- Email: [email protected]
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ADHERENCE TO K/DOQI GUIDELINES FOR BONE METABOLISM & DISEASE IN CHRONIC KIDNEY DISEASE. Tracey Hoy1, Maxine Fisher1, Rohit Borker2, Beth Barber2, Brad Stolshek2, William Goodman2 (1) HealthCore, Inc. Wilmington, DE, USA; (2) Amgen, Inc. Thousand Oaks, CA, USA. Recent research has shown chronic kidney disease (CKD) is associated with poorer health outcomes and high medical expenditures and that early detection and treatment may prevent or delay adverse outcomes. The Kidney Disease Outcomes Quality Initiative (K/DOQI™) guidelines for bone metabolism and disease were developed to improve the management of patients (pts) with CKD. This research investigated adherence to K/DOQI™ guidelines for frequency of testing and for the control of parathyroid hormone (PTH), calcium (Ca) and phosphorus (P). The analysis was performed with pooled data from two large US managed care databases. Pts were identified from June 1, 2002 to May 31, 2004 based on laboratory data. Pts were excluded if they were < 18 years or > 65 years of age, had less than 18 months of continuous eligibility, or had renal cancer. A total of 9,196 pts with CKD stages 3 or 4 (8,875 and 321, respectively) were identified. Ca levels were tested in accordance with K/DOQI™ guidelines in 95.6% of pts with stage 3 CKD. The percentage dropped among pts with stage 4 CKD (43.3%), when K/DOQI™ guidelines recommend increasing the frequency of testing from 1x/year to 4x/year. Frequency of testing PTH and P was low (Table). Among those tested a high percentage of pts were within K/DOQI™ ranges for Ca and P for both stages 3 and 4. However, < 40% of those with measured PTH levels were within the K/DOQI™ target ranges. PTH Ca P CKD3 CKD4 CKD3 CKD4 CKD3 CKD4 Pts tested as per 1.8 0.3 95.6 43.3 4.8 1.6 K/DOQI™ % Pts with > 1 lab 1.8 7.2 95.6 97.5 4.8 20.3 per year % Pts with > 1 lab in 38.5 26.1 99.1 96.8 91.5 89.2 target range % These data demonstrate that there remains substantial opportunity to improve the quality of care with regard to mineral metabolism for pts with CKD.
HYPERPHOSPHATEMIA IS INDEPENDENTLY ASSOCIATED WITH SYSTOLIC AND PULSE BLOOD PRESSURE IN HEMODIALYSIS PATIENTS Huang, CX1, Plantinga L2, Fink NE2, Melamed ML3, Klag MJ2, Powe NR2. 1Johns Hopkins/Sinai Hospital Program in Internal Medicine, 2 Welch Center for Prevention, Epidemiology and Clinical Research, The Johns Hopkins University, Baltimore, MD, USA. 3Albert Einstein College of Medicine, Bronx, NY,USA. Elevated serum phosphate has been shown to be associated with increased mortality in hemodialysis patients. We hypothesized that this association may be partially mediated by increasing blood pressure induced by mineral deposition in blood vessels that subsequently increases stiffness of arterial walls. We examined the relation between serum phosphate level and blood pressure in 729 incident hemodialysis patients from 79 clinics who were enrolled from October 1995 to June 1998 in CHOICE, a prospective cohort study. In cross-sectional analyses, serum phosphate was a significant predictor of systolic blood pressure (SBP) and pre-dialysis pulse pressure in multivariable linear regression models, adjusting for age, sex, race, serum albumin, CRP, IL-6, timing of nephrologist referral, diabetes mellitus (DM), baseline cardiovascular disease (CVD) and co-existing diseases (ICED) (P=0.001) at the start of dialysis. For each 1 mg/dL increase in phosphate, systolic blood pressure was higher by 2.02 mmHg. In longitudinal analyses, we used generalized estimating equations to examine the association between change in serum phosphate and subsequent change in blood pressure with a 3- and 6-month lag between measurement of serum phosphate and blood pressure rise. For each 1 mg/dL change in phosphate from 0 to 3 months, there was a 0.92 mmHg increase in SBP from 3 to 9 months (P=0.01), a 0.70 mmHg increase in SBP from 9 to 15 months (p=0.046) and a 1.13 mmHg increase of SBP from 15 to 21 months (p=0.001), adjusted for the above covariates. The association with pulse pressure was similar. This study suggests that serum phosphate and its change over time are strong independent predictors of systolic and pulse blood pressure in hemodialysis patients. Rigorous control of serum phosphate levels in hemodialysis patients may help to optimize blood pressure and minimize its associated morbidity.
NKF 2007 Spring Clinical Meetings Abstracts
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CHRONIC KIDNEY DISEASE PATIENTS AND RENAL TRANSPLANT RECIPIENTS HAVE AN INCREASED INCIDENCE OF MONOCLONAL GAMMOPATHIES. Colin A. Hutchison,1 Stephen Harding,2 Graham Mead,2 John Townsend,1 Martin Landray4, Paul Cockwell,1 Arthur Bradwell.3 1 Queen Elizabeth Hospital, 2The Binding Site and 3University of Birmingham, Birmingham, 4Radcliffe Hospital, Oxford, UK. The nephrotoxicity of monoclonal free light chains (FLC) is well described. Most commonly they result in tubulointerstitial lesions, but renal amyloidosis and light chain deposition disease are other pathological complications. Less commonly intact immunoglobulins can result in renal injury. Recently a highly sensitive immunoassay (FREELITETM) has become available for quantitatively assessing FLCs in the serum. This assay in combination with protein electrophoresis was used to screen two populations of patients with chronic kidney disease and a population of renal transplant recipients for evidence of monoclonal gammopathies of undetermined significance (MGUS). The demographics, mean serum creatinine and results from the patients, over 50 years of age, are shown in the Table. The three patient groups had significantly raised incidences of MGUS compared with the published incidence of 3.2 percent in the general population of over 50 years old (Kyle R et al, NEJM’06). Both CKD populations had significant proportions of monoclonal FLCs associated with the MGUS, but this was not seen in the transplant patients. In conclusion, renal transplant recipients and patients with CKD had increased incidence of MGUS. Further work is required to determine whether these monoclonal gammopathies could be involved in the pathology of progressive renal damage in some patients. CKD – 2 Transplants CKD – 1 (n-306) (n-265) (n-289) Mean age 60.6 61.4 67 Male % 57 65 61 Mean creatinine umol/L 215 N/A 180 MGUS prevalence 10.4 10.7 10.7 FLC MGUS prevalence 2.8 7 0.8
MATHEMATICAL MODELLING OF FREE LIGHT CHAIN REMOVAL BY PLASMA EXCHANGE AND EXTENDED HEMODIALYSIS IN PATIENTS WITH CAST NEPHROPATHY. Colin A. Hutchison,1 Mark Cook,1 Stephen Harding,2 Graham Mead,2 John Hattersley,4 Neil Evans,4 Mike Chapel,4 Paul Cockwell,1 Arthur Bradwell.3 1 Queen Elizabeth Hospital, 2The Binding Site and 3University of Birmingham, Birmingham, 4University of Warwick, Warwick, UK.
Cast nephropathy is the predominant cause of irreversible renal failure in patients with multiple myeloma. The casts result from the excess of free light chains present in the serum (sFLC). Plasma exchange (PE) has historically been used in an attempt to improve renal outcomes in these patients with disappointing results (Clark et al, Ann Int Med’05). Recent in-vitro and –vivo studies have demonstrated that hemodialysis (HD) using the Gambro HCO 1100 dialyser is an effective method of removing sFLC (Hutchison et al, JASN in press). A two compartment model was devised to compare HD and PE as methods for rapidly lowering sFLC concentrations. Model simulations (Table) demonstrate that even 4hrs of HD 3 times a week was more effective than PE in rapidly lowering sFLC concentrations. The ineffectiveness of PE is because of its short duration. Eighty percent of FLCs are extra-vascular. Therefore, to rapidly reduce the total body load of FLCs a method which allows prolonged clearance of the extravascular compartment is required. The importance of the duration of treatment to cause a sustained reduction in sFLC concentrations is emphasised as the chemotherapy becomes less efficient (Table). Mathematical modelling demonstrates that prolonged daily dialysis is a very effective method of rapidly reducing sFLC concentrations in patients with multiple myeloma and renal failure. Method of FLC removal
Percentage of FLCs removed by intervention (and time, in days, to reduce from 10g/L to 0.5g/L) with different chemotherapeutic tumor killing rates (% per day). 100% 10% 5% 2% 0% None NA (14) NA (30) NA (52) NA (121) NA (*10 g/L) PE x 10 in 10 days 40 (8) 34 (29) 25 (52) 13 (121) 4 (*10 g/L) HD 4 hrs x 3/week 60 (7) 54 (19) 53 (31) 51 (73) 50 (*3.6 g/L) HD 8 hrs daily 87 (3) 85 (7) 84 (14) 83 (29) 82 (*1.0 g/L) HD 12 hrs daily 91 (2) 89 (5) 89 (8) 88 (16) 88 (*0.7 g/L) *sFLC conc. at day 150 for simulations in which reductions to 0.5g/L did not occur.
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ADHERENCE TO K/DOQI GUIDELINES FOR BONE METABOLISM & DISEASE IN CHRONIC KIDNEY DISEASE. Tracey Hoy1, Maxine Fisher1, Rohit Borker2, Beth Barber2, Brad Stolshek2, William Goodman2 (1) HealthCore, Inc. Wilmington, DE, USA; (2) Amgen, Inc. Thousand Oaks, CA, USA. Recent research has shown chronic kidney disease (CKD) is associated with poorer health outcomes and high medical expenditures and that early detection and treatment may prevent or delay adverse outcomes. The Kidney Disease Outcomes Quality Initiative (K/DOQI™) guidelines for bone metabolism and disease were developed to improve the management of patients (pts) with CKD. This research investigated adherence to K/DOQI™ guidelines for frequency of testing and for the control of parathyroid hormone (PTH), calcium (Ca) and phosphorus (P). The analysis was performed with pooled data from two large US managed care databases. Pts were identified from June 1, 2002 to May 31, 2004 based on laboratory data. Pts were excluded if they were < 18 years or > 65 years of age, had less than 18 months of continuous eligibility, or had renal cancer. A total of 9,196 pts with CKD stages 3 or 4 (8,875 and 321, respectively) were identified. Ca levels were tested in accordance with K/DOQI™ guidelines in 95.6% of pts with stage 3 CKD. The percentage dropped among pts with stage 4 CKD (43.3%), when K/DOQI™ guidelines recommend increasing the frequency of testing from 1x/year to 4x/year. Frequency of testing PTH and P was low (Table). Among those tested a high percentage of pts were within K/DOQI™ ranges for Ca and P for both stages 3 and 4. However, < 40% of those with measured PTH levels were within the K/DOQI™ target ranges. PTH Ca P CKD3 CKD4 CKD3 CKD4 CKD3 CKD4 Pts tested as per 1.8 0.3 95.6 43.3 4.8 1.6 K/DOQI™ % Pts with > 1 lab 1.8 7.2 95.6 97.5 4.8 20.3 per year % Pts with > 1 lab in 38.5 26.1 99.1 96.8 91.5 89.2 target range % These data demonstrate that there remains substantial opportunity to improve the quality of care with regard to mineral metabolism for pts with CKD.
HYPERPHOSPHATEMIA IS INDEPENDENTLY ASSOCIATED WITH SYSTOLIC AND PULSE BLOOD PRESSURE IN HEMODIALYSIS PATIENTS Huang, CX1, Plantinga L2, Fink NE2, Melamed ML3, Klag MJ2, Powe NR2. 1Johns Hopkins/Sinai Hospital Program in Internal Medicine, 2 Welch Center for Prevention, Epidemiology and Clinical Research, The Johns Hopkins University, Baltimore, MD, USA. 3Albert Einstein College of Medicine, Bronx, NY,USA. Elevated serum phosphate has been shown to be associated with increased mortality in hemodialysis patients. We hypothesized that this association may be partially mediated by increasing blood pressure induced by mineral deposition in blood vessels that subsequently increases stiffness of arterial walls. We examined the relation between serum phosphate level and blood pressure in 729 incident hemodialysis patients from 79 clinics who were enrolled from October 1995 to June 1998 in CHOICE, a prospective cohort study. In cross-sectional analyses, serum phosphate was a significant predictor of systolic blood pressure (SBP) and pre-dialysis pulse pressure in multivariable linear regression models, adjusting for age, sex, race, serum albumin, CRP, IL-6, timing of nephrologist referral, diabetes mellitus (DM), baseline cardiovascular disease (CVD) and co-existing diseases (ICED) (P=0.001) at the start of dialysis. For each 1 mg/dL increase in phosphate, systolic blood pressure was higher by 2.02 mmHg. In longitudinal analyses, we used generalized estimating equations to examine the association between change in serum phosphate and subsequent change in blood pressure with a 3- and 6-month lag between measurement of serum phosphate and blood pressure rise. For each 1 mg/dL change in phosphate from 0 to 3 months, there was a 0.92 mmHg increase in SBP from 3 to 9 months (P=0.01), a 0.70 mmHg increase in SBP from 9 to 15 months (p=0.046) and a 1.13 mmHg increase of SBP from 15 to 21 months (p=0.001), adjusted for the above covariates. The association with pulse pressure was similar. This study suggests that serum phosphate and its change over time are strong independent predictors of systolic and pulse blood pressure in hemodialysis patients. Rigorous control of serum phosphate levels in hemodialysis patients may help to optimize blood pressure and minimize its associated morbidity.
NKF 2007 Spring Clinical Meetings Abstracts
87
88
CHRONIC KIDNEY DISEASE PATIENTS AND RENAL TRANSPLANT RECIPIENTS HAVE AN INCREASED INCIDENCE OF MONOCLONAL GAMMOPATHIES. Colin A. Hutchison,1 Stephen Harding,2 Graham Mead,2 John Townsend,1 Martin Landray4, Paul Cockwell,1 Arthur Bradwell.3 1 Queen Elizabeth Hospital, 2The Binding Site and 3University of Birmingham, Birmingham, 4Radcliffe Hospital, Oxford, UK. The nephrotoxicity of monoclonal free light chains (FLC) is well described. Most commonly they result in tubulointerstitial lesions, but renal amyloidosis and light chain deposition disease are other pathological complications. Less commonly intact immunoglobulins can result in renal injury. Recently a highly sensitive immunoassay (FREELITETM) has become available for quantitatively assessing FLCs in the serum. This assay in combination with protein electrophoresis was used to screen two populations of patients with chronic kidney disease and a population of renal transplant recipients for evidence of monoclonal gammopathies of undetermined significance (MGUS). The demographics, mean serum creatinine and results from the patients, over 50 years of age, are shown in the Table. The three patient groups had significantly raised incidences of MGUS compared with the published incidence of 3.2 percent in the general population of over 50 years old (Kyle R et al, NEJM’06). Both CKD populations had significant proportions of monoclonal FLCs associated with the MGUS, but this was not seen in the transplant patients. In conclusion, renal transplant recipients and patients with CKD had increased incidence of MGUS. Further work is required to determine whether these monoclonal gammopathies could be involved in the pathology of progressive renal damage in some patients. CKD – 2 Transplants CKD – 1 (n-306) (n-265) (n-289) Mean age 60.6 61.4 67 Male % 57 65 61 Mean creatinine umol/L 215 N/A 180 MGUS prevalence 10.4 10.7 10.7 FLC MGUS prevalence 2.8 7 0.8
MATHEMATICAL MODELLING OF FREE LIGHT CHAIN REMOVAL BY PLASMA EXCHANGE AND EXTENDED HEMODIALYSIS IN PATIENTS WITH CAST NEPHROPATHY. Colin A. Hutchison,1 Mark Cook,1 Stephen Harding,2 Graham Mead,2 John Hattersley,4 Neil Evans,4 Mike Chapel,4 Paul Cockwell,1 Arthur Bradwell.3 1 Queen Elizabeth Hospital, 2The Binding Site and 3University of Birmingham, Birmingham, 4University of Warwick, Warwick, UK.
Cast nephropathy is the predominant cause of irreversible renal failure in patients with multiple myeloma. The casts result from the excess of free light chains present in the serum (sFLC). Plasma exchange (PE) has historically been used in an attempt to improve renal outcomes in these patients with disappointing results (Clark et al, Ann Int Med’05). Recent in-vitro and –vivo studies have demonstrated that hemodialysis (HD) using the Gambro HCO 1100 dialyser is an effective method of removing sFLC (Hutchison et al, JASN in press). A two compartment model was devised to compare HD and PE as methods for rapidly lowering sFLC concentrations. Model simulations (Table) demonstrate that even 4hrs of HD 3 times a week was more effective than PE in rapidly lowering sFLC concentrations. The ineffectiveness of PE is because of its short duration. Eighty percent of FLCs are extra-vascular. Therefore, to rapidly reduce the total body load of FLCs a method which allows prolonged clearance of the extravascular compartment is required. The importance of the duration of treatment to cause a sustained reduction in sFLC concentrations is emphasised as the chemotherapy becomes less efficient (Table). Mathematical modelling demonstrates that prolonged daily dialysis is a very effective method of rapidly reducing sFLC concentrations in patients with multiple myeloma and renal failure. Method of FLC removal
Percentage of FLCs removed by intervention (and time, in days, to reduce from 10g/L to 0.5g/L) with different chemotherapeutic tumor killing rates (% per day). 100% 10% 5% 2% 0% None NA (14) NA (30) NA (52) NA (121) NA (*10 g/L) PE x 10 in 10 days 40 (8) 34 (29) 25 (52) 13 (121) 4 (*10 g/L) HD 4 hrs x 3/week 60 (7) 54 (19) 53 (31) 51 (73) 50 (*3.6 g/L) HD 8 hrs daily 87 (3) 85 (7) 84 (14) 83 (29) 82 (*1.0 g/L) HD 12 hrs daily 91 (2) 89 (5) 89 (8) 88 (16) 88 (*0.7 g/L) *sFLC conc. at day 150 for simulations in which reductions to 0.5g/L did not occur.