{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T22:33:07Z","timestamp":1785537187974,"version":"3.56.0"},"reference-count":33,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T00:00:00Z","timestamp":1728432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T00:00:00Z","timestamp":1728432000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Nephrol"],"abstract":"<jats:p>Introduction: There are conflicting reports about the effect or rapamycin on the kidneys. Rapamycin is known to promote phosphaturia that may be associated to renal injury. Methods: Detailed histopathological studies were performed on the kidneys of rats with normal (control) and reduced (Nx) renal mass that were treated with rapamycin (1.3 mg\/kg for 22 days) or placebo. The effect of rapamycin was also evaluated in control and Nx rats fed different amounts of phosphorus: 0.6% P (NP), 1.2% P (HP), and 0.2% P (LP). Quantitative scores of kidney lesions were obtained for interstitial nephritis (IN), tubular damage (TD), and nephrocalcinosis (NC). Results: When compared with placebo, rapamycin administration to Nx rats resulted in significant increases in IN (4.17 \u00b1 0.74 vs. 1.51 \u00b1 0.53%) and TD (14.45 \u00b1 1.51 vs. 8.61 \u00b1 1.83%). Rapamycin also increased NC both in control (0.86 \u00b1 0.23 vs. 0.14 \u00b1 0.06%) and Nx (0.86 \u00b1 0.32 vs. 0.15 \u00b1 0.14%) rats. In control rats receiving rapamycin, feeding HP aggravated IN (3.25 \u00b1 0.48%), TD (22.47 \u00b1 4.56%), and NC (3.66 \u00b1 0.75%), while feeding LP prevented development of any renal lesions. In Nx rats treated with rapamycin, HP intake also increased IN (8.95 \u00b1 1.94%), TD (26.86 \u00b1 3.95%), and NC (2.77 \u00b1 0.60%), whereas feeding LP reduced all lesions to lower levels than in rats fed NP. Rapamycin treatment increased fractional excretion of P (FEP), and an excellent correlation between scores for renal lesions and FEP was found. Conclusion: Rapamycin has deleterious effects on kidney pathology causing lesions that are located mainly at tubular and tubulointerstitial level. Rapamycin-induced kidney damage is more evident in rats that already have decreased renal function and seems to be related to the phosphaturic effect of the drug. 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