Abstract
There is a rapid increase worldwide in the prevalence of obesity in adults and children. Obesity is not only a comorbidity for chronic kidney disease (CKD) but may also be a risk factor for CKD. Epidemiological correlations and pathophysiological changes have been observed associating obesity with CKD. Low birth weight may be associated with both obesity and low nephron mass, leading to CKD later in life. Elevated levels of adipokines, such as leptin and adiponectin, in obesity may be factors in CKD pathogenesis and progression. Furthermore, various other factors, such as hypertension, increased cardiovascular morbidity, insulin resistance, dyslipidemia, and lipotoxicity, may play significant roles in the pathogenesis of CKD in obesity. Reduction in obesity, which is a potentially modifiable risk factor, might help decrease the burden of CKD in the population. Apart from individualized options, community-based interventions have the potential to create a strong impact in this condition.
References
Troiano RP, Flegal KM, Kuczmarski RJ, Campbell SM, Johnson CL (1995) Overweight prevalence and trends for children and adolescents. The National Health and Nutrition Examination Surveys, 1963 to 1991. Arch Pediatr Adolesc Med 149:1085–1091
Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM (2006) Prevalence of overweight and obesity in the United States, 1999–2004. JAMA 295:1549–1555
Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z (2002) 2000 CDC Growth Charts for the United States: Methods and Development. National Center for Health Statistics. Vital Health Stat 11:1–190
Ogden CL, Carroll MD, Curtin LR, Lamb MM, Flegal KM (2010) Prevalence of high body mass index in US children and adolescents, 2007-2008. JAMA 303:242–249
Wahba IM, Mak RH (2007) Obesity and obesity-initiated metabolic syndrome: mechanistic links to chronic kidney disease. Clin J Am Soc Nephrol 2:550–562
Fox CS, Larson MG, Leip EP, Culleton B, Wilson PW, Levy D (2004) Predictors of new-onset kidney disease in a community-based population. JAMA 291:844–850
Ejerblad E, Fored CM, Lindblad P, Fryzek J, McLaughlin JK, Nyren O (2006) Obesity and risk for chronic renal failure. J Am Soc Nephrol 17:1695–1702
Savino A, Pelliccia P, Chiarelli F, Mohn A (2010) Obesity-related renal injury in childhood. Horm Res Paediatr 73:303–311
Filler G, Reimao SM, Kathiravelu A, Grimmer J, Feber J, Drukker A (2007) Pediatric nephrology patients are overweight: 20 years’ experience in a single Canadian tertiary pediatric nephrology clinic. Int Urol Nephrol 93:1235–1240
Espinoza R, Gracida C, Cancino J, Ibarra A (2006) Effect of obese living donors on the outcome and metabolic features in recipients of kidney transplantation. Transplant Proc 38:888–889
Pantoja-Zuzuarregui JR, Mallios R, Murphy J (2009) The effect of obesity on kidney length in a healthy pediatric population. Pediatr Nephrol 24:2023–2027
Darouich S, Goucha R, Jaafoura MH, Zekri S, Ben Maiz H, Kheder A (2011) Clinicopathological characteristics of obesity-associated focal segmental glomerulosclerosis. Ultrastruct Pathol 35:176–182
Kambham N, Markowitz GS, Valeri AM, Lin J, D’Agati VD (2001) Obesity-related glomerulopathy: An emerging epidemic. Kidney Int 59:1498–1509
Abitbol CL, Chandar J, Rodríguez MM, Berho M, Seeherunvong W, Freundlich M, Zilleruelo G (2009) Obesity and preterm birth: additive risks in the progression of kidney disease in children. Pediatr Nephrol 24:1363–1370
Fowler SM, Kon V, Ma L, Richards WO, Fogo AB, Hunley TE (2009) Obesity-related focal and segmental glomerulosclerosis: normalization of proteinuria in an adolescent after bariatric surgery. Pediatr Nephrol 24:851–855
Wong CS, Gipson DS, Gillen DL, Emerson S, Koepsell T, Sherrard DJ, Watkins SL, Stehman-Breen C (2000) Anthropometric measures and risk of death in children with end-stage renal disease. Am J Kidney Dis 36:811–819
Hanevold CD, Ho PL, Talley L, Mitsnefes M (2005) Obesity and renal transplant outcome: a report of the North American Pediatric Renal Transplant Cooperative Study. Pediatrics 115:352–356
Hoogeveen EK, Aalten J, Rothman KJ, Roodnat JI, Mallat MJ, Borm G, Weimar W, Hoitsma AJ, de Fijter JW (2011) Effect of obesity on the outcome of kidney transplantation: a 20-year follow-up. Transplantation 91:869–874
Mitsnefes M, Khoury P, McEnery PT (2002) Body mass index and allograft function in pediatric renal transplantation. Pediatr Nephrol 7:535–539
Hoy WE, Rees M, Kile E, Mathews JD, Wang Z (1999) A new dimension to the Barker hypothesis: low birthweight and susceptibility to renal disease. Kidney Int 56:1072–1077
Phillips DI, Jones A, Goulden PA (2006) Birth weight, stress, and the metabolic syndrome in adult life. Ann N Y Acad Sci 1083:28–36
Lackland DT, Egan BM, Fan ZJ, Syddall HE (2001) Low birth weight contributes to the excess prevalence of end-stage renal disease in African Americans. J Clin Hypertens 3:29–31
Vikse BE, Irgens LM, Leivestad T, Hallan S, Iversen BM (2008) Low birth weight increases risk for end-stage renal disease. J Am Soc Nephrol 19:151–157
Greenbaum LA, Muñoz A, Schneider MF, Kaskel FJ, Askenazi DJ, Jenkins R, Hotchkiss H, Moxey-Mims M, Furth SL, Warady BA (2011) The association between abnormal birth history and growth in children with CKD. Clin J Am Soc Nephrol 6:14–21
Bacchetta J, Harambat J, Dubourg L, Guy B, Liutkus A, Canterino I, Kassaï B, Putet G, Cochat P (2009) Both extrauterine and intrauterine growth restriction impair renal function in children born very preterm. Kidney Int 76:445–452
Hinchliffe SA, Lynch MR, Sargent PH, Howard CV, van Velzen D (1992) The effect of intrauterine growth retardation on the development of renal nephrons. Br J Obstet Gynaecol 99:296–301
Bagby SP (2004) Obesity-initiated metabolic syndrome and the kidney: A recipe for chronic kidney disease? J Am Soc Nephrol 15:2775–2791
Vehaskari VM, Aviles DH, Manning J (2001) Prenatal programming of adult hypertension in the rat. Kidney Int 59:238–245
Celsi G, Kistner A, Aizman R, Eklöf AC, Ceccatelli S, de Santiago A, Jacobson SH (1998) Prenatal dexamethasone causes oligonephronia, sodium retention, and higher blood pressure in the offspring. Pediatr Res 44:317–322
Nguyen S, McCulloch C, Brakeman P, Portale A, Hsu CY (2008) Being overweight modifies the association between cardiovascular risk factors and microalbuminuria in adolescents. Pediatrics 121:37–45
Chen J, Munter P, Hamm LL, Jones DW, Batuman V, Fonseca V, Whelton PK, He J (2004) The metabolic syndrome and chronic kidney disease in US adults. Ann Intern Med 140:167–174
Batsis JA, Romero-Corral A, Collazo-Clavell ML, Sarr MG, Somers VK, Lopez-Jimenez F (2008) Effect of bariatric surgery on the metabolic syndrome: a population-based, long-term controlled study. Mayo Clin Proc 83:897–907
Wisse BE (2004) The inflammatory syndrome: The role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol 15:2792–2800
Tilg H, Moschen AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6:772–783
Venner AA, Lyon ME, Doyle-Baker PK (2006) Leptin: a potential biomarker for childhood obesity? Clin Biochem 39:1047–1056
Belin de Chantemèle EJ, Mintz JD, Rainey WE, Stepp DW (2011) Impact of leptin-mediated sympatho-activation on cardiovascular function in obese mice. Hypertension 58:271–279
Hasty AH, Shimano H, Osuga J, Namatame I, Takahashi A, Yahagi N, Perrey S, Iizuka Y, Tamura Y, Amemiya-Kudo M, Yoshikawa T, Okazaki H, Ohashi K, Harada K, Matsuzaka T, Sone H, Gotoda T, Nagai R, Ishibashi S, Yamada N (2001) Severe hypercholesterolemia, hypertriglyceridemia, and atherosclerosis in mice lacking both leptin and the low density lipoprotein receptor. J Biol Chem 276:37402–37408
Daschner M, Tönshoff B, Blum WF, Englaro P, Wingen AM, Schaefer F, Wühl E, Rascher W, Mehls O (1998) Inappropriate elevation of serum leptin levels in children with chronic renal failure. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood. J Am Soc Nephrol 9:1074–1079
Wolf G, Ziyadeh FN (2006) Leptin and renal fibrosis. Contrib Nephrol 151:175–183
Tarzi RM, Cook HT, Jackson I, Pusey CD, Lord GM (2004) Leptin-deficient mice are protected from accelerated nephrotoxic nephritis. Am J Pathol 164:385–390
Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 7:941–946
Sharma K, Ramachandrarao S, Qiu G, Usui HK, Zhu Y, Dunn SR, Ouedraogo R, Hough K, McCue P, Chan L, Falkner B, Goldstein BJ (2008) Adiponectin regulates albuminuria and podocyte function in mice. J Clin Invest 118:1645–1656
Kumada M, Kihara S, Sumitsuji S, Kawamoto T, Matsumoto S, Ouchi N, Arita Y, Okamoto Y, Shimomura I, Hiraoka H, Nakamura T, Funahashi T, Matsuzawa Y, Osaka CAD Study Group. Coronary artery disease (2003) Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol 23:85–89
Yoshinaga M, Sameshima K, Tanaka Y, Wada A, Hashiguchi J, Tahara H, Kono Y (2008) Adipokines and the prediction of the accumulation of cardiovascular risk factors or the presence of metabolic syndrome in elementary school children. Circ J 72:1874–1878
Mitsnefes M, Kartal J, Khoury P, Daniels S (2007) Adiponectin in children with chronic kidney disease: role of adiposity and kidney dysfunction. Clin J Am Soc Nephrol 2:46–50
Falkner B, Gidding S (2011) Childhood obesity and blood pressure: Back to the future? Hypertension 58:754–755
Staples AO, Greenbaum LA, Smith JM, Gipson DS, Filler G, Warady BA, Martz K, Wong CS (2010) Association between clinical risk factors and progression of chronic kidney disease in children. Clin J Am Soc Nephrol 5:2172–2179
Tu W, Eckert GJ, DiMeglio LA, Yu Z, Jung J, Pratt JH (2011) Intensified effect of adiposity on blood pressure in overweight and obese children. Hypertension 58:818–824
Sorof JM, Lai D, Turner J, Poffenbarger T, Portman RJ (2004) Overweight, ethnicity, and the prevalence of hypertension in school-aged children. Pediatrics 113:475–482
Lubrano R, Travasso E, Raggi C, Guido G, Masciangelo R, Elli P (2009) Blood pressure load, proteinuria and renal function in prehypertensive children. Pediatr Nephrol 24:823–831
Mitsnefes M, Flynn J, Cohn S, Samuels J, Blydt-Hansen T, Saland J, Kimball T, Furth S, Warady B, CKiD Study Group (2010) Masked hypertension associates with left ventricular hypertrophy in children with CKD. J Am Soc Nephrol 21:137–144
Shatat IF, Flynn JT (2011) Relationships between renin, aldosterone, and 24-hour ambulatory blood pressure in obese adolescents. Pediatr Res 69:336–340
Holl RW, Hoffmeister U, Thamm M, Stachow R, Keller KM, L’Allemand D, Widhalm K, Flechtner-Mors M, Wiegand S (2011) Does obesity lead to a specific lipid disorder? Analysis from the German/Austrian/Swiss APV registry. Int J Pediatr Obes 6(Suppl 1):53–58
Saland JM, Pierce CB, Mitsnefes MM, Flynn JT, Goebel J, Kupferman JC, Warady BA, Furth SL (2010) Dyslipidemia in children with chronic kidney disease. Kidney Int 78:1154–1163
Sandhu S, Wiebe N, Fried LF, Tonelli M (2006) Statins for improving renal outcomes: a meta-analysis. J Am Soc Nephrol 17:2006–2016
Butani L (2005) Prospective monitoring of lipid profiles in children receiving pravastatin preemptively after renal transplantation. Pediatr Transplant 9:746–753
Weinberg JM (2006) Lipotoxicity. Kidney Int 70:1560–1566
Moorhead JF, Chan MK, El-Nahas M, Varghese Z (1982) Lipid nephrotoxicity in chronic progressive glomerular and tubulo- interstitial disease. Lancet 2:1309–1311
Thomas ME, Harris KP, Walls J, Furness PN, Brunskill NJ (2002) Fatty acids exacerbate tubulointerstitial injury in proteinoverload proteinuria. Am J Physiol Renal Physiol 283:F640–F647
Economos CD, Hyatt RR, Goldberg JP, Must A, Naumova EN, Collins JJ, Nelson ME (2007) A community intervention reduces BMI z-score in children: Shape Up Somerville first year results. Obesity (Silver Spring) 15:1325–1336
Demattia L, Denney SL (2008) Childhood obesity prevention: successful community-based efforts. Ann Am Acad Pol Soc Sci 615:83–99
Acknowledgements
Robert Mak is supported by the National Institutes of Health U01 DK-3-012 grant and investigator-initiated grants from the Cystinosis Foundation and Abbott Inc. All authors declare that they have no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
Answers
1. a
2. d
3. c
4. c
5. d
Questions
Questions
1. The following is true about obesity-related glomerulopathy, except:
-
a)
Thickening of the basement membrane.
-
b)
Glomerulomegaly.
-
c)
Focal segmental glomerulosclerosis.
-
d)
Foot-process fusion.
2. The following is true about obesity, low birth weight (LBW), and chronic kidney disease (CKD), except:
-
a)
LBW predisposes to metabolic syndrome.
-
b)
Several studies link LBW to increased risk of CKD in the adult population.
-
c)
Animal models of LBW have fewer glomeruli compared with controls.
-
d)
The prevalence of LBW infants in the ongoing Chronic Kidney Disease in Children (CKiD) Study cohort is the same as in the general US population.
3. The following is true about metabolic syndrome and its relation to chronic kidney disease, except:
-
a)
Obesity is associated with hyperinsulinemia.
-
b)
Insulin is an anti-inflammatory hormone.
-
c)
Bariatric surgery does not lead to any improvement in insulin sensitivity.
-
d)
Insulin resistance predisposes to microalbuminuria.
4. The following is a true statement regarding adipokines:
-
a)
Leptin is an orexigenic hormone.
-
b)
Increased leptin levels seen in obesity help in weight loss.
-
c)
Adiponectin is involved in the regulation of lipid and glucose metabolism.
-
d)
IL-6 is an anti-inflammatory cytokine.
5. The following is true regarding obesity and its comorbidities in the setting of renal transplant, except:
-
a)
Obesity in the renal transplant recipient may have an adverse effect on renal allograft survival.
-
b)
Kidneys from obese donors may have an adverse effect on renal allograft survival.
-
c)
The frequency of obesity in pediatric population eligible for renal transplant is increasing.
-
d)
Incidence and prevalence of dyslipidemia does not improve with preemptive treatment with statins in the posttransplant period.
Rights and permissions
About this article
Cite this article
Gunta, S.S., Mak, R.H. Is obesity a risk factor for chronic kidney disease in children?. Pediatr Nephrol 28, 1949–1956 (2013). https://doi.org/10.1007/s00467-012-2353-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-012-2353-z