Drug May Reduce Proteinuria

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New therapy aids renal transplant patients.

 

SAN FRANCISCO—A new study found that converting from tacrolimus/sirolimus (TAC/SRL) to TAC/enteric-coated mycophenolic sodium (EC-MPS) may reduce proteinuria in renal transplant patients.

 

The effect is independent of BP, TAC levels, and glycemic control. Researchers say the new findings support a putative role of SRL therapy in proteinuria.

 

Moreover, the investigators noted that converting from SRL to EC-MPS improved glomerular filtration rate (GFR) within six months, despite an increase in TAC exposure.

 

“We had seen cases of proteinuria with sirolimus therapy, so we were not surprised by our findings, but we were a little surprised by the consistency in the reduction, with 87% of the patients having a reduction in proteinuria,” said study investigator Joshua Augustine, MD, assistant professor of nephrology at Case Western Reserve University in Cleveland. He and his colleagues reported study findings here at the American Transplant Congress.

 

Proteinuria associated with SRL therapy in kidney transplantation has been described in the literature, often after late conversion from calcineurin inhibitors. In an ongoing conversion study of TAC/SRL to TAC/EC-MPS, he and his colleagues analyzed data on proteinuria and renal function pre-conversion and post-conversion. Patients initiated EC-MPS at a dosage of 720 mg twice a day. The researchers now have six-month follow-up data on 23 kidney recipients converted at a mean of 26 months (range: 3-57 months) post-transplant.

 

At six months, the mean urinary al-bumin:creatinine ratio (ACR) dropped to 48 µg/mg from 157 µg/mg at baseline. It decreased in 20 patients. Nine patients had ACR levels consistent with microalbuminuria (30-300 µg/mg); of these patients, seven con-verted to normal levels. Five patients had gross proteinuria by ACR (greater than 300 µg/mg) and all of them converted to microalbuminuric levels post-conversion.

 

“Proteinuria has been ignored with sirolimus in some respects and even when it is noted, not a lot is done. So I think this [study] is some evidence that by actually stopping the agent you may have an impact on decreasing the proteinuria. So, that is an option,” Dr. Augustine said.

 

The investigators observed no changes in systolic or diastolic BP after conversion and no changes in use or dosages of angiotensin blocking agents. After conversion, mean TAC serum levels increased significantly from 5.1 to 8.5 ng/mL. TAC serum levels often rose despite stable TAC dosage after conversion. Decreases in ACR were independent of TAC levels.

 

Additionally, Dr. Augustine's group observed an overall trend toward decreasing hemoglobin A1c (HbA1c), but six patients experienced an in-crease in HbA1c levels at six months.  Patients also had a mean decrease in ACR from 52 to 8 µg/mg and a mean calculated GFR increase from 44 to 49 mL/min post-conversion.

 

“We haven't seen much difference in terms of renal function in this short-term study, but we have seen improvements in proteinuria—sometimes dramatic improvements—in the non-transplant community that have pointed to improve renal function over time,” Dr. Augustine said. “We now need long-term outcome studies. For now, I think we need to monitor patients [on sirolimus] for possible increased proteinuria. However, the best way to treat it, whether to remove the drug altogether or possibly adding some agents that can reduce proteinuria, is yet to be determined.”

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