Scand J Urol Nephrol26: 279-282, 1992
PLASMA PROTEIN HOMEOSTASIS IN CHRONIC HEMODIALYSIS PATIENTS Stefan C Lindgren,' Carl-Bertil Laurel12 and Gunnar N Sterner' From the Departments of 'Medicine, and 'Clinical Chemistry, University of Lund, Malmo General Hospital, Malmo, Sweden
Scand J Urol Nephrol Downloaded from informahealthcare.com by Chulalongkorn University on 01/01/15 For personal use only.
(Submitted January 3 , 1991; Accepted for publication June 20, 1991)
Abstract. The concentrations of 25 plasma proteins were measured in 29 patients with chronic renal insufficiency. All the patients had terminal renal failure and were treated with intermittent hemodialysis, but were otherwise in good general condition at the time of investigation. The plasma levels of 8 proteins with M , c 50 kD were significantly elevated compared to normal subjects. In contrast, only 2/17 proteins of greater size were found in increased concentrations. The degree of increase in concentration differed substantially between individual low molecular weight proteins, suggesting a complex metabolism in addition to delayed renal elimination. Acute phase proteins and immunoglobulins were not affected by renal insufficiency per se, although erythrocyte sedimentation rates were generally high. The synthesis of acute phase proteins increased normally during the course of inflammation. We conclude that although the sedimentation rate is of no value, complicating inflammatory processes can be traced by quantitative analysis of acute phase proteins, including C-reactive protein, even in patients with severe chronic renal insufficienCY.
Key words: acute phase proteins, erythrocyte sedimentation rate, inflammation, plasma protein analysis, renal insufficiency.
Low molecular weight proteins that cross the renal glomerular membrane are absorbed and catabolized in tubular cells or excreted with the urine (2, 10). The filtration of individual proteins depends on their size and charge and on normal negative charge of the glomerular membrane (3). The filtration through normal glomerular basement membranes is roughly zero at 70 kD and 100%below 10 kD (3). The serum concentrations of proteins below 30 kD are expected to reflect the glomerular filtration rate (GFR) provided other factors such as synthesis, distribution volume and extrarenal catabolism are stable. This has previously been demonstrated for /3,-microglobulin &m), cystatin C
and complement factor D (5, 13, 14). Serum concentrations of Bz-m are also increased in patients with certain inflammatory or neoplastic disorders without impaired GFR (6), but with increased release from cell membranes. The purpose of the present study was to evaluate whether routine quantitative plasma protein analysis might aid in the detection of inflammatory processes in patients with severe renal insufficiency. We therefore studied the influence of renal insufficiency on the erythrocyte sedimentation rate (ESR) and on the homeostasis of a large number of plasma proteins, including acute phase proteins and immunoglobulins. PATIENTS The material consisted of 29 patients with severe renal failure on intermittent hernodialysis (1 3 females and 16 males). Their age ranged from 16 to 80 years. Etiology of the renal insufficiency was chronic glomerulonephritis in 14, chronic pwlnnephritis in 5, polycystic disease or other herediiaiq renal disease in 6, nephrosclerosis in 2, and collagenosis or systemic arteritis in 2. The underlying renal diseases were generally considered inactive. No immunosuppressive treatment was given with one exception, a man with long-standing polyarteritis nodosa, who was treated with low doses of steroids and azathioprin. There was no knowledge of recent infectious complications among the patients. In addition, three hemodialysis patients were studied during an episode of septichemia (two with Staphylococcus aureus, one with Enterococcus). Hemodialysis was performed two to three times a week using conventional cellulose membranes (Cuprophana or cellulose acetate) and acetate containing dialysate. The patients had been on hemodialysis for approximately 3 112 years (range 2 months-14 years). The patient who had been on hemodialysis for 14 years had clinical signs suggesting deposition of beta,-microglobulin derived amyloid. Blood samples were drawn in the morning after a light breakfast before the start of dialysis. The serumScand J Urol Nrphrol26
280
S. C. Lindgren et al.
Table I. Plasma concentrations o f 2 5 proteins in patients with stable renal insufficiency and in healthy controls. The concentrations of some proteins are given in % of pooled normal plasma Molecular weight (kD)
Scand J Urol Nephrol Downloaded from informahealthcare.com by Chulalongkorn University on 01/01/15 For personal use only.
11.9 13.3 14.5 21.0 31.0 41.0 45.0 49.0 50.8 54.0 55.0 55.7 52.0 57.0 65.0 69.0 100 100 130 150 160 185 250 340 900 a
Protein &Microglobulin (mg/l) Cystatin C (mg/l) Lysozyme (mg/l) Retinol binding protein (mg/l) Protein HC (%) Zink az-Microprotein (Yo) Orosomucoid (g/l) &Glycoprotein I (Yo) G C globulin ( O h ) Thyroxine binding gl (mg/l) Transthyretin (g/l) Transcortin (O/O) a,-Antit rypsi n (g/l) Hemopexin (O/o) Albumin (g/l) a,-antichymotrypsin (%) SHBG" (mg/l) Haptoglobin (g/l) Ceruloplasmin (g/l) IgG (g/U IgA W ) Complement C3 (%) Complement C4 (O/O) Fibrinogen (g/l) IgM (g/U
Renal insufficiency mean (SD) 51.2 (2.0) 9.10 (2.1) 7.15 (2.2) 270 (90) 989 (310) 217 (3.2) 1.48 (0.44) 207 (59) 83.0 (8) 13.9 (2.4) 0.341 (0.072) 76.0 (1 3) 1.53 (0.23) 92.0 (1 9) 41.5 (3.0) 101 (17) 1.66 (1.2) 1.85 (0.54) 0.330 (0.036) 1 1.2 (3.4) 1.42 (0.55) 92.0 ( I 2) 144 (56) 4.71 (1.1) 1.03 (0.49)
Controls 1.39 1.06 0.35 79.5 1 I4
103 0.89 151
Significance of difference from normal mean p < 0.001 p < 0.00 I
p
PLASMA PROTEIN HOMEOSTASIS IN CHRONIC HEMODIALYSIS PATIENTS Stefan C Lindgren,' Carl-Bertil Laurel12 and Gunnar N Sterner' From the Departments of 'Medicine, and 'Clinical Chemistry, University of Lund, Malmo General Hospital, Malmo, Sweden
Scand J Urol Nephrol Downloaded from informahealthcare.com by Chulalongkorn University on 01/01/15 For personal use only.
(Submitted January 3 , 1991; Accepted for publication June 20, 1991)
Abstract. The concentrations of 25 plasma proteins were measured in 29 patients with chronic renal insufficiency. All the patients had terminal renal failure and were treated with intermittent hemodialysis, but were otherwise in good general condition at the time of investigation. The plasma levels of 8 proteins with M , c 50 kD were significantly elevated compared to normal subjects. In contrast, only 2/17 proteins of greater size were found in increased concentrations. The degree of increase in concentration differed substantially between individual low molecular weight proteins, suggesting a complex metabolism in addition to delayed renal elimination. Acute phase proteins and immunoglobulins were not affected by renal insufficiency per se, although erythrocyte sedimentation rates were generally high. The synthesis of acute phase proteins increased normally during the course of inflammation. We conclude that although the sedimentation rate is of no value, complicating inflammatory processes can be traced by quantitative analysis of acute phase proteins, including C-reactive protein, even in patients with severe chronic renal insufficienCY.
Key words: acute phase proteins, erythrocyte sedimentation rate, inflammation, plasma protein analysis, renal insufficiency.
Low molecular weight proteins that cross the renal glomerular membrane are absorbed and catabolized in tubular cells or excreted with the urine (2, 10). The filtration of individual proteins depends on their size and charge and on normal negative charge of the glomerular membrane (3). The filtration through normal glomerular basement membranes is roughly zero at 70 kD and 100%below 10 kD (3). The serum concentrations of proteins below 30 kD are expected to reflect the glomerular filtration rate (GFR) provided other factors such as synthesis, distribution volume and extrarenal catabolism are stable. This has previously been demonstrated for /3,-microglobulin &m), cystatin C
and complement factor D (5, 13, 14). Serum concentrations of Bz-m are also increased in patients with certain inflammatory or neoplastic disorders without impaired GFR (6), but with increased release from cell membranes. The purpose of the present study was to evaluate whether routine quantitative plasma protein analysis might aid in the detection of inflammatory processes in patients with severe renal insufficiency. We therefore studied the influence of renal insufficiency on the erythrocyte sedimentation rate (ESR) and on the homeostasis of a large number of plasma proteins, including acute phase proteins and immunoglobulins. PATIENTS The material consisted of 29 patients with severe renal failure on intermittent hernodialysis (1 3 females and 16 males). Their age ranged from 16 to 80 years. Etiology of the renal insufficiency was chronic glomerulonephritis in 14, chronic pwlnnephritis in 5, polycystic disease or other herediiaiq renal disease in 6, nephrosclerosis in 2, and collagenosis or systemic arteritis in 2. The underlying renal diseases were generally considered inactive. No immunosuppressive treatment was given with one exception, a man with long-standing polyarteritis nodosa, who was treated with low doses of steroids and azathioprin. There was no knowledge of recent infectious complications among the patients. In addition, three hemodialysis patients were studied during an episode of septichemia (two with Staphylococcus aureus, one with Enterococcus). Hemodialysis was performed two to three times a week using conventional cellulose membranes (Cuprophana or cellulose acetate) and acetate containing dialysate. The patients had been on hemodialysis for approximately 3 112 years (range 2 months-14 years). The patient who had been on hemodialysis for 14 years had clinical signs suggesting deposition of beta,-microglobulin derived amyloid. Blood samples were drawn in the morning after a light breakfast before the start of dialysis. The serumScand J Urol Nrphrol26
280
S. C. Lindgren et al.
Table I. Plasma concentrations o f 2 5 proteins in patients with stable renal insufficiency and in healthy controls. The concentrations of some proteins are given in % of pooled normal plasma Molecular weight (kD)
Scand J Urol Nephrol Downloaded from informahealthcare.com by Chulalongkorn University on 01/01/15 For personal use only.
11.9 13.3 14.5 21.0 31.0 41.0 45.0 49.0 50.8 54.0 55.0 55.7 52.0 57.0 65.0 69.0 100 100 130 150 160 185 250 340 900 a
Protein &Microglobulin (mg/l) Cystatin C (mg/l) Lysozyme (mg/l) Retinol binding protein (mg/l) Protein HC (%) Zink az-Microprotein (Yo) Orosomucoid (g/l) &Glycoprotein I (Yo) G C globulin ( O h ) Thyroxine binding gl (mg/l) Transthyretin (g/l) Transcortin (O/O) a,-Antit rypsi n (g/l) Hemopexin (O/o) Albumin (g/l) a,-antichymotrypsin (%) SHBG" (mg/l) Haptoglobin (g/l) Ceruloplasmin (g/l) IgG (g/U IgA W ) Complement C3 (%) Complement C4 (O/O) Fibrinogen (g/l) IgM (g/U
Renal insufficiency mean (SD) 51.2 (2.0) 9.10 (2.1) 7.15 (2.2) 270 (90) 989 (310) 217 (3.2) 1.48 (0.44) 207 (59) 83.0 (8) 13.9 (2.4) 0.341 (0.072) 76.0 (1 3) 1.53 (0.23) 92.0 (1 9) 41.5 (3.0) 101 (17) 1.66 (1.2) 1.85 (0.54) 0.330 (0.036) 1 1.2 (3.4) 1.42 (0.55) 92.0 ( I 2) 144 (56) 4.71 (1.1) 1.03 (0.49)
Controls 1.39 1.06 0.35 79.5 1 I4
103 0.89 151
Significance of difference from normal mean p < 0.001 p < 0.00 I
p
