Su-Hyun Kim

Role of IL-1α in Cisplatin-Induced Acute Renal Failure in Mice

Background/Aims For unknown reasons, caspase-1 -/- mice, protected against cisplatin-induced acute renal failure (ARF), are deficient in interleukin (IL)-1α. We thus asked whether IL-1α deficiency underlies the mechanism of protection against cisplatin-induced ARF in these mice. Methods Cisplatin (30 mg/kg) was injected intraperitoneally into wild-type C57BL/6 mice to produce a cisplatin-induced model of ARF. IL-1α was measured in control vehicle- and cisplatin-treated wild-type animals. We also examined whether IL-1α -/- mice were similarly protected against cisplatin-induced ARF. Additionally, infiltration of CD11b- and CD49b-positive cells, as markers of macrophages, natural killer, and natural killer T cells (pan-NK cells), was investigated in wild-type and IL-1α -/- mice. Results Compared with vehicle-treated mice, renal IL-1α increased in cisplatin-treated wild-type mice beginning on day 1. IL-1α -/- mice were shown to be protected against cisplatin-induced ARF. No significant difference in the infiltration of neutrophils or CD11b- and CD49b-positive cells were observed between wild-type and IL-1α -/- mice. Conclusions Mice deficient in IL-1α are protected against cisplatin-induced ARF. The lack of IL-1α may explain, at least in part, the protection against cisplatin-induced ARF observed in caspase-1 -/- mice. Investigation of the protective mechanism (s) in IL-1α -/- mice in cisplatin-induced ARF merits further study.

The ratio of osteoprotegerin to fetuin-a is independently associated with vascular stiffness in hemodialysis patients.

Background: The aim of the present study was to compare levels of fetuin-A, osteoprotegerin (OPG), and heat shock protein (HSP)70 according to the stage of chronic kidney disease (CKD), as well as to evaluate the association between serum fetuin-A, OPG, and HSP70 concentrations with respect to vascular stiffness and calcification in hemodialysis (HD) patients. Methods: We measured fetuin-A, OPG, and HSP70 in 35 healthy controls, 35 patients with stage 3 CKD, 35 patients with stage 4 CKD, and 81 HD patients. Using these data, we studied the association of fetuin-A, OPG, and HSP70 with clinical, biochemical, and vascular measures in HD patients. Results: Levels of OPG and HSP70 were higher and fetuin-A was lower in HD patients than in healthy controls. The cardio-ankle vascular index (CAVI) showed a positive correlation with OPG (r = 0.248, p = 0.040) and the OPG/fetuin-A ratio (r = 0.260, p = 0.031). The ankle-brachial index (ABI) showed a negative correlation with OPG (r = -0.245, p = 0.031) and the OPG/fetuin-A ratio (r = -0.267, p = 0.018). Intima-media thickness (IMT) showed a positive correlation with OPG (r = 0.273, p = 0.014) and the OPG/fetuin-A ratio (r = 0.269, p = 0.015). On stepwise multiple linear regression analyses, only the logarithmic function of the OPG/fetuin-A ratio was independently associated with CAVI (β = 13.325, SE = 6.247, p = 0.038). Conclusions: Our results demonstrate that OPG and the OPG/fetuin-A ratio are correlated with increased vascular stiffness and IMT in HD patients. In addition, the OPG/fetuin-A ratio was independently associated with vascular stiffness in HD patients.

Reduction of natural killer and natural killer T cells is not protective in cisplatin-induced acute renal failure in mice

Aims:u2003 A recent report showed that fractalkine (CX3CL1), which functions as both a potent chemoattractant and adhesion molecule for monocytes and natural killer (NK) cells was significantly increased in cisplatin‐induced acute renal failure (CisARF) in mice. Therefore, we developed the hypothesis that increased CX3CL1 expression in CisARF initiates NK cell infiltration in the kidney. The aim of the present study was to determine the role of NK cells in CisARF in mice.

Disseminated Mycobacterium avium Complex Infection in a Non-HIV-infected Patient Undergoing Continuous Ambulatory Peritoneal Dialysis

Isolated bone marrow infection by nontuberculous mycobacteria (NTM) is extremely rare. Recently, we encountered a case of bone marrow Mycobacterium avium complex (MAC) infection, which presented as a fever of unknown origin shortly after starting continuous ambulatory peritoneal dialysis (CAPD). The patient was diagnosed with MAC infection on the basis of PCR-restriction fragment length polymorphism analysis and sequencing of DNA obtained from bone marrow specimens. Although this was a case of severe MAC infection, there was no evidence of infection of other organs. End-stage renal disease (ESRD) patients undergoing dialysis can be considered immunodeficient; therefore, when these patients present with fever of unknown origin, opportunistic infections such as NTM infection should be considered in the differential diagnosis.

RHABDOMYOLYSIS AFTER A REGULAR EXERCISE SESSION IN A PATIENT WITH GRAVES' DISEASE

Clinically significant exertional rhabdomyolysis can be caused by strenuous, prolonged, and repetitive exercise. A few cases of rhabdomyolysis have been associated with hyperthyroidism, mainly in patients with thyroid storm. Recently, we experienced a patient with Graves’ disease who developed rhabdomyolysis after 40 minutes of his regular weight-lifting routine. A 23-year-old male college student, who is not a weighttrainer, a body-builder or an athlete, but who lifts weights regularly for fitness, presented to our outpatient clinic with bilateral pain in the flank area. Information provided by family members revealed that the symptoms started one day after a 40-minute weight-lifting session. On admission, He had bilateral flank pain and tenderness in the costovertebral area and palpitation (pulse rate 110/min) with sweating. He was not dehydrated. He did not take any protein supplementation/statins and heavy carbohydrate meal before exercise. The laboratory findings were as follows: serum creatinine phosphokinase, 36 640 (38–174) IU/L; urine myoglobin, 214.1 (1.4–4.1) ng/mL; and a urine dipstick test positive for blood with no demonstrable red blood cells upon microscopic assessment. Probably secondary to tubular damage caused by myoglobinuria or metabolism of creatine from muscle breakdown, his serum creatinine level slightly rose to 1.5 (0.6–1.3) mg/dL. Thyroid hormones were found to be elevated T3: 2.40 (0.60–1.81) ng/mL, free T4: 2.96 (0.89–1.76) ng/mL, TSH: <0.01 (0.35–5.5) mIU/mL. His serum potassium and phosphorous levels were 4.8 (3.5–5.3) mEq/L and 3.7 (1.9–4.4) mg/dL, respectively. Thyroid ultrasonography revealed a diffusely enlarged gland. The patient received a diagnosis of Graves’ disease with hyperthyroidism, positive antithyroglobulin (137.20 [0–60] U/mL]) and anti-microsomal (2090.29 [0–60] U/mL) antibody tests, and high thyrotrophin binding-inhibiting immunoglobulin (TBII) (1.98 [0.0– 1.75] IU/L). However, the patient did not meet the criteria for thyroid crisis such as confusion, agitation and headache. The overall findings suggested rhabdomyolysis secondary to a single bout of regular exercise in a hyperthyroid state. To look for muscle necrosis by radiolabelled phosphate uptake, we performed a bone scan using Tc99m-MDP, which revealed abnormal isotope uptake bilaterally in the flank muscles (Fig. 1). Rhabdomyolysis in hyperthyroidism is extremely rare. A few cases of rhabdomyolysis have been associated with hyperthyroidism, mainly in patients with thyroid storm. However, hyperthyroidism without thyroid storm may theoretically cause rhabdomyolysis by increasing energy consumption and thus depleting muscle energy stores and substrates. From this it seems plausible that even regular weight-lifting might trigger rhabdomyolysis in a hyperthyroid patient such as ours. We investigated other possible triggers, including common viral infections and metabolic disorders, but detected none. Hence, we present our patient