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Diabetes Care 31:e23 2008
DOI: 10.2337/dc07-2257
© 2008 by the American Diabetes Association
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Online Letters: Comments and Responses

Serum Levels of Adipokine Retinol-Binding Protein-4 in Relation to Renal Function

Response to Ziegelmeier et al.

Vasileios Papavasileiou, MD1, Vasilios Liakopoulos, MD, PHD1, Georgios K. Sakkas, PHD1, Georgios M. Hadjigeorgiou, MD, PHD1, Georgios Koukoulis, MD, PHD2 and Ioannis Stefanidis, MD, PHD1

1 Department of Nephrology, University of Thessaly, School of Medicine, Larissa, Greece
2 Department of Endocrinology, University of Thessaly, School of Medicine, Larissa, Greece

Address correspondence to Ioannis Stefanidis, MD, PhD, Department of Nephrology , University Hospital of Larissa, Mezourlo Hill, 41110 Larissa, Greece. E-mail: stefanid{at}med.uth.gr

In their recent study, Ziegelmeier et al. (1) showed that remnant kidney function and C-reactive protein are independently associated with elevated serum levels of retinol-binding protein (sRBP)-4 in hemodialysis patients. Markers of kidney function were levels of serum creatinine and glomerular filtration rate estimated by the Cockroft-Gault formula . However, since creatinine can be removed both by dialysis and remnant kidneyfunction, levels of serum creatinine and glomerular filtration rate estimated by the Cockroft-Gault formula do not exactly reflect renal function in hemodialysis patients (2). Additionally, serum creatinine, mainly produced from skeletal muscle creatine, correlates with lean body mass (LBM) (3). Thus, in hemodialysis, levels of serum creatinine depend on dialytic and renal removal but may also be an index of nutritional status (3,4), facts not taken into account by Ziegelmeier et al. (1).

We conducted a cross-sectional study in hemodialysis patients (n = 36; 14 female of mean ± SD age 54 ± 18 years) and healthy control subjects (n = 26; 10 female; aged 51 ± 15 years) to investigate the relationship of treatment adequacy and nutrition with sRBP-4 (micrograms per milliliter, based on enzyme-linked immunosorbent assay). Serum creatinine, adequacy (urea kinetic modeling[Kt/Vurea]), and surrogates of nutrition (kilograms of LBM and protein catabolic rate [PCR ] [grams per kilogram], calculated using urea kinetic modeling) were determined. Levels of sRBP-4, increased in hemodialysis compared with those of control subjects (41.0 ± 7.2 vs. 26.1 ± 5.9 µg/ml, P < 0.01), correlated with levels of serum creatinine (r = 0.342, P = 0.041) and Kt/Vurea (r = –0.308, P = 0.042). On multivariate linear regression, after adjustment for Kt/Vurea (R2 = 0.176, P = 0.045), the relationship between sRBP-4 and serum creatinine (β-coefficient = 0.666, P = 0.086) was not maintained. However, when surrogates of nutrition (LBM and PCR) were added to the model, both serum creatinine (β-coefficient = 1.299, P = 0.004) and PCR (β-coefficient = –12.163, P = 0.020) independently predicted sRBP-4.

Our study implies that in hemodialysis, elevated sRBP-4 is associated with treatment inadequacy and protein malnutrition. This finding is of considerable interest because malnutrition has been closely related to inflammation and mortality in this patient group (4–6). Taking into account that sRBP-4 correlated with C-reactive protein (1), one may readily assume that there is some relationship between protein malnutrition, sRBP-4 , and inflammation in hemodialysis that is yet to be clarified.

References

  1. Ziegelmeier M, Bachmann A, Seeger J, Lossner U, Kratzsch J, Bluher M, Stumvoll M, Fasshauer M: Serum levels of adipokine retinol-binding protein-4 in relation to renal function. Diabetes Care 30:2588–2592, 2007[Abstract/Free Full Text]
  2. Kuan Y, Hossain M, Surman J, El Nahas AM, Haylor J: GFR prediction using the MDRD and Cockcroft and Gault equations in patients with end-stage renal disease. Nephrol Dial Transplant 20:2394–2401, 2005[Abstract/Free Full Text]
  3. Keshaviah PR, Nolph KD, Moore HL, Prowant B, Emerson PF, Meyer M, Twardowski ZJ, Khanna R, Ponferrada L, Collins A: Lean body mass estimation by creatinine kinetics. J Am Soc Nephrol 4:1475–1485, 1994[Abstract]
  4. Qureshi AR, Alvestrand A, Divino-Filho JC, Gutierrez A, Heimburger O, Lindholm B, Bergstrom J: Inflammation, malnutrition, and cardiac disease as predictors of mortality in hemodialysis patients. J Am Soc Nephrol (Suppl. 1):S28–S36, 2002
  5. Filippidis G, Liakopoulos V, Mertens PR, Kiropoulos T, Stakias N, Verikouki C, Patsidis E, Koukoulis G, Stefanidis I: Resistin serum levels are increased but not correlated with insulin resistance in chronic hemodialysis patients. Blood Purif 23:421–428, 2005[Medline]
  6. Cooper BA, Penne EL, Bartlett LH, Pollock CA: Protein malnutrition and hypoalbuminemia as predictors of vascular events and mortality in ESRD. Am J Kidney Dis 43:61–66, 2004[Medline]

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M. Ziegelmeier, A. Bachmann, J. Seeger, U. Lossner, M. Bluher, M. Stumvoll, and M. Fasshauer
Serum Levels of Adipokine Retinol-Binding Protein-4 in Relation to Renal Function: Response to Papavasileiou et al.
Diabetes Care, April 1, 2008; 31(4): e24 - e24.
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