Reducing Urinary Protein Improves Survival for Patients With Rare Kidney Disease

September 20, 2020

Researchers suggest that clinical trial design could be shaped by measuring reductions in urinary protein.

A recent study that measured reductions in urinary protein in patients with a rare kidney disease left researchers looking for more ways to use this important marker of renal function.

An study published August 10 in the American Journal of Kidney Diseases examined the role of proteinuria in focal segmental glomerulosclerosis (FSGS), a condition in which scar tissue forms on the glomeruli, the areas of the kidneys that filter waste from the blood. FSGS is not curable, but treatment can slow its progression.

Jonathan P. Troost, PhD, of the University of Michigan in Ann Arbor, and co-authors studied the connection between reducing urinary protein through treatment and kidney survival. They examined 138 patients with steroid-resistant FSGS who had enrolled in a randomized trial that compared two drugs typically used as immunosuppressants to prevent organ rejection: cyclosporine, or mycophenolate mofetil plus dexamethasone.

Over 26 weeks, changes in urinary protein levels were significantly related to those in the estimated glomerular filtration rate (eGFR). Each 1-unit reduction in urinary protein was associated with a 3.90 mL/year increase in eGFR (95% CI=2.01 to 5.79), and this remained significant after adjusting for remission.

The results translated into survival benefits: the authors wrote that each 1-unit reduction in log-transformed urinary protein to creatinine ratio was associated with a 77% reduction in end-stage kidney disease or renal death.

Such results have many implications. “These novel findings expand on previous reports showing that complete and partial proteinuria remissions are associated with large clinical benefit, and also suggest that reduction in proteinuria — even if not to a complete remission — is still associated with improved survival,” they wrote.

Proteinuria is already an important tool in detecting renal damage, risk of infection, or finding patients at increased cardiovascular risk. Glomerular proteinuria is a key assessment of renal function. Renal outcomes have been a focus of recent trials involving sodium glucose co-transporter 2 (SGLT2) inhibitors, for example, but have focused on eGFR and CV or renal death as end points. The authors suggest adding proteinuria along with other predetermined end points in clinical trials would give researchers an additional tool to evaluate therapies.

"Reductions in proteinuria warrant further evaluation as a potential surrogate for preservation of kidney function that may inform the design of future clinical trials," they write.

Reference

Troost JP, Trachtman H, Spino C, et al. Proteinuria reduction and kidney survival in focal segmental glomerulosclerosis. Am J Kidney Dis. Published online August 10, 2020. doi:10.1053/j.ajkd.2020.04.014