Uremic patients are predisposed to infection possibly due to attenuated innate immunity. We previously showed that uremic patients have compromised cytokine response against an inflammatory challenge such as lipopolyssacharide (LPS). This provoked us to examine whether uremia per se impairs expressions of Toll-like receptors (TLRs) and genes related to TLR signaling. Twenty-one chronic hemodialysis patients and 10 age-matched healthy controls were enrolled in this study. First, gene expressions associated with intracellular TLR signaling were studied by microarray, which profiled the expression of 113 genes including adaptors, effectors, and members of NFκB and interferon regulatory factor (IRF) downstream pathways of TLR signaling. In addition, quantitative real time RT-PCR (qRT²-PCR) was employed to confirm the transcript expression levels of major genes that showed lower levels in the array analysis. Next, we examined protein expressions of TLRs 2 and 4 that are closely relevant to recognition of invasive bacteria and subsequente cytokine synthesis in peripheral monocytes using flow cytometry. Gene analysis showed that TLRs 2 and 4, CD14, and IRF7 expressions were significantly reduced in HD patients, while other key gene expressions were not changed. HD patients showed significantly decreased prevalence of TLRs 2 and 4 in peripheral monocytes compared with healthy controls, which corresponded to lower intracellular synthesis of TNF-α and IL1-β against LPS stimulation. These data suggested that TLRs 2 and 4 and CD14 were constitutively down-regulated in uremia, being responsible for reduced inflammatory cytokine response to pathogens and that expressions of intracellular signaling genes were comparatively preseved except for IRF7, which is relevant to IFN-α generation. Impaired pathogen recognition by TLRs 2 and 4 may contribute to attenuation of the subsequent TLR signalings, resulting in the high suceptibility of uremic patients to bacteria infections.

View full abstract

Careful management of surgical wounds in uremia patients is necessary because there is suppression of the immunologic response and a bleeding tendency at the surgical site as well as other problems in such patients. In recent years, wound dressing in a wet enviroment is recomended. In the present study, we assessed the clinical benefit of wound management using hydrocolloid dressing after continuous intradermal suture in 191 vascular access operations. In only 3 cases, dressings came off within 48 hours postoperatively. There was no surgical site infection (SSI) or skin problem in any case. In conclusion, this approach to wound management is beneficial from the perspective of preventing SSI, saving labor and being cost-effective.

View full abstract

In recent years, there have been an increasing number of patients who had already been diagnosed as having ischemic heart disease (IHD) when they were introduced to hemodialysis therapy. Previously we studied the backgrounds of one hundred and ten patients with IHD who had received treatment for IHD before or during the introduction of hemodialysis during the last 20 years in our hospital. In this study, among the 110 patients, 23 patients who received CABG were selected and the long-term prognosis of this population was examined. There were 21 (91.3%) males, and 17 (73.9%) diabetics. At surgery, mean patient age was 59.9±8.3 years and estimated creatinine clearance (Ccr) was 32±23mL/min. Coronary blood flow was completely restored by CABG in all patients. The age at hemodialysis start of these patients was 64.8±8.4 years and estimated Ccr was 13±7mL/min. The term between CABG and hemodialysis start was 4.0±5.0 years and patients were followed for 5.0±3.0 years after HD. During the follow-up, 16 patients (69.6%) died, 10 of whom (62.5%) died due to cardio-vascular disease including heart failure, leg gangrene, cerebral infarction and intestinal necrosis. Cox hazard model analysis demonstrated that such factors as renal failure etiology, age, Ccr, or left ventricular ejection fraction did not significantly affect the prognosis of these patients after dialysis induction. The prognosis of these patients does not seem to be worse compared to that of dialysis patients overall. Survival through SKD stages 3, 4 may partially explain these interesting findings.

View full abstract

Although heparin is widely used as safe anticoagulant of hemodialysis therapy, heparin-induced thrombocytopenia (HIT) have been reported in hemodialysis initiation. We show here two cases of HIT patients complicated with rheumatoid arthritis. The first case : A 73 year-old woman, who had been consulting our hospital for both chronic renal failure and rheumatoid arthritis, was admitted due to femoral neck fracture. As renal dysfunction progressed after hospitalization, we treated her with hemodialysis therapy with nafamostat mesilate, an alternative anticoagulant used in Japan. One week after surgery, we changed the anticoagulant to unfractionated heparin. Thereafter, she developed thrombocytopenia and clot formation was observed in the dialyzer. When we switched the anticoagulant to nafamostat mesilate, her platelet count was gradually increased to the normal range. The second case was a 70-year-old woman, who had been consulting a local hospital for rheumatoid arthritis and chronic renal failure. Since her renal dysfunction became aggravated, she was admitted to another hospital and hemodialysis therapy was initiated with unfractionated heparin as the anticoagulant. One week after the start of hemodialysis, she suddenly developed thrombocytopenia, liver failure, deep vein thrombosis, and acrocyanosis with regional skin necrosis. After changing the anticoagulant from unfractionated heparin to nafamostat mesilate, thrombocytopenia and liver failure improved. However, severe sepsis developed due to the necrotic-infectious lesions involving the bilateral lower limbs. Necropsy specimens of her liver, kidney, and femoral artery demonstrated amyloid deposition along the vessel walls, but there was no vasculitis. We diagnosed both patients as having HIT type II based on the positive serum antibody against platelet factor 4-heparin complex on ELISA. Although the association of rheumatoid arthritis with HIT had rarely been reported, physicians might be careful regarding the development of HIT on hemodialysis initiation in patients with rheumatoid arthritis.

View full abstract

The patient was a 68-year-old woman undergoing hemodialysis due to chronic glomerulonephritis since 1988. She received steroidal medication for myelodysplastic syndrome (MDS) from May 2005, and developed secondary diabetes mellitus (DM). A mass with 1.5cm in diameter appeared at the genital region on September 17, 2005, and antimicrobial medication was administered. Three days later, subcutaneous emphysema was palpable in the genital region and she was immediately transferred to our hospital. Abdominal X-ray and CT scan demonstrated subcutaneous gases in the genital region, left inguinal and femoral regions. We diagnosed this case as nonclostridial gas gangrene, and extensive incision and debridement were carried out. Bacteroides was identified by culture of the pus. Postoperatively, antimicrobial treatment, irrigation of the skin defect region, and hyperbaric oxygenation exposure of the whole body were performed. After granulation, skin closure was carried out on January 11, 2006. Although our case is rare, we should recognize that DM and steroidal medication can make an infection more severe in hemodialysis patients.

View full abstract

A 66-year-old male was admitted to our hospital for surgical resection of renal cell carcinoma associated with the dialysis kidney. He had been diagnosed with congenital antithrombin III (AT III) deficiency 27 years previously when he had unsuccessful kidney transplantation. Before the present surgery, AT III products were administered at an appropriate dosage in order to maintain AT III activity above 100%. Laparoscopic nephrectomy was performed successfully, and the patient had no surgical complications including thrombosis although continued administration of AT III products was required for a few days postoperatively. We concluded that the most important issue for operating on patients with AT III deficiency, even if they are on maintenance hemodialysis, is to administer an appropriate dosage of AT III products and to maintain AT III activity at an appropriate level.

View full abstract