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Azathioprine as successful maintenance therapy in IgG4-related tubulointerstitial nephritis.

Pozdzik AA, Brochériou I, Demetter P, Matos C, Delhaye M, Devière J, Nortier JL - Clin Kidney J (2012)

Bottom Line: One year later, renal function remains stable.Our clinical observation underlines the importance of biological and radiological long-term follow-up of patients with previous AIP in order to early detect IgG4-related renal involvement.Corticosteroids are the first choice, but in the case of adverse effects or partial remission, AZA could be a useful and safe alternative therapy.

View Article: PubMed Central - PubMed

Affiliation: Nephrology Department, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium ; Experimental Nephrology Unit, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.

ABSTRACT
A 65-year-old man presented with a progressive increase in plasma creatinine (PCr). Two years before, diffusion-weighted magnetic resonance imaging had revealed a relapse of immunoglobulin G4 (IgG4)-related autoimmune pancreatitis (AIP) associated with sclerosing cholangitis. Bilateral hypointense renal cortical nodules were also described. Kidney biopsy showed patchy disappearance of tubules, sparse interstitial fibrosis and IgG4+ plasma cells (>30 per high power field) leading to the diagnosis of IgG4-related tubulointerstitial nephritis (TIN). Despite methylprednisolone, PCr and serum IgG4 levels remained elevated. Starting azathioprine (AZA) normalized IgG4 levels, which elicited corticosteroid withdrawal after 17 months. One year later, renal function remains stable. Our clinical observation underlines the importance of biological and radiological long-term follow-up of patients with previous AIP in order to early detect IgG4-related renal involvement. Corticosteroids are the first choice, but in the case of adverse effects or partial remission, AZA could be a useful and safe alternative therapy.

No MeSH data available.


Related in: MedlinePlus

(A) T2-weighted MRI transverse section at the level of the pancreas and kidneys showing main pancreatic duct enlargement (long arrow) and multiple hyperintense nodular areas involving the cortex and medulla of both kidneys (arrowheads). (B) DW-MRI (b = 1000 mm/s2) at the same level as (A) showing small nodular hypointense areas of increased water diffusion in both kidneys (arrowheads). (C) Arterial phase contrast-enhanced T1-weighted MRI section with fat saturation showing increased uptake (arrowheads) in the nodular areas observed in (A) and (B). (D) Renal interstitium massively infiltrated by inflammatory cells (long arrow), with disappearance of tubules and sparse interstitial fibrosis (arrowhead) (Masson's trichrome staining, original magnification ×200). (E) Several lymphocytes, plasma cells (long arrow) and numerous eosinophils (arrowhead) infiltrating the renal interstitium (haematoxylin and eosin staining, original magnification ×400). (F) Lesions of ‘tubulitis’ (long arrow) (periodic acid-Schiff staining, original magnification ×400). (G) Intracytoplasmic perinuclear IgG4 staining in infiltrating plasma cells IgG4 (long arrow) was found in the subcapsular cortex, in cortical labyrinth and in the medulla (immunoperoxidase staining, original magnification ×1000). (H, I, J and K) CD3+, CD4+, CD8+ and CD68+ cells in the periphery of lymphoid nodules, diffusely infiltrating the interstitium. (L) Tertiary lymphoid nodules containing CD20+ cells. (M) Clusters positive for enhanced nuclear Ki-67 immunostaining forming the germinative centre of tertiary lymphoid organs. (N and O) CD79 alpha+ and CD138+ cells diffusely infiltrating the cortical interstitium. (H–O) Immunoperoxidase stainings, original magnifications: (H–L) ×200, (M) ×40, (N, O) ×200.
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fig1: (A) T2-weighted MRI transverse section at the level of the pancreas and kidneys showing main pancreatic duct enlargement (long arrow) and multiple hyperintense nodular areas involving the cortex and medulla of both kidneys (arrowheads). (B) DW-MRI (b = 1000 mm/s2) at the same level as (A) showing small nodular hypointense areas of increased water diffusion in both kidneys (arrowheads). (C) Arterial phase contrast-enhanced T1-weighted MRI section with fat saturation showing increased uptake (arrowheads) in the nodular areas observed in (A) and (B). (D) Renal interstitium massively infiltrated by inflammatory cells (long arrow), with disappearance of tubules and sparse interstitial fibrosis (arrowhead) (Masson's trichrome staining, original magnification ×200). (E) Several lymphocytes, plasma cells (long arrow) and numerous eosinophils (arrowhead) infiltrating the renal interstitium (haematoxylin and eosin staining, original magnification ×400). (F) Lesions of ‘tubulitis’ (long arrow) (periodic acid-Schiff staining, original magnification ×400). (G) Intracytoplasmic perinuclear IgG4 staining in infiltrating plasma cells IgG4 (long arrow) was found in the subcapsular cortex, in cortical labyrinth and in the medulla (immunoperoxidase staining, original magnification ×1000). (H, I, J and K) CD3+, CD4+, CD8+ and CD68+ cells in the periphery of lymphoid nodules, diffusely infiltrating the interstitium. (L) Tertiary lymphoid nodules containing CD20+ cells. (M) Clusters positive for enhanced nuclear Ki-67 immunostaining forming the germinative centre of tertiary lymphoid organs. (N and O) CD79 alpha+ and CD138+ cells diffusely infiltrating the cortical interstitium. (H–O) Immunoperoxidase stainings, original magnifications: (H–L) ×200, (M) ×40, (N, O) ×200.

Mentions: He was asymptomatic and his physical examination was unremarkable. Blood tests were as follows: urea: 11.2 mmol/L, haemoglobin: 14.1 g/dL, lipase: 26 IU/L, AST: 15 IU/L, ALT: 11 IU/L, AP: 76 IU/L, γ-glutamyltransferase: 25 IU/L, glucose: 4.88 mmol/L, IgG4: 807 mg/dL, total IgE: 1482 IU/mL, CA 19–9: 37.5 IU/mL, absence of circulating immune complexes and normal complement activity. Estimated glomerular filtration rate was reduced to 36 mL/min/1.73m2. Urine dipstick analysis showed 1+ of occult blood and 3+ of proteins. Urine sediment only revealed microscopic haematuria (5 red blood cells/high power field) without any significant proteinuria and microalbuminuria (0.26 and 38.0 mg/dL, respectively). The urinary excretion rate of the active form of transforming growth factor-β1 (TGF-β1) was enhanced (996 ng/g Cr) as compared to healthy controls [mean value (minimum–maximum): 31 (19–52) ng/gr Cr]. Reduction in size of both kidneys (8 and 9 cm for right and left sides, respectively) and marked destruction of the renal parenchyma were established by abdominal ultrasonography. Two years before, a diffusion-weighted magnetic resonance imaging (DW-MRI) had demonstrated a relapse of AIP and IgG4-related sclerosing cholangitis. Bilateral hypointense renal cortical nodules had also been described (Figure 1A–C).


Azathioprine as successful maintenance therapy in IgG4-related tubulointerstitial nephritis.

Pozdzik AA, Brochériou I, Demetter P, Matos C, Delhaye M, Devière J, Nortier JL - Clin Kidney J (2012)

(A) T2-weighted MRI transverse section at the level of the pancreas and kidneys showing main pancreatic duct enlargement (long arrow) and multiple hyperintense nodular areas involving the cortex and medulla of both kidneys (arrowheads). (B) DW-MRI (b = 1000 mm/s2) at the same level as (A) showing small nodular hypointense areas of increased water diffusion in both kidneys (arrowheads). (C) Arterial phase contrast-enhanced T1-weighted MRI section with fat saturation showing increased uptake (arrowheads) in the nodular areas observed in (A) and (B). (D) Renal interstitium massively infiltrated by inflammatory cells (long arrow), with disappearance of tubules and sparse interstitial fibrosis (arrowhead) (Masson's trichrome staining, original magnification ×200). (E) Several lymphocytes, plasma cells (long arrow) and numerous eosinophils (arrowhead) infiltrating the renal interstitium (haematoxylin and eosin staining, original magnification ×400). (F) Lesions of ‘tubulitis’ (long arrow) (periodic acid-Schiff staining, original magnification ×400). (G) Intracytoplasmic perinuclear IgG4 staining in infiltrating plasma cells IgG4 (long arrow) was found in the subcapsular cortex, in cortical labyrinth and in the medulla (immunoperoxidase staining, original magnification ×1000). (H, I, J and K) CD3+, CD4+, CD8+ and CD68+ cells in the periphery of lymphoid nodules, diffusely infiltrating the interstitium. (L) Tertiary lymphoid nodules containing CD20+ cells. (M) Clusters positive for enhanced nuclear Ki-67 immunostaining forming the germinative centre of tertiary lymphoid organs. (N and O) CD79 alpha+ and CD138+ cells diffusely infiltrating the cortical interstitium. (H–O) Immunoperoxidase stainings, original magnifications: (H–L) ×200, (M) ×40, (N, O) ×200.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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fig1: (A) T2-weighted MRI transverse section at the level of the pancreas and kidneys showing main pancreatic duct enlargement (long arrow) and multiple hyperintense nodular areas involving the cortex and medulla of both kidneys (arrowheads). (B) DW-MRI (b = 1000 mm/s2) at the same level as (A) showing small nodular hypointense areas of increased water diffusion in both kidneys (arrowheads). (C) Arterial phase contrast-enhanced T1-weighted MRI section with fat saturation showing increased uptake (arrowheads) in the nodular areas observed in (A) and (B). (D) Renal interstitium massively infiltrated by inflammatory cells (long arrow), with disappearance of tubules and sparse interstitial fibrosis (arrowhead) (Masson's trichrome staining, original magnification ×200). (E) Several lymphocytes, plasma cells (long arrow) and numerous eosinophils (arrowhead) infiltrating the renal interstitium (haematoxylin and eosin staining, original magnification ×400). (F) Lesions of ‘tubulitis’ (long arrow) (periodic acid-Schiff staining, original magnification ×400). (G) Intracytoplasmic perinuclear IgG4 staining in infiltrating plasma cells IgG4 (long arrow) was found in the subcapsular cortex, in cortical labyrinth and in the medulla (immunoperoxidase staining, original magnification ×1000). (H, I, J and K) CD3+, CD4+, CD8+ and CD68+ cells in the periphery of lymphoid nodules, diffusely infiltrating the interstitium. (L) Tertiary lymphoid nodules containing CD20+ cells. (M) Clusters positive for enhanced nuclear Ki-67 immunostaining forming the germinative centre of tertiary lymphoid organs. (N and O) CD79 alpha+ and CD138+ cells diffusely infiltrating the cortical interstitium. (H–O) Immunoperoxidase stainings, original magnifications: (H–L) ×200, (M) ×40, (N, O) ×200.
Mentions: He was asymptomatic and his physical examination was unremarkable. Blood tests were as follows: urea: 11.2 mmol/L, haemoglobin: 14.1 g/dL, lipase: 26 IU/L, AST: 15 IU/L, ALT: 11 IU/L, AP: 76 IU/L, γ-glutamyltransferase: 25 IU/L, glucose: 4.88 mmol/L, IgG4: 807 mg/dL, total IgE: 1482 IU/mL, CA 19–9: 37.5 IU/mL, absence of circulating immune complexes and normal complement activity. Estimated glomerular filtration rate was reduced to 36 mL/min/1.73m2. Urine dipstick analysis showed 1+ of occult blood and 3+ of proteins. Urine sediment only revealed microscopic haematuria (5 red blood cells/high power field) without any significant proteinuria and microalbuminuria (0.26 and 38.0 mg/dL, respectively). The urinary excretion rate of the active form of transforming growth factor-β1 (TGF-β1) was enhanced (996 ng/g Cr) as compared to healthy controls [mean value (minimum–maximum): 31 (19–52) ng/gr Cr]. Reduction in size of both kidneys (8 and 9 cm for right and left sides, respectively) and marked destruction of the renal parenchyma were established by abdominal ultrasonography. Two years before, a diffusion-weighted magnetic resonance imaging (DW-MRI) had demonstrated a relapse of AIP and IgG4-related sclerosing cholangitis. Bilateral hypointense renal cortical nodules had also been described (Figure 1A–C).

Bottom Line: One year later, renal function remains stable.Our clinical observation underlines the importance of biological and radiological long-term follow-up of patients with previous AIP in order to early detect IgG4-related renal involvement.Corticosteroids are the first choice, but in the case of adverse effects or partial remission, AZA could be a useful and safe alternative therapy.

View Article: PubMed Central - PubMed

Affiliation: Nephrology Department, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium ; Experimental Nephrology Unit, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.

ABSTRACT
A 65-year-old man presented with a progressive increase in plasma creatinine (PCr). Two years before, diffusion-weighted magnetic resonance imaging had revealed a relapse of immunoglobulin G4 (IgG4)-related autoimmune pancreatitis (AIP) associated with sclerosing cholangitis. Bilateral hypointense renal cortical nodules were also described. Kidney biopsy showed patchy disappearance of tubules, sparse interstitial fibrosis and IgG4+ plasma cells (>30 per high power field) leading to the diagnosis of IgG4-related tubulointerstitial nephritis (TIN). Despite methylprednisolone, PCr and serum IgG4 levels remained elevated. Starting azathioprine (AZA) normalized IgG4 levels, which elicited corticosteroid withdrawal after 17 months. One year later, renal function remains stable. Our clinical observation underlines the importance of biological and radiological long-term follow-up of patients with previous AIP in order to early detect IgG4-related renal involvement. Corticosteroids are the first choice, but in the case of adverse effects or partial remission, AZA could be a useful and safe alternative therapy.

No MeSH data available.


Related in: MedlinePlus