REVIEW Evidence-based Guidelines for the Nutritional Management of Adult Kidney Transplant Recipients Maria Chan, BSc (Hons), MNutrDiet, GradDip ExSpSc, AdvAPD,* Aditi Patwardhan, BSc (Hons), MNutrDiet, APD,† Catherine Ryan, B.Pharm MNutrDiet,‡ Paul Trevillian, MBBS, FRACP,§ Steven Chadban, MBBS, FRACP,{ Fidye Westgarth, BSc, MPH, GradDip QI Healthcare,** and Karen Fry, BSc(N&D) Hons, APD†† Objective: The present article summarizes the key recommendations of the evidence-based guidelines developed for the nutritional management of adult kidney transplant recipients. Background and Methods: Nutrition interventions play an important role in preventing and managing common health problems associated with renal transplantation such as obesity, hypertension, diabetes, and cardiovascular disease. Two sets of guidelines were developed by a working group of renal dietitians and nephrologists. They were subject to expert panel review, and public consultation by renal clinicians and consumers before final endorsement by 2 authorities in Australia - Caring for Australasians with Renal Impairment (CARI) and Dietitians Association of Australia (DAA). Protocol and rigor of guideline development were previously described and published in the Journal of Renal Nutrition, 2009. Results and Outcomes: These guidelines address 13 priority topics identified by the renal community and complement each other with different emphasis, from research translation to day to day clinical practice recommendations. The published guidelines are available to the public through web-access of CARI and DAA, and journal publications. Information includes the guidelines themselves with level of evidence stated, grading of recommendations, suggestions for clinical care, search strategy, background and summary of evidence, recommendations of other guidelines, practice recommendations, appendices of useful tools, and suggestions for audits and future research. Conclusions: Two sets of comprehensive evidence-based nutrition guidelines from CARI and DAA are now available to help improve health outcomes of adult kidney transplant recipients. Ó 2011 by the National Kidney Foundation, Inc. All rights reserved. R ENAL TRANSPLANTATION CORRECTS metabolic abnormalities associated with uremia and the side effects of life-saving dialysis therapy. However, transplantation itself and the side effects of immunosuppressive medications introduce a new set of metabolic abnormalities which *Department of Nutrition and Dietetics, The St. George Hospital, New South Wales, Australia. †Department of Nutrition and Dietetics, Royal Prince Alfred Hospital, New South Wales, Australia. ‡Department of Nutrition and Dietetics, John Hunter Hospital, New South Wales, Australia. §Department of Nephrology, John Hunter Hospital, New South Wales, Australia. {Department of Nephrology, Royal Prince Alfred Hospital, New South Wales, Australia. **Greater Metropolitan Clinical Taskforce, New South Wales, Australia. ††Greater Metropolitan Clinical Taskforce, New South Wales, Australia. Institution at which work conducted: Greater Metropolitan Clinical Taskforce (GMCT) which has been renamed the NSW Agency of Clinical Innovation (ACI) in March 2010. Address reprint requests to Maria Chan, BSc (Hons), MNutrDiet, Grad Dip, ExSpSc, Department of Nutrition and Dietetics, The St. George Hospital, Kogarah New South Wales 2217 Australia. E-mail: maria.chan@sesiahs.health.nsw.gov.au Ó 2011 by the National Kidney Foundation, Inc. All rights reserved. 1051-2276/$36.00 doi:10.1053/j.jrn.2010.10.021 Journal of Renal Nutrition, Vol 21, No 1 (January), 2011: pp 47–51 47 48 CHAN ET AL may significantly affect the short-term and longterm health outcomes of patients and graft survival. Common concerns include hypophosphatemia,1 risk of food-borne infection,2 weight gain and obesity,3 hypertension,4 cardiovascular disease,5 diabetes,6 and bone disease.7 Studies also indicated undesirable body mass index or its changes; with either gain or loss having a negative effect on graft survival.8,9 Therefore, comprehensive evidence-based guidelines for the nutritional management of kidney transplant recipients were needed to better manage these issues. A project funded by Greater Metropolitan Clinical Taskforce (GMCT) of New South Wales Health, Australia, was undertaken to meet these needs. Guideline Development Process A multidisciplinary steering committee, including nephrologists, practicing and project renal dietitians, a network manager from GMCT and a consumer representative (a kidney transplant recipient), was formed to undertake the systematic review of the previously published data, consult with key stakeholders, and formulate the guidelines document for endorsement by Caring for Australasians with Renal Impairment (CARI) and Dietitians Association of Australia (DAA). Protocols and processes of guideline development were previously elsewhere.10,11 described and published Guidelines Developed and Publications Two sets of guidelines CARI12,13 and DAA14 were developed, endorsed, published, and are now accessible to clinicians and the public. In addition to the key statements of the guidelines, other information includes level of evidence, grading of recommendations, suggestions for clinical care, search strategies, background and summary of evidence, recommendations of other guidelines, practice recommendations, appendices of useful tools to implement best practice, and suggestions for audits and future research. Table 1 summarizes the level of evidence and grading of recommendations appraised. Key Recommendations of the Guidelines This section presents the key guidelines developed (if levels I and II evidence available) and/or the key suggestions for clinical practice on the basis of the evidence of levels III and IV, when evidence for levels I and II is not available. These may include slight modifications from the statements extracted from the original CARI12,13 and DAA14 guidelines for editorial purposes. Table 1. Guidelines, Level of Evidence and Grading of Recommendations15 Guidelines Guideline Topics Management of: Anemia Diabetes mellitus Dyslipidemia Hypertension Hypophosphatemia Overweight/obesity Nutrition assessment: Anthropometry-BMI Biochemistry Clinical Dietary intake Others-SGA Prevention of: Bone disease Requirements of: Protein Others: Food safety Medication Level of Evidence Grading of Recommendations CARI DAA None Level III-1, IV Level III-1, IV Level III-1, -2 Level III-1, IV Level III-3, IV Expert opinion Expert opinion D and expert opinion C and expert opinion D and expert opinion C and expert opinion U U U U U U U U U U U U Level III None None None Level IV Level I, II Level III-1, 2, IV C Expert opinion Expert opinion Expert opinion D and expert opinion B and expert opinion D and expert opinion U U U U U U U U U None None Expert opinion Expert opinion National Health and Medical Research Council of Australia (NHMRC) standards.15 U U U NUTRITIONAL MANAGEMENT OF ADULT KIDNEY TRANSPLANT Anemia Background Anemia is a risk factor for cardiovascular disease and is reported to be common among kidney transplant recipients. Guidelines No recommendations possible based on Level I or II evidence. Suggestions for Clinical Care All adult kidney transplant recipients should be monitored for anemia. Possible dietary causes of anemia, including iron, folate, and vitamin B12 deficiencies, should be investigated. Bone Disease Background Significant abnormalities of bone remodeling at the time of transplantation are caused by chronic kidney disease and further weakening of bones after transplantation is caused by prednisone, reduced calcium absorption, and hyperparathyroidism. Guidelines (1) Daily supplementation with 0.25 to 0.5 mg calcitriol (1,25-dihydroxyvitamin D) has a beneficial effect on bone mineral density in adult kidney transplant recipients (level I evidence), and (2) Combination treatment with calcium and vitamin D supplementation is more effective in preserving bone mineral density than vitamin D supplementation alone (level II evidence). 49 phase. Obesity and choice of immunosuppressive regimen are known to be the key modifiable risk factors. Guidelines No recommendations possible based on Level I or II evidence. Suggestions for Clinical Care (1) Posttransplant weight gain is strongly associated with the development of diabetes; thus, weight management strategies should be a priority posttransplant, (2) until further research specific to the renal Tx population becomes available, patients should be advised to follow guidelines for the management of type 2 diabetes in the general population. Dyslipidemia Background Approximately 60% of patients developed dyslipidemia after renal transplantation, with positive association observed between cholesterol and atherosclerotic cardiovascular disease. Guidelines No recommendations possible based on Level I or II evidence. Suggestions for Clinical Care The physician treating bone diseases should determine the need for and dosage of medications and supplements aimed at minimizing bone mineral density loss, on the basis of available evidence. Suggestions for Clinical Care (1) A diet rich in wholegrain, low glycemic index, and high fiber carbohydrates, as well as rich sources of vitamin E and monounsaturated fat should be recommended to adult kidney transplant recipients with elevated serum total cholesterol, low density lipoprotein (LDL)-cholesterol, and triglycerides. (2) Kidney transplant recipients with dyslipidemia should be advised to eat a diet which reflects the evidence in line with lipid management guidelines for the general population. Diabetes Mellitus (New-onset Diabetes after Renal Transplantation) Background About 20% of patients develop new-onset diabetes after renal transplantation (NODAT) 1-year posttransplantation. It is a life-long problem and not a temporary aberration driven by high dosage of steroid exposure in the acute post-transplant Food Safety Background Food-borne illness, such as listeria, is recognized as a particular risk for a person whose immune system is compromised, including the kidney transplant recipient. However, little data is available regarding listeria infection rates in the kidney transplant recipient population. 50 CHAN ET AL Guidelines No recommendations possible based on Level I or II evidence. Suggestions for Clinical Care Although there is no evidence to support the use of restrictive low bacteria diets, it is prudent to provide general food safety advice to the recipients of kidney transplant. Hypertension Background Hypertension is common in renal transplant recipients and is a risk factor for cardiovascular diease which is a significant cause of morbidity and mortality in this population. Guidelines No recommendations possible based on Level I or II evidence. Suggestions for Clinical Care (1) Stable hypertensive kidney transplant recipients should be advised to restrict sodium intake to 80 to 100 mmol/day. (2) When overweight or obese, these recipients should be encouraged and supported to reduce their weight. Hypophosphatemia Background Hypophosphatemia is common in both earlyand long-term posttransplant patients. It is associated with a range of complications such as bone disorders osteomalacia and osteodystrophy at various phases posttransplantation. Guidelines No recommendations possible based on Level I or II evidence. Suggestions for Clinical Care Physicians should be aware that phosphate supplementation has the potential to worsen hyperparathyroidism and may mask phosphorus deficiency beyond 3 months post-transplant. Supplementation may be considered if hyperphosphatemia persists despite adequate dietary intake. The serum phosphate level at which supplementation should be considered or the dose of replacement to be given is unclear and need clinical judgment. Medication Reference to DAA guidelines14 is recommended for comprehensive evidence-based practice recommendations. Nutrition Assessment Anthropometry-Body Mass Index, Biochemistry, Clinical, Dietary Reference to DAA guidelines14 is recommended for comprehensive evidence based practice recommendations. Overweight/Obesity Background Weight gain after kidney transplantation is common and the resulting overweight and obesity is associated with serious health complications, poor graft function, and graft survival. Guidelines No recommendations possible based on Level I or II evidence. Suggestions for Clinical Care Kidney transplant recipients should be referred to a dietitian as soon as practicable after transplantation, for written and verbal advice to prevent weight gain. The dietitian should arrange regular follow-up for the overweight kidney transplant recipient as appropriate until the desired weight loss is achieved because obesity is associated with an increased risk of steroid induced diabetes and cardiovascular disease risk factors as well as long-term graft function and poor graft survival. Protein Requirements Background Protein requirements change during various phases post-transplant. In the early transplant phase, higher glucocorticoids doses cause higher protein catabolic rate, thus protein requirements are higher. In later stages, excess protein intake may be undesirable in patients with chronic allograft nephropathy. Guidelines No recommendations possible based on Level I or II evidence. NUTRITIONAL MANAGEMENT OF ADULT KIDNEY TRANSPLANT Suggestions for Clinical Care In the first 4 weeks after transplant, a diet providing at least 1.4 g protein/kg/day body weight might reverse negative nitrogen balance and lead to increased muscle mass in kidney transplant recipients. Restricting dietary protein in kidney transplant recipients with chronic allograft nephropathy or chronic rejection might be beneficial with respect to kidney function; however, the magnitude of the benefit and a safe level of intake are yet to be identified. Further to Evidence Based Clinical Practice Although nutrition-related complications after transplantation are largely related to immunosuppressive medications used, it has been strongly suggested that undesirable body weight and a high level of adipose tissue pre- or at time of transplantation contribute to poor health outcomes posttransplant. Therefore, optimizing body weight and body composition should form part of the routine clinical care for patients on the transplant waiting list. Conclusion These guidelines not only set standards for best practice on the basis of the latest scientific evidence and expert opinion, but also help prioritize treatment, funding for resources such as staffing and research development. Acknowledgments The guidelines in present study were developed under a project funded by the GMCT, New South Wales Health, Australia. The authors thank clinicians and kidney transplant recipients who contributed their time and expertise. The collaboration and endorsement by the guidelines committees of CARI and DAA are appreciated. References 1. Ambuhl PM, Meier D, Wolf B, et al: Metabolic aspects of phosphate replacement therapy for hypophosphatemia after renal 51 transplantation: impact on muscular phosphate content, mineral metabolism, and acid/base homeostasis. Am J Kidney Dis 34: 875-883, 1999 2. Gerba CP, Rose JB, Haas CN: Sensitive populations: who is at the greatest risk? Int J Food Microbiol 30:113-123, 1996 3. Teplan V, Poledne R, Scuck O, et al: Hyperlipidemia and obesity after renal transplantation. Ann Transplant 6:21-23, 2001 4. Kasiske BL, Anjum S, Shah R, et al: Hypertension after kidney transplantation. Am J Kidney Dis 43:1071-1081, 2004 5. Fazelzadeh A, Mehdizadeh AR, Ostovan MA, et al: Predictors of cardiovascular events and associated mortality of kidney transplant recipients. Transplant Proc 38:509-511, 2006 6. Kasiske B, Snyder JJ, Gilbertson D, et al: Diabetes mellitus after kidney transplantation in the United States. Am J Transplant 3:178, 2003 7. Veenstra D, Best J, Hornberger J, et al: Incidence and longterm cost of steroid-related side effects after renal transplantation. Am J Kidney Dis 33:829-839, 1999 8. Chang SH, Coates PT, McDonald SP: Effect of body mass index on outcomes of kidney transplantation. Transplantation 84:981-987, 2007 9. Chang SH, McDonald SP: Post-kidney transplant weight change as marker of poor survival outcomes. Transplantation 85: 1443-1448, 2008 10. Fry K, Chan M: Long term nutritional interventions for adult kidney transplant recipients (protocol). Cochrane Libr 4, 2007 11. Fry K, Patwardhan A, Ryan C, et al: Development of evidence based guidelines for the nutritional management of adult kidney transplant recipients. J Renal Nutr 19:101-104, 2009 12. Chadban S, Chan M, Fry K, et al: Caring for Australasians with Renal Impairment (CARI) guidelines: nutrition guidelines for adult kidney transplant recipients. Nephrology (Suppl 1): S35-S71, 2010 13. Chadban S, Chan M, Fry K, et al: Caring for Australasians with Renal Impairment (CARI) guidelines: nutrition in Kidney Transplant Recipients. Available at: http://www.cari.org.au/ trans_nutrition_published.php. 14. Evidence based practice guidelines for the nutritional management of adult kidney transplant recipients, developed by the New South Wales Renal Services Network, Transplant Working Group, Greater Metropolitan Clinical Taskforce (GMCT). Dietitians Association of Australia web-link. Available at: http://www. daa.asn.au/files/DINER/TransplantNutrition_Guidelines_FINAL_ 090628.pdf. 15. National Health and Medical Research Council: A Guide to the Development, Implementation and Evaluation of Clinical Practice Guidelines. Canberra, ACT: Commonwealth of Australia, 2000