At least four definitions of AKI have recently been proposed. This study sought to characterize the epidemiology of AKI according to the most recent consensus definition proposed by the Kidney ...Disease Improving Global Outcomes (KDIGO) Work Group, and to compare it with three other definitions.
This was a retrospective cohort study of 31,970 hospitalizations at an academic medical center in 2010. AKI was defined and staged according to KDIGO criteria, the Acute Dialysis Quality Initiative's RIFLE criteria, the Acute Kidney Injury Network (AKIN) criteria, and a definition based on a model of creatinine kinetics (CK). Outcomes of interest were incidence, in-hospital mortality, length of stay, costs, readmission rates, and posthospitalization disposition.
AKI incidence was highest according to the KDIGO definition (18.3%) followed by the AKIN (16.6%), RIFLE (16.1%), and CK (7.0%) definitions. AKI incidence appeared markedly higher in those with low baseline serum creatinine according to the KDIGO, AKIN, and RIFLE definitions, in which AKI may be defined by a 50% increase over baseline. AKI according to all definitions was associated with a significantly higher risk of death and higher resource utilization. The adjusted odds ratios for in-hospital mortality in those with AKI were highest with the CK definition (5.2; 95% confidence interval 95% CI, 4.1 to 6.6), followed by the RIFLE (2.9; 95% CI, 2.2 to 3.6), KDIGO (2.8; 95% CI, 2.2 to 3.6), and AKIN (2.6; 95% CI, 2.0 to 3.3) definitions. Concordance in diagnosis and staging was high among the KDIGO, AKIN, and RIFLE definitions.
The incidence of AKI in hospitalized individuals varies depending on the definition used. AKI according to all definitions is associated with higher in-hospital mortality and resource utilization. AKI may be inappropriately diagnosed in those with low baseline serum creatinine using definitions that incorporate percentage increases over baseline.
Background Sudden death is a leading cause of death in patients on maintenance hemodialysis therapy. During hemodialysis sessions, the gradient between serum and dialysate levels results in rapid ...electrolyte shifts, which may contribute to arrhythmias and sudden death. Controversies exist about the optimal electrolyte concentration in the dialysate; specifically, it is unclear whether patient outcomes differ among those treated with a dialysate potassium concentration of 3 mEq/L compared to 2 mEq/L. Study Design Prospective cohort study. Setting & Participants 55,183 patients from 20 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 1 to 5 (1996-2015). Predictor Dialysate potassium concentration at study entry. Outcomes Cox regression was used to estimate the association between dialysate potassium concentration and both all-cause mortality and an arrhythmia composite outcome (arrhythmia-related hospitalization or sudden death), adjusting for potential confounders. Results During a median follow-up of 16.5 months, 24% of patients died and 7% had an arrhythmia composite outcome. No meaningful difference in clinical outcomes was observed for patients treated with a dialysate potassium concentration of 3 versus 2 mEq/L (adjusted HRs were 0.96 95% CI, 0.91-1.01 for mortality and 0.98 95% CI, 0.88-1.08 for arrhythmia composite). Results were similar across predialysis serum potassium levels. As in prior studies, higher serum potassium level was associated with adverse outcomes. However, dialysate potassium concentration had only minimal impact on serum potassium level measured predialysis (+0.09 95% CI, 0.05-0.14 mEq/L serum potassium per 1 mEq/L greater dialysate potassium concentration). Limitations Data were not available for delivered (vs prescribed) dialysate potassium concentration and postdialysis serum potassium level; possible unmeasured confounding. Conclusions In combination, these results suggest that approaches other than altering dialysate potassium concentration (eg, education on dietary potassium sources and prescription of potassium-binding medications) may merit further attention to reduce risks associated with high serum potassium levels.
Background Hyperkalemia is common among hemodialysis patients and is associated with morbidity and mortality. The long interdialytic interval is likewise associated with adverse outcomes. However, ...the interplay among serum potassium, dialysis cycle phase, and clinical outcomes has not been examined. Study Design Retrospective observational study. Setting & Participants 52,734 patients receiving in-center hemodialysis at a large dialysis organization during 2010 and 2011 contributed 533,889 potassium measurements (230,634 on Monday; 285,522 on Wednesday; 17,733 on Friday). Predictor Serum potassium concentration, day of the week of potassium measurement. Outcomes Death, hospitalization, emergency department (ED) visit. Results There was a significant association between higher serum potassium and risk of hospitalization within 96 hours that was of greater magnitude on Fridays (389 hospitalizations) than Mondays or Wednesdays (4,582 and 4,629 hospitalizations, respectively; P for interaction = 0.008). Serum potassium of 5.5 to <6.0 (vs the referent category of 4.0-<4.5 mEq/L) was associated with increased risk of hospitalization on Fridays, with an adjusted OR of 1.68 (95% CI, 1.22-2.30). However, serum potassium of 5.5 to <6.0 mEq/L was associated with only mild elevation of risk on Mondays and no significantly increased risk on Wednesdays (adjusted ORs of 1.12 95% CI, 1.00-1.24 and 1.04 95% CI, 0.94-1.16, respectively). Associations of elevated serum potassium (6.0-<6.5 mEq/L or greater) with death and ED visit were significant, but did not differ based on day of the week. Limitations There were insufficient observations to detect effect modification by day of the week for deaths, ED visits, and specific causes of hospitalizations. Confounding may have influenced results. Conclusions Higher serum potassium is associated with increased short-term risk of hospitalization, ED visit, and death. The association between serum potassium and hospitalization risk is modified by day of the week, consistent with a contribution of accumulated potassium to adverse outcomes following the long interdialytic interval. Further work is needed to determine whether directed interventions ameliorate this risk.
In patients with ESRD, residual kidney function (RKF) contributes to achievement of adequate solute clearance. However, few studies have examined RKF in patients on hemodialysis. In a longitudinal ...cohort of 6538 patients who started maintenance hemodialysis over a 4-year period (January 2007 through December 2010) and had available renal urea clearance (CL
) data at baseline and 1 year after hemodialysis initiation, we examined the association of annual change in renal CL
rate with subsequent survival. The median (interquartile range) baseline value and mean±SD annual change of CL
were 3.3 (1.9-5.0) and -1.1±2.8 ml/min per 1.73 m
, respectively. Greater CL
rate 1 year after hemodialysis initiation associated with better survival. Furthermore, we found a gradient association between loss of RKF and all-cause mortality: changes in CL
rate of -6.0 and +3.0 ml/min per 1.73 m
per year associated with case mix-adjusted hazard ratios (95% confidence intervals) of 2.00 (1.55 to 2.59) and 0. 61 (0.50 to 0.74), respectively (reference: -1.5 ml/min per 1.73 m
per year). These associations remained robust against adjustment for laboratory variables and ultrafiltration rate and were consistent across strata of baseline CL
, age, sex, race, diabetes status, presence of congestive heart failure, and hemoglobin, serum albumin, and serum phosphorus levels. Sensitivity analyses using urine volume as another index of RKF yielded consistent associations. In conclusion, RKF decline during the first year of dialysis has a graded association with all-cause mortality among incident hemodialysis patients. The clinical benefits of RKF preservation strategies on mortality should be determined.
Addressing fluid intake and volume control requires alignment and coordination of patients, providers, dialysis facilities, and payers, potentially necessitating a “Volume First” approach. This ...article reports the consensus opinions achieved at the March 2013 symposium of the Chief Medical Officers of 14 of the largest dialysis providers in the United States. These opinions are based on broad experience among participants, but often reinforced by only observational and frequently retrospective studies, highlighting the lack of high-quality clinical trials in nephrology. Given the high morbidity and mortality rates among dialysis patients and the absence of sufficient trial data to guide most aspects of hemodialysis therapy, participants believed that immediate attempts to improve care based on quality improvement initiatives, physiologic principles, and clinical experiences are warranted until such time as rigorous clinical trial data become available. The following overarching consensus opinions emerged. (1) Extracellular fluid status should be a component of sufficient dialysis, such that approaching normalization of extracellular fluid volume should be a primary goal of dialysis care. (2) Fluid removal should be gradual and dialysis treatment duration should not routinely be less than 4 hours without justification based on individual patient factors. (3) Intradialytic sodium loading should be avoided by incorporating dialysate sodium concentrations set routinely in the range of 134-138 mEq/L, avoidance of routine use of sodium modeling, and avoidance of hypertonic saline solution. (4) Dietary counseling should emphasize sodium avoidance.
Highlights • Evasion of immune surveillance, a process defined immune-editing, leads to RCC malignant progression. • The PD-1/PD-L1 axis inhibition by targeted-antibodies, increases T-cell ...proliferation and anti-tumor activity. • PD-1 and PD-L1 inhibitors have been tested in RCC, alone or combined with anti-VEGF/VEGFR drugs or other immunotherapies. • We discuss the role of PD-1/PD-L1 in RCC, focusing on current clinical studies and future perspectives.
Background Hemodialysis patients with erythropoiesis-stimulating agent (ESA) hyporesponsiveness have been a topic of active research. However, there have been no studies of ESA hyporesponsiveness ...among US patients following the dramatic change in anemia management that resulted from the 2011 changes in ESA product labeling and bundling of dialysis remuneration. Study Design Retrospective observational study. Setting & Participants We studied prevalent hemodialysis patients treated at a large dialysis organization in calendar years 2012 to 2013 (N = 98,972). Predictor ESA hyporesponsiveness, defined as 2 consecutive hemoglobin measurements < 10 g/dL (every other week) with contemporaneous ESA dose > 7,700 U/treatment. Patients with ESA hyporesponsiveness were identified during the first quarter of 2012 and followed up through 2013 using intention-to-treat principles. Outcomes Associations between the study exposure (ESA hyporesponsiveness) and mortality, missed hemodialysis treatments, ESA and iron use, and hemoglobin levels were determined using generalized estimating equations adjusting for imbalanced baseline covariates. Results At baseline, 12,361 (12.5%) patients were identified as having ESA hyporesponsiveness. The mean hemoglobin level among patients with ESA hyporesponsiveness was ∼1 g/dL lower than in patients without ESA hyporesponsiveness at baseline, narrowing over follow-up to 0.4 g/dL. Initially, mean ESA use was approximately 3-fold greater for patients with ESA hyporesponsiveness than for those without ESA hyporesponsiveness, decreasing to 2-fold greater at study end; iron use and missed hemodialysis treatment rates were also greater among patients with ESA hyporesponsiveness throughout. ESA hyporesponsiveness was associated with enhanced mortality risk versus non–ESA hyporesponsiveness: adjusted incidence rate ratios were estimated at 2.24 (95% CI, 1.93-2.60) in the second quarter, gradually decreasing to 1.48 (95% CI, 1.18-1.84) by study end. Limitations It is possible that an alternative ESA hyporesponsiveness definition may be optimal. As such, the associations we observed may be conservative estimates of true relationships. Conclusions When using a contemporary definition at one point in time, ESA hyporesponsiveness was potently and persistently associated with greater mortality, greater iron and ESA use, and lower hemoglobin levels compared to non–ESA hyporesponsiveness.
Patients on hemodialysis have an elevated risk for COVID-19 but were not included in efficacy trials of SARS-CoV-2 vaccines.
We conducted a retrospective, observational study to estimate the ...real-world effectiveness and immunogenicity of two mRNA SARS-CoV-2 vaccines in a large, representative population of adult hemodialysis patients in the United States. In separate, parallel analyses, patients who began a vaccination series with BNT162b2 or mRNA-1273 in January and February 2021 were matched with unvaccinated patients and risk for outcomes were compared for days 1-21, 22-42, and ≥43 after first dose. In a subset of consented patients, blood samples were collected approximately 28 days after the second dose and anti-SARS-CoV-2 immunoglobulin G was measured.
A total of 12,169 patients received the BNT162b2 vaccine (matched with 44,377 unvaccinated controls); 23,037 patients received the mRNA-1273 vaccine (matched with 63,243 unvaccinated controls). Compared with controls, vaccinated patients' risk of being diagnosed with COVID-19 postvaccination became progressively lower during the study period (hazard ratio and 95% confidence interval for BNT162b2 was 0.21 0.13, 0.35 and for mRNA-1273 was 0.27 0.17, 0.42 for days ≥43). After a COVID-19 diagnosis, vaccinated patients were significantly less likely than unvaccinated patients to be hospitalized (for BNT162b2, 28.0% versus 43.4%; for mRNA-1273, 37.2% versus 45.6%) and significantly less likely to die (for BNT162b2, 4.0% versus 12.1%; for mRNA-1273, 5.6% versus 14.5%). Antibodies were detected in 98.1% (309/315) and 96.0% (308/321) of BNT162b2 and mRNA-1273 patients, respectively.
In patients on hemodialysis, vaccination with BNT162b2 or mRNA-1273 was associated with a lower risk of COVID-19 diagnosis and lower risk of hospitalization or death among those diagnosed with COVID-19. SARS-CoV-2 antibodies were detected in nearly all patients after vaccination. These findings support the use of these vaccines in this population.
Calcific uremic arteriolopathy (CUA) is an often fatal condition with no effective treatment. Multiple case reports and case series have described intravenous sodium thiosulfate (STS) administration ...in CUA, but no studies have systematically evaluated this treatment.
This study included 172 patients undergoing maintenance hemodialysis who had CUA and were treated with STS between August 2006 and June 2009 at Fresenius Medical Care North America. Of these, 85% completed STS therapy. Clinical, laboratory, and mortality data were abstracted from clinical information systems. Responses to survey questionnaires sent to treating physicians regarding patient-level outcomes were available for 53 patients. Effect on CUA lesions and mortality were summarized as CUA outcomes. Relevant laboratory measures, weight (using pairwise comparisons of values before, during, and after STS), and adverse events were summarized as safety parameters.
Mean age of the cohort was 55 years, and 74% of patients were women. Median STS dose was 25 g, and median number of doses was 38. Among surveyed patients, CUA completely resolved in 26.4%, markedly improved in 18.9%, improved in 28.3%, and did not improve in 5.7%; in the remaining patients (20.8%), the response was unknown. One-year mortality in patients treated with STS was 35%. Adverse events, laboratory abnormalities, and weight-related changes were mild. Significant reductions in serum phosphorous (P=0.02) and parathyroid hormone (P=0.01) were noted during STS treatment in patients who completed the therapy.
Although conclusive evidence regarding its efficacy is lacking, a majority of patients who received STS demonstrated clinical improvement in this study.
By making use of a recently proposed framework for the inference of thermodynamic irreversibility in bosonic quantum systems, we experimentally measure and characterize the entropy production rates ...in the nonequilibrium steady state of two different physical systems-a micromechanical resonator and a Bose-Einstein condensate-each coupled to a high finesse cavity and hence also subject to optical loss. Key features of our setups, such as the cooling of the mechanical resonator and signatures of a structural quantum phase transition in the condensate, are reflected in the entropy production rates. Our work demonstrates the possibility to explore irreversibility in driven mesoscopic quantum systems and paves the way to a systematic experimental assessment of entropy production beyond the microscopic limit.
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