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.

Nephrolithiasis is an increasingly prevalent condition, especially in high income countries, and is associated with high morbidity. Extraordinary progress in genetics made the identification of genetic forms of nephrolithiasis possible. These genetic diseases are usually rare and do not account for the most common forms of nephrolithiasis that are the result of several factors such as environment, dietary habits, and predisposing genes. This knowledge has shaped what we classify as nephrolithiasis, a condition that is now recognized as systemic. How and to what extent all these factors interact with one another and end in kidney stone formation, growth, and recurrence is not completely understood. Two new research fields have recently been trying to give some answers: nutrigenomics and nutrigenetics. These fields have the aim of understanding the intricate diet/genome interface that influences gene expression regulation mainly through epigenetic mechanisms and results in specific medical conditions such as cancer, metabolic syndrome, and cardiovascular diseases. Epigenetics seems to play a crucial role and could represent the link between environmental factors, that we are constantly exposed to, and risk factors for nephrolithiasis. In this systematic review, we summarize all the available evidence of proven or hypothesized epigenetic mechanisms related to nephrolithiasis.

Hereditary transthyretin amyloidosis (ATTRv; v for “variant”) is the most common form of hereditary amyloidosis, with an autosomal dominant inheritance and a variable penetrance. This disease has a significant variability in clinical presentation and multiorgan involvement. While kidney involvement in early-onset ATTRv has been reported in one-third of patients, in late-onset ATTRv it has generally been considered rare. In the present study, we describe trajectories of kidney function over time before and after treatment with gene silencing therapies in a cohort of 17 ATTRv patients with different mutations, coming from Italy (nine subjects treated with inotersen and eight patients treated with patisiran). The analysis of estimated glomerular filtration rate (eGFR) slopes revealed that the average change in eGFR was 0.01 mL/min/1.73 m² per month before initiation and −0.23 mL/min/1.73 m² per month during follow-up for inotersen and −0.62 mL/min/1.73 m² per month before initiation and −0.20 mL/min/1.73 m² per month during follow-up for patisiran. In conclusion, we did not observe any significant difference either between the two groups of treatment or within-group before and after therapy, so gene-silencing therapies may be considered safe for renal function in ATTRv and are not associated with a worsening of eGFR slope.