NDT Advance Access originally published online on June 27, 2007
Nephrology Dialysis Transplantation 2007 22(11):3304-3310; doi:10.1093/ndt/gfm345
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Role of dietary intervention on metabolic abnormalities and nutritional status after renal transplantation
1Department of Neuroscience, Physiology Nutrition Unit and 2Division of Nephrology, University Federico II, Naples, Italy
Correspondence and offprint requests to: Bruna Guida, Department of Physiology, Faculty of Medicine, University ‘Federico II’ of Naples, Via Tasso 91/B 80100 Napoli, Italy. Email: bguida{at}unina.it
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Abstract |
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Background. In these last years, several traditional risk factors for cardiovascular disease, like obesity, dyslipidaemia, hypertension and post-transplant diabetes mellitus have been also identified as important non-immunological risk factors leading to the development of chronic allograft nephropathy, the first cause of graft loss in transplanted patients. The aim of the present study was to determine the effects of a 12-month dietary regimen on the nutritional status and metabolic outcome of renal transplant recipients in the first post-transplant year.
Methods. Forty-six cadaver-donor renal transplant recipients (mean age 40.8 ± 10.1-years), enrolled during the first post-transplant year (4.8 ± 3.3 months) and followed prospectively for a 12 month period. Biochemical and nutritional markers, anthropometric measurements, body composition (by conventional bioelectrical impedance analysis) and dietary records (using a detailed food-frequency questionnaire) at baseline and after 12 months.
Results. Compliance to the diet was related to sex (male better than female) and was associated with weight loss primarily due to a decrease in fat mass, with decrease in total cholesterol and glucose plasma levels and with a concomitant rise in serum albumin.
Conclusion. After renal transplantation, health benefits of proper metabolic balance that include reduced body fat, weight loss, lower cholesterol and triglycerides levels and an improvement, fasting glucose levels can be obtained when dietary intervention occurred.
Keywords: bioelectrical impedance analysis; dietary intervention; metabolic abnormalities; nutritional status; renal transplantation
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Introduction |
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The importance of metabolic factors in conditioning the outcome of a renal graft is widely recognized. There is strong evidence, in fact, that the presence of metabolic syndrome (MS), which includes obesity, dyslipidaemia, hypertension and reduced tolerance to glucose, is associated with impaired renal allograft function after the first post-transplant year [1] and may strongly influence the onset and the progression of cardiovascular (CV) diseases: many of the traditional CV risk factors, in fact, lead to the development of chronic allograft dysfunction (CAD) [2]. The optimal control of metabolic abnormalities and the prevention of MS, therefore, should be considered mandatory for the correct management of renal transplant patients.
The first year after transplantation is crucial in determining important modifications in body weight and body mass index (BMI) and in developing hyperlipidaemia (HLP) or altered peripheral resistance to glucose [3]. A recent study by de Vries et al. [1] has stressed the difficulty to treat efficaciously these metabolic alterations once they have established, clearly suggesting the need of an ‘early’ therapeutic intervention to correct the poor dietary habits of transplant patients, further influenced by a reduced renal function, the presence of proteinuria, the use of immunosuppressive drugs, or by dialysis-related problems. It is well known, in fact, that moderately obese patients gain more weight after transplantation than patients with a normal BMI [4] and that patients with a familiar history of diabetes are more prone to develop reduced tolerance to glucose when treated with tacrolimus; thus, prevention of metabolic risk factors must start when the patients still are on the waiting list [5].
Several studies have investigated the modifications of nutritional status after kidney transplantation, but only a few of them have described these changes during a controlled dietary regimen, started in the first months after transplantation. Therefore, the aim of the present work was to determine the effects of a 12-month dietary regimen on some of the parameters defining the MS and on the nutritional status of renal transplant recipients.
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Patients and methods |
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The preliminary data of this investigation refer to 46 renal transplant recipients from deceased donors (all first transplant), with a mean age of 40.8 ± 10.1 years, enrolled during the first post-transplant year (4.6 ± 3.3 months after surgery) and prospectively followed for a 12 month period. Inclusion criteria were age >18 years stable renal function in the last month, absence of infection, cancer or any acute illness in the last 2 months, constancy in protein and salt intake (±10%) in the last month, as assessed by weekly measurement of routine laboratory examinations (urinary urea, phosphate and sodium chloride excretion).
All the subjects gave their informed consent to the study that was approved by the Ethical Committee of the Medical School of the University Federico II of Naples. The immunosuppressive regimen of the patients included ciclosporin (CYA) or tacrolimus (FK) with steroids and possibly mycophenolate mofetil (MMF), according to our protocol, which includes progressive tapering of steroids (from 16 to 4 mg/day of methylprednisolon in 3 months), with trough blood levels of CYA and FK averaging 150–200 and 7–10 ng/ml, respectively, in the third month after transplantation. Therefore, when starting the study, all the patients were administered 4 mg/day of methylprednisolon, and had calcineurin inhibitor levels in the desired range.
The diet plan was arranged to fit an energy intake higher than 25/kcal/kg/ideal body weight/day, with 55% of carbohydrates and total fat not exceeding 30% of calories (fatty acids <10% of calories and dietary cholesterol limited to 300 mg/day), according to guidelines of the American Heart Association (AHA) Step One Diet [6]. Protein intake was restricted to 0.8 g/kg of ideal body weight/day. Patients were prescribed low-salt food, so that they did not exceed 1.5 g/day of sodium content and were asked to limit the amount of additional salt to 3 g/day [7]. Total sodium and protein intake, however, was assessed by urinary excretion of NaCl and urea from 24-h samples, in agreement with standard formulae.
A critical point of our diet plan was to encourage the patients to increase their level of physical activity to 30 min/day in 5 out of 7 weekdays, strongly recommending them to modify their habits (walking rather than using mechanized transport or the elevator, when possible). In the follow-up interviews, leisure-time physical activity was assessed by the following question: ‘How often do you participate in light physical activity, such as walking, running, exercising, etc.?’ [8].
In all patients’ anthropometric measurements, body composition, biochemical nutritional markers and dietary records were registered in basal condition (Time 0) and after 12 months (Time 12). Body mass index (BMI) was calculated as the ratio body weight/height2 (in kg/m2) [9]; body composition was determined by conventional bioelectrical impedance analysis (BIA). Resistance (R) and reactance (Xc) were measured with a single-frequency 50 kHz bioelectrical impedance analyser (BIA 101 RJL, Akern Bioresearch, Firenze, Italy) according to the standard tetrapolar technique by applying the software provided by the manufacturer, which incorporated validated predictive equations for total body water (TBW), fat mass (FM) and fat free mass (FFM) [10,11]. The same investigators performed anthropometry and BIA measurements.
The degree of compliance to the diet was measured during a personal interview by a detailed food-frequency questionnaire, including 130 foods and beverages [12]. Patients who had 90% compatibility between the questionnaire and the prescribed diet during the first 3 months were considered compliant (group diet). The remaining patients, who did not adhere to the prescriptions, were considered non-compliant and, according to the aim of the study, were used as control group; the patients of both groups, however, received the same number of visits throughout the study.
Renal function was measured by 24 h creatinine clearance, with the evaluation of the creatinine coefficient to validate the ability of the patients to perform a correct urine collection.
Results are expressed as mean ± SD. Differences in mean values were evaluated by Student's t-test for paired data (at baseline and after 12 months), or unpaired data (to compare patients and control). Data were stored and analysed using the SPSS program (Statistical Package for Social Science, release 11.01; SPSS Chicago, IL, USA). P values <0.05 were considered statistically significant.
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Results |
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According to our questionnaire-based classification, 25 patients were considered compliant to our dietary prescriptions (group diet) and the remaining 21 as non-compliant (group control). Analysis of baseline characteristics of these two groups showed no significant difference in most of their demographic and anthropometric data, nor in energy, protein and total fat intake (including cholesterol), even when the patients were split according to gender, with males obviously showing higher values in all the parameters. These data are reported in Table 1. ‘A posteriori’ analysis of urinary data collected at time 0 (T0) and time 12 (T12) confirmed that all the patients previously classified as ‘compliant’ by interview, showed a significant reduction in intake of sodium and protein, as assessed by urinary excretion of NaCl and urea (Table 2), further validating our classification by questionnaire.
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At the end of follow-up (Time 12), as expected, patients of the diet group showed a significant loss of body weight, paralleled by a similar reduction in BMI (Table 3); these changes were associated with concomitant significant reductions in cholesterol and plasma glucose; it is noteworthy that most of these changes occurred in male patients. In the control group, conversely, most of the above-mentioned parameters were increased (Table 2 and Figure 1). No significant change was observed in triglyceride plasma levels in the two groups, although they tended to decrease in both sexes of the diet group and to rise in patients of the control group (Table 2). Moreover, a significant increase in albumin concentration was observed in male patients of the diet group (+8%, P < 0.05 vs baseline), whereas plasma levels of haemoglobin resulted statistically higher only in females of the diet group (+18%, P < 0.05 vs baseline).
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The variations in body weight (BW) and body composition during the study were assessed by BIA (Table 3). The weight loss observed in patients of group diet was mainly due to a decrease in FM, while the BW gain in group control was associated with an increased FM; both groups, however, showed only marginal modifications of FFM and BCM. Again, these changes were mostly represented in men of the diet group, who showed a significant decrease in BW, BMI and particularly in FM (–11.3%; –12.5% and –40.7% compared with time 0, respectively) with a concomitant slight decrease in FFM (–2.4%); no significant difference was detected in the female subjects of this group. Conversely, the increase in BW, BMI and FM of group control was equally represented in both sexes (Table 3).
Paradoxically, the prevalence of post-transplant diabetes mellitus (PTDM) was higher in patients of group diet (5/24, 20.8%) than in group control (3/19, 15.8%), although plasma levels of glucose were better controlled in the former group.
Renal function remained stable in all the patients throughout the study (Table 2). The immunosuppressive treatment was quite similar between the two groups, with exception of mycophenolate mofetil (MMF), more used in patients of group diet (52% vs 24%) (Table 4). A significant decrease in daily doses and blood trough levels of ciclosporin was observed between Time 0 and Time 12 in both groups. There were some differences between groups in rejection episodes (2/1, group diet vs control, respectively) and two additional patients had a rejection episode before their enrollment (one for each group), whereas the prevalence of cytomegalovirus (CMV) infections was double in patients of the diet group (21% vs 10.5%). After 12 months of observation, the need for anti-hypertensive drugs was greater in patients of group control (+50%, P < 0.0003 vs Time 0) than in patients of group diet (+28%, P < 0.02). Statins were administered to a similar percentage of patients (56% in group diet and 48% in control patients; NS): the patients of group diet were already under statins at the time of enrollment in the study; in group control, seven patients were on statins at the beginning of the study, three started during the study.
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Most patients referred to had increased their daily activities according to the prescribed suggestions, although only 7/25 patients of the diet group performed regular moderate exercise 3–5 days/week (six males and only one female).
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Discussion |
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Kidney transplantation represents the treatment of choice for end-stage renal disease. In the last decade, the development of new immunosuppressive strategies has strongly reduced the incidence of acute rejection and has greatly improved the 1-year survival rate of the graft; nevertheless, the long-term survival has not consistently improved, since several non-immunological factors still influence the onset and the progression of CAD [13].
Among these latter factors, metabolic alterations represent one of the major risks for the graft [1]. Weight gain, altered lipid pattern [14] and increased resistance to insulin [15] are common findings after renal transplantation, following the use of immunosuppressive drugs, the sedentary lifestyle of the first post-transplant period and the loss of dialysis-linked restrictions in food and caloric intake. Hence, there is a need to acknowledge these disturbances in order to prevent and treat their consequences as soon as possible.
The data of our study demonstrate that the early referral to skilled dieticians and the good compliance of patients can largely prevent the onset of these disturbances in the first post-transplant period. In fact, the repeated dietary assessments obtained a good compliance in our patients, resulting in a balanced energy intake and an improved nutritional status, particularly in male subjects. These patients consumed less proteins, cholesterol and sodium and had a lower energy intake compared with baseline intakes and with control subjects (Table 2). This resulted in a consistent weight loss which was achieved with no significant decrease in FFM and BCM (Table 3), probably as a result of the balanced diet and of the behavioural changes in physical activity, strongly recommended to avoid muscle mass loss. In females, conversely, weight loss was less satisfactory, as a consequence of a lower compliance both to the diet and to the prescribed exercise program. In our experience, this is mostly explained by the different attitude of men and women towards health care. Probably, the biggest difficulty to self-care in women after renal transplant is to find the correct balance between a new clinical regimen and the different perspectives offered by transplantation, like return to work, family care, household chores, or new relationships. This determines less attention to ‘collateral’ healthcare needs, like physical activity or peculiar eating patterns.
The ideal amount of protein intake for the stable renal recipient is not yet clear: the goal should be to optimize the nutritional status while preserving the long-term graft function by avoiding unnecessary protein loads to a solitary kidney [16]. Our experience suggests that, despite the observed restriction in protein and sodium intake, an adequate nutritional status is maintained as indicated by the constancy of FFM and BCM and by the increased plasma levels of albumin, at least in male patients.
Hyperlipidaemia is described in 
80% of renal transplants and may adversely affect the outcome of the graft, determining a higher risk of acute rejection and chronic allograft failure [14,17,18], as also evidenced for hypertriglyceridaemia [13,19,20]. Despite this, there is strong evidence in the general population that the detrimental effect of hyperlipidaemia are well counterbalanced by modification of diet [21], a previous study failed to demonstrate that the reduction of fat intake could efficaciously normalize the lipid pattern in renal transplant patients [22]; in contrast to Tonstad's study, however, our patients did lose body weight: several studies have clearly demonstrated a significant link between the decrease in body weight or in energy intake and the lowering of serum cholesterol levels, as demonstrated in our patients [23,24,25]. Moreover, most patients of the diet group were already under statins when starting the study; nevertheless, their cholesterol levels were further reduced by 30% with a correct dietary approach: this does emphasize the role of the diet, on one hand, but mostly the need to correctly motivate the patient's adherence to the diet, which could avoid or reduce the use of statins. The reduction in CsA levels after 1 year, however, must be considered as an additive factor in lowering cholesterol in both groups.
The positive impact of the diet is also evident on glycaemic control, which was better attained in patients of the diet group, despite the higher group prevalence of PTDM in this latter group. PTDM pathogenesis is multifactorial and includes the immunosuppressive regimen (mostly calcineurin inhibitors), ethnicity, older age and increased BMI [15,26]; the improvement of blood glucose levels in our diet group was due to the loss in body weight and, probably, to the reduction of insulin resistance, the ‘core’ that all the parameters defining metabolic syndrome finally reach [1].
This study has several limits: the first is that the definition of the groups was determined ‘a posteriori’ after 3 months of diet; according to our policy, however, we did not consider it ethical to randomize the patients to have or not to have the dietary prescription; it is noteworthy, however, that this definition was correct since the analysis of biochemical data after 12 months of observation confirmed that, during the time course of the study, all the patients remained in the group to which they were assigned on a questionnaire-based choice.
A second limit is the absence of clinical outcomes: both the number of patients and the length of follow-up obviously preclude any possible conclusion on the future destiny of the graft. Renal function, however, remained stable in all the patients during the 12-month period and, although creatinine clearance may overestimate the true glomerular filtration rate, all the patients exhibited high values of creatinine clearance.
It must be noted that a higher prevalence of CMV infections (and rejections) was observed in the diet group, possibly as a consequence of the greater immunosuppression of this latter group (52% of these patients were administered MMF): although this should not influence the diet results, these events may condition the evolution of the graft.
Moreover, although it is not possible to prove any link between the reduced intake of sodium and protein and the lower need in anti-hypertensive drugs, in the long-term this difference should not be trivialized and could be responsible for a lower incidence of CV complications.
In conclusion, our data suggest that, in renal transplant patients, an adequate dietary regimen may obtain a proper metabolic balance associated with a reduction in BW and lower plasma levels of cholesterol, triglycerides and glucose. Therefore, a primary requisite to achieving optimal results after renal transplantation should be a comprehensive nutritional program supported by a skilful physician-dietician team. A scrupulous nutritional management is an indispensable option to help reduce the risk of long-term complications. Further studies, however, are necessary to assess the stability of these modifications and the possible beneficial effects on transplant outcome in the long-term.
Conflict of interest statement. None declared.
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Accepted in revised form: 4. 5.07
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