Faculty Bibliography

Micropuncture and microinjection studies were performed in Sprague-Dawley rats 20 h after subcutaneous injection of buffered maleic acid (MA) or buffer alone in experimental and control rats, respectively. Collections were made from earliest and latest accessible portions of proximal tubule (PT). Lissamine green injections and microperfusion of PT demonstrated leakage of lissamine green from late PT sites in MA-treated rats, whereas inulin leakage occurred at a more distal site. Whole kidney GFR was 58% lower in MA-treated rats despite comparable single nephron GFR in PT of both groups. Microinjections of PT with [methoxy-3H]inulin resulted in injected inulin recovery from the contralateral kidney in MA-treated rats of 24.0 +/- 2.0 compared with 4.7 +/- 0.89% in controls, suggesting that tubular leakage of inulin accounted for the lower whole kidney GFR. Net sodium and phosphate transport in early PT was similar in both groups but was decreased in late PT segments in MA-treated rats. Sodium and phosphate excretion in final urine were, however, comparable in both groups. The significantly lower plasma phosphate concentration might account for the blunted phosphaturia in MA-treated rats. These studies demonstrate a segmental effect of MA on 1) tubular leakage to lissamine green from late PT and inulin beyond the late PT, and 2) decreased net sodium and phosphate transport in the PT.

Following single, high dose (3 mg/kg) DDP therapy seven patients with head and neck cancer developed significant serum electrolyte disturbances. Hypocalcemia, hypomagnesemia, hypokalemia, and hypophosphatemia were the most clinically significant electrolyte abnormalities. Renal clearance studies support a pathologic mechanism of a diffuse renal tubular leakage not associated with renal failure.

Clearance experiments were performed in male Sprague-Dawley rats to determine the effect of mannitol on phosphate (Pi) transport. Solutions of 10 per cent mannitol or normal saline were infused at progressively increasing flow rates with or without parathyroid extract (PTE) infusion into the following animals: Group I: Intact Rats-Mannitol Infusion: A--Intact, hypocalcemic; B--Intact, normocalcemic, normomagnesemic; Group II: TPTX Rats: A--Mannitol infusion; B--Mannitol + PTE infusion; C--Hydropenia + PTE infusion; and D--Saline + PTE infusion. In contrast to previous reports, mannitol increased Pi excretion in intact rats. When Ca + Mg were maintained constant in intact rats or after TPTX, mannitol failed to increase Pi excretion. In TPTX rats receiving mannitol + PTE, increased Pi excretion was again noted. Comparison of Pi excretion during PTE infusion during hydropenia and volume expansion with mannitol or saline in TPTX rats revealed significantly higher Pi excretion with volume expansion. Pi excretion paralleled Na excretion in intact mannitol-loaded and PTE-infused TPTX animals undergoing a mannitol or saline diuresis. Pi and Na excretions, however, were dissociated in mannitol-loaded TPTX rats, intact animals receiving simultaneous Ca and Mg infusion, and TPTX hydropenic animals receiving PTE. These studies indicate that (1) mannitol increases Pi excretion in intact rat, (2) the phosphaturia is PTH-mediated, (3) Pi and Na excretions can be dissociated, and (4) volume expansion with either mannitol or saline enhances the effect of PTH on Pi transport in the renal tubule.

Among eight subjects suspected of excessive occupational exposure to lead, detailed examination of renal function identified abnormalities in four. Glomerular filtration rate was less than 87 ml/mim/1.73 m2 in one subject with asymptomatic renal failure, and in three subjects with preclinical renal dysfunction. In the subject with asymptomatic renal failure, chelation therapy increased the glomerular filtration rate, p-aminohippurate (PAH) extraction, the maximal PAH secretion rate (TmPAH) and improved proximal tubule ultrastructure, despite decreased renal plasma flow. This improvement in PAH transport was associated with correction of a proximal tubule defect in tritiated PAH uptake detected by section freeze-dry autoradiography of renal biopsy specimens. In three subjects, the etiologic diagnosis of lead-induced nephropathy was established by exclusion, but tubular dysfunction did not obviously exceed the reduction in blomerular filtration. Proximal tubule abnormalities were seen in each of the three patients who underwent biopsy. These studies suggest that lead nephropathy may be an important occupational hazard in the United States lead industry