Effects of Blood Pressure Control on Progressive Renal Disease in Blacks and Whites
Abstract African Americans (blacks) have a disproportionately high incidence of end-stage renal disease due to hypertension. The Modification of Diet in Renal Disease (MDRD) Study found that strict blood pressure control slowed the decline in glomerular filtration rate (GFR) only in the subgroup of patients with proteinuria. The present report compares the effects of blood pressure control in black and white MDRD Study participants. Fifty-three black and 495 white participants with baseline GFRs of 25 to 55 mL/min/1.73 m2 were randomly assigned to a usual or low mean arterial pressure (MAP) goal of ≤107 or ≤92 mm Hg, respectively. GFR decline was compared between randomized groups and correlated with the level of achieved blood pressure. The mean (±SE) GFR decline over 3 years in the low blood pressure group was 11.8±7.3 mL/min slower than in the usual blood pressure group among blacks (P=.11) compared with 0.3±1.3 mL/min slower among whites (P=.81) (P=.12 between blacks and whites). In both blacks and whites, higher baseline urine protein excretion was associated with a greater beneficial effect of the low MAP goal on GFR decline (P=.02 for both races). Combining both blood pressure groups and controlling for baseline characteristics, higher follow-up achieved MAP was associated with faster GFR decline in both blacks (P<.001) and whites (P=.002), with a sevenfold stronger relationship in blacks (P<.001). These secondary analyses support the prior recommendation for a lower than usual blood pressure goal (MAP ≤92 mm Hg) in black and white patients with proteinuria (>1 g/d). In addition, a lower level of blood pressure control may be even more important in blacks than in whites in slowing the progression of renal disease.
The incidence of ESRD is disproportionately high among African Americans (hereafter referred to as blacks).1 2 3 4 In particular, data from the United States Renal Data System show a marked racial disparity in the age- and sex-adjusted incidence rate of ESRD attributed to hypertension. However, the appropriate target blood pressure for antihypertensive therapy to retard the progression of renal disease has not been defined in this population.
Thus far, only two randomized trials have examined the effects of different levels of blood pressure control on the progression of renal disease in a substantial number of blacks. Toto et al5 assigned 77 participants (75% black) with presumed hypertensive nephrosclerosis to either strict blood pressure control (diastolic blood pressure 65 to 80 mm Hg) or conventional blood pressure control (diastolic blood pressure 85 to 95 mm Hg) and measured the rate of decline in GFR. Both mean diastolic and MAP were significantly lower in the strict blood pressure control group compared with the conventional blood pressure control group. However, the GFR decline was slow (<1 mL/min/y) in both blood pressure groups and was not significantly different between groups. The authors concluded that the conventional blood pressure target was sufficient to retard the progression of renal disease.
The MDRD Study also examined the effect of strict blood pressure control on GFR decline in 840 patients with chronic renal disease of diverse causes.6 7 Mean GFR decline in this trial was faster (approximately 4 mL/min/y) than in the trial by Toto et al.5 The effect of the low blood pressure goal on the rate of decline in GFR was significantly related to the level of urine protein excretion at baseline. No benefit of the low blood pressure intervention was seen among study participants with baseline urine protein excretion <0.25 g/d, but increasing benefits were observed at successively higher levels of urine protein excretion.8 On the basis of these findings, the MDRD Study group recommended a lower than usual blood pressure goal (an MAP ≤92 mm Hg, equivalent to a blood pressure ≤125/75 mm Hg) for patients with chronic renal disease and urine protein excretion ≥1 g/d (a value for proteinuria higher than usually observed in hypertensive nephrosclerosis).
Fifty-three (9%) of the 585 participants in the MDRD Study with baseline GFRs 25 to 55 mL/min/1.73 m2 (moderate renal disease) were black. The aims of the present study are (1) to compare the effects of the usual versus low blood pressure goal on the GFR decline in blacks and whites with moderate renal disease of diverse causes in the MDRD Study and (2) to compare the relationship between achieved blood pressure and GFR decline in these participants.
The MDRD Study was a multicenter randomized clinical trial of the effects of dietary protein restriction and strict blood pressure control on the progression of chronic renal disease.6 7 8 9 10 11 12 13 14 15 Approval was obtained from the review boards of all participating institutions.
Entry criteria included age between 18 and 70 years, evidence of chronic renal disease with serum creatinine between 1.2 and 7.0 mg/dL in women (106 to 619 μmol/L) and 1.4 and 7.0 mg/dL in men (124 to 619 μmol/L) or creatinine clearance <70 mL/min/1.73 m2 (<1.17 mL/s/1.73 m2), and a MAP (defined as two thirds diastolic plus one third systolic) of ≤125 mm Hg. Exclusion criteria included insulin-dependent diabetes, a history of kidney transplantation, and a number of other conditions.6 After a 3-month baseline period, 840 participants with GFR between 13 and 55 mL/min/1.73 m2 were eligible for randomization.
Ascertainment of race was by participant self-report. Overall, 53 (9%) of the 585 participants in Study A (GFR 25 to 55 mL/min/1.73 m2) and 13 (5%) of the 255 participants in Study B (GFR 13 to 24 mL/min/1.73 m2) were black. Because the small number of blacks prevented meaningful analyses of the relationship between GFR decline and blood pressure in Study B, we present analyses of Study A only.
Participants in Study A were randomly assigned to a usual or low protein diet (1.3 or 0.58 g/kg/d, respectively) and to a usual or low blood pressure goal (MAP ≤107 or ≤92 mm Hg, respectively, equivalent to a blood pressure ≤140/90 or ≤125/75 mm Hg, respectively). In participants aged 61 years or more, the usual and low blood pressure goals were 6 mm Hg higher (a MAP ≤113 or ≤98 mm Hg, respectively, equivalent to a blood pressure of ≤160/90 or ≤145/75 mm Hg, respectively).
GFR was measured as the renal clearance of 125I-iothalamate (administered by subcutaneous injection).10 11 Protein intake was monitored monthly during the baseline and follow-up periods by 24-hour urinary excretion of urea nitrogen.16 Blood pressure was measured monthly using a Hawksley random zero sphygmomanometer (WA Baum, Inc) by accepted techniques.17
Both pharmacological and nonpharmacological therapies, including reduction of dietary salt intake, were used to control blood pressure. Although the use of specific classes of antihypertensive drugs was not required, an ACE inhibitor, with or without a diuretic, was encouraged as the initial regimen. A calcium channel blocker, with or without a diuretic, was encouraged as the second regimen.
Baseline MAP was defined as the mean of the baseline MAP measurements obtained at the close of the first and second months of baseline. Mean follow-up MAP was defined as the mean of all MAP measurements obtained at non-GFR visits, beginning with the third monthly follow-up visit (MAP measurements obtained at GFR visits were excluded because they were systematically higher than MAP measured at non-GFR visits).18 The mean length of GFR follow-up was 2.3 years in whites and 1.9 years in blacks. The shorter duration of follow-up in blacks was primarily because of an increased frequency of reaching predefined “stop points” due to rapidly declining GFR or onset of ESRD. A total of 47, 25, and 6 blacks and 472, 333, and 129 whites had GFR follow-up to at least 1, 2, and 3 years, respectively.
Graphical plots of the pattern of change in GFR over time are based on spline models with break points at 2 months, 4 months, and every 4 months thereafter. For formal statistical analyses, the decline in GFR was assessed using two-slope, mixed effects models, in which each participant is assumed to have an initial rate of GFR decline during the first 4 months of follow-up (an initial slope) and possibly a different rate of GFR decline thereafter (a final slope).7
The effect of the diet intervention on the decline in GFR did not differ significantly between whites and blacks in Study A. For both blacks and whites the effect of the blood pressure intervention was similar in the two diet groups. Thus, with no loss of information, comparisons of the blood pressure groups are presented for all study participants regardless of diet assignment.
The effect of blood pressure group on GFR decline was assessed separately for blacks and whites. For these analyses, we calculated the initial slopes, the final slopes, and also the estimated mean changes in GFR from baseline to 2 and 3 years of follow-up (obtained as appropriate time-weighted linear combinations of the initial and final slopes).
For correlational analyses, we controlled for five baseline factors that we have shown to be joint predictors of GFR decline based on a backward selection procedure,19 as well as six other baseline factors regarded as having potential relevance to relationships being investigated. These 11 baseline factors (urine protein excretion, a diagnosis of polycystic kidney disease, MAP, serum transferrin, serum total and HDL cholesterol, age, sex, body mass index, protein intake, and hemogloblin A1C) will be referred to as the “relevant covariates.” These baseline values were averaged over all available measurements (two measurements for the serum biochemistry values and for MAP; four measurements for protein intake, urine protein excretion, and body mass index). We also repeated analyses comparing blacks with whites while controlling for Clinical Center in addition to the 11 relevant covariates. Since the addition of Clinical Center had a negligible effect on the results, Clinical Center was not included as a covariate in the analyses reported here.
Hypothesis tests are regarded as significant if P<.05, two-sided. No adjustments for multiple comparisons were made.
Demographic and Clinical Characteristics at Baseline
At baseline, there were numerous differences between black and white participants (Tables 1⇓ and 2⇓). The two most frequent renal diseases among blacks were hypertensive nephrosclerosis (n=15) and glomerular diseases (n=13); among whites they were polycystic kidney disease (n=127) and glomerular diseases (n=117). Blacks more often had a history of hypertension, higher mean blood pressure (MAP and systolic and diastolic blood pressures), and higher mean urine protein excretion levels. However, baseline MAP, systolic and diastolic blood pressures, GFR, serum creatinine, and urine protein excretion were well balanced between the blood pressure groups for both blacks and whites. In particular, mean GFR at baseline was 41.0 and 40.2 mL/min/1.73 m2 in the usual and low blood pressure groups for blacks and was 38.0 and 39.0 mL/min/1.73 m2 in the usual and low blood pressure groups for whites.
Antihypertensive Drug Use
During follow-up, the mean number of concurrent antihypertensive drugs prescribed for blacks assigned to the usual and low blood pressure goals was 2.0 and 2.7, respectively; for whites the corresponding values were 1.5 and 1.8. Among blacks and among whites, participants in the low blood pressure group were prescribed all major classes of antihypertensive medications more frequently than were participants in the usual blood pressure group. Among blacks, the difference was most marked for ACE inhibitors: This class of medication was prescribed in 74% of participants in the low blood pressure group compared with 27% of participants in the usual blood pressure group. Among whites, ACE inhibitors were prescribed in 51% of patients in the low blood pressure group compared with 35% of participants in the usual blood pressure group.
Combining the usual and low blood pressure groups, similar proportions of blacks (32%) and whites (27%) were prescribed β-blockers. Blacks were prescribed ACE inhibitors, calcium channel blockers, diuretics, and other antihypertensive drugs (51%, 53%, 57%, and 36%, respectively) more often than were whites (43%, 30%, 41%, and 16%, respectively).
Achieved Blood Pressure During Follow-up
Among blacks, mean follow-up MAP was 101.6 and 96.0 mm Hg for participants in the usual and low blood pressure groups, respectively; among whites, mean follow-up MAP was 96.7 and 91.9 mm Hg, respectively (Fig 1⇓). The difference in follow-up MAP between the usual and low blood pressure groups in blacks (5.6 mm Hg) and whites (4.8 mm Hg) was not significantly different (P=.74).
Combining data from both blood pressure groups, follow-up MAP was significantly higher for blacks than whites (P<.001, data not shown). However, reduction in MAP from baseline MAP was similar in blacks (1.3 mm Hg) and whites (1.6 mm Hg).
Effects of Blood Pressure on GFR Decline
Comparison of the Randomized Groups
Fig 2⇓ and Table 3⇓ show the GFR decline in blacks and whites assigned to the usual and low blood pressure goals. Among blacks (Fig 2A⇓), the mean (±SE) GFR decline during the first 4 months of follow-up was 5.1±2.3 mL/min greater in the low blood pressure group than in the usual blood pressure group (P=.03). In contrast, from 4 months to the end of follow-up, the mean rate of GFR decline was 6.4±2.4 mL/min/y (65%) slower in the low blood pressure group than in the usual blood pressure group (P=.01). Therefore, during follow-up, the initial effects of the low blood pressure goal on the GFR decline were eventually offset by the subsequent effects. Although the mean GFR decline from baseline was 5.5±5.0 mL/min (35%) less in the low blood pressure group than in the usual blood pressure group at 2 years, the difference did not approach statistical significance (P=.28). At 3 years, the estimated mean GFR decline was 11.8±7.3 mL/min (46%) less in the low blood pressure group than in the usual blood pressure group (P=.11).
Similarly, among whites (Fig 2B⇑), the mean GFR decline during the first 4 months of follow-up was 1.4±0.6 mL/min greater in the low blood pressure group than in the usual blood pressure group (P=.02). However, after 4 months, the rate of GFR decline was only 0.6±0.4 mL/min/y (18%) slower in the low blood pressure group than in the usual blood pressure group (P=.14). The mean GFR decline from baseline was 0.3±0.9 mL/min (4%) greater in the low blood pressure group at 2 years (P=.71) and 0.3±1.3 mL/min (3%) less in the low blood pressure group estimated at 3 years (P=.81).
Comparison of Between-Group Differences in GFR Decline Between Blacks and Whites
From 4 months to the end of follow-up, the effect of the low blood pressure goal (the difference in the mean GFR decline between the usual and the low blood pressure groups) was significantly greater in blacks than in whites (Table 3⇑, P=.02); this suggests a greater beneficial effect of the low blood pressure goal in blacks than in whites. However, during the first 4 months, the effect of the low blood pressure goal on GFR was also greater in blacks than in whites (Table 3⇑, although not significantly, P=.11), but opposite in direction to the effect after 4 months. Consequently, the effect of the low blood pressure goal on the GFR decline from baseline to 2 or 3 years of follow-up was greater in blacks than whites, but the difference was not statistically significant (P=.31 and P=.12, respectively).
Effect of Baseline Urine Protein Excretion on the Comparison of the Randomized Groups
The effect of the low blood pressure goal after 4 months was significantly greater in participants with higher baseline urine protein excretion among both blacks (P=.02) and whites (P=.02).
Given that blacks had higher mean baseline urine protein excretion than whites, it is reasonable to ask whether the effect in blacks of the low blood pressure goal on GFR decline after 4 months was the result of the greater effect of the low blood pressure goal in participants with higher levels of proteinuria. After we controlled for the greater effect of the low blood pressure goal in participants with higher baseline proteinuria, the greater effect of the low blood pressure goal in blacks persisted (P=.011). This indicates that the greater effect of the low blood pressure goal in blacks is independent of the relationship between proteinuria and blood pressure control.
Comparison of Blacks and Whites Assigned to the Same Blood Pressure Group
In the usual blood pressure group (Fig 2C⇑), the mean rate of GFR decline after 4 months was 2.8 times greater in blacks than whites (P<.001). In addition, the mean GFR decline from baseline to 2 years was 2.0 times greater in blacks than whites (P=.04). These differences persisted after controlling for the relevant baseline covariates.
In contrast, in the low blood pressure group (Fig 2D⇑), neither the rate of GFR decline after 4 months nor the GFR decline from baseline to 2 years differed significantly between blacks and whites. These results were unchanged after controlling for the relevant baseline covariates.
Comparison of Blacks and Whites at the Same Level of Achieved Blood Pressure
As shown in Fig 1⇑, there was substantial variability in the level of achieved blood pressure in both blood pressure groups in blacks and whites. To explore the association between the level of achieved blood pressure and the decline in renal function, we correlated the GFR decline after 4 months with achieved follow-up blood pressure in blacks and whites, regardless of assigned treatment group, while controlling for the relevant baseline covariates. In blacks, the mean (±SE) GFR decline was 0.71±0.14 mL/min/y faster for each 1.0 mm Hg increment in MAP (P<.001); this means that after we controlled for the baseline covariates, mean GFR decline was 7.1 mL/min/y faster for participants with a 10 mm Hg higher mean follow-up MAP. In whites, the mean (±SE) GFR declined 0.10±0.03 mL/min/y faster for each 1.0 mm Hg increment in follow-up MAP (P=.002); this is equivalent to a 1.0 mL/min/y faster GFR decline for participants with a 10 mm Hg higher mean follow-up MAP. The strength of the association between follow-up blood pressure and GFR decline (regression coefficient) was sevenfold greater in blacks than whites (P<.001). Fig 3⇓ displays the relationship between achieved follow-up blood pressure and GFR decline over various ranges of MAP. The rate of GFR decline appeared more rapid in blacks (n=25) than in whites (n=144) for follow-up MAP greater than 98 mm Hg but similar in blacks (n=27) and whites (n=342) for follow-up MAP ≤98 mm Hg. A similar set of results was obtained for analyses relating achieved follow-up blood pressure to the estimated change in GFR from baseline to 2 years and from baseline to 3 years (data not shown).
Finally, we also examined the possible confounding role of ACE inhibitors in the above analyses. When we controlled for the relevant covariates and mean follow-up MAP, use of ACE inhibitors was not significantly associated with GFR decline in either whites or blacks. The significantly stronger association of MAP with the rate of GFR decline in blacks than in whites persisted after we controlled for use of ACE inhibitors (data not shown).
Some investigators have proposed that the high incidence of ESRD attributed to hypertension among blacks is explained by the higher prevalence and greater severity of hypertension in this population.20 21 However, even after the higher prevalence of hypertension in the population and other risk factors are adjusted for, blacks continue to have an excess risk of developing ESRD as a result of hypertension compared with whites.22 23 Both retrospective and prospective studies of blacks and whites with hypertension show that blacks are at a greater risk for renal impairment than whites, despite similar levels of blood pressure control.24 25 26 27 Results from two clinical trials, the Hypertension Detection and Follow-up Program (HDFP) study and the Multiple Risk Factor Intervention Trial (MRFIT), also suggest that blacks may be more susceptible to hypertensive nephrosclerosis.28 29 30 31 In these clinical trials, loss of kidney function (as measured by increases in serum creatinine) was greater in blacks than in whites, despite comparable control of diastolic blood pressure using a stepped-care drug regimen. These studies suggest that there are racial differences in susceptibility to renal damage attributed to hypertension.32
The MDRD Study is one of two reported clinical trials to randomly assign participants with chronic renal disease to two different levels of blood pressure control and to maintain significant differences in achieved blood pressure. The presence of 53 blacks in MDRD Study A with similar baseline characteristics in each blood pressure group permits an evaluation of strict blood pressure control on the progression of moderate renal disease of diverse causes in blacks. However, it is important to note that only a minority of the participants in the MDRD Study were classified as having hypertensive nephrosclerosis. In many clinical trials, participant characteristics do not necessarily correspond to their distribution in the general patient population.33 The MDRD Study did not specifically attempt to recruit a representative (ie, similar to that of the ESRD patient population) sample of patients (either black or white). Our attempt to control blood pressure to a lower than usual blood pressure goal in the present study was well tolerated by both black and white participants; however, patients with symptomatic ischemic heart disease may have been excluded from the study at baseline.15 34
Without controlling for urine protein excretion, we found a 65% slower mean rate of GFR decline beginning after 4 months of follow-up in black participants assigned to the low blood pressure group (P=.01), which did not appear to be due to the use of ACE inhibitors. However, because of a greater mean GFR decline during the first 4 months of follow-up in the low blood pressure group in the MDRD Study, the mean decline in GFR from baseline to 3 years of follow-up was only 11.8 mL/min (46%) less than in the usual blood pressure group (P=.11) (Fig 2A⇑). As reported elsewhere,35 we have demonstrated that faster GFR decline in the low blood pressure group during the first 4 months in the MDRD Study was likely due to alterations in renal hemodynamics rather than progression of renal disease. In principle, because of the opposite effects of the low blood pressure goal before and after 4 months of follow-up, a longer duration of follow-up would have been required to show a significant difference between blood pressure groups in the GFR decline from baseline. Moreover, the smaller number of blacks with shorter duration of follow-up contributes to the larger standard error of the GFR declines in this subgroup (Table 3⇑), making it more difficult to demonstrate statistical significance despite the large effect size. Overall, we interpret the results of the comparisons of randomized groups in blacks as consistent with a beneficial effect of strict blood pressure control in this subgroup, irrespective of baseline urine protein excretion. However, given these limitations and the numerous pitfalls of overinterpreting subgroup analyses,36 further studies will be required to prove this hypothesis.
Consistent with what was previously reported for the entire Study A population,7 the present study demonstrates a greater beneficial effect of the low blood pressure goal in both blacks and whites with higher baseline urine protein excretion levels (for example, >1 g/d). These findings support our previous conclusion that the low blood pressure goal is beneficial in patients with proteinuria, irrespective of race.7 8
The comparison of blacks and whites within each blood pressure group also reveals differences in the relationship of blood pressure to the progression of renal disease. Specifically, we found a significantly faster mean GFR decline in blacks compared with whites who were assigned to the usual blood pressure group (Fig 2C⇑) but not the low blood pressure group (Fig 2D⇑). In addition, when we controlled for baseline covariates, we found a sevenfold faster rate of GFR decline in blacks than in whites at the same achieved follow-up MAPs (P<.001). This difference between blacks and whites was most apparent when the follow-up MAPs were greater than 98 mm Hg (equivalent to blood pressure of ≥130/80 mm Hg) (Fig 3⇑). Below this MAP, there was no apparent difference in GFR decline between blacks and whites.
These findings suggest that achieving control of blood pressure at a level lower than that currently recommended for prevention of cardiovascular disease may be more important in slowing the progression of moderate chronic renal disease in blacks than in whites. However, as discussed below, race was not a randomization strata, and there were a number of differences between blacks and whites in the MDRD Study. For example, blood pressure goals were less well achieved in blacks than in whites. However, since blacks and whites had nearly identical reductions of blood pressure from baseline, this difference in blood pressure control is not likely the result of poor adherence but rather due to the higher baseline blood pressures among blacks. The faster GFR decline in blacks at the achieved higher blood pressures remained after we controlled for follow-up MAP and selected baseline variables, including sex, age, urine protein excretion, hemoglobin A1c, serum total or HDL cholesterol, body mass index, or the presence of polycystic kidney disease. The higher frequency of the use of ACE inhibitors or other classes of antihypertensive agents in blacks compared with whites also did not account for the greater rate of GFR decline in blacks versus whites with higher achieved MAP.
Another possible explanation for our findings is that the black participants had more severe renal disease than whites, despite similar GFRs. Indeed, blacks had higher mean blood pressure and higher mean urine protein excretion rates than whites. Possibly, hypertension secondary to more severe renal disease may respond less well to antihypertensive therapy and may progress more rapidly. In addition, nocturnal blood pressure (not measured in this study) may be higher in blacks than in whites, and nocturnal hypertension may be a better predictor of end-organ damage than diurnal blood pressure.37 38
There were other differences in the baseline characteristics of the blacks and whites enrolled in this study. Blacks had higher body mass index, lower serum potassium and urine potassium excretion, higher serum creatinine (despite similar GFRs), higher blood glucose and lipid levels, lower serum phosphorus and urine phosphorus excretion, and higher serum lactate dehydrogenase levels. The role of these factors in the higher achieved blood pressure and the more rapid decline in renal function in blacks remains to be investigated. In addition, there may be other important characteristics that account for these apparent differences between blacks and whites in the relationship of blood pressure level and the progression of renal disease, which were not measured. It is important that other studies be done to confirm these observations and to define the optimal blood pressure level for blacks with moderate chronic renal disease.
The desirable level of blood pressure has been generally defined as that at which end-organ damage is less likely to occur. The internationally accepted criterion for normal blood pressure is <140/90 mm Hg. The Fifth Report of the Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure has suggested that the target blood pressure for patients with renal disease should be ≤130/85 mm Hg, equivalent to a MAP of ≤100 mm Hg.39 Our results in blacks are consistent with this recommendation. The African-American Study of Kidney (AASK) Disease and Hypertension, a multicenter, randomized clinical trial designed to compare the effects of two levels of blood pressure control and three antihypertensive drug regimens in blacks with hypertensive nephrosclerosis,40 should help define the optimal target blood pressure in this population. The results of this trial are not expected for 5 years.
In summary, these secondary analyses from the MDRD Study provide evidence to suggest that progression of moderate renal disease of diverse causes in blacks may be slowed by a lower than usual blood pressure goal. Comparison of the randomized groups suggests that the low blood pressure goal slowed the decline in GFR, especially in participants with baseline urine protein >1 g/d. When patients in both blood pressure groups were compared and we controlled for a number of baseline factors, blacks had faster GFR decline than whites if follow-up MAP was greater than 98 mm Hg but not at lower MAP values.
These results support our prior recommendation for a lower than usual blood pressure goal (MAP ≤92 mm Hg, equivalent to a blood pressure ≤125/75 mm Hg) for patients with moderate chronic renal disease and urine protein excretion >1 g/d, irrespective of race. In addition, they suggest that attempts to achieve a blood pressure goal of MAP ≤98 mm Hg may be indicated for blacks with moderate chronic renal disease, even if urine protein excretion <1 g/d, as is typical in hypertensive nephrosclerosis. Further studies specifically designed to test this hypothesis are needed.
Selected Abbreviations and Acronyms
|ESRD||=||end-stage renal disease|
|GFR||=||glomerular filtration rate|
|MAP||=||mean arterial pressure|
|MDRD Study||=||Modification of Diet in Renal Disease Study|
This study was supported by the National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, Md, and the Health Care Financing Administration, Washington, DC. We thank Marion Merrell Dow, Kansas City, Mo, who donated diltiazem (CardizemR) and Merck Sharp and Dohme, West Point, Pa, who donated enalapril (Vasotec) to study participants. We are indebted to the patients who participated in the Modification of Diet in Renal Disease Study.
↵1 The institutions and investigators who participated in this study are listed in Reference 8.
Presented in part at the 25th Annual Meeting of the American Society of Nephrology, Boston, Mass, November 14, 1993; published in abstract form (Kusek JW, Aqodoa L, Greene T, Jones C. Comparison of decline in GFR in blacks versus non-blacks in the MDRD Study. J Am Soc Nephrol. 1993;4:253.
- Received October 14, 1996.
- Revision received November 4, 1996.
- Accepted February 10, 1997.
Rettig RA, Levinsky NG, eds. Committee for the Study of the Medicare End-Stage Renal Disease Program, Institute of Medicine. Kidney Failure and the Federal Government. Washington, DC: National Academy Press; 1991.
US Renal Data System. USRDS 1995 Annual Data Report. Bethesda, Md: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; April 1995.
Kusek JW, Agodoa LY, Striker GE, eds. Excerpts from the workshop on the biology of kidney disease and hypertension in blacks. Am J Kidney Dis. 1993;21(suppl 1):1-87.
Peterson JC, Adler S, Burkart JM, Greene T, Hebert LA, Hunsicker LG, King AJ, Klahr S, Massry SG, Seifter JL, for the Modification of Diet in Renal Disease (MDRD) Study Group. Blood pressure control, proteinuria and the progression of renal disease: The Modification of Diet in Renal Disease Study. Ann Intern Med. 1995;123:754-762.
Levey AS, Greene T, Schluchter MD, Cleary PA, Teschan PE, Lorenz RA, Molitch ME, Mitch WE, Siebert C, Hall PM, Steffes MW, for the MDRD Study Group and the DCCT Research Group. GFR measurements in clinical trials. J Am Soc Nephrol. 1993;4:1159-1171.
Perrone R, Steinman T, Beck GJ, Skibinski CI, Royal H, Lawlor M, Hunsicker L, Modification of Diet in Renal Disease Study Group. Utility of radioisotopic filtration markers in chronic renal insufficiency: simultaneous comparison of 125I-iothalamate, 169Yb-DTPA, 99mTc-DTPA to inulin. Am J Kidney Dis. 1990;16:224-235.
Modification of Diet in Renal Disease Study Group (Greene T, Bourgoignie JJ, Habwe V, Kusek JW, Snetselaar LG, Soucie JM, Yamamoto ME, writing group). Baseline characteristics in the Modification of Diet in Renal Disease Study. J Am Soc Nephrol. 1993;4:1221-1236.
Levey AS, Adler S, Caggiula AW, England BK, Greene T, Hunsicker LG, Kusek JW, Rogers NL, Teschan PE, for the MDRD Study Group. Effects of dietary protein restriction on the progression of advanced renal disease in the Modification of Diet in Renal Disease Study. Am J Kidney Dis. 1996;27:652-663.
Modification of Diet in Renal Disease Study Group (Levey AS, Adler S, Caggiula AW, England BK, Greene T, Hunsicker LG, Kusek JW, Rogers NL, Teschan PE, writing group). Effects of dietary protein restriction on the progression of moderate renal disease in the Modification of Diet in Renal Disease Study. J Am Soc Nephrol. 1996;7:2616-2626.
Lazarus JM, Bourgoignie JJ, Buckalew VM, Greene T, Levey AS, Milas NC, Paranandi L, Peterson JC, Porush JG, Rauch S, Soucie JM, Stollar C, for the Modification of Diet in Renal Disease Study Group. Achievement and safety of a low blood pressure goal in chronic renal disease. Hypertension. 1997;29:641-650.
Paranandi L, Wang S, Greene T, Gassman JJ, Beck GJ, Lazarus JM, and the Modification of Diet in Renal Disease Study Group. Considerations regarding ‘measurement visits’ during follow-up of clinical trials. Control Clin Trials. 1995;16:120S-121S. Abstract.
Modification of Diet in Renal Disease Study Group (Hunsicker L, Adler S, Caggiula A, England B, Greene T, Kusek J, Rogers N, Teschan P, writing group). Predictors of the progression of renal disease in the Modification of Diet in Renal Disease Study. Kidney Int. 1997;51:1908-1919.
Whelton PK, Klag MJ. Hypertension as a risk factor for renal disease: review of clinical and epidemiological evidence. Hypertension. 1989;13(suppl I):I-19-I-27.
Drizd T, Dannenberg AL, Engel A, for the National Center for Health Statistics. Blood pressure levels in persons 18-74 years of age in 1976-1980, and trends in blood pressure from 1960-1980 in the United States. Vital and Health Statistics. Series 11, No. 234. DHHS Pub. No. (PHS) 86-1684. Public Health Service, Washington, DC. US Government Printing Office. 1986.
Shulman NB, Ford CE, Hall WD, Blaufox MD, Simon D, Langford HG, Schneider KA, on behalf of the Hypertension Detection and Follow-up Program Cooperative Group. Prognostic value of serum creatinine and effect of treatment of hypertension on renal function. Hypertension. 1989;13(suppl I):I-80-I-93.
Spilker B, Cramer JA. Patient Recruitment in Clinical Trials. New York, NY: Raven Press; 1991.
Modification of Diet in Renal Disease Study Group (Levey AS, Beck GJ, Bosch JP, Caggiula AW, Greene T, Hunsicker LG, Klahr S, writing group). Short-term effects of protein intake, blood pressure, and antihypertensive therapy on glomerular filtration rate in the Modification of Diet in Renal Disease Study. J Am Soc Nephrol. 1996;7:2097-2109.
Harshfield GA, Alpert BS, Pulliam DA, Willey ES, Somes GW, Stapleton FB. Sodium excretion and racial differences in ambulatory blood pressure patterns. Hypertension. 1991;18:813-818.
Wright JT, Kusek JW, Toto RD, Lee JY, Agodoa LY, Randall OS, Kirk KA, Glassock R. Design and baseline characteristics of participants in the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study. Control Clin Trials. 1996;16:3S-16S.