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To determine the effectiveness of Problem-Solving Therapy (PST) in older hemodialysis (HD) patients by assessing changes in health-related quality of life and problem-solving skills.33 HD patients in an outpatient hemodialysis center without active medical and psychiatric illness were enrolled. The intervention group (n = 15) received PST from a licensed social worker for 6 weeks, whereas the control group (n = 18) received usual care treatment.In comparison to the control group, patients receiving PST intervention reported improved perceptions of mental health, were more likely to view their problems with a positive orientation and were more likely to use functional problem-solving methods. Furthermore, this group was also more likely to view their overall health, activity limits, social activities and ability to accomplish desired tasks with a more positive mindset.The results demonstrate that PST may positively impact mental health components of quality of life and problem-solving coping among older HD patients.PST is an effective, efficient, and easy to implement intervention that can benefit problem-solving abilities and mental health-related quality of life in older HD patients. In turn, this will help patients manage their daily living activities related to their medical condition and reduce daily stressors.

Urine protein screening rates among patients with type 2 diabetes are suboptimal despite evidence supporting its efficacy in preventing or slowing the progression of diabetic kidney disease (DKD) [1]. Testing of untimed urine specimens to quantify albumin (urine albumin-creatinine, or uACR)-the recommended screening test based on combination of simplicity, cost, and cardiovascular and renal prognostic value-is particularly underutilized, despite longitudinal efforts to improve awareness and screening among physicians [2].

Background Management trends in early chronic kidney disease (CKD) and their associations with clinical outcomes have not previously been reported. Methods We evaluated incident (Stage G3A) CKD patients from an integrated health care system in 2004–06, 2007–09 and 2010–12 to determine adjusted trends in screening (urinary protein quantification), treatment [prescription for angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), and statin] and nephrology referral. For the same time periods, adjusted rates for mortality, progression to Stage G4 CKD and hospitalization for myocardial infarction or heart failure were calculated and compared across time periods. Results There were 728, 788 and 956 patients with incident CKD in 2004–06, 2007–09 and 2010–12, respectively. Adjusted rates of proteinuria quantification (31, 39 and 51 screens/100 person-years), statin prescription (53, 63 and 64 prescriptions/100 person-years) and nephrology referral (2, 3 and 5 referrals/100 person-years) all increased over time (P for trend 0.4 in all cases). Conclusion In this integrated health care system, management of incident CKD over the past decade has intensified.

Background and objectives A modest protective association between bisphosphonate prescription and mortality among women with CKD but without clinically manifest cardiovascular disease has been shown. Whether a prior cardiovascular event (myocardial infarction, stroke, or heart failure) modifies this association is unknown. Design, setting, participants, & measurements A cohort of adult women with stages 3 and 4 CKD receiving primary care in a rural integrated health care system during the period 2004–2011 without history of advanced malignancy or organ transplantation ( n =6756, median age=74 years, median follow-up=4.3 years) was retrospectively assembled. The primary analysis compared those patients prescribed bisphosphonates (both prevalent and incident use during follow-up) with those patients not prescribed. Additional approaches were taken to account for survival and indication biases. The primary outcome was time to death by Cox multivariable regression. Results In the primary analysis, compared with women not prescribed a bisphosphonate, the hazard ratio (95% confidence interval) for death among women prescribed a bisphosphonate was 0.90 (0.78 to 1.04) if there was no history of cardiovascular event but 1.22 (1.04 to 1.42) if there was history of cardiovascular event ( P for interaction=0.004). In the additional approaches, associations between bisphosphonate prescription and mortality among those patients with a prior cardiovascular history varied: hazard ratios (95% confidence intervals) were 1.25 (1.01 to 1.57), 1.48 (1.16 to 1.88), and 0.94 (0.66 to 1.34). Interaction by prior cardiovascular event history varied across these three approaches ( P =0.07, P =0.22, and P =0.05). Conclusion In this study of women with CKD, the association between bisphosphonate treatment and mortality risk was inconclusive across a series of analyses designed to account for various types of selection and indication bias.

AIMS 30-day readmission rates after hospitalization for heart failure (HF) approach 25%, and patients with chronic kidney disease (CKD) are disproportionately represented. A retrospective cohort study was conducted to develop a prediction tool for 30-day readmission after hospitalization for HF among those with non-dialysis dependent CKD. METHODS Geisinger primary care patients with Stage 3 - 5 CKD hospitalized with a primary discharge diagnosis of HF during the period July 1, 2004 through February 28, 2010 were eligible. Multivariate logistic regression was employed to build models from predictors of 30-day readmission, drawn from demographic, clinical, laboratory, and pharmaceutical variables in the electronic health record. Variables were manually removed to achieve a model with satisfactory goodness-of-fit and parsimony while maximizing area under the receiver operating characteristic curve (AUC). Internal validation was performed using the bootstrap resampling method (1,000 samples) to provide a bias-corrected AUC. RESULTS 607 patients with CKD were admitted for HF during the study period; 116 (19.1%) were readmitted within 30 days. A model incorporating 23 variables across domains of medical history, active outpatient pharmaceuticals, vital signs, laboratory tests, and recent inpatient and outpatient resource utilization yielded an AUC (95% CI) of 0.792 (0.746 - 0.838). The bias-corrected AUC was 0.743. At an estimated readmission probability of 20%, the model correctly classified readmission status for 73% of the population, with a sensitivity of 69% and a specificity of 73%. CONCLUSION A robust electronic health record may facilitate the identification of CKD patients at risk for readmission after hospitalization for HF.

BACKGROUND/AIMS Dynamic changes in estimated glomerular filtration rate (eGFR) predict death among patients with chronic kidney disease (CKD). Whether variability in serial eGFR measurements is associated with risk of end stage renal disease (ESRD) has not been reported. METHODS We retrospectively analyzed the risk of ESRD as a function of eGFR variability (defined as the absolute value of the difference between the obtained clinical eGFR value at a given time and the eGFR value estimated by the linear regression line at the same time point) among a cohort of patients with Stage 3 CKD. The study population was comprised of adult primary care patients enrolled at Geisinger Clinic between January 1, 2004 and December 31, 2006, with Stage 3 CKD and a minimum of 4 serum creatinine results during this 3-year window, and without history of solid-organ transplant or metastatic cancer. Cohort members were followed through March 31, 2011 for ESRD (identified through linkage with the USRDS dataset of ESRD, or first outpatient eGFR < 15 ml/min/1.73 m2). A multivariate Cox proportional hazard model (adjusted for demographic factors, co-morbid conditions, medications, hospital-associated acute kidney injury, proteinuria, kidney function, and serum albumin, among other factors) was developed to test the association of eGFR variability with ESRD. RESULTS 4,219 patients met study criteria. Those with greater eGFR variability were more likely to have diabetes, cardiovascular disease, and better baseline kidney function than those with lesser variability. 193 (4.6%) of the overall cohort developed ESRD during a median follow-up of 3.8 years, while 596 (14.1%) died prior to study end without ESRD. Results of the multivariate-adjusted Cox proportional hazard model showed that eGFR variability is not associated with ESRD (HR 1.00 for the highest-variability quartile, relative to the lowest; 95% CI 0.66 - 1.51). CONCLUSION eGFR variability does not predict ESRD among patients with Stage 3 CKD.

Susmitha Dhanyamraju,1 Michael A Foltzer,2 Xiaoqin Tang,3 H Lester Kirchner,4 Robert M Perkins5,61Department of Nephrology, 2Department of Infectious Diseases, Geisinger Medical Center, Danville, PA, USA; 3Center for Health Research, Danville, PA, USA; 4Division of Medicine, Geisinger Medical Center, Danville, PA, USA; 5Department of Nephrology, Bassett Healthcare, Cooperstown, NY, USA; 6Bassett Research Institute, Bassett Medical Center, Cooperstown, NY, USABackground: The impact of bacteriuria on mortality and cardiovascular risk has not been previously reported for patients with chronic kidney disease (CKD).Objective: To assess the relationship between outpatient episodes of bacteriuria and mortality and cardiovascular risk among women with CKD.Design: Retrospective cohort study using an electronic health database from an integrated healthcare system in central Pennsylvania.Subjects: Adult women with CKD receiving primary care at Geisinger Health System between January 1, 2004 and December 31, 2009 were eligible, and were followed through December 31, 2010 for study outcomes.Main measures: The study exposure was bacteriuria, defined as an outpatient urine culture with bacterial growth of 104 cfu/mL. Treatment history (antibiotic prescription within 90 days) was identified. Study outcomes were death and the composite of hospitalization for myocardial infarction, congestive heart failure, or stroke. Multivariate-adjusted Cox models incorporated all bacteriuria episodes and antibiotic prescriptions in time-dependent fashion (in addition to other covariates) to account for the cumulative impact of infections, treatment, and hospitalization during follow-up.Key results: 6807 women were followed for a median (interquartile range) of 5.2 (3.4, 5.9) years. In adjusted models, each untreated bacteriuria episode was associated with an increased risk of death (hazard ratio [HR] 1.56, 95% CI 1.35–1.81) and the composite cardiovascular outcome (HR 1.32, 95% CI 1.05–1.65); treated episodes were not associated with an increased risk of death or cardiovascular events.Conclusion: Among female patients with CKD, untreated bacteriuria occurring in the outpatient setting is associated with an increased risk of death and cardiovascular morbidity.Keywords: bacteriuria, cardiovascular, chronic kidney disease, death, mortality

Measurement of albuminuria to stratify risk in chronic kidney disease (CKD) is not done universally in the primary care setting despite recommendation in KDIGO (Kidney Disease Improving Global Outcomes) guidelines. Pharmacist medication therapy management (MTM) may be helpful in improving CKD risk stratification and management. We conducted a pragmatic, cluster-randomized trial using seven primary care clinic sites in the Geisinger Health System to evaluate the feasibility of pharmacist MTM in patients with estimated glomerular filtration rate (eGFR) 45–59 ml/min/1.73 m2 and uncontrolled blood pressure (≥150/85 mmHg). In the three pharmacist MTM sites, pharmacists were instructed to follow a protocol aimed to improve adherence to KDIGO guidelines on testing for proteinuria and lipids, and statin and blood pressure medical therapy. In the four control clinics, patients received usual care. The primary outcome was proteinuria screening over a follow-up of 1 year. A telephone survey was administered to physicians, pharmacists, and patients in the pharmacist MTM arm at the end of the trial. Baseline characteristics were similar between pharmacist MTM (n = 24) and control (n = 23) patients, although pharmacist MTM patients tended to be younger (64 vs. 71 y; p = 0.06) and less likely to have diabetes (17 % vs. 35 %; p = 0.2) or baseline proteinuria screening (41.7 % vs. 60.9 %, p = 0.2). Mean eGFR was 54 ml/min/1.73 m2 in both groups. The pharmacist MTM intervention did not significantly improve total proteinuria screening at the population level (OR 2.6, 95 % CI: 0.5–14.0; p = 0.3). However, it tended to increase screening of previously unscreened patients (78.6 % in the pharmacist MTM group compared to 33.3 % in the control group; OR 7.3, 95 % CI: 0.96–56.3; p = 0.05). In general, the intervention was well-received by patients, pharmacists, and providers, who agreed that pharmacists could play an important role in CKD management. A few patients contacted the research team to express anxiety about having a CKD diagnosis without prior knowledge. Pharmacist MTM may be useful in improving risk stratification and management of CKD in the primary care setting, although implementation requires ongoing education and multidisciplinary collaboration and careful communication regarding CKD diagnosis. Future studies are needed to establish the effectiveness of pharmacist MTM on slowing CKD progression and improvement in cardiovascular outcomes. ClinicalTrials.gov, NCT02208674 Registered August 1, 2014, first patient enrolled September 30, 2014

Current knowledge about managing acute kidney injury in disaster situations stems mostly from lessons learned while taking care of crush syndrome patients during major earthquakes. More recently, there has been a greater focus on emergency preparedness for ESRD management. Natural or man-made disasters create an "austere environment," wherein resources to administer standard of care are limited. Advance planning and timely coordinated intervention during disasters are paramount to administer effective therapies and save lives. This article reviews the presentation and management of disaster victims with acute kidney injury and those requiring renal replacement therapies. Major contributions of some key national and international organizations in the field of disaster nephrology are highlighted. The article intends to increase awareness about nephrology care of disaster victims, among nephrology and non-nephrology providers alike.

Aim: Anemia is highly prevalent among patients wait-listed for renal transplant, and management with blood transfusion or erythropoietin stimulating agents may impact transplant wait time. The purpose of this study was to examine the impact of blood transfusion and erythropoiesis stimulating agent therapy on renal transplant wait time. Methods: We retrospectively analyzed all adult patients listed for first deceased donor kidney transplantation at two transplant centers in Central Pennsylvania between 2004 and 2008. The exposures of interest were blood transfusion and erythropoietin stimulating agent therapy. Cox proportional hazards were used to model time to deceased donor kidney transplant. Results: Among 407 patients listed for transplant, 84 received a deceased donor kidney during a median follow-up of 26.3 months. In an adjusted Cox proportional hazards model, with erythropoiesis stimulating agent and transfusion both treated as time-dependent exposures, UNOS inactive status at listing date (hazard ratio [HR] 0.81; 95% CI 0.73 - 0.89; P < 0.001) and transfusion during the wait list period (HR 0.27; 95% CI 0.11 - 0.69; P = 0.01) independently predicted longer transplant wait time. Erythropoiesis stimulating agent use prior to or after transplant wait listing date did not independently predict wait time. Conclusion: Blood transfusion while waitlisted for kidney transplant is strongly associated with prolonged wait time.

Background Pentoxifylline is a nonspecific phosphodiesterase inhibitor with anti-inflammatory properties. It reduces proteinuria in patients with glomerular disease, although its impact on glomerular filtration rate (GFR) is unknown. We hypothesized that pentoxifylline would slow the estimated GFR decrease in patients with chronic kidney disease at high risk of progression. Study Design Pilot randomized double-blind placebo-controlled trial. Setting & Participants 40 outpatients with decreased GFR, hypertension, and proteinuria greater than 1 g/24 h currently treated with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or the combination and followed up in a nephrology clinic at a tertiary medical care facility. Intervention Pentoxifylline, 400 mg twice daily, or matching placebo. Outcomes Difference in rates of estimated GFR change during the 1-year study period between the 2 groups. Measurements Estimated GFR (4-variable Modification of Diet in Renal Disease Study equation) and proteinuria by 24-hour urine collection were assessed at baseline and 6 and 12 months after enrollment. Results Baseline characteristics were similar between the 2 groups. At 1 year, the mean estimated GFR decrease was significantly less in the pentoxifylline group than the placebo group (−1.2 ± 7.0 versus −7.2 ± 8.2 mL/min/1.73 m 2 /y; mean difference, −6.0 mL/min/1.73 m 2 /y; 95% confidence interval, −11.4 to −0.6; P = 0.03). For pentoxifylline-treated participants, the mean estimated GFR decrease during treatment was slower compared with the year before study enrollment (−9.6 ± 11.9 mL/min/1.73 m 2 /y; mean difference, −8.4 mL/min/1.73 m 2 /y; 95% confidence interval, −14.8 to −2.1; P = 0.01). Proteinuria was not different between the pentoxifylline and placebo groups at baseline, 6 months, or 1 year. Limitations Small sample size and incomplete follow-up. Conclusions Pentoxifylline may slow the estimated GFR decrease in high-risk patients. This may be independent of its antiproteinuric properties and warrants further investigation.

Vascular endothelial growth factor (VEGF) is integral to the integrity of the glomerular filtration barrier. Bevacizumab is a humanized monoclonal antibody directed against VEGF with expanding clinical applications for metastatic solid tumours. We describe a case of a 61-year-old female with ovarian cancer and baseline chronic kidney disease who received three doses of bevacizumab and subsequently developed progressive renal clearance dysfunction and nephrotic range proteinuria. A renal biopsy was performed 4 months after drug discontinuation and was consistent with TMA. At baseline, prior to bevacizumab exposure, her estimated glomerular filtration rate (eGFR) was 44 mL/min/1.73 m(2) and she had no proteinuria. At the completion of therapy, eGFR was 27 mL/min/1.73 m(2) with 1+ proteinuria on urinalysis. Her renal failure and proteinuria continued to progress 5 months after discontinuation of bevacizumab therapy, at which time eGFR was 11 mL/min/1.73 m(2) and proteinuria was 5.5 g/24 h. Non-remitting TMA after bevacizumab therapy in patients with pre-existing chronic kidney disease has not been previously reported. Further studies are needed to assess the safety of this drug in patients with chronic kidney disease.

Until recently, it was not apparent whether apparent paradoxical associations of body mass index (BMI), lipids, and blood pressure with survival observed in hemodialysis (HD) patients, which contradict observations from the general population, also applied to peritoneal dialysis (PD) patients. Studies of survival in PD patients must account for differences in adjusted survival relative to HD patients, namely, early equivalent to superior survival, but after about 1-2 years, inferior survival. Several recent observational studies have analyzed the association between BMI and survival in PD patients from different perspectives and using different patient populations. In general, these studies found that any survival advantage associated with obesity is significantly less likely in PD than HD patients. Among PD patients, those who are obese can be said to have equivalent survival to PD patients with normal BMI. Studies of lipids and blood pressure in PD patients also yield conflicting associations with survival. Obese patients, especially if diabetic, may have increased risk of death after starting on PD compared to HD, although firm conclusions are premature given the limitations of current evidence. At present, the levels of lipids and blood pressure which are best associated with survival in PD patients are not well-defined.

Dipsogenic diabetes insipidus is a syndrome of disordered thirst, in patients without psychiatric disease, which may be confused with partial central diabetes insipidus. Distinguishing these entities involves monitored water testing. Therapy with antidiuretic hormone in patients with dipsogenic diabetes insipidus is thought to be contraindicated for fear of inducing water intoxication. We report a case of a 26-year-old woman without psychiatric illness referred for longstanding polyuria and polydipsia. Otherwise healthy, she complained of near-constant thirst and frequent urination, causing severe disruption of her personal and professional life. She had been consistently eunatremic and polyuric, with low urine osmolality. Results of extensive water testing revealed intact urinary concentrating and diluting capacity, physiologic though blunted antidiuretic hormone (ADH) release, and an abnormally low thirst threshold, consistent with the diagnosis of dipsogenic diabetes insipidus. To control her polyuria we initiated treatment with intermittent, low-dose, intranasal desmopressin and strict water restriction during drug dosing. In follow-up she reported excellent control of polyuria and significant functional improvement. The reviewed literature demonstrates a limited number of reports about dipsogenic diabetes insipidus, and no prior report of a similar treatment strategy. Dipsogenic diabetes insipidus is an uncommonly (and not universally) recognized disorder, requiring monitored testing in order to distinguish it from incomplete forms of central diabetes insipidus. Though therapy with desmopressin cannot be recommended based on the results of a single case, the outcome presented here is intriguing and suggests that larger studies in such patients is warranted to assess the broader application of such an intervention.

Background. The incidence, risk factors, recurrence rates and prognosis of thrombotic microangiopathy (TMA) among long-term dialysis patients in the United States have not been previously described in a national population. Methods. 272 024 Medicare primary patients in the United States Renal Data System (USRDS) initiated on end-stage renal disease (ESRD) therapy between 1 April 1995 and 31 December 1999 with Medicare as primary payer were analysed in a retrospective cohort study of USRDS of TMA. Cox regression was used to calculate adjusted hazard ratios (AHR) for risk of TMA and risk of death after TMA. Results. The incidence of TMA in the first year of dialysis was 0.5% overall. Among patients with renal failure due to haemolytic uraemic syndrome (HUS), the incidence of TMA was highest in the first year of dialysis (HUS, 11.3% first year, 4.5% per year thereafter), while among patients without HUS the incidence of TMA was much lower and more constant over time (0.3% per year). In Cox regression analysis, independent risk factors for TMA were renal failure due to HUS (adjusted hazard ratio (AHR) 179, 95% CI 95–338), paediatric age (� 18 years vs older, AHR 2.59, 95% CI 1.48–4.55), female gender (AHR 1.99, 95% CI 1.43–2.78), and systemic lupus erythematosus (SLE, AHR 3.66, 95% CI 1.49–8.51). One-year survival after TMA was poor at 58% (AHR for mortality 2.04, 95% CI 1.23–3.38). Conclusions. TMA is an uncommon cause of hospitalization after dialysis, but does recur in patients with HUS at a substantial rate. Younger age and SLE were risk factors for new onset TMA, which was associated with poor survival. Vigilant monitoring of select patients with HUS-related ESRD and higherrisk patients with SLE is warranted in the dialysis population.

The Russell-Silver syndrome's phenotypic features consist of musculoskeletal abnormalities, genitourinary malformations, craniofacial dysmorphy and cutaneous dyschromia, which is usually reported as café au lait spots. We present the first instances of a large, unilateral, achromic patch as an additional cutaneous manifestation of the Russell-Silver syndrome.

Background/Aims Single time-point GFR estimates are used for risk prognostication among those with CKD. Various applications of longitudinal eGFR using linear models, including time-independent slope and variability, have been shown to independently predict cardiovascular events. We wished to extend these applications by modeling longitudinal eGFR–forming estimates of current eGFR value and time-dependent eGFR slope at any point in time–and then test the independent association with cardiovascular event risk in an adjusted, joint longitudinal-survival model.

Adrian R Levy,1,2 Robert M Perkins,3 Karissa M Johnston,2 Sean D Sullivan,4 Vipan C Sood,5 Wendy Agnese,5 Mark A Schnitzler61Department of Community Health and Epidemiology, Dalhousie University, Halifax, NS, Canada; 2Oxford Outcomes Ltd, Vancouver, BC, Canada; 3Center for Health Research and Division of Nephrology, Geisinger Health System, Danville, PA, USA; 4School of Pharmacy, University of Washington, Seattle, WA, USA; 5Mitsubishi Tanabe Pharma America, Jersey City, NJ, USA; 6Departments of Internal Medicine and Community Health, Saint Louis University, St Louis, MO, USAPurpose: Predicting the timing and number of end-stage renal disease (ESRD) cases from a population of individuals with pre-ESRD chronic kidney disease (CKD) has not previously been reported. The objective is to predict the timing and number of cases of ESRD occurring over the lifetime of a cohort of hypothetical CKD patients in the US based on a range of baseline estimated glomerular filtration rate (eGFR) values and varying rates of eGFR decline.Methods: A three-state Markov model – functioning kidney, ESRD, and death – with an annual cycle length is used to project changes in baseline eGFR on long-term health outcomes in a hypothetical cohort of CKD patients. Using published eGFR-specific risk equations and adjusting for predictive characteristics, the probability of ESRD (eGFR

AIMS Depression is common among dialysis patients and is associated with adverse outcomes. Problem-solving therapy (PST) is effective for treating depression in older patients with chronic illness, but its effectiveness has never been reported in hemodialysis (HD) patients. We investigated the feasibility and satisfaction of PST and its impact on depression scores among older HD patients. METHODS Patients at least 60 years of age receiving maintenance HD at a single outpatient dialysis center were eligible for the study. Randomized patients received either 6 weeks of PST from a licensed renal social worker or usual care. This study modeled the staff-patient ratio standard of most dialysis clinics, and therefore only one social worker provided the interventions. Study outcomes included feasibility (successful completion of 6 weekly sessions) and patient satisfaction with PST as well as impact on depression scores (between-group comparison of mean Beck depression inventory (BDI) and Patient health questionnaire-9 (PHQ-9) scores at 6 weeks, and of mean change-from-baseline scores). RESULTS The recruitment rate was 92% (35/38). All subjects randomized to the intervention arm (n = 17) and who initiated PST (n = 15) completed the study, and all reported overall satisfaction with the intervention. 87% reported that PST helped them to better solve problems and improved their ability to cope with their medical condition. At 6 weeks, there were no significant differences in mean BDI and PHQ scores between the usual care and the intervention group (BDI 11.3 vs. 9.3, p = 0.6; PHQ 5.7 vs. 3.3, p = 0.1). Mean change-from-baseline depression scores were significantly improved in the intervention group relative to the control group (change in BDI 6.3 vs.- 0.6, p = 0.004; change in PHQ 7.2 vs. 0.3, p < 0.001). CONCLUSIONS The results demonstrate that PST is feasible in the dialysis unit setting, acceptable to patients, and may positively impact depression among maintenance hemodialysis patients.

To the Editor: We read with interest the excellent review by Turner et al. of both established and non-traditional treatment options for slowing progression of chronic kidney disease. The authors are to be commended for their consideration of novel applications of established therapies and metabolic targets not traditionally associated with treatments to slow disease progression. We wish to point out an omission in this report of a therapy with great promise. Pentoxifylline has been studied prospectively in more than 1000 patients enrolled in 19 clinical trials to date, with consistently positive results across disparate populations, without apparent toxicity, and with an excellent adverse-effect profile. Pentoxifylline is a non-specific phosphodiesterase inhibitor with renal anti-inflammatory, antioxidant, and anti-fibrotic activity. The drug targets a distinctly different pathophysiological mechanism of chronic kidney disease progression than that of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Pentoxifylline reduces proteinuria and preserves kidney function among patients with diabetic and non-diabetic chronic kidney disease, with or without concomitant inhibition of the renin–angiotensin axis, an important consideration given that a substantial proportion of diabetic patients either cannot tolerate or develop tachyphylaxis to such therapies. Health-care resources in the United States and globally will become increasingly constrained in the years to come; it is therefore essential that the nephrology community continues to explore new applications of existing therapies with demonstrated efficacy for slowing the progression of a disease that may impact X10% of the world’s adult population. We would be foolish to do otherwise.

Ion D Bucaloiu1, G Craig Wood2, Evan R Norfolk1, Christopher D Still3, James E Hartle1, Robert M Perkins41Department of Nephrology, Geisinger Medical Center, Danville, PA; 2Biostatistics and Research Data Core, Henry Hood Center for Health Research, Geisinger Medical Center, Danville, PA; 3Center for Nutrition and Weight Management, Geisinger Medical Center, Danville, PA; 4Department of Nephrology and Henry Hood Center for Health Research, Geisinger Medical Center, Danville, PA, USAPurpose: Precise estimation of creatinine clearance in obese individuals relies on the appropriate assessment of lean body weight (LBW). Anthropometric methods of predicting LBW have not been validated in morbidly obese populations.Patients and methods: Using an existing dataset of anthropometric data for a female cohort with morbid obesity who had undergone measured FFW with dual energy absorptiometry, we evaluated the performance of five previously reported estimating equations for the prediction of LBW. Linear regression was used to derive a new LBW prediction formula and was then compared with the other formulae.Results: Seventy females (mean [standard deviation] age, weight, and body mass index 43.0 [11.0] years, 128.1 [13.8] kg, and 48.3 [4.8] kg/m², respectively) were identified. LBW as estimated by the method of Garrow and Webster correlated well (r = 0.87) with measured mass while demonstrating the highest accuracy, best precision, and smallest bias (93%, 2.1 kg, and 2.9 kg, respectively; P < 0.0001 for all comparisons). The derived formula further improved bias, precision, and accuracy.Conclusion: Among females with morbid obesity, most previously reported estimating equations for LBW predicted FFW poorly. These findings have important clinical implications for the assessment of kidney function and for safe and effective drug dosing.Keywords: body composition, body weight, creatinine clearance, kidney function, lean body mass, obesity, pharmacokinetics

Summary Background and objectives Estimates of the effect of estimated GFR (eGFR) decline on mortality have focused on populations with normal kidney function, or have included limited information on factors previously shown to influence the risk of death among patients with CKD. Design, setting, participants, & measurements We retrospectively assessed the effect of rate of eGFR decline on survival of patients with CKD receiving primary care through a large integrated health care system in central Pennsylvania between January 1, 2004, and December 31, 2009. Results A total of 15,465 patients were followed for a median of 3.4 years. Median rates of eGFR change by those in the lower, middle, and upper tertiles of eGFR slope were −4.8, −0.6, and 3.5 ml/min per 1.73 m 2 /yr, respectively. In Cox proportional hazard modeling for time to death, adjusted for baseline proteinuria, changes in nutritional parameters, and episodes of acute kidney injury during follow-up (among other covariates), the hazard ratio for those in the lower (declining) and upper (increasing) eGFR tertiles (relative to the middle, or stable, tertile) was 1.84 and 1.42, respectively. Longitudinal changes in nutritional status as well as episodes of acute kidney injury attenuated the risk only modestly. These findings were consistent across subgroups. Conclusions eGFR change over time adds prognostic information to traditional mortality risk predictors among patients with CKD. The utility of incorporating eGFR trends into patient-risk assessment should be further investigated.

Background/Aims Dialysis and kidney transplantation adversely impact outcomes of total hip or knee arthroplasty (THA, TKA), but complication rates have not been reported for patients with less advanced stages of chronic kidney disease (CKD). Surgeons lack the data necessary to have informed discussions regarding anticipated outcomes of joint replacement for these patients.

A series of phosphonoalkenyl and (phosphonoalkenyl)oxy derivatives of purines and a pyrimidine were synthesized. These compounds are the first reported acyclonucleotides which incorporate the alpha,beta-unsaturated phosphonic acid moiety as the phosphate mimic and include compounds in which the acyclic substituent is attached to N-9 of a purine or N-1 of a pyrimidine by either a nitrogen-carbon or a nitrogen-oxygen bond. The phosphonoalkenyl-substituted compounds 7a-c, 8a-c, 9, 10, and 12 were prepared either by Mitsunobu coupling of alcohols with purine or pyrimidine derivatives or by alternative alkylations of the heterocyclic bases. The (phosphonoalkenyl) oxy derivatives 7d-g, 8d-g, and 11 were synthesized by coupling of alcohols with 9-hydroxypurines or a 1-hydroxypyrimidine under Mitsunobu conditions. The novel acyclonucleotides were tested for activity against herpes simplex types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV), visna virus, and human immunodeficiency virus type 1 (HIV-1). Guanine derivatives were moderately to extremely cytotoxic, but the adenines were less toxic to cells. At the concentrations tested, (Z)-isomers in the unbranched series had no activity against herpes viruses or HIV-1. (E)-9-[(4-Phosphonobut-3-enyl) oxy]adenine (7d) displayed selective activity against HIV-1, (E)-2,6-diamino-9-(4-phosphonobut-3-enyl) purine (9) showed selective antiretrovirus activity, and (E)-9-[2-(hydroxymethyl)-4-phosphonobut-3-enyl]adenine (7c) showed selective antiherpesvirus (VZV and CMV) activity.

Background: Although a review of the 1-month experience of a British intensive care unit (ICU) deployed in 2003 to Iraq outlining its care of 47 patients exists, a descriptive study outlining patient characteristics, workload, and outcomes of an ICU during a long-term deployment to Operation Iraqi Freedom is lacking in the medical literature. Methods: Between October 19, 2005, and October 19, 2006, the 10th Combat Support Hospital (CSH) deployed in an ICU to Ibn Sina Hospital in Baghdad, Iraq. Staff prospectively collected patient admission data from November 1, 2005, to August 31, 2006, in handwritten logbooks. This information included nationality (United States/Iraqi/other), military versus civilian, mechanism of injury or nontrauma admission diagnosis, ICU length of stay (LOS), and outcome. These data were retrospectively reviewed for the purpose of reporting the experience of the 10th CSH ICU during its deployment. Results: The 10th CSH ICU admitted 875 patients during the study period. This represented 27% of all hospital admissions (n = 3289). Categories of patients admitted to the ICU included United States military, US contractor, Iraqi military, Iraqi civilian, non-US contractor, coalition military personnel, and security internee. Three patients were unable to be classified due to missing information. The most common patient category of admission was Iraqi civilian (n = 472, 53.9%). Noncoalition (Iraqi civilian, Iraqi military, non-US contractors, and other noncoalition military) admissions made up 76.9% (n = 673) of all admissions. US military (n = 165) and US contractors (n = 31) made up 22.4% of all ICU admissions. Trauma-related admissions were the most common diagnoses (n = 730, 83.4%). Other admission diagnostic categories included medical (n = 125, 14.3%) and postoperative (n = 5, 0.6%) patients. A total of 15 patients (1.7%) were unable to be categorized based on diagnosis due to missing information. The most common medical diagnosis requiring ICU admission was related to cardiovascular disease (n = 51, 40.8%). Seven of the admissions to the ICU were pediatric patients (0.8%). US military personnel traumatically injured suffered significantly more explosion injuries and burns than their Iraqi military and other noncoalition military counterparts. The ICU LOS was significantly shorter in US military and US contractor patients compared to all other groups, likely a result of expeditious air evacuation to a higher level of care. This air evacuation of US personnel combined with the fact that Iraqi patients were transferred to local civilian hospitals prior to the completion of intensive care stay limited follow-up. Despite a lack of meaningful follow-up, the observed ICU all-cause mortality was 5.0% (n = 44). Conclusions:The primary mission of a US military ICU deployed in support of combat operations is the care of its injured troops. However, the 10th CSH deployed in an urban region of Iraq in a mature theater of operations and its ICU more commonly cared for non-US patients during combat medical operations. These patients included pediatric patients as well as admissions for nontrauma illnesses. This mission was accomplished by nurses and physicians faced with unique challenges and resulted in an acceptable ICU mortality rate.

Background: Renal replacement therapy has been used by the U.S. Army at the combat support hospital echelon of care since the Korean conflict. Although there has been a general decline in the incidence of wartime acute kidney injury, the mortality associated with acute kidney injury and the use of renal replacement therapy remain unchanged, in the range of 60% to 80%. The U.S. Army official doctrine is that field dialysis is provided through a specialized Hospital Augmentation Team; however, this team has not been deployed to either Iraq or Afghanistan as a result of the ability to rapidly evacuate most cases requiring renal replacement therapy. The history of wartime renal replacement therapy is reviewed along with the general epidemiology of battlefield acute kidney injury and renal replacement therapy. Discussion: Recent literature documents cases of renal replacement therapy performed in and out of theater in support of the current operations. In-theater renal replacement therapy has been provided through a variety of modalities, including conventional hemodialysis, peritoneal dialysis, and both continuous venovenous and continuous arteriovenous hemodialysis. Out of theater, casualties have received both intermittent and continuous hemodialysis at Landstuhl Regional Medical Center and Walter Reed Army Medical Center, whereas patients sustaining burns have undergone aggressive continuous venovenous hemofiltration or hemodiafiltration at Brooke Army Medical Center. Summary: Acute kidney injury requiring renal replacement therapy in wartime casualties is an uncommon occurrence but one with extremely high mortality. Future doctrine should be prepared for contingencies in which the incidence may be increased as a result of mass crush injury casualties or prolonged evacuation times.

Published analyses of clinical outcomes for patients requiring large-volume blood transfusion conflict with respect to the impact upon plasma potassium levels. We analyzed a cohort of trauma patients to ascertain the impact of component product transfusion upon plasma potassium values.We performed an observational analysis of previously, prospectively collected clinical data on 131 noncrush trauma patients undergoing resuscitation during the initial 12 hours after admission to a combat support hospital. Comparisons were made between those who received packed red blood cell (PRBC) transfusion and those who did not. Primary outcome was hyperkalemia (plasma potassium level5.5 mmol/L).Ninety-six of one hundred thirty-one patients (73.3%) received PRBCs (mean number of PRBC units 11.2, range, 0-55.0). For transfusion versus nontransfusion patients, baseline plasma potassium value (3.7 +/- 0.57 mmol/L vs. 3.6 +/- 0.36 mmol/L, p = 0.22) rose significantly after transfusion (5.3 +/- 1.2 mmol/L, vs. 4.0 +/- 0.78 mmol/L, p0.001). During the study period, 38.5% of transfusion patients developed hyperkalemia, versus 2.9% of those who did not (p = 0.003). In multivariate logistic regression analysis, transfusion of greater than 7 units of PRBCs was independently associated with the development of hyperkalemia (RR 4.72, 95% CI 1.01-21.97, p = 0.048). Transfusion of other cell-based products, baseline base deficits, and plasma bicarbonate levels were not. Spearman's rank correlation coefficient for the relationship of number of transfused PRBC units to the highest recorded potassium value was 0.554 (p0.001). The predictive accuracy of the logistic regression model for hyperkalemia was 0.824 (95% CI 0.747-0.901, p0.001).Hyperkalemia is common after PRBC transfusion, and often severe. PRBC transfusion is independently associated with the development of hyperkalemia. The findings suggest the need for interventional studies examining the impact of alternative resuscitative approaches after severe trauma.

Until recently, it was not apparent whether apparent paradoxical associations of body mass index (BMI), lipids, and blood pressure with survival observed in hemodialysis (HD) patients, which contradict observations from the general population, also applied to peritoneal dialysis (PD) patients. Studies of survival in PD patients must account for differences in adjusted survival relative to HD patients, namely, early equivalent to superior survival, but after about 1-2 years, inferior survival. Several recent observational studies have analyzed the association between BMI and survival in PD patients from different perspectives and using different patient populations. In general, these studies found that any survival advantage associated with obesity is significantly less likely in PD than HD patients. Among PD patients, those who are obese can be said to have equivalent survival to PD patients with normal BMI. Studies of lipids and blood pressure in PD patients also yield conflicting associations with survival. Obese patients, especially if diabetic, may have increased risk of death after starting on PD compared to HD, although firm conclusions are premature given the limitations of current evidence. At present, the levels of lipids and blood pressure which are best associated with survival in PD patients are not well-defined.

The trauma patient is exposed to physiologic processes and life-saving interventions that predispose to hyperkalemia. Severe elevations in potassium levels subject this compromised patient to additional cardiac risks in the periresuscitative period. Recent advances in the care of the massively traumatized patient may or may not increase the risk for hyperkalemia. This prospective, observational study was undertaken to define the period prevalence of hyperkalemia (plasma potassium levelor = 5.5 mmol/L) in a noncrush trauma population during the initial resuscitative period and to identify potential risk factors for the development of hyperkalemia. A total of 131 patients were studied during the initial 12 h after admission for noncrush trauma. The period prevalence of hyperkalemia was 29.0%. Hyperkalemic patients had dramatic shifts in plasma potassium levels compared with nonhyperkalemic patients. Five patients, all from the hyperkalemic group, died. By multivariate logistic regression analysis, independent risk factors for hyperkalemia were an emergency department plasma potassium level of 4.0 mmol/L or higher (relative risk 3.40; 95% confidence interval 1.17 to 9.84; P = 0.024 versus baseline potassium level4.0 mmol/L) and transfusion of cell- or plasma-based products (relative risk 10.56; 95% confidence interval 3.62 to 30.78; P0.001 per log-transformed unit). The prevalence of hyperkalemia during trauma resuscitation was not reported previously. Given the arrhythmic risks of hyperkalemia, particular caution is necessary with trauma patients who present with plasma potassium levels4.0 mmol/L and require aggressive transfusion support.

Background Previously, patients with end-stage renal disease (ESRD) with uncontrolled hyperparathyroidism had few options other than parathyroidectomy, which was reserved for patients refractory to medical therapy. Newer calcimimetic agents, such as cinacalcet, may be an alternative, but raise the possibility of indefinite medical treatment that also would increase costs. Study Design Cost utility analysis. Setting & Population Base case consisted of prevalent adult US patients with ESRD refractory to management with standard medical therapy. Characteristics were obtained from patients who underwent parathyroidectomy in 2001, and, for purposes of comparison, patients in whom cinacalcet was used were assigned similar characteristics. All data came from preexisting literature and trials or from US Renal Data System analysis files. Intervention Use of cinacalcet hydrochloride versus parathyroidectomy. Perspective & Time Frame Medicare and societal costs and quality-adjusted life-years from the date of parathyroidectomy or use of cinacalcet followed up for 2 years, respectively. Model & Outcomes Primary outcomes were cost (measured in US dollars) and cost utility measured using cost per quality-adjusted life-years. Results At base-case surgical and drug costs, surgical and drug success rates, complication rates/costs, and benefit from correction of hyperparathyroidism, parathyroidectomy was found to be both less expensive and more cost-effective at 7.25 ± 0.25 months. Parathyroidectomy became more cost-effective at 15.28 to 16.32 months at the upper limit of sensitivity analysis, when drug/surgical costs and success/complication rates/costs were maximally weighted to favor cinacalcet-based medical therapy. Limitations We assumed current costs of both cinacalcet and parathyroidectomy and assumed cinacalcet use would be indefinite. Conclusions For patients with ESRD with uncontrolled hyperparathyroidism who are good candidates for either drug therapy or surgery, cinacalcet hydrochloride is the most cost-effective modality if the patient is to remain on dialysis therapy for 7.25 ± 0.25 months. Cinacalcet may be more optimal if used in patients who have high risk of mortality or who would expect to receive a kidney transplant quickly. For other subgroups, parathyroidectomy dominated.

Whether the previously reported underutilization of standard-of-care medications in the management of patients with acute myocardial infarction (AMI) persists in more recent years or differs by ward of admission has not been reported.We performed a retrospective cross-sectional study of patients hospitalized with a discharge diagnosis of incident AMI to a Department of Defense hospital (Walter Reed Army Medical Center, Washington, DC) from 2001 through 2004. Use of beta-blockers and aspirin at the time of discharge after AMI was assessed according to Modification of Diet in Renal Disease (MDRD) estimated glomerular filtration rate (eGFR) in milliliters per minute per 1.73 m2, stratified by admission to the coronary care unit (CCU) versus other wards. Adjusted odds ratios for discharge beta-blocker and aspirin therapy were calculated by using logistic regression.Among 431 patients, overall discharge use of beta-blockers was 86.8%, and aspirin, 86.8%, both significantly greater after CCU admission than admission to other wards (93%, aspirin use; 91.7%, beta-blocker use; P0.001 and P0.001). In logistic regression, CCU admission was the only independent factor associated with either beta-blocker or aspirin use; MDRD eGFR was not associated significantly with beta-blocker and aspirin use regardless of admission to the CCU or non-CCU.Future studies of disparities in use of standard-of-care medications after AMI according to renal function should account for the primary site of admission, particularly CCU versus others. In addition, legitimate contraindications to the use of beta-blockers and aspirin may be subtle, including appropriate end-of-life decisions.

Patients with chronic kidney disease (CKD) suffer the paradox of high risk for heart disease and yet reduced use of standard therapies for treatment and prevention of heart disease. The classic example in the literature is the reduced use of standard of care medications after acute myocardial infarction (AMI), now shown in a variety of settings even where the cost of prescription drugs should be a minimal factor (1,2). Only since 2002 has the Joint Commission on Accreditation of Hospitals (JCAHO) stipulated ORYX core indicators, which recommend the use of aspirin and β blockers in a setting of AMI unless explicitly contraindicated, a timeframe only one study yet published has included (2,3). Are primary care physicians really basing therapy after AMI on kidney function (and in most studies this means serum creatinine)? This seems difficult to believe, especially as many studies indicate that a large proportion of patients admitted for AMI never have serum creatinine levels drawn. If true, this would seem a potentially “easy” fix in this era of electronic medical records and automated reminders. However, perhaps poor kidney function is strongly associated with other factors that lead to reduced use of standard of care medications. The identification of these other potential factors has been only partially addressed by previous studies, and is …

NKF-KDOQI CKD STAGE PROGRESSION AND REGRESSION AMONG PRIMARY CARE PATIENTS WITH MILD-TOMODERATELY IMPAIRED KIDNEY FUNCTION Walter (Buzz) Stewart, Jennifer Sartorius, Melissa Stahl, Kathleen Fox, Ze Cong, Robert Perkins Center for Health Research, Geisinger Medical Center, Danville, PA; Strategic Healthcare Solutions, LLC, Monkton, MD; Amgen, Inc, Thousand Oaks, CA Little is known about the stability of kidney function over time in large, community-based populations. We identified predominantly Caucasian adult (>30 yrs) primary care patients from The Geisinger Clinic (central/northeastern Pennsylvania). Using electronic health records, patients (n=105,026) were followed from Jan 2004 to Dec 2009 and assigned to 1 of 7 initial CKD stages (stage 1-5, including 3A/3B, or no CKD) based on NKF-KDOQI criteria and the CKD-EPI eGFR formula. The primary outcome was the CKD stage at final follow-up for patients initially in stage 3A or 3B. Patients (n=6267) in stage 3A had a median age of 65 and were 62.7% female. Patients (n= 2891) in stage 3B had a median age of 70 and were 66.5% female. Over a median follow-up period of 5.9 years, only 1/3 of patients with stage 3 CKD changed in stage. For stage 3A patients, progression to 3B was slightly more likely than regression, though regression to a milder CKD stage was 10 times more likely than progression to CKD 4 or 5. For stage 3B patients, 13% progressed to stage 4-5 and regression (largely to stage 3A) was about as likely as progression. CKD cases by initial stage (3A or 3B) and status at final follow-up Initial Stage Final Stage n(%) 0 1-2 3A 3B 4-5 3A (n = 6267) 608 (9.7%) 295 (4.7%) 4176 (66.6%) 1100 (17.6%) 88 (1.4%) 3B (n = 2891) 24 (0.8%) 19 (0.7%) 434 (15.0%) 2030 (70.2%) 384 (13.3%) Regression to relatively milder CKD among patients with stage 3A and 3B CKD is not uncommon, and progression to stage 4-5 is relatively uncommon, particularly for those with stage 3A disease at baseline. The implications of these findings for current NKF/KDOQI screening and risk stratification guidelines should be further investigated.

A series of phosphonoalkenyl and (phosphonoalkenyl)oxy derivatives of purines and a pyrimidine were synthesized. These compounds are the first reported acyclonucleotides which incorporate the alpha,beta-unsaturated phosphonic acid moiety as the phosphate mimic and include compounds in which the acyclic substituent is attached to N-9 of a purine or N-1 of a pyrimidine by either a nitrogen-carbon or a nitrogen-oxygen bond. The phosphonoalkenyl-substituted compounds 7a-c, 8a-c, 9, 10, and 12 were prepared either by Mitsunobu coupling of alcohols with purine or pyrimidine derivatives or by alternative alkylations of the heterocyclic bases. The (phosphonoalkenyl) oxy derivatives 7d-g, 8d-g, and 11 were synthesized by coupling of alcohols with 9-hydroxypurines or a 1-hydroxypyrimidine under Mitsunobu conditions. The novel acyclonucleotides were tested for activity against herpes simplex types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV), visna virus, and human immunodeficiency virus type 1 (HIV-1). Guanine derivatives were moderately to extremely cytotoxic, but the adenines were less toxic to cells. At the concentrations tested, (Z)-isomers in the unbranched series had no activity against herpes viruses or HIV-1. (E)-9-[(4-Phosphonobut-3-enyl) oxy]adenine (7d) displayed selective activity against HIV-1, (E)-2,6-diamino-9-(4-phosphonobut-3-enyl) purine (9) showed selective antiretrovirus activity, and (E)-9-[2-(hydroxymethyl)-4-phosphonobut-3-enyl]adenine (7c) showed selective antiherpesvirus (VZV and CMV) activity.

Evidence has accumulated that di- and trisialogangliosides are involved in the interaction of cells with fibronectin. We have therefore tested the ability of variants of BALB/c 3T3 deficient in such gangliosides to organize a fibronectin matrix and to spread on fibronectin-coated substrates. Whereas BALB/c 3T3 cells contained gangliosides GM3, GM1, and GD1a, direct chemical analysis showed that five out of six variants isolated contained no detectable GD1a. By the overlaying of thin layer chromatograms of cellular gangliosides with 125I-cholera toxin, these variants were also found to lack ganglioside GM1. In contrast, the sialogalactoprotein profile of these cells, analyzed using an 125I-ricin/SDS polyacrylamide gel overlay technique, was similar to that of the parent cell line. All variants organized an extensive fibronectin matrix comparable to that of BALB/c 3T3, as shown using either immunofluorescence or lactoperoxidase-catalyzed iodination. The variants could also spread on fibronectin-coated substrates and adopt a morphology similar to that of BALB/c 3T3 cells, with little or no difference in the concentration of fibronectin required for 50% cell spreading. Cell spreading of the variants was accompanied by the formation of focal contacts and microfilament bundles, in a manner closely resembling that seen with BALB/c 3T3 cells. Treatment of BALB/c 3T3 cells with neuraminidase, which converts much of the cellular GD1a to GM1, did not affect cell spreading on fibronectin. The results clearly demonstrate that complex gangliosides are not essential for retention of a fibronectin matrix or for spreading on fibronectin-coated substrates.

Acute kidney injury increases mortality risk among those with established chronic kidney disease. In this study we used a propensity score-matched cohort method to retrospectively evaluate the risks of death and de novo chronic kidney disease after reversible, hospital-associated acute kidney injury among patients with normal pre-hospitalization kidney function. Of 30,207 discharged patients alive at 90 days, 1610 with reversible acute kidney injury that resolved within the 90 days were successfully matched across multiple parameters with 3652 control patients who had not experienced acute kidney injury. Median follow-up was 3.3 and 3.4 years (injured and control groups, respectively). In Cox proportional hazard models, the risk of death associated with reversible acute kidney injury was significant (hazard ratio 1.50); however, adjustment for the development of chronic kidney injury during follow-up attenuated this risk (hazard ratio 1.18). Reversible acute kidney injury was associated with a significant risk of de novo chronic kidney disease (hazard ratio 1.91). Thus, a resolved episode of hospital-associated acute kidney injury has important implications for the longitudinal surveillance of patients without preexisting, clinically evident kidney disease.