Gastrointestinal bleeding in patients on long-term dialysis.

BACKGROUND: The epidemiology of gastrointestinal bleeding (GIB) in end-stage renal disease (ESRD) has not been adequately characterized. Using United States Renal Data System data we investigated the epidemiology of GIB in hospitalized patients receiving long-term dialysis. METHODS: Medicare ESRD patients who began dialysis between 1996 and 2005 were followed from 90 days after starting dialysis to death, transplant, loss of Medicare, or December 31, 2006. GIB events were identified using claims data. Predictors of GIB incidence were analyzed using over-dispersed Poisson regression and Cox regression was used to evaluate the effect on survival. Repeat episodes were modeled using a partially conditional Cox regression model. RESULTS: 406,836 patients were followed for 832,131 person-years, during which 133,967 events were identified. The incidence of GIB was stable through year 2000 but steadily increased thereafter. Chronic gastric ulcer and colonic diverticulosis were the commonest defined causes of upper and lower GIB respectively. Age >49 years, female gender, hypertension as the cause of ESRD, and initiation on hemodialysis was associated with a greater risk of GIB. An episode of GIB conferred a increased hazard of death (hazard ratio 1.9, 95% CI 1.86-1.93). A previous episode of GIB was associated with greater hazard of another episode (hazard ratio 3.93, 95% CI 3.82-4.05). CONCLUSIONS: In ESRD patients incident to long-term dialysis the incidence of hospital-associated GIB is increasing, is associated with a greater hazard of death, and carries a great hazard of repeat episodes.

Circadian variation of mineral and bone parameters in end-stage renal disease.

BACKGROUND: Mineral and bone parameters are actively managed in end-stage renal disease (ESRD). However, whether these undergo circadian variation is not known. We investigated the circadian variation of mineral and bone parameters in patients on long-term hemodialysis. METHODS: Seventeen ESRD patients on long-term hemodialysis and eight volunteers without kidney disease were enrolled. Subjects had all medications that affect calcium-phosphate-parathyroid hormone balance (phosphate binders, vitamin D analogues, and calcimimetics) discontinued. Thereafter, for a period of 5 days, subjects consumed a diet controlled in calcium (1,200 mg per day) and phosphorus (1,000 mg per day) content. On the sixth day (a non-dialysis day for the ESRD patients), enrollees underwent twelve 2-h blood draws for phosphate, ionized calcium, parathyroid hormone (PTH), total 25-hydroxy vitamin D (25OHD), and fibroblast growth factor-23 (FGF-23). RESULTS: In the ESRD patients plasma phosphate demonstrated significant circadian variation (P < 0.00001). The peak occurred around 3:30 am and nadir occurred around 11:00 am. Ionized calcium (P = 0.0036), PTH (P = 0.0004) and 25OHD (P = 0.009) also varied significantly during the circadian period; for ionized calcium peak and nadir occurred around 12:15 pm and 8:00 pm, parathyroid hormone 5:45 pm and 10:15 am, and 25OHD 9:45 am and 4:00 pm respectively. FGF-23 did not show a significant circadian variation. Only phosphate (P < 0.0001) and PTH (P = 0.00008) demonstrated circadian variation in the control group. CONCLUSIONS: Blood concentrations of phosphate, calcium, PTH and 25-hydroxy vitamin D, exhibit a circadian variation in patients with ESRD. Knowledge of these phenomena is pertinent for the interpretation of clinical testing.

Readability and comprehensibility of over-the-counter medication labels.

Nonprescription medications are relatively safe, but not risk-free and can lead to serious adverse events, particularly if used contrary to directions or without attention to depicted warnings. The question arises whether the information presented on the product label is readable and comprehensible to the average lay person. We examined the product labels of nonprescription medications for readability and comprehensibility characteristics using the Flesch-Kincaid method. The Flesch-Kincaid reading ease scores and grade level scores were derived. We further validated the grade level scores using the Gunning-Fog method. Qualitative assessment of select labels found severe deficiencies such as poor organization and inundation with technical terms. By quantitative assessment the average reading ease score of 40 nonprescription medication labels (including nonsteroidal anti-inflammatory agents, antacids, laxative preparations, anti-allergy medications, H-2 blockers, proton pump inhibitors, sleep aids, an antiasthmatic, and cough and cold remedies) was 38 ± 12. The average Flesch-Kincaid grade level score was 16 ± 5. All labels except one were at reading grade level greater than the eighth grade. The average grade level of education necessary to understand the material according to the Gunning-Fog method was 17 ± 5 and all labels were above the eighth grade reading level. Nonprescription medication labels are written in a language that is not comprehensible to the average member of the general public. There is a need for considerable improvement in the readability of these labels.

Circadian rhythm of salivary cortisol, plasma cortisol, and plasma ACTH in end-stage renal disease.

OBJECTIVE: Patients with end-stage renal disease (ESRD) can display the features of endogenous hypercortisolism but are difficult to evaluate for Cushing's syndrome. We evaluated the circadian rhythm of plasma compared with salivary cortisol in subjects with ESRD. DESIGN: Plasma and salivary cortisol and plasma ACTH samples were drawn frequently over 24 h in an inpatient research unit in stable ESRD subjects on daytime chronic hemodialysis (n=16) vs controls (n=8). METHODS: Plasma cortisol was measured every 2 h from 0800 to 0600 h the following day. Salivary cortisol was measured every 2 h, except between 2400 and 0400 h (sleep time). Plasma ACTH measured in a subset of samples and C-reactive protein (CRP) was measured as a marker of a subclinical inflammatory state in all subjects. RESULTS: ESRD subjects had a discernable circadian rhythm in plasma and salivary cortisol, but with a significantly higher nadir (1800-2400 h) compared with the controls (P=0.016-<0.001). After excluding four ESRD subjects without a normal circadian rhythm, the ESRD subjects still had higher nadir plasma and salivary cortisol and plasma ACTH compared with controls. There was no difference in the correlation of salivary and plasma cortisol in control vs ESRD subjects. ESRD subjects had higher CRP levels compared with controls. CONCLUSIONS: ESRD subjects had increased late-night plasma and salivary cortisol and plasma ACTH levels. Late-night salivary cortisol is a reliable index of plasma cortisol in ESRD patients.

Declining rates of deceased donor renal transplantation in the United States over successive years of listing.

OBJECTIVE: Renal transplantation is the best treatment for end-stage renal disease. However, limited availability of donor organs is a problem. We analyzed the changing trends of transplantation and mortality in subjects listed for deceased donor renal transplantation over successive years. METHODS: By using US Renal Data System data, we identified Medicare patients receiving dialysis who were listed for their first deceased donor renal transplant between January 1996 and December 2005. Subjects were followed to the first occurrence of transplant, death, or September 30, 2007. The effect of the year of listing was analyzed adjusting for age, sex, race, vintage, panel reactive antibody, and cause of end-stage renal disease. RESULTS: There were 70,891 subjects (mean age 50.1 ± 14.3 years, 59.9% were men, 54% were white, average duration of dialysis 2 ± 2.2 years). Multivariate analysis revealed that compared with patients listed in 1996, for patients listed in subsequent years the cumulative incidence of death remained within a narrow boundary and the cumulative incidence of transplant progressively declined. For example, for subjects listed in 1998, 2000, 2002, and 2004, the cumulative incidence of death relative to 1996 was 1.02 (95% confidence interval [CI], 1.01-1.03), 1.02 (CI, 1.01-1.03), 0.99 (CI, 0.98-0.99), and 0.94 (CI, 0.93-0.94), respectively, 12 months after listing. However, correspondingly for these subjects at the 12-month follow-up time point, the cumulative incidence of transplant relative to 1996 was 0.85 (CI, 0.84-0.86), 0.73 (CI, 0.71-0.74), 0.63 (CI, 0.62-0.64), and 0.58 (CI, 0.57-0.59), respectively. CONCLUSION: There is a progressive unfavorable pattern of declining transplantation rates with each successive year of listing in patients listed for deceased donor renal transplantation.

Contrast-induced nephropathy after a second contrast exposure.

BACKGROUND: The risk of contrast-induced nephropathy (CIN) after repeated contrast exposure has not been evaluated. METHODS: We prospectively evaluated the effects of two contrast exposures during an investigational study of a new computerized tomography (CT) scanner. Adult subjects who underwent a variety of contrast-enhanced imaging procedures with conventional apparatus, as part of routine care, were invited to undergo a second contrast-enhanced research scan. Subjects were required to have an estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m(2) and a serum creatinine (sCr) value measured immediately prior to the second contrast exposure that was <125% of that measured prior to the first imaging study. RESULTS: Twenty-eight subjects underwent a second contrast exposure after a mean interval of 20 +/- 13 days (75% males, 89% Caucasians, 21% diabetics, mean age 60.6 +/- 6 years, mean contrast volume 130 +/- 42 mL). There was a significant increase in mean sCr and decline in eGFR after the second contrast exposure (sCr 0.93 +/- 0.14 vs. 0.86 +/- 0.15 mg/dL prior, p = 0.027; eGFR 83.9 +/- 13.5 vs. 89.8 +/- 13 mL/min/1.73 m(2) prior, p = 0.028). Four subjects (14.3% of the population) developed CIN. CONCLUSION: Even in subjects with relatively preserved renal function there is a notable risk of CIN after repeated contrast exposure. This conclusion was unaltered by several sensitivity analyses.

Cost implications of caring for chronic kidney disease: are interventions cost-effective?

Recent data suggest a large, rising burden of chronic kidney disease (CKD) in the general population and rising expenses associated with it. In 2007, CKD contributed 27.6% of costs and CKD subjects constituted 9.8% of the population. Between 1993 and 2007, overall Medicare costs nearly doubled and CKD-associated costs increased about 5-fold. The Medicare cost of end-stage renal disease has risen from $12.2 in 2000 to $20.8 billion in 2007. This review examines cost-effectiveness of prevention and treatment of CKD. Mathematical derivation of savings associated with prevention of CKD is not feasible because of dearth of data. However, examination of various factors that would affect such a hypothetical derivation indicates that prevention of CKD is cost-effective. Better data enable modeling of gross savings of slowing the progression of CKD. Data suggest that if at the beginning of the current decade, the rate of decline in GFR decreased by 10% and 30% in every patient with GFR of 60 mL/min/1.73 m(2) or less the gross direct cumulative health care savings over the next 10 years amount to $18.56 and $60.61 billion, respectively. Additional benefits accrue as a result of diminishing disability and gain in productivity. The analysis suggests that prevention and slowing progression of CKD is cost-effective.

Lack of nephrotoxicity of gadodiamide in unselected hospitalized patients.

BACKGROUND: The nephrotoxicity of gadolinium-based magnetic resonance contrast media has not been adequately studied. METHODS: We evaluated the nephrotoxicity of gadolinium-based contrast media in hospitalized patients who underwent magnetic resonance imaging (MRI) as part of routine clinical care. Subjects who had a serum creatinine measurement during the 7 days before MRI and at least 1 other measurement 2 to 3 days after MRI were included. Patients who underwent noncontrasted MRI served as controls. RESULTS: There were 162 subjects (mean age, 57.8 +/- 16.9 years; 91 men and 71 women) and 125 controls (mean age, 64.6 +/- 18 years; 62 men and 63 women). All contrast-enhanced MRI studies utilized gadodiamide (Omniscan; GE Healthcare, Waukesha, WI). Subjects who received gadodiamide showed no difference in the incidence of acute renal insufficiency compared with controls (increase in serum creatinine >or= 25%, 11.1% vs 12.9%, respectively; P = 0.6; increase in serum creatinine by 0.5 mg/dL, 5.6% vs 3.2%, respectively; P = 0.4). There was no significant increase in serum creatinine baseline versus 48 hours in either the subjects who received gadodiamide (0.95 +/- 0.58 vs 0.96 +/- 0.65 mg/dL; P = 0.7) or controls (0.96 +/- 0.65 vs 0.88 +/- 0.43 mg/dL; P = 0.7). CONCLUSION: Our findings showed a lack of significant nephrotoxicity of gadodiamide in unselected hospitalized patients.

High-dose N-acetylcysteine for the prevention of contrast-induced nephropathy.

BACKGROUND: Whether N-acetylcysteine is beneficial for the prevention of contrast-induced nephropathy is uncertain. METHODS: We conducted a meta-analysis to evaluate the efficacy of high-dose N-acetylcysteine for the prevention of contrast-induced nephropathy. Our prespecified inclusion criteria were as follows: adult subjects; English language literature; administration of high-dose N-acetylcysteine a priori defined as a daily dose greater than 1200 mg or a single periprocedural dose (within 4 hours of contrast exposure) greater than 600 mg; prospective trials of individuals randomized to N-acetylcysteine, administered orally or intravenously, versus a control group; and trials that included the end point of the incidence of contrast-induced nephropathy. Trials that compared N-acetylcysteine with another active treatment were excluded. RESULTS: Sixteen comparisons of patients randomized to high-dose N-acetylcysteine versus controls met our prespecified inclusion criteria with a total sample size of 1677 subjects (842 assigned to high-dose N-acetylcysteine and 835 assigned to the control arm). The average population age was 68 years, 38.7% were diabetic, and the majority was male (67.8% of reported instances). The weighted mean baseline creatinine of the overall population was 1.58 mg/dL. No significant heterogeneity was detected (P = .09; I(2) = 34%). The overall effect size assuming a common odds ratio revealed an odds ratio of 0.46 (95% confidence interval [CI], 0.33-0.63) for the occurrence of contrast-induced nephropathy with the use of high-dose N-acetylcysteine. The results of the more conservative random effects approach were similar (odds ratio = 0.52; 95% CI, 0.34-0.78). There was no evidence of publication bias (P = .34). CONCLUSION: Our results suggest that high-dose N-acetylcysteine decreases the incidence of contrast-induced nephropathy.

MicroRNA: a new frontier in kidney and blood pressure research.

MicroRNA (miRNA) has emerged rapidly as a major new direction in many fields of research including kidney and blood pressure research. A mammalian genome encodes several hundred miRNAs. These miRNAs potentially regulate the expression of thousands of proteins. miRNA expression profiles differ substantially between the kidney and other organs as well as between kidney regions. miRNAs may be functionally important in models of diabetic nephropathy, podocyte development, and polycystic disease. miRNAs may be involved in the regulation of arterial blood pressure, including possible involvement in genetic elements of hypertension. Studies of miRNAs could generate diagnostic biomarkers for kidney disease and new mechanistic insights into the complex regulatory networks underlying kidney disease and hypertension. Further progress in the understanding of miRNA biogenesis and action and technical improvements for target identification and miRNA manipulation will be important for studying miRNAs in renal function and blood pressure regulation.

Risk factors for non-fatal myocardial infarction and cardiac death in incident dialysis patients.

BACKGROUND: The risks of major cardiac events in patients initiating long-term dialysis related to prior coronary disease and various other factors are not well known. METHODS: We used United States Renal Data System data to analyse the outcomes of non-fatal myocardial infarction (MI) and cardiac death in incident dialysis patients from years 1997 through 2001 (n = 214 890). The presence of established coronary artery disease was determined from the Medical Evidence form, non-fatal MI events were determined from Medicare claims' data and cause of death was determined from the Death Notification form. Multivariable analyses were performed employing Cox proportional hazards models using demographics, co-morbidities, laboratory variables, prior erythropoietin use, body mass index and type of dialysis. RESULTS: In patients with prior coronary disease as compared to those without, the adjusted relative risk of non-fatal MI was 1.57 (95% CI, 1.5-1.65) and cardiac death was 1.16 (95% CI, 1.14-1.18). The 5-year cumulative incidence of non-fatal MI was 8.1 and 6% and cardiac death was 48.3 and 40.2%, in patients with and without prior coronary disease, respectively. Amongst important factors, blacks had a lower risk of non-fatal MI and cardiac death as compared to whites. A history of hypertension conferred a lower independent risk of cardiac death events. Lower haemoglobin, higher albumin and higher creatinine values each conferred a lower independent risk of non-fatal MI and cardiac death. CONCLUSIONS: Incident dialysis subjects with prior coronary disease have a risk of non-fatal MI greater by 57% and cardiac death by 16% as compared to subjects without prior coronary disease. In both populations, the competing risk of cardiac death is several-fold greater than that of non-fatal MI. There are several factors suggesting reverse epidemiology phenomena with respect to major cardiac events in the dialysis population.

Outcomes in patients with chronic kidney disease referred late to nephrologists: a meta-analysis.

PURPOSE: The study purpose was to compare differences in mortality and the duration of hospitalization in patients with chronic kidney disease who are referred early versus late to nephrologists. METHODS: We searched English-language literature from 1980 through December 2005, along with national conference proceedings, the Web of Science Citation Index, and reference lists of all included studies. Twenty-two studies with a total sample size of 12,749 met inclusion criteria. RESULTS: There was significantly increased overall mortality in the late referral group as compared with the early referral group (relative risk 1.99; 95% confidence interval [CI], 1.66 to 2.39, P <.0001). The duration of hospital stay, at the time of initiation of renal replacement therapy, was greater in the late referred group by an average of 12 days (95% CI, 8.0 to 16.1, P=.0007). Significant heterogeneity was detected for both outcomes. CONCLUSION: Timing of referral emerged to be a significant factor impacting homogeneity in the mortality outcome. Our results suggest significantly higher mortality and increased early hospitalization of chronic kidney disease subjects referred late to nephrologists as compared with earlier referred subjects.

Acute effect of furosemide on glomerular filtration rate in diastolic dysfunction.

We sought to evaluate the acute effect of furosemide on glomerular filtration rate (GFR) in subjects with diastolic dysfunction. An equal number of subjects with documented diastolic dysfunction (DD) and healthy volunteers (controls) were enrolled and underwent a baseline GFR measurement via plasma clearance of technetium-99m-diethylenetriaminepentaacetic acid. Within three to seven days of the baseline, study subjects were scheduled for a second GFR study, which was performed immediately after administration of furosemide (20 mg orally and 20 mg intravenously). There were eight healthy volunteers (8 males with a mean age 42 +/- 7.8 years; 6 white, 2 Asian) and eight subjects with diastolic dysfunction (7 males, 1 female, with a mean age 64.5 +/- 9.3 years; 7 whites, 1 African-American). There was a significant post-furosemide decline in GFR in the healthy volunteers, baseline vs. post-furosemide 131.6 +/- 19.8 vs. 117 +/- 18.2 mL/min, respectively (p = 0.03), and the patients with DD, baseline vs. post-furosemide 117.5 +/- 22.3 vs. 92 +/- 21.7 mL/min, respectively (p = 0.0002). A strong trend was detected, though not statistically significant, of greater GFR decline in subjects with DD compared to the healthy volunteers, 25.5 +/- 9.9 vs. 14.6 +/- 15.6 mL/min, respectively (p = 0.12). To conclude, acute administration of furosemide might potentially cause a greater decline in GFR in subjects with diastolic dysfunction.

A study of the extracorporeal rate of blood flow and blood pressure during hemodialysis.

Hemodynamic instability is a common problem during hemodialysis (HD). The effect of blood flow rate (BFR) on blood pressure (BP) during HD has not been previously evaluated. Subjects receiving HD for the treatment of renal failure were enrolled (n=34). For each patient, during the last hour of 2 consecutive HD sessions the BFR was set at 200 mL/min for 30 min and at 400 mL/min for 30 min, during which period the fluid removal rate was kept constant. The order of the BFR alterations was randomized. The study procedure was repeated during the next HD session but with reversal of the order of the altered BFR. During each 30-min period, BP was recorded at baseline and subsequently every 10 min. During the BFR of 400 mL/min, subjects had a higher systolic BP by an average of 4.1 mmHg compared with the BFR of 200 mL/min (95% confidence interval [CI] 0.22-7.98; p=0.038). Similarly, during the BFR of 400 mL/min, subjects had a higher diastolic BP by an average of 3.04 mmHg compared with the BFR of 200 mL/min (95% CI 0.55-5.53; p=0.017). Likewise, during the BFR of 400 mL/min, subjects had a higher mean arterial pressure by an average of 3.44 mmHg (95% CI 0.77-6.11; p=0.012). The findings suggest that during HD, BPs are maintained higher at higher BFRs as compared with lower BFRs.

Predictors of hospitalization in patients on peritoneal dialysis: the Missouri experience.

BACKGROUND: We analyzed a large number of demographic and biochemical variables to identify predictors of hospitalization in subjects on peritoneal dialysis (PD). METHODS: All patients initiated on PD at our center from January 1990 through December 1999 were included. The following variables at the initiation of PD were included: demographics, clinical data, nutritional and adequacy parameters, transport characteristics, and various co-morbidities. Co-morbidities were graded for severity using a modified version of the Index of Coexistent Disease. Variables included during the course of PD consisted of weighted time average of a number of laboratory, adequacy, and nutritional parameters along with the number of peritonitis episodes per year. Stepwise linear regression was used following a univariate screening procedure to identify independent predictors of the outcome of hospitalization days per month on PD. RESULTS: The subject population consisted of 191 subjects (105 men, 86 women; 180 Caucasians, 10 African-American, 1 Asian). The mean age was 61 +/- 13 (SD) years and mean duration of follow-up was 21 +/- 18 months. The baseline variable analysis revealed that the presence of partner to perform PD predicted increased hospitalization (p < 0.0001). Additionally, the presence and severity of peripheral vascular disease and residual renal Kt/V at baseline (negative association) predicted increased hospitalization. In the analyses of ongoing variables, stepwise linear regression solely identified weighted time average albumin as a strong negative predictor of hospitalization (p < 0.0001). CONCLUSION: A comprehensive analysis of a large number of variables revealed that serum albumin during the course of PD (negative association) and the need for partner to perform PD strongly predicted increased hospitalization in PD subjects.

Predictors of death in patients on peritoneal dialysis: the Missouri Peritoneal Dialysis Study.

BACKGROUND: The study was designed to identify predictors of death in subjects on peritoneal dialysis (PD). METHODS: The population consisted of patients initiated on PD at the University of Missouri-Columbia and Dialysis Clinic Incorporated from January 1, 1990, through December 31, 1999. Baseline variables included demographics, clinical data, initial measures of nutritional status, adequacy, and transport characteristics. Co-morbidities were scored using a modified version of the Index of Coexistent Disease. Ongoing (during the course of PD) variables consisted of clinical characteristics and weighted time average of a number of laboratory, adequacy, and nutritional variables. The variables were screened using a univariate procedure, and then analyzed using stepwise logistic regression to evaluate their independent relation to death. RESULTS: There were 105 men and 86 women--180 Caucasians, 10 African-American, 1 Asian, mean age 61 +/- 13 (SD) years, and mean duration of follow-up 21 +/- 18 months. Eighty-two patients suffered the outcome of death. Lean body mass (LBM) at the initiation of PD was negatively associated with the risk of death (p < 0.01). In addition, the need for a partner to perform PD, total morbidity count, and the summated severity score of all co-morbidities were associated with an increased risk of death. The analysis of ongoing variables revealed that serum phosphate (negative association, p = 0.02) and number of hospitalization days per month on PD (p = 0.0006) were associated with an increased risk of death. CONCLUSION: Phosphate levels and LBM are strong negative predictors of death in PD subjects. Further, patients who need the assistance of a partner to perform PD have decreased survival.

Subnormal rise of erythropoietin in patients receiving interferon and ribavirin combination therapy for hepatitis C.

OBJECTIVES: Anemia is a common complication during interferon-ribavirin therapy for hepatitis C. While normally a fall in hematocrit in results in an exponential compensatory rise in erythropoietin, such that the correlation between hematocrit and erythropoietin is sharply negative, the erythropoietin response during interferon-ribavirin combination therapy is not known. METHODS: We measured the hematocrit and erythropoietin levels before and after about 4 weeks of interferon-ribavirin therapy for hepatitis C (n = 43), and compared their relation to the normal human response to anemia. RESULTS: The hematocrit fell from an average pre-treatment level of 43.7 +/- 3.7% to 36.9 +/- 5 (P < 0.0001). The erythropoietin level rose from 14.5 +/- 15.1 to 58.5 +/- 94.1 units/L (P < 0.0001), indicating there was an adequate stimulus for erythropoietin release. The rise of erythropoietin was severely impaired in relation to the normal human response to a fall in hematocrit. Using the normal human response to anemia as the population line, for our population there was a significant difference in the slope of hematocrit (x) versus log10 erythropoietin (y) (-8.7 vs. -3.098 respectively, P < 0.001) and y-intercept (4.609 vs. 2.753 respectively, P < 0.001). The Bonferroni adjusted "p" value was derived to be <0.002. There was an approximate 2 log10 reduction in maximal achievable erythropoietin level in subjects exposed to interferon-ribavirin combination. CONCLUSION: There is a subnormal rise of erythropoietin after interferon-ribavirin combination therapy for hepatitis C.

Discrepancy in the epidemiology of nondiabetic chronic renal insufficiency and end-stage renal disease in black and white Americans: the third National Health and Nutrition Examination Survey and United States Renal Data System.

BACKGROUND: Epidemiologic data regarding the prevalence of chronic renal insufficiency (CRI) [from the third National Health and Nutrition Examination Survey (NHANES III)] and the incidence of end-stage renal disease (ESRD) [from the United States Renal Data System (USRDS)] are available. However, reconciliation of these separate particulars has not been performed objectively. The present work examines the epidemiology of CRI of nondiabetic etiology and ESRD in black and white Americans aged 20 years or greater. METHODS: Based on the incidence of ESRD in the study population (USRDS), the numbers of subjects with decreased Modification of Diet in Renal Disease (MDRD) glomerular filtration rate (GFR) <80 ml/min/1.73 m(2), <60 ml/min/1.73 m(2) and <30 ml/ min/1.73 m(2) in 1991 (on December 31 1991) were mathematically obtained based on a linear model of GFR decline. Similarly, the corresponding estimated prevalence figures of CRI were derived based on analyses of NHANES III data and the 1991 census counts of black and white Americans (aged 20 years or more). Unadjusted and adjusted (correcting for calibration differences between the NHANES III and MDRD laboratory) prevalences were calculated. Subsequently, the prevalence of different degrees of CRI based on the incidence of ESRD (USRDS) was compared to the corresponding figures of the estimated prevalence of CRI (NHANES III). RESULTS: By analyses of USRDS data, on December 31 1991, the prevalence of different degrees of reduced GFR in the study population was estimated to be as follows: 396,863 subjects with GFR <80 ml/min/1.73 m(2); 272,932 subjects with GFR <60 ml/min/1.73 m(2), and 115,065 subjects with GFR <30 ml/min/1.73 m(2). Using actual NHANES III creatinine values, the prevalence of different degrees of CRI in the study population was estimated as follows: 92,595,211 people with GFR <80 ml/min/1.73 m(2); 20,754,099 people with GFR <60 ml/min/1.73 m(2), and 415,082 people with GFR <30 ml/min/1.73 m(2). The data suggest that approximately 0.43% of subjects with GFR <80 ml/min/1.73 m(2), 1.32% of subjects with GFR <60 ml/min/1.73 m(2) and 27.72% of subjects with GFR <30 ml/ min/1.73 m(2) reached ESRD (USRDS). Using adjusted NHANES III creatinine values (downwardly correcting the NHANES III creatinine values to account for calibration differences with the MDRD measurements), the prevalence of different degrees of CRI in the study population was estimated as follows: 28,512,939 people with MDRD GFR <80 ml/min/1.73 m(2) (17.86%); 5,364,136 people with MDRD GFR <60 ml/min/1.73 m(2) (3.36%), and 255,435 people with MDRD GFR <30 ml/min/1.73 m(2) (0.16%). Of these, about 1.39% of the people with MDRD GFR <80 ml/min/1.73 m(2), 5.09% of the people with MDRD GFR <60 ml/min/1.73 m(2) and 45.07% of the people with MDRD GFR <30 ml/min/1.73 m(2) in 1991 reached ESRD. CONCLUSION: There is a major discrepancy in the epidemiology of nondiabetic CRI and ESRD amongst black and white Americans. The reasons for this need further study.

A prospective, randomized, open labeled crossover trial of fosinopril and theophylline in post renal transplant erythrocytosis.

Angiotensin converting enzyme inhibitors (ACEI) and theophylline have been reported to decrease the elevated hemoglobin (Hgb) and hematocrit (Hct) levels in the renal transplant recipients with erythrocytosis. We conducted a prospective randomized, open labeled, crossover trial with theophylline, and an ACEI, fosinopril in nine stable renal transplant recipients with erythrocytosis. Aim of the study was to determine and compare the efficacy of these medications in stable renal transplant patients. At three months, compared to baseline, fosinopril significantly reduced the elevated hemoglobin (Hgb 17.2 +/- 0.6 vs. 14.9 +/- 1.4 gm/dL, p = 0.0023), and hematocrit levels (Hct 51.3 +/- 2.4 vs. 43.7 +/- 4.6%, p = 0.003). In contrast theophylline therapy was associated with a non-significant rise in hemoglobin (17.4 +/- 0.7 vs. 18.1 +/- 0.9gm/dL, p > 0.05) and hematocrit (52.4 +/- 2.7 vs. 54.7 +/- 3.9%, p > 0.05). With fosinopril compared to theophylline, there was a significant difference in the change in hemoglobin (baseline to three months 2.8 +/- 1.7 vs. -0.7 +/- 0.69 gm/dL respectively, p = 0.017), and the change in hematocrit (baseline to three months 9 +/- 6 vs. -2.3 +/- 2.7% respectively, p = 0.027). Four patients (44.4%) did not tolerate theophylline and did not complete the theophylline arm. To conclude, in our study, fosinopril effectively decreased the elevated hemoglobin and hematocrit in patients with post transplant erythrocytosis, and was superior to theophylline, while theophylline was ineffective and poorly tolerated in this condition.