Filtration Markers, Cardiovascular Disease, Mortality, and Kidney Outcomes in Stable Kidney Transplant Recipients: The FAVORIT Trial.

Cystatin C and beta-2-microglobulin (B2M) are filtration markers associated with adverse outcomes in nontransplant populations, sometimes with stronger associations than for creatinine. We evaluated associations of estimated glomerular filtration rate from cystatin C (eGFRcys ), B2M (eGFRB2M ), and creatinine (eGFRcr ) with cardiovascular outcomes, mortality, and kidney failure in stable kidney transplant recipients using a case-cohort study nested within the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial. A random subcohort was selected (N = 508; mean age 51.6 years, median transplant vintage 4 years, 38% women, 23.6% nonwhite race) with enrichment for cardiovascular events (N = 306; 54 within the subcohort), mortality (N = 208; 68 within the subcohort), and kidney failure (N = 208; 52 within the subcohort). Mean eGFRcr , eGFRcys , and eGFRB2M were 46.0, 43.8, and 48.8 mL/min/1.73m2 , respectively. After multivariable adjustment, hazard ratios for eGFRcys and eGFRB2M <30 versus 60+ were 2.02 (95% confidence interval [CI] 1.09-3.76; p = 0.03) and 2.56 (1.35-4.88; p = 0.004) for cardiovascular events; 3.92 (2.11-7.31) and 4.09 (2.21-7.54; both p < 0.001) for mortality; and 9.49 (4.28-21.00) and 15.53 (6.99-34.51; both p < 0.001) for kidney failure. Associations persisted with additional adjustment for baseline eGFRcr . We conclude that cystatin C and B2M are strongly associated with cardiovascular events, mortality, and kidney failure in stable kidney transplant recipients.

Estimated GFR for Living Kidney Donor Evaluation.

All living kidney donor candidates undergo evaluation of GFR. Guidelines recommend measured GFR (mGFR), using either an endogenous filtration marker or creatinine clearance, rather than estimated GFR (eGFR), but measurement methods are difficult, time consuming and costly. We investigated whether GFR estimated from serum creatinine (eGFRcr) with or without sequential cystatin C is sufficiently accurate to identify donor candidates with high probability that mGFR is above or below thresholds for clinical decision making. We combined the pretest probability for mGFR thresholds <60, <70, ≥80, and ≥90 mL/min per 1.73 m(2) based on demographic characteristics (from the National Health and Nutrition Examination Survey) with test performance of eGFR (categorical likelihood ratios from the Chronic Kidney Disease Epidemiology Collaboration) to compute posttest probabilities. Using data from the Scientific Registry of Transplant Recipients, 53% of recent living donors had predonation eGFRcr high enough to ensure ≥95% probability that predonation mGFR was ≥90 mL/min per 1.73 m(2) , suggesting that mGFR may not be necessary in a large proportion of donor candidates. We developed a Web-based application to compute the probability, based on eGFR, that mGFR for a donor candidate is above or below a range of thresholds useful in living donor evaluation and selection.

Kidney function and risk of cardiovascular disease and mortality in kidney transplant recipients: the FAVORIT trial.

In kidney transplant recipients, cardiovascular disease (CVD) is the leading cause of death. The relationship of kidney function with CVD outcomes in transplant recipients remains uncertain. We performed a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial to assess risk factors for CVD and mortality in kidney transplant recipients. Following adjustment for demographic, clinical and transplant characteristics, and traditional CVD risk factors, proportional hazards models were used to explore the association of estimated GFR with incident CVD and all-cause mortality. In 4016 participants, mean age was 52 years and 20% had prior CVD. Mean eGFR was 49 ± 18 mL/min/1.73 m(2) . In 3676 participants with complete data, there were 527 CVD events over a median of 3.8 years. Following adjustment, each 5 mL/min/1.73 m(2) higher eGFR at levels below 45 mL/min/1.73 m(2) was associated with a 15% lower risk of both CVD [HR = 0.85 (0.80, 0.90)] and death [HR = 0.85 (0.79, 0.90)], while there was no association between eGFR and outcomes at levels above 45 mL/min/1.73 m(2) . In conclusion, in stable kidney transplant recipients, lower eGFR is independently associated with adverse events, suggesting that reduced kidney function itself rather than preexisting comorbidity may lead to CVD.

Inflammation and cardiovascular events in individuals with and without chronic kidney disease.

Inflammation and chronic kidney disease predict cardiovascular events. Here we evaluated markers of inflammation including fibrinogen, albumin and white blood cell count in individuals with and without stages 3-4 chronic kidney disease to assess inflammation as a risk factor for adverse events, the synergy between inflammation and chronic kidney disease, and the prognostic ability of these inflammatory markers relative to that of C-reactive protein. Using Atherosclerosis Risk in Communities and Cardiovascular Health Study data, inflammation was defined by worst quartile of at least 2 of these 3 markers. In Cox regression models, inflammation was assessed as a risk factor for a composite of cardiac events, stroke and mortality as well as components of this composite. Among 20 413 patients, inflammation was identified in 3594 and chronic kidney disease in 1649. In multivariable analyses, both inflammation and chronic kidney disease predicted all outcomes, but their interaction was non-significant. In 5597 patients with C-reactive protein levels, inflammation and elevated C-reactive protein had similar hazard ratios. When focusing only on individuals with the worst quartile of white cell count and albumin, results remained consistent.

Long-term outcomes in nondiabetic chronic kidney disease.

The Modification of Diet in Renal Disease (MDRD) Study examined the effects of strict blood pressure control and dietary protein restriction on the progression of kidney disease. Here, we retrospectively evaluated outcomes of nondiabetic participants with stages 2-4 chronic kidney disease (CKD) from randomized and nonrandomized cohorts of the MDRD Study. Kidney failure and survival status through December of 2000, were obtained from the US Renal Data System and the National Death Index. Event rates were calculated for kidney failure, death, and a composite outcome of death and kidney failure. In the 1666 patients, rates for kidney failure were four times higher than that for death. Kidney failure was a more likely event than death in subgroups based on baseline glomerular filtration rate, proteinuria, kidney disease etiology, gender, and race. It was only among those older than 65 that the rate for death approximated that for kidney failure. In contrast to other populations with CKD, our study of relatively young subjects with nondiabetic disease has found that the majority of the participants advanced to kidney failure with a low competing risk of death. In such patients, the primary emphasis should be on delaying progression of kidney disease.

Assessment of Glomerular Filtration Rate in Health and Disease: A State of the Art Review.

Acute and chronic kidney diseases affect pharmacokinetics and pharmacodynamics. There has been substantial progress in the past 20 years in the use of glomerular filtration rate (GFR) estimating equations. In principle, use of a single equation for each filtration marker (creatinine, cystatin C, or the combination) for detection, evaluation, and management of kidney disease and for drug development and dosing would facilitate clinical practice. We review the principles for assessment of GFR, provide historical perspectives and updates regarding use of GFR estimating equations, including assay methods for filtration markers, performance of estimating equations, and recommendations by clinical practice guideline groups and regulatory agencies. We conclude that it is time to change from rigid adherence to the use of the Cockcroft-Gault equation for use in drug development and drug dosing to the more accurate and more widely used Modification of Diet in Renal Disease (MDRD) study and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations.

Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction.

OBJECTIVES: We sought to evaluate the relationship between the level of kidney function, level of hematocrit and their interaction on all-cause mortality in patients with left ventricular (LV) dysfunction. BACKGROUND: Anemia and reduced kidney function occur frequently in patients with heart failure. The level of hematocrit and its relationship with renal function have not been evaluated as risk factors for mortality in patients with LV dysfunction. METHODS: We retrospectively examined the Studies Of LV Dysfunction (SOLVD) database. Glomerular filtration rate (GFR) was predicted using a recently validated formula. Kaplan-Meier survival analyses were used to compare survival times between groups stratified by level of kidney function (predicted GFR) and hematocrit. Cox proportional-hazards regression was used to explore the relationship of survival time to level of kidney function, hematocrit and their interaction. RESULTS: Lower GFR and hematocrit were associated with a higher prevalence of traditional cardiovascular risk factors. In univariate analysis, reduced kidney function and lower hematocrit, in men and in women, were risk factors for all-cause mortality (p < 0.001 for both). After adjustment for other factors significant in univariate analysis, a 10 ml/min/1.73 m(2) lower GFR and a 1% lower hematocrit were associated with a 1.064 (95% CI: 1.033, 1.096) and 1.027 (95% CI: 1.015, 1.038) higher risk for mortality, respectively. At lower GFR and lower hematocrit, the risk was higher (p = 0.022 for the interaction) than that predicted by both factors independently. CONCLUSIONS: Decreased kidney function and anemia are risk factors for all-cause mortality in patients with LV dysfunction, especially when both are present. These relationships need to be confirmed in additional studies.

The improving prognosis after kidney transplantation. New strategies to overcome immunologic rejection.

For the 70,000 patients with end-stage renal disease in the United States, renal transplantation offers the only hope of full recovery from chronic renal failure. However, transplantation has had only limited use, principally because of the risks of graft rejection and immunosuppression. The last ten years have witnessed striking improvements in the survival of patients and grafts resulting from advances in immunologic management, including restricted use of immunosuppression, better histocompatibility testing, HLA matching, blood transfusions, and new drugs for prevention and reversal of transplant rejection. Kidney transplantation now is safe and effective and should be considered for most young and middle-aged adults.

Amoxapine-associated acute renal failure.

Acute renal failure, a brief seizure, and mild rhabdomyolysis developed in a 27-year-old man following overdosage with the tricyclic antidepressant, amoxapine. Renal function returned to normal approximately ten days following drug ingestion. Strikingly, of 111 cases of amoxapine overdosage reported to the manufacturer, acute renal failure has occurred in 12. Of these 12 patients, seizures were documented in seven, and presumptive or definitive evidence of rhabdomyolysis or myoglobinuria was documented in eight. Three possible mechanisms of the renal failure are (1) acute tubular necrosis secondary to nontraumatic rhabdomyolysis; (2) hypotension-induced acute tubular necrosis; and (3) direct nephrotoxic reaction from amoxapine. Rapid hydration with intravenously administered saline is proposed as a means of reducing the substantial incidence of acute renal failure following amoxapine overdosage.

Prevalence of high blood pressure and elevated serum creatinine level in the United States: findings from the third National Health and Nutrition Examination Survey (1988-1994).

BACKGROUND: The prevalence and incidence of end-stage renal disease in the United States are increasing, but milder renal disease is much more common and may often go undiagnosed and undertreated. METHODS: A cross-sectional study of a representative sample of the US population was conducted using 16 589 adult participants aged 17 years and older in the Third National Health and Nutrition Examination Survey (NHANES III) conducted from 1988 to 1994. An elevated serum creatinine level was defined as 141 micromol/L or higher (>/=1.6 mg/dL) for men and 124 micromol/L or higher (>/=1.4 mg/dL) for women (>99th percentile for healthy young adults) and was the main outcome measure. RESULTS: Higher systolic and diastolic blood pressures, presence of hypertension, antihypertensive medication use, older age, and diabetes mellitus were all associated with higher serum creatinine levels. An estimated 3.0% (5.6 million) of the civilian, noninstitutionalized US population had elevated serum creatinine levels, 70% of whom were hypertensive. Among hypertensive individuals with an elevated serum creatinine level, 75% received treatment. However, only 11% of all individuals with hypertension had their blood pressure reduced to lower than 130/85 mm Hg (the Sixth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure recommendation for hypertensive individuals with renal disease); 27% had a blood pressure lower than 140/90 mm Hg. Treated hypertensive individuals with an elevated creatinine level had a mean blood pressure of 147/77 mm Hg, 48% of whom were prescribed one antihypertensive medication. CONCLUSION: Elevated serum creatinine level, an indicator of chronic renal disease, is common and strongly related to inadequate treatment of high blood pressure.

Achievement and safety of a low blood pressure goal in chronic renal disease. The Modification of Diet in Renal Disease Study Group.

The Modification of Diet in Renal Disease Study showed a beneficial effect of a lower-than-usual blood pressure (BP) goal on the progression of renal disease in patients with proteinuria. The purpose of the present analyses was to examine the achieved BP, baseline characteristics that helped or hindered achievement of the BP goals, and safety of the BP interventions. Five hundred eighty-five patients with baseline glomerular filtration rate between 13 and 55 mL/min per 1.73 m2 (0.22 to 0.92 mL/s per 1.73 m2) were randomly assigned to either a usual or low BP goal (mean arterial pressure < or = 107 or < or = 92 mm Hg, respectively). Few patients had a history of cardiovascular disease. All antihypertensive agents were permitted, but angiotensin-converting enzyme inhibitors (with or without diuretics) followed by calcium channel blockers were preferred. The mean (+/- SD) of the mean arterial pressures during follow-up in the low and usual BP groups was 93.0 +/- 7.3 and 97.7 +/- 7.7 mm Hg, respectively. Follow-up BP was significantly higher in subgroups of patients with preexisting hypertension, baseline mean arterial pressure > 92 mm Hg, a diagnosis of polycystic kidney disease or glomerular diseases, baseline urinary protein excretion > 1 g/d, age > or = 61 years, and black race. The frequency of medication changes and incidence of symptoms of low BP were greater in the low BP group, but there were no significant differences between BP groups in stop points, hospitalizations, or death. When data from both groups were combined, each 1-mm Hg increase in follow-up systolic BP was associated with a 1.35-times greater risk of hospitalization for cardiovascular or cerebrovascular disease. Lower BP than usually recommended for the prevention of cardiovascular disease is achievable by several medication regimens without serious adverse effects in patients with chronic renal disease without cardiovascular disease. For patients with urinary protein excretion > 1 g/d, target BP should be a mean arterial pressure of < or = 92 mm Hg, equivalent to 125/75 mm Hg.

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

African Americans (blacks) have a disproportionately high incidence of end-stage renal disease due to hypertension. The Modification of Diet in Renal Disease (MDRD) Study found that strict blood pressure control slowed the decline in glomerular filtration rate (GFR) only in the subgroup of patients with proteinuria. The present report compares the effects of blood pressure control in black and white MDRD Study participants. Fifty-three black and 495 white participants with baseline GFRs of 25 to 55 mL/min/1.73 m2 were randomly assigned to a usual or low mean arterial pressure (MAP) goal of < or = 107 or < or = 92 mm Hg, respectively. GFR decline was compared between randomized groups and correlated with the level of achieved blood pressure. The mean (+/-SE) GFR decline over 3 years in the low blood pressure group was 11.8+/-7.3 mL/min slower than in the usual blood pressure group among blacks (P=.11) compared with 0.3+/-1.3 mL/min slower among whites (P=.81) (P=.12 between blacks and whites). In both blacks and whites, higher baseline urine protein excretion was associated with a greater beneficial effect of the low MAP goal on GFR decline (P=.02 for both races). Combining both blood pressure groups and controlling for baseline characteristics, higher follow-up achieved MAP was associated with faster GFR decline in both blacks (P<.001) and whites (P=.002), with a sevenfold stronger relationship in blacks (P<.001). These secondary analyses support the prior recommendation for a lower than usual blood pressure goal (MAP < or = 92 mm Hg) in black and white patients with proteinuria (> 1 g/d). In addition, a lower level of blood pressure control may be even more important in blacks than in whites in slowing the progression of renal disease.

Metabolic alkalosis due to absorption of "nonabsorbable" antacids.

In a patient with end-stage renal disease undergoing long-term maintenance hemodialysis, moderately severe metabolic alkalosis developed in the absence of vomiting or gastric drainage. The cause of the acid-base disorder was exogenous alkali administration, in the form of combined ingestion of "nonabsorbable" antacids (aluminum hydroxide and magnesium hydroxide), neutral phosphate, and a cation-exchange resin (sodium polystyrene sulfonate). In this report, the relevant data of this patient are detailed, and the literature on this well-documented, albeit poorly recognized, acid-base derangement is summarized.

The impact of pretransplantation hepatitis C infection on the outcome of renal transplantation.

Controversy exists regarding the impact of pretransplantation HCV infection on the outcome of renal transplantation. We compared the prevalence of posttransplantation liver disease and graft and patient survival among kidney transplant recipients with and without anti-HCV at the time of transplantation. Pretransplantation sera from 103 randomly selected recipients of kidneys from anti-HCV-negative donors were tested for anti-HCV using a second generation ELISA. Twenty-three (22%) were positive for anti-HCV and 80 (78%) were negative. Anti-HCV-positive recipients had a longer time on dialysis (P = 0.003) and had a higher number of previous transplants (P = 0.01). Further, 61% of anti-HCV-positive patients had a history of liver disease compared with 13% of anti-HCV-negative patients (P < 0.001). HCV RNA was detected in the pretransplantation serum in 61% of anti-HCV positive recipients compared with 5% of anti-HCV-negative recipients (P < 0.001). Clinical follow-up on both anti-HCV-positive and -negative patients was obtained until December, 1993. Median posttransplantation follow-up among recipients with anti-HCV prior to transplantation (45 months) was shorter (P = 0.05) than that for recipients without anti-HCV (66 months). For recipients with anti-HCV prior to transplantation, the relative risk of posttransplantation liver disease was 5.0 (95% confidence intervals of 2.4 to 10.5); the relative risk of graft loss was 1.3 (95% confidence intervals of 0.6 to 2.6); the relative risk of death was 3.3 (95% confidence intervals of 1.4 to 7.9), and the relative risk of death due to sepsis was 9.9 (95% confidence intervals of 2.6 to 38.3). The results of this study demonstrate that pretransplantation HCV infection is associated with an increased risk of liver disease and death after renal transplantation. These results raise the question of whether anti-HCV-positive patients on dialysis should be offered renal transplantation as opposed to continuing dialysis.

Long-term follow-up of hepatitis C virus infection among organ transplant recipients: implications for policies on organ procurement.

BACKGROUND: Hepatitis C virus (HCV) infection causes slowly progressive liver disease. Therefore, the full impact of HCV infection after transplantation may require 5-10 years of follow-up. METHODS: We have previously reported the effect of HCV infection, acquired from the donor (study 1) or acquired before transplantation (study 2), on the incidence of liver disease, and on patient and graft survival with a median follow-up of 3-5 years. In study 1, we compared 24 recipients of organs from donors who were positive to antibody to HCV (anti-HCV) to 74 recipients of organs from anti-HCV-negative donors. In study 2, we compared 23 anti-HCV-positive recipients to 80 anti-HCV-negative recipients of kidneys from anti-HCV-negative donors. In this report, we extend the median follow-up period for patient and graft survival to 6-7 years, and discuss the implications of our finding on policies for organ procurement. RESULTS: In study 2, after extended follow-up, there continued to be no significant difference between groups with respect to graft loss, but mortality remained significantly higher among recipients with anti-HCV before transplantation. Compared with recipients without anti-HCV before transplantation, the relative risk of graft loss among recipients with anti-HCV before transplantation was 1.30 (0.66-2.58), the relative risk of death was 2.60 (1.15-5.90), and the relative risk of death due to sepsis was 6.30 (1.99-20). In study 1, after extended follow-up, there continued to be no significant differences between groups, with respect to graft loss or death. Compared with recipients of organs from anti-HCV-negative donors, the relative risk of graft loss among recipients of organs from anti-HCV-positive donors was 0.95 (0.54-1.67), and the relative risk of death was 1.00 (0.49-2.02). CONCLUSIONS: The two studies presented in this report provide an apparent paradox, with respect to the impact of HCV infection acquired at the time of transplantation versus before transplantation on posttransplantation clinical outcomes. However, the increased mortality among recipients who acquired HCV infection before transplantation, but not among recipients who acquired HCV at the time of transplantation, could be explained by the longer duration of HCV infection in the former group. These findings are consistent with the known slowly progressive nature of HCV infection. However, in the absence of definitive evidence for an adverse effect on patient or graft survival, we believe that the decision to accept a kidney from an anti-HCV-positive donor should be made by the patient, after discussion with the treating physician.

GB hepatitis agent in cadaver organ donors and their recipients.

BACKGROUND: The cloning of yet another hepatitis virus, GB virus-C (GBV-C), has provided the opportunity to study the prevalence, and clinical and laboratory characteristics, associated with GBV-C infection among cadaver organ donors and recipients of organs from infected donors. METHODS: Stored sera from a cohort of cadaver organ donors from eight organ procurement organizations, representing different geographic regions of the United States previously screened for hepatitis C virus (HCV) infection, were tested for GBV-C RNA by polymerase chain reaction using degenerate primers derived from the NS3 helicase and 5'-untranslated regions of the GBV-C genome. Pre- and posttransplantation clinical data, and prevalence of GBV-C RNA among recipients of organs from GBV-C RNA-positive and -negative donors, were studied at one of the organ procurement organizations. RESULTS: Twenty-one of 76 (27.6%) anti-HCV ELISA1-positive donors tested positive for GBV-C RNA compared with 6 of 82 (7.3%) ELISA1-negative donors (P=0.001). The prevalence of GBV-C RNA, extrapolated to all cadaver organ donors, was 8.3% (95% confidence interval [CI]: 5.6-11.1%) and was higher than the prevalence of HCV RNA (2.4%). Among ELISA1-positive donors, GBV-C RNA was present in 13 of 35 (37%) donors with HCV RNA, compared with 8 of 41 (20%) donors without HCV RNA (odds ratio [OR]=2.44, P=0.09). Blood alcohol level of more than 100 mg/dl (OR=9.43, P=0.05) and a positive anti-HCV ELISA2 (OR=4.58, P=0.001) were significantly associated with GBV-C infection. In addition, there was a trend toward an association between history of drug abuse (OR=5.23, P=0.06) and younger age (OR=0.97/year, P=0.06) with GBV-C infection. Organs from four GBVC-positive donors and 47 GBV-C-negative donors procured by the New England Organ Bank (Newton, MA) were transplanted into 6 and 79 recipients, respectively. Among recipients of organs from GBV-C RNA. positive donors, the posttransplantation prevalence of GBV-C RNA (25%) was not significantly higher than among recipients of organs from GBV-C RNA-negative donors (23%). Among recipients in whom both pre- and posttransplantation sera were available, one of three (33%) recipients of kidneys from GBV-C RNA-positive donors acquired GBV-C RNA after transplantation, compared with 4 of 40 (10%) recipients of kidneys from GBV-C RNA-negative donors. After a median follow up of 6 years, the posttransplantation prevalence of liver disease, and graft and patient survival, were not significantly different between recipients of organs from GBV-C RNA-positive and -negative donors. CONCLUSIONS: Although GBV-C could be transmitted by organ transplantation, the results of this study preclude definitive conclusions. Further studies are required to determine the risk of transmission of GBV-C by organ transplantation and its role in posttransplantation liver disease.

Which renal transplant patients should receive cytomegalovirus immune globulin? A cost-effectiveness analysis.

Our study objective was to determine the cost-effectiveness of prophylaxis with cytomegalovirus immune globulin for preventing CMV-associated disease in renal transplant patients. We used a decision analytic model applied to 5 groups of renal transplant recipients at varying risks of developing CMV-associated disease. We obtained the rates of developing CMV-associated disease, graft rejection, and mortality, and the effectiveness of CMV-IG from the published literature. We used actual variable costs of CMV-IG, hospitalization, dialysis, and outpatient follow-up. The incremental cost of administering CMV-IG compared with withholding it ranged from $29,800 per life saved for the highest risk group, CMV-seronegative recipients of kidneys from CMV-seropositive cadaveric donors, to $1.68 million per additional life saved for the lowest risk group, CMV-seronegative recipients of grafts from CMV-seronegative donors. The outcome was somewhat sensitive to the effectiveness of CMV-IG in preventing CMV-associated disease but not sensitive to wide variations in CMV-IG costs, dialysis costs, outpatient costs, and the probability of graft rejection. Our conclusion is that prophylaxis with CMV-IG is very worthwhile for renal transplant recipients at high risk of CMV-associated disease and is possibly worthwhile for some patients at lower risk. The cost-effectiveness of other strategies for preventing CMV-associated disease, such as prophylaxis with acyclovir, CMV vaccine, or unselected immune globulin, should be compared with CMV-IG.

U.S. nephrologists' attitudes towards renal transplantation: results from a national survey.

BACKGROUND: Renal transplantation is the optimal treatment for persons with end-stage renal disease (ESRD). A shortage of kidneys in the U.S. has focused increasing attention on the process by which kidneys are allocated. A national survey was undertaken to determine the relative importance of both clinical and nonclinical factors in the recommendation for renal transplantation by U.S. nephrologists. METHODS: We conducted a national random survey of 271 U.S. nephrologists using hypothetical patient scenarios to determine their recommendation for renal transplantation based on demographic, clinical, and social factors. Specifically, eight unique patient scenarios were randomly distributed to each survey respondent. RESULTS: According to responding nephrologists (response rate 53%), females were less likely than males to be recommended for renal transplantation [adjusted odds ratio (OR)=0.41; confidence interval (CI) 0.21, 0.79; for whites]. Asian males were less likely than white males to be recommended for transplantation (OR=0.46, CI 0.24, 0.91). Black-white differences in rates of recommendation were not found. Other factors associated with low rates of recommendation for renal transplantation included history of noncompliance (OR=0.17, CI 0.13, 0.23), <25% cardiac ejection fraction (OR=0.15, CI 0.10, 0.21), HIV infection (OR=0.01, CI 0.00, 0.01), and being >200 lbs (OR=0.73, CI 0.56, 0.95). CONCLUSIONS: Female gender, and Asian but not black race, were associated with a decreased likelihood that nephrologists would recommend renal transplantation for patients with end stage renal disease. The well-documented black-white disparities in use of renal transplantation may be due to unaccounted for factors or may arise at a subsequent step in the transplantation process.

Serologic and virologic profiles of hepatitis C infection in renal transplant candidates. New England Organ Bank Hepatitis C Study Group.

The development of policies to prevent nosocomial transmission of hepatitis C virus (HCV) infection in hemodialysis units is critically dependent on the understanding of the relationship between tests for anti-HCV, HCV RNA, and HCV genotype and the patients' clinical characteristics. We tested sera from all patients on the renal transplant waiting list at the New England Organ Bank between November 1986 and June 1990 for anti-HCV by a third-generation enzyme-linked immunosorbent assay (ELISA3) and a third-generation recombinant immunoblot assay (RIBA3). All ELISA3-positive sera were tested for HCV RNA by reverse transcriptase "nested" polymerase chain reaction, and the genotype was characterized by restriction fragment length polymorphism. Sera were available in 1,544 of 3,243 (48%) patients on the waiting list, of whom 287 (19%) tested positive for anti-HCV by ELISA3. Two hundred eighty-six randomly selected, anti-HCV-negative patients served as controls. Compared with anti-HCV-negative controls, anti-HCV-positive patients had a longer duration since initiation of renal replacement therapy, higher number of previous kidney transplants and blood transfusions, higher proportion of patients with anti-HBc, history of liver disease, history of non-A, non-B hepatitis, and elevated serum alanine aminotransferase, and lower serum albumin concentrations. Of the 287 anti-HCV-positive sera, 261 (91%) were reactive by RIBA3, 21 (7%) were indeterminate, and five (2%) were nonreactive. HCV RNA was detected in 224 of 275 (81%) ELISA3-positive patients, in whom additional sera were available. There were no significant differences in clinical or laboratory characteristics between ELISA3-positive patients with and without HCV RNA. Genotypes 1a, 1b, 2a, 2b, 3a, and 4 were present in 53%, 23%, 8%, 10%, 4%, and 2% of patients, respectively. Infection with one, two, or three different HCV genotypes was present in 92%, 7%, and 1%, respectively. There was no significant association between the type or number of HCV genotypes and RIBA3 reactivity. There were no major differences in clinical or laboratory characteristics between genotypes or between single and mixed infection. In summary, this study provides detailed information regarding the relationship between tests for anti-HCV, HCV RNA, and HCV genotypes and the clinical and laboratory characteristics of a large, well-characterized cohort of patients referred for renal transplant.

US nephrologists' recommendation of dialysis modality: results of a national survey.

Selection of a dialysis modality for persons with end-stage renal disease (ESRD) has important lifestyle and occupational implications. The factors affecting modality choice remain unclear, resulting in a low rate of peritoneal dialysis (PD) in the United States compared with other countries. A national survey of 271 US nephrologists was conducted from June 1997 to June 1998 to assess the relative importance of nonclinical and clinical factors related to dialysis modality selection for patients with ESRD. Hypothetical patient scenarios were randomly assigned to nephrologists to determine their recommendation for dialytic therapy based on patient demographic, clinical, and social factors. US nephrologists were more likely to recommend PD for men with ESRD compared with women (39% versus 33%; P: < 0.05; adjusted odds ratio, 1.44; 95% confidence interval, 1.15 to 1.80), as well as for patients with good compliance (adjusted odds ratio, 11.80; 95% confidence interval, 9.29 to 15.01), weight less than 200 lb (adjusted odds ratio, 2.3; 95% confidence interval, 1.8 to 2.9), residual renal function (adjusted odds ratio, 2.14; 95% confidence interval, 1.71 to 2.70), absence of diabetes (adjusted odds ratio, 2.0; 95% confidence interval, 1.6 to 2.5), and living with family (adjusted odds ratio, 1.7; 95% confidence interval, 1.4 to 2.1). Nephrologists in practice for 11 or more years were less likely to recommend PD. The association of male sex with PD therapy suggests a potential bias or sensitivity to women's perception of body image. Race was not associated with PD recommendations after controlling for other demographic and clinical characteristics. Because the incident US ESRD population is increasingly characterized by factors associated with not selecting PD (diabetes, obesity, malnourishment, living alone, and substance abuse problems), our results suggest that PD use may decrease over time.