#1760 Four cases of ADTKD: AFM analysis of urine sediment

Abstract

Abstract Background and Aims Autosomal Dominant Tubulointerstitial kidney disease (ADTKD) is a rare disease (16 per million), associated with CV events, hypertension, and gout. ADTKD is characterized by interstitial fibrosis, tubular atrophy, microcysts, and progressive CKD. We describe a case of a family with clinical characteristics of ADTKD and provide for the first time a characterization of their urinary sediment. Given the tendency of a specific type of ADTKD caused by UMOD mutation to form tubular crystals, we have also tested the ability of the urine from ADTKD patients to precipitate and form crystals in vitro. Method We examined clinical features and urinary sediment of a family with ADTKD: a 51 years old woman with CKD (eGFR 30 mL/min/1.73 m2, CDK-EPI 2021) and her three sons, a 20 years old male, two daughters of 26 and 24 years old, all with hyperuricemia. Genetic analysis is not yet available. The test of urine precipitation consisted of the analysis of crystals after air-drying a thin layer of urine after enrichment of the organic quota by triple centrifugation for 10 minutes at 1000 rpm. Urinary sediments were also studied by Atomic Force Microscopy (ICSPI nGauge AFM) to achieve a resolution of 20 nm of crystals. Results Clinical data for the four patients are reported in the table. None of the patients showed proteinuria. The urine sediment of all patients showed rare WBC (in greater amounts only in patient 1), rare amorphous granular casts, and rare tubular cells. Three patients showed formations of variably sized crystals in vitro. The precipitation test did not show crystals in patient 1, whereas patients 2-3 showed several rosette-type crystals often with a wagon-wheel concentric contour which resembled leucine crystals or CaCO3. Adding formalin to the samples resulted in a more clear organization of crystals in wagon-wheel structures. AFM imaging of the crystals showed rod-like structures branching with an angle of 35°. Conclusion ADTKD remains a poorly understood genetic condition with no specific treatment options. Our data suggest that patients with this condition may have an enhanced tendency to form crystals in vitro. Speculatively, this might induce tubular injury in vivo. Data from UMOD-ko animal models showed intrarenal crystals (not better specified). Genetic alterations of branched aminoacids metabolism (such as leucine in Maple syrup disease) can also cause tubular diseases, although the systemic manifestations are very different from our patients. Genetic analysis of our family will give further information on the proteins involved in these crystal structures.