We have analyzed the efficiency with which p-amino-hippuric acid (PAH) is extracted (EPAH) by patients with healthy kidneys (n = 13) or kidneys damaged by chronic cyclosporin nephropathy (n = 21) or primary glomerulopathy (n = 12); respective values (mean +/- SE) for EPAH were 0.87 +/- 0.03, 0.77 +/- 0.03, and 0.69 +/- 0.04. Judged by a 131I-hippuran-to-PAH clearance ratio of 0.75 +/- 0.05, extraction ratio of hippuran was less efficient than EPAH in three glomerulopathic patients. A direct relationship was defined between EPAH and glomerular filtration rate (GFR) (r = 0.54) or calculated efferent oncotic pressure (IIE; r = 0.41, P less than 0.01). Curve fitting by means of quadratic spline functions revealed GFR and IIE to be additive in predicting EPAH (R2 = 0.45). Linear model prediction methods and a sample reuse technique failed to predict EPAH reliably from GFR and preglomerular oncotic pressure (IIA); however, 95% prediction intervals exceed 0.30 EPAH units in width. We conclude that oncotic pressure (presumably reflecting albumin concentration) along with GFR is predictive of EPAH depression in humans with chronic renal disease. However, even sophisticated curve-fitting techniques are too imprecise for accurate prediction of EPAH in a given individual. We submit that renal venous sampling to determine EPAH continues to be necessary for the accurate determination of the rate of plasma flow in the injured human kidney.

A B S T R A C T Recently we demonstrated potassium secretion by the pars recta or by the descending limb of the juxtamedullary nephron. The purpose of this present investigation is to study the effect of a chronic high-potassium intake on this phenomenon. Fractional reabsorption of water and sodium by the juxtamedullary proximal nephron was decreased when compared to that in normal hydropenic rats. There was a striking increase in the fraction of filtered potassium at the end of the juxtamedullary descending limb from 94+11% to 180+18%, which was principally a result of enhanced potassium secretion. When the concentration of potassium in the collecting tubule fluid of potassium-loaded rats was reduced after the administration of amiloride, a sharp fall was observed in the amount of potassium which reached the end of the descending limb (64+8%). A direct correlation was observed between the fraction of filtered potassium at the end of the descending limb and the potassium concentration in the final urine (P < 0.001). The findings suggest that potassium, like urea, normally undergoes medullary recycling, which is enhanced by chronic potassium loading.Portions of this work were presented to

A B S T R A C T Recent models of the urinary concentrating mechanism have postulated that urea in the medullary interstitium creates a transtubular concentration gradient for sodium between fluid at the end of the descending limb of Henle's loop and the medullary interstitium, favoring the passive outward movement of sodium from Henle's thin ascending limb. These experiments were designed to determine whether such a gradient normally exists. Young nondiuretic Munich-Wistar rats were prepared for micropuncture of the exposed left renal papilla. Samples of loop of Henle fluid and vasa recta plasma (assumed to reflect the composition of interstitial fluid) were obtained from adjacent sites. Loop fluid values in 21 comparisons from 18 rats (mean+SE)were: sodium, 344+ 12 meq/liter; potassium, 26+2 meq/liter; osmolality, 938+37 mosmol/kg H20. Vasa recta plasma values (in corresponding units ofmeasurement) were: sodium, 284±11; potassium, 34±2; osmolality, 935±34. Mean values of paired differences (loop fluid minus vasa recta plasma) were: A sodium, 60±11.1 (P < 0.001); A potassium, -8.0±2.1 (P < 0.001); A osmolality, 4±16 (NS). Corrected for plasma water, the loop fluid minus vasa recta differences (in milliequivalents per kilogram H20) were:A sodium, 40±11.4 (P < 0.005); A potassium, -9.7 ±1.9 (P < 0.001). We interpret these findings to indicate that in the papilla of nondiuretic rats, a significant difference in sodium concentration exists across the thin loop of Henle favoring outward movement of sodium, which confirms a key requirement of the pasPortions of this work were presented to the American Society for Clinical Investigation.

We report the pharmacokinetic parameters of ceftriaxone in 11 patients on hemodialysis with end-stage renal disease (ESRD; creatinine clearance < 5 ml/ min/1.73 m²). The patients were studied during the interdialysis period and during 4h of hemodialysis. The mean age was 53.4 years. After the administration of 1 g of ceftriazone during a constant intravenous infusion over a 30-min period, t_½ was 16.6 h, β was 0.0418 ± 0.0106 h^-1, V_D was 14.5 ± 3.0 liters/1.73 m² and Cl_p was 0.40 ± 0.05 liters/h for the interdialysis period. Hemodialysis started 24 h after the infusion. The initial plasma ceftriaxone concentration was 68.6 ± 10.8 μg/ml. This value dropped to 40.4 ± 4.7 μg/ml at the end of the 4th hour, indicating a significant 41% decay in blood levels during hemodialysis (p < 0.001). The t_½ decreased to 4.88 h, k_el rose to 0.142 ± 0.0250 h^-1 and Cl_p increased to 1.73 ± 0.44 liters/h. All values were highly significantly different (p < 0.001) from those during the interdialysis period. The plasma ceftriaxone concentration of 40.4 ± 4.7 μg/ml at the end of hemodialysis was well within the therapeutic range of the drug. We conclude that ceftriaxone has a moderated increase in t_½ in patients with ESRD. Ceftriaxone is significantly dialyz-able, however, the plasma concentrations are in the therapeutic range by the end of a 4-hour hemodialysis, 28 h after the administration of the drug. We propose that 1 g given intravenously before each hemodialysis will be sufficient to keep the patient’s plasma concentrations within the therapeutic range until the next hemodialysis. If the interdialysis period is longer than 48 h an extra dose should be administered.

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