Table 3 The summary of results from studies assessing the use of immunosuppressive therapy and the nutritional status of kTx patients

1. Diabetes

Borda, 2014 [20]

NODAT

Tac vs. CsA (steroid free therapy)

The incidence of diabetes was significantly different in the CsA group compared to the Tac group (14% vs. 26%, p = 0.0002). Tac (OR = 1.258, p = 0.05); CsA (OR = 0.317, p = 0.077)

Yes. Tac

Brzezinska, 2013 [24]

PTDM

Tac vs. CsA

In 103 patients (50%), we diagnosed glucose metabolism disorders. 19% of patients had PTDM, 14% IFG, and 17% IGT. We did not find any differences in the frequency of glucose metabolism disorders between patients treated with tacrolimus and with cyclosporine

No difference

Chen, 2015 [25]

NODAT

Tac vs. CsA

The incidence of NODAT at 24 months was 28.6%. Independent risk factors of NODAT, evaluated by logistic regression, were as follows: age > 50 (p < 0.001), HCV infection (p = 0.004), acute rejection episodes (p = 0.015), and tacrolimus usage (p < 0.001). Tac (OR = 4.45, 95%CI 2.18–9.10; p = 0.000)

Yes. Tac

Tillman, 2018

NODAT

Tac vs. CsA

A small but statistically significant difference in HbA1c levels was observed between the control and the steroid groups (5.56 ± 0.54 vs. 5.67 ± 0.0.45%, p = 0.045). The incidence rates of pre-diabetes and NODAT per 100 patients per year were 9.3 and 3.0, respectively. Regression analysis showed that low-dose steroids (p = 0.026, RR = 1.789, 95%CI = 1.007–3.040) and age (p < 0.001, RR = 1.037/year, 95%CI = 1.018–1.057) were associated with pre- diabetes, whereas BMI (p < 0.001, RR = 1.190, 95%CI = 1.084–1.307), age (p < 0.001,RR = 1.087/year, 95%CI = 1.047–1.129) and Tac use (p = 0.010, RR = 3.300, 95%CI = 1.328–8.196) were associated with NODAT

Yes. Tac

Torres, 2018 [21]

PTDM

Tac vs. CsA (steroids or steroid free)

The study comprised 128 de novo renal transplant recipients without pretransplant diabetes (Tac- SW: 44, Tac-SM: 42, CsA-SM: 42). The 1-year incidence of PTDM in each arm was 37.8% for Tac-SW, 25.7% for Tac- SM, and 9.7% for CsA-SM (Tac-SW vs. CsA-SM 3.9 [RR = 1.2–12.4; p = 0.01]; RR Tac-SM vs. CsA-SM 2.7 [RR = 0.8–8.9; p = 0.1]). Antidiabetic therapy was required less commonly in the CsA-SM arm (p = 0.06); however, acute rejection rate was higher in CsA-SM arm (Tac-SW 11.4%, Tac-SM 4.8%, and CsA-SM 21.4% of patients; cumulative incidence p = 0.04). Graft and patient survival, and graft function were similar among arms. In high-risk patients, tacrolimus-based immunosuppression with SM provides the best balance between PTDM and acute rejection incidence

Yes. Better Tac

Wang, 2023 [39]

NODAT

Tac or CsA

The risk factors of NODAT include age, weight, BMI, smoking habits, drinking habits, preoperative fasting blood glucose, preoperative TG, preoperative TC, acute rejection, and exposure to immunosuppressive agents. Among them, only acute rejection and immunosuppressive agents are modifiable factors. The application of CsA as an immunosuppressive agent after surgery may decrease the incidence rate of NODAT and prolong the longevity of patients receiving renal transplantation. Tac (OR = 2.123; 95%CI 1.142–4.731; p = 0.013)

Yes. Both

Xu, 2018 [40]

PTDM

Tac vs. CsA

30.72% of participants were diagnosed with PTDM. Tacrolimus was a risk factor for developing PTDM: Tac (OR = 1.952; 95%CI 1.169–3.258; p = 0.011)

Yes. Tac

Xue, 2018 [41]

NODAT

Tac vs. CsA

The incidence of NODAT at the end of follow-up was 20.3%. Type of immunosuppressive regimen, and immunosuppressant concentration after renal transplantation, IL-2Ra use remained a protective factor against the development of NODAT (HR 0.12; 95% CI 0.03–0.51; P = 0.004)

Protective effect

Ajabnoor, 2020 [19]

PTDM

Tac

22.5% ➝ patients ➝ (not ➝ diabetic ➝ before ➝ kTx) ➝ developed ➝ PTDM [95%CI = 22,5%]. Age ≥ 40 years at transplant (OR = 2.75, p = 0.004), BMI > 25 kg/ m 2 at transplant (OR = 2.04, p = 0.040), and FK506 level ≥ 10 ng/mL during the first 3 months (OR = 2.65; 95% CI 1.28–5.48; p = 0.009) were all significantly related to PTDM development

Yes

De Lucena, 2020 [26]

PTDM

Tac

Tac (OR = 0.99; 95%CI 0.46–2.11; p = 0.97); CsA (OR = 1.45; 95%CI 0.50- 4.24; p = 0.49)

Yes

van der Burgh, 2019 [38]

PTDM

Tac

Risk factors for the development of PTDM: 1) univariate analysis: Tac (OR = 1.06; 95% CI 0.99–1.00; p = 0.8), serum magnesium (OR = 0.98; 95% CI 0.96–1.00; p = 0.01) 2) multivariate analysis: Tac (OR = 1.00; 95% CI 0.99- 1.00; p = 0.6); serum magnesium (OR = 0.98; 95% CI 0.96–1.00; p = 0.01)

Yes

Yu, 2016 [42]

NODAT

Tac

By multivariate analysis, old age (OR = 1.05; 95%CI = 1.01–1.08), family history of diabetes mellitus (OR = 2.48; 95%CI = 1.04–5.94), pre-transplant high serum glucose level (OR = 1.04; 95%CI = 1.01–1.08), and obesity (OR = 3.46; 95%CI: 1.55–7.73) were independent risk factors for NODAT. In contrast, serum magnesium levels and the use of tacrolimus are not associated with the development of NODAT (OR = 1.50; 95% CI 0.69–3.26; p = 0.311)

No

Khalili, 2013 [31]

Hyperglycaemia

CsA

Risk factors for hyperglycaemia were higher Cyclosporine level, impaired renal function, and reduced HDL level.

Yes

Terrec, 2020 [36]

NODAT

Conversion from CNIs to belacept

A late switch from CNI to belatacept was a valuable therapeutic option for diabetic kidney recipients and substantially improved glycemic parameters.

Yes. Belacept better

2. Body weight

Ruangkanchanasetr, 2014 [34]

Body weight

Tac (and other

immunosuppressants checked)

Univariate Analysis of the Obesity Group and the At Risk of Obesity Group Compared with Normal BMI Patients: 1) obesity BMI > = 25: Cyclosporine (OR = 1.27; 95% CI 0.72–2.26; p = 0.412); Tacrolimus (OR = 0.52; 95%CI

0.28–0.95; p < 0.05); Mycophenolate mofetil (OR = 0.83; 95%CI 0.42–1.64; p = 0.597); Mycophenolic acid (OR = 0.66; 95%CI 0.33–1.31; p = 1.31);

Azathioprine (OR = 0.89; 95%CI 0.38–2.08; p = 0.786); Sirolimus or everolimus (OR = 2.55; 95%CI 0.98–6.64; p = 0.056); Prednisolone (OR = 0.68; 95CI 0.33–1.43; p = 0.309); 2) at risk of obesity BMI = 23–24.9:

Cyclosporine (OR = 0.72; 95%CI 0.36–1.44; p = 0.354); Tacrolimus (OR = 1.22; 95%CI 0.62–2.41; p = 0.563); Mycophenolate mofetil (OR = 0.8; 95%CI 0.36–1.77; p = 0.563); Mycophenolic acid (OR = 0.68; 95%CI 0.3-

1.54; p = 0.35); Azathioprine (OR = 0.84; 95%CI0.3–2.33; p = 0.734);

Sirolimus or everolimus (OR = 1.48; 95%CI 0.44–4.91; p = 0.525); Prednisolone (OR = 0.54; 95%CI 0.24–1.24; p = 0.147)

Yes. Tac

Sayilar, 2022 [35]

Body weight

Tac vs. CsA

Significant increases in body weight and body mass index (between 3 and 48 months), waist and hip circumferences (between 1and 48 months), waist-to-hip ratio (between 1 and 3 or 6 months) and neck circumference (between 1 and 12 or 24 months) were observed in both CsA and Tac groups. A significant increase was noted in post-transplant body fat percentage values for the 3 to 24 months in the CsA group, whereas for the

24 to 48 months in both CsA and Tac groups. Hip circumferences percentage changes from the pre-transplant period to the 1, 12 and 24 months were significantly higher in CsA than in the Tac group. At each time point, there was no significant difference in percentage changes for other anthropometric parameters between the CsA and Tac groups

Yes. Depends on the time measure

De Oliveira, 2014 [27]

Body weight

steroids vs. steroid-free therapy

The following variables were identified as significantly associated with a decreased risk of weight gain within 36 months post-transplantation: male gender of the recipient (OR = 0.304; p = 0.001; 95%CI = 0.147–0.631) and older age of the recipient (OR = 0.933; p < 0.01; 95%CI = 0.902–0.966)

No

3. Lipid profile

Bergmann, 2015 [23]

Lipid profile

steroids vs. steroid-free therapy

There was no statistically significant correlation between total or free prednisolone exposure (tAUC0–6 h or fAUC0–12 h) and HDL, LDL,

triglycerides or HbA1c. Free prednisolone AUC (fAUC0–12 h) was significantly positively correlated with a patient’s waist to upper arm circumference ratio with a Spearman correlation coefficient (r = 0.3, p = 0.02). A trend towards a positive correlation between free prednisolone AUC and a patient’s neck to upper arm circum- ference ratio was also observed, but this did not reach statistical significance (Spearman correlation coefficient

r = 0.24, p = 0.08). No significant association was found between VACS (Cushing phenotype) score and total or free prednisolone exposure

No

Ichimaru, 2015 [30]

Lipid profile

Various immunosuppressants

The relationships among the patients’ immunosuppressant use and lipid abnormalities: MMF (OR = 0.86; 95%CI 0.37–2.03; p > 0.05); Everolimus (OR = 2.26; 95%CI 1.17–4.38; p < 0.05); Mizoribine (OR = 0.08; 95%CI 0.28–2.28; p = ?); Azathioprine (OR = 1.28; 95%CI 0.48–3.40; p > 0.05); CsA (OR = 1.71; 95%CI 0.57–5.15; p > 0.05); Tac (OR = 1.15; 95%CI 0.38–3.45; p > 0.05); Corticosteroids (OR = 3.11; 95%CI 1.27–7.67; p < 0.05)

Yes—Everolimus and corticosteroids

No – CsA

4. Body composition

Kolonko, 2021 [32]

Body composition

Tac (slow and fast metabolizers)

There was no difference in phase angle, visceral fat area, lean body mass index (LBMI) and the proportion of lean mass as a percentage of total body mass between the subgroups of slow and fast metabolizers. However, subjects with LBMI ≥ median value of 18.7 kg/m², despite similar initial tacrolimus dose per kg of body weight, were characterized by a significantly lower tacrolimus C/D ratio (median 1.39 vs. 1.67, respectively; p < 0.05) in comparison with the subgroup of lower LBMI. Multivariate regression analysis confirmed that age (rpartial = 0.322; p < 0.001) and LBMI (rpartial = − 0.254; p < 0.01) independently influenced the tacrolimus C/D ratio. A LBMI assessed by BIA may influence the tacrolimus metabolism in the early post-transplant period and can be a useful in the optimization of initial tacrolimus dosing

No

5. Electrolyte disorders

Beilhack, 2020 [22]

Electrolyte disorders

CNI inhibitors

Patients without any CNI therapy (n = 50) had a lower prevalence of hypomagnesaemia, hyperkalaemia and metabolic acidosis compared with cal- cineurin inhibitor treatment (4% vs 26%; 2% vs 14.1% and 2% vs 11.4%; p < 0.01)

Yes

6. Bone status

Gregorini, 2017 [29]

Bone status

Steroids, mTOR, CsA, Tac

A significant correlation (p < 0.05) was observed for both osteopenia and osteoporosis with menopause, transplantologic age, CSD, previous glomerulonephritis, and mammalian target of rapamycin (mTOR) inhibitors treatment (imTOR)

Yes

7. Vitamin D

Filipov, 2015 [28]

Vitamin D

CNI inhibitors

There was negative association between the concentration of 25(OH)D and female gender, presence of DM and BMI. In addition, CNI intake was also found to negatively affect 25(OH)D

Yes

8. Vitamin B12

Pontes, 2019 [33]

Vitamin B12

MMF

Among individuals with adequate intake of B₁₂, the deficiency of this vitamin was more frequently seen in those using MMF) (17%) vs. azathioprine (2%), p = 0.01. In conclusion, the prevalence of B₁₂ deficiency in kTx was estimated as 14% and was associated with reduced intake of B₁₂

as well as higher adiposity, especially in women, and with the use of MMF

Yes