Abstract Background and Aims IgA deficiency (IgAD) is the most common primary immunoglobulin deficiency in western countries. This entity is associated with increased risk of other autoimmune diseases. Mesangial proliferative glomerulonephritis (MesPGN) is a histological pattern defined by mesangial cell proliferation and expansion of the extracellular matrix within the mesangium. The clinical presentation can vary, from nephrotic syndrome to isolated hematuria. 30-40% of MesPGN cases are associated with IgA nephropathy. Other common diagnostic entities that present with this pattern include IgM nephropathy, C1q nephropathy or lupus nephritis, as well as Hepatitis B or C virus infection; idiopathic MesPGN is poorly described in the literature. To the best of our knowledge, this is the first report of idiopathic MesPGN associated with IgAD. Results A 17-year old woman with a background of IgAD and occasional episodes of bronchitis in her childhood presented in January 2022 with nonspecific abdominal pain and macroscopic hematuria. She had been suffering these symptoms for the last few weeks, usually after physical exercise. She was normotensive and showed no fever, skin rashes or other symptoms. Laboratory tests revealed normal renal function (serum creatinine 0.65 mg/dL), urinary albumin-to-creatinine ratio of 23.9 mg/g, a 24-h protein excretion ranging from 40 to 240 mg and non-dysmorphic hematuria of up to 51-150 erythrocytes/field. Additional laboratory tests repeatedly showed only low IgA serum levels, with normal ANA, ANCA or complement levels. Renal ultrasound showed both kidneys with normal size and cortical thickness. A CT urogram observed multiple, bilateral, non-obstructive small-sized kidney stones and a persistent nephrogram. Genetic tests were negative for Alport syndrome-related mutations. Additional workup included occult blood in the stool, stool culture, rectal biopsy and colonoscopy, which were all negative. Symptoms persisted during the following 12 months. A kidney biopsy was performed, finding 40 glomeruli with normal optical appearance, none of them sclerosed. Discrete mesangial expansion and cell proliferation was observed, with capillary lumens with occasional congestion but without thrombi or fibrinoid necrosis. Tubules and interstitium showed no sign of sclerosis or fibrosis, with conserved basement membranes and brush borders. In vessels, subintimal fibrosis, hyalinosis or concentric arteriolar hyperplasia or endarteritis were ruled out. Immunofluorescence showed low-intensity, discrete granular C3 mesangial deposits and no deposition of IgA, IgG, IgM, fibrinogen, C4, C1q or albumin. A diagnosis of non-IgA MesPGN was reached. The patient stopped performing intense physical exercise on a regular basis. This translated in hematuria and abdominal pain of much lower intensity. The patient is currently receiving only supportive therapy and maintains a normal renal function, with persistence of microscopic non-dysmorphic hematuria and occasional, low-grade proteinuria as described. Conclusion MesPGN is the most diagnosed form of glomerulonephritis worldwide. However, most cases are associated with granular IgA deposition in the mesangium, which was absent in this case. Idiopathic, non-IgA MesPGN is a much rarer condition that has been considered by some authors as a form focal segmental glomerulosclerosis or minimal change disease, although others believe it to be a separate condition. IgAD has been previously associated with Crohn's disease, which could explain this patient's symptoms. Crohn's disease has also been associated with non-IgA MesPGN in a low number of patients. Nevertheless, no findings in the patient workup were suggestive of Crohn's disease. A capsule endoscopy study will be performed to clearly rule out such diagnosis.
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Jun 20, 2024
Wang Tianyu + 38
Open Access