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Signs and symptoms -can't find picture that is free

The clinical signs of minimal change disease are proteinuria (abnormal excretion of proteins, mainly albumin, into the urine), edema (swelling of soft tissues as a consequence of water retention), weight gain, and hypoalbuminemia (low serum albumin). These signs are referred to collectively as nephrotic syndrome.

The first clinical sign of minimal change disease is edema with an associated increase in weight. The swelling may be mild but patients can present with edema in the lower half of the body, periorbital edema, swelling in the scrotal/labial area and anasarca in more severe cases. In older adults, patients may also present with acute kidney injury (20-25% of affected adults) and high blood pressure. Due to the disease process, patients with minimal change disease are also at risk of blood clots and infections.

Pathophysiology - too detailed for layman?

Proteinuria

For years, pathologists found no changes when viewing specimens under light microscopy, hence the name "minimal change disease." With the advent of electron microscopy, the changes now known as the hallmarks of the disease were discovered. These are diffuse loss of visceral epithelial cells' foot processes (i.e., podocyte effacement) on the visceral epithelial cells. The effacement of the podocytes result in increased glomerular permeability to albumin, which leads to loss of high amounts of albumin in the urine.

The cause and pathogenesis of the effacement is unclear and it is currently considered idiopathic. However, it does not appear to involve complement, immunoglobulins, or immune complex deposition. Rather, an altered cell-mediated immunologic response with abnormal secretion of lymphokines by T cells is thought to reduce the production of anions in the glomerular basement membrane, thereby increasing the glomerular permeability to serum albumin through a reduction of electrostatic repulsion. The loss of anionic charges is also thought to favor foot process fusion. Also, the exact cytokine responsible has yet to be elucidated, with IL-12, IL-18 and IL-13 having been most studied in this regard, yet never conclusively implicated.

Edema

While there are many causes of edema, the edema from minimal change disease is due to the loss of albumin in the urine. When albumin is excreted in the urine, its serum (blood) concentration decreases. Consequently, the intravascular oncotic pressure reduces relative to the interstitial tissue. The subsequent movement of fluid from the vascular compartment to the interstitial compartment manifests as the soft tissue swelling referred to as oedema. This fluid collects most commonly in the feet and legs, in response to gravity, particularly in those with poorly functioning valves. In severe cases, fluid can shift into the peritoneal cavity (abdomen) and cause ascites. As a result of the excess fluid, individuals with minimal change disease often gain weight, as they are excreting less water in the urine, and experience fatigue.

Diagnosis

As minimal change disease is a subset of nephrotic syndrome, diagnosis involves looking for a combination of edema, high amounts of protein in urine, low albumin and high serum cholesterol. Initial workup can include a urinalysis, kidney function tests, serum albumin level and a lipid panel.

As MCD is the most common type of nephrotic syndrome in children, renal biopsy is not usually done in children under the age of 10 unless there are concerning features that are unusual for the disease (high blood pressure, bloody urine, renal dysfunction) and if they fail to respond to corticosteroid therapy. In adults, a renal biopsy is required as there is a much wider differential for nephrotic syndrome. As the name suggests, the renal biopsy of a patient with minimal change disease would show minimal or no evidence of disease in light microscopy.

Treatment-unsure if children/adults should be separated

Children

The first line therapy to minimal change disease is corticosteroids. For those are who are unable to tolerate corticosteroid treatment, cyclosporine is an alternative; other immunosuppressants have also been used such as llevamisole, calcineurin inhibitor, mycophenolate mofetil, rituximab though studies on their effectiveness is fairly limited. There is no common consensus on how long the corticosteroid therapy should be, with treatment length ranging from 4-12 weeks. Along with corticosteroid therapy, acute symptomatic management involves salt and fluid restriction to control the swelling.

For children who do not respond to corticosteroids (usually after a trial of 8 weeks), a trial of cyclosporine and corticosteroids can be tried.

Adults

Treatment guidelines for adults is fairly limited, largely based on studies done on children. The mainline therapy is also corticosteroid therapy with other immunosuppressants as possible alternatives though, there is very little data on the these alternatives' efficacy.

Prognosis -unsure if children/adults should be separated

Children

Minimal change disease usually responds well to initial treatment with the first-line therapy: corticosteroids, with 95% responding. Younger children, who are more likely to develop minimal change disease, usually respond faster than adults with 50% of children having complete remission with 8 days of corticosteroid therapy and most other patients responding by the 4th week. Few do not respond to corticosteroids and have to rely on an alternative therapy. However, despite positive response to corticosteroids, relapses are common, requiring repeat treatment with corticosteroids. About 25% never relapse, another 25% relapse infrequently (one relapse within 6 months of initial response or 1-3 relapses in 12 months), and 50% relapse frequently (>2 relapses within 6 months of initial response or >4 relapses in 12 months). The relapse rate is the reason behind a discussion on continuing prednisone treatment to even beyond 12 weeks to possibly decrease relapse rate; several studies trying this have failed to show significant improvement. A majority of relapses seem to be triggered by respiratory infections. Long term, children can relapse several years after having no symptoms though after 2 years, the risk is significantly lower.

Complications primarily arise from the side effects of therapy. Prolonged use of corticosteroids can lead to immunosuppression (leading to infection), growth compications, weight gain.

Adults

While most adults with minimal change disease do respond to corticosteroids, 25% fail to respond after 3-4 months of corticosteroid therapy though it is possible that these patients may not actually have minimal change disease and was incorrectly diagnosed. Adults with MCD tend to also respond more slowly to corticosteroid treatment when compared to children; response is longer, taking up to 3 or 4 months. Data in adults is less complete in comparison to children but relapses are also fairly frequently with 56-76% of patients relapsing.

Like in children, complications primarily arise from the side effects of therapy. Prolonged use of corticosteroids can lead to immunosuppression (leading to infection), growth compications, weight gain.

Epidemiology

Minimal change disease is most common in very young children but can occur in older children and adults. It is by far the most common cause of nephrotic syndrome in children, accounting for 70-90% of children >1 year of age. After puberty, it is caused by minimal change disease about half the time. Among young children, boys seem to be more likely to develop minimal change disease than girls (about 2:1). Minimal change disease is seen in about 16 in every 100,000 children with it being more common in South Asians and Native Americans, but rarer in African Americans.

In adults, it accounts for less than 15% of adults diagnosed with nephrotic syndrome.

People with one or more autoimmune disorders are at increased risk of developing minimal change disease. Having minimal change disease also increases the chances of developing other autoimmune disorders.