Tubulointerstitial nephritis complicating IVIG therapy for X-linked agammaglobulinemia

Abstract

BackgroundPatients with X-linked agammaglobulinemia (XLA) develop immune-complex induced diseases such as nephropathy only rarely, presumably because their immunoglobulin (Ig) G concentration is low. We encountered a patient with XLA who developed tubulointerstitial nephritis during treatment with intravenous immunoglobulin (IVIG).Case presentationA 20-year-old man was diagnosed with XLA 3 months after birth and subsequently received periodic γ-globulin replacement therapy. Renal dysfunction developed at 19 years of age in association with high urinary β2-microglobulin (MG) concentrations. A renal biopsy specimen showed dense CD3-positive lymphocytic infiltration in the tubulointerstitium and tubular atrophy, while no IgG4-bearing cell infiltration was found. Fibrosclerosis and crescent formation were evident in some glomeruli. Fluorescent antibody staining demonstrated deposition of IgG and complement component C3 in tubular basement membranes. After pulse steroid therapy was initiated, urinary β2-MG and serum creatinine concentrations improved.ConclusionNeither drug reactions nor collagen disease were likely causes of tubular interstitial disorder in this patient. Although BK virus was ruled out, IgG in the γ-globulin preparation might have reacted with a pathogen present in the patient to form low-molecular-weight immune complexes that were deposited in the tubular basement membrane.

IVIG‐triggered tubulointerstitial nephritis in X‐linked agammaglobulinemia

“…We were unable to elucidate the relationship between TIN and glomerular lesions, but we detected no infections or immune diseases causing TIN. Furthermore, the previous case also involved crescent formation in the glomeruli, 5 as in the present case. This indicates that TIN was associated with glomerular lesions in both patients.…”

“…These cases of nephritis might be caused by endogenous IgG produced by the patient's residual B lymphocytes. In addition, IgG and C3 deposits have been identified in the tubular basement membranes of a 20‐year‐old man with XLA who developed TIN . In the present case, the first renal biopsy confirmed TIN and deposits of IgG and C 3 in the glomeruli.…”

“…In addition, IgG and C3 deposits have been identified in the tubular basement membranes of a 20year-old man with XLA who developed TIN. 5 In the present case, the first renal biopsy confirmed TIN and deposits of IgG and C 3 in the glomeruli. The second renal biopsy after replacement with F(ab 0 )(2) fragment IgG confirmed the disappearance of these deposits.…”

Rare case of interstitial nephritis in a young adult under IgG therapy

“…Altered kidney function in the context of intravenous immunoglobulin administration has been attributed to the increased osmotic load provided by preparations that use sucrose or similar agents to inhibit IgG aggregation in the intravenous immunoglobulin preparation 12. However, in our case, repeated administration of intravenous immunoglobulin appears to have elicited an inflammatory reaction, progressing to tubulointerstitial scarring.…”

Diffuse Subamniotic Calcification: A Novel Pattern of Placental Calcification

“…16 While IVIG is generally well-tolerated with few side effects, rare adverse outcomes include renal injury. 17 Rare case reports associate IVIG therapy with immune complex deposition in kidneys, causing membranoproliferative glomerulonephritis 18 or tubulointerstitial nephritis, 19 with clinical improvement upon cessation of IVIG. IgG concentrations in amniotic fluid rise proportionately with maternal serum concentrations 20 ; therefore, IVIG likely increases amniotic fluid immunoglobulin concentration.…”