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

Abstract

Background Hereditary transthyretin amyloidosis (ATTRv) is a disabling and life-threatening disease that primarily affects the nervous system and heart. Its kidney involvement has not been systematically studied, particularly in non-V30M mutations, and is not well known to nephrologists. Material and Methods We conducted a retrospective study describing kidney phenotype of all prevalent patients with ATTR mutations, with neurological or cardiac involvement or presymptomatic carriers, followed-up in two university hospitals from the South of France, between June 2011 and June 2021. Results 103 patients were included, among whom 79 were symptomatic and 24 presymptomatic carriers. Patients carried 21 different ATTR mutations, and 54% carried the V30M mutation. After a mean follow up of 7.9 ± 25.7 years, 30.4% of the symptomatic patients had developed chronic kidney disease (CKD), and 20.3% had a urinary protein/creatinine ratio ≥ 0.5 g/g. None of the presymptomatic carriers had CKD or proteinuria. In a multivariate analysis, late onset of symptom (after 60 years), the V122I mutation, and proteinuria were significantly associated with CKD. Median CKD-free survival in symptomatic patients was estimated 81.0 [77.1; 84.9] years. It did not differ between V30M and non-V30M patients, but was lower in patients with the V122I mutation. The average age of CKD onset was 69.3 ± 13.0 years. In one 38-year-old V30M female, who presented a kidney-predominant phenotype, treatment with patisiran resulted in remission of the nephrotic syndrome. Conclusion CKD affects almost one third of patients with symptomatic ATTRv. The role of ATTRv per se in the development of CKD in this population remains to be determined, but some patients may benefit from specific therapies.

Kidney involvement in hereditary transthyretin amyloidosis: is there a role for cystatin C?

“…Although the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines [ 2 ] recommend a GFR estimating equation based on serum creatinine (eGFR crea ) as the first-line assessment, alternative equations such as the one using cystatin C alone (eGFR cys ) or the combined creatinine–cystatin C equation (eGFR crea-cys ) and clearance measurements of exogenous filtration markers (the ‘gold standard’ being inulin) are suggested when serum creatinine's accuracy is limited. On these assumptions, we previously performed a similar analysis in one of the biggest ATTRv cohorts in Italy [ 2 ] and found that the prevalence of kidney involvement based on proteinuria and eGFR crea is similar to that described by Solignac et al [ 1 ]. However, we believe that in this population, estimation of GFR solely relying on creatinine measurements could underestimate kidney involvement.…”

“…We read with interest the article by Solignac et al [ 1 ], a retrospective study describing the prevalence of kidney involvement, defined as either a decreased glomerular filtration rate (GFR) or proteinuria, in a large cohort of patients affected by hereditary transthyretin amyloidosis (hATTRv) with different ATTRv mutations (54% carried the V30M mutation) and both symptomatic and pre-symptomatic. In terms of the prevalence of kidney involvement, results are in agreement with data in the literature [ 2 ], with almost a third of symptomatic patients being affected by chronic kidney disease (CKD), 2.5% of patients developing end-stage kidney disease and 20% having proteinuria.…”

“…With regard to proteinuria, in the study conducted by Solignac et al [ 1 ], ATTRv patients were considered proteinuric if the urinary protein: creatinine ratio was ≥500 mg/g creatinine, defined as severely increased proteinuria as per the KDIGO guidelines [ 4 ]. This could have underestimated the prevalence of proteinuria in their cohort by not including patients with moderately increased proteinuria that are at higher risk of CKD progression and therefore should be carefully evaluated.…”

Amyloidoses in Onco-Nephrology Practice: A Multidisciplinary Case-Based Conference Report

“… 3 Although data on kidney involvement in ATTR amyloidosis are sparse, 2 recent reports suggest that about one-third of symptomatic patients have kidney involvement, commonly abnormal urine protein excretion. 32 , 33 …”

Is Hereditary Transthyretin Amyloidosis the Third Leading Cause of Monogenic Chronic Kidney Disease, Only Behind ADPKD and Alport Disease?

“…These data may support the hypothesis that only about 10% of hATTR patients experience direct renal involvement. Two studies reported a prevalence of CKD of 15% and 37% in patients with hATTR carrying diverse mutations [15,16] while, in a recent study on a French cohort, 24 out of 79 (30.4%) symptomatic patients with hATTR developed CKD [17]. Authors reported that not all TTR mutations were equal in terms of kidney involvement, and the Val122Ile seemed particularly at risk of CKD (OR 57.2 [6.5-7,540]).…”