Time for a comeback of NSAIDs in proteinuric chronic kidney disease?

Before the introduction of renin-angiotensin-aldosterone system (RAAS) inhibitors in the 1980s, non-steroidal anti-inflammatory drugs (NSAIDs) were the only class of drugs available for the reduction of symptomatic proteinuria. Long-term data from those days suggested sustained renoprotective properties in proteinuric chronic kidney disease (CKD), but this potential has not been further explored, due to the adverse effects of NSAIDs, and due to the successful introduction of RAAS blockade for blood pressure control and renoprotection. The renoprotective potential of NSAIDs may seem surprising for the present generation of clinicians, as NSAIDs are well known for their adverse effects on the kidney. Interestingly, the newer selective COX-2 inhibitors (coxibs), such as non-selective (ns) NSAIDs, exert an antiproteinuric effect in CKD patients. This review discusses the role of NSAIDs as a class of drugs representing an old concept for renoprotection in the light of current insights on renoprotection. It has become increasingly clear during the last two decades, from evidence obtained almost exclusively in studies using RAAS blockade, that not only reduction of blood pressure, but also of proteinuria is a prerequisite for long-term renoprotection. Ns-NSAIDs and coxibs reduce proteinuria without reduction of blood pressure. Their possible role as an adjunct in individualised treatment strategies, particularly for individual patients resistant or intolerant to current therapy, will be discussed.