[Amoxicillin induced crystal nephropathy : Monitoring of residual plasma levels]. / Cristalluries sous amoxicilline : intérêt du monitoring des concentrations plasmatiques résiduelles.

Since 2010, a lot of cases of amoxicillin induced crystal nephropathy have been reported to the French pharmacovigilance centers partly due to the high doses recommended by infectious disease guidelines. Typical clinical presentation and exclusion of others toxics or immuno-allergic causes are mandatory to assess the diagnostic. Amoxicillin crystals are rarely found or searched and renal biopsy is not frequently performed due to technical reasons and prompt renal recovery after antibiotics withdrawal. Monitoring of residual plasma concentration is rarely used in clinical practice for diagnostic or prognostic interest. We present 9 consecutive cases of acute kidney injury suspected to be due to amoxicillin crystals with residuals plasma levels to disclose a predictive threshold of tubulopathy. All patients had a high residual rate at diagnosis but we cannot find a threshold that would allow to adapt the antibiotic dose, enhance hydratation and alkalinizide urine to increase the medication solubility and limit renal toxicity.

Conversion to mammalian target of rapamycin inhibitors increases risk of de novo donor-specific antibodies.

In kidney transplantation, conversion to mammalian target of rapamycin (mTOR) inhibitors may avoid calcineurin inhibitor (CNI) nephrotoxicity, but its impact on post-transplant allo-immunization remains largely unexplored. This retrospective cohort study analyzed the emergence of donor-specific antibodies (DSA) in kidney transplant recipients relative to their immunosuppressive therapy. Among 270 recipients without pretransplant immunization who were screened regularly for de novo DSA, 56 were converted to mTOR inhibitors after CNI withdrawal. DSA emergence was increased in patients who were converted to mTOR inhibitors (HR 2.4; 95% CI 1.06-5.41, P = 0.036). DSA were mainly directed against donor HLA-DQB1 antigens. The presence of one or two DQ mismatches was a major risk factor for DQ DSA (HR 5.32; 95% CI 1.58-17.89 and HR 10.43; 95% CI 2.29-47.56, respectively; P < 0.01). Rejection episodes were more likely in patients converted to mTOR inhibitors, but this difference did not reach significance (16% vs. 7.9%, P = 0.185). Concerning graft function, no significant change was observed one year after conversion (P = 0.31). In conclusion, conversion to mTOR inhibitors may increase the risk of developing class II DSA, especially in the presence of DQ mismatches: this strategy may favor chronic antibody-mediated rejection and thus reduce graft survival.