Urine Nephrology Now: A Primer for Students in Nephrology
Edema is the accumulation of excess fluid in the interstitial space. Its formation is governed by the balance of hydrostatic and oncotic pressures across capillary walls, as described by the Starling principle, as well as lymphatic drainage.
Modern understanding emphasizes the role of the endothelial glycocalyx as the primary filtration barrier and recognizes that fluid exchange is a dynamic process, with a constant small net filtration that is normally cleared by the lymphatic system. Edema occurs when filtration exceeds lymphatic clearance.
In heart failure, both "forward failure" (reduced cardiac output and renal perfusion) and "backward failure" (increased venous congestion) contribute to edema. Elevated central venous pressure is transmitted to the capillaries, increasing hydrostatic pressure and driving fluid into the interstitium. This venous congestion also impairs renal function, a concept known as the "renal tamponade" hypothesis, leading to sodium and water retention.
In decompensated heart failure, intestinal wall edema can significantly impair the absorption of oral medications, including loop diuretics like furosemide. This contributes to apparent diuretic resistance.
Bumetanide and Torsemide have better and more predictable oral bioavailability (80-90%) compared to furosemide (40-60%) and are less affected by gut edema, making them useful alternatives when oral furosemide is ineffective.
Many common medications can cause peripheral edema. It is crucial to consider medications as a potential cause in any patient presenting with new-onset swelling.
| Medication Class | Mechanism | Frequency/Notes |
|---|---|---|
| Calcium Channel Blockers (e.g., Amlodipine) | Preferential precapillary arteriolar vasodilation increases capillary hydrostatic pressure. | Very common, dose-dependent. Up to 16% with amlodipine. Can exceed 80% with very high doses. Less common when combined with an ACEi/ARB. |
| NSAIDs | Inhibition of prostaglandins leads to sodium and water retention. | Common, but usually mild (1-2 kg weight gain). Occurs early after initiation. |
| Thiazolidinediones (TZDs) (e.g., Pioglitazone) | Activation of PPAR-gamma receptors in the collecting duct increases sodium reabsorption. | Occurs in <5% on monotherapy, but up to 15% when combined with insulin. Dose-related. |
| Gabapentinoids (Gabapentin, Pregabalin) | Similar to CCBs; effect on voltage-gated calcium channels causes peripheral vasodilation. | Common side effect (1-10% frequency). |
| Corticosteroids | Direct mineralocorticoid effects causing salt and water retention. | Very common. Can cause facial swelling ("moon face") as well as peripheral edema. |
In hypoalbuminemic states, diuretic delivery to the kidney can be impaired because loop diuretics like furosemide are highly protein-bound for transport to their site of action in the renal tubule.
The evidence supports co-administration of albumin with furosemide primarily in patients with severe hypoalbuminemia and diuretic resistance. The benefit is most pronounced when:
The effect is often transient, peaking at 6-8 hours. It should be considered a rescue therapy rather than routine practice. Before using albumin, ensure the diuretic dose is optimized and IV administration has been trialed.