Biocompatible dialysis membranes do not reduce plasma leptin levels

M. J. Wright, G. Woodrow, G. Young, A. M. Brownjohn and J. H. Turney

Renal Unit, Wellcome Wing, Leeds General Infirmary, Leeds, UK

Sir,

There is evidence that biocompatible dialysis membranes (BCM) lead to a lesser degree of malnutrition than bio-incompatible membranes (BICM) [1]. Lindsay et al. suggested [2] that this may be attributable to a beneficial effect on nutrient intake of BCM dialysis, although it was not clear whether this was related to the flux properties or biocompatibility of the membrane.

Leptin suppresses appetite and increases basal metabolic rate in rodent models. It is present in supra-normal concentrations in dialysis patients and may suppress nutrient intake [3]. Leptin synthesis increases in the presence of high concentrations of cytokines, particularly TNF-{alpha} and IL-1 [4]. This led us to hypothesize that dialysis with a BICM may stimulate leptin synthesis and suppress appetite. We tested this hypothesis using a low-flux polyethylene glycol grafted cellulose (PEGC) membrane [5] and standard Cuprophan in this prospective randomized cross-over study.

Thirty-two patients were studied (22 male, 10 female; median age 63, range 28–83; median BMI 23.9 kg/m2, range 17.2–32.7 kg/m2). All patients had been stable on regular bicarbonate haemodialysis with a Cuprophan membrane for at least 3 months. They were randomized to either continue with Cuprophan (Gambro ‘Alwall’, Gambro Dialysatoren, Hechingen, Germany) or change to a PEGC membrane (Asahi AM-Bio-Wet, Asahi Medical Co., Ltd, Tokyo, Japan) with equivalent clearance. They dialysed for 2 months, after which at 07:30 a pre-dialysis blood specimen was taken. Each patient then converted to the other membrane and the blood sample was repeated after two more months. Plasma leptin and CRP were compared on paired samples. In a second study (23 patients; 15 male, 8 female; median age 65; range 28–83) leptin, CRP and albumin levels were measured immediately before and after a morning dialysis session. Leptin and CRP results were not normally distributed so median values and interquartile ranges are quoted and non-parametric analyses used. The other results were normally distributed and compared by paired t-tests.

Contrary to our hypothesis, plasma leptin levels (BCM 11.9 (5.7–40.1) ng/ml vs BICM 10.3 (4.5–36.1) ng/ml, P<0.02) and CRP (BCM 4.5 (1.0–9.0) mg/l vs BICM 3.1 (1.0–7.0) mg/l, P<0.02) were significantly higher with the BCM. There was no correlation between CRP and plasma leptin (BCM r=-0.12 and BICM r=-0.17) suggesting that this alone did not explain the discrepancy.

The pre- and post-dialysis results are shown in Table 1Go. There was a small but significant increase in leptin using the BCM, which was not apparent using the BICM. Serum albumin increased significantly using both membranes. We compared the increment in leptin with that in albumin in order to determine how much of the change could be attributed to volume contraction. There was no correlation between change in albumin and change in leptin. The CRP values decreased using the BICM but not the BCM. There was no relationship between CRP decrement and albumin increment for either membrane.


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Table 1. Pre- and post-dialysis plasma leptin, albumin and CRP

 
Our results did not support the theory that BICMs lead to higher leptin levels, indeed, a small but statistically significant change in the opposite direction was observed. It is possible that leptin may adsorb to Cuprophan to a greater degree than PEGC, which has low adsorption characteristics [6]. A significant increase in leptin during BCM dialysis, in contrast to increases in albumin with both membranes lends some support to this theory. Adsorption may also explain the changes in the CRP results. The significant CRP reduction seen during Cuprophan but not PEGC dialysis would be consistent with this hypothesis. The biological relevance of the very small increase in leptin during BCM dialysis is unclear.

In summary, we did not find lower leptin levels with BCM dialysis. Indeed, we demonstrated that haemodialysis with a PEGC membrane leads to a small increase in plasma leptin levels when compared with Cuprophan. We suggest that the dialysis membrane may affect the plasma leptin level because of its surface adsorption characteristics rather than its capacity for activation of the inflammatory response. Researchers studying leptin biology in haemodialysis patients should be aware that the choice of low-flux dialysis membrane might exert a small effect on their results.

References

  1. Parker TF, Wingard RL, Husni L, Ikizler TA, Parker RA, Hakim RM. Effect of the membrane biocompatibility on nutritional parameters in chronic haemodialysis patients. Kidney Int1996; 49: 551–556[ISI][Medline]
  2. Lindsay RM, Spanner E. A hypothesis: the protein catabolic rate is dependent upon the type and amount of treatment in dialysed uraemic patients. Am J Kidney Dis1989; 13: 382–389[ISI][Medline]
  3. Young GA, Woodrow G, Kendall S et al. Increased plasma leptin/fat ratio in patients with chronic renal failure: a cause of malnutrition? Nephrol Dial Transplant1997; 12: 2318–2323[Abstract]
  4. Grunfeld C, Zhao C, Fuller J et al. Endotoxin and cytokines induce expression of leptin, the Ob gene product, in hamsters. A role for leptin in the anorexia of infection. J Clin Invest1996; 97: 2152–2157[Abstract/Free Full Text]
  5. Kishida A, Ikada Y. Chemical modification of cellulose membranes and the subsequent decrease of complement activation. Jpn J Artif Organs1988; 17: 47–50
  6. Kuriyama R, Goto K, Matsui N et al. The evaluation of blood components deposition on membranes of cellulose, polyethylene glycol (PEG) grafted cellulose, cellulose diacetate and polymethyl methacrylate. Jpn J Artif Organs1992; 21: 909–913




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