Serum albumin— A marker of fluid overload in dialysis patients?

Serum albumin— A marker of fluid overload in dialysis patients?

GUEST EDITORIAL Serum Albumin A Marker of Fluid Overload in Dialysis Patients? he serum albumin concentration is a p o w erfill predictor o f outcome...

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GUEST EDITORIAL

Serum Albumin A Marker of Fluid Overload in Dialysis Patients? he serum albumin concentration is a p o w erfill predictor o f outcome in both haemo -1 and peritoneal dialysis patients. 2 It is unlikely that a decreased albumin per se results in an increased mortality. R a t h e r the serum albumin is low as a consequence o f the same pathophysiological processes that result in an excess risk o f death. Indeed the significance o f serum albumin in determining o u t c o m e is lost in multivariate analyses that include other variables such as c o - m o r b i d disease. 3 5 W h a t are the mechanisms o f hypoalbuminaemia in this patient group? A n u m b e r have been proposed. For m a n y years hypoalbuminaemia has been attributed to the malnutrition that is reported to be so prevalent in dialysis patients. <7 In fact the evidence that serum albumin is dependent on nutrition is not very strong s and serum albumin is predominantly determined by a n u m ber o f other factors. 9 A large b o d y o f evidence has demonstrated that a low serum albumin is related to a poorly defined chronic inflammatory process, as detected by elevated plasma values o f a n u m b e r o f inflammatory markers including C reactive protein, 1° alpha-2 macroglobulin, 1° ferritin 1° and serum amyloid A component. 11'12 In contrast, serum albumin is positively correlated with IGF-1.1° T h e underlying source o f this inflammatory response is unclear but may in part be related to atherosclerotic disease. 13 Inflammation is not the only mechanism o f h y p o a l b u m i n aemia in this patient group as there is also data to correlate a low serum albumin with increasing age TM and increased urinary is and peritoneal protein 16 losses. Every clinician caring for dialysis patients knows that end-stage renal failure is associated with a tendency towards fluid overload, p r e d o m inantly due to expansion o f the extracellular fluid space. T h e concentration o f any c o m p o u n d in

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© 2001 by the National Kidney Foundation, Inc.

doi: 10.1053/jren. 2001.2.3469

.journal ~RenaI Nutrition, Vol 11, No 2 (April), 2001: pp 59-61

the circulation is dependent both on the a m o u n t o f that c o m p o u n d and the plasma volume in which it is contained. Is there any evidence to suggest a relationship between a low serum albumin and fluid overload in this patient group? W h e n fluid is r e m o v e d during haemodialysis haemoconcentration occurs. Serum albumin increases in the same way that haemoglobin concentration or haematocrit increases. In a r a n d o m sample o f 49 chronic haemodialysis patients u n dergoing a net fluid removal o f 2.0 _+ 1.2 kg the serum albumin increased from 36.9 g / L (95% confidence interval 35.7-38.1) to 41.4 g / L (95% confidence interval 39.7-43.3) in a laboratory with a reference range for serum albumin o f 35-50 g/L. 17 The second sample was immediately post dialysis and equilibration w o u l d not have occurred. H o w e v e r the serum albumin did increase from the low normal to normal range and this was clearly related to fluid removal. In a study o f albumin homeostasis, serum albumin was significantly lower in 9 C A P D patients compared to 5 normal controls, is The plasma albumin mass and total albumin mass were not different, but plasma volume was non-significantly greater in the patients (50.6 _+ 20.9 p 36.8 _+ 3.6 mL/kg) suggesting a dilutional effect that could partly explain the lower serum albumin in the C A P D patients. Serum albumin has been negatively correlated with the extracellular fluid volume normalized to the total b o d y water in patients maintained on C A P D . is In haemodialysis the increase in serum albumin over a dialysis session correlated both with the actual amount o f fluid r e m o v e d and the decrease in extracellular water estimated by bioelectric impedance. 17 Ser u m albumin, both pre and post dialysis, showed a negative correlation with extracellular fluid volume normalized to total b o d y water. This relationship was independent o f the significant negative correlation between serum albumin and C-reactive protein. 50

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C.H. JONES

In C A P D s e r u m a l b u m i n is n e g a t i v e l y c o r r e lated w i t h p e r i t o n e a l p r o t e i n loss and this has b e e n a t t r i b u t e d to an excess loss o f p r o t e i n l e a d i n g to a l o w s e r u m a l b u m i n . C A r D patients can b e characterised b y t h e i r dialysate to plasma c r e atinine ( D / P ) ratio, a m a r k e r o f t h e p e r m e a b i l i t y o f the p e r i t o n e a l m e m b r a n e . Patients w i t h a h i g h e r D / r c r e a t i n i n e ratio h a v e a m o r e p e r m e able p e r i t o n e a l m e m b r a n e a n d a greater loss o f p r o t e i n i n t o the dialysate. 19 In o n e study, patients g r o u p e d as high, h i g h average, l o w average a n d l o w transporters had s e r u m a l b u m i n c o n c e n t r a tions o f 32.8, 33.8, 36.2, and 37.8 g / L , r e s p e c t i v e l y and m e a n 2 4 - h o u r d r a i n e d dialysate v o l u m e s o f 8.22, 8.59, 8.93, and 9.38 L, respectively. 2° So h i g h transporters h a v e w o r s e ultrafiltration and this m a y lead to fluid o v e r l o a d and a dilutional h y p o a l b u m i n a e m i a . T h e p r e s e n c e o f fluid o v e r l o a d is s u p p o r t e d b y t h e f i n d i n g o f a h i g h e r b l o o d pressure in h i g h transporters. 21 T h e r e are n o g o o d c o n t r o l l e d studies d e m o n strafing that any t h e r a p e u t i c m a n o e u v r e increases s e r u m a l b u m i n . W h e t h e r the s e r u m a l b u m i n c o n c e n t r a t i o n can b e i n c r e a s e d b y a sustained decrease in intravascular v o l u m e requires a p r o spective study. T h i s study has n o t yet b e e n d o n e . C o u l d t h e relationship b e t w e e n s e r u m a l b u m i n and i n c r e a s e d fluid v o l u m e explain that b e t w e e n s e r u m a l b u m i n and i n c r e a s e d mortality? H e a r t failure is a c o m m o n f i n d i n g at t h e start o f dialysis, often occurs de n o v o in dialysis patients and is a f r e q u e n t cause o f death. A l o w s e r u m a l b u m i n is associated w i t h an i n c r e a s e d risk o f d e v e l o p i n g left v e n t r i c u l a r dilatation and de n o v o or r e c u r rent heart failure in ESP,,F. 22 In C A r D c h r o n i c h y p e r v o l a e m i a is associated w i t h an i n c r e a s e d left v e n t r i c u l a r mass. 23 A h i g h D / P ratio is associated w i t h a decreased p r o b a b i l i t y o f patient and t e c h n i q u e survival at 2 years f r o m start o f dialysis (48%, 52%, 61%, and 86% for high, h i g h average, l o w average, a n d l o w transporters, respectively2°). T h e s e observations offer a possible e x p l a n a t i o n for an i n c r e a s e d m o r t a l i t y in s o m e h y p o a l b u m i n a e m i c ES1KF patients. Is s e r u m a l b u m i n a m a r k e r o f fluid o v e r l o a d in dialysis patients? N o it is not. S e r u m a l b u m i n is d e t e r m i n e d b y a n u m b e r o f m e c h a n i s m s that are associated w i t h a w o r s e prognosis. A n i n creased fluid v o l u m e m a y b e o n e o f these factors and s h o u l d b e a c t i v e l y e x c l u d e d in a n y patient with unexplained hypoalbuminaemia. However,

c h r o n i c i n f l a m m a t i o n , c o - m o r b i d disease, a t h erosclerosis, and p o o r n u t r i t i o n are also p r e v a l e n t and equally plausible explanations for i n c r e a s e d mortality. C.H. Jones, MB, ChB, MD, FRCP Renal Unit Y o r k District H o s p i t a l York, UK

References 1. Lowrie EG, Lew NL: Death risk in haemodialysis patients: The predictive values of commonly measured variables and an evaluation of death rate differences between facilities. Am J Kidney Dis 15:458-482, 1990 2. Jones CH, Newstead CG, Will EJ, et al: Serum albumin and survival in CArD patients: The value of time trends in albumin. Nephrol Dial Transplant 12:554-558, 1997 3. Struijk DG, Krediet RT, Koomen GCM, et al: The effect of serum albumin at the start of continuous ambulatory peritoneal dialysis on patient survival. Petit Dial Int 14:121126, 1994 4. Genestier S, Hedelin G, Schaffer r, et al: Prognostic factors in CArD patients: A retrospective study of a 10 year period. Nephrol Dial Transplant 10:1905-1911, 1995 5. Davies sJ, Russell L, Bryan J, et al: Co-morbidity, urea kinetics, and appetite in continuous ambulatory peritoneal dialysis patients: Their interrelationship and prediction of survival. Am J Kidney Dis 26:353-361, 1995 6. Young GA, Kopple JD, Lindholm B, et al: Nutritional assessment of continuous ambulatory peritoneal dialysis patients: An international study. Am J Kidney Dis 27:462-471, 1991 7. Cianciaruso B, Brunori G, Kopple JD, et al: Cross-sectional comparison of malnutrition in continuous ambulatory peritoneal dialysis and hemodialysis patients. Am J Kidney Dis 26:475-486, 1995 8. Jones CH: Is serum albumin a useful measure of nutritional status in dialysis patients? Semin Dial 11:144-147, 1998 9. Kaysen GA: Hypoalbuminemia in dialysis patients. Semin Dial 9:249-256, 1996 10. Kaysen GA, Rathore V, Shearer GC, et al: Mechanisms of hypoalbuminaemia in haemodialysis patients. Kidney Int 48:510516, 1995 11. Kaysen GA, Stevenson FT, Depner TA: Determinants of albumin concentration in haemodialysis patients. Am J Kidney Dis 29:658-668, 1997 12. YeunJY, Kaysen GA: Acute phase proteins and peritoneal dialysate albumin loss are the main determinants of serum albumin in peritoneal dialysis patients. J Am Soc Nephrol 8:276A, 1997 (abstr) 13. Stenvinkel P, Heimburger O, Paultre F, et al: Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int 55:1899-1911, 1999 14. Blake PG, Flowerdew G, Blake RM, et al: Serum albumin in patients on continuous ambulatory dialysis Predictors and correlations with outcomes. J Am Soc Nephrol 3:15011507, 1993 15. Jones CH, Smye SW, Newstead CG, et al: Extracellular fluid volume determined by bio-electric impedance and serum

GUEST EDITORIAL albumin in CAPD patients. Nephrol Dial Transplant 13:393397, 1998 16. Schoenfidd PY: Albumin is an unreliable marker of nutritional status. Semin Dial 5:218-223, 1992 17. Jones CH, Akbani H, Croft DC, et al: Rdationship of serum albumin to hydration in haemodialysis patients. UK Renal Association 2000 (abstr to be published in Kidney Int) 18. Kaysen GA, Schoenfield PY: Albumin homeostasis in patients undergoing continuous ambulatory peritoneal dialysis. Kidney Int 25:107-114, 1984 19. Malhotra D, Tzamaloukas AH, Murata GH, et al: Serum albumin in continuous peritoneal dialysis: its predictors and relationship to urea clearance. Kidney Int 50:243-249, 1996 20. Churchill DN, Thorpe KE, Nolph KD, et al: Increased

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peritoneal membrane transport is associated with decreased patient and technique survival for continuous peritoneal dialysis patients. The Canada-USA Peritoneal Dialysis Study Group. J Am Soc Nephrol 9:1285-1292, 1998 21. Wang T, Heimburger O, Waniewski J, et al: Increased peritoneal permeability is associated with decreased fluid and small solute removal and higher mortality in CAPD patients. Nephrol Dial Transplant 13:1242-1249, 1998 22. Foley IKN, Parfrey PS, Harnett JD, et al: Hypoalbuminaemia, cardiac morbidity, and mortality in end-stage renal disease. J Am Soc Nephrol 7:728-736, 1996 23. Huting J, Alpert MA: Progression of left ventricular hypertrophy in end-stage renal disease treated by continuous ambulatory dialysis depends on hypertension and hypercirculation. Clin Cardiol 15:190-196, 1992