527315
research-article2014
PENXXX10.1177/0148607114527315Journal of Parenteral and Enteral NutritionSteiber
Tutorial
Chronic Kidney Disease: Considerations for Nutrition Interventions Alison L. Steiber, PhD, RDN1
Journal of Parenteral and Enteral Nutrition Volume 38 Number 4 May 2014 418–426 © 2014 American Society for Parenteral and Enteral Nutrition DOI: 10.1177/0148607114527315 jpen.sagepub.com hosted at online.sagepub.com
Abstract Chronic kidney disease (CKD) is highly prevalent and has major health consequences for patients. Caring for patients with CKD requires knowledge of the food supply, renal pathophysiology, and nutrition-related medications used to work synergistically with diet to control the signs and symptoms of the disease. The nutrition care process and International Dietetic and Nutrition Terminology allow for systematic, holistic, quality care of patients with this complex, progressive disease. Nutrition interventions must be designed with the individual patients needs in mind while prioritizing factors with the largest negative impact on health outcomes and mortality risk. New areas of nutrition treatment are emerging that involve a greater focus on micronutrient needs, the microbiome, and vegetarian-style diets. These interventions may improve outcomes by decreasing inflammation, improving energy and protein delivery, and lowering phosphorus, electrolytes, and fluid retention. (JPEN J Parenter Enteral Nutr. 2014;38:418-426)
Keywords adult; life cycle; minerals/trace elements; nutrition; nutrition assessment; vitamins; renal disease; research and diseases
Chronic kidney disease (CKD) is a major public health concern that affects clinicians from all areas of practice. In the 2005– 2008 edition of the National Health and Nutrition Examination Survey (NHANES), the prevalence of CKD in adults was 14.5% compared with diabetes mellitus (DM) at 8.1% and congestive heart failure at 2.4%.1 This prevalence equates into approximately 20 million adults with some degree of CKD, an indication that clinicians in all areas of practice (community/ wellness facilities, ambulatory clinics, community hospitals, and medical centers) are caring for individuals with CKD on a regular basis. The most common etiologies for CKD are diabetes mellitus, hypertension, and glomerular nephritis.2 While obesity is associated with metabolic syndrome and the diagnosis of DM, it is also an independent, contributing factor for CKD. Nutrition care is important for all these conditions and has the potential to greatly improve patient outcomes. Unfortunately, the current evidence-based guidelines for nutrition care in end-stage renal disease from the National Kidney Foundation’s Kidney Dialysis Outcomes Quality Initiative3 were published in 2000 and are potentially outdated. Therefore, the purpose of this tutorial is to provide an overview of relevant renal nutrition, with an emphasis on improving outcomes and touching on new emerging areas such as micronutrient deficiencies, the microbiome, and vegetarian lifestyles.
Nutrition and Renal Disease Pathophysiology CKD is diagnosed in stages (1–5), with stage 1 indicating the very beginning of the disease process and stage 5 being failure
of the organ. The method of determination between stages is done by glomerular filtration rate (GFR), as defined by the National Kidney Foundation Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification: 2002.4 GFR can be measured directly or calculated using validated equations, the most common of which is the modified diet in renal disease equation. Units for GFR are mL/min/m2, and thus body size and blood flow affect the equation results. Historically, serum creatinine was used as a surrogate marker for kidney function. However, more recently, serum creatinine concentration is believed to reflect protein intake and muscle mass and, therefore, should not be used to determine stage of CKD unless GFR is unavailable. Figure 1 outlines the CKD stages, their corresponding GFR, and the prevalence of the US population at each stage. Reduction of GFR in CKD results in the inability to excreted nitrogenous wastes such as urea, p-cresol,5 and creatinine, ultimately leading to an accumulation of these potentially toxic From the 1Academy of Nutrition and Dietetics, Chicago, Illinois. Financial disclosure: None declared. Received for publication December 16, 2013; accepted for publication February 10, 2014. This article originally appeared online on March 17, 2014. Corresponding Author: Alison L. Steiber, PhD, RDN, Research, International, and Scientific Affairs, Academy of Nutrition and Dietetics, 120 South Riverside Plaza, Suite 2000, Chicago, IL 60606, USA. Email: [email protected]
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Stage 1: 3.1% (GFR 130-90)
Stage 2: 4.1% (GFR 90-60)
Stage 3: 7.6% (GFR 30-60)
Stage 4 & 5 : 0.5% (4 = GFR 30-15 5 = GFR < 15)
Figure 1. Prevalence of chronic kidney disease by stage and glomerular filtration rate (GFR) range.1
metabolites in the serum, a condition called uremia. Patients with CKD are progressively uremic, have multiple comorbidities, and are on numerous medications, all of which result in alterations in metabolism. Uremic symptoms affect dietary intake due to anorexia, nausea, and fatigue, as evidenced by the spontaneous decline of energy and protein as the disease progresses.6 Uremia can affect absorption of nutrients due to changes in the CKD patient’s gut microbiome, as evidenced by altered, short-chain fatty acid concentrations5 and reduced serum vitamin K,7,8 and influence the utilization of nutrients, as evidenced by altered fatty acid9 and amino acid10 profiles in the plasma of patients with CKD. Major kidney function changes resulting from organ failure are as follows: •• reduced or lack of excretion of fluid, toxins, hydrogen ions, phosphorus, and electrolytes such as potassium, and •• reduced production of hormones such as 1,25-dihydroxyvitamin D3, renin, and erythropoietin. These changes result in multiple, undesirable consequences that affect the patient’s nutrition status. Table 1 outlines some key negative consequences, and while this list is not exhaustive, it is representative of important areas for assessment and consideration by the healthcare team and particularly the dietitian.
CKD and Energy Expenditure In addition to specific nutrient or physiologic changes that occur in CKD, progression can also affect the overall metabolic rate and thus total body metabolism. During the
progression of CKD, metabolic changes have been detected in energy expenditure (EE),11 glucose and insulin metabolism,12 protein metabolism,10 and lipid metabolism.9 The generic measurement of EE in patients with CKD has been done in a number of studies using different methodologies (direct and indirect calorimetry); however, the gold standard in EE measurement is rapidly becoming doubly labeled water (DLW). The advantages of DLW are that it measures total EE, is noninvasive, and reflects actual total EE under normal living conditions. A challenge in using this method is the need for urine collection at specific days after isotope ingestion. In patients with CKD who are producing little to no urine, it would be difficult to measure total EE using DLW. It is possible that the dialysate from hemodialysis might be collected and assessed for isotope concentration; however, this has not been validated. While both DC and IC are achievable in patients at all stages of CKD, this method does not account for physical activity throughout the day. It has been shown by Avesani and colleagues13 that patients with CKD are more sedentary than patients without renal disease; thus, the use of typical activity factors may not be appropriate with this population. To date, no EE equations have been validated in the CKD population. Given the possible alterations in overall metabolism, specific substrate metabolism, hormones, fluid, electrolytes, vitamins, and minerals, it should be no surprise that nutrition care in patients with CKD is vital for optimal outcomes.
Nutrition Care at All Stages Similar to nutrition care in other populations, nutrition care in renal disease should follow the nutrition care process (NCP) and include use of the Academy of Nutrition and Dietetics’s standardized language, International Dietetic and Nutrition Terminology (IDNT), at each step (Figure 2a,b). The NCP includes 4 steps: assessment, diagnosis of a nutrition-related problem, intervention, and monitoring and evaluation; each step in the NCP is vital to achievement of optimal patient outcomes. For example, without a complete assessment, including determination of a nutrition diagnosis and potential etiologies, an appropriate nutrition prescription cannot be developed. Furthermore, without monitoring and evaluation, resolution of the nutrition diagnosis cannot be determined. A simple example of this is shown in Figure 2b. It is important that, whenever possible, tools validated in the CKD population be used for assessment. Examples of this are the Subjective Global Assessment (SGA) and the Malnutrition Inflammation Score (MIS), both of which have been validated by numerous studies14-16 in the CKD population. SGA is an assessment tool for determining malnutrition or protein-energy wasting through the examination of 6 key areas: weight, appetite, gastrointestinal (GI) issues, functional ability, metabolic status, and a physical examination to determine muscle and fat wasting.17 The MIS is based on the SGA but has body mass index (BMI) and serum albumin added to the key
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Journal of Parenteral and Enteral Nutrition 38(4)
Table 1. Nutrition Parameter Overview. Consequences of Kidney Disease
Physiologic Response
Uremia
Anorexia
Metabolic acidosis Hyperkalemia Hypervolemia
Increased protein catabolism Increased muscle contraction Edema/ascites
Anemia
Decreased oxygen transport
Hyperphosphatemia
Inhibited 1-α hydroxylase and lower calcium threshold of PTH
Outcome
Assessment Parameters
Malnutrition and increased mortality Muscle wasting Cardiac/respiratory failure Hypertension and increased cardiac output Shortness of breath, fatigue, poor quality of life Secondary hyperparathyroidism
Serum urea nitrogen, dietary intake, SGA Bicarbonate Serum potassium Physical examination for fluid retention Hemoglobin, hematocrit, total iron binding capacity, serum iron Serum phosphorus, PTH, calcium
PTH, parathyroid hormone; SGA, Subjective Global Assessment.
Figure 2. (a) Nutrition care process. (b) Example patient. BMI, body mass index; SGA, Subjective Global Assessment.
areas and is quantitative vs subjective in nature.18 Presence of malnutrition, as diagnosed by either the SGA or the MIS, has been shown to predict poor clinical outcomes and increased mortality rates in patients with CKD.15,16 Serum albumin is an important assessment parameter; however, it is difficult to interpret since many conditions influence its concentration (eg, fluid status, inflammation). Many studies have shown that serum albumin predicts mortality risk. However, in a seminal study on dialysis patients by de Mutsert et al,15 when both SGA and serum albumin were included in a predictive model for mortality, serum albumin was no longer a significant predictor. It is possible that when predicting mortality risk, serum albumin is a good biomarker; however, for diagnosis of malnutrition, SGA and MIS are the parameters with the best evidence. Some clinicians may choose to use both SGA as a diagnostic tool and serum albumin as a predictive tool for morbidity. In CKD, assessment must go far beyond malnutrition; it must also include parameters that span all aspects of nutrition,
such as intake and status of protein, potassium, phosphorus, sodium, fat (saturated vs unsaturated), and, for individuals with metabolic syndrome or DM, carbohydrates. Clinical examples of this are outlined in Table 2. Nutrition diagnosis for patients is driven by the dietitians’ clinical judgment. Patients with CKD can have multiple nutrition diagnoses simultaneously. However, the dietitian needs to prioritize these diagnoses in a way that is useful and has the best impact on patient outcomes. For example, a dietitian conducts a nutrition assessment on an 85-year-old female patient and discovers that due to uremic side effects (loss of appetite and nausea), the patient has been consuming 80%),47 it can still affect serum phosphorus concentrations in patients with limited urine output. Food manufacturers are also using inorganic phosphate in foods already high in both protein and organic phosphorus; a fast-food chicken sandwich45 is an example of this. The management of phosphorus (organic and inorganic) with optimal protein intake by stage of CKD requires a specialist with knowledge of current research, the food supply, and renal physiology. For example, a dietitian caring for a patient with stage 4 CKD completes a 24-hour recall, reviews laboratory values, and does an SGA on the patient as part of the initial nutrition assessment. Results of the assessment are a low-protein, highprocessed-food diet; elevated serum phosphorus and parathyroid hormone; decreased serum albumin; and an SGA score of 3. The patient has (1) malnutrition (NI-5.2) related to inadequate protein intake, as evidenced by low protein intake and an SGA score of 3, and has excessive mineral intake (phosphorus, NI-5.10) related to a high-processed-food diet, as evidenced by elevated serum phosphorus concentration. This patient has moderate malnutrition (SGA 3), and thus nutrition support is warranted; however, serum phosphorus is elevated, and thus the nutrition support needs to be low in phosphorus but high in energy to promote anabolism and low (0.6 g/kg) in protein to preserve kidney function and reduce uremia. It is these types of decisions that make working in renal nutrition complex. A recent movement in the field of renal nutrition is vegetarian diets. Vegetarian diets have the benefits of being high in fiber to promote gut health, low in saturated and trans-fats to
Steiber reduce cardiovascular disease, and low in inorganic phosphorus, thus having a low contribution to the phosphorus load. For healthy adults or those in stage 1 or 2 CKD, a review article by Berstein et al48 in 2007 indicates that vegetarian diets may be reno-protective. This review examined vegetarian diets and kidney function and concluded that (1) there were a limited number of studies in this area; (2) in people with normal kidney function, there are dynamic changes in GFR after consumption of high animal protein but not with vegetable protein, which indicates less renal damage with vegetable protein; (3) substituting vegetable protein or fish may protect against proteinuria; and finally (4) long-term consumption of highprotein diets in healthy persons may cause renal injury. As the first point indicates, there are few studies on this topic, and thus the conclusions should be taken with caution. Furthermore, a study published in 2003 by Knight et al49 involving 1624 women concluded high protein intake was not associated with kidney function loss in women without kidney disease. Rather, it was associated with accelerated loss in women with early CKD. In 3 small clinical trials, the impact of vegetarian diets has been investigated. Barsotti et al50 conducted a 2-arm clinical trial involving patients with stage 3 and 4 CKD. Eleven patients went from an unrestricted protein diet to a specialized vegetarian diet, while the other group went from a conventional lowprotein diet to the same specialized vegetarian diet. During the specialized vegetarian diet (mean [SD] length of follow-up time, 13.4 [5.4] months), body weight, serum total protein, serum albumin, and transferrin all maintained or increased. In another study by Wu et al,51 19 vegetarian hemodialysis patients were compared with 300 nonvegetarian patients. There were no significant differences in serum albumin or prealbumin, and serum phosphorus and parathyroid hormone were significantly lower in the vegetarian group. Finally, in an elegant crossover study by Moe et al,52 8 hemodialysis patients were on a meat-based diet or a vegetarian diet for 1 week, had a 2- to 4-week washout period, and then crossed over to the opposite diet. Similar to the Wu et al51 study, plasma phosphorus was significantly lower while patients were on the vegetarian diet (mean [SD] serum phosphorus 3.7 [0.6] after meat-based diet vs 3.2 [0.5] after vegetarian dirt, P = .02). In addition, a marker sensitive to phosphorus metabolism changes, FG23, was significantly lower in the vegetarian group. In aggregate, these studies show that vegetarian diets are safe and possibly beneficial for patients with CKD, regardless of stage.
Dietitian Factor A challenge to patients is access to a qualified dietitian. Patients are seen by internists, family practice physicians, and, in some cases, nephrologists or cardiologists. Unfortunately, not all physician groups recommend dietitian services for patients prior to dialysis initiation. This was documented in a recent report by the Centers for Medicare & Medicaid Services,
425 which stated only 3% of patients initiating dialysis treatment had been seen by a dietitian for a year prior to dialysis initiation.53 Significantly, adult patients who had been cared for by a dietitian had a 19% lower mortality rate than those who had not been cared for by a dietitian.53 The results reported by Slinin et al53 seem to indicate that nutrition treatment in early stages of CKD prolongs life; however, this has not been tested by a prospective randomized clinical trial. While access to hemodialysis patients is less of a challenge in the United States, the patient-to-dietitian ratio is often not optimal due to limited resources. Similar to the predialysis population, a secondary analysis of data from the Dialysis Outcomes and Practice Patterns Study reported that hemodialysis patients cared for by a dietitian were 15% less likely to have low serum albumin concentrations and were 13% less likely to be cachectic.54 In conclusion, nutrition care of patients with CKD at all stages is vital. Care involves assessment of multiple factors, diagnosis of numerous nutrition problems that need to be prioritized for optimal care, and the synergy of interventions, which can result in improved short- and long-term outcomes.
References 1. O’Seaghdha CM, Lyass A, Massaro JM, et al. A risk score for chronic kidney disease in the general population. Am J Med. 2012;125(3):270-277. 2. USRDS 2013 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2013:215-228. 3. K/DOQI, National Kidney Foundation. Clinical practice guidelines for nutrition in chronic renal failure. Am J Kidney Dis. 2000;35(6)(suppl 2):S1-S140. 4. Goolsby MJ. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. J Am Acad Nurse Pract. 2002;14(6):238-242. 5. Schepers E, Glorieux G, Vanholder R. The gut: the forgotten organ in uremia? Blood Purification. 2010;29(2):130-136. 6. Kopple JD, Greene T, Chumlea WC, et al. Relationship between nutritional status and the glomerular filtration rate: results from the MDRD study. Kidney Int. 2000;57(4):1688-1703. 7. Holden RM, Morton AR, Garland JS, et al. Vitamins K and D status in stages 3-5 chronic kidney disease. Clin J Am Soc Nephrol. 2010;5(4):590-597. 8. Schlieper G, Westenfeld R, Kruger T, et al. Circulating nonphosphorylated carboxylated matrix gla protein predicts survival in ESRD. J Am Soc Nephrol. 2011;22(2):387-395. 9. Samuelsson O, Attman PO, Knight-Gibson C, et al. Lipoprotein abnormalities without hyperlipidaemia in moderate renal insufficiency. Nephrol Dial Transplant. 1994;9(11):1580-1585. 10. Castellino P, Luzi L, Giordano M, et al. Effects of insulin and amino acids on glucose and leucine metabolism in CAPD patients. J Am Soc Nephrol. 1999;10(5):1050-1058. 11. Kuhlmann U, Schwickardi M, Trebst R, et al. Resting metabolic rate in chronic renal failure. J Ren Nutr. 2001;11(4):202-206. 12. Ricanati ES, Tserng KY, Kalhan SC. Glucose metabolism in chronic renal failure: adaptive responses to continuous glucose infusion. Kidney Int Suppl. 1983;16:S121-S127. 13. Avesani CM, Trolonge S, Deleaval P, et al. Physical activity and energy expenditure in haemodialysis patients: an international survey. Nephrol Dial Transplant. 2012;27(6):2430-2434. 14. Steiber A, Leon JB, Secker D, et al. Multicenter study of the validity and reliability of subjective global assessment in the hemodialysis population. J Ren Nutr. 2007;17(5):336-342.
426 15. de Mutsert R, Grootendorst DC, Boeschoten EW, et al. Subjective global assessment of nutritional status is strongly associated with mortality in chronic dialysis patients. Am J Clin Nutr. 2009;89(3):787-793. 16. Rambod M, Bross R, Zitterkoph J, et al. Association of MalnutritionInflammation Score with quality of life and mortality in hemodialysis patients: a 5-year prospective cohort study. Am J Kidney Dis. 2009;53(2):298-309. 17. Detsky AS, McLaughlin JR, Baker JP, et al. What is subjective global assessment of nutritional status? JPEN J Parenter Enteral Nutr. 1987;11(1):8-13. 18. Kalantar-Zadeh K, Kleiner M, Dunne E, et al. A modified quantitative subjective global assessment of nutrition for dialysis patients. Nephrol Dial Transplant. 1999;14(7):1732-1738. 19. Lo JC, Go AS, Chandra M, et al. GFR, body mass index, and low highdensity lipoprotein concentration in adults with and without CKD. Am J Kidney Dis. 2007;50(4):552-558. 20. Go AS, Chertow GM, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351(13):1296-1305. 21. Spiegel DM, Raggi P, Smits G, et al. Factors associated with mortality in patients new to haemodialysis. Nephrol Dial Transplant. 2007;22(12):3568-3572. 22. Fouque D, Kalantar-Zadeh K, Kopple J, et al. A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease. Kidney Int. 2008;73(4):391-398. 23. White JV, Guenter P, Jensen G, et al. Consensus statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition). J Acad Nutr Diet. 2012;112(5):730-738. 24. Krane V, Wanner C. Statins, inflammation and kidney disease. Nat Rev Nephrol. 2011;7(7):385-397. 25. Tripepi G, Mattace Raso F, Sijbrands E, et al. Inflammation and asymmetric dimethylarginine for predicting death and cardiovascular events in ESRD patients. Clin J Am Soc Nephrol. 2011;6(7):1714-1721. 26. Stenvinkel P, Barany P, Chung SH, et al. A comparative analysis of nutritional parameters as predictors of outcome in male and female ESRD patients. Nephrol Dial Transplant. 2002;17(7):1266-1274. 27. Ikizler TA. Nutrition support for the chronically wasted or acutely catabolic chronic kidney disease patient. Semin Nephrol. 2009;29(1):75-84. 28. Kalantar-Zadeh K, Cano NJ, Budde K, et al. Diets and enteral supplements for improving outcomes in chronic kidney disease. Nat Rev Nephrol. 2011;7(7):369-384. 29. Kovesdy CP, Anderson JE, Kalantar-Zadeh K. Association of serum bicarbonate levels with mortality in patients with non–dialysis-dependent CKD. Nephrol Dial Transplant. 2009;24(4):1232-1237. 30. de Brito-Ashurst I, Varagunam M, Raftery MJ, et al. Bicarbonate supplementation slows progression of CKD and improves nutritional status. J Am Soc Nephrol. 2009;20(9):2075-2084. 31. Svensson M, Schmidt EB, Jorgensen KA, et al. N-3 fatty acids as secondary prevention against cardiovascular events in patients who undergo chronic hemodialysis: a randomized, placebo-controlled intervention trial. Clin J Am Soc Nephrol. 2006;1(4):780-786. 32. Noori N, Dukkipati R, Kovesdy CP, et al. Dietary omega-3 fatty acid, ratio of omega-6 to omega-3 intake, inflammation, and survival in long-term hemodialysis patients. Am J Kidney Dis. 2011;58(2):248-256. 33. Salehi M, Sohrabi Z, Ekramzadeh M, et al. Selenium supplementation improves the nutritional status of hemodialysis patients: a randomized, double-blind, placebo-controlled trial. Nephrol Dial Transplant. 2013;28(3):716-723.
Journal of Parenteral and Enteral Nutrition 38(4) 34. Guo CH, Chen PC, Hsu GS, et al. Zinc supplementation alters plasma aluminum and selenium status of patients undergoing dialysis: a pilot study. Nutrients. 2013;5(4):1456-1470. 35. Deved V, Poyah P, James MT, et al. Ascorbic acid for anemia management in hemodialysis patients: a systematic review and meta-analysis. Am J Kidney Dis. 2009;54(6):1089-1097. 36. Zhang K, Liu L, Cheng X, et al. Low levels of vitamin C in dialysis patients is associated with decreased prealbumin and increased C-reactive protein. BMC Nephrol. 2011;12:18. 37. Obermayr RP, Temml C, Gutjahr G, et al. Body mass index modifies the risk of cardiovascular death in proteinuric chronic kidney disease. Nephrol Dial Transplantation. 2009;24(8):2421-2428. 38. MacLaughlin HL, Cook SA, Kariyawasam D, et al. Nonrandomized trial of weight loss with orlistat, nutrition education, diet, and exercise in obese patients with CKD: 2-year follow-up. Am J Kidney Dis. 2010;55(1):69-76. 39. Kopple JD, Mercurio K, Blumenkrantz MJ, et al. Daily requirement for pyridoxine supplements in chronic renal failure. Kidney Int. 1981;19(5):694-704. 40. Walter P, Hornig DH, Moser U, et al. Functions of Vitamins Beyond Recommended Dietary Allowances. Basel, Switzerland: Karger; 2001. 41. Steiber AL, Kopple JD. Vitamin status and needs for people with stages 3-5 chronic kidney disease. J Ren Nutr. 2011;21(5):355-368. 42. Andreucci VE, Fissell RB, Bragg-Gresham JL, et al. Dialysis Outcomes and Practice Patterns Study (DOPPS) data on medications in hemodialysis patients. Am J Kidney Dis. 2004;44(5)(suppl 2):61-67. 43. Block GA. Therapeutic interventions for chronic kidney disease-mineral and bone disorders: focus on mortality. Curr Opin Nephrol Hypertens. 2011;20(4):376-381. 44. Sullivan CM, Leon JB, Sehgal AR. Phosphorus-containing food additives and the accuracy of nutrient databases: implications for renal patients. J Ren Nutr. 2007;17(5):350-354. 45. Sarathy S, Sullivan C, Leon JB, et al. Fast food, phosphorus-containing additives, and the renal diet. J Ren Nutr. 2008;18(5):466-470. 46. Leon JB, Sullivan CM, Sehgal AR. The prevalence of phosphorus-containing food additives in top-selling foods in grocery stores. J Ren Nutr. 2013;23(4):265-270 e262. 47. Cupisti A, Kalantar-Zadeh K. Management of natural and added dietary phosphorus burden in kidney disease. Semin Nephrol. 2013;33(2): 180-190. 48. Bernstein AM, Treyzon L, Li Z. Are high-protein, vegetable-based diets safe for kidney function? A review of the literature. J Am Diet Assoc. 2007;107(4):644-650. 49. Knight EL, Stampfer MJ, Hankinson SE, et al. The impact of protein intake on renal function decline in women with normal renal function or mild renal insufficiency. Ann Intern Med. 2003;138(6):460-467. 50. Barsotti G, Morelli E, Cupisti A, et al. A low-nitrogen low-phosphorus Vegan diet for patients with chronic renal failure. Nephron. 1996;74(2):390-394. 51. Wu TT, Chang CY, Hsu WM, et al. Nutritional status of vegetarians on maintenance haemodialysis. Nephrology (Carlton). 2011;16(6):582-587. 52. Moe SM, Zidehsarai MP, Chambers MA, et al. Vegetarian compared with meat dietary protein source and phosphorus homeostasis in chronic kidney disease. Clin J Am Soc Nephrol. 2011;6(2):257-264. 53. Slinin Y, Guo H, Gilbertson DT, et al. Prehemodialysis care by dietitians and first-year mortality after initiation of hemodialysis. Am J Kidney Dis. 2011;58(4):583-590. 54. Lopes AA, Bragg-Gresham JL, Elder SJ, et al. Independent and joint associations of nutritional status indicators with mortality risk among chronic hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS). J Ren Nutr. 2010;20(4):224-234.
research-article2014
PENXXX10.1177/0148607114527315Journal of Parenteral and Enteral NutritionSteiber
Tutorial
Chronic Kidney Disease: Considerations for Nutrition Interventions Alison L. Steiber, PhD, RDN1
Journal of Parenteral and Enteral Nutrition Volume 38 Number 4 May 2014 418–426 © 2014 American Society for Parenteral and Enteral Nutrition DOI: 10.1177/0148607114527315 jpen.sagepub.com hosted at online.sagepub.com
Abstract Chronic kidney disease (CKD) is highly prevalent and has major health consequences for patients. Caring for patients with CKD requires knowledge of the food supply, renal pathophysiology, and nutrition-related medications used to work synergistically with diet to control the signs and symptoms of the disease. The nutrition care process and International Dietetic and Nutrition Terminology allow for systematic, holistic, quality care of patients with this complex, progressive disease. Nutrition interventions must be designed with the individual patients needs in mind while prioritizing factors with the largest negative impact on health outcomes and mortality risk. New areas of nutrition treatment are emerging that involve a greater focus on micronutrient needs, the microbiome, and vegetarian-style diets. These interventions may improve outcomes by decreasing inflammation, improving energy and protein delivery, and lowering phosphorus, electrolytes, and fluid retention. (JPEN J Parenter Enteral Nutr. 2014;38:418-426)
Keywords adult; life cycle; minerals/trace elements; nutrition; nutrition assessment; vitamins; renal disease; research and diseases
Chronic kidney disease (CKD) is a major public health concern that affects clinicians from all areas of practice. In the 2005– 2008 edition of the National Health and Nutrition Examination Survey (NHANES), the prevalence of CKD in adults was 14.5% compared with diabetes mellitus (DM) at 8.1% and congestive heart failure at 2.4%.1 This prevalence equates into approximately 20 million adults with some degree of CKD, an indication that clinicians in all areas of practice (community/ wellness facilities, ambulatory clinics, community hospitals, and medical centers) are caring for individuals with CKD on a regular basis. The most common etiologies for CKD are diabetes mellitus, hypertension, and glomerular nephritis.2 While obesity is associated with metabolic syndrome and the diagnosis of DM, it is also an independent, contributing factor for CKD. Nutrition care is important for all these conditions and has the potential to greatly improve patient outcomes. Unfortunately, the current evidence-based guidelines for nutrition care in end-stage renal disease from the National Kidney Foundation’s Kidney Dialysis Outcomes Quality Initiative3 were published in 2000 and are potentially outdated. Therefore, the purpose of this tutorial is to provide an overview of relevant renal nutrition, with an emphasis on improving outcomes and touching on new emerging areas such as micronutrient deficiencies, the microbiome, and vegetarian lifestyles.
Nutrition and Renal Disease Pathophysiology CKD is diagnosed in stages (1–5), with stage 1 indicating the very beginning of the disease process and stage 5 being failure
of the organ. The method of determination between stages is done by glomerular filtration rate (GFR), as defined by the National Kidney Foundation Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification: 2002.4 GFR can be measured directly or calculated using validated equations, the most common of which is the modified diet in renal disease equation. Units for GFR are mL/min/m2, and thus body size and blood flow affect the equation results. Historically, serum creatinine was used as a surrogate marker for kidney function. However, more recently, serum creatinine concentration is believed to reflect protein intake and muscle mass and, therefore, should not be used to determine stage of CKD unless GFR is unavailable. Figure 1 outlines the CKD stages, their corresponding GFR, and the prevalence of the US population at each stage. Reduction of GFR in CKD results in the inability to excreted nitrogenous wastes such as urea, p-cresol,5 and creatinine, ultimately leading to an accumulation of these potentially toxic From the 1Academy of Nutrition and Dietetics, Chicago, Illinois. Financial disclosure: None declared. Received for publication December 16, 2013; accepted for publication February 10, 2014. This article originally appeared online on March 17, 2014. Corresponding Author: Alison L. Steiber, PhD, RDN, Research, International, and Scientific Affairs, Academy of Nutrition and Dietetics, 120 South Riverside Plaza, Suite 2000, Chicago, IL 60606, USA. Email: [email protected]
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Stage 1: 3.1% (GFR 130-90)
Stage 2: 4.1% (GFR 90-60)
Stage 3: 7.6% (GFR 30-60)
Stage 4 & 5 : 0.5% (4 = GFR 30-15 5 = GFR < 15)
Figure 1. Prevalence of chronic kidney disease by stage and glomerular filtration rate (GFR) range.1
metabolites in the serum, a condition called uremia. Patients with CKD are progressively uremic, have multiple comorbidities, and are on numerous medications, all of which result in alterations in metabolism. Uremic symptoms affect dietary intake due to anorexia, nausea, and fatigue, as evidenced by the spontaneous decline of energy and protein as the disease progresses.6 Uremia can affect absorption of nutrients due to changes in the CKD patient’s gut microbiome, as evidenced by altered, short-chain fatty acid concentrations5 and reduced serum vitamin K,7,8 and influence the utilization of nutrients, as evidenced by altered fatty acid9 and amino acid10 profiles in the plasma of patients with CKD. Major kidney function changes resulting from organ failure are as follows: •• reduced or lack of excretion of fluid, toxins, hydrogen ions, phosphorus, and electrolytes such as potassium, and •• reduced production of hormones such as 1,25-dihydroxyvitamin D3, renin, and erythropoietin. These changes result in multiple, undesirable consequences that affect the patient’s nutrition status. Table 1 outlines some key negative consequences, and while this list is not exhaustive, it is representative of important areas for assessment and consideration by the healthcare team and particularly the dietitian.
CKD and Energy Expenditure In addition to specific nutrient or physiologic changes that occur in CKD, progression can also affect the overall metabolic rate and thus total body metabolism. During the
progression of CKD, metabolic changes have been detected in energy expenditure (EE),11 glucose and insulin metabolism,12 protein metabolism,10 and lipid metabolism.9 The generic measurement of EE in patients with CKD has been done in a number of studies using different methodologies (direct and indirect calorimetry); however, the gold standard in EE measurement is rapidly becoming doubly labeled water (DLW). The advantages of DLW are that it measures total EE, is noninvasive, and reflects actual total EE under normal living conditions. A challenge in using this method is the need for urine collection at specific days after isotope ingestion. In patients with CKD who are producing little to no urine, it would be difficult to measure total EE using DLW. It is possible that the dialysate from hemodialysis might be collected and assessed for isotope concentration; however, this has not been validated. While both DC and IC are achievable in patients at all stages of CKD, this method does not account for physical activity throughout the day. It has been shown by Avesani and colleagues13 that patients with CKD are more sedentary than patients without renal disease; thus, the use of typical activity factors may not be appropriate with this population. To date, no EE equations have been validated in the CKD population. Given the possible alterations in overall metabolism, specific substrate metabolism, hormones, fluid, electrolytes, vitamins, and minerals, it should be no surprise that nutrition care in patients with CKD is vital for optimal outcomes.
Nutrition Care at All Stages Similar to nutrition care in other populations, nutrition care in renal disease should follow the nutrition care process (NCP) and include use of the Academy of Nutrition and Dietetics’s standardized language, International Dietetic and Nutrition Terminology (IDNT), at each step (Figure 2a,b). The NCP includes 4 steps: assessment, diagnosis of a nutrition-related problem, intervention, and monitoring and evaluation; each step in the NCP is vital to achievement of optimal patient outcomes. For example, without a complete assessment, including determination of a nutrition diagnosis and potential etiologies, an appropriate nutrition prescription cannot be developed. Furthermore, without monitoring and evaluation, resolution of the nutrition diagnosis cannot be determined. A simple example of this is shown in Figure 2b. It is important that, whenever possible, tools validated in the CKD population be used for assessment. Examples of this are the Subjective Global Assessment (SGA) and the Malnutrition Inflammation Score (MIS), both of which have been validated by numerous studies14-16 in the CKD population. SGA is an assessment tool for determining malnutrition or protein-energy wasting through the examination of 6 key areas: weight, appetite, gastrointestinal (GI) issues, functional ability, metabolic status, and a physical examination to determine muscle and fat wasting.17 The MIS is based on the SGA but has body mass index (BMI) and serum albumin added to the key
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Journal of Parenteral and Enteral Nutrition 38(4)
Table 1. Nutrition Parameter Overview. Consequences of Kidney Disease
Physiologic Response
Uremia
Anorexia
Metabolic acidosis Hyperkalemia Hypervolemia
Increased protein catabolism Increased muscle contraction Edema/ascites
Anemia
Decreased oxygen transport
Hyperphosphatemia
Inhibited 1-α hydroxylase and lower calcium threshold of PTH
Outcome
Assessment Parameters
Malnutrition and increased mortality Muscle wasting Cardiac/respiratory failure Hypertension and increased cardiac output Shortness of breath, fatigue, poor quality of life Secondary hyperparathyroidism
Serum urea nitrogen, dietary intake, SGA Bicarbonate Serum potassium Physical examination for fluid retention Hemoglobin, hematocrit, total iron binding capacity, serum iron Serum phosphorus, PTH, calcium
PTH, parathyroid hormone; SGA, Subjective Global Assessment.
Figure 2. (a) Nutrition care process. (b) Example patient. BMI, body mass index; SGA, Subjective Global Assessment.
areas and is quantitative vs subjective in nature.18 Presence of malnutrition, as diagnosed by either the SGA or the MIS, has been shown to predict poor clinical outcomes and increased mortality rates in patients with CKD.15,16 Serum albumin is an important assessment parameter; however, it is difficult to interpret since many conditions influence its concentration (eg, fluid status, inflammation). Many studies have shown that serum albumin predicts mortality risk. However, in a seminal study on dialysis patients by de Mutsert et al,15 when both SGA and serum albumin were included in a predictive model for mortality, serum albumin was no longer a significant predictor. It is possible that when predicting mortality risk, serum albumin is a good biomarker; however, for diagnosis of malnutrition, SGA and MIS are the parameters with the best evidence. Some clinicians may choose to use both SGA as a diagnostic tool and serum albumin as a predictive tool for morbidity. In CKD, assessment must go far beyond malnutrition; it must also include parameters that span all aspects of nutrition,
such as intake and status of protein, potassium, phosphorus, sodium, fat (saturated vs unsaturated), and, for individuals with metabolic syndrome or DM, carbohydrates. Clinical examples of this are outlined in Table 2. Nutrition diagnosis for patients is driven by the dietitians’ clinical judgment. Patients with CKD can have multiple nutrition diagnoses simultaneously. However, the dietitian needs to prioritize these diagnoses in a way that is useful and has the best impact on patient outcomes. For example, a dietitian conducts a nutrition assessment on an 85-year-old female patient and discovers that due to uremic side effects (loss of appetite and nausea), the patient has been consuming 80%),47 it can still affect serum phosphorus concentrations in patients with limited urine output. Food manufacturers are also using inorganic phosphate in foods already high in both protein and organic phosphorus; a fast-food chicken sandwich45 is an example of this. The management of phosphorus (organic and inorganic) with optimal protein intake by stage of CKD requires a specialist with knowledge of current research, the food supply, and renal physiology. For example, a dietitian caring for a patient with stage 4 CKD completes a 24-hour recall, reviews laboratory values, and does an SGA on the patient as part of the initial nutrition assessment. Results of the assessment are a low-protein, highprocessed-food diet; elevated serum phosphorus and parathyroid hormone; decreased serum albumin; and an SGA score of 3. The patient has (1) malnutrition (NI-5.2) related to inadequate protein intake, as evidenced by low protein intake and an SGA score of 3, and has excessive mineral intake (phosphorus, NI-5.10) related to a high-processed-food diet, as evidenced by elevated serum phosphorus concentration. This patient has moderate malnutrition (SGA 3), and thus nutrition support is warranted; however, serum phosphorus is elevated, and thus the nutrition support needs to be low in phosphorus but high in energy to promote anabolism and low (0.6 g/kg) in protein to preserve kidney function and reduce uremia. It is these types of decisions that make working in renal nutrition complex. A recent movement in the field of renal nutrition is vegetarian diets. Vegetarian diets have the benefits of being high in fiber to promote gut health, low in saturated and trans-fats to
Steiber reduce cardiovascular disease, and low in inorganic phosphorus, thus having a low contribution to the phosphorus load. For healthy adults or those in stage 1 or 2 CKD, a review article by Berstein et al48 in 2007 indicates that vegetarian diets may be reno-protective. This review examined vegetarian diets and kidney function and concluded that (1) there were a limited number of studies in this area; (2) in people with normal kidney function, there are dynamic changes in GFR after consumption of high animal protein but not with vegetable protein, which indicates less renal damage with vegetable protein; (3) substituting vegetable protein or fish may protect against proteinuria; and finally (4) long-term consumption of highprotein diets in healthy persons may cause renal injury. As the first point indicates, there are few studies on this topic, and thus the conclusions should be taken with caution. Furthermore, a study published in 2003 by Knight et al49 involving 1624 women concluded high protein intake was not associated with kidney function loss in women without kidney disease. Rather, it was associated with accelerated loss in women with early CKD. In 3 small clinical trials, the impact of vegetarian diets has been investigated. Barsotti et al50 conducted a 2-arm clinical trial involving patients with stage 3 and 4 CKD. Eleven patients went from an unrestricted protein diet to a specialized vegetarian diet, while the other group went from a conventional lowprotein diet to the same specialized vegetarian diet. During the specialized vegetarian diet (mean [SD] length of follow-up time, 13.4 [5.4] months), body weight, serum total protein, serum albumin, and transferrin all maintained or increased. In another study by Wu et al,51 19 vegetarian hemodialysis patients were compared with 300 nonvegetarian patients. There were no significant differences in serum albumin or prealbumin, and serum phosphorus and parathyroid hormone were significantly lower in the vegetarian group. Finally, in an elegant crossover study by Moe et al,52 8 hemodialysis patients were on a meat-based diet or a vegetarian diet for 1 week, had a 2- to 4-week washout period, and then crossed over to the opposite diet. Similar to the Wu et al51 study, plasma phosphorus was significantly lower while patients were on the vegetarian diet (mean [SD] serum phosphorus 3.7 [0.6] after meat-based diet vs 3.2 [0.5] after vegetarian dirt, P = .02). In addition, a marker sensitive to phosphorus metabolism changes, FG23, was significantly lower in the vegetarian group. In aggregate, these studies show that vegetarian diets are safe and possibly beneficial for patients with CKD, regardless of stage.
Dietitian Factor A challenge to patients is access to a qualified dietitian. Patients are seen by internists, family practice physicians, and, in some cases, nephrologists or cardiologists. Unfortunately, not all physician groups recommend dietitian services for patients prior to dialysis initiation. This was documented in a recent report by the Centers for Medicare & Medicaid Services,
425 which stated only 3% of patients initiating dialysis treatment had been seen by a dietitian for a year prior to dialysis initiation.53 Significantly, adult patients who had been cared for by a dietitian had a 19% lower mortality rate than those who had not been cared for by a dietitian.53 The results reported by Slinin et al53 seem to indicate that nutrition treatment in early stages of CKD prolongs life; however, this has not been tested by a prospective randomized clinical trial. While access to hemodialysis patients is less of a challenge in the United States, the patient-to-dietitian ratio is often not optimal due to limited resources. Similar to the predialysis population, a secondary analysis of data from the Dialysis Outcomes and Practice Patterns Study reported that hemodialysis patients cared for by a dietitian were 15% less likely to have low serum albumin concentrations and were 13% less likely to be cachectic.54 In conclusion, nutrition care of patients with CKD at all stages is vital. Care involves assessment of multiple factors, diagnosis of numerous nutrition problems that need to be prioritized for optimal care, and the synergy of interventions, which can result in improved short- and long-term outcomes.
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