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The Kidney in Type I Diabetes

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Pediatric Nephrology

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Abstract

Diabetic kidney disease (DKD) is a serious complication of type 1 diabetes (T1D) and represents a major cause of end stage renal disease (ESRD) and cardiovascular morbidity and mortality. DKD occurs due to interactions between several factors, including hyperglycemia, dyslipidemia, hypertension, oxidative stress, advanced glycated end products, and genetic factors, which induce progressive functional and structural changes in the kidney. Clinically, DKD is characterized by increasing albuminuria, progressive decline in glomerular filtration rate, and elevated blood pressure, which without any treatment progress towards ESRD. Advanced stages of DKD are rare among children and adolescents with T1D, whereas early stages, such as hyperfiltration and moderately increased albuminuria, can be common. Several risk factors contribute to the development of DKD, the main being hyperglycemia, high blood pressure, dyslipidemia, diabetes duration, age at diagnosis, female gender, and puberty, along with genetic and environmental factors. Albuminuria, formerly known as microalbuminuria, is considered the earliest clinical manifestation of DKD and is the basis for screening for this complication. Screening for DKD is recommended starting at age 10–12 years and repeated annually. During adolescence, the primary focus of management the risk of DKD is improvement in glycemic control. Targeting additional risk factors, such as hypertension, dyslipidemia, and obesity, is also recommended. When persistent albuminuria is detected, treatment with angiotensin-converting enzyme inhibitors is indicated. There is still a need for new biomarkers to facilitate early detection of subclinical stages of DKD and to support the implementation of intervention strategies, to ultimately reduce the burden of DKD.

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References

  1. IDF Diabetes Atlas 9th edition 2019 [Internet]. [cited 2019 Nov 16]. Available from: https://www.diabetesatlas.org/en/

  2. Forbes JM, Fotheringham AK. Vascular complications in diabetes: old messages, new thoughts. Diabetologia. 2017;60(11):2129–38.

    Article  Google Scholar 

  3. Rawshani A, Sattar N, Franzén S, Rawshani A, Hattersley AT, Svensson A-M, et al. Excess mortality and cardiovascular disease in young adults with type 1 diabetes in relation to age at onset: a nationwide, register-based cohort study. Lancet. 2018;392(10146):477–86.

    Article  Google Scholar 

  4. Zelnick LR, Weiss NS, Kestenbaum BR, Robinson-Cohen C, Heagerty PJ, Tuttle K, et al. Diabetes and CKD in the United States population, 2009–2014. Clin J Am Soc Nephrol. 2017;12(12):1984–90.

    Article  Google Scholar 

  5. Chen Y, Lee K, Ni Z, He JC. Diabetic kidney disease: challenges, advances, and opportunities. Kidney Dis. 2020;6(4):1–11.

    CAS  Google Scholar 

  6. American Diabetes Association. 11. Microvascular complications and foot care: standards of medical care in diabetes-2020. Diabetes Care. 2020;43(Suppl 1):S135–51.

    Google Scholar 

  7. Anders H-J, Huber TB, Isermann B, Schiffer M. CKD in diabetes: diabetic kidney disease versus nondiabetic kidney disease. Nat Rev Nephrol. 2018;14(6):361–77.

    Article  CAS  Google Scholar 

  8. Mogensen CE, Christensen CK, Vittinghus E. The stages in diabetic renal disease. With emphasis on the stage of incipient diabetic nephropathy. Diabetes. 1983;32(Suppl 2):64–78.

    Article  Google Scholar 

  9. Steinke JM, Mauer M. International diabetic nephropathy study group. Lessons learned from studies of the natural history of diabetic nephropathy in young type 1 diabetic patients. Pediatr Endocrinol Rev. 2008;5(Suppl 4):958–63.

    PubMed  Google Scholar 

  10. Amin R, Widmer B, Prevost a T, Schwarze P, Cooper J, Edge J, et al. Risk of microalbuminuria and progression to macroalbuminuria in a cohort with childhood onset type 1 diabetes: prospective observational study. BMJ. 2008;336(7646):697–701.

    Article  Google Scholar 

  11. Perkins BA, Ficociello LH, Silva KH, Finkelstein DM, Warram JH, Krolewski AS. Regression of microalbuminuria in type 1 diabetes. N Engl J Med. 2003;348(23):2285–93.

    Article  CAS  Google Scholar 

  12. Gorman D, Sochett E, Daneman D. The natural history of microalbuminuria in adolescents with type 1 diabetes. J Pediatr. 1999;134(3):333–7.

    Article  CAS  Google Scholar 

  13. Marcovecchio ML, Chiesa ST, Armitage J, Daneman D, Donaghue KC, Jones TW, et al. Renal and cardiovascular risk according to tertiles of urinary albumin-to-creatinine ratio: the Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT). Diabetes Care. 2018;41(9):1963–9.

    Article  CAS  Google Scholar 

  14. Marcovecchio ML, Dalton RN, Daneman D, Deanfield J, Jones TW, Neil HAW, et al. A new strategy for vascular complications in young people with type 1 diabetes mellitus. Nat Rev Endocrinol. 2019;15(7):429–35.

    Article  Google Scholar 

  15. Gagnum V, Saeed M, Stene LC, Leivestad T, Joner G, Skrivarhaug T. Low incidence of end-stage renal disease in childhood-onset type 1 diabetes followed for up to 42 years. Diabetes Care. 2018;41(3):420–5.

    Article  Google Scholar 

  16. Schultz CJ, Neil HA, Dalton RN, Dunger DB, Oxford Regional Prospective Study Group. Risk of nephropathy can be detected before the onset of microalbuminuria during the early years after diagnosis of type 1 diabetes. Diabetes Care. 2000;23(12):1811–5.

    Article  CAS  Google Scholar 

  17. Cho YH, Craig ME, Donaghue KC. Puberty as an accelerator for diabetes complications. Pediatr Diabetes. 2014;15(1):18–26.

    Article  CAS  Google Scholar 

  18. Lovshin JA, Škrtić M, Bjornstad P, Moineddin R, Daneman D, Dunger D, et al. Hyperfiltration, urinary albumin excretion, and ambulatory blood pressure in adolescents with type 1 diabetes mellitus. Am J Physiol Renal Physiol. 2018;314(4):F667–74.

    Article  CAS  Google Scholar 

  19. Amin R, Turner C, van Aken S, Bahu TK, Watts A, Lindsell DRM, et al. The relationship between microalbuminuria and glomerular filtration rate in young type 1 diabetic subjects: the Oxford Regional Prospective Study. Kidney Int. 2005;68(4):1740–9.

    Article  Google Scholar 

  20. Bjornstad P, Cherney D, Maahs DM. Early diabetic nephropathy in type 1 diabetes: new insights. Curr Opin Endocrinol Diabetes Obes. 2014;21(4):279–86.

    Google Scholar 

  21. Groop P-H, Thomas MC, Moran JL, Wadèn J, Thorn LM, Mäkinen V-P, et al. The presence and severity of chronic kidney disease predicts all-cause mortality in type 1 diabetes. Diabetes. 2009;58(7):1651–8.

    Article  CAS  Google Scholar 

  22. Papadopoulou-Marketou N, Chrousos GP, Kanaka-Gantenbein C. Diabetic nephropathy in type 1 diabetes: a review of early natural history, pathogenesis, and diagnosis. Diabetes Metab Res Rev. 2017;33:e2841.

    Google Scholar 

  23. Forbes JM, Cooper ME. Mechanisms of diabetic complications. Physiol Rev. 2013;93(1):137–88.

    Google Scholar 

  24. Perkins BA, Bebu I, De Boer IH, Molitch M, Tamborlane W, Lorenzi G, et al. Risk factors for kidney disease in type 1 diabetes. Diabetes Care. 2019;42(5):883–90.

    Article  CAS  Google Scholar 

  25. Miller RG, Orchard TJ. Understanding metabolic memory: a tale of two studies. Diabetes. 2020;69(3):291–9.

    Article  CAS  Google Scholar 

  26. Donaghue KC, Marcovecchio ML, Wadwa RP, Chew EY, Wong TY, Calliari LE, et al. ISPAD clinical practice consensus guidelines 2018: microvascular and macrovascular complications in children and adolescents. Pediatr Diabetes. 2018;19(Suppl 27):262–74.

    Article  Google Scholar 

  27. American Diabetes Association. 13. Children and Adolescents. Standards of medical care in diabetes-2020. Diabetes Care. 2020;43(Suppl 1):S163–82.

    Article  Google Scholar 

  28. Lind M, Pivodic A, Svensson AM, Ólafsdóttir AF, Wedel H, Ludvigsson J. HbA1c level as a risk factor for retinopathy and nephropathy in children and adults with type 1 diabetes: Swedish population based cohort study. BMJ. 2019;366:l4894.

    Article  Google Scholar 

  29. Miller KM, Beck RW, Foster NC, Maahs DM. HbA1c levels in type 1 diabetes from early childhood to older adults: a deeper dive into the influence of technology and socioeconomic status on HbA1c in the T1D exchange clinic registry findings. Diabetes Technol Ther. 2020;22(9):645–50.

    Article  Google Scholar 

  30. Cameron FJ, Garvey K, Hood KK, Acerini CL, Codner E. ISPAD clinical practice consensus guidelines 2018: diabetes in adolescence. Pediatr Diabetes. 2018;19(Suppl 27):250–61.

    Article  Google Scholar 

  31. Niechciał E, Marcovecchio ML. Treatment of cardiometabolic risk factors in patients with type 1 diabetes. Curr Opin Pediatr. 2020;32(4):589–94.

    Article  Google Scholar 

  32. Todd JN, Dahlström EH, Salem RM, Sandholm N, Forsblom C, McKnight AJ, et al. Genetic evidence for a causal role of obesity in diabetic kidney disease. Diabetes. 2015;64(12):4238–46.

    Article  CAS  Google Scholar 

  33. McGill JB, Wu M, Pop-Busui R, Mizokami-Stout K, Tamborlane WV, Aleppo G, et al. Biologic and social factors predict incident kidney disease in type 1 diabetes: results from the T1D exchange clinic network. J Diabetes Complicat. 2019;33(10):107400.

    Article  Google Scholar 

  34. Cole JB, Florez JC. Genetics of diabetes mellitus and diabetes complications. Nat Rev Nephrol. 2020;16(7):377–90.

    Article  Google Scholar 

  35. Marcovecchio ML, Tossavainen PH, Owen K, Fullah C, Benitez-Aguirre P, Masi S, et al. Clustering of cardio-metabolic risk factors in parents of adolescents with type 1 diabetes and microalbuminuria. Pediatr Diabetes. 2017;18(8):947–54.

    Article  CAS  Google Scholar 

  36. Colhoun HM, Marcovecchio ML. Biomarkers of diabetic kidney disease. Diabetologia. 2018;61(5):996–1011.

    Article  CAS  Google Scholar 

  37. Papadopoulou-Marketou N, Kanaka-Gantenbein C, Marketos N, Chrousos GP, Papassotiriou I. Biomarkers of diabetic nephropathy: a 2017 update. Crit Rev Clin Lab Sci. 2017;54(5):326–42.

    Article  CAS  Google Scholar 

  38. Marcovecchio ML. Importance of identifying novel biomarkers of microvascular damage in type 1 diabetes. Mol Diagn Ther. 2020;24(5):507–15.

    Article  Google Scholar 

  39. Tofte N, Lindhardt M, Adamova K, Bakker SJL, Beige J, Beulens JWJ, et al. Early detection of diabetic kidney disease by urinary proteomics and subsequent intervention with spironolactone to delay progression (PRIORITY): a prospective observational study and embedded randomised placebo-controlled trial. Lancet Diabetes Endocrinol. 2020;8(4):301–12.

    Article  CAS  Google Scholar 

  40. Tauschmann M, Hovorka R. Technology in the management of type 1 diabetes mellitus-current status and future prospects. Nat Rev Endocrinol. 2018;14(8):464–75.

    Article  Google Scholar 

  41. Battelino T, Danne T, Bergenstal RM, Amiel SA, Beck R, Biester T, et al. Clinical targets for continuous glucose monitoring data interpretation: recommendations from the international consensus on time in range. Diabetes Care. 2019;42(8):1593–603.

    Article  Google Scholar 

  42. Beck RW, Bergenstal RM, Riddlesworth TD, Kollman C, Li Z, Brown AS, et al. Validation of time in range as an outcome measure for diabetes clinical trials. Diabetes Care. 2019;42(3):400–5.

    Article  CAS  Google Scholar 

  43. Marcovecchio ML, Chiesa ST, Bond S, Daneman D, Dawson S, Donaghue KC, et al. ACE inhibitors and statins in adolescents with type 1 diabetes. N Engl J Med. 2017;377(18):1733–45.

    Article  CAS  Google Scholar 

  44. Lytvyn Y, Bjornstad P, Lovshin JA, Boulet G, Farooqi MA, Lai V, et al. Renal hemodynamic function and RAAS activation over the natural history of type 1 diabetes. Am J Kidney Dis. 2019;73(6):786–96.

    Article  CAS  Google Scholar 

  45. Doria A, Galecki AT, Spino C, Pop-Busui R, Cherney DZ, Lingvay I, et al. Serum urate lowering with allopurinol and kidney function in type 1 diabetes. N Engl J Med. 2020;382(26):2493–503.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Paediatrics, University of Cambridge, Cambridge, UK

    M. Loredana Marcovecchio

  2. University Research Institute of Maternal and Child Health and Precision Medicine, National and Kapodistrian University of Athens, Athens, Greece

    Nektaria Papadopoulou-Marketou

Authors
  1. M. Loredana Marcovecchio
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  2. Nektaria Papadopoulou-Marketou
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Correspondence to M. Loredana Marcovecchio .

Editor information

Editors and Affiliations

  1. Division of Nephrology, Department of Pediatric Specialties, Bambino Gesù Children’s Hospital – IRCCS, Rome, Italy

    Francesco Emma

  2. Division of Nephrology and Hypertension, The Heart Institute, Cincinnati Children’s Hospital Medical Center, College of Medicine, Cincinnati, OH, USA

    Stuart L. Goldstein

  3. Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India

    Arvind Bagga

  4. Division of Pediatric Nephrology, UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Carlton M. Bates

  5. Department of Paediatric Nephrology, Great Ormond Street Hospital for Children, NHS Foundation Trust and University College London Institute of Child Health, London, UK

    Rukshana Shroff

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Marcovecchio, M.L., Papadopoulou-Marketou, N. (2022). The Kidney in Type I Diabetes. In: Emma, F., Goldstein, S.L., Bagga, A., Bates, C.M., Shroff, R. (eds) Pediatric Nephrology. Springer, Cham. https://doi.org/10.1007/978-3-030-52719-8_102

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  • DOI: https://doi.org/10.1007/978-3-030-52719-8_102

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-52718-1

  • Online ISBN: 978-3-030-52719-8

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