Renal salt wasting syndrome (RSWS) due to cisplatin has rarely been reported and is often confused with SIADH as a cause of hyponatremia (as discussed by Nate in a prior post). Increased urinary sodium (more than the intake) and increased urinary output in a hypovolemic patient are the key findings that help in differentiating this entity from SIADH (Table). Knowing this difference between these entities is important as RSWS is treated with sodium supplementation as opposed to water restriction with SIADH. Cerebral salt wasting has similar presentation as RSWS but has an associated cerebral lesion.
How hyponatremia occurs with cisplatin therapy can be understood by reviewing the mechanism of cisplatin nephrotoxicity. Briefly, cisplatin is a tubular nephrotoxin and causes;
- Dose dependant nephrotoxicity by particularly affecting the S3 segment of the proximal tubule, and to a lesser extent the loop of henle and the distal collecting system.
- Cisplatin enters the cells via the OCT2 transporters on the basolateral surface.
- Leads to decreased ATPase and mitochondrial activity.
- Activates proinflammatory cytokines
- Induces hypoxia
- All of which contribute to cell apoptosis and death.
Cisplatin, interestingly, may decrease the abundance of aquaporin channels in the cortical and medullary collecting duct, as shown in animal studies, thereby further contributing to impaired urinary concentration and polyuria. This may, in fact, limit the degree of the hyponatremia (secondary to decreased water reabsorption) that develops with salt wasting from proximal tubule dysfunction. Not surprisingly, patients with cisplatin nephrotoxicty often tend to be quite polyuric.
In conclusion, why cisplantin induced RSWS occurs so rarely, is unclear. It is possible that the condition may be under reported or frequently overlooked.
Viresh Mohanlal, MD