Steroid-Resistant Nephrotic Syndrome due to NPHS2 Variants Is Not Associated With Posttransplant Recurrence.

Area of Science:

• Nephrology
• Genetics
• Transplantation

Background:

• Hereditary podocytopathies, unlike idiopathic nephrotic syndrome (NS), are generally not expected to recur post-kidney transplantation.
• However, isolated reports of NS recurrence in patients with NPHS2 gene variants, particularly the p.Arg138Gln variant, have emerged.
• This necessitates a clear understanding of recurrence risk in NPHS2-related hereditary kidney disease.

Purpose of the Study:

• To evaluate the risk of nephrotic syndrome recurrence after kidney transplantation in a large cohort of patients with biallelic NPHS2 pathogenic variants.
• To compare recurrence rates between patients with NPHS2 variants and those with idiopathic steroid-resistant NS (SRNS) without identified variants.

Main Methods:

• A cohort of 117 patients with biallelic NPHS2 variants who underwent kidney transplantation was analyzed.
• These patients were compared with 44 transplanted children with SRNS lacking identified pathogenic variants.
• Data were collected from Necker-Enfants Malades Hospital and the PodoNet Registry, with a median follow-up of 8.5 years.

Main Results:

• Only 1 out of 117 patients (less than 1%) with NPHS2-related SRNS experienced posttransplant recurrence.
• In contrast, 7 out of 44 patients (16%) with SRNS and no identified variants showed recurrence.
• The p.Arg138Gln variant was present in a significant proportion of the NPHS2 cohort (39 patients).

Conclusions:

• The risk of nephrotic syndrome recurrence after kidney transplantation in patients with NPHS2 gene variants is extremely low.
• This finding aligns with the understanding of NPHS2 variants causing intrinsic slit-diaphragm disease.
• These results are reassuring for patient counseling and support living kidney donation, even from related donors.