Dyslipidaemia in children on renal replacement therapy

Bonthuis, Marjolein; Stralen, Karlijn J. van; Jager, Kitty J.; Baiko, Sergey; Jahnukainen, Timo; Laube, Guido F.; Podracká, Ľudmila; Seeman, Tomáš; Tyerman, Kay; Ulinski, Tim; Groothoff, Jaap W.; Schaefer, Franz; Verrina, Enrico

doi:10.1093/ndt/gft429

Cited by 21 publications

(19 citation statements)

References 59 publications

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“…This is in accordance with the observations in adults showing an independent association of hypertriglyceridaemia with impaired renal allograft function beyond the first post-transplant year in multivariate analyses [40]. In a very recent register study, an inverse association between triglyceride levels and estimated GFR was similarly found in paediatric RTx patients [41]. Total cholesterol, HDL, or LDL did not have a comprehensive association with graft function in our patients ( Fig.…”

Section: Variablessupporting

confidence: 93%

Metabolic risk factors and long-term graft function after paediatric renal transplantation

et al. 2014

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SummaryThe aim of this study was to evaluate metabolic risk factors and their impact on long-term allograft function in paediatric renal transplant (RTx) patients. We reviewed the medical records of 210 RTx patients who underwent transplantation at a median age of 4.5 years (range 0.7-18.2) and a median follow-up of 7.0 years (range 1.5-18.0). Data on lipid and glucose metabolism, uric acid levels, weight and blood pressure were collected up to 13 years post-RTx, and the findings were correlated with the measured glomerular filtration rate (GFR). Beyond the first year, GFR showed gradual deterioration with a mean decline of 2.4 ml/min/ 1.73 m 2 /year. Metabolic syndrome, overweight, hypertension and type 2 diabetes were diagnosed in 14-19%, 20-23%, 62-87% and 3-5% of the patients, respectively. These entities showed only mild association with the concomitant or long-term GFR values. Dyslipidaemia was common and hypertriglyceridaemia associated with a lower GFR at 1.5 and 5 years post-RTx (P = 0.008 and P = 0.017, respectively). Similarly, hyperuricaemia was frequent and associated significantly with GFR (P < 0.001). Except for hyperuricaemia and hypertriglyceridaemia, metabolic risk factors beyond the first postoperative year associated modestly with the long-term kidney graft function in paediatric RTx patients.

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Section: Variablessupporting

confidence: 93%

Metabolic risk factors and long-term graft function after paediatric renal transplantation

et al. 2014

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“…The prevalence of dyslipidemia was 88% at 1 year post‐transplant. This rate is higher than in previous studies which observed a broad range of 15%‐67% dyslipidemia in this patient population . However, definitions of dyslipidemia and applied reference values differed from study to study.…”

Section: Discussioncontrasting

confidence: 71%

“…Eventually, in children, prevalence data, reference values as well as treatment recommendations vary depending on country, study, and guideline . We therefore aimed to evaluate the prevalence of dyslipidemia in pediatric renal transplant recipients in a large international multicenter registry, and to identify possible non‐modifiable and modifiable risk factors including the most frequently used immunosuppressive regimens.…”

Section: Introductionmentioning

confidence: 99%

Dyslipidemia after pediatric renal transplantation—The impact of immunosuppressive regimens

Habbig

Volland

Krupka

et al. 2017

Pediatric Transplantation

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Dyslipidemia contributes to cardiovascular morbidity and mortality in pediatric transplant recipients. Data on prevalence and risk factors in pediatric cohorts are, however, scarce. We therefore determined the prevalence of dyslipidemia in 386 pediatric renal transplant recipients enrolled in the CERTAIN registry. Data were obtained before and during the first year after RTx to analyze possible non-modifiable and modifiable risk factors. The prevalence of dyslipidemia was 95% before engraftment and 88% at 1 year post-transplant. Low estimated glomerular filtration rate at 1 year post-transplant was associated with elevated serum triglyceride levels. The use of TAC and of MPA was associated with significantly lower concentrations of all lipid parameters compared to regimens containing CsA and mTORi. Immunosuppressive regimens consisting of CsA, MPA, and steroids as well as of CsA, mTORi, and steroids were associated with a three- and 25-fold (P<.001) increased risk of having more than one pathologic lipid parameter as compared to the use of TAC, MPA, and steroids. Thus, amelioration of the cardiovascular risk profile after pediatric RTx may be attained by adaption of the immunosuppressive regimen according to the individual risk profile.

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“…The baseline incidence of dyslipidaemia (without mTOR-I use) was estimated by Bonthuis et al 213 based on European registry data for child/adolescent RRT recipients. The incidence of dyslipidaemia was 55.5% (313/564) for transplant recipients, versus 85.1% and 76.1% for haemodialysis and peritoneal dialysis recipients, respectively.…”

Section: Dyslipidaemiamentioning

confidence: 99%

Immunosuppressive therapy for kidney transplantation in children and adolescents: systematic review and economic evaluation

Haasova

Snowsill

Jones-Hughes

et al. 2016

Health Technol Assess

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BackgroundEnd-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.ObjectivesTo 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 sourcesClinical 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 methodsTitles 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.ResultsThree 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.LimitationsThe RCT evidence is very limited; analyses comparing all interventions need to rely on adult evidence.ConclusionsTAC 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 registrationThis study is registered as PROSPERO CRD42014013544.FundingThe National Institute for Health Research HTA programme.

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Dyslipidaemia in children on renal replacement therapy

Cited by 21 publications

References 59 publications

Metabolic risk factors and long-term graft function after paediatric renal transplantation

Metabolic risk factors and long-term graft function after paediatric renal transplantation

Dyslipidemia after pediatric renal transplantation—The impact of immunosuppressive regimens

Immunosuppressive therapy for kidney transplantation in children and adolescents: systematic review and economic evaluation

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