Renal outcome after tonsillectomy plus corticosteroid pulse therapy in patients with immunoglobulin A nephropathy: results of a multicenter cohort study

Hoshino, Junichi; Fujii, Takayuki; Usui, Joichi; Fujii, Takeshi; Ohashi, Kenichi; Takaichi, Kenmei; Suzuki, Satoshi; Ubara, Yoshifumi; Yamagata, Kunihiro

doi:10.1007/s10157-015-1194-z

Cited by 18 publications

(10 citation statements)

References 33 publications

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“…У некоторых пациентов после тонзиллэкто-мии отмечают уменьшение макрогематурии [22] при отсутствии замедления прогрессирования заболевания [23]. При этом положительный эф-фект возможен при тонзиллэктомии в сочетании с пульс-терапией глюкокортикоидами (ГК) [24] при хронической болезни почек 1-2-й стадии, с ПУ <1 г/сут [25] и ≥1 г/сут [26].…”

Section: казанский медицинский журнал 2017 г том 98 №5unclassified

Modern classification, progression factors, treatment and outcomes of primary mesangial proliferative glomerulonephritis

et al. 2017

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The choice of treatment of mesangial proliferative glomerulonephritis (post-infection, immunoglobulin A, G and M nephritis) is performed taking into account the remission achievement, slowing of progression and reduction of the risk of recurrences of glomerulonephritis. The efficiency of etiologic factor removing is debatable: glomerulonephritis associated with infections usually resolves after their elimination; individual patients achieve immunoglobulin A nephritis remission with persistent antimicrobial treatment of focal infection, but surgical removal of the focus (tonsillectomy) does not affect the long-term prognosis, therefore it is not recommended. Treatment of immunoglobulin A nephritis with oral prednisone for up to 4 months, sometimes in combination with cyclophosphamide (cyclophosphane), reduces the likelihood of its relapse. At low risk of progression of immunoglobulin A nephritis with proteinuria less than 1 g/day, long-term therapy with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers is indicated with administration of maximum tolerated doses for proteinuria more than 1 g/day. Also fish oil 3 g/day is administered for up to 2 years. If proteinuria more than 1 g/day persists for 3-6 months, corticosteroids are recommended for 6 months. With mild renal dysfunction, corticosteroids are prescribed orally or in pulse-therapy with high doses intravenously and maintenance therapy with low doses orally. Immunosuppressive therapy - cyclophosphamide, cyclosporine, azathioprine, mycophenolate mofetil - in combination with corticosteroids is indicated in rapid loss of renal function or massive/moderate proteinuria. In minimal proteinuria immunosuppressive therapy is considered to be unreasonable. Use of intravenous immunoglobulin for immunoglobulin A nephritis from the point of view of lesser toxic effect is possible only as the induction therapy. Currently, there are no clinical recommendations for the treatment of immunoglobulin M nephritis, in case of nephrotic syndrome, corticosteroids are the drugs of the 1st line. There are isolated studies of the use of cyclophosphamide, mycophenolate mofetil, and cyclosporine, with the achievement of remission in frequent relapses of nephrotic syndrome or steroid drug resistance. The cases of immunoglobulin M nephritis treates with retuximab with a positive effect are described. The effectiveness of immunoglobulin G nephritis treatment is less studied, the choice of treatment is similar to that of immunoglobulin A and M nephritis.

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Section: казанский медицинский журнал 2017 г том 98 №5unclassified

Modern classification, progression factors, treatment and outcomes of primary mesangial proliferative glomerulonephritis

et al. 2017

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“…Accordingly, a long-term cohort study may be the only way to reveal renal outcome, especially for serious outcomes such as end-stage kidney disease (ESKD). Therefore, we previously established a large-scale and long-term multicenter cohort study of patients with biopsy-proven IgAN, with a long-term median follow-up duration of 70.0 months [ 15 ]. Based on the results of that study, we reported that steroid pulse therapy with or without tonsillectomy was potentially effective for IgAN patients with chronic kidney disease (CKD) stage G1–G3 and high urine protein levels [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, we previously established a large-scale and long-term multicenter cohort study of patients with biopsy-proven IgAN, with a long-term median follow-up duration of 70.0 months [ 15 ]. Based on the results of that study, we reported that steroid pulse therapy with or without tonsillectomy was potentially effective for IgAN patients with chronic kidney disease (CKD) stage G1–G3 and high urine protein levels [ 15 ]. Our analyses indicated that tonsillectomy did not seem to enhance the benefit of corticosteroids monotherapy.…”

Section: Introductionmentioning

confidence: 99%

Corticosteroids pulse therapy and oral corticosteroids therapy for IgA nephropathy patients with advanced chronic kidney disease: results of a multicenter, large-scale, long-term observational cohort study

et al. 2018

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BackgroundCorticosteroids are widely used to reduce the urine protein levels of patients with immunoglobulin A nephropathy (IgAN). However, their potential preventive effects on end-stage kidney disease (ESKD) are unclear.MethodsWe previously performed a large-scale, long-term multicenter cohort study of patients with biopsy-proven IgAN treated between 1981 and 2013 (n = 1923). Based on the results, we reported that corticosteroids pulse therapy was potentially effective for the treatment of patients with an eGFR ≥30 ml/min/1.73m2 and a urine protein amount of ≥1 g/gCr. In the present study, we extracted 766 patients with chronic kidney disease (CKD), stage G3–G4 (15 ≤ estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m2) from the same cohort. We divided these patients into a steroid pulse (SP) group, oral steroid (OS) group, and no steroid (NS) group, and analyzed the risk of end-stage kidney disease (ESKD) stratified by eGFR and urine protein (UP) amounts.ResultsOver the median long-term follow-up of 70 ± 115 months, 37.1% of the patients with UP ≥1.0 g/day and 11.2% of the patients with UP < 1.0 g/day reached ESKD. Among the patients with UP ≥1 g/gCr, the SP group showed significantly better renal outcome (p < 0.001) than the OS and NS groups. In patients with UP < 1 g/gCr, there were no differences in renal survival among the treatment groups. These trends appeared even in the CKD stage G4 patients, and were also apparent in patients taking renin-angiotensin system inhibitors. The unprecedented long-term observation period in this study may have been necessary to reveal the favorable effect of corticosteroids on ESKD progression.ConclusionsIn our long-term multicenter study, Corticosteroids pulse therapy was associated with better renal outcomes in IgAN patients with higher UP values, even if their eGFR values were low.

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“…Recently a large amount of researches have revealed that tonsillitis, usually caused by α-hemolytic streptococcus (α-HS), is closely associated with the pathogenesis of IgAN [2,3]. Tonsillar mononuclear cells (TMCs), primarily consist of lymphocytes, are mainly responsible for nephropathic IgA secretion in IgAN patients [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…These nephropathic IgA can be reduced after tonsillectomy in most tonsillitis-associated IgAN patients [6]. A longterm remission and low risk of ESRD (end stage renal disease) could also be achieved after tonsillectomy in these patients [2,6]. Hence, tonsillectomy may be a feasible approach to treat IgAN.…”

Section: Introductionmentioning

confidence: 99%

Impact of GADD34 on Apoptosis of Tonsillar Mononuclear Cells from IgA Nephropathy Patients by Regulating Eif2α Phosphorylation

Peng

Yang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Tonsillectomy may be an important method to achieve a long-term remission of IgAN, but patients’ physical status may limit their access to this surgery. We proposed an encouraging solution through inhibiting GADD34 expression in order to promote tonsillar mononuclear cells (TMCs) apoptosis and reduce nephropathic IgA secretion. Methods: A total of 12 IgAN and 9 non-IgAN patients were involved from March 2015 to May 2016. After TMCs were extracted by density gradient centrifugation and stimulated by inactivated hemolytic streptococcus, the mRNA and protein expression of GADD34, GRP78, CHOP, Bcl-2, Bcl-XL, AID, Iα-Cα, and cleaved caspase-3 were examined by fluorescent RT-PCR and Western blotting. Guanabenz treatment and siRNA interference were applied to downregulate GADD34 in tonsillar mononuclear cells from IgAN patients, and P-eIF2α expression was examined by Western Blotting. Cell apoptosis was evaluated by Annexin V FITC/PI flowcytometry, and IgA secretion in cultural supernatant was inspected by enzyme linked immunosorbent assay. Results: After stimulation, the expression of GADD34 was significantly increased in IgAN patients (P< 0.05). Cell apoptosis was mitigated and IgA secretion level was elevated (P< 0.05). To be noticed, CHOP expression had no significant difference between two groups. After guanabenz treatment and siRNA interference, a prolonged elevation of P-eIF2α expression was observed. Cell apoptosis was reinforced and IgA secretion level was decreased (P< 0.05). Conclusion: GADD34 may be a potential therapeutic target for IgAN treatment due to its effect on cell apoptosis.

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Renal outcome after tonsillectomy plus corticosteroid pulse therapy in patients with immunoglobulin A nephropathy: results of a multicenter cohort study

Cited by 18 publications

References 33 publications

Modern classification, progression factors, treatment and outcomes of primary mesangial proliferative glomerulonephritis

Modern classification, progression factors, treatment and outcomes of primary mesangial proliferative glomerulonephritis

Corticosteroids pulse therapy and oral corticosteroids therapy for IgA nephropathy patients with advanced chronic kidney disease: results of a multicenter, large-scale, long-term observational cohort study

Impact of GADD34 on Apoptosis of Tonsillar Mononuclear Cells from IgA Nephropathy Patients by Regulating Eif2α Phosphorylation

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