Low Birth Weight Contributes to the Excess Prevalence of End-Stage Renal Disease in African Americans

The risk of hypertension and related target organ damage is much greater in African Americans than in Caucasians. The risk of hypertensive end-stage renal disease is approximately five-fold higher in African Americans. Many studies have shown that low birth weight is strongly associated with increased risk of hypertension, stroke, and myocardial infarction. However, until recently the relationship between birth weight and hypertension-related diseases was not clearly established in African Americans. Moreover, it was also unclear if low birth weight in humans heightened the risk for end-stage renal disease. This is a critical gap in the literature, since low birth weight occurs at twice the rate in African Americans as among Caucasians. We identified a significant relationship between end-stage renal disease and low birth weight in both African Americans and Caucasians. Given the higher rates of low birth weight in African Americans, differences in fetal development may, therefore, contribute to the racial disparity in end-stage renal disease. Continued study of the biological factors linking early development with later risk of hypertension-related diseases is important and may shed light on racial disparities in health outcomes.     

Blood pressure predicts risk of developing end-stage renal disease in men and women

Blood pressure as a risk factor for development of end-stage renal disease has not been fully studied, particularly in women. We studied the development of end-stage renal disease from 1983 through 2000 in 98 759 subjects, 46 881 men and 51 878 women, 20 to 98 years of age, who were screened in 1983 in Okinawa, Japan. Data for all dialysis patients registered from 1983 to 2000 in Okinawa were used to identify the screened subjects in whom end-stage renal disease developed. In follow-up, 400 subjects, 231 men and 169 women, had end-stage renal disease. Age, body mass index, and adjusted relative risk for systolic and diastolic blood pressure for both men and women were measured. When these results were compared with an optimal blood pressure, the relative risk of development of end-stage renal disease for those with high-normal blood pressure and hypertension were significant in both men and women. Hypertension is a significant risk factor for development of end-stage renal disease not only in men but also in women. Control of blood pressure within normal levels should be stressed as a strategy to prevent end-stage renal disease in both men and women.     

Determinants of end-stage renal disease in Pima Indians with Type 2 (non-insulin-dependent) diabetes mellitus and proteinuria

Summary To identify factors related to the development of end-stage renal disease after the onset of proteinuria, its incidence was determined in 364 Pima Indians aged 35 years or older with Type 2 (non-insulin-dependent) diabetes mellitus and proteinuria (protein-to-creatinine ratio ≥0.5 g/g). Of these 364 subjects, 95 (36 men, 59 women) developed end-stage renal disease. The cumulative incidence was 40% 10 years after and 61% 15 years after the onset of proteinuria. The incidence of end-stage renal disease was significantly related to the duration of diabetes, the duration of proteinuria, higher 2-h plasma glucose concentration, type of diabetes treatment, and the presence of retinopathy at the time of recognition of the proteinuria, but not to age, sex, or blood pressure. Duration of proteinuria influenced the risk of end-stage renal disease, contingent, however, upon the duration of diabetes at the onset of proteinuria. The higher cumulative incidence of end-stage renal disease 15 years after the onset of proteinuria in Pima Indians (61 %) than in Caucasians from Rochester, Minnesota (17%) may be attributable, in part, to the younger age of onset of Type 2 diabetes in Pima Indians than in Caucasians, to ethnic differences in susceptibility to renal disease, or to lower death rates among the Pima Indians from competing causes of death, such as coronary heart disease.     

Increased incidence of end-stage renal failure secondary to diabetes mellitus in Asian ethnic groups in the United Kingdom.

Diabetic renal disease is more common in patients of Asian ethnic origin than White Caucasians in the United Kingdom. This study determines whether a disparity in the incidence of end-stage renal failure secondary to diabetes mellitus exists between these ethnic groups. The incidence of treated end-stage renal failure was estimated using the person-time at risk incidence rate for patients receiving renal replacement therapy secondary to diabetes mellitus in the county of Leicestershire from 1979 to 1988. The incidence rate of end-stage renal failure expressed for the estimated population of patients with diabetes mellitus in patients of Asian ethnic origin was 486.6 (95% CI, 185.1 to 788.1) cases per million person-years per year, compared to 35.6 (17 to 54.2) in White Caucasians. All patients of Asian ethnic origin developing end-stage renal failure had non-insulin-dependent diabetes. The high incidence of end-stage renal failure secondary to diabetes mellitus in patients of Asian ethnic origin in the UK imparts significant public health implications for resource planning and allocation, and the need to initiate strategies to ameliorate renal disease in this ethnic group.     

Contrôle de la pression artérielle chez le patient en insuffisance rénale chronique avancée : quelles données,quelles recommandations ?

Several epidemiological studies have indicated that high blood pressure is associated with deterioration of renal function in patients with renal disease. Target blood pressures in patients with renal diseases have been defined and proposed to the community in several national and international guidelines. However, some of these targets have been recently changed to take into account results of studies, including randomized clinical trials. The aim of this paper is to put into perspective the history of ideas regarding adequate blood pressure control in patients with renal disease in the light of these results, and explain how these trials have changed our perception, practice and guidelines.     

Hypertension in African-Americans

A considerable disparity exists between African-Americans and US Caucasians in the incidence, severity, and management of hypertension. As a consequence, overall hypertension-related morbidity and mortality rates are at least threefold to fivefold higher in African-Americans than in Caucasians. Alarmingly high frequencies of stroke, end-stage renal disease, congestive heart failure, and left ventricular hypertrophy occur in African-Americans. To bring this crisis under control will require a renewed commitment to expanded research, improved public health measures, and more effective clinical intervention. Current hypertension control programs must be expanded and adequately funded. In addition, primary prevention of hypertension should be strongly recommended for the US population, especially African-Americans.     

Incidence of end-stage renal disease in Type 2 (non-insulin-dependent) diabetes mellitus in pima indians

Summary The incidence of end-stage renal disease was determined in the Pima Indians of the Gila River Indian Community in Arizona, a population with a high prevalence of Type 2 (non-insulin-dependent) diabetes mellitus. Between 1975 and 1986, from a study population of 5059 subjects, end-stage renal disease occurred in 80 persons, 76 (95%) of whom had Type 2 diabetes. A review of the cases with end-stage renal disease indicated that among the diabetic subjects only two cases could be attributed to nondiabetic renal disease; all other cases were attributable to diabetic nephropathy. In diabetic Pima Indians the incidence rate of end-stage renal disease did not change during the study period, was similar in men and women, and was not effected by age at diagnosis of diabetes or by attained age, but did increase significantly with hypertension (p<0.05). The incidence of end-stage renal disease attributed to diabetic nephropathy increased from 0 cases/1000 person-years at 0–5 years to 40.8 cases/1000 person-years at 20 years duration of diabetes. In these subjects with Type 2 diabetes, the incidence rate of end-stage renal disease was similar to that in subjects with Type 1 (insulin-dependent) diabetes who were followed at the Joslin Clinic in Boston, Massachusetts when those with similar duration of diabetes were compared.     

Renal vascular disease in African-Americans and other racial minorities

Hypertensive end-stage renal disease is about 10-fold more common nationwide in African-Americans than in Caucasians and 17-fold higher in some sections of the United States. These figures are alarming and require a much greater effort in understanding the causes of this disparity and improving blood pressure control in this population to prevent catastrophic renal damage. More information is also needed about the renovascular status of other minorities. Financial obstacles to antihypertensive care appear to be an important contributing factor to the disparities of end-stage renal disease in African-Americans and perhaps other minorities.     

Ambulatory blood pressure during diseases of the kidney.

During the last few years there has been a renewal of interest in blood-pressure-induced kidney damage due to a progressive increase in the incidence and prevalence of hypertension and vascular diseases as a cause of end-stage renal disease (ESRD). The need to prevent ESRD demands a continuation of effort to make the early identification of hypertensives who are at risk possible and to provide them with effective antihypertensive therapy. Since ambulatory blood pressure monitoring has been used successfully to assess blood pressure and identify risk markers for cardiovascular diseases, a logical approach would be to use it also to identify the risk markers for ESRD. Higher than normal percentages of non-dippers have been found among subjects with renal failure, during dialysis (haemofiltration, peritoneal dialysis and continuous ambulatory peritoneal dialysis), among cases of renovascular hypertension or cystic kidney disease and among cases of renal transplantation. Although this non-dipping pattern might be related to the presence of severe hypertension in some patients, such as those who have renovascular hypertension, in other cases the abnormal circadian variability is present with milder forms of hypertension or even in the absence of hypertension. Monitoring ambulatory blood pressure could offer advantages for protection of renal function during antihypertensive treatment of subjects with mild renal insufficiency. Furthermore, ambulatory blood pressure monitoring seems to have been prognostic for the development of proteinuria in a group of refractory hypertensives. Whether higher than normal nocturnal blood pressures and the non-dipping pattern are causes or consequences of renal disease should be addressed in prospective studies. The above notwithstanding, assessment of nocturnal blood pressure seems to be an important aid in the management of patients with hypertension-related renal disease and of patients who are susceptible to developing it.     

Plasma digitalislike activity in essential hypertension or end-stage renal disease

Plasma extracts from 119 subjects showed a digitalislike activity, as evidenced by the ability of these extracts to inhibit ouabain binding to the Na+-K+ pump. High levels of the digitalislike compound were found in 18 of 54 untreated hypertensive subjects, 7 of 21 normotensive subjects with a family history of hypertension, and 10 of 14 patients with end-stage renal failure. Dialysis significantly reduced the activity of this compound. These results suggest 1) that endogenous digitalislike factor is not directly linked to hypertension but rather is related to sodium balance and 2) that it neither originates nor is activated by renal tissue, as it was present in four of six anephric patients.     

Increased advanced glycation end products in atherosclerotic lesions of patients with end-stage renal disease

Although advanced glycation end products (AGEs) are increased in the serum and tissues of patients with end-stage renal disease, little is known about the role of AGEs in atherogenesis. We therefore carried out an immunohistochemical study on the accumulation of AGEs and apolipoprotein B in the human aortas of diabetic and nondiabetic subjects with end-stage renal disease. The atherosclerotic lesions included diffuse intimal thickening, fatty streaks and atherosclerotic plaque. We used antibodies against two different epitopes of AGE structures, i.e. an N^ε-(carboxymethyl)lysine-protein adduct (CML) and a structure(s) other than CML (nonCML). The area that was positive for an antigen as a percentage of the total area (%Ar) was determined morphometrically, using an NIH-image program. In diffuse intimal thickening, atherosclerotic plaque and tunica media, the %Ar of CML and nonCML was significantly greater in diabetic or nondiabetic subjects with end-stage renal disease than in control subjects without end-stage renal disease. In fatty streaks, the %Ar of nonCML was significantly greater in nondiabetic subjects with end-stage renal disease than in control subjects, while no difference in the %Ar of CML was found between the subjects with or without end-stage renal disease. Nondiabetic subjects with end-stage renal disease showed a significantly increased %Ar of apolipoprotein B in fatty streaks and atherosclerotic plaque than the control subjects. The %Ar of CML and nonCML significantly correlated with the duration of hemodialysis in diffuse intimal thickening and atherosclerotic plaque of subjects with end-stage renal disease, but not in fatty streaks. On the other hand, the %Ar was not related to the duration of diabetes in any of the lesions in the diabetic subjects with end-stage renal disease. In diffuse intimal thickening and atherosclerotic plaque, subjects with end-stage renal disease showed a significant correlation between the %Ar of apolipoprotein B and AGEs (CML and nonCML), as well as their immunohistochemical colocalization. These results suggest that impaired AGE clearance may cause the increased accumulation of AGEs in the aortic wall of subjects with end-stage renal disease, thus resulting in the rapid progression of atherosclerosis. The accumulation of AGEs may be related to an enhanced LDL deposition in atherosclerotic lesions of subjects with end-stage renal disease.     

Hypertension in chronic kidney disease and dialysis: pathophysiology and management

Hypertension affects 24% of the adult US population. In the United States, 3% of the adult population has an elevated serum creatinine level, and 70% of these patients have hypertension. The prevalence of hypertension in chronic kidney disease (CKD) depends on the patient's age and the severity of renal failure, proteinuria, and underlying renal disease. As patients with CKD progress to end-stage renal disease (ESRD), 86% are diagnosed with hypertension. It has long been recognized that kidney function affects and is affected by hypertension. This article discusses the pathophysiology and management of hypertension in patients with CKD.     

Hypertension and the kidney

Hypertension and kidney function are intimately related, with each having significant influences on the other. Given the major role played by the kidney in maintenance of extracellular fluid volume and peripheral vascular resistance, the kidney is justifiably a target of investigation to determine its potential role in essential hypertension. Conversely, hypertension is associated with progressive renal failure, and hypertension-associated end-stage renal disease is the second leading cause of end-stage renal disease in the United States. It is therefore important that we continue to investigate the hypertension/renal relationship in an effort to better understand the determinants of essential hypertension and to prevent a major cause of end-stage renal disease.     

Impact of calcium entry blockers on glomerular injury in experimental hypertension

Summary A major problem for patients with kidney disease and their physicians is that most chronic renal diseases progress to global glomerular sclerosis and end-stage renal failure. Studies in experimental models of hypertension and renal insufficiency have advanced our understanding of the pathogenesis of progressive kidney damage. In a number of settings, sclerosis has been related to the presence of intrarenal hypertension, a consequence of the hemodynamic adaptation to a reduction in the number of functioning nephrons. A growing body of evidence also supports the hypothesis that kidney and glomerular hypetrophy constitute an independent risk factor for glomerular sclerosis. Recent studies suggest that calcium antagonists can reduce glomerular injury in experimental hypertension. Renal protection may be related to the ability of these agents to inhibit compensatory renal growth.     

Renal dialysis as a risk factor for appropriate therapies and mortality in implantable cardioverter-defibrillator recipients

BACKGROUND: Patients with end-stage renal disease are at increased risk for sudden cardiac death, although the utility of implantable cardioverter-defibrillators (ICDs) in these patients is unknown. OBJECTIVES: The purpose of this study was to evaluate whether end-stage renal disease is an independent risk factor for appropriate ICD therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF) and to compare the long-term survival of ICD recipients with and without end-stage renal disease. METHODS: A retrospective cohort study was performed on ICD recipients at a single center. The primary endpoint was first appropriate ICD therapy for VT/VF. The secondary endpoint was survival. RESULTS: The study included 585 patients, 19 (3.2%) of whom had end-stage renal disease prior to device implantation. Average follow-up time was 2.2 +/- 2.4 years, during which time 156 patients (26.7%) received appropriate ICD therapy. End-stage renal disease was strongly associated with appropriate ICD therapy (hazard ratio 2.30, 95% confidence interval 1.17-4.54) and remained a significant predictor following adjustment for implant indication, ejection fraction, diabetes, hypertension, and beta-blocker use. Survival was significantly shorter in the end-stage renal disease patients, with a median survival time of 3.2 +/- 0.6 (SEM) years in the dialysis cohort and 7.4 +/- 0.5 (SEM) years in those without end-stage renal disease (log rank P = .009). The majority of deaths in the end-stage renal disease cohort were due to non-device-related infection. CONCLUSION: In this cohort, end-stage renal disease was the single greatest predictor of ICD therapies for VT/VF. The survival rate was significantly shorter than that of ICD recipients without end-stage renal disease, suggesting that comorbidities in end-stage renal disease patients meeting current implant indications may reduce the survival benefit of ICD placement in this population.     

Transforming growth factor-beta 1 hyperexpression in African-American hypertensives: A novel mediator of hypertension and/or target organ damage

Hypertension, a remediable risk factor for stroke, cardiovascular disease, and renal failure, affects 50 million individuals in the United States alone. African Americans (blacks) have a higher incidence and prevalence of hypertension and hypertension-associated target organ damage compared with Caucasian Americans (whites). Herein, we explored the hypotheses that transforming growth factor-beta(1) (TGF-beta(1)) is hyperexpressed in hypertensives compared with normotensives and that TGF-beta(1) overexpression is more frequent in blacks compared with whites. These hypotheses were stimulated by our recent demonstration that TGF-beta(1) is hyperexpressed in blacks with end-stage renal disease compared with white end-stage renal disease patients and by the biological attributes of TGF-beta(1), which include induction of endothelin-1 expression, stimulation of renin release, and promotion of vascular and renal disease when TGF-beta(1) is produced in excess. TGF-beta(1) profiles were determined in black and white hypertensive subjects and normotensive controls and included circulating protein concentrations, mRNA steady-state levels, and codon 10 genotype. Our investigation demonstrated that TGF-beta(1) protein levels are highest in black hypertensives, and TGF-beta(1) protein as well as TGF-beta(1) mRNA levels are higher in hypertensives compared with normotensives. The proline allele at codon 10 (Pro(10)) was more frequent in blacks compared with whites, and its presence was associated with higher levels of TGF-beta(1) mRNA and protein. Our findings support the idea that TGF-beta(1) hyperexpression is a risk factor for hypertension and hypertensive complications and provides a mechanism for the excess burden of hypertension in blacks.     

Primary renal disease as a cardiovascular risk factor

Cardiovascular disease (CVD) is the No. 1 cause of death in patients with end-stage renal disease (ESRD) and is approximately 3 to 5 times that of non-uremic control subjects. Moreover, higher rates of CVD are seen in patients with moderate and even mild renal dysfunction, particularly if the patient has hypertension or diabetes. Recent studies have indicated that even modest elevations in serum creatinine and urinary albumin excretion are associated with increased CVD risk, not only in persons with diabetes or hypertension but also in the general population. In addition, recent studies have suggested that targeting the kidney and/or kidney specific endpoints (via the renin-angiotensin-aldosterone-kinin system) in the treatment of hypertension, diabetes, and heart failure slows progression of renal disease and reduces the risk of extra-renal micro- and macrovascular complications. We conclude that it is important to screen for renal disease in those with hypertension, diabetes, and other CVD risk factors because it predicts those who are at high risk for major CVD events.     

Comparison of the course to end-stage renal disease of Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic nephropathy

Summary Is the course leading to diabetic end-stage renal disease similar for Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes mellitus? We identified all diabetic end-stage renal disease patients starting renal replacement therapy from 1989 to 1991 in two urban counties in Texas. Three ethnic/racial groups were enrolled: Mexican Americans, non-Hispanic Whites, African Americans. Patients were interviewed and their medical records, both inpatient and out-patient, were abstracted for relevant diagnostic and therapeutic information. We attempted to obtain records as far back as the onset of diabetes or hypertension and from all physicians who had cared for the patient. An historical algorithm was used to determine diabetic type. Of the patients enrolled, 91 were Type 1 and 438 were Type 2 diabetic patients. Type 1 diabetic patients had higher mean glucose levels in the first 10 years of diabetes (16.3 vs 11.4 mmol/l) but lower systolic blood pressures (148 vs 157 mmHg). The duration of diabetes prior to end-stage renal disease was longer for Type 1 than Type 2 patients (22 vs 17 years). Type 1 diabetic patients were more likely to have other microvascular complications (retinopathy, neuropathy, gastroparesis), less likely to have coronary disease (myocardial infarction and congestive heart failure), and had similar rates of stroke and vascular surgery procedures (carotid endarterectomy, coronary artery bypass surgery, aortofemoral bypass). Type 1 and Type 2 diabetic patients were just as likely to have a first degree relative with hypertension (60.5 vs 65.5%). The late manifestations of end-stage renal disease were similar between the two groups (kidney size, proteinuria, slope of the inverse of creatinine, laboratory data prior to end-stage renal disease, reasons for starting dialysis). The course to end-stage renal disease may be different for Type 1 and Type 2 diabetes, with hyperglycaemia playing a more dominant role in Type 1 and hypertension playing a more dominant role for Type 2. The Type 1/Type 2 differences in patterns of other diabetic complications add weight to this hypothesis. However, the late course of the renal disease and the end result on the kidney is very similar.     

Combination antihypertensive therapy in the treatment of diabetic nephropathy

Diabetic nephropathy is one of the major causes of end-stage renal disease and is often associated with other macrovascular complications such as ischemic heart disease and peripheral vascular disease. Angiotensin converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (AIIR) have both been shown to have a protective effect on the progression of diabetic nephropathy and have thus become the first choice for treatment of hypertension and/or renal involvement in patients with diabetes. However, most of these patients, especially those with type 2 diabetes, require two of more medications in order to reduce their blood pressure to the levels, which have been proposed in recently published consensus papers. These target blood pressure levels are 130/80 mm Hg in diabetic subjects with proteinuria of up to 1 g/day and 125/75 mm Hg in those with proteinuria in excess of 1 g/day. Combinations of different medications may have a synergistic effect. Some of the early studies using a combination of either a nondihydropyridine or a dihydropyridine calcium channel blocker with ACE-I demonstrated a synergistic effect on proteinuria in patients with diabetic nephropathy. However, these studies have not been substantiated, but calcium channel blockers, with their proven ability to reduce blood pressure, play an important role in the treatment of patients with diabetic nephropathy and hypertension. The combination of ACE-I with AIIR may have several theoretical advantages. Many studies using this combination have been performed in animal models of diabetes and in patients with diabetic and nondiabetic renal disease. Some of these studies have demonstrated a synergistic effect of the combination on proteinuria or hypertension, but the results have not been consistent in all studies. It may be concluded that, until additional studies provide more convincing evidence, this combination could be used in patients whose proteinuria or hypertension has not responded to either one of the agents as monotherapy or to a combination of other medications.     

Genetic determinants of human hypertension.

Hypertension is a common trait of multifactorial determination imparting an increased risk of myocardial infarction, stroke, and end-stage renal disease. The primary determinants of hypertension, as well as the factors which determine specific morbid sequelae, remain unknown in the vast majority of subjects. Knowledge that a large fraction of the interindividual variation in this trait is genetically determined motivates the application of genetic approaches to the identification of these primary determinants. Success in this effort will afford insights into pathophysiology, permit preclinical identification of subjects with specific inherited susceptibility, and provide opportunities to tailor therapy to specific underlying abnormalities. To date, mutations in three genes have been implicated in the pathogenesis of human hypertension: mutations resulting in ectopic expression of aldosterone synthase enzymatic activity cause a mendelian form of hypertension known as glucocorticoid-remediable aldosteronism; mutations in the beta subunit of the amiloride-sensitive epithelial sodium channel cause constitutive activation of this channel and the mendelian form of hypertension known as Liddle syndrome; finally, common variants at the angiotensinogen locus have been implicated in the pathogenesis of essential hypertension in Caucasian subjects, although the nature of the functional variants and their mechanism of action remain uncertain. These early findings demonstrate the feasibility and utility of the application of genetic analysis to dissection of this trait.