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.

Obstructive Sleep Apnea and Hypertension: Updates to a Critical Relationship.

PURPOSE OF REVIEW: Obstructive sleep apnea (OSA) is an underdiagnosed illness linked to essential hypertension (HTN), resistant hypertension (r-HTN), and cardiovascular disease (CVD). This review provides updates on the epidemiology, pathophysiology, and treatments of OSA-associated HTN. RECENT FINDINGS: Mild sleep apnea increases the risk for HTN. Eighty-nine percent of young patients aged 18-35 with HTN not attributed to secondary causes have underlying OSA. Home sleep studies are noninferior to formal polysomnography for OSA diagnosis. Nocturnal oxygen desaturation rate is positively correlated with HTN severity. Gut microbiome neo-colonization in response to high-fat diet cravings in patients with OSA alters immune function and worsens HTN. Carbonic anhydrase inhibitors and probiotics show newfound potential for OSA-associated HTN treatment. OSA recognition improves hospital outcomes after a STEMI. Hypoxia-inducible factor (HIF) transcription increases in a dose-dependent manner to hypoxia, and HIFs are strongly linked to cancer growth. OSA and HTN are comorbid conditions with adversely connected pathophysiology including sympathetic hyperactivity, gut dysbiosis, proinflammation, endothelial damage, rostral fluid shifts, pharyngeal collapse, intravascular fluid retention, nocturnal energy expenditure, and metabolic derangements. The dose-response effect of OSA on HTN severity challenges blood pressure (BP) control, so those with refractory HTN should be screened for OSA.

The Incidence and Pathophysiology of the Obesity Paradox: Should Peritoneal Dialysis and Kidney Transplant Be Offered to Patients with Obesity and End-Stage Renal Disease?

PURPOSE OF REVIEW: To educate nephrologists and primary-care physicians about the incidence, pathophysiology, and survival benefits of the obesity paradox in end-stage renal disease (ESRD). This review also discusses the future of kidney transplant and peritoneal dialysis in obese dialysis patients. RECENT FINDINGS: Obesity paradox in ESRD was first reported three decades ago, and since then, there have been several epidemiological studies that confirmed the phenomenon. Regardless of the anthropometric indices used to define obesity in ESRD patients, these markers serve to predict the dialysis patient's survival. The pathophysiology of obesity paradox tends to be multifactorial. Recent cohort studies demonstrated a survival benefit in all race and ethnic groups, but Hispanics and blacks experienced increased survival rates when compared to non-Hispanic whites. Obese dialysis patients should be offered peritoneal dialysis, especially if they are new to dialysis and have an adequate renal residual function. Several studies have shown that the benefit of receiving kidney transplant in obese patients exceeds the risks. The robotic-assisted kidney transplant (RAKT) procedure is the latest innovation that could offer hope for obese dialysis patients who have been denied or are waiting for kidney transplant. The obesity paradox phenomenon in ESRD is a unique illustration of survival benefit in a population that has a high overall annual mortality. Peritoneal dialysis should be encouraged for obese patients who have preserved residual renal function. Kidney transplant centers should encourage RAKT utilization in obese dialysis patients instead of denying them a kidney transplant.

Bariatric Surgery and Hypertension.

Obesity continues to increase in prevalence worldwide. Hypertension has long been associated with obesity, and weight loss continues to be a first-line therapy in the treatment of hypertension. Lifestyle modification and pharmacologic therapy, however, often meet with treatment failure. Bariatric surgery continues to be the most successful approach to sustained weight loss. This review focuses on the underlying physiologic mechanisms of obesity-hypertension, and the impact of bariatric surgery on the treatment of hypertension. Current available literature on the physiologic mechanisms of obesity-hypertension, and the major trials, meta-analyses and systematic reviews of the impact of bariatric surgery procedures on hypertension are reviewed. Evidence suggests significant improvement in obesity-hypertension in patients who undergo surgical weight-reduction procedures. Malabsorptive techniques such as the Roux-en-Y gastric bypass or surgical resection techniques such as laparoscopic sleeve gastrectomy appear to offer superior results in regards to hypertension control over restrictive techniques such as Gastric Banding. Though long-term control of hypertension following surgery remains a concern, available follow-up post-operative data of up to 10 years suggests a sustained, if lessened, effect on hypertension control over time.

Ferric Citrate Reduces Intravenous Iron and Erythropoiesis-Stimulating Agent Use in ESRD.

Ferric citrate (FC) is a phosphate binder with shown efficacy and additional effects on iron stores and use of intravenous (iv) iron and erythropoiesis-stimulating agents (ESAs). We provide detailed analyses of changes in iron/hematologic parameters and iv iron/ESA use at time points throughout the active control period of a phase 3 international randomized clinical trial. In all, 441 subjects were randomized (292 to FC and 149 to sevelamer carbonate and/or calcium acetate [active control (AC)]) and followed for 52 weeks. Subjects on FC had increased ferritin and transferrin saturation (TSAT) levels compared with subjects on AC by week 12 (change in ferritin, 114.1±29.35 ng/ml; P<0.001; change in TSAT, 8.62%±1.57%; P<0.001). Change in TSAT plateaued at this point, whereas change in ferritin increased through week 24, remaining relatively stable thereafter. Subjects on FC needed less iv iron compared with subjects on AC over 52 weeks (median [interquartile range] dose=12.9 [1.0-28.9] versus 26.8 [13.4-47.6] mg/wk; P<0.001), and the percentage of subjects not requiring iv iron was higher with FC (P<0.001). Cumulative ESA over 52 weeks was lower with FC than AC (median [interquartile range] dose=5303 [2023-9695] versus 6954 [2664-12,375] units/wk; P=0.04). Overall, 90.3% of subjects on FC and 89.3% of subjects on AC experienced adverse events. In conclusion, treatment with FC as a phosphate binder results in increased iron parameters apparent after 12 weeks and reduces iv iron and ESA use while maintaining hemoglobin over 52 weeks, with a safety profile similar to that of available binders.

The obesity paradox and cardiovascular disease.

Obesity is increasingly recognized as a global pandemic that threatens the health of millions of people. Obesity is considered to be an important cardiovascular risk factor, but there is increasing evidence that patients with elevated body mass index may be better off than others if they develop cardiovascular or renal disease. This phenomenon has been described as the "obesity paradox" or "reverse epidemiology." This article reviews some recent publications that have studied this phenomenon as it relates to heart failure, coronary artery disease, peripheral arterial disease, kidney disease, and a cohort of patients undergoing nonbariatric surgery.

Obesity, hypertension, and the heart.

Controversy exists regarding the amount of risk caused by obesity, but there is general consensus that it is associated with many serious disorders, mostly cardiovascular and neoplastic. Obesity is clearly associated with hypertension, ventricular remodeling with subsequent congestive heart failure, sleep-disordered breathing, and sudden death. The physiologic alterations associated with establishing and perpetuating the obese state are complex but are becoming clear. In discussing the cardiovascular consequences of obesity, the implications and mechanism of the associated hypertension need to be understood. There is growing recognition that adipose tissue is a very active in the neurohormonal axis and is not simply a passive storage depot. Among other things, adipocyte-related hormonal activity and resistance to feedback mechanisms are associated with increased plasma volume and increased sympathetic tone.

Kidney transplantation: the evolving challenges.

Kidney transplantation is the treatment of choice for patients with end stage renal disease. Kidney transplantation not only improves the quality of life but also prolongs life. Over the last decade, the short-term allograft survival rate has been improved dramatically. Chronic allograft nephropathy and death from cardiovascular diseases become predominant causes of later graft loss. Prevention and treatment of these disease processes require a comprehensive approach. The ever-increasing shortage of organ supply becomes the greatest challenge for the transplant community and modern medicine. More and more patients are waiting for organs; many of them are dying while waiting. Xenotransplantation and organ engineering and cloning are promising techniques and can potentially provide organs for transplantation in the future.

Interferon-alpha-associated sarcoidosis responsive to infliximab therapy.

Sarcoidosis, a multisystem disease characterized by noncaseating granulomas, has been reported to be associated with interferon alpha (IFN-alpha) therapy for hepatitis C infection. INF-alpha is known to stimulate T helper cells with a Th1 profile immune response, which is the key immunologic event of a sarcoid granuloma formation. We report a patient treated with IFN-alpha who developed hypercalcemia and renal insufficiency as presenting clinical manifestation of sarcoidosis. Prednisone therapy was effective in controlling hypercalcemia but had to be discontinued due to an increase in hepatitis C viral RNA count. Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor alpha was used as therapy in our patient for its known potent anti-inflammatory effects. The patient received three doses of infliximab (5 mg/kg) and achieved a rapid decline in serum calcium to normal levels in 7 days; the serum calcium level has remained normal 3 months after the last infusion.