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K V Lemley

Publications and source records attributed to K V Lemley.

15 recordsLinked to original sources
PubMed1996

A frequent pathway to glomerulosclerosis: deterioration of tuft architecture-podocyte damage-segmental sclerosis.

Lesions in glomerular architecture include mesangial expansion, capillary ballooning, capillary unfolding and microaneurysm formation. Such lesions appear to develop in response to mechanical overextension. A frequent pathway to segmental glomerulosclerosis starts from capillary ballooning and unfolding. Podocytes supporting those deranged capillaries are exposed to increased mechanical stress. This may lead to podocyte injury terminating in detachments from the GBM. Naked GBM areas at peripheral capillary loops allow the attachment of parietal cells to the GBM, i.e. the formation of a tuft adhesion to Bowman's capsule. An adhesion has a strong tendency to progress to segmental sclerosis.

Animals↗
PubMed1995

Glomerular hypertrophy after subtotal nephrectomy: relationship to early glomerular injury.

Structural adaptations in response to approx. 70% nephrectomy were studied in male Sprague-Dawley rats. Rats developed systemic hypertension as well as progressive albuminuria after nephrectomy. At 18-26 weeks after nephrectomy (n = 6) or sham treatment (n = 6) kidneys were perfusion-fixed and examined by light and electron microscopy. Glomerular tuft volume (+140%), capillary volume (+151%) and length (+77%), mesangial volume (+115%), podocyte volume (+96%), glomerular basement membrane surface area (+107%) and filtration slit length (+85%) were all significantly greater in nephrectomized rats. The incidence of segmental glomerular sclerosis was low and variable among these rats, but was significantly higher than in controls (P = 0.037). Urinary albumin excretion was elevated in the nephrectomized rats (89 +/- 72 SD mg/day vs 11 +/- 11 mg/day in control rats, P = 0.01) and correlated significantly with the incidence of sclerosis (r = +0.8311, P < 0.05). The relationships of the level of albuminuria and the sclerosis rate to various morphometric parameters were examined by regression analysis for the nephrectomy group. A significant negative correlation was found between albuminuria and average tuft volume (r = -0.8136) and glomerular basement membrane surface area (r = -0.8168). Both sclerosis rate and albuminuria showed negative correlations with filtration slit length (r = -0.8180 and r = -0.8598). These findings suggest that under some circumstances, glomerular hypertrophy may prevent or ameliorate the early stages of glomerular injury after subtotal nephrectomy.

Animals↗
PubMed1995

Structure-stabilizing forces in the glomerular tuft.

The glomerular tuft is constantly exposed to considerable expansile forces resulting from high capillary pressures. Counterforces must be generated in order to maintain structural stability. This review analyzes those structures of the glomerular tuft capable of developing such stabilizing forces. Two systems are described. A basic system consists of the glomerular basement membrane (GBM) and the mesangium. The GBM represents the main skeletal element of the glomerular tuft. In general, opposing portions of the GBM are bridged by contractile mesangial cell processes, generating inwardly directed forces that balance the expansile forces resulting from pressure gradients across the GBM. A second structure-stabilizing role of the podocytes appears to be superimposed on this system. Podocytes are attached to the GBM by numerous foot processes that contain a contractile system. The foot process attachments probably stabilize small patches of the underlying GBM, counteracting local elastic distension. In addition, podocytes may contribute to the stabilization of the folding pattern of the tuft by linking neighboring capillary loops to each other.

Animals↗
PubMed1993

Glomerular size selectivity during protein overload in the rat.

Differential glomerular permeability to macromolecules as a function of their size (size permselectivity) is altered in experimental models of proteinuric renal disease. Size permselectivity during protein overload proteinuria was examined using urinary clearances of neutral dextrans in anesthetized Wistar-Furth rats. The animals were studied 3-4 h after the last of six twice-a-day intraperitoneal injections of either bovine serum albumin (BSA) or ovalbumin (OA) or of vehicle alone (controls). Glomerular filtration rates did not differ significantly among the three groups. OA-treated (n = 4) and control (n = 5) rats had virtually identical fractional dextran clearances over almost the entire molecular size range from 18 to 58 A Stokes-Einstein radius. In contrast, BSA-treated rats (n = 5) had elevated fractional clearances for medium-sized dextrans with the increases reaching statistical significance at radii of 40 A (+22.7% vs. control) and 44 A (+20.4%). Fractional clearances for BSA-treated rats returned to control values for larger dextrans. These findings demonstrate a significant size permselectivity defect in BSA overload, although not in OA overload.

Animals↗
PubMed1992

The glomerular mesangium: capillary support function and its failure under experimental conditions.

We present a structural analysis of the ability of the biomechanical unit consisting of mesangium and glomerular basement membrane to maintain normal capillary architecture in the face of mechanical challenges due to high intraglomerular pressures. Capillary support function may be considered in terms of the stabilization of local form (development of wall tension against capillary dilation) and global form (centripetal fixation of capillary loops to maintain higher order form). The pathologic consequences of the loss of this support are illustrated by way of experimental models of mechanical mesangial failure. Such failure may express itself as mesangial widening, increased transmesangial macromolecule "traffic," ballooning of capillary segments, and unfolding of capillary loops. Mechanisms are described by which these structural changes may lead to segmental glomerular sclerosis.

Animals↗
PubMed1991

Glomerular injury in analbuminemic rats after subtotal nephrectomy.

Progressive proteinuria has been suggested not just to reflect but also to contribute to the development of focal glomerular sclerosis. Development of proteinuria and glomerular lesions was examined up to 18 weeks after 3/4 nephrectomy in Sprague-Dawley (SDR) rats and an analbuminemic SDR variant (NAR). Nephrectomy led to a significantly lesser degree of proteinuria in NAR (42 +/- 14 SD mg/day) than in SDR (140 +/- 54 mg/day), consistent with the fact that 50-60% of urinary protein in SDR after nephrectomy is serum albumin. Nevertheless at 18 weeks NAR showed a significantly higher frequency of moderate and severe glomerular lesions than SDR. We conclude that, in this model, proteinuria itself is not a major cause of progressive glomerular injury.

Animals↗
PubMed1991

Hypercalcemia, hypertension and acute renal insufficiency in an immobilized adolescent.

Immobilization hypercalcemia was initially described by Albright in 1941, and has most often been noted in adolescent males, presumably because their high rates of skeletal growth increase the likelihood that alterations in the equilibrium between bone deposition and resorption will have clinically apparent effects. The etiology of immobilization hypercalcemia is controversial, but is thought to result from normal levels of PTH acting with increased activity in the abnormal environment of immobilized bone. We describe a patient, immobilized following the resection of a large, locally invasive tumor, who developed hypercalcemia in conjunction with renal insufficiency and hypertension. The pathophysiology of immobilization hypercalcemia is discussed, as are the potential contributions of renal feedback mechanisms to the patient's hypertension and renal insufficiency.

Acute Kidney Injury↗
PubMed1990

Mesangial cell-glomerular basement membrane connections counteract glomerular capillary and mesangium expansion.

Glomerular capillaries are perfused at a high hydraulic pressure. Since the capillary mesangium interface presents no morphologically apparent pressure barrier, it is suggested that the hydraulic pressure in the mesangium may also be high. This paper analyzes the structures in the glomerular tuft that are capable of counteracting the distending forces exerted on the tuft by the high hydraulic pressure in its center. The skeletal element of the glomerular tuft is the glomerular basement membrane (GBM). The combination of the GBM with the contractile apparatus of mesangial cells represents the main system stabilizing the glomerular tuft. The mesangial cell-GBM connections counteracting the expansion of glomerular capillaries appear less susceptible to injury than those counteracting mesangial expansion.

Animals↗
PubMed1987

Cycles and separations: the histotopography of the urinary concentrating process.

We have analyzed the histotopography of the renal medulla of the rat in terms of cycles and separations. Cycles are pathways by which solute leaving the medulla in an ascending structure (AVR, AHL) is returned to a deeper medullary level. Separations are based on spatial incontiguity and special characteristics of the interstitium and blood supply. The two concepts are complementary: the compartmentalization resulting from separations imparts specificity to the cycles. Structural lateral heterogeneity, consisting in distinct domains organized around vascular bundles, is present in one form or another in all three medullary zones. Such compartmentalization probably leads to heterogeneity in interstitial solute concentrations, a state of affairs inconsistent with the requirements of a "central core". In all such considerations of exchanges between compartments, the lack of a unitary interstitium must be borne in mind. Instead, three general types of interstitium may be distinguished: corresponding roughly to those of the OS and VB, the interbundle region of the IS, and the IM. Among the histotopographic features of the renal medulla not usually included in models of the urinary concentrating mechanism but likely to have functional significance are the association of CD with completely distinct populations of AVR and AHL in the OM and IM; a clear-cut separation throughout the medulla between cycles involving long loops and those involving short loops; the lack of an effective countercurrent association between ascending and descending limbs of short loops in the IS; and a pronounced separation of the venous drainage of the IM from that of the OM.

Animals↗
PubMed1986

The shape of renal vasa recta capillaries and its effect on calculation of single capillary blood flow.

Previous studies of the renal papilla of the rat have suggested that the vasa recta capillaries can be well approximated by elliptical cylinders (C. Holliger, K. V. Lemley, S. L. Schmitt, F. C. Thomas, C. R. Robertson, and R. L. Jamison, 1983, Circ. Res., 53, 401-413). This hypothesis was validated in a morphological study employing several methods of specimen fixation and preparation. Papillas of young (body wt = 90 g) Wistar rats were fixed and subsequently examined by light and electron microscopy. Cross-sectional shapes and orientations were determined for 300 superficial vasa recta. The ratio, beta, of vessel cross-sectional major-axis-to-minor-axis lengths was 1.39 +/- 0.24 (SD). Values of beta greater than 1.0 (the value expected for circular vessels) could not be accounted for by either fixation artifact or the angle of histologic sectioning of the papillas. A quantitative estimate of the relationship between the apparent capillary diameter measured in vivo and the capillary cross-sectional area was made using a mathematical model which accounts for cross-sectional shapes and orientations of the vasa recta. This estimate implies that current methods of calculating single vas rectum blood flow using apparent diameters and blood velocities determined in vivo probably overestimate actual blood flow by about 25%.

Animals↗
PubMed1984

Prostaglandin synthesis inhibitors and vasa recta erythrocyte velocities in the rat.

Vasa recta erythrocyte velocities (VRBC) in the exposed renal papilla of anesthetized water-loaded rats were determined before and 60 min after intravenous administration of a prostaglandin synthesis inhibitor (indomethacin, meclofenamate) or the inhibitor vehicle alone. The change in VRBC of ascending and descending vasa recta for the inhibitor group [-17 +/- 5% (SE)] was different from that for controls (+12 +/- 4%, P less than 0.002). Erythrocyte velocities were also determined in vasa recta of antidiuretic rats before and 30 min after administration of indomethacin or vehicle alone. Prostaglandin synthesis inhibition was again associated with a significant decrease in VRBC compared with control (-24 +/- 4% vs. +28 +/- 20%, respectively, P less than 0.025). These findings suggest that prostaglandins play a similar role in regulating blood flow in the renal medulla in water diuresis and antidiuresis.

Animals↗
PubMed1983

Direct determination of vasa recta blood flow in the rat renal papilla.

Blood flow in vasa recta capillaries of the exposed renal papilla of young antidiuretic rats (n = 18) was determined by an adaptation of the video-photometric technique of Intaglietta. The erythrocyte velocity and capillary diameter in vasa recta (n = 97) were measured at the same location by means of fluorescence video microscopy, with fluorescein-labeled bovine gamma-globulin as a plasma marker. A factor relating erythrocyte velocity to mean cross-sectional blood velocity was determined in vitro to permit the calculation of single vasa recta blood flows from the measured indices, erythrocyte velocity and capillary diameter. Mean blood flow in descending vasa recta was 8.83 +/- 0.96 (SE) nl/min, significantly greater than that in ascending vasa recta, 4.82 +/- 0.34 nl/min. The total numbers of ascending and descending vasa recta at the base of the exposed papilla were also determined. Over 1500 vasa recta were identified as ascending vasa recta or descending vasa recta in electron micrographs of three papillas. At this level in the papilla (2 mm from the tip), there were four ascending vasa recta for each descending vas rectum. From the total numbers of ascending vasa recta and descending vas rectum, single vessel blood flows were converted to total blood flow. Total blood outflow in all ascending vasa recta, 11.3 microliter/min, substantially exceeded total blood inflow in all descending vasa recta, 5.2 microliter/min. The difference between outflow and inflow (6.1 microliter/min) represents an estimate of water by the papillary microcirculation, and is more than adequate to accommodate the known rate of water reabsorption from the collecting ducts of the exposed papilla.

Animals↗