Functional and histopathologic correlation in the fabry nephropathy with N215S genotype

Area of Science:

• Nephrology
• Genetics
• Histopathology

Background:

• Late-onset Anderson-Fabry disease (AFD) typically presents in adulthood with cardiac involvement.
• The N215S missense mutation is the most common late-onset AFD variant in Europe.
• Investigating N215S nephropathy is crucial for understanding disease progression and management.

Purpose of the Study:

• To clinically and histopathologically investigate nephropathy in patients with the N215S variant of AFD.
• To evaluate the long-term renal function in treated N215S AFD patients.
• To correlate histological findings with clinical parameters.

Main Methods:

• Retrospective analysis of 27 patients (11 males, 16 females) with the N215S variant.
• Renal and cardiac assessments at baseline, with kidney biopsies analyzed using the International Study Group of Fabry Nephropathy scoring system.
• Evaluation of renal function (eGFR) at diagnosis (T0), 5 years (T1), and 10 years (T2) post-treatment initiation.

Main Results:

• At diagnosis, mean eGFR was 84.98 mL/min/1.73m²; 6 patients had CKD stages 3-5.
• Over time, treated patients showed a decline in mean eGFR, with an increasing percentage of patients in CKD stages 3-5.
• Kidney biopsies revealed podocyte vacuolization in all patients and interstitial fibrosis, particularly in males. Arteriolar intimal fibrosis correlated with baseline eGFR.

Conclusions:

• N215S AFD patients exhibit characteristic histological abnormalities of Fabry disease even at early stages.
• Chronic kidney disease appears to progress in treated N215S AFD patients, associated with arterial and arteriolar intimal fibrosis.
• The study highlights the importance of long-term monitoring and understanding histological changes in managing N215S AFD.