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Incretin based therapies and SGLT-2 inhibitors in kidney transplant recipients with diabetes: A systematic review and meta-analysis.
Oikonomaki, D, Dounousi, E, Duni, A, Roumeliotis, S, Liakopoulos, V
Diabetes research and clinical practice. 2021;:108604
Abstract
AIMS: We aimed to conduct a systematic review and meta-analysis regarding the use of incretin-based therapies including dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists as well as sodium-glucose co-transporter-2 (SGLT2) inhibitorsin persons with posttransplantation diabetes mellitus (PTDM) so as to assess both their efficacy and safety. METHODS We searched for publications on Kidney/Renal Transplantation and DPP-4 inhibitors, GLP-1-receptor agonists and SGLT-2 inhibitors and included every study using these antidiabetics. A p-value < 0.05 was considered statistical significant. RESULTS Sixteen studies and 310 individuals with a mean age of 55.98 ± 8.81 years were included in the analysis. Participants received DPP-4 inhibitors in 8 studies, SGLT-2 inhibitors in 6 studies and GLP-1 receptor agonists in 2 studies, with a mean follow-up of 22.03 ± 14.95 weeks. Hemoglobin A1c (HbA1c) reduction was demonstrated in 10 studies (mean +/- standard deviation (MD) = - 0.38%, I2 = 45%). MD of HbA1c was -0.3741 and -0.4596 mg/dl for DPP-4 inhibitors and SGLT-2 inhibitors respectively. Nine studies demonstrated differences in fasting plasma glucose (FPG) (MD = - 25,76) and 5 studies in post-prandial glucose (PPG) (MD = - 6.61) before and following treatment. Most studies did not show adverse effects on the glomerular filtration rate (GFR) and hepatic function. CONCLUSIONS DPP-4 inhibitors and SGLT2 inhibitors appear both efficacious and safe in renal transplant recipients. More high-quality studies are required to guide therapeutic choices for PTDM.
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Effectiveness and Safety of Bariatric Surgery in Patients with End-Stage Chronic Kidney Disease or Kidney Transplant.
Guggino, J, Coumes, S, Wion, N, Reche, F, Arvieux, C, Borel, AL
Obesity (Silver Spring, Md.). 2020;(12):2290-2304
Abstract
OBJECTIVE This study aimed to evaluate (1) the effectiveness, complications, and postoperative access to transplantation in end-stage chronic kidney disease (ECKD) and (2) the effectiveness and complications of bariatric surgery in patients who had already undergone kidney transplant. METHODS A systematic review and meta-analysis of mortality and complications rates were performed. Thirty studies were reviewed. RESULTS After bariatric surgery, patients with ECKD had similar postoperative weight loss to patients from the general population. Meta-analysis showed post-bariatric surgery rates of 2% (95% CI: 0%-3%) for mortality and 7% (95% CI: 2%-14%) for complications. Approximately one-fifth of the patients had access to a transplant. This rate may be underestimated because of the short duration of follow-up. The lack of control groups did not allow for a conclusion on the role of bariatric surgery in facilitating access to kidney transplantation. In patients who had received a kidney transplant, bariatric surgery seemed to improve renal function but increased graft-rejection risk, possibly because of changes in the bioavailability of immunosuppressant drugs. CONCLUSIONS Bariatric surgery yields significant weight loss in patients with ECKD that improves patients' chances of accessing a transplant but does not guarantee it; however, the risk for complications and death is higher than in other patients. After transplantation, bariatric surgery-induced weight loss appeared to positively impact the function of the grafted kidney, but careful monitoring of immunosuppressant medications is required.
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Glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients.
Lo, C, Toyama, T, Oshima, M, Jun, M, Chin, KL, Hawley, CM, Zoungas, S
The Cochrane database of systematic reviews. 2020;(8):CD009966
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Abstract
BACKGROUND Kidney transplantation is the preferred management for patients with end-stage kidney disease (ESKD). However, it is often complicated by worsening or new-onset diabetes. The safety and efficacy of glucose-lowering agents after kidney transplantation is largely unknown. This is an update of a review first published in 2017. OBJECTIVES To evaluate the efficacy and safety of glucose-lowering agents for treating pre-existing and new onset diabetes in people who have undergone kidney transplantation. SEARCH METHODS We searched the Cochrane Kidney and Transplant Register of Studies up to 16 January 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA All randomised controlled trials (RCTs), quasi-RCTs and cross-over studies examining head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in patients who have received a kidney transplant and have diabetes were eligible for inclusion. DATA COLLECTION AND ANALYSIS Four authors independently assessed study eligibility and quality and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD) or standardised mean difference (SMD). Adverse events were expressed as post-treatment absolute risk differences (RD). Dichotomous clinical outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI). MAIN RESULTS Ten studies (21 records, 603 randomised participants) were included - three additional studies (five records) since our last review. Four studies compared more intensive versus less intensive insulin therapy; two studies compared dipeptidyl peptidase-4 (DPP-4) inhibitors to placebo; one study compared DPP-4 inhibitors to insulin glargine; one study compared sodium glucose co-transporter 2 (SGLT2) inhibitors to placebo; and two studies compared glitazones and insulin to insulin therapy alone. The majority of studies had an unclear to a high risk of bias. There were no studies examining the effects of biguanides, glinides, GLP-1 agonists, or sulphonylureas. Compared to less intensive insulin therapy, it is unclear if more intensive insulin therapy has an effect on transplant or graft survival (4 studies, 301 participants: RR 1.12, 95% CI 0.32 to 3.94; I2 = 49%; very low certainty evidence), delayed graft function (2 studies, 153 participants: RR 0.63, 0.42 to 0.93; I2 = 0%; very low certainty evidence), HbA1c (1 study, 16 participants; very low certainty evidence), fasting blood glucose (1 study, 24 participants; very low certainty evidence), kidney function markers (1 study, 26 participants; very low certainty evidence), death (any cause) (3 studies, 208 participants" RR 0.68, 0.29 to 1.58; I2 = 0%; very low certainty evidence), hypoglycaemia (4 studies, 301 participants; very low certainty evidence) and medication discontinuation due to adverse effects (1 study, 60 participants; very low certainty evidence). Compared to placebo, it is unclear whether DPP-4 inhibitors have an effect on hypoglycaemia and medication discontinuation (2 studies, 51 participants; very low certainty evidence). However, DPP-4 inhibitors may reduce HbA1c and fasting blood glucose but not kidney function markers (1 study, 32 participants; low certainty evidence). Compared to insulin glargine, it is unclear if DPP-4 inhibitors have an effect on HbA1c, fasting blood glucose, hypoglycaemia or discontinuation due to adverse events (1 study, 45 participants; very low certainty evidence). Compared to placebo, SGLT2 inhibitors probably do not affect kidney graft survival (1 study, 44 participants; moderate certainty evidence), but may reduce HbA1c without affecting fasting blood glucose and eGFR long-term (1 study, 44 participants, low certainty evidence). SGLT2 inhibitors probably do not increase hypoglycaemia, and probably have little or no effect on medication discontinuation due to adverse events. However, all participants discontinuing SGLT2 inhibitors had urinary tract infections (1 study, 44 participants, moderate certainty evidence). Compared to insulin therapy alone, it is unclear if glitazones added to insulin have an effect on HbA1c or kidney function markers (1 study, 62 participants; very low certainty evidence). However, glitazones may make little or no difference to fasting blood glucose (2 studies, 120 participants; low certainty evidence), and medication discontinuation due to adverse events (1 study, 62 participants; low certainty evidence). No studies of DPP-4 inhibitors, or glitazones reported effects on transplant or graft survival, delayed graft function or death (any cause). AUTHORS' CONCLUSIONS The efficacy and safety of glucose-lowering agents in the treatment of pre-existing and new-onset diabetes in kidney transplant recipients is questionable. Evidence from existing studies examining the effect of intensive insulin therapy, DPP-4 inhibitors, SGLT inhibitors and glitazones is mostly of low to very low certainty. Appropriately blinded, larger, and higher quality RCTs are needed to evaluate and compare the safety and efficacy of contemporary glucose-lowering agents in the kidney transplant population.
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Robot-Assisted versus Conventional Open Kidney Transplantation: A Meta-Analysis.
Liu, G, Deng, Y, Zhang, S, Lin, T, Guo, H
BioMed research international. 2020;:2358028
Abstract
BACKGROUND Perioperative and follow-up outcomes for patients that received robot-assisted kidney transplant (RAKT), compared to patients that received conventional open kidney transplant (OKT), remain unknown. We performed a meta-analysis of controlled studies to compare the safety and efficacy of RAKT versus OKT. METHODS Systematic searching of PubMed, Embase, and Cochrane Library databases was performed to identify relevant randomized or nonrandomized controlled studies. Perioperative, in-hospital, and follow-up outcomes were summarized. A random-effect model incorporating the potential heterogeneity was used to synthesize the results. RESULTS Six nonrandomized controlled studies including 263 patients with RAKT and 804 patients with OKT were included. Pooled results showed that compared to those that received OKT, patients that received RAKT had significant higher rewarming time (mean difference (MD): 20.8 min, p < 0.001) and total ischemia time (MD: 17.8 min, p = 0.008) but a lower incidence of surgical site infection (SSI, risk ratio (RR): 0.22, p = 0.03). The incidence of delayed graft function was comparable between groups (RR: 1.10, p = 0.82), and the length of hospital stay was similar (MD: -2.03 days, p = 0.21). During a follow-up of 31 months, patients that received RAKT and OKT had similar serum creatinine levels (MD: 10.12 mmol/L, p = 0.42) and similar incidences of graft rejection (RR: 1.16, p = 0.53), graft failure (RR: 0.94, p = 0.79), and all-cause mortality (RR: 1.16, p = 0.77). CONCLUSION Current evidence from nonrandomized studies suggests that RAKT is associated with a lower risk of SSI and similar midterm functional and clinical efficacy compared to OKT. Randomized studies are needed to validate these findings.
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Comparative effectiveness of different antihypertensive agents in kidney transplantation: a systematic review and meta-analysis.
Pisano, A, Bolignano, D, Mallamaci, F, D'Arrigo, G, Halimi, JM, Persu, A, Wuerzner, G, Sarafidis, P, Watschinger, B, Burnier, M, et al
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2020;(5):878-887
Abstract
BACKGROUND We conducted a systematic review and meta-analysis to compare benefits and harms of different antihypertensive drug classes in kidney transplant recipients, as post-transplant hypertension (HTN) associates with increased cardiovascular (CV) morbidity and mortality. METHODS The Ovid-MEDLINE, PubMed and CENTRAL databases were searched for randomized controlled trials (RCTs) comparing all main antihypertensive agents versus placebo/no treatment, routine treatment. RESULTS The search identified 71 RCTs. Calcium channel blockers (CCBs) (26 trials) reduced the risk for graft loss {risk ratio [RR] 0.58 [95% confidence interval (CI) 0.38-0.89]}, increased glomerular filtration rate (GFR) [mean difference (MD) 3.08 mL/min (95% CI 0.38-5.78)] and reduced blood pressure (BP). Angiotensin-converting enzyme inhibitors (ACEIs) (13 trials) reduced the risk for graft loss [RR 0.62 (95% CI 0.40-0.96)] but decreased renal function and increased the risk for hyperkalaemia. Angiotensin receptor blockers (ARBs) (10 trials) did not modify the risk of death, graft loss and non-fatal CV events and increased the risk for hyperkalaemia. When pooling ACEI and ARB data, the risk for graft failure was lower in renin-angiotensin system (RAS) blockade as compared with control treatments. In direct comparison with ACEIs or ARBs (11 trials), CCBs increased GFR [MD 11.07 mL/min (95% CI 6.04-16.09)] and reduced potassium levels but were not more effective in reducing BP. There are few available data on mortality, graft loss and rejection. Very few studies performed comparisons with other active drugs. CONCLUSIONS CCBs could be the preferred first-step antihypertensive agents in kidney transplant patients, as they improve graft function and reduce graft loss. No definite patient or graft survival benefits were associated with RAS inhibitor use over conventional treatment.
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Effects of denosumab on bone metabolism and bone mineral density in kidney transplant patients: a systematic review and meta-analysis.
Thongprayoon, C, Acharya, P, Aeddula, NR, Torres-Ortiz, A, Bathini, T, Sharma, K, Ungprasert, P, Watthanasuntorn, K, Suarez, MLG, Salim, SA, et al
Archives of osteoporosis. 2019;(1):35
Abstract
OBJECTIVE The use of immunosuppressive agents, especially glucocorticoids, are associated with increased risks of bone loss in kidney transplant patients. Denosumab, a potent antiresorptive agent, has been shown to increase bone mineral density (BMD) in patients with CKD. However, its effects on bone metabolism and BMD in kidney transplant patients remain unclear. METHODS A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through April 2018 to identify studies evaluating denosumab's effect on changes in bone metabolism and BMD from baseline to post-treatment course in kidney transplant patients. Study results were pooled and analyzed utilizing random-effects model. The protocol for this systematic review is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018095055). RESULTS Five studies (a clinical trial and four cohort studies) with a total of 162 kidney transplant patients were identified. The majority of patients had a baseline eGFR ≥ 30 mL/min/1.73 m2. After treatment (≥ 6 to 12 months), there were significant increases in BMD with standardized mean differences (SMDs) of 3.26 (95% CI 0.88-5.64) and 1.83 (95% CI 0.43 to 3.22) for lumbar spine and femoral neck, respectively. There were also significant increases in T scores with SMDs of 0.92 (95% CI 0.58 to 1.25) and 1.14 (95% CI 0.17 to 2.10) for lumbar spine and femoral neck, respectively. After treatment, there were no significant changes in serum calcium (Ca) or parathyroid hormone (PTH) from baseline to post-treatment course (≥ 6 months) with mean differences (MDs) of 0.52 (95% CI, - 0.13 to 1.16) mmol/L and - 13.24 (95% CI, - 43.85 to 17.37) ng/L, respectively. The clinical trial data demonstrated more asymptomatic hypocalcemia in the denosumab (12 episodes in 39 patients) than in the control (1 episode in 42 patients) group. From the cohort studies, the pooled incidence of hypocalcemia following denosumab treatment was 1.7% (95% CI 0.4 to 6.6%). All reported hypocalcemic episodes were mild and asymptomatic, but the majority of patients required Ca and vitamin D supplements. CONCLUSION Among kidney transplant patients with good allograft function, denosumab effectively increases BMD and T scores in the lumbar spine and femur neck. From baseline to post-treatment, there are no differences in serum Ca and PTH. However, mild hypocalcemia can occur following denosumab treatment, requiring monitoring and titration of Ca and vitamin D supplements.
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Efficacy and Safety of Different Bisphosphonates for Bone Loss Prevention in Kidney Transplant Recipients: A Network Meta-Analysis of Randomized Controlled Trials.
Yang, Y, Qiu, S, Tang, X, Li, XR, Deng, LH, Wei, Q, Fu, P
Chinese medical journal. 2018;(7):818-828
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Abstract
BACKGROUND Mineral and bone disorder is one of the severe complications in kidney transplant recipients (KTRs). Previous studies showed that bisphosphonates had favorable effects on bone mineral density (BMD). We sought to compare different bisphosphonate regimens and rank their strategies. METHODS We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to April 01, 2017, for randomized controlled trials (RCTs) comparing bisphosphonate treatments in adult KTRs. The primary outcome was BMD change. We executed the tool recommended by the Cochrane Collaboration to evaluate the risk of bias. We performed pairwise meta-analyses using random effects models and network meta-analysis (NMA) using Bayesian models and assessed the quality of evidence. RESULTS A total of 21 RCTs (1332 participants) comparing 6 bisphosphonate regimens were included. All bisphosphonates showed a significantly increased percentage change in BMD at the lumbar spine compared to calcium except clodronate. Pamidronate with calcium and Vitamin D analogs showed improved BMD in comparison to clodronate with calcium (mean difference [MD], 9.84; 95% credibility interval [CrI], 1.06-19.70). The combination of calcium and Vitamin D analogs had a significantly lower influence than adding either pamidronate or alendronate (MD, 6.34; 95% CrI, 2.59-11.01 and MD, 6.16; 95% CrI, 0.54-13.24, respectively). In terms of percentage BMD change at the femoral neck, both pamidronate and ibandronate combined with calcium demonstrated a remarkable gain compared with calcium (MD, 7.02; 95% CrI, 0.30-13.29 and MD, 7.30; 95% CrI, 0.32-14.22, respectively). The combination of ibandronate with calcium displayed a significant increase in absolute BMD compared to any other treatments and was ranked best. CONCLUSIONS Our NMA suggested that new-generation bisphosphonates such as ibandronate were more favorable in KTRs to improve BMD. However, the conclusion should be treated with caution due to indirect comparisons.
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Risk of Colorectal Cancer in Chronic Kidney Disease: A Systematic Review and Meta-Analysis.
Komaki, Y, Komaki, F, Micic, D, Ido, A, Sakuraba, A
Journal of clinical gastroenterology. 2018;(9):796-804
Abstract
BACKGROUND Association between chronic kidney disease and colorectal cancer (CRC) remains unclear. GOALS To assess the risk of CRC in patients with various chronic kidney diseases before and after kidney transplantation. STUDY Electronic databases were searched for cohort studies assessing the risk of CRC in patients with chronic kidney diseases. The primary outcome was the risk of CRC among studies that reported the risk as standardized incidence rate (SIR). RESULTS Fifty-four studies, including 1,208,767 patients that reported the incidence of CRC in chronic kidney diseases were identified. SIR of CRC were obtained from 17 retrospective cohort studies. Among the 3 studies (4 reports) that included chronic kidney disease patients without kidney transplantation, there was a significant increased risk of CRC (pooled SIR 1.18) (95% confidence interval, 1.01-1.37; P=0.033). High heterogeneity was seen (I=85.6%), and metaregression showed that there were positive correlations between the risk of CRC and the proportions of males, age and follow-up period. Among the 15 studies (17 reports) that included postkidney transplant patients, the pooled SIR was significantly increased at 1.40 (95% confidence interval, 1.15-1.71; P=0.00080). High heterogeneity was seen (I=88.9%), and metaregression showed that the follow-up period correlated with the risk of CRC. CONCLUSIONS In the present systematic review and meta-analysis, we demonstrated that patients with chronic kidney disease, regardless of a history of transplant, have a significant increased risk of CRC. A more intensive surveillance for CRC is required in this population.
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Prognostic value of bone- and vascular-derived molecular biomarkers in hemodialysis and renal transplant patients: a systematic review and meta-analysis.
Pichler, G, Haller, MC, Kainz, A, Wolf, M, Redon, J, Oberbauer, R
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2017;(9):1566-1578
Abstract
BACKGROUND Patients undergoing hemodialysis and kidney graft recipients are high-risk populations for cardiovascular and all-cause mortality. Fibroblast growth factor 23 (FGF23), osteoprotegerin (OPG), RANK ligand, osteopontin (OPN), Klotho protein and bone morphogenetic protein-7 (BMP-7) are bone- and vascular-derived molecular biomarkers that have been shown to be associated with cardiovascular surrogate end points; however, currently available data on the prognostic value of these biomarkers is inconsistent. The aim of the present study was to conduct a systematic review and meta-analysis in order to summarize the available evidence on the association of molecular biomarkers with mortality in individuals undergoing hemodialysis and renal transplant patients. METHODS Two databases (MEDLINE and Embase) were systematically searched. Studies were eligible if the association of biomarker and mortality was reported as time-to-event data [hazard Ratio (HR)] or as effect size with a fixed time of follow-up [odds Ratio (OR)]. Abstracted HRs were converted onto a standard scale of effect and combined using a random effects model. RESULTS From a total of 1170 studies identified in initial searches, 21 met the inclusion criteria. In hemodialysis patients, comparing the lower third with the upper third of baseline FGF23 distribution, pooled HRs (95% confidence intervals) were 1.94 (1.47, 2.56) for all-cause mortality and 2.4 (1.64, 3.51) for cardiovascular mortality. For the same comparison of baseline OPG distribution, pooled HRs were 1.8 (0.95, 3.39) for all-cause mortality and 2.53 (1.29, 4.94) for cardiovascular mortality. Reported risk estimates of RANK ligand, OPN, Klotho protein and BMP-7 were not suitable for pooling; however, only Klotho protein was significantly related to mortality. For kidney graft recipients, four studies that investigated the relationship of FGF23 and OPG with mortality were identified, all of which reported a significant association. CONCLUSIONS In hemodialysis patients, FGF23 is a predictor of all-cause and cardiovascular mortality, whereas the predictive value of OPG is restricted to cardiovascular mortality. Further studies are needed in order to gain insight into the prognostic value of these biomarkers in renal transplant recipients.
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Immunosuppressive therapy for kidney transplantation in children and adolescents: systematic review and economic evaluation.
Haasova, M, Snowsill, T, Jones-Hughes, T, Crathorne, L, Cooper, C, Varley-Campbell, J, Mujica-Mota, R, Coelho, H, Huxley, N, Lowe, J, et al
Health technology assessment (Winchester, England). 2016;(61):1-324
Abstract
BACKGROUND End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation followed by induction and maintenance immunosuppressive therapy to reduce the risk of kidney rejection and prolong graft survival. OBJECTIVES To systematically review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect,(®) Novartis Pharmaceuticals) and rabbit antihuman thymocyte immunoglobulin (Thymoglobuline,(®) Sanofi) as induction therapy and immediate-release tacrolimus [Adoport(®) (Sandoz); Capexion(®) (Mylan); Modigraf(®) (Astellas Pharma); Perixis(®) (Accord Healthcare); Prograf(®) (Astellas Pharma); Tacni(®) (Teva); Vivadex(®) (Dexcel Pharma)], prolonged-release tacrolimus (Advagraf,(®) Astellas Pharma); belatacept (BEL) (Nulojix,(®) Bristol-Myers Squibb), mycophenolate mofetil (MMF) [Arzip(®) (Zentiva), CellCept(®) (Roche Products), Myfenax(®) (Teva), generic MMF is manufactured by Accord Healthcare, Actavis, Arrow Pharmaceuticals, Dr Reddy's Laboratories, Mylan, Sandoz and Wockhardt], mycophenolate sodium, sirolimus (Rapamune,(®) Pfizer) and everolimus (Certican,(®) Novartis Pharmaceuticals) as maintenance therapy in children and adolescents undergoing renal transplantation. DATA SOURCES Clinical effectiveness searches were conducted to 7 January 2015 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science [via Institute for Scientific Information (ISI)], Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (HTA) (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted to 15 January 2015 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Databases (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations Database (via Wiley Online Library) and EconLit (via EBSCOhost). REVIEW METHODS Titles and abstracts were screened according to predefined inclusion criteria, as were full texts of identified studies. Included studies were extracted and quality appraised. Data were meta-analysed when appropriate. A new discrete time state transition economic model (semi-Markov) was developed; graft function, and incidences of acute rejection and new-onset diabetes mellitus were used to extrapolate graft survival. Recipients were assumed to be in one of three health states: functioning graft, graft loss or death. RESULTS Three randomised controlled trials (RCTs) and four non-RCTs were included. The RCTs only evaluated BAS and tacrolimus (TAC). No statistically significant differences in key outcomes were found between BAS and placebo/no induction. Statistically significantly higher graft function (p < 0.01) and less biopsy-proven acute rejection (odds ratio 0.29, 95% confidence interval 0.15 to 0.57) was found between TAC and ciclosporin (CSA). Only one cost-effectiveness study was identified, which informed NICE guidance TA99. BAS [with TAC and azathioprine (AZA)] was predicted to be cost-effective at £20,000-30,000 per quality-adjusted life year (QALY) versus no induction (BAS was dominant). BAS (with CSA and MMF) was not predicted to be cost-effective at £20,000-30,000 per QALY versus no induction (BAS was dominated). TAC (with AZA) was predicted to be cost-effective at £20,000-30,000 per QALY versus CSA (TAC was dominant). A model based on adult evidence suggests that at a cost-effectiveness threshold of £20,000-30,000 per QALY, BAS and TAC are cost-effective in all considered combinations; MMF was also cost-effective with CSA but not TAC. LIMITATIONS The RCT evidence is very limited; analyses comparing all interventions need to rely on adult evidence. CONCLUSIONS TAC is likely to be cost-effective (vs. CSA, in combination with AZA) at £20,000-30,000 per QALY. Analysis based on one RCT found BAS to be dominant, but analysis based on another RCT found BAS to be dominated. BAS plus TAC and AZA was predicted to be cost-effective at £20,000-30,000 per QALY when all regimens were compared using extrapolated adult evidence. High-quality primary effectiveness research is needed. The UK Renal Registry could form the basis for a prospective primary study. STUDY REGISTRATION This study is registered as PROSPERO CRD42014013544. FUNDING The National Institute for Health Research HTA programme.