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Patterns of medication use and the burden of polypharmacy in patients with chronic kidney disease: the German Chronic Kidney Disease study.

ABSTRACT: Background:Patients with chronic kidney disease (CKD) bear a substantial burden of comorbidities leading to the prescription of multiple drugs and a risk of polypharmacy. However, data on medication use in this population are scarce. Methods:A total of 5217 adults with an estimated glomerular filtration rate (eGFR) between 30 and 60?mL/min/1.73 m2 or an eGFR ?60?mL/min/1.73m2 and overt proteinuria (>500?mg/day) were studied. Self-reported data on current medication use were assessed at baseline (2010-12) and after 4?years of follow-up (FU). Prevalence and risk factors associated with polypharmacy (defined as the regular use of five or more drugs per day) as well as initiation or termination of polypharmacy were evaluated using multivariable logistic regression. Results:The prevalence of polypharmacy at baseline and FU was almost 80%, ranging from 62% in patients with CKD Stage G1 to 86% in those with CKD Stage G3b. The median number of different medications taken per day was eight (range 0-27). ?-blockers, angiotensin-converting enzyme inhibitors and statins were most frequently used. Increasing CKD G stage, age and body mass index, diabetes mellitus, cardiovascular disease and a history of smoking were significantly associated with both the prevalence of polypharmacy and its maintenance during FU. Diabetes mellitus was also significantly associated with the initiation of polypharmacy [odds ratio (OR) 2.46, (95% confidence interval 1.36-4.45); P?=?0.003]. Conclusion:Medication burden in CKD patients is high. Further research appears warranted to address the implications of polypharmacy, risks of drug interactions and strategies for risk reduction in this vulnerable patient population.

SUBMITTER: Schmidt IM

PROVIDER: S-EPMC6768303 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Patterns of medication use and the burden of polypharmacy in patients with chronic kidney disease: the German Chronic Kidney Disease study.

Schmidt Insa M IM Hübner Silvia S Nadal Jennifer J Titze Stephanie S Schmid Matthias M Bärthlein Barbara B Schlieper Georg G Dienemann Thomas T Schultheiss Ulla T UT Meiselbach Heike H Köttgen Anna A Flöge Jürgen J Busch Martin M Kreutz Reinhold R Kielstein Jan T JT Eckardt Kai-Uwe KU

Clinical kidney journal 20190524 5

<h4>Background</h4>Patients with chronic kidney disease (CKD) bear a substantial burden of comorbidities leading to the prescription of multiple drugs and a risk of polypharmacy. However, data on medication use in this population are scarce.<h4>Methods</h4>A total of 5217 adults with an estimated glomerular filtration rate (eGFR) between 30 and 60 mL/min/1.73 m<sup>2</sup> or an eGFR ≥60 mL/min/1.73m<sup>2</sup> and overt proteinuria (>500 mg/day) were studied. Self-reported data on current medi ...[more]

PMID: 31584562

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Project description:BackgroundPolypharmacy is common among patients with CKD, but little is known about the urinary excretion of many drugs and their metabolites among patients with CKD.MethodsTo evaluate self-reported medication use in relation to urine drug metabolite levels in a large cohort of patients with CKD, the German Chronic Kidney Disease study, we ascertained self-reported use of 158 substances and 41 medication groups, and coded active ingredients according to the Anatomical Therapeutic Chemical Classification System. We used a nontargeted mass spectrometry-based approach to quantify metabolites in urine; calculated specificity, sensitivity, and accuracy of medication use and corresponding metabolite measurements; and used multivariable regression models to evaluate associations and prescription patterns.ResultsAmong 4885 participants, there were 108 medication-drug metabolite pairs on the basis of reported medication use and 78 drug metabolites. Accuracy was excellent for measurements of 36 individual substances in which the unchanged drug was measured in urine (median, 98.5%; range, 61.1%-100%). For 66 pairs of substances and their related drug metabolites, median measurement-based specificity and sensitivity were 99.2% (range, 84.0%-100%) and 71.7% (range, 1.2%-100%), respectively. Commonly prescribed medications for hypertension and cardiovascular risk reduction-including angiotensin II receptor blockers, calcium channel blockers, and metoprolol-showed high sensitivity and specificity. Although self-reported use of prescribed analgesics (acetaminophen, ibuprofen) was <3% each, drug metabolite levels indicated higher usage (acetaminophen, 10%-26%; ibuprofen, 10%-18%).ConclusionsThis comprehensive screen of associations between urine drug metabolite levels and self-reported medication use supports the use of pharmacometabolomics to assess medication adherence and prescription patterns in persons with CKD, and indicates under-reported use of medications available over the counter, such as analgesics.

Project description:BACKGROUND:The population of cancer survivors is rapidly growing in the United States. Long-term and late effects of cancer, combined with the ongoing management of other chronic conditions, make survivors particularly vulnerable to polypharmacy and its adverse effects. In the current study, the authors examined patterns of prescription medication use and polypharmacy in a population-based sample of cancer survivors. METHODS:Using data from the Medical Expenditure Panel Survey (MEPS), the authors matched cancer survivors (5216 survivors) with noncancer controls (19,588 controls) by age, sex, and survey year. Polypharmacy was defined as ?5 unique medications. The authors estimated the percentage of respondents prescribed medications within therapeutic classes and total prescription expenditures. RESULTS:A higher percentage of cancer survivors were prescribed ?5 unique medications (64.0%; 95% confidence interval [95% CI], 62.3%-65.8%) compared with noncancer controls (51.5%; 95% CI, 50.4%-52.6%), including drugs with abuse potential. Across all therapeutic classes, a higher percentage of newly (?1 year since diagnosis) and previously (>1 years since diagnosis) diagnosed survivors were prescribed medications compared with controls, with large differences observed with regard to central nervous system agents (65.8% [95% CI, 62.3%-69.3%] vs 57.4% [95% CI, 55.3%-59.5%] vs 46.0% [95% CI, 45.0%-46.9%]). Specifically, nearly 10% of survivors were prescribed benzodiazepines and/or opioids compared with approximately 5% of controls. Survivors had more than double the prescription expenditures (median of $1633 vs $784 among controls). Findings persisted across age and comorbidity categories. CONCLUSIONS:Cancer survivors were prescribed a higher number of unique medications, including drugs with abuse potential, thereby increasing their risk of adverse drug events, financial toxicity, poor adherence, and drug-drug interactions. Cancer 2018;124:2850-2857. © 2018 American Cancer Society.

Project description:ObjectiveIn the general population, "healthy" dietary patterns are associated with improved health outcomes, but data on associations between observance of specific dietary patterns and kidney function in patients with chronic kidney disease (CKD) are sparse.MethodsDietary intake was evaluated using food frequency questionnaires in patients with moderately severe CKD under nephrology care enrolled into the observational multicenter German CKD study. The Dietary Approaches to Stop Hypertension (DASH) diet score, Mediterranean diet score, and German Food Pyramid Index (GFPI) were calculated and their association with estimated glomerular filtration rate (eGFR) and albuminuria was assessed by multivariable linear regression analysis, adjusted for gender, age, body mass index, energy intake, smoking status, alcohol intake, education, high-density lipoprotein-cholesterol (HDL- cholesterol), low-density lipoprotein-cholesterol (LDL-cholesterol), hypertension, and diabetes mellitus.ResultsA total of 2,813 patients (41% women; age 60.1 ± 11.6 years) were included in the analysis. High DASH diet score and GFPI were associated with lower systolic blood pressure and lower intake of antihypertensive medication, higher HDL, and lower uric acid levels. Mediterranean-style diet was associated with lower prevalence of diabetes mellitus. Higher DASH and Mediterranean diet scores were associated with higher eGFR (β-coefficient = 1.226, P < .001; β-coefficient = 0.932, P = .007, respectively). In contrast, GFPI was not associated with eGFR. For the individual components of the dietary patterns, higher intake of nuts and legumes, cereals, fish, and polyunsaturated fats was associated with higher eGFR and higher intake of dairy, composed of low- and whole-fat dairy, was associated with lower eGFR. No association was found between dietary patterns and albuminuria.ConclusionHigher observance of the DASH or Mediterranean diet, but not German food pyramid recommendations, was associated with higher eGFR among patients with CKD. Improving dietary habits may offer an opportunity to better control comorbidities and kidney function decline in patients with CKD.

Project description:Osteopontin (OPN), encoded by SPP1, is a phosphorylated glycoprotein predominantly synthesized in kidney tissue. Increased OPN mRNA and protein expression correlates with proteinuria, reduced creatinine clearance, and kidney fibrosis in animal models of kidney disease. But its genetic underpinnings are incompletely understood. We therefore conducted a genome-wide association study (GWAS) of OPN in a European chronic kidney disease (CKD) population. Using data from participants of the German Chronic Kidney Disease (GCKD) study (N = 4,897), a GWAS (minor allele frequency [MAF]≥1%) and aggregated variant testing (AVT, MAF<1%) of ELISA-quantified serum OPN, adjusted for age, sex, estimated glomerular filtration rate (eGFR), and urinary albumin-to-creatinine ratio (UACR) was conducted. In the project, GCKD participants had a mean age of 60 years (SD 12), median eGFR of 46 mL/min/1.73m2 (p25: 37, p75: 57) and median UACR of 50 mg/g (p25: 9, p75: 383). GWAS revealed 3 loci (p<5.0E-08), two of which replicated in the population-based Young Finns Study (YFS) cohort (p<1.67E-03): rs10011284, upstream of SPP1 encoding the OPN protein and related to OPN production, and rs4253311, mapping into KLKB1 encoding prekallikrein (PK), which is processed to kallikrein (KAL) implicated through the kinin-kallikrein system (KKS) in blood pressure control, inflammation, blood coagulation, cancer, and cardiovascular disease. The SPP1 gene was also identified by AVT (p = 2.5E-8), comprising 7 splice-site and missense variants. Among others, downstream analyses revealed colocalization of the OPN association signal at SPP1 with expression in pancreas tissue, and at KLKB1 with various plasma proteins in trans, and with phenotypes (bone disorder, deep venous thrombosis) in human tissue. In summary, this GWAS of OPN levels revealed two replicated associations. The KLKB1 locus connects the function of OPN with PK, suggestive of possible further post-translation processing of OPN. Further studies are needed to elucidate the complex role of OPN within human (patho)physiology.

Project description:BACKGROUND:Elderly patients with chronic kidney disease (CKD) frequently present comorbidities that put them at risk of polypharmacy and medication-related problems. This study aims to describe the overall medication profile of patients aged ?75?years with advanced CKD from a multicenter French study and specifically the renally (RIMs) and potentially inappropriate-for-the-elderly medications (PIMs) that they take. METHODS:This is a cross-sectional analysis of medication profiles of individuals aged ?75?years with eGFR <?20?ml/min/1.73?m2 followed by a nephrologist, who collected their active prescriptions at the study inclusion visit. Medication profiles were first analyzed according to route of administration, therapeutic classification. Second, patients were classified according to their risk of potential medication-related problems, based on whether the prescription was a RIM or a PIM. RIMs and PIMs have been defined according to renal appropriateness guidelines and to Beer's criteria in the elderly. RIMs were subclassified by 4 types of category: (a) contraindication; (b) dose modification is recommended based on creatinine clearance (CrCl); (c) dose modification based on CrCl is not recommended but a maximum daily dose is mentioned, (d) no specific recommendations based on CrCl: "use with caution", "avoid in severe impairment", "careful monitoring of dose is required" "reduce the dose". RESULTS:We collected 5196 individual medication prescriptions for 556 patients, for a median of 9 daily medications [7-11]. Antihypertensive agents, antithrombotics, and antianemics were the classes most frequently prescribed. Moreover, 77.0% of patients had at least 1 medication classified as a RIM. They accounted 31.3% of the drugs prescribed and 9.25% was contraindicated drugs. At least 1 PIM was taken by 57.6 and 45.5% of patients had at least one medication classified as RIM and PIM. The prescriptions most frequently requiring reassessment due to potential adverse effects were for proton pump inhibitors and allopurinol. The PIMs for which deprescription is especially important in this population are rilmenidine, long-term benzodiazepines, and anticholinergic drugs such as hydroxyzine. CONCLUSION:We showed potential drug-related problems in elderly patients with advanced CKD. Healthcare providers must reassess each medication prescribed for this population, particularly the specific medications identified here. TRIAL REGISTRATION:NCT02910908.

Project description:BackgroundHypothyroidism and low free triiodothyronine (FT3) syndrome [low FT3 levels with normal thyroid-stimulating hormone (TSH)] have been associated with reduced kidney function cross-sectionally in chronic kidney disease (CKD) patients with severely reduced estimated glomerular filtration rate (eGFR) or end-stage kidney disease (ESKD). Results on the prospective effects of impaired thyroid function on renal events and mortality for patients with severely reduced eGFR or from population-based cohorts are conflicting. Here we evaluated the association between thyroid and kidney function with eGFR (cross-sectionally) as well as renal events and mortality (prospectively) in a large, prospective cohort of CKD patients with mild to moderately reduced kidney function.MethodsThyroid markers were measured among CKD patients from the German Chronic Kidney Disease study. Incident renal endpoints (combined ESKD, acute kidney injury and renal death) and all-cause mortality were abstracted from hospital records and death certificates. Time to first event analysis of complete data from baseline to the 4-year follow-up (median follow-up time 4.04 years) of 4600 patients was conducted. Multivariable linear regression and Cox proportional hazards models were fitted for single and combined continuous thyroid markers [TSH, free thyroxine (FT4), FT3] and thyroid status.ResultsCross-sectionally, the presence of low-FT3 syndrome showed a significant inverse association with eGFR and continuous FT3 levels alone showed a significant positive association with eGFR; in combination with FT4 and TSH, FT3 levels also showed a positive association and FT4 levels showed a negative association with eGFR. Prospectively, higher FT4 and lower FT3 levels were significantly associated with a higher risk of all-cause mortality (N events = 297). Per picomole per litre higher FT3 levels the risk of reaching the composite renal endpoint was 0.73-fold lower (95% confidence interval 0.65-0.82; N events = 615). Compared with euthyroid patients, patients with low-FT3 syndrome had a 2.2-fold higher risk and patients with hypothyroidism had a 1.6-fold higher risk of experiencing the composite renal endpoint.ConclusionsPatients with mild to moderate CKD suffering from thyroid function abnormalities are at an increased risk of adverse renal events and all-cause mortality over time.

Project description:Background and objectivesThe transition from CKD to ESRD can be particularly unstable, with high rates of death and hospitalizations. Few studies have examined medication use during this critical period. We examined patterns of antihypertensive medication use from the four quarters before and eight quarters after incident ESRD treated with maintenance dialysis.Design, setting, participants, & measurementsWe used the US Renal Data System to identify patients aged ≥67 years initiating dialysis for ESRD between January 2008 and December 2010 with Medicare Part D and a low-income subsidy. We ascertained the incidence of AKI and hyperkalemia during each quarter on the basis of having at least 1 payment claim for the condition. We used Poisson regression with robust SEMs to formally test for changes in the trend and level of antihypertensive medication use in a series of intervention analyses.ResultsThe number of antihypertensive drugs used increased as patients neared ESRD, peaking at an average of 3.4 in the quarter immediately preceding dialysis initiation, then declining to 2.2 medications by 2 years later. Angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use was stable at approximately 40%, even among patients with coronary disease and systolic heart failure, and did not correlate with AKI or hyperkalemia. Dialysis initiation was associated with a 40% (95% confidence interval, 38% to 43%) lower adjusted level of diuretic use, which continued to decline after ESRD. Three- and four-drug combinations that included a diuretic were most common before ESRD, whereas after ESRD, one- and two-drug β-blocker or calcium-channel blocker-based combinations were most common.ConclusionsThe use of antihypertensive medications, particularly angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers and diuretics, may be suboptimal during the transition from CKD to ESRD, especially in patients with coronary disease or systolic heart failure. Future studies are needed to identify strategies to increase the appropriate use of antihypertensive medications during this critical transition period.

Dataset Information

Patterns of medication use and the burden of polypharmacy in patients with chronic kidney disease: the German Chronic Kidney Disease study.

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Patterns of medication use and the burden of polypharmacy in patients with chronic kidney disease: the German Chronic Kidney Disease study.

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