Table of Contents
Search Result Description
Our search yielded a total of 2682 results. After eliminating replicates, 2322 results were screened for title and abstraction. Of these, 2245 were excluded due to lack of association, and a total of 77 studies were included. After further screening, 77 articles were accessed to qualify and the full text was screened. Of these, 53 were excluded for specific reasons such as false study design, overlapping, false exposure or outcome, wrong language (different from English), or missing full text. The final number of studies included was 24. [19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42] (Figure 2).
Explanation of research characteristics
As shown in Table 2, most of the studies included in the review were cohort studies (n = 16).
Additionally, two RCTs were included and six cross-sectional studies were included. The included study had a total of 9,536 participants, with a minimum and maximum sample size of 56 and 3,342, respectively. The majority of the studies were conducted in a hospital setting (n = 16). Although male participants were higher in all studies than female participants; [35]. Studies have been conducted in various regions of the world, from Saudi Arabia to Australia, with the highest numbers from China (n = 5), Brazil (n = 3), and Poland (n = 2). The most common outcome assessed was diabetes (n = 14). Other following results considered body weight (n = 3), lipid profile (n = 2), body composition (n = 1), electrolyte disorder (n = 1), bone condition (n = 1), vitamin D (n = 1), and vitamin B12 (n = 1) deficiency. The most common immunosuppressant assessed was tacrolimus (n = 16). Participants' time after KTX was included in the study changed from 0 to 8.4 years. The majority of the studies were conducted one year after KTX (n = 9). Only five studies were conducted within one year after transplantation, and the majority (n = 10) were conducted over a long period.
Follow-up time for studies included in reviews
Quality evaluation
Figures 5 and 6 show quality assessments of observations and RCT included studies, respectively. 22 observational studies included current moderate (n = 13), serious (n = 7), or significant risk of bias (n = 2). Two RCTs included in the review show a low risk of bias ratings and a “some concerns” rating.
Risks of bias assessment of observational studies included in reviews using the Robins-I tool
Risks of bias assessment of RCTs included in reviews using the Rob 2 tool
Summary of results
In the summary, we evaluated seven key nutritional outcomes: diabetes, weight, lipid profile, body composition, electrolyte disorders, bone status, vitamin D, and vitamin B12 deficiency. A summary of the results is shown in Table 3.
Diabetes
In total, 14 studies evaluated the effect of immunosuppressive therapy on the development of diabetes after kidney transplantation. [19,20,21, 24,25,26, 31, 36,37,38,39,40,41,42]. Of these, we investigated nodat (n = 7) in seven studies and PTDM (n = 6) in six studies and one study focused on hyperglycemia (n = 1). In general, immunosuppressive regimen under consideration included combinations primarily containing calcineurin inhibitors. I) TAC vs CSA (n = 8). ii) TAC alone (n = 4) and CSA alone (n = 1). Additionally, one study examined the transition from CNIS to Belatacept. Overall, except for two studies [73,91]all concluded that CNIS is a risk factor for the development of diabetes. Nodat outbreak within the first year where KTX was investigated in three studies. However, variations in the assessment of immunosuppressive regimens have proven difficult to compare findings [36, 41, 42]. Xue et al. According to the incidence of Nodat is 20.3%, and the type of immunosuppressive regimen shows a consistent protective effect on its onset. On the contrary, Yu et al. We found a link between the use of tacrolimus and the onset of nodat. Finally, Terrec et al. We conclude that the slow transition from CNIS to Belacept proved to be a beneficial treatment strategy and significantly strengthens blood glucose parameters. NoDAT incidence in patients over 1 year after KTX was depicted in four studies, all of which examined the effects of tacrolimus or cyclosporine (TAC vs. CSA). [20, 25, 37, 39]. Three of them identified tacrolimus as having a higher risk of developing nodat compared to cyclosporine. [20, 25, 37]. One of them did not differ in the occurrence of nodat between tacrolimus and cyclosporine. [39]. A forest plot showing the relationship between tacrolimus and nodat development between KTX patients is described in Figure 3. Eight studies investigated the relationship between nodat development and tacrolimus use. Six studies showed an increased risk of nodat (OR>1, p <0.05). The study was too heterogeneous to perform subgroup analyses. Torres et al. We describe PTDM within the first year after KTX and conclude that in high-risk patients, adopting tacrolimus-based immunosuppression with steroid minimization provides an optimal balance between the incidence of PTDM. [21]. Two studies examining the incidence of PTDM in patients beyond the first year after KTX [24, 38]. Brzezinska et al. No differences were found between tacrolimus and cyclosporine regarding the incidence of PTDM after KTX. But Van Del Berg et al. We found that the use of tacrolimus is a risk factor for PTDM development. Three studies examined the long-term incidence of PTDM [19, 26, 40]. In them, tacrolimus has been identified as a risk factor for developing PTDM. Finally, cyclosporine was identified as a higher risk factor for hyperglycemia [31].
body weight
Three studies analyzed the effects of immunosuppressive therapy on body weight. Two of these were cohort studies and one section. [27, 33, 34]. Ruangkanchanasetr et al. According to the prevalence of obesity reached 12.6% in the first year, escalating to 28.6% within the first three years, and surged to 39.7% three years after transplantation. mTOR inhibitors were administered more frequently in obese patients compared to patients with normal BMI (16.1% vs. 7%; P = 0.056). Conversely, obese recipients showed significantly lower tacrolimus usage compared to those with normal BMI [8]. In contrast, Sayilar et al. The observed marked rise in body weight and body mass index are increased in both the CSA and TAC groups. After a successful kidney transplant, anthropometric measurements are usually increased in most recipients. The effect of calcineurin inhibitor types on weight gain remains unknown, but regression analysis showed that CNI types had not been identified as risk factors for obesity development by month 48. However, it is prudent to pay attention to its effects on lipid lipidemia in patients using CSA. Additionally, potential risks associated with TAC use in patients with predisposition to diabetes [35]. Another study found that obesity de Oliveira et al. On average, the percentage of weight gain reached 9% at 36 months after implantation, consistent with a significant increase in the prevalence of overweight and obesity during this period. Interestingly, steroid therapy had no effect on the percentage of weight gain after transplantation. Instead, weight gain can be attributed to factors such as increased appetite, fluid retention, and changes in energy balance that are indirectly generated by the use of steroids. However, it should be outlined that low-dose steroids play an important role in managing chronic inflammation and autoimmune conditions by reducing inflammation with fewer side effects than high-dose doses. Their use requires careful monitoring to balance risks with benefits such as osteoporosis and adrenal suppression. Instead, an association was found between younger recipient age, female gender, younger donor age, and higher creatinine levels with the most significant weight gain after transplant [27]. All studies were conducted in the long term within one year and within one year after implantation.
Lipid Profile
Two studies investigated the relationship between immunosuppression and lipid profiles between renal transplant receivers [23, 30]. One study was conducted within one year of KTX, one was conducted over a long period. The results were inconsistent. Bergmann et al. No statistically significant correlations have been reported between total or free prednisolone exposure (TAUC 0-6 hours or FAUC 0-12 hours) and serum levels of HDL cholesterol, LDL cholesterol, and triglycerides [23]. However, Ichimaru et al. The use of everolimus and corticosteroids was found to be a significant risk factor for lipid dysfunction. In the same study, cyclosporine was not identified as an important risk factor for the development of lipid dysfunction [30].
Body composition
In our review, we evaluated body composition between resapients in kidney transplants in one study. [32]. In this cohort study, significant increases were observed in various anthropometric measurements in both the CSA and TAC groups. These included hip and hip circumference at 1st and 48th and 48th months, hip and hip ratios between the first and third and sixth or sixth months, and neck circumference at 1st and 12th or 24th or 24th month. Additionally, there was a significant increase in post-transplant body fat percentage values from 3 to 24 months in the CSA group and for 24 to 48 months in both the CSA group and the TAC group. Furthermore, the rate of peri-hip change from the pre-implant period to the first, 12, and 24 months was significantly higher in the CSA group compared to the CSA group. However, there was no significant difference in percentage changes in other anthropometric parameters between the CSA and TAC groups at each time point. [35]. Recognizing the essential role that weight and BMI play in the care of patients after kidney transplants, it deserves another paragraph considering its importance for post-transplant health and well-being.
Electrolyte disorders
Electrolyte disorders in our review are explained in one study [22]. Patients without CNI therapy (n = 50) had a lower prevalence of hypochomaniemia, hypercaliaemia, and metabolic acidosis compared to calcineurin inhibitor treatment (4% vs 26%; 2% vs 14.1% and 2% vs 11.4%; P < 0.01). This study was conducted one year or later after transplantation.
Bone status
One study investigated the relationship between immunosuppressive therapy and bone status in kidney transplant patients. [29]. Gregorini et al. We found that there was a significant correlation (P < 0.05) between patients with KTX, both osteopenia and osteoporosis with the mammalian target of rapamycin (mTOR) inhibitor therapy (IMTOR). This study was conducted one year or later after transplantation. None of the studies included in this review mentioned the effect of steroids on bone status in patients with KTX.
Vitamin d
The relationship between immunosuppressive therapy and serum 25(OH)D levels in KTX patients in our review is explained in one study [28]. CNI was found to have a negative effect on serum 25(OH)D levels by Filipov et. Al. Furthermore, there was a negative association between the concentration of 25(OH)D and the gender of females, as well as the presence of DM and BMI. This study was conducted over a long period.
Vitamin B12
The association between immunosuppressants and vitamin B12 deficiency is explained in one study [33]. Pontes et al. found that among individuals with an appropriate intake of B12, this vitamin deficiency is more frequent in those using MMF (17%) vs. azathioprine (2%), p = 0.01. In conclusion, the prevalence of B12 deficiency in KTX was estimated to be 14%, which was associated with reduced B12 intake and reduced obesity, particularly in women, and MMF use.
