Oral Coenzyme Q10 supplementation leads to better preservation of kidney function in steroid-resistant nephrotic syndrome due to primary Coenzyme Q10 deficiency

被引：37

作者：

Drovandi, Stefania ^{[1
,2
,3
,4
]}

Lipska-Zietkiewicz, Beata S. ^{[5
,6
]}

Ozaltin, Fatih ^{[7
]}

Emma, Francesco ^{[8
]}

Gulhan, Bora ^{[7
]}

Boyer, Olivia ^{[9
,10
,11
]}

Trautmann, Agnes ^{[1
]}

Xu, Hong ^{[12
]}

Shen, Qian ^{[12
]}

Rao, Jia ^{[12
]}

Riedhammer, Korbinian M. ^{[13
,14
]}

Heemann, Uwe ^{[13
,14
]}

Hoefele, Julia

Stenton, Sarah L. ^{[15
]}

Tsygin, Alexey N. ^{[16
]}

Ng, Kar-Hui ^{[17
]}

Fomina, Svitlana ^{[18
]}

Benetti, Elisa ^{[19
]}

Aurelle, Manon ^{[20
]}

Prikhodina, Larisa ^{[21
]}

Schreuder, Michiel F. ^{[22
]}

Tabatabaeifar, Mansoureh ^{[1
]}

Jankowski, Maciej ^{[6
]}

Baiko, Sergey ^{[23
]}

Mao, Jianhua ^{[24
]}

Feng, Chunyue ^{[24
]}

Liu, Cuihua ^{[25
]}

Sun, Shuzhen ^{[26
]}

Deng, Fang ^{[27
]}

Wang, Xiaowen ^{[28
]}

Clave, Stephanie ^{[29
]}

Stanczyk, Malgorzata ^{[30
]}

Balasz-Chmielewska, Irena ^{[31
]}

Fila, Marc ^{[32
]}

Durkan, Anne M. ^{[33
]}

Levart, Tanja Kersnik ^{[34
]}

Dursun, Ismail ^{[35
]}

Esfandiar, Nasrin ^{[36
]}

Haas, Dorothea ^{[37
]}

Bjerre, Anna ^{[38
,39
]}

Anarat, Ali ^{[40
]}

Benz, Marcus R. ^{[41
]}

Talebi, Saeed ^{[42
]}

Hooman, Nakysa ^{[43
]}

Ariceta, Gema ^{[44
]}

Schaefer, Franz

机构：

[1] Heidelberg Univ, Div Pediat Nephrol, Ctr Pediat & Adolescent Med, Heidelberg, Germany

[2] Giannina Gaslini Childrens Hosp, Div Nephrol Dialysis Transplantat, Genoa, Italy

[3] Osped Policlin San Martino, Dept Internal Med, Div Nephrol Dialysis & Transplantat, Genoa, Italy

[4] Univ Genoa, Genoa, Italy

[5] Med Univ Gdansk, Rare Dis Ctr, Gdansk, Poland

[6] Med Univ Gdansk, Dept Biol & Med Genet, Clin Genet Unit, Gdansk, Poland

[7] Hacettepe Univ, Div Pediat Nephrol, Dept Pediat, Fac Med, Ankara, Turkey

[8] Bambino Gesu Pediat Hosp, Div Nephrol & Dialysis, Dept Pediat Subspecialties, IRCCS, Rome, Italy

[9] Necker Enfants Malades Hosp, Assistance Publ Hop Paris AP HP, Pediat Nephrol, MARHEA, Paris, France

[10] SNI Reference Ctr, Paris, France

[11] Paris Univ, Imagine Inst, Paris, France

[12] Fudan Univ, Childrens Natl Med Ctr, Childrens Hosp, Shanghai, Peoples R China

[13] Tech Univ Munich, Sch Med, Inst Human Genet, Klinikum Rechts Isar, Munich, Germany

[14] Tech Univ Munich, Sch Med, Dept Nephrol, Klinikum Rechts Isar, Munich, Germany

[15] Helmholtz Zentrum Munchen, Inst Neurogen, Munich, Germany

[16] Natl Med & Res Ctr Childrens Hlth, Dept Pediat Nephrol, Moscow, Russia

[17] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Paediat, Singapore, Singapore

[18] Inst Nephrol NAMS Ukraine, Dept Pediat Nephrol, Kiev, Ukraine

[19] Padua Univ Hosp, Dept Womens & Childrens Hlth, Pediatr Nephrol Dialysis & Transplant Unit, Padua, Italy

[20] Univ Childrens Hosp, Dept Pediat Nephrol, Lyon, France

[21] Pirogov Russian Natl Res Med Univ, Res & Clin Inst Pediat, Moscow, Russia

[22] Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Amalia Childrens Hosp, Dept Pediat Nephrol,Med Ctr, Nijmegen, Netherlands

[23] Belarusian State Med Univ, Dept Pediat, Minsk, BELARUS

[24] Univ Sch Med, Children Hosp Zhejiang, Dept Nephrol, Hangzhou, Peoples R China

[25] Henan Childrens Hosp, Dept Nephrol & Rheumatol, Zhengzhou, Peoples R China

[26] Shandong Prov Hosp, Dept Pediat Nephrol & Rheumatism & Immuno, Jinan, Peoples R China

[27] Anhui Prov Childrens Hosp, Dept Nephrol, Hefei, Peoples R China

[28] Huazhong Univ Sci Technol, Tongji Med Coll, Wuhan Childrens Hosp, Wuhan Maternal & Child Healthcare Hosp,Dept Nephr, Wuhan, Peoples R China

[29] Univ Hosp Marseille, Dept Multidisciplinary Pediat, Marseille, France

[30] Polish Mothers Mem Hosp Res Insitute, Dept Pediat Immunol & Nephrol, Lodz, Poland

[31] Med Univ Gdansk, Dept Pediat Nephrol & Hypertens, Fac Med, Gdansk, Poland

[32] Montpellier Univ Hosp, CHU Arnaud Villeneuve, Pediat Nephrol Dept, Montpellier, France

[33] Childrens Hosp Westmead, Dept Nephrol, Sydney, NSW, Australia

[34] Univ Med Ctr, Div Paediat, Dept Nephrol, Ljubljana, Slovenia

[35] Erciyes Univ, Div Nephrol, Dept Pediat, Fac Med, Kayseri, Turkey

[36] Shahid Beheshti Univ Med Sci, Res Inst Childrens Hlth, Pediat Nephrol Res Ctr, Tehran, Iran

[37] Univ Hosp Heidelberg, Ctr Pediat & Adolescent Med, Div Pediat Neurol & Metab Med, Heidelberg, Germany

[38] Oslo Univ Hosp, Div Pediat & Adolescent Med, Oslo, Norway

[39] Univ Oslo, Inst Clin Med, Oslo, Norway

[40] Cukurova Univ, Dept Pediat Nephrol, Adana, Turkey

[41] Pediat Med Dachau, Pediatr Nephrol, Dachau, Germany

[42] Iran Univ Med Sci, Sch Med, Dept Med Genet, Tehran, Iran

[43] Iran Univ Med Sci IUMS, Sch Med, Aliasghar Clin Res Dev Ctr, Dept Pediat, Tehran, Iran

[44] Univ Hosp Vall Hebron, Dept Pediat Nephrol, Barcelona, Spain

来源：

KIDNEY INTERNATIONAL | 2022年 / 102卷 / 03期

基金：

欧盟第七框架计划;

关键词：

coenzyme Q(10); coenzyme Q(10) deficiency; COQ2; COQ6; COQ8B; CoQ(10); CoQ(10) supplementation therapy; end-stage kidney disease; ESKD; genetic kidney disease; hereditary; kidney survival; outcome; proteinuria reduction; ADCK4; MUTATIONS;

D O I：

10.1016/j.kint.2022.04.029

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Primary Coenzyme Q10 (CoQ(10)) deficiency is an ultra-rare disorder caused by defects in genes involved in CoQ(10) biosynthesis leading to multidrug-resistant nephrotic syndrome as the hallmark kidney manifestation. Promising early results have been reported anecdotally with oral CoQ(10) supplementation. However, the long-term efficacy and optimal prescription remain to be established. In a global effort, we collected and analyzed information from 116 patients who received CoQ(10) supplements for primary CoQ(10) deficiency due to biallelic pathogenic variants in either the COQ2, COQ6 or COQ8B genes. Median duration of follow up on treatment was two years. The effect of treatment on proteinuria was assessed, and kidney survival was analyzed in 41 patients younger than 18 years with chronic kidney disease stage 1-4 at the start of treatment compared with that of an untreated cohort matched by genotype, age, kidney function, and proteinuria. CoQ(10) supplementation was associated with a substantial and significant sustained reduction of proteinuria by 88% at 12 months. Complete remission of proteinuria was more frequently observed in COQ6 disease. CoQ(10) supplementation led to significantly better preservation of kidney function (5-year kidney failure-free survival 62% vs. 19%) with an improvement in general condition and neurological manifestations. Side effects of treatment were uncommon and mild. Thus, our findings indicate that all patients diagnosed with primary CoQ(10) deficiency should receive early and life-long CoQ(10) supplementation to decelerate the progression of kidney disease and prevent further damage to other organs.

引用

页码：604 / 612

页数：9

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