden of hypertension-related chronic kidney disease and ESRD is especially high among black patients. Yet few trials have tested whether intensive blood-pressure control retards the progression of chronic kidney disease among black patients. METHODS We randomly assigned 1094 black patients with hypertensive chronic kidney disease to receive either intensive or standard blood-pressure control. After completing the trial phase, patients were invited to enroll in a cohort phase in which the blood-pressure target was less than 130/80 mm Hg. The primary clinical outcome in the cohort phase was the progression of chronic kidney disease, which was defined as a doubling of the serum creatinine level, a diagnosis of ESRD, or death. Follow-up ranged from 8.8 to 12.2 years. RESULTS During the trial phase, the mean blood pressure was 130/78 mm Hg in the intensive-control group and 141/86 mm Hg in the standard-control group. During the cohort phase, corresponding mean blood pressures were 131/78 mm Hg and 134/78 mm Hg. In both phases, there was no significant between-group difference in the risk of the primary outcome (hazard ratio in the intensive-control group, 0.91; P = 0.27). However, the effects differed according to the baseline level of proteinuria (P = 0.02 for interaction), with a potential benefit in patients with a protein-to-creatinine ratio of more than 0.22 (hazard ratio, 0.73; P = 0.01). CONCLUSIONS In overall analyses, intensive blood-pressure control had no effect on kidney disease progression. However, there may be differential effects of intensive blood-pressure control in patients with and those without baseline proteinuria. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center on Minority Health and Health Disparities, and others.)

Background The traditional paradigm of glomerular filtration rate (GFR) progression among chronic kidney disease (CKD) patients is a steady, nearly linear decline over time. We describe individual GFR progression trajectories over twelve years of follow-up among participants in the African American Study of Kidney Disease and Hypertension (AASK). Study Design Longitudinal, observational study Setting & Participants 846 AASK patients with at least 3 years of follow-up and 8 GFR estimates. Measurements Longitudinal GFR estimates (eGFR) from creatinine-based equations. Predictors Patient demographic and clinical features. Outcomes Probability of a nonlinear trajectory and probability of a period of nonprogression, calculated for each patient from a Bayesian model of individual eGFR trajectories. Results Three hundred and fifty-two (41.6%) patients exhibited a greater than 0.9 probability of having either a nonlinear trajectory or a prolonged nonprogression period; in 559 (66.1%), the probability was larger than 0.5. Baseline eGFR > 40 mL/min/1.73m2 and urine protein-creatinine < 0.22 g/g were associated with a higher likelihood of a nonprogression period. Seventy-four patients (8.7%) had both a substantial period of stable or increasing eGFR and a substantial period of rapid eGFR decline. Limitations Clinical trial population; absence of direct GFR measurements. Conclusions In contrast to the traditional paradigm of steady GFR progression over time, many CKD patients have a non-linear GFR trajectory or a prolonged period of nonprogression. These findings highlight the possibility that stable kidney disease progression can accelerate, and, conversely provide hope that CKD need not be relentlessly progressive. These results should encourage researchers to identify time-dependent factors associated with periods of nonprogression and other desirable trajectories.

Abstract-Ambulatory blood pressure (ABP) monitoring provides unique information about day-night patterns of blood pressure (BP). The objectives of this article were to describe ABP patterns in African Americans with hypertensive kidney disease, to examine the joint distribution of clinic BP and ABP, and to determine associations of hypertensive target organ damage with clinic BP and ABP. This study is a cross-sectional analysis of baseline data from the African American Study of Kidney Disease Cohort Study. Masked hypertension was defined by elevated daytime (Ն135/ 85 mm Hg) or elevated nighttime (Ն120/70 mm Hg) ABP in those with controlled clinic BP (Ͻ140/90 mm Hg); nondipping was defined by a Յ10% decrease in mean nighttime systolic BP; reverse dipping was defined by a higher nighttime than daytime systolic BP. Of the 617 participants (mean age: 60.2 years; 62% male; mean estimated glomerular filtration rate: 43.8 mL/min per 1.73 m 2 ) with both clinic BP and ABP, 498 participants (80%) had a nondipping or reverse dipping profile. Of the 377 participants with controlled clinic BP (61%), 70% had masked hypertension. Compared with those with controlled clinic BP or white-coat hypertension, target organ damage (proteinuria and left ventricular hypertrophy) was more common in those with elevated nighttime BP, masked hypertension, or sustained hypertension. In conclusion, clinic BP provides an incomplete and potentially misleading assessment of the severity of hypertension in African Americans with hypertensive kidney disease, in large part because of increased nighttime BP. Whether lowering nighttime BP improves clinical outcomes is unknown but should be tested given the substantial burden of BP-related morbidity in this population.