Association of Body Mass Index with Multiple Organ Failure in Hospitalized Patients with COVID-19: A Multicenter Retrospective Cohort Study.

Purpose: This study examines whether excessive adipose tissue, as measured by the body mass index (BMI), is associated with higher systemic markers of inflammation and higher risk of severe acute organ failure among patients with coronavirus disease 2019 (COVID-19). Methods: This was a multicenter retrospective cohort study of 1370 hospitalized adults (18 years or older) with COVID-19 during the first wave of the pandemic. Patient-level variables were extracted from the electronic medical record. The primary predictor variable was the BMI at time of hospital admission, in accordance with the World Health Organization classification. Multivariable logistic regression analyses examined the association of BMI with the composite of acute respiratory distress syndrome (ARDS), as defined by the use of high-flow nasal canula, non-invasive ventilation, or mechanical ventilation, severe acute kidney injury (AKI), as defined by acute dialysis requirement, or in-hospital death. Results: After adjustment for important cofounders, the BMI stratum of > 40 kg/m2 (compared to the BMI < 25 kg/m2 reference group) was associated with higher odds for the composite of ARDS, severe AKI, or in-hospital death (adjusted odds ratio [ORadj] 1.69; 95% confidence interval [CI]1.03, 2.78). As a continuous variable, BMI (per 5-kg/m2 increase) remained independently associated with the composite outcome (ORadj 1.13; 95% CI 1.03, 1.23); patients in higher BMI categories exhibited significantly higher peak levels of C-reactive protein (CRP), a systemic marker of inflammation (P = .01). In a sub-cohort of 889 patients, the association of BMI with the composite outcome was no longer significant after adjustment for the peak level of CRP. Conclusions: Among hospitalized patients with COVID-19, a higher BMI is associated with higher risk of severe organ failure or in-hospital death, which dissipates after adjustment for CRP level. This supports the hypothesis that inflammation is a downstream mediator of adipose tissue on acute organ dysfunction.

Revising the Maximal Contrast Dose for Predicting Acute Kidney Injury following Coronary Intervention.

INTRODUCTION: The maximal allowable contrast dose (MACD = 5 × body weight/serum creatinine) is an empiric equation that has been used and validated in several studies to mitigate the risk of contrast-induced acute kidney injury (CI-AKI). However, coefficient 5 (referred to as factor K) was empirically devised and never disputed. The aim of this study was to refine the MACD equation for the prediction of CI-AKI following percutaneous coronary interventions (PCIs). METHODS: This is a single-center, retrospective cohort study of adults undergoing PCI. Electronic medical records were reviewed to identify patients who underwent PCI between 2010 and 2019, derived from the National Cardiovascular Data Registry Cath-PCI registry for our hospital. Factor K (defined as contrast volume × serum creatinine/body weight) was calculated for every patient. A receiver operating characteristic (ROC) curve was constructed, and the Youden index was used to identify the optimal cut-off value for factor K in predicting severe (stages 2-3) CI-AKI. RESULTS: Of the 3,506 patients undergoing PCI, 255 (7.2%) developed CI-AKI, and 68 (26.7%) of the 255 experienced severe AKI. Factor K predicted all-stage CI-AKI (area under the ROC curve 0.649; 95% CI 0.611, 0.686) but had better performance for predicting severe (stages 2-3) AKI (0.736; 95% CI 0.674, 0.800). The optimal cut-off value for factor K in predicting severe CI-AKI was 2.5, with a corresponding sensitivity of 68.7% and specificity of 70.5%. On subgroup analyses, optimal cut-off values for factor K for high-risk groups were not significantly different from those of low-risk groups. CONCLUSION: Our study indicates that factor K in the MACD equation is an independent risk factor for the development of severe CI-AKI, with an optimal cut-off value of 2.5. If our findings are validated, the MACD equation should be revised to incorporate the coefficient of 2.5 instead of 5.

Malignancy-induced lactic acidosis in adult lymphoma.

Malignancy-induced lactic acidosis (MILA), a rare paraneoplastic phenomenon, is mostly described with hematologic malignancies (lymphomas and leukemias) but has also been reported with solid tumors. It is a subset of type B lactic acidosis being mediated without evidence of tissue hypoperfusion. Lymphoma-induced lactic acidosis is often considered an oncologic emergency and is associated with an increased risk of mortality and poor prognosis. It has a complex pathophysiology centered in the "Warburg effect," i.e., the programming of cancer cells to depend on aerobic glycolysis for promotion of their proliferation and anabolic growth. The treatment of lymphoma-induced lactic acidosis is focused on prompt administration of chemotherapy. The role of alkali therapy in this setting is controversial and has limited proven benefit with a potential for worsening the lactic acidosis. If alkali therapy is used in the presence of severe acidemia to optimize cardiovascular status, it should be administered judiciously.

Effect of dialysate potassium and lactate on serum potassium and bicarbonate concentrations during daily hemodialysis at low dialysate flow rates.

BACKGROUND: Observational studies of hemodialysis patients treated thrice weekly have shown that serum and dialysate potassium and bicarbonate concentrations are associated with patient outcomes. The effect of more frequent hemodialysis on serum potassium and bicarbonate concentrations has rarely been studied, especially for treatments at low dialysate flow rate. METHODS: These post-hoc analyses evaluated data from patients who transferred from in-center hemodialysis (HD) to daily HD at low dialysate flow rates during the FREEDOM Study. The primary outcomes were the change in predialysis serum potassium and bicarbonate concentrations after transfer from in-center HD (mean during the last 3 months) to daily HD (mean during the first 3 months). RESULTS: After transfer from in-center HD to daily HD (data from 345 patients, 51 ± 15 years of age, mean ± standard deviation), predialysis serum potassium decreased (P < 0.001) by approximately 0.4 mEq/L when dialysate potassium concentration during daily HD was 1 mEq/L; no change occurred when dialysate potassium concentration during daily HD was 2 mEq/L. After transfer from in-center HD to daily HD (data from 284 patients, 51 ± 15 years of age), predialysis serum bicarbonate concentration decreased (P = 0.0022) by 1.0 ± 3.3 mEq/L when dialysate lactate concentration was 40 mEq/L but increased (P < 0.001) by 2.5 ± 3.5 mEq/L when dialysate lactate concentration was 45 mEq/L. These relationships were dependent on serum potassium and bicarbonate concentrations during in-center HD. CONCLUSIONS: Control of serum potassium and bicarbonate concentrations during daily HD at low dialysate flow rates is readily achievable; the choice of dialysate potassium and lactate concentration can be informed when transfer is from in-center HD to daily HD.

Chronic kidney disease and acquired mitochondrial myopathy.

PURPOSE OF REVIEW: Sarcopenia and muscle weakness contribute to fragility and limit exercise tolerance among patients with CKD. This review focuses on the role of reduction in mitochondrial mass and function in the myopathy associated with CKD, causes for these muscle mitochondrial abnormalities, and potential therapeutic interventions that may improve mitochondrial biogenesis and function as well as skeletal muscle function and performance in patients with CKD. RECENT FINDINGS: Multiple abnormalities of mitochondrial structure, function, and composition have been shown in both experimental models and patients with CKD. A significant reduction in mitochondrial respiratory function and an increase in mitochondrial complex 1 enzyme activity has been demonstrated in the muscle tissue of male Sprague-Dawley rats following 5/6 nephrectomy. These changes were associated with a substantial reduction in skeletal muscle mitochondrial mass. In patients with CKD, in-vivo magnetic resonance and optical spectroscopy show significantly elevated resting skeletal muscle oxygen consumption and lower mean mitochondrial coupling ratio indicating disrupted muscle mitochondrial metabolism and uncoupling of oxidative phosphorylation. Skeletal muscle biopsies from patients with advanced CKD show lower mitochondrial volume density and mitochondrial DNA (mtDNA) copy number than controls. SUMMARY: Advanced CKD is associated with decreased exercise capacity, skeletal muscle weakness, and muscle atrophy. Impaired mitochondrial respiratory function, reduced muscle mitochondrial mass, and decreased energy production in skeletal muscle play a critical role in this 'acquired mitochondrial myopathy' of CKD. It is reasonable, therefore, to develop therapeutic interventions that enhance mitochondrial biogenesis and function as well as skeletal muscle function and performance in patients with CKD.

Maximum allowable contrast dose and prevention of acute kidney injury following cardiovascular procedures.

PURPOSE OF REVIEW: Contrast-induced acute kidney injury (CI-AKI) is a serious complication. Although nonmodifiable and modifiable risk factors have been thoroughly characterized, the utility of the maximal allowable contrast dose (MACD) has not received adequate attention. The focus of this review is to provide a critical appraisal of this modifiable risk factor. RECENT FINDINGS: Several retrospective and prospective cohort studies have demonstrated that the incidence of CI-AKI among patients receiving contrast media in volumes exceeding the MACD is consistently higher compared with those who do not exceed the MACD (an average of 24 vs. 6%). Furthermore, the MACD is independent predictor of CI-AKI and other adverse events. A two-step algorithm incorporating the determination of the MACD and the contrast volume to eGFR ratio prior to a planned cardiovascular procedure is a sound approach to minimize contrast volume and prevent CI-AKI. SUMMARY: Prevention of CI-AKI must remain a clinical priority. Intraprocedural preventive measures should include a priori calculation of the MACD and contrast volume to eGFR ratio to limit contrast volume. Other measures may include the adoption of the transradial approach, the use of automated contrast injectors and small catheters to limit contrast volume, the use of low-osmolar contrast agents, and if necessary the use of staged procedures. We call for the system-wide implementation of evidence-based care bundles to prevent CI-AKI.

Ultrapure versus standard dialysate: A cost-benefit analysis.

Low-level bacterial and endotoxin contamination of water used to generate dialysate propagates chronic inflammation in patients with a wide-range of potential adverse consequences, including erythropoietin hyporesponsiveness. Advancements in hemodialysis systems now allow for the generation of ultrapure dialysate that has lower bacterial and endotoxin levels than the standard dialysate. The cost associated with ultrapure dialysate is thought to be a major barrier to its widespread adoption. In this report, we conduct a cost-benefit analysis examining the excess cost of generating ultrapure dialysate and the potential cost saving from a lower erythropoietin dose requirement. Our analysis suggests a potential cost saving of approximately $371 to $425 million per year with full adoption of ultrapure dialysate in the United States.

Reuse and Biocompatibility of Hemodialysis Membranes: Clinically Relevant?

The practice of reprocessing dialyzers for reuse, once predominant in the United States, has been steadily declining over the last 20 years. The professed roles of reuse in improving dialyzer membrane biocompatibility and lowering the risk of first-use syndrome have lost relevance with the advent of biocompatible dialyzer membranes and favorable sterilization techniques. The potential for cost-savings from reuse is also called into question by the easy availability of comparatively cheaper dialyzers and rising regulatory demands and operational cost of reprocessing systems. While the environmental concerns from additional dialyzer-related solid waste from rising single-use practice remains pertinent and requires development of safer dialyzer disposable system technologies, there is no meaningful medical rationale for the continued practice of dialyzer reuse in the twenty-first century.

Nephrologist-Facilitated Advance Care Planning for Hemodialysis Patients: A Quality Improvement Project.

BACKGROUND: The Renal Physicians Association's clinical practice guideline recommends that physicians address advance care planning with dialysis patients. However, data are lacking about how best to implement this recommendation. STUDY DESIGN: Quality improvement project. SETTINGS & PARTICIPANTS: Nephrologists caring for patients treated with maintenance hemodialysis at 2 dialysis facilities identified patients who might benefit most from advance care planning using the "surprise" question ("Would I be surprised if this patient died in the next year?"). QUALITY IMPROVEMENT PLAN: Patients identified with a "no" response to the surprise question were invited to participate in nephrologist-facilitated advance care planning, including completion of a Medical Orders for Life-Sustaining Treatment (MOLST) form. OUTCOMES: Change in MOLST completion rate and identification of preferences for limits on life-sustaining treatment. MEASUREMENTS: Pre- and postintervention code status, MOLST completion rate, and vital status at 1 year. RESULTS: Nephrologists answered "no" to the surprise question for 50 of 201 (25%) hemodialysis patients. Of these, 41 (82%) patients had a full-code status and 9 (18%) had a do-not-resuscitate (DNR) status. Encounters lasted 15 to 60 minutes. Following the encounter, 21 (42%) patients expressed preference for a DNR status and 29 (58%) maintained full-code status (P=0.001). The MOLST completion rate increased from 10% to 90%. One-year survival for patients whose nephrologists answered "no" to the surprise question was 58% compared to 92% for those with a "yes" answer (P<0.001). LIMITATIONS: Sample size and possible nonrepresentative dialysis population. CONCLUSIONS: Nephrologist-facilitated advance care planning targeting hemodialysis patients with limited life expectancy led to significant changes in documented patient preferences for cardiopulmonary resuscitation and limits on life-sustaining treatment. These changes demonstrate the benefit of advance care planning with dialysis patients and likely reflect better understanding of end-of-life treatment options.

Bioavailability, Efficacy and Safety of Generic Immunosuppressive Drugs for Kidney Transplantation: A Systematic Review and Meta-Analysis.

BACKGROUND: Concerns exist over the extrapolation of bioavailability studies of generic immunosuppressive drugs in healthy volunteers, regarding their efficacy and safety in kidney transplant recipients. We conducted a meta-analysis of trials examining the bioavailability of generic (test) immunosuppressive drugs relative to their brand (reference) counterparts in healthy volunteers, based on the US Food and Drug Administration requirements for approval of generics, and their efficacy and safety in kidney transplant recipients. METHODS: Eligible studies were identified in PubMed, Cochrane Central Register of Controlled Trials, Scopus, ClinicalTrials.gov, and conference abstracts. RESULTS: Twenty crossover trials of healthy volunteers (n = 641) and 6 parallel-arm randomized controlled trials of kidney transplant recipients (n = 594) were identified. The 90% CI of the pooled test-to-reference drug ratio for maximum or peak plasma concentration (Cmax) and area under the plasma concentration time-curve from time 0 to time of last determinable concentration (AUC(0-t)) fell within the required range (0.80-1.25) for cyclosporine (Cmax 0.91; 90% CI 0.86-0.95; and AUC(0-t) 0.97; 90% CI 0.94-1.00), tacrolimus (Cmax 1.17; 90% CI 1.09-1.24; and AUC(0-t) 1.00; 90% CI 0.97-1.03) and mycophenolate mofetil (Cmax 0.98; 90% CI 0.96-1.01; and AUC(0-t) 1.00; 90% CI 0.99-1.01). In subgroup analyses, some generic cyclosporine formulations did not meet criteria for bioequivalence. No significant differences were observed in the time to maximum plasma concentration and terminal plasma half-life between generic and brand drugs. In parallel-arm trials, generic cyclosporine was non-inferior to brand counterpart in terms of acute allograft rejection, infections, and death. CONCLUSIONS: Not all generic immunosuppressive drugs have similar relative bioavailability to their brand name counterparts. Evidence on their efficacy and safety is inconclusive. Tighter regulatory requirement for approval of generic drugs with narrow therapeutic index is needed.

We Use Impure Water to Make Dialysate for Hemodialysis.

Patients receiving hemodialysis are exposed to a large volume of water, used to prepare dialysate for each treatment session. Technological advancements now make it possible to generate ultrapure dialysate that has substantially lower bacterial and endotoxin counts than the standard dialysate used in the United States. Low-level water contamination is thought to propagate a state of chronic inflammation seen in hemodialysis patients, and a number of studies demonstrate that the use of ultrapure dialysate has a favorable effect on laboratory parameters of inflammation, nutrition, erythropoietin responsiveness, dialysis-associated amyloidosis, and atherosclerosis. Few studies even suggest a direct clinical benefit of adopting ultrapure dialysate. As there is no proven harm with use of ultrapure dialysate and the economic implication appears to be minimal when using modern dialysis machines, it is imperative for regulatory agencies and the dialysis community to ensure that our vulnerable patients are no longer exposed to impure water during their hemodialysis treatments.

Hospital-acquired acute kidney injury and hospital readmission: a cohort study.

BACKGROUND: Hospital-acquired acute kidney injury (AKI) is associated with increased mortality and resource consumption. Little is known about the association of AKI with short-term hospital readmissions. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: We investigated whether adult survivors of hospital-acquired AKI were at increased odds for early hospital readmission. PREDICTOR: The peak-to-nadir serum creatinine difference during the index hospitalization was used to define AKI according to the KDIGO (Kidney Disease: Improving Global Outcomes) classification and staging system. MEASUREMENTS: Multivariable logistic regression analyses examined the association of AKI with 30-, 60-, and 90-day hospital readmission, adjusting for age, sex, race, Charlson-Deyo comorbidity index score, acute hospital-related factors, common causes of hospitalization, and baseline estimated glomerular filtration rate. RESULTS: 3,345 (15%) of 22,001 included patients experienced AKI during the index hospitalization. Compared to the non-AKI group, the AKI group had a significantly higher 30-day hospital readmission rate (11% vs 15%; P<0.001), which persisted at 60 and 90 days. The AKI group also was more likely to be readmitted to the hospital within 30 days for cardiovascular-related conditions, mainly heart failure (P<0.001) and acute myocardial infarction (P=0.01). AKI associated independently with higher odds of 30-day hospital readmission (OR, 1.21; 95% CI, 1.08-1.36), which persisted at 60 (OR, 1.15; 95% CI, 1.03-1.27) and 90 days (adjusted OR, 1.13; 95% CI, 1.02-1.25). Results were attenuated in a propensity score-matched cohort of 5,912 patients. LIMITATIONS: Single-center study of mild forms of AKI; ascertainment bias and outcome misclassification due to the use of administrative codes. CONCLUSIONS: Our results suggest that survivors of hospital-acquired AKI experience higher odds of early hospital readmission. Transitions of care services may be warranted for such patients to prevent readmissions and reduce health care costs.

Acute oxalate nephropathy associated with Clostridium difficile colitis.

We report the case of a 69-year-old man who presented with acute kidney injury in the setting of community-acquired Clostridium difficile-associated diarrhea and biopsy-proven acute oxalate nephropathy. We discuss potential mechanisms, including increased colonic permeability to oxalate. We conclude that C difficile-associated diarrhea is a potential cause of acute oxalate nephropathy.

The daily burden of acute kidney injury: a survey of U.S. nephrologists on World Kidney Day.

BACKGROUND: World Kidney Day 2013 focused on raising awareness of the impact and consequences of acute kidney injury (AKI). Although many studies have examined rates of AKI in hospitalized patients, we were interested in the impact of AKI on the workload of nephrologists. STUDY DESIGN: Cross-sectional forced-choice internet-based survey. SETTING & PARTICIPANTS: 598 survey respondents who were US-based nephrologist members of the American Society of Nephrology. OUTCOMES: Numbers of inpatients and outpatients seen on World Kidney Day 2013 for the management of AKI or other conditions (and specifically in-hospital renal replacement therapies [RRTs]), based on self-report of number/percentage of patients seen on World Kidney Day and in the prior year. RESULTS: Of 598 physician respondents (response rate, 12%), 310 saw patients in the hospital on World Kidney Day. Of 3,285 patients seen by respondents, 1,500 were seen for AKI (46%); 1,233, for end-stage renal disease (37%); and 552, for non-AKI/end-stage renal disease-related problems (17%). Of patients with AKI, 688 (46%) were in the intensive care unit and 415 (28%) received RRT. Intermittent hemodialysis was performed in 315 patients (76%) who received RRT. Delivered dialysis dose was quantified in only 48 (15%) of those receiving intermittent hemodialysis. 260 respondents saw 2,380 patients in the ambulatory setting, of whom 207 (9%) were seen for follow-up of AKI. LIMITATIONS: There was a low response rate to the survey. Numbers of patients were self-reported. CONCLUSIONS: This is the first physician survey examining the care of patients and impact of AKI on current in-hospital and ambulatory nephrology practices. In our sample, AKI was the most common reason for in-hospital nephrology consultation. Furthermore, our findings point to significant areas in which improvement is needed, including inadequate quantification of dialysis delivered dose. Finally, our survey highlights that AKI is a major public health issue.

Efficacy and safety of intravenous iron therapy for functional iron deficiency anemia in hemodialysis patients: a meta-analysis.

BACKGROUND: Studies on benefits of intravenous iron therapy among hemodialysis patients with functional iron deficiency anemia have shown conflicting results. We conducted a meta-analysis to assess the efficacy and safety of intravenous iron in this subset of patients. METHODS: We searched MEDLINE (through December 2012), the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov for single-arm studies and randomized controlled trials (RCT) that examined the effect of intravenous iron for functional iron deficiency anemia in hemodialysis patients on anemia parameters and markers of oxidative stress and inflammation. Studies of absolute iron deficiency were excluded. Random-effect model meta-analyses were used to compute changes in outcomes of interest. RESULTS: We identified 34 studies (2,658 patients), representing 24 single-arm studies, and 10 parallel-arm RCT. In the analyses of the study arms, intravenous iron therapy resulted in a significant increase in hemoglobin, serum ferritin, transferrin saturation rate, serum iron, reticulocyte hemoglobin content as well as a significant decrease in the percentage of hypochromic erythrocytes and erythropoietin dose. There were significant increases in plasma malonyldialdehyde level and thiobarbituric acid-reactive substances, and a decrease in neutrophil respiratory burst. The analyses of the RCT revealed less robust net changes in these parameters, and there was no increased risk of adverse events including infections, cardiac events and mortality. CONCLUSIONS: Intravenous iron therapy for functional iron deficiency anemia in hemodialysis patients improves anemia parameters but exerts some effects on markers of oxidative stress that are of unclear clinical significance. The long-term safety and efficacy of this treatment strategy requires further study.

Association of Serum Free Light Chain Level with Long-Term Kidney Function in Patients with Newly Diagnosed Multiple Myeloma.

INTRODUCTION: Multiple myeloma (MM) frequently involves the kidneys, resulting in acute, subacute, or chronic kidney disease (CKD). Patient- and treatment-related factors are associated with the long-term development of CKD. The aim of our study was to examine the association of serum free light chain (FLC) levels, measured at the time of diagnosis of MM, and CKD at subsequent follow-up. METHODS: Patients with newly diagnosed MM were identified using cancer registries at five hospitals. The primary outcome was low eGFR (<60 mL/min/1.73 m2) or dialysis dependence and a secondary composite outcome of low eGFR, dialysis dependence, or death at the last follow-up, up to 12 months from diagnosis. Logistic regression analyses were performed. RESULTS: A total of 149 patients met the inclusion criteria. Patients with an FLC level above the median had a higher frequency of hypertension (54% vs. 81%; p < 0.001), hyperlipidemia (37% vs. 56%; p = 0.018), low eGFR at the time of diagnosis (43% vs. 66%; p = 0.006), and a higher MM stage (p = 0.018). On multivariable analyses, after adjustment for several covariates, serum FLC level (per each 100 mg/L) was independently associated with low eGFR or dialysis dependence at follow-up (adjusted odds ratio [aOR] 1.021; 95% CI: 1.002, 1.041; p = 0.033). This association persisted for the composite outcome of low eGFR, dialysis dependence, or death (aOR 1.034; 95% CI: 1.006, 1.063; p = 0.018). DISCUSSION/CONCLUSION: Higher serum FLC level measured at the time of MM diagnosis is independently associated with CKD at up to 12 months of follow-up.

Early access flow rate predicts vascular access patency-related intervention in the first year: A retrospective cohort study.

INTRODUCTION: Arteriovenous fistulas and grafts are lifelines for most hemodialysis patients, and a low access flow rate often requires patency-related intervention, such as angioplasty or thrombectomy, to prevent access failure. We examined whether early access flow rate, measured after initial fistula/graft cannulation, predicts vascular access patency-related intervention within 1 year. METHODS: This was a single-center retrospective cohort study. Among 172 patients undergoing surgical creation of a fistula/graft, 52 (30.2%) had documented access flow rates measurement by the Transonic™ ultrasound dilution technique, performed within an average of 48 days from initial access cannulation. The need for a patency-related intervention, defined as undergoing a fistulogram, angioplasty, thrombectomy, or surgical revision, was ascertained within 1 year. A receiver-operating characteristic curve (ROC) was generated to evaluate the diagnostic performance of first and average access flow rates for predicting patency-related intervention within 1 year. FINDINGS: Twenty-eight (53.8%) of the 52 study subjects required a patency-related intervention within 1 year. Their characteristics were not significantly different from those who did not require patency-related interventions. However, first access flow rates were significantly lower in patients requiring patency-related intervention compared to those who did not (898 vs. 1471 mL/min; p = 0.003), as were average access flow rates (841 vs. 1506 mL/min; p < 0.001). The ROC analyses revealed that first access flow rates and average access flow rates predicted the need for patency-related intervention within 1 year, with an area under-the-ROC curve of 0.743 (95% confidence interval [CI] 0.608, 0.877) and 0.775 (95% CI 0.648, 0.903), respectively, demonstrating acceptable discrimination. DISCUSSION: In adults undergoing hemodialysis, early access flow rate measurement can predict patency-related intervention within 1 year after initial vascular access cannulation. Additional studies are required to confirm these findings and identify optimal access flow rate cut-off values to predict vascular accesses at higher risk of stenosis.

Dose of erythropoiesis-stimulating agents and adverse outcomes in CKD: a metaregression analysis.

BACKGROUND: Targeting higher hemoglobin levels with erythropoiesis-stimulating agents (ESAs) to treat the anemia of chronic kidney disease (CKD) is associated with increased cardiovascular risk. STUDY DESIGN: Metaregression analysis examining the association of ESA dose with adverse outcomes independent of target or achieved hemoglobin level. SETTING & POPULATION: Patients with anemia of CKD irrespective of dialysis status. SELECTION CRITERIA FOR STUDIES: We searched MEDLINE (inception to August 2010) and bibliographies of published meta-analyses and selected randomized controlled trials assessing the efficacy of ESAs for the treatment of anemia in adults with CKD, with a minimum 3-month duration. Two authors independently screened citations and extracted relevant data. Individual study arms were treated as cohorts and constituted the unit of analysis. PREDICTORS: ESA dose standardized to a weekly epoetin alfa equivalent, and hemoglobin levels. OUTCOMES: All-cause and cardiovascular mortality, cardiovascular events, kidney disease progression, or transfusion requirement. RESULTS: 31 trials (12,956 patients) met the criteria. All-cause mortality was associated with higher (per epoetin alfa-equivalent 10,000-U/wk increment) first-3-month mean ESA dose (incidence rate ratio [IRR], 1.42; 95% CI, 1.10-1.83) and higher total-study-period mean ESA dose (IRR, 1.09; 95% CI, 1.02-1.18). First-3-month ESA dose remained significant after adjusting for first-3-month mean hemoglobin level (IRR, 1.48; 95% CI, 1.02-2.14), as did total-study-period mean ESA dose adjusting for target hemoglobin level (IRR, 1.41; 95% CI, 1.08-1.82). Parameter estimates between ESA dose and cardiovascular mortality were similar in magnitude and direction, but not statistically significant. Higher total-study-period mean ESA dose also was associated with increased rate of hypertension, stroke, and thrombotic events, including dialysis vascular access-related thrombotic events. LIMITATIONS: Use of study-level aggregated data; use of epoetin alfa-equivalent doses; lack of adjustment for confounders. CONCLUSIONS: In patients with CKD, higher ESA dose might be associated with all-cause mortality and cardiovascular complications independent of hemoglobin level.