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Is autosomal dominant polycystic kidney disease an early sweet disease?

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A Correction to this article was published on 21 June 2022

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Abstract

The clinical course of autosomal dominant polycystic kidney disease (ADPKD) starts in childhood. Evidence of the beneficial impact of early nephron-protective strategies and lifestyle modifications on ADPKD prognosis is accumulating. Recent studies have described the association of overweight and obesity with rapid disease progression in adults with ADPKD. Moreover, defective glucose metabolism and metabolic reprogramming have been reported in distinct ADPKD models highlighting these pathways as potential therapeutic targets in ADPKD. Several “metabolic” approaches are currently under evaluation in adults, including ketogenic diet, food restriction, and metformin therapy. No data are available on the impact of these approaches in childhood thus far. Yet, according to World Health Organization (WHO), we are currently facing a childhood obesity crisis with an increased prevalence of overweight/obesity in the pediatric population associated with a cardio-metabolic risk profile. The present review summarizes the knowledge about the role of glucose metabolism in the pathophysiology of ADPKD and underscores the possible harm of overweight and obesity in ADPKD especially in terms of long-term cardiovascular outcomes and renal prognosis.

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Abbreviations

ADPKD:

Autosomal dominant polycystic kidney disease

AMPK:

AMP-activated protein kinase

BMI:

Body mass index

BP:

Blood pressure

CKD:

Chronic kidney disease

2-DG:

2-Deoxy-D-glucose

eGFR:

Estimated glomerular filtration rate

Han:SPRD:

Harlan Sprague–Dawley

mTORC:

Mammalian/mechanistic target of rapamycin complex

PC1:

Polycystin-1

PT:

Proximal tubule

SGLT:

Sodium-glucose cotransporter

TKV:

Total kidney volume

WHO:

World Health Organization

References

  1. Rowe I, Boletta A (2014) Defective metabolism in polycystic kidney disease: potential for therapy and open questions. Nephrol Dial Transplant 29:1480–1486. https://doi.org/10.1093/ndt/gft521

    Article  CAS  PubMed  Google Scholar 

  2. Rowe I, Chiaravalli M, Mannella V, Ulisse V et al (2013) Defective glucose metabolism in polycystic kidney disease identifies a new therapeutic strategy. Nat Med 19:488–493. https://doi.org/10.1038/nm.3092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Nowak KL, Hopp K (2020) Metabolic reprogramming in autosomal dominant polycystic kidney disease evidence and therapeutic potential. Clin J Am Soc Nephrol 15:577–584. https://doi.org/10.2215/CJN.13291019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Podrini C, Rowe I, Pagliarini R, Costa ASH et al (2018) Dissection of metabolic reprogramming in polycystic kidney disease reveals coordinated rewiring of bioenergetic pathways. Commun Biol 1:194. https://doi.org/10.1038/s42003-018-0200-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kipp KR, Rezaei M, Lin L, Dewey EC, Weimbs T (2016) A mild reduction of food intake slows disease progression in an orthologous mouse model of polycystic kidney disease. Am J Physiol Physiol 310:F726–F731. https://doi.org/10.1152/ajprenal.00551.2015

    Article  CAS  Google Scholar 

  6. Warner G, Hein KZ, Nin V, Edwards M et al (2016) Food restriction ameliorates the development of polycystic kidney disease. J Am Soc Nephrol 27:1437–1447. https://doi.org/10.1681/ASN.2015020132

    Article  CAS  PubMed  Google Scholar 

  7. Torres JA, Kruger SL, Broderick C, Amarlkhagva T et al (2019) Ketosis ameliorates renal cyst growth in polycystic kidney disease. Cell Metab 30:1007–1023. https://doi.org/10.1016/j.cmet.2019.09.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Takiar V, Nishio S, Seo-Mayer P, King JD Jr et al (2011) Activating AMP-activated protein kinase (AMPK) slows renal cystogenesis. Proc Natl Acad Sci U S A 108:2462–2467. https://doi.org/10.1073/pnas.1011498108

    Article  PubMed  PubMed Central  Google Scholar 

  9. Chang MY, Ma TL, Hung CC, Tian YC et al (2017) Metformin inhibits cyst formation in a zebrafish model of polycystin-2 deficiency. Sci Rep 7:7161. https://doi.org/10.1038/s41598-017-07300-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Perrone RD, Abebe KZ, Watnick T, Althouse AD et al (2021) Primary results of the randomized trial of metformin administration in polycystic kidney disease (TAME PKD). Kidney Int 100:684–696. https://doi.org/10.1016/j.kint.2021.06.013

    Article  CAS  PubMed  Google Scholar 

  11. Brosnahan GM, Wang W, Gitomer B, Struemph T et al (2021) Metformin therapy in autosomal dominant polycystic kidney disease: a feasibility study. Am J Kidney Dis 12:S0272-6386(21)00790-3. https://doi.org/10.1053/j.ajkd.2021.06.026

  12. Wang X, Zhang S, Liu Y, Spichtig D et al (2013) Targeting of sodium-glucose cotransporters with phlorizin inhibits polycystic kidney disease progression in Han:SPRD rats. Kidney Int 84:962–968. https://doi.org/10.1038/ki.2013.199

    Article  CAS  PubMed  Google Scholar 

  13. Kapoor S, Rodriguez D, Riwanto M, Edenhofer I et al (2015) Effect of sodium-glucose cotransport inhibition on polycystic kidney disease progression in PCK rats. PLoS ONE 10:e0125603. https://doi.org/10.1371/journal.pone.0125603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Rodriguez D, Kapoor S, Edenhofer I, Segerer S et al (2015) Inhibition of sodium-glucose cotransporter 2 with dapagliflozin in Han: SPRD rats with polycystic kidney disease. Kidney Blood Press Res 40:638–647. https://doi.org/10.1159/000368540

    Article  CAS  PubMed  Google Scholar 

  15. Leonhard WN, Song X, Kanhai AA, Iliuta IA et al (2019) Salsalate, but not metformin or canagliflozin, slows kidney cyst growth in an adult-onset mouse model of polycystic kidney disease. EBioMedicine 47:436–445. https://doi.org/10.1016/j.ebiom.2019.08.041

    Article  PubMed  PubMed Central  Google Scholar 

  16. Fliszkiewicz M, Niemczyk M, Kulesza A, Łabuś A, Pączek L (2019) Glucose and lipid metabolism abnormalities among patients with autosomal dominant polycystic kidney disease. Kidney Blood Press Res 44:1416–1422. https://doi.org/10.1159/000503423

    Article  CAS  PubMed  Google Scholar 

  17. Pietrzak-Nowacka M, Safranow K, Byra E, Nowosiad M, Marchelek-Myśliwiec M, Ciechanowski K (2010) Glucose metabolism parameters during an oral glucose tolerance test in patients with autosomal dominant polycystic kidney disease. Scand J Clin Lab Invest 70:561–567. https://doi.org/10.3109/00365513.2010.527012

    Article  CAS  PubMed  Google Scholar 

  18. Nowak KL, You Z, Gitomer B, Brosnahan G et al (2018) Overweight and obesity are predictors of progression in early autosomal dominant polycystic kidney disease. J Am Soc Nephrol 29:571–578. https://doi.org/10.1681/ASN.2017070819

    Article  CAS  PubMed  Google Scholar 

  19. Baliga MM, Klawitter J, Christians U, Hopp K et al (2021) Metabolic profiling in children and young adults with autosomal dominant polycystic kidney disease. Sci Rep 11:6629. https://doi.org/10.1038/s41598-021-84609-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yun H-R, Kim H, Park JT, Chang TI et al (2018) Obesity, metabolic abnormality, and progression of CKD. Am J Kidney Dis 72:400–410. https://doi.org/10.1053/j.ajkd.2018.02.362

    Article  CAS  PubMed  Google Scholar 

  21. Spoto B, Pisano A, Zoccali C (2016) Insulin resistance in chronic kidney disease: a systematic review. Am J Physiol Renal Physiol 311:F1087–F1108. https://doi.org/10.1152/ajprenal.00340.2016

    Article  CAS  PubMed  Google Scholar 

  22. Lalan S, Jiang S, Ng DK, Kupferman F et al (2018) Cardiometabolic risk factors, metabolic syndrome, and chronic kidney disease progression in children. J Pediatr 202:163–170. https://doi.org/10.1016/j.jpeds.2018.06.007

    Article  PubMed  PubMed Central  Google Scholar 

  23. Foster MC, Hwang S-J, Larson MG, Lichtman JH et al (2008) Overweight, obesity, and the development of stage 3 CKD: the Framingham heart study. Am J kidney Dis 52:39–48. https://doi.org/10.1053/j.ajkd.2008.03.003

    Article  PubMed  PubMed Central  Google Scholar 

  24. Spinelli A, Buoncristiano M, Kovacs VA, Yngve A et al (2019) Prevalence of severe obesity among primary school children in 21 European countries. Obes Facts 12:244–258. https://doi.org/10.1159/000500436

    Article  PubMed  PubMed Central  Google Scholar 

  25. Sorof JM, Poffenbarger T, Franco K, Bernard L et al (2002) Isolated systolic hypertension, obesity, and hyperkinetic hemodynamic states in children. J Pediatr 140:660–666. https://doi.org/10.1067/mpd.2002.125228

    Article  PubMed  Google Scholar 

  26. Sinha R, Fisch G, Teague B, Tamborlane WV et al (2002) Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med 346:802–810. https://doi.org/10.1056/NEJMoa012578

    Article  CAS  PubMed  Google Scholar 

  27. Shaw J (2007) Epidemiology of childhood type 2 diabetes and obesity. Pediatr Diabetes 8(Suppl 9):7–15. https://doi.org/10.1111/j.1399-5448.2007.00329.x

    Article  PubMed  Google Scholar 

  28. Skinner AC, Perrin EM, Moss LA, Skelton JA (2015) Cardiometabolic risks and severity of obesity in children and young adults. N Engl J Med 373:1307–1317. https://doi.org/10.1056/NEJMoa1502821

    Article  PubMed  Google Scholar 

  29. Baker JL, Olsen LW, Sørensen TIA (2007) Childhood body-mass index and the risk of coronary heart disease in adulthood. N Engl J Med 357:2329–2337. https://doi.org/10.1056/NEJMoa072515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wilson PWF, D’Agostino RB, Sullivan L, Parise H, Kannel WB (2002) Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch Intern Med 162:1867–1872. https://doi.org/10.1001/archinte.162.16.1867

    Article  PubMed  Google Scholar 

  31. Yajnik CS, Katre PA, Joshi SM, Kumaran K et al (2015) Higher glucose, insulin and insulin resistance (HOMA-IR) in childhood predict adverse cardiovascular risk in early adulthood: the Pune children’s study. Diabetologia 58:1626–1636. https://doi.org/10.1007/s00125-015-3602-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Nowak KL, Steele C, Gitomer B, Wang W et al (2021) Overweight and obesity and progression of ADPKD. Clin J Am Soc Nephrol 16:908–915. https://doi.org/10.2215/CJN.16871020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Vareesangthip K, Tong P, Wilkinson R, Thomas TH (1997) Insulin resistance in adult polycystic kidney disease. Kidney Int 52:503–508. https://doi.org/10.1038/ki.1997.360

    Article  CAS  PubMed  Google Scholar 

  34. Fliser D, Pacini G, Engelleiter R, Kautzky-Willer A et al (1998) Insulin resistance and hyperinsulinemia are already present in patients with incipient renal disease. Kidney Int 53:1343–1347. https://doi.org/10.1046/j.1523-1755.1998.00898.x

    Article  CAS  PubMed  Google Scholar 

  35. Turkmen K, Tufan F, Selçuk E, Akpınar T, Oflaz H, Ecder T (2013) Neutrophil-to-lymphocyte ratio, insulin resistance, and endothelial dysfunction in patients with autosomal dominant polycystic kidney disease. Indian J Nephrol 23:34–40. https://doi.org/10.4103/0971-4065.107195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Menon V, Rudym D, Chandra P, Miskulin D, Perrone R, Sarnak M (2011) Inflammation, oxidative stress, and insulin resistance in polycystic kidney disease. Clin J Am Soc Nephrol 6:7–13. https://doi.org/10.2215/CJN.04140510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. DeFronzo RA, Tobin JD, Andres R (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol Endocrinol Metab Gastrointest Physiol 6:E214. https://doi.org/10.1152/ajpendo.1979.237.3.e214

    Article  Google Scholar 

  38. Hamer RA, Chow CL, Ong ACM, McKane WS (2007) Polycystic kidney disease is a risk factor for new-onset diabetes after transplantation. Transplantation 83:36–40. https://doi.org/10.1097/01.tp.0000248759.37146.3d

    Article  PubMed  Google Scholar 

  39. Caillard S, Eprinchard L, Perrin P, Braun L et al (2011) Incidence and risk factors of glucose metabolism disorders in kidney transplant recipients: role of systematic screening by oral glucose tolerance test. Transplantation 91:757–764. https://doi.org/10.1097/TP.0b013e31820f0877

    Article  CAS  PubMed  Google Scholar 

  40. de Mattos AM, Olyaei AJ, Prather JC, Golconda MS et al (2005) Autosomal-dominant polycystic kidney disease as a risk factor for diabetes mellitus following renal transplantation. Kidney Int 67:714–720. https://doi.org/10.1111/j.1523-1755.2005.67132.x

    Article  PubMed  Google Scholar 

  41. Reed B, Helal I, McFann K, Wang W et al (2011) The impact of type II diabetes mellitus in patients with autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 27:2862–2865. https://doi.org/10.1093/ndt/gfr744

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kuo IY, Chapman AB (2020) Polycystins, ADPKD, and cardiovascular disease. Kidney Int reports 5:396–406. https://doi.org/10.1016/j.ekir.2019.12.007

    Article  Google Scholar 

  43. Major RW, Cheng MRI, Grant RA, Shantikumar S et al (2018) Cardiovascular disease risk factors in chronic kidney disease: a systematic review and meta-analysis. PLoS ONE 13:e0192895. https://doi.org/10.1371/journal.pone.0192895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Sans L, Pascual J, Radosevic A, Quintian C et al (2016) Renal volume and cardiovascular risk assessment in normotensive autosomal dominant polycystic kidney disease patients. Medicine (Baltimore) 95:e5595. https://doi.org/10.1097/MD.0000000000005595

    Article  CAS  Google Scholar 

  45. Lai S, Mastroluca D, Matino S, Panebianco V et al (2017) Early markers of cardiovascular risk in autosomal dominant polycystic kidney disease. Kidney Blood Press Res 42:1290–1302. https://doi.org/10.1159/000486011

    Article  CAS  PubMed  Google Scholar 

  46. Gorriz JL, Arroyo D, D’Marco L, Torra R et al (2021) Cardiovascular risk factors and the impact on prognosis in patients with chronic kidney disease secondary to autosomal dominant polycystic kidney disease. BMC Nephrol 22:110. https://doi.org/10.1186/s12882-021-02313-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Nowak KL, Murray K, You Z, Gitomer B et al (2021) Pain and obesity in autosomal dominant polycystic kidney disease: a post hoc analysis of the halt progression of polycystic kidney disease (HALT-PKD) studies. Kidney Med 3:536-545.e1. https://doi.org/10.1016/j.xkme.2021.03.004

    Article  PubMed  PubMed Central  Google Scholar 

  48. Bajwa ZH, Gupta S, Warfield CA, Steinman TI (2001) Pain management in polycystic kidney disease. Kidney Int 60:1631–1644. https://doi.org/10.1046/j.1523-1755.2001.00985.x

    Article  CAS  PubMed  Google Scholar 

  49. World Health Organization (2017) Tenfold increase in childhood and adolescent obesity in four decades: new study by Imperial College London and WHO. In: Available online. https://www.who.int/news/item/11-10-2017-. Accessed 3 Jun 2021

  50. Franks PW, Hanson RL, Knowler WC, Sievers ML et al (2010) Childhood obesity, other cardiovascular risk factors, and premature death. N Engl J Med 362:485–493. https://doi.org/10.1056/NEJMoa0904130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Whaley-Connell A, Sowers JR (2017) Insulin resistance in kidney disease: is there a distinct role separate from that of diabetes or obesity? Cardiorenal Med 8:41–49. https://doi.org/10.1159/000479801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Helal I, Reed B, Mcfann K, Yan XD et al (2011) Glomerular hyperfiltration and renal progression in children with autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 6:2439–2443. https://doi.org/10.2215/CJN.01010211

    Article  PubMed  PubMed Central  Google Scholar 

  53. Chagnac A, Weinstein T, Korzets A, Ramadan E et al (2000) Glomerular hemodynamics in severe obesity. Am J Physiol Renal Physiol 278:F817-822. https://doi.org/10.1152/ajprenal.2000.278.5.F817

    Article  CAS  PubMed  Google Scholar 

  54. Kahveci AS, Barnatan TT, Kahveci A, Adrian AE et al (2020) Oxidative stress and mitochondrial abnormalities contribute to decreased endothelial nitric oxide synthase expression and renal disease progression in early experimental polycystic kidney disease. Int J Mol Sci 21:1994. https://doi.org/10.3390/ijms21061994

    Article  CAS  PubMed Central  Google Scholar 

  55. Murphy MO, Huang H, Bauer JA, Schadler A et al (2021) Impact of pediatric obesity on diurnal blood pressure assessment and cardiovascular risk markers. Front Pediatr 9:123. https://doi.org/10.3389/fped.2021.596142

    Article  Google Scholar 

  56. Litwin M, Kułaga Z (2021) Obesity, metabolic syndrome, and primary hypertension. Pediatr Nephrol 36:825–837. https://doi.org/10.1007/s00467-020-04579-3

    Article  PubMed  Google Scholar 

  57. Marlais M, Cuthell O, Langan D, Dudley J et al (2016) Hypertension in autosomal dominant polycystic kidney disease: a meta-analysis. Arch Dis Child 101:1142–1147. https://doi.org/10.1136/archdischild-2015-310221

    Article  PubMed  Google Scholar 

  58. Massella L, Mekahli D, Paripović D, Prikhodina L et al (2018) Prevalence of hypertension in children with early-stage ADPKD. Clin J Am Soc Nephrol 13:874–883. https://doi.org/10.2215/CJN.11401017

    Article  PubMed  PubMed Central  Google Scholar 

  59. Fick-Brosnahan GM, Tran ZV, Johnson AM, Strain JD, Gabow PA (2001) Progression of autosomal-dominant polycystic kidney disease in children. Kidney Int 59:1654–1662. https://doi.org/10.1046/j.1523-1755.2001.0590051654.x

    Article  CAS  PubMed  Google Scholar 

  60. Cadnapaphornchai MA, McFann K, Strain JD, Masoumi A, Schrier RW (2008) Increased left ventricular mass in children with autosomal dominant polycystic kidney disease and borderline hypertension. Kidney Int 74:1192–1196. https://doi.org/10.1038/ki.2008.397

    Article  PubMed  PubMed Central  Google Scholar 

  61. Mastrangelo A, Martos-Moreno GÁ, García A, Barrios V et al (2016) Insulin resistance in prepubertal obese children correlates with sex-dependent early onset metabolomic alterations. Int J Obes (Lond) 40:1494–1502. https://doi.org/10.1038/ijo.2016.92

    Article  CAS  Google Scholar 

  62. Kwaifa IK, Bahari H, Yong YK, Noor SM (2020) Endothelial dysfunction in obesity-induced inflammation: molecular mechanisms and clinical implications. Biomolecules 10:291. https://doi.org/10.3390/biom10020291

    Article  CAS  PubMed Central  Google Scholar 

  63. Chiaravalli M, Rowe I, Mannella V, Quilici G et al (2016) 2-Deoxy-D-glucose ameliorates PKD progression. J Am Soc Nephrol 27:1958–1969. https://doi.org/10.1681/ASN.2015030231

    Article  CAS  PubMed  Google Scholar 

  64. Riwanto M, Kapoor S, Rodriguez D, Edenhofer I et al (2016) Inhibition of aerobic glycolysis attenuates disease progression in polycystic kidney disease. PLoS ONE 11:e0146654. https://doi.org/10.1371/journal.pone.0146654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Grahammer F, Ramakrishnan SK, Rinschen MM, Larionov AA et al (2017) mTOR regulates endocytosis and nutrient transport in proximal tubular cells. J Am Soc Nephrol 28:230–241. https://doi.org/10.1681/ASN.2015111224

    Article  CAS  PubMed  Google Scholar 

  66. Zhang H, Kong W-J, Shan Y-Q, Song D-Q et al (2010) Protein kinase D activation stimulates the transcription of the insulin receptor gene. Mol Cell Endocrinol 330:25–32. https://doi.org/10.1016/j.mce.2010.07.022

    Article  CAS  PubMed  Google Scholar 

  67. Khan S, Ferdaoussi M, Bautista A, Bergeron V et al (2019) A role for PKD1 in insulin secretion downstream of P2Y1 receptor activation in mouse and human islets. Physiol Rep 7:e14250. https://doi.org/10.14814/phy2.14250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kashyap S, Hein KZ, Chini CC, Lika J et al (2020) Metalloproteinase PAPP - a regulation of IGF-1 contributes to polycystic kidney disease pathogenesis. JCI Insight 5:e135700. https://doi.org/10.1172/jci.insight.135700

    Article  PubMed Central  Google Scholar 

  69. Kashyap S, Zeidler JD, Chini CCS, Chini EN (2020) Implications of the PAPP-A-IGFBP-IGF-1 pathway in the pathogenesis and treatment of polycystic kidney disease. Cell Signal 73:109698. https://doi.org/10.1016/j.cellsig.2020.109698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Ramalingam H, Kashyap S, Cobo-Stark P, Flaten A et al (2021) A methionine-Mettl3-N6-methyladenosine axis promotes polycystic kidney disease. Cell Metab 33:1234-1247.e7. https://doi.org/10.1016/j.cmet.2021.03.024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF et al (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393–403. https://doi.org/10.1056/NEJMoa012512

    Article  CAS  PubMed  Google Scholar 

  72. Seifarth C, Schehler B, Schneider HJ (2013) Effectiveness of metformin on weight loss in non-diabetic individuals with obesity. Exp Clin Endocrinol Diabetes 121:27–31. https://doi.org/10.1055/s-0032-1327734

    Article  CAS  PubMed  Google Scholar 

  73. Soliman A, DeSanctis V, Alaaraj N, Hamed N (2020) The clinical application of metformin in children and adolescents: a short update. Acta Biomed 91:e2020086. https://doi.org/10.23750/abm.v91i3.10127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Masarwa R, Brunetti VC, Aloe S, Henderson M, Platt RW, Filion KB (2021) Efficacy and safety of metformin for obesity: a systematic review. Pediatrics 147:e20201610. https://doi.org/10.1542/peds.2020-1610

  75. Bassols J, Martínez-Calcerrada J-M, Osiniri I, Díaz-Roldán F et al (2019) Effects of metformin administration on endocrine-metabolic parameters, visceral adiposity and cardiovascular risk factors in children with obesity and risk markers for metabolic syndrome: a pilot study. PLoS ONE 14:e0226303. https://doi.org/10.1371/journal.pone.0226303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Bjornstad P, Schäfer M, Truong U, Cree-Green M et al (2018) Metformin improves insulin sensitivity and vascular health in youth with type 1 diabetes mellitus. Circulation 138:2895–2907. https://doi.org/10.1161/CIRCULATIONAHA.118.035525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Park MH, Kinra S, Ward KJ, White B, Viner RM (2009) Metformin for obesity in children and adolescents: a systematic review. Diabetes Care 32:1743–1745. https://doi.org/10.2337/dc09-0258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Kendall D, Vail A, Amin R, Barrett T et al (2013) Metformin in obese children and adolescents: the MOCA trial. J Clin Endocrinol Metab 98:322–329. https://doi.org/10.1210/jc.2012-2710

    Article  CAS  PubMed  Google Scholar 

  79. De Broe ME, Jouret F (2020) Does metformin do more benefit or harm in chronic kidney disease patients? Kidney Int 98:1098–1101. https://doi.org/10.1016/j.kint.2020.04.059

    Article  CAS  PubMed  Google Scholar 

  80. Crowley MJ, Diamantidis CJ, McDuffie JR, Cameron CB et al (2017) Clinical outcomes of metformin use in populations with chronic kidney disease, congestive heart failure, or chronic liver disease: a systematic review. Ann Intern Med 166:191–200. https://doi.org/10.7326/M16-1901

    Article  PubMed  PubMed Central  Google Scholar 

  81. Ong ACM, Gansevoort RT (2021) TAMEing ADPKD with metformin: safe and effective? Kidney Int 100:513–515. https://doi.org/10.1016/j.kint.2021.07.021

    Article  CAS  PubMed  Google Scholar 

  82. Heerspink HJL, Kosiborod M, Inzucchi SE, Cherney DZI (2018) Renoprotective effects of sodium-glucose cotransporter-2 inhibitors. Kidney Int 94:26–39. https://doi.org/10.1016/j.kint.2017.12.027

    Article  CAS  PubMed  Google Scholar 

  83. Perkovic V, Jardine MJ, Neal B, Bompoint S et al (2019) Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 380:2295–2306. https://doi.org/10.1056/NEJMoa1811744

    Article  CAS  PubMed  Google Scholar 

  84. Levin A, Perkovic V, Wheeler DC, Hantel S et al (2020) Empagliflozin and cardiovascular and kidney outcomes across KDIGO risk categories: post hoc analysis of a randomized, double-blind, placebo-controlled, multinational trial. Clin J Am Soc Nephrol 15:1433–1444. https://doi.org/10.2215/CJN.14901219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. PKD Research Group, GPURE, Department of Development and Regeneration, KU Leuven, Leuven, Belgium

    Angélique Dachy, Jean-Paul Decuypere & Djalila Mekahli

  2. Department of Pediatrics, ULiège Academic Hospital, Liège, Belgium

    Angélique Dachy

  3. Laboratory of Translational Research in Nephrology (LTRN), GIGA Cardiovascular Sciences, ULiège, Liège, Belgium

    Angélique Dachy & François Jouret

  4. Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, VIB Center for Brain and Disease Research, KU Leuven, Leuven, Belgium

    Rudi Vennekens

  5. Division of Nephrology, Department of Internal Medicine, ULiège Academic Hospital, Liège, Belgium

    François Jouret

  6. Department of Pediatric Nephrology, University Hospitals Leuven, Herestraat 49, B-3000, Leuven, Belgium

    Djalila Mekahli

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  1. Angélique Dachy
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  2. Jean-Paul Decuypere
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  3. Rudi Vennekens
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  5. Djalila Mekahli
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Correspondence to Djalila Mekahli.

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Dachy, A., Decuypere, JP., Vennekens, R. et al. Is autosomal dominant polycystic kidney disease an early sweet disease?. Pediatr Nephrol 37, 1945–1955 (2022). https://doi.org/10.1007/s00467-021-05406-z

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