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Managing End-Stage Renal Disease: An Alphabetized Mnemonic Strategy
The Journal for Nurse Practitioners 15 (2019) 732e736
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Managing End-Stage Renal Disease: An Alphabetized Mnemonic Strategy Mohamed Toufic El Hussein, PhD, ACNP, Lauren Kilfoil a b s t r a c t Keywords: anemia CKD-MBD ESRD GERD hyperkalemia mnemonics
End-stage renal disease (ESRD) is a complex condition that requires knowledge and expertise for its effective management. Nurse practitioners continuously strive to provide adequate and safe care based on rigorous research. The objective of this article is to provide a structured and applicable approach to managing ESRD that is up-to-date and evidence based. To achieve this objective, we created an alphabetized mnemonic and synthesized our discussion to address Anemia, Bone health, Cardiovascular issues, vitamin D deficiency, Electrolytes imbalances, Fluid overload, and Gastroesophageal reflux in patients with ESRD. © 2019 Elsevier Inc. All rights reserved.
Mnemonics have been described as a form of working memory used to encode information for ease of recall.1 The differences in recall and cognition between individuals with extensive training in memory strategies through the use of mnemonics, described as memory sport athletes, and a control group with no experience in memory training through mnemonic strategies were assessed in a randomized controlled trial conducted by Dresler et al in Europe.2 Memory athletes, compared with a control group with no training in memory skills, had significantly superior skills in encoding and recalling of information with the use of mnemonic learning strategies. With the implementation of a mnemonic training program, a group of nonemnemonic-trained control participants showed significant improvements in memory skills, including encoding and recall of information. In this article, we examine the clinical implications of prolonged renal damage, ultimately resulting in end-stage renal disease (ESRD). An alphabetized mnemonic from A to G, including Anemia, Bone health, Cardiovascular issues, vitamin D deficiency, Electrolytes imbalances, Fluid overload, and Gastroesophageal reflux disease, is proposed as an organizational and recall tool for nurse practitioners (NPs) to help guide in the identification and management of systemic complications associated with ESRD based on best evidence.
loss of regenerative capacity within the kidney, resulting in the inevitable apoptosis of tubular epithelial cells.3 Diagnosis Chronic kidney disease (CKD) is first diagnosed with a glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 alone or paired with the presence of diagnostic markers of kidney damage for a period of at least 3 continuous months.3 ESRD is reached when the GFR decreases to 15 mL/min/1.73 m2 and renal function is no longer able to meet the physiological demand. The Mnemonic Anemia Under normal conditions, the kidneys aid in the process of homeostasis by producing erythropoietin, a hormone responsible for signaling the production of red blood cells within the bone marrow. Erythropoietin production is impaired in patients with failing kidneys, as seen in ESRD, resulting in the development of anemia.4 Erythropoiesis also relies on iron stores throughout the body, which are often depleted in CKD because of blood loss, infection, and inflammation, among other causes, as well as decreases in systemic iron absorption and release.5
Pathophysiology With sustained intrinsic renal damage from chronic hypertension and diabetes mellitus, the release of proinflammatory and growth factors inhibits successful recovery of the renal interstitium and leads to renal fibrosis.3 As renal fibrosis progresses, there is a https://doi.org/10.1016/j.nurpra.2019.07.014 1555-4155/© 2019 Elsevier Inc. All rights reserved.
Diagnosis Anemia in adults with ESRD is diagnosed when serum hemoglobin (Hb) concentration falls below 13.0 g/dL in men and below 12.0 g/dL in women.6 In children, anemia is diagnosed when Hb falls below 11 g/dL in ages 0.5 to 5 years, < 11.5 g/dL in ages 5 to
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12 years, and < 12.0 g/dL in ages 12 to 15.6 The Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend monthly routine testing of Hb levels in patients with ESRD.6 In addition to monitoring serum Hb concentrations, the NP should have consideration for related tests including a complete blood count, absolute reticulocyte count, serum ferritin, and serum transferrin saturation. Iron Therapy In the patient not on dialysis, the NP should prescribe 500 to 1,000 mg iron orally and monitor for efficacy or intolerance.7 For the patient on dialysis, a weekly intravenous dose of 50 to 60 mg/ wk is recommended. If Hb levels do not reach target range within a 3-month period with oral treatment, an intravenous route is recommended for patients who are not on dialysis. Fishbane et al8 conducted a randomized, double-blind, 16-week trial in the United States comparing the effects of oral ferric citrate versus control in patients with nonedialysis-dependent CKD and iron deficiency (N ¼ 234). With a starting dose of 1-g tablets of ferric citrate or matching placebo 3 times daily, the treatment group achieved a greater increase in serum Hb concentrations, transferrin saturation, and ferritin compared with the control group over the treatment period. Fishbane et al established that a starting dose of 1 g ferric citrate is a safe and effective method of treating anemia in ESRD and recommended titrating its dosage in order to maintain a Hb concentration greater than 1 g/dL above the patient’s baseline. Erythropoiesis-Stimulating Agents Before the initiation of erythropoiesis-stimulating agents (ESAs) in the management of anemia in CKD, the NP should prescribe oral or intravenous iron therapy. If anemia persists because of a lack of response to iron supplementation, ESA therapy may be required in order to correct anemia. Recent evidence notes that irregularities in plasma Hb levels because of ESAs may increase the risk of cardiac events.9 According to the American Management of Chronic Kidney Disease Working Group clinical practice guidelines, ESA therapy should not be initiated at serum Hb levels higher than 10 g/dL.10 The NP should titrate the dose of ESA in order to achieve a target Hb range of 10 to 12 g/dL and should ensure that serum Hb levels do not increase at a rate surpassing 1 to 2 g/dL/mo.7 Adjuvant Therapies According to KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease, the use of vitamin D or other forms of adjuvant ESA treatment (eg, androgens, vitamin C, vitamin E, folic acid, and L-carnitine) in the management of anemia is not recommended.6 In a recent randomized controlled trial conducted in the US (N ¼ 252), ergocalciferol supplementation was tested against a placebo control in order to evaluate its effect in reducing the required ESA dose among vitamin Dedeficient hemodialysis patients over a 6-month period. It was determined that although ergocalciferol administration increased serum 25-hydroxy vitamin D (calcifediol) levels, it had no effect on epoetin use or secondary biochemical and clinical outcomes.11 Bone Health Patients diagnosed with ESRD are at an increased risk of chronic kidney disease mineral and bone disorder (CKD-MBD), a diagnosis that includes a variety of disorders including irregular bone turnover and vascular calcification.12 The development of CKD-MBD is associated with alterations in the contributing factors of homeostatic mineral metabolism, including fibroblast growth factor,13 followed by an increase in parathyroid hormone, a decrease in vitamin D levels, and hypocalcemia and hyperphosphatemia.12,14
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These metabolic alterations ultimately impact bone microarchitecture and function.15 Diagnosis A diagnosis of CKD-MBD relies on bone biopsy and dual-energy X-ray absorptiometry in order to determine bone quality and density, respectively,15 as well as fracture risk.14 Upon diagnostic imaging, patients with advanced CKD will likely present with irregularities including porosity and thinning of compact bone, osteomalacia, and alterations in bone turnover.15 Treatment of Bone Bone biopsy aids in distinguishing between high and low turnover disorders.14 Current KDIGO guidelines in the US recommend screening of ESRD patients through bone biopsy in order to determine the degree of pathology and the type of renal osteodystrophy before the initiation of treatment.14 The use of antiresorptive agents, bisphosphonates, and osteoanabolic agents among patients with ESRD lacks conclusive evidence,14 and each method of treatment requires identification of underlying bone pathology before initiation.12,15 Management of Minerals Parathyroid Hormone. In patients with serum parathyroid concentrations consistently above the normal limit, KDIGO guidelines recommend assessing factors including hyperphosphatemia, hypocalcemia, and low-serum vitamin D concentration.14 In the management of secondary hyperparathyroidism in ESRD, Block et al16 evaluated the efficacy of 2 calcimimetics, intravenous etelcalcetide and oral cinacalcet, compared with placebo controls over a 26-week period in patients undergoing hemodialysis at 164 sites in the US, Canada, Europe, Russia and New Zealand (N ¼ 683).16 Hyperparathyroidism was determined as a predialysis serum concentration > 500 pg/mL. With a mean dose of 15.0 mg/ d etelcalcetide, the treatment group (52.4%) achieved a 50% reduction in serum parathyroid hormone concentration, whereas 40.2% of the cinacalcet treatment group with a median dose of 51.4 mg/d experienced a 50% reduction from baseline parathyroid hormone concentrations. In the management of hyperparathyroidism in ESRD, a daily dose of 15.0 mg etelcalcetide is considered an effective and safe treatment option.16 Vitamin D. Vitamin D deficiency is diagnosed when serum concentration falls below 30 ng/mL.11 American guidelines recommend the use of low-dose vitamin D analogs in instances of persistent and severe hyperphosphatemia and titrating the dose according to patient response while avoiding hypercalcemia.14 Calcium. In order to maintain homeostatic serum calcium levels in ESRD, KDIGO guidelines recommend that dietary calcium intake be limited to 800 to 1,000 mg/d.14 Additionally, in patients with ESRD undergoing dialysis, it is recommended that the NP prescribes dialysate with a calcium concentration between 1.25 mmol/L and 1.50 mmol/L.14 Phosphate. In the management of mineral and bone disorders in ESRD, the National Institute for Health and Care Excellence guidelines recommend that serum phosphate be maintained between 0.9 and 1.5 mmol/L, whereas patients undergoing dialysis maintain a serum concentration of 1.1 and 1.7 mmol/L.17 US guidelines recommend the use of nonecalcium-based phosphate binders,14 specifically the use of sevelamer hydrochloride to manage hyperphosphatemia.17 The NP should prescribe 800 mg sevelamer hydrochloride 3 times daily with meals in patients with ESRD experiencing hyperphosphatemia.
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Cardiovascular Issues ESRD is associated with cardiovascular implications, specifically because of an increased risk of atherosclerosis.10,18 In a controlled trial, Liu et al19 investigated the association between inflammation and the degree of vascular calcification in patients with ESRD in China (N ¼ 48). Patient groups were determined based on plasma C-reactive protein levels, with the control group’s levels < 8.0 mg/L (n ¼ 25) and the inflammation group’s levels > 8.0 mg/L (n ¼ 23). Liu et al determined that patients diagnosed with ESRD who had elevated inflammation experienced increased calcium deposition in radial arteries compared with the control (P < .001). Liu et al concluded that inflammation commonly seen in patients with ESRD, specifically elevated plasma CRP levels, is a risk factor for the development of atherosclerosis. Statin Therapy Although previous KDIGO guidelines do not support the use of statins in patients on hemodialysis, the American Heart Association has recently established a potential benefit of using statins in these patients.20 Both the KDIGO guidelines and the American Heart Association recommend the use of statins in all patients with nonedialysis-dependent CKD in the pre-ESRD stage. Antiplatelet Therapy Although patients with a reduced GFR (< 30 mL/min) are considered to be at an increased risk for bleeding in a seminal study conducted in the US, Berger et al21 concluded that the use of aspirin therapy was associated with a 50% relative reduction in mortality in those receiving dialysis (P < .001). Renin-Angiotensin-Aldosterone System Inhibitors In patients with ESRD experiencing hypertension and albuminuria, the initiation of angiotensin-converting enzyme inhibitors or angiotensin II receptor blocker therapy is advised with a dose titrated to maintain blood pressure in the ideal range of below 140/ 90 mm Hg.10 However, the use of a combination of 2 reninangiotensin-aldosterone system therapies should be avoided.10,22 Additionally, current National Institute for Health and Care Excellence guidelines recommend avoiding the administration of reninangiotensin-aldosterone system therapy in patients with serum potassium concentrations exceeding 5.0 mmol/L.22 Vitamin D Deficiency The production of vitamin D, or cholecalciferol, occurs in the proximal tubules of the kidneys.23 Once hydroxylated in the liver, the activated vitamin D circulates and plays an essential role in maintaining calcium and phosphorus homeostasis. In the failing kidney, as seen in ESRD, the production of vitamin D decreases. Nutritional Supplementation In a 3-arm, double-blind, randomized controlled trial, Bhan et al24 evaluated the efficacy of nutritional supplementation of vitamin D in the management of 25-hydroxy vitamin D deficiency in patients undergoing long-term dialysis in the US (N ¼ 105). Two treatment groups receiving a low-dose (5,000 IU monthly) and a high-dose (50,000 IU 4 times weekly) of ergocalciferol over a 12week period were compared with a placebo-controlled group. Over a 12-week study period, a high dose of ergocalciferol yielded the best results in achieving a serum vitamin D concentration of > 32 ng/mL. In the management of vitamin deficiency in ESRD, the US Management of Chronic Kidney Disease Working Group guidelines recommend the use of supplemental vitamin D,10 and Bhan et al specifically concluded that a weekly 4-time dose of 50,000 IU
ergocalciferol is a safe and effective treatment for vitamin D deficiency in ESRD. Active Vitamin D Analogs In a prospective, randomized, double-blind trial in the US, Kendrick et al25 evaluated the efficacy of active vitamin D supplementation (calcitriol) versus dietary supplementation (cholecalciferol) in reaching a primary end point of changes in vascular functioning and a secondary end point of changes in vitamin Delinked biochemical markers among patients with an estimated GFR between 15 and 44 mL/1.73 m2 (N ¼ 128) over a 6-month study period. The calcitriol treatment group was given a preliminary daily dose of 0.25 mg, with the dose increasing to 0.5 mg after 1 month. The cholecalciferol treatment group received a loading dose of 4,000 IU daily for 1 month followed by a 2,000 IU daily maintenance dose for the duration of the study. In both groups, there was no statistically significant impact of brachial artery flowemediated dilation; however, the calcitriol treatment group experienced a significant decrease in serum parathyroid hormone levels compared with the cholecalciferol group. In order to manage alterations in bone health, the NP should offer a daily low 0.25-mg dose of calcitriol and increased the dose to 0.5 mg after 1 month. Dietary Management In managing altered metabolism and excretion in ESRD, the NP should have special consideration for diet. Protein. In order to preserve the estimated GFR and minimize proteinuria, the US guidelines recommend the implementation of a low protein diet, ranging between 0.6 and 0.8 g/kg/d.10 Phosphorus. Patients should be advised to follow a low phosphorus diet, paying special attention to foods with phosphorus additives, in order to maintain a serum phosphorus level within the target range (2.5-4.5 mg/dL).10,14,26 Restricting dietary phosphorus to a daily intake of 800 to 1,000 mg reduces the risk of the development of hyperphosphatemia.27 Electrolyte Imbalance Because of alterations in renal clearance, managing electrolyte imbalance is an essential aspect of ESRD treatment. In maintaining electrolyte balance, special consideration must be taken regarding serum potassium levels. Metabolic Acidosis Metabolic acidosis is a common disorder associated with ESRD because metabolically produced acids accumulate because of impaired renal excretion. In the management of metabolic acidosis in ESRD, guidelines from the Management of Chronic Kidney Disease Working Group in the US recommend the use of sodium bicarbonate.10 According to the National Institute for Health and Care Excellence guidelines, the use of sodium bicarbonate is indicated in patients with a GFR below 30 mL/min/1.73 m2 in addition to a serum bicarbonate level below 20 mmol/L.22 Dosing and frequency should be titrated in order to maintain a serum bicarbonate concentration slightly above 20 mmol/L.28 Management of Hyperkalemia As kidney function declines, the capacity for Kþ excretion decreases because of the loss of nephron mass and Kþ secretion in collecting ducts.29 Through compensatory mechanisms, the decompensating kidneys are able to maintain serum potassium levels within the ideal range of < 5.5 mEq/L until glomerular filtration decreases to < 15 mL/min. In a retrospective cohort study
M.T. El Hussein, L. Kilfoil / The Journal for Nurse Practitioners 15 (2019) 732e736
conducted by Pun et al30 in the US (N ¼ 6181), they studied the association between elevated serum potassium levels and the risk of cardiac events in predialysis patients with CKD and coronary artery disease. It was determined that patients experiencing hyperkalemia (> 5.0 mmol/L) were twice as likely to experience sudden cardiac arrest, indicating the urgent need to maintain serum potassium balance in these patients. The management of hyperkalemia in ESRD involves reduced dietary intake, diuretic therapy, and the establishment of an effective Kþ concentration gradient through a low Kþ dialysate solution.29 Because of the increased risk of potassium imbalance with the use of an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker, the US Management of Chronic Kidney Disease Working Group guidelines recommend reducing the dose or terminating angiotensin-converting enzyme/angiotensin receptor blocker therapy if serum potassium exceeds the upper normal limit.10 The National Kidney Foundation recommends a systematic approach in the treatment of hyperkalemia in CKD that starts with the administration of 6.8 mmol calcium, corresponding to 10 mL CaCl (10%) or 30 mL calcium gluconate (10%) solutions, to prevent cardiac arrest by stabilizing the cardiac membrane potential.31 Although the administration of calcium does not affect the serum levels of potassium, its effect is seen on the normalization of electrocardiographic changes. Attempts to redistribute serum potassium by shifting it inside the cells are done concurrently with stabilization of cardiac membrane potential. Redistribution is done by either administering 50 to 100 mmol sodium bicarbonate intravenously or 10 U regular insulin intravenously with 50 g glucose. The redistribution of potassium can also be achieved through the use of 10 to 20 mg aerosol (nebulized) or 0.5 mg in 100 mL 5% dextrose in water (intravenous). Although redistribution of serum potassium temporarily helps in neutralizing the impact of hyperkalemia on the heart, the excretion of potassium must be addressed by administering loop diuretics such as 40 mg furosemide intravenously. Higher doses of loop diuretics are used in patients with advanced CKD. Fludrocortisone acetate 0.1 mg (up to 0.4-1.0 mg daily) orally can also be used to help with the excretion of potassium, especially in patients with aldosterone deficiency. The NP should be cautious about the use of cation exchange resins such as sodium polystyrene sulfonate 25 to 50 g to excrete potassium via the gastrointestinal track to decrease the potential of causing intestinal necrosis. Finally, dialysis should be considered if the aforementioned interventions were unsuccessful or if the patient’s condition required rapid correction of potassium levels.31 Diet The NP should advise patients to adhere to dietary modifications in order to manage electrolyte imbalance caused by impaired renal excretion. Current guidelines recommend a daily sodium intake of < 2,000 mg32 and a potassium intake of 2500 mg/d in patients with ESRD.33
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Diagnosis Parameters for the diagnosis of fluid overload were defined as a relative fluid overload of > 15% in men and > 13% in women.33 In an observational study of patients with stage 4 and 5 CKD (N ¼ 478) conducted in Taiwan, it was determined that increasing fluid status by a factor of 1% increased the risk of a cardiovascular event or all-cause mortality by 8%.35 Diuretic Therapy In an observational retrospective study in the US (N ¼ 11,297), Sibbel et al36 determined that among hemodialysis patients, there was a 7% decrease in the risk of all-cause hospitalization in patients who continued loop diuretic therapy throughout dialysis therapy (1.84 admissions per patient per year) compared with the control group (2.10 admissions per patient per year). In fact, current Hypertension Canada guidelines recommend the use of loop diuretics in instances of volume overload in patients with CKD.37 Dialysate In a prospective, randomized, double-blind trial conducted in Canada and Europe (N ¼ 108), Rutkowski et al38 evaluated differences in sodium clearance in dialysate with a standard sodium solution (134 mmol/L) compared with a low-sodium solution (125 mmol/L) over a 6-month period. It was determined that the lowsodium solution yielded a higher mean daily sodium excretion and a subsequent reduction in blood pressure. Gastroesophageal Reflux Disease Gastroesophageal reflux disease (GERD) occurs as acidic gastric secretions enter into the esophagus, most frequently because of alterations of the lower esophageal sphincter.39 Symptoms of gastroesophageal reflux disease often present as heartburn, noncardiac chest pain, and regurgitation.40 Treatment In a cross-sectional/cohort study in Japan (N ¼ 385), Namikoshi et al41 determined that among patients receiving maintenance hemodialysis, there was a 10.6% prevalence rate of GERD symptoms. Among these patients, it was determined that GERD symptoms influenced quality of life. In order to enhance quality of life and ease discomfort associated with the symptoms of gastroesophageal reflux disease in patients with ESRD undergoing dialysis, the NP should collaborate with patients to develop an individualized treatment plan. Conclusion Through the use of a mnemonic strategy specific to ESRD, the NP will have the ability to apply best evidence to clinical practice and decision making. In the management of ESRD, there are a multitude of systemic factors that influence patient outcomes. The implementation of a mnemonic tool offers ease of recall and organization, ultimately aiding the NP in recognizing, preventing, and treating the systematic degradation associated with ESRD.
Fluid Overload References Among patients with ESRD with renal clearance of < 15 mL/min, there is a risk of fluid overload when left untreated. In fact, in a recent multinational observational cohort study of patients with ESRD receiving hemodialysis therapy (N ¼ 39,566), those with chronic exposure to fluid overload had a significantly higher risk of mortality than a nonoverhydrated group over a 1-year study period.34
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25. Kendrick J, Andrews E, You Z, et al. Cholecalciferol, calcitriol, and vascular function in CKD: a randomized, double blind trial. Clin J Am Soc Nephrol. 2017;12:1438-1446. https://doi.org/10.2215/CJN.01870217. 26. National Kidney Foundation. Phosphorus and your CKD diet. 2019. https:// www.kidney.org/atoz/content/phosphorus. Accessed June 15, 2019. 27. St-Jules DE, Goldfarb DS, Pompeii ML, Sevick MA. Phosphate additive avoidance in chronic kidney disease. Diabetes Spectr. 2017;30(2):101-106. https:// doi.org/10.2337/ds16-0048. 28. Kraut JA, Madias NE. Metabolic acidosis of CKD: an update. Am J Kidney Dis. 2016;67(2):307-317. https://doi.org/10.1053/j.ajkd.2015.08.028. 29. Palmer BF, Clegg DJ. Hyperkalemia across the continuum of kidney function. Clin J Am Soc Nephrol. 2018;13:155-157. https://doi.org/10.2215/ CJN.09340817. 30. Pun PH, Goldstein BA, Gallis JA, Middleton JP, Svetkey LP. Serum potassium levels and risk of sudden cardiac death among patients with chronic kidney disease and significant coronary artery disease. Kidney Int Rep. 2017;2: 1122-1131. https://doi.org/10.1016/j.ekir.2017.07.001. 31. National Kidney Foundation. Best practices in managing hyperkalemia in chronic kidney disease. 2016. 1-7. https://www.kidney.org/sites/default/files/ 02-10-7259%20Hyperkalemia%20Tool.pdf. Accessed June 20, 2019. 32. Kidney Disease Improving Global Outcomes. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3(1):1-150. https://doi.org/10.1038/kisup.2012.73. 33. Vanholder R, Van Laecke S, Glorieux G, Verbeke F, Castillo-Rodriguez E, Ortiz A. Deleting death and dialysis: conservative care of cardio-vascular risk and kidney function loss in chronic kidney disease (CKD). Toxins (Basel). 2018;10(237):1-71. https://doi.org/10.3390/toxins10060237. 34. Zoccali C, Moissl U, Chazot C, et al. Chronic fluid overload and mortality in ESRD. J Am Soc Nephrol. 2017;28:2491-2497. https://doi.org/10.1681/ ASN.2016121341. 35. Tsai Y-C, Chiu Y-W, Tsai J-C, et al. Association of fluid overload with cardiovascular morbidity and all-cause mortality in stages 4 and 5 CKD. Clin J Am Soc Nephrol. 2015;10:39-46. https://doi.org/10.2215/CJN.03610414. 36. Sibbel S, Walker A, Colson C, Tentori F, Brunelli SM, Flythe J. Association of continuation of loop diuretics at hemodialysis initiation with clinical outcomes. Clin J Am Soc Nephrol. 2019;14:95-102. https://doi.org/10.2215/ CJN.05080418. 37. Nerenberg KA, Zarnke KB, Leung AA, et al. Hypertension Canada’s 2018 guidelines for the diagnosis, risk assessment, prevention and treatment of hypertension in adults and children. Can J Cardiol. 2018;34:506-525. https:// doi.org/10.1016/j.cjca.2018.02.022. 38. Rutkowski B, Tam P, van der Sande FM, et al. Low-sodium versus standardsodium peritoneal dialysis solution in hypertensive patients: a randomized controlled trial. Am J Kidney Dis. 2016;67(5):753-761. https://doi.org/10.1053/ j.ajkd.2015.07.031. 39. Tack J, Pandolfino JE. Pathophysiology of gastroesophageal reflux disease. Gastroenterology. 2018;1(53):277-288. https://doi.org/10.1053/j.gastro. 2017.09.047. 40. Katz PO, Gerson LB, Velo MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108:308-328. https://doi.org/10.1038/ajg.2012.444. 41. Namikoshi T, Harada K, Hatta H, et al. Prevalence of gastroesophageal reflux disease symptoms and effects of esomeprazole on the quality of life related to reflux and dyspepsia in patients on maintenance hemodialysis. Clin Exp Nephrol. 2016;20:134-142. https://doi.org/10.1007/s10157-015-1130-2.
Mohamed Toufic El Hussein, PhD, ACNP, is an associate professor at the School of Nursing and Midwifery, Faculty of Health Community and Education, Mount Royal University in Calgary, Alberta, Canada, an acute care nurse practitioner with the Medical Cardiology Coronary Care Unit, Rockyview General Hospital in Calgary, Alberta, Canada and an adjunct associate professor, Faculty of Nursing, University of Calgary, Alberta, Canada. He can be contacted at [email protected]. Lauren Kilfoil is a BSN student at Mount Royal University. In compliance with national ethical guidelines, the authors report no relationships with business or industry that would pose a conflict of interest.
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Managing End-Stage Renal Disease: An Alphabetized Mnemonic Strategy Mohamed Toufic El Hussein, PhD, ACNP, Lauren Kilfoil a b s t r a c t Keywords: anemia CKD-MBD ESRD GERD hyperkalemia mnemonics
End-stage renal disease (ESRD) is a complex condition that requires knowledge and expertise for its effective management. Nurse practitioners continuously strive to provide adequate and safe care based on rigorous research. The objective of this article is to provide a structured and applicable approach to managing ESRD that is up-to-date and evidence based. To achieve this objective, we created an alphabetized mnemonic and synthesized our discussion to address Anemia, Bone health, Cardiovascular issues, vitamin D deficiency, Electrolytes imbalances, Fluid overload, and Gastroesophageal reflux in patients with ESRD. © 2019 Elsevier Inc. All rights reserved.
Mnemonics have been described as a form of working memory used to encode information for ease of recall.1 The differences in recall and cognition between individuals with extensive training in memory strategies through the use of mnemonics, described as memory sport athletes, and a control group with no experience in memory training through mnemonic strategies were assessed in a randomized controlled trial conducted by Dresler et al in Europe.2 Memory athletes, compared with a control group with no training in memory skills, had significantly superior skills in encoding and recalling of information with the use of mnemonic learning strategies. With the implementation of a mnemonic training program, a group of nonemnemonic-trained control participants showed significant improvements in memory skills, including encoding and recall of information. In this article, we examine the clinical implications of prolonged renal damage, ultimately resulting in end-stage renal disease (ESRD). An alphabetized mnemonic from A to G, including Anemia, Bone health, Cardiovascular issues, vitamin D deficiency, Electrolytes imbalances, Fluid overload, and Gastroesophageal reflux disease, is proposed as an organizational and recall tool for nurse practitioners (NPs) to help guide in the identification and management of systemic complications associated with ESRD based on best evidence.
loss of regenerative capacity within the kidney, resulting in the inevitable apoptosis of tubular epithelial cells.3 Diagnosis Chronic kidney disease (CKD) is first diagnosed with a glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 alone or paired with the presence of diagnostic markers of kidney damage for a period of at least 3 continuous months.3 ESRD is reached when the GFR decreases to 15 mL/min/1.73 m2 and renal function is no longer able to meet the physiological demand. The Mnemonic Anemia Under normal conditions, the kidneys aid in the process of homeostasis by producing erythropoietin, a hormone responsible for signaling the production of red blood cells within the bone marrow. Erythropoietin production is impaired in patients with failing kidneys, as seen in ESRD, resulting in the development of anemia.4 Erythropoiesis also relies on iron stores throughout the body, which are often depleted in CKD because of blood loss, infection, and inflammation, among other causes, as well as decreases in systemic iron absorption and release.5
Pathophysiology With sustained intrinsic renal damage from chronic hypertension and diabetes mellitus, the release of proinflammatory and growth factors inhibits successful recovery of the renal interstitium and leads to renal fibrosis.3 As renal fibrosis progresses, there is a https://doi.org/10.1016/j.nurpra.2019.07.014 1555-4155/© 2019 Elsevier Inc. All rights reserved.
Diagnosis Anemia in adults with ESRD is diagnosed when serum hemoglobin (Hb) concentration falls below 13.0 g/dL in men and below 12.0 g/dL in women.6 In children, anemia is diagnosed when Hb falls below 11 g/dL in ages 0.5 to 5 years, < 11.5 g/dL in ages 5 to
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12 years, and < 12.0 g/dL in ages 12 to 15.6 The Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend monthly routine testing of Hb levels in patients with ESRD.6 In addition to monitoring serum Hb concentrations, the NP should have consideration for related tests including a complete blood count, absolute reticulocyte count, serum ferritin, and serum transferrin saturation. Iron Therapy In the patient not on dialysis, the NP should prescribe 500 to 1,000 mg iron orally and monitor for efficacy or intolerance.7 For the patient on dialysis, a weekly intravenous dose of 50 to 60 mg/ wk is recommended. If Hb levels do not reach target range within a 3-month period with oral treatment, an intravenous route is recommended for patients who are not on dialysis. Fishbane et al8 conducted a randomized, double-blind, 16-week trial in the United States comparing the effects of oral ferric citrate versus control in patients with nonedialysis-dependent CKD and iron deficiency (N ¼ 234). With a starting dose of 1-g tablets of ferric citrate or matching placebo 3 times daily, the treatment group achieved a greater increase in serum Hb concentrations, transferrin saturation, and ferritin compared with the control group over the treatment period. Fishbane et al established that a starting dose of 1 g ferric citrate is a safe and effective method of treating anemia in ESRD and recommended titrating its dosage in order to maintain a Hb concentration greater than 1 g/dL above the patient’s baseline. Erythropoiesis-Stimulating Agents Before the initiation of erythropoiesis-stimulating agents (ESAs) in the management of anemia in CKD, the NP should prescribe oral or intravenous iron therapy. If anemia persists because of a lack of response to iron supplementation, ESA therapy may be required in order to correct anemia. Recent evidence notes that irregularities in plasma Hb levels because of ESAs may increase the risk of cardiac events.9 According to the American Management of Chronic Kidney Disease Working Group clinical practice guidelines, ESA therapy should not be initiated at serum Hb levels higher than 10 g/dL.10 The NP should titrate the dose of ESA in order to achieve a target Hb range of 10 to 12 g/dL and should ensure that serum Hb levels do not increase at a rate surpassing 1 to 2 g/dL/mo.7 Adjuvant Therapies According to KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease, the use of vitamin D or other forms of adjuvant ESA treatment (eg, androgens, vitamin C, vitamin E, folic acid, and L-carnitine) in the management of anemia is not recommended.6 In a recent randomized controlled trial conducted in the US (N ¼ 252), ergocalciferol supplementation was tested against a placebo control in order to evaluate its effect in reducing the required ESA dose among vitamin Dedeficient hemodialysis patients over a 6-month period. It was determined that although ergocalciferol administration increased serum 25-hydroxy vitamin D (calcifediol) levels, it had no effect on epoetin use or secondary biochemical and clinical outcomes.11 Bone Health Patients diagnosed with ESRD are at an increased risk of chronic kidney disease mineral and bone disorder (CKD-MBD), a diagnosis that includes a variety of disorders including irregular bone turnover and vascular calcification.12 The development of CKD-MBD is associated with alterations in the contributing factors of homeostatic mineral metabolism, including fibroblast growth factor,13 followed by an increase in parathyroid hormone, a decrease in vitamin D levels, and hypocalcemia and hyperphosphatemia.12,14
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These metabolic alterations ultimately impact bone microarchitecture and function.15 Diagnosis A diagnosis of CKD-MBD relies on bone biopsy and dual-energy X-ray absorptiometry in order to determine bone quality and density, respectively,15 as well as fracture risk.14 Upon diagnostic imaging, patients with advanced CKD will likely present with irregularities including porosity and thinning of compact bone, osteomalacia, and alterations in bone turnover.15 Treatment of Bone Bone biopsy aids in distinguishing between high and low turnover disorders.14 Current KDIGO guidelines in the US recommend screening of ESRD patients through bone biopsy in order to determine the degree of pathology and the type of renal osteodystrophy before the initiation of treatment.14 The use of antiresorptive agents, bisphosphonates, and osteoanabolic agents among patients with ESRD lacks conclusive evidence,14 and each method of treatment requires identification of underlying bone pathology before initiation.12,15 Management of Minerals Parathyroid Hormone. In patients with serum parathyroid concentrations consistently above the normal limit, KDIGO guidelines recommend assessing factors including hyperphosphatemia, hypocalcemia, and low-serum vitamin D concentration.14 In the management of secondary hyperparathyroidism in ESRD, Block et al16 evaluated the efficacy of 2 calcimimetics, intravenous etelcalcetide and oral cinacalcet, compared with placebo controls over a 26-week period in patients undergoing hemodialysis at 164 sites in the US, Canada, Europe, Russia and New Zealand (N ¼ 683).16 Hyperparathyroidism was determined as a predialysis serum concentration > 500 pg/mL. With a mean dose of 15.0 mg/ d etelcalcetide, the treatment group (52.4%) achieved a 50% reduction in serum parathyroid hormone concentration, whereas 40.2% of the cinacalcet treatment group with a median dose of 51.4 mg/d experienced a 50% reduction from baseline parathyroid hormone concentrations. In the management of hyperparathyroidism in ESRD, a daily dose of 15.0 mg etelcalcetide is considered an effective and safe treatment option.16 Vitamin D. Vitamin D deficiency is diagnosed when serum concentration falls below 30 ng/mL.11 American guidelines recommend the use of low-dose vitamin D analogs in instances of persistent and severe hyperphosphatemia and titrating the dose according to patient response while avoiding hypercalcemia.14 Calcium. In order to maintain homeostatic serum calcium levels in ESRD, KDIGO guidelines recommend that dietary calcium intake be limited to 800 to 1,000 mg/d.14 Additionally, in patients with ESRD undergoing dialysis, it is recommended that the NP prescribes dialysate with a calcium concentration between 1.25 mmol/L and 1.50 mmol/L.14 Phosphate. In the management of mineral and bone disorders in ESRD, the National Institute for Health and Care Excellence guidelines recommend that serum phosphate be maintained between 0.9 and 1.5 mmol/L, whereas patients undergoing dialysis maintain a serum concentration of 1.1 and 1.7 mmol/L.17 US guidelines recommend the use of nonecalcium-based phosphate binders,14 specifically the use of sevelamer hydrochloride to manage hyperphosphatemia.17 The NP should prescribe 800 mg sevelamer hydrochloride 3 times daily with meals in patients with ESRD experiencing hyperphosphatemia.
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Cardiovascular Issues ESRD is associated with cardiovascular implications, specifically because of an increased risk of atherosclerosis.10,18 In a controlled trial, Liu et al19 investigated the association between inflammation and the degree of vascular calcification in patients with ESRD in China (N ¼ 48). Patient groups were determined based on plasma C-reactive protein levels, with the control group’s levels < 8.0 mg/L (n ¼ 25) and the inflammation group’s levels > 8.0 mg/L (n ¼ 23). Liu et al determined that patients diagnosed with ESRD who had elevated inflammation experienced increased calcium deposition in radial arteries compared with the control (P < .001). Liu et al concluded that inflammation commonly seen in patients with ESRD, specifically elevated plasma CRP levels, is a risk factor for the development of atherosclerosis. Statin Therapy Although previous KDIGO guidelines do not support the use of statins in patients on hemodialysis, the American Heart Association has recently established a potential benefit of using statins in these patients.20 Both the KDIGO guidelines and the American Heart Association recommend the use of statins in all patients with nonedialysis-dependent CKD in the pre-ESRD stage. Antiplatelet Therapy Although patients with a reduced GFR (< 30 mL/min) are considered to be at an increased risk for bleeding in a seminal study conducted in the US, Berger et al21 concluded that the use of aspirin therapy was associated with a 50% relative reduction in mortality in those receiving dialysis (P < .001). Renin-Angiotensin-Aldosterone System Inhibitors In patients with ESRD experiencing hypertension and albuminuria, the initiation of angiotensin-converting enzyme inhibitors or angiotensin II receptor blocker therapy is advised with a dose titrated to maintain blood pressure in the ideal range of below 140/ 90 mm Hg.10 However, the use of a combination of 2 reninangiotensin-aldosterone system therapies should be avoided.10,22 Additionally, current National Institute for Health and Care Excellence guidelines recommend avoiding the administration of reninangiotensin-aldosterone system therapy in patients with serum potassium concentrations exceeding 5.0 mmol/L.22 Vitamin D Deficiency The production of vitamin D, or cholecalciferol, occurs in the proximal tubules of the kidneys.23 Once hydroxylated in the liver, the activated vitamin D circulates and plays an essential role in maintaining calcium and phosphorus homeostasis. In the failing kidney, as seen in ESRD, the production of vitamin D decreases. Nutritional Supplementation In a 3-arm, double-blind, randomized controlled trial, Bhan et al24 evaluated the efficacy of nutritional supplementation of vitamin D in the management of 25-hydroxy vitamin D deficiency in patients undergoing long-term dialysis in the US (N ¼ 105). Two treatment groups receiving a low-dose (5,000 IU monthly) and a high-dose (50,000 IU 4 times weekly) of ergocalciferol over a 12week period were compared with a placebo-controlled group. Over a 12-week study period, a high dose of ergocalciferol yielded the best results in achieving a serum vitamin D concentration of > 32 ng/mL. In the management of vitamin deficiency in ESRD, the US Management of Chronic Kidney Disease Working Group guidelines recommend the use of supplemental vitamin D,10 and Bhan et al specifically concluded that a weekly 4-time dose of 50,000 IU
ergocalciferol is a safe and effective treatment for vitamin D deficiency in ESRD. Active Vitamin D Analogs In a prospective, randomized, double-blind trial in the US, Kendrick et al25 evaluated the efficacy of active vitamin D supplementation (calcitriol) versus dietary supplementation (cholecalciferol) in reaching a primary end point of changes in vascular functioning and a secondary end point of changes in vitamin Delinked biochemical markers among patients with an estimated GFR between 15 and 44 mL/1.73 m2 (N ¼ 128) over a 6-month study period. The calcitriol treatment group was given a preliminary daily dose of 0.25 mg, with the dose increasing to 0.5 mg after 1 month. The cholecalciferol treatment group received a loading dose of 4,000 IU daily for 1 month followed by a 2,000 IU daily maintenance dose for the duration of the study. In both groups, there was no statistically significant impact of brachial artery flowemediated dilation; however, the calcitriol treatment group experienced a significant decrease in serum parathyroid hormone levels compared with the cholecalciferol group. In order to manage alterations in bone health, the NP should offer a daily low 0.25-mg dose of calcitriol and increased the dose to 0.5 mg after 1 month. Dietary Management In managing altered metabolism and excretion in ESRD, the NP should have special consideration for diet. Protein. In order to preserve the estimated GFR and minimize proteinuria, the US guidelines recommend the implementation of a low protein diet, ranging between 0.6 and 0.8 g/kg/d.10 Phosphorus. Patients should be advised to follow a low phosphorus diet, paying special attention to foods with phosphorus additives, in order to maintain a serum phosphorus level within the target range (2.5-4.5 mg/dL).10,14,26 Restricting dietary phosphorus to a daily intake of 800 to 1,000 mg reduces the risk of the development of hyperphosphatemia.27 Electrolyte Imbalance Because of alterations in renal clearance, managing electrolyte imbalance is an essential aspect of ESRD treatment. In maintaining electrolyte balance, special consideration must be taken regarding serum potassium levels. Metabolic Acidosis Metabolic acidosis is a common disorder associated with ESRD because metabolically produced acids accumulate because of impaired renal excretion. In the management of metabolic acidosis in ESRD, guidelines from the Management of Chronic Kidney Disease Working Group in the US recommend the use of sodium bicarbonate.10 According to the National Institute for Health and Care Excellence guidelines, the use of sodium bicarbonate is indicated in patients with a GFR below 30 mL/min/1.73 m2 in addition to a serum bicarbonate level below 20 mmol/L.22 Dosing and frequency should be titrated in order to maintain a serum bicarbonate concentration slightly above 20 mmol/L.28 Management of Hyperkalemia As kidney function declines, the capacity for Kþ excretion decreases because of the loss of nephron mass and Kþ secretion in collecting ducts.29 Through compensatory mechanisms, the decompensating kidneys are able to maintain serum potassium levels within the ideal range of < 5.5 mEq/L until glomerular filtration decreases to < 15 mL/min. In a retrospective cohort study
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conducted by Pun et al30 in the US (N ¼ 6181), they studied the association between elevated serum potassium levels and the risk of cardiac events in predialysis patients with CKD and coronary artery disease. It was determined that patients experiencing hyperkalemia (> 5.0 mmol/L) were twice as likely to experience sudden cardiac arrest, indicating the urgent need to maintain serum potassium balance in these patients. The management of hyperkalemia in ESRD involves reduced dietary intake, diuretic therapy, and the establishment of an effective Kþ concentration gradient through a low Kþ dialysate solution.29 Because of the increased risk of potassium imbalance with the use of an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker, the US Management of Chronic Kidney Disease Working Group guidelines recommend reducing the dose or terminating angiotensin-converting enzyme/angiotensin receptor blocker therapy if serum potassium exceeds the upper normal limit.10 The National Kidney Foundation recommends a systematic approach in the treatment of hyperkalemia in CKD that starts with the administration of 6.8 mmol calcium, corresponding to 10 mL CaCl (10%) or 30 mL calcium gluconate (10%) solutions, to prevent cardiac arrest by stabilizing the cardiac membrane potential.31 Although the administration of calcium does not affect the serum levels of potassium, its effect is seen on the normalization of electrocardiographic changes. Attempts to redistribute serum potassium by shifting it inside the cells are done concurrently with stabilization of cardiac membrane potential. Redistribution is done by either administering 50 to 100 mmol sodium bicarbonate intravenously or 10 U regular insulin intravenously with 50 g glucose. The redistribution of potassium can also be achieved through the use of 10 to 20 mg aerosol (nebulized) or 0.5 mg in 100 mL 5% dextrose in water (intravenous). Although redistribution of serum potassium temporarily helps in neutralizing the impact of hyperkalemia on the heart, the excretion of potassium must be addressed by administering loop diuretics such as 40 mg furosemide intravenously. Higher doses of loop diuretics are used in patients with advanced CKD. Fludrocortisone acetate 0.1 mg (up to 0.4-1.0 mg daily) orally can also be used to help with the excretion of potassium, especially in patients with aldosterone deficiency. The NP should be cautious about the use of cation exchange resins such as sodium polystyrene sulfonate 25 to 50 g to excrete potassium via the gastrointestinal track to decrease the potential of causing intestinal necrosis. Finally, dialysis should be considered if the aforementioned interventions were unsuccessful or if the patient’s condition required rapid correction of potassium levels.31 Diet The NP should advise patients to adhere to dietary modifications in order to manage electrolyte imbalance caused by impaired renal excretion. Current guidelines recommend a daily sodium intake of < 2,000 mg32 and a potassium intake of 2500 mg/d in patients with ESRD.33
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Diagnosis Parameters for the diagnosis of fluid overload were defined as a relative fluid overload of > 15% in men and > 13% in women.33 In an observational study of patients with stage 4 and 5 CKD (N ¼ 478) conducted in Taiwan, it was determined that increasing fluid status by a factor of 1% increased the risk of a cardiovascular event or all-cause mortality by 8%.35 Diuretic Therapy In an observational retrospective study in the US (N ¼ 11,297), Sibbel et al36 determined that among hemodialysis patients, there was a 7% decrease in the risk of all-cause hospitalization in patients who continued loop diuretic therapy throughout dialysis therapy (1.84 admissions per patient per year) compared with the control group (2.10 admissions per patient per year). In fact, current Hypertension Canada guidelines recommend the use of loop diuretics in instances of volume overload in patients with CKD.37 Dialysate In a prospective, randomized, double-blind trial conducted in Canada and Europe (N ¼ 108), Rutkowski et al38 evaluated differences in sodium clearance in dialysate with a standard sodium solution (134 mmol/L) compared with a low-sodium solution (125 mmol/L) over a 6-month period. It was determined that the lowsodium solution yielded a higher mean daily sodium excretion and a subsequent reduction in blood pressure. Gastroesophageal Reflux Disease Gastroesophageal reflux disease (GERD) occurs as acidic gastric secretions enter into the esophagus, most frequently because of alterations of the lower esophageal sphincter.39 Symptoms of gastroesophageal reflux disease often present as heartburn, noncardiac chest pain, and regurgitation.40 Treatment In a cross-sectional/cohort study in Japan (N ¼ 385), Namikoshi et al41 determined that among patients receiving maintenance hemodialysis, there was a 10.6% prevalence rate of GERD symptoms. Among these patients, it was determined that GERD symptoms influenced quality of life. In order to enhance quality of life and ease discomfort associated with the symptoms of gastroesophageal reflux disease in patients with ESRD undergoing dialysis, the NP should collaborate with patients to develop an individualized treatment plan. Conclusion Through the use of a mnemonic strategy specific to ESRD, the NP will have the ability to apply best evidence to clinical practice and decision making. In the management of ESRD, there are a multitude of systemic factors that influence patient outcomes. The implementation of a mnemonic tool offers ease of recall and organization, ultimately aiding the NP in recognizing, preventing, and treating the systematic degradation associated with ESRD.
Fluid Overload References Among patients with ESRD with renal clearance of < 15 mL/min, there is a risk of fluid overload when left untreated. In fact, in a recent multinational observational cohort study of patients with ESRD receiving hemodialysis therapy (N ¼ 39,566), those with chronic exposure to fluid overload had a significantly higher risk of mortality than a nonoverhydrated group over a 1-year study period.34
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4. Bhandari S, Pereira DI, Chappell HF, Drakesmith H. Intravenous irons: from basic science to clinical practice. Pharmaceuticals. 2018;11(82):1-20. https:// doi.org/10.3390/ph11030082. 5. Fishbane S, Spinowitz B. Update on anemia in ESRD and earlier stages of CKD: Core curriculum 2018. Am J Kidney Dis. 2018;71(3):423-435. https://doi.org/ 10.1053/j.ajkd.2017.09.026. 6. Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. Kidney Int Suppl. 2012;2:279-335. https://doi.org/10.1038/kisup.2012.37. 7. National Institute for Health and Care Excellence. Chronic kidney disease: managing anemia. (NICE guideline NG8). 2015. http://www.nice.org.uk/ guidance/ng8. Accessed June 10, 2019. 8. Fishbane S, Block GA, Loram L, et al. Effects of ferric citrate in patients with nondialysis-dependent CKD and iron deficiency anemia. J Am Soc Nephrol. 2017;28:1851-1858. https://doi.org/10.1681/ASN.2016101053. 9. Pergola PE, Spinowitz BS, Hartman CS, Maroni BJ, Haase VH. Vadadustat, a novel oral HIF stabilizer, provides effective anemia treatment in non-dialysisdependent chronic kidney disease. Kidney Int. 2016;90:1115-1122. https:// doi.org/10.1016/j.kint.2016.07.019. 10. The Management of Chronic Kidney Disease Working Group. Veterans affairs/ Department of defense clinical practice guidelines for the management of chronic kidney disease in primary care. 2014. https://www.healthquality.va. gov/guidelines/CD/ ckd/VADoDCKDCPG2014.pdf. Accessed June 15, 2019. 11. Miskulin DC, Majchrzak K, Tighiouart H, et al. Ergocalciferol supplementation in hemodialysis patients with vitamin D deficiency: a randomized clinical trial. J Am Soc Nephrol. 2016;27(6):1801-1810. 12. Khairallah P, Nickolas T. Updates in CKD-associated osteoporosis. Curr Osteoporosis Rep. 2018;16:712-723. https://doi.org/10.1007/s11914-018-0491-3. 13. Kaludjerovic J, Komaba H, Lanske B. Effects of klotho deletion from bone during chronic kidney disease. Bone. 2017;100:50-55. https://doi.org/10.1016/ j.bone .2017.02.006. 14. Kidney Disease Improving Global Outcomes. KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease- mineral and bone disorder (CKD-MBD). Kidney Int Suppl. 2017;7:1-59. https://doi.org/10.1016/j.kisu.2017.04.001. 15. McNerny EM, Nickolas TL. Bone quality in chronic kidney disease: definitions and diagnostics. Curr Osteoporos Rep. 2017;15:207-213. https://doi.org/ 10.1007/s11914-017-0366-z. 16. Block GA, Bushinsky DA, Cheng S, et al. Effect of etelcalcetide vs cinacalcet on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism: a randomized clinical trial. JAMA. 2017;317(2): 156-164. https://doi.org/10.1001/jama.2016.19468. 17. National Institute for Health and Care Excellence. Chronic kidney disease (stage 4 or 5): management of hyperphosphatemia. (Clinical guideline 157). 2013. https://www.nice.org.uk/guidance/cg157. Accessed June 20, 2019. 18. Viane L, Behets GJ, Heye S, et al. Inflammation and the bone-vascular axis in end stage renal disease. Osteoporos Int. 2016;27:489-497. https://doi.org/ 10.1007/s00198-015-3233-8. 19. Liu J, Zhu W, Jiang CM, et al. Activation of the mTORC1 pathway by inflammation contributes to vascular calcification in patients with end-stage renal disease. J Nephrol. 2019;32:101-110. https://doi.org/10.1007/s40620-0180486-2. 20. Soohoo M, Moradi H, Obi Y, et al. Statin therapy before transition to end-stage renal disease with posttransition outcomes. J Am Heart Assoc. 2019;8(6): e011869. 21. Berger AK, Duval S, Krumholz HM. Aspirin, beta-blocker, and angiotensinconverting enzyme inhibitor therapy in patients with end-stage renal disease and an acute myocardial infarction. J Am Coll Cardiol. 2003;42(2):201-208. 22. National Institute for Health and Care Excellence. Chronic kidney disease in adults: assessment and management. (Clinical guideline 182). 2014. https:// www.nice.org.uk/guidance/cg182/resources/chronic-kidney-disease-in-adultsassessment-and-management-35109809343205. Accessed June 20, 2019. 23. Keung L, Perwad F. Vitamin D and kidney disease. Bone Rep. 2018;9:93-100. https://doi.org/10.1016/j.bonr.2018.07.002. 24. Bhan I, Dobens D, Tamez H, et al. Nutritional vitamin D supplementation in dialysis: a randomized trial. Clin J Am Soc Nephrol. 2015;10:611-619. https:// doi.org/10.2215/CJN.06910714.
25. Kendrick J, Andrews E, You Z, et al. Cholecalciferol, calcitriol, and vascular function in CKD: a randomized, double blind trial. Clin J Am Soc Nephrol. 2017;12:1438-1446. https://doi.org/10.2215/CJN.01870217. 26. National Kidney Foundation. Phosphorus and your CKD diet. 2019. https:// www.kidney.org/atoz/content/phosphorus. Accessed June 15, 2019. 27. St-Jules DE, Goldfarb DS, Pompeii ML, Sevick MA. Phosphate additive avoidance in chronic kidney disease. Diabetes Spectr. 2017;30(2):101-106. https:// doi.org/10.2337/ds16-0048. 28. Kraut JA, Madias NE. Metabolic acidosis of CKD: an update. Am J Kidney Dis. 2016;67(2):307-317. https://doi.org/10.1053/j.ajkd.2015.08.028. 29. Palmer BF, Clegg DJ. Hyperkalemia across the continuum of kidney function. Clin J Am Soc Nephrol. 2018;13:155-157. https://doi.org/10.2215/ CJN.09340817. 30. Pun PH, Goldstein BA, Gallis JA, Middleton JP, Svetkey LP. Serum potassium levels and risk of sudden cardiac death among patients with chronic kidney disease and significant coronary artery disease. Kidney Int Rep. 2017;2: 1122-1131. https://doi.org/10.1016/j.ekir.2017.07.001. 31. National Kidney Foundation. Best practices in managing hyperkalemia in chronic kidney disease. 2016. 1-7. https://www.kidney.org/sites/default/files/ 02-10-7259%20Hyperkalemia%20Tool.pdf. Accessed June 20, 2019. 32. Kidney Disease Improving Global Outcomes. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3(1):1-150. https://doi.org/10.1038/kisup.2012.73. 33. Vanholder R, Van Laecke S, Glorieux G, Verbeke F, Castillo-Rodriguez E, Ortiz A. Deleting death and dialysis: conservative care of cardio-vascular risk and kidney function loss in chronic kidney disease (CKD). Toxins (Basel). 2018;10(237):1-71. https://doi.org/10.3390/toxins10060237. 34. Zoccali C, Moissl U, Chazot C, et al. Chronic fluid overload and mortality in ESRD. J Am Soc Nephrol. 2017;28:2491-2497. https://doi.org/10.1681/ ASN.2016121341. 35. Tsai Y-C, Chiu Y-W, Tsai J-C, et al. Association of fluid overload with cardiovascular morbidity and all-cause mortality in stages 4 and 5 CKD. Clin J Am Soc Nephrol. 2015;10:39-46. https://doi.org/10.2215/CJN.03610414. 36. Sibbel S, Walker A, Colson C, Tentori F, Brunelli SM, Flythe J. Association of continuation of loop diuretics at hemodialysis initiation with clinical outcomes. Clin J Am Soc Nephrol. 2019;14:95-102. https://doi.org/10.2215/ CJN.05080418. 37. Nerenberg KA, Zarnke KB, Leung AA, et al. Hypertension Canada’s 2018 guidelines for the diagnosis, risk assessment, prevention and treatment of hypertension in adults and children. Can J Cardiol. 2018;34:506-525. https:// doi.org/10.1016/j.cjca.2018.02.022. 38. Rutkowski B, Tam P, van der Sande FM, et al. Low-sodium versus standardsodium peritoneal dialysis solution in hypertensive patients: a randomized controlled trial. Am J Kidney Dis. 2016;67(5):753-761. https://doi.org/10.1053/ j.ajkd.2015.07.031. 39. Tack J, Pandolfino JE. Pathophysiology of gastroesophageal reflux disease. Gastroenterology. 2018;1(53):277-288. https://doi.org/10.1053/j.gastro. 2017.09.047. 40. Katz PO, Gerson LB, Velo MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108:308-328. https://doi.org/10.1038/ajg.2012.444. 41. Namikoshi T, Harada K, Hatta H, et al. Prevalence of gastroesophageal reflux disease symptoms and effects of esomeprazole on the quality of life related to reflux and dyspepsia in patients on maintenance hemodialysis. Clin Exp Nephrol. 2016;20:134-142. https://doi.org/10.1007/s10157-015-1130-2.
Mohamed Toufic El Hussein, PhD, ACNP, is an associate professor at the School of Nursing and Midwifery, Faculty of Health Community and Education, Mount Royal University in Calgary, Alberta, Canada, an acute care nurse practitioner with the Medical Cardiology Coronary Care Unit, Rockyview General Hospital in Calgary, Alberta, Canada and an adjunct associate professor, Faculty of Nursing, University of Calgary, Alberta, Canada. He can be contacted at [email protected]. Lauren Kilfoil is a BSN student at Mount Royal University. In compliance with national ethical guidelines, the authors report no relationships with business or industry that would pose a conflict of interest.