Based on observations in 110 children with nephrotic syndrome (NS) and data from the literature, existing concepts on the pathogenesis of edema formation in the NS have been modified. The data suggest that the basic abnormality is a primary disturbance in renal sodium excretion. Depending on the stage in the development of the NS, the rate of progression in the development of hypoproteinemia, and the absolute levels of plasma oncotic pressure, functional hypovolemia may develop, resulting in stimulation of hemostatic mechanisms and secondary sodium retention. This applies as much to patients with minimal change NS as to patients with histological lesions. Alterations in kidney function (glomerular filtration rate, renal plasma flow, filtration fraction) in the NS cannot be explained by hypo- or hypervolemia, but reflect variations in plasma oncotic pressure and glomerular basement membrane permeability. These abnormalities will also influence sodium excretion. Evaluation of the presence of functional hypovolemia will have therapeutic consequences. A quick diagnosis can be made by assessment of FENa+ and UK+/ (UK+ + UNa+) Sodium retention associated with increased distal Na/K exchange indicates functional hypovolemia, and may be treated by albumin infusion if clinically required.

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.

The association of fever, nasal congestion and reversible rise in serum creatinine in a patient receiving azathioprine is reported. An identical pattern of symptoms was induced after two rechallenges with azathioprine. The increases in serum creatinine were not associated with renal parenchymal abnormalities. This paper illustrates that in transplanted patients, fever and rises in serum creatinine are not only related to rejection or infection, but may also involve drug hypersensitivity.