A case of non-lupus full-house nephropathy diagnosed by kidney biopsy but observed IgA nephropathy on second biopsy.

We describe a case of full-house nephropathy without any underlying disease, including systemic lupus erythematosus. A 40-year-old woman was referred to our hospital with mild proteinuria and microscopic hematuria. The patient was diagnosed with immune complex-mediated glomerulonephritis with a predominant mesangioproliferative pattern based on renal histopathological results using full-house immunofluorescence staining. She showed no clinical criteria for the diagnosis of systemic lupus erythematosus, except for kidney disorders, and tested negative for antinuclear antibodies throughout her clinical course. However, in the second kidney biopsy, no C1q or C4 were detected in the immunofluorescence study, suggesting an immunoglobulin A nephropathy-like pattern. The patient responded favorably to corticosteroid treatment. We found a heterozygous CFHR3-CFHR1 deletion. The association between full-house nephropathy and CFHR3-CFHR1 deletion is unknown, but its influence on the histological pattern in our case is suspected. This indicates the diversity in the pathogenesis of non-lupus full-house nephropathy and warrants further investigation.

A Case of Dabigatran-related Nephropathy Complicated by Tubulointerstitial Nephritis in a Patient with a Normal Renal Function and Undiagnosed IgA Nephropathy.

A 69-year-old woman was referred to our hospital because of an acute kidney injury with macroscopic hematuria. She had been taking dabigatran for atrial flutter for six years. Based on the typical histological findings of her kidney biopsy and her history of dabigatran use with prolonged activated partial thromboplastin time, she was diagnosed with dabigatran-related nephropathy complicated by tubulointerstitial nephritis with IgA nephropathy. After prednisolone therapy, the renal function improved. Direct-acting oral anticoagulants, including dabigatran, may cause anticoagulant-related nephropathy similar to warfarin, even in patients with a normal renal function. Tubulointerstitial nephritis may coexist with dabigatran-related nephropathy, and prednisolone therapy should be considered in such cases. IgA nephropathy has been reported as a background disease, and caution should be exercised when encountering it.

Late recurrence of low-risk gastrointestinal stromal tumor of jejunum diagnosed 30 years after tumor resection: A case report and literature review.

Gastrointestinal stromal tumors (GISTs) have a significant risk of metastasis, although the degree varies in each case. The present report describes a case of late recurrence of GIST that was diagnosed 30 years after the primary tumor resection. An 80-year-old man was transported to Sanjo General Hospital (Sanjo, Japan) with hemorrhagic shock from gastrointestinal bleeding. Abdominal contrast-enhanced computed tomography revealed an 11.7-cm heterogenous tumor in the retroperitoneum adjacent to the third portion of the duodenum. The patient had a medical history of resection of 'leiomyoma' of the upper jejunum when he was 50 years old. Pathological examination using archival pathological samples revealed that the previously excised tumor was GIST because the tumor cells showed positive immunoreactivity for KIT and DOG1. Treatment was started with imatinib, a selective KIT tyrosine inhibitor, even though endoscopy failed to provide biopsy specimens. Positron emission tomography conducted on the 28th treatment day revealed that imatinib completely shut down 18F-fluorodeoxyglucose uptake in the tumor, confirming that the tumor was imatinib-sensitive. A literature review yielded 12 GIST cases wherein metastases were diagnosed >10 years after primary tumor resection. Of the 12, four were originally diagnosed as benign. Clinicians should keep in mind that GISTs were formerly confused with non-GIST tumors and that there is a risk of relapse 10 years or later after curative surgery.

A case of hypercalcemia because of adrenal insufficiency induced by glucocorticoid withdrawal in a patient undergoing hemodialysis.

Glucocorticoids are widely used for treating underlying renal diseases and following renal transplantation and are often tapered or discontinued upon reaching end-stage renal failure. Although glucocorticoid withdrawal is the predominant cause of secondary adrenal insufficiency, no consensus has been established regarding its prevalence, clinical manifestations, or therapeutic regimen, for prevention of this pathological condition. We describe a 29-year-old woman admitted to our hospital because of 1-week history of fever, diarrhea, and general fatigue. She was affected with nephrotic syndrome and diagnosed with focal segmental glomerulonephritis at 15 years old, and had since been treated with glucocorticoids. She suffered from frequent relapse of nephrotic syndrome, which became refractory to other immunosuppressants and low-density lipoprotein apheresis, making discontinuation of glucocorticoids difficult. Renal function deteriorated gradually and hemodialysis was initiated 8 months before admission. She was infected with type A influenza roughly 2 weeks prior and treated with oseltamivir. She exhibited hypercalcemia (albumin corrected, 14.4 mg/dl) and hypoglycemia (31.0 mg/dl) for the first time. She was suspected of, and diagnosed with, adrenal insufficiency, because long-term glucocorticoid use was incidentally discontinued only 2 days before she contracted influenza. Clinical symptoms and hypercalcemia improved dramatically following initiation of treatment with hydrocortisone. Adrenal insufficiency is an unusual cause of hypercalcemia. However, hemodialysis patients tend to develop more severe hypercalcemia because of lack of urinary calcium excretion, which should not be overlooked because it may result in critical situations. In conclusion, clinicians should be aware of adrenal insufficiency with glucocorticoid withdrawal and hypercalcemia in hemodialysis patients.

A case of smoldering antineutrophil cytoplasmic antibody-associated vasculitis development during the course of primary Sjögren's syndrome.

Various forms of glomerular lesions have been described in primary Sjögren's syndrome (pSjS); however, myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is rarely reported, and the disease onset and clinical course of ANCA-associated vasculitis (AAV) complicated by pSjS are not well understood. A 51-year-old woman was referred to our hospital because of mild proteinuria and microscopic hematuria. She fulfilled the classification criteria for pSjS. We performed a kidney biopsy; however, it revealed no characteristic findings for pSjS, vasculitis, or other autoimmune diseases, including systemic lupus erythematosus. After 9 months, urinalysis abnormalities worsened and renal function was slowly declining, and ANCA was found to be positive. A second kidney biopsy was performed, revealing MPO-ANCA-associated pauci-immune segmental necrotizing glomerulonephritis with crescent formation. Even though immunofluorescence microscopy did not reveal any positive findings, additional electron microscopy demonstrated the presence of mesangial electron-dense deposits in both kidney biopsies. Based on kidney biopsy results and sequential serum ANCA measurements, we considered that smoldering ANCA-associated vasculitis had developed in this patient as this can develop during the clinical course of pSjS. She responded well to steroid therapy. Serum measurement, especially perinuclear, ANCA levels can be useful in patients with pSjS to detect the onset of ANCA-associated vasculitis, even in the absence of acute renal deterioration or severe urinary abnormalities.

Complement Factor H Gene Variant in a Patient with Thrombotic Microangiopathy on a Mixed Clinical Background.

We report the case of a patient with complement factor H gene variant, who developed thrombotic microangiopathy on a mixed clinical background. A 79-year-old woman was transferred to Sanjo General Hospital for maintenance hemodialysis. She suffered from gastric non-Hodgkin lymphoma about two years ago and received chemotherapy and radiation therapy, leading to complete remission. About 13 weeks prior to her transfer to our hospital, she was referred to another hospital due to acute kidney injury, hemolytic anemia, and thrombocytopenia. Hemodialysis was immediately initiated, after which intravenous methylprednisolone and oral prednisolone were started; however, she became anuric within approximately week. The possibility of thrombotic microangiopathy was examined. However, she was in poor general condition and did not get the consent of her family, so no invasive searches such as a kidney biopsy were performed. Despite the cause of acute kidney insufficiency being unclear, she was transferred to us for maintenance hemodialysis. Her general condition was stable, and her renal function improved; hence, two months after transfer, a kidney biopsy was performed. Her clinical and typical renal histological findings indicated a diagnosis of thrombotic microangiopathy. There was a possible CFH gene of a very rare variant "c.526 T > C (p.Phe176Leu)" in exon 5. She was able to withdraw from hemodialysis therapy two weeks after the initiation of an angiotensin-converting enzyme inhibitor. Based on her clinical course and kidney biopsy findings, she was diagnosed with thrombotic microangiopathy with a very rare CFH variant. To ensure proper treatment choices such as eculizumab, the presence of complement dysregulation should be considered in cases of secondary thrombotic microangiopathy.

Acute Kidney Injury Associated with Minimal Change Nephrotic Syndrome in an Elderly Patient Successfully Treated with both Fluid Management and Specific Therapy Based on Kidney Biopsy Findings.

Oliguric acute kidney injury (AKI) with minimal change nephrotic syndrome (MCNS) has long been recognized. Several mechanisms such as hypovolemia due to hypoalbuminemia and the nephrosarca hypothesis have been proposed. However, the precise mechanism by which MCNS causes AKI has not been fully elucidated. Herein, we describe an elderly patient with AKI caused by MCNS who fully recovered after aggressive volume withdrawal by hemodialysis and administration of a glucocorticoid. A 75-year-old woman presented with diarrhea and oliguria, and laboratory examination revealed nephrotic syndrome (NS) and severe azotemia. Fluid administration had no effect on renal dysfunction, and hemodialysis was initiated. Her renal function improved upon aggressive fluid removal through hemodialysis. Renal pathological findings revealed minimal change disease with faint mesangial deposits of IgA. After administration of methylprednisolone pulse therapy followed by oral prednisolone, she achieved complete remission from NS. The clinical course of this case supports the nephrosarca hypothesis regarding the mechanism of AKI caused by MCNS. Furthermore, appropriate fluid management and kidney biopsy are also important in elderly patients with AKI caused by NS.

Huge internal iliac artery aneurysm and post-renal AKI.

We report a rare case of a huge internal iliac artery aneurysm (IAA) complicated by post-renal acute kidney injury. Huge internal IAA should be considered for one of differential diagnoses for post-renal acute kidney injury.

TGFBI-associated corneal dystrophy and nephropathy: a novel syndrome?

Transforming growth factor beta-induced (TGFBI)-associated corneal dystrophies are a group of inherited progressive corneal diseases. One of these TGFBI-associated corneal dystrophies is Avellino corneal dystrophy, an autosomal dominant corneal dystrophy characterized by multiple asymmetric stromal opacities that potentially impair vision. Recently, a case with corneal dystrophy complicated by nephropathy possessing a pathogenic variant of the TGFBI gene was reported for the first time. Here, we report the second case with the same condition and the same mutation in the TGFBI gene. The patient was an 18-year-old male. He and his father had already been diagnosed with corneal dystrophy. Proteinuria was revealed in the patient during urine screening at school. Since his serum creatinine level was raised, a percutaneous renal biopsy was performed. Light microscopy demonstrated oligomeganephronia. Electron microscopy demonstrated an irregular basement membrane. TGFBI was analyzed by direct sequencing. A heterozygous mutation c.371G > A in exon 4, which caused an amino acid substitution from arginine to histidine at codon 124, was identified in the patient and his father. Although only one case of TGFBI-associated corneal dystrophy and nephropathy has been reported, our case's clinical and pathological findings were almost identical to those in that reported case. Further investigations of this new disease entity should be reported to all nephrologists and ophthalmologists.

Enzyme replacement therapy in a patient of heterozygous Fabry disease: clinical and pathological evaluations by repeat kidney biopsy and a successful pregnancy.

Fabry disease is a rare X-linked lysosomal storage disorder of glycosphingolipid catabolism caused by deficient activity of the lysosomal hydrolase alpha-galactosidase A (ɑ-Gal A). A 20-year-old woman was referred to our hospital because of proteinuria and persistent macroscopic hematuria. Based on the typical renal pathological findings, deficient activity of the ɑ-Gal A, and heterozygous mutation in the ɑ-Gal A gene, she was diagnosed with Fabry disease. After 1 year of enzyme replacement therapy with agalsidase alfa at 0.2 mg/kg every other week, the patient's proteinuria and hematuria were disappeared. In our patient, enzyme replacement therapy with agalsidase alfa was observed to be safe and well-tolerated during her pregnancy, with no significant negative effects on her or her child. Here, we report clinical and pathological evaluations of a patient through repeat kidney biopsy after 6 years of enzyme replacement therapy. Furthermore, we discussed the appropriate enzyme replacement therapy and its safety in pregnant women with Fabry disease.

A Case of Transforming Growth Factor-ß-Induced Gene-Related Oculorenal Syndrome: Granular Corneal Dystrophy Type II with a Unique Nephropathy.

Many types of inherited renal diseases have ocular features that occasionally support a diagnosis. The following study describes an unusual example of a 40-year-old woman with granular corneal dystrophy type II complicated by renal involvement. These two conditions may coincidentally coexist; however, there are some reports that demonstrate an association between renal involvement and granular corneal dystrophy type II. Granular corneal dystrophy type II is caused by a mutation in the transforming growth factor-ß-induced (TGFBI) gene. The patient was referred to us because of the presence of mild proteinuria without hematuria that was subsequently suggested to be granular corneal dystrophy type II. A kidney biopsy revealed various glomerular and tubular basement membrane changes and widening of the subendothelial space of the glomerular basement membrane by electron microscopy. However, next-generation sequencing revealed that she had no mutation in a gene that is known to be associated with monogenic kidney diseases. Conversely, real-time polymerase chain reaction, using a simple buccal swab, revealed TGFBI heteromutation (R124H). The TGFBI protein plays an important role in cell-collagen signaling interactions, including extracellular matrix proteins which compose the renal basement membrane. This mutation can present not only as corneal dystrophy but also as renal disease. TGFBI-related oculorenal syndrome may have been unrecognized. It is difficult to diagnose this condition without renal electron microscopic studies. To the best of our knowledge, this is the first detailed report of nephropathy associated with a TGFBI mutation.

Diverse Renal Phenotypes Observed in a Single Family with a Genetic Mutation in Paired Box Protein 2.

A common renal phenotype of paired box protein 2 (PAX2) mutations is renal coloboma syndrome. We report a single family with diverse renal phenotypes associated with PAX2 mutation. The proband presented steroid-resistant focal segmental glomerulosclerosis with optic coloboma, whereas his two sons showed severe renal hypoplasia with end-stage renal disease, with or without optic coloboma. In all three cases, a heterozygous PAX2 genetic mutation was identified (exon 2; NM_003987.3:c.76dupG, p.Val26Glyfs*28). Based on histopathological findings of the proband, we hypothesized that autophagic dysfunction was associated with the pathophysiology of the focal segmental glomerulosclerosis with PAX2 mutation. Detailed funduscopic examination - including the optic disc - might be useful for the diagnosis of renal anomalies associated with PAX2 mutation.

Nephrotic Syndrome without Hematuria due to Infection-Related Glomerulonephritis Mimicking Minimal-Change Disease in a Child.

Nephrotic syndrome without hematuria due to infection-related glomerulonephritis is uncommon. The present report describes a case of nephrotic syndrome due to infection-related glomerulonephritis without hematuria and hypertension in an older child. A 14-year-old boy was referred to our hospital because of a 5-day history of fever, nausea, weight gain and recent leg edema without hypertension. Laboratory data showed nephrotic-range proteinuria, hypoalbuminemia, mild hypocomplementemia and acute renal injury without hematuria. Although, due to the clinical presentation, minimal-change nephrotic syndrome was mostly suspected, a renal biopsy showed endocapillary hypercellularity mainly of mononuclear cells with segmental mesangiolytic changes. Fine granular IgG and C3 deposits were noted by an immunofluorescent study; many relatively small electron-dense deposits were observed electron-microscopically. These findings led to the diagnosis of nephrotic syndrome due to infection-related endocapillary proliferative glomerulonephritis, although the causative organism of his nephritis was not detected. He recovered with rest and dietary cure. When we examine an acute nephrotic child, infection-related glomerulonephritis should be considered as the differential diagnosis to avoid unnecessary use of corticosteroids.

Posterior Reversible Encephalopathy Syndrome in a Patient with Severe Uremia without Hypertension.

A 28-year-old man was admitted to our hospital with nausea, headache and weakness of the left hand. He had severe uremia without hypertension due to recurrent/chronic pyelonephritis. Brain magnetic resonance imaging showed reversible vasogenic edema in the brainstem and bilateral frontal centrum semiovale. All of his neurological symptoms immediately improved after the introduction of hemodialysis. When a patient with uremia presents with neurological symptoms, posterior reversible encephalopathy syndrome should be considered in the differential diagnosis even if high blood pressure is not observed. Brain magnetic resonance imaging may be helpful in such a case, and an appropriate therapy could be subsequently initiated.

De novo acute hepatitis B in myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody-related microscopic polyangiitis treated with corticosteroids.

An 82-year-old female was referred to our hospital because of low-grade fever, anemia, and rapidly progressive nephritic syndrome. Her laboratory data showed mild proteinuria, mild renal failure, and the presence of myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody. A skin biopsy specimen taken from the erythematous purpura revealed neutrophilic infiltration around the blood vessels with fibrinoid changes in the vessel walls. A renal biopsy specimen revealed segmental necrotizing glomerulonephritis with fibro-cellular crescent formation without deposits of immunoglobulin or complement components, indicating microscopic polyangiitis. The use of corticosteroid treatment, including intravenous methylprednisolone, improved renal failure. After 4 years with low-dose maintenance corticosteroid therapy, she developed de novo acute hepatitis B, and entecavir was remarkably effective, showing a rapid recovery from liver dysfunction with jaundice. To prevent hepatitis B virus (HBV) reactivation and de novo acute hepatitis B induced by immunosuppressive or cytotoxic therapy, including corticosteroids alone, the measurement of HBV-related serological markers needs to be performed prior to the initiation of such therapy, even in renal diseases.