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Venous congestion and renal function in heart failure … it's complicated

For quite some time, venous congestion has been suspected as a cause of renal dysfunction (RD). Notably, in experiments dating back to the 1860s, it was shown that partial occlusion of the renal vein led to an immediate decline in renal blood flow, glomerular filtration rate (GFR), and sodium excretion, with resolution of the abnormalities after relief of the congestion. The concept of decreased perfusion pressure (arterial pressure – venous pressure) causing organ dysfunction is an intuitive explanation for these observations. Perhaps as a result, the recent publication of several studies demonstrating an association between venous congestion and RD appeared to confirm that the observations from animal models translate to human heart failure (HF). –8 However, upon close inspection of these data, we see that many of the reported associations were actually not consistent with findings from animal models. Notably, the association between baseline RD and venous congestion was heterogeneous across studies, and either improvement, no change, or even worsening of renal function (WRF) was observed with relief of the congestion. One possible explanation for these seemingly contradictory results could be that some studies were wrong. However, it is more likely that the interaction between biology, treatment, and epidemiology resulted in a situation substantially more complex than that found in an animal with a partially occluded renal vein. That being said, even in the experimental setting, the physiology appears to be more complicated than a simple direct hydraulic effect of decreased perfusion pressure causing worsened organ function. One of the primary mechanisms actually appears to involve an increase in renal vascular resistance, including an increase in afferent arteriolar resistance. Notably, this reflex appears to involve the sympathetic nervous system, since intrarenal infusion of phentolamine or renal denervation largely abolishes the effect. Additionally, a direct effect of increased renal interstitial pressure causing tubular collapse and opposition of flow into Bowman’s space has been proposed. However depending on the hydration status of the animal, an experimental increase in renal venous pressure produces differential effects on renal interstitial pressure and renal function, highlighting the secondary importance of direct hydraulic effects. Notably, in dogs without volume overload, an increase in renal venous pressure up to 40 mmHg actually caused an increase in sodium excretion and no change in GFR or renal blood flow. However, it must be stressed that the venous congestion induced in these experimental set-ups is completely different from that seen clinically in HF. In these experiments, the most common approach was to constrict the renal veins selectively. In human HF, the entire venous system is congested. This is important due to the pronatriuretic/renal-preserving effects of overall venous congestion that may counterbalance the direct local effects of renal venous congestion (i.e. increased natriuretic peptide release and decrease in renal sympathetic nerve activity with cardiac distention). Furthermore, the techniques by which venous congestion is investigated in human research vary by study, and each has its own limitations, such as limited reproducibility and large interobserver variability. For example, the most commonly employed surrogate for venous congestion has been central venous pressure (CVP). However, we often forget that due to the remarkable compliance of the venous system, pressure and volume have very poor correlation. A recent meta-analysis of studies comparing CVP with directly measured blood volume found a pooled correlation coefficient of 0.16, indicating that only 2.5% of the variability in CVP across a population can be explained by differences in blood volume. The reason for this lack of correlation stems from the fact that venous pressure is the combined representation of both volume and venous tone, a relationship evolved for the critical purpose of maintenance of cardiac preload over the physiological range of blood volume encountered in life. This is relevant to the study of venous congestion-induced RD for two reasons. (i) In animal models,