Effectiveness of using STOPP/START criteria to identify potentially inappropriate medication in people aged ≥ 65 years with chronic kidney disease: a randomized clinical trial.

PURPOSE: Polypharmacy and inappropriate prescribing are common in elderly with chronic kidney disease (CKD). This study identified potentially inappropriate prescriptions (PIPs) and potential prescribing omissions (PPOs) using the Screening Tool of Older Persons' Prescriptions (STOPP) and the Screening Tool to Alert doctors to the Right Treatment (START) criteria in elderly with advanced CKD and determined the effect of a medication review on medication adherence and health-related quality of life (HRQoL). METHODS: The intervention consisted of a medication review using STOPP/START criteria with a recommendation to a nephrologist or similar review without a recommendation. End points were prevalence of PIP and PPO, medication adherence, and HRQoL. Group differences in outcomes were assessed using a generalized linear mixed model. The trial was registered under www.clinicaltrial.gov (ID: NCT02424786). RESULTS: We randomized 180 patients with advanced CKD (mean age 77 years, 23% female). The prevalence of PIPs and PPOs in the intervention group was 54% and 50%, respectively. The odds of PPOs were lower in the intervention than the control group (OR 0.42, 95% CI 0.19-0.92, p = 0.032), while there was no intergroup difference in the number of PIPs (OR 0.57, CI 0.27-1.20, p = 0.14). There was no difference in changes in medication adherence or HRQoL from baseline to 6 months between the groups. CONCLUSIONS: The intervention with the STOPP/START criteria identified a high prevalence of inappropriate medications in the elderly with advanced CKD and reduced the number of PPOs. However, there was no detectable impact of the intervention on medication adherence or HRQoL.

Medication regimen complexity and medication adherence in elderly patients with chronic kidney disease.

INTRODUCTION: Elderly patients with chronic kidney disease (CKD) stage 5 with or without dialysis treatment usually have concomitant comorbidities, which often result in multiple pharmacological therapies. This study aimed to identify factors associated with medication complexity and medication adherence, as well as the association between medication complexity and medication adherence, in elderly patients with CKD. METHODS: This prospective study involved elderly patients with CKD stage 5 (estimated glomerular filtration rate < 15 ml/min/1.73m2 ) recruited from three Norwegian hospitals. Most of the patients were receiving either hemodialysis or peritoneal dialysis. We used the Medication Regimen Complexity Index (MRCI) to assess the complexity of medication regimens, and the eight-item Morisky Medication Adherence Scale (MMAS-8) to assess medication adherence. Factors associated with the MRCI and MMAS-8 score were determined using either multivariable linear or ordinal logistic regression analysis. FINDINGS: In total, 157 patients aged 76 ± 7.2 years (mean ± SD) were included in the analysis. Their overall MRCI score was 22.8 ± 7.7. In multivariable linear regression analyses, female sex (P = 0.044), Charlson Comorbidity Index of 4 or 5 (P = 0.029) and using several categories of phosphate binders (P < 0.001 to 0.04) were associated with the MRCI. Moderate or high adherence (MMAS-8 score ≥ 6) was demonstrated by 83% of the patients. The multivariable logistic regression analyses found no association of medication complexity, age or other variables with medication adherence as assessed using the MMAS-8. DISCUSSION: Female sex, comorbidity and use of phosphate binders were associated with more-complex medication regimens in this population. No association was found between medication regimen complexity, phosphate binders or age and medication adherence. These findings are based on a homogeneous elderly group, and so future studies should test if they can be generalized to patients of all ages with CKD.

Increased levels of inflammatory mediators and proinflammatory monocytes in patients with type I diabetes mellitus and nephropathy.

AIMS: To investigate and describe the relationship between diabetic nephropathy and systemic inflammation in patients with type 1 diabetes mellitus (T1DM). METHODS: Patients with T1DM, with or without reduced renal function due to diabetic nephropathy, were included. Differences in inflammatory mediators, adhesion molecules, markers of endothelial dysfunction and subsets of monocytes were studied in patients with mean disease duration of 31years. RESULTS: Patients with T1DM with and without renal failure were compared. Patients with nephropathy had increased plasma levels of proinflammatory monocytes, as well as circulatory PAI-1, syndecan-1, VEGF, IL-1ß, IL-1Ra and CCL4. Peripheral blood mononuclear cells from patients with nephropathy numerically increased soluble ICAM and PAI-1 in co-culture with primary endothelial cells compared to cells from patients without nephropathy. CONCLUSIONS: T1DM patients with kidney failure have higher levels of proinflammatory monocytes and circulatory inflammatory mediators compared to patients with T1DM alone. The results highlight the importance of inflammation and endothelial dysfunction in diabetic nephropathy with reduced GFR.

Potentially Inappropriate Medications in Elderly Haemodialysis Patients Using the STOPP Criteria.

BACKGROUND: Polypharmacy is commonly applied to elderly haemodialysis patients for treating terminal renal failure and multiple co-morbidities. Potentially inappropriate medications (PIMs) in multidrug regimens in geriatric populations can be identified using specially designed screening tools. OBJECTIVE: The aims of this study were to estimate the prevalence of PIMs by applying the Screening Tool of Older Persons' Prescriptions (STOPP) criteria and the Beers criteria to elderly haemodialysis patients and to assess the association of some risk factors with the presence of PIMs. METHODS: Fifty-one elderly haemodialysis patients participated; their median age was 74 (range 65-89) years, and 77 % of them were male. Demographic data, co-morbidity and medication lists were collected from the electronic medical records of the patients. The STOPP criteria were applied by two physicians independently to identify PIMs. The association of some risk factors with PIMs were assessed using Fisher's exact test. RESULTS: The patients used a median of 13 (range 7-21) medications per day. The overall prevalence of PIMs using the STOPP criteria was 63 %, and using the Beers criteria was 43 %. The most prevalent PIMs were proton-pump inhibitors. Benzodiazepines and first-generation antihistamines were related to side effects such as falls in the previous 3 months, and calcium-channel blockers were associated with chronic constipation. The number of PIMs was not significantly associated with number of medications, age, sex and co-morbidity. CONCLUSIONS: The STOPP criteria revealed a high prevalence of PIMs in a population of elderly patients receiving haemodialysis.

Relationship between cytochrome P450 polymorphisms and prescribed medication in elderly haemodialysis patients.

BACKGROUND: Elderly patients on haemodialysis have a high prevalence of polypharmacy and are at risk of drug-related complications. More than 80 % of all prescribed drugs are metabolized by the cytochrome P450 (CYP) enzyme system. The aims of this study were to describe the prevalence of polymorphism in three CYP isoenzymes and the relationship between CYP polymorphism and prescribed drugs. METHODS: Fifty-one elderly haemodialysis patients aged ≥65 years were included. CYP-genotyping was carried out in whole blood by a real-time PCR method for detecting common variant alleles in CYP2C9, CYP2C19 and CYP2D6. The allele frequencies were calculated using the Hardy-Weinberg equation. RESULTS: The overall prevalence of CYP polymorphisms (heterozygous and homozygous) was 77 %. The prevalence of heterozygous carriers of variant alleles coding for defective CYP2D6, CYP2C9 and CYP2C19 was 64, 22 and 55 %, respectively; the prevalence of homozygous carriers was 6 % for each of the CYP2D6, CYP2C9 and CYP2C19 enzymes. The prevalence of the CYP2D6*6, CYP2D6*9 and CYP2D6*41 variant alleles did not differ (p = 0.31) from that in a European Caucasian reference population. Twenty-three patients (45 %) had at least one CYP mutation and used drugs that are metabolized by the CYP isoenzymes. Metoprolol and proton-pump inhibitors were the most commonly used drugs that could be affected by a heterozygous or homozygous mutation. CONCLUSIONS: Polymorphisms of CYP2C9, CYP2C19 and CYP2D6 are common in elderly haemodialysis patients. Many of these patients have a phenotype with altered CYP enzyme activity and could benefit from close drug monitoring or a drug switch.