Matthew A. Weir

Comparison of standard and accelerated initiation of renal replacement therapy in acute kidney injury.

In patients with severe acute kidney injury (AKI) but no urgent indication for renal replacement therapy (RRT), the optimal time to initiate RRT remains controversial. While starting RRT preemptively may have benefits, this may expose patients to unnecessary RRT. To study this, we conducted a 12-center open-label pilot trial of critically ill adults with volume replete severe AKI. Patients were randomized to accelerated (12 h or less from eligibility) or standard RRT initiation. Outcomes were adherence to protocol-defined time windows for RRT initiation (primary), proportion of eligible patients enrolled, follow-up to 90 days, and safety in 101 fully eligible patients (57 with sepsis) with a mean age of 63 years. Median serum creatinine and urine output at enrollment were 268 micromoles/l and 356 ml per 24 h, respectively. In the accelerated arm, all patients commenced RRT and 45/48 did so within 12 h from eligibility (median 7.4 h). In the standard arm, 33 patients started RRT at a median of 31.6 h from eligibility, of which 19 did not receive RRT (6 died and 13 recovered kidney function). Clinical outcomes were available for all patients at 90 days following enrollment, with mortality 38% in the accelerated and 37% in the standard arm. Two surviving patients, both randomized to standard RRT initiation, were still RRT dependent at day 90. No safety signal was evident in either arm. Our findings can inform the design of a large-scale effectiveness randomized control trial.

Validity of the International Classification of Diseases, Tenth Revision code for acute kidney injury in elderly patients at presentation to the emergency department and at hospital admission

Objective To evaluate the validity of the International Classification of Diseases, Tenth Revision (ICD-10) code N17x for acute kidney injury (AKI) in elderly patients in two settings: at presentation to the emergency department and at hospital admission. Design A population-based retrospective validation study. Setting Southwestern Ontario, Canada, from 2003 to 2010. Participants Elderly patients with serum creatinine measurements at presentation to the emergency department (n=36 049) or hospital admission (n=38 566). The baseline serum creatinine measurement was a median of 102 and 39 days prior to presentation to the emergency department and hospital admission, respectively. Main outcome measures Sensitivity, specificity and positive and negative predictive values of ICD-10 diagnostic coding algorithms for AKI using a reference standard based on changes in serum creatinine from the baseline value. Median changes in serum creatinine of patients who were code positive and code negative for AKI. Results The sensitivity of the best-performing coding algorithm for AKI (defined as a ≥2-fold increase in serum creatinine concentration) was 37.4% (95% CI 32.1% to 43.1%) at presentation to the emergency department and 61.6% (95% CI 57.5% to 65.5%) at hospital admission. The specificity was greater than 95% in both settings. In patients who were code positive for AKI, the median (IQR) increase in serum creatinine from the baseline was 133 (62 to 288) µmol/l at presentation to the emergency department and 98 (43 to 200) µmol/l at hospital admission. In those who were code negative, the increase in serum creatinine was 2 (−8 to 14) and 6 (−4 to 20) µmol/l, respectively. Conclusions The presence or absence of ICD-10 code N17× differentiates two groups of patients with distinct changes in serum creatinine at the time of a hospital encounter. However, the code underestimates the true incidence of AKI due to a limited sensitivity.

Retrieving Clinical Evidence: A Comparison of PubMed and Google Scholar for Quick Clinical Searches

Background Physicians frequently search PubMed for information to guide patient care. More recently, Google Scholar has gained popularity as another freely accessible bibliographic database. Objective To compare the performance of searches in PubMed and Google Scholar. Methods We surveyed nephrologists (kidney specialists) and provided each with a unique clinical question derived from 100 renal therapy systematic reviews. Each physician provided the search terms they would type into a bibliographic database to locate evidence to answer the clinical question. We executed each of these searches in PubMed and Google Scholar and compared results for the first 40 records retrieved (equivalent to 2 default search pages in PubMed). We evaluated the recall (proportion of relevant articles found) and precision (ratio of relevant to nonrelevant articles) of the searches performed in PubMed and Google Scholar. Primary studies included in the systematic reviews served as the reference standard for relevant articles. We further documented whether relevant articles were available as free full-texts. Results Compared with PubMed, the average search in Google Scholar retrieved twice as many relevant articles (PubMed: 11%; Google Scholar: 22%; P<.001). Precision was similar in both databases (PubMed: 6%; Google Scholar: 8%; P=.07). Google Scholar provided significantly greater access to free full-text publications (PubMed: 5%; Google Scholar: 14%; P<.001). Conclusions For quick clinical searches, Google Scholar returns twice as many relevant articles as PubMed and provides greater access to free full-text articles.

Impact of Estimated GFR Reporting on Patients, Clinicians, and Health-Care Systems: A Systematic Review

BACKGROUND Many laboratories now report estimated glomerular filtration rate (eGFR) when a serum creatinine measurement is ordered. A summary of the impact of eGFR reporting in health care systems around the world for which it has been adopted is lacking. STUDY DESIGN Systematic review of MEDLINE, EMBASE, other major databases, and conference proceedings of major nephrology meetings. SETTING & POPULATION Any health care system in which eGFR reporting was introduced. SELECTION CRITERIA FOR STUDIES Published studies or abstracts reporting patient, clinician, or health system outcomes of eGFR reporting. INTERVENTION eGFR reporting. OUTCOMES Volume of referrals or consults seen by nephrologists, changes in characteristics of patients who were seen, and prescription rates of kidney-related medications. RESULTS 22 studies (10 full text and 12 conference abstracts) were identified in 2004-2010 from 5 countries. Nephrologist referrals and consultations increased after eGFR reporting, ranging from 13%-270%. The greatest increases in referrals were seen for the elderly, females, and those with stage 3 or higher chronic kidney disease (eGFR <60 mL/min/1.73 m(2)). Change in renin-angiotensin-aldosterone system-blocking drug use ranged from increases of 0%-6%. LIMITATIONS Studies were highly variable in definition of outcomes. Reports were not available for many health care systems in which eGFR reporting was implemented. CONCLUSIONS eGFR reporting has been associated with greater identification of patients with decreased kidney function in most health care systems that have reported its impact.

Standard versus accelerated initiation of renal replacement therapy in acute kidney injury (STARRT-AKI): study protocol for a randomized controlled trial

BackgroundAcute kidney injury is a common and devastating complication of critical illness, for which renal replacement therapy is frequently needed to manage severe cases. While a recent systematic review suggested that “earlier” initiation of renal replacement therapy improves survival, completed trials are limited due to small size, single-centre status, and use of variable definitions to define “early” renal replacement therapy initiation.Methods/designThis is an open-label pilot randomized controlled trial. One hundred critically ill patients with severe acute kidney injury will be randomly allocated 1:1 to receive “accelerated” initiation of renal replacement therapy or “standard” initiation at 12 centers across Canada. In the accelerated arm, participants will have a venous catheter placed and renal replacement therapy will be initiated within 12 hours of fulfilling eligibility. In the standard initiation arm, participants will be monitored over 7 days to identify indications for renal replacement therapy. For participants in the standard arm with persistent acute kidney injury, defined as a serum creatinine not declining >50% from the value at the time of eligibility, the initiation of RRT will be discouraged unless one or more of the following criteria are fulfilled: serum potassium ≥6.0 mmol/L; serum bicarbonate ≤10 mmol/L; severe respiratory failure (PaO2/FiO2<200) or persisting acute kidney injury for ≥72 hours after fulfilling eligibility. The inclusion criteria are designed to identify a population of critically ill adults with severe acute kidney injury who are likely to need renal replacement therapy during their hospitalization, but not immediately. The primary outcome is protocol adherence (>90%). Secondary outcomes include measures of feasibility (proportion of eligible patients enrolled in the trial, proportion of enrolled patients followed to 90 days for assessment of vital status and the need for renal replacement therapy) and safety (occurrence of adverse events).DiscussionThe optimal timing of renal replacement therapy initiation in patients with severe acute kidney injury remains uncertain, representing an important knowledge gap and a priority for high-quality research. This pilot trial is necessary to establish protocol feasibility, confirm the safety of participants and obtain estimated events rates for design of a large definitive trial.Trial registration numberNCT01557361

Orlistat and acute kidney injury: an analysis of 953 patients.

Lewis), San Francisco General Hospital, San Francisco. Correspondence: Dr Fiebig, Clinical Laboratory, San Francisco General Hospital, Bldg NH, Room 2M24, 1001 Potrero Ave, San Francisco, CA 94110 (efiebig@ucsf.edu). Author Contributions: Study concept and design: Fiebig, Jones, Logan, Wang, and Lewis. Acquisition of data: Fiebig, Jones, Logan, Wang, and Lewis. Analysis and interpretation of data: Fiebig, Jones, and Lewis. Drafting of the manuscript: Fiebig. Critical revision of the manuscript for important intellectual content: Fiebig, Jones, Logan, Wang, and Lewis. Statistical analysis: Fiebig. Administrative, technical, and material support: Jones. Study supervision: Jones. Financial Disclosure: None reported.

Oral bisphosphonate use in the elderly is not associated with acute kidney injury

Intravenous bisphosphonates can cause acute kidney injury; however, this risk was not found with oral bisphosphonates in randomized clinical trials with restrictive eligibility criteria. In order to provide complementary safety data, we studied the risk of acute kidney injury in a population-based cohort of 122,727 patients aged 66 years and older discharged from hospital following a new fragility fracture and no history of bisphosphonate use in the prior year. Bisphosphonate treatment was identified within 120 days after discharge and event rates were measured from 90 days of therapy initiation. The primary outcome was hospitalization with acute kidney injury with secondary outcomes of new nephrology consultation and, in a subset of patients with laboratory values, acute kidney injury was defined as an increase in serum creatinine. We identified 18,286 bisphosphonate users and 104,441 non-users with a mean age of 81 years. Of 5772 patients with laboratory values, 40% had chronic kidney disease (eGFR <60 ml/min per 1.73 m(2)). Overall, there was no statistically significant difference in the risk of acute kidney injury among bisphosphonate users compared to non-users (adjusted odds ratio 1.03), and no significant differences in other outcomes or in subgroups of patients with baseline chronic kidney disease. Thus, in this older population-based cohort, oral bisphosphonate use was not associated with acute kidney injury.

Trimethoprim-sulfamethoxazole induced hyperkalaemia in elderly patients receiving spironolactone: nested case-control study

Objectives To characterise the risk of admission to hospital for hyperkalaemia in elderly patients treated with trimethoprim-sulfamethoxazole in combination with spironolactone. Design Population based nested case-control study. Setting Ontario, Canada, from 1 April 1992 to 1 March 2010. Participants Cases were residents of Ontario aged 66 years or above receiving chronic treatment with spironolactone and admitted to hospital with hyperkalaemia within 14 days of receiving a prescription for either trimethoprim-sulfamethoxazole, amoxicillin, norfloxacin, or nitrofurantoin. Up to four controls for each case were identified from the same cohort, matched on age, sex, and presence or absence of chronic kidney disease and diabetes, and required to have received one of the study antibiotics within 14 days before the case’s index date. Main outcome measures Odds ratio for association between admission to hospital with hyperkalaemia and receipt of a study antibiotic in the preceding 14 days, adjusted for conditions and drugs that may influence risk of hyperkalaemia. Results During the 18 year study period, 6903 admissions for hyperkalaemia were identified, 306 of which occurred within 14 days of antibiotic use. Of these, 248 (81%) cases were matched to 783 controls. 10.8% (17 859/165 754) of spironolactone users received at least one prescription for trimethoprim-sulfamethoxazole. Compared with amoxicillin, prescription of trimethoprim-sulfamethoxazole was associated with a marked increase in the risk of admission to hospital for hyperkalaemia (adjusted odds ratio 12.4, 95% confidence interval 7.1 to 21.6). The population attributable fraction was 59.7%, suggesting that approximately 60% of all cases of hyperkalaemia in older patients taking spironolactone and treated with an antibiotic for a urinary tract infection could be avoided if trimethoprim-sulfamethoxazole was not prescribed. Treatment with nitrofurantoin was also associated with an increase in the risk of hyperkalaemia (adjusted odds ratio 2.4, 1.3 to 4.6), but no such risk was found with norfloxacin (adjusted odds ratio 1.6, 0.8 to 3.4) Conclusions Among older patients receiving spironolactone, treatment with trimethoprim-sulfamethoxazole was associated with a major increase in the risk of admission to hospital for hyperkalaemia. This drug combination should be avoided when possible.

Filtering Medline for a clinical discipline: diagnostic test assessment framework

Objective To develop and test a Medline filter that allows clinicians to search for articles within a clinical discipline, rather than searching the entire Medline database. Design Diagnostic test assessment framework with development and validation phases. Setting Sample of 4657 articles published in 2006 from 40 journals. Reviews Each article was manually reviewed, and 19.8% contained information relevant to the discipline of nephrology. The performance of 1 155 087 unique renal filters was compared with the manual review. Main outcome measures Sensitivity, specificity, precision, and accuracy of each filter. Results The best renal filters combined two to 14 terms or phrases and included the terms “kidney” with multiple endings (that is, truncation), “renal replacement therapy”, “renal dialysis”, “kidney function tests”, “renal”, “nephr” truncated, “glomerul” truncated, and “proteinuria”. These filters achieved peak sensitivities of 97.8% and specificities of 98.5%. Performance of filters remained excellent in the validation phase. Conclusions Medline can be filtered for the discipline of nephrology in a reliable manner. Storing these high performance renal filters in PubMed could help clinicians with their everyday searching. Filters can also be developed for other clinical disciplines by using similar methods.

Risk of Acute Kidney Injury From Oral Acyclovir: A Population-Based Study

BACKGROUND Intravenous acyclovir-induced acute kidney injury (AKI) from drug crystallization in the renal tubules is described in case reports, review articles, and drug prescribing manuals. Similarly, AKI from oral acyclovir is described in case reports, but the risk in routine practice is unknown. STUDY DESIGN Retrospective population-based cohort study. SETTING & PARTICIPANTS We studied a large cohort of older patients in Ontario, Canada, receiving new outpatient prescriptions from 1997 to 2011 for oral acyclovir or valacyclovir (which is metabolized to acyclovir). The comparison drug was famciclovir, an antiviral used for indications similar to acyclovir, but with no known renal toxicity. PREDICTOR Outpatient prescription for oral acyclovir, valacyclovir, or famciclovir. OUTCOMES The primary outcome was hospital admission with AKI in the 30 days after the initial prescription. MEASUREMENTS We assessed the primary outcome with health care diagnostic codes. In a subpopulation, we assessed AKI using available laboratory serum creatinine measurements. RESULTS 76,269 patients received acyclovir or valacyclovir and 84,646 received famciclovir. On average, patients were aged 76 [IQR, 71-81] years and prescription duration was 7 days. Acyclovir or valacyclovir use was not associated with a higher risk of hospital admission with AKI (209 [0.27%] events with acyclovir or valacyclovir vs 238 [0.28%] events with famciclovir [relative risk, 0.97; 95% CI, 0.81-1.17]). Results were consistent in adjusted analyses, in all subgroups, and in the subpopulation with laboratory measurements. LIMITATIONS Diagnostic codes had high specificity but low sensitivity and underestimated the incidence of AKI. Only a limited number of patients (n = 2,729) had serum creatinine values available. CONCLUSIONS In this population-based study of older adults, oral acyclovir use was not associated with a higher risk of AKI compared to famciclovir.