Micropuncture Study of Albumin Transfer in Aminonucleoside Nephrosis in the Rat

Lewy, John E.; Pesce, Amadeo J.

doi:10.1203/00006450-197306000-00002

Cited by 60 publications

(31 citation statements)

References 14 publications

(18 reference statements)

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“…4,5,7,23,51,52 Such concentrations are higher than those measured in the proximal tubular fluid of rats with experimental proteinuria using micropuncture studies in which the reported maximum albumin concentration was 7 g/L. 53 However, since the duration of protein exposure is much longer in in vivo settings, the total amount of proteins processed by proximal tubular cells in vivo far exceeds that of the cultured HK-2 cells. Therefore, 15 g/L of OA-Alb usedformostofourexperimentsisappropriateforin vitro protein-overload model.…”

Section: Cell Culturementioning

confidence: 75%

Luminal Alkalinization Attenuates Proteinuria-Induced Oxidative Damage in Proximal Tubular Cells

Souma¹,

Abe²,

Moriguchi³

et al. 2011

Journal of the American Society of Nephrology

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alkalinization abrogates proteinuria-induced tubular damage, we studied a mouse model of protein-overload nephropathy. NaHCO 3 feeding selectively alkalinized the urine and dramatically attenuated the accumulation of O 2 ⅐ Ϫ -induced DNA damage and proximal tubular injury. Overall, these observations suggest that luminal acidity aggravates proteinuria-induced tubular damage and that modulation of this acidic environment may hold potential as a therapeutic target for proteinuric kidney disease.

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Section: Cell Culturementioning

confidence: 75%

Luminal Alkalinization Attenuates Proteinuria-Induced Oxidative Damage in Proximal Tubular Cells

Souma¹,

Abe²,

Moriguchi³

et al. 2011

Journal of the American Society of Nephrology

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“…For example, direct micropuncture experiments demonstrated that proximal tubular fluid albumin concentration of rats increased from 6 g/ml in the normal condition to 74 g/ml with immunologically induced nephrotic syndrome (39). In aminonucleoside nephrosis, the proximal tubule fluid albumin concentration ranged between 0.16 and 2.3 mg/ml (40). In the setting of a plasma cell dyscrasia, light chain production increases significantly, producing circulating concentrations of monoclonal light chain that can approach 100,000 mg/L (7,14).…”

Section: Discussionmentioning

confidence: 99%

Immunoglobulin Light Chains Generate Hydrogen Peroxide

Wang

Sanders²

2007

Journal of the American Society of Nephrology

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As low molecular weight proteins, restriction from glomerular filtration is minimized, permitting significant amounts of Ig light chains to be endocytosed into the proximal tubule epithelium, particularly in plasma cell dyscrasias. Recent studies have shown that this effect of concentrating light chains within the proximal tubule alters cell function. This study demonstrated that light chains belonged to a class of proteins that are capable of catalyzing the formation of hydrogen peroxide. Sufficient amounts of hydrogen peroxide were produced in HK-2 cells to stimulate the production of monocyte chemoattractant protein-1 (MCP-1), a key chemokine involved in monocyte/macrophage migration and activation of the proximal tubule, and to increase lactate dehydrogenase release into the medium. The light chain-mediated effect on MCP-1 production was inhibited by co-incubation with 1,3-dimethyl-2-thiourea, which also inhibited lactate dehydrogenase release, and by pyrrolidine dithiocarbamate, an inhibitor of NF-B. The amount of light chain that stimulated an intracellular redox-signaling pathway in the proximal tubule cells was well within levels that are seen in patients who have plasma cell dyscrasias. The conclusion is that light chains possess a unique property that permits the development of intracellular oxidative stress that in turn promotes activation of the proximal tubule and elaboration of MCP-1.

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“…Significant absorption and metabolism of protein occur along the proximal tubule, and the absorption rate varies according to the proximal tubular protein concentration (46). Micropuncture studies have demonstrated that single nephron albuminuria is increased after reduction of nephron number in rats with ADR nephrosis (37,47,53). Results (41 ).…”

Section: Histochemistrymentioning

confidence: 99%

Enhanced Hexachloro-1:3-butadiene Nephrotoxicity in Rats with a Preexisting Adriamycin-Induced Nephrotic Syndrome

Kirby

Bach

1995

Toxicol Pathol

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Renal damage was assessed by histopathology and urinalysis in male Wistar rats treated with either hexachloro-1:3-butadiene (HCBD; a single 170-mg/kg ip dose that caused proximal tubule necrosis), adriamycin (ADR; a single 5-mg/kg ip dose that caused minimal glomerular changes up to 35 days), or HCBD given 2 wk after ADR and compared with age-matched control rats for 21 days. Urinalysis values in ADRtreated rats showed minimal renal changes. HCBD significantly elevated urine volume (10-fold), protein (5-fold), glucose (175-fold), and brush border enzymes (10-600-fold), indicating severe proximal tubular damage, but most parameters returned to pretreatment levels 6 days after treatment. In ADR-pretreated rats subsequently given HCBD, both the urinary alkaline phosphatase and the ratio of kidney : body weight were significantly higher for longer periods. Histopathology demonstrated that the HCBD-induced proximal tubular lesion was confined to the outer stripe of the outer medulla. Advanced regeneration and repair was evident 21 days after HCBD treatment. In the ADR-pretreated rats the HCBD-induced lesion was more severe and affected the entire cortex (24).Statistics. Statistically significant differences between groups were determined by 2-tailed Students' t-test, with p < 0.05 considered to be statistically significant. RESULTS UrinanalysisThere were no significant differences in the urinary parameters in the control and ADR groups ( (Fig. 1 a). Tubules were dilated and filled with homogenous eosinophilic material and necrotic epithelial cells. Signs of regeneration and restitution (i.e., tubular re-epithelialization and loss of tubular casts and debris) were evident by day 7 and complete 21 days after treatment (Fig. 1 b).Histologically, animals in the ADR/HCBD group showed much more extensive renal damage (Fig. 2a) when compared to those treated with HCBD alone (see Fig. 1 a). Extensive tubular damage was present throughout the entire cortex 2 days after HCBD treatment, and tubules were dilated and filled with homogeneous proteinaceous material. Sloughed necrotic calcified epithelial cells were observed in tubular lumens and casts extended deep into the medulla (Fig. 2b). Extensive calcification was evident by day 7 (which was not seen in the HCBD only group) and by day 21, regeneration, although apparent, was less advanced and marked tubular calcification was still evident (Fig. 2c). Table 2 summarizes the differences between the ADR/HCBD group and HCBD alone. HistochemistryControl kidneys demonstrated normal GGT staining of the tubular epithelium of the outer stripe of the outer medulla (Fig. 3a). ADR caused no changes in this staining pattern. GGT staining in the outer stripe of the outer medulla was diminished 24 hr after HCBD treatment, was barely evident by day 3 (Fig. 3b) HCBD is a useful model toxin for damaging the proximal tubule. It is metabolized in the liver, ex-

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Micropuncture Study of Albumin Transfer in Aminonucleoside Nephrosis in the Rat

Cited by 60 publications

References 14 publications

Luminal Alkalinization Attenuates Proteinuria-Induced Oxidative Damage in Proximal Tubular Cells

Luminal Alkalinization Attenuates Proteinuria-Induced Oxidative Damage in Proximal Tubular Cells

Immunoglobulin Light Chains Generate Hydrogen Peroxide

Enhanced Hexachloro-1:3-butadiene Nephrotoxicity in Rats with a Preexisting Adriamycin-Induced Nephrotic Syndrome

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