Flashcards in Renal - Nephrotic syndrome Deck (14):
What is nephrotic syndrome?
Heavy proteinuria sufficient to cause hypoalbuminaemia, with associated retention of salt and water causing oedema. All causes of nephrotic proteinuria result in abnormal foot processes consistent with defects in their slit diaphragm and the size selectivity of filtration.
Nephrotic syndrome always causes proteinuria, but nephrotic syndrome is not the only cause of proteinuria.
Causes of proteinuria
Proteinuria is always abnormal and is an early indication of renal disease. Causes can be:
1) Overflow (increased plasma levels)
- single: myeloma Ig light chain, haemoglobinuria, myoglobinuria
- multiple: inflammation
2) Tubular (decreased tubular reabsorption)
- tubulointerstitial disease
3) Glomerular (filtration leak)
Name some congenital causes of nephrotic syndrome
Congenital nephrotic syndrome in children can result from defects in the slit membrane proteins nephrin and podocin, and the glomerular basement protein laminin beta 2 and the CD2AP protein. In many renal diseases, there are high levels of ATII, which can downregulate nephrin, causing disruption of slit membrane structure and proteinuria. Mutations in alpha actinin 4, a podocyte actin binding protein, can cause congenital focal segmental glomerulosclerosis as can mutations in the TRPC6 calcium channel gene.
Causes of nephrotic syndrome
- minimal change
- focal segmental glomerulosclerosis
- proliferative (rarer) - IgA, post infective, SLE
Difference between selective and non selective proteinuria
There are different "types" of proteinuria. Plasma proteins are filtered at the glomerulus according to their size and charge. Small proteins <20kDa are freely filtered, then reabsorbed and degraded in the proximal tubule. Reabsorption involves uptake by endocytosis (megalin and cubilin receptors). This process catabolizes hormones, such as insulin, and small immunological molecules such as Ig light chains. So, isolated loss of small proteins in the urine (SELECTIVE PROTEINURIA) indicates either overflow proteinuria (caused by excess serum and filtered proteins overwhelming normal tubular reabsorption) or tubular proteinuria (resulting from impaired tubular reabsorption). The filtration barrier is normal. Large proteins such as albumin, transferrin and IgG are not normally filtered and are lost in the urine only if glomerular filtration barrier is damaged. This NON SELECTIVE PROTEINURIA is called glomerular proteinuria.
Quantified with 24 hour urine collection
- nephrotic range = >3.5g/24 h
- high urine protein/ creatinine ratio above 400mg/mmol or 45mg/mg or g/g also signifies nephrotic range proteinuria
Urinary protein electrophoresis can distinguish different types of proteinuria
- tubular and overflow proteinuria only low molecular weight proteins are present
- overflow proteinuria - tends to be one abundant protein in urine - e.g. Ig light chain resulting from a B cell disorder such as myeloma
- inflammation rarely causes overflow proteinuria of many small acute phase proteins
- glomerular proteinuria - albumin most common
Clinical features of nephrotic syndrome
Patients usually present with oedema.
Urine may be frothy because of high protein content.
MCC are minimal change glomerulonephritis in children and membranous nephropathy or focal segmental glomerulosclerosis in adults.
Prothrombotic state, hypertension, hyperlipidaemia - contribute to higher incidence of ischaemic heart disease.
Unless obvious diabetic nephropathy, or clinically typical childhood minimal change glomerulonephritis, histological diagnosis is made by renal biopsy.
What causes oedema and sodium retention in nephrotic patients?
Hypoalbuminaemia may reduce intravascular volume leading to hypoperfusion and renin mediated hyperaldosteronism. Loss of vascular oncotic pressure leads to interstitial extravasation.
Complications of protein loss in nephrotic syndrome
Negative protein balance and protein malnutrition.
Tendency for infection due to loss of IgG, esp pneumococcus - vaccination and prophylactic antibiotics help
Why is nephrotic syndrome a prothrombotic state?
Thromboregulatory proteins - e.g. antithrombin III, protein S and protein C are lost in the urine
Hypoproteinaemia increases liver synthesis of fibrinogen, raising fibrinogen levels
These changes promote venous thrombosis, especially for renal and deep leg veins. Pulmonary emboli can occur. Renal vein thrombosis can result in sudden deterioration in renal function with flank pain and haematuria.
Hyperlipidaemia in nephrotic syndrome
Increased hepatic lipid and apolipoprotein synthesis and reduced chylomicron and VLDL catabolism. These changes may result in urinary loss of liporegulatory substances and cause a rise in plasma LDL cholesterol and VLDL. Hyperlipidaemia requires diet and drug therapy, usually with a statin.
Renal impairment in nephrotic syndrome
Glomerular filtration is often reduced and nephrotic kidneys are vulnerable to pre renal acute failure. Disruption of the normal arrangement of epithelial foot processes probably reduces the number of functional interpodocyte filtration slits. Although each slit has a high permeability, there may be a reduction in the total surface area for filtration so GFR decreases.
Treatment of proteinuria
Treat underlying renal disease
- minimal change and FSG may respond to steroids
- renal biopsy required in adults, assumed minimal change in children - give steroids
ACEi/ARBs - reduce proteinuria
- block effects of ATII on the filtration barrier
NSAIDs - e.g. indomethacin
- reduce proteinuria
- BUT...reduce GFR, filtration fraction and can worsen sodium retention (---> AKI)
Both ACEi and NSAIDs can cause hyperkalaemia
Treat oedema with sodium restriction and diuretics (depending on renal function)
Thromboprophylaxis (severe proteinuria and hypoalbuminaemia)