Predicting decline of kidney function in lupus nephritis using urine biomarkers.

OBJECTIVE: To evaluate candidate biomarkers to predict future renal function decline (RFD) in children and adults with lupus nephritis (LN). METHODS: At the time of enrollment into prospective observational LN cohort studies liver-type fatty acid binding protein (LFABP), albumin, monocyte chemoattractant protein-1 (MCP-1), uromodulin, transferrin, and hepcidin were measured in urine samples of two cohorts of patients with LN, one followed at a pediatric (cohort-1; n = 28) and one at an adult institution (cohort-2; n = 69). The primary outcome was RFD, defined in cohort-1 as a decrease in estimated glomerular filtration rate (eGFR) of ≥20% and in cohort-2 as a sustained increase of ≥25% in serum creatinine concentration (SCr), both from baseline. RESULTS: All patients (n = 97) had normal eGFR or SCr at the time of urine collection at baseline. RFD occurred in 29% (8/28) of patients in cohort-1 during a mean follow-up of 6.1 months, and in 30% (21/69) of those in cohort-2 during a mean follow-up of 60 months. Individually, in cohort-1, levels of MCP-1, transferrin, LFABP, and albumin were higher in the RFD group than those who maintained renal function, with statistical significance for LFABP and albumin. In cohort-2 the RFD group also had higher levels of urine MCP-1 and albumin than others. The combination of LFABP, MCP-1, albumin, and transferrin had good predictive accuracy for RFD in both cohorts (area under the ROC curve = 0.77-0.82). CONCLUSION: The combinatorial urine biomarker LFABP, MCP-1, albumin, and transferrin shows promise as a predictor of renal functional decline in LN, and warrants further investigation.

Mortality and cardiovascular disease among older live kidney donors.

Over the past two decades, live kidney donation by older individuals (≥55 years) has become more common. Given the strong associations of older age with cardiovascular disease (CVD), nephrectomy could make older donors vulnerable to death and cardiovascular events. We performed a cohort study among older live kidney donors who were matched to healthy older individuals in the Health and Retirement Study. The primary outcome was mortality ascertained through national death registries. Secondary outcomes ascertained among pairs with Medicare coverage included death or CVD ascertained through Medicare claims data. During the period from 1996 to 2006, there were 5717 older donors in the United States. We matched 3368 donors 1:1 to older healthy nondonors. Among donors and matched pairs, the mean age was 59 years; 41% were male and 7% were black race. In median follow-up of 7.8 years, mortality was not different between donors and matched pairs (p = 0.21). Among donors with Medicare, the combined outcome of death/CVD (p = 0.70) was also not different between donors and nondonors. In summary, carefully selected older kidney donors do not face a higher risk of death or CVD. These findings should be provided to older individuals considering live kidney donation.

Prescriber adherence to pharmacokinetic monitoring service recommendations for aminoglycoside dosing and the risk of acute kidney injury.

OBJECTIVE: The importance of adherence to aminoglycoside dosing recommendations by a pharmacokinetic monitoring service for preventing acute kidney injury (AKI) is unknown. We aimed to examine the association between AKI and discordance in aminoglycoside dosing between physician orders and recommendations by a pharmacokinetic monitoring service. MATERIALS: We utilized 2000 - 2003 data from a large quaternary care academic medical center, including: hand-written pharmacokinetic monitoring service recommendations; computerized physician order entry inpatient medication orders; and electronic inpatient laboratory orders and results. METHODS: We conducted a case-control study, nested within users of intravenous aminoglycosides. Outcomes of interest were cases of AKI, as determined by changes in serum creatinine. Exposures of interest were discordances between pharmacokinetic monitoring service recommendations and physician orders in the past 2 days with regard to total daily aminoglycoside dose. RESULTS: Most patients received once-daily or less frequent aminoglycoside dosing. In 1,414 evaluable aminoglycoside courses, 220 patients developed AKI, for a cumulative incidence of 15.6%. We identified 690 controls, matched these to 220 cases, and found adjusted odds ratios of 0.72 (95% CI: 0.37 - 1.39) for overdose discordance and of 0.83 (0.51 - 1.34) for underdose discordance, suggesting that discordance in dosing is not associated with AKI. CONCLUSION: Non-adherence to dosing recommendations for aminoglycosides was not associated with risk of AKI in a setting primarily of once-daily aminoglycoside administration.

Predictors of having a potential live donor: a prospective cohort study of kidney transplant candidates.

The barriers to live donor transplantation are poorly understood. We performed a prospective cohort study of individuals undergoing renal transplant evaluation. Participants completed a questionnaire that assessed clinical characteristics as well as knowledge and beliefs about transplantation. A participant satisfied the primary outcome if anyone contacted the transplant center to be considered as a live donor for that participant. The final cohort comprised 203 transplant candidates, among whom 80 (39.4%) had a potential donor contact the center and 19 (9.4%) underwent live donor transplantation. In multivariable logistic regression, younger candidates (OR 1.65 per 10 fewer years, p < 0.01) and those with annual income >or=US$ 15 000 (OR 4.22, p = 0.03) were more likely to attract a potential live donor. Greater self-efficacy, a measure of the participant's belief in his or her ability to attract a donor, was a predictor of having a potential live donor contact the center (OR 2.73 per point, p < 0.01), while knowledge was not (p = 0.56). The lack of association between knowledge and having a potential donor suggests that more intensive education of transplant candidates will not increase live donor transplantation. On the other hand, self-efficacy may be an important target in designing interventions to help candidates find live donors.

Transplantation of kidneys from donors at increased risk for blood-borne viral infection: recipient outcomes and patterns of organ use.

Kidney transplantation from deceased donors classified as increased risk for viral infection by the Centers for Disease Control (CDC) is controversial. Analyses of Organ Procurement and Transplantation Network (OPTN) data from 7/1/2004 to 7/1/2006 were performed. The primary cohort included 48 054 adults added to the kidney transplant wait list. Compared to receiving a standard criteria donor (SCD) kidney or remaining wait-listed, CDC recipients (HR 0.80, p = 0.18) had no significant difference in mortality. In a secondary cohort of 19 872 kidney recipients at 180 centers, SCD (reference) and CDC (HR 0.91, p = 0.16) recipients had no difference in the combined endpoint of allograft failure or death. Among centers performing >10 kidney transplants during the study period, the median proportion of CDC transplants/total transplants was 7.2% (range 1.1-35.6%). Higher volume transplant centers were more likely to use CDC kidneys compared to low and intermediate volume centers (p < 0.01). An analysis of procured kidneys revealed that 6.8% of SCD versus 7.8% of CDC (p = 0.13) kidneys were discarded. In summary, center use of CDC kidneys varied widely, and recipients had good short-term outcomes. OPTN should collect detailed data about long-term outcomes and recipient viral testing so the potential risks of CDC kidneys can be fully evaluated.

Substantial variation in the acceptance of medically complex live kidney donors across US renal transplant centers.

Concern exists about accepting live kidney donation from 'medically complex donors'--those with risk factors for future kidney disease. This study's aim was to examine variation in complex kidney donor use across US transplant centers. We conducted a retrospective cohort study of live kidney donors using organ procurement and transplantation network data. Donors with hypertension, obesity or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) were considered medically complex. Among 9319 donors, 2254 (24.2%) were complex: 1194 (12.8%) were obese, 956 (10.3%) hypertensive and 392 (4.2%) had low eGFR. The mean proportion of medically complex donors at a center was 24% (range 0-65%). In multivariate analysis, donor characteristics associated with medical complexity included spousal relationship to the recipient (OR 1.29, CI 1.06-1.56, p < 0.01), low education (OR 1.19, CI 1.04-1.37, p = 0.01), older age (OR 1.01 per year, CI 1.01-1.02, p < 0.01) and non-US citizenship (OR 0.70, CI 0.51-0.97, p = 0.03). Renal transplant centers with the highest transplant volume (OR 1.26, CI 1.02-1.57, p = 0.03), and with a higher proportion of (living donation)/(all kidney transplants) (OR 1.97, CI 1.23-3.16, p < 0.01) were more likely to use medically complex donors. Though controversial, the use of medically complex donors is widespread and varies widely across centers.

Assessment of differences in HLA-A, -B, and -DRB1 allele mismatches among African-American and non-African-American recipients of deceased kidney transplants.

Among recipients of deceased donor kidney transplants, African-Americans experience a more rapid rate of kidney allograft loss than non-African-Americans. The purpose of this study was to characterize and quantify the HLA-A, -B, and -DRB1 allele mismatches and amino acid substitutions at antigen recognition sites among African-American and non-African-American recipients of deceased donor kidney transplants matched at the antigen level. In recipients with zero HLA antigen mismatches, the degree of one or two HLA allele mismatches for both racial groups combined was 47%, 29%, and 11% at HLA-DRB1, HLA-B, and HLA-A, respectively. There was a greater number of allele mismatches in African-Americans than non-African-Americans at HLA-A (P < .0001), -B (P = .096), and -DRB1 loci (P < .0001). For both racial groups, the HLA allele mismatches were predominantly at A2 for HLA-A; B35 and B44 for HLA-B; but multiple specificities for HLA-DRB1. The observed amino acid mismatches were concentrated at a few functional positions in the antigen binding site of HLA-A and -B and -DRB1 molecules. Future studies are ongoing to assess the impact of these HLA mismatches on kidney allograft loss.

Adverse neurologic events associated with rebound hypertension after using short-acting nifedipine in childhood hypertension.

INTRODUCTION: Short-acting nifedipine (SA-NIF) is widely prescribed for acute hypertension (HTN) in children despite reports of ischemic complications in adults. We describe two children with neurologic events caused by rebound hypertension following SA-NIF use. CASES: Patient 1 is a 7-year-old with acute nephritis and blood pressure (BP) of 185/130. She received SA-NIF which decreased BP to 114/79. When BP rebounded to 160/103, she developed severe cortical visual impairment. Head CT demonstrated edema and petechial hemorrhages in the watershed region. Patient 2 is a 10-year-old renal transplant recipient who received SA-NIF for a BP of 155/98, which resulted in a prompt decrease to 114/74. Two hours later he developed aphasia and right-sided neglect. His BP increased to 168/88 and he developed partial complex seizures. Brain MRI showed high signal intensity in the watershed areas with early gadolinium enhancement. DISCUSSION: The temporal association of the neurologic events with the rebound increase in BP suggests a possible role for the SA-NIF, consistent with its pharmacokinetic profile. Although the adult literature has focused on the unpredictable decline in BP after SA-NIF treatment, these cases suggest that rapid increases in BP following the maximal SA-NIF effect may be associated with impaired cerebral autoregulation and encephalopathy in children. These cases underscore the need for frequent blood pressure determinations and therapy to prevent rebound hypertension.

Prevalence and determinants of erectile dysfunction in hemodialysis patients.

BACKGROUND: The prevalence of erectile dysfunction (ED) among patients with end-stage renal disease (ESRD) is not known. METHODS: A cross-sectional study was conducted to determine the prevalence of ED among a community-based hemodialysis (HD) population using a two-stage cluster random sampling design. The presence and severity of ED were assessed among 302 ESRD patients using the self-administered International Index of Erectile Function-5 (IIEF-5). Logistic regression was used to examine and test associations between ED and other medical conditions. RESULTS: The prevalence of any level of ED was 82% (95% CI, 76 to 87%) for all HD subjects. The prevalence of severe ED was 45% (CI, 36 to 55%). Subjects younger than 50 years had a prevalence of ED of 63% (CI, 53 to 71%), while in subjects 50 years or older, it was 90% (CI, 84 to 94%). A multivariable analysis demonstrated increasing age (50 to 59, OR = 2.04, 95% CI, 1.3 to 3.1; 60 to 69, OR = 5.5, 95% CI, 1.9 to 15.6) and diabetes (OR = 2.0, 95% CI, 1.2 to 3.3) to be independently associated with the presence of any level of ED. However, neither the subjects' age nor history of diabetes predicted the severity of ED among subjects with ED. The use of angiotensin-converting enzyme inhibitors (ACEIs) was inversely associated with ED (OR = 0.41, 95% CI, 0.17 to 0.98). Poor functional status (Karnofsky score or the Index of Physical Impairment) was not associated with ED. CONCLUSIONS: ED is extremely prevalent among HD patients. Increasing age, diabetes, and nonuse of ACEIs were associated with higher prevalence of ED. The high prevalence of ED was seen even among patients with good functional status.

Testing the reliability of old and new features of a new electronic monitor for metered dose inhalers.

BACKGROUND: Poor adherence to treatment regimens is hypothesized to be, in part, responsible for the extensive morbidity and mortality associated with asthma. Electronic monitors are the most accurate means available for measuring adherence, but their use has been limited by reports questioning the reliability and validity of their data. OBJECTIVE: To test the reliability and accuracy of the MDILog (Medtrac Technologies, Lakewood, CO), a new electronic monitor of metered dose inhalers (MDIs), and to test its unique features. METHODS: Brief experiments were performed comparing a written diary to the electronic record using three MDILogs. The following features were studied: reporting of time and date of an actuation, recording of the occurrence of an actuation of the MDI, sensing and timing of inhalations, sensing of shaking of the MDI canister, and recording of multiple actuations. RESULTS: Clocking was accurate 100% of the time. Actuation agreed with the paper record 97% to 100%, inhalation 82% to 100%, shaking 86% to 95%. Agreement of late inhalations and multiple actuations with paper records was at least 98%. CONCLUSIONS: The MDILog yields accurate information and is more reliable than previously described monitors. Its new features allow more detailed study of how patients use inhalers by allowing evaluation of how patients inhale and whether they shake the inhaler canister before use.

Effect of the use or nonuse of long-term dialysis on the subsequent survival of renal transplants from living donors.

BACKGROUND: The effect on allograft survival of the transplantation of kidneys from living donors without the previous initiation of long-term dialysis is controversial. METHODS: Using data from the U.S. Renal Data System, we performed a retrospective cohort study of 8481 patients who were or who were not treated by long-term dialysis before receiving a kidney transplant from a living donor. The relative rate of allograft failure for patients who received a transplant without previously undergoing long-term dialysis, as compared with patients who underwent long-term dialysis before transplantation, was assessed by proportional-hazards analysis, with adjustment for potential confounding variables, including the transplantation center and median household income. The association between the receipt of a kidney transplant from a living donor without previous dialysis ("preemptive transplantation") and the risk of biopsy-confirmed acute rejection within six months after transplantation was evaluated by conditional logistic-regression analysis, with adjustment for the transplantation center. RESULTS: Transplantation of a kidney from a living donor without previous long-term dialysis was associated with a 52 percent reduction in the risk of allograft failure during the first year after transplantation (rate ratio, 0.48; P=0.002), an 82 percent reduction during the second year (rate ratio, 0.18; P=0.001), and an 86 percent reduction during subsequent years (rate ratio, 0.14; P=0.001), as compared with transplantation after dialysis. The reduction in the rate of allograft failure during the first year was attenuated when adjustment was made for the timing of acute rejection within the first year (rate ratio, 0.69; 95 percent confidence interval, 0.44 to 1.10; P=0.10). Increasing duration of dialysis was associated with increasing odds of rejection within six months after transplantation (P=0.001). CONCLUSIONS: Preemptive transplantation of kidneys from living donors without the previous initiation of dialysis is associated with longer allograft survival than transplantation performed after the initiation of dialysis.

Preliminary observations of sildenafil treatment for erectile dysfunction in dialysis patients.

Erectile dysfunction is common in dialysis patients. We report our experience with sildenafil citrate in patients undergoing dialysis therapy. Male subjects attending the Outpatient Dialysis Unit at the University of Pennsylvania (Philadelphia, PA) who were prescribed sildenafil by their primary physician or nephrologist were asked to complete the International Index of Erectile Function before their first dose of sildenafil and after at least 4 weeks of therapy. Subjects' mean age was 50.3 +/- 14.63 (SD) years. Ninety-three percent of the subjects were black. Based on a global efficacy question, 66.7% of the subjects believed that treatment had improved their erections. Subjects reported no increase in the sexual desire domain despite experiencing a significant increase in erectile function, orgasmic function, and satisfaction with intercourse. Sildenafil was well tolerated in a selected group of patients who reported improved sexual function with no major adverse effects.

Arterial hypertension and renal allograft survival.

CONTEXT: Several observational studies have investigated the significance of hypertension in renal allograft failure; however, these studies have been complicated by the lack of adjustment for baseline renal function, leaving the role of elevated blood pressure in allograft failure unclear. OBJECTIVE: To examine the relationship between blood pressure adjusted for renal function and survival after cadaveric allograft transplantation. DESIGN: Nonconcurrent historical cohort study conducted from 1985 through 1997. SETTING: University teaching hospital. PARTICIPANTS: A total of 277 patients aged 18 years or older who underwent cadaveric renal transplantation without another simultaneous organ transplantation and whose allograft was functioning for a minimum of 1 year. Follow-up continued through 1997 (mean follow-up, 5.7 years). MAIN OUTCOME MEASURE: Time to allograft failure (defined as death, return to dialysis, or retransplantation) by systolic, diastolic, and mean arterial blood pressure measurements at 1 year after transplantation. RESULTS: Multivariate Cox proportional hazards modeling demonstrated that nonwhite ethnicity, history of acute rejection, and nondiabetic kidney disease were significant predictors of failure (P = .01 for all). In addition, the calculated creatinine clearance at 1 year had an adjusted rate ratio (RR) for allograft failure per 10 mL/min (0.17 mL/s) of 0.74 (95% confidence interval [CI], 0.62-0.88). The RR per 10-mm Hg increase in blood pressure measured at 1 year after transplantation, after adjustment for creatinine clearance, was 1.15 (95% CI, 1.02-1.30) for systolic pressure, 1.27 (95% CI, 1.01-1.60) for diastolic pressure, and 1.30 (95% CI, 1.05-1.61) for mean arterial pressure. Supplemental analyses that did not include death as a failure event or reduce the minimum allograft survival time for study subjects to 6 months yielded results consistent with the primary analysis. There was no evidence of modification of the blood pressure-allograft failure relationship by ethnicity or diabetes mellitus. CONCLUSIONS: Systolic, diastolic, and mean arterial blood pressures at 1 year posttransplantation strongly predict allograft survival adjusted for baseline renal function. More aggressive control of blood pressure may prolong cadaveric allograft survival.

Dialyzer reuse: an evolving search for efficiency.

The evolution of dialyzer reuse in the United States provides an opportunity to examine the dialysis community's response to changing financial conditions and incentives. As background, we provide a conceptual framework to explain the factors governing the diffusion of dialysis technologies and then describe the clinical context in which reuse programs have developed. Early in its evolution, dialyzer reuse arose principally from the desire to reduce costs under a system of capitated payments. More recently, despite evidence of an adverse health effect, cost-savings from reuse have permitted the adoption of new and expensive technologies. The net effect of the tradeoff's between cost and quality should, ideally, drive the decision to reuse dialyzers. However, even if such tradeoffs can be fully characterized, incentives to implement efficiencies created by capitated systems of payment will continue to influence practice.

Association of dialyzer reuse and hospitalization rates among hemodialysis patients in the US.

OBJECTIVES: To determine if reuse of hemodialyzers is associated with higher rates of hospitalization and their resulting costs among end-stage renal disease (ESRD) patients. METHODS: Noncurrent cohort study of hospitalization rates among 27,264 ESRD patients beginning hemodialysis in the United States in 1986 and 1987. RESULTS: Dialysis in free-standing facilities reprocessing dialyzers was associated with a greater rate of hospitalization than in facilities not reprocessing (relative rate (RR) = 1.08, 95% confidence interval (CI), 1.02-1.14). This higher rate of hospitalization was observed with dialyzer reuse using peracetic/acetic acids (RR = 1.11, CI 1. 04-1.18) and formaldehyde (RR = 1.07, CI 1.00-1.14), but not glutaraldehyde (p = 0.97). There was no difference among hospitalization rates in hospital-based facilities reprocessing dialyzers with any sterilant and those not reprocessing. Hospitalization for causes other than vascular access morbidity in free-standing facilities reusing dialyzers with formaldehyde was not different from hospitalization in facilities not reusing. However, reuse with peracetic/acetic acids was associated with higher rates of hospitalization than formaldehyde (RR = 1.08, CI 1.03-1.15). CONCLUSIONS: Dialysis in free-standing facilities reprocessing dialyzers with peracetic/acetic acids or formaldehyde was associated with greater hospitalization than dialysis without dialyzer reprocessing. This greater hospitalization accounts for a large increment in inpatient stays in the USA. These findings raise important concerns about potentially avoidable morbidity among hemodialysis patients.

Membranoproliferative glomerulonephritis type I, mixed cryoglobulinemia and lymphoma in the absence of hepatitis C infection.

Chronic hepatitis C virus infection has been linked to cryoglobulinemia, membranoproliferative glomerulonephritis, and malignant B-cell lymphoproliferation, suggesting a possible pathogenetic link between these disorders. We report a patient with the latter clinical triad in the absence of hepatitis C infection. We postulate that the persistent and dysregulated immunologic activity associated with chronic antigen stimulation, inflammation and/or B-cell malignancy induces nephritogenic autoantibodies, including cryoglobulins, that produce a similar clinical syndrome in genetically susceptible individuals.

Discrepancies in pediatric bone mineral density reference data: potential for misdiagnosis of osteopenia.

OBJECTIVE: To evaluate published pediatric dual-energy x-ray absorptiometry bone mineral density (BMD) reference data by comparing the diagnostic classification of measured BMD in children at risk for osteopenia as healthy or osteopenic according to reference source. STUDY DESIGN: Spine BMD was measured in 95 children, ages 9 to 15 years, at risk for osteopenia because of childhood disease. The BMD results were converted to age-specific z scores for each of the 5 reference data sets, and the z -score distributions were compared. RESULTS: Between 11% and 30% of children were classified as osteopenic (z score < -2.0) depending on the reference data set. The 2 sex-specific reference data sets yielded similar diagnostic classification of boys and girls: 10% of boys and 11% to 16% of girls were osteopenic (P =.4). The 3 sex-nonspecific reference data sets classified 9% to 13% of girls and 24% to 44% of boys as osteopenic; the diagnosis of osteopenia was significantly greater in boys (P <.01). CONCLUSIONS: The use of different published reference data for the assessment of children at risk for osteopenia results in inconsistent diagnostic classification of BMD results. These inconsistencies can be partially attributed to sex-nonspecific reference data that result in misclassification of boys as osteopenic.

US, CT, and MR evaluation of accessory renal arteries and proximal renal arterial branches.

RATIONALE AND OBJECTIVES: The purpose of this study was to compare color Doppler ultrasound (US), computed tomographic (CT) angiography, and magnetic resonance (MR) angiography for the evaluation of accessory renal arteries and proximal branches of the main renal artery. MATERIALS AND METHODS: Fifty-six subjects who had undergone conventional arteriography of the renal arteries participated in a prospective comparison of Doppler US (45 patients), CT angiography (52 patients), and nonenhanced MR angiography (28 patients). Conventional arteriography depicted 28 accessory renal arteries and 21 proximal branches of the main renal artery within 2 cm of the aorta. RESULTS: US depicted five of 24 accessory renal arteries seen at arteriography but no proximal arterial branches. CT angiography depicted 24 of 26 accessory renal arteries and 13 of 17 proximal arterial branches, as well as 15 additional accessory renal arteries not seen at conventional arteriography. MR demonstrated 11 of 15 accessory arteries, as well as four additional accessory arteries not seen at conventional arteriography. MR did not depict any of nine proximal arterial branches seen at conventional arteriography. CONCLUSION: When compared with US or nonenhanced MR angiography, CT is the preferred method for evaluation of accessory renal arteries and proximal branches of the renal artery.

Effect of anti-lymphocyte antibody induction therapy on renal allograft survival.

Our two meta-analyses show that antilymphocyte antibody induction therapy extends allograft survival when compared to induction therapy with cyclosporine, azathioprine, and prednisone with the majority of the benefit seen during the first 2 years after transplant. The benefit of induction therapy with respect to allograft survival is particularly important among patients with pretransplant panel reactive antibodies greater than 20%. Although our understanding of the role of antilymphocyte antibody induction therapy continues to evolve, these two meta-analyses provide evidence for its use in clinical renal transplantation.