Li, Pang

Introduction: Serum creatinine (sCr) is routinely used to calculate estimated glomerular filtration rate (eGFR) in heart failure (HF) pts. However, changes in muscle mass may limit the accuracy of sCr as marker of renal function in this population. Cystatin C (CysC) is independent of muscle mass and provides an alternative measure of eGFR. In prior studies, higher sCr/CysC ratio has been associated with higher muscle mass. Herein, we compared CysC- and sCr-based eGFR at serial time points among pts admitted with HF. We hypothesized that muscle mass would decline during HF admission and this would result in a decrease of sCr/CysC ratio. Methods: We pooled pts from 3 trials performed in pts admitted with HF (DOSE, ROSE and CARRESS-HF). eGFR was calculated using CKD-EPI-CysC equation (eGFRCysC) and sCr-based MDRD equation (eGFRsCr). The relative difference between eGFRCysC and eGFRsCr (ΔeGFR) was calculated as follows: (eGFRCysC-eGFRsCr)/ eGFRsCr. To control for confounders, we analyzed changes in sCr/CysC ratio and in ΔeGFR among pts with samples available at both admission and a subsequent time point. Results: A total of 2849 samples were available in 841 pts (age 68 ± 13, 26% female, left ventricular ejection fraction 36 ± 17%). Compared with eGFRsCr, eGFRCysC reclassified 50% of the samples to different GFR categories, mainly to more advanced renal dysfunction (Fig. A). eGFRCysC was significantly lower than eGFRsCr at all time points (Fig. B). From time of admission to all subsequent time points, sCr/CysC ratio declined while ΔeGFR widened (all p-values<0.001). At time of enrollment in CARRESS-HF, each additional day of HF admission was associated with a decline in sCr/CysC ratio of 1.5% (p=0.04). Conclusions: The use of CysC reclassifies a large proportion of pts admitted with HF to more advanced renal dysfunction when compared to sCr-based assessment. The discrepancy between CysC- and sCr-based eGFR appears to widen during HF admission, likely due to muscle mass wasting.

8049 Background: Monoclonal gammopathy of undetermined significance (MGUS) is rare in young patients (pts; age <40 years at diagnosis), with a prevalence of < 0.3%, representing approximately 2% of all patients with MGUS. We hypothesized that MGUS detected in pts <40 years of age may be associated with a higher risk of progression. Methods: We identified 249 pts with MGUS <40 yrs old, evaluated at Mayo Clinic, Rochester from 1997 to 2016. The endpoint was time to progression assessed by Kaplan-Meier method. Results: 119 were male, 130 were female. Most (n= 179, 72%) were diagnosed between the ages of 30-39. The type of MGUS was IgG 69%, IgA 10%, IgM 15%, and other 5%. 135 pts (54%) had concurrent immune-related conditions, including autoimmune, inflammatory, and infectious disorders at the time of diagnosis of MGUS. Pts without immune-related conditions tend to have higher M protein compared to pts with immune-related conditions (mean, 0.36 gm/dl VS 0.20 gm/dl, p =0.057). During follow up, the M protein resolved in 36 patients. The M protein was more likely to resolve in pts with immune-related conditions compared with pts without immune-related conditions (RR 1.91, 95% CI 1.02-3.59). Progression was seen in 16 pts: 9 smoldering multiple myeloma (SMM), 4 multiple myeloma (MM), 1 macroglobulinemia, 2 non-Hodgkin’s lymphoma. The rate of progression to SMM, MM, or related disorder at 5 and 10 years was 6.0% and 13.8%, respectively. The size of M protein was a significant risk factor for progression (HR 4.23, 95% CI 2.17-7.91) The risk of progression at 5 and 10 years for pts with immune-related conditions concurrently present when MGUS was first diagnosed was 1.5% and 10.1% respectively; corresponding rate in pts without immune-related conditions at the time of diagnosis was higher at 12.3% and 18.9%, respectively (p =0.016), (HR 2.36, 95% CI 0.85-6.52). Similar results were seen when patients in whom the M protein resolved were excluded. Conclusions: Young patients with MGUS may have a higher risk of progression, 1.4% per year; approximately 50% are diagnosed in the setting of immune-related disorders. When occurring in the setting of immune related disorders, the M protein is smaller, more likely to resolve, and may have a lower risk of progression than in pts in whom MGUS is detected without concurrent immune-related disorder.