Circadian rhythm in glomerular transport of macromolecules through large pores and shunt pathway

In previous studies we have demonstrated that the circadian rhythm in renal clearance of serum proteins is more pronounced than the variability in glomerular filtration rate, and that the highest day-night fluctuations are found for the largest proteins. To analyze whether additional circadian rhythmicity in size-selective glomerular transport could 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 with nephrotic syndrome and a GFR > 60 ml/min and 6 healthy volunteers were studied during a protocol of bed rest and spaced protein and fluid intake. After administration of a loading dose, inulin and dextran were continuously infused. Blood and urine were sampled every three hours. In patients, but not in normals, fractional clearances of dextrans larger than 45 Angstrom showed a circadian rhythm with a peak in daytime and a close phase-relationship with the rhythm in GFR. The day-night differences were the most pronounced for the largest dextrans. Analysis 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.