Mg. Koopman et al., CIRCADIAN-RHYTHM IN GLOMERULAR TRANSPORT OF MACROMOLECULES THROUGH LARGE PORES AND SHUNT PATHWAY, Kidney international, 49(5), 1996, pp. 1242-1249
In previous studies we have demonstrated that the circadian rhythm in
renal clearance of serum proteins is more pronounced than the variabil
ity in glomerular filtration rate, and that the highest day-night fluc
tuations are found for the largest proteins. To analyze whether additi
onal circadian rhythmicity in size-selective glomerular transport coul
d explain these phenomena, we measured renal clearances of inulin and
dextrans in a range of 30 to 90 Angstrom over a period of one day and
compared these data with renal clearance in proteins. Eight patients w
ith nephrotic syndrome and a GFR > 60 ml/min and 6 healthy volunteers
were studied during a protocol of bed rest and spaced protein and flui
d intake. After administration of a loading dose, inulin and dextran w
ere continuously infused. Blood and urine were sampled every three hou
rs. In patients, but not in normals, fractional clearances of dextrans
larger than 45 Angstrom showed a circadian rhythm with a peak in dayt
ime and a close phase-relationship with the rhythm in GFR. The day-nig
ht differences were the most pronounced for the largest dextrans. Anal
ysis of the day-night differences in a computer model showed circadian
variability in transport through the shunt pathway and through large
pores. These results can, to an important degree, explain our previous
observations on circadian variability in renal clearance of proteins
in patients with nephrotic syndrome.