ACEI/ATRA therapy decreases proteinuria by improving glomerular permselectivity in IgA nephritis

Woo, Keng Thye; Lau, Ying; Wong, Kok‐Seng; Chiang, G. S. C.

doi:10.1046/j.1523-1755.2000.00432.x

Cited by 94 publications

(76 citation statements)

References 26 publications

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“…The use of ACEi/ARB was the only intervention associated with a slower rate of renal function decline and prolonged renal survival, in keeping with both published randomized, controlled trials and retrospective reviews demonstrating the renoprotective effect of renin-angiotensin-aldosterone system blockade. 30 -39 These beneficial effects may reflect both hemodynamic and nonhemodynamic antiproteinuric effects of ACEi/ARB 24,35,40 -42 or alterations in glomerular permselectivity 43 ; however, this study was not designed to determine causality or mechanism. Similarly, although MAP was an important determinant of outcome and patients with the highest quartile of MAP had the highest levels of proteinuria, this is not necessarily a causal relationship.…”

Section: Discussionmentioning

confidence: 99%

Remission of Proteinuria Improves Prognosis in IgA Nephropathy

Reich

Troyanov²,

Scholey³

et al. 2007

Journal of the American Society of Nephrology

497

413

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Proteinuria has been shown to be an adverse prognostic factor in IgA nephropathy. The benefit of achieving a partial remission of proteinuria, however, has not been well described. We studied 542 patients with biopsy-proven primary IgA nephropathy in the Toronto Glomerulonephritis Registry and found that glomerular filtration rate (GFR) declined at Ϫ0.38 Ϯ 0.61 ml/min per 1.73 m 2 /mo overall, with 30% of subjects reaching end-stage renal disease. Multivariate analysis revealed that proteinuria during follow-up was the most important predictor of the rate of GFR decline. Among the 171 patients with Ͻ1 g/d of sustained proteinuria, the rate of decline was 90% slower than the mean rate. The rate of decline increased with the amount of proteinuria, such that those with sustained proteinuria Ͼ3 g/d (n ϭ 121) lost renal function 25-fold faster than those with Ͻ1 g/d. Patients who presented with Ն3 g/d who achieved a partial remission (Ͻ1 g/d) had a similar course to patients who had Յ1 g/d throughout, and fared far better than patients who never achieved remission. These results underscore the relationship between proteinuria and prognosis in IgA nephropathy and establish the importance of remission.

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Section: Discussionmentioning

confidence: 99%

Remission of Proteinuria Improves Prognosis in IgA Nephropathy

Reich

Troyanov²,

Scholey³

et al. 2007

Journal of the American Society of Nephrology

497

413

View full text Add to dashboard Cite

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“…One strength of this study is that only stable patients were selected and confirmed over a 3-mo run-in phase, which is at variance with most studies on IgAN that enrolled patients shortly after the onset of clinical symptoms and renal biopsy (1,21). Despite these precautions, several patients, who were not as stable as expected, were excluded from entering the follow-up phase.…”

Section: Discussionmentioning

confidence: 99%

“…here are very few randomized, controlled trials (RCT) in IgA nephropathy (IgAN), even though it is the most common glomerular disease worldwide (1)(2)(3). In the past decade, angiotensin-converting enzyme inhibitors (ACE-I) have raised great hopes of successfully treating chronic renal disease; they show beneficial effects not only in controlling hypertension but also in reducing the process of renal sclerosis (4 -5).…”

mentioning

confidence: 99%

IgACE

Coppo

Peruzzi

Amore

et al. 2007

Journal of the American Society of Nephrology

223

130

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2 ) for >6 mo. Analysis was by intention to treat. A single patient (3.1%) in the ACE-I group and five (14.7%) in the placebo group showed a worsening of CrCl >30%. The composite end point of >30% decrease of CrCl or worsening of proteinuria until nephrotic range was reached by one (3.1%) of 32 patients in the ACE-I group, and nine (26.5%) of 34 in the placebo group; the difference was significant (log-rank P ‫؍‬ 0.035). A stable, partial remission of proteinuria was observed in 13 (40.6%) of 32 patients in the ACE-I group versus three (8.8%) of 34 in the placebo group (log-rank P ‫؍‬ 0.033), with total remission in 12.5% of ACE-I-treated patients and in none in the placebo group (log-rank P ‫؍‬ 0.029). The multivariate Cox analysis showed that treatment with ACE-I was the independent predictor of prognosis; no influence on the composite end point was found for gender, age, baseline CrCl, systolic or diastolic BP, mean arterial pressure, or proteinuria.

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“…In addition, electrophoretic patterns of urine proteins have been used to predict outcomes in CKD. A predominantly low molecular weight (LMW) pattern of urinary proteins on sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) predicts progression in IgA nephropathy [44], and changes in protein selectivity may parallel patterns of response to therapy in that disease [45]. The protein selectivity index (SI), which dates back to the 1960s, can be highly predictive of steroid responsiveness in idiopathic nephrotic syndrome [46].…”

Section: Proteinuriamentioning

confidence: 99%

An introduction to biomarkers: applications to chronic kidney disease

Lemley

2007

Pediatr Nephrol

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Diagnosis and management of chronic kidney disease (CKD) will be characterized in the future by an increasing use of biomarkers-quantitative indicators of biologic or pathologic processes that vary continuously with progression of the process. "Classical" biomarkers of CKD progression include quantitative proteinuria, the percentage of sclerotic glomeruli or fractional interstitial fibrosis. New candidate biomarkers (e.g., urinary proteomic patterns) are being developed based on both mechanistic and "shotgun" approaches. Validation of potential biomarkers in prospective studies as surrogate endpoints for hard clinical outcomes is often complicated by the long lag time to the ultimate clinical outcome (e.g., end-stage renal disease). The very dense data sets that result from shotgun approaches on small numbers of patients carry a significant risk of model overfitting, leading to spurious associations. New analytic methods can help to decrease this risk. It is likely that clinical practice will come to depend increasingly on multiplex (vector) biomarkers used in conjunction with risk markers in early diagnosis as well as to guide therapy.

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ACEI/ATRA therapy decreases proteinuria by improving glomerular permselectivity in IgA nephritis

Cited by 94 publications

References 26 publications

Remission of Proteinuria Improves Prognosis in IgA Nephropathy

Remission of Proteinuria Improves Prognosis in IgA Nephropathy

IgACE

An introduction to biomarkers: applications to chronic kidney disease

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