Sirolimus for Polycystic Kidney Disease

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New treatment options for polycystic kidney disease do not come along very often. The nature of the disease is such that treatment is inherently difficult as the pathophysiology is incompletely understood.

Despite that various methods are currently being investigated. One such is the drug sirolimus, which  has been mentioned before. More recently however a pilot study performed in adult polycystic kidney disease patients has added further hope that sirolimus may one day be used routinely in this disease.



The effect of the drug sirolimus on development and growth of cysts was investigated over 6 consecutive months in 8 patients. Patients also received angiotensin receptor blockers which are considered standard therapy in kidney disease. A control group that consisted of another 8 patients were assigned to angiotensin receptor blocker alone.

Unfortunatley sirolimus is not an innocuous drug its use results in suppression of the native immune system resulting increased risk of infection and negative metabolic effects. There is however a good history of safety in transplantation where it is used primarily.

The use of sirolimus will require close monitoring for possible infectious complications if it is to provide an overall benefit. Patients with adult polycystic kidney disease already have an increased risk of infection and these may include infection of cysts and pyelonephritis which can cause sepsis. An increase in the rate of these infections would have a negative effect on survival of the kidney. The drug may therefore prove to have what is called a narrow therapeutic index for treatment of patients with ADPKD.

The overall result of this small study showed a beneficial effect of sirolimus in patients with ADPKD however please note there was a significant rate of infectious complication. A larger study would have been able to tell us whether the benefits of sirolimus administration truly outweigh the risks for LONG term treatment of patients with polycystic kidney disease.

ABSTRACT below.

A pilot study was performed on adult polycystic kidney disease (PCKD) patients to examine the effects of the anti-proliferative mammalian target of rapamycin inhibitor sirolimus on the growth of renal cysts. Eight consecutive PCKD patients were given sirolimus (1 mg/d PO) for 6 consecutive months, in addition to an angiotensin receptor blocker (ARB), namely telmisartan. Another 8 PCKD patients served as a control group given only telmisartan. All PCKD patients had a serum creatinine value <2 mg/dL with a negative urine culture before enrollment. All patients were diagnosed by renal magnetic resonance imaging (MRI) to measure renal volumes. After a 6-month follow-up, patients were rescanned to remeasure the MRI volumes. Renal function was stable in 5/8 subjects in the sirolimus group, improved in 2 cases, and worsened in 1 with an increase of serum creatinine to >2 mg/dL resulting in his withdrawal after 5 months of follow-up. In contrast, the serum creatinine value was stable in 3 control group subjects, worsen in 3, and improved in 2. Four patients in the sirolimus group experienced infectious complications, namely, urinary tract infections (UTI) in 2 which were treated with antibiotics, and monilial pharyngitis in 2, who were treated and cured with a topical antifungal. In the control group, only 2 developed and were treated for UTIs. Hematologic tests were normal in all patients. There was an insignificant rise in kidney volume as measured by MRI in the sirolimus group (2845 vs 3221 mL after 6 months; P = NS) compared with a significant increase in the control group (2667 vs 3590 mL after 6 months; P < .05). We concluded that sirolimus, in addition to an ARB, might be beneficial for PCKD patients who present early in their illness.