Effect of childhood obesity and obesity-related cardiovascular risk factors on glomerular and tubular protein excretion (original) (raw)

Abstract

There is increasing evidence that obesity may damage the kidney in otherwise healthy individuals. Our study investigated the effect of childhood obesity on urinary albumin and beta-2-microglobulin excretion, and the association of these with obesity-related cardiovascular risk factors. Random morning spot urine samples were collected from clinically healthy obese ( n =86; median age 12.9 years, range 8.9–17.2 years; median weight 80.6 kg, range 46.1–136.8 kg; median body mass index 30.4 kg/m2, range 24.5–43.2 kg/m2) and normal weight children ( n =79; median age 13.5 years, range 10.7–14.9 years; median weight 51.0 kg, range 27.3–72.5 kg; median body mass index 18.2 kg/m2, range 13.2–23.9 kg/m2). The obese children were examined for the presence of common obesity-related cardiovascular risk factors including hyperinsulinaemia, impaired glucose tolerance (IGT), dyslipidaemia, hypercholesterolaemia, and hypertension. Obese children had a significantly higher urinary albumin/creatinine ratio (U-ACR) (median 11.7 mg/g, interquartile range 12.9 mg/g versus median 9.0 mg/g, interquartile range 5.1 mg/g; P =0.003) and urinary beta-2-microglobulin/creatinine ratio (U-BMCR) (median 63.9 µg/g, interquartile range 34.7 µg/g versus median 34.6 µg/g, interquartile range 44.1 µg/g; P <0.001) than normal weight children. Among the obese children, the U-ACR was associated with fasting hyperinsulinaemia, IGT, and hypercholesterolaemia (all P <0.05), and significantly correlated with the fasting ( r =0.23, P <0.05) and 2-h ( r =0.37, P <0.001) plasma glucose levels measured during an oral glucose tolerance test. Obese children with no more than one of the features of the metabolic syndrome had significantly lower U-ACRs than obese children with two or more features (median 10.4 mg/g, interquartile range 5.8 mg/g versus median 15.3 mg/g, interquartile range 14.9 mg/g; P <0.05). _Conclusion:_According to our results, clinically healthy obese children have a higher degree of albuminuria and beta-2-microglobulinuria than normal weight children, indicating early renal glomerular and tubular dysfunction as a consequence of childhood obesity. The urinary albumin/creatinine ratio in the obese children was associated with certain metabolic derangements linked to obesity, and also with the clustering of features of the metabolic syndrome.

Access this article

Log in via an institution

Subscribe and save

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

Abbreviations

ABPM :

ambulatory blood pressure monitoring

BMI :

body mass index

IGT :

impaired glucose tolerance

OGTT :

oral glucose tolerance test

U-ACR :

urinary albumin/creatinine ratio

U-BMCR :

urinary beta-2-microglobulin/creatinine ratio

References

  1. Adelman RD, Restaino IG, Alon US, Blowey DL (2001) Proteinuria and focal segmental glomerulosclerosis in severely obese adolescents. J Pediatr 138: 481–485
    Article CAS Google Scholar
  2. Bianchi S, Bigazzi R, Valtriani C, Chiapponi I, Sgherri G, Baldari G, Natali A, Ferrannini E, Campese VM (1994) Elevated serum insulin levels in patients with essential hypertension and microalbuminuria. Hypertension 23: 681–687
    Article CAS Google Scholar
  3. Branten AJ, Wetzels JF (1999) Influence of albumin infusion on the urinary excretion of beta-2-microglobulin in patients with proteinuria. Nephron 81: 329–333
    Article CAS Google Scholar
  4. Burton CJ, Harper SJ, Bailey E, Feehally J, Harris KP, Walls J (2001) Turnover of human tubular cells exposed to proteins in vivo and in vitro. Kidney Int 59: 507–514
    Article CAS Google Scholar
  5. Cole TJ, Bellizzi MC, Flegal KM, Dietz WH (2000) Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 320: 1240–1243
    Article CAS Google Scholar
  6. Csabi G, Torok K, Jeges S, Molnar D (2000) Presence of metabolic cardiovascular syndrome in obese children. Eur J Pediatr 159: 91–94
    Article CAS Google Scholar
  7. Eiben O, Pantó E (1987) Body measurement in the Hungarian youth at the 1980s, based on the Hungarian National Growth Study. Antropol Közl 31: 49–68
    Google Scholar
  8. Expert Committee on the diagnosis and classification of diabetes mellitus (1997) Report of the Expert Committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 20: 1183–1197
    Article Google Scholar
  9. Gerstein HC, Mann JF, Yi Q, Zinman B, Dinneen SF, Hoogwerf B, Halle JP, Young J, Rashkow A, Joyce C, Nawaz S, Yusuf S (2001) Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA 286: 421–426
    Article CAS Google Scholar
  10. Groop L, Orho-Melander M (2001) The dysmetabolic syndrome. J Intern Med 250: 105–120
    Article CAS Google Scholar
  11. Hidaka S, Kaneko O, Shirai M, Kojima K, Igarashi Y, Oda K, Chimata M, Nakamura K, Nagase M (1998) Do obesity and non-insulin dependent diabetes mellitus aggravate exercise-induced microproteinuria? Clin Chim Acta 275: 115–126
    Article CAS Google Scholar
  12. Hillege HL, Janssen WM, Bak AA, Diercks GF, Grobbee DE, Crijns HJ, Van Gilst WH, De Zeeuw D, De Jong PE (2001) Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity. J Intern Med 249: 519–526
    Article CAS Google Scholar
  13. Hiratsuka N, Shiba K, Nishida K, Iizima S, Kimura M, Kobayashi S (1998) Analysis of urinary albumin, transferrin, N-acetyl-beta-D-glucosaminidase and beta-2-microglobulin in patients with impaired glucose tolerance. J Clin Lab Anal 12: 351–355
    Article CAS Google Scholar
  14. Hoffmann IS, Jimenez E, Cubeddu LX (2001) Urinary albumin excretion in lean, overweight and obese glucose tolerant individuals: its relationship with dyslipidaemia, hyperinsulinaemia and blood pressure. J Hum Hypertens 15: 407–412
    Article CAS Google Scholar
  15. Hong CY, Chia KS (1998) Markers of diabetic nephropathy. J Diabetes Complications 12: 43–60
    Article CAS Google Scholar
  16. Jager A, Kostense PJ, Nijpels G, Heine RJ, Bouter LM, Stehouwer CD (1998) Microalbuminuria is strongly associated with NIDDM and hypertension, but not with the insulin resistance syndrome: the Hoorn Study. Diabetologia 41: 649–700
    Article Google Scholar
  17. Jensen JS, Borch-Johnsen K, Jensen G, Feldt-Rasmussen B (1995) Microalbuminuria reflects a generalized transvascular albumin leakiness in clinically healthy subjects. Clin Sci 88: 629–633
    Article CAS Google Scholar
  18. Kuusisto J, Mykkanen L, Pyorala K, Laakso M (1995) Hyperinsulinemic microalbuminuria: a new risk indicator for coronary heart disease. Circulation 91: 831–837
    Article CAS Google Scholar
  19. Liese AD, Hense HW, Doring A, Stieber J, Keil U (2001) Microalbuminuria, central adiposity and hypertension in the non-diabetic urban population of the MONICA Augsburg survey 1994/95. J Hum Hypertens 15: 799–804
    Article CAS Google Scholar
  20. Lokkegaard N, Haupter I, Kristensen TB (1992) Microalbuminuria in obesity. Scand J Urol Nephrol 26: 275–278
    Article CAS Google Scholar
  21. Maddox DA, Alavi FK, Silbernick EM, Zawada ET (2002) Protective effects of soy diet in preventing obesity-linked renal disease. Kidney Int 61: 96–104
    Article CAS Google Scholar
  22. Meigs JB, D’Agostino RB Sr, Nathan DM, Rifai N, Wilson PW (2002) Longitudinal association of glycemia and microalbuminuria: the Framingham Offspring Study. Diabetes Care 25: 977–983
    Article Google Scholar
  23. Mykkanen L, Zaccaro DJ, Wagenknecht LE, Robbins DC, Gabriel M, Haffner SM (1998) Microalbuminuria is associated with insulin resistance in nondiabetic subjects – the insulin resistance atherosclerosis study. Diabetes 47: 793–800
    Article CAS Google Scholar
  24. Palaniappan L, Carnethon M, Fortmann SP (2003) Association between microalbuminuria and the metabolic syndrome: NHANES III. Am J Hypertens 16: 952–958
    Article CAS Google Scholar
  25. Reilly JJ, Mefhren E, McDowell ZC, Hacking B, Alexander D, Stewart L, Kelnar CJH (2003) Health consequences of obesity. Arch Dis Child 88: 748–752
    Article CAS Google Scholar
  26. Reisin E, Messerli FG, Ventura HO, Froflich ED (1987) Renal hemodynamic studies in obesity hypertension. J Hypertens 5: 397–400
    CAS PubMed Google Scholar
  27. Ribstein J, du Cailar G, Mimran A (1995) Combined renal effects of overweight and hypertension. Hypertension 26: 610–615
    Article CAS Google Scholar
  28. Romics L, Szollar L, Zajkas G (1993) Treatment of disturbances of fat metabolism associated with atherosclerosis (in Hungarian). Orv Hetil 134: 227–238
    CAS PubMed Google Scholar
  29. Soergel M, Kirschstein M, Busch C, Danne T, Gellermann J, Holl R, Krull F, Reichert H, Reusz GS, Rascher W (1997) Oscillometric twenty-four-hour ambulatory blood pressure values in healthy children and adolescents: a multicenter trial including 1141 subjects. J Pediatr 130: 178–184
    Article CAS Google Scholar
  30. Tritos NA, Mantzoros CS (1998) Syndromes of severe insulin resistance. J Clin Endocrinol Metab 83: 3025–3030
    Article CAS Google Scholar
  31. Update on the task force report on high blood pressure in children and adolescents: a working group report from the national high blood pressure education program (1996) Pediatrics 98: 649–658
    Google Scholar
  32. Verani RR (1992) Obesity-associated focal segmental glomerulosclerosis: pathological features of the lesion and relationship with cardiomegaly and hyperlipidaemia. Am J Kidney Dis 20: 629–634
    Article CAS Google Scholar
  33. Yudkin JS, Forrest RD, Jackson CA (1988) Microalbuminuria as predictor of vascular disease in non-diabetic subjects. Islington Diabetes Survey. Lancet 2: 530–533
    Article CAS Google Scholar
  34. Zavaroni I, Bonini L, Gasparini P, Zuccarelli A, Dall’Aglio E, Barilli L, Cioni F, Strata A, Reaven GM (1996) Dissociation between urinary albumin excretion and variables associated with insulin resistance in a healthy population. J Intern Med 240: 151–156
    Article CAS Google Scholar

Download references

Acknowledgements

Support was provided by Hungarian National Research Grant (OTKA T033066/2000) to D. Molnar, the Hungarian Ministry of Welfare (ETT 113/2003) to D. Molnar and the Agency for Research Fund Management and Research Exploitation (BIO-00023/2002) to D. Molnar.

Author information

Authors and Affiliations

  1. Department of Paediatrics, University of Pécs, József A. út 7, 7624 , Pécs, Hungary
    Katalin Csernus, Eva Lanyi, Eva Erhardt & Denes Molnar

Authors

  1. Katalin Csernus
    You can also search for this author inPubMed Google Scholar
  2. Eva Lanyi
    You can also search for this author inPubMed Google Scholar
  3. Eva Erhardt
    You can also search for this author inPubMed Google Scholar
  4. Denes Molnar
    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toKatalin Csernus.

Rights and permissions

About this article

Cite this article

Csernus, K., Lanyi, E., Erhardt, E. et al. Effect of childhood obesity and obesity-related cardiovascular risk factors on glomerular and tubular protein excretion.Eur J Pediatr 164, 44–49 (2005). https://doi.org/10.1007/s00431-004-1546-2

Download citation

Keywords