The Product of Duration and Amount of Proteinuria (Proteinuria Index) Is a Possible Marker for Glomerular and Tubulointerstitial Damage in IgA Nephropathy

Abstract

Background/Aims: IgA nephropathy (IgAN) is one of the major causes for chronic renal failure (CRF). Presence of massive proteinuria, hypertension, increased serum creatinine level and sclerotic histopathological changes of the glomerulus are known to be determinants for the progression of CRF. However, the relationships between duration of proteinuria/hematuria and histopathological changes, which may be correlated with the renal prognosis, have not been clarified. Methods: A cross-sectional, univariate analysis of clinical parameters on the four glomerular and three tubulointerstitial histopathological grades in 57 untreated biopsy-proven IgAN patients (M/F = 32/25) was performed. Results: The age at the time of renal biopsy (35.2 ± 13.0 years; mean ± SD), average duration of proteinuria (5.3 ± 5.8 years), mean urinary protein excretion (0.99 ± 1.22 g/day), serum creatinine (Cr 0.97 ± 0.28 mg/dl), Cr clearance (Ccr 75.5 ± 29.4 ml/min), and blood urea nitrogen (BUN 15.4 ± 3.9 mg/dl) were well correlated with both histopathological grades. The product of duration (years) and urinary protein excretion (g/day) at the time of renal biopsy was more significantly correlated with glomerular and tubulointerstitial histopathological grades and serum Cr. Conclusion: The natural course of IgAN is steadily progressive depending on the duration and amount of proteinuria. The product of these two factors (proteinuria index) may be a useful predictor for glomerular and interstitial histopathological changes and the fate of renal function in IgAN.

Impact of Hypertension and Hypertension-Related Vascular Lesions in IgA Nephropathy

“…The duration of abnormal urinalysis prior to biopsy was 4.7 years (range 0. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. The mean Ccr was 84.4 ml/min/1.73 m 2 (range 24.3-156.9).…”

“…In the present study, therefore, we wanted to investigate the relationship between vascular lesions and hypertension in renal parenchymal disease. To avoid unnecessary complexity of the histopathological findings, we chose IgAN, which is known as the most common primary glomerular disease in Japan (13), as a single disease entity of renal parenchymal disease. Moreover, although nephrologists tend to regard patients with hypertension and mild proteinuria as having benign nephrosclerosis, it is important to reveal whether this diagnosis is correct.…”

Podocyte number predicts progression of proteinuria in IgA nephropathy

“…37 Several clinical studies have shown that proteinuria is a strong prognostic factor for IgAN progression. 8,9,12 Our study revealed multiple podocyte injuries in proteinuric IgAN, including decreased cell-cycle protein p27, decreased type IV intermediate filament nestin expression, widened foot process and ultimately decreased podocyte density. We further showed that podocyte injury, especially the number of podocytes is a better predictor of progression than the level of proteinuria at the time of biopsy in IgAN.…”

“…8 However, emerging studies have found that, rather than the amount of proteinuria appearing at diagnosis, it is the change in magnitude of the proteinuria that is a stronger predictor of renal outcome. 4,[8][9][10][11][12] Consistent with these findings, a recent study reported that patients who achieved a sustained reduction in proteinuria have a better prognosis regardless the initial proteinuria level. 13 Another study also showed that mean proteinuria during follow-up was a powerful independent prognostic predictor in IgAN.…”

Corticotherapy response in primary IgA nephropathy

“…10 Proteinuria is an important and independent predictor of adverse outcomes in patients with glomerulopathies, including IgAN. 3,[11][12][13] While nephrotic range proteinuria levels are necessary to confirm a poor prognosis in most glomerular diseases, this seems to happen at much lower levels in primary IgAN. 3,11,12 The goal of any treatment of IgAN aims to decrease the proteinuria levels in order to provide a cure or at least achieve better long-term renal survival.…”