Primary Focal Segmental Glomerulosclerosis. Clinical Course, Predictors of Renal Outcome and Treatment.

Sasaki, Hideo; Dohi, Kazuhiro

doi:10.2169/internalmedicine.39.606

Cited by 17 publications

(10 citation statements)

References 44 publications

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“…However, apart from its hemodynamic effects, the direct effects of ANG II on kidney cells are being increasingly recognized (2,6,9,25,27). It has been demonstrated that in addition to circulating ANG II, tissue (intrarenal) generation of ANG II is also important for its net effect (35).Tubulointerstitial lesions have been demonstrated to correlate with the progression of renal failure (5,11,18,21,26), thus suggesting their contribution to the progression of renal failure (11). Transforming growth factor (TGF)-␤, a fibrogenic cytokine, has been shown to play a role in the inception and progression of renal lesions in both human renal diseases and experimental animal models of human immunodeficiency virus-associated nephropathy, renal ablation, and ureteric obstruction (16,33,36).…”

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confidence: 99%

“…Tubulointerstitial lesions have been demonstrated to correlate with the progression of renal failure (5,11,18,21,26), thus suggesting their contribution to the progression of renal failure (11). Transforming growth factor (TGF)-␤, a fibrogenic cytokine, has been shown to play a role in the inception and progression of renal lesions in both human renal diseases and experimental animal models of human immunodeficiency virus-associated nephropathy, renal ablation, and ureteric obstruction (16,33,36).…”

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Angiotensin II induces apoptosis in renal proximal tubular cells

Bhaskaran

Reddy

Radhakrishanan

et al. 2003

American Journal of Physiology-Renal Physiology

137

112

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II induces apoptosis in renal proximal tubular cells. Am J Physiol Renal Physiol 284: F955-F965, 2003; 10.1152/ajprenal.00246.2002-ANG II has been demonstrated to play a role in the progression of tubulointerstial injury. We studied the direct effect of ANG II on apoptosis of cultured rat renal proximal tubular epithelial cells (RPTECs). ANG II promoted RPTEC apoptosis in a dose-and time-dependent manner. This effect of ANG II was attenuated by anti-transforming growth factor (TGF)-␤ antibody. Moreover, TGF-␤ triggered RPTEC apoptosis in a dose-dependent manner. ANG II also enhanced RPTEC expression of Fas and Fas ligand (FasL); furthermore, anti-FasL antibody attenuated ANG II-induced RPTEC apoptosis. In addition, ANG II increased RPTEC expression of Bax, a cell death protein. Both ANG II type 1 (AT1) and type 2 (AT2) receptor blockers inhibited ANG II-induced RPTEC apoptosis. SB-202190, an inhibitor of p38 MAPK phosphorylation, and caspase-3 inhibitor also attenuated ANG II-induced RPTEC apoptosis. ANG II enhanced RPTEC heme oxygenase (HO)-1 expression. Interestingly, pretreatment with hemin as well as curcumin (inducers of HO-1) inhibited the ANG II-induced tubular cell apoptosis; conversely, pretreatment with zinc protoporphyrin, an inhibitor of HO-1 expression, promoted the effect of ANG II. These results suggest that ANG II-induced apoptosis is mediated via both AT1 and AT2 receptors through the generation of TGF-␤, followed by the transcription of cell death genes such as Fas, FasL, and Bax. Modulation of tubular cell expression of HO-1 has an inverse relationship with the ANG II-induced tubular cell apoptosis.Bax; Bcl-2; Fas; Fas ligand; proximal tubular epithelial cells; heme oxygenase-1 ANG II HAS BEEN DEMONSTRATED to contribute to the progression of renal injury through its hemodynamic effects (35, 36). These effects are confirmed by blocking its production and receptor sites (15,16,20). However, apart from its hemodynamic effects, the direct effects of ANG II on kidney cells are being increasingly recognized (2,6,9,25,27). It has been demonstrated that in addition to circulating ANG II, tissue (intrarenal) generation of ANG II is also important for its net effect (35).Tubulointerstitial lesions have been demonstrated to correlate with the progression of renal failure (5,11,18,21,26), thus suggesting their contribution to the progression of renal failure (11). Transforming growth factor (TGF)-␤, a fibrogenic cytokine, has been shown to play a role in the inception and progression of renal lesions in both human renal diseases and experimental animal models of human immunodeficiency virus-associated nephropathy, renal ablation, and ureteric obstruction (16,33,36). Interestingly, in these conditions, elevated blood ANG II levels have been reported. Moreover, modalities, which inhibit the production of ANG II, have been demonstrated to slow the progression of renal lesions (15,16,20).The effect of ANG II on the growth of proximal tubular cells has been evaluated in both in vivo and in vitro studies (4, 3...

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confidence: 99%

mentioning

confidence: 99%

Angiotensin II induces apoptosis in renal proximal tubular cells

Bhaskaran

Reddy

Radhakrishanan

et al. 2003

American Journal of Physiology-Renal Physiology

137

112

View full text Add to dashboard Cite

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“…TI lesions have been associated with poor outcome in patients with FSGS [25,26], but they have received little attention in recently published FSGS classification schemes or case series [2,27,28]. TI infiltrates and fibrosis are generally viewed as a consequence of podocyte loss.…”

Section: Discussionmentioning

confidence: 99%

Rituximab treatment of collapsing C1q glomerulopathy: clinical and histopathological evolution

et al. 2008

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A 13-year-old girl with obesity and hyperinsulinism developed steroid-resistant nephrotic syndrome due to collapsing glomerulopathy with dominant C1q-containing mesangial immune deposits (CG/C1qN). She became overtly diabetic while receiving alternate-day prednisone and tacrolimus, requiring insulin injections. Despite the addition of mycophenolate mofetil to the treatment regimen, renal function subsequently declined. Rituximab (four weekly doses of 375 mg/m 2 ) was tried 6 months after initial presentation and 3 months after weaning all glucocorticoids. Glomerular filtration rate (GFR) and proteinuria improved. Unexpectedly, blood sugar control normalized 6 weeks after antibody infusion. Rituximab was readministered 20 months after the first course because of deteriorating renal function, but the effect on GFR and proteinuria was modest. A retrospective analysis revealed that tubulointerstitial infiltrates present in the biopsies prior to treatment with rituximab contained numerous CD20 + and CD3 + (CD4>CD8) lymphocyte aggregates. Rebiopsy 10 weeks after repeat rituximab therapy demonstrated the elimination of B-cell infiltrates and the apparent decrease of interstitial T-cell infiltrates, yet persistent, advanced global glomerulosclerosis, interstitial fibrosis and tubular atrophy. In conclusion, CG/C1qN was associated with B-and T-cell-rich tubulointerstitial infiltrates. B-cell-directed therapy delayed clinical progression during early disease but failed to prevent or ameliorate chronic changes, despite effective tissue B-cell clearance. The incidental resolution of diabetes was noted after rituximab treatment.

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“…Arguments against such a practice would be that repeated courses of cytotoxic therapy would increase the risk of future malignancies and gonadal toxicity and possibly increase the risk of post-transplant lymphoproliferative disease [7,28]. Therefore the intensity of immunosuppressive therapy in NS should be meticulously balanced against its potential side-effects [29]. The results also confirm that patients who have evidence of renal impairment at presentation have a poor renal outcome despite aggressive immunosuppressive therapy [30] and therefore should be considered for conservative management and subsequent renal replacement therapy.…”

Section: Discussionmentioning

confidence: 99%

Predictors of long-term outcome of children with idiopathic focal segmental glomerulosclerosis

et al. 2007

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Clinical and histological data of children presenting with steroid-resistant nephrotic syndrome and renal biopsy showing focal and segmental glomerulosclerosis from 1980 with a follow-up of over 10 years were reviewed. There were 66 patients; 38 male and 28 female. Age at onset ranged from 0.4-14.1 years (mean 6.4). Tubular atrophy was present at first biopsy in 50/66, capsular adhesions in 35/66, glomerular tip lesions in 8/66 and mesangial expansion in 31/66 patients. In 51 children, cyclophosphamide was prescribed as the first cytotoxic agent, while 15 received cyclosporine A and complete remission was induced in 43 and 40% of the children, respectively. Complete and stable remission was maintained in 35 children, while 22 had reduction of proteinuria with symptomatic relief. Nine were refractory to cytotoxic therapy. Of the 35 patients who entered complete and stable remission, the renal survival was over 90%, while in the 31 non-responders it was 48% in 10 years. The multivariate analysis using unconditional logistic regression method identified the presence of mesangial expansion (p=0.011) and tip lesions (p=0.005) as the independent predictors of favourable response to cytotoxic therapy and the presence of renal impairment (p=0.008) and extensive focal segmental sclerosis (p=0.025) as independent predictors of unfavourable response.

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Primary Focal Segmental Glomerulosclerosis. Clinical Course, Predictors of Renal Outcome and Treatment.

Cited by 17 publications

References 44 publications

Angiotensin II induces apoptosis in renal proximal tubular cells

Angiotensin II induces apoptosis in renal proximal tubular cells

Rituximab treatment of collapsing C1q glomerulopathy: clinical and histopathological evolution

Predictors of long-term outcome of children with idiopathic focal segmental glomerulosclerosis

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