Steroid Resistant Nephrotic Syndrome (SRNS) is a kidney disorder. Nephrotic syndrome is characterized by the kidneys excreting excessive protein into the urine, leading to symptoms like swelling. SRNS is a form of this condition distinguished by its failure to respond to standard corticosteroid treatments.
Understanding Steroid Resistance
Steroid resistance in nephrotic syndrome results from genetic predispositions and specific patterns of kidney damage.
Genetic Factors
Genetic factors are key, with mutations in certain genes directly affecting the kidney’s filtration barrier. For instance, mutations in the NPHS1 gene, which codes for nephrin, can lead to congenital nephrotic syndrome. Nephrin helps maintain the structure and function of the kidney’s filtering units (glomeruli).
Similarly, mutations in the NPHS2 gene, encoding podocin, are linked to an autosomal recessive form of SRNS. Podocin is another protein important for glomerular filtration. Mutations in other genes, such as TRPC6 and WT1, have also been linked to SRNS, affecting podocytes, specialized cells in the glomeruli.
Beyond genetics, certain types of kidney damage, like focal segmental glomerulosclerosis (FSGS), also contribute to steroid resistance.
Identifying Steroid Resistant Nephrotic Syndrome
Steroid resistance is defined by persistent protein in the urine after a course of high-dose corticosteroid treatment. For children, this often means no urinary remission after 4 to 8 weeks of daily oral prednisone at a dosage of 60 mg/m² per day or 2 mg/kg per day.
Diagnostic tests include urine analysis to measure protein levels, showing high protein levels, sometimes appearing frothy. Blood tests are also conducted to assess kidney function and albumin levels, as low albumin in the blood (hypoalbuminemia) is a common feature of nephrotic syndrome. A kidney biopsy is performed to determine the specific type of kidney damage present, such as Focal Segmental Glomerulosclerosis (FSGS) or minimal change disease. Genetic testing is used to identify underlying gene mutations, which can influence treatment decisions.
Treatment Approaches
When standard steroid treatments are ineffective for SRNS, alternative strategies are necessary. Immunosuppressive medications manage the condition.
Calcineurin inhibitors (CNIs), such as cyclosporine and tacrolimus, are used to suppress the immune system and reduce proteinuria. These medications are typically continued for a minimum of 6 months, and if partial or complete remission is achieved, they may be continued for at least 12 months.
Other medications like mycophenolate mofetil are also used, sometimes in combination with CNIs or after rituximab therapy. Rituximab, a monoclonal antibody that targets B-lymphocytes, has shown varying degrees of success in inducing and maintaining remission in some SRNS patients, particularly in those with focal segmental glomerulosclerosis.
Treatment plans are highly individualized, taking into account the specific cause of resistance, the patient’s age, and their response to different therapies. For instance, children with genetic forms of SRNS may primarily receive symptomatic treatment due to their limited response to immunosuppressive drugs.
Long-Term Management and Outlook
Long-term management of SRNS involves addressing associated complications and monitoring for disease progression. Patients with SRNS face an increased risk of complications such as high blood pressure, fluid retention (edema), infections due to loss of antibodies, and blood clots. These complications require ongoing medical attention, often involving medications like angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) to reduce proteinuria, and diuretics to manage swelling.
Progression to end-stage kidney disease (ESRD) is a significant concern for individuals with SRNS, especially if they do not achieve remission with treatment. Historically, over 50% of children with SRNS who did not respond to initial steroid therapy would progress to ESRD within 3 to 5 years. In such cases, dialysis or kidney transplantation may become necessary to sustain life.
The long-term outlook for SRNS is variable, depending heavily on the underlying cause, the patient’s response to therapy, and the specific kidney pathology identified through biopsy. Ongoing monitoring by a multidisciplinary medical team is important for adapting treatment strategies and managing the disease effectively over time.