Abstract
Purpose: We aimed to determine serum mitochondrial open reading frame 12S rRNA-c (MOTS-C) levels as an indicator of mitochondrial dysfunction in childhood chronic kidney disease patients and to investigate the relationship of this parameter, which is a metabolic regulatory factor, with renal anemia, hypertension metabolic acidosis and renal osteodystrophy.
Materials and methods: The study included 46 children with chronic kidney disease and 46 healthy children of similar age and gender. The patient group was divided into G1-G5 subgroups according to glomerular filtration rate, etiology, renal replacement therapies and the presence of anemia, hypertension, hyperparathyroidism and metabolic acidosis. Data were analyzed using SPSS 25.0 package program.
Results: The mean MOTS-C level was 60.47±11.1 ng/ml in patients with chronic kidney disease and 105.2±54.7 ng/ml in healthy children (p=0.001). The MOTS-C level was significantly lower in children with chronic kidney disease. In addition, there was no significant difference between patients who underwent renal transplantation and patients on chronic dialysis or predialysis. MOTS-C levels were significantly lower in patients with hyperparathyroidism and anemia compared to those without.
Conclusion: In our study, we demonstrated that mitochondrial damage in children with chronic kidney disease begins even in the early stages, renal osteodystrophy and anemia contribute to this condition, and mitochondrial inflammation persists even after kidney transplantation in these patients.
Keywords
Project Number
YOK
References
- Gamboa JL, Billings FT 4th, Bojanowski MT, et al. Mitochondrial dysfunction and oxidative stress in patients with chronic kidney disease. Physiol Rep. 2016;4(9):e12780. doi:10.14814/phy2.12780
- Granata S, Dalla Gassa A, Bellin G, Lupo A, Zaza G. Transcriptomics: A Step behind the Comprehension of the Polygenic Influence on Oxidative Stress, Immune Deregulation, and Mitochondrial Dysfunction in Chronic Kidney Disease. Biomed Res Int. 2016;2016:9290857. doi:10.1155/2016/9290857
- Rani V, Deep G, Singh RK, Palle K, Yadav UC. Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies. Life Sci. 2016;148:183-193. doi:10.1016/j.lfs.2016.02.002
- Liu C, Gidlund EK, Witasp A, et al. Reduced skeletal muscle expression of mitochondrial-derived peptides humanin and MOTS-C and Nrf2 in chronic kidney disease. Am J Physiol Renal Physiol. 2019;317(5):1122-1131. doi:10.1152/ajprenal.00202.2019
- Daenen K, Andries A, Mekahli D, Van Schepdael A, Jouret F, Bammens B. Oxidative stress in chronic kidney disease. Pediatr Nephrol. 2019;34(6):975-991. doi:10.1007/s00467-018-4005-4
- Schwartz GJ, Muñoz A, Schneider MF, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009;20(3):629-637. doi:10.1681/asn.2008030287
- Stevens PE, Levin A. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013;158(11):825-830. doi:10.7326/0003-4819-158-11-201306040-00007
- Iatridi F, Carrero JJ, Gall EC, et al. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease in Children and Adults: a commentary from the European Renal Best Practice (ERBP). Nephrol Dial Transplant. 2025;40(2):273-282. doi:10.1093/ndt/gfae209
- Nutritional anaemias. Report of a WHO scientific group. World Health Organ Tech Rep Ser. 1968;405:5-37.
- National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004;114(2 Suppl 4th Report):555-576.
- Uribarri J, National Kidney Foundation. K/DOQI guidelines for bone metabolism and disease in chronic kidney disease patients: some therapeutic implications. Semin Dial. 2004;17(5):349-350. doi:10.1111/j.0894-0959.2004.17354.x
- Gambardella J, De Rosa M, Sorriento D, et al. Parathyroid Hormone Causes Endothelial Dysfunction by Inducing Mitochondrial ROS and Specific Oxidative Signal Transduction Modifications. Oxid Med Cell Longev. 2018;2018:9582319. doi:10.1155/2018/9582319
- Deska M, Romuk E, Segiet OA, et al. Oxidative stress and angiogenesis in primary hyperparathyroidism. Eur Surg. 2017;49(3):118-126. doi:10.1007/s10353-016-0457-6
- Abdulrahman SMF, Kilboz BB, Teksöz D, Soylu S, Bolayirli M, Teksöz S. Effect of parathyroidectomy on oxidative stress in patients with primary hyperparathyroidism. Acta Endocrinol (Buchar). 2022;18(1):20-23. doi:10.4183/aeb.2022.20
- Dikalov SI, Ungvari Z. Role of mitochondrial oxidative stress in hypertension. Am J Physiol Heart Circ Physiol. 2013;305(10):H1417-1427. doi:10.1152/ajpheart.00089.2013
- Aslan M, Horoz M, Kocyigit A, et al. Lymphocyte DNA damage and oxidative stress in patients with iron deficiency anemia. Mutat Res. 2006;601(1-2):144-149. doi:10.1016/j.mrfmmm.2006.06.013
- El Shimi MS, El Farrash RA, Ismail EA, et al. Renal functional and structural integrity in infants with iron deficiency anemia: relation to oxidative stress and response to iron therapy. Pediatr Nephrol. 2015;30(10):1835-1842. doi:10.1007/s00467-015-3122-6
- Akchurin OM, Kaskel F. Update on inflammation in chronic kidney disease. Blood Purif. 2015;39(1-3):84-92. doi:10.1159/000368940
- Du C, Zhang C, Wu W, et al. Circulating MOTS-c levels are decreased in obese male children and adolescents and associated with insulin resistance. Pediatr Diabetes. Published online 2018. doi:10.1111/pedi.12685
Abstract
Amaç: Çocukluk çağı kronik böbrek hastalarında mitokondriyal disfonksiyonun bir göstergesi olarak serum MOTS-C düzeylerini belirlemeyi ve metabolik düzenleyici bir faktör olan bu parametrenin renal anemi, hipertansiyon, metabolik asidoz ve renal osteodistrofi ile ilişkisini araştırmayı amaçladık.
Gereç ve yöntem: Çalışmaya kronik böbrek hastalığı olan 46 çocuk ve benzer yaş ve cinsiyette 46 sağlıklı çocuk dahil edildi. Hasta grubu glomerüler filtrasyon hızına göre G1-G5, etiyoloji, renal replasman tedavileri ve anemi, hipertansiyon, hiperparatiroidizm ve metabolik asidoz varlığına göre alt gruplarına ayrıldı. Veriler SPSS 25.0 paket programı kullanılarak analiz edildi.
Bulgular: Ortalama MOTS-C düzeyi kronik böbrek hastalığı olanlarda 60,47±11,1 ng/ml iken sağlıklı çocuklarda 105,2±54,7 ng/ml idi (p=0,001). MOTS-C düzeyi kronik böbrek hastalığı olan çocuklarda anlamlı derecede düşüktü. Ayrıca, böbrek nakli yapılan hastalar ile kronik diyaliz veya prediyaliz hastaları arasında anlamlı bir fark yoktu. MOTS-C düzeyleri hiperparatiroidizm ve anemisi olan hastalarda olmayanlara kıyasla anlamlı derecede düşüktü.
Sonuç: Çalışmamızda, kronik böbrek hastalığı olan çocuklarda mitokondriyal hasarın erken evrelerde bile başladığını, renal osteodistrofi ve aneminin bu duruma katkıda bulunduğunu ve mitokondriyal inflamasyonun bu hastalarda böbrek naklinden sonra bile devam ettiğini gösterdik.
Keywords
Ethical Statement
Permission was obtained from Pamukkale University Non-Interventional Clinical Research Ethics Committee for the study (04.03.2025 No:5, E-60116787-020-665941).
Supporting Institution
YOK
Project Number
YOK
Thanks
YOK
References
- Gamboa JL, Billings FT 4th, Bojanowski MT, et al. Mitochondrial dysfunction and oxidative stress in patients with chronic kidney disease. Physiol Rep. 2016;4(9):e12780. doi:10.14814/phy2.12780
- Granata S, Dalla Gassa A, Bellin G, Lupo A, Zaza G. Transcriptomics: A Step behind the Comprehension of the Polygenic Influence on Oxidative Stress, Immune Deregulation, and Mitochondrial Dysfunction in Chronic Kidney Disease. Biomed Res Int. 2016;2016:9290857. doi:10.1155/2016/9290857
- Rani V, Deep G, Singh RK, Palle K, Yadav UC. Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies. Life Sci. 2016;148:183-193. doi:10.1016/j.lfs.2016.02.002
- Liu C, Gidlund EK, Witasp A, et al. Reduced skeletal muscle expression of mitochondrial-derived peptides humanin and MOTS-C and Nrf2 in chronic kidney disease. Am J Physiol Renal Physiol. 2019;317(5):1122-1131. doi:10.1152/ajprenal.00202.2019
- Daenen K, Andries A, Mekahli D, Van Schepdael A, Jouret F, Bammens B. Oxidative stress in chronic kidney disease. Pediatr Nephrol. 2019;34(6):975-991. doi:10.1007/s00467-018-4005-4
- Schwartz GJ, Muñoz A, Schneider MF, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009;20(3):629-637. doi:10.1681/asn.2008030287
- Stevens PE, Levin A. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013;158(11):825-830. doi:10.7326/0003-4819-158-11-201306040-00007
- Iatridi F, Carrero JJ, Gall EC, et al. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease in Children and Adults: a commentary from the European Renal Best Practice (ERBP). Nephrol Dial Transplant. 2025;40(2):273-282. doi:10.1093/ndt/gfae209
- Nutritional anaemias. Report of a WHO scientific group. World Health Organ Tech Rep Ser. 1968;405:5-37.
- National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004;114(2 Suppl 4th Report):555-576.
- Uribarri J, National Kidney Foundation. K/DOQI guidelines for bone metabolism and disease in chronic kidney disease patients: some therapeutic implications. Semin Dial. 2004;17(5):349-350. doi:10.1111/j.0894-0959.2004.17354.x
- Gambardella J, De Rosa M, Sorriento D, et al. Parathyroid Hormone Causes Endothelial Dysfunction by Inducing Mitochondrial ROS and Specific Oxidative Signal Transduction Modifications. Oxid Med Cell Longev. 2018;2018:9582319. doi:10.1155/2018/9582319
- Deska M, Romuk E, Segiet OA, et al. Oxidative stress and angiogenesis in primary hyperparathyroidism. Eur Surg. 2017;49(3):118-126. doi:10.1007/s10353-016-0457-6
- Abdulrahman SMF, Kilboz BB, Teksöz D, Soylu S, Bolayirli M, Teksöz S. Effect of parathyroidectomy on oxidative stress in patients with primary hyperparathyroidism. Acta Endocrinol (Buchar). 2022;18(1):20-23. doi:10.4183/aeb.2022.20
- Dikalov SI, Ungvari Z. Role of mitochondrial oxidative stress in hypertension. Am J Physiol Heart Circ Physiol. 2013;305(10):H1417-1427. doi:10.1152/ajpheart.00089.2013
- Aslan M, Horoz M, Kocyigit A, et al. Lymphocyte DNA damage and oxidative stress in patients with iron deficiency anemia. Mutat Res. 2006;601(1-2):144-149. doi:10.1016/j.mrfmmm.2006.06.013
- El Shimi MS, El Farrash RA, Ismail EA, et al. Renal functional and structural integrity in infants with iron deficiency anemia: relation to oxidative stress and response to iron therapy. Pediatr Nephrol. 2015;30(10):1835-1842. doi:10.1007/s00467-015-3122-6
- Akchurin OM, Kaskel F. Update on inflammation in chronic kidney disease. Blood Purif. 2015;39(1-3):84-92. doi:10.1159/000368940
- Du C, Zhang C, Wu W, et al. Circulating MOTS-c levels are decreased in obese male children and adolescents and associated with insulin resistance. Pediatr Diabetes. Published online 2018. doi:10.1111/pedi.12685
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Pediatric Nephrology |
| Journal Section | Research Article |
| Authors | |
| Project Number | YOK |
| Early Pub Date | April 29, 2025 |
| Publication Date | |
| Submission Date | March 16, 2025 |
| Acceptance Date | April 29, 2025 |
| Published in Issue | Year 2025 Volume: 18 Issue: 3 |
