Progression of nephropathy in type 2 diabetic patients

BACKGROUND: Nephropathy in type 2 diabetes is the single most common cause of end-stage renal disease (ESRD), but the decline in kidney function varies considerably between individuals, and determinants of renal function loss, early in the course of renal disease, have not been clearly identified. METHODS: In a prospective observational study, we followed 227 (60 female) Caucasian type 2 diabetic patients with nephropathy for 6.5 (range 3 to 17) years from a baseline glomerular filtration rate (GFR) of 83 (SD30) mL/min/1.73m(2) with 7 (range 3 to 22) measurements of GFR ((51)Cr-EDTA) per patient. We evaluated determinants of (1) rate of decline in GFR, (2) risk of doubling in serum creatinine or ESRD, and (3) mortality using potential risk factors at baseline and during follow-up. RESULTS: The mean (SD) rate of decline in GFR was 5.2 (4.1) mL/min/year. In multivariate regression analysis, higher baseline albuminuria, systolic blood pressure (SBP), hemoglobin A1c, GFR, age, and degree of diabetic retinopathy were significantly associated with increased rate of decline in GFR (R(2) (adj) 0.24). During follow-up, elevated mean albuminuria, SBP, hemoglobin A1c, and lower hemoglobin, heavy smoking, and presence of diabetic retinopathy were significantly associated with increased decline in GFR (R(2) (adj) 0.26). During follow-up, 63 patients had a doubling in serum creatinine or developed ESRD, and 79 patients died, primarily due to cardiovascular disease. In Cox regression analysis, higher baseline albuminuria, hemoglobin A1c, and SBP, together with lower GFR and hemoglobin, were significantly associated with shorter time to doubling of serum creatinine or ESRD. Higher baseline albuminuria, hemoglobin A1c, SBP, and age were significantly associated with increased mortality. CONCLUSION: Our long-term prospective study of type 2 diabetic patients with nephropathy has revealed several modifiable risk factors of enhanced progression in kidney disease and increased mortality.     

Treatment of osteoporosis in chronic kidney disease and end-stage renal disease

As glomerular filtration rate (GFR) declines from age-related bone loss or disease that specifically induces a decline in GFR, there are a number of metabolic bone conditions that may accompany the decline in GFR. These metabolic bone conditions span a spectrum from mild-to-severe secondary hyperparathyroidism in early stages of chronic kidney disease (CKD) to the development of additional heterogeneous forms of bone diseases each with its distinctly quantitative bone histomorphometric characteristics. Osteoporosis can also develop in patients with CKD and ESRD for many reasons beyond age-related bone loss and postmenopausal bone loss. The diagnosis of osteoporosis in patients with severe CKD or end-stage renal disease (ESRD) is not as easy to do as it is in patients with postmenopausal osteoporosis (PMO)—neither fragility fractures nor The World Health Organization bone mineral density criteria can be used to diagnose osteoporosis in this population since all forms of renal bone disease may fracture or have low "T scores". The diagnosis of osteoporosis in patients with CKD/ ESRD must be done by first the exclusion of the other forms of renal osteodystrophy, by biochemical profiling or by double tetracycline-labeled bone biopsy; and the finding of low trabecular bone volume. In such patients, preliminary data would suggest that oral bisphosphonates seem to be safe and effective down to GFR levels of 15 mL/min. In patients with stage 5 CKD who are fracturing because of osteoporosis or who are on chronic glucocorticoids, reducing the oral bisphosphonate dosage to half of its usual prescribed dosing for PMO seems reasonable from known bisphosphonate pharmacokinetics, though we do need better scientific data to fully understand bisphosphonate usage in this population.     

Level of renal function at the initiation of dialysis in the U.S. end-stage renal disease population

Level of renal function at the initiation of dialysis in the U.S. end-stage renal disease population. BACKGROUND: More than 285,000 individuals in the United States suffer from end-stage renal disease (ESRD) and are treated predominantly by dialysis. Despite the high cost and poor outcomes of dialysis treatment for ESRD, there are few data about the level of renal function at the onset of ESRD and no established medical criteria for the initiation of dialysis. METHODS: We report the level of serum creatinine and glomerular filtration rate (GFR) in 90,897 patients who began dialysis in the U. S. between April 1995 through September 1997. Data were obtained from the U.S. Renal Data System. GFR was predicted by an equation developed from the Modification of Diet in Renal Disease Study. RESULTS: The mean (SD) serum creatinine was 8.5 (3.8) mg/dl. The mean (SD) predicted GFR was 7.1 (3.1) ml/min/1.73 m2, with a range from 1 to 42 ml/min/1.73 m2. The proportion of patients with predicted GFR of > 10, 5 to 10, and <5 ml/min/1.73 m2 was 14, 63, and 23%, respectively. The mean predicted GFR was significantly lower among younger patients, women, African Americans, patients with a higher body weight, patients with ESRD because of diseases other than diabetes, uninsured patients, patients who were employed, homemakers or students, and patients selecting hemodialysis. CONCLUSIONS: There is wide variation in renal function at the initiation of dialysis in the U.S. ESRD population, and a substantial fraction of patients start dialysis at very low levels of predicted GFR. Further analyses are needed to examine the factors associated with late initiation of dialysis and its impact on the cost and outcomes of ESRD.     

Kidney function is inversely associated with coronary artery calcification in men and women free of cardiovascular disease: the Framingham Heart Study

BACKGROUND: Among patients with end-stage renal disease (ESRD), the risk of cardiovascular disease is 10 to 20 times higher than the general population. Adults with ESRD have increased coronary-artery calcification (CAC) detected by electron-beam computed tomography (EBCT). Because the risk of coronary heart disease is increased even at moderate declines in kidney function, we sought to test whether high CAC scores are seen among those with mild reductions in kidney function. METHODS: Men and women free of symptomatic cardiovascular disease underwent EBCT. Coronary calcium was quantified using the method described by Agatston. Renal function was estimated by glomerular filtration rate (GFR). Spearman correlation coefficients were used to test the association between GFR and CAC. RESULTS: Three hundred nineteen subjects (162 men/157 women), mean age 60, were included. Mean GFR was 86 +/- 23 mL/min/1.73 m2 (range 31-169; 10% with GFR <60 mL/min/1.73 m2). The median CAC scores by quartile of GFR were 85.9, 48.1, 7.9, and 2.7. Overall, the unadjusted correlation of GFR and CAC was -0.28 (P < 0.0001). This remained significant after adjustment for age and sex (-0.11, P < 0.05), and additionally after adjustment for body mass index (-0.11, P < 0.05), hypertension (-0.11, P < 0.05), or total cholesterol (-0.12, P= 0.04). A similar correlation was noted after multivariable adjustment (-0.10, P < 0.08). CONCLUSION: Mild declines in kidney function are associated with subclinical coronary artery calcification in a sample of subjects free of clinically apparent cardiovascular disease. This might help explain the increased risk of cardiovascular disease among individuals with renal dysfunction. Larger ongoing studies are needed to better quantify this finding.     

Role of remission clinics in the longitudinal treatment of CKD

Heavy proteinuria is a major determinant of progression to ESRD for patients with chronic nephropathies and reducing proteinuria should be a key target for renoprotective therapy. In the Remission Clinic, we applied a multimodal intervention to target urinary proteins in 56 consecutive patients who had >3 g proteinuria/d despite angiotensin-converting enzyme inhibitor therapy. We compared the rate of GFR decline and incidence of ESRD in this cohort with 56 matched historical reference subjects who had received conventional therapy titrated to a target BP. During a median follow-up of 4 yr, the monthly rate of GFR decline was significantly lower in the Remission Clinic cohort (median -0.17 versus -0.56 ml/min per 1.73 m2; P < 0.0001), and ESRD events were significantly reduced (3.6 versus 30.4% reached ESRD). Follow-up BP, cholesterol, and proteinuria were lower in Remission Clinic patients than in reference subjects, such that disease remission or regression was achieved in up to 50% of patients who would have been otherwise expected to progress rapidly to ESRD on conventional therapy. Proteinuria reduction independently predicted a slower rate of GFR decline and ESRD incidence, but response to treatment differed depending on the underlying disease. Regarding safety, no patient was with drawn because of hyperkalemia. In summary, multidrug treatment titrated to urinary protein level can be safely and effectively applied to normalize proteinuria and to slow the loss of renal function significantly,especially among patients without type 2 diabetes and with otherwise rapidly progressing chronic nephropathies.     

Plasma pentosidine is associated with inflammation and malnutrition in end-stage renal disease patients starting on dialysis therapy

Pentosidine is an advanced glycation end-product (AGE), formed by glycosylation and oxidation, that accumulates markedly in end-stage renal disease (ESRD). It has been speculated that AGE and carbonyl stress contributes to long-term complications such as cardiovascular disease (CVD) in ESRD patients. This study determined plasma levels of pentosidine as well as the presence of inflammation (CRP > or = 10 mg/L), clinical CVD (CVD(clin)), and malnutrition (subjective global assessment [SGA] > 1) in a cohort of 191 ESRD patients, median age of 55 yr (range, 23 to 70 yr) and median GFR = 7 ml/min (range, 2 to 17 ml/min), close to start of renal replacement therapy. Fifty-one elderly subjects, median age of 82 yr (range, 71 to 110 yr), with mild renal impairment, median GFR = 67 ml/min (range, 38 to 113 ml/min), were also studied for comparative analysis of plasma pentosidine. The plasma pentosidine content was elevated in all patients compared with the levels in the elderly subjects and were negatively correlated with GFR both in the ESRD patients (Rho = -0.24; P < 0.01; n = 159) and in the elderly subjects (Rho = -0.31; P < 0.05). Moreover, the plasma pentosidine content was correlated with age in the ESRD patients (Rho = 0.26; P < 0.001) and in the elderly subjects (Rho = 0.44; P < 0.001). The 63 malnourished ESRD patients (35%) had a significantly higher (P < 0.05) median plasma pentosidine than the well-nourished patients (39 versus 27 pmol/mg albumin). Similarly, 73 inflamed patients (38%) had a significantly higher (P < 0.001) median pentosidine content compared with 118 non-inflamed patients (37 versus 24 pmol/mg albumin). Also, the plasma pentosidine content showed weak but significant positive correlations with CRP (Rho = 0.28; P < 0.0001), fibrinogen (Rho = 0.23; P < 0.01; n = 126), IL-6 (Rho = 0.22; P < 0.01; n = 169), and soluble vascular cellular adhesion molecule-1 (Rho = 0.38; P < 0.001; n = 74). On the other hand, no significant differences in plasma pentosidine content were noted between the patients with and those without CVD(clin) (32 versus 27 pmol/mg albumin, respectively). Analyses of all-cause mortality, by Kaplan-Meier, showed that mortality was not linked to the plasma pentosidine content. Moreover, survival analysis by the Cox regression model showed that age (P < 0.001), diabetes mellitus (P < 0.01), malnutrition (P < 0.01), and CVD(clin) (P < 0.01) independently predicted poor outcome, whereas an elevated plasma pentosidine content did not. The present study shows that an elevated plasma pentosidine content in ESRD patients is significantly associated with both inflammation and malnutrition and confirms that low residual renal function and high age further contribute to an increased plasma pentosidine content. However, in this small cohort, the plasma pentosidine content did not predict outcome. Thus, accumulation of plasma pentosidine is unlikely to be an appropriate clinically useful marker to predict mortality in ESRD patients.     

Levobupivacaine for axillary brachial plexus block: a pharmacokinetic and clinical comparison in patients with normal renal function or renal disease

We compared the pharmacokinetics and clinical characteristics of 0.5% levobupivacaine for axillary block in patients with normal renal function versus patients with end-stage renal disease (ESRD). Twenty patients with normal renal function and eight patients with ESRD received an axillary block with 50-60 mL of 0.5% levobupivacaine. Patients were evaluated for onset and duration of sensory/motor block. Eleven patients with normal renal function and eight patients with ESRD underwent pharmacokinetic analysis. No differences between groups were found in the onset, duration, or quality of block. The median time to sensory block was 12.5 min and 12.9 min, and mean duration of the block was 19 h and 22 h in normal versus ESRD patients, respectively. No significant differences in noncompartmental pharmacokinetic variables (median) were found between normal and ESRD patients with an AUC(0-t) (microg. h(-1). mL(-1)) of 11 and 13, peak concentration (C(max)) (microg/mL) of 1.2 and 1.6, and a time to peak concentration (T(max)) (min) of 55 and 48, respectively. This study demonstrates the clinical efficacy and equivalence of the pharmacokinetic characteristics of 0.5% levobupivacaine for axillary brachial plexus block in patients with ESRD and normal renal function. IMPLICATIONS: This study demonstrates the clinical efficacy and equivalence of the pharmacokinetic characteristics of 0.5% levobupivacaine for axillary brachial plexus block in patients with renal disease and normal renal function.     

ACE inhibitors to prevent end-stage renal disease: when to start and why possibly never to stop: a post hoc analysis of the REIN trial results. Ramipril Efficacy in Nephropathy.

In this post hoc, secondary analysis of the Ramipril Efficacy In Nephropathy (REIN) trial, an angiotensin-converting enzyme (ACE) inhibition risk/benefit profile was assessed in 322 patients with nondiabetic, proteinuric chronic nephropathies and different degrees of renal insufficiency. The rate of GFR decline (Delta GFR) and the incidence of end-stage renal disease (ESRD) during ramipril or non-ACE inhibitor treatment were compared within three tertiles of basal GFR. Delta GFR was comparable in the three tertiles, whereas the incidence of ESRD was higher in the lowest tertile than in the middle and highest tertiles. Ramipril decreased Delta GFR by 22%, 22%, and 35% and the incidence of ESRD by 33% (P < 0.05), 37%, and 100% (P < 0.01) in the lowest, middle, and highest tertiles, respectively. Delta GFR reduction was predicted by basal systolic (P < 0.0001), diastolic (P = 0.02), and mean (P < 0.001) BP and proteinuria (P < 0.0001) but not by basal GFR (P = 0.12). ESRD risk reduction was predicted by basal proteinuria (P < 0.01) and GFR (P < 0.0001) and was strongly dependent on treatment duration (P < 0.0001). Adverse events were comparable among the three tertiles and within each tertile in the two treatment groups. Thus, disease progression and response to ACE inhibition do not depend on severity of renal insufficiency. The risk of ESRD and the absolute number of events saved by ACE inhibition is highest in patients with the lowest GFR. However, renoprotection is maximized when ACE inhibition is started earlier and when long-lasting treatment may result in GFR stabilization and definitive prevention of ESRD.     

Renal Function and Serum Albumin at the Start of Dialysis in 514 Chinese ESRD In-Patients

Background. The dialysis population has grown rapidly in recent decades. Despite the high cost and poor outcomes of dialysis treatment for ESRD, there are scant data about the level of renal function and the relationship of renal function and serum albumin at the start of dialysis in Chinese ESRD patients. Method. We report the level of serum creatinine (Scr), glomerular filtration rate (GFR), and serum albumin (Salb) in 514 ESRD in-patients who began their dialysis treatment between January 2001 through December 2007 at two large dialysis centers in Changsha, Hunan, China. Data were obtained through reviewing the case records of all 514 patients. GFR was predicted by an equation developed from the Modification of Diet in Renal Disease Study. In addition, serum albumin was analyzed in relation to levels of predicted GFR. Results. The mean (SD) and median predialysis serum creatinine was 1121.92 ± 458.24 and 1032 μmol/L. The mean (SD) and median predicted GFR was 4.98 ± 2.24 and 4.47mL/min/1.73m². The proportion of patients with predicted GFR of >10, 5 to 10, and <5 mL/min/1.73m² was 3.7, 36.2, and 60.1%, respectively. The mean predicted GFR was significantly lower among younger patients, uninsured patients, unemployed or farmer patients, patients who were employed, students, patients who selected hemodialysis, patients with ESRD caused by diseases other than diabetes, patients with BUN above the mean, and patients with hemoglobulin beneath the mean. Compared with patients who started with GFR >5mL/min, the patients who started with GFR ≤5mL/min had significantly higher plasma urea and creatinine levels but significantly lower creatinine clearance (mL/min per 1.73m²) and parameters of nutritional status, such as serum albumin, body weight, and BMI. Conclusion. A wide variation existed in renal function at the initiation of dialysis in partial Chinese ESRD patients. Most patients start dialysis at very low levels of predicted GFR. The nutritional status in patients who start dialysis early was better than those in patients who start dialysis when GFR ≤ 5mL/min. Further studies are needed to analyze the impact of level of renal function and nutritional status at the start of dialysis on the outcomes of ESRD.     

The progression of chronic kidney disease: a 10-year population-based study of the effects of gender and age

The increase in demand for renal replacement therapy makes it important to investigate the prognosis of the earlier stages of chronic kidney disease (CKD). We examined the change in glomerular filtration rate (GFR), and patient and renal survival in CKD stage 3 in the municipality of Troms?, a well-defined European community with a population of 58,000. All patients with estimated GFR between 30 and 59 ml/min/1.73 m(2) for more than 3 months during a 10-year study period were identified from a complete database of all 248 560 measurements of serum creatinine made in the community in the study period. Change in GFR was estimated for each patient using a multilevel model. A complete follow-up with respect to patient and renal survival was obtained from hospital databases. A total of 3047 patients was included. The median number of measurements of creatinine for each patient was 9, and the median observation time was 44 months. Mean estimated change in GFR was--1.03 ml/min/1.73 m(2)/year. Seventy-three percent of the patients experienced a decline in GFR. The 10-year cumulative incidence of renal failure was 0.04 (95% CI 0.03-0.06) and mortality 0.51 (95% CI 0.48-0.55). Female gender was associated with slower decline in GFR and better patient and renal survival. In this population-based study, the decline in GFR in CKD was slower than in previously studied selected patient groups. A high mortality pre-empted the development of renal failure in many patients. The prognosis of CKD depended strongly on gender.     

Inhibitors of the renin-angiotensin system reduce the rate of GFR decline and end-stage renal disease in patients with severe renal insufficiency

Drugs that inhibit the renin-angiotensin system (RAS) are of proven benefit in the treatment of hypertension, congestive heart failure, or acute myocardial infarction. In the last decade, several clinical trials have shown that RAS inhibitors also offer significant renoprotection in both diabetic and non-diabetic nephropathy. However, patients with advanced renal insufficiency did not take part in these trials because of the risk of acute renal failure (ARF) and hyperkalemia, and, for the same reason, most physicians do not offer these drugs to patients with impaired renal function. Recently, a post-hoc analysis of the Ramipril Efficacy In Nephropathy (REIN) study which included patients with severe renal insufficiency, showed that RAS inhibition slows glomerular filtration rate (GFR) decline over time and progression to end-stage renal disease (ESRD) in a safe way in patients quite close to ESRD (basal GFR, 10 to 30 ml/min/1.73m2). These beneficial effects have also been shown in the Reduction of Endpoints in NIDDM with the All Antagonist Losartan (RENAAL) study, in patients with type 2 diabetes mellitus, clinical proteinuria, and renal insufficiency, where RAS inhibition therapy significantly reduced the risk of ESRD once doubling of baseline serum creatinine levels had been achieved as compared to non-RAS anti-hypertensive treatment. Thus, these data suggest that RAS inhibition therapy should be given to all patients with proteinuric chronic nephropathy, independently of the level of renal function.     

Effect of dietary protein restriction on prognosis in patients with diabetic nephropathy

BACKGROUND: Recent data suggest that dietary protein restriction improves survival and delays the progression to end-stage renal disease (ESRD) in non-diabetic nephropathies. The purpose of our study was to determine the effect of dietary protein restriction on survival and progression to ESRD in diabetic nephropathy. METHODS: A four-year prospective, controlled trial with concealed randomization was performed comparing the effects of a low-protein diet (0.6 g/kg/day) with a usual-protein diet. The study included 82 type 1 diabetic patients with progressive diabetic nephropathy [pre-study mean decline in glomerular filtration rate (GFR) 7.1 mL/min/year (95% CI, 5.8 to 8.5)]. The main outcome measures were decline in GFR and development of ESRD or death. RESULTS: During the follow-up period the usual-protein diet group consumed 1.02 g/kg/day (95% CI; 0.95 to 1.10) as compared with 0.89 (0.83 to 0.95) in the low-protein diet group (P = 0.005). The mean declines in GFR were 3.9 mL/min/year (2.7 to 5.2) in the usual-protein diet group and 3.8 (2.8 to 4.8) in the low-protein diet group. ESRD or death occurred in 27% of patients on a usual-protein diet as compared with 10% on a low-protein diet (log-rank test; P = 0.042). The relative risk of ESRD or death was 0.23 (0.07 to 0.72) for patients assigned to a low-protein diet, after an adjustment at baseline for the presence of cardiovascular disease (P = 0.01). Blood pressure and glycemic control were comparable in the two diet groups during the follow-up period. CONCLUSION: Moderate dietary protein restriction improves prognosis in type 1 diabetic patients with progressive diabetic nephropathy in addition to the beneficial effect of antihypertensive treatment.     

Renal insufficiency and end-stage renal disease in the heart transplant population.

BACKGROUND: Renal insufficiency and end-stage renal disease (ESRD) are important problems in the cardiac transplant population, and are associated with significant morbidity, mortality and financial cost. We undertook this study to define pre-operative or early post-operative predictors of subsequent renal insufficiency and ESRD. METHODS: We studied 370 patients at Brigham and Women's Hospital who received heart transplants between 1984 and 1999, with up to 10-year follow-up. We evaluated 2 time-dependent primary outcomes: early reduction in GFR, and development of ESRD at any timepoint. Cox proportional hazards modeling was used in both univariate and multivariate analyses. RESULTS: The mean estimated glomerular filtration rate (GFR) fell 24% within the first post-transplant year, and remained stable thereafter. By actuarial analysis, 23% of patients developed a 50% reduction in GFR by the third year, and 20% developed ESRD by the tenth year of follow-up. In Cox multivariate analysis, significant predictors of post-transplant ESRD included: GFR <50 ml/min (hazards ratio [HR] 3.69, p = 0.024); high mean cyclosporine trough in the first 6 months (HR 5.10, p = 0.0059); and presence of diabetes (HR 3.53, p = 0.021). Conclusions about renal insufficiency outcome were limited by difficulties with accurate estimation of GFR and with definition of renal insufficiency. CONCLUSIONS: The results of this study underscore the magnitude of the problem of renal insufficiency and ESRD in the heart transplant population. In addition, these data suggest that patients at high risk for these outcomes can be identified early, even pre-operatively, to guide post-operative management.     

Angiotensin-converting enzyme polymorphism gene and evolution of nephropathy to end-stage renal disease

Genetic polymorphisms of the renin-angiotensin system (RAS) have been implicated in the pathogenesis of nephropathy and end-stage renal disease (ESRD). The association between angiotensin-converting enzyme (ACE) gene polymorphism and nephropathy evolution was studied. A random sample of 161 subjects from the Nephrology Department (of Hospital de Sant Pau) were divided into two groups: (i) 117 with end-stage renal disease; (ii) 44 with established nephropathy; and (iii) control groups of 129 subjects. The ACE gene polymorphism was performed by using polymerase chain reaction. High DD genotype presentation was observed in the two groups of subjects with nephropathy (46.12 and 61.37%, respectively vs 35.66% in controls; P < 0.0482), and also, a decrease was observed in the II genotype (6.4 and 4.54%, respectively vs 13.17% in controls, P < 0.0404). Glomerular filtration rate (GFR) was evaluated after 44 months of follow up. An important decrease of GFR was observed in patients with DD polymorphism versus other genotypes (initial, 32.3 +/- 7.9 and at 44 months, 18.35 +/- 3.3 mL/min vs 31.4 +/- 11.9 and 11.7 +/- 3.2 mL/min; P < 0.039). In a non-longitudinal study of patients in ESRD, patients with an ACE-DD genotype had a lower period of time between diagnosis of nephropathy and ESRD than patients with other genotypes (10.45 +/- 9.32 vs 19.5 +/- 8.4 years; P < 0.034). In conclusion, the ACE gene that controls RAS response may influence the development and progression of nephropathy to ESRD. Patients who develop several types of nephropathy have a higher risk of severe evolution if they have a profile of ACE-DD genotype.     

Nighttime hospital blood pressure – a predictor of death,ESRD, and decline in GFR

Nighttime systolic blood pressure (BP) from ambulatory blood pressure monitoring (ABPM) is more predictive than clinic BP for cardiovascular disease, stroke, and death even after controlling for clinic BP. However, ABPM is expensive and burdensome to obtain regularly. BPs obtained in the hospital may provide a window into nighttime BP. We conducted a retrospective cohort study of all hypertensive patients admitted to the Louis Stokes Cleveland Department of Veterans Affairs Medical Center (LSCDVAMC) in 2002 and 2003 with one or more BP recorded between midnight and 6 am on the day of or the day before discharge. The mean age of the study population (n = 1085) was 62 years and 96% were male. Twenty-two percent had coronary artery disease (CAD) and 34% had diabetes. The mean nighttime systolic BP was 132 mmHg and baseline glomerular filtration rate (GFR) was 83 mL/min per 1.73 m². Over a median follow-up period of 4.3 years, 266 subjects died, 22 developed end-stage renal disease (ESRD), 99 had a 50% decline in GFR, and 136 developed myocardial infarction (MI). The adjusted hazard ratios (HRs) associated with a 10 mmHg increase in nighttime systolic BP were 1.03 (95% confidence interval, 0.93–1.15) for death, 1.30 (0.94–1.80) for ESRD, 1.26 (1.08–1.47) for a 50% decline in GFR, 1.07 (0.92–1.23) for myocardial infarction, and 1.12 (1.03–1.23) for a composite of death, ESRD, or a 50% decline in GFR. In conclusion, nighttime systolic BP in hospitalized patients is an independent predictor of important clinical outcomes such as a composite of death, ESRD, or a 50% decline in GFR.     

Evaluating patients with renal failure for renal artery stenosis with gadolinium-enhanced magnetic resonance angiography

The incidence and prevalence of end-stage renal disease (ESRD) continues to increase, especially in the elderly population. The role of renovascular disease in contributing to ESRD is still not well defined. The objective of this study was to determine the utility of gadolinium (Gd)-enhanced magnetic resonance angiography (MRA) in evaluating elderly patients with renal insufficiency for renal artery stenosis (RAS). A 7-month prospective study conducted in a tertiary referral center evaluated 40 consecutive patients with progressive renal insufficiency (18 men and 22 women; mean age, 70 +/- 5.6 [standard deviation] years) and high clinical suspicion for renovascular disease with Gd-enhanced MRA. Digital subtraction angiography (DSA) was obtained in only those patients with significant RAS detected by MRA. Twelve patients had significant RAS. Six of these patients had percutaneous transluminal renal angioplasty (PTRA), five patients had renal artery bypass surgery, and one patient had a stent placed after PTRA. Seventy-eight renal arteries were satisfactorily evaluated by MRA. Twenty-two renal arteries were evaluated by both MRA and DSA. Of the 12 significant stenoses detected by the MRA, 11 were confirmed by DSA and 1 was confirmed at the time of surgical revascularization. It is concluded that Gd-enhanced MRA is a useful test for the evaluation of RAS in patients with compromised renal function.     

Epidemiology of renal dysfunction and patient outcome in atherosclerotic renal artery occlusion.

Patients with atherosclerotic renal artery occlusion (RAO) effectively have only a single functioning kidney, so they constitute an ideal group in whom to study the relationship of atherosclerotic renovascular disease (ARVD) severity to renal functional outcome. Of 299 patients with ARVD who had presented to a single center over a 12-yr period, 142 (47.5%) patients with RAO were identified. There was no relationship between baseline renal function and contralateral renovascular anatomy. Patients with contralateral normal, insignificant (<50%), or significant (>50%) renal artery stenoses had baseline creatinine of 243 +/- 235, 292 +/- 197, or 210 +/- 102 micromol/L, respectively, but patients with bilateral RAO (creatinine, 540 +/- 304 micromol/L; P < 0.0001) were significantly worse. There were significant correlations between baseline GFR and both proteinuria (r = -0.32; P < 0.01) and contralateral bipolar renal length (r = 0.44; P < 0.0001). Over a mean follow-up period of 31 +/- 21 (2 to 82) mo, the overall rate of progressive renal functional decline was -4.1 ml/min per yr. Nine patients required dialysis at presentation and a further 15 (10.5%) during the course of the study. There were 85 (59.9%) deaths; median survival of the whole group was 25 mo, and 5-yr survival was 31%. Multivariate analysis indicated that low baseline GFR was the chief variable independently associated with increased probability of death or need of dialysis but that renal vascular anatomy had no prognostic impact. This study reinforces the importance of intrarenal vascular and parenchymal disease in the etiology of renal dysfunction in ARVD.     

The early decline in renal function in patients with type 1 diabetes and proteinuria predicts the risk of end-stage renal disease

The risk of end-stage renal disease (ESRD) remains high in patients with type 1 diabetes and proteinuria; however, little is known about the rate of decline in their renal function. To help determine this, we enrolled patients with type 1 diabetes and proteinuria whose estimated glomerular filtration rate (eGFR) was normal (equal to or above 60?ml/min per 1.73?m(2)). Using a minimum of five serial measurements of serum creatinine for 161 patients, we determined individual trajectories of eGFR change and the occurrence of ESRD during 5-18 years of follow-up. The rates were linear for 110 patients, for 24 the nonlinear rate was mild enough to satisfy a linear model, and the rates were clearly nonlinear for only 27 patients. Overall, in more than one-third of patients, the eGFR decline was less than 3.5?ml/min per 1.73?m(2) per year and the lifetime risk of ESRD could be considered negligible. In the remainder of patients, eGFR declined with widely different slopes and ESRD developed within 2 to 18 years. Based on up to 5 years observation, when renal function was within the normal range, the estimates of early eGFR slope predicted the risk of ESRD during subsequent follow-up better than the baseline clinical characteristics of glycated hemoglobin, blood pressure, or the albumin to creatinine ratio. Thus, the early slope of eGFR decline in patients with type 1 diabetes and proteinuria can be used to predict the risk of ESRD.     

End-stage renal disease in the United States: an update from the United States Renal Data System

Patients with ESRD consume a vastly disproportionate amount of financial and human resources. Approximately 0.03% of the US population began renal replacement therapy in 2004, an adjusted incidence rate of 339 per million. Declining incidence rates were observed for most primary causes of ESRD and in most major demographic categories; the worry is that rates of diabetic ESRD continue to rise in younger black adults. Although diabetes and hypertension remain the most commonly reported cause of ESRD, rates of end-stage atherosclerotic renovascular disease seem to be on the rise in older patients. Although clinical care indicators, such as the proportion of hemodialysis patients using fistulas, continue to improve gradually, the proportion of patients overshooting target hemoglobin levels under epoetin therapy may be a source of concern. Survival probabilities have improved steadily in the US ESRD population since the late 1980s, which is remarkable when one considers the ever-expanding burden of comorbidity in incident patients. However, although first-year dialysis mortality rates have clearly improved since 1987, meaningful improvements do not seem to have accrued since 1993, in contrast to steady annual improvements in years 2 through 5. Although most of these findings are grounds for cautious optimism, the same cannot be said for issues of cost; reflecting the growth in the size of the ESRD population, associated costs grew by 57% between 1999 and 2004 and now account for 6.7% of total Medicare expenditures.     

Seropositivity for cytomegalovirus in patients with end-stage renal disease is strongly associated with atherosclerotic disease.

BACKGROUND: Infection with cytomegalovirus (CMV) is considered a risk factor for progression of atherosclerotic disease. Patients with end-stage renal disease (ESRD) display signs of frequent CMV re-activation, which may be caused by the uraemia-associated defect in cellular immunity. The possible contribution of CMV seropositivity to the hugely increased risk for cardiovascular disease in patients with ESRD is not clear. METHODS: In a retrospective study we analysed the clinical data of patients with ESRD that were evaluated for renal transplantation from January 2002 to March 2006. Classical cardiovascular risk factors and CMV seropositivity were related to the prevalence of atherosclerotic disease. RESULTS: A total of 408 patients were evaluated with a median age of 52 years (range 18-81 years). Multivariate logistic regression identified age (odds ratio; OR 2.7 per decade), smoking (OR 2.2), hypertension (OR 1.9), C-reactive protein (CRP) (OR 2.6) and CMV seropositivity (OR 2.7) as independent variables that were significantly associated with a positive medical history of atherosclerotic disease. The average titre for anti-CMV immunoglobulin G was higher in patients with atherosclerotic disease (100 AU/ml vs 71 AU/ml, P < 0.05). CMV seropositivity was independently associated with an elevated CRP. In addition, patients with the combination of a high CRP and CMV seropositivity showed the highest prevalence of atherosclerotic disease. CONCLUSION: CMV seropositivity is significantly associated with atherosclerotic disease in ESRD patients. Our data suggest that the risk for progressive atherosclerosis is specifically increased in patients with an inflammatory response to CMV.