Biomarkers associated with worsening renal function and progression in chronic kidney disease among patients hospitalized for acute heart failure.

Introduction: Worsening renal function (WRF) is associated with poor prognosis in patients with heart failure (HF). Osteopontin (OPN) and Matrix extracellular phosphoglycoprotein (MEPE) are expressed in the kidneys and are involved in bone mineralization processes. Higher OPN levels have been associated with a higher risk for adverse outcomes in patients with chronic kidney disease (CKD), and MEPE has been shown to promote renal phosphate excretion. Here, we explored if MEPE and OPN are associated with WRF and CKD in patients admitted for acute HF.

Methods: WRF was defined as an increase in plasma creatinine of >26.5 mmol/L or 50% higher than admission concentration within 48 hours of admission. OPN and MEPE were analyzed in 315 HF patients at baseline, and in 120 patients at 6-month follow-up. Associations between MEPE and OPN, and a) WRF, b) CKD stage 3-5, and c) markers of kidney function were explored. Further, OPN and MEPE at baseline and at 6 month follow-up (delta (Δ) values) were related to CKD progression.

Results: The study population had a mean age of 75 (±12) years and 31% were women. Higher levels of MEPE and OPN were associated with WRF (n=30; OR 2.80 (1.49-5.25); p=0.001, and OR 1.84; (1.05-3.23); p=0.034, respectively)). On admission, both MEPE and OPN were associated with CKD stage 3-5 (OR 5.27; (2.76-10.07); p<0.001, and OR 3.26; (1.90-5.60); p<0.001, respectively)). At 6-month follow-up, progression in CKD stage was associated with ΔMEPE and ΔOPN (HR 2.53; (1.48-4.31); p<0.001, and HR 2.66; (1.51-4.71); p<0.001)).

Conclusion: Here, MEPE and OPN are for the first time shown to be independently associated with WRF and subsequent deterioration in CKD in a HF cohort. The mechanisms of these associations are currently largely unknown and need to be investigated further.