- Email: [email protected]
Nutritional Surviellance After Renal Transplant: Review
Indian J Transplant 2009; 3: 5-12
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ARTICLE
Nutritional Surviellance After Renal Transplant : Review Anita Saxena and RK Sharma Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raibareli Road, Lucknow
The recipients of renal transplants experience an improvement in general sense of well being along with marked improvement in appetite and increase in body weight. It is expected that a successfully transplanted kidney would restore near-normal renal function and correct nutritional abnormalities arising from pre-transplant renal insufficiency. What actually happens is that some patients do not attain optimal renal function, while others experience decline in renal function with the passage of time. Hence, many recipients of transplant may require nutritional management as appropriate for patients with chronic renal failure even though these patients do not require dialysis. Furthermore, transplant patients face many nutritional challenges because of metabolic complications of pre-existing medical conditions and as a consequence of transplant related immunosuppression. Hence, evaluation of nutritional status, body composition and resting energy expenditure (REE) is a must in post transplant patients with functioning renal graft and longer survival of the transplanted kidney1-4. Changes in body composition after renal transplantation are due to increased appetite and reversal of the uremic state, as well as immunosuppressive therapy, in particular Address for correspondance:
Prof. R. K. Sharma Head Department of nephrology Sanjay Gandhi Post Graduate Institute of Medical Sciences, Rae Bareli Road, Lucknow 226 014 Email: [email protected]
immediately after surgery. Therefore there are two clearly distinct phases regarding nutritional changes: the early and late post transplant phases. The major nutritional and metabolic problems of the early phase are malnutrition (associated or not associated with systemic inflammation), obesity, lipid abnormalities, glucose intolerance, hyper tension, as well as calcium, phosphorus, and vitamin D imbalance.
Malnutrition Malnutrition during the pre-transplant phase is associated with higher post-transplant morbidity and mortality rates, which are due in part to impaired surgical wound healing and higher risk of infection. Despite increase in weight which is partially attributed to immunosuppression, malnutrition is present in >20% of the post transplant patients5. Malnutrition can best be defined by a body mass index (BMI) <216. 15% of the 452 kidney transplant patients had BMI less than 21 kgm2 which the investigators attributed to malnutrition. Co morbidity and graft failure-two main causes of malnutrition in kidney transplant patients7,8. There is depletion of protein stores at the cellular level after 45 days of transplantation, which normalizes in long term9
Effect of Immuno-suppression on body weight Within two to three weeks a significant increase in body weight is due to high doses of cyclosporine and steroids which cause an increase in total body water (TBW). On an average body weight increases by 14% in men and Copyright © 2009 by The Indian Society of Organ Transplantation
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10% in women when compared with their respective dialytic dry weight. Evaluation of body composition by bioelectrical impedance shows that patients with a renal transplant show a tendency towards higher fat-free mass compared to healthy control. Some authors have found no correlation between cumulative steroid dose and post transplant weight gain. On the contrary, a slight tendency toward weight loss has even been observed8,10 . Lower whole body contents of nitrogen, serum potassium and calcium during first year of transplantation have been reported11 . Significant decreases in serum albumin, transferrin and retinol binding protein levels have been reported in the first year posttransplant12. Lean body mass of 115 transplanted patients when compared with healthy individuals was 4% to 5% lower as evaluated by DEXA 13. Nevertheless the actual prevalence and incidence of poor nutritional state , especially as it relates to episodes of graft failure, remain to be examined, and more studies need to be undertaken. Nearly up to the first post transplantation year, serum albumin levels may be below normal suggesting that protein malnutrition may persist after renal transplantation. Thus although weight gain is common, malnutrition is not negligible9. The presence of malnutrition may affect graft and patient survival. Conversely factors such as co-morbidity and graft failure may result in malnutrition14.
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thereby activated that immunosuppressant agents (calcineurin inhibitors type) aim to block. Chronic transplant nephropathy, a combination immunological factors and a chronic rejection reaction, is generally considered to be responsible for long term loss of function of a transplanted kidney. It is possible that a decreased energy supply exacerbates chronic transplant rejection and early loss of transplant function. This mechanism can be interpreted as an adaptive and protective reaction in the presence of systemic inflammation, which occurs during phylogenesis after injuries and infections, a reduction in appetite leads to reduced food seeking to conserve resources19,20 and the immune system is activated in order to tackle disruption. The most recent studies on immunological effects of calorie restriction have shown that there are probably a number of activation targets on different cell lines in the immune system leading to improved immunological reactivity overall. This has been linked with positive effect of calorie restriction on, among other things, the origin of cancer. The clear prolongation of life span resulting from calorie restriction has been confirmed in many species21,22.
Immunological effects of calorie intake:
Relatively little data has been published on the effect of recipient and donor body mass index (BMI) on graft survival. Studies have shown that obesity places patients at higher risk for post operative complications including wound infections, delayed wound healing, incisional hernias, delayed graft function and cardiovascular disease23,24. Some studies have shown that differences in graft survival between obese and non-obese25. It seems that both abnormally low and abnormally high BMI may be considered risk factors for death censored graft loss26 . The concept of nephron dosing is also applicable to recipient BMI. Nephron dose may influence allograft survival, especially when a relatively small kidney is transplanted. However, this concept remains unproven and controversial for two reasons: a) successful transplant of pediatric donor kidney into adult recipients with good results27. The feared development of a hyperfiltration syndrome leading to early graft loss has not been consistently documented. B) There is no absolute or consistent relationship between BMI and nephron mass, especially when obesity is considered. It is however possible that graft survival may be improved by matching donor and recipient BMI- providing recipients with greater nephron mass (dose) 28 .
One of the key elements of immune reaction, the release of the mediator interleukin 2 (IL2) from T cells is promoted by diminishing energy supply17,18. It can be assumed that the actual cause of a decreased calories supply plays no role here, whether the body’s energy supply is reduced or the energy is consumed by inflammatory processes (injury, infection, transplant rejection) or physical activity, the result should be the same, T cell activation. In transplant recipients, it is precisely the signal pathways
Introduction of proper nutritional counseling at an early stage in renal transplant patients with a low BMI might allow the functional life of the kidney graft to be prolonged long-term without any significant side effects, such as occur with almost all of the medicinal products used in transplantation medicine. There is impaired long-term kidney graft survival among patients with reduced nutritional status which reflects improved immune function due to reduced nutrient availability, thus leading to
Obesity Weight gain during post-transplant period is very frequent, and its prevalence is >40% of kidney transplant patients .Obesity is also associated with decreased patient and graft survival15 particularly due to a greater incidence of surgical, metabolic, and cardiovascular complications. Potential mechanisms for the negative effect of obesity include greater chance for mismatches in recipients and donor size and hence for nephron underdosing and hyperfiltration; underdosing or perhaps impaired bioavailability of immunosuppresiive agents; or the effect of effect of hyperlipidemia to promote chronic graft dysfunction. Dislipidemias and vascular calcifications are also common among ESRD patients, as characterized by elevated triglycerides, LDL, and VLDL and lower HDL serum levels as well as disturbances in calcium-phosphorus metabolism 16 . All of these abnormalities are risk factors for atherosclerosis.
Copyright © 2009 by The Indian Society of Organ Transplantation
Indian J Transplant 2009; 3: 5-12
reinforcement of chronic rejection processes. This assumption is consistent with already known immunomodulatory effect of calorie restriction to mitigate T-cell activation29. The most recent studies on immunological effects of calorie restriction have shown that there are probably a number of activation targets on different cell lines in the immune system, leading to improved immunological reactivity overall. This has been linked with the positive effect of calorie restriction on, among other things, the origin of cancer30,31.
Protein Metabolism and Protein Intake Recommendation: The early phase of renal transplantation namely 4-6 weeks after surgery is characterized by increased nutritional demands due to a combination of the surgical stress and the high doses of immunosuppressive medications. Acute rejection and infection are also major concern. Both the surgical stress and high corticosteroid doses may lead to severe protein catabolism. One possible metabolic effect of corticosteroids is an increase in hepatic gluconeogenesis leading to hyperglycemia and hyperinsulinemia associated with elevated protein and aminoacid catabolism and decreased anabolism32. All these effects may be exacerbated in the previously malnourished patient, adding substantial problems in the immediate posttransplant phase such as wound healing and increased infection susceptibility. When higher corticosteroid doses are used, protein hypercatabolism may lead to excessive urea production that may be aggravated by acute rejection treatment. Negative nitrogen balance can be prevented in immediate post transplant period by increasing protein intake. In randomized studies, the use of steroid withdrawal and steroid avoidance protocols suggest that steroid withdrawal does not have much effect on post transplant weight gain and that weight gain is not significantly related to steroid dose. Instead, some of these studies suggest that limited physical activity may be the most important factor in post transplant obesity. These observations also suggest that greater emphasis on activity and exercise would be a more effective approach to preventing post transplant obesity33,34. Recent randomized studies in obese subjects demonstrate that following a low carbohydrate diet modest loss in weight along improvement in lipid profile can be observed over a period of 6 to 12 months. Since these studies are not based on transplant patients therefore these patients should not be counseled to pursue such diets. The daily protein intake recommendation in the immediate post transplant phase is 1.3 to 1.5 g/kg/day. Protein intake should be controlled in the presence of acute tubular necrosis with associated uremic symptoms. Similar to protein metabolism, surgical stress and high
7 doses of immunosuppressive medication may increase energy expenditures of these patients. It has been observed that these patients have a significantly higher REE (27.6 ±2.5 kcal/kg) compared to controls (23.7± 2.7 kcal/kg: P<0.001)35. This suggests that transplant patients present increased energy expenditure (30-35 kcal/ kg/d) during immediate post transplant phase. High doses of corticosteroids may produce a moon face, truncal obesity and other cushingoid characteristics. Limiting carbohydrate intake by up to 50 % of total calories, fractionated in several meals, can help avoid hyperglycemia and also possibly avoid cushingoid effects of corticosteroids. The fluid and electrolyte needs may vary in the immediate post-transplant phase, depending Mainly on the renal function and presence of acute tubular necrosis. Hypophosphatemia is very common during early weeks as a result of phosphaturia36 Recommendations for fluid and electrolyte should be evaluated daily. After 4 weeks if the patients has recovered well, then protein intake should be brought down to 1 g/kg/d and should continue till three months post transplant. At three months protein intake should be brought down to 0.8 g/ kg/d for proper functioning of graft. Patients should be advised not to indulge in excessive water drinking. Water intake should be thirst driven. The late post transplant period is frequently marked by a variety of nutritional problems, which may impact patient and graft survival. Despite adjusted doses, long-term immunosuppression is associated with protein hypercatabolism, obesity, dyslipidemia, glucose intolerance, hypertension, hypercalcemia, and alteration of vitamin D metabolism and action. Serum albumin levels may still continue to be below normal up to 1 year post transplant. suggesting that protein malnutrition may persist after transplant. This situation seems to normalize subsequently in patients with functioning renal grafts. Additionally there are abnormalities in amino acid metabolism, causing long term elevations of plasma and muscle concentrations9. Although the true mechanism of these abnormalities is still unknown, corticosteroids may be involved by increasing gluconeogenesis and protein catabolism. But a diet containing large amounts of protein may lead to renal hyperfiltration. It has been shown that 0.8g/kg/d protein intake as well as sodium restriction stabilized long term renal function as well as maintained an adequate nutritional status of recipient37. Also regular exercise is usually recommended to avoid muscle mass loss. Water intake should be thirst driven.
Nutritional recommendations to prevent atherosclerotic cardiovascular disease: The major cause of long term morbidity and mortality in these patients is atherosclerotic cardiovascular disease. In dialysis population development of this disease is due to traditional risk factors such as dyslipidemia, Copyright © 2009 by The Indian Society of Organ Transplantation
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Indian Journal of Transplantation
hypertension, glucose intolerance and sedentary lifestyle. Nontraditional risk factors such as altered calcium and phosphate homeostasis, homocystein, inflammation and oxidative stress have also been associated with cardiovascular disease16. Among these, dyslipidemia is an important and potentially modifiable risk factor in transplant patients. Approximately 60% of renal recipients develop dyslipidemia after 1 month, and 50%-70% after 10 years postransplant38. Low LDL and high triglycerides are the main predictors of cardiovascular disease in this population. Alterations in lipid metabolism may be associated with medications, such as corticosteroids, cyclosporine, sirolimus, thiazide diuretics, or betablockers as well as with renal dysfunction, nephrotic syndrome, glucose intolerance, insulin resistance or obesity39. Initial intervention involves diet modification (weight reduction along with low fat diet American Heart Association (AHA) “step one” diet ), which frequently results in improvement of the lipid profile. It appears reasonable to advocate 3 months of a low fat diet before recommending drug therapy. In addition, other strategies include regular exercise and a high fiber (25to 30 g/d) diet and the lowest possible cor ticosteroid and cyclosporine doses. Omega-3 fatty acid supplementation has been proposed to reduce serum triglycerides and consequently the vascular burden40. It has been observed that in recipients who do not gain weight their lipid levels do not worsen indicating that control of body weight by a combination of diet and exercise is critical in this patient population. Dietary salt restriction is another recommendation with important impacts on cardiovascular burden since salt intake may play a role in cyclosporine induced hypertension caused by sodium retention. Long-term 3g/ d sodium restriction along with control of protein intake stabilized renal function. A lower range (1-3 g/d) may be indicated in cases of hypertension related to fluid retension37.
Indian J Transplant 2009; 3: 5-12
Nutritional Recommendations regarding Potassium Calcium and Phosphorus and Vitamin D: During immediate post transplant phase, high doses of cyclosporine have been implicated with substantial incidence of hypercalcemia. Additionally, antihypertensive treatment with beta blocker agents or with ACE inhibitors may exacerbate hypercalcemia. In case of hypercalcemia or oliguria, dietary restrictions of potassium to 1-3 g/d may be indicated. Calcium, phosphorus and vitamin D metabolism are influenced by several interlinked factors (necrosis, fractures, bone mass loss, prolonged therapy with steroids leading to osteopenia and osteonecrosis as well as incomplete restoration of renal function after transplant (Table 1 ), resulting in the earlier period of the chronic renal failure. The daily recommendation for dietary calcium is about 800-1500 mg/d. The diet should contain adequate amount of calcium and phosphorus content and be relatively free of phosphate binders including magnesium-containing antacids. Administration of calcitiol can significantly ameliorate the renal phosphate leak and hyperparathyroidism and the depressed intestinal absorption of calcium and perhaps increase rate of bone formation. One large randomized double blind study showed that use of calcitriol (0.5 to 1 μg/d) could significantly reduce bone loss from lumbar spine in patients during 1 year of corticosteroid therapy given for a variety of reasons including organ transplantation38. However, calcitriol must be used judiciously because it can cause hypercalcemia and hypercalciuria and lead to stone formation in transplanted kidney. Hypercalcemia can also lead to vascular calcification which occurs at much higher frequency in the population of patients with end stage renal disease. Dietary intake of phosphorus should be individualized according to patients serum levels. The daily intake should be 1200-1500 mg/d as
Table 1 - Factors affecting Mineral Metabolism in transplant patients Prior renal insufficiency Hyperplastic, poorly suppressible parathyroid glands with hyperparathyroidism Pre-existing parathyroid bone disease, osteomalacia with depletion of bone mineral, or both Effects of glucocorticoid immunosuppressive therapy Inhibition of osteoblast division, maturation and function Inhibition of calcitriol-dependent absorption of calcium and phosphorus by the gut Increased urinary excretion of calcium and phosphorus Effects of incomplete restoration of normal renal function Persistent hyperparathyroidism related to reduced glomerular filtration rate Parathyroid hormone-independent renal “leak” of phosphate Other factors Vitamin D-receptor genotype Copyright © 2009 by The Indian Society of Organ Transplantation
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hypophosphatemia may persist indefinitely for majority of renal recipients. Some patients may require phosphorus supplementation and some may require supplementation of active vitamin D in doses 1-2μg/d.
Nutritional Recommendations regarding magnesium, uric acid and vitamins: Hypomagnesemia (serum magnesium< 1.5 mg/dl) may occur secondary to cyclosporine (25 % of patients) and hyperlipediemia 37 . Hypomagnesemia requires supplementation. Hyperuricemia is common in recipients with reduced renal function or those treated with diuretics37. Cyclosporin and tacrolimus induce renal magnesium wasting. Consequences of hypomagnesemia may include muscle weakness, hypokalemia, hypocalcemia, and elevated LDL. The nutritional therapy for this condition would be to avoid excessive protein intake.
Nutritional recommendations in chronic rejection: Chronic rejection (GFR <40-50 mL/min) is one of the commonest cause of graft loss. Although immunological mechanisms play a central role in the renal graft failure, a component of progressive loss of renal function may be related to initially adaptive and but eventually
maladaptive functional and structural alterations which are common to many progressive diseases. Low protein diets can reduce proteinuria and may slow the rate of progression of graft dysfunction. Protein restriction suppresses the rennin-angiotensin system and blunts the deleterious adaptive responses to nephron loss including effect on glomerular capillary hemodynamics, renal growth, ammoniagenesis and metabolic rate39. The pathogenesis of chronic rejection is poorly understood and there is no specific therapy. Nutritional intervention may have a role to play in such a situation. Dietary protein restriction has been shown to slow the course of chronic kidney disease40. Studies have shown that low protein diet (0.6g/kg/d) along with adequate calories (>25 kcal/kg/d) can maintain nitrogen balance41. Another long term study has shown that 0.8 g/kg/d protein maintained nutritional status and kidney function for all renal transplant patients37. Dietary restriction of 0.6 -0.8 g/kg/d should be considered for patients with adequate calorie intake, if prednisone dosage does not exceed 0.2 mg/kg/d balance42. Bernardi et al 2000 moderate protein intake may improve the course of chronic rejection and that restriction in protein intake may be a useful strategy in slowing the progression of renal disease in chronic rejection.
Table 2 : Methods of Nutritional Assessment Nutritional Laboratory Parameters S erum Albumin (g/dL) Serum Prealbumin (mg/dL) Serum cholesterol Subjective Global Assessment Serum Phosphorus (mg/dL) Serum Calcium (mg/dL) Lipid profile LDL (mg/dL) HDL (mg/dL) Triglycerides (mg/dL) Cardiovascular disease Anthropometry Body weight (kg) BMI MUAC (cm) Skin folds (mm) Waist/Hip ratio Body shape Malnutrition Inflammation Score Bioimpedance analysis DEXA
Goal = 4.0 (bromcresol green assay) >30 >150-180 <200 =6-7 3.5-5.5 8.4-10.5
Outcome Prevention Focus Protein-energy malnutriton Protein-energy malnutriton Protein-energy malnutriton Malnutrition Bone disease Bone Disease
<100 >40 <150
Neither Apple in men nor Pear in women
Underweight/obesity Malnutrition Malnutrition Cardiovascular disease Obesity Malnutrition
Copyright © 2009 by The Indian Society of Organ Transplantation
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Indian Journal of Transplantation
On restricted protein diet nutritional status and body muscle mass should be regularly monitored. Patients on low protein diets may require regular multivitamin supplements. Dietary phosphorus restriction (800 mg/d) would be necessary. Hyperlipidemia is yet another important aspect of chronic rejection as abnormal lipoprotein levels may lead to glomerulosclerosis and renal disease progression and even graft failure43. Hence hyperlipidemia control may have a crucial role to play in progression of chronic vascular rejection. Hence frequent nutritional evaluation (Table 2) and repeated nutritional intervention to facilitate improvement in dietary habits are important in all renal transplant phases, including pretransplant phase. During the first year the goal is to treat preexisting malnutrition and prevent excessive weight gain. Nutritional status is a major determinant of long term outcome of renal patients. Malnutrition (decreased fat and body cell mass) and over hydration (increased extracellular fluids), is seen in transplant patients even in those with good graft function44-47 Body impedance analysis (BIA) is a useful tool in assessing body composition in renal patients48,50. It has been shown that in renal patients with varying degree of renal function, BIA derived values of fat free mass (FFM) and body cell mass (BCM) correlate with 24 hour urinary creatinine excretion and hence muscle mass. Transplant patients have reduced BMI, FFM and BCM in comparison with pre-end stage renal patients51. Is there a female advantage: Variable body composition before transplant should determine different behaviour of body composition parameters post transplant for male and female patients. Significant differences in anthropometric parameters have been reported when comparing women with men pretransplant. They also show a different evolution during the first 3 months after a successful kidney graft. Males still presented signs of undernutrition at the end of the study52 period contrary to females. At month 1 and 3 after transplant women maintained body composition parameters similar to health controls. On the other hand men moved slowly toward normal body composition parameters with only Triceps skinfold normalizing at month 1. There was significant difference in muscle mass at month1 in men with partial recovery at month 3. The data suggest that with current doses, immunosuppressive drugs do not have major influences on anthropometric parameters, at least during the first months post transplant. If normal body composition in males is attained later than females, it may be due to their previous condition, and greater nutritional requirements during early post transplant period. Men may therefore benefit from a greater protein and energy intake compared to women in order to recover normal weight, fat free mass and muscle mass
Copyright © 2009 by The Indian Society of Organ Transplantation
Indian J Transplant 2009; 3: 5-12
Body composition: Factors influencing body composition in renal transplant recipients are manifold, including steroid administration, acute or chronic infection, rejection, nutritional behaviour, and higher grade uremia-the later evidently involving only a small proportion of patients. The pathogenetic background to an impaired nutritional status is “malnutrition-inflammation complex syndrome” which probably palys a central role not just in renal transplant patients, resulting in breakdown of energy stores, reduced energy uptake, and thus ultimately reduced energy availability53,54. Body composition is prone to rapid change after transplantation. Thus the BMI at 1 year after transplantation seems to be a suitable parameter to assess long-term effects as it is recorded at a point where it is expected that stabilization of graft function, drug dosage and overall well-being has been achieved. The determination of REE, nitrogen urinary loss with the MicroKjeldah method in healthy and transplanted subjects shows that in the patients with at least a functioning renal graft of 1 years duration, the REE is greater in subjects treated with CsA and low doses of steroids and lower in patients treated with steroids and azathioprine.
Post Transplantation Diabetes The post transplant nutritional care of diabetic patients is considerably complicated by insulin resistance induced by steroid therapy. Some patients develop clinical diabetes as a result of immunosuppressive therapy with glucocorticoids and calcineurin inhibitors (cyclosporine and tacrolimus). The side effects of immunosuppresssion drugs steroids, cyclosporine, tacrolimus, azathioprine, mycophenolate and sirolimus lead to a gain in weight or obesity, which significantly increase morbidity and mortality in kidney transplant recipients. The most important problems are hypertension, diabetes, hyperlipidemia, coronary artery disease and accelerated atherosclerosis. Recommendations for diet in the immediate and long-term post transplant period are necessary. Not surprisingly, even recipients of renal transplantation with overtly normal glucose tolerance have evidence of insulin resistance when studied by insulinclamp technique. The development of clinical diabetes seems to occur when relative insulin deficiency develops, such that insulinproduction is inadequate, relative to the degree of insulin resistance. Post transplant diabetes is more common with tacrolimus based immunosuppression . In a randomiozed study of 412 patients the incidence of posttransplant diabetes during first post transplant year (defined as need for insulin for 30 days or more) was 20% in patients receiving tacrolimus as compared to 4% in those receiving cyclosporine based immunosuppression. The diabetogenic effect of tacrolimus is dose dependent so that with downward dose adjustment the long term prevalence of diabetes decreases and may eventually be similar to the rate
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observed in cyclosporine based immunosuppression55. Study conducted on patients with post transplant diabetes discerns the most common nutritional errors among these patients during nutritional, therapeutic and educational intervention. All the affected patients were overweight, had sedentary lifestyle, with a mean number of meals of three. There was a ponderal excess among females with most frequent nutritional error being a low number of meals, excessive use of proteins and fat, chiefly by the female group56
Conclusion Frequent evaluation of nutritional status may be of great importance in all renal transplant patients as well as in the pre-renal transplantation period and should be complemented by intervention in the nutritional intake.
References 1.
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33. Jindal RM Zawada ET Obesity and kidney transplantation Am J Kidney Dis 2004 43 :943 34. Johnson CP, Gallagher-Lepak S, Zhu Y R etal Factors influencing weight gain after renal transplantation Transplantation 1993 56: 822 . 35. Unpublished data Martins C, Pecoits-Filho and Riella MC Nutrition for the post renal transplant recipients. Transplantation Proceedings 2004 36 1650). 36. Kasiske BL, Vazquez MA, Harmon WE et al Recommendations for the out patient surveillance of renal transplant recipients. American Society of Transplantation J Am Soc Nephrol 2000 11 Supp S 1. 37. Bernardi A, Biasia F,Pati T et al Long-term protein intake control in kidney transplant recipients: effect in kidney graft function and in nutritional status. Am J Kidney Dis 2003 41 (Suppl 1) S 146. 38. Nuti R, Vattimo A, Turchetti etal 25-hydroxy cholecalciferol as an agonist of adverse corticosteroid effects on phosphate and calcium metabolism in man J Endocrinol Invest 1984 7: 455 39. Brenner BM, Meyer TW, Hostetter TH Dietary protein intake and progressive nature of kidney disease: The role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in ageing, renal ablation and intrinsic renal disease. N England J Med 1982 307: 652-659 40. Fouque D, Wang P, Laville m et al Low protein diets for chronic renal failure in non diabetic adults. Cochrane Database Syst Rev 2001 (2): CD 001892 41. Windus Dw, Lacson S, Delmez JA The short term effects of low protein diet in stable renal transplant recipients. 1991 Am J Kidney disease 17: 693 42. Drueke TB, Abdulmassih Z, Lacour B et al Atherosclerosis and lipid disorders after renal transplantation. Kidney Int Suppl 1991 31: S 24. 39. Kasiske BL, Guijarro C, Massy ZA et al Cardiovascular disease after renal transplantation J Am Soc Nephrol 1998 7: 158. 43. Jevnikar AM, Petric R, Holub BJ et al Effect of cyclosporine on plasma lipids and modification with dietary fish oil Transplantation 1988 46: 722. 41. Windus Dw, Lacson S, Delmez JA The short term effects of low protein diet in stable renal transplant recipients. Am J Kidney disease 1991 17: 693
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44. Patel MG The effect of dietary intervention on weight gain after renal transplant. J Ren Nutr 1998 8: 137 . 45. Lucchesi A, Ardini M, Donadio E et al Nutritional status in renal transplant recipients evaluated by means of body composition analysis. Transplantation Proceedings 2001 33:3398, 46. Saxena Anita and Sharma RK Bioelectrical Impedance analysis for monitoring changes in body composition for improving nutritional intake of hemodilaysis patients. In J Nephrol presented at ISN 2006, held at Cohin. 47. Saxena Anita and Sharma RK Body composition and volume overload in renal transplant patients In J Nephrol presented at ISN 2007 held at New Delhi ISN 48 Saxena Anita and Sharma RK Nutrition in patients with chronic kidney disease In Renal Disease Prevention and management A Physician’s Perspective 2008 Editor OP Kalra Chapter 30 216-223 49. Cooper BA, Aslani A, Ryan M et al Comparing different methods of assessing body composition in end-stage renal failure. Kidney Intr 2000 58: 408-416 50. Macdonald JH, Marcora SM, Jibani M etal Bioelectrical impedance can be used to predict muscle mass and hence improve estimation of GFR in non-diabetic patients with chronic kidney disease. Nephrol Dial Transplant 2006 21: 3481. 51. Dumbler F and KIlates C: Nutritional status assessment and body composition analysis in pre-end. Miner Electrolyte Metab1999. 25: 397 52. Coroas A, Oliveira JGG, Sampaio C et al Nutritional status and body composition evolution in early post renal transplantation: is there a female advantage Transplant proceedings 2005 37 2765 53. Kalantar-Zadeh K, Stenvinkel P, Pillon L, et al. Inflammation and nutrition in renal insufficiency. Adv Ren Peplace Ther 2003 10: 155 54. Bengmark S Nutritional modulations of acute-andchronic phase responses. Nutrition 2001 17: 489 55. Markell M New onset diabetes in transplant patients: pathogenesis, complications and management. Am J Kidney Dis 2004 43: 953-965 56. Loureiro H, Siva RS, Machado C etal Kidney transplantation and posttransplant diabetes. Nutritional evaluation Transplanation Proceedings 2003 35 10911092
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ARTICLE
Nutritional Surviellance After Renal Transplant : Review Anita Saxena and RK Sharma Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raibareli Road, Lucknow
The recipients of renal transplants experience an improvement in general sense of well being along with marked improvement in appetite and increase in body weight. It is expected that a successfully transplanted kidney would restore near-normal renal function and correct nutritional abnormalities arising from pre-transplant renal insufficiency. What actually happens is that some patients do not attain optimal renal function, while others experience decline in renal function with the passage of time. Hence, many recipients of transplant may require nutritional management as appropriate for patients with chronic renal failure even though these patients do not require dialysis. Furthermore, transplant patients face many nutritional challenges because of metabolic complications of pre-existing medical conditions and as a consequence of transplant related immunosuppression. Hence, evaluation of nutritional status, body composition and resting energy expenditure (REE) is a must in post transplant patients with functioning renal graft and longer survival of the transplanted kidney1-4. Changes in body composition after renal transplantation are due to increased appetite and reversal of the uremic state, as well as immunosuppressive therapy, in particular Address for correspondance:
Prof. R. K. Sharma Head Department of nephrology Sanjay Gandhi Post Graduate Institute of Medical Sciences, Rae Bareli Road, Lucknow 226 014 Email: [email protected]
immediately after surgery. Therefore there are two clearly distinct phases regarding nutritional changes: the early and late post transplant phases. The major nutritional and metabolic problems of the early phase are malnutrition (associated or not associated with systemic inflammation), obesity, lipid abnormalities, glucose intolerance, hyper tension, as well as calcium, phosphorus, and vitamin D imbalance.
Malnutrition Malnutrition during the pre-transplant phase is associated with higher post-transplant morbidity and mortality rates, which are due in part to impaired surgical wound healing and higher risk of infection. Despite increase in weight which is partially attributed to immunosuppression, malnutrition is present in >20% of the post transplant patients5. Malnutrition can best be defined by a body mass index (BMI) <216. 15% of the 452 kidney transplant patients had BMI less than 21 kgm2 which the investigators attributed to malnutrition. Co morbidity and graft failure-two main causes of malnutrition in kidney transplant patients7,8. There is depletion of protein stores at the cellular level after 45 days of transplantation, which normalizes in long term9
Effect of Immuno-suppression on body weight Within two to three weeks a significant increase in body weight is due to high doses of cyclosporine and steroids which cause an increase in total body water (TBW). On an average body weight increases by 14% in men and Copyright © 2009 by The Indian Society of Organ Transplantation
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10% in women when compared with their respective dialytic dry weight. Evaluation of body composition by bioelectrical impedance shows that patients with a renal transplant show a tendency towards higher fat-free mass compared to healthy control. Some authors have found no correlation between cumulative steroid dose and post transplant weight gain. On the contrary, a slight tendency toward weight loss has even been observed8,10 . Lower whole body contents of nitrogen, serum potassium and calcium during first year of transplantation have been reported11 . Significant decreases in serum albumin, transferrin and retinol binding protein levels have been reported in the first year posttransplant12. Lean body mass of 115 transplanted patients when compared with healthy individuals was 4% to 5% lower as evaluated by DEXA 13. Nevertheless the actual prevalence and incidence of poor nutritional state , especially as it relates to episodes of graft failure, remain to be examined, and more studies need to be undertaken. Nearly up to the first post transplantation year, serum albumin levels may be below normal suggesting that protein malnutrition may persist after renal transplantation. Thus although weight gain is common, malnutrition is not negligible9. The presence of malnutrition may affect graft and patient survival. Conversely factors such as co-morbidity and graft failure may result in malnutrition14.
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thereby activated that immunosuppressant agents (calcineurin inhibitors type) aim to block. Chronic transplant nephropathy, a combination immunological factors and a chronic rejection reaction, is generally considered to be responsible for long term loss of function of a transplanted kidney. It is possible that a decreased energy supply exacerbates chronic transplant rejection and early loss of transplant function. This mechanism can be interpreted as an adaptive and protective reaction in the presence of systemic inflammation, which occurs during phylogenesis after injuries and infections, a reduction in appetite leads to reduced food seeking to conserve resources19,20 and the immune system is activated in order to tackle disruption. The most recent studies on immunological effects of calorie restriction have shown that there are probably a number of activation targets on different cell lines in the immune system leading to improved immunological reactivity overall. This has been linked with positive effect of calorie restriction on, among other things, the origin of cancer. The clear prolongation of life span resulting from calorie restriction has been confirmed in many species21,22.
Immunological effects of calorie intake:
Relatively little data has been published on the effect of recipient and donor body mass index (BMI) on graft survival. Studies have shown that obesity places patients at higher risk for post operative complications including wound infections, delayed wound healing, incisional hernias, delayed graft function and cardiovascular disease23,24. Some studies have shown that differences in graft survival between obese and non-obese25. It seems that both abnormally low and abnormally high BMI may be considered risk factors for death censored graft loss26 . The concept of nephron dosing is also applicable to recipient BMI. Nephron dose may influence allograft survival, especially when a relatively small kidney is transplanted. However, this concept remains unproven and controversial for two reasons: a) successful transplant of pediatric donor kidney into adult recipients with good results27. The feared development of a hyperfiltration syndrome leading to early graft loss has not been consistently documented. B) There is no absolute or consistent relationship between BMI and nephron mass, especially when obesity is considered. It is however possible that graft survival may be improved by matching donor and recipient BMI- providing recipients with greater nephron mass (dose) 28 .
One of the key elements of immune reaction, the release of the mediator interleukin 2 (IL2) from T cells is promoted by diminishing energy supply17,18. It can be assumed that the actual cause of a decreased calories supply plays no role here, whether the body’s energy supply is reduced or the energy is consumed by inflammatory processes (injury, infection, transplant rejection) or physical activity, the result should be the same, T cell activation. In transplant recipients, it is precisely the signal pathways
Introduction of proper nutritional counseling at an early stage in renal transplant patients with a low BMI might allow the functional life of the kidney graft to be prolonged long-term without any significant side effects, such as occur with almost all of the medicinal products used in transplantation medicine. There is impaired long-term kidney graft survival among patients with reduced nutritional status which reflects improved immune function due to reduced nutrient availability, thus leading to
Obesity Weight gain during post-transplant period is very frequent, and its prevalence is >40% of kidney transplant patients .Obesity is also associated with decreased patient and graft survival15 particularly due to a greater incidence of surgical, metabolic, and cardiovascular complications. Potential mechanisms for the negative effect of obesity include greater chance for mismatches in recipients and donor size and hence for nephron underdosing and hyperfiltration; underdosing or perhaps impaired bioavailability of immunosuppresiive agents; or the effect of effect of hyperlipidemia to promote chronic graft dysfunction. Dislipidemias and vascular calcifications are also common among ESRD patients, as characterized by elevated triglycerides, LDL, and VLDL and lower HDL serum levels as well as disturbances in calcium-phosphorus metabolism 16 . All of these abnormalities are risk factors for atherosclerosis.
Copyright © 2009 by The Indian Society of Organ Transplantation
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reinforcement of chronic rejection processes. This assumption is consistent with already known immunomodulatory effect of calorie restriction to mitigate T-cell activation29. The most recent studies on immunological effects of calorie restriction have shown that there are probably a number of activation targets on different cell lines in the immune system, leading to improved immunological reactivity overall. This has been linked with the positive effect of calorie restriction on, among other things, the origin of cancer30,31.
Protein Metabolism and Protein Intake Recommendation: The early phase of renal transplantation namely 4-6 weeks after surgery is characterized by increased nutritional demands due to a combination of the surgical stress and the high doses of immunosuppressive medications. Acute rejection and infection are also major concern. Both the surgical stress and high corticosteroid doses may lead to severe protein catabolism. One possible metabolic effect of corticosteroids is an increase in hepatic gluconeogenesis leading to hyperglycemia and hyperinsulinemia associated with elevated protein and aminoacid catabolism and decreased anabolism32. All these effects may be exacerbated in the previously malnourished patient, adding substantial problems in the immediate posttransplant phase such as wound healing and increased infection susceptibility. When higher corticosteroid doses are used, protein hypercatabolism may lead to excessive urea production that may be aggravated by acute rejection treatment. Negative nitrogen balance can be prevented in immediate post transplant period by increasing protein intake. In randomized studies, the use of steroid withdrawal and steroid avoidance protocols suggest that steroid withdrawal does not have much effect on post transplant weight gain and that weight gain is not significantly related to steroid dose. Instead, some of these studies suggest that limited physical activity may be the most important factor in post transplant obesity. These observations also suggest that greater emphasis on activity and exercise would be a more effective approach to preventing post transplant obesity33,34. Recent randomized studies in obese subjects demonstrate that following a low carbohydrate diet modest loss in weight along improvement in lipid profile can be observed over a period of 6 to 12 months. Since these studies are not based on transplant patients therefore these patients should not be counseled to pursue such diets. The daily protein intake recommendation in the immediate post transplant phase is 1.3 to 1.5 g/kg/day. Protein intake should be controlled in the presence of acute tubular necrosis with associated uremic symptoms. Similar to protein metabolism, surgical stress and high
7 doses of immunosuppressive medication may increase energy expenditures of these patients. It has been observed that these patients have a significantly higher REE (27.6 ±2.5 kcal/kg) compared to controls (23.7± 2.7 kcal/kg: P<0.001)35. This suggests that transplant patients present increased energy expenditure (30-35 kcal/ kg/d) during immediate post transplant phase. High doses of corticosteroids may produce a moon face, truncal obesity and other cushingoid characteristics. Limiting carbohydrate intake by up to 50 % of total calories, fractionated in several meals, can help avoid hyperglycemia and also possibly avoid cushingoid effects of corticosteroids. The fluid and electrolyte needs may vary in the immediate post-transplant phase, depending Mainly on the renal function and presence of acute tubular necrosis. Hypophosphatemia is very common during early weeks as a result of phosphaturia36 Recommendations for fluid and electrolyte should be evaluated daily. After 4 weeks if the patients has recovered well, then protein intake should be brought down to 1 g/kg/d and should continue till three months post transplant. At three months protein intake should be brought down to 0.8 g/ kg/d for proper functioning of graft. Patients should be advised not to indulge in excessive water drinking. Water intake should be thirst driven. The late post transplant period is frequently marked by a variety of nutritional problems, which may impact patient and graft survival. Despite adjusted doses, long-term immunosuppression is associated with protein hypercatabolism, obesity, dyslipidemia, glucose intolerance, hypertension, hypercalcemia, and alteration of vitamin D metabolism and action. Serum albumin levels may still continue to be below normal up to 1 year post transplant. suggesting that protein malnutrition may persist after transplant. This situation seems to normalize subsequently in patients with functioning renal grafts. Additionally there are abnormalities in amino acid metabolism, causing long term elevations of plasma and muscle concentrations9. Although the true mechanism of these abnormalities is still unknown, corticosteroids may be involved by increasing gluconeogenesis and protein catabolism. But a diet containing large amounts of protein may lead to renal hyperfiltration. It has been shown that 0.8g/kg/d protein intake as well as sodium restriction stabilized long term renal function as well as maintained an adequate nutritional status of recipient37. Also regular exercise is usually recommended to avoid muscle mass loss. Water intake should be thirst driven.
Nutritional recommendations to prevent atherosclerotic cardiovascular disease: The major cause of long term morbidity and mortality in these patients is atherosclerotic cardiovascular disease. In dialysis population development of this disease is due to traditional risk factors such as dyslipidemia, Copyright © 2009 by The Indian Society of Organ Transplantation
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hypertension, glucose intolerance and sedentary lifestyle. Nontraditional risk factors such as altered calcium and phosphate homeostasis, homocystein, inflammation and oxidative stress have also been associated with cardiovascular disease16. Among these, dyslipidemia is an important and potentially modifiable risk factor in transplant patients. Approximately 60% of renal recipients develop dyslipidemia after 1 month, and 50%-70% after 10 years postransplant38. Low LDL and high triglycerides are the main predictors of cardiovascular disease in this population. Alterations in lipid metabolism may be associated with medications, such as corticosteroids, cyclosporine, sirolimus, thiazide diuretics, or betablockers as well as with renal dysfunction, nephrotic syndrome, glucose intolerance, insulin resistance or obesity39. Initial intervention involves diet modification (weight reduction along with low fat diet American Heart Association (AHA) “step one” diet ), which frequently results in improvement of the lipid profile. It appears reasonable to advocate 3 months of a low fat diet before recommending drug therapy. In addition, other strategies include regular exercise and a high fiber (25to 30 g/d) diet and the lowest possible cor ticosteroid and cyclosporine doses. Omega-3 fatty acid supplementation has been proposed to reduce serum triglycerides and consequently the vascular burden40. It has been observed that in recipients who do not gain weight their lipid levels do not worsen indicating that control of body weight by a combination of diet and exercise is critical in this patient population. Dietary salt restriction is another recommendation with important impacts on cardiovascular burden since salt intake may play a role in cyclosporine induced hypertension caused by sodium retention. Long-term 3g/ d sodium restriction along with control of protein intake stabilized renal function. A lower range (1-3 g/d) may be indicated in cases of hypertension related to fluid retension37.
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Nutritional Recommendations regarding Potassium Calcium and Phosphorus and Vitamin D: During immediate post transplant phase, high doses of cyclosporine have been implicated with substantial incidence of hypercalcemia. Additionally, antihypertensive treatment with beta blocker agents or with ACE inhibitors may exacerbate hypercalcemia. In case of hypercalcemia or oliguria, dietary restrictions of potassium to 1-3 g/d may be indicated. Calcium, phosphorus and vitamin D metabolism are influenced by several interlinked factors (necrosis, fractures, bone mass loss, prolonged therapy with steroids leading to osteopenia and osteonecrosis as well as incomplete restoration of renal function after transplant (Table 1 ), resulting in the earlier period of the chronic renal failure. The daily recommendation for dietary calcium is about 800-1500 mg/d. The diet should contain adequate amount of calcium and phosphorus content and be relatively free of phosphate binders including magnesium-containing antacids. Administration of calcitiol can significantly ameliorate the renal phosphate leak and hyperparathyroidism and the depressed intestinal absorption of calcium and perhaps increase rate of bone formation. One large randomized double blind study showed that use of calcitriol (0.5 to 1 μg/d) could significantly reduce bone loss from lumbar spine in patients during 1 year of corticosteroid therapy given for a variety of reasons including organ transplantation38. However, calcitriol must be used judiciously because it can cause hypercalcemia and hypercalciuria and lead to stone formation in transplanted kidney. Hypercalcemia can also lead to vascular calcification which occurs at much higher frequency in the population of patients with end stage renal disease. Dietary intake of phosphorus should be individualized according to patients serum levels. The daily intake should be 1200-1500 mg/d as
Table 1 - Factors affecting Mineral Metabolism in transplant patients Prior renal insufficiency Hyperplastic, poorly suppressible parathyroid glands with hyperparathyroidism Pre-existing parathyroid bone disease, osteomalacia with depletion of bone mineral, or both Effects of glucocorticoid immunosuppressive therapy Inhibition of osteoblast division, maturation and function Inhibition of calcitriol-dependent absorption of calcium and phosphorus by the gut Increased urinary excretion of calcium and phosphorus Effects of incomplete restoration of normal renal function Persistent hyperparathyroidism related to reduced glomerular filtration rate Parathyroid hormone-independent renal “leak” of phosphate Other factors Vitamin D-receptor genotype Copyright © 2009 by The Indian Society of Organ Transplantation
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hypophosphatemia may persist indefinitely for majority of renal recipients. Some patients may require phosphorus supplementation and some may require supplementation of active vitamin D in doses 1-2μg/d.
Nutritional Recommendations regarding magnesium, uric acid and vitamins: Hypomagnesemia (serum magnesium< 1.5 mg/dl) may occur secondary to cyclosporine (25 % of patients) and hyperlipediemia 37 . Hypomagnesemia requires supplementation. Hyperuricemia is common in recipients with reduced renal function or those treated with diuretics37. Cyclosporin and tacrolimus induce renal magnesium wasting. Consequences of hypomagnesemia may include muscle weakness, hypokalemia, hypocalcemia, and elevated LDL. The nutritional therapy for this condition would be to avoid excessive protein intake.
Nutritional recommendations in chronic rejection: Chronic rejection (GFR <40-50 mL/min) is one of the commonest cause of graft loss. Although immunological mechanisms play a central role in the renal graft failure, a component of progressive loss of renal function may be related to initially adaptive and but eventually
maladaptive functional and structural alterations which are common to many progressive diseases. Low protein diets can reduce proteinuria and may slow the rate of progression of graft dysfunction. Protein restriction suppresses the rennin-angiotensin system and blunts the deleterious adaptive responses to nephron loss including effect on glomerular capillary hemodynamics, renal growth, ammoniagenesis and metabolic rate39. The pathogenesis of chronic rejection is poorly understood and there is no specific therapy. Nutritional intervention may have a role to play in such a situation. Dietary protein restriction has been shown to slow the course of chronic kidney disease40. Studies have shown that low protein diet (0.6g/kg/d) along with adequate calories (>25 kcal/kg/d) can maintain nitrogen balance41. Another long term study has shown that 0.8 g/kg/d protein maintained nutritional status and kidney function for all renal transplant patients37. Dietary restriction of 0.6 -0.8 g/kg/d should be considered for patients with adequate calorie intake, if prednisone dosage does not exceed 0.2 mg/kg/d balance42. Bernardi et al 2000 moderate protein intake may improve the course of chronic rejection and that restriction in protein intake may be a useful strategy in slowing the progression of renal disease in chronic rejection.
Table 2 : Methods of Nutritional Assessment Nutritional Laboratory Parameters S erum Albumin (g/dL) Serum Prealbumin (mg/dL) Serum cholesterol Subjective Global Assessment Serum Phosphorus (mg/dL) Serum Calcium (mg/dL) Lipid profile LDL (mg/dL) HDL (mg/dL) Triglycerides (mg/dL) Cardiovascular disease Anthropometry Body weight (kg) BMI MUAC (cm) Skin folds (mm) Waist/Hip ratio Body shape Malnutrition Inflammation Score Bioimpedance analysis DEXA
Goal = 4.0 (bromcresol green assay) >30 >150-180 <200 =6-7 3.5-5.5 8.4-10.5
Outcome Prevention Focus Protein-energy malnutriton Protein-energy malnutriton Protein-energy malnutriton Malnutrition Bone disease Bone Disease
<100 >40 <150
Neither Apple in men nor Pear in women
Underweight/obesity Malnutrition Malnutrition Cardiovascular disease Obesity Malnutrition
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On restricted protein diet nutritional status and body muscle mass should be regularly monitored. Patients on low protein diets may require regular multivitamin supplements. Dietary phosphorus restriction (800 mg/d) would be necessary. Hyperlipidemia is yet another important aspect of chronic rejection as abnormal lipoprotein levels may lead to glomerulosclerosis and renal disease progression and even graft failure43. Hence hyperlipidemia control may have a crucial role to play in progression of chronic vascular rejection. Hence frequent nutritional evaluation (Table 2) and repeated nutritional intervention to facilitate improvement in dietary habits are important in all renal transplant phases, including pretransplant phase. During the first year the goal is to treat preexisting malnutrition and prevent excessive weight gain. Nutritional status is a major determinant of long term outcome of renal patients. Malnutrition (decreased fat and body cell mass) and over hydration (increased extracellular fluids), is seen in transplant patients even in those with good graft function44-47 Body impedance analysis (BIA) is a useful tool in assessing body composition in renal patients48,50. It has been shown that in renal patients with varying degree of renal function, BIA derived values of fat free mass (FFM) and body cell mass (BCM) correlate with 24 hour urinary creatinine excretion and hence muscle mass. Transplant patients have reduced BMI, FFM and BCM in comparison with pre-end stage renal patients51. Is there a female advantage: Variable body composition before transplant should determine different behaviour of body composition parameters post transplant for male and female patients. Significant differences in anthropometric parameters have been reported when comparing women with men pretransplant. They also show a different evolution during the first 3 months after a successful kidney graft. Males still presented signs of undernutrition at the end of the study52 period contrary to females. At month 1 and 3 after transplant women maintained body composition parameters similar to health controls. On the other hand men moved slowly toward normal body composition parameters with only Triceps skinfold normalizing at month 1. There was significant difference in muscle mass at month1 in men with partial recovery at month 3. The data suggest that with current doses, immunosuppressive drugs do not have major influences on anthropometric parameters, at least during the first months post transplant. If normal body composition in males is attained later than females, it may be due to their previous condition, and greater nutritional requirements during early post transplant period. Men may therefore benefit from a greater protein and energy intake compared to women in order to recover normal weight, fat free mass and muscle mass
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Body composition: Factors influencing body composition in renal transplant recipients are manifold, including steroid administration, acute or chronic infection, rejection, nutritional behaviour, and higher grade uremia-the later evidently involving only a small proportion of patients. The pathogenetic background to an impaired nutritional status is “malnutrition-inflammation complex syndrome” which probably palys a central role not just in renal transplant patients, resulting in breakdown of energy stores, reduced energy uptake, and thus ultimately reduced energy availability53,54. Body composition is prone to rapid change after transplantation. Thus the BMI at 1 year after transplantation seems to be a suitable parameter to assess long-term effects as it is recorded at a point where it is expected that stabilization of graft function, drug dosage and overall well-being has been achieved. The determination of REE, nitrogen urinary loss with the MicroKjeldah method in healthy and transplanted subjects shows that in the patients with at least a functioning renal graft of 1 years duration, the REE is greater in subjects treated with CsA and low doses of steroids and lower in patients treated with steroids and azathioprine.
Post Transplantation Diabetes The post transplant nutritional care of diabetic patients is considerably complicated by insulin resistance induced by steroid therapy. Some patients develop clinical diabetes as a result of immunosuppressive therapy with glucocorticoids and calcineurin inhibitors (cyclosporine and tacrolimus). The side effects of immunosuppresssion drugs steroids, cyclosporine, tacrolimus, azathioprine, mycophenolate and sirolimus lead to a gain in weight or obesity, which significantly increase morbidity and mortality in kidney transplant recipients. The most important problems are hypertension, diabetes, hyperlipidemia, coronary artery disease and accelerated atherosclerosis. Recommendations for diet in the immediate and long-term post transplant period are necessary. Not surprisingly, even recipients of renal transplantation with overtly normal glucose tolerance have evidence of insulin resistance when studied by insulinclamp technique. The development of clinical diabetes seems to occur when relative insulin deficiency develops, such that insulinproduction is inadequate, relative to the degree of insulin resistance. Post transplant diabetes is more common with tacrolimus based immunosuppression . In a randomiozed study of 412 patients the incidence of posttransplant diabetes during first post transplant year (defined as need for insulin for 30 days or more) was 20% in patients receiving tacrolimus as compared to 4% in those receiving cyclosporine based immunosuppression. The diabetogenic effect of tacrolimus is dose dependent so that with downward dose adjustment the long term prevalence of diabetes decreases and may eventually be similar to the rate
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observed in cyclosporine based immunosuppression55. Study conducted on patients with post transplant diabetes discerns the most common nutritional errors among these patients during nutritional, therapeutic and educational intervention. All the affected patients were overweight, had sedentary lifestyle, with a mean number of meals of three. There was a ponderal excess among females with most frequent nutritional error being a low number of meals, excessive use of proteins and fat, chiefly by the female group56
Conclusion Frequent evaluation of nutritional status may be of great importance in all renal transplant patients as well as in the pre-renal transplantation period and should be complemented by intervention in the nutritional intake.
References 1.
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33. Jindal RM Zawada ET Obesity and kidney transplantation Am J Kidney Dis 2004 43 :943 34. Johnson CP, Gallagher-Lepak S, Zhu Y R etal Factors influencing weight gain after renal transplantation Transplantation 1993 56: 822 . 35. Unpublished data Martins C, Pecoits-Filho and Riella MC Nutrition for the post renal transplant recipients. Transplantation Proceedings 2004 36 1650). 36. Kasiske BL, Vazquez MA, Harmon WE et al Recommendations for the out patient surveillance of renal transplant recipients. American Society of Transplantation J Am Soc Nephrol 2000 11 Supp S 1. 37. Bernardi A, Biasia F,Pati T et al Long-term protein intake control in kidney transplant recipients: effect in kidney graft function and in nutritional status. Am J Kidney Dis 2003 41 (Suppl 1) S 146. 38. Nuti R, Vattimo A, Turchetti etal 25-hydroxy cholecalciferol as an agonist of adverse corticosteroid effects on phosphate and calcium metabolism in man J Endocrinol Invest 1984 7: 455 39. Brenner BM, Meyer TW, Hostetter TH Dietary protein intake and progressive nature of kidney disease: The role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in ageing, renal ablation and intrinsic renal disease. N England J Med 1982 307: 652-659 40. Fouque D, Wang P, Laville m et al Low protein diets for chronic renal failure in non diabetic adults. Cochrane Database Syst Rev 2001 (2): CD 001892 41. Windus Dw, Lacson S, Delmez JA The short term effects of low protein diet in stable renal transplant recipients. 1991 Am J Kidney disease 17: 693 42. Drueke TB, Abdulmassih Z, Lacour B et al Atherosclerosis and lipid disorders after renal transplantation. Kidney Int Suppl 1991 31: S 24. 39. Kasiske BL, Guijarro C, Massy ZA et al Cardiovascular disease after renal transplantation J Am Soc Nephrol 1998 7: 158. 43. Jevnikar AM, Petric R, Holub BJ et al Effect of cyclosporine on plasma lipids and modification with dietary fish oil Transplantation 1988 46: 722. 41. Windus Dw, Lacson S, Delmez JA The short term effects of low protein diet in stable renal transplant recipients. Am J Kidney disease 1991 17: 693
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44. Patel MG The effect of dietary intervention on weight gain after renal transplant. J Ren Nutr 1998 8: 137 . 45. Lucchesi A, Ardini M, Donadio E et al Nutritional status in renal transplant recipients evaluated by means of body composition analysis. Transplantation Proceedings 2001 33:3398, 46. Saxena Anita and Sharma RK Bioelectrical Impedance analysis for monitoring changes in body composition for improving nutritional intake of hemodilaysis patients. In J Nephrol presented at ISN 2006, held at Cohin. 47. Saxena Anita and Sharma RK Body composition and volume overload in renal transplant patients In J Nephrol presented at ISN 2007 held at New Delhi ISN 48 Saxena Anita and Sharma RK Nutrition in patients with chronic kidney disease In Renal Disease Prevention and management A Physician’s Perspective 2008 Editor OP Kalra Chapter 30 216-223 49. Cooper BA, Aslani A, Ryan M et al Comparing different methods of assessing body composition in end-stage renal failure. Kidney Intr 2000 58: 408-416 50. Macdonald JH, Marcora SM, Jibani M etal Bioelectrical impedance can be used to predict muscle mass and hence improve estimation of GFR in non-diabetic patients with chronic kidney disease. Nephrol Dial Transplant 2006 21: 3481. 51. Dumbler F and KIlates C: Nutritional status assessment and body composition analysis in pre-end. Miner Electrolyte Metab1999. 25: 397 52. Coroas A, Oliveira JGG, Sampaio C et al Nutritional status and body composition evolution in early post renal transplantation: is there a female advantage Transplant proceedings 2005 37 2765 53. Kalantar-Zadeh K, Stenvinkel P, Pillon L, et al. Inflammation and nutrition in renal insufficiency. Adv Ren Peplace Ther 2003 10: 155 54. Bengmark S Nutritional modulations of acute-andchronic phase responses. Nutrition 2001 17: 489 55. Markell M New onset diabetes in transplant patients: pathogenesis, complications and management. Am J Kidney Dis 2004 43: 953-965 56. Loureiro H, Siva RS, Machado C etal Kidney transplantation and posttransplant diabetes. Nutritional evaluation Transplanation Proceedings 2003 35 10911092