Nutrition in Clinical Practice

http://ncp.sagepub.com/ Gastric Bypass in Chronic Renal Failure and Renal Transplant

J. Wesley Alexander and Hope Goodman Nutr Clin Pract 2007 22: 16 DOI: 10.1177/011542650702200116 The online version of this article can be found at: http://ncp.sagepub.com/content/22/1/16

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Clinical Research
Gastric Bypass in Chronic Renal Failure and Renal Transplant
J. Wesley Alexander, MD, ScD; and Hope Goodman, MPT
Center for Surgical Weight Loss, University of Cincinnati, Cincinnati, Ohio ABSTRACT: Background: Morbid obesity has reached epidemic proportions in developed nations worldwide, causing considerable mortality and increased healthcare expenditures. The use of gastric bypass surgery to achieve weight loss in morbidly obese patients with chronic renal failure (CRF) and postrenal transplant patients has not been studied adequately. Methods: Forty-one patients with different stages of CRF (25 already receiving dialysis) underwent a gastric bypass (GBP), and an additional 10 patients underwent a GBP after becoming morbidly obese after transplantation. Results: Of the 41 patients with CRF, 5 stabilized or resolved their kidney disease and 9 underwent successful transplantation. These patients had a loss of 68% excess body mass index (BMI) by 12 months after GBP. Of the 10 patients with GBP after transplant, the mean loss of excess BMI was 70.5%. There were no in-hospital or 30-day mortalities, but 8 of the 51 patients died from 112 to 2869 days postoperatively, 7 from cardiac or vascular events and 1 from an automobile accident. This compares with an approximate 10% mortality per year for patients receiving dialysis. Comorbid conditions associated with morbid obesity improved in all patients and permitted eligibility for transplantation. Conclusions: GBP for massive weight reduction in morbidly obese renal failure and transplant patients leads to a reduction in comorbid conditions that are associated with an increased risk for cardiovascular deaths. There was no operative mortality in this series, and all but 1 death were related to previously existing disease of the cardiovascular system.

healthcare costs.2 Years of life lost because of morbid obesity is as much as 20 years for African American men with a body mass index (BMI) 45.3 On a yearly basis, the overall incidence of mortality in morbidly obese patients is at least twice as much as in patients who are not morbidly obese.4 Bariatric surgery has emerged as the most effective treatment for massive and sustained weight loss in patients with morbid obesity. More than 90% of the associated comorbid conditions are improved or resolved completely with gastric bypass (GBP), which has become the gold standard for bariatric surgical procedures. Very few studies are currently available regarding the improvement of survival in patients with GBP compared with those that do not receive bariatric surgery, but 1 large study from Canada reported a reduction of approximately 89% over a 5-year period in patients receiving bariatric surgery compared with those who do not.5 The benet of GBP has been extended to patients with increasingly complex comorbidities, some of which have been felt to be a contraindication to surgery. We recently reported our initial experience with this procedure in 30 patients with chronic renal failure (CRF) or kidney transplant.6 The current report documents an additional 2-year follow-up and includes 18 more patients, representing the majority of the worlds published experience.

Materials and Methods

Obesity has become an increasingly important cause of morbidity and mortality worldwide. In the United States, 300,000 deaths per year are caused by obesity and its related comorbidities.1 This is associated with more than $117 billion per year in Three groups of patients were analyzed: 32 patients with CRF who had GBP without transplant, 9 patients who had a GBP and then a kidney transplant, and 10 patients who had a prior transplant with a subsequent GBP because of signicant weight gain. No patient referred for a GBP was denied according to the severity of their illness. A standard GBP modied for limb length, as previously described,6 was used for all patients. One GBP surgery was performed laparoscopically and 31 by an open procedure using double-layer hand-sewn anastomosis, which is associated with fewer serious complications. The rst GBP in our series was performed March 16, 1993. Only 1 patient has been lost to follow-up. This study was approved by the institutional review board.
16
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Correspondence: J. Wesley Alexander, University of Cincinnati, 2123 Auburn Avenue, MOB Suite 315, Cincinnati, OH 45219. Electronic mail may be sent to jwesley.alexander@uc.edu.
0884-5336/07/2201-0016$03.00/0 Nutrition in Clinical Practice 22:1621, February 2007 Copyright 2007 American Society for Parenteral and Enteral Nutrition

February 2007
Table 1 Causes of death
Patient # Age at time of GBP

GASTRIC BYPASS IN RENAL FAILURE AND TRANSPLANT

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Gender

BMI at Comorbid conditions GBP

Length of dialysis, mo

Cause of death

POD

Renal failure without transplant 1 2 3 4 5 GBP, then transplant 6 Transplant, then GBP 7 8

62 35 54 48 53

M F F F F

53 52.3 41.6 56.8

DM, HTN, HL, DJD HTN, SA DM, HTN, HL, DJD DM, HL, SA, DJD

22.7 2.1 21.7 7.3 ?

62.9 HL, DJD

Cardiac 1185 Failure of vascular access 777 Cardiac 669 Cardiac arrest while receiving 175 dialysis Chronic severe hypotension while 112 receiving dialysis, causing bowel necrosis Cardiac MVA Cardiac 2869 270 120

54 34 52

F M F

37.5 DM, HTN, HL 51.2 HTN, HL, DJD 46.4 DM, HTN, DJD

0.8 0 0

BMI, body mass index; DJD, degenerative joint disease; DM, diabetes mellitus; GBP, gastric bypass; HL, hyperlipidemia; HTN, hypertension; MVA, motor vehicle accident; POD, postoperative day; SA, sleep apnea.

Results
The median hospital stay was 4 days for the patients with CRF, 5 days for the patients with GBP then transplant, and 6 days for patients with transplant then GBP. This was longer than our median stay of 2 days because of the complexity of their disease and the need for dialysis in some patients. No patient required blood transfusions related to the surgery, and there were no surgical leaks or splenic injuries. A technique was used in which antibiotics were infused into the wound as previously described.7 One patient developed wound separation and secondary infection after the sutures were prematurely removed, but there were no other wound infections that started in the subcutaneous tissues. Eight patients have died in this series during the 13-year follow-up, all 3 months or more after GBP as described in Table 1. One-year patient survival was 92%. CRF Patients Thirty-two patients had established renal disease at the time of GBP; they have not yet received a transplant. The average age was 44.4 years, and average BMI was 48 kg/m2. Changes in BMI after GBP for individual patients are shown in Figure 1. Mean length of time receiving dialysis for those receiving dialysis was 2.5 years. Changes in BMI and comorbid conditions at 12 months postoperatively are shown in Table 2. Also shown are pre- and post-GBP serum albumin levels. GBP and Then Transplant Nine patients had a kidney transplant after they lost a signicant amount of weight after GBP.

Changes in BMI and time after GBP are shown in Figure 2. Transplant and Then GBP Ten patients who had a transplant became morbidly obese afterwards and developed secondary complications. Their mean age was 44 years. All were receiving immunosuppression and 9 were taking corticosteroids. GBP occurred on average 5.3 years after transplant. Changes in BMI for up to 5 years are shown in Figure 3. Resolution or Stabilization of CRF Five patients experienced resolution or stabilization of their CRF after GBP. Because of the particular interest in these cases, these patients are discussed individually. Patient 1 is a 42-year-old female with chronic membranous glomerulonephritis diagnosed by biopsy. She had proteinuria consistently 300 mg/L and had unsuccessful treatment with prednisone. Her BMI was 53.3 kg/m2 at the time of GBP on August 26, 1999, but dropped to a 1-year postoperative BMI of 32.3 kg/m2 and a 5-year postoperative BMI of 29 kg/m2. The proteinuria resolved completely, and repeat biopsy showed resolution of the glomerulonephritis. Her creatinine has remained stable at 0.7 mg/dL since her bypass. Patient 2 is a 48-year-old woman who had a GBP on January 16, 2003. Her BMI was 49.4 kg/m2, and she had hypertension, diabetes, hyperlipidemia, and sleep apnea. She had heavy proteinuria, with a diagnosis of focal segmental glomerulosclerosis. Her BMI had dropped to only 37.9 kg/m2 by 3 years post-GBP, but her creatinine has stabilized at 1.5 mg/dL, which is at the level when she was rst diagnosed with renal insufciency.

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Figure 1. Weight loss after gastric bypass in renal failure patients without transplant.

Patient 3 is a 21-year-old woman with a BMI of 44.5 kg/m2 when she underwent GBP surgery in August 2003. At that time, she had biopsy-proven glomerulonephritis, and her creatinine was 1.7 mg/dL. She continued to have proteinuria, but her creatinine dropped to 0.6 mg/dL at the end of the second year, associated with a drop in BMI to 28.4 kg/m2. Patient 4 is a 47-year-old woman who underwent GBP on August 5, 2003. Her initial BMI was 51.0 kg/m2, and creatinine was 2.6 mg/dL. With a reduction in BMI to 34.5 at 2 years postoperatively, her serum creatinine level had dropped to 2.2 mg/dL, and creatinine clearance increased from 23 to 35 mL/min. The original diagnosis was diabetic nephropathy. Patient 5 is a 25-year-old woman with an initial BMI of 39 kg/m2 who underwent GBP in November 2004. Her original diagnosis was glomerulonephritis, and she had been receiving dialysis for 9 months. Four months after her GBP, she was able to discontinue dialysis, and her creatinine is now stable at 5.1
Table 2 Changes in comorbid conditions at 12 months
Group (pts, no.) Diabetes (avg. meds)* Preop 12 mo Preop

mg/dL. She recently underwent an abdominoplasty, and her current BMI is 25 kg/m2. It is anticipated that she will eventually need preemptive transplantation.

Discussion
Effects of Morbid Obesity on Outcome Patients requiring dialysis for CRF have been noted to have a paradoxic relationship between weight and mortality.8 This was rst suggested by the Diaphane Collaborative Study in 1982.9 Subsequent studies have also shown that overweight and obese dialysis patients had a signicantly greater 12-month survival than those of normal weight10 and suggest that for every unit increase in BMI, the relative risk for mortality was reduced by 6%. More striking, increasingly underweight patients had the highest mortality, and a loss in BMI in obese patients receiving dialysis was associated with increased mortality. Johansen et al11 examined data for 418,055 patients

Blood pressure (avg. meds)* 12 mo

Cholesterol (mg/dL) Preop 12 mo

Triglycerides (mg/dL) Preop 12 mo

Albumin (g/dL) Preop 12 mo

GBP, no Tx (32) GBP, then Tx (9) Tx, then GBP (10)

16 (1.3) 6 (1.0) 4 (1.3)

7 (1.1) 2 (1.0) 2 (1.0)

145/84 (1.6) 137/82 (1.3) 151/80 (1.8)

124/76 (0.9) 126/73 (0.6) 133/78 (1.4)

184 191 232

133 181 191

258 297 205

149 234 183

4.0 3.3 3.8

3.9 3.8 3.9

GBP, gastric bypass; meds, medications; Tx, transplant. *Average number of medications daily/patient. p .05, remainder of groups too small for analysis.
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Figure 2. Weight loss after gastric bypass followed by kidney transplantation.

beginning dialysis between April 1, 1995, and November 1, 2000. A high BMI (highest reported 37) had increased survival over the 2-year average follow-up. Kalantar-Zadeh et al12 reviewed the subject in 2005 and also concluded that a high BMI was associated with improved survival. This paradox seemed to be related primarily to improved nutrition status. However, additional reports did not nd a positive inuence of high BMI on 2-year survival.13 Contrary ndings were also shown by Caravaca et al,14 who studied 376 patients with advanced CRF, not yet receiving

dialysis. Obese patients (BMI 30 k/m2) had a worse survival, notably in patients without signicant comorbidities. Unfortunately, most studies have been relatively short term, and only a small number of patients with BMI 35 kg/m2 have been studied. The paradoxic benecial effect of obesity in dialysis patients has not been found to apply to transplant patients. The most extensive study on this topic was presented by Meier-Kriesche et al,15 who analyzed the data from the United States Renal Data System (USRDS) database between 1988 and

Figure 3. Weight change after kidney transplantation followed by gastric bypass.

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1997 involving 51,927 adult transplant recipients. In their study, the relative risk for graft loss was approximately 1.4 in patients with a BMI 36 kg/m2. Similar risk ratios were found for death censored graft loss (RR 1.45 for BMI 36 kg/m2), death with a functioning graft (RR 1.36), and for cardiovascular-related complications (RR 1.4). The best overall results were found in patients with a BMI of 2224 kg/m2. It is well documented that obese patients have a higher incidence of wound complications and delayed graft function when they receive transplants.16 18 Furthermore, patients with comorbid conditions that are associated with cardiovascular events (eg, diabetes, hypertension, and hyperlipidemia) are at much higher risk than both dialysis and transplant patients.19 Because of the increased incidence of surgical complications and death from cardiovascular diseases, most transplant centers will often not transplant patients with a BMI 35 kg/m2. It is also generally perceived that the patients with super morbid obesity (BMI 50 kg/m2) do even worse, but this has not been well documented. Jardine et al20 studied cardiovascular risk factors after renal transplantation and conrmed that transplant recipients shared risk factors for myocardial disease with the general population. el-Agroudy et al21 compared obese transplant patients (BMI 30 kg/m2) to nonobese patients. The presence of hypertension, diabetes, and ischemic heart disease were clearly higher in the obese group, and there was a signicant difference observed for decreased graft and patient survival at 5 and 10 years after transplant. From the current data, it seems clear that extremely obese patients fare better with a transplant compared with similar patients who continue to receive dialysis.19 It is also clear that the comorbid conditions in dialysis patients related to cardiovascular disease can be markedly decreased by GBP, to a similar amount that occurs in morbidly obese patients who are not receiving dialysis.22 Resolution and Stabilization of Renal Function There has been recent evidence that dietary factors and obesity relate to the development of CRF. Reversal or stabilization of CRF by dietary means was suggested by Nielsen et al,23 who described a 60-year-old man with type 2 diabetes and increasing albuminuria. He began receiving a low-carbohydrate/high-fat diet, which caused a reversal in the albuminuria and improvement of renal function. The nding that 5 of our patients had stabilization or even reversal of their CRF is particularly interesting and strongly supports a contributing role of obesity for CRF. The mechanisms are not well established but could involve reversal of hyperltration injury, resolution of diabetes, or resolution of hypertension. There have been 3 additional case reports where bariatric surgery has stabilized CRF or has actually reversed renal disease after a GBP.24 26

Bariatric Surgery in Preparation for Transplantation We were able to identify only 3 case reports where a laparoscopic adjustable banding was used to prepare a patient for a renal transplant,27 and another report where an adjustable gastric band was used after transplant.28 One of the major reasons for performing a GBP in morbidly obese dialysis patients is to improve their comorbidities and prepare them for transplantation. Meier-Kriesche et al29 provided clear evidence that progression of vascular disease is ameliorated by kidney transplantation. By reversing the comorbid conditions leading to cardiovascular disease, it is felt that GBP will achieve the same reduction in risk as for nontransplant patients. However, this remains to be veried by larger studies. Pischon and Sharma30 compared overall reported mortality in obese compared with nonobese transplant patients. The 5-year mortality in obese patients was 23% 45% vs 10%11% in nonobese patients, and the mortality was caused primarily by an increase in cardiac events. Infections, wound complications, and delayed graft function were also more common in obese vs nonobese patients, but acute rejection was not different. In their review, hypertension, dialysis, death with a functioning graft, and worsening of long-term allograft survival were all higher in obese patients. Srinivas and Meier-Kriesche31 concluded that it was unclear whether dialysis patients should be made to lose substantial amounts of weight before kidney transplantation. They did acknowledge, however, that obesity clearly had adverse effects on outcome after transplantation. Data provided by UNOS indicated that 5-year patient survival was 80% for patients with BMI 40 kg/m2. Our experience would suggest that the indications should be the same as for patients without CRF (ie, BMI 40 kg/m2 or 35 kg/m2 with comorbid conditions). Although it is technically possible to conduct a transplant for some patients with a BMI 40 kg/m2, it is apparent that the comorbid conditions associated with morbid obesity lead to heart disease and increase the risk of cardiovascular death, and that a GBP will reduce these comorbid conditions. In our experience with 51 patients with renal failure/transplant, there have been no perioperative (30-day) deaths, despite that 26 had diabetes, 40 had hypertension, and 20 had dyslipidemia. Although these conditions improved, preexisting disease was not reversed, and all but 1 patient who died did so from cardiac or vascular disease. In our series of patients, nutrient deciencies were not limiting, although nutrition modications needed to be made for dialysis, transplantation, and GBP. Protein supplementation is sometimes difcult in GBP because of loss of appetite, aversion to certain protein-containing foods, and distasteful protein supplements. In dialysis patients with a GBP, particular attention should be given to supple-

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mentation with calcium with vitamin D, watersoluble vitamins, and iron. Careful monitoring can easily prevent signicant dietary deciencies. It is clear that patients with GBP may have changes in the pharmacokinetics of immunosuppressive drugs as we have previously reported (unpublished data). However, immunosuppression is usually driven by drug levels, making this less important. The literature is silent on the pharmacokinetics of most other drugs after GBP. We conclude that GBP is a highly effective procedure for achieving long-lasting weight loss and resolution of serious comorbid conditions in dialysis/ transplant patients with an acceptable morbidity/ mortality. Nutrition deciencies occur infrequently with appropriate supplements. Weight loss after GBP also seems to stabilize or improve renal disease in some patients, suggesting additional benets for GBP early in CRF. Early GBP may also allow preemptive transplantation.

References
1. McGinnis JM, Foege WH. Actual causes of death in the United States. JAMA. 1993;270:22072212. 2. U.S. Department of Health and Human Services. The Surgeon Generals call to action to prevent and decrease overweight and obesity 2001. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service, Ofce of the Surgeon General, 2001. 3. Fontaine KR, Redden DT, Wang C, Westfall AO, Allison DB. Years of life lost due to obesity. JAMA. 2003;289:187193. 4. Stevens J, Cai J, Pamuk ER, Williamson DF, Thun MJ, Wood JL. The effect of age on the association between body-mass index and mortality. N Engl J Med. 1998;338:17. 5. Christou NV, Sampolis JS, Liberman M, et al. Surgery decreases long-term mortality, morbidity, and health care use in morbidly obese patients. Ann Surg. 2004;240:416 423. 6. Alexander JW, Goodman HR, Gersin K, et al. Gastric bypass in morbidly obese patients with chronic renal failure and kidney transplant. Transplantation. 2004;78:469 474. 7. Alexander JW, Rahn R. Prevention of deep wound infection in morbidly obese patients by infusion of an antibiotic into the subcutaneous space at the time of wound closure. Obes Surg. 2004;14:970 974. 8. Salahudeen AK. Obesity and survival on dialysis. Am J Kidney Dis. 2003;41:925932. 9. Degoulet P, Legrain M, Reach I, et al. Mortality risk factors in patients treated by chronic hemodialysis: report of the Diaphane Collaborative Study. Nephron. 1982;31:103110. 10. Fleischmann E, Teal N, Dudley J, May W, Bower JD, Salahudeen AK. Inuence of excessive weight on mortality and hospital stay in 1346 hemodialysis patients. Kidney Int. 1999;55:1560 1567. 11. Johansen KL, Young B, Kaysen GA, Chertow GM. Association of body size with outcomes among patients beginning dialysis. Am J Clin Nutr. 2004;80:324 332. 12. Kalantar-Zadeh K, Abbott KC, Salahudeen AK, Kilpatrick RD, Horwich TB. Survival advantages of obesity in dialysis patients. Am J Clin Nutr. 2005;81:543554.

13. Combe C, Chauveau P, Laville M, et al; French Study Group. Nutrition in Dialysis. Inuence of nutritional factors and hemodialysis adequacy on the survival of 1,610 French patients. Am J Kidney Dis. 2001;37(suppl 2):S81S88. 14. Caravaca F, Martin MV, Barroso S, et al. Obesity and mortality in advanced chronic renal failure patients. Nefrologia. 2004;24:453 462. 15. Meier-Kriesche H-U, Arndorfer JA, Kaplan B. The impact of body mass index on renal transplant outcomes: a signicant independent risk factor for graft failure and patient death. Transplantation. 2002;73:70 74. 16. Bennett WM, McEvoy KM, Hennell KR, Valente JF, Douzdjian V. Morbid obesity does not preclude successful renal transplantation. Clin Transplant. 2004;18:89 93. 17. Marks WH, Florence LS, Chapman PH, Precht AF, Perkinson DT. Morbid obesity is not a contraindication to kidney transplantation. Am J Surg. 2004;187:635 638. 18. Armstrong KA, Campbell SB, Hawley CM, Johnson DW, Isbel NM. Impact of obesity on renal transplant outcomes. Nephrology. 2005;10:405 413. 19. Pelletier SJ, Maraschio MA, Schaubel DE, et al. Survival benet of kidney and liver transplantation for obese patients on the waiting list. Clin Transplant. 2003;77 88. 20. Jardine AG, Fellstrom B, Logan JO, et al. Cardiovascular risk and renal transplantation: post hoc analyses of the Assessment of Lescol in Renal Transplantation (ALERT) Study. Am J Kidney Dis. 2005;46:529 536. 21. el-Agroudy AE, Wafa EW, Gheith OE, Shehab el-Dein AB, Ghoneim MA. Weight gain after renal transplantation is a risk factor for patient and graft outcome. Transplantation. 2004;77:1381 1385. 22. Alsabrook GD, Goodman HR, Alexander JW. Gastric bypass surgery for morbidly obese patients with established cardiac disease. Obes Surg. 2006;16:12721277. 23. Nielsen JV, Westerlund P, Bygren P. A low-carbohydrate diet may prevent end-stage renal 2 diabetes: a case report. Nutr Metab. 2006;3:2327. 24. Agnani S, Vachharajani VT, Gupta R, Atray NK, Vachharajani TJ. Does treating obesity stabilize chronic kidney disease? BMC Nephrol. 2005;6:710. 25. Soto FC, Higa-Sansone G, Copley JB, et al. Renal failure, glomerulonephritis and morbid obesity: improvement after rapid weight loss following laparoscopic gastric bypass. Obes Surg. 2005;15: 137140. 26. Izzedine H, Coupaye M, Reach I, Deray G. Gastric bypass and resolution of proteinuria in an obese diabetic patient. Diabet Med. 2005;22:17611762. 27. Newcombe V, Blanch A, Slater GH, Szold A, Fielding GA. Laparoscopic adjustable gastric banding prior to renal transplantation. Obes Surg. 2005;15:567570. 28. Weiss H, Nehoda H, Labeck B, Oberwalder M, Konigsrainer A, Margreiter R. Organ transplantation and obesity: evaluation, risks and benets of therapeutic strategies. Obes Surg. 2000;10: 465 469. 29. Meier-Kriesche HU, Schold JD, Srinivas TR, Reed A, Kaplan B. Kidney transplantation halts cardiovascular disease progression in patients with end-stage renal disease. Am J Transplant. 2004;4:16621668. 30. Pischon T, Sharma A. Obesity as a risk factor in renal transplant patients. Nephrol Dial Transplant. 2001;16:14 17. 31. Srinivas TR, Meier-Kriesche H-U. Obesity and kidney transplantation. Contrib Nephrol. 2006;151:19 41.

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