Adding the herbal preparation silymarin to a renin-angiotensin system (RAS) inhibitor may decrease proteinuria in patients with diabetic nephropathy, new findings suggest.

Researchers studied 60 patients with type 2 diabetes and macroalbuminuria (urinary albumin excretion greater than 300 mg/24 hours) despite treatment with the maximum dose of an RAS inhibitor for more than six months. All subjects had an estimated glomerular filtration rate above 30 mL/min/1.73 m2. The researchers, led by Mohammad Kazem Fallahzadeh, MD, of Shiraz University of Medical Sciences in Shiraz, Iran, randomly allocated patients to receive three 140 mg tablets of silymarin or three tables of placebo daily for three months.

Compared with patients in the placebo arm, silymarin recipients experienced a significantly greater decrease in the urinary albumin-creatinine ratio (UACR) from baseline to the end of the treatment period, according to an online report in the American Journal of Kidney Diseases. The UACR decreased by a mean of 566 mg/g in the silymarin recipients versus 219 mg/g in the placebo group.

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In addition, urinary levels of the inflammatory marker tumor necrosis factor (TNF)-alpha and urinary and serum levels of malondialdehyde (an oxidative stress marker) decreased significantly in the silymarin group compared with the placebo arm.

The possible mechanisms underlying the observed efficacy of silymarin may be inhibition of inflammatory mediators such as TNF-alpha and attenuation of oxidative stress.

Except for gastrointestinal disturbances and headache in a few patients, the authors stated, silymarin was safe and without major adverse effects.

Silymarin is a lipophilic extract that has potent antioxidant, anti-inflammatory, and antifibrotic properties, the researchers noted, and it has been used for various ailments since ancient times. Recent studies have shown the efficacy of this extract in reducing proteinuria and halting progression of diabetic nephropathy in animal models of diabetes, they stated.

Dr. Fallahzadeh and his colleagues noted that RAS activation has a major role in the pathogenesis of diabetic nephropathy, and RAS inhibition with ACE inhibitors or angiotensin receptor blockers is the mainstay of diabetic nephropathy management. Despite RAS inhibition, however, diabetic nephropathy progresses to end-stage renal disease in a large proportion of patients, the investigators observed. “This shows that in addition to the RAS, other pathways are involved in the pathogenesis of diabetic nephropathy, and suggests that finding ways to block these pathways could lead to new treatments.”