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Background Hyperphosphatemia occurs frequently in end-stage renal disease patients on hemodialysis and is associated with increased mortality. Hyperphosphatemia contributes to vascular calcification in these patients, but there is emerging evidence that it is also associated with endothelial cell dysfunction. Methods We conducted a cross-sectional study in hypertensive hemodialysis patients. We obtained pre-hemodialysis measurements of total peripheral resistance index (TPRI, non-invasive cardiac output monitor) and plasma levels of endothelin-1 (ET-1) and asymmetric dimethylarginine (ADMA). We ascertained the routine peridialytic blood pressure (BP) measurements from that treatment and the most recent pre-hemodialysis serum phosphate levels. We used generalized linear regression analyses to determine independent associations between serum phosphate with BP, TPRI, ET-1, and ADMA while controlling for demographic variables, parathyroid hormone (PTH), and interdialytic weight gain. Results There were 54 patients analyzed. Mean pre-HD supine and seated systolic and diastolic BP were 164 (27), 158 (21), 91.5 (17), and 86.1 (16) mmHg. Mean serum phosphate was 5.89 (1.8) mg/dL. There were significant correlations between phosphate with all pre-hemodialysis BP measurements (r = 0.3, p = .04; r = 0.4, p = .002; r = 0.5, p r = 0.5, p = .0003.) The correlations with phosphate and TPRI, ET-1, and ADMA were 0.3 (p = .01), 0.4 (p = .007), and 0.3 (p = .04). In our final linear regression analyses controlling for baseline characteristics, PTH, and interdialytic weight gain, independent associations between phosphate with pre-hemodialysis diastolic BP, TPRI, and ET-1 were retained (β = 4.33, p = .0002; log transformed β = 0.05, p = .005; reciprocal transformed β = -0.03, p = .047). Conclusions Serum phosphate concentration is independently associated with higher pre-HD BP, vasoconstriction, and markers of endothelial cell dysfunction. These findings demonstrate an additional negative impact of hyperphosphatemia on cardiovascular health beyond vascular calcification. Trial registration The study was part of a registered clinical trial, NCT01862497 (May 24, 2013).

Billions of COVID-19 vaccine doses have been administered to combat the ongoing global pandemic caused by severe acute respiratory syndrome coronavirus-2. While these vaccines are considered safe, with most adverse events being mild to moderate and transient, uncommon systemic side effects of the vaccines, including de novo or re-activation of various glomerular diseases have recently been observed. We report 6 patients who developed glomerular or acute tubulointerstitial disease shortly after receiving COVID-19 vaccinations. Five of these patients received mRNA vaccines (3 Moderna, 2 Pfizer-BioNTech) and 1 received adenovirus-26 vector vaccine (Johnson and Johnson/Janssen). Four of our patients developed de novo glomerulonephritis or acute tubulointerstitial nephritis (ATIN), while the other 2 had re-activation of prior glomerulonephritis. Two patients presented with acute kidney injury (AKI) characterized by severe ATIN. While both of them also had evidence of immune complex glomerular disease, ATIN was the dominant feature on the biopsies. Two other patients presented with high-grade proteinuria and AKI. Like the aforementioned patients, these patients had evidence of immune complex glomerular disease, but acute onset nephrotic syndrome was the leading clinical feature. Another patient presented with de novo myeloperoxidase-anti-neutrophil-cytoplasmic-antibody-associated pauci-immune crescentic glomerulonephritis. Yet another patient had re-activation of immunoglobulin-A glomerulonephritis that had been quiescent for several years prior to the vaccination. It is difficult to ascertain any causal relationship between COVID-19 vaccination and onset/recurrence of kidney diseases. However, vigilance about occurrence of such complications is imperative. Importantly, all our cases responded well to the immunosuppressive treatment.

Objective To determine whether surge conditions were associated with increased mortality. Design Multicenter cohort study. Setting U.S. ICUs participating in STOP-COVID. Patients Consecutive adults with COVID-19 admitted to participating ICUs between March 4 and July 1, 2020. Interventions None Measurements and Main Results The main outcome was 28-day in-hospital mortality. To assess the association between admission to an ICU during a surge period and mortality, we used two different strategies: (1) an inverse probability weighted difference-in-differences model limited to appropriately matched surge and non-surge patients and (2) a meta-regression of 50 multivariable difference-in-differences models (each based on sets of randomly matched surge- and non-surge hospitals). In the first analysis, we considered a single surge period for the cohort (March 23 – May 6). In the second, each surge hospital had its own surge period (which was compared to the same time periods in matched non-surge hospitals). Our cohort consisted of 4342 ICU patients (average age 60.8 [sd 14.8], 63.5% men) in 53 U.S. hospitals. Of these, 13 hospitals encountered surge conditions. In analysis 1, the increase in mortality seen during surge was not statistically significant (odds ratio [95% CI]: 1.30 [0.47-3.58], p = .6). In analysis 2, surge was associated with an increased odds of death (odds ratio 1.39 [95% CI, 1.34-1.43], p Conclusions Admission to an ICU with COVID-19 in a hospital that is experiencing surge conditions may be associated with an increased odds of death. Given the high incidence of COVID-19, such increases would translate into substantial excess mortality.

Rationale & Objective Acute kidney injury treated with kidney replacement therapy (AKI-KRT) occurs frequently in critically ill patients with COVID-19. We examined the clinical factors that determine kidney recovery in this population. Study Design Multicenter cohort study. Setting & Participants 4221 adults with COVID-19 not receiving kidney replacement therapy who were admitted to intensive care units at 68 US hospitals with COVID-19 from March 1 to June 22, 2020 (the “ICU cohort”). Among these, 876 developed AKI-KRT after admission to the ICU (the “AKI-KRT subcohort”). Exposure(s) The ICU cohort was analyzed using AKI severity as the exposure. For the AKI-KRT subcohort, exposures included demographics, comorbidities, initial mode of KRT, and markers of illness severity at the time of dialysis initiation. Outcome(s) The outcome for the ICU cohort was estimated glomerular filtration rate (GFR) at hospital discharge. A three-level outcome including death, kidney nonrecovery, and kidney recovery at discharge, was analyzed for the AKI-KRT subcohort. Analytical approach The ICU cohort was characterized using descriptive analyses. The AKI-KRT subcohort was characterized with both descriptive analyses and multinomial logistic regression to assess factors associated with kidney nonrecovery while accounting for death. Results Among a total of 4221 patients in the ICU cohort, 2361 (56%) developed AKI, including 876 (21%) who received KRT. More severe AKI was associated with higher mortality. Among survivors, more severe AKI was associated with an increased rate of kidney nonrecovery and lower kidney function at discharge. Among the 876 patients with AKI-KRT, 588 (67%) died, 95 (11%) had kidney nonrecovery, and 193 (22%) had kidney recovery by the time of discharge. The odds of kidney nonrecovery was greater for lower estimated GFR with odds ratios (ORs) of 2.09 (95% CI, 1.09-4.04), 4.27 (95% CI, 1.99-9.17), and 8.69 (95% CI, 3.07-24.55) for CKD GFR categories 3, 4, and 5, respectively, compared to estimated GFR > 60 mL/min/1.73 m2. Oliguria at the time of KRT initiation was also associated with nonrecovery (OR 2.10 [95% CI, 1.14-3.88] and 4.02 [95% CI, 1.72-9.39] for patients with 50-499 and, Critically ill patients with COVID-19 often develop acute kidney injury (AKI). This study of 4221 patients demonstrated that more severe AKI was associated with greater in-hospital mortality and poorer kidney function at hospital discharge. Among the 876 patients who required dialysis for AKI, almost two-thirds died. Among those who survived to discharge, about two-thirds recovered kidney function and were discharged without the need for dialysis. Lower baseline kidney function and reduced urine output were associated with non-recovery of kidney function. Identification of such predictors is important in assessing prognosis among these critically ill patients and has implications for clinical care of individuals critically ill with COVID-19.

Variation in hospital mortality has been described for coronavirus disease 2019 (COVID-19), but the factors that explain these differences remain unclear.Our objective was to utilize a large, nationally representative dataset of critically ill adults with COVID-19 to determine which factors explain mortality variability.In this multicenter cohort study, we examined adults hospitalized in intensive care units with COVID-19 at 70 United States hospitals between March and June 2020. The primary outcome was 28-day mortality. We examined patient-level and hospital-level variables. Mixed-effects logistic regression was used to identify factors associated with interhospital variation. The median odds ratio (OR) was calculated to compare outcomes in higher- vs. lower-mortality hospitals. A gradient boosted machine algorithm was developed for individual-level mortality models.A total of 4,019 patients were included, 1537 (38%) of whom died by 28 days. Mortality varied considerably across hospitals (0-82%). After adjustment for patient- and hospital-level domains, interhospital variation was attenuated (OR decline from 2.06 [95% CI, 1.73-2.37] to 1.22 [95% CI, 1.00-1.38]), with the greatest changes occurring with adjustment for acute physiology, socioeconomic status, and strain. For individual patients, the relative contribution of each domain to mortality risk was: acute physiology (49%), demographics and comorbidities (20%), socioeconomic status (12%), strain (9%), hospital quality (8%), and treatments (3%).There is considerable interhospital variation in mortality for critically ill patients with COVID-19, which is mostly explained by hospital-level socioeconomic status, strain, and acute physiologic differences. Individual mortality is driven mostly by patient-level factors. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Summary: Many US states published crisis standards of care (CSC) guidelines for allocating scarce critical care resources during the COVID-19 pandemic. However, the performance of these guidelines in maximizing their population benefit has not been well tested. In 2,272 adults with COVID-19 requiring mechanical ventilation drawn from the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID) multicenter cohort, we test the following three approaches to CSC algorithms: Sequential Organ Failure Assessment (SOFA) scores grouped into ranges, SOFA score ranges plus comorbidities, and a hypothetical approach using raw SOFA scores not grouped into ranges. We find that area under receiver operating characteristic (AUROC) curves for all three algorithms demonstrate only modest discrimination for 28-day mortality. Adding comorbidity scoring modestly improves algorithm performance over SOFA scores alone. The algorithm incorporating comorbidities has modestly worse predictive performance for Black compared to white patients. CSC algorithms should be empirically examined to refine approaches to the allocation of scarce resources during pandemics and to avoid potential exacerbation of racial inequities.

Hypercoagulability may be a key mechanism of death in patients with COVID-19. This cohort study evaluated the incidence of venous thromboembolism and major bleeding in critically ill patients with COVID-19 and examined the observational effect of early therapeutic anticoagulation on survival., Visual Abstract. Early Anticoagulation in COVID-19 Hypercoagulability may be a key mechanism of death in patients with COVID-19. This cohort study evaluated the incidence of venous thromboembolism and major bleeding in critically ill patients with COVID-19 and examined the observational effect of early therapeutic anticoagulation on survival. Visual Abstract. Early Anticoagulation in COVID-19 Hypercoagulability may be a key mechanism of death in patients with COVID-19. This cohort study evaluated the incidence of venous thromboembolism and major bleeding in critically ill patients with COVID-19 and examined the observational effect of early therapeutic anticoagulation on survival., Background: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). Objective: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival. Design: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used. Setting: 67 hospitals in the United States. Participants: Adults with COVID-19 admitted to a participating ICU. Measurements: Time to death, censored at hospital discharge, or date of last follow-up. Results: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]). Limitation: Observational design. Conclusion: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation. Primary Funding Source: None.

In-center hemodialysis (HD) remains the predominant dialysis therapy in patients with ESKD. Many patients with ESKD present in late stage, requiring urgent dialysis initiation, and the majority start HD with central venous catheters (CVCs), which are associated with poor outcomes and high cost of care. Peritoneal dialysis (PD) catheters can be safely placed in such patients with late-presenting ESKD, obviating the need for CVCs. PD can begin almost immediately in the recumbent position, using low fill volumes. Such PD initiations, commencing within 2 weeks of the catheter placement, are termed urgent-start PD (USPD). Most patients with an intact peritoneal cavity and stable home situation are eligible for USPD. Although there is a small risk of PD catheter–related mechanical complications, most can be managed conservatively. Moreover, overall outcomes of USPD are comparable to those with planned PD initiations, in contrast to the high rate of catheter-related infections and bacteremia associated with urgent-start HD. The ongoing coronavirus disease 2019 pandemic has further exposed the vulnerability of patients with ESKD getting in-center HD. PD can mitigate the risk of infection by reducing environmental exposure to the virus. Thus, USPD is a safe and cost-effective option for unplanned dialysis initiation in patients with late-presenting ESKD. To develop a successful USPD program, a strong infrastructure with clear pathways is essential. Coordination of care between nephrologists, surgeons or interventionalists, and hospital and PD center staff is imperative so that patient education, home visits, PD catheter placements, and urgent PD initiations are accomplished expeditiously. Implementation of urgent-start PD will help to increase PD use, reduce cost, and improve patient outcomes, and will be a step forward in fostering the goal set by the Advancing American Kidney Health initiative.

Background and objectives Lifetime risk estimates of CKD can be used effectively in public education campaigns. This study sought to estimate lifetime risk of incident CKD stage 3 and higher in Iceland for people without CKD by the age of 45 years. Design, setting, participants, & measurements This was a prospective cohort study with longitudinal creatinine measurements of residents in Reykjavik, Iceland, from 1967 to 2005. CKD was ascertained by two consecutive eGFR measurements 2 , development of treated kidney failure, one eGFR 2 if the participant died before the next evaluation, or one eGFR 2 if it was the last eGFR. Results Mean follow-up was 25 (SD 10) years. Of the study participants, 727 (19%) developed the outcome and 942 (24%) died first. By age 85 years, the lifetime risks for 45-year-old women and men without prevalent CKD were 35.8% (95% confidence interval [95% CI], 32.7 to 38.9) and 21.3% (95% CI, 18.7 to 23.8), respectively. Risk was higher in individuals with a lower eGFR, hypertension, and a higher body mass index. Lifetime risk for higher stages of CKD 3b and 4 were less common than stage 3a; by age 85 years, the lifetime risks for CKD stages 3a, 3b, and 4 in women were 38.5% (95% CI, 25.8 to 51.1), 19.4% (95% CI, 8.9 to 29.9), and 3.6% (95% CI, 2.2 to 5.0), respectively. Conclusions The lifetime risk of developing CKD stage 3 or higher is substantial, emphasizing the importance of strategies to prevent development of CKD throughout the course of life. Estimates are lower than reported using single estimates of GFR, emphasizing the importance of confirming estimates of reduced GFR in studies of CKD.

Background/Aims: Extracellular volume (ECV) overload is a mortality risk factor in hemodialysis patients, but no standard approach exists to objectively assess this clinically. We aimed to quantify relationships between slopes of repeated intradialytic blood pressure (BP) measurements and ECV. Methods: In a cross-sectional study of 71 hemodialysis patients, we calculated BP slopes from all intradialytic measurements using Gaussian regression. We measured extracellular and total body water (TBW) with bioimpedance spectroscopy. We analyzed unconditional and conditional associations between BP slope and volume metrics with mixed linear models and sensitivity analyses using non-linear intradialytic BP trajectory. Results: Mean systolic intradialytic BP slope (IBPS) was –0.06 (0.1) mm Hg/min. Post-dialysis extracellular water (ECW)/weight was the volume metric mostly strongly associated with slope (r = 0.34, p = 0.007 for unconditional analysis; β = 1.45, p = 0.001 for conditional analysis). Among subjects with post-dialysis systolic BP ≥130 mm Hg, the association strengthened (r = 0.40, p = 0.006; β = 1.42, p = 0.003). ECV was more strongly associated with the BP slope than with pre-dialysis, post-dialysis, or delta systolic BP (r = –0.07, 0.19, 0.28; p = 0.6, 0.1, 0.03). In nonlinear models, BP trajectory also had the strongest association with post-dialysis ECW/body weight (p < 0.001). Conclusions: In hypertensive hemodialysis patients, measurements of ECV excess are more strongly associated with IBPSs than with pre-dialysis, post-dialysis, or change in systolic BP. Among varying volume metrics, post-dialysis ECW/weight has the strongest association with these slopes. Determining IBPS is a novel method to optimize clinical assessment of ECV in hemodialysis patients.

Objective : The associations of some risk factors with cardiovascular disease (CVD) are attenuated in older age; whereas others appear robust. The present study aimed to compare CVD risk factors across older age. Methods : Participants ( n = 4883) in the Cardiovascular Health Study free of prevalent CVD, were stratified into three age groups: 65–74, 75–84, 85+ years. Traditional risk factors included systolic blood pressure (BP), LDL-cholesterol, HDL-cholesterol, obesity, and diabetes. Novel risk factors included kidney function, C-reactive protein (CRP), and N-terminal pro-B-type natriuretic peptide (NT pro-BNP). Results : There were 1498 composite CVD events (stroke, myocardial infarction, and cardiovascular death) over 5 years. The associations of high systolic BP and diabetes appeared strongest, though both were attenuated with age ( p -values for interaction = 0.01 and 0.002, respectively). The demographic-adjusted hazard ratios (HR) for elevated systolic BP were 1.79 (95% confidence interval: 1.49, 2.15), 1.59 (1.37, 1.85) and 1.10 (0.86, 1.41) in participants aged 65–74, 75–84, 85+, and for diabetes, 2.36 (1.89, 2.95), 1.55 (1.27, 1.89), 1.51 (1.10, 2.09). The novel risk factors had consistent associations with the outcome across the age spectrum; low kidney function: 1.69 (1.31, 2.19), 1.61 (1.36, 1.90), and 1.57 (1.16, 2.14) for 65–74, 75–84, and 85+ years, respectively; elevated CRP: 1.54 (1.28, 1.87), 1.33 (1.13, 1.55), and 1.51 (1.15, 1.97); elevated NT pro-BNP: 2.67 (1.96, 3.64), 2.71 (2.25, 3.27), and 2.18 (1.43, 3.45). Conclusions : The associations of most traditional risk factors with CVD were minimal in the oldest old, whereas diabetes, eGFR, CRP, and NT pro-BNP were associated with CVD across older age.

BackgroundFibroblast growth factor 23 (FGF23) has emerged as a novel risk factor for mortality and cardiovascular events. Its association with the ankle-brachial index (ABI) and clinical peripheral artery disease (PAD) is less known.MethodsUsing data (N = 3143) from the Cardiovascular Health Study (CHS), a cohort of community dwelling adults >65 years of age, we analyzed the cross-sectional association of FGF23 with ABI and its association with incident clinical PAD events during 9.8 years of follow up using multinomial logistic regression and Cox proportional hazards models respectively.ResultsThe prevalence of cardiovascular disease (CVD) and traditional risk factors like diabetes, coronary artery disease, and heart failure increased across higher quartiles of FGF23. Compared to those with ABI of 1.1-1.4, FGF23 per doubling at baseline was associated with prevalent PAD (ABI < 0.9) although this association was attenuated after adjusting for CVD risk factors, and kidney function (OR 0.91, 95% CI 0.76-1.08). FGF23 was not associated with high ABI (>1.4) (OR 1.06, 95% CI 0.75-1.51). Higher FGF23 was associated with incidence of PAD events in unadjusted, demographic adjusted, and CVD risk factor adjusted models (HR 2.26, 95% CI 1.28-3.98; highest versus lowest quartile). The addition of estimated glomerular filtration and urine albumin to creatinine ratio to the model however, attenuated these findings (HR 1.46, 95% CI, 0.79-2.70).ConclusionsIn community dwelling older adults, FGF23 was not associated with baseline low or high ABI or incident PAD events after adjusting for confounding variables. These results suggest that FGF23 may primarily be associated with adverse cardiovascular outcomes through non atherosclerotic mechanisms.

Summary Background and objectives There are few data on risk factors for sudden cardiac death (SCD) in patients undergoing hemodialysis (HD). The study objective was to identify predictors associated with various causes of death in the Hemodialysis (HEMO) Study and to develop a prediction model for SCD using a competing risk approach. Design, setting, participants, & measurements In this analysis of 1745 HEMO participants, all-cause mortality was classified as SCD, non-SCD, and noncardiac death. Predictors for each cause of death were evaluated using cause-specific Cox proportional hazards models, and a competing risk approach was used to calculate absolute risk predictions for SCD. Results During a median follow-up of 2.5 years, 808 patients died. Rates of SCD, non-SCD, and noncardiac death were 22%, 17%, and 61%, respectively. Predictors of various causes of death differ somewhat in HD patients. Age, diabetes, peripheral vascular disease, ischemic heart disease, serum creatinine, and alkaline phosphatase were independent predictors of SCD. The 3-year C-statistic for SCD was 0.75 (95% confidence interval, 0.70–0.79), and calibration was good (χ2=1.1; P=0.89). At years 3 and 5 of follow-up, the standard Cox model overestimated the risk for SCD as compared with the competing risk approach on the relative scale by 25% and 46%, respectively, and on the absolute scale by 2% and 6%, respectively. Conclusions Predictors of various causes of death differ in HD patients. The proposed prediction model for SCD accounts for competing causes of death. External validation of this model is required.

Background Hemodialysis patients have an elevated risk of sudden cardiac death. Although the efficacy of β-blockers for the prevention of sudden cardiac death has been proven in the general population, little evidence exists in patients with kidney failure. Study Design Post hoc analysis of the Hemodialysis (HEMO) Study. Setting & Participants Participants enrolled in the HEMO Study from May 1995 to February 2001. Intervention β-Blocker use ascertained through self-reported questionnaires and dialysis clinic charts. Outcomes Sudden cardiac death adjudicated by a committee as a secondary outcome of interest. Measurements We used Cox proportional hazards regression models, competing risk survival analysis, propensity score matching, and covariate adjustment to study the association of β-blockers with sudden cardiac death. Results 1,747 patients were included in this study, and 521 were on β-blocker therapy at baseline. Mean age was 58 years, 57% were women, and 39% had ischemic heart disease (IHD) at baseline. Baseline β-blocker use was not associated with lower risk of sudden cardiac death in univariate (cause-specific HR, 0.89; 95% CI, 0.64-1.24), multivariable (cause-specific HR, 0.87; 95% CI, 0.62-1.22), or propensity-matched (cause-specific HR, 0.91; 95% CI, 0.55-1.50) analyses. There was a significant interaction between β-blocker use and sudden cardiac death (interaction P = 0.03) in patients with (cause-specific HR, 0.65; 95% CI, 0.42-1.01) and without IHD (cause-specific HR, 1.61; 95% CI, 0.92-2.80). Limitations Observational nature of the study. Conclusions In hemodialysis patients without preexisting IHD, β-blocker use was not associated with lower risk of sudden cardiac death. However, there was a trend toward benefit in those with IHD.

There are limited data on the prevalence of chronic kidney disease (CKD) and its clinical importance in the very old. We examined the prevalence of CKD in octogenarians and its association with cardiovascular disease (CVD).In a cross-sectional analysis of 1028 participants from the Cardiovascular Health Study All Stars, we evaluated association of prevalent CKD with CVD using multivariable logistic regression. CKD was defined as eGFR of60 ml/min per 1.73 m(2). GFR was estimated using CKD-Epi creatinine and cystatin C equations that incorporate coefficients for age, gender, and race (eGFR(EPI), eGFR(CYS3var)) and the one-variable cystatin C equation (eGFR(CYS1var)). Prevalent CVD was defined as a composite of coronary heart disease, heart failure, and stroke.Mean age was 86 years, 64% were women, 86% were Caucasians, 14% had diabetes, and 39% had prevalent CVD. Mean eGFR(EPI), eGFR(CYS3var), and eGFR(CYS1var) were 59, 62, and 70 ml/min per 1.73 m(2), and 51%, 46%, and 33% had CKD, respectively. Associations of CKD with CVD varied by equation in adjusted analyses: CKD(EPI) (OR, 1.53; 95% CI, 1.15 to 2.03), CKD(CYS3var) (OR, 1.67; 95% CI, 1.25, 2.23), and CKD(CYS1var) (OR, 2.09; 95% CI, 1.55, 2.83).Reduced eGFR is highly prevalent in octogenarians, and the eGFR(CYS1var) equation yielded the lowest prevalence of CKD but the strongest association with prevalent CVD. Because there are no validated estimating equations in the elderly, estimation of kidney function on the basis of on any one equation should be interpreted with caution.

We report the outcome of revision hip arthroplasty for patients with acetabular bone loss in whom the femoral head retrieved from arthritic contralateral hip during the same anesthesia was used as autograft for acetabular reconstruction. Thirty-two hips in 16 patients with a mean age of 63.8 years (range, 43-79 years) were followed for an average of 3.5 years. All primary arthroplasties were successful. Evidence of autograft incorporation was found in all except 2 patients. The acetabular component failed and required revision in the latter 2 patients. The use of femoral head autograft in a select group of patients with symptomatic arthritis of hip and a failed prosthetic hip with severe bone loss in the contralateral side is a viable option. However, this technique should not be applied to acetabular reconstructions in which protected weight-bearing in the postoperative period may be necessary.

The purpose of this research was to investigate the utility of 1 surgical exposure method, extensor mechanism tenolysis (EMT), for total knee revision, and to evaluate complications associated with this technique. Two hundred seven knee revisions were performed on 198 patients (9 bilateral) over a 3-year period (September 1997 to October 2000). The surgical exposures used were EMT in 203 cases, V-Y quadricepsplasty in 2 knees, and patellectomy in 2 additional cases. The complications associated with EMT were peripatellar fibrosis requiring arthroscopy, 7.2%; hematoma, 4.8%; stiffness requiring manipulation, 3.9%; patellar subluxation, 1.4%; extensor lag >5 degrees, 1.0%; quadriceps tendon rupture, 0.5%; and instability, 0.5%. EMT is associated with a low complication rate comparable with or better than other exposure methods.

This retrospective study explored the relationship between the volume of total hip arthroplasties (THA) and postoperative mortality and early complications from a single institution. One thousand hip arthroplasties in 932 patients were identified during a 1-year period, which included 786 primary and 214 revision hip arthroplasties. The postoperative 6-month combined medical and orthopedic complication rate for primary and revision THA was 7.9% and 16.5%, respectively. The 6-month mortality rate for the overall group was 0.5% (5 deaths), for the primary hips was 0.4% (3 deaths), and for the revision hip was 0.9% (2 deaths). The mortality and complication rates of many surgical procedures, including joint arthroplasties, are inversely related to hospital and surgical volume. The reduction in complication rate, however, approaches a plateau and does not improve regardless of an increase in the surgical and hospital volume.

Fifty-eight patients received an Osteonics constrained acetabular implant for recurrent instability (46), girdlestone reimplant (8), correction of leg lengthening (3), and periprosthetic fracture (1). The constrained liner was inserted into a cementless shell (49), cemented into a pre-existing cementless shell (6), cemented into a cage (2), and cemented directly into the acetabular bone (1). Eight patients (13.8%) required reoperation for failure of the constrained implant. Type I failure (bone-prosthesis interface) occurred in 3 cases. Two cementless shells became loose, and in 1 patient, the constrained liner was cemented into an acetabular cage, which then failed by pivoting laterally about the superior fixation screws. Type II failure (liner locking mechanism) occurred in 2 cases. Type III failure (femoral head locking mechanism) occurred in 3 patients. Seven of the 8 failures occurred in patients with recurrent instability. Constrained liners are an effective method for treatment during revision total hip arthroplasty but should be used in select cases only.

The incidence of failure after knee replacement is low, yet it has been reported that more than 22,000 knee replacements are revised yearly. The purpose of the current study was to determine current mechanisms of failure of total knee arthroplasties. A retrospective review was done on all patients who had revision total knee arthroplasty during a 3-year period (September 1997-October 2000) at one institution. The preoperative evaluation in conjunction with radiographs, laboratory data, and intraoperative findings were used to determine causes of failure. Two hundred twelve surgeries were done on 203 patients (nine patients had bilateral surgeries). The reasons for failure listed in order of prevalence among the patients in this study include polyethylene wear, aseptic loosening, instability, infection, arthrofibrosis, malalignment or malposition, deficient extensor mechanism, avascular necrosis in the patella, periprosthetic fracture, and isolated patellar resurfacing. The cases reviewed included patients who had revision surgery within 9 days to 28 years (average, 3.7 years) after the previous surgery. More than half of the revisions in this group of patients were done less than 2 years after the index operation. Fifty percent of early revision total knee arthroplasties in this series were related to instability, malalignment or malposition, and failure of fixation.

A recent report from the Alberta Kidney Disease Network demonstrates that high estimated glomerular filtration rate is associated with an increased risk of all-cause mortality in both young and elderly individuals, as well as in those with and without proteinuria. Potential explanations and implications of these findings are discussed.

Introduction: There is evidence that some traditional cardiovascular risk factors have weaker associations with outcomes in elderly adults; whereas, some novel risk factors appear important in old age. Whether the risk factors for cardiovascular disease differ in the oldest old compared with younger elders is uncertain. Hypothesis: The associations of traditional risk factors - systolic blood pressure, LDL-cholesterol, HDL-cholesterol, obesity, and diabetes - will be attenuated with age, whereas the associations of novel risk factors - kidney disease, inflammation, and cardiac stiffness - will be robust across older age. Methods: Participants in the Cardiovascular Health Study ≥65 years (n=4,853), were stratified into three age cohorts: 65-74, 75-84, 85+ years based on the age at the time of risk factor measure (baseline, 3, 7, or 16 years of follow-up). Proportional hazards models were used to assess the associations of the risk factors assessed at the most recent visit and a composite outcome of incident stroke, myocardial infarction, and cardiovascular death over 5 years. Results: There were 1,481 events. In adults 65-84 years, systolic blood pressure, HDL-cholesterol, diabetes, kidney disease, inflammation, and cardiac stiffness were associated with the composite outcome, after adjustment for demographic factors. In adults 85+ years, only the novel risk factors were associated with the outcome in demographic-adjusted analyses (Figure). In fully adjusted models, only inflammation was associated with the outcome across the age spectrum. HDL-cholesterol was independently associated with the outcome in adults Conclusions: The associations of traditional risk factors with cardiovascular outcomes appear attenuated in adults ≥85 years; this could impact optimal prevention strategies in the oldest old. Inflammation is a robust risk factor across the spectrum of old age.

We report the case of a 60- year- old man who presented with newly diagnosed multiple myeloma complicated by biopsy-proven acute cast nephropathy, requiring hemodialysis, plasmapheresis and chemotherapy. After remaining dialysis dependent for 5 weeks, a high cut-off (HCO) dialyzer, intended to use for the removal of plasma substances with a molecular weight of up to 45 kDa such as free light chains, was introduced to his outpatient 4-hour hemodialysis regimen with an increase in treatment frequency to 4 sessions per week. Following 6 weeks of dialysis with the HCO dialyzer, serum levels of free κ light chains declined by more than 75%. Concurrently, he recovered kidney function and discontinued dialysis. He subsequently received a successful autologous stem-cell transplant. We discuss the potential merit of using the HCO dialyzer late in the course of the care of patients with myeloma cast nephropathy who are dialysis dependent.

To examine the association between kidney function and all-cause mortality in octogenarians.Retrospective analysis of prospectively collected data.Community.Serum creatinine and cystatin C were measured in 1,053 Cardiovascular Health Study (CHS) All Stars participants.Estimated glomerular filtration rate (eGFR) was determined using the Chronic Kidney Disease Epidemiology Collaboration creatinine (eGFR(CR) ) and cystatin C one-variable (eGFR(CYS) ) equations. The association between quintiles of kidney function and all-cause mortality was analyzed using unadjusted and adjusted Cox proportional hazards models.Mean age of the participants was 85, 64% were female, 66% had hypertension, 14% had diabetes mellitus, and 39% had prevalent cardiovascular disease. There were 154 deaths over a median follow-up of 2.6 years. The association between eGFR(CR) and all-cause mortality was U-shaped. In comparison with the reference quintile (64-75 mL/min per 1.73 m(2) ), the highest (≥ 75 mL/min per 1.73 m(2) ) and lowest (≤ 43 mL/min per 1.73 m(2) ) quintiles of eGFR(CR) were independently associated with mortality (hazard ratio (HR) = 2.49, 95% confidence interval (CI) = 1.36-4.55; HR = 2.28, 95% CI = 1.26-4.10, respectively). The association between eGFR(CYS) and all-cause mortality was linear in those with eGFR(CYS) of less than 60 mL/min per 1.73 m(2) , and in the multivariate analyses, the lowest quintile of eGFR(CYS) (52 mL/min per 1.73 m(2) ) was significantly associated with mortality (HR = 2.04, 95% CI = 1.12-3.71) compared with the highest quintile (0.88 mL/min per 1.73 m(2) ).Moderate reduction in kidney function is a risk factor for all-cause mortality in octogenarians. The association between eGFR(CR) and all-cause mortality differed from that observed with eGFR(CYS) ; the relationship was U-shaped for eGFR(CR) , whereas the risk was primarily present in the lowest quintile for eGFR(CYS) .

Background The growing burden and morbidity of chronic kidney disease (CKD) warrant effective strategies for identifying those at increased risk. We examined the association of cystatin C level and albuminuria with the development of CKD stage 3. Study Design Prospective observational study. Setting & Participants 5,422 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m 2 . Predictor Participants were categorized into 4 mutually exclusive groups: the presence or absence of microalbuminuria (albumin-creatinine ratio >17 and >25 μg/mg in men and women, respectively) in those with or without cystatin C level ≥1.0 mg/L. Outcomes & Measurements Incident CKD stage 3 was defined as eGFR 2 at the third or fourth visit and an annual decrease >1 mL/min/1.73 m 2 . Poisson regression was used to evaluate incident rate ratios in unadjusted and adjusted analyses that include baseline eGFR. Results Mean age was 61 years, 49% were men, 38% were white, 11% had diabetes, 13.7% had cystatin C level ≥1 mg/L, 8.4% had microalbuminuria, and 2.7% had cystatin C level ≥1 mg/L with microalbuminuria. 554 (10%) participants developed CKD stage 3 during a median follow-up of 4.7 years, and adjusted incidence rate ratios were 1.57 (95% CI, 1.19-2.07), 1.37 (95% CI, 1.13-1.66), and 2.12 (95% CI, 1.61-2.80) in those with microalbuminuria, cystatin C level ≥1 mg/L, and both, respectively, compared with those with neither. Limitations Relatively short follow-up and absence of measured GFR. Conclusions Cystatin C level and microalbuminuria are independent risk factors for incident CKD stage 3 and could be useful as screening tools to identify those at increased risk.

This retrospective study explored the relationship between the volume of total hip arthroplasties (THA) and postoperative mortality and early complications from a single institution. One thousand hip arthroplasties in 932 patients were identified during a 1-year period, which included 786 primary and 214 revision hip arthroplasties. The postoperative 6-month combined medical and orthopedic complication rate for primary and revision THA was 7.9% and 16.5%, respectively. The 6-month mortality rate for the overall group was 0.5% (5 deaths), for the primary hips was 0.4% (3 deaths), and for the revision hip was 0.9% (2 deaths). The mortality and complication rates of many surgical procedures, including joint arthroplasties, are inversely related to hospital and surgical volume. The reduction in complication rate, however, approaches a plateau and does not improve regardless of an increase in the surgical and hospital volume.

The incidence of failure after knee replacement is low, yet it has been reported that more than 22,000 knee replacements are revised yearly. The purpose of the current study was to determine current mechanisms of failure of total knee arthroplasties. A retrospective review was done on all patients who had revision total knee arthroplasty during a 3-year period (September 1997-October 2000) at one institution. The preoperative evaluation in conjunction with radiographs, laboratory data, and intraoperative findings were used to determine causes of failure. Two hundred twelve surgeries were done on 203 patients (nine patients had bilateral surgeries). The reasons for failure listed in order of prevalence among the patients in this study include polyethylene wear, aseptic loosening, instability, infection, arthrofibrosis, malalignment or malposition, deficient extensor mechanism, avascular necrosis in the patella, periprosthetic fracture, and isolated patellar resurfacing. The cases reviewed included patients who had revision surgery within 9 days to 28 years (average, 3.7 years) after the previous surgery. More than half of the revisions in this group of patients were done less than 2 years after the index operation. Fifty percent of early revision total knee arthroplasties in this series were related to instability, malalignment or malposition, and failure of fixation.