Therapeutic update on oral potassium exchange resin use in chronic kidney disease patients: a systematic review of randomized controlled clinical trials.

Hyperkalemia is a common electrolyte disorder in patients with chronic kidney disease (CKD) that increases in prevalence with the decline of glomerular fltration rate (GFR). Another risk of hyperkalemia is the use of renin-angiotensin-aldosterone system inhibitors (RAASi) and/or mineralocorticoid receptor antagonists (MRAs) in managing CKD and proteinuria. The treatment of chronic hyperkalemia is challenging especially for outpatients. Treatment options for hyperkalemia include the potassium exchange resins of which two new potassium binders, Patiromer Sorbitex Calcium, and Sodium Zirconium Cyclosilicate (SZC) have demonstrated their clinical efficacy in reducing serum potassium with a positive safety profile. The old potassium exchange resin sodium polystyrene sulfonate (Kayexalate™) has some negative side effects including colonic necrosis, hypomagnesemia, and hypernatremia. In this review and literature search, we compare the available oral potassium exchange resins, highlight their advantages and disadvantages and comment on efficacy and safety parameters specifically in CKD patients.

Tenapanor: A new treatment option for hyperphosphatemia in end stage kidney disease.

PURPOSE: This narrative review explores the currently published studies that have evaluated tenapanor for the treatment of hyperphosphatemia in end-stage kidney disease (ESKD) patients on hemodialysis. This medication's new phosphate lowering mechanism of action reduces intestinal phosphate absorption predominantly through reduction of passive paracellular phosphate flux by inhibition of the sodium/hydrogen exporter isoform 3 (NHE3). Tenapanor additionally prevents active transcellular phosphate absorption compensation by decreasing the expression of sodium phosphorus 2b transport protein (NaPi2b). METHODS: A comprehensive search of the literature was conducted using PubMed and ClinicalTrials.gov search engines. The search term "tenapanor hyperphosphatemia" was used for study retrieval. Results were limited to studies published in the English language and excluded review articles. Human, animal, and in vitro studies were included. No date range was specified. RESULTS: A total of 11 primary studies were identified and included in this review, the largest human study of which enrolled 236 patients. Each study is presented in table format along with measured end points. CONCLUSIONS: Tenapanor is the first drug in its class that lowers hyperphosphatemia in ESKD patients through a novel mechanism of action involving paracellular inactive transport. Although more studies are needed, early results indicate that tenapanor may have a place in managing hyperphosphatemia in ESKD patients both as monotherapy and as an adjunct to existing phosphate binder therapy.

Hypertension Pharmacological Treatment in Adults: A World Health Organization Guideline Executive Summary.

Hypertension is a major cause of cardiovascular disease and deaths worldwide especially in low- and middle-income countries. Despite the availability of safe, well-tolerated, and cost-effective blood pressure (BP)-lowering therapies, <14% of adults with hypertension have BP controlled to a systolic/diastolic BP <140/90 mm Hg. We report new hypertension treatment guidelines, developed in accordance with the World Health Organization Handbook for Guideline Development. Overviews of reviews of the evidence were conducted and summary tables were developed according to the Grading of Recommendations, Assessment, Development, and Evaluations approach. In these guidelines, the World Health Organization provides the most current and relevant evidence-based guidance for the pharmacological treatment of nonpregnant adults with hypertension. The recommendations pertain to adults with an accurate diagnosis of hypertension who have already received lifestyle modification counseling. The guidelines recommend BP threshold to initiate pharmacological therapy, BP treatment targets, intervals for follow-up visits, and best use of health care workers in the management of hypertension. The guidelines provide guidance for choice of monotherapy or dual therapy, treatment with single pill combination medications, and use of treatment algorithms for hypertension management. Strength of the recommendations was guided by the quality of the underlying evidence; the tradeoffs between desirable and undesirable effects; patient's values, resource considerations and cost-effectiveness; health equity; acceptability, and feasibility consideration of different treatment options. The goal of the guideline is to facilitate standard approaches to pharmacological treatment and management of hypertension which, if widely implemented, will increase the hypertension control rate world-wide.

End-Stage Kidney Disease in Areas of Armed Conflicts: Challenges and Solutions.

Violent and protracted conflicts are disastrous to civilian populations and their health care systems. The complex requirements of caring for end-stage kidney disease (ESKD) dialysis patients in such contexts pose unique challenges. Dialysis is procedurally complex and resource-intensive. Delivering ESKD care in man-made conflict settings presents added challenges beyond what is required in natural disasters and resource-limited situations. In this article, we review the medical literature on, and document experience with, managing dialysis ESKD patients in conflict zones. We discuss the impact of war on patient outcomes, dialysis system infrastructure, operational funding, and risks to providers and organizations. This article provides recommendations to health care providers, educators, and policymakers on how to mitigate associated challenges.

Ergocalciferol Versus Cholecalciferol in Non-Dialysis Dependent Chronic Kidney Disease Patients: A Small Retrospective Cohort Study.

PURPOSE: The purpose of this retrospective cohort study was to measure the difference between cholecalciferol and ergocalciferol in their ability to effect vitamin D, parathyroid hormone (PTH), calcium, and phosphorous serum concentrations in patients with stage 3 or 4 chronic kidney disease. METHODS: This was a retrospective cohort study conducted within a single-center ambulatory nephrology clinic. Patients eligible for the study were identified through medical records displaying each patient's initiation on either ergocalciferol or cholecalciferol from 2013 to 2016. Patients' baseline vitamin D, PTH, calcium, and phosphorous serum concentrations were taken prior to treatment initiation, and patients were reassessed with a second measurement within 12 months of therapy. RESULTS: Out of 149 eligible patients, 110 were excluded. There were 33 patients included on cholecalciferol and 6 patients on ergocalciferol. A significant difference was observed in the percent change of phosphorous serum concentrations from baseline following drug administration (p=0.03). The mean changes from baseline to final serum phosphorous concentrations (mg/dL) were 0.12 and -0.3 for cholecalciferol and ergocalciferol, respectively. There was no significant difference in vitamin D (14.9, 15.1, p=0.97), PTH (5.6, 2.3, p=0.72), or calcium (0.05, -0.17, p=0.08) serum concentrations between cholecalciferol and ergocalciferol, respectively. There was a statistically significant increase in the mean change in serum phosphorous concentrations within the cholecalciferol group compared to the ergocalciferol group. CONCLUSION: In this small pilot study, cholecalciferol treatment appeared to increase serum phosphorous concentrations compared to ergocalciferol. These observations may warrant further large-scale studies that are appropriately powered to validate such findings.

Use of Paricalcitol as Adjunctive Therapy to Renin-Angiotensin-Aldosterone System Inhibition for Diabetic Nephropathy: A Systematic Review of the Literature.

PURPOSE: Diabetic nephropathy (DN) is a major complication of diabetes. Paricalcitol is a vitamin D analog that is typically used for secondary hyperparathyroidism in patients with chronic kidney disease but may have some beneficial effect on DN. This review evaluates the effect of paricalcitol in combination with renin-angiotensin-aldosterone system inhibitor therapy in managing DN. METHODS: A literature search was conducted of PubMed and ClinicalTrials.gov. Limits were set to include only clinical trials in humans written in English. The search terms used were paricalcitol and diabetic nephropathy. The following outcomes of kidney function and damage as well as adverse drug events were assessed and included: 24-h urine albumin excretion, serum phosphorus and calcium concentrations, urinary albumin excretion rates, estimated glomerular filtration rate, and markers of inflammation and endothelial function. FINDINGS: Four studies with a total of 389 patients were identified for review through the process described above. Two of the 6 studies provide evidence of the effect of paricalcitol on DN by way of reduction in urine albumin to creatinine ratio and urinary albumin excretion rate when compared with placebo. One study reported an increase in serum phosphorous, 1 study observed a decrease in estimated glomerular filtration rate, and 1 study reported no effect on inflammatory markers or endothelial function. IMPLICATIONS: The number of clinical trials examining the effect of paricalcitol in DN is small. The studies that have been completed enrolled <300 patients. Paricalcitol can reduce protein in the urine, but there is no compelling evidence that it preserves kidney function.

A Daily Hospital Progress Note that Increases Physician Usability of the Electronic Health Record by Facilitating a Problem-Oriented Approach to the Patient and Reducing Physician Clerical Burden.

We suggest changes in the electronic health record (EHR) in hospitalized patients to increase EHR usability by optimizing the physician's ability to approach the patient in a problem-oriented fashion and by reducing physician data entry and chart navigation. The framework for these changes is a Physician's Daily Hospital Progress Note organized into 3 sections: Subjective, Objective, and a combined Assessment and Plan section, subdivided by problem titles. The EHR would consolidate information for each problem by: 1) juxtaposing to each problem title relevant medications, key durable results, and limitations; 2) entering in the running lists under Assessment and Plan the most relevant information for that day, including abbreviated versions of relevant reports; and 3) generating a flow sheet in a problem's progress note for any key results tracked daily. To reduce physician EHR navigation, the EHR would place in the Objective section abbreviated versions of notes of other physicians, nurses, and allied health professionals as well as recent orders. The physician would enter only the analysis and plan and new information not included in the EHR. The consolidation of information for each problem would facilitate physician communication at points of transition of care including generation of a problem-oriented discharge summary.

Hydralazine-associated Amenorrhea in a Premenopausal Patient With Chronic Kidney Disease: A Case Report and Review of Literature.

PURPOSE: Several antihypertensive medications have been associated with various forms of sexual dysfunction. We present a case report of a premenopausal patient with hydralazine-associated amenorrhea. METHODS: The Naranjo adverse drug reaction probability scale was used to assess causality. We also performed a literature search on PubMed to find publications that report hydralazine-associated amenorrhea. RESULTS: The Naranjo scale generated a score of 6, suggesting a probable relationship between amenorrhea and hydralazine therapy. No publications associating hydralazine with amenorrhea were identified. IMPLICATIONS: A probable relationship exists between hydralazine and the development of amenorrhea.

A Review of Ferric Pyrophosphate Citrate (Triferic) Use in Hemodialysis Patients.

PURPOSE: The objective of this short review is to evaluate the efficacy of ferric pyrophosphate citrate and to determine its place in therapy based on the current published literature. METHODS: A literature search was conducted and pared down to yield 4 placebo controlled Phase II and III clinically relevant trials. FINDINGS: Ferric pyrophosphate citrate is a new intradialytic iron supplementation product that has been found to reduce the dose of erythropoiesis-stimulating agents and intravenous iron supplementation and to increase serum ferritin concentrations. IMPLICATIONS: This agent may be administered to patients with stage 5 chronic kidney disease receiving hemodialysis as a new iron supplementation option to maintain hemoglobin, transferrin saturation, and ferritin concentrations.

Can Pentoxifylline be used as Adjunct Therapy to ACE Inhibitors and ARBs in Preserving Kidney Function?

PURPOSE: To determine if there is sufficient evidence to recommend the addition of pentoxifylline to standard ACE inhibitor and ARB therapy in chronic kidney disease patients to reduce proteinuria and preserve kidney function.  METHODS: A search of the literature was conducted using the PubMed.gov and ClinicalTrials.gov search engines and the search terms "pentoxifylline renoprotection", "pentoxifylline CKD", and "pentoxifylline nephropathy". RESULTS were limited to studies in human subjects and published in the English language. No date range was specified. Studies focused on the effects of pentoxifylline on drug induced nephropathy were excluded.  RESULTS: Nine relevant articles were retrieved and evaluated. The two main populations studied were patients with chronic kidney disease (CKD) and patients with CKD and comorbid type 2 diabetes. Six of the nine studies reported a significant reduction in proteinuria in pentoxifylline treated patients. Four studies reported a significant change in estimated glomerular filtration rate (eGFR).  CONCLUSION: Addition of pentoxifylline to ACE inhibitor and ARB therapy may improve proteinuria in CKD patients. There is conflicting evidence as to whether pentoxifylline will improve kidney function as measured by eGFR. KEY WORDS: pentoxifylline renoprotection, pentoxifylline CKD , pentoxifylline nephropathy.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Care and outcomes of end-stage kidney disease patients in times of armed conflict: recommendations for action.

BACKGROUND: Conflicts can lead to significant disruption in the care of endstage kidney disease (ESKD) patients. The purpose of this paper is to review the available literature on the care of ESKD patients in times of armed conflict and make recommendations for action. METHOD: A review of all PubMed-published reports between 1965 and 2015 about the care of ESKD patients at the time of conflict. We excluded articles that reported on acute kidney injury and natural disasters. RESULTS: We found a total of 12 reports on dialysis care and/or kidney transplant care from five armed conflicts and resulting refugee crises. These conflicts led to significant shortage of staff and resources and caused several obstacles in providing adequate dialysis to ESKD patients. In one study, the mortality rate of patients on automated peritoneal dialysis was as high as 95%. The kidney transplantation rate decreased in all but one of the reports about kidney transplant care and patients had difficulties securing their immunosuppressive medications. CONCLUSIONS: ESKD patients, especially dialysis patients, comprise a severely vulnerable population during conflicts. Their care can be disrupted and altered leading to a substantial increase in their mortality rate. Efforts to improve their care during conflicts are needed.

A review of sucroferric oxyhydroxide for the treatment of hyperphosphatemia in patients receiving dialysis.

PURPOSE: Sucroferric oxyhydroxide is the newest phosphate binder to receive US Food and Drug Administration approval for patients on dialysis. The purpose of this review is to critically evaluate the studies that have been conducted with this medication and determine where it may fit in the clinician's overall treatment plan for hyperphosphatemia in patients with chronic kidney disease. METHODS: Literature searches were performed in the PubMed database and www.ClinicalTrials.gov using the search terms sucroferric oxyhydroxide, and PA21 phosphate binder. Limits were set to include only clinical trials performed in human subjects. FINDINGS: Four completed clinical trials and 3 ongoing studies were identified. Completed clinical trials included Phase I, Phase II, and Phase III studies that all demonstrated the ability of sucroferric oxyhydroxide to lower serum phosphorus concentrations. One study compared sucroferric oxyhydroxide with sevelamer and reported no statistically significant difference in serum phosphorus-lowering ability. The ongoing trials are evaluating sucroferric oxyhydroxide for long term use, in peritoneal dialysis patients, and compared with calcium-based phosphate binders. IMPLICATIONS: Sucroferric oxyhydroxide is an effective phosphate binder for chronic kidney disease patients receiving hemodialysis and may offer an advantage in terms of pill burden. Gastrointestinal side effects are similar to those of current phosphate binders. Advantages of other phosphate binders (ie, the lipid- and uric acid-lowering abilities of sevelamer) may outweigh the pill burden benefits of sucroferric oxyhydroxide.