Nephrotic syndrome

Published on 23/06/2015 by admin

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Last modified 23/06/2015

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16.6 Nephrotic syndrome

Karen McCarthy

Essentials

1 Nephrotic syndrome refers to the clinical findings of hypoalbuminaemia, heavy proteinuria, oedema and hyperlipidaemia. Every child has albuminaemia but not all features are necessary for diagnosis.
2 Despite the presence of oedema, shock still needs to be treated with 20 mL kg–1 0.9% saline or albumin boluses.
3 Renal function is usually normal though serum creatinine may be slightly elevated at presentation.
4 There is 1–2% mortality despite good long-term prognosis.
5 The physical findings of peritonitis in nephrotic syndrome may be very subtle, thus the emergency physician must have a very high index of suspicion for peritonitis.
6 Death from peritonitis and thrombosis can occur despite very good care.
7 All children with nephritic syndrome should receive pneumococcal vaccine.
8 All non-immune children on steroid therapy who are exposed to varicella require prompt administration of zoster immune globulin. Should they develop lesions, they require treatment with intravenous aciclovir.

Introduction

Definition

Nephrotic syndrome (NS) refers to the findings of heavy proteinuria, hypoalbuminaemia, oedema and hyperlipidaemia, which result from a massive loss of protein in the urine secondary to glomerular disease. All components of the disease do not need to be present for diagnosis. The protein lost in the urine includes plasma proteins of molecular weight up to and including albumin. Generalised glomerular leak to macro-molecules does not occur in most cases, but can occur in severe disease. In severe disease, as there is progressive loss of glomerular permselectivity, renal clearance of IgG approaches that of albumin. Protein selectivity is seen mainly in minimal change nephrotic syndrome. The determination of protein selectivity has little clinical value but does increase the likelihood of response to steroid therapy.

The hallmarks of nephrotic syndrome are hypoalbuminaemia (serum albumin <30 g L–1), heavy proteinuria (>50 mg kg–1 body weight per 24 hours, or >1000 mg m–2 per 24 hours), generalised oedema and hyperlipidaemia (triglycerides and cholesterol).

Primary nephrotic syndrome (idiopathic) represents disease limited to the kidney. Disease is classified by responsiveness to steroid therapy (steroid sensitive, steroid dependent or steroid resistant) and histology on renal biopsy (minimal change, mesangial proliferative glomerulonephritis (GN) and focal segmental glomerulosclerosis, FSGS).

Secondary nephrotic syndrome represents multisystem disease that has kidney involvement, e.g. lupus nephritis, hereditary nephritis and Henoch–Schönlein purpura.

Certain drugs and chemicals can cause nephrotic syndrome, e.g. phenytoin, non-steroidal anti-inflammatory drugs, and captopril.

Epidemiology

Minimal change nephrotic syndrome (MCNS) is more common in males. Mean age of onset is <6 years for primary nephrotic syndrome, and >6 years for secondary. It is usually sporadic. A congenital form, inherited in an autosomal recessive manner, presents in the newborn period.

Aetiology

The cause of primary nephrotic syndrome is unknown and hence is referred to as idiopathic. The commonest form is minimal change disease (85%). Renal biopsy findings in this form show no abnormality of the glomeruli on light microscopy. Electron microscopy shows effacement of the epithelial foot processes. Biopsy findings of FSGS (10%) reveal normal appearing glomeruli but may show some mesangial proliferation. Some biopsy specimens may demonstrate segmental scarring. Mesangial proliferative disease (5%) shows diffuse increase in mesangial cells and matrix on biopsy.

Pathophysiology

An immune basis for MCNS was proposed in 1974 but no primary immune abnormality has been identified. Studies have shown increased levels of circulating soluble interleukin-2 receptor in patients with active MCNS and FSGS. This soluble interleukin-2 receptor is shed by activated lymphocytes and may therefore indicate generalised activation of the immune system. However, this circulating soluble interleukin-2 receptor could serve as a neutraliser of circulating interleukin-2. It is unknown whether circulating levels represent evidence of activation or an attempt to down-regulate the immune responses.

There is hypercoagulability resulting from serum protein abnormalities introduced by renal protein wasting. All children with acute NS have increased platelet aggregation. Blood viscosity is increased and blood flow is reduced. Fibrinogen concentration is increased and antithrombin III is lost in the urine. All these factors contribute to this problem in NS.

The cause of cholesterolaemia and hypertriglyceridaemia remains uncertain. One theory is that reduced plasma oncotic pressure may stimulate lipoprotein synthesis and perhaps lipolytic factors may be lost in the urine.

Oedema reflects retention of salt and water. Reduced serum albumin causes a reduction in plasma oncotic pressure. When plasma oncotic pressure falls, intravascular volume is reduced, which stimulates proximal tubular reabsorption of sodium. The renin–angiotensin system is also stimulated, raising the serum aldosterone, which further increases distal tubular reabsorption of sodium. There is an increase in filtration capacity in patients with nephrotic syndrome along with an increase in glomerular permeability, resulting in proteinuria.

There is also evidence in some patients for primary salt and water retention by the kidney.

History

The presence of the following may be noted on history:

• recent flu-like illness;
• anorexia;
• abdominal pain;
• diarrhoea;
• recent ant bites or bee stings.

Examination

Periorbital oedema is noted initially, but in time oedema becomes generalised. Oedema of the lower extremities is usually ‘pitting’ in type and accumulates in dependent sites. The rate and degree of oedema formation is directly related to salt intake and to the degree of hypoalbuminaemia and therefore can vary from child to child. Ascites may be present. Pleural effusions or pulmonary oedema may develop. Scrotal or perineal oedema may be very distressing to the patient. Blood pressure may be decreased when hypovolaemia exists or may be elevated if there is significant renal disease by activation of the renin–angiotensin system or primary salt retention.

Investigations

• Hypoalbuminaemia (serum albumin <30 g L–1) occurs in every child with nephrotic syndrome.
• Reliably timed 24-hour urine collections are difficult to obtain in children (protein excretion exceeds 50 mg kg–1 per 24 hours or 1000 mg m–2 per 24 hours in nephrotic syndrome), so the proteinuria is generally quantified by the ratio of urine protein to urine creatinine. Spot urine protein:creatinine ratio is >300 mg nmol–1 in nephrotic syndrome. Normal is <0.2 mg protein per mg creatinine (or protein per mmol creatinine).
• Microscopic haematuria is seen in < 15% but macroscopic haematuria is rare.
• Urinalysis by dipstick reveals + 3 or + 4 proteinuria.
• Urine specific gravity is usually high at >1.020, but may be lower.
• Haematocrit is often elevated due to intravascular depletion and can be followed to assess fluid status.
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