Cyclosporin A nephropathy: standardization of the evaluation of kidney biopsies

An advisory board of nephropathologists with personal experience in the evaluation of biopsies from patients treated with cyclosporin A (CyA) was set up to address the following problems: 1. Definition of CyA nephropathy as seen in patients with autoimmune diseases; 2. Evaluation of the reliability and reproducibility of the diagnostic criteria for the different morphological lesions seen in CyA nephropathy; 3. Classification of the morphological lesions according to their clinical relevance; 4. Estimation of the possible progression of CyA nephropathy with continuous CyA therapy. The most frequent lesions attributable to CyA therapy in patients with autoimmune diseases are tubular atrophy, interstitial fibrosis, and arteriolar hyalinosis. All other lesions are rare. The reproducibility and diagnostic reliability is high for tubular atrophy and interstitial fibrosis, but low for arteriolar lesions even among experienced nephropathologists. The biopsies may be classified according to the severity of tubular atrophy, interstitial fibrosis and arteriolar hyalinosis with regard to their clinical relevance: In group I (within normal limits), CyA therapy can be continued; in group III (moderate-to-severe CyA-related lesions), CyA should be stopped if possible. Among group II biopsies (slight CyA-related abnormalities), no recommendation can be made in the absence of a second biopsy after a further year of CyA therapy. No clear-cut answer can be given concerning the progression of CyA-induced lesions. However, no significant progression has been found in the cases studied to date.