The glomerular mesangium. II. Studies of macromolecular uptake in nephrotoxic nephritis in rats.

Sm, Mauer; Fish, Alfred J.; Day, Noorbibi K.; Michael, A F

doi:10.1172/jci107577

Cited by 73 publications

(52 citation statements)

References 14 publications

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“…After cooling to room temperature, 0.5 pg '? Clq in 100 pl 1% BSA-VBS was added to the reaction mixture and incubated at 37°C (19) suspended in normal human serum were used to generate a standard curve. Mean values of test duplicates were calculated as a percent of maximum binding of AHG at saturation, and the results were expressed as pg/rnl AHG equivalents.…”

Section: Methodsmentioning

confidence: 99%

Correlation and predictive accuracy of circulating immune complexes with disease activity in patients with systemic lupus erythematosus

Abrass

Nies

Louie

et al. 1980

Arthritis & Rheumatism

133

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contention includes: the presence of circulating DNA (l), antibodies to DNA (2), immune complexes composed of DNA and anti-DNA antibody (3), activation of the complement cascade leading to hypocomplementemia, and deposition of DNA, anti-DNA antibody, and complement components in tissues, particularly in glomeruli (4). The emergence of immunologic methods for measuring complement components (6) and antibodies to DNA (7,8) provided a rich source of serologic data in patients with SLE. However, the correlation of results from these tests with clinical data has proved disappointing.Application of recently developed sensitive and specific methods for detecting circulating immune complexes (CIC) has documented an increased prevalence of immune complexes in SLE (9-13). These assays for CIC may have value in the assessment of clinical activity of disease. Tron and Bach (14) have demonstrated that patients with more severe manifestations of SLE tend to have higher levels of CIC, but to date, determinations of CIC have not been specifically correlated with clinical assessment, thus none have proved to be of consistent value in predicting change in disease activity in SLE.The present study was undertaken to prospectively evaluate the potential value of serial measurements of CIC in patients with SLE, unselected for particular organ system involvement. A panel of serologic tests including C3, anti-DNA antibody, and two methods for detecting CIC were performed and correlated with the presence of, as well as changes in, disease activity. The results indicate that the solid phase Clq binding assay for circulating immune complexes correlates best with the presence of clinical manifestations and changes in activity of SLE.

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Section: Methodsmentioning

confidence: 99%

Correlation and predictive accuracy of circulating immune complexes with disease activity in patients with systemic lupus erythematosus

Abrass

Nies

Louie

et al. 1980

Arthritis & Rheumatism

133

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“…In view of the wide spectrum of renal diseases leading to the nephrotic syndrome, more than a single mechanism may be responsible for the renal salt retention observed in these diverse conditions. Puromycin aminonucleoside (PAN) induces heavy proteinuria, avid renal salt retention, and structural changes in the glomerulus and renal tubules characteristic of minimal change glomerulopathy (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), namely, effacement of glomerular epithelial cell foot processes and protein reabsorption droplets in proximal tubule epithelia. To distinguish between the intrarenal vs. extrarenal mechanisms in mediating the observed salt retention, we studied a unilateral form of PAN glomerulopathy induced in the Munich-Wistar rat by selective in vivo perfusion of a single kidney with PAN.…”

Section: Introductionmentioning

confidence: 99%

Role for intrarenal mechanisms in the impaired salt excretion of experimental nephrotic syndrome.

Ichikawa¹,

Rennke²,

Hoyer³

et al. 1983

J. Clin. Invest.

250

175

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A B S T R A C T A unilateral model of puromycin aminonucleoside (PAN)-induced albuminuria was produced in Munich-Wistar rats to examine the mechanisms responsible for renal salt retention. 2 wk after selective perfusion of left kidneys with PAN (n = 8 rats) or isotonic saline (control, n = 7 rats), increases in albumin excretion and decreases in sodium excretion were demonstrated in PAN-perfused but not in nonperfused kidneys of PAN-treated rats although systemic plasma protein concentration remained at control level. Total kidney glomerular filtration rate (GFR) and superficial single nephron (SN) GFR were also reduced selectively in PAN-perfused kidneys, on average by -30%, due primarily to a marked decline in the glomerular capillary ultrafiltration coefficient (Kf), which was also confined to PAN-perfused kidneys. Values for absolute proximal reabsorption (APR) were also selectively depressed in PAN-perfused kidneys, in keeping with a similarly selective decline in peritubular capillary oncotic pressure measured in these kidneys, the latter also a consequence of the fall in Kf. In a separate group of seven PAN-treated rats, however, no differences were detected between PANperfused and nonperfused kidneys in the absolute amount of sodium reaching the early (0. In two additional groups of PAN-treated rats, infusion of saralasin (0.3 mg/kg per h, iv.) led to substantial increases in total kidney GFR and SNGFR in PAN-perfused but not in nonperfused kidneys. Despite these increases in total and SNGFR, urinary sodium excretion by PAN-perfused kidneys remained at a level far below that for nonperfused kidneys, again indicating that the antinatriuresis characterizing the PAN-perfused kidney is due to alterations in sodium handling by the tubules rather than changes in GFR. These results therefore indicate (a) that reductions in Kf and depressed sodium reabsorption by proximal tubules and Henle's loop segments in this model are brought about by intrarenal rather than circulating or systemic factors, and (b) assuming that superficial nephrons are representative of the entire nephron population, renal salt retention in this model is due primarily to intrarenal factor(s) acting beyond the distal convolution.77±0

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“…Of note, glomerular sclerosis is characterized by expansion of extracellular matrix in the mesangial area; nevertheless, pure mesangial injury, typically observed in rat anti-Thy1 nephropathy, causes only reversible changes but not glomerular sclerosis (2). Of further note, podocyte injury is closely associated with glomerulosclerosis in many human and animal kidney diseases (3)(4)(5)(6).…”

mentioning

confidence: 99%

Genetic Engineering of Glomerular Sclerosis in the Mouse via Control of Onset and Severity of Podocyte-Specific Injury

Matsusaka¹,

Jing²,

Niwa³

et al. 2005

Journal of the American Society of Nephrology

223

228

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This study aimed to generate a mouse model of acquired glomerular sclerosis. A model system that allows induction of podocyte injury in a manner in which onset and severity can be controlled was designed. A transgenic mouse strain (NEP25) that expresses human CD25 selectively in podocytes was first generated. Injection of anti-Tac (Fv)-PE38 (LMB2), an immunotoxin with specific binding to human CD25, induced progressive nonselective proteinuria, ascites, and edema in NEP25 mice. Podocytes showed foot process effacement, vacuolar degeneration, detachment and downregulation of synaptopodin, WT-1, nephrin, and podocalyxin. Mesangial cells showed matrix expansion, increased collagen, mesangiolysis, and, later, sclerosis. Parietal epithelial cells showed vacuolar degeneration and proliferation, whereas endothelial cells were swollen. The severity of the glomerular injury was LMB2 dose dependent. With 1.25 ng/g body wt or more, NEP25 mice developed progressive glomerular damage and died within 2 wk. With 0.625 ng/g body wt of LMB2, NEP25 mice survived >4 wk and developed focal segmental glomerular sclerosis. Thus, the study has established a mouse model of acquired progressive glomerular sclerosis in which onset and severity can be preprogrammed by experimental maneuvers.

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The glomerular mesangium. II. Studies of macromolecular uptake in nephrotoxic nephritis in rats.

Cited by 73 publications

References 14 publications

Correlation and predictive accuracy of circulating immune complexes with disease activity in patients with systemic lupus erythematosus

Correlation and predictive accuracy of circulating immune complexes with disease activity in patients with systemic lupus erythematosus

Role for intrarenal mechanisms in the impaired salt excretion of experimental nephrotic syndrome.

Genetic Engineering of Glomerular Sclerosis in the Mouse via Control of Onset and Severity of Podocyte-Specific Injury

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