Successful rituximab treatment of TAFRO syndrome with pathological findings of glomerular endothelial damage

Noda, Yuhei; Saka, Yosuke; Kato, Aki; Mimura, Tetsushi; Naruse, Tomohiko

doi:10.5414/cncs109400

Cited by 15 publications

(12 citation statements)

References 15 publications

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“…There were 8 males and 17 Asians (2 Caucasian); the median age at diagnosis of TAFRO was 69 years [53; 76]. Serum interleukin-6 (IL-6) and VEGF level, when available, were elevated in all but one case (13). The median creatinine level at the time of renal biopsy was 2.13 mg/dL [1.25; 2.52], and urinary sediment was present in most cases (glomerular hematuria in 13 cases and proteinuria over 1 g per gram of creatinine or per day in 7 cases).…”

Section: Review Of Literaturementioning

confidence: 99%

Renal Pathologic Findings in TAFRO Syndrome: Is There a Continuum Between Thrombotic Microangiopathy and Membranoproliferative Glomerulonephritis? A Case Report and Literature Review

et al. 2019

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Background: TAFRO syndrome is a clinical subtype of idiopathic multicentric Castleman disease (iMCD) that is characterized by thrombocytopenia, anasarca, fever and/or elevated serum C-reactive protein, renal dysfunction, and organomegaly. Case Presentation: A 28-year-old woman with fever, weight gain of 13 kgs, lower extremity edema, hepatosplenomegaly, and multicentric peripheral lymphadenopathy was referred to our center. Laboratory investigations revealed anemia, thrombocytopenia, creatinine at 1.19 mg/dL and hypoalbuminemia at 33 g/L. Proteinuria was measured at 2 g/day including albuminuria at 1.5 g/day. Urinary sediment examination found leukocyturia at 44,000/mL and hematuria at 645,000/mL. Vascular endothelial growth factor (VEGF) level was elevated. A cervical lymph node biopsy found features consistent with the mixed histopathological subtype of iMCD. A renal biopsy revealed a membranoproliferative glomerulonephritis (MPGN) pattern. We initiated 3 days of methylprednisolone pulse-therapy at 1,000 mg per day, followed by prednisone 1 mg/kg/day and evolution was favorable. Review of Literature: 19 iMCD patients with TAFRO syndrome had undergone a renal biopsy: 8 cases with author's diagnosis consistent with MPGN-like and 11 cases of thrombotic microangiopathy (TMA)-like glomerulopathy without fibrin thrombi in glomerular capillaries or arterioles and without typical biological signs. Clinical, biological, and outcome characteristics were similar between the cases described as having MPGN and TMA-like presentation. After a thorough review of histopathological descriptions for each case, MPGN lesions seems to be the consequences of chronic glomerular endothelial injury in persistent TMA. We suspect that VEGF and IL-6 play a key role in the physiopathology of the spectrum of renal involvement from TMA-like to MPGN observed in TAFRO syndrome. Conclusion: We present a Caucasian iMCD patient with TAFRO syndrome with renal insufficiency secondary to MPGN, which might be secondary to a chronic TMA-like disease. We suspect that there is a continuum between TMA and MPGN lesions in TAFRO syndrome favored by VEGF and IL-6.

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Section: Review Of Literaturementioning

confidence: 99%

Renal Pathologic Findings in TAFRO Syndrome: Is There a Continuum Between Thrombotic Microangiopathy and Membranoproliferative Glomerulonephritis? A Case Report and Literature Review

et al. 2019

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“…Renal histology in the 10 patients [4–13] and our patient mainly showed MPGN-like lesions or TMA-like glomerulopathy. The timing of the kidney biopsy performed in these patients varied from the acute phase [8–13] to the chronic phase [4–7]; however, glomerular microangiopathy was a common finding. We explored the details of kidney biopsy findings in the literature review and found that 3 (Case no.3 and 5–6, Table 3) out of 5 cases diagnosed as MPGN-like glomerulopathy had no glomerular immune deposits.…”

Section: Resultsmentioning

confidence: 99%

TAFRO syndrome as a cause of glomerular microangiopathy: a case report and literature review

et al. 2019

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BackgroundTAFRO syndrome is a systemic inflammatory disorder that manifests as thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). Renal dysfunction is frequently complicated with TAFRO syndrome, however, it is challenging to perform kidney biopsy in patients with TAFRO syndrome in the presence of thrombocytopenia. Renal histology in TAFRO syndrome mainly shows membranoproliferative glomerulonephritis (MPGN)-like lesions or thrombotic microangiopathy (TMA)-like glomerulopathy. We review our case and previous reports of TAFRO syndrome with kidney biopsy findings and discuss the renal pathophysiology of TAFRO syndrome.Case presentationWe describe a previously healthy 48- year-old woman with TAFRO syndrome. Kidney biopsy performed before the treatment showed diffuse global endocapillary proliferative changes with endothelial cell swelling, double contours of partial capillary walls, and mesangiolysis, consistent with TMA-like glomerulopathy. Glucocorticoid therapy including steroid pulse was ineffective and she developed anasarca, renal dysfunction and oliguria. Hemodialysis was required. However, the anti-Interleukin (IL)-6 receptor antibody (tocilizumab) therapy was very effective. An increase in urinary volume was achieved about 2 weeks after the tocilizumab therapy and hemodialysis was discontinued. To investigate the renal pathophysiology of TAFRO syndrome, we performed immunohistological staining of vascular endothelial growth factor (VEGF)-A, CD34, and D2–40, in our case and a normal control kidney. Glomerular VEGF-A was especially positive in podocytes both, in the control and in the case, with no significant difference and there was a significant increase of VEGF-A staining area in the cortical peritubular capillaries in the case. Both glomerular and renal cortical CD34 expression were significantly decreased in our case. D2–40 expression in cortex was not significantly different.ConclusionsWe reviewed our case and other 10 previous reports about renal biopsy findings in TAFRO syndrome and found that glomerular microangiopathy was a common finding. IL-6-VEGF-axis-induced glomerular microangiopathy may play a crucial role in developing acute kidney injury in TAFRO syndrome and the anti-IL-6 receptor antibody therapy may be useful for TAFRO syndrome refractory to glucocorticoids. About the pathophysiology of VEGF in TAFRO syndrome, VEGF balance in the glomerulus and perhaps in the peritubular capillary system as well may be critical. Further investigation is needed.

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Section: Discussionmentioning

confidence: 99%

“…To our knowledge, biopsy findings of TAFRO syndrome have been reported in 14 cases, all of which, including our cases, consistently demonstrated findings suggesting marked glomerular endothelial cell injury (Table 1). [2][3][4][5][6][7][8][9][10][11][12][13][14][15] Castleman disease and POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes) syndrome are considered to be similar pathologic entities to TAFRO syndrome, and abnormal secretion and biological actions of IL-6 and VEGF may be involved in the pathogenesis of these diseases. In animal experiments, overproduction of IL-6 induces endothelial cell injury, whereas VEGF is known to increase vascular permeability.…”

Section: Discussionmentioning

confidence: 99%

TAFRO Syndrome With Kidney Involvement: A Case Series of Patients With Kidney Biopsies

et al. 2021

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TAFRO (thrombocytopenia, anasarca, fever, reticulin myelofibrosis/renal insufficiency, and organomegaly) syndrome is a systemic inflammatory disease sharing some features with Castleman disease and POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) syndrome in relation to abnormal secretions of interleukin 6 and vascular endothelial growth factor. The kidney is a main target organ of TAFRO syndrome but the kidney histopathology associated with TAFRO syndrome is yet to be completely defined. We report 3 TAFRO syndrome cases with different clinical courses in which kidney biopsies were performed. In all 3 cases, kidney biopsies showed similar glomerular lesions of diffuse global swelling of the endothelium and expansion of subendothelial spaces, consistent with severe glomerular endothelial injury. Case 3 showed an additional finding of focal tubulointerstitial injury characterized by marked plasma cell infiltration, which was absent in the other 2 cases. Clinical symptoms in cases 1 and 2, which had lower disease severity scores of TAFRO syndrome, were effectively treated with the administration of corticosteroids or a combination of corticosteroids and cyclosporine A. Case 3, with a higher disease severity score, had an aggressive clinical course that was refractory to corticosteroids and tocilizumab; the patient ultimately died of multiple organ failure. In all 3 cases, kidney biopsy provided indications for the diagnosis process and clinical management of TAFRO syndrome.

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Successful rituximab treatment of TAFRO syndrome with pathological findings of glomerular endothelial damage

Cited by 15 publications

References 15 publications

Renal Pathologic Findings in TAFRO Syndrome: Is There a Continuum Between Thrombotic Microangiopathy and Membranoproliferative Glomerulonephritis? A Case Report and Literature Review

Renal Pathologic Findings in TAFRO Syndrome: Is There a Continuum Between Thrombotic Microangiopathy and Membranoproliferative Glomerulonephritis? A Case Report and Literature Review

TAFRO syndrome as a cause of glomerular microangiopathy: a case report and literature review

TAFRO Syndrome With Kidney Involvement: A Case Series of Patients With Kidney Biopsies

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