Renal involvement in hereditary transthyretin amyloidosis (hATTR) is relatively rare, although it may be underdiagnosed, according to a multicenter, retrospective, observational study involving 3 Italian ATTR referral centers.

“Our data showed that renal involvement in hATTR is apparently uncommon in our country, and the underlying etiopathogenetic mechanism is cardiorenal syndrome without detectable proteinuria in most of the hATTR patients with CKD [chronic kidney disease],” the study’s authors said.

However, it is possible that the number of hATTR cases with renal involvement is underestimated because renal biopsy is not a standard procedure in patients with hATTR.

The study found that 44 of 165 patients had CKD. Of those, 18 presented with renal injury without a known cause, thus the renal involvement was considered as possibly secondary to the TTR mutation. One patient with Val30Met mutation-associated hATTR had TTR amyloid deposits on their renal tissue and developed CKD at 43 years of age. Moreover, 4 other patients had nephropathies, including membranous nephropathy in 2 cases.

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In addition, the analysis of a subgroup with Val142Ile mutation-associated hATTR showed that 6 of 10 patients had CKD, but only 1 patient had proteinuria unrelated to any other disease. Furthermore, 8 patients of the subgroup had cardiorenal syndrome due to severe chronic heart failure or previous decompensated heart failure episodes.

“Although renal biopsy is not routinely required, it might be recommended when determining the indication for tafamidis, patisiran, or inotersen treatment in hATTR amyloidosis patients,” the authors suggested.

Allinovi et al conducted a survey based on questionnaires from 165 hATTR-symptomatic patients. The study cohort encompassed 34 different TTR mutations.

Renal involvement in hATTR could be caused by cardiorenal syndrome or direct amyloid deposition. In the case of cardiorenal syndrome, patients usually present with stage 2 or 3 CKD with or without mild proteinuria. On the other hand, direct amyloid deposition leads to renal injury outbreaks with microalbuminuria, which eventually progress to overt proteinuria and renal failure. Nearly 15 different TTR mutations have been associated with this renal phenotype.

Reference

Allinovi M, Bergesio F, Cappelli F, et al. Is hereditary transthyretin amyloidosis the third leading cause of monogenic chronic kidney disease, only behind ADPKD and Alport disease? Am J Nephrol. 2022; 53:624–627. doi:10.1159/000526955