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175: Calciphylaxis Induced by Paricalcitol
A66 173 INCIDENT MANAGEMENT OF HEMODIALYSIS PATIENTS: MANAGING THE FIRST 90 DAYS John Robertson1, Pooja Goel1, Grace Chen1, Ronald Levine1, Debbie Benner1, and Amy Burdan1 1 DaVita Inc., El Segundo, CA, USA IMPACT (Incident Management of Patients, Actions Centered on Treatment) is a program to reduce mortality and morbidity in new patients during the first 3 months of dialysis, when these patients are most vulnerable. IMPACT was designed to standardize the onboarding process of incident patients from their 0 to 90-day period. We report on an observational (non-randomized), un-blinded study of 606 incident patients evaluated over 12 months (Oct07 – Oct08) at 44 US DaVita facilities. The study focused on 4 key predictive indicators associated with lower mortality and morbidity – anemia, albumin, adequacy and access (4As). IMPACT consisted of (1) Structured New Patient Intake Process with a standardized admission order, referral fax, and an intake checklist; (2) 90- day Patient Education Program with an education manual and tracking checklist; (3) Tools for 90-Day Patient Management Pathway including QOL; and (4) Data Monitoring Reports. Data as of July, 2008 is reported. Patients in the IMPACT group were 60.6 ± 15.1 years old (mean±SD), 42.8% Caucasian, 61% male with 25% having a fistula. Results showed a reduction in 90-day mortality almost 2 percentage points lower (6.14% vs. 7.98%; p<0.10) among IMPACT versus nonIMPACT patients. Changes among the 4As showed higher albumin levels from 3.5 to 3.6 g/dL (note that some IMPACT patients were on protein supplementation during this period) and patients achieving fistula access during their first 90-days was 25% vs. 21.4%, IMPACT and nonIMPACT, respectively (p≤0.05). However, only 20.6% of IMPACT patients achieved Hct targets (33≤3xHb≤36) vs. 23.4% for controls (p<0.10); some IMPACT patients may still have >36-level Hcts. Mean calculated Kt/V was 1.54 for IMPACT patients vs. 1.58 for nonIMPACT patients (p≤0.05). IMPACT is a first step toward a comprehensive approach to reduce mortality of incident patients. We believe this focus may help us to better manage CKD as a continuum of care. Long-term mortality measures will help determine if this process really impacts patients in the intended way, resulting in longer lives and better outcomes.
174 ELECTRONIC MEDICAL RECORDS SYSTEM VALIDATION OF CLAIMS-BASED QUERIES FOR ACUTE RENAL FAILURE Marc B. Rosenman,1,2 Peter Wahl,3 Greg Daniel,3 J. Marc Overhage,1,2 Patricia McGuire,1 Dan Thompson,1 Keith Rodgers,3 Louise Short,3 Rhonda Bohn,3 William M. Tierney.1,2 1) Regenstrief Institute and 2) Indiana University School of Medicine (Indianapolis, IN, USA); 3) HealthCore (Wilmington, DE, USA) Purpose: To explore the value of different types of data, we compared diagnostic coding of acute renal failure (ARF) in commercial payer claims data versus clinical results in the Regenstrief Medical Records System/Indiana Network for Patient Care (RMRS/INPC). Methods: The HealthCore Integrated Research Database (HIRD) contains eligibility, medical, and pharmacy claims for approximately 1.3 million fully-insured members in WellPoint’s Indiana-based health plan. The RMRS/INPC contains clinical data from the five major Indianapolis hospital systems. Patients from the HIRD were selected if they had an acute renal failure ICD9 code (584.** or 593.9*) with a service date from 6/2005 to 7/2007, preceded by >6 months with 1) no ICD9 codes for acute or chronic renal disease, and 2) continuous eligibility in the plan. To be analyzed in RMRS/INPC, we required two serum creatinine (Cr) values in the period 90 days before to 30 days after the index HIRD ARF ICD9 code. Simplified “RIFLE” criteria were used, with max:min Cr ratio >1.5 considered “risk” of ARF, >2.0 “injury,” and >3.0 (or [max Cr >4.0 mg/dl and {(max Cr – min Cr) >0.5 mg/dl}] “failure.” Minimum Cr could precede or follow the max. Results: There were 679 patients (54% female, 93% white) who met inclusion criteria in the HIRD and also had, in the RMRS/INPC, >2 Cr values from 90 days before to 30 days after the (index date) payer claim for ARF. Among the 679, 364 (54%) had “risk” for ARF, 210 (31%) had “injury,” and 107 (16%) had “failure”; 310 (46%) did not meet any RIFLE criteria for ARF. Thus, the positive predictive value of the payer claims-based ARF query was 54%, 31%, or 16% using RIFLE “risk,” “injury,” and “failure” as the gold standard, respectively. Conclusion: To the extent that populations overlap, clinical data can be used to explore the accuracy of ARF queries based on payer claims. The definition of ARF in payer claims may require refinement in order to improve the positive predictive value of the claims-based approach.
NKF 2009 Spring Clinical Meetings Abstracts 175 CALCIPHYLAXIS INDUCED BY PARICALCITOL Ugo Rotolo, Maria Damiana Pilloni*, Calogera Tortorici, Carlo Giammarresi, Onofrio Schillaci, Ignazio Cutaja, Irene Parrino UU.OO. of Nephrology and Dialysis, Ospedale Civico Palermo and Azienda USL.7 P.O. Sirai Carbonia*, Italy. Calcific uraemic arteriolopathy (CUA) is a rare disease associated to end-stage chronic renal failure. The prognosis is poor due to high mortality. CUA is characterized by skin necrosis and gangrene secondary to thrombosis and calcification of small dermoepidermal arterioles. Pathogenetic mechanisms are still unknown. We report two cases found in two patients undergoing regular hemodialysis treatment for over ten years. The patients live and are treated in two different hospitals situated on the two biggest islands of Italy (Sicily and Sardinia). Both patients showed normal total calciumphosphate levels with severe secondary hyperparathyroidism. These patients were correctly treated with the new therapeutic agent launched on the market for osteodistrophy -paricalcitol- as best medical practice recommends. In one patient paricalcitol was associated with calciomimetic agent cinacalcet. Despite normal calcium-phosphate product and decreased PTH levels, two months after starting treatment with paricalcitol these patients presented erythematous nodules which progressed to ulcerative necrotic skin lesions. After suspending 19-nor vitamin D treatment these skin lesions gradually improved and eventually completely healed. To date PTH levels in our patients are still high and parathyroidectomy will be performed upon consent. We stress that the incidence of calciphylaxis could greatly increase with the use of the new therapeutic agents like paricalcitol for aggressive control of secondary hyperparathyroidism.
176 RANDOMIZED, OPEN-LABEL CROSS-OVER STUDIES TO ASSESS THE POTENTIAL PHARMACOKINETIC INTERACTION OF WARFARIN OR DIGOXIN AND SEVELAMER CARBONATE Dennis Ruff, Healthcare Discoveries LLC, A Division of ICON Development Solutions, San Antonio, TX, USA; Jeremy Heaton, Genzyme Corporation, Cambridge UK Sevelamer carbonate (SC; Renvela®) was developed as a pharmaceutical alternative to sevelamer hydrochloride (SH). Studies have demonstrated that SH did not affect the bioavailability of warfarin or digoxin. After exposure to gastric contents, both SC and SH are similarly protonated salts of cross-linked poly(allylamine hydrochloride) and were expected to have similar drug-drug interactions. These studies were conducted to confirm that SC does not affect the pharmacokinetics of warfarin or digoxin. These were randomized, open-label, cross-over studies in healthy volunteers. In the warfarin study, 18 subjects received 20 mg of warfarin alone or co-administered with 9.6 g of sevelamer carbonate powder. In the digoxin study, 18 subjects received 1 mg of digoxin alone or co-administered with 9.6 g of sevelamer carbonate powder. The simultaneous administration of SC did not alter the mean plasma concentrations of warfarin or digoxin. The 90% CIs for Cmax, AUC(0-72), and AUC(0-inf) were within the 80% to 125% range for warfarin. All values were within the 80% to 125% range for digoxin after excluding a subject with an anomalous Cmax after digoxin alone. Table 1: Geometric Means* for R-warfarin, S-Warfarin and Digoxin AUC(0-inf) (hr*ng/mL) AUC(0-72) (hr*ng/mL) Cmax (ng/mL)
R-Warfarin W +S W 69122 63312 42990 41566 1168 1204
S-Warfarin W+S W 44359 42125 31831 30879 1125 1168
Digoxin D+S D 68.0 67.6 50.7 52.0 4.2 4.4
W: warfarin; S: sevelamer; D: digoxin *Geometric mean based on least squares mean of log-transformed parameter values
In healthy volunteers, the co-administration of a single dose of sevelamer carbonate did not alter the pharmacokinetics of a single dose of warfarin or digoxin.
174 ELECTRONIC MEDICAL RECORDS SYSTEM VALIDATION OF CLAIMS-BASED QUERIES FOR ACUTE RENAL FAILURE Marc B. Rosenman,1,2 Peter Wahl,3 Greg Daniel,3 J. Marc Overhage,1,2 Patricia McGuire,1 Dan Thompson,1 Keith Rodgers,3 Louise Short,3 Rhonda Bohn,3 William M. Tierney.1,2 1) Regenstrief Institute and 2) Indiana University School of Medicine (Indianapolis, IN, USA); 3) HealthCore (Wilmington, DE, USA) Purpose: To explore the value of different types of data, we compared diagnostic coding of acute renal failure (ARF) in commercial payer claims data versus clinical results in the Regenstrief Medical Records System/Indiana Network for Patient Care (RMRS/INPC). Methods: The HealthCore Integrated Research Database (HIRD) contains eligibility, medical, and pharmacy claims for approximately 1.3 million fully-insured members in WellPoint’s Indiana-based health plan. The RMRS/INPC contains clinical data from the five major Indianapolis hospital systems. Patients from the HIRD were selected if they had an acute renal failure ICD9 code (584.** or 593.9*) with a service date from 6/2005 to 7/2007, preceded by >6 months with 1) no ICD9 codes for acute or chronic renal disease, and 2) continuous eligibility in the plan. To be analyzed in RMRS/INPC, we required two serum creatinine (Cr) values in the period 90 days before to 30 days after the index HIRD ARF ICD9 code. Simplified “RIFLE” criteria were used, with max:min Cr ratio >1.5 considered “risk” of ARF, >2.0 “injury,” and >3.0 (or [max Cr >4.0 mg/dl and {(max Cr – min Cr) >0.5 mg/dl}] “failure.” Minimum Cr could precede or follow the max. Results: There were 679 patients (54% female, 93% white) who met inclusion criteria in the HIRD and also had, in the RMRS/INPC, >2 Cr values from 90 days before to 30 days after the (index date) payer claim for ARF. Among the 679, 364 (54%) had “risk” for ARF, 210 (31%) had “injury,” and 107 (16%) had “failure”; 310 (46%) did not meet any RIFLE criteria for ARF. Thus, the positive predictive value of the payer claims-based ARF query was 54%, 31%, or 16% using RIFLE “risk,” “injury,” and “failure” as the gold standard, respectively. Conclusion: To the extent that populations overlap, clinical data can be used to explore the accuracy of ARF queries based on payer claims. The definition of ARF in payer claims may require refinement in order to improve the positive predictive value of the claims-based approach.
NKF 2009 Spring Clinical Meetings Abstracts 175 CALCIPHYLAXIS INDUCED BY PARICALCITOL Ugo Rotolo, Maria Damiana Pilloni*, Calogera Tortorici, Carlo Giammarresi, Onofrio Schillaci, Ignazio Cutaja, Irene Parrino UU.OO. of Nephrology and Dialysis, Ospedale Civico Palermo and Azienda USL.7 P.O. Sirai Carbonia*, Italy. Calcific uraemic arteriolopathy (CUA) is a rare disease associated to end-stage chronic renal failure. The prognosis is poor due to high mortality. CUA is characterized by skin necrosis and gangrene secondary to thrombosis and calcification of small dermoepidermal arterioles. Pathogenetic mechanisms are still unknown. We report two cases found in two patients undergoing regular hemodialysis treatment for over ten years. The patients live and are treated in two different hospitals situated on the two biggest islands of Italy (Sicily and Sardinia). Both patients showed normal total calciumphosphate levels with severe secondary hyperparathyroidism. These patients were correctly treated with the new therapeutic agent launched on the market for osteodistrophy -paricalcitol- as best medical practice recommends. In one patient paricalcitol was associated with calciomimetic agent cinacalcet. Despite normal calcium-phosphate product and decreased PTH levels, two months after starting treatment with paricalcitol these patients presented erythematous nodules which progressed to ulcerative necrotic skin lesions. After suspending 19-nor vitamin D treatment these skin lesions gradually improved and eventually completely healed. To date PTH levels in our patients are still high and parathyroidectomy will be performed upon consent. We stress that the incidence of calciphylaxis could greatly increase with the use of the new therapeutic agents like paricalcitol for aggressive control of secondary hyperparathyroidism.
176 RANDOMIZED, OPEN-LABEL CROSS-OVER STUDIES TO ASSESS THE POTENTIAL PHARMACOKINETIC INTERACTION OF WARFARIN OR DIGOXIN AND SEVELAMER CARBONATE Dennis Ruff, Healthcare Discoveries LLC, A Division of ICON Development Solutions, San Antonio, TX, USA; Jeremy Heaton, Genzyme Corporation, Cambridge UK Sevelamer carbonate (SC; Renvela®) was developed as a pharmaceutical alternative to sevelamer hydrochloride (SH). Studies have demonstrated that SH did not affect the bioavailability of warfarin or digoxin. After exposure to gastric contents, both SC and SH are similarly protonated salts of cross-linked poly(allylamine hydrochloride) and were expected to have similar drug-drug interactions. These studies were conducted to confirm that SC does not affect the pharmacokinetics of warfarin or digoxin. These were randomized, open-label, cross-over studies in healthy volunteers. In the warfarin study, 18 subjects received 20 mg of warfarin alone or co-administered with 9.6 g of sevelamer carbonate powder. In the digoxin study, 18 subjects received 1 mg of digoxin alone or co-administered with 9.6 g of sevelamer carbonate powder. The simultaneous administration of SC did not alter the mean plasma concentrations of warfarin or digoxin. The 90% CIs for Cmax, AUC(0-72), and AUC(0-inf) were within the 80% to 125% range for warfarin. All values were within the 80% to 125% range for digoxin after excluding a subject with an anomalous Cmax after digoxin alone. Table 1: Geometric Means* for R-warfarin, S-Warfarin and Digoxin AUC(0-inf) (hr*ng/mL) AUC(0-72) (hr*ng/mL) Cmax (ng/mL)
R-Warfarin W +S W 69122 63312 42990 41566 1168 1204
S-Warfarin W+S W 44359 42125 31831 30879 1125 1168
Digoxin D+S D 68.0 67.6 50.7 52.0 4.2 4.4
W: warfarin; S: sevelamer; D: digoxin *Geometric mean based on least squares mean of log-transformed parameter values
In healthy volunteers, the co-administration of a single dose of sevelamer carbonate did not alter the pharmacokinetics of a single dose of warfarin or digoxin.