Polypharmacy in chronic kidney disease: Health outcomes & pharmacy-based strategies to mitigate inappropriate polypharmacy.

The rising prevalence of comorbidities in an increasingly aging population has sparked a reciprocal rise in polypharmacy. Patients with chronic kidney disease (CKD) have a greater burden of polypharmacy due to the comorbidities and complications associated with their disease. Polypharmacy in CKD patients has been linked to myriad direct and indirect costs for patients and the society at large. Pharmacists are uniquely positioned within the healthcare team to streamline polypharmacy management in the setting of CKD. In this article, we review the landscape of polypharmacy and examine its impacts through the lens of the ECHO model of Economic, Clinical, and Humanistic Outcomes. We also present strategies for healthcare teams to improve polypharmacy care through comprehensive medication management process that includes medication reconciliation during transitions of care, medication therapy management, and deprescribing. These pharmacist-led interventions have the potential to mitigate adverse outcomes associated with polypharmacy in CKD.

Evaluating Factors Contributing to Dropout in a Large Peritoneal Dialysis Program.

BACKGROUND: The low prevalence of peritoneal dialysis (PD) (9%) vs. hemodialysis (HD) (88.2%) is partly due to patient dropout from therapy. METHODS: This retrospective study identified patients who withdrew from PD between 2016 and 2018 in our program. We evaluated all other factors as controllable losses. Analysis included time on therapy at dropout (very early, early or late) and method of initiation (HD to PD conversion, unplanned PD, or planned start). RESULTS: Eighty-three patients enrolled into our PD program. 27 dropped out; 24 were due to controllable factors, 3 due to death, with a median age at dropout of 52 years old. We determined psychosocial factors (PF) to be the largest controllable factor influencing dropout; contributing a 63% rate among all controllable factors. When considering time until dropout, 100% of very early dropout patients and 50% of late dropout patients did so due to PF. Among early dropout patients 67% dropped out due to other medical reasons. The mean time to dropout for PF, other, and infection (INF) were 13, 26, and 33 months, respectively. When considering type of initiation, we found PF to be the largest attributable factor with 50% of unplanned, 100% of planned, and 50% of conversions stopping therapy. CONCLUSIONS: Our study indicates that the primary reason for controllable loss from therapy was secondary to PF regardless of the time on therapy or the method of initiation to therapy.

Adherence rates to ferric citrate as compared to active control in patients with end stage kidney disease on dialysis.

INTRODUCTION: Oral phosphate binders are the main stay of treatment of hyperphosphatemia. Adherence rates to ferric citrate, a recently approved phosphate binder, are unknown. METHODS: We conducted a post-hoc analysis to evaluate whether adherence rates were different for ferric citrate vs. active control in 412 subjects with end stage kidney disease (ESKD) who were randomized to ferric citrate vs. active control (sevelamer carbonate and/or calcium acetate). Adherence was defined as percent of actual number of pills taken to total number of pills prescribed. FINDINGS: There were no significant differences in baseline characteristics including gender, race/ethnicity, and age between the ferric citrate and active control groups. Baseline phosphorus, calcium, and parathyroid hormone levels were similar. Mean (SD) adherence was 81.4% (17.4) and 81.7% (15.9) in the ferric citrate and active control groups, respectively (P = 0.88). Adherence remained similar between both groups after adjusting for gender, race/ethnicity, age, cardiovascular disease (CVD), and diabetic nephropathy (mean [95% CI]: 81.4% [78.2, 84.6] and 81.5% [77.7, 85.2] for ferric citrate and active control, respectively). Gender, race/ethnicity, age, and diagnosis of diabetic nephropathy did not influence adherence to the prescribed phosphate binder. Subjects with CVD had lower adherence rates to phosphate binder; this was significant only in the active control group. DISCUSSION: Adherence rates to the phosphate binder, ferric citrate, were similar to adherence rates to active control. Similar adherence rates to ferric citrate are notable since tolerance to active control was an entry criteria and the study was open label. Gender, race/ethnicity, nor age influenced adherence.

Osteoporosis Diagnosis and Management in Long-Term Care Facility.

BACKGROUND: Contemporary estimates of the prevalence of diagnosed osteoporosis among long-term care facility residents are limited. METHODS: This chart review collected data between April 1, 2012 and August 31, 2013 for adult (age ≥ 30 years) residents of 11 long-term care facilities affiliated with the Louisiana State University Health Sciences Center in the New Orleans metropolitan area. Data (demographics; comorbidities; osteoporosis diagnosis, risk factors, diagnostic assessments, treatments; fracture history; fall risk; activities of daily living) were summarized. Data for residents with and without diagnosed osteoporosis were compared using χ tests and t tests. RESULTS: The study included 746 residents (69% women, mean [SD] age: 76.3 [13.9] years, median length of stay approximately 18.5 months). An osteoporosis diagnosis was recorded for 132 residents (18%), 30% of whom received a pharmacologic osteoporosis therapy. Fewer than 2% of residents had bone mineral density assessments; 10% had previous fracture. Calcium and vitamin D use was more prevalent in residents with diagnosed osteoporosis compared with other residents (calcium: 49% versus 12%, vitamin D: 52% versus 28%; both P < 0.001). Over half (304/545) of assessed residents had a high fall risk. Activities of daily living were similarly limited regardless of osteoporosis status. CONCLUSIONS: The prevalence of diagnosed osteoporosis was higher than previously reported for long-term care residents, but lower than epidemiologic estimates of osteoporosis prevalence for the noninstitutional U.S. POPULATION: In our sample, osteoporosis diagnostic testing was rare and treatment rates were low. Our results suggest that osteoporosis may be underdiagnosed and undertreated in long-term care settings.

Obesity and hypertension in the Argentinian population compared to the white Hispanic population of the United States.

Hypertension and obesity are two closely related pathologies in clinical practice. Currently, about one billion adults worldwide are overweight, and it is estimated that, if no serious action is taken to effect profound change, that figure will continue to rise throughout this century. Hypertension is also a serious public health problem worldwide, one that, along with type 2 diabetes, is growing due to increases in both life expectancy and obesity. However, the rate of increase varies by population group. For example, in the United States, the prevalence of obesity differs quite markedly among the white population of European origin, African American individuals, and the Latin American population. This disparity exists among other populations as well, such as that of Argentina, where obesity is less prevalent than in the United States. This significant difference between the Argentinean population and that of American whites may be explained by the former population's migratory origin and distinct eating habits.

An analysis of chronic kidney disease risk factors in a Louisiana nursing home population: a cross-sectional study.

BACKGROUND: Chronic Kidney Disease (CKD) and its progression are associated with multiple risk factors. CKD is prevalent in nursing homes residents, but factors related to CKD in this setting have not been defined. METHODS: A cross-sectional study was conducted (n=103). Data was abstracted using standardized forms and analyzed (SAS 9.2). Chi square and t-test statistics were used to compare proportions and means; correlation coefficients were used to describe associations. Logistic models were fit to the data to determine multivariate associations. Modification of Diet in Renal Disease (MDRD) formula was used to estimate GFR. CKD was defined according to established standards. A cutoff point of 60 was chosen for further analysis. RESULTS: Twenty-three percent of subjects had CKD. Mean age for eGFR <60 was 70.8 +/- 13 and for eGFR >60 was 61.7 +/-14. Frequent co-morbidities were hypertension (75%), GERD (40%), obesity (39%), dyslipidemia (35%), depression (34%), anemia (32%), and diabetes (32%). CONCLUSIONS: Our population is unique in terms of its age and reasons for nursing home admission. Factors associated with CKD in our study include age >65 years old, being male, having a positive history of cardiovascular disease (including congestive heart failure and coronary artery disease,) anemia, polypharmacy, and being obese (BMI >30). Further analysis showed that age and anemia are the strongest factors associated with CKD in our population. Management targeted at CKD risk factor reduction may play a vital role in controlling the magnitude of this disease. Prospective studies to investigate the relationship between gender, a BMI greater than 30, cardiovascular disease, and CKD and its complications are warranted.

Tesaglitazar, a dual peroxisome proliferator-activated receptor agonist (PPAR alpha/gamma), improves metabolic abnormalities and reduces renal injury in obese Zucker rats.

Metabolic syndrome increases the risk of developing diabetes as well as cardiovascular and kidney diseases. This research studied the effects of tesaglitazar, a dual-acting peroxisome proliferator-activated receptor (PPAR)alpha/gamma agonist, on metabolic abnormalities and kidney injury in obese Zucker rats (OZR). Lean Zucker rats (LZR) and OZR were used as control groups. Tesaglitazar (1 micromol/kg/day) was given for 8 weeks in the treatment group (OZR-T). Metabolic parameters, 24-hour urine albumin excretion, and tail blood pressure were measured. Glomerular filtration rate by inulin clearance, abdominal fat and renal histology were determined at the end of the study. In comparison with the OZR and OZR-T groups, the LZR control animals' parameters were significantly more favorable in all measures. Tesaglitazar treatment in OZR significantly reduced nonfasting glucose, C-reactive protein levels and improved dyslipidemia. Body weight, blood pressure and urine albumin excretion were lower, but the adjusted glomerular filtration rate higher, in the OZR-T group than in the OZR controls. Glomerular area, mesangial expansion and tubulointerstitial changes were ameliorated, and the glomerular expression of desmin was markedly more decreased in the OZR-T group than in the OZR controls. Therefore, the PPAR alpha/gamma agonist tesaglitazar significantly improved metabolic abnormalities and renal function, decreased blood pressure, and protected against glomerular and interstitial damage in OZR.

End-stage renal disease in young black males in a black-white population: longitudinal analysis of the Bogalusa Heart Study.

BACKGROUND: Risk factors in childhood create a life-long burden important in the development of cardiovascular (CV) disease in adulthood. Many risk factors for CV disease (e.g., hypertension) also increase the risk of renal disease. However, the importance of childhood risk factors on the development of chronic kidney disease and end-stage renal disease (ESRD) is not well characterized. METHODS: The current observations include data from Bogalusa Heart Study participants who were examined multiple times as children between 1973 and 1988. RESULTS: Through 2006, fifteen study participants subsequently developed ESRD in adulthood; seven with no known overt cause. Although the Bogalusa Heart Study population is 63% white and 37% black and 51% male and 49% female, all seven ESRD cases with no known overt cause were black males (p < 0.001). Mean age-adjusted systolic and diastolic blood pressure in childhood was higher among the ESRD cases (114.5 mmHg and 70.1 mmHg, respectively) compared to black (103.0 mmHg and 62.3 mmHg, respectively) and white (mean = 103.3 mmHg and 62.3 mmHg, respectively) boys who didn't develop ESRD. The mean age-adjusted body mass index in childhood was 23.5 kg/m2 among ESRD cases and 18.6 kg/m2 and 18.9 kg/m2 among black and white boys who didn't develop ESRD, respectively. Plasma glucose in childhood was not significantly associated with ESRD. CONCLUSION: These data suggest black males have an increased risk of ESRD in young adulthood. Elevated body mass index and blood pressure in childhood may increase the risk for developing ESRD as young adults.

Effect of the HMG-CoA reductase inhibitor rosuvastatin on early chronic kidney injury in obese zucker rats fed with an atherogenic diet.

The obese Zucker rat (OZR) spontaneously develops hyperlipidemia, insulin resistance, and microalbuminuria. In this study, the initial metabolic, functional, and glomerular pathology in young OZR fed with an atherogenic diet resembles the characteristics of metabolic syndrome. Hyperlipidemia and other metabolic derangement cause early glomerular damage in OZR by 10 weeks of age, before overt diabetes is developed. Consequently, the effects of potential interventions should also be evaluated at the young age. In OZR fed with an atherogenic high-fat diet, low (5 mg/kg) and high (20 mg/kg) dosages of rosuvastatin started at 5 weeks and maintained for 10 weeks induced a significant improvement in metabolic abnormalities, blood pressure, and renal function, including microalbuminuria. The low dose of rosuvastatin significantly decreased mesangial expansion, and the high dose exerted a marked protective effect on the development of both glomerular hypertrophy and mesangial expansion. The statin also attenuated the inflammatory expression in the kidney cortex.

Leptin and hypertension in obesity.

Leptin, a peptide discovered more than 10 years ago, decreases food intake and increases sympathetic nerve activity to both thermogenic and non-thermogenic tissue. Leptin was initially believed to be an anti-obesity hormone, owing to its metabolic effects. However, obese individuals, for unknown reasons, become resistant to the satiety and weight-reducing effect of the hormone, but preserve leptin-mediated sympathetic activation to non-thermogenic tissue such as kidney, heart, and adrenal glands. Leptin has been shown to influence nitric oxide production and natriuresis, and along with chronic sympathetic activation, especially to the kidney, it may lead to sodium retention, systemic vasoconstriction, and blood pressure elevation. Consequently, leptin is currently considered to play an important role in the development of hypertension in obesity.