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Associations of Opioid Prescriptions with Death and Hospitalization across the Spectrum of Estimated GFR.

ABSTRACT: BACKGROUND AND OBJECTIVES:Most opioids undergo kidney excretion. The goal of this study was to evaluate opioid-associated risks of death and hospitalization across the range of eGFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:The study population included adult primary care patients in Geisinger Health (Danville, PA) between 2008 and 2017. People receiving their first opioid prescription were propensity matched to people receiving NSAIDS (and, in sensitivity analysis, gabapentinoids) and the risk of death and hospitalization were compared, classifying opioid medication exposure as time-varying daily oral morphine milligram equivalents (MMEs) across time-varying eGFR. RESULTS:The propensity-matched cohort included 46,246 patients prescribed either opioids or NSAIDs between 2008 and 2017 (mean [SD] age, 54 [16] years; 56% female; 3% of black race). Prescriptions for 1-59 and ?60 MMEs were associated with higher risk of death (HR, 1.70; 95% CI, 1.41 to 2.05 for 1-59 MMEs; HR, 2.25; 95% CI, 1.82 to 2.79 for ?60 MMEs) and hospitalization (HR, 1.38; 95% CI, 1.30 to 1.46 for 1-59 MMEs; HR, 1.68; 95% CI, 1.56 to 1.81 for ?60 MMEs) compared with NSAID prescriptions, when evaluated at eGFR 80 ml/min per 1.73 m2. The relative risk of death associated with ?60 MMEs was higher at lower GFR (e.g., eGFR, 40 ml/min per 1.73 m2; HR, 3.94; 95% CI, 2.70 to 5.75; P for interaction, 0.01). When gabapentinoids were used as the comparison medication, only ?60 MMEs were significantly associated with higher risk of death (HR, 2.72; 95% CI, 1.71 to 4.34), although both 1-59 and ?60 MMEs were associated with risk of hospitalization (HR, 1.22; 95% CI, 1.04 to 1.43 for 1-59 MMEs; HR, 1.54; 95% CI, 1.28 to 1.86 for ?60 MMEs). CONCLUSIONS:The receipt of prescription opioids was associated with a higher risk of death and hospitalization compared with other pain medications, particularly with higher doses and at lower eGFR.

SUBMITTER: Novick TK

PROVIDER: S-EPMC6832057 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Associations of Opioid Prescriptions with Death and Hospitalization across the Spectrum of Estimated GFR.

Novick Tessa K TK Surapaneni Aditya A Shin Jung-Im JI Alexander G Caleb GC Inker Lesley A LA Wright Eric A EA Chang Alex R AR Grams Morgan E ME

Clinical journal of the American Society of Nephrology : CJASN 20191003 11

<h4>Background and objectives</h4>Most opioids undergo kidney excretion. The goal of this study was to evaluate opioid-associated risks of death and hospitalization across the range of eGFR.<h4>Design, setting, participants, & measurements</h4>The study population included adult primary care patients in Geisinger Health (Danville, PA) between 2008 and 2017. People receiving their first opioid prescription were propensity matched to people receiving NSAIDS (and, in sensitivity analysis, gabapenti ...[more]

PMID: 31582462

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Project description:BackgroundDespite the interrelationships between obesity, eGFR and albuminuria, few large studies examine how obesity modifies the association between these markers of kidney function and adverse clinical outcomes.MethodsWe examined the joint associations between obesity, eGFR and albuminuria on four clinical outcomes (death, end-stage renal disease [ESRD], myocardial infarction [MI], and placement in a long-term care facility) using a population-based cohort with procedures from Alberta. Obesity was defined by body mass index ≥35 kg/m2 as defined by a fee modifier applied to an eligible procedure.ResultsWe studied 1,293,362 participants, of whom 171,650 (13.3%) had documented obesity (BMI ≥ 35 kg/m2 based on claims data) and 1,121,712 (86.7%) did not. The association between eGFR and death was J-shaped for participants with and without documented obesity. After full adjustment, obesity tended to be associated with slightly lower odds of mortality (OR range 0.71-1.02; p for interaction between obesity and eGFR 0.008). For participants with and without obesity, the adjusted odds of ESRD were lowest for participants with eGFR > 90 mL/min*1.73m2 and increased with lower eGFR, with no evidence of an interaction with obesity (p = 0.37). Although albuminuria and obesity were both associated with higher odds of ESRD, the excess risk associated with obesity was substantially attenuated at higher levels of albuminuria (p for interaction 0.0006). The excess risk of MI associated with obesity was observed at eGFR > 60 mL/min*1.73m2 but not at lower eGFR (p for interaction < 0.0001). Participants with obesity had a higher adjusted likelihood of placement in long-term care than those without, and the likelihood of such placement was higher at lower eGFR for those with and without obesity (p for interaction = 0.57).ConclusionsWe found significant interactions between obesity and eGFR and/or albuminuria on the likelihood of adverse outcomes including death and ESRD. Since obesity is common, risk prediction tools for people with CKD might be improved by adding information on BMI or other proxies for body size in addition to eGFR and albuminuria.

Project description:BackgroundHigher serum cystatin C level is associated with an increased risk of hip fracture in postmenopausal white women, but there is a paucity of data for men. Whether estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) is superior in predicting hip fracture risk to eGFR based on creatinine (eGFRcr) or the combination (eGFR(cr-cys)) also is uncertain.Study designNested case-cohort.Setting & participantsParticipants enrolled in the Osteoporotic Fractures in Men (MrOS) Study (5,994 men aged ≥ 65 years from 6 US centers) including a random subcohort of 1,602 men and 168 men with incident hip fractures (51 of whom were in the subcohort).PredictoreGFR(cys), eGFR(cr), and eGFR(cr-cys) computed using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations and expressed in categories of <60, 60-74, and ≥ 75 mL/min/1.73 m(2) (referent group).OutcomeIncident hip fracture ascertained by participant contacts every 4 months and confirmed with radiographic reports.ResultsMedian eGFR(cys) was 72.9 (IQR, 60.5-85.7) mL/min/1.73 m(2). In unadjusted models, all measures of eGFR were associated with increased hip fracture risk. However, after adjustment for age, race, site, and body mass index, the association of lower eGFR(cys) (but not lower eGFR(cr) or lower eGFR(cr-cys)) with higher hip fracture risk remained: for <60 versus ≥ 75 mL/min/1.73 m(2), HRs were 1.96 [95% CI, 1.25-3.09], 0.84 [95% CI, 0.52-1.37], and 1.08 [95% CI, 0.66-1.77] for eGFR(cys), eGFR(cr), and eGFR(cr-cys), respectively. Similarly, after adjustment for age, race, site, and body mass index, eGFR < 60 mL/min/1.73 m(2) defined by eGFR(cys), but not eGFR(cr) or eGFR(cr-cys), was associated with higher hip fracture risk. The association between eGFR(cys) and hip fracture was not explained by levels of calciotropic hormones or inflammatory markers, but the relationship was attenuated and no longer reached significance (for <60 vs ≥ 75 mL/min/1.73 m(2): HR, 1.43; 95% CI, 0.88-2.34) after consideration of additional clinical risk factors and bone mineral density.LimitationsFindings not generalizable to other populations; residual confounding may exist.ConclusionsOlder community-dwelling men with lower eGFR(cys) have an increased risk of hip fracture that is explained in large part by greater burden of risk factors among men with lower eGFR(cys). In contrast, lower eGFR(cr) or lower eGFR(cr-cys) was not associated with a higher age-adjusted hip fracture risk.

Project description:BACKGROUND:Several reviews have recently detailed the beneficial effects of weight loss surgery for kidney function. However, these studies have a number of limitations, including small sample size, few done in chronic kidney disease (CKD) stages 3 and 4, and many not including the main bariatric surgery procedures used in the United States today. STUDY DESIGN:This was an observational retrospective cohort study comparing propensity score-matched bariatric surgery patients and nonsurgery control patients who were referred for, but did not have, surgery. Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy were also compared using propensity matching. SETTING & PARTICIPANTS:Patients (714 surgery patients; 714 controls) were from a large integrated health care system, a mean of 58±8 (SD) years old, and mostly women (77%) and non-Hispanic whites (56%) and had diabetes mellitus (66%) and/or hypertension (91%). PREDICTOR:Predictors at the time of surgery or referral to surgery were age, sex, race/ethnicity, weight, and presence of diabetes and/or hypertension. OUTCOMES:The primary outcome for this study was change in estimated glomerular filtration rate (eGFR) from serum creatinine level over a median 3-year follow-up period. MEASUREMENTS:Serum creatinine was used to calculate eGFR using the CKD-EPI (CKD Epidemiology Collaboration) creatinine equation. RESULTS:Surgery patients had 9.84 (95% CI, 8.05-11.62) mL/min/1.73m2 greater eGFRs than controls at a median 3 years' follow-up and RYGB patients had 6.60 (95% CI, 3.42-9.78) mL/min/1.73m2 greater eGFRs than sleeve gastrectomy patients during the same period. LIMITATIONS:This study is limited by its nonrandomized observational study design, estimation of GFR, and large changes in muscle mass, which may affect serum creatinine level independent of changes in kidney function. CONCLUSIONS:Bariatric surgery, especially the RYGB procedure, results in significant improvements for up to 3 years in eGFRs for patients with CKD stages 3 and 4.

Project description:Rationale & objectiveDetermining whether a change in estimated glomerular filtration rate (eGFR) or albuminuria is clinically significant requires knowledge of short-term within-person variability of the measurements, which few studies have addressed in the setting of chronic kidney disease.Study designCross-sectional study with multiple collections over less than 4 weeks.Setting & participantsClinically stable outpatients with chronic kidney disease (N=50; mean age, 56.8 years; median eGFR, 40mL/min/1.73m2; median urinary albumin-creatinine ratio (UACR), 173mg/g).ExposureRepeat measurements from serially collected samples across 3 study visits.OutcomesMeasurements of urine albumin concentration (UAC), UACR, and plasma creatinine, cystatin C, β2-microglobulin (B2M), and beta trace protein (BTP).Analytical approachWe calculated within-person coefficients of variation (CVw) values and corresponding reference change positive and negative (RCVpos and RCVneg) values using log-transformed measurements.ResultsMedian CVw (RCVpos; RCVneg) values of filtration markers were 5.4% (+16%; -14%) for serum creatinine, 4.1% (+12%; -11%) for cystatin C, 7.4% (+23%; -18%) for BTP, and 5.6% (+17%; -14%) for B2M. Results for albuminuria were 33.2% (+145%; -59%) for first-morning UAC, 50.6% (+276%; -73%) for random spot UAC, 32.5% (+141%; -58%) for first-morning UACR, and 29.7% (124%; -55%) for random spot UACR. CVw values for filtration markers were comparable across the range of baseline eGFRs. CVw values for UAC and UACR were comparable across the range of baseline albuminuria values.LimitationsSmall sample size limits the ability to detect differences in variability across markers. Participants were recruited and followed up in a clinical and not research setting, so some preanalytical factors could not be controlled.ConclusionseGFR markers appear to have relatively low short-term within-person variability, whereas variability in albuminuria appears to be high, making it difficult to distinguish random variability from meaningful biologic changes.

Project description:BackgroundEstimated glomerular filtration (eGFR) results based on serum creatinine are frequently inaccurate with differences against measured GFR (mGFR) often attributed to unmeasured non-functional factors, such as muscle mass.MethodsThe influence of muscle mass (measured by dual-energy x-ray absorptiometry, DEXA) on eGFR error (eGFR-mGFR) was evaluated using isotopic mGFR (Tc99m DTPA plasma clearance) in 137 kidney transplant recipients. Serum creatinine was measured by isotopic-calibrated enzymatic analysis, converted to eGFR using Chronic Kidney Disease EPIdemiology (CKD-EPI) formula, then unindexed from body surface area.FindingsUnindexed CKD-EPI eGFR error displayed absent fixed bias but modest proportional bias against reference mGFR. eGFR error correlated with total lean mass by DEXA (r=-0·350, P<0·001) and appendicular skeletal muscle index (ASMI), a proxy for muscularity (r=-0·420, P<0·001). eGFR was falsely reduced by -5·9 ± 1·4 mls/min per 10 kg lean mass. Adipose mass and percentage fat had no effect on error. Muscle-associated error varied with each eGFR formula and influenced all CKD stages. Systemic eGFR error was predicted by ASMI, mGFR, recipient age, and trimethoprim use using multivariable regression. Residual plots demonstrated heteroscedasticity and greater imprecision at higher mGFR levels (P<0·001), from increased variance corresponding to higher absolute values and unreliable prediction by serum creatinine of high mGFR. Serum creatinine correlated with ASMI independent of mGFR level (r = 0·416, P<0·001). The diagnostic test performance of CKD-EPI eGFR to predict CKD stage 3 (by mGFR) was weakest in cachexia (sensitivity 68·4%) and muscularity (specificity 47·4%, positive predictive value 54·5% for the highest ASMI quartile).InterpretationSerum creatinine and eGFR are imperfect estimates of true renal function, with systemic errors from muscle mass, tubular secretion, and intrinsic proportional bias; and additional inaccuracy at the extremes of renal function and patient muscularity. Cautious interpretation of eGFR results in the context of body habitus and clinical condition is recommended.

Dataset Information

Associations of Opioid Prescriptions with Death and Hospitalization across the Spectrum of Estimated GFR.

Publications

Associations of Opioid Prescriptions with Death and Hospitalization across the Spectrum of Estimated GFR.

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