Nephrotic syndrome

Common to various diseases, the nephrotic syndrome is a clinical picture characterized by:

• presence of proteins in the urine (proteinuria), which become foamy
• reduction in the amount of proteins in the blood (dysplotemia with hypoalbuminemia)
• appearance of generalized swelling (edema), initially at the level of the face, then extended to other bodily sites, such as feet, ankles and abdomen

Often they are also present:

• Hyperlipidemia (mainly increase in total cholesterol or even triglyceridemia)
• Hypercoagulability of the blood: risk of thrombo-embolism

In order to be able to speak of a nephrotic syndrome, the presence of proteins in the urine must have a glomerular origin, that is to say an expression of a serious alteration of the permeability of the glomerular capillary wall.

The renal glomerulus and kidney functions

The nephron is the functional unit of the kidney, that is the smallest anatomical formation able to carry out all the functions to which the organ is deputy. Each of the two million nephrons roughly present in each of the two kidneys is divided into two components:

• renal corpus or Malpinghi (glomerulus + Bowman's capsule): responsible for filtration
• tubular system: responsible for resorption and secretion

that carry out three fundamental processes:

• filtration: it takes place in the glomerulus, a highly specialized capillary system that allows all the small molecules of the blood to pass through, opposing only the passage of larger proteins and corpuscular elements (red, white and thrombocyte cells). The larger proteins do not pass through physical problems, the smaller ones are rejected by the presence of negative electric charges
• reabsorption and secretion: they occur in the tubular system with the aim of reabsorbing excessively filtered substances (eg glucose, which the body cannot afford to lose with urine) and to increase the excretion of those filtered in a insufficient

In the presence of a nephrotic syndrome there is a loss of selectivity of the glomerular barrier both in terms of molecular size and electric charge: consequently, important amounts of protein are lost with urine.

Symptoms

Edema is the most characteristic symptom and clinical sign of nephrotic syndrome.

Subcutaneous and soft, initially located in the periorbital area, especially in the morning, the edema then tends to extend to other areas, such as the dorsum of the feet, the presacral region and the abdomen, or to become generalized (anasarca) with ascites and pleural effusion and / or pericardial. The evolution of edema is appreciable through the daily evaluation of body weight: the more this increases, the greater is the accumulation of liquids in the interstitial spaces.

The presence of foam in the urine is a sign attributable to proteinuria. Dark, tea-colored or coca-cola urines are typical of the nephritic syndrome, a condition similar to the previous one, but also characterized by the urinary loss of red blood cells.

The urinary loss of proteins, in particular of immunoglobulins, can be associated with an increased susceptibility to infections. The patient may feel weak, asthenic, appearing to be cachectic only in the most severe and nowadays rare cases.

The serum protein electrophoresis shows, in addition to albumin reduction, an increase in α2 globulins and Β globulins.

Causes and classification

Depending on its origin, the nephrotic syndrome is first of all distinguished between primary and secondary; in the first case it is the expression of renal diseases, in the second of systemic diseases or that in any case involve other organs besides the kidney.

Primary or primitive forms of nephrotic syndrome (the diagnosis is histological and therefore requires renal biopsy):

1. Glomerulopathy in minimal injury
2. Membranous glomerulonephritis
3. Focal segmental glomerulosclerosis
4. Membrano-proliferative glomerulonephritis

Secondary forms of nephrotic syndrome:

1. Metabolic diseases: Diabetes Mellitus; Amyloidosis
2. Immune diseases: systemic lupus erythematosus; Schonlein-Henoch purpura, Polyarteritis nodosa, Sjogren's syndrome, Sarcoidosis
3. Neoplasms: Leukemias, Lymphomas, Multiple myeloma; Carcinomas (lung, stomach, colon, breast, kidney); Melanoma
4. Nephro-toxicity: Gold salts, Penicillamine, Non-steroidal anti-inflammatory; Lithium, Heroin
5. Allergens: Insect bites; Snake bite; Antitoxin serum
6. Infectious diseases
   • Bacteria: post-infectious glomerulonephritis; from an infected shunt; bacterial endocarditis, lue
   • Viral: hepatitis B and C, HIV, Epstein-Barr, Herpes zooster
   • Protozoaries: malaria
   • Helminths: schistosomes, filarias
7. Family members: Alport syndrome, Fabry disease
8. Others: Toxemia of pregnancy (Pre-eclampsia); Malignant hypertension

In young children, the nephrotic syndrome is caused, in 90% of cases, by a glomerulonephritis with minimal lesions or by focal and segmental glomerulosclerosis. This percentage drops to 50% in children over 10 years.

In adults, the nephrotic syndrome is more frequently caused by a membranous glomerulonephritis, followed by incidence of focal and segmental glomerulosclerosis and glomerulonephritis at minimal injury. About 30% of adults with nephrotic syndrome have a systemic disease (diabetes mellitus, amyloidosis, systemic lupus erythematosus or neoplasms, particularly of the colon or lung).

In pediatric age, the nephrotic syndrome is more common among males, while in adulthood the incidence between the two sexes is uniform.

How do the symptoms and complications of the nephrotic syndrome arise?

Increased wall permeability of glomerular capillaries

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Transfer of protein into the urine (proteinuria)

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Reduction of plasma proteins (Hypoproteinemia or hypoprotidemia or hypoalbuminemia)

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In the presence of nephrotic syndrome, the main protein found in urine is albumin (selective proteinuria); however, other plasma proteins (non-selective proteinuria), such as transferrin, coagulation inhibitors and hormonal carriers may also be present to varying degrees; the loss of these elements explains the possible complications of the pathology (malnutrition, infections, thrombosis, anemia, weakness). For example, in response to the reduction of plasma proteins, the liver produces a large amount of fibrinogen. If we add to this the renal loss of antithrombin III and other anticoagulant factors, a picture of hypercoagulability emerges that is frequently found in the nephrotic syndrome. A complication of hypercoagulability is the possible thrombosis of the renal vein, in addition to the general increase in cardiovascular risk. The loss of transferrin facilitates anemia instead, while the decrease in IgG and some complement factors, such as Properdina, increases sensitivity to infections. The lack of Globulin that binds Colecalciferol leads to an alteration of the metabolism of Vitamin D3 with reduced intestinal absorption of Calcium and secondary hyperparathyroidism.

Therapy

The choice of therapy obviously depends on the disease of which the Nephrotic syndrome is a consequence and expression.

Generally the treatment involves the administration of diuretic drugs, possibly associated with the infusion of human albumin; this approach aims to reduce edema. Among the drugs useful to counteract proteinuria, we recall ACE inhibitors, particularly indicated in cases of nephrotic syndrome associated with hypertension. Possible alterations of lipid metabolism can be corrected by taking lipid-lowering drugs, such as statins. The increase in thrombotic risk can be corrected by using anticoagulant drugs. If the nephrotic syndrome is an expression of inflammatory diseases or autoimmune aetiology, the patient can benefit from immunosuppressive drugs (ciclosporin) and steroidal anti-inflammatory drugs (corticosterids).

This is associated with bed rest, the overall restriction of fluid intake, the intake of a hyposodic and hypolipidic diet and abstention from drugs that can worsen renal damage associated with the nephrotic syndrome (contrast agents, antibiotics and NSAIDs such as ibuprofen, naproxen and celecoxib).