Jean‐Philippe Lafrance

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.

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). χ(2) 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.

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.

PURPOSE: 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. METHODS: We conducted a retrospective nested case-control study in the U.S. Department of Veterans Affairs health care system. From a cohort of 1 459 271 new NSAID users, we identified 22 824 cases of AKI (97% male; mean age: 63 years), and 336 734 matched controls between 2000 and 2006. AKI was defined as a creatinine increase of greater than 50%. RESULTS: We found higher risk of AKI in new users of any single NSAID (adjusted odds ratio = 1.82; 95%CI: 1.68, 1.98) compared to non-users without recent use. The risk of AKI varied among different NSAIDs with risk generally increasing with decrease in selectivity: rofecoxib (0.95; 0.64, 1.42), celecoxib (0.96; 0.63, 1.47), meloxicam (1.13; 0.63, 2.05), etodolac (1.31; 1.08, 1.59), diclofenac (1.11; 0.84, 1.48), piroxicam (1.53; 1.05, 2.23), salsalate (1.51; 1.22, 1.87), sulindac (1.61; 1.12, 2.30), ibuprofen (2.25, 2.04, 2.49), naproxen (1.72; 1.52, 1.95), high dose aspirin (3.64; 2.46, 5.37), indomethacin (1.94; 1.56, 2.42), keterolac (2.07; 1.78, 2.41). Those using multiple NSAIDs appeared to have higher risk (2.90; 2.62, 3.22). CONCLUSIONS: This study provides evidence that risk of AKI may be lower with more selective agents than with naproxen or other non-selective NSAIDs.