- Email: [email protected]
The incidence of side effects associated with high dose ferric gluconate (ferrlecit™) in patients with severe chronic renal failure (CRF)
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TENTH ANNUAL CLINICAL NEPHROLOGY MEETING ABSTRACTS
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5 THE IMPACT OF COMORB1DITY ON VASCULAR ACCESS RELATED EVENTS 1N INCIDENT HEMODIALYSIS PATIENTS. Nabeel Aslam, Renee Burr, Kelly DeVoogd, MicheUe Shields, and Frank Bmns. Renal & Electrolyte Division, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA The impact of comorbidity at the start of hemodialysis (HI)) on the choice of initial vascular access and subseque m vascular events is unknown. In this study, all incident HD patients between 1/1/99 to 12/31/00 were evaluated at the start of HD for demographics and comorbidity using the Charlson Comorbidity Index (CC1). Data was retrieved from the UPMC hemodialysis registry. Patients were divided into groups; Low CCI:=< 6 (n=30), High CCI:=>7 (n=29). Data was collected on the type of first vascular access and subsequent vascular access events. Both groups were similar regarding gender (males 60% vs 52% p~as), race (white 37% vs 52% p-~as)and time on HD (mean 8.6 vs 8.9 months p-~as)~Patients with High CCI were significantly older than Low CCI (71 vs 51 yr. p<0.000l). Vascular access events are listed below. Low CCI High CCI Catheter as first access 18(60%) 21 (72%) p--us No. of accesses/pt yr 2.9 2.4 p---as Access thrombosis/pt yr 1.02 1.63 p=0.006 Access infection/pt yr 0.8 0.7 p=as In conclusion, patients with higher comorbidity scores are at significantly greater risk of vascular access thrombosis when compared to patients with lower comorbidity scores. This may be due to the more frequent use of catheters in sicker patients although there was no statistical difference in catheter use between groups. Further studies exploring specific factors leading to higher risk of access thrombosis are underway.
AMPHIBIAN PROXIMAL TUBULE CELLS CONTAIN CFTR CI- CHANNELS IN THE BASOLATERAL MEMBRANE. Srisaila Basavappa and Emile L. Boulpaep. Yale University School of Medicine, Dept. of Cellular & Molecular Physiology, New Haven, CT. A basolateraI membrane (BLM) cAMP-activated C1- conductance has been reported in proximal tubule cells from the salamander Ambystoma tigrinium. Whether this Cf channel is related to the CFTR CF channel was examined on single polarized ceils. With symmetrical NMDG-C1 containing solutions, 10gM forskolin significantly increased whnle-cell CI- conductance. NPPB (50gM) or 0.SmM glibennlamide inhibited the whole-cell currents, while 0.5mM DIDS had insignificant effects. Replacement of extracelhdar CI- with equimolar BF or I- resulted in anion selectivity sequence of F > Br- > CI'. tn cell-attached patch-clmnp studies on the BLM with symmetrical NMDG-C1 containing solutions, 101.tM forskolin significantly increased CI channel activity at all tested voltages between -100mV and +100mV. The I-V relationship was linear with a single-channel conductance of -9 pS. In inside-out BLM patches excised from untreated cells into a bath containing 0.25mM ATP, channel activity was rarely observed. The subsequent addition of lmM ATP-~,-S did not activate CI- currents. However, further addition of 75nM PKA in the continued presence of ImM ATP-y-S and 75 nM PKA markedly stimulated CI" channel activity. The subsequent removal of ATPq,-S and PKA decreased channel activity. A second addition of ATP-7-S in the absence of PKA restored CI- channel activity, lmmunofluorescence studies with c~-1468 indicate that CFTR is localized to the BLM in single proximal tubule cells. These results suggest that the BLM of Ambystoma proximal tubule cells contain CFTR C1- channels with biophysical and regulatory properties similar to those of secretory CFTR CI" channels.
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6 PAMIDRONATE (PAM) THERAPY FOR BONE LOSS (BL) AFTER HEART (HTX) OR KIDNEY TRANSPLANTATION (KTX). Avanelle Jack Jill Lindberg, Katherine R. Tnttle, Lynn R. Dahlstrom, Truman E. Cantrell, Robert A. Short, Donald Sherrard, John B. Copley, Catherine Staffeld. Ochsner Clinic, New Orleans, LA and The Heart Institute of Spokane, Spokane WA, and the University of Washington School of Medicine, Seattle, WA. After solid organ tx, bl is common previously, pare has been shown to reduce bl in recipients (rec) of KTX and HTX. We conducted an open labeled, 24 month (too) trial designed to evaluate the effects of Para on preventing bl in KTX and HTX rec. Dual energy X-ray absorptiometry (DEXA) is obtained at baseline (bal), 6, 12, and 24 mo post TX. Pam, 60 m~ intravenously, is given within 2 weeks post tx and at 6,12, 18, and 24 mos. This is a report of bal characteristics and early follow-up (flu). Total hip DEXA T-scores for HTX and KTX rec did not decrease from_baseline after 6-12 mo f/u (see Table 1). Table 1. Bal and follow-up T scores b~ type oftx Total hip Bal Follow-up (6-12 too) Heart -0.58_+ 0.97 -0.39 + 0.70 N 15 9 Kidney -0.84 + 1.13 -0.78 + 0.96 N 43 20 P 0.423 0.281 Bal T-scores for the total hip were lower in female KTX rec (u=14) versus male rec (n=29), -1.56±0.44 and [email protected], p<0.001. Among female KTX rec who had 6-12 mo f/u studies (n=8), an increase in DEXA T- scores were observed (obs), -1.62-~034 and -1.48±52, p=0.06. Our data suggest that R X with pare prevents the early bl after TX. In female KTX rec, the group with the lowest D E X A , a trend toward an actual inc was obs.
THE INCIDENCE OF SIDE EFPECTS ASSOCIATED WITH HIGH DOSE FERRIC GLUCONATE (FERRLECIT TM)IN PATIENTS WITH SEVERE CHRONIC RENAL FAILURE (CRF). Bahar Bastani, Anll Jain, Gopal Pandurangan. Division of Nephrology, Saint Louis University School of Medicine, St. Louis, Missouri, USA. Iron deficiency is the most frequent cause of poor response to erythropoietin (EPO) in patients with severe CRF. Parenteral iron dextran, which can be administer at high doses of 500 to 1000 mg per treatment, has been associated with up to 26% incidence of side effects, 3% being more serious and 0.6% life-threatening anaphylaxis, Ferric gluconate complex in sucrose (Ferrlecit) has been associated with far less side effects and no fatalities, however, the recommended dose has been 62.5 to 125 mg per treatment, which is only suitable for hemodialysis patients. We retrospectively analyzed the incidence and the side effects associated with high dose Ferrlecit infusion (20 treatments in 13 patients; 10 treatments of 250 mg/3-4 hrs, and I0 treatments of 500 rag/5 hrs infusion). The patients were 38.5% male, 77% African-American, with age range of 32 to 75 years (mean -- SD, 57.6 ± 15 years), 7 with CRY, and 6 on dialysis treatment. One of the 10 (10%) tceatments of 250 mg (severe nansea/vomiting, diarrhea, and burning sensation in feet), and 3 of the 10 (30%) treatments of 500 mg (chills, severe nausea, vomiting, hypotension, syncope in 1; severe nausea, vomiting, diarrhea, and hypoteusion in 1; and one episode of vomiting in 1 patient) were complicated with side effects. Treatment with 250 mg dose resulted in no significant change in serum iron, Hgb, Hct, ferritin, or percent transferrin saturation levels pre- vs. 1-2 months post-infusion. However, the treatments with the 500 mg dose resulted in significant increase in Hgb (9 ± 1A vs. l 1 ± 2, p = 0.03), and Hct (28± 5 vs. 32 :~ 6, p = 0.03), but only a trend (statistically not significant) rise in serum iron (26 ± 10 vs. 38 ± 12.5, p = 0.08), transferrin saturation ( 12 ÷ 7 vs. 18 ± 5, p = 0.06), or ferrifin ( 151 ± 15l vs. 217 • 180, p = 0.06), pre- vs. 1-2 months post-infusion, respectively. Conclusion: While Ferrlecit infusion at the recommended dose ( 62.5 or 125 rag) is only rarely associated with any side effects, higher doses of 250 or 500 mg are complicated with significant untoward reactions in 10-30%. Only a single dose of 500 mg Felrlecit was associated with a significant rise in Hgb and Hct levels.
TENTH ANNUAL CLINICAL NEPHROLOGY MEETING ABSTRACTS
7
5 THE IMPACT OF COMORB1DITY ON VASCULAR ACCESS RELATED EVENTS 1N INCIDENT HEMODIALYSIS PATIENTS. Nabeel Aslam, Renee Burr, Kelly DeVoogd, MicheUe Shields, and Frank Bmns. Renal & Electrolyte Division, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA The impact of comorbidity at the start of hemodialysis (HI)) on the choice of initial vascular access and subseque m vascular events is unknown. In this study, all incident HD patients between 1/1/99 to 12/31/00 were evaluated at the start of HD for demographics and comorbidity using the Charlson Comorbidity Index (CC1). Data was retrieved from the UPMC hemodialysis registry. Patients were divided into groups; Low CCI:=< 6 (n=30), High CCI:=>7 (n=29). Data was collected on the type of first vascular access and subsequent vascular access events. Both groups were similar regarding gender (males 60% vs 52% p~as), race (white 37% vs 52% p-~as)and time on HD (mean 8.6 vs 8.9 months p-~as)~Patients with High CCI were significantly older than Low CCI (71 vs 51 yr. p<0.000l). Vascular access events are listed below. Low CCI High CCI Catheter as first access 18(60%) 21 (72%) p--us No. of accesses/pt yr 2.9 2.4 p---as Access thrombosis/pt yr 1.02 1.63 p=0.006 Access infection/pt yr 0.8 0.7 p=as In conclusion, patients with higher comorbidity scores are at significantly greater risk of vascular access thrombosis when compared to patients with lower comorbidity scores. This may be due to the more frequent use of catheters in sicker patients although there was no statistical difference in catheter use between groups. Further studies exploring specific factors leading to higher risk of access thrombosis are underway.
AMPHIBIAN PROXIMAL TUBULE CELLS CONTAIN CFTR CI- CHANNELS IN THE BASOLATERAL MEMBRANE. Srisaila Basavappa and Emile L. Boulpaep. Yale University School of Medicine, Dept. of Cellular & Molecular Physiology, New Haven, CT. A basolateraI membrane (BLM) cAMP-activated C1- conductance has been reported in proximal tubule cells from the salamander Ambystoma tigrinium. Whether this Cf channel is related to the CFTR CF channel was examined on single polarized ceils. With symmetrical NMDG-C1 containing solutions, 10gM forskolin significantly increased whnle-cell CI- conductance. NPPB (50gM) or 0.SmM glibennlamide inhibited the whole-cell currents, while 0.5mM DIDS had insignificant effects. Replacement of extracelhdar CI- with equimolar BF or I- resulted in anion selectivity sequence of F > Br- > CI'. tn cell-attached patch-clmnp studies on the BLM with symmetrical NMDG-C1 containing solutions, 101.tM forskolin significantly increased CI channel activity at all tested voltages between -100mV and +100mV. The I-V relationship was linear with a single-channel conductance of -9 pS. In inside-out BLM patches excised from untreated cells into a bath containing 0.25mM ATP, channel activity was rarely observed. The subsequent addition of lmM ATP-~,-S did not activate CI- currents. However, further addition of 75nM PKA in the continued presence of ImM ATP-y-S and 75 nM PKA markedly stimulated CI" channel activity. The subsequent removal of ATPq,-S and PKA decreased channel activity. A second addition of ATP-7-S in the absence of PKA restored CI- channel activity, lmmunofluorescence studies with c~-1468 indicate that CFTR is localized to the BLM in single proximal tubule cells. These results suggest that the BLM of Ambystoma proximal tubule cells contain CFTR C1- channels with biophysical and regulatory properties similar to those of secretory CFTR CI" channels.
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6 PAMIDRONATE (PAM) THERAPY FOR BONE LOSS (BL) AFTER HEART (HTX) OR KIDNEY TRANSPLANTATION (KTX). Avanelle Jack Jill Lindberg, Katherine R. Tnttle, Lynn R. Dahlstrom, Truman E. Cantrell, Robert A. Short, Donald Sherrard, John B. Copley, Catherine Staffeld. Ochsner Clinic, New Orleans, LA and The Heart Institute of Spokane, Spokane WA, and the University of Washington School of Medicine, Seattle, WA. After solid organ tx, bl is common previously, pare has been shown to reduce bl in recipients (rec) of KTX and HTX. We conducted an open labeled, 24 month (too) trial designed to evaluate the effects of Para on preventing bl in KTX and HTX rec. Dual energy X-ray absorptiometry (DEXA) is obtained at baseline (bal), 6, 12, and 24 mo post TX. Pam, 60 m~ intravenously, is given within 2 weeks post tx and at 6,12, 18, and 24 mos. This is a report of bal characteristics and early follow-up (flu). Total hip DEXA T-scores for HTX and KTX rec did not decrease from_baseline after 6-12 mo f/u (see Table 1). Table 1. Bal and follow-up T scores b~ type oftx Total hip Bal Follow-up (6-12 too) Heart -0.58_+ 0.97 -0.39 + 0.70 N 15 9 Kidney -0.84 + 1.13 -0.78 + 0.96 N 43 20 P 0.423 0.281 Bal T-scores for the total hip were lower in female KTX rec (u=14) versus male rec (n=29), -1.56±0.44 and [email protected], p<0.001. Among female KTX rec who had 6-12 mo f/u studies (n=8), an increase in DEXA T- scores were observed (obs), -1.62-~034 and -1.48±52, p=0.06. Our data suggest that R X with pare prevents the early bl after TX. In female KTX rec, the group with the lowest D E X A , a trend toward an actual inc was obs.
THE INCIDENCE OF SIDE EFPECTS ASSOCIATED WITH HIGH DOSE FERRIC GLUCONATE (FERRLECIT TM)IN PATIENTS WITH SEVERE CHRONIC RENAL FAILURE (CRF). Bahar Bastani, Anll Jain, Gopal Pandurangan. Division of Nephrology, Saint Louis University School of Medicine, St. Louis, Missouri, USA. Iron deficiency is the most frequent cause of poor response to erythropoietin (EPO) in patients with severe CRF. Parenteral iron dextran, which can be administer at high doses of 500 to 1000 mg per treatment, has been associated with up to 26% incidence of side effects, 3% being more serious and 0.6% life-threatening anaphylaxis, Ferric gluconate complex in sucrose (Ferrlecit) has been associated with far less side effects and no fatalities, however, the recommended dose has been 62.5 to 125 mg per treatment, which is only suitable for hemodialysis patients. We retrospectively analyzed the incidence and the side effects associated with high dose Ferrlecit infusion (20 treatments in 13 patients; 10 treatments of 250 mg/3-4 hrs, and I0 treatments of 500 rag/5 hrs infusion). The patients were 38.5% male, 77% African-American, with age range of 32 to 75 years (mean -- SD, 57.6 ± 15 years), 7 with CRY, and 6 on dialysis treatment. One of the 10 (10%) tceatments of 250 mg (severe nansea/vomiting, diarrhea, and burning sensation in feet), and 3 of the 10 (30%) treatments of 500 mg (chills, severe nausea, vomiting, hypotension, syncope in 1; severe nausea, vomiting, diarrhea, and hypoteusion in 1; and one episode of vomiting in 1 patient) were complicated with side effects. Treatment with 250 mg dose resulted in no significant change in serum iron, Hgb, Hct, ferritin, or percent transferrin saturation levels pre- vs. 1-2 months post-infusion. However, the treatments with the 500 mg dose resulted in significant increase in Hgb (9 ± 1A vs. l 1 ± 2, p = 0.03), and Hct (28± 5 vs. 32 :~ 6, p = 0.03), but only a trend (statistically not significant) rise in serum iron (26 ± 10 vs. 38 ± 12.5, p = 0.08), transferrin saturation ( 12 ÷ 7 vs. 18 ± 5, p = 0.06), or ferrifin ( 151 ± 15l vs. 217 • 180, p = 0.06), pre- vs. 1-2 months post-infusion, respectively. Conclusion: While Ferrlecit infusion at the recommended dose ( 62.5 or 125 rag) is only rarely associated with any side effects, higher doses of 250 or 500 mg are complicated with significant untoward reactions in 10-30%. Only a single dose of 500 mg Felrlecit was associated with a significant rise in Hgb and Hct levels.