Renal Involvement in Hereditary Transthyretin Amyloidosis: An Italian Single-Centre Experience

Abstract

Objective: Hereditary transthyretin amyloidosis (ATTRv) represents a diagnostic challenge considering the great variability of clinical presentation and multiorgan involvement. In the present study, we report the prevalence of kidney involvement and kidney function over time in a cohort of ATTRv patients with different transthyretin gene mutations. Patients and Methods: For this study, we systematically collected data from all patients with a diagnosis of ATTRv followed at the Neurology Unit of Fondazione Policlinico Universitario A. Gemelli IRCCS. Kidney involvement was defined as presence of estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 obtained with CKD-EPI equation, abnormal urinary protein excretion (UPE) (>150 mg/24 h) and/or albuminuria >30 mg/24 h (or mg/g creatinine). The analysis included data from 46 patients with 122 measurements of serum creatinine. Results: Among the 46 patients included in the analysis, kidney involvement was present in 37%, with 15% showing reduced eGFR and 22% abnormal UPE (63% of patients with available UPE data). No single predictor was associated with either eGFR values or its slope over time. Conclusions: Kidney involvement is quite common in patients with ATTRv regardless of the underlying genetic variant. In particular, abnormal UPE appears to be a common feature of the disease.

Kidney involvement in hereditary transthyretin amyloidosis: a cohort study of 103 patients

“…Ferraro et al . [ 13 ] reported a prevalence of CKD of 15% in a cohort of 46 patients with ATTRv (mostly with the F64L and V30M mutations). Gertz et al .…”

“…In France, due to a more important intermingling of the population, the mutations are more diverse [ 11 , 12 ]. Patients with a TTR gene mutation other than V30M may actually present kidney involvement [ 1 , 13 ], and they are still under represented in the literature.…”

Novel approaches to diagnosis and management of hereditary transthyretin amyloidosis

“…Renal disease, manifesting as proteinuria, nephrotic syndrome and progressive renal failure, occurs in one-third of Portuguese patients (Val30Met), most commonly evident in the late-onset phenotype 38 39. Microalbuminuria can be the first abnormality, and 10% develop end-stage renal disease secondary to vascular and glomerular amyloid depositions.…”

“…Renal disease, manifesting as proteinuria, nephrotic syndrome and progressive renal failure, occurs in one-third of Portuguese patients (Val30Met), most commonly evident in the late-onset phenotype. 38 39 Microalbuminuria can be the first abnormality, and 10% develop end-stage renal disease secondary to vascular and glomerular amyloid depositions. Ocular involvement, manifesting as dry eyes and keratoconjunctivitis, vitreous opacity due to amyloid deposition, cataracts, secondary open-angle glaucoma and retinal amyloid angiopathy may be evident in up to 25% of patients with ATTRv typically evident with Val30Met mutations.…”

Nerve Conduction Studies of Dorsal Sural Nerve: Normative Data and Its Potential Application in ATTRv Pre-Symptomatic Subjects

“…Hereditary transthyretin amyloidosis (ATTRv; v for “variant”) is an autosomal dominant, progressive, and life-threatening disorder caused by mutations in the transthyretin (TTR) gene [ 1 , 2 ]. The disease results from an extracellular deposition of amyloid fibrils in a variety of organs, leading to a multisystemic condition with a prevalent involvement of the peripheral nervous system (transthyretin amyloid polyneuropathy, ATTR-PN) and heart (transthyretin amyloid cardiomyopathy, ATTR-CM), but kidney, ocular vitreous, liver, and gastrointestinal tract may also be involved [ 3 , 4 , 5 , 6 ]. In the past decades, significant advances have been achieved in the treatment of ATTRv amyloidosis as several therapies with the potential to delay the disease progression have emerged [ 7 , 8 , 9 , 10 ], especially if started early during the course of the illness [ 11 ].…”