Granulomatous interstitial nephritis with CTLA-4 haploinsufficiency: a case report.

BACKGROUND: Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential inhibitory regulator of immune activation. CTLA-4 haploinsufficiency is known to be associated with dysregulation of FOXP3+ regulatory T cells, hyperactivation of effector T cells, and lymphocytic infiltration of multiple organs. However, there have only been a few reports of renal involvement with CTLA-4. Herein, we present a case of acute granulomatous tubulointerstitial nephritis (TIN) in a patient with CTLA-4 haploinsufficiency. CASE PRESENTATION: A 44-year-old man presented with a 3-week history of fever and malaise, and subsequently developed acute kidney injury (AKI) a few days after treatment with levofloxacin (LVFX). A kidney biopsy and immunohistochemical staining revealed granulomatous TIN with dominantly infiltrating CD4+ T cells. General symptoms and renal impairment showed improvement after discontinuation of LVFX and initiation of oral steroids. However, they worsened following steroid tapering. Further, a colon biopsy analysis showed similar findings to the renal tissue analysis. We suspected that granulomatous TIN was possibly associated with CTLA-4 haploinsufficiency. Therefore, the patient was transferred to another hospital for further treatment of CTLA-4 haploinsufficiency using immunosuppressive agents. CONCLUSIONS: There have been few reports regarding renal involvement of CTLA-4 haploinsufficiency. In the present case, granulomatous TIN could have arisen due to instability of immune regulatory functions, such as CTLA-4 haploinsufficiency, and treatment with LVFX could have triggered immunologic activation and severe inflammation as well as renal dysfunction.

Development of ileocolic artery pseudoaneurysm after renal biopsy.

The rate of bleeding complications related to percutaneous native renal biopsy is low, and pseudoaneurysms of the extrarenal arteries are rare. There have been a few reports of extrarenal artery injuries related to renal biopsy; however, to the best of our knowledge, there have not been any reports of injuries to the ileocolic artery or multiple injuries to extrarenal arteries. Herein, we report the case of an 87-year-old man who developed multiple vascular injuries: an arteriovenous fistula at the lower pole of the right kidney, pseudoaneurysms of the second lumbar artery, and an ileocolic artery 19 days after renal biopsy. Although identifying an ileocolic artery pseudoaneurysm was slightly delayed due to its rarity, all vascular injuries were successfully embolized with microcoils.

Nephrotic syndrome due to preeclampsia before 20 weeks of gestation: a case report.

BACKGROUND: Preeclampsia (PE) refers to the development of hypertension and new-onset proteinuria or progressive organ damage (especially kidney) in a previously normotensive pregnant women after 20 weeks of gestation. Thus, new-onset nephrotic syndrome due to PE before 20 weeks of gestation seems to be rare, making its diagnosis difficult in this time period. CASE PRESENTATION: A 28-year-old woman presented with a new-onset nephrotic syndrome at 16 weeks of gestation. A high dose of oral glucocorticoids (prednisolone, 40 mg) was initiated for presumed glomerulonephritis since she presented with severe nephrotic syndrome before 20 weeks of gestation, however, the treatment was not effective. At 21 weeks of gestation, we confirmed that the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio was very high (sFlt-1, 13,400 pg/mL; PlGF, 21.9 pg/mL; serum sFlt-1/PlGF ratio 611.9). Therefore, we diagnosed nephrotic syndrome due to PE, and oral glucocorticoids were discontinued. After she underwent a cesarean section at 24 weeks & 3 days, we performed a kidney biopsy. Focal segmental sclerotic lesions with epithelial cell hyperplasia and foam cells in the tubular poles were seen on light microscopy. On immunofluorescence tests, C4d staining showed linear peripheral patterns in the glomeruli. Electron microscopy revealed diffuse subendothelial edema with focal foot process effacement. The histological diagnosis was severe glomerular endotheliosis with focal segmental glomerulosclerosis. Furthermore, the histology of placenta was consistent with PE. Eight months after delivery, her proteinuria disappeared completely. CONCLUSIONS: We not only confirmed an abnormal serum sFlt-1/PlGF ratio but also presented the histology compatible with pure PE in the kidney and placenta in a case of nephrotic syndrome before 20 weeks of gestation. The serum sFlt-1/PlGF ratio may be useful in determining the treatment strategy for atypical cases of pregnant women with nephrotic syndrome, particularly before 20 weeks of gestation.

Morphological Features of Minimal Change Disease and Focal Segmental Glomerulosclerosis Using Repeat Biopsy and Parietal Epithelial Cell Marker.

INTRODUCTION: Minimal change disease (MCD) and primary focal segmental glomerulosclerosis (FSGS) are representative podocyte diseases. The clinical cause of MCD and FSGS has not been clearly elucidated yet. However, it is important to distinguish MCD and FSGS because their prognoses and responses to treatment are quite different. OBJECTIVE: This study aimed to examine whether parietal epithelial cell (PEC) marker and repeat biopsy are useful for diagnosing primary FSGS. METHODS: Clinicopathological features of 17 patients with the nephrotic syndrome, who underwent kidney biopsy ≥2 times from 1975 to 2017, and had MCD or FSGS were analyzed using PAX8. We defined patients with PAX8+ cells as PAX8+ and the remainder as PAX8- patients. Three cases of sample insufficiency and 1 non-steroid-resistant or frequently relapsing case indicated for repeat biopsy were excluded. RESULTS: Among the 13 patients studied, 4 were PAX8+ and 9 were PAX8- (median age: 41 and 46 years, -respectively, at first biopsy). PAX8+ and PAX8- patients showed no significant differences in clinical data and histological diagnosis except for a significant difference in histological diagnosis at the second biopsy. The number of PAX8+ patients increased to 6. Unlike the first biopsy results, FSGS was present in 5 of 6 (83.3%) PAX8+ patients; MCD occurred in all 7 (100%) PAX8- patients. Three of 6 (50.0%) PAX8+ patients undergoing repeat biopsy were steroid resistant; no (0%) PAX8- patient was steroid resistant. All cases of final FSGS diagnosis were PAX8+ at the first or second biopsy. Only 1 PAX8+ MCD patient was steroid resistant. All PAX8- MCD patients were frequently relapsing. CONCLUSIONS: More PAX8+ patients were diagnosed with FSGS than PAX8- patients. Clinical presentation of MCD in PAX8- patients was frequently relapsing. PEC marker staining in patients with the nephrotic syndrome, e.g., MCD, may help to diagnose FSGS.