Changing Paradigms in the Management of Rejection in Kidney Transplantation

Maier, Mirela; Takano, Tomoko; Sapir‐Pichhadze, Ruth

doi:10.1177/2054358116688227

Cited by 11 publications

(4 citation statements)

References 136 publications

(174 reference statements)

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“…13 Therefore, further research, including systems medicine approaches, is needed to better understand the effects of CMV prevention strategies from an immune, virological and pharmacokinetic point of viewwith emphasis on sex-associated differencesand their effects on transplantation outcome. 44,45 Of interest, the prophylactic strategy group showed a higher incidence of late-onset CMV (from month six on); such increases of viral (re)activation incidence after the end of prophylaxis have been observed before. 30,31 We also observed a tendency towards higher incidence of rejection and severe BK virus (re)activation among patients in the prophylactic strategy group, although these tendencies could not be confirmed through multi-parameter analysis.…”

Section: Discussionmentioning

confidence: 89%

Sex-associated differences in cytomegalovirus prevention: Prophylactic strategy is associated with a strong kidney function impairment in female renal transplant patients

Blázquez-Navarro

Dang-Heine

Bauer

et al. 2019

Preprint

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Post-transplantation cytomegalovirus (CMV) syndrome can be prevented using the antiviral drug (val)ganciclovir. (Val)ganciclovir is typically administered following a prophylactic or a pre-emptive strategy. The prophylactic strategy entails early universal administration, the pre-emptive strategy, early treatment in case of infection. However, it is not clear which strategy is superior with respect to transplantation outcome; sex-specific effects of these prevention strategies are not known. We have retrospectively analysed 540 patients from the multi-centre Harmony study along eight pre-defined visits: 308 were treated according to a prophylactic, 232 according to a pre-emptive strategy. As expected, we observed an association of prophylactic strategy with lower incidence of CMV syndrome, delayed onset and lower viral loads compared to the pre-emptive strategy. However, in female patients, the prophylactic strategy was associated with a strong impairment of glomerular filtration rate one year post-transplant (difference: -12.0±4.2 mL·min -1 ·1.73m -2 , P=0.005). Additionally, we observed a tendency of higher incidence of acute rejection and severe BK virus reactivation in the prophylactic strategy group. While the prophylactic strategy was more effective for preventing CMV syndrome, our results suggest for the first time that the prophylactic strategy might lead to inferior transplantation outcomes in female patients, providing evidence for a strong association with sex.

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Section: Discussionmentioning

confidence: 89%

Sex-associated differences in cytomegalovirus prevention: Prophylactic strategy is associated with a strong kidney function impairment in female renal transplant patients

Blázquez-Navarro

Dang-Heine

Bauer

et al. 2019

Preprint

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“…Plasma and urinary amino acid profiles are demonstrably affected by acute and chronic kidney disease and by glomerulonephritis. 7 , 8 , 9 , 10 , 11 Dysregulation of acylcarnitine excretion as a result of renal failure has also been observed in CKD and diabetic nephropathy. It is unknown whether the biological processes associated with acute illness, inflammatory processes, and kidney disease are established at the time of birth.…”

mentioning

confidence: 99%

Association Between Newborn Metabolic Profiles and Pediatric Kidney Disease

Sood

Murphy

Hawken

et al. 2018

Kidney International Reports

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IntroductionMetabolomics offers considerable promise in early disease detection. We set out to test the hypothesis that routine newborn metabolic profiles at birth, obtained through screening for inborn errors of metabolism, would be associated with kidney disease and add incremental information to known clinical risk factors.MethodsWe conducted a population-level cohort study in Ontario, Canada, using metabolic profiles from 1,288,905 newborns from 2006 to 2015. The primary outcome was chronic kidney disease (CKD) or dialysis. Individual metabolites and their ratio combinations were examined by logistic regression after adjustment for established risk factors for kidney disease and incremental risk prediction measured.ResultsCKD occurred in 2086 (0.16%, median time 612 days) and dialysis in 641 (0.05%, median time 99 days) infants and children. Individual metabolites consisted of amino acids, acylcarnitines, markers of fatty acid oxidation, and others. Base models incorporating clinical risk factors only provided c-statistics of 0.61 for CKD and 0.70 for dialysis. The addition of identified metabolites to risk prediciton models resulted in significant incremental improvement in the performance of both models (CKD model: c-statistic 0.66 NRI 0.36 IDI 0.04, dialysis model: c-statistic 0.77 NRI 0.57 IDI 0.09). This was consistent after internal validation using bootstrapping and a sensitivity analysis excluding outcomes within the first 30 days.ConclusionRoutinely collected screening metabolites at birth are associated with CKD and the need for dialytic therapies in infants and children, and add incremental information to traditional clinical risk factors.

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“…This observation shows how sex and anti-CMV immunity could potentially interact and affect eGFR ( Lindemann et al, 2018 ). Therefore, further research, including systems medicine approaches, is needed to better understand the effects of CMV prevention strategies from an immune, virological and pharmacokinetic point of view – with emphasis on sex-associated differences–and their effects on transplantation outcome ( Maier et al, 2017 ; Blazquez-Navarro et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Sex-Associated Differences in Cytomegalovirus Prevention: Prophylactic Strategy is Potentially Associated With a Strong Kidney Function Impairment in Female Renal Transplant Patients

et al. 2020

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Post-transplantation cytomegalovirus (CMV) syndrome can be prevented using the antiviral drug (val)ganciclovir. (Val)ganciclovir is typically administered following a prophylactic or a pre-emptive strategy. The prophylactic strategy entails early universal administration, the pre-emptive strategy, early treatment in case of infection. However, it is not clear which strategy is superior with respect to transplantation outcome; sex-specific effects of these prevention strategies are not known. We have retrospectively analyzed 540 patients from the multi-centre Harmony study along eight pre-defined visits: 308 were treated according to a prophylactic, 232 according to a pre-emptive strategy. As expected, we observed an association of prophylactic strategy with lower incidence of CMV syndrome, delayed onset and lower viral loads compared to the pre-emptive strategy. However, in female patients, the prophylactic strategy was associated with a strong impairment of glomerular filtration rate one year post-transplant (difference: −11.8 ± 4.3 ml min−1·1.73 m−2, p = 0.006). Additionally, we observed a tendency of higher incidence of acute rejection and severe BK virus reactivation in the prophylactic strategy group. While the prophylactic strategy was more effective for preventing CMV syndrome, our results suggest for the first time that the prophylactic strategy might lead to inferior transplantation outcomes in female patients, providing evidence for a strong association with sex. Further randomized controlled studies are necessary to confirm this potential negative effect.

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Changing Paradigms in the Management of Rejection in Kidney Transplantation

Cited by 11 publications

References 136 publications

Sex-associated differences in cytomegalovirus prevention: Prophylactic strategy is associated with a strong kidney function impairment in female renal transplant patients

Sex-associated differences in cytomegalovirus prevention: Prophylactic strategy is associated with a strong kidney function impairment in female renal transplant patients

Association Between Newborn Metabolic Profiles and Pediatric Kidney Disease

Sex-Associated Differences in Cytomegalovirus Prevention: Prophylactic Strategy is Potentially Associated With a Strong Kidney Function Impairment in Female Renal Transplant Patients

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