The kidney in congestive heart failure: ‘are natriuresis, sodium, and diuretics really the good, the bad and the ugly?’

Abstract

This review discusses renal sodium handling in heart failure. Increased sodium avidity and tendency to extracellular volume overload, i.e. congestion, are hallmark features of the heart failure syndrome. Particularly in the case of concomitant renal dysfunction, the kidneys often fail to elicit potent natriuresis. Yet, assessment of renal function is generally performed by measuring serum creatinine, which has inherent limitations as a biomarker for the glomerular filtration rate (GFR). Moreover, glomerular filtration only represents part of the nephron's function. Alterations in the fractional reabsorptive rate of sodium are at least equally important in emerging therapy‐refractory congestion. Indeed, renal blood flow decreases before the GFR is affected in congestive heart failure. The resulting increased filtration fraction changes Starling forces in peritubular capillaries, which drive sodium reabsorption in the proximal tubules. Congestion further stimulates this process by augmenting renal lymph flow. Consequently, fractional sodium reabsorption in the proximal tubules is significantly increased, limiting sodium delivery to the distal nephron. Orthosympathetic activation probably plays a pivotal role in those deranged intrarenal haemodynamics, which ultimately enhance diuretic resistance, stimulate neurohumoral activation with aldosterone breakthrough, and compromise the counter‐regulatory function of natriuretic peptides. Recent evidence even suggests that intrinsic renal derangements might impair natriuresis early on, before clinical congestion or neurohumoral activation are evident. This represents a paradigm shift in heart failure pathophysiology, as it suggests that renal dysfunction—although not by conventional GFR measurements—is driving disease progression. In this respect, a better understanding of renal sodium handling in congestive heart failure is crucial to achieve more tailored decongestive therapy, while preserving renal function.

Urinary Composition During Decongestive Treatment in Heart Failure With Reduced Ejection Fraction

“…16 Finally, increased proximal Na + reabsorption because of poor renal perfusion and intravascular underfilling might contribute to the braking phenomenon. 11 Alternatively, if effective decongestion is achieved and, therefore, diuretic resistance is unlikely, a drop in urinary Na + and Cl − concentrations after diuretic administration might indicate electrolyte depletion.…”

“…[7][8][9][10] From a pathophysiological perspective, volume status is in fact governed by renal sodium (Na + ) homeostasis, which might be substantially altered in HF. 11 Yet, surprisingly few studies have actually assessed urinary composition, including Na + and chloride (Cl − ) concentrations, in addition to urine output during decongestive treatment. We hypothesized that such qualitative analysis of diuresis might offer additional information in support to quantitative measurements of urine volume that are classically performed.…”

Effects of Additive Tolvaptan vs. Increased Furosemide on Heart Failure With Diuretic Resistance and Renal Impairment ― Results From the K-STAR Study ―

“…There are many reasons for loop diuretic resistance, 20 with scant evidence from high-quality randomized clinical trials. Particularly in HF patients, diuretic resistance may occur when renal perfusion decreases, likely from low cardiac output.…”

Determinants and impact of the natriuretic response to diuretic therapy in heart failure with reduced ejection fraction and volume overload

“…Finally, as combination therapy with potassium-wasting diuretics increases the risk of hypokalaemia, all patients received once daily oral spironolactone at a dose of 25 mg, unless serum potassium levels were > 5.0 mmol/L. All oral diuretics, including spironolactone, were administered in the morning, 1 h before the intravenous nephron with increased aldosterone production after prolonged use of loop diuretics, excessive sodium reabsorption in the proximal tubules, and post-diuretic sodium retention because of diuretic-induced neurohumoral activation may all contribute to diuretic resistance with insufficient natriuresis [3][4][5] . Consequently, it remains very difficult in clinical practice to predict how an individual patient with decompensated HF will respond to diuretic therapy and to appropriately choose the right dose and type of diuretics.…”

“…in peritubular capillaries, driving sodium reabsorption in the proximal tubules and potentially contributing to loop diuretic resistance 5,[13][14][15] . Only a few small-scale and largely outdated studies have evaluated combination therapy with acetazolamide in decompensated HF, yet they did show promising results to break loop diuretic resistance 16,17 .…”