Survival advantage of pediatric recipients of a first kidney transplant among children awaiting kidney transplantation.

The mortality rate in children with ESRD is substantially lower than the rate experienced by adults. However, the risk of death while awaiting kidney transplantation and the impact of transplantation on long-term survival has not been well characterized in the pediatric population. We performed a longitudinal study of 5961 patients under age 19 who were placed on the kidney transplant waiting list in the United States. Of these, 5270 received their first kidney transplant between 1990 and 2003. Survival was assessed via a time-varying nonproportional hazards model adjusted for potential confounders. Transplanted children had a lower mortality rate (13.1 deaths/1000 patient-years) compared to patients on the waiting list (17.6 deaths/1000 patient-years). Within the first 6 months of transplant, there was no significant excess in mortality compared to patients remaining on the waiting list (adjusted Relative Risk (aRR) = 1.01; p = 0.93). After 6 months, the risk of death was significantly lower: at 6-12 months (aRR = 0.37; p < 0.001) and at 30 months (aRR 0.26; p < 0.001). Compared to children who remain on the kidney transplant waiting list, those who receive a transplant have a long-term survival advantage. With the potential for unmeasured bias in this observational data, the results of the analysis should be interpreted conservatively.

Vascular access survival and incidence of revisions: a comparison of prosthetic grafts, simple autogenous fistulas, and venous transposition fistulas from the United States Renal Data System Dialysis Morbidity and Mortality Study.

OBJECTIVE: The study's aim was to evaluate access patency and incidence of revisions in patients initiating hemodialysis and to determine differences in access performance by type of access among patient subgroups. METHODS: The study used data from the United States Renal Data System Dialysis Morbidity and Mortality Study Wave 2, which contained a random sample of dialysis patients initiating dialysis in 1996 and early 1997. Failures and revisions were evaluated among 2247 newly placed hemodialysis accesses by using Cox proportional hazards regression model and Poisson regression. Primary and secondary patency rates were estimated using the Kaplan-Meier method. RESULTS: Fifteen hundred seventy-four prosthetic grafts, 492 simple autogenous fistulas, and 181 venous transposition fistulas were available for evaluation. Prosthetic grafts had a 41% greater risk of primary failure compared with simple fistulas (relative risk, 1.41; 95% CI, 1.22-1.64; P < .001) and a 91% higher incidence of revision (relative risk, 1.91; 95% CI, 1.60-2.28; P <.001). At 2 years, autogenous fistulas demonstrated superior primary patency (39.8% versus 24.6%, P < .001) and equivalent secondary patency (64.3% versus 59.5%, P = .24) compared with prosthetic grafts. When compared with simple fistulas, vein transpositions demonstrated equivalent secondary patency at 2 years (61.5% versus 64.3%, P = .43) but inferior primary patency (27.7% versus 39.8%, P = .008) and had a 32% increased incidence of revision (P = .04). Autogenous fistulas had superior primary patency compared with prosthetic grafts in all patient subgroups except for patients with previously failed access. Vein transpositions showed the greatest benefit in terms of patency and incidence of revision in women and in patients with previously failed access. CONCLUSIONS: The preferential placement of autogenous fistulas may increase primary patency and decrease the incidence of revisions. Vein transpositions had similar secondary patency compared with simple fistulas, but required more revisions. The greatest benefit of a vein transposition fistula was seen in women and in patients with a history of access failure.

Use of the vascular diagnostic laboratory in improving the success of angioaccess procedures.

The goal of hemodialysis access placement is long-term patency with as few revisions as possible. Autogenous fistulas have superior performance compared with prosthetic grafts, but up to 70% fail to mature sufficiently for dialysis. Accurate preoperative evaluation of arterial and venous anatomy can increase the successful use of autogenous fistulas, thereby increasing long-term access patency. Duplex ultrasonography has an important role in identifying usable autogenous conduit and detecting venous outflow disease, another important cause of access failure. The use of the vascular diagnostic laboratory in preoperative planning can increase the percentage of autogenous fistulas placed, increase the percentage that mature, and reduce the rate of negative explorations for vein at the time of surgery.

Assessment of a policy to reduce placement of prosthetic hemodialysis access.

BACKGROUND: The aim of this study was to evaluate the determinants of access patency and revision, including the effects of reducing the placement of prosthetic hemodialysis access. METHODS: A retrospective cohort study of all hemodialysis accesses placed at the Veteran's Administration Puget Sound Health Care System between 1992 and 1999 was conducted. A policy was instituted in 1996 that maximized the use of autogenous hemodialysis access. The impacts of the policy change, demographics, and comorbid factors on access type and patency, were examined. Primary and secondary patency rates were examined using the Kaplan--Meier method, and factors associated with failure and revision were examined using Cox proportional hazard models and Poisson regression. RESULTS: During the study, 104 accesses (61 prosthetic grafts and 43 autogenous fistulas) were placed prior to 1996, and 118 (31 prosthetic grafts and 87 autogenous fistulas) were placed after 1996. There was a significant increase in autogenous fistulas placed after 1996 (87 out of 118) compared with before 1996 (43 out of 104, P < 0.001). At one year, autogenous fistulas demonstrated superior primary patency (56 vs. 36%, P = 0.001) and secondary patency (72 vs. 58%, P = 0.003) compared with prosthetic grafts. After adjustment for age, race, side of access placement, and history of prior access placement, patients with a prosthetic graft were estimated to experience a 78% increase in the risk of primary access failure when compared with similar patients having an autogenous access [adjusted relative risk (aRR) = 1.78, 95% CI 1.21--2.62, P = 0.003)]. Similarly, the adjusted relative risk of secondary access failure for comparing prosthetic grafts with autogenous fistulas was estimated to be 2.21 (95% CI 1.38--3.54, P = 0.001). The adjusted risk of access revision was 2.89-fold higher for prosthetic grafts than for autogenous fistulas (95% CI 1.88--4.44, P < 0.001). CONCLUSIONS: Autogenous conduits demonstrated superior performance when compared with prosthetic grafts in terms of primary and secondary patency and number of revisions. A policy emphasizing the preferential placement of autogenous fistulas over prosthetic grafts may result in improved patency and a reduction in the number of procedures required to maintain dialysis access patency.

Risk factors and mortality associated with calciphylaxis in end-stage renal disease.

BACKGROUND: We conducted a case control study to determine risk factors and mortality associated with calciphylaxis in end-stage renal disease. METHODS: Cases of calciphylaxis diagnosed between December 1989 and January 2000 were identified. Three controls were identified for each hemodialysis patient, with calciphylaxis matched to the date of initiation of hemodialysis. Laboratory data and medication doses were recorded during the 12 months prior to the date of diagnosis and at the time of diagnosis of calciphylaxis. Conditional logistic regression was used to identify risk factors for calciphylaxis. Cox proportional hazards models were used to estimate the risk of death associated with calciphylaxis. RESULTS: Nineteen cases and 54 controls were identified. Eighteen patients were hemodialysis patients, and one had a functioning renal allograft. Diagnosis was confirmed by skin biopsy in 16 cases. Women were at a sixfold higher risk of developing calciphylaxis (OR = 6.04, 95% CI 1.62 to 22.6, P = 0.007). There was a 21% lower risk of calciphylaxis associated with each 0.1 g/dL increase in the mean serum albumin during the year prior to diagnosis and at the time of diagnosis of calciphylaxis (OR = 0.79, 95% CI, 0.64 to 0.99, P = 0.037, and OR = 0.80, 95% CI, 0.67 to 0.96, P = 0.019, respectively). There was a 3.51-fold increase in the risk of calciphylaxis associated with each mg/dL increase in the mean serum phosphate during the year prior to diagnosis (95% CI, 0.99 to 12.5, P = 0.052). At the time of diagnosis of calciphylaxis, for each 10 IU/L increment in alkaline phosphatase, the risk of calciphylaxis increased by 19% (OR = 1.19, 95% CI, 1.00 to 1.40, P = 0.045). Body mass index, diabetes, blood pressure, aluminum, and higher dosage of erythropoietin and iron dextran were not independent predictors of calciphylaxis. Calciphylaxis independently increased the risk of death by eightfold (OR = 8.58, 95% CI, 3.26 to 22.6, P < 0.001). CONCLUSIONS: Female gender, hyperphosphatemia, high alkaline phosphatase, and low serum albumin are risk factors for calciphylaxis. Calciphylaxis is associated with a very high mortality.

Risk factors for hip fracture among patients with end-stage renal disease.

BACKGROUND: Although bone disease is well described among end-stage renal disease (ESRD) patients, little attention has been paid to the occurrence of fracture. We sought to identify factors that are associated with hip fracture among ESRD patients. METHODS: Data from patients who participated in the United States Renal Data System Dialysis Morbidity and Mortality Study Wave 1 were used for this study. Hip fractures occurring among these patients between 1993 and 1996 were identified from Medicare claims data available from the United States Renal Data System. Cox proportional hazards models were used to estimate the risk of hip fracture associated with demographic and medical variables. RESULTS: Of the 4952 patients included in this analysis, 103 sustained a hip fracture. In the multivariate analysis, age (per increasing decade, RR = 1.40, 95% CI 1.20, 1.64), female gender (RR = 2.26, 95% CI 1.48, 3.44), race (blacks compared with whites, RR = 0.58, 95% CI 0.37, 0.91), body mass index (per 1 unit increase, RR 0.89, 95% CI 0.86, 0.93), and the presence of peripheral vascular disease (RR 1.94, 95% CI 1.29, 2.92) were independently associated with hip fracture. Serum intact parathyroid hormone (iPTH), aluminum, diabetes, and bicarbonate levels did not appreciably influence the risk of hip fracture. CONCLUSIONS: Demographic and other characteristics that predict risk of hip fracture in the population at large also do so in ESRD patients. However, we could identify no characteristics of ESRD or its treatment that were independently related to hip fracture incidence.

Determinants of type and timing of initial permanent hemodialysis vascular access.

BACKGROUND: We undertook a population-based study of hemodialysis (HD) patients to determine which factors are important in predicting the type of permanent access initially placed and if a functional permanent access is in place at the start of HD. METHODS: Selected characteristics were abstracted from the United States Renal Data System (USRDS) Dialysis Morbidity and Mortality Study (DMMS) Wave 2. Logistic regression was used to estimate the independent contribution of specific characteristics in predicting whether the initial permanent access placed was an arteriovenous (AV) fistula compared with a polytetrafluoroethylene (PTFE) graft, and in predicting whether permanent access (fistula or graft) was in place at the initiation of dialysis. RESULTS: Sixty-seven percent of the patients had an AV graft placed as their first permanent access. Characteristics important in predicting if a fistula was initially placed included age (per decade; aOR = 0.84, P < 0.001), female gender (aOR = 0.52, P < 0.001), body mass index (per standard deviation; aOR = 0.70, P = 0.09), avoiding blood draws (aOR = 1.96, P < 0.001), ability to ambulate (aOR = 2.24, P = 0.008), underlying renal disease (glomerular compared with diabetes, aOR = 2.19, P = 0.009), college education (aOR = 1.72, P = 0.002), and sharing in decision making (aOR = 1.50, P = 0.02). Thirty-four percent of patients (34.4%) had functional permanent access at the start of HD. Characteristics important in predicting which patients had functional permanent access included serum albumin (per 1 mg/dL increase, aOR =1.55, P = 0.003), erythropoietin prior to starting HD (aOR = 1.79, P = 0.002), fewer predialysis nephrologist visits (aOR = 0.21, P < 0.001), and when the patient was told they had renal disease (aOR = 0.33, P = 0.002). CONCLUSIONS: PTFE grafts were the most common initial permanent access. The majority of patients did not have permanent access at the start of dialysis. Factors that are thought to compromise identification of adequate veins were important predictors of PTFE graft placement. Permanent access at the start of HD was largely a function of early patient education and early referral to a nephrologist.

Prescription of hormone replacement therapy in postmenopausal women with renal failure.

UNLABELLED: Prescription of hormone replacement therapy in postmenopausal women with renal failure. BACKGROUND: Although patients with end-stage renal disease (ESRD) are at increased risk for early menopause, osteoporosis, cognitive dysfunction, and cardiovascular disease, few postmenopausal women are prescribed hormone replacement therapy (HRT). The reasons for the low prescription rate are not known. This study uses data from the United States Renal Data System (USRDS) to assess the prevalence and predictors of HRT use in postmenopausal women with ESRD. METHODS: Data were obtained from the USRDS Dialysis Morbidity and Mortality Study Wave 2. All women who were at least 45 years of age were considered postmenopausal and were selected for our analysis. Demographics, behavior and medical characteristics were abstracted from the database. Logistic regression was used to estimate the independent contribution of population characteristics in predicting the use of HRT. Linear regression models were used to estimate the relationship between HRT use and both triglycerides and total cholesterol. RESULTS: The overall prevalence of HRT prescription was 10.8%. Important predictors of HRT use included age (aOR = 0.74, 95% CI 0.13 to 0.88, P < 0.001), black ethnicity (aOR = 0.50, 95% CI, 0.31 to 0.78, P < 0.002), college education (aOR = 3. 00, 95% CI, 1.70 to 5.24, P < 0.001), and the ability to ambulate (aOR = 1.99, 95% CI, 1.01 to 3.91, P = 0.05). Serum triglyceride and total cholesterol levels were higher among women treated with HRT than among those not treated with HRT (264 +/- 155 vs. 217 +/- 159 mg/dl, P = 0.001 and 220 +/- 62 vs. 209 +/- 55 mg/dl, P = 0.02, respectively). CONCLUSIONS: HRT is prescribed less frequently in postmenopausal ESRD patients than in the general population. Younger age, higher education levels, white race, and the ability to ambulate were important predictors of HRT use. Targeting populations of patients who are likely to benefit from but less likely to be prescribed HRT may increase the prescription of HRT.

The cyclin kinase inhibitor p21WAF1/CIP1 is required for glomerular hypertrophy in experimental diabetic nephropathy.

BACKGROUND: Diabetic nephropathy is characterized by glomerular hypertrophy. We have recently shown that experimental diabetes mellitus is associated with an increase in glomerular expression of the cyclin kinase inhibitor p21WAF1/CIP1 (p21). Furthermore, in vitro glucose-induced mesangial cell hypertrophy is also associated with an up-regulated expression of p21. In this study, we tested the hypothesis that p21 mediates diabetic glomerular hypertrophy in vivo. METHODS: Experimental diabetes mellitus was induced by streptozotocin in mice in which p21 was genetically deleted (p21 -/-) and in wild-type mice (p21 +/+). Kidney biopsies were obtained from diabetic and control (citrate injected) p21 +/+ and p21 -/- mice at day 60. The tissue was used for morphologic studies of glomerular size (measured by computer image-analysis system), glomerular cellularity (cell count), glomerular matrix expansion (silver stain), apoptosis (TUNEL), and expression of transforming growth factor-beta1 (TGF-beta1) by in situ hybridization. RESULTS: The glomerular tuft area increased 11.21% in diabetic p21 +/+ mice at day 60 compared with control (3329.98 +/- 244.05 micrometer(2) vs. 2994. 39 +/- 176.22 micrometer(2), P = 0.03), and the glomerular cell count did not change in diabetic p21 +/+ mice at day 60 compared with the control. These findings are consistent with glomerular hypertrophy. In contrast, the glomerular tuft area did not increase in diabetic p21 -/- mice at day 60 compared with the control (3544.15 +/- 826.49 vs. 3449.15 +/- 109.65, P = 0.82), nor was there an increase in glomerular cell count (41.41 +/- 13.18 vs. 46.95 +/- 3.00, P = 0.43). Diabetic p21 +/+ mice, but not p21 -/- mice, developed an increase in proteinuria at day 60 compared with the control. Tubular cell proliferation, measured by proliferating cell nuclear antigen immunostaining, was increased in both diabetic p21 +/+ (2.1-fold) and p21 -/- (7.61-fold) mice compared with controls. Glomerular cell apoptosis did not increase in diabetic mice. Although glomerular TGF-beta1 mRNA levels increased in both strains of diabetic mice at day 60, the glomerular matrix did not expand. CONCLUSIONS: Hyperglycemia was associated with glomerular hypertrophy in p21 +/+ mice. Despite the increase in TGF-beta1 mRNA, diabetic p21 -/- mice did not develop glomerular hypertrophy, providing evidence that the cyclin kinase inhibitor p21 may be required for diabetic glomerular hypertrophy induced by TGF-beta1. The loss of p21 increases tubular but not glomerular cell proliferation in diabetic nephropathy. The absence of glomerular hypertrophy appears protective of renal function in diabetic mice.

Racial differences in bone mineral density and bone loss among end-stage renal disease patients.

Although black patients without end-stage renal disease (ESRD) have a greater bone mineral density (BMD) than whites, the impact of race on BMD among patients with ESRD who are likely to have varying degrees of renal osteodystrophy is not known. We undertook a cohort study of 106 hemodialysis patients comparing BMD and bone loss between black and white patients with ESRD to determine if black patients have a greater BMD and less bone loss than white patients with ESRD. BMD was determined by dual-energy radiograph absorptiometry (DEXA). Osteopenia was defined as greater than 1 standard deviation (SD) less than the mean of peak bone mass (T score <-1), and osteoporosis was defined as greater than 2.5 SDs less than the mean of peak bone mass (T score <-2.5). The association between BMD and race was estimated using linear regression. The risk for osteopenia among black compared with white patients was calculated using logistic regression. Black patients were similar to white patients with respect to all characteristics noted, except black patients were less likely to be men (69.7% v 49. 4%) and tended to have greater intact parathyroid hormone (PTH) values (mean, 403.2 +/- 384.5 pg/mL v 161.4 +/- 129.0 pg/mL). Compared with whites, the BMD of blacks was a mean of 1.15 (95% confidence interval [CI], 0.54 to 1.78) SDs greater at the femoral neck after adjusting for age, PTH level, and sex. The percentage of bone loss per year was similar between blacks and whites. The risk for osteopenia among blacks was significantly less than that among whites (odds ratio = 0.15; 95% CI, 0.04 to 0.59) after adjusting for age, sex, and PTH level. Black patients with ESRD have a greater BMD and are at decreased risk for osteopenia compared with whites, independent of renal osteodystrophy. When considering bone disease among patients with ESRD, physicians should also consider osteoporosis and the impact of race on BMD.

Risk of death among chronic dialysis patients infected with hepatitis C virus.

Hepatitis C virus (HCV) infection is highly prevalent among chronic dialysis patients (10% to 40%) and is the most common cause of chronic liver disease. However, there are no studies estimating the risk for death among dialysis patients infected with HCV compared with those not infected. We conducted a prospective cohort study to estimate the risk for death among chronic dialysis patients infected with HCV compared with those not infected. In 1992, 200 patients (91%) who had been undergoing dialysis therapy for at least 6 months consented to be screened for HCV infection by enzyme immunoblot assay and polymerase chain reaction (PCR). Information about potential confounders and potential risk factors for death and HCV infection was obtained from the dialysis center database. Patient outcomes collected included death, transplantation, and loss to follow-up. The Cox proportional hazards model was used to estimate the odds of death among dialysis patients who were positive for the HCV antibody and HCV RNA compared with negative patients. Forty-four patients (22%) were HCV antibody positive. Thirty-four patients (17%) were HCV RNA positive. Patients in the HCV RNA-positive group were more likely to be younger (51.8+/-12.6 v 57.2+/-17.3 years of age), men (77% v 54%), and black (65% v 37%). None of the home hemodialysis or peritoneal dialysis patients were HCV RNA positive, whereas one of the home hemodialysis and one of the peritoneal dialysis patients were HCV antibody positive. Two patients became infected with HCV during the follow-up period. Patients who were HCV RNA positive and those who were HCV antibody positive were at increased risk for death compared with patients who were negative (adjusted relative risk [aRR]=1.78; 95% confidence interval [CI], 1.01 to 3.14; P=0.045; and aRR=1.97; 95% CI, 1.16 to 3.33; P=0.012, respectively), after adjusting for time on dialysis, race, transplantation, and age. We conclude that HCV infection increased the risk for death during the study period compared with those not infected. Further studies should assess the measures used to prevent and treat HCV infection.

Increased risk of adverse maternal and infant outcomes among women with renal disease.

We conducted a retrospective population-based study to estimate the risk of adverse maternal and neonatal outcomes in women with a diagnosis of renal disease during pregnancy. One hundred and sixty-nine women with renal disease who gave birth to a singleton infant between 1987 and 1993 were identified through linked Washington State hospital discharge and birth certificate databases. For comparison, 506 women without renal disease matched for year of delivery were selected. Women with renal disease were at increased risk of pre-eclampsia [OR = 7.2, 95% CI 4.2-12.5], preterm labour [OR = 7.9, 95% CI 1.9-32.6], dysfunctional labour [OR = 3.6, 95% CI 1.1-11.5], and caesarean section [OR = 3.1, 95% CI 2.0-4.8]. They were also at increased risk of delivering infants who were small for gestational age [OR = 5.3, 95% CI 2.8-10.0], preterm [OR = 6.1, 95% CI 3.3-11.3], and had 5-minute Apgar scores of less than 7 [OR = 3.9, 95% CI 1.1-14.6]. These associations persisted in analyses restricted to women without chronic hypertension. Women with renal disease and their infants also had median hospital charges that were more than twice those of women without renal disease and were more likely to be hospitalised longer. These data demonstrate that, independent of chronic hypertension, women with underlying renal disease are at increased risk of adverse maternal and perinatal outcomes and use more resources than women without renal disease.

Association of hepatitis C virus infection with mortality and graft survival in kidney-pancreas transplant recipients.

BACKGROUND: Although most studies have not demonstrated decreased patient or graft survival in kidney-alone allograft recipients infected with hepatitis C virus (HCV), the impact of HCV infection on patient and graft survival in HCV-infected kidney-pancreas recipients has not been studied. METHODS: We undertook a retrospective cohort analysis of 137 kidney-pancreas transplant recipients who were transplanted between January 1989 and May 1996. HCV infection was determined by a positive polymerase chain reaction. Relative risk of death and graft failure was calculated using the Cox proportional hazards model with time-dependent covariates. Relative risks were adjusted (aRR) to control for the number of OKT3-treated rejections and cytomegalovirus status of the recipient at the time of transplantation. RESULTS: Mean length of follow-up was 30.4 months in the HCV-infected patients compared with 31.7 months in noninfected patients. Seven (5.1%) patients were infected with HCV before transplant, one (1%) relapsed after transplantation, and four (2.9%) acquired the infection after transplantation. The HCV-infected group had a 3.7-fold (95% confidence interval [CI], 1.0-13.5) increased risk of death after transplant compared with the HCV-negative group, with an aRR of 5.5 (95% CI, 1.5-20.0). Death in the HCV-infected group (n=3) was generally the result of liver failure and sepsis, whereas death for those in the uninfected group (n=11) was primarily of cardiovascular origin. Patients infected with HCV were 3.4-fold (95% CI, 1.1-10.1) more likely to develop kidney graft failure than HCV-negative patients with an aRR of 5.1 (95% CI, 1.7-15.4). The risk of pancreatic allograft failure was not significantly increased. CONCLUSIONS: We conclude that HCV infection in kidney-pancreas transplant patients results in a significantly increased risk of kidney allograft failure and death.