No abstract

Simultaneous capillary and luminal microperfusion studies in the proximal convoluted tubule of the rat were performed to examine the transepithelial secretory flux of [14C]oxalate. Increases in the concentration of oxalate in the capillary solution from 0.096 to 4.3 mM resulted in progressively higher rates of oxalate secretion into the lumen. Further increases in the capillary concentration of oxalate indicated a tendency toward a plateau. The inclusion of para-chloromercuribenzoate, sodium cyanide, indanyloxyacetic acid, furosemide, or para-aminohippurate in the capillary solution significantly lowered the secretory flux of oxalate. the addition of probenecid in a concentration of 10(-4) M inhibited oxalate secretion when the oxalate concentration in the capillary solution ranged between 1.1 and 4.3 mM, but did not affect oxalate secretion at higher capillary concentrations of oxalate. These results indicate that oxalate secretion in the rat proximal tubule is an active carrier-mediated process. When considered in conjunction with prior studies, the present investigations suggest the possibility that more than one oxalate secretory system exists in the rat proximal tubule.

Simultaneous capillary and luminal microperfusion studies were performed in the rat proximal tubule to determine the effects of the beta agonist isoproterenol and the alpha agonist phenylephrine on water absorption. Capillary and luminal perfusion solutions were composed such that organic solutes were not present, no bicarbonate was present in the lumen, and no chloride gradient was imposed. Under such conditions, water absorption (Jv) averaged 0.36 +/- 0.11 nl . min-1 . mm-1. the addition of isoproterenol to the capillary solution in concentrations of 10(-6) and 10(-4) M resulted in significantly higher Jv's of 0.68 +/- 0.10 and 0.71 +/- 0.11 nl . min-1 . mm-1, respectively. The enhancing effect of isoproterenol was inhibited by the beta blocker propranolol (10(-4) M), but not by the alpha blocker phentolamine (10(-7) M). The addition of phenylephrine (10(-6) M) to the capillary perfusion solution also resulted in a significantly higher Jv of 0.84 +/- 0.14 nl . min-1, an effect inhibited by phentolamine (10(-7) M), but not by propranolol (10(-4) M). Neither phentolamine nor propranolol alone in the concentrations indicated had an effect on water absorption. These experiments indicate that both alpha and beta agonists stimulate water absorption in the superficial proximal tubule of the rat. This effect appears to be relatively specific for each class of agonist, as demonstrated by the effects of the specific antagonists.

No abstract

Oxalate transport was examined in isolated perfused segments of the proximal tubule of the rabbit. When oxalate was present in a concentration of 10(-5) M in the bathing and perfusing solutions, there was a net secretory flux of oxalate of 36.4 +/- 1.4, 34.7 +/- 4.3, and 20.7 +/- 2.8 x 10(-15) mol . min-1 . mm-1 in the superficial S1, S2, and S3 segments, respectively, at a bath temperature of 37 degrees C. The net secretory flux of oxalate in the juxtamedullary S1 and S2 segments was 12.8 +/- 2.5 and 12.5 +/- 3.6 x 10(-15) mol . min-1 . mm-1, respectively. Cooling to 25 degrees C resulted in a significant decrease in the net flux of oxalate. When oxalate was present in the bathing solution only (10(-5) M), the bath-to-lumen flux of oxalate was not different from the net flux in the superficial and juxtamedullary S2 segments. These studies demonstrate that oxalate undergoes net secretion in the rabbit proximal tubule. This occurs against an electrical gradient, in the absence of concentration gradients, and can be inhibited by cooling, suggesting an active transport process. There is significant internephronal heterogeneity in the proximal tubule for oxalate secretion.

No abstract

Prescribing hemodialysis by monitoring only predialysis BUN concentrations is not sufficient to guarantee adequate therapy. Results from the National Cooperative Dialysis Study have suggested that hemodialysis therapy is adequate if the protein catabolic rate is maintained greater than 1 g/day/kg body weight and simultaneously if sufficient hemodialysis is prescribed to maintain either a time-averaged BUN concentration (TACurea) less than 50 mg/dl or a value of Kt/V greater than unity. In the present study mathematical relationships were derived from a weekly urea mass balance model that permit an evaluation of TACurea and of protein catabolism via the urea generation rate (G) without the need for conventional urea kinetic modeling. The parameters TACurea and G were simply calculated from a midweek predialysis BUN concentration (BUNMw) by:TACurea = 0.7 BUNMw G =0.7BUNMw(Kr+Kdτ/T) where Kr, Kd,τ and T denote residual renal urea clearance, dialyzer urea clearance, number of minutes of hemodialysis per week, and number of minutes total in a week, respectively. Clinical results from 139 modeling sessions on 91 patients demonstrated that TACurea and G derived from urea kinetic modeling correlated highly with those calculated from the above equations (r = 0.96 and 0.94, respectively). It is concluded that individualized hemodialysis prescription and adequacy of therapy can be assessed by monitoring TACurea and G by calculation from a weekly urea mass balance model.

The renal handlinig of oxalate was examinied by free-flow micropuncture, intratubular microinijectioni, an(d droplet precessioni techniques in the rat. After the stustained i.v. infusionj of [14C]oxalate, the fractional (Ieliverv of oxalate from the early portions of the proximal tul)ule was 120.1+4.4%, indicating net secretioin. Fractionial delivery rates from the late proximal tubtule (124.6+6.1), distal tubule (120.9+2.9), and final urine (126.2+2.9%) were not different froml that of the early proximal tubule. Direct intratubular miicroinjections of oxalate into the early proximal tubule anid late proximal tubule yielded urinary re-coverv rates of 85+3% and 101+2%, respectively, suggesting that oxalate absorption does occur in the mlid-portionis of the proximal tubule. Droplet pre-cessioni studies confirmed a secretorv flux for oxalate. In contrast to oxalate, para-aminlohippurate (PAH), the more traditional marker for organic acid transport, was secreted in the late portions of the proximal tubule and in large measure at a site between the late proximal and distal tubules, presumably the pars recta. Probenecid inhibited PAH secretion but was w%ithout effect on net oxalate transport, oxalate absorption , or oxalate secretion. These studies demiionistrate that net oxalate secretion ocecurs in the earlx portions of the proximlal convoltuted tubule, uinidergoes bidirectional trainsport of approxi-m-atel e(qulal milagnittude in later segmiienits of the proximual tubtule, aind problalyl is not transported in imiore distal nephroni sites. The secretory mechaniism for oxalate differs fromn that of PAH in that it is located in a differenit segment of the nephroni and is not inhibited by probenecid. These differences These studies wvere performiied wvhile Dr.