Renal outcome and plasma methylmalonic acid levels after isolated or combined liver or kidney transplantation in patients with methylmalonic acidemia: A multicenter analysis

Luca Dello Strologo; Marco Spada; Carlo Dionisi Vici; Marta Ciofi Degli Atti; Michelle Rheault; Anna Kristina Bjerre; Olivia Boyer; Pier Luigi Calvo; Lorenzo D'Antiga; Lyndsay A. Harshman; Friederike Hörster; Stefan Kölker; Timo Jahnukainen; Noël Knops; Pauline Krug; Kai Krupka; Angela Lee; Elena Levtchenko; Stephen D. Marks; Jelena Stojanovic; Laura Martelli; George Mazariegos; Giovanni Montini; Mohan Shenoy; Sangeet Sidhu; Trine Tangeras; Sara Testa; Suresh Vijay; Katarzyna Wac; Lars Wennberg; Waldo Concepcion; Sven F. Garbade; Burkhard Tönshoff

doi:10.1016/j.ymgme.2022.09.010

Renal outcome and plasma methylmalonic acid levels after isolated or combined liver or kidney transplantation in patients with methylmalonic acidemia: A multicenter analysis

Luca Dello Strologo, Marco Spada, Carlo Dionisi Vici, Marta Ciofi Degli Atti, Michelle Rheault, Anna Kristina Bjerre, Olivia Boyer, Pier Luigi Calvo, Lorenzo D'Antiga, Lyndsay A. Harshman, Friederike Hörster, Stefan Kölker, Timo Jahnukainen, Noël Knops, Pauline Krug, Kai Krupka, Angela Lee, Elena Levtchenko, Stephen D. Marks, Jelena StojanovicLaura Martelli, George Mazariegos, Giovanni Montini, Mohan Shenoy, Sangeet Sidhu, Trine Tangeras, Sara Testa, Suresh Vijay, Katarzyna Wac, Lars Wennberg, Waldo Concepcion, Sven F. Garbade, Burkhard Tönshoff

Pediatric Nephrology

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Background: Methylmalonic acidemia (MMAemia) is characterized by accumulation of methylmalonic acid (MMA) in all body tissues. To minimize disease-related complications, isolated kidney (KTx), liver (LTx) or combined liver-kidney transplantation (LKTx) have been suggested. However, the impact of these different transplant strategies on outcome are unclear. Methods: In this multicenter retrospective observational study, we compared plasma MMA levels and estimated glomerular filtration rate (eGFR) data of 83 patients. Sixty-eight patients (82%) had a mut⁰-type MMAemia, one patient had a mut⁻-type MMAemia, and seven (7.3%) had an inherited defect in cobalamin metabolism (cblA- or cblB-type MMAemia). Median observation period was 3.7 years (0–15.1 years). Results: Twenty-six (31%) patients underwent KTx, 24 (29%) LTx and 33 (40%) LKTx. Posttransplant, mean plasma MMA concentration significantly decreased in all three cohorts; but at month 12, plasma MMA in KTx (1372 ± 1101 μmol/L) was 7.8-fold higher than in LTx (176 ± 103 μmol/L; P < 0.001) and 6.4-fold higher than in LKTx (215 ± 110 μmol/L; P < 0.001). Comparable data were observed at month 24. At time of transplantation, mean eGFR in KTx was 18.1 ± 24.3 mL/min/1.73 m², in LTx 99.8 ± 29.9 mL/min/1.73 m², and in LKTx 31.5 ± 21.2 mL/min/1.73 m². At month 12 posttransplant, mean eGFR in KTx (62.3 ± 30.3 mL/min/1.73 m²) was 33.4% lower than in LTx (93.5 ± 18.3 mL/min/1.73 m²; P = 0.0053) and 25.4% lower than in LKTx (83.5 ± 26.9 mL/min/1.73 m²; P = 0.0403). Conclusions: In patients with isolated MMAemia, LTx and LKTx lead to markedly lower plasma MMA levels during the first 2 years posttransplant than KTx and are associated with a better preservation of kidney function. LTx should therefore be part of the transplant strategy in MMAemia.

Original language	English (US)
Pages (from-to)	265-272
Number of pages	8
Journal	Molecular Genetics and Metabolism
Volume	137
Issue number	3
DOIs	https://doi.org/10.1016/j.ymgme.2022.09.010
State	Published - Nov 2022

Bibliographical note

Funding Information:
We thank the European Society for Paediatric Nephrology and the Midwest Pediatric Nephrology consortium for their support with patient recruitment. Trine Tangeraas and Stefan Kölker are members of the European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN). The authors gratefully acknowledge the funding of the CERTAIN Registry by a grant from the Dietmar Hopp Stiftung , the European Society for Paediatric Nephrology (ESPN) , The German Society for Pediatric Nephrology (GPN) , and by grants from the pharmaceutical companies Astellas and Novartis .

Funding Information:
We thank the European Society for Paediatric Nephrology and the Midwest Pediatric Nephrology consortium for their support with patient recruitment. Trine Tangeraas and Stefan Kölker are members of the European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN). The authors gratefully acknowledge the funding of the CERTAIN Registry by a grant from the Dietmar Hopp Stiftung, the European Society for Paediatric Nephrology (ESPN), The German Society for Pediatric Nephrology (GPN), and by grants from the pharmaceutical companies Astellas and Novartis.

Publisher Copyright:
© 2022 Elsevier Inc.

Keywords

Combined liver-kidney transplantation
Estimated glomerular filtration rate
Kidney transplantation
Liver transplantation
Methylmalonic acid
Methylmalonic acidemia
Humans
Liver
Kidney Transplantation
Methylmalonic Acid
Amino Acid Metabolism, Inborn Errors/genetics
Kidney

PubMed: MeSH publication types

Research Support, Non-U.S. Gov't
Observational Study
Multicenter Study
Journal Article

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10.1016/j.ymgme.2022.09.010

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Dello Strologo, L., Spada, M., Vici, C. D., Atti, M. C. D., Rheault, M., Bjerre, A. K., Boyer, O., Calvo, P. L., D'Antiga, L., Harshman, L. A., Hörster, F., Kölker, S., Jahnukainen, T., Knops, N., Krug, P., Krupka, K., Lee, A., Levtchenko, E., Marks, S. D., ... Tönshoff, B. (2022). Renal outcome and plasma methylmalonic acid levels after isolated or combined liver or kidney transplantation in patients with methylmalonic acidemia: A multicenter analysis. Molecular Genetics and Metabolism, 137(3), 265-272. https://doi.org/10.1016/j.ymgme.2022.09.010

Renal outcome and plasma methylmalonic acid levels after isolated or combined liver or kidney transplantation in patients with methylmalonic acidemia: A multicenter analysis. / Dello Strologo, Luca; Spada, Marco; Vici, Carlo Dionisi et al.
In: Molecular Genetics and Metabolism, Vol. 137, No. 3, 11.2022, p. 265-272.

Research output: Contribution to journal › Article › peer-review

Dello Strologo, L, Spada, M, Vici, CD, Atti, MCD, Rheault, M, Bjerre, AK, Boyer, O, Calvo, PL, D'Antiga, L, Harshman, LA, Hörster, F, Kölker, S, Jahnukainen, T, Knops, N, Krug, P, Krupka, K, Lee, A, Levtchenko, E, Marks, SD, Stojanovic, J, Martelli, L, Mazariegos, G, Montini, G, Shenoy, M, Sidhu, S, Tangeras, T, Testa, S, Vijay, S, Wac, K, Wennberg, L, Concepcion, W, Garbade, SF & Tönshoff, B 2022, 'Renal outcome and plasma methylmalonic acid levels after isolated or combined liver or kidney transplantation in patients with methylmalonic acidemia: A multicenter analysis', Molecular Genetics and Metabolism, vol. 137, no. 3, pp. 265-272. https://doi.org/10.1016/j.ymgme.2022.09.010

@article{e82e2759feeb4a748eee6d878c76700a,

title = "Renal outcome and plasma methylmalonic acid levels after isolated or combined liver or kidney transplantation in patients with methylmalonic acidemia: A multicenter analysis",

abstract = "Background: Methylmalonic acidemia (MMAemia) is characterized by accumulation of methylmalonic acid (MMA) in all body tissues. To minimize disease-related complications, isolated kidney (KTx), liver (LTx) or combined liver-kidney transplantation (LKTx) have been suggested. However, the impact of these different transplant strategies on outcome are unclear. Methods: In this multicenter retrospective observational study, we compared plasma MMA levels and estimated glomerular filtration rate (eGFR) data of 83 patients. Sixty-eight patients (82%) had a mut0-type MMAemia, one patient had a mut−-type MMAemia, and seven (7.3%) had an inherited defect in cobalamin metabolism (cblA- or cblB-type MMAemia). Median observation period was 3.7 years (0–15.1 years). Results: Twenty-six (31%) patients underwent KTx, 24 (29%) LTx and 33 (40%) LKTx. Posttransplant, mean plasma MMA concentration significantly decreased in all three cohorts; but at month 12, plasma MMA in KTx (1372 ± 1101 μmol/L) was 7.8-fold higher than in LTx (176 ± 103 μmol/L; P < 0.001) and 6.4-fold higher than in LKTx (215 ± 110 μmol/L; P < 0.001). Comparable data were observed at month 24. At time of transplantation, mean eGFR in KTx was 18.1 ± 24.3 mL/min/1.73 m2, in LTx 99.8 ± 29.9 mL/min/1.73 m2, and in LKTx 31.5 ± 21.2 mL/min/1.73 m2. At month 12 posttransplant, mean eGFR in KTx (62.3 ± 30.3 mL/min/1.73 m2) was 33.4% lower than in LTx (93.5 ± 18.3 mL/min/1.73 m2; P = 0.0053) and 25.4% lower than in LKTx (83.5 ± 26.9 mL/min/1.73 m2; P = 0.0403). Conclusions: In patients with isolated MMAemia, LTx and LKTx lead to markedly lower plasma MMA levels during the first 2 years posttransplant than KTx and are associated with a better preservation of kidney function. LTx should therefore be part of the transplant strategy in MMAemia.",

keywords = "Combined liver-kidney transplantation, Estimated glomerular filtration rate, Kidney transplantation, Liver transplantation, Methylmalonic acid, Methylmalonic acidemia, Humans, Liver, Kidney Transplantation, Methylmalonic Acid, Amino Acid Metabolism, Inborn Errors/genetics, Kidney",

author = "{Dello Strologo}, Luca and Marco Spada and Vici, {Carlo Dionisi} and Atti, {Marta Ciofi Degli} and Michelle Rheault and Bjerre, {Anna Kristina} and Olivia Boyer and Calvo, {Pier Luigi} and Lorenzo D'Antiga and Harshman, {Lyndsay A.} and Friederike H{\"o}rster and Stefan K{\"o}lker and Timo Jahnukainen and No{\"e}l Knops and Pauline Krug and Kai Krupka and Angela Lee and Elena Levtchenko and Marks, {Stephen D.} and Jelena Stojanovic and Laura Martelli and George Mazariegos and Giovanni Montini and Mohan Shenoy and Sangeet Sidhu and Trine Tangeras and Sara Testa and Suresh Vijay and Katarzyna Wac and Lars Wennberg and Waldo Concepcion and Garbade, {Sven F.} and Burkhard T{\"o}nshoff",

note = "Funding Information: We thank the European Society for Paediatric Nephrology and the Midwest Pediatric Nephrology consortium for their support with patient recruitment. Trine Tangeraas and Stefan K{\"o}lker are members of the European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN). The authors gratefully acknowledge the funding of the CERTAIN Registry by a grant from the Dietmar Hopp Stiftung , the European Society for Paediatric Nephrology (ESPN) , The German Society for Pediatric Nephrology (GPN) , and by grants from the pharmaceutical companies Astellas and Novartis . Funding Information: We thank the European Society for Paediatric Nephrology and the Midwest Pediatric Nephrology consortium for their support with patient recruitment. Trine Tangeraas and Stefan K{\"o}lker are members of the European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN). The authors gratefully acknowledge the funding of the CERTAIN Registry by a grant from the Dietmar Hopp Stiftung, the European Society for Paediatric Nephrology (ESPN), The German Society for Pediatric Nephrology (GPN), and by grants from the pharmaceutical companies Astellas and Novartis. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",

year = "2022",

month = nov,

doi = "10.1016/j.ymgme.2022.09.010",

language = "English (US)",

volume = "137",

pages = "265--272",

journal = "Molecular Genetics and Metabolism",

issn = "1096-7192",

publisher = "Academic Press Inc.",

number = "3",

}

TY - JOUR

T1 - Renal outcome and plasma methylmalonic acid levels after isolated or combined liver or kidney transplantation in patients with methylmalonic acidemia

T2 - A multicenter analysis

AU - Dello Strologo, Luca

AU - Spada, Marco

AU - Vici, Carlo Dionisi

AU - Atti, Marta Ciofi Degli

AU - Rheault, Michelle

AU - Bjerre, Anna Kristina

AU - Boyer, Olivia

AU - Calvo, Pier Luigi

AU - D'Antiga, Lorenzo

AU - Harshman, Lyndsay A.

AU - Hörster, Friederike

AU - Kölker, Stefan

AU - Jahnukainen, Timo

AU - Knops, Noël

AU - Krug, Pauline

AU - Krupka, Kai

AU - Lee, Angela

AU - Levtchenko, Elena

AU - Marks, Stephen D.

AU - Stojanovic, Jelena

AU - Martelli, Laura

AU - Mazariegos, George

AU - Montini, Giovanni

AU - Shenoy, Mohan

AU - Sidhu, Sangeet

AU - Tangeras, Trine

AU - Testa, Sara

AU - Vijay, Suresh

AU - Wac, Katarzyna

AU - Wennberg, Lars

AU - Concepcion, Waldo

AU - Garbade, Sven F.

AU - Tönshoff, Burkhard

N1 - Funding Information: We thank the European Society for Paediatric Nephrology and the Midwest Pediatric Nephrology consortium for their support with patient recruitment. Trine Tangeraas and Stefan Kölker are members of the European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN). The authors gratefully acknowledge the funding of the CERTAIN Registry by a grant from the Dietmar Hopp Stiftung , the European Society for Paediatric Nephrology (ESPN) , The German Society for Pediatric Nephrology (GPN) , and by grants from the pharmaceutical companies Astellas and Novartis . Funding Information: We thank the European Society for Paediatric Nephrology and the Midwest Pediatric Nephrology consortium for their support with patient recruitment. Trine Tangeraas and Stefan Kölker are members of the European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN). The authors gratefully acknowledge the funding of the CERTAIN Registry by a grant from the Dietmar Hopp Stiftung, the European Society for Paediatric Nephrology (ESPN), The German Society for Pediatric Nephrology (GPN), and by grants from the pharmaceutical companies Astellas and Novartis. Publisher Copyright: © 2022 Elsevier Inc.

PY - 2022/11

Y1 - 2022/11

N2 - Background: Methylmalonic acidemia (MMAemia) is characterized by accumulation of methylmalonic acid (MMA) in all body tissues. To minimize disease-related complications, isolated kidney (KTx), liver (LTx) or combined liver-kidney transplantation (LKTx) have been suggested. However, the impact of these different transplant strategies on outcome are unclear. Methods: In this multicenter retrospective observational study, we compared plasma MMA levels and estimated glomerular filtration rate (eGFR) data of 83 patients. Sixty-eight patients (82%) had a mut0-type MMAemia, one patient had a mut−-type MMAemia, and seven (7.3%) had an inherited defect in cobalamin metabolism (cblA- or cblB-type MMAemia). Median observation period was 3.7 years (0–15.1 years). Results: Twenty-six (31%) patients underwent KTx, 24 (29%) LTx and 33 (40%) LKTx. Posttransplant, mean plasma MMA concentration significantly decreased in all three cohorts; but at month 12, plasma MMA in KTx (1372 ± 1101 μmol/L) was 7.8-fold higher than in LTx (176 ± 103 μmol/L; P < 0.001) and 6.4-fold higher than in LKTx (215 ± 110 μmol/L; P < 0.001). Comparable data were observed at month 24. At time of transplantation, mean eGFR in KTx was 18.1 ± 24.3 mL/min/1.73 m2, in LTx 99.8 ± 29.9 mL/min/1.73 m2, and in LKTx 31.5 ± 21.2 mL/min/1.73 m2. At month 12 posttransplant, mean eGFR in KTx (62.3 ± 30.3 mL/min/1.73 m2) was 33.4% lower than in LTx (93.5 ± 18.3 mL/min/1.73 m2; P = 0.0053) and 25.4% lower than in LKTx (83.5 ± 26.9 mL/min/1.73 m2; P = 0.0403). Conclusions: In patients with isolated MMAemia, LTx and LKTx lead to markedly lower plasma MMA levels during the first 2 years posttransplant than KTx and are associated with a better preservation of kidney function. LTx should therefore be part of the transplant strategy in MMAemia.

AB - Background: Methylmalonic acidemia (MMAemia) is characterized by accumulation of methylmalonic acid (MMA) in all body tissues. To minimize disease-related complications, isolated kidney (KTx), liver (LTx) or combined liver-kidney transplantation (LKTx) have been suggested. However, the impact of these different transplant strategies on outcome are unclear. Methods: In this multicenter retrospective observational study, we compared plasma MMA levels and estimated glomerular filtration rate (eGFR) data of 83 patients. Sixty-eight patients (82%) had a mut0-type MMAemia, one patient had a mut−-type MMAemia, and seven (7.3%) had an inherited defect in cobalamin metabolism (cblA- or cblB-type MMAemia). Median observation period was 3.7 years (0–15.1 years). Results: Twenty-six (31%) patients underwent KTx, 24 (29%) LTx and 33 (40%) LKTx. Posttransplant, mean plasma MMA concentration significantly decreased in all three cohorts; but at month 12, plasma MMA in KTx (1372 ± 1101 μmol/L) was 7.8-fold higher than in LTx (176 ± 103 μmol/L; P < 0.001) and 6.4-fold higher than in LKTx (215 ± 110 μmol/L; P < 0.001). Comparable data were observed at month 24. At time of transplantation, mean eGFR in KTx was 18.1 ± 24.3 mL/min/1.73 m2, in LTx 99.8 ± 29.9 mL/min/1.73 m2, and in LKTx 31.5 ± 21.2 mL/min/1.73 m2. At month 12 posttransplant, mean eGFR in KTx (62.3 ± 30.3 mL/min/1.73 m2) was 33.4% lower than in LTx (93.5 ± 18.3 mL/min/1.73 m2; P = 0.0053) and 25.4% lower than in LKTx (83.5 ± 26.9 mL/min/1.73 m2; P = 0.0403). Conclusions: In patients with isolated MMAemia, LTx and LKTx lead to markedly lower plasma MMA levels during the first 2 years posttransplant than KTx and are associated with a better preservation of kidney function. LTx should therefore be part of the transplant strategy in MMAemia.

KW - Combined liver-kidney transplantation

KW - Estimated glomerular filtration rate

KW - Kidney transplantation

KW - Liver transplantation

KW - Methylmalonic acid

KW - Methylmalonic acidemia

KW - Humans

KW - Liver

KW - Kidney Transplantation

KW - Methylmalonic Acid

KW - Amino Acid Metabolism, Inborn Errors/genetics

KW - Kidney

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UR - http://www.scopus.com/inward/citedby.url?scp=85139729626&partnerID=8YFLogxK

U2 - 10.1016/j.ymgme.2022.09.010

DO - 10.1016/j.ymgme.2022.09.010

M3 - Article

C2 - 36240580

AN - SCOPUS:85139729626

SN - 1096-7192

VL - 137

SP - 265

EP - 272

JO - Molecular Genetics and Metabolism

JF - Molecular Genetics and Metabolism

IS - 3

ER -

Renal outcome and plasma methylmalonic acid levels after isolated or combined liver or kidney transplantation in patients with methylmalonic acidemia: A multicenter analysis

Abstract

Bibliographical note

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