Hyperuricemia: An Intriguing Connection to Metabolic Syndrome, Diabetes, Kidney Disease, and Hypertension.

PURPOSE OF THE REVIEW: Our review explores the epidemiology, physiology, and clinical data surrounding the connection between hyperuricemia and metabolic syndrome, chronic kidney disease, and hypertension. RECENT FINDINGS: Compelling physiologic mechanisms have been proposed to explain a causal relationship between hyperuricemia and metabolic syndrome, chronic kidney disease, and hypertension but clinical studies have given mixed results in terms of whether intervening with hyperuricemia using urate-lowering therapy has any beneficial effects for patients with these conditions. Despite the large amount of research already put into this topic, more randomized placebo-controlled trials are needed to more firmly establish whether a cause-effect relationship exists and whether lowering uric acid levels in patients with these conditions is beneficial.

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.

Hypertension, Obesity, and COVID-19: a Collision of Pandemics.

PURPOSE OF REVIEW: To highlight the epidemiology and pathophysiology of hypertension and obesity in COVID-19 infection RECENT FINDINGS: Hypertension and obesity have emerged as significant risk factors for contracting the COVID-19 virus and the subsequent severity of illness. ACE2 receptor expression and dysregulation of the RAAS pathway play important roles in the pathophysiology of these associations, as do the pro-inflammatory state and cytokine dysregulation seen in obesity. Some of these patterns have also been seen historically in other viral illnesses. Understanding the mechanisms behind the associations between COVID-19, hypertension, and obesity is important in developing effective targeted therapies and monitoring vaccine response and efficacy. More research is needed to apply our growing knowledge of the pathophysiology of COVID-19, hypertension, and obesity to prevention and treatment. Interventions focusing on lifestyle modification in managing hypertension and obesity can potentially have a positive impact on containing this pandemic and future viral illness outbreaks.

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.

First Course DASH, Second Course Mediterranean: Comparing Renal Outcomes for Two "Heart-Healthy" Diets.

PURPOSE OF REVIEW: To review studies evaluating renal outcomes based on patient adherence to the Mediterranean diet or to the Dietary Approaches to Stop Hypertension (DASH) diet and to determine which diet is most effective in preventing and managing renal disease. RECENT FINDINGS: Both the DASH and Mediterranean diets have shown many health benefits, including reduced risk for chronic kidney disease (CKD), nephrolithiasis, mortality due to all renal causes and composite outcomes. Both diets have shown a decrease in estimated glomerular filtration rates (eGFR) decline with a concomitant improvement in mortality and dialysis initiation. In summary, both diets resulted in similar magnitudes of risk reduction when comparing equivocal levels of adherence to each diet. Review of evidence for renal outcomes shows strikingly similar effects for both DASH and Mediterranean diets. We hypothesize that these results are due to the overlap in nutritional composition. Both encourage whole foods such as fruits, vegetables, beans/legumes, whole grains, and nuts. Additionally, they restrict animal protein consumption and limit processed and fast foods. Determining a nutritional management intervention for renal impairment is clinically important as approximately 1% of the USA annual budget is spent on end stage renal disease (ESRD) treatment. We believe either diet could be incorporated into a patient's management when considering their renal health. In conclusion, we urge physicians to help patients choose either the DASH diet or Mediterranean diet based on the patient preference.

Using manual exchanges for an urgent-start peritoneal dialysis program.

BACKGROUND: Urgent-start peritoneal dialysis (USPD) was designed to avoid temporary hemodialysis initiation with a hemodialysis catheter. In these patients, PD is initiated within 2 weeks of catheter placement, but typically these prescriptions utilize automated peritoneal dialysis (APD) with a cycler. Manual exchanges have not been reported previously for USPD. We hypothesize that using multiple, low-volume manual exchanges, patients will have similar rates of peritonitis, exit-site infection (ESI), pericatheter leaks and discontinuation of PD in the first 3 months after initiation. METHODS: This retrospective study included patients who initiated PD in our unit from May 2014 until August 2016 using our USPD protocol. Patients with a body surface area <1.7 m2 used 750 mL dwell volumes and those >1.7 m2 used 1000 mL dwell volumes during the first 7 days. Dwell times were 2-2.5 h for two to three exchanges per day. After 7 days of successful therapy, the dwell volumes were doubled. All patients were maintained on furosemide 160 mg twice daily. RESULTS: There were 20 patients enrolled in our USPD program. Our rates of peritonitis, ESI, pericatheter leak and discontinuation of PD were 5%, 0%, 5% and 5%, respectively. CONCLUSIONS: Manual exchange during USPD is a viable modality with similar results as APD. Using manual exchanges allows patients to be more ambulatory during the day when they are not dwelling, allows nurses to evaluate the amount of ultrafiltration and effluent characteristics and allows for training in manual exchanges as well.

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.

Recognition and Management of Resistant Hypertension.

Despite improvements in hypertension awareness and treatment, 30%-60% of hypertensive patients do not achieve BP targets and subsequently remain at risk for target organ damage. This therapeutic gap is particularly important to nephrologists, who frequently encounter treatment-resistant hypertension in patients with CKD. Data are limited on how best to treat patients with CKD and resistant hypertension, because patients with CKD have historically been excluded from hypertension treatment trials. First, we propose a consistent definition of resistant hypertension as BP levels confirmed by both in-office and out-of-office measurements that exceed appropriate targets while the patient is receiving treatment with at least three antihypertensive medications, including a diuretic, at dosages optimized to provide maximum benefit in the absence of intolerable side effects. Second, we recommend that each patient undergo a standardized, stepwise evaluation to assess adherence to dietary and lifestyle modifications and antihypertensive medications to identify and reduce barriers and discontinue use of substances that may exacerbate hypertension. Patients in whom there is high clinical suspicion should be evaluated for potential secondary causes of hypertension. Evidence-based management of resistant hypertension is discussed with special considerations of the differences in approach to patients with and without CKD, including the specific roles of diuretics and mineralocorticoid receptor antagonists and the current place of emerging therapies, such as renal denervation and baroreceptor stimulation. We endorse use of such a systematic approach to improve recognition and care for this vulnerable patient group that is at high risk for future kidney and cardiovascular events.

Successful return to peritoneal dialysis after a case of relapsing Sphingomonas paucimobilis peritonitis
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Sphingomonas paucimobilis is an uncommon source of peritonitis in patients undergoing peritoneal dialysis (PD). Although only a small number of cases have been reported, treatment failure rate is extremely high, with removal of the peritoneal dialysis catheter noted in ~ 50% of reported cases. The potential damage to the peritoneal membrane from peritonitis with this organism and the ability to return to PD after infection is unknown. We report a unique case in which a patient was able to successfully return to PD after relapsing Sphingomonas paucimobilis peritonitis, without apparent effects to dialysis clearance or ultrafiltration.
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Anti-hypertensive drug treatment of patients with and the metabolic syndrome and obesity: a review of evidence, meta-analysis, post hoc and guidelines publications.

Epidemiological studies have shown an increasing prevalence of obesity and the metabolic syndrome worldwide. Lifestyle modifications that include dietary changes, weight reduction, and exercise are the cornerstones in the treatment of this pathology. However, adherence to this approach often meets with failure in clinical practice; therefore, drug therapy should not be delayed. The ideal pharmacological antihypertensive regimen should target the underlying mechanisms involved in this syndrome, including sympathetic activation, increased renal tubular sodium reabsorption, and overexpression of the renin-angiotensin-aldosterone system by the adipocyte. Few prospective trials have been conducted in the search of the ideal antihypertensive regimen in patients with obesity and the metabolic syndrome. We summarize previously published ad hoc studies, prospective studies, and guideline publications regarding the treatment of hypertension in patients with obesity and the metabolic syndrome. We conclude that the optimal antihypertensive drug therapy in these patients has not been defined. Though caution exists regarding the use of thiazide diuretics due to potential metabolic derangements, there is insufficient data to show worsened cardiovascular or renal outcomes in patients treated with these drugs. In regard to beta blockers, the risk of accelerating conversion to diabetes and worsening of inflammatory mediators described in patients treated with traditional beta blockers appears much less pronounced or absent when using the vasodilating beta blockers. Renin-angiotensin-aldosterone system (RAAS) inhibition with an ACE or an ARB and treatment with calcium channel blockers appears safe and well tolerated in obesity-related hypertension and in patients with metabolic syndrome. Future prospective pharmacological studies in this population are needed.

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 impacts of obesity on the cardiovascular and renal systems: cascade of events and therapeutic approaches.

There is a neglected epidemic of both obesity and metabolic syndrome in industrialized and unindustrialized countries all over the globe. Both conditions are associated with a high incidence of other serious pathologies, such as cardiovascular and renal diseases. In this article, we review the potential underlying mechanisms by which obesity and metabolic syndrome promote hypertension, including changes in cardiovascular-renal physiology induced by leptin, the sympathetic nervous system, the renin-angiotensin-aldosterone system, insulin resistance, free fatty acids, natriuretic peptides, and proinflammatory cytokines. We also discuss the potential underlying mechanisms by which obesity promotes other cardiovascular and renal conditions, as well as available nonpharmacologic and pharmacologic approaches for treating obesity-induced hypertension. The findings presented herein suggest that adipocytes may be a key regulator of cardiovascular and renal function.

Commentary on the 2014 BP guidelines from the panel appointed to the Eighth Joint National Committee (JNC 8).

The recently published article "2014 Evidence-based guideline for the management of high blood pressure in adults: Report from the panel members appointed to the Eighth Joint National Committee (JNC 8)" (James et al., JAMA 311: 507-520, 2014) has generated considerable controversy. In this commentary, we evaluate the document and compare the recommendations contained within it with those of the JNC 7 and other national and international guidelines. The evidence quality rating approach followed by the article "2014 Evidence-based guideline for the management of high blood pressure in adults: Report from the panel members appointed to the Eighth Joint National Committee (JNC 8)" (James et al., JAMA 311: 507-520, 2014) disqualified nearly 98% of previous studies from review; as a result, some of the key recommendations were on the basis of expert opinion alone. We are especially concerned that the recommendation to raise the systolic/diastolic BP levels at which treatment is initiated to ≥150/≥90 mmHg in adults≥60 years old may affect cardiovascular and renal health in these patients. Additionally, we recommend that hypertension guidelines should be updated every 3-4 years with a fresh approach to the definition of target BP levels, the use of modern technology in the diagnosis of hypertension, and the treatment of hypertension in special populations not addressed in earlier guidelines.

Blood pressure control and cardiovascular outcomes in normal-weight, overweight, and obese hypertensive patients treated with three different antihypertensives in ALLHAT.

OBJECTIVE: Epidemiologically, there is a strong relationship between BMI and blood pressure (BP) levels. We prospectively examined randomization to first-step chlorthalidone, a thiazide-type diuretic; amlodipine, a calcium-channel blocker; and lisinopril, an angiotensin-converting enzyme inhibitor, on BP control and cardiovascular outcomes in a hypertensive cohort stratified by baseline BMI [kg/m(2); normal weight (BMI <25), overweight (BMI = 25-29.9), and obese (BMI >30)]. METHODS: In a randomized, double-blind, practice-based Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, 33,357 hypertensive participants, aged at least 55 years, were followed for an average of 4.9 years, for a primary outcome of fatal coronary heart disease or nonfatal myocardial infarction, and secondary outcomes of stroke, heart failure, combined cardiovascular disease, mortality, and renal failure. RESULTS: Of participants, 37.9% were overweight and 42.1% were obese at randomization. For each medication, BP control (<140/90 mmHg) was equivalent in each BMI stratum. At the fifth year, 66.1, 66.5, and 65.1% of normal-weight, overweight, and obese participants, respectively, were controlled. Those randomized to chlorthalidone had highest BP control (67.2, 68.3, and 68.4%, respectively) and to lisinopril the lowest (60.4, 63.2, and 59.6%, respectively) in each BMI stratum. A significant interaction (P = 0.004) suggests a lower coronary heart disease risk in the obese for lisinopril versus chlorthalidone (hazard ratio 0.85, 95% confidence interval 0.74-0.98) and a significant interaction (P = 0.011) suggests a higher risk of end-stage renal disease for amlodipine versus chlorthalidone in obese participants (hazard ratio 1.49, 95% confidence interval 1.06-2.08). However, these results were not consistent among other outcomes. CONCLUSION: BMI status does not modify the effects of antihypertensive medications on BP control or cardiovascular disease outcomes.