Effects of blood pressure control on progressive renal disease in blacks and whites. Modification of Diet in Renal Disease Study Group.

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 < or = 107 or < 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 < or = 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.

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.

Therapeutic interventions for nephropathy in type I diabetes mellitus.

Diabetic nephropathy is the single most common cause of end-stage renal disease in the United States. Recently, several major therapeutic interventions have been developed and shown to slow or halt the progression of renal failure in patients with diabetes and diabetic kidney disease. Studies have shown that in patients with insulin-dependent diabetes and proteinuria, lowering systemic blood pressure slows the rate of decline in renal function and improves patients' survival. In the recently completed trial of angiotensin converting enzyme (ACE) inhibition in diabetic nephropathy, ACE inhibitors were specifically shown to decrease dramatically the risk of doubling of serum creatinine or reaching a combined outcome of end-stage renal disease or death independent of their effect on systemic blood pressure. In studies with small numbers of patients, dietary protein restriction has also been shown to slow the rate of decline of renal function. New potential interventions currently undergoing study include treatment with aldose reductase inhibitors, treatment with inhibitors of the formation of advanced glycosylation end-products, treatment of dyslipidemia, and a variety of other less well-studied interventions.

Atherosclerotic ischemic renal disease.

Over the past decade, ischemic nephropathy has gained recognition as a distinct and treatable clinical entity. Atherosclerotic renal artery stenosis is the leading cause of ischemic renal disease. Among the aging population entering renal replacement programs, both renal artery and systemic atherosclerosis are common. Over recent years, patients with ischemic renal disease are presenting later and have diffuse atherosclerosis and other comorbid conditions. Improved screening techniques, patient selection, and interventional approaches have resulted in better outcomes in most centers. Percutaneous transluminal renal angioplasty has emerged as the treatment of choice in some centers for nonostial renal artery stenosis. Both percutaneous transluminal renal angioplasty and surgical repair have proven beneficial for renal function salvage. Many studies have elegantly demonstrated the pathophysiologic consequences of acute ischemia to the kidney. The concepts derived from acute studies have served as a springboard for considering the adaptive and maladaptive renal responses to chronic ischemia.

Accuracy of the diagnosis of hypertensive nephrosclerosis in African Americans: a report from the African American Study of Kidney Disease (AASK) Trial. AASK Pilot Study Investigators.

African Americans have excess hypertension and end-stage renal disease presumed due to hypertension compared to Caucasians. The AASK was designed to examine the impact of antihypertensive therapies and two levels of blood pressure control on the rate of decline of GFR in African Americans with presumed hypertensive renal disease. During the pilot phase of the trial, eligible participants were requested to undergo renal biopsy to assess the underlying lesions in this population. Eighty-eight hypertensive (diastolic BP > 95 mm Hg) non-diabetic African American patients between the ages of 18 to 70 years, with GFR between 25 to 70 ml/min/1.73 m2 and without marked proteinuria were assessed for possible renal biopsy. Forty-three patients did not undergo renal biopsy due to refusal or contraindications. Adequate renal biopsies were obtained in 39 of the remaining 46 patients. Biopsy findings were analyzed and then compared to clinical parameters. The 39 patients studied, 29 men and 10 women, were on average 53.0 +/- 11.0 years old, and had a MAP of 109 +/- 15 mm Hg and GFR 51.7 +/- 13.6 ml/min/1.73 m2 (not significantly different from nonbiopsied patients). Thirty-eight of these 39 biopsies showed arteriosclerosis and/or arteriolosclerosis, severity on average 1.5 +/- 0.9 and 1.5 +/- 0.8, respectively on a 0 to 3+ scale. Interstitial fibrosis was moderate, 1.3 +/- 0.9 (0 to 3+ scale). Segmental glomerulosclerosis was present in five biopsies, and in one patient, biopsy and clinical findings were consistent with idiopathic focal segmental glomerulosclerosis. Additional lesions included mesangiopathic glomerulonephritis in one patient, basement membrane thickening suggestive of diabetic nephropathy in one, and cholesterol emboli in two cases. Arteriolar and arterial sclerosis were tightly linked, and correlated with interstitial fibrosis and the reciprocal of serum creatinine. Global glomerulosclerosis was extensive, involving on average 43 +/- 26% of glomeruli. The extent of this lesion did not correlate with degree of arteriolar or arterial thickening, but did correlate with systolic blood pressure (P = 0.0174), the reciprocal of serum creatinine (P = 0.0009), serum cholesterol (P = 0.0129) and interstitial fibrosis (P < 0.0001). These data underscore that renal biopsies in non-diabetic hypertensive African-Americans with mild to moderate renal insufficiency in the absence of marked proteinuria are overwhelmingly likely to show renal vascular lesions consistent with the clinical diagnosis of hypertensive nephrosclerosis.

Cholesterol as a predictor of progression in nondiabetic chronic renal disease.

In summary, then, there is an accumulating body of clinical human data supporting the concept that lipid nephrotoxicity may be important in the initiation of renal injury, and that lipids play a synergistic role in the inexorable process of progression to end-stage renal disease in nondiabetic as well as diabetic chronic renal disease. Further clarification of the role of lipid nephrotoxicity and impact of therapeutic interventions await data from larger prospective studies aimed at this specific question.

Predictors of the progression of renal insufficiency in patients with insulin-dependent diabetes and overt diabetic nephropathy. The Collaborative Study Group.

We designed a prospective, double-blind controlled trial to determine predictors of loss of renal function in patients with insulin dependent diabetes and established nephropathy. A total of 409 insulin-dependent diabetic patients with established nephropathy enrolled in a trial on the effect of Captopril on the rate of progression of renal disease. Baseline demographic, clinical (history and physical) and laboratory parameters were analyzed as risk factors for time to progression. Dichotomous characteristics were compared by Fisher's exact test and continuous characteristics with the Wilcoxon rank-sum test. Univariate proportional hazards regression analysis was used to estimate relative risk of nephropathy progression, and bivariate proportional hazard regression to identify interactions with the treatment group assignment. Multivariate proportional hazard regression was employed to determine which characteristics were independent risk factors. We found that a number of demographic and clinical characteristics were significantly associated with nephropathy progression even after adjustment for treatment group. However, after multivariate analysis, the risk factors that independently predicted progression were onset of IDDM later in life, parental diagnosis of IDDM, the presence of edema, increased mean arterial pressure, and an abnormal electrocardiogram. Likewise, a number of laboratory characteristics were also predictive of nephropathy progression. A low hematocrit, high blood sugar, and higher protein excretion predicted nephropathy progression as did a higher serum creatinine, particularly in the face of a normal serum albumin. In conclusion, this study identifies a number of clinical and laboratory risk factors that can predict which patients with insulin-dependent diabetes with established nephropathy are more likely to sustain a clinically important decrease in renal function over a median follow-up of three years.

Carcinoid tumor and the nephrotic syndrome: a novel association between neoplasia and glomerular disease.

Various malignancies are associated with the paraneoplastic evolution of the nephrotic syndrome. Renal biopsy in these instances frequently shows membranous glomerulonephritis. We describe a patient who had metastatic bronchial carcinoid tumor with development of microscopic hematuria and subsequent nephrotic syndrome in conjunction with another paraneoplastic process, a malignancy-related neuropathy. A decline in actual glomerular filtration rate led to percutaneous renal biopsy, which revealed fine holes in the glomerular basement membrane and focal capillary corrugation. Electron microscopy showed numerous small subepithelial dense deposits and fusion of foot processes, confirming the diagnosis of stage I membranous nephropathy. We believe this is the first published case of true carcinoid tumor associated with the nephrotic syndrome and a specific paraneoplastic glomerular lesion. Carcinoid tumor should be considered in the spectrum of malignancies associated with paraneoplastic development of the nephrotic syndrome.

The natural history of renal artery stenosis: who should be evaluated for suspected ischemic nephropathy?

Ischemic renal disease is defined as a clinically significant reduction in glomerular filtration rate in patients with hemodynamically significant renal artery stenosis. The most common etiology for this is atherosclerotic renal artery disease. The three major clinical settings in which one must suspect ischemic renal disease include acute renal failure precipitated by the treatment of hypertension particularly with angiotensin-converting enzyme inhibitors; progressive azotemia in a patient with known renal vascular hypertension treated medically; and unexplained progressive azotemia in an elderly patient with refractory hypertension and other evidence of atherosclerotic disease. Prevalence of ischemic renal disease secondary to atherosclerosis can be estimated from the incidence of atherosclerotic renal artery lesions leading to renal vascular hypertension and the natural history of these lesions. Autopsy series, arteriography studies, and review of populations of patients in end-stage renal disease programs all suggest that ischemic renal disease has a high and increasing prevalence in our aging population.

Medical management of nephropathy in type I diabetes mellitus: current recommendations.

Diabetic nephropathy is the single most common cause of end-stage renal disease in the United States. Recently, several major therapeutic interventions have been developed and demonstrated to slow or halt the progression of renal failure in patients with diabetes and diabetic kidney disease. The Diabetes Control and Complications Trial demonstrated that microalbuminuria developed in fewer patients in the intensive blood sugar control group than in the conventional therapy group. Similarly, the risk of developing proteinuria was reduced by intensive blood sugar control. Multiple studies have demonstrated that in patients with insulin-dependent diabetes and proteinuria, lowering the systemic blood pressure slows the rate of decline in renal function and improves patients' survival. In the recently completed trial of ACE inhibition in diabetic nephropathy, ACE inhibitors were specifically shown to decrease dramatically the risk of doubling of serum creatinine or reaching a combined outcome of end-stage renal disease or death. In studies in small numbers of patients with insulin-dependent diabetes and established diabetic nephropathy, dietary protein restriction has also been demonstrated to slow the rate of decline of renal function. New potential interventions currently undergoing study include the use of aldose reductase inhibitors, the use of drugs that prevent the formation of advanced glycosylation end-products, and the use of angiotensin II receptor antagonists. Thus, several established benefits have recently been demonstrated to help prevent the development of or slow the progression of diabetic nephropathy, including blood pressure control, blood sugar control, and treatment with ACE inhibitors. Dietary protein restriction may also be of benefit. Multiple new interventions are undergoing clinical trials currently.

Dietary protein restriction, blood pressure control, and the progression of polycystic kidney disease. Modification of Diet in Renal Disease Study Group.

In the Modification of Diet in Renal Disease Study, a follow-up (mean, 2.2 yr) of 200 study participants with autosomal dominant polycystic kidney disease (ADPKD) was conducted to determine the effect of lowering protein intake and blood pressure on the rate of decline in GFR. The rate of decline was faster in participants with ADPKD than in persons with other diagnoses, reflecting, in part, faster disease progression in the ADPKD group. Baseline characteristics that predicted a faster rate of decline in GFR in persons with ADPKD were greater serum creatinine (independent of GFR), greater urinary protein excretion, higher mean arterial pressure (MAP), and younger age. In patients with initial GFR values between 25 and 55 mL/min per 1.73 m2, neither assignment to a low-protein diet group nor assignment to a low blood pressure group significantly reduced the rate of decline of GFR in ADPKD participants. Similarly, the decline in GFR was not related to achieved protein intake or MAP. In participants with GFR values between 13 and 24 mL/min per 1.73 m2, assignment to the low MAP group led to a somewhat more rapid decline in GFR. However, the more rapid decline in GFR did not appear to be due to a detrimental effect of low blood pressure or the antihypertensive agents used to reach the low blood pressure goal. Lower protein intake, but not prescription of the keto acid-amino acid supplement, was marginally associated with a slower progression of renal disease.

Short-term effects of recombinant human growth hormone in CAPD patients.

Protein and calorie malnutrition is common in chronic dialysis patients. Several interventions have been proposed to prevent and/or to treat malnutrition. Recombinant human growth hormone (rhGH) is a drug with anabolic properties and has been used in several catabolic conditions, such as patients with severe burns as well as in pediatric patients with chronic renal failure. In this study, we evaluated the short-term effects and safety of rhGH on urea kinetics and commonly measured biochemical parameters in 10 stable adult continuous ambulatory peritoneal dialysis (CAPD) patients. The design of the study was prospective, cross-over with the patients serving as their own controls. There were three study periods: baseline (PreGH), treatment (Tx), and follow-up (PostGH). During the seven day Tx period, patients self-administered 5 mg/day s.c. of rhGH. During this time, there was a significant decrease in blood urea nitrogen (BUN) (54 +/- 15 to 40 +/- 12 mg/dl), as well as in the combined dialysate and urine urea nitrogen excretion rate (5.69 +/- 1.86 to 4.04 +/- 1.13 g/day), and protein catabolic rate (0.82 +/- 0.13 to 0.67 +/- 0.09 g/kg/day), (all P < 0.001). Serum phosphorus (4.8 +/- 1.6 to 4.4 +/- 1.8 mg/dl) and potassium (4.0 +/- 0.4 to 3.6 +/- 0.2 mEq/liter) levels also showed a small but statistically significant decrease, in conjunction with a statistically significant increase in serum creatinine levels (12.2 +/- 5.7 to 12.9 +/- 5.7 mg/dl). Dietary protein intake, determined by dietary recall, did not change during the study (66.1 +/- 20.5 vs. 75.8 +/- 22.1 grams/day).(ABSTRACT TRUNCATED AT 250 WORDS)

Macroscopic hematuria secondary to hypercalciuria and hyperuricosuria.

An adult presenting with asymptomatic gross hematuria attributable to hypercalciuria and hyperuricosuria is described. Extensive evaluations for other causes of hematuria were negative, and the gross hematuria resolved with treatment of the hypercalciuria and hyperuricosuria. Hematuria commonly attributable to these metabolic causes in children may also occur in adults. A 24-hour urine collection for the measurement of calcium and uric acid excretion in adults without nephrolithiasis may play an important role in the evaluation of hematuria.

Serum albumin: a predictor of long-term outcome in peritoneal dialysis patients.

We report a long-term follow-up of 71 peritoneal dialysis patients who participated in a prior study that evaluated the serum albumin concentration as a predictor of short-term morbidity. In this study the use of the original serum albumin level to predict failure of peritoneal dialysis or death was investigated. Sixty-nine of the original 71 study patients were followed for 2 years from the time of enrollment in the initial study. Patients who died within this 2-year period had a significantly lower serum albumin concentration during the original study period (2.7 +/- 0.7; n = 8) than those remaining on peritoneal dialysis (3.6 +/- 0.4, n = 31), those transferred to hemodialysis (3.4 +/- 0.5; n = 13), or those receiving renal transplants (3.6 +/- 0.4 g/dL; n = 17) (P < 0.05 for all comparisons v the group that died). A low serum albumin during the original study period was not predictive of patients who transferred to hemodialysis. We conclude that the stable outpatient serum albumin concentration in peritoneal dialysis patients is a powerful predictor of mortality as well as of short-term morbidity.

Ischemic nephropathy.

Data suggest that ischemic renal disease secondary to atherosclerotic renal artery stenosis is a prevalent health problem. Atherosclerotic renal artery stenosis is a rapidly progressive process that can result in end-stage renal disease. Renal arteriography is the current diagnostic method of choice for the demonstration of renal artery stenosis. Captopril renography, nuclear magnetic resonance angiography, and duplex scanning are promising screening tests for this disorder. Therapeutic options include medical management, percutaneous angioplasty, and surgical revascularization.

Occurrence of pyuria and bacteriuria in asymptomatic hemodialysis patients.

Patients with end-stage renal disease on hemodialysis have documented defects in their immune responses, and infections contribute significantly to their morbidity and mortality. This study prospectively detected and quantitated leukocyturia and bacteriuria in asymptomatic hemodialysis patients. Thirty-one percent of asymptomatic hemodialysis patients had significant pyuria (> 10 white blood cells per high-power field) and 25% had bacteriuria of pathologic dimensions, (> 1 x 10(5)/mL of a single microorganism). Pyuria was a good marker for significant bacteriuria in these patients. These results demonstrate that the urinary tract, even in ESRD patients on hemodialysis, may represent a significant reservoir for infection.

Isolation of human immunodeficiency virus from peritoneal dialysate.

Human immunodeficiency virus (HIV)-seropositive individuals represent a growing population of peritoneal dialysis (PD) patients. An important health care issue in these patients is the potential for their PD fluid to transmit virus. Some body fluids, such as urine, have been demonstrated to be negative for HIV and therefore presumably to be of low risk for virus transmission. To determine whether HIV could be recovered from PD fluid, we cultured the PD fluid from two asymptomatic HIV-seropositive patients and one patient with the acquired immunodeficiency syndrome (AIDS). HIV was isolated from both the PD fluid and the blood of two of the three patients tested, one being only HIV-seropositive and one with AIDS. These findings indicate that such fluid could potentially be a source of viral transmission and emphasize the need for conscientious application of universal precautions both in and out of the hospital.

Serum albumin: a marker for morbidity in peritoneal dialysis patients.

This study was designed to determine if the serum albumin is a marker for morbidity or mortality in peritoneal dialysis (PD) patients. The impact of a low serum albumin on the risk of hospitalization, peritonitis, or death was examined in 71 patients. Blood urea nitrogen (BUN), cholesterol, age, and the presence or absence of diabetes were also examined. In independent analyses, the serum albumin was lower (32.7 +/- 5.6 v 36.3 +/- 4.3 g/L, P < 0.01), the diagnosis of diabetes was more frequent (41% v 7%, P < 0.01), and the number of episodes of peritonitis were greater (2.0 +/- 1.6 v 0.7 +/- 1.3, P < 0.01) in the group of patients hospitalized compared with those not hospitalized. When diabetics were excluded from analysis, the serum albumin remained significantly lower in hospitalized patients. Stepwise logistic regression analysis, excluding the 10 patients hospitalized only for treatment of peritonitis, confirmed that only a low serum albumin and the diagnosis of diabetes were independent predictors of increased morbidity as evident by the increased frequency of hospitalization. Every 10 g/L decrease in the serum albumin increased the odds ratio for hospitalization by 5.2. The diagnosis of diabetes resulted in a 10-fold increase in the odds ratio. We conclude that a low serum albumin serves as a marker of morbidity in PD patients, primarily as a marker of increased risk for hospitalization. The diagnosis of diabetes also greatly increases the likelihood of hospitalization. Peritonitis is a cause for hospitalization, but not an independent risk factor.