Nutrition Disturbances And Metabolic Complications in Kidney Transplant Recipients: Etiology, Methods Of Assessment And Prevention—A Review Ⅱ

7. Hyperuricemia

KTx patients are prone to hyperuricemia, which is an important risk factor of CV complications. It has been established that uric acid levels rise alongside decreasing eGFR— from both transplanted and native kidneys—which is the main risk factor of hyperuricemia aside from CsA treatment [68]. Uric acid levels ought to be periodically monitored in all KTx recipients, but especially in those with impaired eGFR or receiving CsA; a low-purine diet ought to be introduced. Key products to avoid include beer, meat, and its by-products, including animal-derived fats, as well as fatty fish and seafood. Dietitians and clinicians often provide patients with detailed tables with the purine load of different products [69]. 

The high intake of fructose by patients with kidney failure, including KTx patients, leads to increased serum levels of uric acid and TG [70]. KTx recipients tend to lean towards fructose- and cholesterol-rich diets [31]. Fructose is a popular substance used in the food industry, found in most processed foods; thus, when recommending dietary changes for KTx recipients, one should warn against store-bought jams, sweeteners, and processed snacks.

CLICK HERE TO KNOW CISTANCHE FOR CKD TREATMENT

8. Macronutrients: Recommendations for KTx 

Several studies prospectively analyzed the macronutrient pre- and post-transplantation intake with inconclusive results ranging from no signifificant changes within the first 6 months [64] to an increased fat intake observed both at the 3rd and 12th month timepoints [71]. A study conducted in Mexico analyzing the dietary compositions in long-term KTx follow-ups showed that the average recipient’s diet consisted of 25% fat, 15% protein, and 55% carbohydrates [72]. Polish KTx recipients in a long-term follow-up often chose energy-dense foods such as sweets and snacks, which provided them with an average of 449 kcal per day. Moreover, saturated fatty acids accounted for over half of their total fat intake. KTx recipients exceeded the general population recommendations of protein, cholesterol, sugar, phosphorus, and sodium while consuming insufficient amounts of fiber, potassium, and magnesium [73]. Another research group linked nutritional patterns and the associated changes in body composition to gender, steroid doses, delayed graft function, and the occurrence of acute rejection. Females consumed more protein and calories, and thus experienced post-transplant weight gain [74]. However, according to the CORPOS study, the disadvantageous shift in body composition may be mitigated through lifestyle adjustments, such as increased physical activity [75]. 

KTx recipients have no fixed set of dietary guidelines safe for those related to food–drug interactions. Most restrictions and recommendations result from individual comorbid conditions (DM, CV diseases, and hypertension), metabolic disorders, and of course graft function and the presence of proteinuria. The daily protein intake varies based on the time after KTx, graft function, and proteinuria.

9. Dietary Recommendations in the Early Post-KTx Period 

In the first 4 to 6 weeks after transplantation, tissue recovery combined with stress, increased catabolism, and high doses of GCSs lead to protein hypercatabolism. An adequate protein supply is necessary for quick recovery, wound healing, and lesser susceptibility to infections. Therefore, the early post-KTx period revolves around recovery. The target daily protein intake ranges from 1.2 to 2 g/kg of the ideal body weight [71,76]. As weight loss is not the focus, the caloric intake should fall between 30 and 35 kcal/kilogram of body mass/day [76], 50–70% of that obtained from carbohydrates.

Due to low tubular reabsorption and disproportionately high parathormone levels, hypophosphatemia is common in the first few weeks following KTx [77]. In the early post-KTx period, it is necessary to monitor phosphorus blood levels on a weekly basis, especially in patients with rapidly improving graft function, as they may require high-phosphate products or even oral supplementation [78,79]. In the early post-transplant period, there is a tendency towards either hyper hyperkaliemia. Hyperkalemia is usually a sideeffect of medications; 5 to 40% of patients treated with CNIs develop hyperkalemia [79]; other medications include i. a. sulfamethoxazole with trimethoprim, β-blockers, and heparin. If hyperkalemia occurs (mainly in patients with impaired graft function), the potassium intake should be reduced to 3 g/day [80], once other reversible causes of hyperkalemia such as metabolic acidosis, which is common in the early post-KTx period, have been excluded. Without surgical contraindications, oral nutrition including solid meals may be introduced 2–3 days following the procedure. Enteral or parenteral nutrition should be considered if nausea, ileus, or persistent vomiting prevent oral nutrition for more than 5 days [2]. 

Gastrointestinal distress, dyspepsia, and diarrhea are often observed in the early weeks after transplantation. These often result from immunosuppressive medications, mainly mycophenolate mofetil and TAC. Thus, from our clinical practice, products including or based on milk, as well as rich in fiber, should be excluded to avoid the further exacerbation of gastrointestinal distress. Instead, an easily digestible diet is preferred. In addition, as hyperglycemia is often observed, monosaccharide intake is restricted. 

Recipients’ physical fitness in the early post-KTx phase is limited by their low activity level from the dialysis period, early post-operation stage and frequently suboptimal allograft function, anemia, fluid overload, and mineral disturbances [81,82]. As soon as there are no contraindications, patients ought to perform moderate exercise for at least 30 minutes five times a week [83]. 

10. Dietary Recommendations in the Long Term after KTx 

Dietary recommendations for recipients in the long term after KTx depend largely on kidney graft function, maintenance therapy, including immunosuppressive drugs, and pre-existing and new comorbidities, as well as PTDM, HA, CV diseases, lipid disturbances, or hyperuricemia. Patients with good and stable graft function ought to follow the same basic recommendations as the general population. Likewise, they can partake in the same physical activity recommended for their age and non-renal comorbidity burden [84,85]. 

A prospective study showed that the physical activity of KTx recipients increased up to 30% and reached a plateau after the first 12 months of follow-up [85]. The KDOQI recommends moderate-intensity physical activity to be performed five times a week for 30 min. Aside from physical health benefits, exercise interventions potentially improve quality of life [86]. They also positively impact the lipid profile, particularly HDL levels [81]. In these times, patients should be encouraged to take advantage of mobile applications and wearable gear dedicated to fitness in order to track progress and increase mental motivation.

During the maintenance period, the recommended daily energy intake for KTx patients should be 25–35 kcal/kg/day [2]; adjustments ought to be made accordingly for under or overweight patients. Unlike in the first 4–6 weeks post-KTx, about 45–50% of the daily caloric intake should come from carbohydrates [76]. The 2020 KDOQI guidelines do not specify the target protein intake for KTx recipients, only referring to CKD and ESKD populations. According to other sources, the estimated protein intake would be 0.6–0.8 g/kg/day in the case of non-diabetic and 0.8–0.9 g/kg/day in the case of diabetic patients [76]. Other sources indicate that KTx recipients should not exceed 0.75 g/kg/d for females and 0.84 g/kg/d for males to maintain good graft function and overall well-being [87]. Per KDOQI, we lack sufficient data to proclaim if either plant- or animal-based sources of protein are superior and thus preferred [2]. Patients with preexisting diabetes or those who develop PTDM should rather choose complex carbohydrates over monosaccharides and maintain a high fiber intake. The daily fiber intake should be 25–35 g per day [88]; this also helps prevent constipation and thus hyperkalemia, bacterial translocation, and diverticulitis.

Due to the high prevalence and risk of dyslipidemia, KTx recipients are recommended to follow a low-fat, low-cholesterol diet. Between 30 and 35% of calories consumed daily should come from fats with less than 8–10% coming from polyunsaturated and trans fatty acids, while some sources suggest that monounsaturated fatty acids may account for up to 20% of daily calories [29]. Additionally, a diet high in fiber and low in trans fats helps maintain normal blood glucose levels and lower TG and LDL cholesterol. KDOQI guidelines suggest prescribing the Mediterranean diet to improve the lipid profile. 

As hypertension arteriosum is highly prevalent in the KTx population, over 90% of recipients require anti-hypertensive medication [89]; HA necessitates a low-sodium diet, the recommended intake of which per KDOQI guidelines is 2–3 g/day [2]. 

11. Dietary Patterns in the KTx Population 

While recommendations individually refer to macro- and micronutrients, patients consume their meals as a whole, and thus, while specifific guidelines prove useful for clinicians, individual patients require a more realistic, comprehensible approach, such as whole dietary patterns.

The Dietary Approaches to Stop Hypertension (DASH) has been investigated as a potentially beneficial intervention in KTx due to its proven effect on high blood pressure. The key principles include a low sodium intake and the moderate consumption of lean protein and finish with the avoidance of red and processed meats, combined with a high intake of fruits, vegetables, whole grains, low-fat dairy, and fiber. This pattern facilitates low-fat consumption, with a preference of monounsaturated fats over saturated and trans fats. In a large cohort study of over 600 KTx recipients, the DASH eating pattern was associated with a lower risk of decreased graft function and all-cause mortality [90]. In the general population, the DASH diet signifificantly improves blood pressure, total cholesterol, and LDL serum concentrations. 

Likewise, the Mediterranean diet has a proven beneficial effect on kidney graft function [91]. It focuses on planning meals rich in whole grains, vegetables, fruits, seeds, nuts, beans, legumes, and olive oil, with fish consumed on a twice-a-week basis. The predominance of unsaturated fats over saturated fats found in red meat reduces oxidative stress, chronic inflflammation, and atherosclerosis [92,93]. Vuˇckovi´c et al. explored the links between sticking to a Mediterranean diet, body composition, and depression symptoms and found an association between low muscle mass and depression symptoms [94].

Both of these eating patterns appear beneficial against insulin resistance, inflflammation, oxidative stress, and dyslipidemia [93]. Interestingly enough, the 2020 KDQOI guidelines mention only the Mediterranean diet as a potential means of improving lipid profiles. 

In recent years, the interest in vegetarian and vegan diets has increased worldwide. The potential superiority of plant-based sources of protein has spiked an ongoing debate in the nephrology community [95]. Plant-based diets help alleviate acidosis and prevent hyperphosphatemia, as the phosphorus derived from plants is more difficult to absorb into the gastrointestinal tract. Moreover, they have a higher fiber content, which is necessary to maintain a healthy gut microbiome. High-fiber diets help decrease the production of uremic toxins associated with the microbiome and lower the risk of obesity, diabetes, and dyslipidemia. However, patients who follow vegetarian diets are at a higher risk of iron-deficiency anemia; dairy and eggs remain the only source of vitamin B12; in addition, plant-based iron has lower bioavailability [96]. Owing to multiple drug–food interactions, monitoring immunosuppressant trough levels is crucial during major dietary changes. 

Due to the high incidence of mineral and bone disorders in this population, recipients must monitor their calcium intake; the recommended daily dose is 800–1000 mg, unless hypercalcemia occurs [2], with a phosphorus intake of 1200–1500 mg/day [71,83]. 

12. Nutritional Screening 

The key to preventing malnutrition is screening; bi-annual assessments are recommended to find patients at risk of developing both PEW and obesity [2]. In KTx recipients, DXA remains the gold standard for body composition analysis; however, skinfold calipers suffice for body fat measurements in individuals without edema. According to experts, it may prove useful to assess body composition alongside classic measurements such as body mass and BMI at the first appointment and periodically monitor them every 3 months in the case of KTx recipients [2]. In addition, the Malnutrition Inflflammation Score may be applied; serum biomarkers such as albumin and transthyretin may serve as complementary tools.

13. Conclusions

Preventing nutrition disturbances is crucial in the KTx population in order to minimize the risk of CV events, and metabolic complications, and to maintain good graft function. A comprehensive set of guidelines dedicated to kidney transplant recipients ought to be developed to aid physicians and clinical dietitians in providing patients with the best care possible.

Author Contributions: 

M.G.: Conceptualization, methodology, investigation, writing—original draft preparation, writing—review and editing. I.K.: Conceptualization, methodology, investigation, writing—review and editing, supervision. All authors have read and agreed to the published version of the manuscript. 

Informed Consent Statement: Not applicable. 

Data Availability Statement: Not applicable. 

Conflicts of Interest: The authors declare no conflict of interest.

References 

1. Kovesdy, C.P. Epidemiology of Chronic Kidney Disease: An Update 2022. Kidney Int. Suppl. 2022, 12, 7–11. [CrossRef] [PubMed] 

2. Ikizler, T.A.; Burrowes, J.D.; Byham-Gray, L.D.; Campbell, K.L.; Carrero, J.J.; Chan, W.; Fouque, D.; Friedman, A.N.; Ghaddar, S.; Goldstein-Fuchs, D.J.; et al. KDOQI Clinical Practice Guideline for Nutrition in CKD: 2020 Update. Am. J. Kidney Dis. 2020, 76, S1–S107. [CrossRef] [PubMed]

3. Hwang, J.H.; Ryu, J.; An, J.N.; Kim, C.T.; Kim, H.; Yang, J.; Ha, J.; Chae, D.W.; Ahn, C.; Jung, I.M.; et al. Pretransplant Malnutrition, Inflflammation, and Atherosclerosis Affect Cardiovascular Outcomes after Kidney Transplantation Dialysis and Transplantation. BMC Nephrol. 2015, 16, 109. [CrossRef] [PubMed] 

4. Fouque, D.; Kalantar-Zadeh, K.; Kopple, J.; Cano, N.; Chauveau, P.; Cuppari, L.; Franch, H.; Guarnieri, G.; Ikizler, T.A.; Kaysen, G.; et al. A Proposed Nomenclature and Diagnostic Criteria for Protein-Energy Wasting in Acute and Chronic Kidney Disease. Kidney Int. 2008, 73, 391–398. [CrossRef] [PubMed] 

5. Guida, B.; di Maro, M.; di Lauro, M.; di Lauro, T.; Trio, R.; Santillo, M.; Belfifiore, A.; Memoli, A.; Cataldi, M. Identifification of Sarcopenia and Dynapenia in CKD Predialysis Patients with EGWSOP2 Criteria: An Observational, Cross-Sectional Study. Nutrition 2020, 78, 110815. [CrossRef] [PubMed] 

6. Turshudzhyan, A.; Inyangetor, D. Uremic and Post-Transplant Gastropathy in Patients with Chronic Kidney Disease and End-Stage Renal Disease. Cureus 2020, 12, e10578. [CrossRef] 

7. McIntyre, C.W.; Harrison, L.E.A.; Eldehni, M.T.; Jefferies, H.J.; Szeto, C.C.; John, S.G.; Sigrist, M.K.; Burton, J.O.; Hothi, D.; Korsheed, S.; et al. Circulating Endotoxemia: A Novel Factor in Systemic Inflflammation and Cardiovascular Disease in Chronic Kidney Disease. Clin. J. Am. Soc. Nephrol. 2011, 6, 133–141. [CrossRef]

8. Szczeci ´nska, K.; Wajdlich, M.; Nowicka, M.; Nowicki, M.; Kurnatowska, I. Effects of Oral Bicarbonate Supplementation on the Cardiovascular Risk Factors and Serum Nutritional Markers in Non-Dialysed Chronic Kidney Disease Patients. Medicina 2022, 58, 518. [CrossRef] [PubMed]

9. Carron, C.; de Barros, J.P.P.; Gaiffe, E.; Deckert, V.; Adda-Rezig, H.; Roubiou, C.; Laheurte, C.; Masson, D.; Simula-Faivre, D.; Louvat, P.; et al. End-Stage Renal Disease-Associated Gut Bacterial Translocation: Evolution and Impact on Chronic Inflflammation and Acute Rejection after Renal Transplantation. Front. Immunol. 2019, 10, 1630. [CrossRef] 

10. Zarififi, S.H.; Shadnoush, M.; Pahlavani, N.; Malekahmadi, M.; Firouzi, S.; Sabbagh, M.G.; Rezaiyan, M.K.; Islam, S.M.S.; Yahyapoor, F.; Arabi, S.M.; et al. Nutritional Status in Kidney Transplant Patients before and 6-Month after Transplantation: Result of PNSI Study. Clin. Nutr. ESPEN 2021, 41, 268–274. [CrossRef] 

Supportive Service:

Email:wallence.suen@wecistanche.com 

Whatsapp/Tel:+86 15292862950

Shop:

https://www.xjcistanche.com/cistanche-shop