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Preliminary results of the prevalence of anemia in patients with early renal insufficiency study
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TENTH ANNUAL CLINICAL NEPHROLOGY MEETING ABSTRACTS
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55
LONG TERM CYCLOSPORINE KINETIKS AND ITS INFLUENCE ON LIPID STATUS IN RENAL TRANSPLANT RECIPIENTS. F. K. Matzkies, W. Keuthage, U. Gerhardt, B. Suwelack, and H. Hohage. University of Muenster, Medical Department, Mnenster, Germany We retrospectively investigated the influence of cyclosporine A treatment on cholesterol levels in 261 patients with stable renal function over a time period of 60 months. Patients were eligible if fasting serum-chnlesterul values and baseline CYA levels were available at 1, 3, 9, 12, 24, 36, 48, 60 months after transplantation. Correlation and regression analysis was perfomed on creatinine (SCr), total cholesterol, total CYA dosage (CYA d), CYA baseline values (CYA b) relation of CYA dosage and bodyweight (CYA d/w) and relation of CYA dosage to CYA baseline values (CYA d/b). Mean age was 42--12 years, mean body weight showed an increase from 64± 11 kg after transplantation to 69± 12 kg after nine months remaining stable at 60 months. CYA d was 323:~105 mg at first month with a linear reduction over time to 247±87 mg at 60 mouth (23%). CYA b showed a comparable reduction from 290~252 to 121,~63 ng/ml, respectively. CYA d/w reduced from 5,1±1.6 to 3.5±1.3 mg/kg/d over the time period of 60 months. The correlation of CYA d/b showed a slight increase from baseline 52±39 to 61±48 (9 months) and a continous decrease to 35±25 g/1. SCr was 2.0±2.5 mg/dl at baseline and fell to 1.7±1.5 mg/dl at three month with a contiuons increase to 2,0:~1.4 mg/dl after 60 months. Cholesterol values were 254±50 mg/dl at baseline with a slight linear increase over the time to 276±59 rag/d1 at 60 months. There was no significant correlation between CYA d, CYA h, CYA d/b, CYA d/w and cholesterol. Stratification of patients according to age, sex, time from transplantation and cholesterol value did not identify subgroups of patients with correlation to CYA values. Multiple regression analysis showed no correlation between cholesterol values and creatinine or CYA values. According to these findings We conclude: The influence of CYA on cholesterol levels is not dose dependent. Even so CYA b values were reduced by half over the entire time period, a slight increase in cholesterol values occurred. Therefore, mechanisms independent from CYA may contribute to cholesterol values.
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Anti-GBM disease in XenoMouse II is induced by human MAb versus a3(IV)NCI collagen. KEC Meyers1'2, J Allenl, J Gehret1, M Gall03, H Hopfer4, R Kalluri4, and MP MadaioI. UPENN l, CHOP2; ABGENIX s and Boston, HARVARD4. We have established a unique anti-GBM disease model in XenoMouse 11 animals that produce human IgG~ (3'2~) by immunization with ~3(IV)NCI GBM collagen preparations. All mice developed human anti-GBM Ab (ELISA) and proteinuria (2.5 - 10.7 x control). LM showed proliferative GN with crescents. By direct IF all mice had linear IgG deposits along the murine GBM and TBM with weaker staining for C3. Fully human Ig72K anti-c~3(IV) MAb were isolated, and some produce nephritis, after transfer to Xenomouse IL In particul~, MAbFhl, derived frum an animal immunized with bovine NCI collagen bound to bovine dimers, 293 fetal kidney cell, and to E. coli expressed r h a3(IV)NCI by ELISA and Western blotting. By indirect IF, MAbFI,1 produced linear GBM staining of normal human glomertdi as for serum Ab ti:om diseased patients. VII 3'4 and VL ~¢3 gene families encode MAbFhh Comparison to other MAb is ongoing. Normal SJL m i c e given MAbFI.I develop linear BM deposits of human IgG associated with mild GN and proteinuria (1.98 mg Upr/24h vs, 0.72mg/24h, control) that is accentuated by administration of CFA prior to MAbFI.I. (>Proliferation., 4.5 mg Upr/24h). Administration of MAbFhl to XMII results in linear IgG deposits, crescentic GN and heavy proteinorla (I0.6 mg, Upr/24 hrs). The results indicate that anti-GBM disease can be initiated in susceptible strains by human anti-a3(IV)NC1 antibody with an single specificity for ot3(IV)NC1. This model is being developed to test therapeutic strategies targeted at human anti-cG(IV)NCl autoAb and the B cells that produce them.
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PRELIMINARY RESULTS OF THE PREVALENCE OF ANEMIA IN PATIENTS WITH EARLY RENAL INSUFFICIENCY STUDY. William McClellan ~. ~Rollins School of Public Health, Emory University, Atlanta, GA. The prevalence of anemia among patients (pts) with early renal insufficiency (ERI) has not been well defined. Correction of anemia in ERI can improve quality of life, cognitive function, exercise capacity, and regression ofventricular hypertrophy. The objectives of this study are to determine the prevalence of anemia (Hb 18 years of age with serum creatinine (SCr) 1.5-6.0 mg/dL for women and 2.06.0 mg/dL for men. Patients who received dialysis within 2 months or recombinant human erythropoietin (r-HuEPO, epoetin alfa) or iron supplements within 3 months are ineligible. This preliminary analysis includes 1713 pts. Mean age was 68.7 y and 43% were men. Diabetes (52%) and hypertension (30%) were the most common reported causes for ERI. Serum creatinine was _>2.0mg/dL in 56% ofpts and ->3.0 mg/dL in 15% of pts (mean SCr=2.23+_0.88 mg/dL). Mean hemoglobin (Hb) was 12.0+_1.5g/dL. Hemoglobin distribution is shown in the table*. F o r t y - s e v e n ~ f p t s hadHb<12 g/dL. Hb
Hb
Hb
~ g / d ~ ~ (g/dL) n (%) (g/dL) n (%) _ ->7-<8 2(0.1) ->11-<12 406(23.7) ->15-<16 51(3.0) ->8-<9 24 (1.4) _>12-<13 404 (23.6) >-16-<17 20(1.2) ->9-<10 108 (6.3) _>13-<14 281 (16.4) ->17-<18 6 (0.4) ->10-<11 258(15.1) _>14-<15 147(8,6) _>18 4(0.2) ~ ; data missing for 2 pts. Preliminary results from the first large-scale study of this type suggest a high prevalence of anemia in the ERr population. Final data should provide a basis for early identification of specific ERI subgroups at increased risk of anemia and enhance its management in these pts.
END-STAGE LUPUS NEPHRITIS (ES-LN), RISK FACTORS FOR CORONARY HEART DISEASE (CHD) AND ECHOCARDIOGRAPHYC STUDY M. Milovaneeva-Popovska, L.Grcevska, V.Ristovska, M.Polenakovic Dept. of Nephrulogy, Medical Faculty, Univ. "Sts.Cyril and Methodius", Skopje, R.Macedonia. Cardiac complications of Systemic Lupus Erithematosus (SLE) are numeruus and can involve all components of the heart including the pericardium, myocardium, valves, conduction system and coronary vessels. The purpose of this study was to estimate the frequency of and examine risk factors for CHD and to assess the incidence and spectrum of cardiac abnormalities in patients (pts) with SLE and ES-LN. We studied 35 pts, 30 female and 5 males, aged 24.14+-16.01 years. All of them met ARA revised criteria for SLE. A two-dimensional and Doppler echocurdiographic studies were performed on 19 pts. Almost all our pts had one or more risk factors for CHD: hypertension (85.7% had HTA or received treatment for HTA), abnormal lipid profile (72%), prednisolon use (34 pts) and positive family history of CHD (57.14%). Only one patient had diabetes. Valvular abnormalities were found in 11/19pts. Mitxal valve abnormalities were the most common finding, in all 11 pts. Chronic pericardial involvement was observed in 7/19 pts, Acute pericardial effusion was identified in 5/19 pts. 6/19 pts had increased dimension of left atrium or interventricular septum. Only 2/! 9 pts present reduction of ejection fraction. Coronary prevention measures should be routinely implemented in care for these pts. Further investigations are needed to find correlation between uremic heart, action of hypertension and cardiac involvement in SLE patients.
TENTH ANNUAL CLINICAL NEPHROLOGY MEETING ABSTRACTS
53
55
LONG TERM CYCLOSPORINE KINETIKS AND ITS INFLUENCE ON LIPID STATUS IN RENAL TRANSPLANT RECIPIENTS. F. K. Matzkies, W. Keuthage, U. Gerhardt, B. Suwelack, and H. Hohage. University of Muenster, Medical Department, Mnenster, Germany We retrospectively investigated the influence of cyclosporine A treatment on cholesterol levels in 261 patients with stable renal function over a time period of 60 months. Patients were eligible if fasting serum-chnlesterul values and baseline CYA levels were available at 1, 3, 9, 12, 24, 36, 48, 60 months after transplantation. Correlation and regression analysis was perfomed on creatinine (SCr), total cholesterol, total CYA dosage (CYA d), CYA baseline values (CYA b) relation of CYA dosage and bodyweight (CYA d/w) and relation of CYA dosage to CYA baseline values (CYA d/b). Mean age was 42--12 years, mean body weight showed an increase from 64± 11 kg after transplantation to 69± 12 kg after nine months remaining stable at 60 months. CYA d was 323:~105 mg at first month with a linear reduction over time to 247±87 mg at 60 mouth (23%). CYA b showed a comparable reduction from 290~252 to 121,~63 ng/ml, respectively. CYA d/w reduced from 5,1±1.6 to 3.5±1.3 mg/kg/d over the time period of 60 months. The correlation of CYA d/b showed a slight increase from baseline 52±39 to 61±48 (9 months) and a continous decrease to 35±25 g/1. SCr was 2.0±2.5 mg/dl at baseline and fell to 1.7±1.5 mg/dl at three month with a contiuons increase to 2,0:~1.4 mg/dl after 60 months. Cholesterol values were 254±50 mg/dl at baseline with a slight linear increase over the time to 276±59 rag/d1 at 60 months. There was no significant correlation between CYA d, CYA h, CYA d/b, CYA d/w and cholesterol. Stratification of patients according to age, sex, time from transplantation and cholesterol value did not identify subgroups of patients with correlation to CYA values. Multiple regression analysis showed no correlation between cholesterol values and creatinine or CYA values. According to these findings We conclude: The influence of CYA on cholesterol levels is not dose dependent. Even so CYA b values were reduced by half over the entire time period, a slight increase in cholesterol values occurred. Therefore, mechanisms independent from CYA may contribute to cholesterol values.
54
Anti-GBM disease in XenoMouse II is induced by human MAb versus a3(IV)NCI collagen. KEC Meyers1'2, J Allenl, J Gehret1, M Gall03, H Hopfer4, R Kalluri4, and MP MadaioI. UPENN l, CHOP2; ABGENIX s and Boston, HARVARD4. We have established a unique anti-GBM disease model in XenoMouse 11 animals that produce human IgG~ (3'2~) by immunization with ~3(IV)NCI GBM collagen preparations. All mice developed human anti-GBM Ab (ELISA) and proteinuria (2.5 - 10.7 x control). LM showed proliferative GN with crescents. By direct IF all mice had linear IgG deposits along the murine GBM and TBM with weaker staining for C3. Fully human Ig72K anti-c~3(IV) MAb were isolated, and some produce nephritis, after transfer to Xenomouse IL In particul~, MAbFhl, derived frum an animal immunized with bovine NCI collagen bound to bovine dimers, 293 fetal kidney cell, and to E. coli expressed r h a3(IV)NCI by ELISA and Western blotting. By indirect IF, MAbFI,1 produced linear GBM staining of normal human glomertdi as for serum Ab ti:om diseased patients. VII 3'4 and VL ~¢3 gene families encode MAbFhh Comparison to other MAb is ongoing. Normal SJL m i c e given MAbFI.I develop linear BM deposits of human IgG associated with mild GN and proteinuria (1.98 mg Upr/24h vs, 0.72mg/24h, control) that is accentuated by administration of CFA prior to MAbFI.I. (>Proliferation., 4.5 mg Upr/24h). Administration of MAbFhl to XMII results in linear IgG deposits, crescentic GN and heavy proteinorla (I0.6 mg, Upr/24 hrs). The results indicate that anti-GBM disease can be initiated in susceptible strains by human anti-a3(IV)NC1 antibody with an single specificity for ot3(IV)NC1. This model is being developed to test therapeutic strategies targeted at human anti-cG(IV)NCl autoAb and the B cells that produce them.
56
PRELIMINARY RESULTS OF THE PREVALENCE OF ANEMIA IN PATIENTS WITH EARLY RENAL INSUFFICIENCY STUDY. William McClellan ~. ~Rollins School of Public Health, Emory University, Atlanta, GA. The prevalence of anemia among patients (pts) with early renal insufficiency (ERI) has not been well defined. Correction of anemia in ERI can improve quality of life, cognitive function, exercise capacity, and regression ofventricular hypertrophy. The objectives of this study are to determine the prevalence of anemia (Hb
Hb
Hb
~ g / d ~ ~ (g/dL) n (%) (g/dL) n (%) _ ->7-<8 2(0.1) ->11-<12 406(23.7) ->15-<16 51(3.0) ->8-<9 24 (1.4) _>12-<13 404 (23.6) >-16-<17 20(1.2) ->9-<10 108 (6.3) _>13-<14 281 (16.4) ->17-<18 6 (0.4) ->10-<11 258(15.1) _>14-<15 147(8,6) _>18 4(0.2) ~ ; data missing for 2 pts. Preliminary results from the first large-scale study of this type suggest a high prevalence of anemia in the ERr population. Final data should provide a basis for early identification of specific ERI subgroups at increased risk of anemia and enhance its management in these pts.
END-STAGE LUPUS NEPHRITIS (ES-LN), RISK FACTORS FOR CORONARY HEART DISEASE (CHD) AND ECHOCARDIOGRAPHYC STUDY M. Milovaneeva-Popovska, L.Grcevska, V.Ristovska, M.Polenakovic Dept. of Nephrulogy, Medical Faculty, Univ. "Sts.Cyril and Methodius", Skopje, R.Macedonia. Cardiac complications of Systemic Lupus Erithematosus (SLE) are numeruus and can involve all components of the heart including the pericardium, myocardium, valves, conduction system and coronary vessels. The purpose of this study was to estimate the frequency of and examine risk factors for CHD and to assess the incidence and spectrum of cardiac abnormalities in patients (pts) with SLE and ES-LN. We studied 35 pts, 30 female and 5 males, aged 24.14+-16.01 years. All of them met ARA revised criteria for SLE. A two-dimensional and Doppler echocurdiographic studies were performed on 19 pts. Almost all our pts had one or more risk factors for CHD: hypertension (85.7% had HTA or received treatment for HTA), abnormal lipid profile (72%), prednisolon use (34 pts) and positive family history of CHD (57.14%). Only one patient had diabetes. Valvular abnormalities were found in 11/19pts. Mitxal valve abnormalities were the most common finding, in all 11 pts. Chronic pericardial involvement was observed in 7/19 pts, Acute pericardial effusion was identified in 5/19 pts. 6/19 pts had increased dimension of left atrium or interventricular septum. Only 2/! 9 pts present reduction of ejection fraction. Coronary prevention measures should be routinely implemented in care for these pts. Further investigations are needed to find correlation between uremic heart, action of hypertension and cardiac involvement in SLE patients.