Yoshiro Fujita

Induction of Irreversible Glomerulosclerosis in the Rat by Repeated Injections of a Monoclonal Anti-Thy-1.1 Antibody

The present experiment demonstrated that an irreversible glomerulosclerosis could be induced in the rat through repeated intravenous administrations of OX-7 (a monoclonal anti-Thy-1.1 antibody). Rats were injected with 0.2 mg of affinity-purified OX-7 at 1-week intervals for a period of 4 weeks. Glomerular damage was periodically examined at light-microscopic level. Thirty-five days after the initial injection (7 days after the final injection), capillary aneurysms and expansion of the mesangial areas with hypercellularity were frequently observed. Similar glomerular damage was also observed in rats 7 days after they received a single injection of either 1.0 or 0.2 mg of OX-7. After repeated injections, 112 days from the initial administration (84 days after the final injection), approximately 60% of the glomeruli had expanded mesangial areas with an apparent increase in the mesangial matrix. The result contrasts sharply with that obtained from a single injection of OX-7 in that more than 85% of the glomeruli showed no abnormalities 84 days after the injection. This chronic model, as a result of repeated injections of the antibody, could serve as a potential for further investigation of the mechanisms involved in the development of chronic glomerulonephritis.

Mechanism of dialysis-induced hypotension

Dialysis-induced hypotension, the sharp decrease in blood pressure occurring during hemodialysis, remains one of the most difficult problems associated with hemodialysis even today. However, there is yet no established theory to explain the mechanism triggering dialysis-induced hypotension. This review attempts to offer a consistent and cohesive source of information on the hemodynamics during dialysis-induced hypotension, and then analyzes etiologic factors in such hypotension reported by various investigators. Finally, three hypotheses concerning the mechanism of dialysis-induced hypotension including our own are introduced.

Myoclonus after Dextromethorphan Administration in Peritoneal Dialysis

Objective To report a case of myoclonus that developed after administration of dextromethorphan. Case Summary: A 64-year-old man was diagnosed with chronic renal failure due to diabetic nephropathy. The patient started on peritoneal dialysis 6 months before he was hospitalized. Two days before hospitalization, he developed cough and sputum and he visited an outpatient clinic, where dextromethorphan was prescribed. After taking a total of 30 mg of dextromethorphan, the patient developed myoclonus, tremor, agitation, slurred speech, and diaphoresis, which continued after he stopped taking the prescribed medicine. He visited an emergency department and was hospitalized for examination and treatment of myoclonus. Discussion: As the patients dialysis schedule was adequate, these symptoms were likely not due to uremia. The blood concentration of dextromethorphan (2.68 ng/mL) 60 hours after the 30-mg dose was higher than expected, and the blood concentration of dextrorphan, a metabolite, was lower than expected. We suspected that myoclonus was due to dextromethorphan-related symptoms induced by CYP2D6, which primarily metabolizes dextromethorphan. We analyzed the CYP2D6 gene for polymorphisms and identified CYP2D6 *1/*10. The patient had been taking metoprolol 40 mg/day for 2 years. The btood concentration of metoprolol 6 hours after administration was 13 ng/mL, which suggests that it was metabolized normally. Metoprolol has another metabolic pathway, via CYP2C19, and this may have led to its lack of accumulation. Moreover, metoprolol may have bound to active CYP2D6. Thus, affinity for CYP2D6, protein-binding rate, and lipid solubility may influence these drug interactions. Total scores for the Adverse Drug Reaction (ADR) probability scale and the Drug Interaction Probability Scale (DIPS) were 9 (highly probable) and 3 (possible), respectively. Conclusions: Myoclonus and other symptoms in this patient may have been caused by a prolonged high concentration of dextromethorphan due to CYP2D6 polymorphisms and drug interactions.

Relationship of protein catabolic rate or Kt/V with morbidity.

The authors investigated the influence of Kt/V and protein catabolic rate (PCR) on dialysis failure for 689 hemodialysis (HD) outpatients treated at the seven dialysis facilities in Aichi Prefecture, Japan. Dialysis failure was defined as death or hospitalization for reasons other than blood access, accident, wound, or mental disease. Patients were followed for 2 years. The rate of patients who developed dialysis failure during the observation period relative to the total patient population was defined as the dialysis failure rate. A total of 123 patients developed dialysis failure, which was fatal in 33 cases. In patients with Kt/V values of 1.6 or higher, the mean dialysis failure rate was significantly lower at 12.0% than that (19.2%) of patients with Kt/V values between 0.8 and 1.6 (p < 0.04). In patients that had PCR values under 0.8 g/kg/day, the dialysis failure rate was significantly higher at 32.5% than that (15.8%) of patients with PCR values between 0.8 and 1.4 g/kg/day (p < 0.0001).

Rare Cause of Nuchal Pain: Calcification of the Alar Ligament

Calcification of the alar ligament is a rare condition, which usually develops in the elderly and tends to occur following traumatic injury or as a consequence of inflammatory disease. In crowned dens syndrome, calcium pyrophosphate dehydrate crystals deposit on the atlantoaxial joint. A 38-year-old woman with no history of traumatic injury presented with acute-onset neck pain. The patient was diagnosed with rheumatoid arthritis (RA) and …

A Fatal Case of Metformin-associated Lactic Acidosis

A 72-year-old woman with a history of type 2 diabetes mellitus was brought to the ER with metformin-associated lactic acidosis. She received continuous hemofiltration and hemodialysis, but the laboratory analyses showed no improvement. She died 11 hours after admission. Metformin is minimally bound to proteins and is readily dialyzable, but a prolonged period of dialysis is required, because metformin has a very large distribution volume and is distributed to multiple compartments. The peak blood metformin level was 432 mg/L in this case, which is one of the highest metformin concentrations ever reported, and eight hours of hemodialysis were not sufficient to reduce the serum level.

Anti-neutrophil cytoplasmic antibody-associated vasculitis associated with infectious mononucleosis due to primary Epstein–Barr virus infection: report of three cases

Although the aetiology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis remains unclear, it is generally believed that environmental factors such as infections contribute to its development of ANCA-associated vasculitis. Prior Epstein–Barr virus (EBV) infection is reported to be a trigger of systemic vasculitis. We herein report three cases of ANCA-associated vasculitis presenting with infectious mononucleosis due to primary EBV infection. The causal link between the two pathologies could not be proved, but primary EBV infection may play a role in the initiation or exacerbation of ANCA-associated vasculitis. Future studies are necessary to determine the interaction between these diseases conditions.

Association Between Staphylococcus aureus Bacteremia and Hospital Mortality in Hemodialysis Patients With Bloodstream Infection: A Multicenter Cohort From Japanese Tertiary Care Centers

Multiple studies have shown that Staphylococcus aureus bacteremia (SAB) has been a major cause of death in hemodialysis patients. We examined whether SAB is a risk for mortality among chronic hemodialysis patients in Japan where the standard vascular access is arteriovenous fistula (AVF). This was a multicenter, retrospective study of maintenance hemodialysis patients with bloodstream infection (BSI) from 2011 to 2013 at tertiary care centers in Japan. The endpoint was hospital mortality. Our cohort contained 32 SAB cases (14 MRSA and 18 MSSA) and 42 non‐SAB cases. Hospital mortality was higher among SAB cases than non‐SAB cases (46.9% vs. 23.8%, P = 0.038). In patients with BSI, SAB was significantly associated with hospital mortality after adjustment for potential confounders, including type of vascular access (OR 3.26). S. aureus was the leading cause of BSI and hospital mortality among this cohort. Therefore, initial empiric treatment should cover for S. aureus.

The Type of Vascular Access and the Incidence of Mortality in Japanese Dialysis Patients

Objective The National Kidney Foundation (NKF) Kidney Disease Outcome Quality Initiative (KDOQI) guidelines have recommended the use of arteriovenous fistula (AVF) at the initiation of dialysis. However, there are significant differences in the dialysis environments of Japan and the United States, and there are few people who receive hemodialysis via a central venous catheter (CVC) in Japan. The aim of the present study was to examine the association between the type of vascular access at the initiation of dialysis and the incidence of mortality in Japan. Methods This study was a prospective, multicenter, cohort study. The data was collected by the Aichi Cohort study of Prognosis in Patients newly initiated into dialysis (AICOPP) in which 18 Japanese tertiary care centers participated. The present study enrolled 1,524 patients who were newly introduced to dialysis (the patients started maintenance dialysis between October 2011 and September 2013). After excluding 183 patients with missing data, 1,341 patients were enrolled. The Cox proportional hazards model was used to evaluate mortality based on the type of vascular access. The types of vascular access were divided into four categories: AVF, arteriovenous graft (AVG), CVC changed to AVF during the course (CAVF), CVC changed to AVG during the course (CAVG). Results A multivariate analysis revealed that AVG, CAVF and CAVG were associated with a higher risk of mortality in comparison to AVF [hazard ratio (HR), 1.60; p=0.048; HR, 2.26; p= 0.003; and HR, 2.45; p=0.001, respectively]. Conclusion The research proved that the survival rate among patients in whom hemodialysis was initiated with AVF was significantly higher than that in patients in whom hemodialysis was initiated with AVG or CVC.

Ischemic Acute Tubular Necrosis due to Diltiazem Overdose

Diltiazem overdose has a high mortality rate due to cardiotoxicity associated with bradycardia and hypotension. A previous article reported that this type of overdose can cause acute tubular necrosis, which was not pathologically, but rather clinically, diagnosed. We herein report the case of a 55-year-old man who sustained nonoliguric acute kidney injury after taking 60 diltiazem tablets. A kidney biopsy performed six days after admission showed ischemic, not toxic, acute tubular necrosis. The patients kidney function improved spontaneously. In this case report, we clarify the cause of renal impairment caused by diltiazem overdose pathologically. Physicians should therefore consider ischemic acute tubular necrosis as a cause of kidney injury in patients with diltiazem overdose.