Steroid-Resistant Nephrotic Syndrome (SRNS) Management

Definition and Diagnosis

Steroid-resistant nephrotic syndrome (SRNS) is defined as persistent proteinuria despite treatment with corticosteroids for at least 8 weeks, representing a challenging subset of nephrotic syndrome with higher risk of progression to end-stage renal disease, according to the Kidney International guidelines 1
The diagnosis of SRNS requires confirmation of steroid resistance after a minimum of 8 weeks of treatment, kidney biopsy to determine histological subtype, evaluation of kidney function (GFR/eGFR), and quantification of urine protein excretion, as recommended by the American Journal of Kidney Diseases and Kidney International 2, 3
Kidney biopsy is mandatory in all SRNS cases to determine the histological pattern, most commonly focal segmental glomerulosclerosis, as stated by the Kidney International and American Journal of Kidney Diseases guidelines 1, 2

Calcineurin inhibitors (CNIs) are the recommended first-line therapy for SRNS patients after confirming diagnosis, according to the American Journal of Kidney Diseases and Kidney International guidelines 2, 3
Cyclosporine is recommended at a dose of 3 mg/kg twice daily with target trough levels of 50-100 ng/ml, and should be continued for a minimum of 6 months to assess response, as stated by the Kidney International guideline 1
Combined therapy with low-dose corticosteroids should be given with CNI therapy, as recommended by the American Journal of Kidney Diseases guideline 2
For patients who fail to achieve remission with CNIs, mycophenolate mofetil (MMF) may be considered at a dose of 600 mg/m² per dose twice daily for 6-24 months, as stated by the Kidney International and American Journal of Kidney Diseases guidelines 1, 2
ACE inhibitors or ARBs are recommended for all SRNS patients to reduce proteinuria, according to the American Journal of Kidney Diseases and Kidney International guidelines 2, 3

Regular assessment of kidney function, monitoring for CNI nephrotoxicity, blood pressure monitoring, growth monitoring in children, and surveillance for infections are essential, as recommended by the Kidney International and American Journal of Kidney Diseases guidelines 1, 2
Monthly monitoring of serum creatinine and white blood count is necessary, as stated by the Kidney International guideline 1

Genetic testing is crucial in patients with SRNS, particularly those who develop the disease before age 25, as it may provide a definitive diagnosis, identify treatable forms, and guide transplant decisions, although the specific details are not provided in the cited references
Patients with certain genetic mutations may benefit from specific treatments, such as coenzyme Q10 supplementation, although the specific details are not provided in the cited references