Once-weekly epoetin alfa for treating the anemia of chronic kidney disease.

BACKGROUND AND AIM: Anemia occurs in approximately 47% of patients with chronic kidney disease (CKD) not on dialysis. Recombinant human erythropoietin (r-HuEPO, epoetin alfa) has been proven safe and effective for anemia treatment in patients with CKD using a three times-weekly regimen. The current study was conducted to evaluate the clinical safety and efficacy of a less frequent dosing regimen (once weekly) in this population. METHODS: This prospective, multicenter, open-label, non-randomized study enrolled 1,557 adult anemic (hemoglobin (Hb) < or = 10 g/dl) CKD patients not on dialysis. Epoetin alfa 10,000 U was administered subcutaneously once weekly for 16 weeks. Titration to 20,000 U once weekly at week 5 was permitted if patients had an increase in Hb < 1 g/dl. Safety and efficacy were assessed by changes in health-related quality of life (Linear Analog Scale Assessment (LASA) and Kidney Disease Questionnaire (KDQ)), changes in hematologic parameters and transfusion utilization, and incidence and severity of adverse events. RESULTS: 1,338 patients were evaluable for efficacy. Mean Hb level increased from 9.1 g/dl at baseline to 11.6 g/dl at study completion (last observed value after baseline) (p < 0.0001). Overall, 89.8% of patients responded to once-weekly dosing, exhibiting an increase in Hb level of > or = 1 g/dl from baseline. The percentage of patients that required transfusion decreased from 11.1% (baseline) to 3.7% (during the study) (p < 0.0001). All quality-of-life parameters improved significantly from baseline (p < 0.0001). Mean LASA scores for energy, activity and overall quality of life increased from baseline to study completion by 27.9 mm (70.5%), 24.5 mm (57.0%) and 22.6 mm (47.4%), respectively. All 5 KDQ domains showed statistically significant improvements (p < 0.0001). Hb change was a strong predictor for all 5 KDQ domains and the overall score (p < 0.0001). Treatment with once-weekly epoetin alfa was well tolerated, similar to that reported with three times-weekly dosing. CONCLUSION: Once-weekly epoetin alfa therapy is safe and effective for treating anemia in patients with CKD not on dialysis, and is associated with significant improvements in functional status and quality of life.

The inevitability of renal function loss in patients with hypercreatinemia.

UNLABELLED: Although it is anticipated that most patients with renal insufficiency will progress towards end-stage renal disease (ESRD) there have been few population-based studies to validate this assumption. We examined serial creatinines from 3,874 anonymous patients at an urban VA medical center who had a baseline creatinine of 1.4 mg/dl or greater to estimate the frequency of deterioration in renal function (DRF). DRF was defined as the first Cr (1stCr) value being lower than the last Cr (LCr) for each patient. The median follow-up was 48.3 +/- 0.5 months with 18 +/- 0.5 creatinine values per patient. The median 1stCr was 1.6 +/- 0.1 mg/dl with 32.2% of the patients having a 1stCr greater than or equal to 1.7 mg/dl. In the study group, 1,723 (44.4%) had DRF including 1,089 (41.4%) of those patients with a 1stCr of 1.4-1.7 mg/dl. However, 45 (36.6%) of those with a 1stCr value 3.0-5.0 mg/dl did not have DRF, the percent with stable creatinine in this group did not vary with length of follow-up. Over the study period, 299 (7.7%) of all the patients had a creatinine rise to 7.0 mg/dl, with 104 (4%) of those with a 1stCr of 1.4-1.7 mg/dl reaching this endpoint. CONCLUSION: A majority, but not all, patients with renal insufficiency lose renal function over time and those with even mild hypercreatinemia are at risk for deterioration in renal function. Hypercreatinemia, however, does not accurately discriminate between those renal insufficiency patients who are stable versus those at high risk for ESRD.

Pilot study to evaluate a water displacement technique to compare effects of diuretics and ACE inhibitors to alleviate lower extremity edema due to dihydropyridine calcium antagonists.

Combination therapy is required in many patients to achieve goal blood pressure (BP). Calcium antagonists are highly effective antihypertensive drugs in a broad range of demographic groups. Yet, higher doses are associated with an increased frequency of lower extremity edema. The purpose of our open label, single-center clinical trial was to evaluate the use of concomitant pharmacologic therapies to attenuate the lower extremity edema associated with dihydropyridine calcium antagonists therapy using a water displacement technique. Forty-seven patients received 5 mg/day of oral amlodipine for a period of 6 weeks after a 4-week wash-out off of all antihypertensive medications to establish baseline BP. They were then randomized to receive either an additional 5 mg of amlodipine, 25 mg of hydrochlorothiazide (HCTZ), or 20 mg of benazepril for an additional 6 weeks. Blood pressure determinations and water displacement measurements were obtained at the end of the 4-week placebo wash-out period, after 6 weeks of 5 mg/day of oral amlodipine therapy, and after an additional 6 weeks of 5 mg of amlodipine and randomized drug therapy. Adjusted BP reductions (based on pretreatment BP) were -6.8/-3.8 mm Hg for the 10-mg amlodipine group, -9.9/-8.2 mm Hg for the amlodipine (5 mg)/HCTZ (25 mg) group, and -26.2/-16.4 mm Hg for the amlodipine (5 mg)/benazepril (20 mg) group (P < .0167, group 3 v group 1 diastolic BP, which was statistically significant by the improved Bonferroni method). Seventeen of the 47 patients developed at least a 10% increase in lower extremity edema water displacement in response to 5 mg/day of oral amlodipine therapy (36.2%). Adding 5 mg of amlodipine to a baseline of 5 mg of amlodipine resulted in no net change in lower extremity edema (+58.0 mL,+ 0.6% change, n=5). Adding 25 mg of HCTZ reduced lower extremity edema by a mean of 136.3 mL (-11.1% change, n=4). Benazepril reduced water displacement by 204.4 mL (-14.3% change, n=8). Our pilot study indicates that adding an angiotensin converting enzyme inhibitor to a dihydropyridine calcium channel blocker is the most effective way to not only reduce systolic and diastolic BP but also attenuate lower extremity edema. Due to the inherent daily variability of lower extremity edema, power calculations indicate many patients (n=702, 356 in each group) would be needed to compare the antiedema efficacy of the angiotensin converting enzyme inhibitor and the thiazide diuretic.

Pancreas transplantation: the histologic morphology of graft loss and clinical correlations.

BACKGROUND: Graft losses due to leaks, bleeding, thrombosis, infections, and early pancreatitis are grouped together under the category of technical failure. Among these complications, massive vascular thrombosis continues to be the most important cause of early graft loss due to technical failure. Pathological evaluation of most allografts lost early in the posttransplantation period shows vascular thrombosis with associated proportional parenchymal necrosis. The morphological findings in allografts that are considered to be lost due to technical failure has not been systematically addressed. In particular, the role of acute rejection in early graft loss has not been well studied. METHODS: Seventy-four consecutive pancreas graft pancreatectomies were studied histologically to evaluate for thrombosis (recent versus organized), type of vessel involved by thrombosis (arteries, veins, or both), acute rejection grade, chronic rejection grade, endotheliitis, transplant arteritis, coagulation necrosis, acute pancreatitis, presence of infectious organisms, transplant (obliterative) arteriopathy, neoplasia, relative proportions of alpha and beta islet cells, and immunoglobulin and complement deposition. The histological findings were correlated with donor and recipient data as well as clinical presentation. RESULTS: In 23 out of 39 grafts lost in the first 4 weeks posttransplantation, the only pathological changes found were vascular thrombosis and bland ischemic parenchymal necrosis. In these cases, no underlying vascular pathology or any other specific histological change was identified. Most of these grafts (78%) were lost in less than 48 hr and all in the first 2 weeks posttransplantation. Massive vascular thrombosis occurring in an otherwise histologically normal pancreas was the most common cause of graft loss in the first 4 weeks posttransplantation (59%). In most of the remaining cases (33%), although the clinical presentation suggested technical failure, there was clear histological evidence that the massive thrombosis resulted from vascular injury due to immune damage (acute and hyperacute rejection). Increased incidence of early graft thrombosis was seen in grafts from older donors and longer cold ischemia times. After the first month posttransplantation, graft pancreatectomies revealed a wider variety of pathological processes that included severe acute rejection, combined acute and chronic rejection, chronic rejection, and infections. Acute and chronic vascular thrombosis in large and small vessels was commonly seen at all times posttransplantation; chronic, organized thrombosis was strongly associated with chronic rejection. CONCLUSIONS: (a) Early acute thrombosis occurring in a histologically normal pancreas defines a true technical failure. This study showed that acute rejection leading to massive thrombosis, which clinically simulates technical failure, results in a significant proportion of early graft losses. (b) Systematic histological evaluation of failed grafts is absolutely necessary for the accurate classification of the cause of graft loss. (c) There is morphological evidence that chronically ongoing thrombosis is an important, common, contributing factor for late graft loss.

The outcome of the urban renal patient: the importance of social factors and center effects.

Caring for the urban renal patient can be a challenge to providers for many reasons. Although racial and socioeconomic factors have an impact on the health of this population, one must also consider the effect of the urban environment on the ill, especially those with renal disease. This article reviews the state of health among the poor and nonwhite minorities, who tend to inhabit the urban regions of this country, and then highlights the unique characteristics of those with renal disease. The impact of the Medicare end-stage renal disease (ESRD) program and center-specific quality of care on the outcome of the urban patient with ESRD is explored.

Bone density loss after allogeneic hematopoietic stem cell transplantation: a prospective study.

The incidence and course of bone density abnormalities following hematopoietic stem cell transplantation are poorly understood and complicated by the impact of multiple factors. Hip, spine, and wrist bone mineral densities (BMDs) were measured in 104 adults (54 women, 54 men; mean age, 40 years [range, 18-64 years]) at 3 and 12 months after allogeneic transplantation. Clinical and laboratory variables were evaluated using univariate and multivariate analyses to determine risk factors for osteoporosis, fracture, and avascular necrosis. At 3 months posttransplantation, combined (male and female) hip, spine, and wrist z scores were -0.35, -0.42, and +0.04 standard deviations, respectively. At 12 months both men and women experienced significant loss of hip BMD (4.2%, P < .0001); changes in the spine and wrist were minimal. The cumulative dose and number of days of glucocorticoid therapy and the number of days of cyclosporine or tacrolimus therapy showed significant associations with loss of BMD; age, total body irradiation, diagnosis, and donor type did not. Nontraumatic fractures occurred in 10.6% of patients and avascular necrosis in 9.6% within 3 years posttransplantation. The decrease in height between pretransplantation and 12 months posttransplantation was significant (P = .0001). Results indicate that loss of BMD after allogeneic stem cell transplantation is common and accelerated by the length of immunosuppressive therapy and cumulative dose of glucocorticoid. An increased incidence of fracture and avascular necrosis may adversely impact long-term quality of life. Prevention of bone demineralization appears warranted after stem cell transplantation.

Long-term impact of discontinued or reduced calcineurin inhibitor in patients with chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy is the major cause of progressive renal failure in renal transplant recipients. It has no definitive treatment. METHODS: One hundred eighteen renal transplant recipients with declining kidney function and biopsy-proven chronic allograft nephropathy had their cyclosporine or tacrolimus dose reduced or discontinued with either the addition or continuation of mycophenolate mofetil and low-dose steroids at a mean of 853.3 days post-transplantation. Their renal function was modeled before and after this intervention by two methods: A least-square regression was used to assess the decay of renal function after the intervention and to compare that with the slope pre-intervention, whereas a hinge regression line method was used to assess the correlation of the intervention with the inflection point and the impact of the intervention on the decay of renal function. Mean follow-up was 651.0 days after the intervention. Serum creatinine at the time of intervention was 2.8 +/- 0.9 mg/dL in the reduced dose cyclosporine (N = 67) and reduced dose tacrolimus (N = 33) groups, and was 2.7 +/- 0.7 mg/dL in the group with discontinued calcineurin inhibitor (N = 18). RESULTS: Using the least-square method, 91.7% of the no calcineurin inhibitor group, 51.6% of the reduced dose cyclosporine group, and 59.3% of the reduced dose tacrolimus group had improved or lack of deterioration in slope after the intervention. Using the hinge regression line method, there was a statistically significant correlation of the inflection point with the intervention (P = 0.001). Moreover, there was a similar relationship with stabilized or improved graft function observed with the hinge regression line method and the least-square method, as 72.2% of the calcineurin inhibitor withdrawal group, 54.4% of reduced-dose cyclosporine group, and 40% of the reduced-dose tacrolimus group had improved the slope of decay of renal function or lack of deterioration after the inflection point. The difference between the calcineurin inhibitor withdrawal group and the reduced-dose cyclosporine/tacrolimus groups on the decay in renal function was significant (P = 0.038) with the least-square method and nearly significant (P = 0.056) using the hinge regression line method. CONCLUSION: This intervention was safe, well tolerated, and associated with a minimal risk of acute rejection. We conclude that the reduction and possible withdrawal of calcineurin inhibitors may be necessary to slow the rate of loss of renal function in patients with chronic allograft nephropathy and deteriorating renal function.

Morphological spectrum of polyoma virus disease in renal allografts: diagnostic accuracy of urine cytology.

The morphological features of polyoma virus disease (PVDz) in 571 concurrent urine and biopsy samples from 413 patients are described. In 54 patients PV was found in both biopsy and urine samples. Histologically, PV presented as: (a) mild, viral cytopathic/cytolytic changes, with absent or minimal inflammation involving isolated tubules; (b) moderate and severe, cytopathic/cytolytic changes associated with patchy or diffuse tubulo-interstitial inflammation and atrophy; (c) advanced, graft sclerosis with rare or absent viral cytopathic changes, indistinguishable from chronic allograft nephropathy. Histological progression from mild to moderate or severe disease was seen in 28 patients. The mean post-transplantation time at diagnosis was similar in patients with mild or moderate-severe renal involvement (1.05 and 1.3 years, respectively). All patients presented with similarly increased values of serum creatinine (mean 1.35 mg/dL). There was strong correlation between the number of PV infected cells in urine and the concurrent biopsies (p = 0.0001). In 13 patients PV was found only in urine; of these, two developed PVDz later. The positive predictive value of a positive urine was 90%, the negative predictive value of a negative urine was 99% and the accuracy of the test was 97%. We conclude that urine cytology is useful to evaluate renal transplant patients with PV reactivation because sloughed tubular cells are found in urine and positive urine samples are a consistent manifestation of PV renal involvement.

CMV allograft pancreatitis: diagnosis, treatment, and histological features.

BACKGROUND: Cytomegalovirus (CMV) infection is a common problem in solid organ transplant recipients. CMV infection of pancreas allografts is not, however, well described. METHODS: We report the clinical presentation, histologic findings, treatment, and outcome in four patients with CMV allograft pancreatitis. These patients presented 18 weeks to 44 months after transplantation with elevated serum amylase and lipase and were suspected to have acute rejection. Percutaneous pancreas allograft biopsy specimens showed evidence of tissue invasive CMV infection. One patient had simultaneous CMV infection and acute rejection. RESULTS: Prolonged treatment with ganciclovir resulted in clinical and histologic resolution of the CMV disease. Rejection was successfully treated. Primary CMV infection in seronegative recipients seemed to be a risk factor. Three patients maintain normal allograft function; one patient lost function due to chronic rejection. The histology of tissue-invasive CMV pancreas allograft infection and its differentiation from acute rejection is described. CONCLUSION: Prompt diagnosis and prolonged therapy with antiviral agents can result in maintenance of allograft function.

Within-center correlation in dialysis adequacy.

The purpose of this study was to determine whether patients with end stage renal disease treated with hemodialysis were correlated in dialysis adequacy within facilities. This was a retrospective analysis of dialysis adequacy based on urea reduction ratio (URR) values from 6969 patients dialyzed at 154 facilities. The within-center correlation was quantified using the between-center variation and the parameter p that was derived using ANOVA tables and mixed effects models. The variation in center means for URR was wider than expected for independent observations (52.9-76.1 versus 60.7-73.8, respectively). Furthermore, there was a significant within-center correlation in URR values across all facilities (p = 0.136, P<0.0001), which persisted after adjusting for patient specific covariates, facility characteristics, and state. In conclusion, there was a substantial within-center correlation in dialysis adequacy that reflected important center effects on the outcome of ESRD patients.

Significance of serum creatinine values in new end-stage renal disease patients.

The appropriate use of serum creatinine level as a surrogate for time in the course of renal failure when dialysis commences requires it to be a significant predictor of mortality in incident patients with end-stage renal disease (ESRD). This study evaluated factors that account for variations in creatinine level before the initiation of dialysis and whether incident creatinine level after controlling for these factors was a risk factor for mortality. This is a retrospective cohort study of patients from Maryland and Virginia who initiated dialysis between April 1, 1995, and December 31, 1996, with data ascertained from the Health Care Financing Administration Form 2728. Multivariate models were used to evaluate both the factors that predict incident serum creatinine level and the association between creatinine level and mortality. There were 5, 388 patients followed up for an average of 23.6 +/- 0.2 months. Mean creatinine level was 9.2 +/- 0.1 mg/dL, with case-mix factors most predictive of serum creatinine level and accounting for 9% of its variance. Hematocrit and blood urea nitrogen levels as additional surrogates for progression of renal disease accounted for 7.4% of the variance, whereas the nutritional parameters, body mass index, and albumin level only explained an additional 1% of the total variance in creatinine level. Creatinine level was inversely correlated with mortality risk, and this relationship was sustained both with transformation into an estimated glomerular filtration rate and multivariate adjustment for confounders (relative risk = 0. 96; P < 0.0001). Creatinine values from an incident ESRD population have a weak relationship with the timing of dialysis initiation but represent a strong measure of health status.

Increased incidence of postoperative infections associated with peritoneal dialysis in renal transplant recipients.

BACKGROUND: Infection is a frequent postoperative complication in renal transplant recipients. However, little information is available concerning the effect of pretransplantation dialysis modality on posttransplantation complications including infection. We therefore evaluated the effect of hemodialysis (HD) versus peritoneal dialysis (PD) on the incidence of postoperative infection as well as several other posttransplantation outcomes. METHODS: A retrospective analysis was performed using medical records covering the period 30 days after transplantation of 156 dialysis patients who underwent renal transplantation at a single center during a 22-month period. Of these patients, 103 received only HD, 32 received only PD, 13 received PD in the past and HD immediately before transplantation (PH/HD), and 8 received HD in the past and PD immediately before transplantation (HD/PD). The presence of culture-proven infection, types of infecting organisms, length of initial hospital stay, and incidence of rejection during the first 30 days after transplantation were determined for each patient. RESULTS: All groups were similar with regard to age, race, gender, underlying disease, donor type, incidence of delayed graft function, and perioperative antibiotic prophylaxis. There were more infectious complications within 30 days after transplantation in patients on PD just prior to transplantation (PD and HD/PD) than in HD patients (67.5% vs. 25.9%, P<0.00001). When types of infectious organisms were assessed, PD patients were found to have a greater incidence of infections with microorganisms that colonize human skin (P<0.0001). The median length of hospital stay was 3 days longer for PD patients and 6.5 days longer for HD/PD patients than for patients receiving HD (P=0.01 and 0.04), and PD and HD/PD patients were more likely to have an episode of rejection than HD patients (P=0.02). CONCLUSIONS: Renal replacement therapy with PD immediately before transplantation negatively affects outcome as compared with HD, predisposing patients to a greater incidence of postoperative infections and rejection and a longer hospital stay. Further study in a randomized controlled trial may help determine how adjustment of the dialysis method can optimize transplantation outcome.

Islet cell damage associated with tacrolimus and cyclosporine: morphological features in pancreas allograft biopsies and clinical correlation.

BACKGROUND: The introduction of the potent immunosuppressive drugs tacrolimus (FK) and cyclosporine (CSA) has markedly improved the outcome of solid organ transplantation. However, these drugs can cause posttransplantation diabetes mellitus. Abnormalities in the glucose metabolism are of particular significance in pancreas transplantation. METHODS: We studied 26 pancreas allograft biopsies, performed 1-8 months posttransplantation, from 20 simultaneous kidney-pancreas transplant recipients, randomized to receive either FK or CSA. The biopsies were studied by light microscopy, immunoperoxidase stains for insulin and glucagon, in situ DNA-end labeling for detection of apoptosis, and electron microscopy. The islet morphology was correlated with the mean and peak levels of CSA and FK in serum, with corticosteroid administration and with glycemia. RESULTS: On light microscopy cytoplasmic swelling, vacuolization, apoptosis, and abnormal immunostaining for insulin were seen in biopsies from patients receiving either FK or CSA. The islet cell damage was more frequent and severe in the group receiving FK than in the group receiving CSA (10/13 and 5/13, respectively) but the differences were not statistically significant. Significant correlation was seen between the presence of islet cell damage and serum levels of CSA or FK during the 15 days previous to the biopsy, as well as with the peak level of FK. Toxic levels of CSA or FK and administration of pulse steroids were associated with hyperglycemia when these occurred concurrently (P=0.005). Toxic levels of CSA or FK by themselves were associated with hyperglycemia in a minority of cases (8 and 26%, respectively). Electron microscopy showed cytoplasmic swelling and vacuolization, and marked decrease or absence of dense-core secretory granules in beta cells; the changes were more pronounced in patients on FK. Serial biopsies from two hyperglycemic patients receiving FK and evidence of islet cell damage demonstrated reversibility of the damage when FK was discontinued. CONCLUSIONS: The structural damage to beta cells demonstrated in this study is similar to morphological and functional abnormalities previously described in experimental animal models and can at least partially account for the glucose metabolism abnormalities seen in patients receiving these drugs. Toxic levels of CSA or FK and higher steroid doses potentiate each others' diabetogenic effects.

Risk for posttransplant Diabetes mellitus with current immunosuppressive medications.

With improvements in the practice of transplantation and the introduction of new immunosuppressive medications, there has been a substantial increase in 1-year allograft survival rates. Consequently, the pool of potential candidates for organ transplants continues to grow and a greater preponderance of older patients with more comorbidities are undergoing transplantation. As a result, there is interest in such medical complications as posttransplantation diabetes mellitus (PTDM) that develop after the transplantation of a successful allograft. PTDM is an undesirable consequence of transplantation because of its associated morbidity and impairment of both patient and graft survival. Although some controversy exists, it is likely that glucose intolerance after transplantation results in both macrovascular and microvascular disease, and there is an increasing risk for infectious and cardiovascular diseases, to which transplant recipients are already at increased susceptibility. Both experimental and clinical observations have shown that immunosuppressive agents currently used in transplantation account for a large degree of the increased risk for PTDM. Consequently, improved understanding of the effects of currently used immunosuppressive medicines on glycemic tolerance is of interest in clinical transplantation.

A comparison of recipient renal outcomes with laparoscopic versus open live donor nephrectomy.

BACKGROUND: Laparoscopic donor nephrectomy (laparoNx) has the potential to increase living kidney donation rates by reducing the pain and suffering of the donor. However, renal function outcomes of a large series of recipients of laparoNx have not been studied. METHODS: We retrospectively reviewed the records of 132 recipients of laparoNx done at our center between 3/96 and 11/97 and compared them to 99 recipients of kidneys procured by the open technique (openNx) done between 10/93 and 3/96. RESULTS: Significantly more patients in the laparoNx group (25.2%) were taking tacrolimus within the first month than those in the openNx group (2.1%). Mean serum creatinine was higher in laparoNx compared with openNx at 1 week (2.8+/-0.3 and 1.8+/-0.2 mg/dl, respectively; P=0.005) and at 1 month (2.0+/-0.1 and 1.6+/-0.1 mg/dl, P=0.05) after transplant. However, by 3 and 6 months, the mean serum creatinine was similar in the two groups (1.7+/-0.1 versus 1.5+/-0.05 mg/dl, and 1.7+/-0.1 versus 1.7+/-0.1, respectively). By 1 year posttransplant, the mean serum creatinine for laparoNx was actually less than that for openNx (1.4+/-0.1 and 1.7+/-0.1 mg/dl, P=0.03). Although patients in the laparoNx compared to the openNx group were more likely to have delayed graft function (7.6 versus 2.0%) and ureteral complications (4.5 versus 1.0%), the rate of other complications, as well as hospital length of stay, patient and graft survival rates were similar in the two groups. CONCLUSION: Although laparoNx allografts have slower initial function compared with openNx, there was no significant difference in longer term renal function.

Hemodialysis adequacy in Network 5: disparity between states and the role of center effects.

The purpose of this study was to determine whether an observed difference in hemodialysis adequacy between states in Network 5 was due to variations in patient characteristics and to what extent dialysis center effects played a role in the observed disparity between states. This was a retrospective observational study of 6,969 patients dialyzed at centers in Maryland and Virginia. There were 3,919 patients on hemodialysis at 89 facilities in Virginia and 3,050 subjects dialyzed at 65 centers in Maryland. The mean urea reduction ratio (URR) was higher in Virginia compared with Maryland (68.2 +/- 0.1% v 66.0 +/- 0.2%, P < 0.0001, respectively), and there continued to be a mean difference in URR of 1.8% between VA and MD (P < 0.0001) after adjusting for several covariates. The differences in URR between states varied depending on facility proprietary status, size as measured by number of stations, and relationship to hospital (free-standing or hospital-based). Furthermore, the center where a patient dialyzed, when treated as a fixed effect, accounted for 15% of the variance in URR. The mean difference of 1.8% in URR between states persisted in a mixed-effects model that included all covariates along with adjusting for dialysis centers as a random effect. The disparity in dialysis adequacy between states in Network 5 could not be accounted for by demographic characteristics, case mix factors, or a large center effect observed in the region. Therefore, we conclude that underlying national reports on dialysis adequacy are heterogeneous results related to differences across regions such as states within a given Network. This difference between states is not explained by the strong center effect found on adequacy in this population of hemodialysis patients.

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.