Multiple Sclerosis Drug Fingolimod Induces Thrombotic Microangiopathy in Deoxycorticosterone Acetate/Salt Hypertension.

We examined whether fingolimod (FTY720), an S1PR (sphingosine-1-phosphate receptor) modulator, has beneficial or harmful effects on mineralocorticoid/salt-induced renal injury. Uninephrectomized rats on 0.9% NaCl/0.3% KCl drinking solution were randomly divided into control, control+FTY720, deoxycorticosterone acetate (DOCA), and DOCA+FTY720 groups and administered vehicle, vehicle+FTY720, DOCA+vehicle, and DOCA+FTY720 for 4 weeks, respectively. Only the DOCA+FTY720 group had reduced survival rates and showed hemolysis because of intravascular mechanical fragmentation of erythrocytes and thrombocytopenia. Both the DOCA+FTY720 and DOCA groups developed malignant hypertension, which was more severe in the DOCA+FTY720 group. In the DOCA+FTY720 group only, thrombotic microangiopathy involving severe renal arteriole endothelial cell injury was observed and was characterized by fibrinoid necrosis and onion-skin lesions in arterioles. There were fewer circulating endothelial progenitor cells in the DOCA+FTY720 group but more in the DOCA group compared with the control group. Expression levels of VEGF (vascular endothelial growth factor), S1PR1, and S1PR3 in renal arteriole endothelial cells were significantly greater in the DOCA+FTY720 and DOCA groups compared with the control group, with levels being similar between the 2 groups. Expression levels of endothelial nitric oxide synthase in renal arteriole endothelial cells were significantly lower in the DOCA+FTY720 group only. The control+FTY720 group showed reduced circulating endothelial progenitor cells but no significant functional or pathological changes in kidneys or changes in blood pressure. Exposure of uninephrectomized rats to DOCA/salt+FTY720 for 4 weeks induced renal arteriolar endothelial cell injury, resulting in the development of thrombotic microangiopathy. Consideration of this possibility is recommended when prescribing FTY720.

Purpura with ulcerative skin lesions and mixed cryoglobulinemia in a quiescent hepatitis B virus carrier.

Mixed cryoglobulinemia is occasionally seen in patients with hepatitis B virus (HBV) infection. This report presents the case of a quiescent HBV carrier who had type II mixed cryoglobulinemia, protracted purpura, ulcerative skin lesions and advanced chronic kidney disease. The cutaneous manifestations of the patient improved along with a decrease in the serum cryoglobulin and HBV-deoxyribonucleic acid levels following the initiation of oral entecavir in combination with plasmapheresis. However, the patient ultimately required prednisolone due to the limited benefits of these treatments. We also discuss various concerns regarding steroid treatment in patients with mixed cryoglobulinemia complicated by HBV infection.

Acute post-streptococcal glomerulonephritis with acute kidney injury in nephrotic syndrome with the glomerular deposition of nephritis-associated plasmin receptor antigen.

We herein report the case of a 17-year-old man who developed an increased plasma creatinine level (11.1 mg/dL) and oliguria with massive proteinuria (27.3 g/day) four weeks after an abraded wound to his right knee. The histology of the renal biopsy specimens showed diffuse endocapillary proliferative glomerulonephritis with the deposition of nephritis-associated plasmin receptor in the glomerulus. A case of acute kidney injury due to nephrotic syndrome caused by acute post-streptococcal glomerulonephritis was diagnosed. His renal function and proteinuria were improved with supportive care, including hemodialysis, without the administration of immunosuppressive agents.

Acute kidney injury in a patient with nephrotic syndrome due to focal segmental glomerular nephritis induced by a single oral administration of high-dose bisphosphonate (minodronate).

We herein report the case of a 75-year-old man who developed an increased serum creatinine level (4.93 mg/dL) and oliguria with massive proteinuria (7.14 g/day) on the second day after a single oral administration of high-dose (56 mg) minodronate. The histology of a renal biopsy showed one area of glomerular sclerosis among 20 glomeruli with global foot process effacement of podocytes and mild infiltration of lymphocytes and eosinophils into the interstitial space. Acute kidney injury in nephrotic syndrome due to focal segmental glomerular sclerosis induced by minodronate was diagnosed. Following cessation of minodronate without the administration of immunosuppressive agents, the patient's renal function and proteinuria markedly improved.

Characteristics of urinary and serum soluble Klotho protein in patients with different degrees of chronic kidney disease.

BACKGROUND: Klotho is a single-pass transmembrane protein, which appears to be implicated in aging. The purpose of the present study was to characterize the relationship between the soluble Klotho level and renal function in patients with various degrees of chronic kidney disease (CKD). METHODS: The levels of soluble Klotho in the serum and urine obtained from one hundred thirty-one CKD patients were determined by a sandwich enzyme-linked immunosorbent assay system. RESULTS: The amount of urinary excreted Klotho during the 24 hr period ranged from 1.6 to 5178 ng/day (median 427 ng/day; interquartile range [IR] 56.8-1293.1), and the serum Klotho concentration ranged from 163.9 to 2123.7 pg/ml (median 759.7 pg/ml; IR 579.5-1069.1). The estimated glomerular filtration rate (eGFR) was significantly correlated with the log-transformed values of the amount of 24 hr urinary excreted Klotho (r = 0.407, p < 0.01) and the serum Klotho levels (r = 0.232, p < 0.01). However, a stepwise multiple regression analysis identified eGFR to be a variable independently associated only with the log-transformed value of the amount of 24-hr urinary excreted Klotho but not with the log-transformed serum Klotho concentration. Despite the strong correlation between random urine protein-to-creatinine ratio and the 24 hr urinary protein excretion (r = 0.834, p < 0.01), a moderate linear association was observed between the log-transformed value of the amount of 24 hr urinary excreted Klotho and that of the urinary Klotho-to-creatinine ratio (Klotho/Cr) in random urine specimens (r = 0.726, p < 0.01). CONCLUSIONS: The amount of urinary Klotho, rather than the serum Klotho levels, should be linked to the magnitude of the functioning nephrons in CKD patients. The use of random urine Klotho/Cr as a surrogate for the amount of 24-hr urinary excreted Klotho needs to be evaluated more carefully.

Successful treatment of serial opportunistic infections including disseminated nocardiosis and cryptococcal meningitis in a patient with ANCA-associated vasculitis.

We herein present a case of serial opportunistic infections that included disseminated nocardiosis and cryptococcal meningitis in a 67-year-old man who was diagnosed with ANCA-associated vasculitis and treated with corticosteroids. Upon admission, the initial manifestations of the disease included subcutaneous tumors and multiple lesions in the brain and lungs. Nocardia farcinica was identified in a culture of the aspirated pus. The patient was successfully treated for disseminated nocardiosis with antibiotics. However, three months after discharge, he was hospitalized with complaints of nuchal pain. Cryptococcus neoformans was identified on a culture of the cerebrospinal fluid. Anti-fungal treatment resulted in the remission of cryptococcal meningitis.

Accelerated recovery from nephrotic syndrome with acute renal failure by double filtration plasmapheresis in a patient with lupus podocytopathy.

We describe a case of an adult female who presented with nephrotic syndrome. She was diagnosed with systemic lupus erythematosus with serum antinuclear antibodies, leucopenia with lymphopenia, butterfly erythema, and nephrotic syndrome. Renal biopsy revealed normal glomeruli with diffuse effacement of the foot processes, consistent with lupus podocytopathy. Although human albumin replacement was performed initially, acute renal failure developed rapidly. Therefore, she was treated with double filtration plasmapheresis (DFPP) in addition to oral steroid. After steroid therapy combined with DFPP, the renal function and proteinuria improved rapidly. Although the impact of DFPP on the treatment of lupus nephritis remains to be delineated, our observations suggest that DFPP in lupus podocytopathy played a pivotal role in facilitating the early recovery from renal injuries. Because of the rapid improvement of renal function without any change in body weight by DFPP, acute renal failure in the setting of lupus podocytopathy might contribute to an alternative pathophysiological factor for the diminished glomerular filtration rate, similar to that observed in the setting of idiopathic minimal change glomerulopathy.