Age-related Changes in the Sirtuin1-NFE2-related Factor 2 Signaling System in the Kidney / 대한내과학회지

BACKGROUND/AIMS: Renal aging-related changes are characterized by oxidative stress. SIRT1 regulates cellular conditions by activating Nrf2. The present study investigated the processes of renal changes by antioxidant enzymes and the relationship between SIRT1 and Nrf2. METHODS: We used male 2-, 12-, and 24-month-old C57BL/6 mice. We measured renal function, histological changes, oxidative stress, and expression of SIRT1–Nrf2 signaling in the kidneys. RESULTS: 24-month-old mice exhibited increased albuminuria and serum creatinine. Creatinine clearance was decreased in 24-month-old mice compared with 12-month-old mice. There were increases in mesangial volume and tubulointerstitial fibrosis in 24-month-old mice. Moreover, oxidative stress marker, 3-Nitrotyrosine, expression and apoptosis were increased in 24-month-old mice. The 24 h urinary 8-isoprostane and 8-hydroxy-deoxyguanosine excretion increased with aging. The levels of expression of SIRT1 and nuclear Nrf2 were decreased in 24-month-old mice. The antioxidant enzymes HO-1 and NQO-1 were down-regulated in 24-month-old mice. Another antioxidant enzyme, SOD2, was decreased in 24-month-old mice. CONCLUSIONS: Our results demonstrated that SIRT1 was down-regulated with aging, and this may be related to changes in the expression of target molecules including Nrf2. As a result, oxidative stress was induced. The pharmacological targeting of these signaling molecules may reduce the pathological changes associated with aging in the kidney.

Erratum: Age-related Changes in the Sirtuin1-NFE2-related Factor 2 Signaling System in the Kidney / 대한내과학회지

The authors apologize for any inconvenience that this may have caused.

Posterior nutcracker phenomenon with Down syndrome

No abstract available.

IgG4-Related Tubulointerstitial Nephritis Accompanied by Henoch-Schonlein Purpura / 대한내과학회지

Tubulointerstitial nephritis is one of the common manifestations of immunoglobulin G (IgG)4-related disease; however, among all cases of tubulointerstitial nephritis undergoing renal biopsies, IgG4-related tubulointerstitial nephritis seems to be relatively rare because of its trivial urinary findings. A previously healthy 54-year-old man was referred to our clinic with a 4-week history of lower leg purpura and renal dysfunction. A kidney biopsy was planned because of bilateral renomegaly, by imaging studies, and elevated serum creatinine levels. Pathological findings in the kidney showed prominent infiltration of IgG4-postive plasma cells in the tubulointerstitium, but not the glumeruli. A skin biopsy revealed leukocytoclastic vasculitis, accompanied by deposition of IgA and C3 in the vascular wall, indicating Henoch-Schonlein purpura (HSP). Although cases of combined IgG4-related disease and microvasculitis, including HSP, are extremely rare, the possibility of an association between two diseases deserves attention.

Risk Factors and Reversibility of Renal Failure in Patients with Newly Diagnosed Multiple Myeloma / 대한내과학회지

BACKGROUND/AIMS: Multiple myeloma (MM) is frequently accompanied by renal insufficiency, which has been regarded as a poor prognostic factor for MM. It is known that the incidence and characteristics of MM in Asia differ from those in Western countries. The aim of this study was to evaluate risk factors for renal impairment and to investigate reversible factors for renal failure in patients with MM. METHODS: Patients newly diagnosed with MM from 2005 to 2008 were included. We investigated factors associated with renal insufficiency and those related to recovery from renal dysfunction after 12 weeks of treatment of MM. RESULTS: Renal failure was recognized in 86 (39%) of 221 patients at diagnosis. In the binary logistic regression analysis, low hemoglobin (odds ratio [OR], 0.813; p = 0.02), high beta2microglobulin (OR, 1.006; p < 0.01), and use of angiotensin-converting enzyme inhibitors (ACEi) (OR, 2.783; p < 0.04) at initial presentation were independent risk factors for renal failure in patients with multiple myeloma. After 12 weeks of treatment, 25 of 86 (29%) patients with renal failure had recovered renal function. Good response to chemotherapy (OR, 6.044; p < 0.01) and higher eGFR (OR, 1.084; p < 0.01) were associated with renal function recovery. CONCLUSIONS: Levels of hemoglobin and beta2microglobulin, and use of ACEi were independent risk factors for the development of renal failure in MM patients. The response to chemotherapy and eGFR at diagnosis significantly influenced recovery of renal function.

Risk Factors and Reversibility of Renal Failure in Patients with Newly Diagnosed Multiple Myeloma / 대한내과학회지

BACKGROUND/AIMS: Multiple myeloma (MM) is frequently accompanied by renal insufficiency, which has been regarded as a poor prognostic factor for MM. It is known that the incidence and characteristics of MM in Asia differ from those in Western countries. The aim of this study was to evaluate risk factors for renal impairment and to investigate reversible factors for renal failure in patients with MM. METHODS: Patients newly diagnosed with MM from 2005 to 2008 were included. We investigated factors associated with renal insufficiency and those related to recovery from renal dysfunction after 12 weeks of treatment of MM. RESULTS: Renal failure was recognized in 86 (39%) of 221 patients at diagnosis. In the binary logistic regression analysis, low hemoglobin (odds ratio [OR], 0.813; p = 0.02), high beta2microglobulin (OR, 1.006; p < 0.01), and use of angiotensin-converting enzyme inhibitors (ACEi) (OR, 2.783; p < 0.04) at initial presentation were independent risk factors for renal failure in patients with multiple myeloma. After 12 weeks of treatment, 25 of 86 (29%) patients with renal failure had recovered renal function. Good response to chemotherapy (OR, 6.044; p < 0.01) and higher eGFR (OR, 1.084; p < 0.01) were associated with renal function recovery. CONCLUSIONS: Levels of hemoglobin and beta2microglobulin, and use of ACEi were independent risk factors for the development of renal failure in MM patients. The response to chemotherapy and eGFR at diagnosis significantly influenced recovery of renal function.

Very-Late Onset Diffuse Large B-cell Lymphoma with CD3 Coexpression in a Kidney Transplant Patient / 대한신장학회지

B-lineage non-Hodgkin lymphoma may aberrantly coexpress T-cell markers. In general population, however, cases of diffuse large B-cell lymphomas with CD3 co-expression are rare because the CD3 marker is the most lineage specific T-cell antigen. We report a case of CD3 coexpressed diffuse large B-cell lymphoma in a 47-year-old male patient presented with dyspepsia who had transplanted a kidney 17 years ago. An esophagogastroduodenoscopy displayed an ulcerated mass in the gastric antrum. The pathology of the mass was monomorphic post-transplant lymphoproliferative disorder - specifically, CD20- and CD3-positive diffuse large B-cell lymphoma. Resection of the mass and postop chemotherapy were performed. A follow-up computerized tomography showed disapperance of tumor. No recurrence was observed until 7 month after treatment. Nevertheless, the patient's renal function gradually aggrevated and progressed to end stage renal disease. As far as we know, this is the first case of diffuse large B-cell lymphoma with CD3 coexpression after kidney transplant.

The Treatment of Post Transplant Tuberculosis: Rifampin Sparing Regimen / 대한이식학회지

BACKGROUND: Rifampin reduces the blood levels of cyclosporin (CsA) and steroids by increasing the activity of hepatic cytochrome P450 system and the inclusion of rifampin in the anti-tuberculosis treatment protocol increases the risk of acute allograft rejection and mortality due to its interaction with cyclosporine. We report the successful treatment outcome of post-renal transplant tuberculosis patients who were treated with quinolone substituted for rifampin in anti-tuberculosis regimen. METHODS: This was a retrospective study of 14 patients with tuberculosis diagnosed among 218 transplant recipients from Feb. 1988 through Dec. 2003 at Daejeon St. Mary's hospital of catholic university of Korea and 6 patients with tuberculosis who underwent transplantation in other hospital and followed up in our hospital. RESULTS: The incidence of post-renal transplant tuberculosis was 6.4%. The mean time to diagnosis of tuberculosis after transplantation was 58.6 months (3.3~180.7). 9 were pulmonary and 11 were extrapulmonary tuberculosis. The graft failure was not occurred in quinolone group (0/15) and 2 of 3 in rifampin group. The serum creatinine levels before tuberculosis were not different to that of post-treatment in quinolone group. (P=0.58) The CsA levels before tuberculosis were not also different to that of posttreatment in quinolone group (P=0.68). CONCLUSIONS: The treatment of post-renal transplant tuberculosis with rifampin sparing anti-tuberculosis regimen was successful. Rifampin, although a mainstay drug in the treatment of tuberculosis, can be avoided in patients receiving cyclosporine, thus avoiding the risk of precipitating allograft rejection.

The Preconditioning with AICAR Protects Against Subsequent Renal Ischemia Reperfusion Injury / 대한신장학회지

PURPOSE:Preconditioning due to activation of AMPK might reduce ischemia-reperfusion (I/R) injury in the kidney, based on the key role of AMPK in preserving ATP. To evaluate this possibility, the effect of preconditioning with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), AMPK activator, before sustained ischemia was investigated. METHODS:Adult male Sprague-Dawley rats weighing approximately 220-250 g were used. To induce renal ischemia, a laparotomy was performed under ketamine and xylazine hydrochloride, and the blood supply to both kidneys was interrupted by placement of vessel clamps at the level of the renal pedicles. Reflow was initiated by removing the clamps. The following experimental groups were defined 1. Acute renal ischemia 0 sec, 10 min, 15 min, 2. AICAR treatment, 3. Sham group (S), 4. Ischemia/ Reperfusion group (I/R), 5. AICAR+I/R group (A+I/R), 6. AraA (Adenine-9-b-D-arabinofuranoside, an AMPK) inhibitor+AICAR+I/R group (AraA+A+I/R) RESULTS:There was only faint AMPK phosphorylation in the sham group. After 10 minutes of ischemia, or AICAR preconditioning however, Thr172 phosphorylation of AMPK was increased (p<0.05). The serum levels of BUN and creatinine were significantly decreased in AICAR preconditioning group (A+I/R). (128.0+/-7.33 mg/dL, 4.18+/-0.27 mg/dL vs. 90.2+/-11.13 mg/dL, 2.58+/-0.7 mg/dL, p<0.05), but these effects were attenuated by AMPK inhibitor, AraA (AraA+A+I/R group). In quantitative analysis of tubular injury, tubular injury score in AICAR preconditioning group significantly decreased (p<0.05). CONCLUSION:The AMPK activator AICAR has a protective effect against renal I/R injury.

Status of Initiating Pattern of Hemodialysis: A Multi-center Study

This study was to evaluate the status of initiating pattern of hemodialysis (HD). Five hundred-three patients in 8 University Hospitals were included. Presentation mode (planned vs. unplanned), and access type (central venous catheters [CVC] vs. permanent access) at initiation of HD were evaluated, and the influence of predialysis care on determining the mode of HD and access type was also assessed. Most patients started unplanned HD (81.9%) and the most common initial access type was CVC (86.3%). The main reason for unplanned HD and high rate of CVC use was patient-related factors such as refusal of permanent access creation and failure to attend scheduled clinic appointments. Predialysis care was performed in 57.9% of patients and only 24.1% of these patients started planned HD and 18.9% used permanent accesses initially. Only a minority of patients initiated planned HD with permanent accesses in spite of predialysis care. To overcome this, efforts to improve the quality of predialysis care are needed.

Ultrasound Measurements of Kidney Size in the Elderly without Renal Disease / 대한신장학회지

PURPOSE: Kidney size (KS) is used to diagnose the patients with renal disease. When the length of a kidney is measured under 9 cm, it is considered to indicate an irreversible disease. Because glomerular filtration rate (GFR) decreases with age, the normal range of KS in the elderly is indefinite. Therefore, we measured KS in adults older than 80 years old and investigated correlated factors. METHODS: One hundreds six adults (51 men, 55 women: mean age 83+/-0.3) without renal disease were included. Their serum creatinine (Scr) levels did not exceed 1.3 mg/dL, and the calculated GFR were over 60 mL/min/1.73m2. Abdominal ultrasonography were performed to all of them and their body indexes (BI) were measured. RESULTS: 1) The mean length of kidney was 9.9+/-0.07 cm. 2) KS in the early eighties was larger than that of adults over ninety. 3) KS showed negative correlations with age and Scr, but a positive correlation with body surface area . 4) The calculated GFR showed correlations with the surface areas of both kidney (BK) by C-G equation and with the size of BK by MDRD equation. 4) The GFR calculated by MDRD and C-G equation presented inverse correlations with Scr, but only MDRD equation showed a statistic significance. CONCLUSION:In the elderly, KS may be smaller than that of younger adults. Other factors such as either surface area or volume of BK and BI should be considered to estimate the individual KS to decide whether the size is within normal range.

A Case of Hypermagnesemia with Cardio-respiratory Failure in a Patient with Chronic Renal Failure / 대한신장학회지

A 46-year-old woman with chronic renal failure due to polyarteritis nodosa was referred to the hospital for evaluation of abdominal pain. She had been treated with cathartics (magnesium oxidate 2.0 g/day) for constipation for several days. One day before the admission, the patient had been taken magnesium enema twice at another hospital. On admission, she was comatose, suffering from lethargy and respiratory failure. Her serum magnesium and amylase concentrations were markedly elevated (8.2 mg/dL and 1,698 IU/L respectively), and plain abdominal image and abdominal computed tomography revealed acute pancreatitis and non-obstuctive ileus. Thereafter, aggressive cardiopulomonary support with mechanical ventilation and continuous renal replacement therapy using continuous veno-venous hemofiltration (CVVH) applied due to cardio-respiratory failure and hypermagnesemia. After 3 days of CVVH treatment, the concentration of serum magnesium was normalized to 3.2 mg/dL, and respiratory failure and abdominal ileus were markedly improved. Four days after aggressive treatment, her hemodynamic and gastroenteric symptoms stabilized. Therefore, we report the case of hypermagnesemia with acute pancreatitis, severe hypotension and respiratory failure after cathartic ingestion and enema containing magnesium oxidate treated with CVVH.

Association of Arterial Stiffness with the Decrease of Post-Dialysis Blood Pressure in Maintained Hemodialysis Patients / 대한신장학회지

PURPOSE: Cardiovascular disease is one of the leading causes of mortality and morbidity in hemodialysis patients. Arterial stiffness is known to be associated with vascular calcification in HD patients. Post-dialysis hypotension is a risk factor for cardiovascular mortality. We evaluated the relation between arterial stiffness and post-dialysis blood pressure in maintained HD patients. METHODS: 72 HD patients were enrolled in this study. They had been under maintenance HD for more than 3 months. We checked the biochemical data, including the troponin T, CRP and OPG (osteoprotegerin) levels before their dialysis session and the baPWV (brachio-ankle pulse wave velocity) after the session. We defined post-dialysis BP decrease as a drop of BP of more than 5% of the average MAP for 2 weeks (6 sessions). RESULTS: There were 34 and 38 patients with and without post-dialysis BP decrease, respectively. The BP decrease group had higher CRP, troponin T and OPG levels (p<0.05, 0.01 and 0.01, respectively). The PWV was higher in the BP decrease group (p<0.001). The CRP and troponin T levels were positively correlated with the PWV (r=0.26, p<0.05; r=0.31, p<0.01, respectively). The OPG level was positively correlated with the PWV (r=0.44, p<0.001). Age, pre-dialysis pulse pressure and drops in the patients MAP were correlated with the PWV (r=0.33, p<0.05; r=0.31, p<0.05; r=0.30, p<0.05, respectively). On multivariate analysis, PWV was the independent factor related to the drops in the MAP of the patients (beta=0.311, p=0.021). CONCLUSION: Arterial stiffness is associated with post-dialysis blood pressure decrease.

A Case of Post-Streptococcal Glomerulonephritis with Diffuse Alveolar Hemorrhage

Acute post-streptococcal glomerulonephritis (PSGN) is characterized by an abrupt onset of edema, hypertension, and hematuria. Life-threatening diffuse alveolar hemorrhage (DAH) is rarely associated with acute PSGN. There have been only two reported cases worldwide, and no case has been reported previously in Korea. Here, we present a patient who clinically presented with pulmonary-renal syndrome; the renal histology revealed post-infectious glomerulonephritis of immune complex origin. A 59-yr-old woman was admitted with oliguria and hemoptysis two weeks after pharyngitis. Renal insufficiency rapidly progressed, and respiratory distress developed. Chest radiography showed acute progressive bilateral pulmonary infiltrates. The clinical presentation suggested DAH with PSGN. Three days after treatment with high-dose steroids, the respiratory distress and pulmonary infiltrates resolved. Electron microscopy of a renal biopsy specimen sample revealed diffuse proliferative glomerulonephritis with characteristic subendothelial deposits of immune complex ("hump''). The renal function of the patient was restored, and the serum creatinine level was normalized after treatment.

Two cases of hypokalemic rhabdomyolysis due to thiazide treatment / 대한내과학회지

Hypokalemia is a common metabolic cause of rhabdomyolysis. Although treatment with thiazide causes hypokalemia frequently, hypokalemic rhabdomyolysis after administration with thiazide is very rare. Here we report two cases of hypokalemic rhabdomyolysis due to thiazide treatment. A 50-year-old woman who had been treated with thiazide for hypertension was admitted due to quadriplegia. The patient had a potassium level of 1.5 mEq/L, a creatinine phosphokinase (CPK) level of 21,346 IU/L, and a lactic dehydrogenase level (LDH) of 2,389 IU/L. An 80-year-old man who had been treated with thiazide for hypertension was admitted due to generalized weakness. His potassium level was 1.9 mEq/L, CPK was 29,000 IU/L, and LDH was 2,393 IU/L. There were no any other causes of rhabdomyolysis except hypokalemia due to thiazide treatment for both patients. With adequate hydration and potassium replacement, hypokalemic rhabdomyolysis recovered completely without sequele.

Static Venous Pressure Measurement by Access Alert in Detecting Vascular Access Stenosis / 대한신장학회잡지

BACKGOUND: K/DOQI guideline recommends measurement of vascular access blood flow and static intra-access pressure (SIAP) as important vascular access monitoring methods. Vascular access blood flow is measured by ultrasongraphic dilution method or Doppler sonographic examination. But these two examinations are expensive and the former needs special apparatus and the latter has the limitation of inter- and intra-observer variability. This study was performed to evaluate the utility of SIAP measured by Access Alert in detecting vascular access monitoring in hemodialysis (HD) patients. METHODS: Ninety-two patients on chronic HD via arteriovenous fistulas (AVF) and grafts (AVG) were included in this study. Mean age was 5513 and the number of man was 34. Sixteen patients had AVG. We measured both dialysis venous pressure (DVP) and SIAP. SIAP was measured by Access Alert (Medisystems, Seattle, WA) via arterial and venous canulation into vascular access and then static intra-access pressure ratio (SIAPR) was calculated by SIAP/MAP (mean arterial pressure. Venography was performed to find venous stenosis in patients who had abnormal levels of SIAPR. RESULTS: Arterial and venous SIAPRs in patients with AVG were higher than those in patients with AVF, respectively (arterial line:0.69+/-0.24 vs. 0.29+/-0.18, pp<0.001, venous line:0.60+/-0.23 vs. 0.23+/-0.16, p<;0.001). Of the total 92 patients, 30 patients had abnormal SIAPR. We performed venography in 19 out of these 30 patients. Of the 19 patients, 17 patients had stenotic venous lesions in which 14 patients had severe stenotic lesions and required radiologic intervention. In 14 patients with severe stenotic lesions, only 2 patients showed abnormal DVP and other patients showed normal DVP. CONCLUSION: The measurement of static intra-access pressure by Access Alert is simple and effective in detecting vascular access stenosis.

Chinese Herbs Induced End-Stage Renal Disease in a Patient with Minimal Change Nephrotic Syndrome / 대한신장학회잡지

An outbreak of rapidly progressive renal failure was observed in Belgium in 1993 and was related to a slimming regimen involving Chinese herbs. Extensive interstitial fibrosis with atrophy and tubular loss was the major histological lesion. Aristolochic acid has been suspected to be responsible for nephrotoxicity. The use of Chinese herbal medicines is very popular in Korea. We report the presence of a nephrotoxic compound in herb medications, which led to end-stage renal failure in a patient with complete remission state of minimal change disease. The typical and sequential pathologic changes in our patient following the consumption of herbs suggest possible relationship to herbal medicines, and end-stage renal disease, despite the fact that a cause-and-effect relationship cannot be automatically inferred.

The Effect of Cutting Balloon Angioplasty on Vascular Access Dysfunction in Hemodialysis Patients / 대한신장학회잡지

BACKGROUND:When angioplasty is performed using conventional balloon to treat arteriovenous fistula stenosis, treatment failure frequently occurs in case stenosis is very seve or tight. Cutting balloons were made to overcome these disadvantages. The purpose of this study is to evaluate the clinical effectiveness of cutting balloon angioplasty (CBA). METHODS:Twenty-four patients treated with CBA were included in this study. We evaluated clinical signs of venous stenosis, fistulographic findings, indications of CBA, procedure outcomes, and its complications. RESULTS:Out of the total 24 patients, the most common indication for fistulogram was increased negative arterial pressure (n=8). The stenotic lesions were juxta-anastomotic vein (n=19), graft-venous anastomosis (n=3), artery-venous anastomosis (n=1), and axillary vein (n=1), retrospectively. Conventional angioplasty had been attempted but failed in all 24 patients who were treated with CBA. The initial success rate of CBA was 100%, and the follow-up patency rate at 6, 12, 24 month after the procedure were 73.1%, 65.8%, and 49.3%, respectively. Procedure- related complications were minimal leakage of contrast media (n=3), partial rupture of vessel wall (n= 3), and vessel dissection (n=2). Three partial ruptures and one severe dissection were successfully treated only with balloon inflation without surgical operation. And leakages and one mild dissection spontaneously improved without specific treatment. CONCLUSION:This study suggests that cutting balloon angioplasty is relatively safe and effective in treating failed stenotic lesions when compared with conventional angioplasty in hemodialysis patients.

Effect of Lamivudine Treatment in Renal Transplant Recipient with HBsAg-Positivity / 대한신장학회잡지

BACKGROUND:Immunosuppressive therapy after renal transplantation stimulates the replication of hepatitis B virus (HBV) and may lead to increased liver-related mortality. We investigated the effectiveness of lamivudine for the treatment of HBV reactivation in renal transplant recipients. METHODS:We reviewed the clinical course of 16 HBsAg-positive renal transplant patients (M:F=13:3) treated with lamivudine for chronic hepatitis B. The outcome of prophylactic (HBV-DNA negative, n=5) and preemptive (HBV-DNA positive, n=4) therapy without hepatic dysfunction was analyzed in compared with that of salvage (n=7) therapy for post-transplantation hepatic dysfunction. RESULTS:Chronic hepatitis developed in four (25 %) of the enrolled 16 recipients, including one fulminant hepatic failure in prophylactic group and one hepatocellular carcinoma in the salvage group. We found that three (33%) of 9 patients under prophylactic and preemptive therapy showed post-transplantation hepatic dysfunction, but that only one (14%) of 7 patients showed elevated liver enzyme after salvage therapy. During a mean follow-up, under prophylactic and preemptive therapy, of 38 months, five (56%) of 9 patients showed resistance to lamivudine. In seven patients under salvage therapy for a mean follow-up of 26 months, only one patient (14%) showed resistance. At the last follow-up, liver enzyme levels were normal in 14 patients (87.5%). CONCLUSION:It may be beneficial to use lamivudine for the prevention of liver-related mortality in renal transplant recipients with HBs-Ag positivity. Prophylactic and preemptive lamivudine therapy tend to show higher viral resistance compared with salvage therapy.

A Case of Renal Infarction associated with Protein C and S Deficiency / 대한신장학회잡지

Renal infarction usually occurs in patients with atrial fibrillation, valvular heart disease, trauma, renal artery stenosis, atherosclerosis, vasculitis, and hypercoagulable state. Protein C or S deficiency is an uncommon condition among hypercoagulable states and manifests deep vein thrombosis, pulmonary thromboembolism, cerebrovascular accident. In this report, we present a case of renal infarction occurred in 36-year-old male without underlying diseases except a family history of thromboembolism. He was admitted to our hospital due to an abrupt and continuous left flank pain. He had no previous history of an arterial or venous thrombosis. Tomography and renal angiography showed a left renal artery occlusion. He was treated with heparin and warfarin therapy. In laboratory tests, Protein C antigen level and protein S activity was 51.80% (72-160%) and 48% (65-140%). Thus, we concluded that renal infarction was secondary to combined type 1 protein C deficiency and type 2 protein S deficiency.