H. Rondon-Berrios.Oedema in nephrotic syndrome
only six had oedema. These six patients with oedema hadan alternative diagnosis that clearly explained the presenceof oedema (
). During the study, they foundsome patients with serum albumin levels below 1.5g/dl,but none of them had oedema.
Natriuresis in the recovery phase of nephroticsyndrome begins when proteinuria disappears butbefore serum albumin returns to normal levels
The absolute decrease in plasma oncotic pressuredoes not affect the volume of the intravascularspace in nephrotic syndrome
Studies performed on dogs suggest that the absolutedecrease in plasma oncotic pressure would not affectplasma or blood volume.
Patients with NS caused byglomerulonephritis were studied by measuring theirplasma and interstitial oncotic pressure: 12 patients in theactive phase, 3 in complete remission and 3 in partialremission.
The researchers found that plasma andinterstitial oncotic pressure were decreased in the activephase of NS but slowly returned to normal values duringremission. During this time, the oncotic pressure gradientbetween plasma and interstitium was constant.
Thesestudies show that it is the change in the oncotic pressuregradient between plasma and interstitium and not just theabsolute decrease in plasma oncotic pressure that causesthe movement of fluid from the intravascular to theinterstitial space.
Plasma and blood volumes are normal or increasedin nephrotic syndrome
Geers et al
measured plasma volumes in 88 patients withNS and in 51 controls. Plasma volume was measured byadministration of radioactive albumin I.
Blood volumewas calculated based on plasma volume and haematocrit.The plasma and blood volume of NS patients was foundto be high in 14%, normal in 84% and low in only 2% of cases.
Intravascular space expansion with albumin doesnot increase natriuresis in patients with nephroticsyndrome
The effect of an intravenous infusion of hyperoncoticalbumin (75g) was observed in patients with NS.
Afterthe infusion, blood volume increased up to 120% of baseline. Plasma renin activity and serum aldosteroneconcentration decreased to the point of beingsuppressed. Urinary sodium excretion did not changesignificantly.
The activation of the renin-angiotensin-aldosteronesystem is not involved in the development ofoedema in nephrotic syndrome
Brown et al
administered captopril to a group of NSpatients and observed no change in sodium excretion despitesuppressing serum aldosterone concentrations. In anotherstudy, Usberti et al
reported similar findings when usingspironolactone.
Adrenalectomy does not prevent sodium retentionand the development of ascites in nephroticsyndrome in laboratory rats
De Seigneux et al studied a group of rats from which theyhad removed both adrenal glands. The rats wereadministered dexamethasone to prevent adrenal failure.
Theresearchers induced NS in the rats by administeringpuromycin. The rats developed oedema and sodium retentiondespite having been adrenalectomised. These findingssuggest that aldosterone does not play a major role in sodiumretention that is characteristic of NS.
ALTERNATIVE HYPOTHESIS OR
HYPOTHESIS OF OEDEMA FORMATION INNEPHROTIC SYNDROME
Contrary to the classic hypothesis, the alternative hypothesis(also called the
hypothesis) postulates that sodiumretention in many NS patients is a primary renalphenomenon and may be caused by an intrinsic renal defectin sodium excretion, which in turn causes an expansion inplasma volume (hence the term
). Although themolecular mechanism of sodium retention in the kidneys hasnot been clearly explained, there are a number of studies onthis topic, which we describe below.
Molecular mechanisms of sodium retentionin nephrotic syndrome
The first observations supporting the
hypothesiswere made by Chandra
Most of ourunderstanding of the molecular mechanisms of sodiumretention in NS has come from the use of animal models thatinduced NS by puromycin aminonucleoside (PAN). WhenPAN is administered to rats, it causes massive proteinuriaand sodium retention. The renal histopathology induced byPAN resembles minimal change disease.
Using thetechnique of selective unilateral perfusion through the leftrenal artery with PAN first described by Bricker in dogs
and later by Hoyer in rats,
showedthat proteinuria and sodium retention were confined to thekidney perfused with PAN. The unilateral NS model allows