Elevated fecal calprotectin and lactoferrin associated with small intestinal lesions in patients with Behçet disease.

BACKGROUND AND AIMS: Small intestinal lesions in patients with Behçet disease (BD) have a risk of perforation and hemorrhage requiring surgery. However, no screening strategy for such lesions has been established. We investigated small intestinal lesions in BD patients with video capsule endoscopy (VCE) and analyzed clinical characteristics to identify noninvasive biomarkers of such lesions. METHODS: This study included 33 BD patients who underwent VCE (PillCam® SB3) at our institution from June 2016 to January 2019. Clinical characteristics, including age, sex, disease duration, body mass index, gastrointestinal symptoms, eye involvement, and blood examinations, were obtained from the medical records of 27 of the 33 patients. Fecal immunochemical tests for hemoglobin, fecal calprotectin (FC), and fecal lactoferrin (FL) were measured. VCE findings of 145 healthy Japanese individuals from a previous report were used as controls. RESULTS: Two intestinal BD patients were included in the 27 patients. We observed that BD patients exhibit more small intestinal lesions compared with healthy individuals, including erosions, ulcers, and total lesions (erosions or ulcers). FC and FL levels were significantly higher in patients with versus without small intestinal lesions (P = 0.034 and P = 0.046, respectively). Receiver operating characteristic analyses demonstrated that FC (cutoff value = 119 µg/g) and FL (cutoff value = 17 µg/g) were biomarkers for small intestinal lesions in patients with BD. CONCLUSION: The present study using VCE showed that patients with BD had more small intestinal lesions than healthy individuals. FC and FL could be useful for screening BD patients who may have small intestinal lesions.

TAFRO Syndrome in a Kidney Transplant Recipient That Was Diagnosed on Autopsy: A Case Report.

A 57-year-old man who received a kidney transplant 4 years previously owing to unknown underlying disease presented with thrombocytopenia and fever. Hepatosplenomegaly and lymphadenopathy were observed, and development of prominent anasarca and worsening of renal function yielded the diagnosis of TAFRO syndrome. He was treated with high-dose steroids and plasmapheresis, and a thrombopoietin receptor agonist was administered for refractory thrombocytopenia. However, his general condition worsened, and he died on day 92. Histopathological analysis of a kidney autopsy specimen showed thrombotic microangiopathy characterized by glomerular endothelial swelling, mesangiolysis, and double contours of the glomerular capillary walls. His bone marrow showed megakaryocytic hyperplasia with mild reticulin fibrosis. Interestingly, these clinical and pathological features were remarkably similar to those the patient demonstrated before the kidney transplant, suggesting the recurrence of TAFRO syndrome. TAFRO syndrome is a rare systemic disorder whose concept has recently been established, but information on its long-term outcome is scarce. To our knowledge, this is the first case of TAFRO syndrome developing in a kidney transplant recipient, which suggests that disease recurrence occurs many years after the kidney transplant.

Membranous nephropathy with masked polyclonal IgG deposits associated with primary Sjögren's syndrome.

Tubulointerstitial nephritis and renal tubular acidosis are well-known renal involvements with primary Sjögren's syndrome. However, several types of glomerulonephritis such as membranoproliferative glomerulonephritis and membranous nephropathy are also known to develop in patients with this syndrome. We here report a case of membranous nephropathy that developed 8 years after a diagnosis of primary Sjögren's syndrome in a female patient. Interestingly, the deposition was not identified by routine immunofluorescence using snap frozen tissue, but was revealed by immunofluorescence on formalin-fixed paraffin-embedded sections treated with proteinase K. We further performed immunofluorescence analysis on the treated paraffin-embedded sections with the identified antigen but found that the deposited IgG was not monoclonal and that serum amyloid P, a sensitive marker for membranous-like glomerulopathy with masked IgG κ deposits, was not evident in the glomeruli. To the best of our knowledge, this report depicted the first case of masked polyclonal IgG deposits and further analysis is needed to clarify the underlying mechanisms of IgG masking and possible association with autoantibodies.

Extensive bilateral renal metastases of non-small cell lung carcinoma caused acute kidney injury resulting in end-stage renal disease.

Non-small cell lung carcinoma unusually causes clinically relevant metastases in the kidney while they are usually found only in autopsy. Acute kidney injury (AKI) due to direct metastatic invasion of a solid tumor is also very rare whereas it usually happens with hematologic malignancy, including lymphoma. We report a case with these two rarities. A 54-year-old man who had a 6.7 × 6.0 cm-sized tumor in the left upper lobe of the lung in computed tomography was diagnosed as squamous cell lung carcinoma with bronchoscopy with biopsy. His renal function was normal and no proteinuria or hematuria was recognized. He underwent left upper lobectomy and the pathologic examination revealed pT4N1M0 stage IIIA disease. Four months after the surgery, a single brain metastasis in the right frontal lobe found in brain magnetic resonance imaging was treated with Gamma Knife radiosurgery. He presented with macroscopic hematuria and AKI (the serum creatinine level was 1.35 mg/dL) nine months after surgery. The cause was enormous bilateral renal metastases, maximally 8 cm-sized lesions with poor enhancement, which were found in enlarged bilateral kidneys in enhanced CT. Intrapulmonary metastatic lesions were also newly detected. Chemotherapy with pembrolizumab, an antibody against anti-programmed cell death protein 1, had little effect and his renal function continued to decline rapidly, resulting in end-stage renal disease and maintenance hemodialysis. Chemotherapy with carboplatin and paclitaxel was additionally performed. However, two months after hemodialysis induction, the patient died with pneumonia and acute respiratory distress syndrome.

Tubulointerstitial nephritis without glomerular lesions in three patients with myeloperoxidase-ANCA-associated vasculitis.

BACKGROUND: Myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis frequently induces crescentic glomerulonephritis. However, a few cases have so far been reported to have only tubulointerstitial (TI) nephritis without any apparent glomerular lesions. We recently treated three similar cases. Therefore, their pathological features as well as clinical manifestations were studied in detail. METHODS: The pathological study was performed with immunohistochemical staining using various antibodies to the vascular endothelial cell surface markers, von Willebrand factor, type IV collagen, cytokeratin, E-cadherin, and MPO in addition to the routine histochemical examination. RESULTS: The study disclosed the loss of CD34 endothelial cell surface markers with and without the destruction of type IV collagen (capillary basement membrane) in the peritubular capillaries, even though the glomeruli showed good staining of these factors. Electron microscopy showed breaks in the capillary basement membrane. The loss of CD34 staining was associated with the infiltration of a few mononuclear cells and neutrophils in the lumen of peritubular capillaries and the surrounding interstitial tissues. The cytokeratin staining in the tubular epithelial cells was also diminished around these areas. Tubulitis was demonstrated with or without the destruction of the tubular basement membrane. The clinical manifestations of these three cases were only a few red blood cells and granular casts in the urinary sediment as well as slightly increased beta2-microglobulin in the urine, but no proteinuria. CONCLUSION: Based on these findings, the loss of CD34 vascular endothelial markers occurs in the early phase of the disease because of the MPO, which is presumed to have burst out from the infiltrated, activated neutrophils. This MPO, which releases proteolytic enzymes and radical oxygen species, acts on tissue destruction, namely the lysis of endothelial cell membranes as well as vascular basement membranes in the peritubular capillary. This mechanism eventually proceeds to the destruction of the peritubular capillary walls (vasculitis). This pathogenesis is thought to play an important role in the pathogenesis of TI nephritis, which is associated with MPO-ANCA vasculitis.

Classification of clinical subtypes, patient survival, kidney prognosis, and relapse in patients with MPO-ANCA-associated vasculitis: a single-center experience.

Myeloperoxidase-type antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis may manifest various organ symptoms. Treatment allows recovery from early, but severe, organ involvement. However, the relationship between the initial organ involvement and the eventual clinical course has not been studied in this disease. Therefore, the current study evaluated 30 patients who were hospitalized and then categorized into ten clinical subtypes based on organ involvement. The relationship of these subtypes to development of clinical features, patient survival, kidney prognosis, and relapse were evaluated over an average observation period of 4.3 years. During this study, the most common clinical features were lung and kidney involvement. Twenty-one patients already manifested clinical features around the time of admission and did not commonly present new symptoms as long as they were receiving the treatment for vasculitis. In contrast, as far as pulmonary involvement type at the initial time was concerned and in those not being treated for vasculitis, 7 of the 12 patients progressed to pulmo-renal involvement and 5 of them went onto renal failure. Progression to renal failure also occurred frequently in patients with pulmo-renal type manifesting at the initial time. Thirteen patients died, including three patients due to vasculitis of systemic type, seven due to infections, and three due to malignancy. Death due to vasculitis occurred in the early phase of treatment and was associated with either pulmonary hemorrhage or gastrointestinal bleeding. Infectious death occurred throughout the entire course of treatment, mostly in patients with pulmo-renal or pulmonary type, and tended to be associated with opportunistic organisms. Death with malignancy was observed after several years of treatment. Regarding renal prognosis, ten patients underwent hemodialysis. At initiation of hemodialysis, nine patients had pulmo-renal type and only one had renal type. A relapse was observed in ten patients, mainly in patients with pulmo-renal or pulmonary type, and it occurred after about 2.7 years, even with treatment. Such relapses manifested in a similar manner to their initial clinical subtypes. These results suggest that pulmo-renal type as well as pulmonary type have a high chance to progress to renal failure or systemic type, and they were fairly commonly associated with vasculitic or infectious death. Therefore, classification of clinical subtypes at the initial time and on admission is meaningful to some extent for predicting patient survival, kidney prognosis, and relapse, in addition to indicating the appropriate treatment regimen.

Lipoprotein glomerulopathy-like disease in a patient with type III hyperlipoproteinemia due to apolipoprotein E2 (Arg158 Cys)/3 heterozygosity.

A 77-year-old woman developed nephrotic syndrome associated with type III hyperlipoproteinemia (III HLP) and increased apolipoprotein E (apo E). Apo E analysis disclosed E2/E3 heterozygosity in phenotypic and genotypic expressions, without any other mutations. A renal biopsy showed intraluminal and subendothelial thrombus-like deposits in the dilated capillary loops of the glomerulus that stained positive for lipids and apo E. Electron microscopy revealed tiny granular particles in the capillary lumina, as well as between the glomerular basement membrane and the endothelial cells. It was therefore concluded that III HLP associated with apo E2/E3 heterozygosity could induce lipoprotein glomerulopathy-like disease and nephrotic syndrome.

Tubulointerstitial immune complex nephritis in a patient with systemic lupus erythematosus: role of peritubular capillaritis with immune complex deposits in the pathogenesis of the tubulointerstitial nephritis.

Class IV-G (A/C) diffuse lupus nephritis and tubulointerstitial (TI) nephritis in a 31-year old woman was studied by light, immunofluorescence (IF), and electron microscopy (EM), to determine the pathogenesis of the TI lesions. The light microscopic findings showed peritubular capillaritis in the interstitium, with ruptures in the capillary structure, lysis of the surrounding tubular basement membrane (TBM), extravasated red blood cells (RBCs), the infiltration of neutrophils and mononuclear cells, and edema. The IF study revealed IgG, IgA, IgM, C1q, C3, and C4 depositions along the TBM, on the capillary walls, and in the interstitium proper. The EM study disclosed the deposition of immune complexes in the TBM, the capillary wall, and the interstitium proper. Based on these findings, the TI nephritis in this patient was considered to be due to peritubular capillaritis secondary to the immune complex depositions in the capillary wall of the interstitium.