Nrf2-Heme oxygenase-1 modulates autophagy and inhibits apoptosis triggered by elevated glucose levels in renal tubule cells

BACKGROUND: Autophagy is a highly balanced process in which lysosomes remove aged and damaged organelles and cellular proteins. Autophagy is essential to maintain homeostasis in the kidneys. METHODS: Using human renal tubule cells HK-2, we assessed the impact of high glucose (HG) on autophagy. We also evaluated the capability of sulforaphane (SFN) to protect the HK-2 cells from HG-induced apoptosis by modulating autophagy. RESULTS: SFN modulated autophagy and decreased apoptosis in the HK-2 cells that were cultured in 250 mM glucose medium for two days. The reactive oxygen species (ROS) levels increased, as expected, in the cells cultured in the 250 mM glucose medium. However, the SFN decreased the ROS levels in the HK-2 cells. The overexpression of heme oxygenase-1 (HO-1) by SFN decreased the expression of LC3 and beclin-1. LC3 and beclin-1 were involved in the downregulation of caspase-3 that was observed in the HG-induced cells. CONCLUSION: The activation of nuclear factor E2-related factor 2 (Nrf2)–HO–1 inhibited ROS expression and subsequently attenuated autophagy and cell apoptosis after HG injury was decreased. HG injury led to the activation of autophagy and HO-1 in order to combat oxidative stress and protect against cell apoptosis. Therefore, HO-1 activation can prevent ROS development and oxidative stress during HG injury, which considerably decreases autophagy and apoptosis.

Malignant Hypertension with Pulmonary Alveolar Hemorrhage Needing Dialysis / 이화의대지

A 35-year-old man presented with progressive dyspnea and hemoptysis. His blood pressure was 230/140 mmHg and serum creatinine level was 20.13 mg/dL. Chest radiography and computed tomography revealed pulmonary hemorrhage. His renal function was low, thus emergent renal replacement therapy was required. Malignant hypertension and acute kidney injury were diagnosed, and antihypertensive therapy and hemodialysis started immediately. Renal biopsy was performed to examine the underlying disease. Typical pathological changes of malignant hypertension, fibrinoid necrosis of the afferent arterioles, and proliferative endoarteritis at the interlobular arteries were observed. His renal function improved gradually and pulmonary hemorrhage completely disappeared with administration of antihypertensive agents. Here, we report this rare case of malignant hypertension with pulmonary alveolar hemorrhage and speculate that the hemorrhage may be related to vascular injuries at the alveolar capillary level caused by malignant hypertension.

Fibrillary glomerulonephritis combined with chronic inflammatory demyelinating polyneuropathy

A 58-yr-old man presented with leg edema and subacute weakness of his bilateral lower extremities. Urinary and serum immunoelectrophoresis revealed the presence of lambda-type Bence Jones proteins. He was ultimately diagnosed with monoclonal gammopathy of undetermined significance (MGUS). A renal biopsy specimen showed fibrillary glomerulonephritis (FGN), which was randomly arranged as 12-20 m nonbranching fibrils in the basement membranes. Immunofluorescence studies were negative for immunoglobulin (Ig)G, IgM, IgA, C3, and kappa light chains in the capillary walls and mesangial areas. A Congo red stain for amyloid was negative. Electromyography and nerve conduction velocity examinations results were compatible with the presence of demyelinating polyneuropathy. This case showed a rare combination of FGN, without Ig deposition, and MGUS combined with chronic inflammatory demyelinating polyneuropathy (CIDP).

A Case of Acute Pancreatitis: Portal Vein Superimposed Thrombosis in a Nephritic Syndrome Patient / 대한내과학회지

Nephrotic syndrome is characterized by hypercoagulability and thrombosis of the renal and deep veins. We describe a case of unusual thrombosis in the portal and superior mesenteric veins of a 41-year-old female, admitted for treatment of abdominal pain, who simultaneously presented with nephrotic syndrome and acute pancreatitis. Laboratory analysis revealed hypoalbuminemia, hyperlipidemia, and proteinuria. Abdominal computed tomography revealed acute pancreatitis, thrombosis at the portal and superior mesenteric veins, and ischemic changes in the colon and small intestines. Anticoagulation therapy was started immediately. Abdominal pain was subsequently reduced and the ischemic lesion disappeared. Warfarin use could not be terminated immediately. Empirical steroid therapy commenced without a kidney biopsy. Complete remission occurred after 4 weeks. Following warfarin cessation, a kidney biopsy was performed, confirming the diagnosis of minimal change disease.

A Case of Acute Kidney Injury in A 62 Year Old Man Who Took Atractylodes Macrocephala Koidzumi

The drug inducing tubulointerstitial nephritis is a crucial cause of acute kidney injury. Use of herbal plants in disease treatment is generally practiced in Korea. Although there are a small number of case reports, tubulointerstitial nephritis caused by taking Atractylodes macrocephala Koidzumi in human has never been reported. A 62-year-old man visited our hospital with symptoms of systemic edema accompanied by reduced urine volume and dyspnea after taking herbal plant 1 week ago. Chest radiographs showed both sided pleural effusion. Blood test results showed elevation of serum blood urea nitrogen and creatinine level and urine test results showed hematuria and proteinuria. Renal biopsy result showed evidence of tubulointerstitial nephritis by tubulitis and inflammatory cell expansion in the interstitium was observed. The patient's renal function recovered after administration of active renal replacement treatment and conservative therapy such as supplementation of fluid and electrolytes, and there was no disease recurrence for 1 year. Therefore, this case proved that Atractylodes macrocephala Koidzumi could cause acute kidney injury by the drug induced tubulointerstitial nephritis in human.

A Case of Idiopathic Aortitis with Left Renal Vein Thrombosis

A 38-year-old man was admitted to the hospital because of abrupt left flank pain. He had no fever and physical examination revealed tenderness of the left costovertebral angle. Laboratory data revealed white blood cell 16,060/microL, C-reactive protein 0.93 mg/dL. Urinalysis showed more than 1/2 red cells per high-power field with severe proteinuria (4+). Enhanced computed tomography (CT) showed the thickened abdominal aorta wall with partial thrombus. The thickened aorta wall compressed the left renal vein and it caused left renal vein thrombosis. Abdominal CT findings suggested aortitis of the abdominal aorta with complication of left renal vein. We could exclude other types of aortitis including autoimmune aortitis, Takayasu's arteritis, giant cell arteritis, and infectious causes based on a serologic test and the history of the patient. Therefore, the patient was diagnosed with idiopathic aortitis and treated with glucocorticoid. After treatment, his symptoms disappeared and a follow-up CT showed decreased mural thickening of the abdominal aorta. Isolated idiopathic aortitis presented with renal vein thrombosis is extremely rare and has not been reported in Korea yet. We present a rare case report on idiopathic aortitis of the abdominal aorta with complication of left renal vein thrombosis.

A Case of Different Organ Responses to Immunosuppressive Therapy In a Microscopic Polyangiitis Patient with Interstitial Lung Disease / 대한내과학회지

Microscopic polyangiitis (MPA) is an idiopathic autoimmune disease characterized by systemic vasculitis associated with antineutrophil cytoplasmic autoantibodies. Interstitial lung disease is a less recognized manifestation of MPA and has a poor prognosis. A 61-year-old man presented with persistent cough, sputum and dyspnea. Laboratory examination revealed microscopic hematuria and renal insufficiency. Perinuclear anti-neutrophil cytoplasmic autoantibodies were positive according to serological testing. Computed tomography scans showed bibasilar reticulation and honeycombing in a peripheral distribution. Therefore, renal biopsy was performed, and MPA was diagnosed. After treating with corticosteroids and immunosuppressive agents, the patient had a complete renal response but progressive interstitial lung disease. We report a case of MPA presenting with interstitial lung disease in which the patient experienced different responses in each organ.

A Case of Systemic Lupus Erythematosus Occurring after H1N1 Influenza Vaccination / 대한내과학회지

The recent worldwide outbreak of H1N1 has led to the universal administration of H1N1 influenza vaccination, including in South Korea. Several complications have been reported with use of H1N1 influenza vaccine, but systemic lupus erythematosus (SLE) has not been reported as a complication until now. Here, we report a case of SLE occurrence after H1N1 influenza vaccination. A 17-year-old girl who had not been diagnosed with SLE was hospitalized with fever, myalgia, and arthralgia after H1N1 influenza vaccination. Laboratory tests revealed increased levels of antinuclear antibody and anti-ds-DNA antibody, and decreased levels of C3 and C4 as well as proteinuria. The pathological findings confirmed a diagnosis of lupus nephritis. The patient was treated with high-dose corticosteroid and hydroxychloroquine. This is the first report of SLE following H1N1 influenza vaccination in South Korea.

Operational and Regulatory System Requirements for Pursuing Self-sufficiency in Deceased Donor Organ Transplantation Program in Korea / 대한이식학회지

Since beginning with the first organ transplantation from brain-dead donor in 1979, organ transplantation has been developing continuously in Korea. However, organ shortage still is a serious problem in the field of solid organ transplantation. For this reason, it is necessary to promote deceased donor organ transplantation and achieve self sufficiency. There are two system requirements managing deceased donor organ transplantation; operational and regulatory systems. In operational system, mutual and balanced cooperation between transplantation centers, organ procurement organism (OPO), registration/allocation system and NGOs is one of most important determinants to maximize brain dead donor. Especially, transplantation center and OPO need to improve in their organ donation process through evaluating donation practices and developing critical pathway for each step. In addition, public education program focusing on the hospital staff, the family of deceased donors and students should be enhanced to increase public awareness for organ donation. In regulatory system, national transplantation authority for the transplant coordination among various structures and policy-making on the issue of organ donation is necessary. For this purpose, Korean Network for Organ Sharing (KONOS) has to be improved into professional and authoritative body and establish more expanded national database network system. Further improvement in operational and regulatory systems to activate organ donation could enable to achieve the Asian leadership in the field of transplantation as well as self sufficiency for organ transplantation.

The Role of NGO in Deceased Organ Transplantation / 대한이식학회지

Solid organ transplantations give end stage organ failure patients new, healthy and normal lives and have them return to their families, friends and communities. But, there has been a donor organ shortage and it has been considered a major obstacle. A national report in 2009 showed a severe disparity between the annual numbers of organ donors (1,787) and the number of patients (12,235) on the deceased donor waiting list. In terms of donor action, and to meet the demands of organs for transplantation, we need to educate the public on the need for organs, eye and tissue donations, and we need to motivate the public to make an actionable donor designation. The unification of non-governmental organization (NGO) is necessary to educate the public about organ, eye and tissue donations and to avoid duplication of effort.

Cardiac tamponade in a patient with lupus nephritis / 대한내과학회지

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that involves many different organ systems, and this illness exhibits a wide spectrum of clinical manifestations. The renal involvement in SLE is called lupus nephritis and 50~80% of patients with SLE suffer from lupus nephritis. Although pericarditis or pericardial effusion is a common cardiac manifestation of SLE, cardiac tamponade is rare. Cardiac tamponade may be fatal if it is not recognized quickly and treated promptly. We report a case of cardiac tamponade associated with lupus nephritis. Treatment consisted of pericardiocentesis and high-dose corticosteroid.

A Proposal to Activate Organ Donation: Report of Organ Allocation Study Group / 대한이식학회지

Organ shortage is a serious problem in the field of solid organ transplantation. Increasing number of death on the waiting list, transplant tourism, black market for organ selling are all caused by organ shortage and these eventually causing poor quality of life for patient and family, and may give rise to a serious confusion in domestic transplant system. Since the KONOS launched in the year 2000, some portion of the illegal side of organ supply were corrected but the number of organ donor was hardly to increase. In order to search any solution for this problem, organ allocation study group under the Korean society for organ transplantation was actively worked from August 2008 through February 2009, and got some solution. Among them, amendment of the transplantation law including brain death committee, reporting system of suspected brain dead patients, and set up an independent organ procurement organization system for an effective organ procurement. Organ donation and increasing the number of donor is not a task only for transplant society, but is closely related with quality of life for peoples. This also can change the execution of budget of national medical health insurance. To give a correct understanding about this and activate the nationwide organ donation, the transplant society should have a key role with various medical and nursing society, hospital association, government, national assembly and every voluntary groups.

Concurrence of Sjogren's Syndrome in a Patient with Chlamydia-induced Reactive Arthritis: An Unusual Finding

A 40-year-old Korean man presented with painful swelling and tenderness of both ankle joints as well as the plantar surfaces of both feet, along with inflammatory back pain, and a purulent discharge from the urethral orifice. The patient also complained of sicca-like symptoms including dry eyes and dry mouth. An immunological analysis revealed a high titer of rheumatoid factor, positive results for antinuclear antibody and anti-Ro antibody, and a positive result for HLA-B27. An antibody titer for Chlamydia was also significantly increased. Positive results of the Schirmer's test and for keratoconjunctivitis sicca were confirmed by an ophthalmologist. These clinical manifestations were compatible with Chlamydia-induced reactive arthritis (ReA) accompanied by Sjogren's syndrome (SS). This is the first report of the combination of these two distinct disease entities in the Korean population.

Optimal Cut-off Value of PIVKA-II for Diagnosis of Hepatocellular Carcinoma: Using ROC Curve / 대한간학회지

BACKGROUND/AIMS: Protein induced by vitamin K absence or antagonist-II (PIVKA-II), also known as des-carboxyprothrombin (DCP), can be used as an alternative tool to alpha-fetoprotein (AFP) for surveillance of hepatocellular carcinoma (HCC). The aims of the present study were to compare PIVKA-II levels between the patients with HCC and patients with non-HCC chronic liver disease, to evaluate the correlation of PIVKA-II and AFP in HCC patients, and finally to estimate the optimal cut-off value for PIVKA-II for the diagnosis of HCC with using the receiver operating characteristic (ROC) curve. METHODS: A total of 227 consecutive patients with HCC (n=42) or chronic liver disease (n=185) were enrolled in this study. HCC was diagnosed histologically or by imaging such as computed tomography, magnetic resonance imaging or angiography. The serum PIVKA-II and AFP levels were measured by electrochemiluminoimmunoassay with using the Haicatch PIVKA-II kit and by immunoradiometric assay, respectively. RESULTS: The PIVKA-II level in the HCC patients was significantly higher than the non-HCC chronic liver disease patients (903.0+/-1156.7 vs. 111.7+/-211.0 mAU/ mL, respectively, P<0.01). PIVKA-II and AFP showed a statistical correlation in HCC patients (r=0.46, P<0.01). The sensitivity and specificity of PIVKA-II for the diagnosis of HCC were 66.7% and 74.1%, respectively, and when tasted together with AFP, the sensitivity was increased by 85.7%. For the ROC curve of PIVKA-II in HCC patients, the specificity of a 250 mAU/mL level of PIVKA-II was 95%. CONCLUSIONS: PIVKA-II was as useful surveillance tool for differentiating HCC from chronic liver disease, and a PIVKA-II value of 250 mAU/ mL was proposed as a significant cut-off value for diagnosis of hepatocellular carcinoma.

A Case of Sarcoidosis with Cavitation / 결핵및호흡기질환

Sarcoidosis is a rare systemic disorder with unknown cause that is characterized pathologically by non-caseating granuloma. The lung and mediastinal lymph nodes are almost always involved, and most patients experience acute or insidious respiratory symptom. Because sarcoidosis is an interstitial lung disorder involving the alveoli and bronchioles, the most common radiological finding is a reticularnodular lesion with lymphatic distribution. However, cavitation is quite rare. Sarcoidosis is also a major cause of hepatic granuloma in Western countries, accounting for 12% to 30% of cases. In most patients, the course of hepatic sarcoidosis is benign. However, chronic intrahepatic cholestasis or portal hypertension may develop in some patients. We report a case of sarcoidosis with cavitation and hepatic involvement.

Vasculo-Behcet's Disease Developing in a Patient with Ebstein Anomaly / 대한류마티스학회지

Behcet's disease (BD) is a chronic inflammatory disease, involving several organs. It is well known that there are the marked regional differences in the disease expression of BD. In case of the vascular involvement in BD, the frequency rate has been described in 25~30% among the patients from the MiddLe East, whereas it has been noted in 5~15% in our country. In general, BD associated with large vessel lesions is named vasculo-BD. On the other hand, the cardiac involvement in BD has rarely been reported in the literature. Ebstein anomaly is a kind of malformation that is characterized by a downward displacement of the tricuspid valve into the right ventricle. We reported a 54-year-old male patient with vasculo-BD who had inferior vena cava obstruction and Ebstein anomaly. The association of Ebstein anomaly with vasculo-BD is considered to be coincidental. To the best of our knowledge, this is the first case of Ebstein anomaly associated with BD.

Three Cases with Cutaneous Polyarteritis Nodosa / 대한류마티스학회지

Systemic polyarteritis nodosa is a necrotizing vasculitis that involves small and medium-sized muscular arteries in the multiple organ systems, whereas cutaneous polyarteritis nodosa (CPAN) is a localized disease characterized by necrotizing vasculitis of small and medium-sized arteries in the skin without life-threatening organ involvement. CPAN is usually limited to skin, muscle, and joints. It is chronic but takes a benign course. The most common cutaneous manifestations include nodules, ulcers and a livedo reticularis pattern on the extremities. We describe three cases with CPAN showing necrotizing vasculitis on the skin without systemic symptoms or visceral involvement. In Korea, most previously published cases with CPAN have shown a good response to a short term of corticosteroids or colchicine administration. However, two of our three patients required another immunosuppressive agent in addition to corticosteroids to manage their intractable skin lesions, and the remaining one showed a good response to a short course of prednisolone. In addition, there was one patient with CPAN having hepatitis B surface antigen, which might be associated with his refractory skin disease.