Genetic Steroid-Resistant Nephrotic Syndrome (SRNS)

Genetic steroid-resistant nephrotic syndrome (SRNS) is a hereditary form of nephrotic syndrome that does not respond to corticosteroid treatment, wich are commonly used to manage nephrotic syndrome. It is caused by genetic mutations. There are several genes associated with the development of SRNS when mutated. Some of the most commonly implicated genes include:

Mutations in the NPHS1 gene can lead to congenital nephrotic syndrome, which usually presents in infancy. Nephrin is a protein that plays a critical role in maintaining the structure and function of the glomerular filtration barrier in the kidney.

Mutations in the NPHS2 gene can result in a form of SRNS known as autosomal recessive steroid-resistant nephrotic syndrome. Podocin is another important protein involved in maintaining the integrity of the kidney's filtration barrier.

Mutations in the WT1 gene can lead to SRNS in the context of Denys-Drash syndrome or Frasier syndrome. WT1 is a transcription factor involved in kidney development and function.

Mutations in the PLCE1 gene have been associated with SRNS. This gene encodes a protein involved in signaling pathways in the kidney.

There are many other genes that, when mutated, can cause genetic SRNS. Research in this field is ongoing, and new genetic associations are still being discovered.

It's important to note that the severity of symptoms can vary among individuals with genetic SRNS, and the age of onset can also differ. Some forms of genetic SRNS may present in infancy or childhood, while others may not become apparent until later in life.

The hallmark symptom of SRNS is the presence of abnormally high levels of protein in the urine. This is often one of the first signs of the condition and can lead to frothy or foamy urine.

Edema or swelling is a common symptom of SRNS. It typically starts in the face and around the eyes and can progress to swelling in the legs, ankles, and abdomen. The swelling is due to the loss of protein in the urine, which leads to a decrease in blood protein levels and a subsequent shift of fluid into the tissues.

Reduced levels of albumin in the blood. Albumin is responsible for maintaining fluid balance in the bloodstream, and reduced levels can contribute to edema.

Elevated levels of lipids in the blood, including cholesterol and triglycerides can be detected through blood tests and may contribute to the increased risk of cardiovascular problems.

Due to the loss of essential proteins in the urine and fluid imbalances.

Some individuals with SRNS may develop high blood pressure as a complication of kidney dysfunction.

The diagnosis and management of steroid-resistant nephrotic syndrome (SRNS) remains a challenge to pediatric nephrologists. Identification of an underlying genetic basis allows clinical observations in molecularly defined patient cohorts, which impacts prognosis and treatment. Indeed, several reports so far indicate that children with genetic SRNS do not respond to immunosuppressive treatment.

Treatment strategies aim to manage symptoms, slow disease progression, and may include medications such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), diuretics, and dietary modifications. In some cases, individuals with SRNS may require dialysis or kidney transplantation if the disease progresses to end-stage kidneyl disease (ESKD). The specific treatment plan will depend on the underlying genetic mutation and the patient's clinical condition.