Characterizing Renal Dysfunction in the Face of Hypertension and Heart Failure

Recent work highlights how small decrements in renal function, even those that are transient, have significant negative prognostic effects on outcomes in patients with heart failure. Yet, it is unclear if heart failure secondarily leads to diminished renal function or if mild renal dysfunction leads to progression of functional cardiac deterioration. To better understand the association between the concomitant development of renal dysfunction and heart failure, a comprehensive assessment of renal function in the male spontaneously hypertensive, heart failure‐prone rat (SHHF) was performed. Various biomarkers of renal function were evaluated. At 37‐40 weeks, severe hypertension (MAP greater than 170) was measured in all SHHF rats. Serum albumin content in the SHHF was significantly diminished throughout the experimental period, indicating the possibility of renal dysfunction. Although the ratio of serum urea to creatinine increased significantly in SHHF, creatinine levels remained normal, suggesting that renal filtration is likely not compromised and that the increase is a reflection of inadequate blood flow. To corroborate this possibility further, cortical peritubular capillary networks were imaged using intravital microscopy and showed that renal microvascular blood flow in SHHF was, in fact, diminished. Together, these data confirm that renal dysfunction occurs in the setting of hypertension and heart failure, and is an early manifestation of blood flow deficits. We now offer an alternative pathway to the conventional thinking of the cardiorenal axis that should serve as a stimulus for developing novel therapeutic interventions for heart failure.