Fatty acid-bearing albumin induces VCAM-1 expression through c-Src kinase-AP-1/NF-kB pathways: effect of L-carnitine.

BACKGROUND: Fatty acid-bearing albumin [FA(+) albumin] exerts more deleterious effects in tubular cells than albumin alone. We investigated the effect of FA(+) albumin on the vascular cell adhesion molecule-1 (VCAM-1) expression and elucidated the underlying signaling pathways. We further examined the effect of L-carnitine, since it was known to modulate intracellular fatty acid concentration. METHODS: Activation of AP-1 and NF-kappaB was assessed by electrophoretic mobility shift assay. Phosphorylation of protein kinase was examined by Western blot analysis. VCAM-1 mRNA and protein expression were measured by Northern blot analysis and cell ELISA. RESULTS: FA(+) albumin induced VCAM-1 expression via activation of AP-1 and NF-kappaB, which was mediated through activation of c-Src kinase, followed by MAP kinases (p38, ERK 1/2, JNK-1) and IkappaB kinase and IkappaB-alpha, respectively. Inhibitors of protein kinase C and tyrosine kinase, anti-oxidants and intracellular calcium chelator suppressed the FA(+) albumin-induced activation of c-Src kinase. L-Carnitine suppressed the FA(+) albumin-induced VCAM-1 expression via inhibition of c-Src kinase. CONCLUSIONS: VCAM-1 expression with activation of c-Src kinase-AP-1/NFkappaB pathways might be one of the possible mechanisms that linked FA(+) albumin to tubulointerstitial injury. L-Carnitine might be beneficial in attenuating FA(+) albumin-induced tubular injury.

Serum high-sensitivity C-reactive protein is not increased in patients with IgA nephropathy.

BACKGROUND/AIMS: The development of renal injury in glomerulonephritis (GN) has been related to systemic inflammatory mediators. We investigated whether serum high-sensitivity C-reactive protein (hs-CRP) is a marker reflecting the inflammatory pathogenesis of primary GN. METHODS: We compared serum hs-CRP levels in 192 patients with IgA nephropathy (IgAN), 43 patients with membranous nephropathy (MN), and 25 patients with minimal change disease (MCD) undergoing kidney biopsy and 638 matched controls. RESULTS: There were no differences in hs-CRP levels between controls (median 0.08 mg/dl; range 0.03-1.87 mg/dl) and patients with IgAN (0.08 mg/dl; 0.03-3.13 mg/dl), MN (0.07 mg/dl; 0.03-0.99 mg/dl) or MCD (0.08 mg/dl; 0.03-1.75 mg/dl). In patients with IgAN, hs-CRP levels did not differ according to Haas' pathological subclasses or subsequent renal outcomes. In the IgAN group, hs-CRP showed positive correlations with IgA, uric acid, systolic blood pressure, BMI and age. Hs-CRP level was significantly higher in male than in female IgAN patients. Serum IgA concentration was the strongest independent correlate with hs-CRP levels, and gender and BMI were also independently associated with hs-CRP. There were no correlations between hs-CRP and markers of disease activity. CONCLUSION: It is likely that hs-CRP does not closely reflect inflammatory pathogenesis in patients with IgAN, MN and MCD.

The clinical characteristics of rhabdomyolysis in patients with liver cirrhosis.

BACKGROUND: We have frequently seen idiopathic rhabdomyolysis developed after liver cirrhosis (LC) in our hospital. This has rarely been reported, and no studies have compared it with other cases of rhabdomyolysis. GOALS: We attempted to examine the pathologic characteristics of rhabdomyolysis development and to assess the prognosis in patients with LC. STUDY: We retrospectively reviewed the medical records of 243 patients (261 cases) with rhabdomyolysis and selected 74 patients (91 cases) for the study group, who concurrently had LC. Seventy-five patients (76 cases) with no evidence of LC were served as controls. RESULTS: In 59.3% of the LC-group patients, the causes of rhabdomyolysis were not identified. In 10.5% of the control-group patients, the causes of rhabdomyolysis proved to be unknown (P=0.000). In 17.6% of the LC-group patients, 30 cases (33.0%) of the recurrent rhabdomyolysis were identified. In the control group, only one case of the recurrent rhabdomyolysis was noted (P=0.001). The mortality was significantly higher in the LC group than the control group (27.5% vs. 14.5%) (P=0.042). Of 25 LC-group patients who died, 96.0% had Child-Pugh classification C. In addition, 84.0% developed acute renal failure during the course. Coexistent infection, hepatic encephalopathy, and the elevated levels of serum lactate dehydrogenase and C-reactive protein were also important prognostic factors. CONCLUSIONS: In conclusion, rhabdomyolysis is developed without specific causes in patients with LC, and it is serious and often fatal particularly in cases in which acute renal failure and severe hepatic dysfunction exist. Our results indicate that LC is the underlying disease for the development of rhabdomyolysis.

Relapsing Bacillus licheniformis peritonitis in a continuous ambulatory peritoneal dialysis patient.

Bacillus licheniformis is a rare pathogen in continuous ambulatory peritoneal dialysis (CAPD) peritonitis. Only one case of B. licheniformis peritonitis has been previously reported but relapsing peritonitis by same species has not been reported. A 31-year-old man undergoing CAPD was admitted to our hospital with diarrhoea and turbid peritoneal effluent. Although B. licheniformis was cultured at his previous admission, we did not consider the species as a pathogen. After the same species was cultured twice consecutively at the subsequent admission, we confirmed that B. licheniformis was a pathogen of CAPD peritonitis. After appropriate intraperitoneal antibiotics therapy, the patient improved. He is currently undergoing CAPD without catheter removal.

Stenotrophomonas maltophilia infection in patients receiving continuous ambulatory peritoneal dialysis.

BACKGROUND: Stenotrophomonas maltophilia is a gram-negative bacillus that has become increasingly recognized as an important nosocomial pathogen, particularly in individuals with severe debilitation or immunosuppression. S. maltophilia is also characterized by its resistance to multiple antibiotics. S maltophilia peritonitis in CAPD (continuous ambulatory peritoneal dialysis) patients is associated with a poor prognosis and loss of CAPD catheter. No report concerning this entity has been presented in Korea. Therefore, we describe and discuss five cases of the S. maltophilia infection associated with CAPD in three patients with peritonitis and two with exit-site infections. METHODS: We performed a retrospective search for episodes of S. maltophilia infections related to CAPD in our renal unit. The baseline levels of hemoglobin, albumin, cholesterol, BUN and creatinine were compared with age, sex and, if possible, the underlying disease-matched controls. RESULTS: All the patients with S. maltophilia peritonitis had diabetes mellitus as the underlying disease. The individual patients also had other significant combined morbidities, such as panhypopituitarism, COPD chronic obstructive pulmonary disease, cerebrovascular accident and myocardial infarction. The level of hemoglobin in these patients was significantly lower than in the controls, and the mean values of serum albumin, creatinine and BUN were also low. CONCLUSION: Immune dysfunction due to uremia, anemia, malnutrition, other comorbidities (e.g. diabetes mellitus), and also, an indwelling peritoneal catheter may be predisposing factors for the S. maltophilia infection in CAPD patients. Once the S. maltophilia infection is diagnosed in CAPD patient, the patient should be treated based on the understanding of this particular organism.