Temporal trends in the incidence, treatment and outcomes of hip fracture after first kidney transplantation in the United States.

It is currently unknown whether any secular trends exist in the incidence and outcomes of hip fracture in kidney transplant recipients (KTR). We identified first-time KTR (1997-2010) who had >1 year of Medicare coverage and no recorded history of hip fracture. New hip fractures were identified from corresponding diagnosis and surgical procedure codes. Outcomes studied included time to hip fracture, type of surgery received and 30-day mortality. Of 69,740 KTR transplanted in 1997-2010, 597 experienced a hip fracture event during 155,341 person-years of follow-up for an incidence rate of 3.8 per 1000 person-years. While unadjusted hip fracture incidence did not change, strong confounding by case mix was present. Using year of transplantation as a continuous variable, the hazard ratio (HR) for hip fracture in 2010 compared with 1997, adjusted for demographic, dialysis, comorbid and most transplant-related factors, was 0.56 (95% confidence interval [CI]: 0.41-0.77). Adjusting for baseline immunosuppression modestly attenuated the HR (0.68; 95% CI: 0.47-0.99). The 30-day mortality was 2.2 (95% CI: 1.3-3.7) per 100 events. In summary, hip fractures remain an important complication after kidney transplantation. Since 1997, case-mix adjusted posttransplant hip fracture rates have declined substantially. Changes in immunosuppressive therapy appear to be partly responsible for these favorable findings.

Vitamin D deficiency and frailty in older Americans.

OBJECTIVE: To explore the relation between 25-hydroxyvitamin D deficiency and frailty. Frailty is a multidimensional phenotype that describes declining physical function and a vulnerability to adverse outcomes in the setting of physical stress such as illness or hospitalization. Low serum concentrations of 25-hydroxyvitamin D are known to be associated with multiple chronic diseases such as cardiovascular disease and diabetes, in addition to all cause mortality. DESIGN: Using data from the Third National Health and Nutrition Survey (NHANES III), we evaluated the association between low serum 25-hydroxyvitamin D concentration and frailty, defined according to a set of criteria derived from a definition previously described and validated. SUBJECTS: Nationally representative survey of noninstitutionalized US residents collected between 1988 and 1994. RESULTS: 25-Hydroxyvitamin D deficiency, defined as a serum concentration <15 ng mL(-1), was associated with a 3.7-fold increase in the odds of frailty amongst whites and a fourfold increase in the odds of frailty amongst non-whites. This association persisted after sensitivity analyses adjusting for season of the year and latitude of residence, intended to reduce misclassification of persons as 25-hydroxyvitamin D deficient or insufficient. CONCLUSION: Low serum 25-hydroxyvitamin D concentrations are associated with frailty amongst older adults.

The elderly patients on hemodialysis.

Nephrologists care for an increasing number of elderly patients on hemodialysis. As such, an understanding of the overlap among complications of hemodialysis and geriatric syndromes is crucial. This article reviews hemodialysis management issues including vascular access, hypertension, anemia and bone and mineral disorders with an attention towards the distinct medical needs of the elderly. Key concepts of geriatrics frailty, dementia and palliative care are also discussed, as nephrologists frequently participate in decision-making directed toward balancing longevity, functional status and the burden of therapy.

The risk of acute renal failure in patients with chronic kidney disease.

Few studies have defined how the risk of hospital-acquired acute renal failure varies with the level of estimated glomerular filtration rate (GFR). It is also not clear whether common factors such as diabetes mellitus, hypertension and proteinuria increase the risk of nosocomial acute renal failure independent of GFR. To determine this we compared 1,746 hospitalized adult members of Kaiser Permanente Northern California who developed dialysis-requiring acute renal failure with 600,820 hospitalized members who did not. Patient GFR was estimated from the most recent outpatient serum creatinine measurement prior to admission. The adjusted odds ratios were significantly and progressively elevated from 1.95 to 40.07 for stage 3 through stage 5 patients (not yet on maintenance dialysis) compared to patients with estimated GFR in the stage 1 and 2 range. Similar associations were seen after controlling for inpatient risk factors. Pre-admission baseline diabetes mellitus, diagnosed hypertension and known proteinuria were also independent risk factors for acute kidney failure. Our study shows that the propensity to develop in-hospital acute kidney failure is another complication of chronic kidney disease whose risk markedly increases even in the upper half of stage 3 estimated GFR. Several common risk factors for chronic kidney disease also increase the peril of nosocomial acute kidney failure.

Neighborhood poverty and kidney transplantation among US Asians and Pacific Islanders with end-stage renal disease.

The degree to which low transplant rates among Asians and Pacific Islanders in the United States are confounded by poverty and reduced access to care is unknown. We examined the relationship between neighborhood poverty and kidney transplant rates among 22 152 patients initiating dialysis during 1995-2003 within 1800 ZIP codes in California, Hawaii and the US-Pacific Islands. Asians and whites on dialysis were distributed across the spectrum of poverty, while Pacific Islanders were clustered in the poorest areas. Overall, worsening neighborhood poverty was associated with lower relative rates of transplant (adjusted HR [95% CI] for areas with > or =20% vs. <5% residents living in poverty, 0.41 [0.32-0.53], p < 0.001). At every level of poverty, Asians and Pacific Islanders experienced lower transplant rates compared with whites. The degree of disparity increased with worsening neighborhood poverty (adjusted HR [95% CI] for Asians-Pacific Islanders vs. whites, 0.64 [0.51-0.80], p < 0.001 for areas with <5% and 0.30 [0.21-0.44], p < 0.001 for areas with > or =20% residents living in poverty; race-poverty level interaction, p = 0.039). High levels of neighborhood poverty are associated with lower transplant rates among Asians and Pacific Islanders compared with whites. Our findings call for studies to identify cultural and local barriers to transplant among Asians and Pacific Islanders, particularly those residing in resource-poor neighborhoods.

The effects of cinacalcet on blood pressure, mortality and cardiovascular endpoints in the EVOLVE trial.

Patients with end-stage renal disease often have derangements in calcium and phosphorus homeostasis and resultant secondary hyperparathyroidism (sHPT), which may contribute to the high prevalence of arterial stiffness and hypertension. We conducted a secondary analysis of the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial, in which patients receiving hemodialysis with sHPT were randomly assigned to receive cinacalcet or placebo. We sought to examine whether the effect of cinacalcet on death and major cardiovascular events was modified by baseline pulse pressure as a marker of arterial stiffness, and whether cinacalcet yielded any effects on blood pressure. As reported previously, an unadjusted intention-to-treat analysis failed to conclude that randomization to cinacalcet reduces the risk of the primary composite end point (all-cause mortality or non-fatal myocardial infarction, heart failure, hospitalization for unstable angina or peripheral vascular event). However, after prespecified adjustment for baseline characteristics, patients randomized to cinacalcet experienced a nominally significant 13% lower adjusted risk (95% confidence limit 4-20%) of the primary composite end point. The effect of cinacalcet was not modified by baseline pulse pressure (Pinteraction=0.44). In adjusted models, at 20 weeks cinacalcet resulted in a 2.2 mm Hg larger average decrease in systolic blood pressure (P=0.002) and a 1.3 mm Hg larger average decrease in diastolic blood pressure (P=0.002) compared with placebo. In summary, in the EVOLVE trial, the effect of cinacalcet on death and major cardiovascular events was independent of baseline pulse pressure.

Prognostic stratification in critically ill patients with acute renal failure requiring dialysis.

BACKGROUND: Despite the widespread availability of dialytic and intensive care unit technology, the probability of early mortality in critically ill persons with acute renal failure is distressingly high. Previous efforts to predict outcome in this population have been limited by small sample size and the absence of uniform exclusion criteria. Additionally, data obtained decades ago may not apply today owing to changes in case mix. METHODS: The medical records of 132 consecutive patients in the intensive care unit with acute renal failure who required dialysis from 1991 through 1993 were evaluated by a blinded reviewer. RESULTS: The overall in-hospital mortality rate was 70%. Twelve readily available historical, clinical, and laboratory variables were significantly associated with in-hospital mortality. Multivariate logistic regression analysis showed that mechanical ventilation, malignancy, and nonrespiratory organ system failure were independently associated with in-hospital mortality. Using a 95% positivity criterion, this model identified 24% of high-risk patients who died, without misclassification of any survivors. Of those who survived to hospital discharge, 33% were dialysis dependent and 28% were institutionalized long-term. CONCLUSIONS: Among critically ill patients, acute renal failure requiring dialysis is an ominous condition with a high risk of in-hospital mortality. This risk appears to depend largely on comorbid conditions, such as the need for mechanical ventilation and underlying malignancy. While this prognostic model requires prospective validation, it appears to identify a substantial fraction of patients for whom dialysis may be of limited or no benefit.

Cost-effectiveness of cancer screening in end-stage renal disease.

BACKGROUND: Limited evidence suggests that persons with end-stage renal disease (ESRD) may be at increased risk for malignancy. The appropriateness of screening procedures in this population has not been evaluated. OBJECTIVE: To determine the relative cost-effectiveness of hypothetical cancer screening programs in the population with ESRD compared with the general population. METHODS: We performed a cost-effectiveness analysis, employing the declining exponential approximation of life expectancy. Assumptions were put forth to bias the model in favor of cancer screening. Secondary comparisons were made between cancer screening and other interventions targeted to patients with ESRD. RESULTS: The costs per unit of survival benefit conferred by cancer screening were 1.6 to 19.3 times greater among patients with ESRD than in the general population, depending on age, sex, and race, and assumptions outlined herein. For persons with ESRD, the net gain in life expectancy from a typical cancer screening program was calculated to be 5 days or less. Similar survival gains could be obtained via a reduction of 0.02% or less in the baseline ESRD-related mortality rate. CONCLUSIONS: These analyses suggest that routine cancer screening in the population with ESRD is a relatively inefficient allocation of financial resources. Direction of funds toward improving the quality of dialysis could attain such an objective at substantially lower cost. Furthermore, these findings highlight the importance of competing risks as a consideration in the evaluation of screening strategies and other interventions targeted to patients with ESRD and to other populations with chronic diseases associated with reduced survival.

Evidence-based organ allocation.

BACKGROUND: There are not enough cadaveric kidneys to meet the demands of transplant candidates. The equity and efficiency of alternative organ allocation strategies have not been rigorously compared. METHODS: We developed a five-compartment Monte Carlo simulation model to compare alternative organ allocation strategies, accommodating dynamic changes in recipient and donor characteristics, patient and graft survival rates, and quality of life. The model simulated the operations of a single organ procurement organization and attempted to predict the evolution of the transplant waiting list for 10 years. Four allocation strategies were compared: a first-come first-transplanted system; a point system currently utilized by the United Network of Organ Sharing; an efficiency-based algorithm that incorporated correlates of patient and graft survival; and a distributive efficiency algorithm, which had an additional goal of promoting equitable allocation among African-American and other candidates. RESULTS: A 10-year computer simulation was performed. The distributive efficiency policy was associated with a 3.5%+/-0.8% (mean +/- SD) increase in quality-adjusted life expectancy (33.9 months vs 32.7 months), a decrease in the median waiting time to transplantation among those who were transplanted (6.6 months vs 16.3 months), and an increase in the overall likelihood of transplantation (61% vs 45%), compared with the United Network of Organ Sharing algorithm. Improved equity and efficiency were also seen by race (African-American vs other), sex, and age (<50 or > or =50 years). Sensitivity analyses did not appreciably change the qualitative results. CONCLUSION: Evidence-based organ allocation strategies in cadaveric kidney transplantation would yield improved equity and efficiency measures compared with existing algorithms.

Independent association between acute renal failure and mortality following cardiac surgery.

PURPOSE: To determine whether there is an independent association of acute renal failure requiring dialysis with operative mortality after cardiac surgery. PATIENTS AND METHODS: The 42,773 patients who underwent coronary artery bypass or valvular heart surgery at 43 Department of Veterans Affairs Medical Centers between 1987 and 1994 were evaluated to determine the association between acute renal failure sufficient to require dialysis and operative mortality, with and without adjustment for comorbidity and postoperative complications. Crude and adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were derived from logistic regression analysis. RESULTS: Acute renal failure occurred in 460 (1.1%) patients. Overall operative mortality was 63.7% in these patients, compared with 4.3% in patients without this complication. The unadjusted OR for death was 39 (95% CI 32 to 48). After adjustment for comorbid factors related to the development of acute renal failure (surgery type, baseline renal function, preoperative intraaortic balloon pump, prior heart surgery, NYHA class IV status, peripheral vascular disease, pulmonary rales, left ventricular ejection fraction below 35%, chronic obstructive pulmonary disease, systolic blood pressure, and the cross-product of systolic blood pressure and surgery type), the OR was 27 (95% CI 22 to 34). Further adjustment was made for seven postoperative complications (low cardiac output, cardiac arrest, perioperative myocardial infarction, prolonged mechanical ventilation, reoperation for bleeding or repeat cardiopulmonary bypass, stroke or coma, and mediastinitis), that were independently associated with operative mortality. The OR adjusted for comorbidity and postoperative complications associated with acute renal failure was 7.9 (95% CI 6 to 10). CONCLUSIONS: Acute renal failure was independently associated with early mortality following cardiac surgery, even after adjustment for comorbidity and postoperative complications. Interventions to prevent or improve treatment of this condition are urgently needed.

Is the administration of dopamine associated with adverse or favorable outcomes in acute renal failure? Auriculin Anaritide Acute Renal Failure Study Group.

PURPOSE: To explore the relationship between the administration of low-dose dopamine and outcomes in acute renal failure. PATIENTS: Two hundred and fifty-six patients with acute renal failure randomized to the placebo arm of a multicenter intervention trial were examined. Independent correlates of low-dose (arbitrarily defined as < 3 micrograms/kg/min) and high-dose (arbitrarily defined as > or = 3 micrograms/kg/min) dopamine administration were identified. The relative risks of death, and the combined outcome of death or dialysis, were estimated using proportional hazards regression with and without adjustment for potential confounding and bias. RESULTS: There were 93 (36%) deaths documented; an additional 52 (20%) patients who survived required dialysis during the 60-day study period. The relative risk (RR) of death associated with the administration of low-dose dopamine was 1.11 (95% confidence interval [95% Cl] 0.66 to 1.89). The RR of death was modestly but not significantly reduced, after adjustment for the probability of treatment assignment and for relevant covariates (RR 0.82, 95% Cl 0.42 to 1.60). The RR of death or dialysis associated with the administration of low-dose dopamine was 1.10 (95% Cl 0.71 to 1.71). The RR of death or dialysis was attenuated by adjustment, but not significantly (RR 0.95, 95% Cl 0.58 to 1.58). CONCLUSION: There is insufficient evidence that the administration of low-dose dopamine improves survival or obviates the need for dialysis in persons with acute renal failure. The routine use of low-dose dopamine should be discouraged until a prospective, randomized, placebo-controlled trial establishes its safety and efficacy.

Modality-specific nutrition support in ESRD: weighing the evidence.

Protein-calorie malnutrition affects a large fraction of patients with end-stage renal disease (ESRD) and contributes significantly to the high rates of mortality and morbidity observed in this population. Observational studies of specific interventions, including intradialytic parenteral nutrition (IDPN), suggest that aggressive nutrition support may be of some benefit to some patients with ESRD. Due in part to lack of data derived from prospective, randomized clinical trials, and to the large expense associated with these therapies, Medicare and other payers have strongly discouraged the prescription of IDPN and other intermittent, dialysis-specific methods of nutrition support, such as intraperitoneal nutrition (IPN). The "burden of proof" has been placed on the dialysis community. In response, we must continue to emphasize the importance of securing nutritional health for all patients on or anticipating renal replacement therapy. Intradialytic parenteral nutrition should be reserved for patients who are taking in sufficient calories yet are unable to tolerate oral or enteral protein-rich foods or formulas designed to meet daily protein requirements (> or = 1.5 g/kg in some patients). Intradialytic parenteral nutrition should not be prescribed in place of total parenteral nutrition (TPN) if the latter is truly needed. Creative methods of nutrition support, including the use of dietary supplements at dialysis (intradialytic oral or enteral nutrition), should be explored. Prospective clinical trials investigating the effects of nutrition support on survival, hospitalization rates, health-related quality of life, and functional status, are urgently needed.

Ochrobactrum anthropi bacteremia in a patient on hemodialysis.

Although newer tunneled dialysis catheters offer improved capacity for blood flow and efficiency of dialysis, catheter-associated bacteremia remains an extremely important complication of this access strategy. This is a report of a case of catheter-associated bacteremia with Ochrobactrum anthropi, a water-borne gram-negative rod with an unusual pattern of antibiotic resistance. Given the organism's hydrophilic property and the frequency of catheter use in debilitated individuals with end-stage renal disease, Ochrobactrum anthropi infection should be considered in the differential diagnosis of a hemodialysis patient with unexplained fever.

Chronic renal confusion: insufficiency, failure, dysfunction, or disease.

The terms routinely used to describe states of reduced glomerular filtration rate (GFR) not requiring renal replacement therapy are poorly defined. With increasing interest in the epidemiology of chronic renal insufficiency and the timing of initiation of dialysis, terms such as "pre-ESRD" and "pre-dialysis" have been popularized, again without clear definition. Unambiguous terminology should be adopted. The authors favor using the term chronic renal insufficiency to describe states of reduced GFR not severe enough to require dialysis or transplantation. The authors propose classifying patients with GFR of 60 to 41 mL/min, 40 to 21 mL/min, and 20 mL/min or below as having mild, moderate, and advanced degrees of chronic renal insufficiency, respectively. The use of this terminology will facilitate communication among nephrologists and other physicians and provide a framework for comparison of populations across cohort studies and clinical trials.

Suspected iron dextran-related adverse drug events in hemodialysis patients.

Despite the use of recombinant erythropoietin, anemia remains a significant problem for patients with end-stage renal disease, in part related to chronic dialysis-related blood loss and resultant iron deficiency. Because oral iron preparations have been relatively ineffective and poorly tolerated in this population, intravenous (IV) iron dextran has been widely prescribed, despite a finite risk for adverse effects associated with its use. We analyzed data from Fresenius Medical Care North America (FMCNA) clinical variance reports to determine the incidence of suspected iron dextran-related adverse drug events (ADEs) and associated patient characteristics, dialysis practice patterns, and outcomes. We used a case-cohort study design, comparing individuals who experienced suspected ADEs with the overall FMCNA population. Among 841,252 IV iron dextran administrations from October 1998 through March 1999, there were 165 reported suspected ADEs, corresponding to an overall rate of 0.000196%, or approximately 20 per 100,000 doses. Forty-three patients (26%) required an independent emergency department evaluation, 18 patients (11%) required hospitalization, and 1 patient (0.6%) died. Dyspnea (43%), hypotension (23%), and neurological symptoms (23%) were the most common major ADEs; nausea (34%), vomiting (23%), flushing (27%), and pruritus (25%) were the most common other ADEs. ADEs were 8.1-fold more common among patients administered Dexferrum (American Regent Laboratories, Inc, Shirley, NY) compared with those administered InFed (Watson Pharmaceuticals, Phoenix, AZ). In summary, serious adverse reactions to IV iron dextran are rare in clinical practice. The risk appears to depend on the specific formulation of IV iron dextran. Otherwise, iron dextran-related ADEs are difficult to predict.

Survival after acute myocardial infarction in patients with end-stage renal disease: results from the cooperative cardiovascular project.

Cardiovascular disease (CVD) is the most common cause of death in patients with end-stage renal disease (ESRD). The optimal management strategy in this population is unknown. We studied 640 patients with ESRD and acute myocardial infarction during 1994 to 1995 as part of the Health Care Financing Administration's Cooperative Cardiovascular Project. The majority of patients were treated with medical therapy alone, 46 patients (7%) were treated with percutaneous transluminal coronary angioplasty (PTCA), and 29 patients (5%) underwent coronary artery bypass grafting (CABG). Patient characteristics and comorbid conditions were similar among the three groups. The overall 1-year mortality rate was 53%. Advanced age, low or high body mass index, history of peripheral vascular disease or stroke, the inability to walk independently, and several indicators of cardiac dysfunction were associated with an increased relative risk (RR) for death. Survival curves differed significantly by treatment modality, with 1-year survival rates of 45%, 54%, and 69% in the medical therapy alone, PTCA, and CABG groups, respectively (P = 0.03). After adjustment for confounding variables, the RR for death was less (but not significantly so) in the CABG group (RR, 0.6; 95% confidence interval, 0.3 to 1.1). There are no randomized clinical trial data to guide therapy of CVD in patients with ESRD. On the basis of these and other available data, CABG may be the optimal therapy for CVD in ESRD. In light of the exceptionally poor outcomes observed for patients treated with medical therapy alone, it may be premature to dismiss PTCA as a therapeutic option in this population.

Atrial natriuretic factor in oliguric acute renal failure. Anaritide Acute Renal Failure Study Group.

Atrial natriuretic peptide (ANP), an endogenous hormone synthesized by the cardiac atria, has been shown to improve renal function in multiple animal models of acute renal failure. In a recent multicenter clinical trial of 504 patients with acute tubular necrosis (oliguric and nonoliguric), ANP decreased the need for dialysis only in the oliguric patients. In the present study, 222 patients with oliguric acute renal failure were enrolled into a multicenter, randomized, double-blind, placebo-controlled trial designed to assess prospectively the safety and efficacy of ANP compared with placebo. Subjects were randomized to treatment with a 24-hour infusion of ANP (anaritide, 0.2 microgram/kg/min; synthetic form of human ANP) or placebo. Dialysis and mortality status were followed up for 60 days. The primary efficacy end point was dialysis-free survival through day 21. Dialysis-free survival rates were 21% in the ANP group and 15% in the placebo group (P = 0.22). By day 14 of the study, 64% and 77% of the ANP and placebo groups had undergone dialysis, respectively (P = 0.054), and 9 additional patients (7 patients, ANP group; 2 patients, placebo group) needed dialysis but did not receive it. Although a trend was present, there was no statistically significant beneficial effect of ANP in dialysis-free survival or reduction in dialysis in these subjects with oliguric acute renal failure. Mortality rates through day 60 were 60% versus 56% in the ANP and placebo groups, respectively (P = 0.541). One hundred two of 108 (95%) versus 63 of 114 (55%) patients in the ANP and placebo groups had systolic blood pressures less than 90 mm Hg during the study-drug infusion (P < 0.001). The maximal absolute decrease in systolic blood pressure was significantly greater in the anaritide group than placebo group (33.6 versus 23.9 mm Hg; P < 0.001). This well-characterized population with oliguric acute renal failure had an overall high morbidity and mortality.

Clearance of Pneumocystis carinii cysts in acute P carinii pneumonia: assessment by serial sputum induction.

STUDY OBJECTIVES: To determine the feasibility of repeat sputum induction in acute Pneumocystis carinii pneumonia (PCP) and to define the rate of clearance of P carinii cysts from the respiratory tract of HIV-seropositive patients with acute PCP. DESIGN: Prospective cohort evaluation. SETTING: University medical center. PARTICIPANTS: Twenty-four HIV-seropositive subjects with acute PCP. MEASUREMENTS: Sputum induction for P carinii 2, 3, 4, and 6 weeks after initial diagnosis, and follow-up for 1 year. RESULTS: Eighty-eight percent of subjects had residual cysts at 2 weeks, 76% at 3 weeks, 29% at 4 weeks, and 24% at 6 weeks postdiagnosis. A prior AIDS-defining illness (p = 0.033) or prior PCP (p = 0.004) predicted relapse within 6 months, but persistent cysts at 3 weeks did not; 8 of 16 sputum-positive subjects and 1 of 5 sputum-negative subjects experienced a relapse within 6 months (p = 0.34). Secondary prophylaxis with trimethoprim-sulfamethoxazole was associated with a reduced risk of relapse. CONCLUSIONS: Serial sputum induction coupled with direct fluorescent antibody staining is a feasible, noninvasive method of respiratory tract surveillance for the eradication of P carinii during and after acute PCP. Three-quarters of HIV-seropositive patients with acute PCP have persistent cysts in their lungs at the end of antimicrobial treatment, despite clinical recuperation, but only one quarter have residual cysts 6 weeks postdiagnosis. A prior AIDS-defining illness and prior PCP are positively associated, and subsequent trimethoprim-sulfamethoxazole prophylaxis is negatively associated, with relapse within 6 months, while persistent organisms at 3 weeks do not appear to be a significant predictor of relapse risk.