- Email: [email protected]
Acute phase reactants in hemodialysis and renal transplantation
Acute Phase Reactants in Hemodialysis and Renal Transplantation H. Argani, S. Mozaffari, Y. Zadefatah, and M. Rahbani
A
CUTE PHASE REACTANTS (APRs) are increased after inflammation. In chronic renal failure and dialysis these markers are increased because of recurrent infections, contact with bioincompatible dialysis membranes, and malnutrition.1,2 In all of the conditions, inflammatory mediators, such as cytokines, would cause secretion of C-reactive protein (CRP), complements, haptoglobulin, ceruloplasmin, and ferritin from hepatocytes.3 However, negative APRs, including albumin and transferrin, would be decreased with response to inflammation. After renal transplantation (RTx), APR levels would be within normal range because of elimination of the inflammatory factors and because of administration of immunosuppressive drugs. However, infections and dysfunctional allograft kidneys may cause persistently high levels of APR. In this regard, we measured APRs in patients with stable chronic dialysis before and after renal transplantation. PATIENTS AND METHOD This study was performed prospectively in 36 chronic hemodialysis patients before (B) and after (A) RTx. Their results were compared with the control group, 36 patients with chronic renal failure who had not received dialysis (C). CRP, alpha 1 antitrypsin, serum ferritin, serum ceruloplasmin, and Cu as positive markers for inflammation and albumin and APO-A1 as negative markers for inflammation were measured in these three situations. Their levels were evaluated prior to transplantation in relationship to their age, longevity of dialysis, uremic complications, and membrane bioincompatible hemodialysis. Also, effect of allograft dysfunction and presence or absence of Hbs Ag and HCV Ab was evaluated on the level of APRs, 1 month after RTx. Etiology of renal failure was due to chronic glomerulonephritis (26%), hypertension (13%), obstruction (8%), polycystic kidney diseases (11%), and unknown etiology (41%). Infection, in any site, and synthetic graft accesses were exclusion criteria. Results were analyzed by paired t, McNemar, and Mann-Whitney tests. P ⬍ .05 was significant.
RESULTS
The mean age was 33.7 ⫾ 7 years and longevity of dialysis was 24 ⫾ 10 months. Male to female ratio was 20:16. Positive HbsAg and hepatitis C virus antibody were present in 3 and 6 patients, respectively. Although CRP in B and C groups were not different significantly, it was higher in A group, ie, 4 mg/L and 3.8 mg/L vs 11 mg/L (P ⫽ .039). Ceruloplasmin in B and C groups (17.9 mg/dL vs 21.2; P ⫽ .009) and Cu (61.6 mic/dL vs 72 mic/dL; P ⫽ .01) in B and C groups were significantly higher than A group (P ⫽ .001). 0041-1345/02/$–see front matter PII S0041-1345(02)03161-5 2420
Serum ferritin in B group (339 mic/mL) was higher than A (232 mic/mL) and C (97 mic/mL) groups. Alpha 1 antitrypsin in B group (154 mg/dL; P ⫽ .02) was significantly lower than A (199 mg/dL) and C groups (189 mg/dL). However, APO-A1, as a negative APR, was lower in A (119 mg/dL; P ⫽ .001) as compared to B (131 mg/dL) and C (130 mg/dL) groups. Albumin, another negative APR, was not different among the three groups. Presence of HCV Ab and HbsAg had no influence on the APRs level. Except serum ferritin, other APRs did not have any correlation with the degree of allograft dysfunction.
DISCUSSION
Occurrence of inflammation is more common in patients with chronic dialysis. This high inflammatory response is due to chronic infections, malnutrition, bioincompatible membrane during dialysis, and uremic toxins.4 As has been reported, inflammation can cause early morbidity and mortality in these patients.5 After RTx many of the injuries are healed and quality of life is improved. As we showed, APRs, such as serum ferritin, cerruloplasmin, and Cu, significantly decreased after RTx. However, CRP and alpha 1 antitrypsin after RTx were higher than before. This is due to their high sensitivity to tissue damage after surgery.6 Also, albumin, a negative APR, reproduces slowly, thus its level would be increased only after several months. It is clear that in the first month after RTx the level of albumin would be the same as before RTx. Another negative APR, APO-A1 is a protective factor for atherosclerosis.7 Its level increases shortly after RTx. Although hepatitis B and HCV can induce inflammation and APRs, our patients did not have higher levels of APRs, possibly because they did not have active hepatitis. Among the APRs, in the dysfunctional renal allograft group, only serum ferritin increased more than during the pretransplantation period because of erythropoiesis. Consequently ferritin consumption would be sluggish in the group. From the Department of Dialysis and Transplantation, Emam Hospital, Tabriz, Iran. Address reprint requests to Hassan Argani, Department of Dialysis and Transplantation, Emam Hospital, University of Medical Sciences of Tabriz, Tabriz, Iran. E-mail: hassanargani@ hotmail.com © 2002 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 34, 2420 –2421 (2002)
ACUTE PHASE REACTANTS
We conclude that levels of APRs in patients undergoing hemodialysis are increased. Levels of APRs would be within normal range after renal transplantation according to the allograft function. REFERENCES 1. Kimmel PL, Phillips TM, Simmens SJ, et al: Kidney Int 54:236, 1998
2421 2. Bergstrom J, Lindholm B, Lacson E Jr, et al: Semin Dial 13:163, 2000 3. Bologa RM, Levine DM, Parker TS, et al: Am J Kidney Dis 32:107, 1998 4. Kopple JD, Berg R, Houser H, et al: Kidney Int 36:S184, 1989 5. Lowrie EG, Lew NL: Am J Kidney Dis 15:458, 1990 6. Owen WF, Lowrie EG: Kidney Int 54:627, 1998 7. Stevenson T: Semin Dial 2:119, 1998
A
CUTE PHASE REACTANTS (APRs) are increased after inflammation. In chronic renal failure and dialysis these markers are increased because of recurrent infections, contact with bioincompatible dialysis membranes, and malnutrition.1,2 In all of the conditions, inflammatory mediators, such as cytokines, would cause secretion of C-reactive protein (CRP), complements, haptoglobulin, ceruloplasmin, and ferritin from hepatocytes.3 However, negative APRs, including albumin and transferrin, would be decreased with response to inflammation. After renal transplantation (RTx), APR levels would be within normal range because of elimination of the inflammatory factors and because of administration of immunosuppressive drugs. However, infections and dysfunctional allograft kidneys may cause persistently high levels of APR. In this regard, we measured APRs in patients with stable chronic dialysis before and after renal transplantation. PATIENTS AND METHOD This study was performed prospectively in 36 chronic hemodialysis patients before (B) and after (A) RTx. Their results were compared with the control group, 36 patients with chronic renal failure who had not received dialysis (C). CRP, alpha 1 antitrypsin, serum ferritin, serum ceruloplasmin, and Cu as positive markers for inflammation and albumin and APO-A1 as negative markers for inflammation were measured in these three situations. Their levels were evaluated prior to transplantation in relationship to their age, longevity of dialysis, uremic complications, and membrane bioincompatible hemodialysis. Also, effect of allograft dysfunction and presence or absence of Hbs Ag and HCV Ab was evaluated on the level of APRs, 1 month after RTx. Etiology of renal failure was due to chronic glomerulonephritis (26%), hypertension (13%), obstruction (8%), polycystic kidney diseases (11%), and unknown etiology (41%). Infection, in any site, and synthetic graft accesses were exclusion criteria. Results were analyzed by paired t, McNemar, and Mann-Whitney tests. P ⬍ .05 was significant.
RESULTS
The mean age was 33.7 ⫾ 7 years and longevity of dialysis was 24 ⫾ 10 months. Male to female ratio was 20:16. Positive HbsAg and hepatitis C virus antibody were present in 3 and 6 patients, respectively. Although CRP in B and C groups were not different significantly, it was higher in A group, ie, 4 mg/L and 3.8 mg/L vs 11 mg/L (P ⫽ .039). Ceruloplasmin in B and C groups (17.9 mg/dL vs 21.2; P ⫽ .009) and Cu (61.6 mic/dL vs 72 mic/dL; P ⫽ .01) in B and C groups were significantly higher than A group (P ⫽ .001). 0041-1345/02/$–see front matter PII S0041-1345(02)03161-5 2420
Serum ferritin in B group (339 mic/mL) was higher than A (232 mic/mL) and C (97 mic/mL) groups. Alpha 1 antitrypsin in B group (154 mg/dL; P ⫽ .02) was significantly lower than A (199 mg/dL) and C groups (189 mg/dL). However, APO-A1, as a negative APR, was lower in A (119 mg/dL; P ⫽ .001) as compared to B (131 mg/dL) and C (130 mg/dL) groups. Albumin, another negative APR, was not different among the three groups. Presence of HCV Ab and HbsAg had no influence on the APRs level. Except serum ferritin, other APRs did not have any correlation with the degree of allograft dysfunction.
DISCUSSION
Occurrence of inflammation is more common in patients with chronic dialysis. This high inflammatory response is due to chronic infections, malnutrition, bioincompatible membrane during dialysis, and uremic toxins.4 As has been reported, inflammation can cause early morbidity and mortality in these patients.5 After RTx many of the injuries are healed and quality of life is improved. As we showed, APRs, such as serum ferritin, cerruloplasmin, and Cu, significantly decreased after RTx. However, CRP and alpha 1 antitrypsin after RTx were higher than before. This is due to their high sensitivity to tissue damage after surgery.6 Also, albumin, a negative APR, reproduces slowly, thus its level would be increased only after several months. It is clear that in the first month after RTx the level of albumin would be the same as before RTx. Another negative APR, APO-A1 is a protective factor for atherosclerosis.7 Its level increases shortly after RTx. Although hepatitis B and HCV can induce inflammation and APRs, our patients did not have higher levels of APRs, possibly because they did not have active hepatitis. Among the APRs, in the dysfunctional renal allograft group, only serum ferritin increased more than during the pretransplantation period because of erythropoiesis. Consequently ferritin consumption would be sluggish in the group. From the Department of Dialysis and Transplantation, Emam Hospital, Tabriz, Iran. Address reprint requests to Hassan Argani, Department of Dialysis and Transplantation, Emam Hospital, University of Medical Sciences of Tabriz, Tabriz, Iran. E-mail: hassanargani@ hotmail.com © 2002 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010 Transplantation Proceedings, 34, 2420 –2421 (2002)
ACUTE PHASE REACTANTS
We conclude that levels of APRs in patients undergoing hemodialysis are increased. Levels of APRs would be within normal range after renal transplantation according to the allograft function. REFERENCES 1. Kimmel PL, Phillips TM, Simmens SJ, et al: Kidney Int 54:236, 1998
2421 2. Bergstrom J, Lindholm B, Lacson E Jr, et al: Semin Dial 13:163, 2000 3. Bologa RM, Levine DM, Parker TS, et al: Am J Kidney Dis 32:107, 1998 4. Kopple JD, Berg R, Houser H, et al: Kidney Int 36:S184, 1989 5. Lowrie EG, Lew NL: Am J Kidney Dis 15:458, 1990 6. Owen WF, Lowrie EG: Kidney Int 54:627, 1998 7. Stevenson T: Semin Dial 2:119, 1998