A micropuncture study of renal sodium retention in nephrotic syndrome in rats: Evidence for increased resistance to tubular fluid flow

Abstract

Micropuncture studies were carried out in surface nephrons of rats with nephrotoxic-serum (NTS)-induced nephrotic syndrome during a period of active sodium and water retention. It was found that hydrostatic pressure and tubular diameter were increased in the proximal tubules (13.4 +/- 0.2 vs. 10.4 +/- 0.2 mm Hg; 31.3 +/- 0.9 vs. 18.4 +/- 0.7 mu), whereas pressure and tubular diameter were normal in the distal tubules. Single nephron glomerular filtration rate (SNGFR) was decreased and fractional reabsorption of fluid was markedly increased in the proximal tubules (74.1 vs. 61.7%). The increased pressure gradient between the proximal and distal tubules suggests a condition of increased resistance to flow between the proximal and distal tubules. Microinfusion of proximal tubules with an isotonic "equilibrium" solution led to little or no rise in intratubular pressure in normal rats but it led to a significant rise in nephrotic rats. When proximal tubules of normal rats were infused with a solution containing 100 mg/100 ml albumin, pressure rose to levels observed in nephrotic rats. The mechanism of the increased resistance to flow appeared to be related, therfore, to the presence of protein in the tubular fluid. Sodium retention in the nephrotic animals might be attributed to the reduction in GFR. In other types of renal disease in animals and man with comparable or greater reductions in GFR, sodium retention does not occur, however, and fractional excretion of sodium in the urine is increased in proportion to the reduction in GFR. Thus, the rise in proximal fractional reabsorption secondary to impaired fluid flow could be an important factor in the sodium retention of this disease.

Effect of Albumin Microinfusion on Proximal Tubular Pressure

“…In a second group. Kuroda et al [2] observed increases in PTP on microinfusion of lOOmg BSA/lOOml equilibrium solution which are close to those which we found with an albumin-free solution. In a single group of rats, we tested higher and lower BSA concentrations and observed the same pressure response as with an albumin-free solution (table I).…”

“…With every solution, infusion at 16nl/min and at 40nl/min pro duced significant (p< 0.01) increments in PTP. Mean arterial blood pressure averaged presence of albumin in tubular fluid ex plains the elevated loop of Henle resistance in nephrotic rats [2] is not supported by our data.…”

“…[2] that the presence of albumin in tubular fluid increases loop of Henle resistance. A limitation of their study is that they tested albumin-free and albu min-containing solutions in two different groups of normal rats.…”

“…Kuroda et al [2] found that moderate concentrations of albumin in tubular fluid were associated with increased resistance to flow in both nephrotic and normal rats. Our data suggest that the presence of moderate concentrations of albumin in the tubular fluid has no detectable effect on resistance in normal nephrons.…”

“…An increased resistance to flow through Henle's loop has been observed in nephroticrats, and was ascribed to the presence of pro tein in the tubular fluid [2]. Since serum albumin is the major urinary protein in the nephrotic syndrome, we have examined whether the introduction of albumin into the tubular fluid of normal rats influences flow resistance.…”