Medication Holds in CKD During Acute Volume-Depleting Illnesses: A Randomized Controlled Trial of a "Sick-Day" Protocol.

Rationale & Objective: Some drugs prescribed for chronic kidney disease (CKD) may become hazardous on sick days with volume depletion by increasing the risk of acute kidney injury (AKI) and kidney function loss; however, the risks and benefits of their use during intercurrent illness is unknown. Study Design: 6-month pragmatic trial examining a sick-day protocol to determine if withholding prespecified drugs during a volume-depleting illness reduces the incidence AKI or kidney function loss in CKD. Setting & Participants: 315 veterans with stage 3-5 CKD, treated with a renin-angiotensin-aldosterone inhibitor blocker, diuretic, nonsteroidal anti-inflammatory drug, or metformin were randomized into the study with n = 159 and n = 156 in sick-day protocol and usual care groups, respectively. Intervention: Sick-day protocol administered via interactive voice response system (IVRS) or usual care with 6-month follow-up. Outcomes: The outcomes of the study are as follows: (1) Change in kidney function, (2) incidence of AKI based on International Classification of Diseases, Tenth Revision codes and ambulatory laboratory testing, (3) urgent service utilizations, and (4) sick days. Results: The mean age was 70.1 ± 7.4 and 69.2 ± 8.1 years, with a mean baseline glomerular filtration rate (GFR) of 43.1 ± 13.1 and 43.8 ± 13.0 mL/min/1.73 m2, and 112 (70%) and 100 (64%) of participants with diabetes in the sick-day protocol and usual care groups, respectively. The mean change in GFR in the sick-day protocol and usual care groups from baseline to 6-month follow-up, adjusting for baseline GFR, was -0.71 (95% CI, -2.11 to 0.69) and -0.72 (95% CI, -2.12 to 0.68), respectively, with no significant difference, P = 0.99. Hospitalizations in the sick-day protocol and usual care groups were 11.5/100 and 8.4/100 events per person-months, respectively, with the adjusted rate ratio not significantly increased (prevalence ratio, 1.30; 95% CI, 0.96-1.76). Participants interacted with the IVRS in 81% of expected weeks and 19 had one or more qualifying events. In 33 true sick days, participants correctly followed the protocol in only 14. Limitations: Low incidence of sick days over the 6-month period of the study. Conclusions: The sick-day protocol was not associated with a significant reduction in AKI episodes or kidney function loss in a high-risk CKD population. Engagement with the IVRS was high, but successful implementation of the sick-day protocol was not optimal. Trial Registration: ClinicalTrials.gov; NCT03141905.

Risk of Potentially Inappropriate Medications in Adults With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Adults with chronic kidney disease (CKD) may be at increased risk of adverse effects from use of potentially inappropriate medications (PIMs). Our objective was to assess whether PIM exposure has an independent association with CKD progression, hospitalizations, mortality, or falls. STUDY DESIGN: Retrospective observational study. SETTING & PARTICIPANTS: Chronic Renal Insufficiency Cohort (CRIC) study; 3,929 adults with CKD enrolled 2003-2008 and followed prospectively until December 2011. EXPOSURE: PIM exposure was defined as prescriptions for any medications to be avoided in older adults as defined by the 2015 American Geriatrics Society Beers Criteria. OUTCOME: Hospitalization count, death, a composite kidney disease end point of CKD progression or initiation of kidney replacement therapy (KRT), KRT, and fall events assessed 1 year after PIM exposure. ANALYTICAL APPROACH: Logistic regression and Poisson regression to estimate the associations of PIM exposure with each outcome. RESULTS: The most commonly prescribed PIMs were proton pump inhibitors and α-blockers. In unadjusted models, any PIM exposure (compared to none) was associated with hospitalizations, death, and fall events. After adjustment, exposure to 1, 2, or≥3 PIMs had a graded association with a higher hospitalization rate (rate ratios of 1.09 [95% CI, 1.01-1.17], 1.18 [95% CI, 1.07-1.30], and 1.35 [95% CI, 1.19-1.53], respectively) and higher odds of mortality (odds ratios of 1.19 [95% CI, 0.91-1.54], 1.62 [95% CI, 1.21-2.17], and 1.65 [95% CI, 1.14-2.41], respectively). In a cohort subset reporting falls (n=1,109), prescriptions for≥3 PIMs were associated with an increased risk of falls (adjusted OR, 2.85 [95% CI, 1.54-5.26]). PIMs were not associated with CKD progression or KRT. Age did not modify the association between PIM count and outcomes. LIMITATIONS: Measurement bias; confounding by indication. CONCLUSIONS: Adults of any age with CKD who are prescribed PIMs have an increased risk of hospitalization, mortality, and falls with the greatest risk occurring after more than 1 PIM prescription.

Electric cigarette-related lung injury and cardiovascular insult.

The cardiovascular effects of electronic cigarette use are unknown. Here we present a case describing a young, previously healthy patient without prior cardiopulmonary comorbidities who developed severe, acute cardiac dysfunction in the setting of e-cigarette use, in addition to the more commonly encountered respiratory symptoms. While pulmonary manifestations are characteristic of e-cigarette or vaping product use-associated lung injury (EVALI), the acute and reversible cardiomyopathy seen here has not been previously described in association with either EVALI or e-cigarette use.

Associations of Performance-Based Functional Assessments and Adverse Outcomes in CKD.

Background: The comparative utility of performance-based functional assessments in predicting adverse outcomes in CKD is unknown. To examine their relative utility, we examined three performance-based functional assessments in an observational cohort of patients with CKD. Methods: We recruited 350 participants with stage II-V, predialysis CKD. Participants were administered three performance-based functional assessments: Short Physical Performance Battery (SPPB), Modified Mini-Mental Status Exam (M3SE), and Lawton Instrumental Activities of Daily Living (IADL). Scores were dichotomized on the basis of the median and combined into a summary score. Outcomes included 50% GFR reduction, ESKD, and death. We used Cox proportional hazards to assess the association of performance-based functional assessments with outcomes. Results: Compared with high performers, low SPPB performers had the highest adjusted rate of death, ESKD, or 50% reduction in GFR (HR, 1.96; 95% CI, 1.28 to 2.99). Low SPPB had the strongest association with death when adjusted for multiple covariates (HR, 2.43; 95% CI, 1.36 to 4.34). M3SE performance was not associated with any adverse outcome. None of the performance-based functional assessments were associated with ESKD, but a low IADL score was associated with a lower hazard ratio for ESKD or 50% decline GFR (HR, 0.49; 95% CI, 0.24 to 1.00). Conclusions: Low SPPB score was the strongest predictor of death and all adverse outcomes as a composite. Future trials should determine if outcomes for patients with CKD who have poor physical performance and low SPPB scores are improved by targeted interventions. Clinical Trial registry name and registration number: Safe Kidney Care Cohort Study, NCT01407367.

Association of Opioids and Nonsteroidal Anti-inflammatory Drugs With Outcomes in CKD: Findings From the CRIC (Chronic Renal Insufficiency Cohort) Study.

RATIONALE & OBJECTIVE: Safe analgesic choices are limited in chronic kidney disease (CKD). We conducted a comparative analysis of harm from opioids versus nonsteroidal anti-inflammatory drugs (NSAIDs) in CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 3,939 patients with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study. EXPOSURES: 30-day analgesic use reported at annual visits. OUTCOMES: A composite outcome of 50% glomerular filtration rate reduction and kidney failure requiring kidney replacement therapy (KRT), as well as the outcomes of kidney failure requiring KRT, hospitalization, and pre-kidney failure death. ANALYTICAL APPROACH: Marginal structural models with time-updated exposures. RESULTS: Participants were followed up for a median of 6.84 years, with 391 (9.9%) and 612 (15.5%) reporting baseline opioid and NSAID use, respectively. Time-updated opioid use was associated with the kidney disease composite outcome, kidney failure with KRT, death (HRs of 1.4 [95% CI, 1.2-1.7], 1.4 [95% CI, 1.1-1.7], and 1.5 [95% CI, 1.2-2.0], respectively), and hospitalization (rate ratio [RR], 1.7; 95% CI, 1.6-1.9) versus opioid nonusers. Similar results were found in an analysis restricted to a subcohort of participants reporting ever using other (nonopioid and non-NSAID) analgesics or tramadol. Time-updated NSAID use was associated with increased risk for the kidney disease composite (HR, 1.2; 95% CI, 1.0-1.5) and hospitalization (RR, 1.1; 95% CI, 1.0-1.3); however, these associations were not significant in the subcohort. The association of NSAID use with the kidney disease composite outcome varied by race, with a significant risk in blacks (HR, 1.3; 95% CI, 1.0-1.7). NSAID use was associated with lower risk for kidney failure with KRT in women and individuals with glomerular filtration rate<45mL/min/1.73m2 (HRs of 0.63 [95% CI, 0.45-0.88] and 0.77 [95% CI, 0.59-0.99], respectively). LIMITATIONS: Limited periods of recall of analgesic use and potential confounding by indication. CONCLUSIONS: Opioid use had a stronger association with adverse events than NSAIDs, with the latter's association with kidney disease outcomes limited to specific subgroups, notably those of black race.

Ensuring Patient Safety During the Transition to ESRD.

Patients with chronic kidney disease (CKD) are at risk for complications both inherent to the disease and as a consequence of its treatment. The dangers that CKD patients face change across the spectrum of the disease. Providers who are well-versed in these safety threats are best poised to safeguard patients as their CKD progresses.

Adverse safety events in patients with Chronic Kidney Disease (CKD).

INTRODUCTION: Chronic kidney disease (CKD) confers a higher risk of adverse safety events as a result of many factors including medication dosing errors and use of nephrotoxic drugs, which can cause kidney injury and renal function decline. CKD patients may also have comorbidities such as hypertension and diabetes for which they require more frequent care from different providers, and for which standard, but countervailing treatments, may put them at risk for adverse safety events. Areas covered: In addition to the well-known agents such as iodinated radiocontrast, antimicrobials, diuretics and angiotensin converting enzyme (ACE) inhibitors which can directly affect renal function, safety considerations in the treatment of common CKD complications such as anemia, diabetes, analgesia and thrombosis will also be discussed. Expert opinion: Better outcomes in CKD may be achieved by alerting care providers to the special care needs of kidney patients and encouraging patients to self-manage their disease with the decision support of multidisciplinary patient care teams.

Lack of fluoroquinolone resistance in non-typhoidal salmonella bacteremia in HIV-infected patients in an urban US setting.

Non-typhoidal salmonella (NTS) bacteremia is a significant cause of morbidity and mortality in HIV-infected individuals worldwide. Recent reports have noted increasing resistance of NTS isolates to fluoroquinolones, the recommended first-line therapy for NTS bacteremia. The outcomes and risk factors for NTS bacteremia in HIV-infected patients in an urban US setting were evaluated. From January 2002 to December 2006, 26 episodes of NTS bacteremia were identified in 16 patients. The risk factors for NTS bacteremia were low CD4 count, high viral load, and lack of antiretroviral therapy (ART). Recurrences appeared related to lack of immune reconstitution in patients not on ART. Unlike reports from Asia, no fluoroquinolone resistance was identified in any of the Salmonella strains isolated in this setting. Optimal treatment of NTS in the HIV-infected patient in the United States should include therapy with fluoroquinolones as well as attaining complete viral suppression and immune reconstitution with ART.