Pharmacological monitoring of antiepileptic drugs in epilepsy patients on haemodialysis.

To retrospectively evaluate the pharmacological profiles of antiepileptic drugs (AEDs) in epilepsy patients during haemodialysis using therapeutic drug monitoring data. The serum concentration of AEDs was collected before and after haemodialysis, and the clearance rate and concentration-to-dose ratio were calculated as pharmacological parameters. Thirty-six patients were enrolled in the study (25 males, 11 females; age: 65.3 ± 14.8 years). In 24 of the 36 patients, epilepsy was associated with cerebrovascular disorders, and diabetes was the most common reason for haemodialysis in 16 patients. With regards to seizure type, focal aware seizures were less frequent than focal impaired awareness seizures and focal-to-bilateral tonic-clonic seizures. Interictal EEG showed intermittent rhythmic slow waves and intermittent slow waves more often than spikes or sharp waves. Levetiracetam was the most commonly used AED and led to the highest percentage of responders (80%; 16/20 patients). However, the clearance rate of levetiracetam during dialysis was highest among the antiepileptic drugs used, requiring supplementary doses after haemodialysis in all 20 patients. Valproic acid was not effective for focal epilepsy for patients on haemodialysis, and non-responders to phenytoin had low serum concentration of phenytoin both before and after haemodialysis. The pre-haemodialysis concentration of levetiracetam tended to be higher than the reference range, suggesting a potential risk of overdosing before haemodialysis. The pre- and post-haemodialysis concentrations of valproic acid tended to be lower than the reference range, suggesting a potential risk of underdosing. The concentration-to-dose ratios for levetiracetam, valproic acid, phenytoin, and carbamazepine were significantly lower after than before haemodialysis. The majority of patients with epilepsy on haemodialysis had cerebrovascular diseases, and therapeutic drug monitoring for levetiracetam, valproic acid, and phenytoin, before and after haemodialysis, is needed to ensure proper dosing.

Plasma cell-rich acute rejection after renal transplantation in a patient with pyoderma gangrenosum: a case report.

A 40-yr-old female received a living-related renal transplantation on January 29, 2008. She had type I diabetes mellitus and pyoderma gangrenosum (PG). Induction immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil, basiliximab, and prednisolone. Intravenous methylprednisolone pulse therapy was administered to prevent ulceration at the surgical site. The postoperative outcome was almost uneventful, and renal graft function was well preserved for 11 months. Her graft function deteriorated on December 24, 2008 and thus an episode biopsy was performed. The histopathological findings were consistent with plasma cell-rich acute rejection (PCAR). During hospitalization, it was noted that the patient was non-compliant. We then performed steroid pulse therapy, and her graft function and histological findings improved. This is the first report of PCAR in a patient with PG who received a renal allograft. It was thought that PCAR was triggered because of her non-compliance. Thus, we should recognize the importance of enhancing compliance in transplant recipients.

Does MICA influence acute rejection in kidney transplantation?

MHC class 1-related chain A (MICA) has been reported to be recognized by specific antibodies in the sera of transplanted patients, and it may be a target molecule in allograft rejection. MICA was originally pointed out to be an HLA-related polymorphic gene, the product of which may be recognized by a subpopulation of intestinal gamma delta T-cells and may play a role in the activation of a subpopulation of natural killer cells. Although their association with chronic rejection has been demonstrated before, there are few reports of any relation with acute rejection. We encountered a possible case of MICA-related acute early rejection. The recipient was a 25-year-old female; the original disease was IgA nephropathy, and the hemodialysis period was 12 months. She underwent ABO-compatible living-related renal transplantation from her mother. The HLA type was A24, A31, B7, B52, DR1, and DR15 in the donor and A31, A33, B7, B44, DR1, and DR12 in the recipient. A pre-operative direct cross-match was negative by a conventional cytotoxic test, and HLA class 1 and 2 antibodies were negative by LABScreen single antigen testing. Induction immunosuppressive therapy was started with TAC, MMF, MP, and BXM. The graft functioned at once, and SCr was 2.4 mg/dl on post-transplant day 1. SCr increased from post-transplant day 2, and oliguria progressed. Hemodialysis was restarted on post-transplant day 6. A biopsy revealed Banff 2b vascular rejection. The graft was finally rescued by steroid pulse and plasma exchange therapy. SCr went down to 1.07 mg/dl, and a re-biopsy showed improvement on post-transplant day 42. HLA class 1 and 2 antibodies were negative during this period, and MICA019 antibody was higher before transplantation retrospectively. Additionally, this antibody titer was decreased at the time of discharge. These data show that MICA may induce rejection in the early phase of renal transplantation. Further study is needed to evaluate this phenomenon.

Lipid peroxidation and advanced glycation end products in the brain in normal aging and in Alzheimer's disease.

The cellular distribution of malondialdehyde (MDA) was assessed immunohistochemically in brain specimens from young and normal elderly subjects as well as patients with Alzheimer's disease (AD). MDA was increased in the cytoplasm of neurons and astrocytes in both normal aging and AD, but was rarely detected in normal young subjects. By electron microscopic immunohistochemistry, neuronal MDA formed cap-like linear deposits associated with lipofuscin, while glial MDA deposits surrounded the vacuoles in a linear distribution. In the hippocampus, neuronal and glial MDA deposition was marked in the CA4 region but mild in CA1. By examination of serial sections stained with anti-MDA and antibodies against an advanced glycation end product, N(epsilon)-(carboxymethyl)lysine (CML), neuronal and glial MDA deposition was colocalized with CML in AD, but only neuronal MDA was colocalized with CML in normal aged brains. Glial MDA, although abundant in the aged brain, typically was not colocalized with CML. In AD cases, MDA was colocalized with tau protein in CA2 hippocampal neurons; such colocalization was rare in CA1. MDA also was stained in cores of senile plaques. Thus, while both MDA and CML accumulate under oxidative stress, CML accumulation is largely limited to neurons, in normal aging, while MDA also accumulates in glia. In AD, both MDA and CML are deposited in both astrocytes and neurons.