IgA nephropathy in a patient receiving infliximab for generalized pustular psoriasis.

BACKGROUND: IgA nephropathy is the most common glomerulonephritis. Secondary IgA nephropathy complicated with systemic diseases, including psoriasis, is also often reported. Generalized pustular psoriasis is a form of psoriasis characterized by sterile pustules on reddened skin and fever. Infliximab, one of the first-line therapies for severe psoriasis, has also been reported to cause systemic vasculitis and IgA nephropathy. We herein report a case of IgA nephropathy activated during infliximab treatment for generalized pustular psoriasis. CASE PRESENTATION: A 28-year-old woman presented with episodic gross hematuria, increasing proteinuria, and renal dysfunction. She had been receiving anti-TNFα therapy with infliximab because of generalized pustular psoriasis for 3 years, but her skin symptoms worsened following withdrawal during pregnancy. After delivery, her skin symptoms improved with the resumption of infliximab, but clinical signs suggested glomerulonephritis, and renal biopsy showed active IgA nephropathy. Infliximab was discontinued, and the combination of corticosteroids, tonsillectomy, and secukinumab, an IL-17A inhibitor, improved both the skin symptoms and the glomerulonephritis. CONCLUSIONS: In our case, the activity of IgA nephropathy was exacerbated by anti-TNFα therapy but was improved by the combination of corticosteroids, tonsillectomy, and an IL-17A inhibitor against the original disease. Autoimmune diseases may underlie the development of secondary IgA nephropathy associated with anti-TNFα therapy, and so further studies are needed to better understand the association between molecular-targeted drugs and IgA nephropathy.

Percutaneous transluminal renal angioplasty remarkably improved severe hypertension and renal function in a patient with renal artery stenosis and postrenal kidney failure.

A 69-year-old man was admitted to our hospital with severe hypertension and rapidly worsening renal function. He presented with a 10-year history of chronic renal failure caused by bilateral ureteral obstruction due to retroperitoneal fibrosis. Magnetic resonance angiography and Doppler ultrasonography suggested severe right renal artery stenosis (RAS). Renal angiography revealed 99% stenosis at the ostium of the right renal artery. We performed percutaneous transluminal renal angioplasty (PTRA) with the support of intravascular ultrasound to decrease the amount of contrast agent needed. In addition, to prevent distal atheroembolism, a distal protection device was used. The procedure was completed without any adverse effects. After PTRA, renal function and blood pressure improved remarkably and remained stable for one year. PTRA for RAS remains controversial, especially in patients with renal insufficiency. Use of new devices should be considered to decrease catheterization-related adverse effects.

A Case of Minimal Change Nephrotic Syndrome Secondary to Methotrexate-associated Hodgkin Lymphoma.

The patient was a 64-year-old man who had been receiving methotrexate (MTX) for rheumatoid arthritis for 8 years. Computed tomography (CT) obtained one month prior to admission revealed numerous enlarged lymph nodes. Lower leg edema appeared two weeks prior to admission. Severe proteinuria was confirmed, and the patient was admitted. A renal biopsy revealed minimal changes in glomeruli. CT on day 14 revealed shrinking lymph nodes, and the patient was diagnosed with Hodgkin lymphoma by a neck lymph node biopsy. This is the first report of secondary minimal change nephrotic syndrome caused by an MTX-associated lymphoproliferative disorder.

Tubulointerstitial nephritis with IgA kappa-positive plasma cells in a patient with primary Sjögren's syndrome and monoclonal gammopathy.

This is a case report of a 69-year-old Japanese man who has been undergoing treatment for primary Sjögren's syndrome (pSS) since he was 62 years. A renal biopsy, which revealed diffuse and severe mononuclear cell infiltration in the tubulointerstitium, was performed because of progressive renal dysfunction. Immunostaining demonstrated most of the infiltrating cells to be IgA, kappa, CD38, and CD138 positive. Immunofixation blood test revealed IgA kappa-type M protein; however, bone marrow abnormalities or lymph node enlargements on examination or imaging, respectively, were not observed. Tubulointerstitial nephritis caused by monotypic plasmacytic infiltration in pSS, accompanied with a monoclonal gammopathy of undetermined significance (MGUS), was diagnosed. A treatment of prednisolone 40 mg/day was initiated, promptly improving the patient's serum creatinine levels from 3.0 to 1.5 mg/dl. The infiltrating cells in pSS-associated tubulointerstitial nephritis are generally polytypic plasmacytes and lymphocytes, but in the present case, monotypic plasmacytes were predominant. This case is remarkable and rare and can be considered a complication of pSS or MGUS. Since it may become a new disease entity, it is important to accumulate similar cases.

Nephritis-associated plasmin receptor (NAPlr)-positive glomerulonephritis in a case of ANCA-negative small vessel vasculitis.

A 75-year-old man with fever was diagnosed with alveolar hemorrhage. Antineutrophil cytoplasmic antibodies for myeloperoxidase and proteinase 3 were absent. He received corticosteroid therapy, which immediately improved his symptoms and chest radiological findings. After the discontinuation of corticosteroids, fever and general fatigue relapsed, and renal function deteriorated with hematuria and proteinuria. A nerve conduction study revealed mononeuritis multiplex. Renal biopsy demonstrated focal necrotizing crescentic glomerulonephritis with endocapillary proliferative lesions, immunofluorescence C3 deposits, and electron-microscopic subepithelial hump-like deposits. Nephritis-associated plasmin receptor (NAPlr) and plasmin activity, biomarkers of infection-related glomerulonephritis, were positive in glomeruli. Although pathological findings suggested infection-related glomerulonephritis (IRGN), clinical manifestations, such as alveolar hemorrhage and mononeuritis multiplex, suggested systemic small vessel vasculitis. After corticosteroid therapy, systemic symptoms disappeared, and the gradual amelioration of hematuria and proteinuria was observed. Based on the clinical symptoms for which steroid therapy was effective, the patient was considered to have systemic small vessel vasculitis, the etiology of which may have been associated with infection.

[Case of an hemodialysis patient with MYH9 disorders].

A 70-year-old woman was admitted to our hospital for repair of vascular access for maintenance hemodialysis. She had been undergoing the maintenance hemodialysis for 20 years, however, her underlying renal disease had not been identified. The laboratory data on admission revealed marked thrombocytopenia with giant platelets and a Dohle body-like cytoplasmic inclusion body in granulocytes. The same hematological abnormalities were also detected in the peripheral blood smear of her daughter. We suspected hereditary macrothrombocytopenia and performed gene analysis of the MYH9 gene that encodes the nonmuscle myosin heavy chain-II A (NMMHC- II A). Mutational analysis showed the heterozygous mutation, c. 1841 G>A, in exon 38 of the MYH9 gene (E1841 K). We further examined intracellular NMMHC- II A localization in granulocytes by immunofluorescent analysis. The results revealed that one or two NMMHC- II A-positive granules were observed in neutrophils, whereas these granules were not detected in the granulocytes of normal healthy volunteers. From these analyses, we diagnosed her disease as MYH9 disorder, especially as a May-Hegglin abnormality. Thrombocytopenia is sometimes observed in maintenance hemodialysis patients. To avoid inappropriate medical intervention for the thrombocytopenia, MYH9 disorders should be differentiated.

Morphological analysis of biofilm of peritoneal dialysis catheter in refractory peritonitis patient.

A 66-year-old man undergoing peritoneal dialysis (PD) was admitted to our hospital for treatment of PD-related peritonitis. Culture of the PD fluid revealed the presence of Citrobacter freundii, and therapy with ceftazidime was started intraperitoneally. The cell count in PD fluid slowly decreased over time during the first 2 weeks of treatment, but increased again on the 14th hospital day. A second culture of the PD fluid revealed the presence of Enterococcus species. A switch in antibiotic therapy to vancomycin did not improve the cell count in the PD fluid. A third culture of the PD fluid revealed the presence of Stenotrophomonas maltophilia. The PD was discontinued and the catheter removed on the 28th hospital day. Examination of the catheter revealed that the inner tip was coated with a fibrous sheet of cells, suggesting biofilm formation. Following catheter removal, the patient was administered intravenous ciprofloxacin, and the inflammatory reaction started to disappear immediately and had completely disappeared after 1 week of treatment. Microscopic analysis of the fibrous structure on the catheter revealed multiple layers of various inflammatory cells. Immunostaining revealed the presence of CD44-positive polynuclear cells, indicating neutrophils, facing the catheter lumen. CD68-positive cells, indicating macrophages, were observed in the following layer, and keratin-positive cells, indicating peritoneal mesothelial cells, were present at the bottom of the structure. Based on the immediate improvement of PD-related peritonitis after catheter removal, we presumed that this biofilm contributed to the intractability of the patient's peritonitis. Morphological analysis of catheter revealed that both the mesothelial cells and the various inflammatory cells may have contributed to biofilm development.

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.

Effect of darbepoetin alfa on renal anemia in Japanese hemodialysis patients.

INTRODUCTION: A long-acting erythropoiesis-stimulating agent named "darbepoetin alfa" (CAS 11096-26-7) was recently developed. Though it is already in use worldwide, especially in western countries, its efficacy and safety for Asian patients have not been well evaluated yet. The purpose of this study was to evaluate the efficacy and safety of short-term darbepoetin alfa administration for Japanese hemodialysis patients. METHODS: Patients who had undergone maintenance hemodialysis were enrolled in this study. The erythropoiesis-stimulating agent was switched from epoetin alfa (CAS 113427-24-0) to darbepoetin alfa so as to control the hemoglobin (Hgb) value between 10 and 12 g/dl. The initial conversion ratio was made according to the manufacturer's recommendations. The factors relevant to the responsiveness to erythropoiesis were analyzed. RESULTS: One hundred and fifty-nine patients with a mean age of 67.6 years were enrolled. Two months after switching to darbepoetin alfa, the Hgb value had increased significantly (10.3 +/- 1.2 to 10.6 +/- 1.4 g/dl). Only iron supplementation correlated positively with the change of Hgb. In addition, 14.3% of patients had excess Hgb (Hgb > 12 g/dl) at the end of the study period, but only 5.6% patients at the run-in. Serious cardiovascular disease did not occur during the study period; however, the mean systolic blood pressure at the start of hemodialysis increased significantly and there was no correlation between the change of Hgb value and blood pressure. CONCLUSION: Darbepoetin alfa increases the Hgb value effectively in Japanese hemodialysis patients. Although no serious adverse events were apparent in our short-term analysis, the incidence of hypertension and excessive increase of the Hgb value must be noted.

Chronic pericardial constriction induced severe ischemic hepatitis manifesting as hypoglycemic attack.

Ischemic hepatitis, otherwise known as "shock liver", is characterized by a massive, but transient increase in serum transaminase levels, usually associated with cardiac failure. A patient who did not have a predisposition to hypoglycemia was discovered at home with disturbed consciousness caused by hypoglycemia. She had been diagnosed as having constrictive pericarditis several years earlier and had developed ischemic hepatitis. Though the high serum transaminase levels were rapidly normalized, severe jaundice gradually developed and the patient finally died of multiple organ failure. Hypoglycemia, which is considered secondary to reduced gluconeogenesis in the exhausted liver, is a rare complication of constrictive pericarditis.