Complications of nephrotic syndrome include infections, thrombotic events, and renal failure. Mortality and overall prognosis depends on the occurrence of complications and adherence to medications.

In children, the mean age for presentation of nephrotic syndrome is approximately 1-8 years. According to Madani and colleagues^[1], who studied nephrotic syndrome in 502 pediatric patients, 67% of patients were in the range of 1-5 years of age. Other studies showed similar age distribution in children.^[2][3][4][5] The mean age among adults is much more difficult to calculate because unlike children whose primary disease is almost always minimal change disease, secondary etiologies of nephrotic syndrome, such as HIV and diabetes, are much more common and corresponding age distribution is very wide.^[6]

Patients with nephrotic syndrome are at increased risk of infections due to several mechanisms:

• Urinary loss of immunoglobulins^[6]

• Delay in complement-dependent opsonisation of encapsulated organisms, such as S. pneumoniae^[7]

• Reduction in factors B and I^[7]
• Decrease of blood flow to mesenteric regions^[6]

Patients with nephrotic syndrome who complain of abdominal pain must always be assessed for peritonitis that requires paracentesis. The rate of spontaneous bacterial peritonitis is 2-6%^[8] which contributes to 1-2% of mortality in these patients. In addition to encapsulated bacteria, gram-negative bacterial organisms, such as E. coli, are also especially important infectious agents in patients with nephrotic syndrome.^[9] Pneumonias, urinary tract infections, and skin infections, such as cellulitis, erysipelas, and lymphangitis are also common.^[6] Since patients are often treated with immunosuppressants, the susceptibility to bacterial and viral infections is further heightened in these patients.^[10][7]

The rate of thromboembolism may be as high as 40% in adults; whereas it is much lower in children at a rate of 2-5%.^[11] Several factors contribute to thromboembolism in nephrotic syndrome^[11]:

• Increase in platelet aggregation
• Increase in concentration of fibrinogen
• Urinary loss of antithrombin III
• Increase in blood viscosity
• Decrease in blood flow

Thromboembolism is considered the second most important cause of mortality in nephrotic syndrome. The risk of thromboembolism increases as other risk factors of thrombosis are also present, such as immobility, indwelling catheters, use of diuretics or steroids.^[6] Thromboembolism may occur at any site; common locations include deep veins of the extremities, cerebral veins, renal veins, and pulmonary veins. Although arterial occlusion is much less common, its prognostic significance is much graver than venous thromboembolism and is associated with mortality.^[11] Considerably, the use of heparin may not be as efficient in nephrotic syndrome due to the insufficiency of antithrombin III required by the drug for anticoagulation.^[12]

The clinical presentation of nephrotic syndrome per represents a high-risk profile for cardiovascular disease. Patients may present with hypertension, hyperlipidemia, anemia, renal disease, and exposure to steroids, all of which are considered risk factors for the development of cardiovascular disease and cardiovascular events.^[13][14]

Acute renal failure, in as early as within 4 weeks of nephrotic syndrome, is a more common complication in adult males > 60 years.^[15] Additional cardiovascular risk factors, like hypertension, and iatrogenic causes, like fluid withdrawal and surgeries, are also important in the development of acute renal failure.^[15] Renal failure in nephrotic syndrome is due to multiple factors. Acute tubular necrosis (ATN) corresponds to approximately 60% of acute renal failure in nephrotic syndrome. Interstitial edema, especially due to medications given for patients, like diuretics and steroids, are responsible for the remainder of cases.^[15]

Osteoporosis is generally a complication of corticosteroid use in nephrotic syndrome. However, medication-induced osteoporosis is not the only factor that predisposes patients to loss of bone density. Urinary loss of components required for osteogenesis, such as vitamin D-binding protein is also involved.^[16][17][18]

Anemia is commonly seen in patients with nephrotic syndrome but has been poorly evaluated. Recent studies have shown that perhaps the association between anemia and nephrotic syndrome are exaggerated and may not be as important as once believed.^[19] Anemia be present even without the presence of worsening kidney function. Several reasons predispose patients with nephrotic syndrome to the development of anemia, but the true pathogenesis has not been revealed yet. Some hypothesize that urinary loss of erythropoietin (EPO) and abnormal physiological response to EPO are the culprit of anemia.^[20][13] Nonetheless, these claims have not been validated in the literature and are still prone to debate.^{[21][22][23][24]} Additionally, iron stores are thought to be depleted in nephrotic syndrome with urinary loss of transferrin, contributing to the pathogenesis as an iron-resistant microcytic hypochromic anemia. Similarly, some researchers noted that ferritin is in fact increased in patients with nephrotic syndrome, not decreased as once postulated.^[25][19] The reason behind such elevation in ferritin remains unclear. Generally, administration of EPO resolves the anemia in these patients.^[13]

Urinary loss of insulin-like growth factor (IGF) binding proteins may cause a decrease in serum concentration of IGF-I and IGF-II. Corticosteroids, often used in the treatment of nephrotic syndrome, may also suppress growth.^[11]

• Prognosis of nephrotic syndrome is highly dependent on the underlying etiology.
• In children, most cases of nephrotic syndrome are due to minimal change disease (MCD), which generally carries an excellent prognosis when appropriate treatment with steroid is initiated.^[6]
• Children with congenital nephrotic syndrome and those whose MCD progress into focal segmental glomerulosclerosis (FSGS) are not responsive to steroids and thus have a poorer prognosis and end up requiring renal replacement therapy.^[6][26]