130: Use of Home Telemonitoring System in Hemodialysis Patients at High Risk for Volume Overload

NKF 2009 Spring Clinical Meetings Abstracts 129 BARDOXOLONE, A NOVEL ORAL ANTIINFLAMMATORY AGENT SHOWN TO IMPROVE RENAL FUNCTION Colin Meyer, Reata Pharmaceuticals, Irving, TX, USA. Bardoxolone methyl (BARD) is a first-in-class Antioxidant Inflammation Modulator (AIM) in clinical trials for CKD. BARD potently induces Nrf2, a transcription factor that is a well-validated target for CKD. Nrf2 activates over 250 antioxidant and detoxifications genes within the cell, thereby modulating ROS-mediated endothelial dysfunction and structural remodeling in the kidney. BARD has demonstrated significant nephroprotective activity in animal models of kidney injury. In preclinical toxicology studies, reductions in serum creatinine (SC) have been observed across multiple species. These effects on SC are independent of tubular secretion and creatinine production and thus likely reflect an increase in GFR. These observations have been replicated in two Phase 1 trials of oncology patients. Within 21 days, 82% (49/60) of BARDtreated patients experienced a mean decrease in SC of 19.3%, corresponding to a mean 20.9% increase in GFR. Baseline SC and GFR were 1.00 mg/dl and 79.9 ml/min/1.73m2, respectively. GFR improvements were more pronounced in a subset (n=13) of patients with established CKD (GFR < 60 ml/min/1.73m2 at baseline). In these patients, GFR increased a mean of 27.6%. Changes in GFR were unrelated to weight changes. Decreases in BUN were also observed in these patients. Importantly, these results were sustained throughout the study period (6+ months). Based on this data, a Phase 2 study in diabetic patients with CKD was initiated in May of 2008. This trial is measuring a number of markers of CKD, endothelial dysfunction, and glycemic control. Enrollment of this trial was completed in November, 2008.

130 USE OF HOME TELEMONITORING SYSTEM IN HEMODIALYSIS PATIENTS AT HIGH RISK FOR VOLUME OVERLOAD. Beckie Michael, Susan McAnally, Evelyn Rhoads, Thomas Lepetich, Marcos Rothstein, Jerome Tannenbaum, DSI Renal, Inc. The care of hemodialysis (HD) patients (pts) can be complicated by hospitalizations for fluid overload and difficulty managing blood pressure (BP). Cardiocom® (CC) manufactures telehealth devices which allow central monitoring of blood pressure (BP), pulse, weight and oxygen saturation. In nondialysis pts with cardiomyopathy, the use of these devices has been shown to significantly reduce hospitalization. The purpose of this 90 day pilot was to determine if the use of CC would reduce hospitalizations for fluid overload and/or improve BP in chronic maintenance HD patients with a history of excessive interdialytic weight gains (>5% EDW) or difficult to manage hypertension. 35 pts at 2 dialysis units received CC devices at home. Pts checked their vital signs, weight, and answered prompted questions twice daily on nondialysis days and once daily on dialysis days. A dialysis nurse, using a web-based program, contacted pts who met predetermined alert exception criteria. 27 pts were compliant with the telehealth devices. In the 90 days prior to the study, one patient experienced one hospitalization for volume overload. There was one hospitalization for volume overload during the study. 10 pts (37%) required 10 extra HD treatments to achieve new EDW. 6 pts (22%) required adjustment of BP medications due to home BP recordings, including one pt with bradycardia. Some pts benefited by reducing interdialytic weight gain via behavior modification and reinforcement. Overall, the telehealth devices were well received by pts, although some required home visits by staff and detailed one-on-one instruction. Others were excluded due to lack of telephone line. In summary, in selected HD pts, home monitoring with CC can help optimize volume status and improve BP control. Limitations include pt compliance and cost. Due to frequent nursing assessment of in-center HD pts, similar benefits may be achieved in compliant dialysis patients using a home BP cuff and scale.

A55 131 SPROUTY1 AND GDNF/RET SIGNALLING IN KIDNEY DEVELOPMENT. Odyssé Michos1, Debbie Hyink2, Jon Licht3, and Frank Costantini1 1. Columbia University Med. Center, New York, NY. 2. Mount Sinai School Of Medicine, New York, NY. 3. Northwestern Univ. Feinberg School of Medicine, Chicago, IL. The development of the metanephric kidney begins when the Wolffian duct, an epithelial tube derived from intermediate mesoderm, gives rise to an out-pocketing called the ureteric bud (UB). The UB then undergoes a complex process of growth, branching and remodelling, to eventually give rise to the entire urinary collecting system. Signalling by GDNF through its receptor tyrosine kinase (RTK) Ret is required for normal growth of the ureteric bud during kidney development. However, the precise role of GDNF/Ret signalling in renal branching morphogenesis and the specific responses of UB cells to GDNF remain unclear. Recent studies have shown that Sprouty1 (Spry1), an intercellular RTK antagonist, was an important regulator of GDNF/Ret signalling. However, it is still not clear whether or not Spry1 only regulates GDNF signalling and especially how it acts? To gain insight into the mechanism of action of Spry1 we have now, generated chimeras by injecting Spry1-/- ES cells into wild type blastocysts. Our data show that Spry1-/- UB cells preferentially contribute to the tips of the developing UB. These observations support the model that Spry1 opposes GDNF/Ret signalling, and also suggest that Spry1 acts in a cell-autonomous manner. Interestingly, we have generated double mutant animal lacking both Spry1 and Gdnf and found that such mutant develop fairly normal kidneys. Moreover, we also found that FGF10 is an important factor necessary to promote kidney development in absence of GDNF and Spry1. These results suggested that several RTK signals are required for proper branching morphogenesis and kidney development.

132 MORTALITY OF 5-YEAR TIME-AVERAGED LOW SERUM CALCIUM <8.5 MG/DL IN SUBGROUPS OF HEMODIALYSIS (HD) PATIENTS Jessica E Miller, Elani Streja, Csaba P Kovesdy, David Van Wyck, Allen R Nissenson, and Kamyar Kalantar-Zadeh. Harold Simmons Center, Torrance, CA; VA Salem, VA;& DaVita Inc, El Segundo, CA Low serum calcium levels may be associated with cardiovascular, neurological and other adverse outcomes. We examined these associations by accounting for all monthly measured serum calcium levels up to the time of death or censorship in different subgroups of a large and contemporary cohort of 151,555 HD patients in all legacy DaVita dialysis clinics during 7/2001-6/2006. All monthly measured (and albumin adjusted) serum calcium levels were averaged into one single value per patient during the entire follow-up time, i.e., up to 5 years. Patients were 61.1±15.6 years old and included 45% women, 31% Blacks, 14% Hispanics and 43% diabetics. In multivariate Cox models adjusted for case-mix and malnutrition-inflammation cachexia syndrome (MICS) Ca <8.5 mg/dL is good Ca <8.5 mg/dL is bad All MHD patients (BMI, serum Caucasians Blacks creatinine, albumin, Asians Hispanics TIBC, WBC, phos., Diabetic Non-Diabetic PTH, lymphocyte Women percentage and blood Men Age <65 yrs hemoglobin), albumin Age >=65 yrs Vintage < 6 mo adjusted serum calcium Vintage 6-24 mo Vintage 2-5 yrs Vintage >=5 yrs <8.5 mg/dL (compared to 8.5 to 10.2 mg/dl) Albumin <3.8 Albumin>=3.8 associated with 20% nPCR<1.0 nPCR>=1.0 increased death risk Phos <3.5 Phos 3.5-5.5 (hazard ratio:. 1.20, Phos>5.5 PTH<150 95% CI: 1.12-1.27). PTH 150-300 PTH 300-600 The increased death PTH>600 Paricalcitol 1 tertile risk of hypocalcemia 2 tertile 3 tertile was consistent across 0.6 0.8 1 1.2 1.4 1.6 1.8 2 almost all subgroups (see Figure). Hence, in HD patients, time-averaged hypocalcemia (<8.5 mg/dL), when compared to normo-calcemia (8.5-10.2 mg/dL), is associated with increased mortality. nd rd

All All c&m RACE Caucasian Caucasian_c&m Black Black_c&m Asian Asian_c&m Hispanic Hispanic_c&m DIABETES Diabetic Diabetic_c&m Non-diabetic Non-diabetic_c&m GENDER Female Female_c&m Male Male_c&m AGE <65 Years <65 Years_c&m >= 65 Years >= 65 Years_c&m VINTAGE < 6 months < 6 months_c&m 6-24 months 6-24 months_c&m 2-5 years 2-5 years_c&m >5 years >5 years_c&m ALBUMIN <= 3.8 <= 3.8_c&m > 3.8 > 3.8_c&m PROTEIN INTAKE <= 1.0 <= 1.0_c&m > 1.0 > 1.0_c&m PHOSPHOROUS < 3.5 < 3.5_c&m 3.5 - 5.5 3.5 - 5.5_c&m >= 5.5 >= 5.5_c&m PTH < 150 < 150_c&m 150 - 300 150 - 300_c&m 300 - 600 300 - 600_c&m >= 600 >= 600_c&m ZEMPLAR 1st tertile st 1st tertile_c&m 2nd tertile 2nd tertile_c&m 3rd tertile 3rd tertile_c&m O Unadjusted

Fully adjusted