Proximal Tubular Cell, Proteinuria and Tubulo-lnterstitial Scarring

Burton, Christopher J.; Walls, J.

doi:10.1159/000188389

Cited by 39 publications

(20 citation statements)

References 28 publications

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“…Recent studies have indicated that proteinuria is not merely a reflection of glomerular damage, but in itself contributes to further renal injury, in particular by causing tubulointerstitial inflammation [2]. The mechanisms involved in this latter process are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Urinary Excretion of Glutathione S Transferases Alpha and Pi in Patients with Proteinuria: Reflection of the Site of Tubular Injury

Branten¹,

Mulder²,

Peters³

et al. 2000

Nephron

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In patients with renal diseases, proteinuria is a major determinant of progressive renal failure, probably by causing tubular cell injury. Little is known on extent and site of tubular cell injury in patients with proteinuria. Glutathione S transferases (GST) are cytosolic enzymes. The alpha isoform is present only in proximal tubular cells, whereas the pi isoform is confined to distal tubular cells. We have studied the urinary excretion of both isoenzymes in 56 (38 male and 18 female) patients with glomerular diseases and proteinuria. The mean age was 45 ± (SD) 16 years, the median creatinine clearance was 80 (range 27–159) ml/min, and the median albuminuria was 4.2 (range 0.7–16.9) g/10 mmol creatinine. The excretions of both GST alpha (median 35.9 ng/10 mmol creatinine) and GST pi (median 24.8 ng/10 mmol creatinine) were elevated as compared with control values (upper limits 10 and 12 ng/10 mmol creatinine, respectively). The urinary excretion of GST pi, but not that of GST alpha, was inversely correlated with the creatinine clearance. The highest levels of GST alpha were found in patients with a well-preserved renal function, whereas highest levels of GST pi were found in patients with renal failure. In a small number of patients we performed immunofluorescent studies of renal tissue. An increased urinary excretion of GST alpha correlated with brush border damage and decreased staining of proximal tubules for that isoenzyme. Our data suggest that in patients with proteinuria initial injury is apparent at the proximal tubules. Measurements of GST alpha and GST pi appear useful to study longitudinal timing and site of proteinuria-induced tubular cell injury.

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Section: Introductionmentioning

confidence: 99%

Urinary Excretion of Glutathione S Transferases Alpha and Pi in Patients with Proteinuria: Reflection of the Site of Tubular Injury

Branten¹,

Mulder²,

Peters³

et al. 2000

Nephron

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“…The enzyme can be detected in the circulation; however, plasma NAG is unable to pass through the intact glomerular basement membrane due to its high molecular weight (140,000 daltons). Therefore, in healthy subjects urinary NAG represents the amount physiologically released by the renewal of renal tubular cells [11].…”

Section: Introductionmentioning

confidence: 99%

Follow-up of steroid-resistant nephrotic syndrome: tubular proteinuria and enzymuria

Vallés

Peralta²,

Carrizo

et al. 2000

Pediatric Nephrology

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The aim of this study was to examine the compromise of proximal tubule cells in steroid-resistant nephrotic syndrome patients with a histologic diagnosis of focal segmental glomerulosclerosis (FSGS) through assessment of the urinary levels of beta 2-microglobulin (beta 2M) and N-acetyl-beta-D-glucosaminidase (NAG) during active disease and remission over a follow-up period of 3 years. We studied 34 children with nephrotic syndrome: 12 with steroid-resistant nephrotic syndrome (SRNS) and massive proteinuria, 7 with steroid-dependent nephrotic syndrome (SDNS) and 15 with steroid-sensitive nephrotic syndrome (SSNS). Of the SSNS patients, 8 children were in remission (RM) and 7 were in relapse (RL). Seven healthy children were included as controls. Urinary beta 2M, measured by enzyme-linked immunosorbent assay, was significantly increased in the SRNS group as compared to the SDNS group (P < 0.01), SSNS in remission (P < 0.01), and controls (P < 0.01). There were no differences between the SRNS group and SSNS in relapse. Analysis of urinary N-acetyl-beta-D-glucosaminidase (U-NAG) by colorimetric assay showed significantly higher values in the SRNS group of patients than in SDNS, SSNS, and control groups. A positive correlation between U-NAG and proteinuria was demonstrated (r = 0.73, P < 0.01). The SRNS group of patients (n = 12, 11 with a histologic diagnosis of FSGS and one with diffuse mesangial proliferation) was treated with the same protocol of i.v. methylprednisone and oral cyclophosphamide. Long-term follow-up showed a progressive decrease in U-beta 2M and U-NAG excretion to control values in the 3rd year, except in one patient who did not respond to the treatment. In the FSGS patients, evaluation of the contribution of structural interstitial histological abnormalities, including each of the histological parameters considered in interstitial scarring to the functional tubule abnormalities assessed by beta 2M and NAG excretion, was performed by multiple regression analysis. The r2 values for beta 2M and NAG were 53.99%, P = 0.19, and 57.90%, P = 0.14, respectively; neither was significant. We conclude that: (1) proximal tubule cell dysfunction, partially affected by massive albuminuria, may account for the higher values of beta 2M and NAG excretion in the SRNS patients and (2) urine beta 2M and NAG levels are not helpful in identifying histological evidence of structural tubulointerstitial damage in children with steroid-resistant nephrotic syndrome.

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“…We recently suggested that hepatocyte growth factor (HGF) may be correlated with tubular damage in primary glomerulonephritis, including IgA nephropathy [1], The serum creatinine (s-Cr) level and the glomerular Filtration rate are affected by tubulointerstitial lesions (TILs) in var ious types of glomerulonephritis, so TILs may serve as an important prognostic indicator [2][3][4][5]. Therefore, it seems possible that HGF may be related to the exacerbation of primary glomerulonephritis (such as IgA nephropathy) and tubular damage, although this is difficult to deter mine.…”

Section: Introductionmentioning

confidence: 99%

Localization of Hepatocyte Growth Factor and Tubulointerstitial Lesions in IgA Nephropathy

Taniguchi

Yorioka²,

Yamashita³

et al. 1997

Am J Nephrol

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To investigate the relationship between localization of hepatocyte growth factor (HGF) and tubulointerstitial lesions (TILs) in the cortical area of renal biopsy specimens, a clinicopathological study was performed in 35 patients with IgA nephropathy. HGF was detected by an enzyme-antibody method and TILs were assessed semiquantitatively by light microscopy. HGF was observed mainly on epithelial cells in the tubules, but not in the glomeruli. Fourteen patients had biopsies that were positive for HGF. There was a correlation between HGF positivity and histological damage, the TIL grade, and several clinical parameters determined at biopsy. Thus, HGF is related to TILs in IgA nephropathy, and may be a factor in the exacerbation of this disease.

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Proximal Tubular Cell, Proteinuria and Tubulo-lnterstitial Scarring

Cited by 39 publications

References 28 publications

Urinary Excretion of Glutathione S Transferases Alpha and Pi in Patients with Proteinuria: Reflection of the Site of Tubular Injury

Urinary Excretion of Glutathione S Transferases Alpha and Pi in Patients with Proteinuria: Reflection of the Site of Tubular Injury

Follow-up of steroid-resistant nephrotic syndrome: tubular proteinuria and enzymuria

Localization of Hepatocyte Growth Factor and Tubulointerstitial Lesions in IgA Nephropathy

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