Effects of different ACE inhibitor combinations on albuminuria: results of the GUARD study.

Clinical practice guidelines recommend blockers of the renin-angiotensin system alone or in combination with other agents to reduce blood pressure and albuminuria in patients with type 2 diabetes. Dihydropyridine calcium channel blockers, however, may lower blood pressure but not albuminuria in these patients. Here we tested the hypothesis that combining an ACE inhibitor with either a thiazide diuretic or a calcium channel blocker will cause similar reductions in blood pressure and albuminuria in hypertensive type 2 diabetics. We conducted a double blind randomized controlled trial on 332 hypertensive, albuminuric type 2 diabetic patients treated with benazepril with either amlodipine or hydrochlorothiazide for 1 year. The trial employed a non-inferiority design. Both combinations significantly reduced the urinary albumin to creatinine ratio and sitting blood pressure of the entire cohort. The percentage of patients progressing to overt proteinuria was similar for both groups. When we examined patients who had only microalbuminuria and hypertension we found that a larger percentage of the diuretic and ACE inhibitor normalized their albuminuria. We conclude that initial treatment using benzaepril with a diuretic resulted in a greater reduction in albuminuria compared to the group of ACE inhibitor and calcium channel blocker. In contrast, blood pressure reduction, particularly the diastolic component, favored the combination with amilodipine. The dissociation between reductions in blood pressure and albuminuria may be related to factors other than blood pressure.

Non-traditional risk factors predict coronary calcification in chronic kidney disease in a population-based cohort.

The increased burden of cardiovascular disease in chronic kidney disease cannot be explained by traditional risk factors alone. Here, we evaluated the impact of non-traditional factors on the association of chronic kidney disease with coronary artery calcification using logistic regression among 2672 Dallas Heart Study patients of whom 220 had chronic kidney disease. The prevalence of coronary calcification significantly increased across all chronic kidney disease stages and this remained independently associated with coronary calcification after adjusting for traditional factors. The calcium x phosphorus product, homocysteine, and osteoprotegerin each diminished the magnitude of association between kidney disease and coronary calcification. After adjustment for these, the association between kidney disease and coronary calcification was no longer significant with the effects most prominent in the stages 3-5 subgroup. Our study has identified three non-traditional independent predictors of coronary calcification that diminished the association between chronic kidney disease and coronary calcification. These factors may represent novel mechanistic links warranting further investigation.

The effect of losartan on hemoglobin concentration and renal outcome in diabetic nephropathy of type 2 diabetes.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can decrease hemoglobin, causing anemia and this may be an independent risk factor for chronic kidney disease progression. We studied the relationship between a decline in hemoglobin and outcome in 1513 patients with type 2 diabetes and kidney disease by a post hoc analysis of the RENAAL Study (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan) with an average follow-up of 3.4 years. The relationship between baseline and year-1 hemoglobin and treatment on end-stage renal disease (ESRD) and ESRD or death was evaluated using multivariate Cox models (covariates: baseline hemoglobin, proteinuria, serum albumin, serum creatinine, and year-1 hemoglobin). Compared with placebo, losartan treatment was associated with a significant decrease of hemoglobin, with the largest between-group difference at 1 year. After adjustment, there were significant relative risk reductions for losartan compared with placebo for ESRD and for ESRD or death regardless of the baseline hemoglobin even in those patients with a baseline hemoglobin below 120 g l(-1). Hence, the renoprotective properties of losartan were maintained despite a significant lowering of the hemoglobin concentration.

Rationale and design of a study comparing two fixed-dose combination regimens to reduce albuminuria in patients with type II diabetes and hypertension.

Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD). The early stage of nephropathy is manifested by the presence of low levels of urinary albumin (microalbuminuria or urinary albumin excretion >or=30 and <299 mg/day). Albuminuria is a marker for development of nephropathy in type II diabetes and for increased cardiovascular morbidity and mortality. Recent studies have demonstrated the importance of antihypertensive agents that inhibit the renin-angiotensin-aldosterone (RAA) system to reduce the risk and slow down the progression of renal disease. A new clinical trial, GUARD (Gauging Albuminuria Reduction With Lotrel in Diabetic Patients With Hypertension), is designed to compare the change in urinary albumin to creatinine ratio after 1 year of initial treatment with either amlodipine besylate/benazepril HCl or benazepril HCl/hydrochlorothiazide. Other objectives include a comparison of the proportion of patients who progress to overt diabetic nephropathy and the safety of these two combination therapies in these high-risk patients.

Hypertension and kidney literature review 2000.

Important advances in our understanding of the mechanisms and treatment of hypertension in patients at risk for renal disease and those with overt renal disease are taking place. Thus, new data suggest that hyperfiltration may be an important antecedent to the development of kidney disease in hypertensive African-Americans. Also new studies provide evidence for differential responses of endothelial function and sympathetic nerve traffic to ACE inhibitors versus dihydropyridine calcium channel blockers in hypertensives with and without overt renal disease. Important new studies also show that in proteinuric subjects ACE inhibitor treatment is superior to non-ACE treatment at reducing proteinuria and the risk of developing ESRD in non-diabetics with renal disease. In hemodialysis patients, both systolic hypertension and hypotension predict increased mortality in hemodialysis patients. And, identification of factors important in persisting hypertension in patients on hemodialysis provide new insights into improving BP control in this population. The purpose of this review is to highlight the key elements and clinical relevance of these recent studies.

Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial.

CONTEXT: Incidence of end-stage renal disease due to hypertension has increased in recent decades, but the optimal strategy for treatment of hypertension to prevent renal failure is unknown, especially among African Americans. OBJECTIVE: To compare the effects of an angiotensin-converting enzyme (ACE) inhibitor (ramipril), a dihydropyridine calcium channel blocker (amlodipine), and a beta-blocker (metoprolol) on hypertensive renal disease progression. DESIGN, SETTING, AND PARTICIPANTS: Interim analysis of a randomized, double-blind, 3 x 2 factorial trial conducted in 1094 African Americans aged 18 to 70 years with hypertensive renal disease (glomerular filtration rate [GFR] of 20-65 mL/min per 1.73 m(2)) enrolled between February 1995 and September 1998. This report compares the ramipril and amlodipine groups following discontinuation of the amlodipine intervention in September 2000. INTERVENTIONS: Participants were randomly assigned to receive amlodipine, 5 to 10 mg/d (n = 217), ramipril, 2.5 to 10 mg/d (n = 436), or metoprolol, 50 to 200 mg/d (n = 441), with other agents added to achieve 1 of 2 blood pressure goals. MAIN OUTCOME MEASURES: The primary outcome measure was the rate of change in GFR; the main secondary outcome was a composite index of the clinical end points of reduction in GFR of more than 50% or 25 mL/min per 1.73 m(2), end-stage renal disease, or death. RESULTS: Among participants with a urinary protein to creatinine ratio of >0.22 (corresponding approximately to proteinuria of more than 300 mg/d), the ramipril group had a 36% (2.02 [SE, 0.74] mL/min per 1.73 m(2)/y) slower mean decline in GFR over 3 years (P =.006) and a 48% reduced risk of the clinical end points vs the amlodipine group (95% confidence interval [CI], 20%-66%). In the entire cohort, there was no significant difference in mean GFR decline from baseline to 3 years between treatment groups (P =.38). However, compared with the amlodipine group, after adjustment for baseline covariates the ramipril group had a 38% reduced risk of clinical end points (95% CI, 13%-56%), a 36% slower mean decline in GFR after 3 months (P =.002), and less proteinuria (P<.001). CONCLUSION: Ramipril, compared with amlodipine, retards renal disease progression in patients with hypertensive renal disease and proteinuria and may offer benefit to patients without proteinuria.

Pravastatin treatment of very low density, intermediate density and low density lipoproteins in hypercholesterolemia and combined hyperlipidemia secondary to the nephrotic syndrome.

BACKGROUND/AIMS: In the current study pravastatin was used in nephrotic syndrome patients with hypercholesterolemia and combined hyperlipidemia to test whether the drug decreases production of LDL and reduces levels of VLDL and IDL. METHODS: Thirteen patients (7 with high LDL alone and 6 with high VLDL, IDL and LDL) were randomized in a placebo-controlled study that had a crossover design. Patients were treated 8 weeks with pravastatin (40 mg/day) (or placebo) and switched to the corresponding placebo/drug for another 8 weeks. During each phase of the trial, patients had measurement of plasma levels of lipoprotein lipids, and turnover rates of autologous LDL apo B. RESULTS: Pravastatin increased LDL clearance by 16.7% and reduced total cholesterol content per LDL particle in patients with hypercholesterolemia. In combined hyperlipidemia, LDL clearance increased by 19% and there was no significant change in the production of LDL-apo B. Levels of VLDL+IDL apo B were not reduced significantly, while the total cholesterol content of these particles was reduced by 31.7%. CONCLUSION: Pravastatin effectively reduced LDL levels in both types of dyslipidemia by increasing LDL clearance. Treatment had no effect on production of LDL or on levels of VLDL+IDL-apo B. Thus, pravastatin increases LDL clearance. Statins do not seem to affect production rates of apo B-containing lipoproteins. Treatment of combined hyperlipidemia may require pravastatin and an added drug targeted to normalize levels of VLDL and IDL.

Reversible renal toxicity resulting from high single doses of the new radiosensitizer gadolinium texaphyrin.

Gadolinium (III) texaphyrin (Gd-Tex) (NSC 695238) is a potential radiation sensitizer that selectively localizes in tumors and is detectable by magnetic resonance imaging (MRI). In this single-dose phase I trial, reversible renal injury was the dose-limiting toxicity. This report details that renal injury. A single intravenous dose of Gd-Tex was followed 2 hours later by radiation therapy. The Gd-Tex dose was escalated in 13 patient cohorts. Doses ranged from 0.6 to 29.6 mg/kg. The maximum tolerated dosage (MTD) was 22.3 mg/kg. Three patients had grade II and one had grade III acute nonoliguric renal failure at the 22.3 and 29.6 mg/kg dose levels. The injury was always transient, and responded to fluid restriction and renal diet. In all patients, transient green discoloration including urine developed at doses > or =7.1 mg/kg. MRI studies demonstrated image enhancement in the liver, kidneys, and in primary and metastatic tumors in all patients receiving >5.4 mg/kg. It is important that the liver and kidneys be excluded from the radiation volume. Gd-Tex was well tolerated at doses below the MTD. It is important that the liver and kidneys be excluded from the radiation volume. We recommend that 16.7 mg/kg be used as the maximum single dose to obviate even low grade renal toxicity.

Creatinine clearance as a measure of GFR in screenees for the African-American Study of Kidney Disease and Hypertension pilot study.

Serum creatinine and endogenous creatinine clearance (CrCl) are widely used measures of renal function. This study compares the precision, bias, and sources of error in using different CrCl measures to estimate the glomerular filtration rate (GFR) in 118 men and women screened for the African-American Study of Kidney Disease and Hypertension (AASK) pilot study. We measured serum creatinine, 24-hour CrCl, and CrCl during timed clearance periods conducted simultaneously with an 125I-iothalamate GFR study. Serum creatinine was measured using two different kinetic rate Jaffe methods (CX3 and Hitachi). After standardization for body surface area, the different measures of renal function available for each individual were compared with the 125I-iothalamate GFR simultaneous to the CrCl. In a subset of 50 participants, the CrCl measures were compared with a follow-up GFR (fGFR). The mean 125I-iothalamate GFR was 65.2 (SD, 26.4), with a range of 11 to 122 mL/min/1.73 m2. The mean +/- SD percentage differences from the GFR were -9%+/-22% for the Cockcroft-Gault estimated CrCl, 1%+/-29% for the 24-hour CrCl, and 8%+/-16% for the CX3 simultaneous CrCl. The Hitachi method overestimated serum creatinine and underestimated GFR. Compared with an fGFR, the mean +/- SD differences were 2%+/-19% for the first GFR, -6%+/-20% for the Cockcroft-Gault estimated CrCl, 10%+/-28% for the 24-hour CrCl, and 14%+/-29% for the CX3 simultaneous CrCl. Thus, the increased precision with which the timed CrCl predicted its simultaneous GFR did not extend to improved ability to predict a future GFR. The fractional excretion of creatinine, measured as the ratio of the CX3 simultaneous CrCl to 125I-iothalamate clearance, increased with decreasing GFR but was lower than expected (mean +/- SD of 1.21+/-0.16 for GFRs between 20 and 40 mL/min/1.73 m2). The lower fractional excretion explains why the 24-hour and Cockcroft-Gault CrCls did not overestimate GFR, but the reasons for this lower excretion are uncertain. Creatinine assay specificity and calibration are important sources of variability that must be examined in any CrCl measure of GFR. We conclude that despite requiring substantially more time and effort, neither the outpatient 24-hour urine nor the timed CrCl offered increased precision over a calculation based on serum creatinine, sex, age, and weight in predicting GFR.

Racial differences in the renal response to blood pressure lowering during chronic angiotensin-converting enzyme inhibition: a prospective double-blind randomized comparison of fosinopril and lisinopril in older hypertensive patients with chronic renal insufficiency.

This study was undertaken to compare the effects of chronic angiotensin-converting enzyme (ACE) inhibition on blood pressure (BP) and renal hemodynamics in older black and nonblack hypertensive patients with chronic renal insufficiency. A multicenter, placebo lead-in double-blind, parallel group study was performed to compare the antihypertensive efficacy and renal hemodynamic response to the once-daily ACE inhibitor fosinopril (n = 14) and lisinopril (n = 13) over a 22-week period. The study goal was to lower diastolic blood pressure (DBP) to 90 mm Hg or less. Furosemide was added after 6 weeks if blood pressure goal was not achieved. At outpatient clinics at university medical centers, 27 older hypertensive patients (> or = 45 years; 12 blacks, 15 nonblacks; 19 male, eight female) with DBP of 95 mm Hg or higher and 4-hour creatinine clearance 20 to 70 mL/min/1.73 m2 were studied. Changes (delta) from baseline in BP, glomerular filtration rate (GFR), and renal plasma flow (RPF) were measured. Mean systolic blood pressure (SBP) and DBP decreased significantly and to a similar extent in randomized groups: fosinopril (mean +/- SEM) delta DBP at 6 weeks was -13 +/- 2 (P < 0.0001; 95% CI, -16 to -9) and at 22 weeks was -12 +/- 2 (P < 0.0001; 95% CI, -16 to -9); lisinopril delta DBP at 6 weeks was -14 +/- 6 (P < 0.0001; 95% CI, -10 to -18) and at 22 weeks was -16 +/- 2 (P < 0.0001; 95% CI, -12 to -21). GFR and RPF did not change significantly in either group. BP was significantly reduced and to a similar extent in blacks and nonblacks: for blacks, delta DBP at 6 weeks was -11 +/- 3 (P < 0.05; 95% CI, -0.01 to -9) and at 22 weeks was -16 +/- 2 (P < 0.0001; 95% CI, -11 to -20); for nonblacks, delta DBP at 6 weeks was -14 +/- 1 (P < 0.0001; 95% CI, -12 to -17) and at 22 weeks was -12 +/- 2 (P < 0.0001; 95% CI, -16 to -8). Eight patients (five blacks and three nonblacks) required an addition of furosemide after 6 weeks to reach the DBP goal of < or = 90 mm Hg at 22 weeks. GFR was not significantly altered for either racial group at 6 weeks; however, at 22 weeks; however, at 22 weeks, GFR decreased significantly in blacks (delta GFR, -16 +/- 5; P < 0.006; 95% CI, -26 to -5) and tended to increase in nonblacks (delta GFR, 7 +/- 6; P > 0.25). delta GFR correlated directly with the delta RPF (delta GFR = 0.0611* delta RPF -2.35 +; r = 0.68; P < 0.003). There was no correlation between delta MAP and delta GFR or delta RPF in blacks or nonblacks. We conclude that chronic ACE inhibition with fosinopril and lisinopril alone or in combination with furosemide lowers BP in older blacks and nonblacks with hypertension and chronic renal insufficiency. Racial differences in the renal hemodynamic response to chronic ACE inhibition were noted and appear to be independent of diuretic use and the magnitude of BP lowering.

Evaluation of serum creatinine for estimating glomerular filtration rate in African Americans with hypertensive nephrosclerosis: results from the African-American Study of Kidney Disease and Hypertension (AASK) Pilot Study.

Measurement of GFR is considered the standard for estimating renal function. However, standardized accurate GFR methodology is expensive and cumbersome; therefore, estimates of GFR based on serum creatinine concentration have been employed. The purpose of the study presented here was to assess the accuracy and precision of using serum creatinine measurements to estimate GFR in the screen cohort of The African-American Study of Kidney Disease and Hypertension (AASK) Pilot Study. GFR was estimated by four methods: 100/serum creatinine, Cockcroft-Gault equation, creatinine clearance from 24-h urine collection, and a new regression equation derived from the pilot study data. These methods were compared with renal clearance of 125I-iothalamate GFR (GFR1) in 193 hypertensive (diastolic blood pressure > or = 95 mm Hg) African-American screen (142 men, 51 women). A second GFR (GFR2) was performed in 98 screen who were eligible (GFR1 25-70 mL/min per 1.73 m2) for the pilot study. Accuracy was assessed by the difference of 125I-iothalamate GFR-estimated GFR (delta GFR), and precision was estimated from the combined root mean squared error (CRMSE) and the coefficient of determination (r2). The results for accuracy (+/- SD) and precision were as follows: (1) 100/Scr, delta GFR = -0.76 +/- 16.5, CRMSE = 16.5, r2 = 0.69; (2) Cockcroft-Gault, delta GFR = 9.56 +/- 14.9, CRMSE = 17.7, r2 = 0.66; 3) 24-h creatinine clearance, delta GFR = 0.79 +/- 20.7, CRMSE = 20.7, r2 = 0.49; 4) New equation delta GFR = -0.08 +/- 12.8, CRMSE 12.7, r2 = 0.75. In comparison, a second GFR (GFR2, N = 98) had delta GFR = 1.36 +/- 8.48, CRMSE 8.6, r2 = 0.75. Estimates based on 100/SCr and the new equation were the most precise. It was concluded that GFR estimated by serum creatinine is superior to outpatient 24-h urine creatinine clearance in this population. Serum creatinine values can be used to provide a reasonably accurate estimate of GFR in hypertensive African Americans.

Effect of ramipril on blood pressure and protein excretion rate in normotensive nondiabetic patients with proteinuria.

Angiotensin-converting enzyme inhibitors reduce proteinuria in both normotensive and hypertensive patients with proteinuric renal disease. However, the mechanism of the antiproteinuric effect has not been clarified. We performed a prospective, double-blind, placebo-controlled, randomized crossover trial to test the hypothesis that the antiproteinuric effect of ramipril was due to an improvement in glomerular permselectivity independent of blood pressure and glomerular filtration rate. The effect of low-dose (1.25 mg/d) and high-dose (5 mg/d) ramipril was assessed in 15 normotensive nondiabetic patients with proteinuria (> 150 mg/d). The study was divided into four 12-week periods: placebo, high- or low-dose ramipril, crossover to low- or high-dose ramipril, and placebo. Blood pressure, glomerular filtration rate, renal plasma flow rate, urinary protein excretion rate, and plasma angiotensin II levels were measured at the end of each period. Mean arterial pressure, urine protein to creatinine ratio, and albumin excretion rate decreased significantly during low- and high-dose ramipril. Glomerular filtration rate and renal plasma flow rate were not changed significantly. Plasma angiotensin II levels decreased with both low- and high-dose ramipril. There were no episodes of hypotension and only one subject developed cough during ramipril that did not require discontinuation of the study drug. In conclusion, administration of ramipril in both low and high doses lowered blood pressure and reduced proteinuria in this cohort of normotensive patients with a variety of proteinuric renal diseases. The antiproteinuric effect of ramipril is probably mediated by a reduction in glomerular capillary pressure.

Design and baseline characteristics of participants in the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study.

Hypertension and end-stage renal disease (ESRD) are major causes of morbidity and mortality in the United States, especially among African Americans. The African American Study of Kidney Disease and Hypertension (AASK) Pilot Study evaluated the feasibility of conducting a long-term clinical trial to compare the effects of two levels of blood pressure control and three different antihypertensive drug regimens on the rate of decline in glomerular filtration rate (GFR) in African Americans with clinically diagnosed hypertensive renal disease. African American men and women aged 18-70 years with a GFR of 25-70 ml/min/ 1.73m2 and hypertension were randomized in a 3 x 2 factorial design to initial treatment with either an angiotensin-converting enzyme inhibitor (enalapril), a calcium channel blocker (amlodipine), or a beta blocker (atenolol) and to a mean arterial blood pressure (goal MAP) of either 102-107 mm Hg or < or = 92 mm Hg. Furosemide, doxazosin, clonidine, hydralazine, and minoxidil were added sequentially until goal MAP was achieved. To compare the pathologic diagnosis with the clinical diagnosis of renal disease, study participants without contraindication were also asked to undergo a renal biopsy. The goals of the AASK Pilot Study were to evaluate recruitment techniques, adherence to prescribed antihypertensive drug regimens, ability of the antihypertensive regimens to achieve blood pressure goals, rates of participation in scheduled clinic visits and procedures, and variability of GFR measurements. A further goal was to obtain renal biopsy data in at least 75% of the randomized study participants. Compared to the ESRD patient population whose renal disease is caused by hypertension, women were underrepresented in the AASK Pilot Study. AASK Pilot Study participants had higher unemployment rates and lower income levels than African Americans in the general U.S. population.

Treatment of dyslipidemia in chronic renal failure.

Dyslipidemia in end-stage renal disease is a common problem and may contribute to the high rates of morbidity and mortality in this population. Recent studies indicate that defective lipolysis is a major factor in the development of this disorder which is characterized by increased levels of very-low-density-lipoprotein remnant particles, hypertriglyceridemia and occasionally hypercholesterolemia. There are no prospective long-term studies on the effect of lipid-lowering treatment on morbidity and mortality related to dyslipidemia. Therefore, at present pharmacologic treatment of hyperlipidemia should be undertaken in patients with severe hypertriglyceridemia (> 500 mg/dl) or hypercholesterolemia (LDL > 130 mg/dl) who are at high risk for coronary artery disease. This review discusses the pathogenesis of dyslipidemia, common clinical patterns of hyperlipidemia and various nonpharmacologic and pharmacologic treatment options.

Conventional measurement of renal function utilizing serum creatinine, creatinine clearance, inulin and para-aminohippuric acid clearance.

Inulin and para-aminohippuric acid clearances, determined by the conventional method of continuous intravenous infusion with blood and urine sample collections, are the gold standards for estimating glomerular filtration rate and renal plasma flow, respectively. Creatinine clearance provides a reasonably good estimate of glomerular filtration rate but is still subject to errors in accuracy and precision. However, novel methods employing cimetidine to block renal tubular creatinine secretion hold promise for improving the accuracy of estimates. More importantly, a large (and growing) number of studies have consistently demonstrated that estimating glomerular filtration rate by creatinine clearance calculated from the Cockcroft-Gault formula is better than measuring creatinine clearance with a 24-h urine collection. Until newer, more simple methods are developed, calculating creatinine clearance using fasting serum creatinine level, body weight, age and sex provides a reasonable and clinically useful bedside measure of glomerular filtration rate for the practising clinician.

Accuracy of urea removal estimated by kinetic models.

The most accurate method for assessing the dialysis dose delivered during high efficiency/flux hemodialysis has not been established. Most current indices of dialysis dose are based on blood-side urea measurements, and thus estimate urea removal. Unfortunately, these methods may lead to inappropriately short dialysis during high flux or high efficiency dialysis, perhaps because of inaccuracies in estimating the amount of urea removal. It is unknown whether these clearance-based approaches can accurately predict either absolute or fractional net urea removal, the latter being equivalent to the solute removal index (SRI). Therefore, we compared the urea removal calculated by five blood-side kinetic methods: (1) urea reduction ration, (2) 1-pool, (3) 2-pool models, and the (4) Smye and (5) Daugirdas formulae. These were compared with the gold standard measurement by direct dialysate quantification. Eight stable patients receiving high-flux hemodialysis were studied over four sessions each. BUN was measured at 0, 45 minutes, 90 minutes, end dialysis, one hour after dialysis (equilibrium value), and 48 hours later. Total body water was determined from the dialysate urea removal; the urea generation rate was calculated using one hour post-dialysis and 48-hour BUN values. Both the total body water and urea generation rate were provided to the 1- and 2-pool models to optimize accuracy. The urea reduction ratio overestimated SRI. The 1-pool model overestimated both absolute urea removal and SRI in 28 of 32 sessions. The 2-pool model slightly underestimated both absolute urea removal and SRI. In contrast, the Smye and Daugirdas formulas accurately estimated SRI.(ABSTRACT TRUNCATED AT 250 WORDS)

"Strict" blood pressure control and progression of renal disease in hypertensive nephrosclerosis.

Hypertensive nephrosclerosis is a progressive renal disease and the leading cause of end-stage renal disease (ESRD) in blacks in the United States. It is generally believed that hypertensive renal injury is responsible for progressive renal failure; however, it is not known whether pharmacologic lowering of blood pressure to any level prevents progression of renal disease. Accordingly, we performed a long-term prospective randomized trial to determine whether "strict" [diastolic blood pressure (DBP) 65 to 80 mm Hg] versus "conventional" (DBP 85 to 95 mm Hg) blood pressure control is associated with a slower rate of decline in glomerular filtration rate. Eighty-seven non-diabetic patients (age 25 to 73; 68 black, 58 male) with long-standing hypertension (DBP > or = 95 mm Hg), chronic renal insufficiency (GFR < or = 70 m/min/1.73 m2) and a normal urine sediment were studied. DBP was pharmacologically lowered to < or = 80 mm Hg (3 of 4 consecutive measurements at 1 to 4 weeks intervals) after which patients were randomized. DBP and GFR (renal clearance of 125I-iothalamate) were measured at baseline, at three months and every six months post-randomization. The rate of decline in GFR (GFR slope, in ml/min/1.73 m2/year), estimated by the method of maximum likelihood in a mixed effects model, was the primary outcome variable. In a secondary analysis, 50% reduction in GFR (or a doubling of serum creatinine) from baseline, ESRD and death were combined.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolism of low density lipoproteins in nephrotic dyslipidemia: comparison of hypercholesterolemia alone and combined hyperlipidemia.

High levels of low-density lipoprotein cholesterol (LDL) (hypercholesterolemia) are commonly present in the nephrotic syndrome. Another pattern of dyslipidemia in nephrotic patients is an elevation of both cholesterol and triglyceride levels (combined hyperlipidemia). It has been postulated that the underlying cause of nephrotic dyslipidemia is an hepatic overproduction of apolipoprotein B (apo B)-containing lipoproteins. To examine this hypothesis, the metabolism of LDL-apo B was compared between nephrotic patients with hypercholesterolemia and with combined hyperlipidemia. Thirteen patients (7 with hypercholesterolemia, and 6 with combined hyperlipidemia) underwent measurements of turnover rates of autologous LDL apo B. The results were compared to normolipidemic controls and to patients with primary combined hyperlipidemia previously studied in our laboratory. Nephrotic patients with hypercholesterolemia generally had: (a) lower fractional catabolic rates of LDL apo B than normolipidemic healthy individuals; (b) LDL particles enriched in cholesterol; but (c) no overproduction of LDL apo B. In contrast, patients with combined hyperlipidemia were found to have: (a) high fractional catabolic rates for LDL apo B compared to normolipidemic controls; (b) cholesterol-poor LDL particles; and (c) markedly elevated production rates for LDL. Also, for the group as a whole, there was a positive correlation between plasma triglyceride levels and fractional catabolic rates. These data indicate that the metabolism of LDL is strikingly different between the two forms of nephrotic dyslipidemia. Although there may be common mechanisms contributing to LDL levels in nephrotic patients, there also appears to be a divergence of mechanisms depending on whether hypertriglyceridemia is associated with hypercholesterolemia.