Renal tubule cell volume is thought to be kept constant by a cation pump. When active transport is blocked, intracellular impermeant solutes cause cells to swell. Cell size is then determined by transmembrane hydrostatic and colloid osmotic forces. We studied the importance of passive transmembrane forces in determining cell size in isolated rabbit proximal straight tubules (PST). We blocked active solute transport with ouabain and evaluated subsequent changes in cell size by measuring outer diameter of nonperfused tubules. Tubules in a ouabain and 6 g/100 ml protein bath swelled only 40% above control. However, removal of the tubule basement membrane with collagenase dissipated a transmembrane hydrostatic pressure and caused more swelling. Final cell volume was determined largely by bath protein concentration. Tubules in ouabain and collagenase swelled enormously in hyponcotic protein, moderately in isoncotic protein, and could be shrunk below control in hyperoncotic protein. Intracellular colloid osmotic pressure was estimated to exceed 38 cmH20. We conclude that hydrostatic and colloid osmotic forces are major determinants of cell size in isolated PST treated with ouabain.
Para-aminohippurate (PAH) is secreted at different rates in S1, S2, and S3 segments of isolated perfused proximal tubules of rabbit kidney. To characterize PAH transport we determined the maximal rate of secretion (Vmax) and the apparent Michaelis constant (Km) for each segment by examining the relationship between bath concentration of PAH and net PAH secretion (Jb leads to lPAH) transposed for Lineweaver-Burk analysis. The passive component of secretion for all segments was estimated by slope analysis at relatively high concentrations of PAH, by the component of PAH secretion insensitive to inhibition by probenecid, and, additionally, in S2 segments, from PAH efflux from lumen to bath. Subtraction of the passive component from Jb leads to lPAH (probenecid method) gave Vmax values for S1, S2, and S3 segments of 1,097 +/- 336 (n = 6), 7,430 +/- 1,338 (n = 6), 1,647 +/- 138 (n = 8) X 10(-15) mol.min-1.mm-1 (+/- SE) and apparent Km values of 139 +/- 37 (n = 6), 195 +/- 37 (n = 6), and 113 +/- 16 (n = 6) X 10(-6) M, respectively. Thus, Vmax for S2 greater than S3 congruent to S1, whereas apparent Km was not consistently different among the segments. On the basis of these results we suggest that axial heterogeneity of PAH secretion may reflect an increased basolateral membrane density of PAH transporters of common affinity in the S2 segment of the proximal tubule.
Patients with end-stage kidney disease, particularly those treated with dialysis, develop proliferative processes in their native kidneys that result in the formation of multiple acquired renal cysts, renal adenomas, and carcinomas. Data about these abnormalities have been acquired mainly from retrospective studies. We undertook a longitudinal prospective study in which the native kidneys of 30 dialysis patients were surveyed by serial CT during a 7-year period to study the natural history of acquired renal cystic disease and the frequency of associated complications. Acquired cysts were seen in 87% of patients at the end of the study compared with 57% at the study's onset, and a significant increase was seen in mean renal volume with time. Five patients (17%) developed large hemorrhagic renal cysts and four (13%) developed large perinephric hematomas. Renal cell carcinomas developed in two patients (7%) without renal symptoms. One carcinoma invaded the renal capsule, but did not cause metastases. The other carcinoma was widely metastatic. Our findings are consistent with those of earlier studies documenting an increased prevalence of renal cell carcinoma in dialysis patients as compared with the general population. However, our conclusions are limited because the study sample is small and no control population was studied. We conclude that acquired renal cystic disease in dialysis patients is a progressive disorder often associated with cyst hemorrhage. Dialysis patients may also have an increased prevalence of renal cell carcinoma.
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