Document Type : original article

Authors

1 Pediatric Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

2 Pediatric Health Research Center, Department of Pediatrics, Tabriz University of Medical Sciences, Tabriz, Iran.

3 Clinical Research Development Unit of Children Educational and Treatment Center, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract

Background: Diabetes mellitus is the most common childhood metabolic disease whose prevalence has been increasing worldwide in recent decades. Diabetic nephropathy is one of the most important chronic complications of both types of diabetes (type one and two), which seriously increases the morbidity and mortality of diabetes. The present study evaluated the epidemiology and risk factors of diabetic nephropathy in children with diabetes in the northwestern region of Iran.
Method: In this cross-sectional study, 80 diabetic children, 33 (41.3%) males and 47 (58.7%) females with a mean age of 16.69± 4.50 years at the time of assessment, have been identified, evaluated, and followed up in the endocrinology clinic of Tabriz Children's Hospital from 2000 to 2015. The patients were divided into two groups based on the presence or absence of micro- or overt albuminuria, and different variables were compared between the two groups to determine risk factors.
Results: The mean age at the diagnosis was 7.75 ± 3.69 and the mean duration of diabetes was 8.98± 4.07 years. Good glycemic control was presented in 19 (23.8%), microalbuminuria in 36 (45%), overt albuminuria in 1 (1.3%), and retinopathy in 5 (6.3%) of patients; 7 (8.8%) had hypertension. Chronic kidney disease was found to be stage I in 90% and stage II in 10% of the patients. There was a significant difference between cases with and without albuminuria in terms of age at the time of the study (p=0.003), duration of diabetes (p=0.02), and serum cholesterol level (p=0.04). Linear Regression test showed that «the age at diagnosis» has a significant ability to predict the incidence of albuminuria (p = 0.03).
Conclusion: Due to the significant frequency of poor glycemic control in children and adolescents and the high prevalence of albuminuria in them, it is recommended to evaluate the renal function in diabetic children, especially in older patients, those with longer duration of diabetes or poor glycemic control.

Keywords

  1. Ahmed H, Elshaikh T, Abdullah M. Early Diabetic Nephropathy and Retinopathy in Patients with Type 1 Diabetes Mellitus Attending Sudan Childhood Diabetes Center. J Diabetes Res. 2020 Nov 24, 2020: 7181383. doi: 10.1155/2020/7181383. PMID: 33299891; PMCID: PMC7708000.
  2. Pasi R, Ravi KS. Type 1 diabetes mellitus in pediatric age group: A rising endemic. J Family Med Prim Care. 2022 Jan; 11(1):27-31. doi: 10.4103/jfmpc.jfmpc_975_21. Epub 2022 Jan 31. PMID: 35309606; PMCID: PMC8930152.
  3. Chi-Yu Huang, Wei-Hsin Ting, Fu-Sung Lo, Jeng-Daw Tsai, Fang-Ju Sun, Chan CI, Chiang YT, Lin CH, Cheng BW, Wu YL, Hung CM, Lee YJ. Factors associated with diabetic nephropathy in children, adolescents, and adults with type 1 diabetes, Journal of the Formosan Medical Association, 2017, 116(12):924-932, https://doi.org/10.1016/j.jfma.2017.09.015.
  4. Mohammed Emam SS, El–Behiedy RM, Elshal AS, Mohammed MA. Frequency of Diabetic Nephropathy in Diabetic Children and Adolescents at Children Hospital of Zagazig University. European Journal of Molecular & Clinical Medicine, 2021; 8(3): 2850-2861.
  5. Bogdanović R. Diabetic nephropathy in children and adolescents. Pediatr Nephrol. 2008 Apr; 23(4):507-25. doi: 10.1007/s00467-007-0583-2. Epub 2007 Oct 17. PMID: 17940807.
  6. Al-Agha AE, Ocheltree A, Hakeem A. Occurrence of microalbuminuria among children and adolescents with insulin-dependent diabetes mellitus. Saudi J Kidney Dis Transpl. 2013 Nov; 24(6):1180-8. doi: 10.4103/1319-2442.121276. PMID: 24231481.
  7. Mamilly L, Mastrandrea LD, Mosquera Vasquez C, Klamer B, Kallash M, Aldughiem A. Evidence of Early Diabetic Nephropathy in Pediatric Type 1 Diabetes. Front Endocrinol (Lausanne). 2021 Apr 28; 12:669954. doi: 10.3389/fendo.2021.669954. PMID: 33995287; PMCID: PMC8113955.
  8. Zabeen B, Nahar J, Islam N, Azad K, Donaghue K. Risk Factors Associated with Microalbuminuria in Children and Adolescents with Diabetes in Bangladesh. Indian J Endocrinol Metab. 2018 Jan-Feb; 22(1):85-88. doi: 10.4103/ijem.IJEM_269_17. PMID: 29535943; PMCID: PMC5838918.
  9. Zachwieja J, Soltysiak J, Fichna P, Lipkowska K, Stankiewicz W, Skowronska B, Kroll P, Lewandowska-Stachowiak M. Normal-range albuminuria does not exclude nephropathy in diabetic children. Pediatr Nephrol. 2010 Aug; 25(8):1445-51. doi: 10.1007/s00467-010-1443-z. Epub 2010 Feb 16. Erratum in: Pediatr Nephrol. 2010 Aug; 25(8):1581. PMID: 20157738.
  10. Son MK, Yoo HY, Kwak BO, Park HW, Kim KS, Chung S, Chae HW, Kim HS, Kim DH. Regression and progression of microalbuminuria in adolescents with childhood onset diabetes mellitus. Ann Pediatr Endocrinol Metab. 2015 Mar; 20(1):13-20. doi: 10.6065/apem.2015.20.1.13. Epub 2015 Mar 31. PMID: 25883922; PMCID: PMC4397268.
  11. Razavi Z, Momtaz HE, Sahari S. Frequency of microalbuminuria in type 1 diabetic children. Iran J Pediatr, 2009; 19(4), 404-408.
  12. Donaghue KC, Marcovecchio ML, Wadhwa RP, Chew EY, Wong TY, Calliari LE, Zabeen B, Salem MA, Craig ME. ISPAD Clinical Practice Consensus Guidelines 2018: Microvascular and macrovascular complications in children and adolescents. Pediatr Diabetes. 2018 Oct; 19 Suppl 27(Suppl 27):262-274. doi: 10.1111/pedi.12742. PMID: 30079595; PMCID: PMC8559793.
  13. Afkarian M. Diabetic kidney disease in children and adolescents. Pediatr Nephrol. 2015; 30(1):65-71. DOI:10.1007/s00467-014-2796-5.
  14. Dorchy H. Dépistage des complications subcliniques chez les jeunes diabétiques de type 1: expérience bruxelloise [Screening for subclinical complications in children and adolescents with type 1 diabetes: experience acquired in Brussels]. Rev Med Brux. 2010; 31(2 Suppl):S87-108. French. PMID: 21812221.
  15. Fioretto P, Barzon I, Mauer M. Is diabetic nephropathy reversible? Diabetes Res Clin Pract. 2014 Jun; 104(3):323-8. doi: 10.1016/j.diabres.2014.01.017. Epub 2014 Jan 20. PMID: 24513120.
  16. Sulaiman MK. Diabetic nephropathy: recent advances in pathophysiology and challenges in dietary management. Diabetol Metab Syndr. 2019; 11:7. DOI: 10.1186/s13098-019-0403-4.
  17. Raile K, Galler A, Hofer S, Herbst A, Dunstheimer D, Busch P, Holl RW. Diabetic nephropathy in 27,805 children, adolescents, and adults with type 1 diabetes: effect of diabetes duration, A1C, hypertension, dyslipidemia, diabetes onset, and sex. Diabetes Care, 2007; 30: 2523–2528.
  18. Nathan DM; DCCT/EDIC Research Group. The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: overview. Diabetes Care. 2014; 37(1):9-16. DOI: 10.2337/dc13-2112.
  19. Chen Y, Lee K, Ni Z, He JC. Diabetic Kidney Disease: Challenges, Advances, and Opportunities. Kidney Dis (Basel). 2020 Jul; 6(4):215-225. DOI: 10.1159/000506634. Epub 2020 Mar 31. PMID: 32903946; PMCID: PMC7445658.
  20. Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the Epidemiology of Diabetes Interventions and Complications (EDIC) study. JAMA. 2003; 290(16):2159-2167. doi:10.1001/jama.290.16.2159.
  21. Alicic RZ, Rooney MT, Tuttle KR. Diabetic Kidney Disease: Challenges, Progress, and Possibilities. Clin J Am Soc Nephrol. 2017; 12(12):2032-2045. doi:10.2215/CJN.11491116.
  22. Hovind P, Tarnow L, Rossing P, Jensen BR, Graae M, Torp I, Binder C, Parving HH. Predictors for the development of microalbuminuria and microalbuminuria in patients with type 1 diabetes: inception cohort study. BMJ, 2004; 328, 1105.
  23. Jenkins AJ, Lyons TJ, Zheng D, Otvos JD, Lackland DT, McGee D, Garvey WT, Klein RL, DCCT/EDIC Research Group. Lipoproteins in the DCCT/EDIC cohort: associations with diabetic nephropathy. Kidney Int, 2003; 64, 817– 828.
  24. Tziomalos K, Athyros VG. Diabetic Nephropathy: New Risk Factors and Improvements in Diagnosis. Rev Diabet Stud. 2015; 12(1-2):110-118. doi:10.1900/RDS.2015.12.110.
  25. Natesan V, Kim SJ. Diabetic Nephropathy - a Review of Risk Factors, Progression, Mechanism, and Dietary Management. Biomol Ther (Seoul). 2021; 29(4):365-372. doi:10.4062/biomolther.2020.204.
  26. Al-Rubeaan K, Youssef AM, Subhani SN, et al. Diabetic nephropathy and its risk factors in a society with a type 2 diabetes epidemic: a Saudi National Diabetes Registry-based study. PLoS One. 2014; 9(2):e88956. doi:10.1371/journal.pone.0088956.
  27. Krolewski AS, Warram JH, Christlieb AR, Busick EJ, Kahn CR. The Changing Natural History of Nephropathy in Type I Diabetes. Am J Med, 1985; 78, 785-794.
  28. Mathiesen ER, Sauerbrey N, Hommel E, Parving HH. Prevalence of microalbuminuria in children with type 1 (insulin-dependent) diabetes mellitus. Diabetologia, 1986; 29, 640-643.
  29. Al-Hermi BE, Al-Abbasi AM, Rajab MH, Al-Jenaidi FA, Al-Ekri ZE. Diabetic nephropathy in children with type 1 diabetes mellitus in Bahrain. Saudi Med J, 2005; 26(2), 294-7.
  30. Mogensen CE, Christensen CK. Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med, 1984; 311, 89–93.
  31. Lutale JJ, Thordarson H, Abbas ZG, Vetvik K. Microalbuminuria among type 1 and type 2 diabetic patients of African origin in Dar Es Salaam, Tanzania. BMC Nephrol, 2007; 8, 2.
  32. Chaturvedi N, Bandinelli S, Mangili R, Penno G, Rottiers RE, Fuller JH. Microalbuminuria in Type 1 diabetes: rates, risk factors and glycemic threshold. Kidney Int, 2001; 60(1), 219-27.
  33. Hovind P, Tarnow L, Rossing P, Jensen BR, Graae M, Torp I, Binder C, Parving HH. Predictors of the development of microalbuminuria in patients with type 1 diabetes: inception cohort study. BMJ, 2004; 328(7448), 1105-8.
  34. Bramlage P, Pittrow D, Lehnert H, Höfler M, Kirch W, Ritz E, Wittchen HU. Frequency of Microalbuminuria in primary care: cross-sectional study. Eur J Cardiovasc Prev Rehabil, 2007; 14(1), 107-13.
  35. Emma F, Goldstein SL, Bagga A, Bates CM, Shroff R. Pediatric Nephrology. 8th edition, Springer, 2022; 1200-1202.
  36. Schernthaner G, Schernthaner GH. Diabetic nephropathy: new approaches for improving glycemic control and reducing risk. J Nephrol. 2013 Nov-Dec; 26(6):975-85. doi: 10.5301/jn.5000281. Epub 2013 Jun 14. PMID: 23807645.