Pathophysiology of Edema Formation in Children with Nephrotic Syndrome Not Due to Minimal Change Disease

Abstract

Abstract. It has been shown that children with nephrotic syndrome due to minimal change disease (MCD) can present with avid salt retention and stimulated vasoactive hormones, as well as with stable edema. The present study examines these conditions in children with nephrotic syndrome not due to MCD (non-MCD). In six children with hypovolemic symptoms (congenital nephrotic syndrome in four), strong sodium retention (fractional sodium excretion, FENa, 0.2 ± 0.2%) was found. Lithium clearance (FELi) and maximal water excretion (Vmax) were suppressed, suggesting avid sodium reabsorption throughout the nephron. Aldosterone, renin, and norepinephrine were elevated. Sixteen other children with non-MCD had stable edema. FENa was 1.8 ± 1.1%, whereas FELi, Vmax, and hormones were normal, and not different from data in 35 nonproteinuric children. In children with MCD, 12 presented with hypovolemic symptoms and strong sodium retention (FENa 0.3 ± 0.3%), whereas 15 were stable (FENa 1.1 ± 0.7%). Regarding tubular sodium handling and hormones, the same distinction could be made as for the children with non-MCD. However, hypoproteinemia differed. In the children with non-MCD lesions, plasma colloid osmotic pressure was significantly lower in the hypovolemic types (4.2 ± 0.4 mmHg) than in those with stable edema (13.0 ± 3.8 mmHg; P < 0.05); in MCD, no such difference existed (respectively, 8.1 ± 3.0 and 9.9 ± 2.2 mmHg). In summary, children with nephrotic syndrome may present with pathophysiologic pictures of decreased effective circulating volume or of stable edema, regardless of whether they have non-MCD or MCD. The pathogenesis of the hypovolemic picture seems to be different, since it is associated with extreme hypoproteinemia only in the children with non-MCD.

Proteasuria: The Link between Physiopathogenesis and Edema Management in Nephrotic Syndrome?

“…Vande Walleet et al, compared children with NS secondary to minimum change disease versus those without minimal changes and subsequently divided them by the presence or absence of signs and symptoms of hypovolemia. Patients with hypovolemia symptoms in both groups had significantly high levels of norepinephrine, renin, and aldosterone unlike their non -symptomatic counterpart [6].…”

Nephrotic Syndrome: From Pathophysiology to Novel Therapeutic Approaches

“…The migration of water from one compartment to another is linked to the close relationship between the hydrostatic and oncotic pressures of capillary and interstitial fluids, which can be explained by the presence of Starling forces [ 6 , 7 ]. There seem to be differences between these pressures in relation to age—some children tend to have lower oncotic capillary pressure than most adults, as is seen in the case of children with MCD [ 3 ] and the etiology of nephrotic syndrome, including (1) various permeability factors with different influences on protein permeability [ 8 ], (2) different plasma or interstitial oncotic pressures [ 9 , 10 , 11 ], and (3) an increase in capillary hydrostatic pressure secondary to sodium retention, as in acute poststreptococcal glomerulonephritis [ 3 , 12 ].…”

Albumin is an interface between blood plasma and cell membrane, and not just a sponge

“…The hypothesis implied that patients with NS are hypovolaemic, but data from clinical studies demonstrated that only a small portion actually are hypovolaemic and that the majority of patients are euvolaemic or hypervolaemic [ 15–18 ]. Plasma oncotic pressure was reduced in children with NS, while hypovolemic symptoms were only present in ∼27% of the children with NS [ 19 ]. Hypovolaemia was accompanied with an activation of the RAAS; however, in a large cohort of NS patients, RAAS activation was not associated with blood volume [ 20 ].…”

“…Hypovolaemia was accompanied with an activation of the RAAS; however, in a large cohort of NS patients, RAAS activation was not associated with blood volume [ 20 ]. Additionally, increased plasma renin activity was only increased in NS patients with hypovolemic symptoms [ 19 ]. It is suggested that minimal change disease represents a unique NS phenotype with increased neurohumoral activity, independent of blood volume [ 21 ].…”

“…After steroid-induced remission of NS is achieved, natriuresis is promoted while plasma protein content and blood volume are still low [ 23 ]. In contrast to all this evidence against the hypovolaemia hypothesis, there is one study showing that fractional sodium excretion is only reduced in NS patients with symptoms of hypovolaemia [ 19 ].…”