Gerald Schulman

Prevalence of hypertension in 1,795 subjects with chronic renal disease: The modification of diet in renal disease study baseline cohort

The Modification of Diet in Renal Disease Study was a multicenter trial of the effect of protein restriction and strict blood pressure control on the progression rate of chronic renal failure of multiple causes. At the first baseline visit, 1,795 screened patients with renal disease had blood pressure measured, antihypertensive medications recorded, glomerular filtration rate (GFR) determined by 125I-iothalamate clearance, a nutritional assessment, and a 24-hour urine collection to determine sodium and potassium levels. A total of 1,494 patients in this cohort were classified as hypertensive (83%) and the remainder (301 patients) as nonhypertensive. Ninety-one percent of the hypertensive subjects were on treatment, 54% being controlled to a blood pressure of < or = 140/90 mm Hg. To better understand the factors that contribute to the development of hypertension in chronic renal disease, some determinants of the prevalence of hypertension in this cohort were investigated. Compared with normotensive subjects, hypertensive patients were older (51.2 +/- 12.7 years v 46.6 +/- 13.1 years [mean +/- SD]), had a higher body mass index (BMI; 27.5 +/- 4.7 kg/m2 v 25.4 +/- 4.2 kg/m2), and had a lower GFR (37.8 +/- 19.6 mL/min/1.73 m2 v 50.1 +/- 25 mL/min/1.73 m2). All these differences were significant (P < 0.01). The prevalence of hypertension was significantly higher for men than for women (86% v 80%; P = 0.001), and for blacks than for whites (93% v 81%; P < 0.001). The prevalence of hypertension was higher in subjects with glomerular disease than in those with tubulointerstitial disease (85% v 62.6%; P < 0.001). The prevalence of hypertension varied inversely with GFR (from 66% at a GFR of 83 mL/min/1.73 m2 to 95% at a GFR of 12 mL/min/1.73 m2). The prevalence of hypertension varied directly with BMI (from 70% with a BMI at the 10th percentile to 94% with a BMI at the 97th percentile). This relationship was independent of GFR. Multiple logistic regression analysis showed five predictors in decreasing order of significance as determined by chi-square values: GFR, 83.2; BMI, 36.7; black race, 19.9; increasing age, 14.5 (all P < 0.001); and male gender, 5.1 (P = 0.024). Salt intake was not a determinant of blood pressure status. These results confirm previous reports indicating that hypertension in renal disease is determined by the level of renal function. For the first time, three factors known to predict blood pressure levels in populations with normal renal function were also shown to be determinants of blood pressure in renal disease: BMI, black race, and age. In addition, the data suggest that hypertension is inadequately treated in more than half of patients with chronic renal disease in the United States.

Long-term Effects of Renin-Angiotensin System–Blocking Therapy and a Low Blood Pressure Goal on Progression of Hypertensive Chronic Kidney Disease in African Americans

BACKGROUNDnAntihypertensive drugs that block the renin-angiotensin system (angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin receptor blockers) are recommended for patients with chronic kidney disease (CKD). A low blood pressure (BP) goal (BP, <130/80 mm Hg) is also recommended. The objective of this study was to determine the long-term effects of currently recommended BP therapy in 1094 African Americans with hypertensive CKD.nnnMETHODSnMulticenter cohort study following a randomized trial. Participants were 1094 African Americans with hypertensive renal disease (glomerular filtration rate, 20-65 mL/min/1.73 m2). Following a 3x2-factorial trial (1995-2001) that tested 3 drugs used as initial antihypertensive therapy (ACEIs, calcium channel blockers, and beta-blockers) and 2 levels of BP control (usual and low), we conducted a cohort study (2002-2007) in which participants were treated with ACEIs to a BP lower than 130/80 mm Hg. The outcome measures were a composite of doubling of the serum creatinine level, end-stage renal disease, or death.nnnRESULTSnDuring each year of the cohort study, the annual use of an ACEI or an angiotensin receptor blocker ranged from 83.7% to 89.0% (vs 38.5% to 49.8% during the trial). The mean BP in the cohort study was 133/78 mm Hg (vs 136/82 mm Hg in the trial). Overall, 567 participants experienced the primary outcome; the 10-year cumulative incidence rate was 53.9%. Of 576 participants with at least 7 years of follow-up, 33.5% experienced a slow decline in kidney function (mean annual decline in the estimated glomerular filtration rate, <1 mL/min/1.73 m2).nnnCONCLUSIONnDespite the benefits of renin-angiotensin system-blocking therapy on CKD progression, most African Americans with hypertensive CKD who are treated with currently recommended BP therapy continue to progress during the long term.

Ambulatory Blood Pressure Monitoring in Dialysis Patients and Estimation of Mean Interdialytic Blood Pressure

To define blood pressure (BP) patterns and control in dialysis patients, 48-hour ambulatory BP monitoring was performed in 36 hemodialysis and 18 peritoneal dialysis patients. Monitoring began during a dialysis session for hemodialysis patients. Data revealed significantly lower diastolic BP (DBP) and lower diastolic load (percentage of diastolic values > 90 mm Hg) in hemodialysis patients compared with peritoneal dialysis patients (80.6 mm Hg v 88.8 mm Hg, respectively, [P < 0.03] and 26% v 45%, respectively [P < 0.03]) for the 48-hour period. When the 2 days were analyzed separately, the difference in diastolic pressures and loads was significant only for the first (dialysis) day. Similarly, trends toward lower systolic BP (SBP) and systolic load in hemodialysis patients existed throughout monitoring and were greater in magnitude during the first day. BP data were fit to a random-coefficient growth curve model to detect periodicity. This sensitive model did not detect diurnal variation of BP in either group. The incidence of hypotension did not differ between the two groups (2.0% v 1.0% of total observations, hemodialysis v peritoneal dialysis). In the hemodialysis group, the proportion of hypotensive observations was significantly greater during the 4 hours postdialysis compared with other periods (5.6% v 1.6%; P < 0.02), a finding that likely reflects the practice of holding antihypertensives until after hemodialysis. However, patient diaries did not reflect hypotensive symptoms during this time. In the hemodialysis group, mean BP and predialysis BP did not correlate with interdialytic sodium load or weight gain. Predialysis and postdialysis BP (recorded by dialysis nurses) correlated significantly with mean BP. Predialysis SBP overestimated mean SBP by an average of 10 mm Hg, while postdialysis SBP underestimated mean SBP by an average of 7 mm Hg. To create formulas to estimate mean SBP and DBP in hemodialysis patients, multiple linear regression was used to model these variables against age, sex, race, and average prehemodialysis/posthemodialysis BP. The model achieved a high degree of fit (r2 = 0.72 for SBP; r2 = 0.65 for DBP), demonstrating that prehemodialysis and posthemodialysis BP can be used to predict mean BP in hemodialysis patients. In summary, our data show the absence of a diurnal variation of BP in dialysis patients and lower BP in hemodialysis patients compared with peritoneal dialysis patients. Among hemodialysis patients, more hypotension occurred after dialysis compared with other periods, and predialysis and postdialysis BP can be used to model mean BP levels.

Factors that affect postdialysis rebound in serum urea concentration, including the rate of dialysis: results from the HEMO Study.

Previous studies have suggested that postdialysis urea rebound is related to K/V, the rate of dialysis, but a systematic analysis of factors that affect rebound has not been reported. With the use of 30-min and, in a subset, 60-min postdialysis samples, postdialysis urea rebound was measured to (1) determine how well previously proposed equations based on the rate of dialysis (K/V) predict rebound in a large sample of patients with varying characteristics, (2) determine whether other factors besides K/V affect rebound, and (3) estimate more precise values for coefficients in prediction equations for rebound. Rebound was calculated relative to both immediate and 20-s postdialysis samples to study early components of rebound unrelated to access recirculation. The equilibrated Kt/V (eKt/V) computed by fitting the two-pool variable volume model to the 30-min postdialysis sample agreed well with eKt/V based on the 60-min postdialysis sample. Using the pre-, post-, and 30-min postdialysis samples for 1245 patients with arteriovenous (AV) accesses, the median intercompartmental mass transfer coefficient (Kc) was 797 ml/min for rebound computed relative to the 20-s postdialysis samples and 592 ml/min relative to the immediate postdialysis samples. K/V was the strongest predictor of rebound among 22 factors considered. Other factors associated with greater rebound for 1331 patients using AV accesses or venous catheters included access type, black race, male gender, absence of congestive heart failure, greater age, ultrafiltration rate, and low predialysis or intradialysis systolic BP. Equations of the form eKt/V = single-pool Kt/V - B x (K/V) were fit to the data. With AV access, the optimum values for the slope term (B) were 0.39 and 0.46 (in h(-1)) for single-pool Kt/V calculated based on 20-s postdialysis or immediate postdialysis samples, respectively. For patients using venous catheters, the respective values for B were 0.22 and 0.29. Postdialysis urea rebound can be predicted with acceptable accuracy from a postdialysis sample using a zero-intercept, K/V-based rate equation. Several patient or treatment-specific factors predict enhanced or reduced rebound. Rate equation slope coefficients for K/V of 0.39 (AV access) and 0.22 (venous access) are proposed when a 15- to 20-s slow-flow method is used to draw the postdialysis blood. Slightly higher K/V slope coefficients (0.46 and 0.29, respectively) should be used if a shorter (e.g., 10 s) slow-flow period is used.

Short-term effects of blood pressure control and antihypertensive drug regimen on glomerular filtration rate: The African-American study of kidney disease and hypertension pilot study

The African-American Study of Kidney Disease and Hypertension pilot study randomized 94 nondiabetic black men and women (mean age, 53 years; 75% male) with presumed hypertensive nephrosclerosis and a baseline glomerular filtration rate (GFR) of 25 to 70 mL/min/1.73 m2 (mean, 52.3 mL/min/1.73 m2) to blood pressure control at either a low mean arterial pressure (MAP) goal of < or = 92 mm Hg or a usual MAP goal of 102 to 107 mm Hg and an antihypertensive drug regimen that included either a calcium antagonist (amlodipine), a beta-blocker (atenolol), or an angiotensin-converting enzyme (ACE) inhibitor (enalapril). After 3 months of follow-up (n = 90), the mean GFR was similar (53.0 mL/min/1.73 m2 v 53.7 mL/min/1.73 m2) to the baseline levels in participants randomized to the low MAP group (n = 44), whereas the mean GFR increased by 3.9 mL/min/1.73 m2 (P = 0.02) in participants randomized to the usual MAP group (n = 46). During the same period of time, the mean GFR increased significantly in participants randomized to the calcium channel blocker regimen (n = 28) (5.7 mL/min/ 1.73 m2; P = 0.01) but not in participants randomized to the beta-blocker regimen (n = 31) (1.7 mL/min/1.73 m2; P = 0.10) or the ACE inhibitor regimen (n = 31) (1.1 mL/min/1.73 m2; P = 0.52). Changes in GFR at 3 months were significantly different among the three treatment groups (P = 0.04). We conclude that the magnitude of short-term effects of blood pressure control and antihypertensive drug regimens on GFR should be considered when estimating sample size for clinical trials designed to evaluate the effects of these interventions on long-term changes in GFR slope.

Care pathway reduces hospitalizations and cost for hemodialysis vascular access surgery

Hemodialysis vascular access-related hospitalizations account for more than 20% of United States end-stage renal disease (ESRD) hospitalizations, with an annual cost approximating

Nephrotoxicity of antiviral therapies.

675 million. Limiting access-related costs while delivering similar degrees of quality care thus would enhance alternative utilization of ESRD funding. We implemented a vascular access care pathway emphasizing coordinated patient evaluation and outpatient surgery to determine whether such an intervention affected outcomes associated with vascular access surgery. Data examining hospitalization and vascular access surgery charges, complications, and patient satisfaction (determined by questionnaire) were analyzed, comparing patients who underwent vascular access surgery in 1994 and 1995 as inpatients (non-care pathway patients) and patients who underwent vascular access surgery via the care pathway in 1995. Inpatient days declined in 1995 (1994: 582 days; 1995: 85 days; P < 0.03) and the average charges per patient for the care pathway cohort were significantly less than charges per patient in 1994 and charges for non-care pathway patients in 1995 (1994 patients:

Improving Outcomes in Chronic Hemodialysis Patients: Should Dialysis be Initiated Earlier?

10,524 +/-

Effect of Ramipril vs Amlodipine on Renal Outcomes in Hypertensive Nephrosclerosis: A Randomized Controlled Trial

5,209; 1995 non-care pathway patients:

Relationship between nutritional status and the glomerular filtration rate: Results from the MDRD Study

11,196 +/-