In Critically Ill Patients Requiring CRRT,AKI Is Associated with Increased Respiratory Failure and Death Versus ESRD

Background/aims: To compare outcomes of critically ill patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) versus those with pre-existing end-stage renal disease (ESRD) requiring CRRT to identify factors that contribute to the increased mortality seen in AKI patients. Methods: Retrospective cohort of 257 intensive care unit (ICU) patients who received CRRT. AKI is defined as requiring CRRT with an admission serum creatinine ≤1 mg/dL; ESRD is defined as chronic dialysis dependence. Primary outcome was hospital mortality. Multivariate logistic regression was performed to determine the impact of APACHE II score, intubation, vasopressors, infection, diabetes, hypertension, gender, and race on mortality. Results: Of 257 patients requiring CRRT, 28 had ESRD and 108 had AKI. Hospital mortality was higher in patients with AKI versus ESRD (69% vs. 39%, p = 0.0032). Severity of illness using APACHE II was similar in AKI and ESRD. Patients with AKI were more likely to require mechanical ventilation (89% vs. 57%, p = 0.0003). After multivariate analysis, the requirement for mechanical ventilation was the single factor associated with increased hospital mortality [odds ratio (OR): 3.1]. Conclusions: In ICU patients requiring CRRT, patients with AKI have a higher mortality than patients with ESRD due to an increased need for mechanical ventilation.     

Long-Term Risk of Coronary Events after AKI

The incidence rate of AKI in hospitalized patients is increasing. However, relatively little attention has been paid to the association of AKI with long-term risk of adverse coronary events. Our study investigated hospitalized patients who recovered from de novo dialysis-requiring AKI between 1999 and 2008 using patient data collected from inpatient claims from Taiwan National Health Insurance. We used Cox regression with time-varying covariates to adjust for subsequent CKD and ESRD after discharge. Results were further validated by analysis of a prospectively constructed database. Among 17,106 acute dialysis patients who were discharged, 4869 patients recovered from dialysis-requiring AKI (AKI recovery group) and were matched with 4869 patients without AKI (non-AKI group). The incidence rates of coronary events were 19.8 and 10.3 per 1000 person-years in the AKI recovery and non-AKI groups, respectively. AKI recovery associated with higher risk of coronary events (hazard ratio [HR], 1.67; 95% confidence interval [95% CI], 1.36 to 2.04) and all-cause mortality (HR, 1.67; 95% CI, 1.57 to 1.79) independent of the effects of subsequent progression to CKD and ESRD. The risk levels of de novo coronary events after hospital discharge were similar in patients with diabetes alone and patients with AKI alone (P=0.23). Our results reveal that AKI with recovery associated with higher long-term risks of coronary events and death in this cohort, suggesting that AKI may identify patients with high risk of future coronary events. Enhanced postdischarge follow-up of renal function of patients who have recovered from temporary dialysis may be warranted.The incidence rate of AKI in hospitalized patients is increasing¹ and the number of deaths associated with dialysis-requiring AKI has more than doubled.² In hospitalized patients, AKI results in increased in-hospital and posthospitalization resource use.³Currently, the incidence rate of dialysis-requiring AKI is higher than the rate of ESRD, and its annual growth rate is as high as 10% in the United States.⁴ Along with the advances in critical care medicine and dialysis technologies, the probability of being discharged alive after temporary AKI has been rising among hospitalized patients.⁵ It has been noticed that patients ever suffering AKI have a greater risk for ESRD and higher long-term mortality than individuals with no such episode.^4,6,7 It is unclear whether patients ever having AKI have higher risk for other long-term adverse events.Diabetes mellitus (DM) is well recognized as a contributing risk factor for coronary events, and advanced CKD has been recently acknowledged as another risk factor.⁸ Rapidly declining kidney function could associate with higher risk for cardiovascular disease (CVD) among patients with or without CKD.⁹ Nevertheless, relatively little effort has been devoted to establishing a clear association between AKI and the long-term incidence of adverse coronary events. In contrast to the currently accepted criteria that include diabetes as a CVD risk factor,¹⁰ no study has ascertained the contributing role of AKI in subsequent CVD incidence.We hypothesized that hospitalized patients surviving temporary dialysis would have higher probability of developing coronary events in the long term and higher all-cause mortality than their counterpart patients with no such experience. We used data from a large population-based cohort to examine whether dialysis-requiring AKI would have a long-term effect similar to the effect from diabetes in terms of risk for coronary events.     

Impact of dialysis requirement on outcomes in tumor lysis syndrome

Tumor lysis syndrome (TLS) is a life threatening emergency due to destruction and massive release of intracellular metabolites from cancer cells often resulting in acute kidney injury (AKI), sometimes severe enough to require dialysis (AKI‐D). The impact of dialysis requirement in AKI has not been explored. We utilized data from the Nationwide Inpatient Sample and using International Classification of Diseases, 9th Revision, diagnoses codes for TLS, AKI and dialysis, evaluated the incidence, risk factors and impact of AKI‐D on mortality, adverse discharge and length of stay (LOS). Survey multivariable logistic regression was used to compute adjusted Odds Ratios (aOR and 95% confidence intervals (CI). An estimated 12% (2,919) of all TLS hospitalizations (n = 22 875) develop AK‐D. After adjustment for confounders, AKI‐D was associated with greater odds of mortality (aOR 1.98; (95% CI 1.60–2.45)), adverse discharge (aOR 1.63 (95% CI 1.19–2.24)) and longer LOS (19 vs 14.6 days; P < 0.01) compared with those without AKI‐D. Further studies to evaluate the association of AKI‐D on long‐term outcomes in patients with TLS are needed.     

Does Early Initiation of Continuous Renal Replacement Therapy Affect Outcome: Experience in a Tertiary Care Center

Abstract

Background: Acute kidney injury (AKI) requiring dialysis commonly occurs in critically ill patients and is associated with high mortality. Factors impacting outcomes of individuals with AKI who underwent continuous renal replacement therapy (CRRT), including early versus late initiation and duration of CRRT, were examined. Methods: Survival and recovery of renal function for patients with AKI in the intensive care unit were retrospectively examined over a 7-year period. Factors associated with mortality and renal recovery were analyzed based on severity of illness as defined by Cleveland Clinic Foundation (CCF) score. Univariate and multivariate logistic regression analysis with backward elimination was performed to determine the most significant risk factors. Results: Of patients who underwent CRRT, 230/330 met inclusion criteria. During index admission 112/230 (48.7%) patients died. Median survival was 15.5 days [95% confidence interval (12.0, 18.0)]. Among survivors, renal recovery occurred in 84/118 (71.2%). Renal recovery overall was observed in 90/230 subjects (39.13%). A higher baseline CCF score correlated with higher mortality and lower probability of renal recovery. Patients initiated on CRRT > 6 days after AKI diagnosis had significantly higher mortality compared with those initiated earlier (odds ratio = 11.66, p = 0.0305). Patients receiving CRRT >10 days had a higher mortality rate compared with those with shorter exposure (71.3% vs. 45.5%, respectively, p = 0.012). Conclusions: CRRT remains an important dialysis modality in hemodynamically unstable patients with AKI. Mortality in these patients continues to be high. Renal recovery is high in survivors. Delay in initiation and length of CRRT exposure may portend poorer prognosis.     

Acute kidney injury: Epidemiology,outcomes, complications,and therapeutic strategies

Acute kidney injury (AKI) is one of the most common serious complications for all hospital admissions, with its incidence increasing among hospitalized patients, particularly those in the intensive care unit. Despite significant improvements in critical care and dialysis technology, AKI is associated with an increased risk of short‐ and long‐term mortality, prolonged hospital stays, and dialysis dependence. These risks are particularly relevant for critically ill patients with AKI severe enough to require renal replacement therapy (RRT). No specific pharmacologic treatment has been established to treat AKI. Hence, the mainstay treatment for patients with AKI is RRT even though there are still several problematic issues regarding its use including RRT modality, dose, and timing. Recently, the impact of AKI on an increased risk of progression to chronic kidney disease (CKD) and end‐stage renal disease requiring dialysis or transplantation is attracting increased attention.     

Effects of Different Dialysis Modalities on Cardiac Autonomic Dysfunctions in End‐Stage Renal Disease Patients: One Year Prospective Study

Cardiac autonomic dysfunction (CAD) is a common problem in patients with end‐stage renal disease (ESRD) and may contribute to the risk of cardiac mortality. Long‐term effects of dialysis modalities on CAD in ESRD patients are not clear. In this one‐year prospective study, we studied the effects of different dialysis modalities on CAD in ESRD patients. The study consisted of 20 ESRD patients who had the indications for initiating dialysis therapy (13 hemodialysis and 7 CAPD patients) and 15 healthy controls (M/F: 5/10; age 30 ± 4). In all the subjects, first at the beginning of study (in patient groups just before initiating dialysis therapy) and then after 12 months, we studied 24 hours ECG‐Holter monitoring and heart rate variability parameters (time and frequency domain analysis parameters; SDNN: standard deviations of nn intervals, rMSSD: square root of the median of standard deviation, HRVI: heart rate variability index, LF/HF: low frequency/high frequency). In ESRD patients, before dialysis therapy, all the parameters of time domain analysis were significantly lower compared to control group (p = 0.001). In patient groups, after dialysis therapy (on the 12th month), significant improvement was observed in time domain analysis parameters (p = 0.001). When dialysis modalities were compared, the increase in the time domain analysis parameters was significantly greater in the CAPD group compared to hemodialysis (HD) group. Our findings suggest that CAD is frequent in ESRD patients, a dialysis therapy of 12 months can cause significant improvement on CAD and the ameliorative effect of CAPD is better than HD.     

Acute Kidney Injury Increases Risk of ESRD among Elderly

Risk for ESRD among elderly patients with acute kidney injury (AKI) has not been studied in a large, representative sample. This study aimed to determine incidence rates and hazard ratios for developing ESRD in elderly individuals, with and without chronic kidney disease (CKD), who had AKI. In the 2000 5% random sample of Medicare beneficiaries, clinical conditions were identified using Medicare claims; ESRD treatment information was obtained from ESRD registration during 2 yr of follow-up. Our cohort of 233,803 patients were hospitalized in 2000, were aged ≥67 yr on discharge, did not have previous ESRD or AKI, and were Medicare-entitled for ≥2 yr before discharge. In this cohort, 3.1% survived to discharge with a diagnosis of AKI, and 5.3 per 1000 developed ESRD. Among patients who received treatment for ESRD, 25.2% had a previous history of AKI. After adjustment for age, gender, race, diabetes, and hypertension, the hazard ratio for developing ESRD was 41.2 (95% confidence interval [CI] 34.6 to 49.1) for patients with AKI and CKD relative to those without kidney disease, 13.0 (95% CI 10.6 to 16.0) for patients with AKI and without previous CKD, and 8.4 (95% CI 7.4 to 9.6) for patients with CKD and without AKI. In summary, elderly individuals with AKI, particularly those with previously diagnosed CKD, are at significantly increased risk for ESRD, suggesting that episodes of AKI may accelerate progression of renal disease.Although short-term consequences of acute kidney injury (AKI) have been extensively studied,^1–4 the rate of development of end-stage renal disease (ESRD) after AKI has been poorly defined in a representative sample. Moreover, the potential linkage between patients with AKI, chronic kidney disease (CKD), and ESRD has been poorly studied and remains ill defined, particularly among elderly individuals, who represent the fastest growing segment of the ESRD population. Since 1972, all patients who have ESRD and are eligible for Social Security in the United States have been entitled to all Medicare benefits, regardless of age. All US renal dialysis units and transplant facilities are required to complete the Centers for Medicare & Medicaid Services (CMS) End-Stage Renal Disease Medical Evidence Report (CMS-2728) for each patient receiving initial treatment at that site. The Medical Evidence Report registers all patients who have ESRD with the US Renal Data System (USRDS), which maintains the data. Thus, patients entitled to ESRD therapy after AKI can be found in the USRDS database.The primary objective of our study was to determine the postdischarge incidence rates and hazard ratios (HR) for developing ESRD in elderly individuals who sustain AKI. A secondary objective was to assess the difference in developing ESRD between elderly individuals with and without CKD.     

Incidence, risk factors and prognosis of acute kidney injury after transcatheter aortic valve implantation

Aim: Transcatheter aortic valve implantation (TAVI) poses a significant risk of acute kidney injury (AKI). Little is known of the impact of TAVI and AKI on long‐term kidney function and health cost. We explored the predictive factors and prognostic implications of AKI following TAVI. Methods: Single‐centre retrospective analysis of 52 elderly patients undergoing TAVI was conducted. The primary endpoint was renal outcome which included the incidence of AKI and 12‐month renal function after TAVI. Secondary endpoints were mortality, the length of hospital stay (LOS) and cost. Results: AKI occurred in 15/52 (28.8%) patients (mean age 84 ± 6) and three patients (6%) required dialysis. Patients with AKI (AKI+) had greater comorbidity (diabetes and cerebrovascular disease) and a trend towards reduced estimated glomerular filtration rate (eGFR) at baseline compared with those without AKI (56.6 vs AKI?: 65.7 mL/min per 1.73 m², P = 0.07). Following TAVI, AKI? patients experienced an immediate improvement in eGFR, which remained significantly higher at all time points compared with AKI+ patients (70.4 vs 46.9 at 6 months and 73.7 vs 53.0 at 12 months, P < 0.001). Cumulative mortality for AKI+versus AKI? group was 26.7% and 2.7% (P = 0.006). LOS doubled (P < 0.001) and average hospitalization cost per patient was 1.5 times higher in the AKI+ group (P < 0.001). Independent predictors of AKI were peri‐procedural blood transfusion (OR: 2.4, 95% CI: 2.0–3.1), trans‐apical approach (OR: 9.3, 95% CI: 4.3–23.7) and hypertension (OR: 6.4, 95% CI: 2.9–17.3). Conclusion: AKI developed in 28.8% of patients after TAVI and was associated with procedural technique and transfusion requirement, and an increased LOS and mortality. However, most patients achieved a significant and sustained improvement in eGFR.     

Survival analysis of pediatric dialysis patients in Taiwan

Aim: The long‐term survival of Taiwanese children with end‐stage renal disease (ESRD) has not been reported before. This study aimed to determine the long‐term survival, mortality hazards and causes of death in paediatric patients receiving dialysis. Methods: Paediatric patients (aged 19 years and younger) with incident ESRD who were reported to the Taiwan Renal Registry from 1995 to 2004 were included. A total of 319 haemodialysis (HD) and 156 peritoneal dialysis (PD) patients formed the database. After stratification by dialysis modality, multivariate Cox proportional‐hazards model was constructed with age, sex and co‐morbidity as predictive variables. Results: The annual paediatric ESRD incidence rate was 8.12 per million of age‐related populations. The overall 1‐, 5‐, and 10‐year survival rates for PD patients were 98.1%, 88.0% and 68.4%, respectively, and were 96.9%, 87.3% and 78.5% for HD patients. The survival analysis showed no significant difference between HD and PD (P = 0.4878). Using ‘15–19 years’ as a reference group, the relative risk (RR) of the youngest group (0–4 years) was 6.60 (95% CI: 2.50–17.38) for HD, and 5.03 (95% CI: 1.23–20.67) for PD. The death rate was 24.66 per 1000 dialysis patient‐years. The three major causes of death were infection (23.4%), cardiovascular disease (13.0%) and cerebrovascular disease (10.4%). Hemorrhagic stroke (87.5%) was the main type of foetal cerebrovascular accident. Conclusion: We conclude that there was no significant difference of paediatric ESRD patient survival between HD and PD treatment in Taiwan. The older paediatric ESRD patients had better survival than younger patients.     

Long‐Term Proton Pump Inhibitor Therapy and Falls and Fractures in Elderly Women: A Prospective Cohort Study

Proton pump inhibitors (PPIs) are widely used in the elderly. Recent studies have suggested that long‐term PPI therapy is associated with fractures in the elderly, however the mechanism remains unknown. We investigated the association between long‐term PPI therapy ≥1 year and fracture risk factors including bone structure, falls, and balance‐related function in a post hoc analysis of a longitudinal population‐based prospective cohort of elderly postmenopausal women and replicated the findings in a second prospective study of falling in elderly postmenopausal women. Long‐term PPI therapy was associated with increased risk of falls and fracture‐related hospitalizations; adjusted odds ratio (AOR) 2.17; 95% CI, 1.25–3.77; p = 0.006 and 1.95; 95% CI, 1.20–3.16; p = 0.007, respectively. In the replication study, long‐term PPI use was associated with an increased risk of self‐reported falling; AOR, 1.51; 95% CI, 1.00–2.27; p = 0.049. No association of long‐term PPI therapy with bone structure was observed; however, questionnaire‐assessed falls‐associated metrics such as limiting outdoor activity (p = 0.002) and indoor activity (p = 0.001) due to fear of falling, dizziness (p < 0.001) and numbness of feet (p = 0.017) and objective clinical measurement such as Timed Up and Go (p = 0.002) and Romberg eyes closed (p = 0.025) tests were all significantly impaired in long‐term PPI users. Long‐term PPI users were also more likely to have low vitamin B12 levels than non‐users (50% versus 21%, p = 0.003). In conclusion, similar to previous studies, we identified an increased fracture risk in subjects on long‐term PPI therapy. This increase in fracture risk in elderly women, already at high risk of fracture, appears to be mediated via increased falls risk and falling rather than impaired bone structure and should be carefully considered when prescribing long‐term PPI therapy. © 2014 American Society for Bone and Mineral Research.     

Subtrochanteric and Diaphyseal Femur Fractures in Patients Treated With Alendronate: A Register‐Based National Cohort Study

Alendronate (aln) is a potent bisphosphonate with a prolonged duration of action. Recent reports have found long‐term aln use to be common in patients with subtrochanteric or proximal diaphyseal femur fracture, raising concerns that these fractures could be a consequence of excessive suppression of bone turnover. Two national observational register‐based studies were performed: (1) cross‐sectional study (N = 11,944) comparing age distribution, exposure, and trauma mechanisms between different types of proximal femur fractures and (2) matched cohort study in patients with prior nonhip fractures (N = 5187 + 10,374), testing the hypothesis that the increase in the risk of subsequent atypical femur fractures exceeded the increase in typical hip fractures. We also sought evidence of a dose‐response relationship, where high adherence to or long‐term use of aln led to more atypical femur fractures. We found that 7% of patients with atypical fractures were aln exposed, and the same was found for typical hip fractures. In the cohort study, the HR for subtrochanteric/diaphyseal fracture with aln was 1.46 (0.91–2.35, p = 0·12) compared with 1.45 (1.21–1.74, p < 0·001) for hip fracture after adjustment for comorbidity and co‐medications. The risk was reduced by high adherence, and the ratio between hip and subtrochanteric/diaphyseal femur fractures was identical in aln‐treated patients and the control cohort even in the limited number of patients who received long‐term treatment. Subtrochanteric/diaphyseal femur fractures share the epidemiology and treatment response of classical hip fractures and are best classified as osteoporotic fractures.     

Breastfeeding protects against hip fracture in postmenopausal women: The Tromsø study

Despite reported bone loss during pregnancy and lactation, no study has shown deleterious long‐term effects of parity or breastfeeding. Studies have shown higher bone mineral density and reduced risk for fracture in parous than in nulliparous women or no effect of parity and breastfeeding, so long‐term effects are uncertain. We studied the effect of parity and breastfeeding on risk for hip, wrist and non‐vertebral fragility fractures (hip, wrist, or proximal humerus) in 4681 postmenopausal women aged 50 to 94 years in the Tromsø Study from 1994–95 to 2010, using Cox's proportional hazard models. During 51 906 person‐years, and a median of 14.5 years follow‐up, 442, 621, and 1105 of 4681 women suffered incident hip, wrist, and fragility fractures, and the fracture rates were 7.8, 11.4, and 21.3 per 1000 person‐years, respectively. The risk for hip, wrist, and fragility fracture did not differ between parous (n = 4230, 90.4%) and nulliparous women (n = 451, 9.6%). Compared with women who did not breast‐feed after birth (n = 184, 4.9%), those who breastfed (n = 3564, 95.1%) had 50% lower risk for hip fracture (HR 0.50; 95% CI 0.32 to 0.78), and 27% lower risk for fragility fracture (HR 0.73; 95% CI 0.54 to 0.99), but similar risk for wrist fracture, after adjustment for age, BMI, height, physical activity, smoking, a history of diabetes, previous fracture of hip or wrist, use of hormone replacement therapy, and length of education. Each 10 months longer total duration of breastfeeding reduced the age‐adjusted risk for hip fracture by 12% (HR 0.88; 95% CI 0.78 to 0.99, p for trend = 0.03) before, and marginally after, adjustment for BMI and other covariates (HR 0.91; 95% CI 0.80 to 1.04). In conclusion, this data indicates that pregnancy and breastfeeding has no long‐term deleterious effect on bone fragility and fractures, and that breastfeeding may contribute to a reduced risk for hip fracture after menopause. © 2011 American Society for Bone and Mineral Research     

Acute kidney injury in Xinjiang: a cross-sectional survey

Objective To evaluate the etiology, epidemiological characteristics, clinical diagnosis, and outcomes of hospitalized patients with AKI in Xinjiang, analyzing the risk factors of their clinical prognosis. Methods A multicenter retrospective survey was conducted, investigating adult patients admitted to four hospitals in Xinjiang in January and July 2013. Patients with AKI were screened out based on KDIGO's inclusion and exclusion criteria. Clinical variables of patients with AKI including demographics, clinical data, laboratory tests, treatment measures and prognosis were collected. Results Among 32,157 adult hospitalized patients, there were 722 AKI patients. Excluding those with incomplete data, 719 patients were enrolled in this study. The detection rate of AKI was 2.25% (722 of 32,157) by KDIGO criteria. The main cause for AKI was pre-renal injury, led mainly by cardiac output, low blood volume, and the use of nephrotoxic drugs. The non-recognition rate of AKI was 72.4%(407/557). Multivariate binary logistic regression analysis showed that AKI stage, peripheral vasodilation and renal parenchyma were protective factors of the omission diagnosis. In the short-term prognostic analysis, the overall mortality rate was 12.8%(92/719). Among the 323 patients with AKI who survived discharge, 43.7%(141) had renal function recovery; 40.2%(130) did not fully recover their renal function but ceased maintenance dialysis; 16.4%(53) were still on dialysis at discharge. Multivariate Cox regression model suggested that DIC, shock and department of obstetrics were independent risk factors for death during hospitalization of AKI. In addition, the risk of death for AKI from department of obstetrics and gynecology patients was higher than that of other departments. Conclusions The most common reason for AKI in hospitalized patients in Xinjiang was pre-renal injury. The main risk factors were low cardiac output and low blood volume. The omission diagnosis of AKI was serious; AKI stage, peripheral vasodilation and renal parenchymal injury however were its protective factors. Poor-DIC, shock, hospitalization in obstetrics were independent risk factors for death in patients with AKI.     

High incidence and recurrence of transitional cell carcinoma in Taiwanese patients with end-stage renal disease

Aim: This study examines the epidemiology of transitional cell carcinoma (TCC) in end‐stage renal disease (ESRD) population from Taiwan, the area with the highest incidence and prevalence of ESRD. Methods: A total of 98 out of 10 890 ESRD patients were referred for management of TCC between 2000 and 2008. Demographic, clinical and laboratory data were collected and patient mortality and tumour recurrence rates were analyzed. Results: TCC patients were aged 61.4 ± 10.2 years and 66.3% were female. The average time from initiation of dialysis to tumour detection was 51.2 ± 36.4 months. Hypertensive nephrosclerosis, diabetes mellitus, chronic glomerulonephritis and unknown aetiology accounted for 25.5%, 20.4%, 22.4% and 31.6% of the causes of renal failure, respectively. The aetiology of renal failure for the 31.6% of patients was unclear, but chronic tubulointerstitial nephritis following long‐term consumption of Chinese herbs (19.4%) or analgesic compounds (3.1%) was considered in some patients. Almost all (98.0%) patients presented with gross haematuria. Most TCC were in early stage (stage 0, 3.1%; stage I, 56.1%) during diagnosis. At the end of this study, 17 of 98 (17.3%) patients died. Multivariate Cox regression analysis found that age (odds ratio = 1.140, 95% confidence interval = 1.049–1.239, P = 0.002) and tumour pain (odds ratio = 0.234, 95% confidence interval = 0.057–0.961, P = 0.044) were significant risk factors for all‐cause mortality. Furthermore, 35.7% of TCC recurred during follow up. The 5 year patient and tumour‐free survival rates were 72.4% and 14.4%, respectively. Conclusion: The data shows that Taiwanese patients with ESRD had high incidence (0.9%) and recurrence (35.7%) of TCC.     

Declining Rates of Hip Fracture in End‐Stage Renal Disease: Analysis From the 2003–2011 Nationwide Inpatient Sample

The incidence of hip fracture in patients with end‐stage renal disease (ESRD) is considerably higher than that in the general age‐ and sex‐matched population. Although medical therapy for chronic kidney disease mineral bone disorder (CKD‐MBD) has changed considerably over the last decade, rates of hip fracture in the entire ESRD population have not been well‐characterized. Herein, we evaluated temporal trends in rates of hip fracture, in‐hospital mortality, and costs of associated hospital stay in ESRD. We identified hospitalizations for hip fracture from 2003 to 2011 using the Nationwide Inpatient Sample, a representative national database inclusive of all ages and payers. We incorporated data from the United States Renal Data System and the US Census to calculate population‐specific rates. Between 2003 and 2011, we identified 47,510 hip fractures in the ESRD population. The overall rate of hip fracture was 10.04/1000 person‐years. The rate was 3.73/1000 person‐years in patients aged less than 65 years, and 20.97/1000 person‐years in patients aged 65 or older. Age‐ and sex‐standardized rates decreased by 12.6% from 2003 (10.23/1000 person‐years; 95% confidence interval [CI], 7.99/1000 to 12.47/1000) to 2011 (8.94/1000 person‐years; 95% CI, 7.12/1000 to 10.75/1000). Hip fracture rates over time were virtually identical in patients aged less than 65 years; however, rates decreased by 15.3% among patients aged 65 years or older; rates declined more rapidly in older women compared with older men (p for interaction = 0.047). In‐hospital mortality rate after hip fracture operation declined by 26.7% from 2003 (8.6%; 95% CI, 6.8 to 10.4) to 2011 (6.3%; 95% CI, 4.9 to 7.7). In ESRD, age‐ and sex‐standardized hip fracture rates and associated in‐hospital mortality have declined substantially over the last decade. © 2017 American Society for Bone and Mineral Research.     

Hemodialysis Adequacy and the Hospitalized End‐Stage Renal Disease Patient—Raising Awareness

Assessment of hemodialysis adequacy may require different approaches for the stable, outpatient with end‐stage renal disease (ESRD) and for the sick, inpatient with acute kidney injury (AKI). Variability of urea distribution volume, urea generation, and treatment schedule, for instance, complicates dialysis dosing in the latter group although progress has been made in our understanding of their needs. There is a third population, however, for whom hemodialysis dosing requirements remain unclear—the hospitalized ESRD patient. This commentary discusses the key urea kinetic differences between stable ESRD and AKI to give the context to where, on the intervening spectrum, the hospitalized ESRD patient might lie. The limited literature examining hemodialysis dosing in this population is discussed along with those outstanding questions that might form the basis of a future research agenda.     

Diagnosis and Treatment of Low Testosterone among Patients with End‐Stage Renal Disease

The prevalence of low testosterone level is particularly high among patients with end‐stage renal disease (ESRD) and has been associated with mortality. In populations without ESRD, low testosterone level has also been associated with a number of morbidities including cardiovascular disease, diabetes mellitus, low muscle mass, low bone mass, low physical performance, and frailty. However, there is controversy regarding what constitutes low testosterone level in the aging population and at what level replacement therapy with testosterone is indicated. There are no randomized controlled trials investigating long‐term outcomes of testosterone replacement therapy in populations with or without ESRD. Available trial results suggest equivocal improvements in sexual function. Muscle mass and bone mineral density appear to improve, but results in physical function and performance are mixed and there are no data on fracture prevention. Some recent data suggest harm when testosterone was given to men with limited mobility. Finally, there is little evidence that testosterone adds to existing erythropoietin agents in the treatment of anemia in ESRD. Due to lack of evidence supporting long‐term use of testosterone, the authors recommend against the routine use of testosterone in ESRD patients with low testosterone levels. Testosterone treatment can be considered in those with low bone mass and total testosterone level <200 ng/dl, or in younger patients with sexual complaints with total testosterone level lower than the reference range. It is important to engage patients in discussion of risks and benefits before initiating testosterone therapy; testosterone therapy should be discontinued if the intended treatment effect is not observed after short‐term use.     

Hip Fracture in Patients With Non‐Dialysis‐Requiring Chronic Kidney Disease

Patients with end‐stage renal disease (ESRD) are at a high risk for hip fracture. Little is known about the risk for, and consequences of, hip fracture among patients with non‐dialysis‐requiring chronic kidney disease (CKD). We examined the incidence of hip fracture, in‐hospital mortality, length of stay, and costs among patients with ESRD, non‐dialysis‐requiring CKD, and normal or near normal kidney function. Using the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample, a nationally representative database, we identified hospitalizations for hip fracture in 2010. We incorporated data from the United States Renal Data System (USRDS) and the US census to calculate population‐specific rates. Age‐standardized incidence of hip fracture was highest among patients with ESRD (3.89/1000 person‐years), followed by non‐dialysis‐requiring CKD (1.81/1000 persons) and patients with normal or near normal kidney function (1.18/1000 persons). In‐hospital mo rtality (odds ratio [OR] = 1.69, 95% confidence interval [CI] 1.46 to 1.96), lengths of stay (median [10th, 90th percentiles] 5 [3 to 11] versus 5 [3 to 10] days) and costs (median $14,807 versus $13,314) were significantly higher in patients with non‐dialysis‐requiring CKD relative to patients with normal or near normal kidney function. In summary, non‐dialysis‐requiring CKD is associated with higher age‐standardized rates of hip fracture and post‐hip fracture mortality and higher resource utilization. © 2016 American Society for Bone and Mineral Research.     

Klotho Variants and Chronic Hemodialysis Mortality

Patients with end‐stage renal disease (ESRD) suffer exceptionally high mortality rates in their first year of chronic hemodialysis. Both vitamin D and fibroblast growth factor (FGF)‐23 levels correlate with survival in these patients. Klotho is a protein in the vitamin D/FGF‐23 signaling pathway that has been linked with accelerated aging and early mortality in animal models. We therefore hypothesized that genetic variation in the Klotho gene might be associated with survival in subjects with ESRD. We tested the association between 12 single nucleotide polymorphisms (SNPs) in the Klotho gene and mortality in a cohort of ESRD patients during their first year on hemodialysis (n = 1307 white and Asian). We found a significant association between the CC genotype of one tag SNP, rs577912, and increased risk for 1‐yr mortality (RR, 1.76; 95% CI, 1.19–2.59; p = 0.003). This effect was even more marked among patients who were not treated with activated vitamin D supplementation (HR, 2.51; 95% CI, 1.18–5.34; p = 0.005). In lymphoblastoid cell lines derived from HapMap subjects, the CC genotype was associated with a 16–21% lower Klotho expression compared with the AA/AC genotype. Our data suggest that a specific Klotho variant (rs577912) is linked to survival in ESRD patients initiating chronic hemodialysis and that therapy with activated vitamin D may modify this risk.     

The impact of severe acute kidney injury requiring renal replacement therapy on survival and renal function of heart transplant recipients – a UK cohort study

Severe acute kidney injury (AKI), defined as requiring renal replacement therapy (RRT), is associated with higher mortality postheart transplantation, but its long-term renal consequences are not known. Anonymized data of 3365 patients, who underwent heart transplantation between 1995 and 2017, were retrieved from the UK Transplant Registry. Multivariable binary logistic regression was performed to identify risk factors for severe AKI requiring RRT, Kaplan–Meier analysis to compare survival and renal function deterioration of the RRT and non-RRT groups, and multivariable Cox regression model to identify predicting factors of mortality and end-stage renal disease (ESRD). 26.0% of heart recipients received RRT post-transplant. The RRT group has lower survival rates at all time points, especially in the immediate post-transplant period. However, conditional on 3 months survival, older age, diabetes and coronary heart disease, but not post-transplant RRT, were the risk factors for long-term survival. The predicting factors for ESRD were insulin-dependent diabetes, renal function at transplantation, eGFR decline in the first 3 months post-transplant, post-transplant severe AKI and transplantation era. Severe AKI requiring RRT post-transplant is associated with worse short-term survival, but has no impact on long-term mortality. It also accelerates recipients’ renal function deterioration in the long term.