Evaluation of tubular renal function in hereditary transthyretin amyloidosis.

Hereditary transthyretin amyloidosis (ATTRv) is a progressive, autosomal dominant multisystem disorder. While nerves and heart are most affected, the kidneys may also be involved. Renal amyloid deposition may involve glomeruli and other compartments. Subclinical tubulointerstitial involvement may be an early sign. We aimed to assess tubular function in ATTRv. We conducted a cross-sectional study of ATTRv patients aged>18 years with an estimated GFR>45mL/min/1.73m2. Participants underwent a 12-h water deprivation test. We assessed urine biomarkers: albumin, protein, β2-microglobulin (uβ2M), gamma-glutamyltransferase (uϒGT), specific gravity by dipstick (uSG), and urine osmolality (uOSM) to detect urinary concentrating disorder (UCD). Fractional excretion was calculated from a 24-h urine collection. We used Spearman correlation and ROC curve analysis. Among 49 subjects (median age 40; 63% female; 84% Caucasian), 94% had the V50M variant and 57% had neurologic or cardiac symptoms. Uβ2M was elevated in 2 subjects; 53% had UCD. uSG correlated with uOSM (Rho=0.78, p<0.001); uSG>1.015 excluded UCD (AUC=0.89). The symptomatic subgroup (n=28) had a higher prevalence of UCD. The UCD subgroup (n=26) had more neuro/cardiac symptoms. uϒGT was elevated in 35%. uϒGT levels did not differ between subgroups. ATTRv individuals with preserved renal function had a high prevalence of UCD and increased uϒGT. Further studies should explore the clinical impact and treatments.