Jean-Philippe Lafrance

Acute Kidney Injury Associates with Increased Long-Term Mortality

Acute kidney injury (AKI) associates with higher in-hospital mortality, but whether it also associates with increased long-term mortality is unknown, particularly after accounting for residual kidney function after hospital discharge. We retrospectively analyzed data from US veteran patients who survived at least 90 d after discharge from a hospitalization. We identified AKI events not requiring dialysis from laboratory data and classified them according to the ratio of the highest creatinine during the hospitalization to the lowest creatinine measured between 90 d before hospitalization and the date of discharge. We estimated mortality risks using multivariable Cox regression models adjusting for demographics, comorbidities, medication use, primary diagnosis of admission, length of stay, mechanical ventilation, and postdischarge estimated GFR (residual kidney function). Among the 864,933 hospitalized patients in the study cohort, we identified 82,711 hospitalizations of patients with AKI. In the study population of patients who survived at least 90 d after discharge, 17.4% died during follow-up (AKI 29.8%, without AKI 16.1%). The adjusted mortality risk associated with AKI was 1.41 (95% confidence interval [CI] 1.39 to 1.43) and increased with increasing AKI stage: 1.36 (95% CI 1.34 to 1.38), 1.46 (95% CI 1.42 to 1.50), and 1.59 (95% CI 1.54 to 1.65; P < 0.001 for trend). In conclusion, AKI that does not require dialysis associates with increased long-term mortality risk, independent of residual kidney function, for patients who survive 90 d after discharge. Long-term mortality risk is highest among the most severe cases of AKI.

Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases

Objective To quantify an association between acute kidney injury and use of high potency statins versus low potency statins. Design Retrospective observational analysis of administrative databases, using nine population based cohort studies and meta-analysis. We performed as treated analyses in each database with a nested case-control design. Rate ratios for different durations of current and past statin exposure to high potency or low potency statins were estimated using conditional logistic regression. Ratios were adjusted for confounding by high dimensional propensity scores. Meta-analytic methods estimated overall effects across participating sites. Setting Seven Canadian provinces and two databases in the United Kingdom and the United States. Participants 2 067 639 patients aged 40 years or older and newly treated with statins between 1 January 1997 and 30 April 2008. Each person hospitalized for acute kidney injury was matched with ten controls. Intervention A dispensing event was new if no cholesterol lowering drug or niacin prescription was dispensed in the previous year. High potency statin treatment was defined as ≥10 mg rosuvastatin, ≥20 mg atorvastatin, and ≥40 mg simvastatin; all other statin treatments were defined as low potency. Statin potency groups were further divided into cohorts with or without chronic kidney disease. Main outcome measure Relative hospitalization rates for acute kidney injury. Results Of more than two million statin users (2 008 003 with non-chronic kidney disease; 59 636 with chronic kidney disease), patients with similar propensity scores were comparable on measured characteristics. Within 120 days of current treatment, there were 4691 hospitalizations for acute kidney injury in patients with non-chronic kidney injury, and 1896 hospitalizations in those with chronic kidney injury. In patients with non-chronic kidney disease, current users of high potency statins were 34% more likely to be hospitalized with acute kidney injury within 120 days after starting treatment (fixed effect rate ratio 1.34, 95% confidence interval 1.25 to 1.43). Users of high potency statins with chronic kidney disease did not have as large an increase in admission rate (1.10, 0.99 to 1.23). χ2 tests for heterogeneity confirmed that the observed association was robust across participating sites. Conclusions Use of high potency statins is associated with an increased rate of diagnosis for acute kidney injury in hospital admissions compared with low potency statins. The effect seems to be strongest in the first 120 days after initiation of statin treatment.

Vascular Access–Related Infections: Definitions, Incidence Rates, and Risk Factors

Hemodialysis is associated with a high risk of morbidity and mortality, often caused by infections. Infections account for approximately 15% of all deaths in this patient population (the second leading cause after cardiovascular events) and for about one-fifth of admissions. Approximately one-fourth of infection-related admissions are caused by dialysis-associated peritonitis or vascular access infection that may lead to such significant complications as endocarditis or death. Published studies that assessed the determinants of hemodialysis-related vascular infections reported inconsistent findings. Variations in the definitions of infection among these studies despite the existence of standard guidelines proposed by at least 3 major work groups may explain, at least in part, these inconsistencies. A comprehensive in-depth review of those studies is needed to examine the inconsistencies in the published results. We first revised the existing vascular access-related infection definitions, then conducted a narrative review of the published literature that examined predictors of vascular access-related infections, highlighting the heterogeneity in methods and findings. Better understanding of the risk factors for vascular access-related infections may inform efficacious prevention strategies and lead to early detection of infections and improved patient care.

Incidence and outcomes of acute kidney injury in a referred chronic kidney disease cohort.

BACKGROUND Whilst chronic kidney disease (CKD) has been identified as a risk factor for the development of acute kidney injury (AKI), little has been published about the incidence and outcomes of those acute injuries on chronic stable kidney disease and even less in a referred cohort of CKD patients followed up by nephrologists. METHODS We followed up 6862 patients registered as CKD in British Columbia, Canada for a median time of 19.4 months after they achieved an estimated glomerular filtration rate (eGFR) value < or =30 mL/min/1.73 m(2). AKI was defined as a decrease in eGFR of > or =25% compared to a moving baseline eGFR within 25 days. RESULTS Of the CKD patients, 44.9% had at least one AKI episode. Crude incidence rate for a first AKI event was 34.8 per 100 person-years. Older age [adjusted relative risks (RR) = 0.93 by 10 years, 95% confidence intervals (CI) = 0.90, 0.95] was associated with a lower risk of AKI. Of the patients, 15.3% died before dialysis and 18.1% initiated dialysis. AKI was associated with both a higher risk of death (adjusted RR = 2.32, 95% CI = 2.04, 2.64) and an increased risk of dialysis (adjusted RR = 2.33, 95% CI = 2.07, 2.61). CONCLUSIONS In a referred CKD population, AKI was a frequent event and associated with higher risks of dialysis and mortality. The incidence of AKI appears to be less with older age in this population. Quantification of AKI incidence and its risk factors in different populations is important for clinicians and planners, so that appropriate identification, prevention and treatment strategies can be tested.

Defining Acute Kidney Injury in Database Studies: The Effects of Varying the Baseline Kidney Function Assessment Period and Considering CKD Status

BACKGROUND Existing acute kidney injury (AKI) definitions are not well adapted for database studies, leading to a great variety of methods used in research. Variations in time before hospitalization used to assess baseline kidney function when identifying episodes of AKI may lead to different case samples and mortality risks in database studies, but the magnitude of these effects is not known. STUDY DESIGN A retrospective cohort study. SETTINGS & PARTICIPANTS 1,126,636 veterans hospitalized at least once within the US Department of Veterans Affairs health care system between 2000 and 2005. PREDICTOR AKI was defined by comparing (using ratio [≥1.5] or difference [increase of 0.3-0.5 mg/dL]) the highest serum creatinine level during hospitalization with the lowest level during 4 different baseline assessment periods (in-hospital only and 3, 6, or 12 months preadmission). OUTCOMES & MEASUREMENTS In-hospital mortality risk was estimated using multivariable logistic regression models. RESULTS Using the ratio definition, the cumulative incidence of AKI ranged from 12.5% (in-hospital only) to 18.3% (12 months preadmission). Newly added cases had milder AKI and lower mortality risk. The discriminative power increased slightly (C statistic increased from 0.846 to 0.855; P = 0.001) by extending the baseline period to at least 3 months. Both the ratio and difference definitions did not perform well in patients with chronic kidney disease stages 4 and 5. LIMITATIONS Possibility of residual confounding and under-representation of women (4.5%). CONCLUSIONS Many additional AKI cases may be identified by extending the baseline assessment period; however, added cases may be less severe with lower mortality risk. The relative strengths of these biases and combined effects of reducing misclassification (identification of more AKI cases) and increasing risk dilution (identifying milder cases) may vary across populations. Consensus regarding how baseline kidney function should be determined in database studies should be reached.

Selective and non-selective non-steroidal anti-inflammatory drugs and the risk of acute kidney injury†

Use of non‐steroidal anti‐inflammatory drugs (NSAID) is associated with risk of acute kidney injury (AKI). Risk of AKI may vary with selectivity of the NSAID, but this has not been studied in a large cohort where AKI was assessed directly from laboratory data. The objective was to compare AKI risk between selective and non‐selective NSAIDs using a laboratory‐based definition of AKI.

Successful Treatment of Encapsulating Peritoneal Sclerosis With Immunosuppressive Therapy

Encapsulating peritoneal sclerosis is a rare, but potentially lethal, complication of peritoneal dialysis. Treatment of patients with encapsulating peritoneal sclerosis is controversial. Conservative treatment carries a poor outcome, and immunosuppressive drugs are now used frequently. Most commonly, these immunosuppressive regimens include steroids with or without azathioprine or cyclosporine. Mycophenolate mofetil is a reversible DNA synthesis inhibitor that frequently replaces azathioprine in renal transplantation because of its improved immunosuppressive potency and better side-effect profile. We report 3 cases of encapsulating peritoneal sclerosis in continuous ambulatory peritoneal dialysis patients for which an association of prednisone and mycophenolate mofetil significantly modified the evolution of the disease. All 3 patients showed significant improvement within a month and are still alive more than 2 years after the diagnosis of encapsulating peritoneal sclerosis. None experienced a relapse or abdominal symptoms, and body weights are stable. This is the first report of 3 cases of successful treatment of patients with encapsulating peritoneal sclerosis with prednisone and mycophenolate mofetil.

Trends in Initial Lower Extremity Amputation Rates Among Veterans Health Administration Health Care System Users From 2000 to 2004

OBJECTIVE To evaluate temporal trends in rates of initial lower extremity amputation (ILEA) among patients with diabetes in the Veterans Health Administration (VHA). RESEARCH DESIGN AND METHODS Retrospective administrative data analysis of VHA clinic users with diabetes in fiscal years (FY) 2000 to 2004 (1 October 1999–30 September 2004). We calculated annual age– and sex–standardized rates of initial major, minor, and total amputations for the overall population and for various racial/ethnic groups (African Americans, Hispanics, and whites). Trends in ILEA risk were evaluated with and without adjustment for demographic characteristics and other potential risk factors, including presence of microvascular and macrovascular diseases, and antiglycemic treatment. RESULTS Study populations of VHA patients with diabetes and without prior amputations ranged from 405,580 in FY 2000 to 739,377 in FY 2004. Age- and sex-standardized ILEA rates decreased by 34% (7.08/1,000 patients in FY 2000 to 4.65/1,000 patients in FY 2005) during the 5-year period. Minor and major amputation rates decreased by 33% (4.59 to 3.06/1,000) and 36% (2.49 to 1.59/1,000), respectively. Of major amputations, below-knee rates decreased from 1.08 to 0.87/1,000 (−19%), and above-knee decreased from 1.41 to 0.72/1,000 (−49%). Similar trends were seen for all racial groups. ILEA risk decreased by 28% (odds ratio 0.72 [95% CI 0.68–0.75]) when FY 2004 was compared with FY 2000 in the model, adjusting for demographic characteristics. This risk decrease was 22% in the model adjusting for all independent variables (odds ratio 0.78 [95% CI 0.74–0.82]). CONCLUSIONS Downward 5-year trends in ILEA rates were observed for all amputation levels and among all racial groups, even after adjustment for risk differences over time.

Randomized Clinical Trial of Sodium Polystyrene Sulfonate for the Treatment of Mild Hyperkalemia in CKD

BACKGROUND AND OBJECTIVES Hyperkalemia affects up to 10% of patients with CKD. Sodium polystyrene sulfonate has long been prescribed for this condition, although evidence is lacking on its efficacy for the treatment of mild hyperkalemia over several days. This study aimed to evaluate the efficacy of sodium polystyrene sulfonate in the treatment of mild hyperkalemia. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In total, 33 outpatients with CKD and mild hyperkalemia (5.0-5.9 mEq/L) in a single teaching hospital were included in this double-blind randomized clinical trial. We randomly assigned these patients to receive either placebo or sodium polystyrene sulfonate of 30 g orally one time per day for 7 days. The primary outcome was the comparison between study groups of the mean difference of serum potassium levels between the day after the last dose of treatment and baseline. RESULTS The mean duration of treatment was 6.9 days. Sodium polystyrene sulfonate was superior to placebo in the reduction of serum potassium levels (mean difference between groups, -1.04 mEq/L; 95% confidence interval, -1.37 to -0.71). A higher proportion of patients in the sodium polystyrene sulfonate group attained normokalemia at the end of their treatment compared with those in the placebo group, but the difference did not reach statistical significance (73% versus 38%; P=0.07). There was a trend toward higher rates of electrolytic disturbances and an increase in gastrointestinal side effects in the group receiving sodium polystyrene sulfonate. CONCLUSIONS Sodium polystyrene sulfonate was superior to placebo in reducing serum potassium over 7 days in patients with mild hyperkalemia and CKD.

Depression and incident lower limb amputations in veterans with diabetes

PROBLEM Depression is associated with a higher risk of macrovascular and microvascular complications and mortality in diabetes, but whether depression is linked to an increased risk of incident amputations is unknown. We examined the association between diagnosed depression and incident non-traumatic lower limb amputations in veterans with diabetes. METHODS This was a retrospective cohort study from 2000-2004 that included 531,973 veterans from the Diabetes Epidemiology Cohorts, a national Veterans Affairs (VA) registry with VA and Medicare data. Depression was defined by diagnostic codes or antidepressant prescriptions. Amputations were defined by diagnostic and procedural codes. We determined the HR and 95% CI for incident non-traumatic lower limb amputation by major (transtibial and above) and minor (ankle and below) subtypes, comparing veterans with and without diagnosed depression and adjusting for demographics, health care utilization, diabetes severity and comorbid medical and mental health conditions. RESULTS Over a mean 4.1 years of follow-up, there were 1289 major and 2541 minor amputations. Diagnosed depression was associated with an adjusted HR of 1.33 (95% CI: 1.15-1.55) for major amputations. There was no statistically significant association between depression and minor amputations (adjusted HR 1.01, 95% CI: 0.90-1.13). CONCLUSIONS Diagnosed depression is associated with a 33% higher risk of incident major lower limb amputation in veterans with diabetes. Further study is needed to understand this relationship and to determine whether depression screening and treatment in patients with diabetes could decrease amputation rates.