Nephrotic syndrome, idiopathic

[MIM 615 861]

(nephrosis)

It is the most common kidney disease in children: 2 to 7 cases/100,000 children per year. 70 % of the cases begin before the age of 5 years.

The diagnostic triad is:

-        proteinuria > 50 mg/kg/day, with foaming urines

-        hypoproteinaemia 

-         widespread, soft, painless edema: due to the retention of Na and the reduction in plasma oncotic pressure.

It is the result of a massive urinary loss of proteins. The pathophysiology is variable and not well known: 

-        immune dysfunction; modified podocytes of the glomeruli are found at electron microscopy

-         glomerular pathology due to variable causes: immunologic [MIM 612 551] or infectious

-         structural anomaly of the filtration barrier: mutation of genes involved in the structure or function of the podocytes: NPHS1, NPHS2 (1q25-q31), LAMB2 [MIM 614 194], ACTN4, TRPC6, WT1 (corticoresistant forms). The likelihood of a genetic cause increases as the age of onset decreases (< 1 year of age)

-        presence of a circulating factor modifying the permeability of the filtration barrier: heparanase, hemopexine, angiopoietin-like 4 (ANGPTL4), cardiotrophin-like cytokine 1, soluble urokinase plasminogen activator receptor (suPAR).

The nephrotic syndrome is said to be 'pure' if it is not accompanied by high blood pressure, hematuria or renal failure. It is said steroid-sensitive if it responds favorably to corticosteroids within less a 4 weeks period time, with a variable risk of relapse when the treatment is stopped, or steroid-resistant with a high risk of evolution towards chronic renal failure  [MIM 256 370, 600 995, 603 278, 607 832, 610 725, 613 237, 614 196, 615 244, 615 573, 615 861, 616 002, 616 032, 616 220, 616 730, 616 893]


The most common form is the primitive idiopathic nephrotic syndrome. Its histological picture at biopsy is either:

-        a glomerulopathy with minimal glomerular lesions ("minimal changes") [MIM 614 196]: 90 % of cases are cortiocresistant

-        a diffuse mesangeal proliferation [MIM 614 196]

-        a segmental and focal glomerulosclerosis (or hyalinosis) [MIM 603 278, 614 196]: 20 % of cases are corticosensitive.


The onset is often brutal, after a viral infection. It is more common in boys. There seems to be a genetic predisposition for the steroid-sensitive forms: HLA-DQA1 and HLADQB1 polymorphism are frequently observed.

Less frequent, non-idiopathic forms are:

-        associated with a rare genetic diseases: Alport, Frasier, Pierson, nail-patella, Denys-Drash, Galloway-Mowat, Finnish type nephrotic syndrome.

-        forms secondary to immune glomerulonephritis: extramembranous or membranoproliferative glomerulonephritis (generally "impure"), sickle cell anemia

-        forms secondary to a systemic disease: rheumatoid purpura, lupus (generally "impure")

-        forms due to a medication: NSAID's, D-penicillamine, bisphosphonates, rifampicin

-        forms due to infection: perinatal (CMV, toxoplasmosis, rubella) or later (hepatitis B or C, HIV1, malaria, chicken pox)

-        forms secondary to malignancy: thymoma, lymphoma, leukemia

The treatment is:

-        salt-free diet, water restriction

-        corticosteroid therapy for 8 to 12 weeks with a starting dose of 60 mg/m2/day. In case of corticosensitivity, proteinuria improves in 1 to 2 weeks time. However, 60 % of corticosensible cases present at least one relapse that requires restarting corticosteroid therapy. These relapses are often preceded by an infectious episode

-        in case of corticoresistance, immunosuppressants: levamisole (anthelminthic with immunomodulating properties), cyclophosphamide, cyclosporine, tacrolimus, mofetil, rituximab, mizoribine

-        in some cases, a conversion enzyme inhibitor or an antagonist of the angiotensin 2 receptors can be added to decrease proteinuria, especially if high arterial blood pressure is present.

-        sometimes, albumin infusion; diuretics with caution (can worsen the hypovolemia).


The complications of nephrotic syndrome are:

-         infections due to decreased IgG levels: notably, spontaneous bacterial peritonitis (Str. pneumoniae), pneumonia (Str. pneumoniae, H. influenzae, St. aureus...)

-        thrombosis: usually venous, more rarely arterial due to thrombocytosis and a decreased plasma level of antithrombin III, protein C and S and to fibrinolysis disorders 

-         anemia

-        hyperlipemia: cholesterol, triglycerides and its cardiovascular complications

-        acute renal failure in a context of hypovolemia, sepsis or interstitial nephritis caused by NSAIDs, or chronic renal failure in case of corticoresistance

-         complications of corticosteroid therapy.

 


Anesthetic implications: 

check the electrolytes, serum creatinine, complete blood count; corticosteroid replacement therapy in case of treatment with cortisone; venous access difficulties and risk of thrombosis (central venous access); antibiotic prophylaxis. The nephrotic syndrome is the only situation where hypoalbuminemia is not offset by an increase in α1 -glycoprotein: the existence of nephrotic syndrome therefore results in a significant decrease in the protein binding of local anesthetics and other anesthetic drugs.


References :  


Updated: July 2018