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.
Project description:BACKGROUND:The Japan Chronic Kidney Disease Database (J-CKD-DB) is a nationwide clinical database of patients with chronic kidney disease (CKD) based on electronic health records. The objective of this study was to assess the prevalence of anemia and the utilization rate of erythropoiesis-stimulating agents (ESAs) in Japanese patients with CKD. METHODS:In total, 31,082 adult outpatients with estimated glomerular filtration rates of 5-60 ml/min/1.73 m2 in seven university hospitals were included this analysis. The proportions of patients with CKD stages G3b, G4, and G5 were 23.5%, 7.6%, and 3.1%, respectively. RESULTS:The mean (standard deviation) hemoglobin level of male patients was 13.6 (1.9) g/dl, which was significantly higher than the mean hemoglobin level of female patients (12.4 (1.6) g/dl). The mean (standard deviation) hemoglobin levels were 11.4 (2.1) g/dl in patients with CKD stage G4 and 11.2 (1.8) g/dl in patients with CKD stage G5. The prevalences of anemia were 40.1% in patients with CKD stage G4 and 60.3% in patients with CKD stage G5. Logistic regression analysis showed that diagnoses of CKD stage G3b (adjusted odds ratio [95% confidence interval]: 2.32 [2.09-2.58]), G4 (5.50 [4.80-6.31]), and G5 (9.75 [8.13-11.7]) were associated with increased prevalence of anemia. The utilization rates of ESAs were 7.9% in patients with CKD stage G4 and 22.4% in patients with CKD stage G5. CONCLUSIONS:We determined the prevalence of anemia and utilization rate of ESAs in Japanese patients with CKD using data from a nationwide cohort study.
Project description:BACKGROUND:The Japan Chronic Kidney Disease Database (J-CKD-DB) is a nationwide clinical database of patients with chronic kidney disease (CKD) based on electronic health records. The objective of this study was to assess the prevalences of hyperuricemia and electrolyte abnormalities in Japanese patients with CKD. METHODS:In total, 35,508 adult outpatients with estimated glomerular filtration rates of 5-60 ml/min/1.73 m2 in seven university hospitals were included this analysis. The proportions of patients with CKD stages G3b, G4, and G5 were 23.5%, 7.6%, and 3.1%, respectively. RESULTS:Logistic regression analysis showed that prevalence of hyperuricemia was associated with CKD stages G3b (adjusted odds ratio [95% confidence interval]: 2.12 [1.90-2.37]), G4 (4.57 [3.92-5.32]), and G5 (2.25 [1.80-2.80]). The respective prevalences of hyponatremia, hypercalcemia, hyperphosphatemia, and narrower difference between serum sodium and chloride concentrations were elevated in patients with CKD stages G3b, G4, and G5, compared with those prevalences in patients with CKD stage G3a. The prevalences of hyperkalemia were 8.3% and 11.6% in patients with CKD stages G4 and G5, respectively. In patients with CKD stage G5, the proportions of patients with optimal ranges of serum uric acid, potassium, corrected calcium, and phosphate were 49.6%, 73.5%, 81.9%, and 56.1%, respectively. CONCLUSIONS:We determined the prevalences of hyperuricemia and electrolyte abnormalities in Japanese patients with CKD using data from a nationwide cohort study.
Project description:<h4>Background</h4>Polypharmacy, often defined as the concomitant use of ≥ 5 medications, has been identified as a significant global public health threat. Aging and multimorbidity are key drivers of polypharmacy and have been linked to a broad range of adverse health outcomes and mortality. Patients with chronic kidney disease (CKD) are particularly at high risk of polypharmacy and use of potentially inappropriate medications given the numerous risk factors and complications associated with CKD. The aim of this systematic review will be to assess the prevalence of polypharmacy among adult patients with CKD, and the potential association between polypharmacy and adverse health outcomes within this population.<h4>Methods/design</h4>We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, and PsycINFO and grey literature from inception onwards (with no language restrictions) for observational studies (e.g., cross-sectional or cohort studies) reporting the prevalence of polypharmacy in adult patients with CKD (all stages including dialysis). Two reviewers will independently screen all citations, full-text articles, and extract data. Potential conflicts will be resolved through discussion. The study methodological quality will be appraised using an appropriate tool. The primary outcome will be the prevalence of polypharmacy. Secondary outcomes will include any adverse health outcomes (e.g., worsening kidney function) in association with polypharmacy. If appropriate, we will conduct random effects meta-analysis of observational data to summarize the pooled prevalence of polypharmacy and the associations between polypharmacy and adverse outcomes. Statistical heterogeneity will be estimated using Cochran's Q and I<sup>2</sup> index. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., sex, kidney replacement therapy, multimorbidity).<h4>Discussion</h4>Given that polypharmacy is a major and a growing public health issue, our findings will highlight the prevalence of polypharmacy, hazards associated with it, and medication thresholds associated with adverse outcomes in patients with CKD. Our study will also draw attention to the prognostic importance of improving medication practices as a key priority area to help minimize the use of inappropriate medications in patients with CKD.<h4>Systematic review registration</h4>PROSPERO registration number: [ CRD42020206514 ].
Project description:BACKGROUND:Chronic kidney disease (CKD) afflicts many older adults and increases the risk for medication-related adverse events. OBJECTIVE:The aim of this study was to assess the prevalence and associated morbidity and mortality of polypharmacy (use of several medications concurrently), and potentially inappropriate medication (PIM) use in older adults, looking for differences by CKD status. METHODS:We quantified medication and PIM use (from Beers criteria, the Screening Tool of Older People's Prescriptions, and Micromedex®) by level of estimated glomerular filtration rate (eGFR) for participants aged 65 years or older attending a baseline study visit in the Atherosclerosis Risk in Communities study (n =6392). We used zero-inflated negative binomial and Cox proportional hazards regressions to assess the relationship between baseline polypharmacy, PIM use, and subsequent hospitalization and death. RESULTS:Mean age at baseline was 76 (± 5) years, 59% were female, and 29% had CKD (eGFR < 60 ml/min/1.73 m2). Overall, participants reported 6.1 (± 3.5) medications and 2.3 (± 2.2) vitamins/supplements; 16% reported ≥ 10 medications; 31% reported a PIM based on their age. On average, participants with CKD reported more medications. A PIM based on kidney function was used by 36% of those with eGFR < 30 ml/min/1.73 m2. Over a median of 2.6 years, more concurrent medications were associated with higher risk of hospitalization and death, but PIM use was not. While those with CKD had higher absolute risks, there was no difference in the relative risks associated with greater numbers of medications by CKD status. CONCLUSION:Polypharmacy and PIM use were common, with greater numbers of medications associated with higher risk of hospitalization and death; relative risks were similar for those with and without CKD.
Project description:Inappropriate polypharmacy is likely in older adults with chronic kidney disease (CKD) owing to the considerable burden of comorbidities. We aimed to describe the impact of pharmacist-led geriatric medication management service (MMS) on the quality of medication use. This retrospective descriptive study included 95 patients who received geriatric MMS in an ambulatory care clinic in a single tertiary-care teaching hospital from May 2019 to December 2019. The average age of the patients was 74.9 ± 7.3 years; 40% of them had CKD Stage 4 or 5. Medication use quality was assessed in 87 patients. After providing MMS, the total number of medications and potentially inappropriate medications (PIMs) decreased from 13.5 ± 4.3 to 10.9 ± 3.8 and 1.6 ± 1.4 to 1.0 ± 1.2 (both <i>p</i> < 0.001), respectively. Furthermore, the number of patients who received three or more central nervous system-active drugs and strong anticholinergic drugs decreased. Among the 354 drug-related problems identified, "missing patient documentation" was the most common, followed by "adverse effect" and "drug not indicated." The most frequent intervention was "therapy stopped". In conclusion, polypharmacy and PIMs were prevalent in older adults with CKD; pharmacist-led geriatric MMS improved the quality of medication use in this population.
Project description:Chronic kidney disease (CKD) is a global health problem with a genetic component. Genome-wide association studies have identified variants associated with specific CKD etiologies, but their genetic overlap has not been well studied. This study examined SNP associations across different CKD etiologies and CKD stages using data from 5,034 CKD patients of the German Chronic Kidney Disease study. In addition to confirming known associations, a systemic lupus erythematosus-associated risk variant at TNXB was also associated with CKD attributed to type 1 diabetes (p?=?2.5?×?10-7), a membranous nephropathy-associated variant at HLA-DQA1 was also associated with CKD attributed to systemic lupus erythematosus (p?=?5.9?×?10-6), and an IgA risk variant at HLA-DRB1 was associated with both CKD attributed to granulomatosis with polyangiitis (p?=?2.0?×?10-4) and to type 1 diabetes (p?=?4.6?×?10-11). Associations were independent of additional risk variants in the respective genetic regions. Evaluation of CKD stage showed a significant association of the UMOD risk variant, previously identified in population-based studies for association with kidney function, for advanced (stage ?G3b) compared to early-stage CKD (?stage G2). Shared genetic associations across CKD etiologies and stages highlight the role of the immune response in CKD. Association studies with detailed information on CKD etiology can reveal shared genetic risk variants.
Project description:The widely used Modification of Diet in Renal Disease (MDRD) formula adapts a 1.212 multiplier for individuals who are identified as African Americans (AAs) or Blacks, which leads to a higher GFR estimation. As it stands, AAs have a lower prevalence of chronic kidney disease (CKD) but higher incidence of end-stage renal disease (ESRD) compared with Whites. Many hypotheses have been postulated to explain this paradox, but the imprecision of the GFR estimation with race-adaptation could be contributory. We performed a single-center, longitudinal, retrospective study on a cohort of outpatient AA patients using the MDRD and MDRDrace removed and CKD-EPI and CKD-EPIrace removed and their progression to CKD G5 (eGFR <15 ml/min/1.73 m2). 327 patients were analyzed. Median follow-up was 88.1 months (interquartile range, 34.4–129.1). When race was removed from MDRD, 39.9% of patients in CKD G1/2 were reclassified to CKD G3a, 72.6% of patients in CKD G3a would be reclassified to CKD G3b, and 54.1% and 36.4% of patients would be reclassified from CKD 3b to CKD G4 and CKD G4 to CKD G5, respectively (p < 0.0001). Comparing the CKD-EPI formula against the MDRD in our cohort, we found that 8.2%, 18.8%, and 11.4% of patients were reclassified from CKD G1/2 to CKD G3a, CKD G3a to G3b, and CKD G3b to CKD G4 respectively. Overall median time to progression to CKD G5 was 137.4 (131.9–142.8) months in patients who were not reclassified and 133.6 (127.6–139.6) months for patients who were reclassified by MDRDrace removed(p < 0.288). Concerns of inequitable access to healthcare have elicited calls to review race-corrected eGFR equations. A substantial number of individuals would have their CKD stage reclassified should have the MDRDrace removed equation be adopted en masse on an AA-only population. The discrepancy is highest at the 45–59 and >60 ml/min/1.72 min2 ranges. This will have tremendous impact on our center's approach to pharmacological dosing, referral system, best practices, and outcome surveillance. Comprehensive review of the current “race-corrected” eGFR will require a multifaceted approach and adjunctive use of noncreatinine-based approach.
Project description:Several microRNAs (miRNAs) have been linked to chronic kidney disease (CKD) mortality, cardiovascular (CV) complications and kidney disease progression. However, their association with clinical outcomes remains poorly evaluated. We used real-time qPCR to measure serum levels of miR-126 and miR-223 in a large cohort of 601 CKD patients (CKD stage G1 to G5 patients or on renal replacement therapy - CKD G5D) from Ghent University Hospital and 31 healthy controls. All-cause mortality and cardiovascular and renal events were registered as endpoints over a 6 year follow-up period. miR-126 levels were significantly lower from CKD stage G2 on, compared to controls. The serum levels of miR-223 were significantly lower from CKD stage G3B on. When considering overall mortality, patients with levels of either miR-126 or miR-223 below the median had a lower survival rate. Similar results were observed for CV and renal events. The observed link between the two miRNAs' seric levels and mortality, cardiovascular events or renal events in CKD appears to depend on eGFR. However, this does not preclude their potential role in the pathophysiology of CKD. In conclusion, CKD is associated with a decrease in circulating miR-223 and miR-126 levels.
Project description:Introduction:Although early intervention for chronic kidney disease (CKD) and renal anemia are desirable, these conditions are often asymptomatic during their early stages and may be underdiagnosed. Methods:We retrospectively analyzed Japanese administrative claims data for general and hospital populations. The data period for the general and hospital data ranged from January 2011 to December 2016 and from April 2008 to July 2017, respectively. CKD stage was determined by estimated glomerular filtration rate (eGFR). Anemia was defined per Japanese guidelines using hemoglobin (Hb) values. The proportion of patients who had eGFR-defined stages G3-G5 CKD without a CKD diagnosis, and Hb-defined anemia without an anemia diagnosis or treatment records, was estimated. Results:Among 16,779 (general) and 68,161 (hospital) patients, a high proportion of G3 CKD patients did not have a CKD-related diagnosis (general: G3a, 95.0%; G3b, 68.4%; hospital: G3a, 89.2%; G3b, 67.9%); however, some patients were treated with antihypertensives. Among anemic patients, 75.7% (G3a) and 66.7% (G3b) of the general population, and 56.2% (G3a) and 47.5% (G3b) of the hospital population, did not have an anemia-related diagnosis or treatment. CKD and anemia were more likely to be diagnosed in patients with G4 and G5 CKD. Conclusion:A high proportion of G3 CKD patients did not have a CKD-related diagnosis. Likewise, many anemic patients with G3 CKD did not have an anemia-related diagnosis. Despite the lack of a CKD-related diagnosis, some patients received appropriate treatment (e.g., antihypertensives). Further outreach to CKD and anemia patients at earlier stages may be warranted.
Project description:Background:Immunosuppressive agents are being investigated for the treatment of chronic kidney disease (CKD) but may increase risk of infection. This was a retrospective observational study intended to evaluate the risk of hospitalized infection in patients with CKD, by estimated glomerular filtration rate (eGFR) and proteinuria status, aiming to identify the most appropriate disease stage for immunosuppressive intervention. Methods:Routine UK primary-care and linked secondary-care data were extracted from the Clinical Practice Research Datalink. Patients with a record of CKD were identified and grouped into type 2, type 1 and nondiabetes cohorts. Time-dependent, Cox proportional hazard models were used to determine the likelihood of hospitalized infection. Results:We identified 97 839 patients with a record of CKD, of these 11 719 (12%) had type 2 diabetes. In these latter patients, the adjusted hazard ratios (aHR) were 1.00 (95% CI: 0.80-1.25), 1.00, 1.03 (95% CI: 0.92-1.15), 1.36 (95% CI: 0.20-1.54), 1.82 (95% CI: 1.54-2.15) and 2.41 (95% CI: 1.60-3.63) at eGFR stages G1, G2 (reference), G3a, G3b, G4 and G5, respectively; and 1.00, 1.45 (95% CI: 1.29-1.63) and 1.91 (95% CI: 1.67-2.20) at proteinuria stages A1 (reference), A2 and A3, respectively. All aHRs (except G1 and G3a) were significant, with similar patterns observed within the non-DM and overall cohorts. Conclusions:eGFR and degree of albuminuria were independent markers of hospitalized infection in both patients with and without diabetes. The same patterns of hazard ratios of eGFR and proteinuria were seen in CKD patients regardless of diabetes status, with the risk of each outcome increasing with a decreasing eGFR and increasing proteinuria. Infection risk increased significantly from eGFR stage G3b and proteinuria stage A2 in type 2 diabetes. Treating type 2 DM patients with CKD at eGFR stages G1-G3a with immunosuppressive therapy may therefore provide a favourable risk-benefit ratio (G1-G3a in type 2 diabetes; G1-G2 in nondiabetes and overall cohorts) although the degree of proteinuria needs to be considered.