Young Joo Kwon

Nonocclusive mesenteric ischemia in a patient on maintenance hemodialysis.

Nonocclusive mesenteric ischemia (NOMI) is known to occupy about 25% to 60% of intestinal infarction. NOMI has been reported to be responsible for 9% of the deaths in the dialysis population and the postulated causes of NOMI include intradialytic hypotension, atherosclerosis and medications, such as diuretics, digitalis and vasopressors. Clinical manifestations, such as fever, diarrhea and leukocytosis, are nonspecific, which makes early diagnosis of NOMI very difficult. Case: A 66-year-old woman on maintenance hemodialysis for 5 years was admitted with syncope, abdominal pain and chilly sensation. Since 7 days prior to admission, blood pressure on the supine position during hemodialysis had frequently fallen to 80/50 mmHg. Four days later, she complained of progressive abdominal pain. Rebound tenderness and leukocytosis (WBC 13900/mm3) with left shift were noted. Stool examination was positive for occult blood. Abdominal CT scan showed a distended gall bladder with sludge. Under the impression of acalculous cholecystitis, she was operated on. Surgical and pathologic findings of colon colon were compatible with NOMI. Because of recurrent intradialytic hypotension, we started midodrine 2.5 mg just before hemodialysis and increased the dose up to 7.5 mg. After midodrine therapy, blood pressure during dialysis became stable and the symptoms associated with hypotension did not recur. Conclusion: As NOMI may occur within several hours or days after an intradialytic hypotensive episode, abdominal pain should be carefully observed and NOMI should be considered as a differential diagnosis. In addition, we suggest that midodrine be considered to prevent intradialytic hypotensive episodes.

ACE gene polymorphism and renal responsiveness to ACE inhibitors in IgA nephropathy patients.

We examined the renal responsiveness to ACE inhibitor in IgA nephropathy (IgAN) patients according to the grouping of ACE gene polymorphism. Sixty one patients diagnosed as IgAN by renal biopsy and prescribed with ACE inhibitors were enrolled. Genomic DNA was extracted from whole blood and PCR was performed. The I/D polymorphism was determined by the presence of the 287 bp fragment in intron 16 of chromosome 17. During the follow-up period (mean; 44.6 months, median: 44.5 months, 5 to 113 months), the blood pressure of 61 patients was controlled below 130/80 mmHg. The renal responsiveness was determined by the degree of changes of proteinuria at 12 months after initiation of ACE inhibitors and by the slope of reciprocal variation of the serum creatinine against follow-up duration {(1/Cr2-1/Cr1)/durations}. The distribution of the II, ID and DD genotype among 61 patients was 21, 16 and 24 patients, respectively. There were no differences among three genotypes in age, sex, the number of patients with initial blood pressure over 140/90 mmHg, initial serum creatinine level, the number of patients with initial azotemia(> 1.4mg/dL) and with initial 24-hr proteinuria amount over 2.0 g. Significant anti-proteinuric effect of ACE inhibitor was found in IgAN(p =0.001), but no significant difference was found among genotypes. Significant difference (p =0.011) was noticed between II type and DD type in the slope of reciprocal variation of the serum creatinine against follow-up duration. In conclusion, efficacy of ACE inhibitors on renal function preservation in IgAN was more pronounced in DD genotype than II genotype.

The Association of Klotho Polymorphism with Disease Progression and Mortality in IgA Nephropathy

Backgrounds: IgA nephropathy (IgAN) is the most common primary glomerulonephritis causing end stage renal disease (ESRD), and vasculopathy is known to involve disease progression. Klotho, a gene related to aging, has been reported to play a role in atherosclerosis and endothelial dysfunction. We investigated whether klotho gene polymorphism affect clinical course of IgAN. Methods: The data registered for PREMIER study which enrolled the patients with biopsy proven IgAN were analyzed. Two single nucleotide polymorphisms for klotho gene, G395A of promoter region and C1818T of exon 4, were examined, and investigated the association klotho genotypes with the progression of IgAN and patient survival. Results: Clinical data from 973 patients confirmed about survival were analyzed. The allele frequency was 0.830 and 0.170 for allele G and A, and 0.816 and 0.184 for allele C and T, which were complied with Hardy-Weinberg equilibrium (p=0.996 and 0.531 respectively). Death was observed more frequently in A-allele carriers of G395A polymorphism (0.7 vs 2.6 %, GG vs GA+AA, p=0.022). Renal survival in Kaplan-Meier survival curve was also worse in same group (p=0.04). Conclusion: Klotho gene polymorphism was associated with patient survival and disease progression of IgAN.

A case of Wegener's granulomatosis complicated by diffuse pulmonary hemorrhage and thrombotic thrombocytopenic purpura.

Wegener’s granulomatosis is a distinct form of necrotizing granulomatous vasculitis which usually affects the kidneys and the upper and lower respiratory tracts. Unusual manifestations have also been reported, and these include colitis, urethritis and diabetes insipidus. We describe a case of Wegener’s granulomatosis which presented with rapidly progressive renal insufficiency, sudden deafness, red eye, facial palsy, and complicated by uncommon manifestations that were diffuse pulmonary hemorrhage and thrombotic thrombocytopenic purpura.

The association of Klotho gene polymorphism with the mortality of patients on maintenance dialysis

Despite medical progress, high morbidity and mortality rates have persisted in patients with end-stage renal disease (ESRD). The role in atherosclerosis and cardiovascular disease of klotho, an aging process-related gene, has been highlighted. Genetic variation in klotho has been reported to be a risk factor for coronary artery disease and ischemic stroke. Regarding the significance of cardiovascular disease for the outcome of ESRD patients, we investigated whether genetic variation of klotho was associated with mortality in ESRD patients on hemodialysis. 478 patients on maintenance hemodialysis for more than 3 months at dialysis facilities affiliated with the Western Dialysis Physician Association were enrolled in September 2004. Patient survival was checked annually until September 2007. Genotypings of klotho in terms of G395A in the promoter region, C1818T in exon 4, and KL-VS was performed. 45 deaths (11.2%) occurred over 3 years. Mortality was higher in the GA+AA group than in the GG group (18.9% vs. 6.7%, respectively, p < 0.001). Kaplan-Meier analysis also revealed that the survival of the GA+AA group was worse than that of GG group (p = 0.002). Coxs proportional hazards regression analysis showed that age, A allele carrier status in G395A of klotho, hemoglobin, albumin and HDL cholesterol levels were the significant factors affecting survival of hemodialysis patients. The A allele of the G395A polymorphism of klotho may be associated with the risk of mortality in Korean hemodialysis patients. Age, hemoglobin, albumin and HDLC were also significant prognostic factors for survival in the present study.

Alpha-Lipoic Acid Attenuates Cisplatin-Induced Tubulointerstitial Injuries through Inhibition of Mitochondrial Bax Translocation in Rats

Background: Renal tubule cell apoptosis plays a pivotal role in cisplatin-induced nephrotoxicity. α-Lipoic acid (LA), a thiol antioxidant, is well known to be cytoprotective in various cell death models through its involvement in the death receptor apoptosis pathway. However, we hypothesized that LA would attenuate cisplatin-induced nephrotoxicity through inhibition of mitochondrial bax translocation in rats. Methods and Materials: Sprague-Dawley rats were treated with cisplatin (7 mg/kg) with or without pretreatment with LA (100 mg/kg × 3 times). Renal function was evaluated based on blood urea nitrogen (BUN), serum creatinine, and fractional excretion of sodium. Tubular necrosis scores were assessed by light microscopy findings and apoptotic cell deaths by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Cytosolic bax, mitochondrial bax, cytochrome c, caspase-9 and caspase-3 were investigated using Western blot in each group. Results: LA pretreatment significantly decreased both BUN and serum creatinine. Morphologically, both tubular necrosis and apoptosis of tubular cells were decreased significantly with LA pretreatment. LA attenuated the translocation of mitochondrial bax, reduced the release of cytochrome c, and decreased the expression of caspase-3 and caspase-9 serially in cisplatin nephrotoxicity. Conclusion: We demonstrated that LA attenuates cisplatin-induced renal tubular damages by inhibition of mitochondrial bax translocation in vivo.

Epstein–Barr virus-induced acute myocarditis diagnosed using cardiac magnetic resonance imaging

A15-year-old boy came to the emergency room complaining of general weakness that had started 2 days previously. He was relatively healthy. For the last 5 days, he had suffered from intermittent vomiting, watery diarrhea, and mild febrile sensation. Then, the general weakness developed. On physical examination, his blood pressure was 80/60 mmHg, pulse was 60 beats/min, respiratory rate was 20 breaths/min, and body temperature was 36 °C. The laboratory revealed an increased leukocyte count of 12,100/L. On echocardiography, the left ventricle was not dilated, but systolic function was markedly reduced with an ejection fraction of about 30%. No regional wall motion abnormality was observed. He was treated under the impression of myocarditis and admitted to the intensive care unit. Four hours after admission, an intermittent generalized tonic–clonic convulsion occurred. A complete atrioventricular block with a ventricular rate about 25 beats/min developed and was managed with insertion of a temporary transvenous pacemaker. Emergency brain computed tomography revealed no abnormality and the seizure stopped spontaneously. The level of myocardial enzymes showed an increase: troponin T, 9.24 ng/mL (normalb0.1 ng/dL); creatine kinase MB isoenzyme, 70 ng/mL; myoglobin, 127 ng/mL. We also

Diameter of parathyroid glands measured by computed tomography as a predictive indicator for response to cinacalcet in dialysis patients with secondary hyperparathyroidism.

Background/Aims: Cinacalcet is one of the important treatments of secondary hyperparathyroidism (SHPT). We evaluated the role of computed tomography (CT) for parathyroid glands (PTGs) to determine the response to cinacalcet therapy in dialysis patients. Methods: In study 1, we compared the predictive cutoff values of the largest volume or diameter of PTGs on ultrasonography or CT for achievement of target intact parathyroid hormone (iPTH) level according to K/DOQI guideline after cinacalcet treatment in a single dialysis center. In study 2, the role of the cutoff diameter of PTGs on CT in predicting responsive to cinacalcet therapy was reevaluated in dialysis patients with SHPT in multiple centers. Results: In study 1, among the total population of 26 patients, the number of patients with baseline iPTH over 600 pg/mL was 16 (61%). In study 2, it was 45 (54%), among 82 patients. In study 1, the number of PTGs equal to or larger than the cutoff value (≥ 11.2 mm) on CT, not ultrasonography, was significantly higher in non-responders than in responders (p=0.038). In study 2, the proportion of patients with PTGs ≥ 11.2 mm on CT was significantly higher in non-responders than responders (p=0.003). Multivariate analysis showed that pretreatment iPTH (odds ratio [OR] 1.498, p=0.003) and the existence of enlarged PTGs on CT (OR 8.940, p=0.015) were significant clinical factors affecting the response to cinacalcet. Conclusions: The diameter of PTGs on CT could predict the response to cinacalcet in dialysis patients with SHPT.

Resveratrol Ameliorates Contrast Induced Nephropathy Through the Activation of SIRT1-PGC-1α-Foxo1 Signaling in Mice

Background/Aims: SIRT1 activation promotes the resistance of renal tubular cells to oxidative stress, and resveratrol is known as a SIRT1 activator. Methods: Resveratrol was injected intraperitoneally with iohexol for 24 hours. NRK-52E cells were pretreated with resveratrol for 24 hours and then exposed to iohexol for 3 hours. Renal function was measured by serum creatinine and cell survival was assessed by MTT assay. We investigated whether resveratrol attenuates oxidative stress and apoptosis in contrast-induced nephropathy (CIN). Results: Serum creatinine and tubular injury increased significantly after iohexol treatment, and resveratrol co-treatment attenuated the renal injury. Cell survival decreased after iohexol exposure and resveratrol reduced cell death induced by iohexol. Resveratrol was accompanied with the activation of SIRT1 and PGC-1α and dephosphorylation of FoxO1 in mice with CIN. SIRT1 and PGC-1α expression were decreased by iohexol, and increased significantly in resveratrol-pretreated cells. These processes resulted in reduction of oxidative stress and apoptosis both in vivo and in vitro experiments. Resveratrol decreased inflammatory cell infiltration induced by iohexol in mice with CIN. SIRT1 inhibition using siRNA in tubular cells accentuated the decrease of cell viability by iohexol. Conclusion: Resveratrol attenuated CIN by modulating renal oxidative stress and apoptosis through activation of SIRT1-PGC-1α-FoxO1 signaling.

Development of Brugada Syndrome Following Photodynamic Therapy in a Patient with Cholangiocarcinoma

Brugada syndrome can be unmasked by several conditions including a febrile state, marked leukocytosis, and electrolyte disturbances. Herein, we describe a 62-year-old man with cholangiocarcinoma in the first reported case of Brugada syndrome onset following photodynamic therapy.