NADH dehydrogenase 5 (ND5) is one of 44 subunits composed of Complex I in mitochondrial respiratory chain. Therefore, a mitochondrially encoded ND5 (MT-ND5) gene mutation causes mitochondrial ...oxidative phosphorylation (OXPHOS) disorder, resulting in the development of mitochondrial diseases. Focal segmental glomerulosclerosis (FSGS) which had podocytes filled with abnormal mitochondria is induced by mitochondrial diseases. An MT-ND5 mutation also causes FSGS. We herein report a Japanese woman who was found to have proteinuria and renal dysfunction in an annual health check-up at 29 years old. Because her proteinuria and renal dysfunction were persistent, she had a kidney biopsy at 33 years of age. The renal histology showed FSGS with podocytes filled with abnormal mitochondria. The podocytes also had foot process effacement and cytoplasmic vacuolization. In addition, the renal pathological findings showed granular swollen epithelial cells (GSECs) in tubular cells, age-inappropriately disarranged and irregularly sized vascular smooth muscle cells (AiDIVs), and red-coloured podocytes (ReCPos) by acidic dye. A genetic analysis using peripheral mononuclear blood cells and urine sediment cells detected the m.13513 G > A variant in the MT-ND5 gene. Therefore, this patient was diagnosed with FSGS due to an MT-ND5 gene mutation. Although this is not the first case report to show that an MT-ND5 gene mutation causes FSGS, this is the first to demonstrate podocyte injuries accompanied with accumulation of abnormal mitochondria in the cytoplasm.
Attribute-based medicine is essential for patient-centered medicine. To date, the groups of patients with chronic kidney disease (CKD) requiring urate-lowering therapy are clinically unknown. Herein, ...we evaluated the efficacy of febuxostat using a cross-classification, attribute-based research approach. We performed post hoc analysis of multicenter, randomized, double-blind, placebo-controlled trial data for 395 patients with stage 3 CKD and asymptomatic hyperuricemia. Participants were divided into febuxostat or placebo groups and subcohorts stratified and cross-classified by proteinuria and serum creatinine concentrations. In patients stratified based on proteinuria, the mean eGFR slopes were significantly higher in the febuxostat group than in the placebo group (P = 0.007) in the subcohort without proteinuria. The interaction between febuxostat treatment and presence of proteinuria in terms of eGFR slope was significant (P for interaction = 0.019). When cross-classified by the presence of proteinuria and serum creatinine level, the mean eGFR slopes significantly differed between the febuxostat and placebo groups (P = 0.040) in cross-classified subcohorts without proteinuria and with serum creatinine level ≥ median, but not in the cross-classified subcohorts with proteinuria and serum creatinine level < median. Febuxostat mitigated the decline in kidney function among stage 3 CKD patients with asymptomatic hyperuricemia without proteinuria.
The patient was an 89-year-old man who had been diagnosed with type 2 diabetes at 54 years of age and who had been treated with repaglinide (1.5 mg/day), teneligliptin (20 mg/day), and voglibose (0.6 ...mg/day). Two days after the administration of clopidogrel (75 mg/day), he was admitted to our hospital in a hypoglycemic coma. Although oral antidiabetic agents were discontinued, hypoglycemia persisted until the third hospital day. After discharge, the administration of repaglinide was restarted. Two days later, he was readmitted in a hypoglycemic coma for a second time, with hypoglycemia-remaining until the second hospital day. Because repaglinide is a rapid-short-acting insulinotropic SU receptor ligand, it rarely causes prolonged hypoglycemia by itself. Tornio reported that the inhibition of CYP2C8 by clopidogrel increased the blood concentration of repaglinide. The present case shows that concomitant use of repaglinide and clopidogrel may induce prolonged hypoglycemia. Careful attention must therefore be paid when repaglinide is prescribed with clopidogrel, because these two agents are frequently used in the treatment of diabetic macroangiopathy
We report two cases having a similar clinical profile of systemic lupus erythematosus (SLE) complicated by hydronephrosis that developed concurrently with a similar pathological recognition of ...numerous unique microspherical and microtubular structures in the glomerular basement membrane (GBM). Case 1 refers to a 29-year-old woman with SLE. An increase in the level of proteinuria had been triggered by hydronephrosis. The pathological findings of the kidney revealed “bubbling” of the GBM, microspherical and microtubular structures in the GBM, and a suspicion of podocytic infolding into the GBM. Case 2 refers to a 46-year-old woman with SLE complicated with hydronephrosis. The level of proteinuria had increased, which was followed by renal biopsy. Similar pathological findings detected in Case 1 were also recognized in Case 2. The renal disorder of the two cases exhibited pathological abnormality atypical of lupus nephritis. Histopathological abnormality similar to that detected in the two cases has rarely been reported until recently. The pathogenesis of the GBM lesions of the two cases has not yet been elucidated, but we believe that there is a possibility the persistent mild autoimmune disorder and the concurrence of an obstructive state of the urinary tract may facilitate the occurrence of the pathological abnormality, because the clinical feature of the two cases are conspicuously similar to each other.
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