Chronic Uremic Acidosis Nutritional Effects 2 Hypoalbuminemia Osteomalacia (bone mineral loss) Decreased muscle mass Increased incidence of morbidity and mortality Nutritional Effects 2 Hypoalbuminemia Osteomalacia (bone mineral loss) Decreased muscle mass Increased incidence of morbidity and mortality 2 Blair, D, et al., “Nutritional Effects of Delivered Bicarbonate Dose in Maintenance Hemodialysis Patients”, Journal of Renal Nutrition, 2003 Vol 13;

2004 RETROSPECTIVE STUDY Conversion to Acid Concentrate with Additional Acetate GranuFlo is a dry acid concentrate product that contains 8 mEq/L of acetate. This effectively increases the “total buffer” by 4 mEq/L over what the patient saw when liquid acid concentrate was used.

Prevalence of Acidosis among Dialysis Patients

FMCNA Steps in Reducing Acidosis Medical Director memorandum (2000) to raise awareness among physicians. Bicarbonate goal added to Quality Reports (Jan 2001) to provide feedback to dialysis facilities. Dry acid w/ Diacetate made available (2002). Medical Director memorandum (2000) to raise awareness among physicians. Bicarbonate goal added to Quality Reports (Jan 2001) to provide feedback to dialysis facilities. Dry acid w/ Diacetate made available (2002).

Study Design Retrospective of patients converted to dry acid concentrate between August 2002 and April Determine pre-conversion 3-month average pre- dialysis serum bicarbonate. Exclude labs during 60 day washout period. Determine post-washout 3-month average pre- dialysis serum bicarbonate. - Total 4,793 patients with Standard Dialysate and GranuFlo Diacetate data. Retrospective of patients converted to dry acid concentrate between August 2002 and April Determine pre-conversion 3-month average pre- dialysis serum bicarbonate. Exclude labs during 60 day washout period. Determine post-washout 3-month average pre- dialysis serum bicarbonate. - Total 4,793 patients with Standard Dialysate and GranuFlo Diacetate data.

Desired Range N = 4,793

Desired Range N = 4,793

Desired Range Acidosis Concern < 20 mEq/l Alkalosis Concern > 30 mEq/l N = 4,793

Pre-Dialysis Serum Bicarbonate Before and After Conversion to GranuFlo NMeanSD Range  SD Standard Dialysate GranuFlo % Patients <20 mEq/L % Patients >30 mEq/L Standard Dialysate15%0.9% GranuFlo10%1.5%

2003 Death Risk vs. Bicarbonate Notes: Case mix adjustment accounts for the differences in age, gender, race and diabetes among bicarbonate groups. Because bicarbonate values are inversely correlated with adequate diet, lab (albumin) adjustment is necessary to separate out the nutritional effect. After case mix and lab adjustment, death risk is statistically different from the reference only in the lowest ( 28 meq/l) group (13% higher risk, p=0.044) N = 74,089 * Statistically significant at p=0.05 Decrease Total Buffer Increase Total Buffer Monitor Labs May Require Rx Change

Conclusions Diacetate resulted in a one-third reduction (15% to 10%) in the prevalence of acidosis, defined as pre-dialysis bicarbonate < 20 mEq/l. At the same time, the prevalence of alkalosis (pre-dialysis bicarbonate levels >30 mEq/l) rose only slightly, from 0.9% to 1.5%. Care should be taken to lower dialysate bicarbonate prescriptions in patients whose bicarbonate value rises too high after switching to a dry dialysate w/Diacetate. Diacetate resulted in a one-third reduction (15% to 10%) in the prevalence of acidosis, defined as pre-dialysis bicarbonate < 20 mEq/l. At the same time, the prevalence of alkalosis (pre-dialysis bicarbonate levels >30 mEq/l) rose only slightly, from 0.9% to 1.5%. Care should be taken to lower dialysate bicarbonate prescriptions in patients whose bicarbonate value rises too high after switching to a dry dialysate w/Diacetate.