Immunotactoid glomerulopathy (ORPHA:97567)
Immunotactoid glomerulopathy (ITG) is a very rare condition characterized by glomerular accumulation of microtubules in the mesangium and the glomerular basement membrane, that mainly presents with proteinuria, micro-hematuria, nephrotic syndrome, renal insufficiency and hematologic malignancy. ITG and non-amyloid fibrillary glomerulopathy (non-amyloid FGP, see this term) are often grouped together as pathogenetically related diseases.
Epidemiology
In native renal biopsies, ITG comprises an estimated incidence of 0.06% of adult GN. The disease mainly affect Caucasian population and patients over 50 years old. Men are slightly more affected than women.
Clinical description
ITG may manifest with proteinuria (usually nephrotic), hematuria, renal insufficiency and hypertension. Patients present with edema, ascites, pleural effusion and have an elevated risk of blood clots and infection. ITG patients manifest at a high frequency with hypocomplementemia, dysproteinemia, monoclonal gammopathy, cryoglobulinemia and lymphoproliferative disorders (mainly B-cell lymphocytic leukemia or small lymphocytic non-Hodgkin's lymphoma).
Etiology
Etiopathology of ITG is unknown. It may arise spontaneously or be associated with lymphoproliferative disorders, hepatitis C virus infection, leukocytoclastic vasculitis and hypocomplementemia.
Diagnostic methods
Diagnosis of ITG is based on renal biopsy. Common histological patterns include those of membranoproliferative, diffuse proliferative or membranous glomerulopathy. The diagnosis is also based on the absence of reactivity with Congo red and other agents typically used for the histochemical demonstration of amyloid tissues (e.g. thioflavin T), as well as observation on light, fluorescence and electron microscopy. At the ultrastructural level, deposits consist of usually parallel, hollow microtubular structures (10-90 nm in diameter, often >30 nm), mainly composed of monoclonal immunoglobulin G and complement component 3 (C3). Other laboratory findings may include low serum albumin and an increase in creatinine and in blood cholesterol.
Differential diagnosis
Differential diagnosis of ITG includes simple cryoglobulinemia, systemic lupus erythematosus, amyloidosis and non-amyloid FGP (see these terms).
Management and treatment
No proven effective therapy has been reported for ITG so far. Diuretics (e.g. furosemide) and dietary/fluid restrictions may be recommended in order to reduce fluid retention and prevent the accumulation of salt in the blood. An angiotensin-converting enzyme inhibitor may be prescribed in case of mild renal damage and low levels of protein loss. A statin and blood-thinning medication may be required to reduce cholesterol and the risk of blood clotting respectively, in case of a heavier protein leak. In case of rapidly progressive GN, cyclophosphamide and high doses of steroids may be indicated. Finally, when the disease is associated with an underlying condition, effective therapy directed at this underlying disorder may have some beneficial effect on the renal disease.
Prognosis
The overall course of ITG is usually slowly progressive, with about half of the patients developing end-stage renal disease over 2-4 years, requiring dialysis or renal transplantation. ITG recurrence in the transplanted kidney has been reported. A more extensive glomerular involvement or the presence of systemic involvement renders ITG prognosis poorer.

                            Last update: 
                            March 2016


                            - Expert reviewer(s): 
                            Dr Laure Hélène NOEL