Renal amyloidosis in Norway: how the disease has evolved over 30 years

English title: Epidemiology and clinical presentation of kidney amyloidosis have changed over the past three decades: a nationwide population-based study

First author: Hilde J. Vasstrand

Journal : BMC Nephrology

Reference : BMC Nephrol. 2025 Jun 2;26(1):272.

PubMed link : https://pubmed.ncbi.nlm.nih.gov/40457206/

Article summarized by: Dr Catherine Grandpeix-Guyodo

Introduction:

Amyloidoses are diseases related to protein deposits in the form of amyloid fibrils. Protein typing helps understand the presentation of the disease, its progression, prognosis, and allows treatment adaptation. Early diagnosis of kidney amyloidosis is essential for treatment optimization and prognosis improvement. This Norwegian nationwide study conducted over 30 years explores changes in the epidemiology and clinical presentation of kidney amyloidosis to raise awareness about these conditions.

Patients and methods: Over a 30-year period, 479 patients with amyloidosis on kidney biopsy were identified in the registries, including 209 AA amyloidoses (SAA protein deposits) and 270 non-AA amyloidoses (mainly AL amyloidoses from immunoglobulin light chain deposits). Patient records were studied and cases were separated into AA amyloidosis and non-AA amyloidosis.

Results:

The frequency of renal amyloidosis was stable over time (4% of kidney biopsies), but AL amyloidosis became the predominant form of non-AA amyloidoses with a frequency increasing from 1.9% to 2.8% of kidney biopsies (p = 0.014). In parallel, the proportion of AA amyloidosis decreased from 2.6% to 1.3% (p < 0.001), due to the reduction in amyloidoses secondary to inflammatory rheumatic diseases, partly offset by AA amyloidoses secondary to drug injections.

Advances in typing amyloid deposits significantly reduced undetermined amyloidoses (p < 0.001) and led to more precise diagnoses. Clinical presentations were varied, but proteinuria was present in 94% of patients. Nephrotic syndrome was noted more frequently in patients with non-AA amyloidosis (70%) than in those with AA amyloidosis (51%). Kidney function was better preserved in non-AA amyloidoses (median GFR 53 ml/min/1.73 m²) than in AA amyloidoses (median GFR 27 ml/min/1.73 m²). Patients with AA amyloidosis were younger (p < 0.001) and more often hypertensive (53% versus 38%, p < 0.001).

Regarding patients developing AA amyloidosis following drug injection, they were younger, more often male, and presented more advanced kidney disease with half in end-stage kidney disease.

Recently, the authors noted that patients with non-AA amyloidosis had better albumin, hemoglobin, and ESR levels (p < 0.05). Additionally, the proportion of non-AA amyloidosis with end-stage kidney disease dropped from 26.8% to 8.7% (p = 0.005), which could indicate earlier diagnoses.

Conclusion:

There have been changes in the epidemiology of kidney amyloidosis in Norway over the past 30 years. The rate of non-AA amyloidosis in biopsies has increased, and certain indicators suggest that diagnosis is made earlier. Amyloid typing has improved, which is reflected in more precise diagnoses with a decrease in undetermined forms. AA amyloidoses related to inflammatory rheumatic diseases have significantly decreased, but the increase in AA amyloidoses in patients who inject drugs is becoming a growing problem.

Awareness of amyloidoses remains necessary, especially during this period when epidemiology is changing with, as a consequence, the possibility of changes in clinical presentation and therapeutic needs.

Genetic and clinical features of Familial Mediterranean Fever in a cohort of patients with kidney failure

First author: Ahmed Sheyyab

Journal: Journal of Nephrology

Link to the article: doi.org/10.1007/s40620-025-02272-y

Author of the abstract: Rim BOURGUIBA

Introduction

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide. In its classic form, it is mainly associated with mutations in exon 10 of the MEFV gene. AA amyloidosis is the most severe complication of FMF.

The aim of this study was to compare the frequency of MEFV variants in hemodialysis patients versus healthy controls in a Mediterranean country, Jordan.

Methods

This was a cross‑sectional study including 78 patients with end‑stage kidney disease on hemodialysis and 201 healthy controls in Jordan. All patients underwent Sanger sequencing for the main MEFV variants. The following variants were tested: p.E148Q, p.P369S, p.F479L, p.M680I (G/C), p.M680I (G/A), p.I692del, p.M694V, p.M694I, p.K695R, p.V726A, p.A744S, and p.R761H.

Patients carrying a variant were then clinically assessed according to the Tel‑Hashomer criteria. Five underwent rectal biopsy to detect amyloidosis.

Results

Among dialysis patients, 16% had at least one MEFV variant versus 12.9% in the control group (not significant). The two most frequent mutations in the hemodialysis group were M694V (p = 0.035) and V726A (p = 0.009). The variants detected in both groups are summarized in Table 1. In the control group without renal failure, 22 individuals were heterozygous for the E148Q variant. Three patients met diagnostic criteria for FMF, and one case of AA amyloidosis was confirmed by biopsy.

Conclusion

FMF is the most common autoinflammatory disease in Mediterranean countries, yet it remains underdiagnosed even in high‑risk populations. This diagnostic delay leads to complications, notably AA amyloidosis. This study shows that 4% of hemodialysis patients were diagnosed with FMF. It also confirms the non‑pathogenic nature of the E148Q variant, which was detected in 22 healthy, asymptomatic individuals.

Overall, these findings underscore the importance of testing for MEFV mutations in patients with AA amyloidosis in countries where FMF is highly prevalent, in order to offer appropriate treatment to prevent AA amyloidosis and progression to renal failure.

Genetic and clinical features of familial Mediterranean fever in a cohort of patients with.

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Could tocilizumab be used in familial Mediterranean fever? A systematic review

First author : P. Mertz

Review: Rheumatology

Link to article: https://doi.org/10.1093/rheumatology/keae338

Could tocilizumab be used in Familial Mediterranean Fever ?

Abstract:

Introduction:

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease characterized by recurrent fever and serosal inflammation. Although colchicine is the primary treatment, around 10% of FMF patients do not respond to it, necessitating alternative therapies. Biologic treatments, such as IL-1β, TNF-α and IL-6 inhibitors, have been considered. However, the accessibility and cost of IL-1β inhibitors may limit their use in certain regions. Tocilizumab (TCZ), an IL-6 receptor inhibitor, offers an alternative, but its efficacy in FMF is not well-documented.

Results:

After selection, 14 articles were included: two double-blind RCTs, two retrospective studies and 10 case reports. Multicentre double-blind RCTs reported mixed results in FMF patients without AA amyloidosis due to genetic/classification heterogeneity of the available studies, possible misdiagnosed FMF patients and study design. Retrospective studies suggest that TCZ may benefit FMF patients with established renal AA amyloidosis, potentially preventing progression and managing flares more effectively. TCZ showed a safe profile with no specific adverse events, but data on its use during pregnancy or breastfeeding are lacking. There was no available data on the use of TCZ in paediatric FMF.

Conclusion:

This review summarizes the current state of research, safety and efficacy of TCZ in FMF. While IL1β inhibitors remain the first choice for colchicine-resistant or intolerant FMF patients, TCZ might be of interest in some selected FMF patients with established AA amyloidosis and resistance to colchicine and interleukin 1 inhibitors.

Could tocilizumab be used in familial Mediterranean fever?.pdf

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