Spontaneous Remission of Thrombospondin Type-1 Domain-Containing-Associated Membranous Nephropathy.

Membranous nephropathy often achieves spontaneous remission. However, there are scarce reports of spontaneous remission of thrombospondin type-1 domain-containing 7A (THSD7A)-associated membranous nephropathy. A 64-year-old female presented with nephrotic syndrome and edema of the lower extremities. We diagnosed membranous nephropathy by kidney biopsy and confirmed positive THSD7A on immunofluorescence using frozen sections; serum THSD7A antibodies were also detected. Thirty-four months after the initial diagnosis, she achieved a spontaneous complete remission without immunosuppressive therapy. With the complete remission, no serum THSD7A levels were detected. In this study, we describe serial examinations of kidney biopsies and serum THSD7A antibodies.

Galactose-deficient IgA1 and nephritis-associated plasmin receptors as markers for IgA-dominant infection-related glomerulonephritis: A case report.

RATIONAL: Immunoglobulin A (IgA) nephropathy is a common heterogeneous kidney disease. One of the causes of secondary immunoglobulin A nephropathy is infection-related glomerulonephritis (IRGN), however, its accurate diagnosis is difficult. PATIENT CONCERNS: We report a rare case of an 82-year-old male presenting rapidly progressive glomerulonephritis. Assessment of a kidney biopsy by light microscopy revealed endocapillary glomerulonephritis with subendothelial deposits, such as wire loop lesions and cellular crescents. Immunofluorescence demonstrated strong staining for IgA and C3 along the glomerular capillary. Additional tests included positive staining for nephritis-associated plasmin receptor and positive plasmin activity in the glomeruli. Moreover, IgA and galactose-deficient IgA1 (Gd-IgA1) staining merged using immunofluorescence, followed by confirmation of high serum levels of Gd-IgA1 (9.3 µg/mL) by ELISA was observed. DIAGNOSIS: The diagnosis of IgA-dominant IRGN was made. INTERVENTIONS AND OUTCOMES: We have initiated treatment with intravenous methylprednisolone 500 mg/day for 3 days, followed by oral prednisolone 25 mg/d as rapidly progressive glomerulonephritis. However immunosuppressive therapy was halted because of a poor response, and hemodialysis was initiated. LESSONS: This is a case of IgA-dominant IRGN patient exhibiting positive glomerular staining for nephritis-associated plasmin receptor accompanied with high titers of serum Gd-IgA1. Our observations suggest that serum and kidney tissue of Gd-IgA1 may be useful for the diagnosis of IgA-dominant IRGN.

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.

Unusual Proliferative Glomerulonephritis in a Patient Diagnosed to Have Hypoparathyroidism, Sensorineural Deafness, and Renal Dysplasia (HDR) Syndrome with a Novel Mutation in the GATA3 Gene.

Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome is a rare autosomal dominant disease caused by GATA3 mutations. Although several cases with variable renal features have been reported, the presence of histological changes within the glomeruli in adult patients is unclear. We herein report an adult case of HDR syndrome with a novel p.C288W (TGC>TGG) missense mutation in GATA3. His renal histology showed a membranoproliferative glomerulonephritis-like glomerular lesion. Additional renal histological analyses of HDR syndrome patients will be needed to clarify the role of GATA3 in both the developing and adult kidney.

Hematopoietic Stem Cell Transplantation Nephropathy Associated with Chronic Graft-versus-Host Disease without Extrarenal Involvement.

A 30-year-old woman with myelodysplastic syndrome underwent allogeneic hematopoietic stem cell transplantation (HSCT) derived from her HLA-matched sister six years previously. She received preconditioning total body irradiation with renal shielding and was subsequently administered cyclosporin A (CyA) as prophylaxis against graft-versus-host disease (GVHD). Four months after HSCT, asymptomatic proteinuria and glomerular hematuria developed during CyA tapering without obvious extrarenal involvements of GVHD, and persisted for six years. A renal biopsy revealed endothelial injury in the glomeruli, and the deposition of C4d was detected diffusely on glomerular capillaries and focally on peritubular capillaries, suggesting that nephropathy involved antibody- or complement-associated immune reactions.

A Japanese Family Suffering from Familial Juvenile Hyperuricemic Nephropathy due to a Rare Mutation of the Uromodulin Gene.

We report the case of a Japanese family suffering from familial juvenile hyperuricemic nephropathy (FJHN) due to a rare missense mutation of the uromodulin (UMOD) gene. An 18-year-old male presented with gout, hyperuricemia, and stage 3 chronic kidney disease. Mostly, FJHN is caused by a mutation altering the cystine residue of UMOD/Tamm-Horsfall protein. However, in the present case, a T688C mutation was identified in exon 4, resulting in amino acid substitution with arginine replacing tryptophan at position 230 (Trp230Arg). This mutation was also found in his brother and father with the same phenotype, indicating autosomal dominant inheritance. The affected amino acid was conserved in 200 healthy Japanese controls. Therefore, mutation T688C most likely causes rare structural and/or functional abnormalities in UMOD/Tamm-Horsfall protein.