The Effect of Mycophenolate Mofetil versus Cyclosporine as Combination Therapy with Low Dose Corticosteroids in High-risk Patients with Idiopathic Membranous Nephropathy: a Multicenter Randomized Trial

BACKGROUND: Appropriate immunosuppressive therapy for patients with idiopathic membranous nephropathy (MN) remains controversial. The effect of mycophenolate mofetil (MMF) versus cyclosporine (CsA) combined with low-dose corticosteroids was evaluated in patients with idiopathic MN in a multi-center randomized trial (www.ClinicalTrials.gov NCT01282073). METHODS: A total of 39 biopsy-proven idiopathic MN patients with severe proteinuria were randomly assigned to receive MMF combined with low-dose corticosteroids (MMF group) versus CsA combined with low-dose corticosteroids (CsA group), respectively, and followed up for 48 weeks. Complete or partial remission rate of proteinuria and estimated glomerular filtration rate (eGFR) at 48 weeks were compared. RESULTS: The level of proteinuria at baseline and at 48 weeks was 8.9 ± 5.9 and 2.1 ± 3.1 g/day, respectively, in the MMF group compared to 8.4 ± 3.5 and 3.2 ± 5.7 g/day, respectively, in the CsA group. In total, 76.1% of the MMF group and 66.7% of the CsA group achieved remission at 48 weeks (95% confidence interval, −0.18 to 0.38). There was no difference in eGFR between the two groups. Anti-phospholipase A2 receptor Ab levels at baseline decreased at 48 weeks in the complete or partial remission group (P = 0.001), but were unchanged in the no-response group. There were no significant differences between the two groups in changes in the Gastrointestinal Symptom Rating Scale and Gastrointestinal Quality of Life Index scores from baseline to 48 weeks. CONCLUSION: In combination with low-dose corticosteroids, the effect of MMF may not be inferior to that of CsA in patients with idiopathic MN, with similar adverse effects including gastrointestinal symptoms. Trial registry at ClinicalTrials.gov (www.ClinicalTrials.gov NCT01282073).

Myelodysplastic Syndrome and Minimal Change Nephrotic Syndrome treated with Steroid Challenge / 대한내과학회지

Glomerulonephritis associated with malignancy is deemed to be paraneoplastic glomerulonephritis. Myelodysplastic syndrome (MDS) is a group of heterogeneous clonal hematopoietic stem cell disorders characterized by impaired hematopoietic cell differentiation and cytopenia. The pathophysiology of MDS is thought to be immune-mediated in part. A few reports have documented various forms of glomerulonephritis in patients with MDS and suggested that immune dysregulation is important in the development of paraneoplastic glomerulonephritis. Here, we report a patient with MDS and refractory anemia with excess blast-2 accompanied by minimal change nephrotic syndrome. The patient was treated with prednisolone, and the nephrotic-range proteinuria and pancytopenia improved markedly.

Erratum: Spontaneous Lumbar Artery Bleeding and Retroperitoneal Hematoma in a Patient Treated with Continuous Renal Replacement Therapy / 대한중환자의학회지

We found an error in this article. The Fig. 2B should be corrected.

Erratum: Spontaneous Lumbar Artery Bleeding and Retroperitoneal Hematoma in a Patient Treated with Continuous Renal Replacement Therapy / 대한구급학회지

We found an error in this article. The Fig. 2B should be corrected.

Spontaneous Lumbar Artery Bleeding and Retroperitoneal Hematoma in a Patient Treated with Continuous Renal Replacement Therapy / 대한중환자의학회지

Rupture of the lumbar artery is usually associated with trauma but rarely has been reported in association with anticoagulation. We present a 71-year-old man who developed spontaneous rupture of the lumbar artery leading to a retroperitoneal hematoma while receiving continuous renal replacement therapy (CRRT). The bleeding was confirmed by computed tomography and angiography and was controlled successfully using selective angiographic embolization. We suggest that spontaneous retroperitoneal bleeding should be considered in a case of sudden decrease in hemoglobin in a CRRT patient.

Spontaneous Lumbar Artery Bleeding and Retroperitoneal Hematoma in a Patient Treated with Continuous Renal Replacement Therapy / 대한구급학회지

Rupture of the lumbar artery is usually associated with trauma but rarely has been reported in association with anticoagulation. We present a 71-year-old man who developed spontaneous rupture of the lumbar artery leading to a retroperitoneal hematoma while receiving continuous renal replacement therapy (CRRT). The bleeding was confirmed by computed tomography and angiography and was controlled successfully using selective angiographic embolization. We suggest that spontaneous retroperitoneal bleeding should be considered in a case of sudden decrease in hemoglobin in a CRRT patient.

Bisphosphonate-induced Severe Hypocalcemia: A Case Report

Bisphosphonate generally seems to be safe, but hypocalcemia may occasionally develop in the course of bisphosphonate treatment. Hypocalcemia induced by bisphosphonate is usually mild and asymptomatic, but unrecognized or poorly treated hypocalcemia can lead to life-threatening state. A 78-year-old woman who had a history of hip arthroplasty and intravenous zoledronate treatment for femur neck fracture was presented to emergency department with altered mental status. It turned out that her symptom was due to severe hypocalcemia which was caused by intravenous zoledronate treatment. She also had renal dysfunction. She was treated by intravenous calcium gluconate and calcitriol administration. This case supports the need for evaluation of renal dysfunction, vitamin D deficiency and parathyroid gland dysfunction before bisphosphonate treatment and accurate monitoring of plasma calcium and creatinine levels. In addition, vitamin D and calcium supply during treatment with bisphosphonate is mandatory.

A Case of Tubulointerstitial Nephritis and Uveitis Syndrome in An Old Age Female / 대한신장학회지

We report a case of tubulointerstitial nephritis and uveitis (TINU) syndrome in an old age female. A 66-year-old woman presented with nonspecific systemic symptoms and severe renal dysfunction. Renal biopsy showed acute interstitial nephritis and ophthalmologic examination revealed bilateral panuveitis. Evaluations for connective tissue diseases and infectious diseases were negative. She was treated with total eight sessions of hemodialysis, oral steroids and topical steroids. Renal function had improved significantly and remained stable at follow-up, although it did not fully recovered yet. TINU syndrome should be considered in cases of unexplained tubulointerstitial nephritis, especially in the presence of ocular symptom.

Acute pancreatitis complicated by acute renal failure successfully treated with peritoneal dialysis / 대한내과학회지

The mortality of acute pancreatitis complicated by acute renal failure (ARF) remains high. Among several therapeutic modalities, peritoneal dialysis (PD) has advantages due to its ability to remove toxic materials in the peritoneal exudate as well as urotoxic substances in the blood. We report successful treatment with PD in a patient with acute pancreatitis and ARF. A 41-year-old heavy drinker was admitted due to acute pancreatitis complicated by ARF. A therapeutic plan of PD was designed. A Tenckhoff PD catheter was used, considering its lower potential for infection compared to conventional catheters. The frequency of PD was set at 8 times per day, considering the catabolic state in pancreatitis. The clinical symptoms and biochemical parameters showed remarkable improvement during the follow up period. In conclusion, PD is one of the effective treatment modalities for treating ARF in patients with pancreatitis.

Two Cases of Heparin-Induced Thrombocytopenia in Hemodialysis Patients / 대한신장학회잡지

Heparin, a widely used anticoagulant, is currently the anticoagulant of choice in long-term hemodialysis (HD). Heparin-induced thrombocytopenia (HIT) is one of the most serious side effects of heparin which can cause arterial or venous thromboembolism associated with substantial morbidity and mortality. We experienced two patients who had thrombocytopenia and vascular access occlusion during the induction period of HD with the use of unfractionated heparin. Thrombocytopenia was improved after discontinuation of heparin. HIT was confirmed with anti-heparin/platelet factor 4 antibody test. HD was conducted and arteriovenous fistula was created successfully after switch of heparin to argatroban (Novastan(R)) or nafamostat mesilate (Futhan(R)). Nephrologist should rule out HIT first when thrombocytopenia and thromboembolic complications occur after use of heparin, especially during the induction period of HD. For suspicious patients, immediate cessation of heparin and switch to alternative anticoagulant is very important to avoid serious complications.

The Reasons for Use of Temporary Catheter Instead of Arteriovenous Fistula at the Start of Chronic Hemodialysis Therapy / 대한신장학회잡지

PURPOSE: Placement of an arteriovenous fistula (AVF) before initiation of chronic hemodialysis (HD) is recommended to avoid the use of a dialysis catheter. However, many patients use temporary catheter at the start of HD for many reasons. We conducted a study to examine the reasons for use of temporary catheter instead of AVF at initial HD therapy. METHODS: We investigated 61 chronic renal failure (CRF) patients who started HD from January 2001 to August 2004 at Daegu Fatima Hospital. Fourty one of them used temporary catheter (catheter group) and 20 used AVF (AVF group) at initial HD. The causes of CRF, clinical presentation at initial HD, reasons that required start of HD and reasons for use of temporary catheter were investigated. RESULTS: The reasons that required start of HD were dyspnea (23), uremic symptoms (11), severe edema (4) and metabolic abnormalities (3) in catheter group and uremic symptoms (8), progression of CRF with minimal uremic symptoms (8) in AVF group. Those causes of unpreparedness of AVF in catheter group were delayed referral (12), rapid progression of CRF (12), unawareness of CRF (10), and noncompliance (7). The systolic and diastolic blood pressure were higher in catheter group than AVF group (171.3+/-33.5 vs 146.0+/-18.0 mmHg, 94.0+/-18.5 vs 80.6+/-10.8 mmHg, respectively). Serum albumin level was lower (3.0+/-0.6 vs 3.4+/-0.7 g/dL) and serum phosphorus level was higher (6.8+/-1.9 vs 5.7+/-1.7 mg/dL) in catheter group. CONCLUSION: To avoid temporary vascular catheter, early diagnosis of CRF, early referral to nephrologist and preparation of AVF is essential.

Effect of Peritoneal Dialysis Duration on the Outcome of Peritonitis in CAPD Patients / 대한신장학회잡지

BACKGROUND: The clinical manifestations of peritonitis in long-term PD patients may be more severe due to structural and functional alterations of the peritoneum caused by repeated exposure to the bioincompatible dialysate. However, the study in which outcome of peritonitis was compared to the duration of PD has been reported rarely. This study was performed to evaluate the effect of PD duration on the outcome of peritonitis. METHODS: Medical records of patients cared for in Kyungpook University Hospital between June 1998 and May 2001 were reviewed retrospectively. Patients were divided into three groups by PD duration: group 1, or =37 months. RESULTS: There were 303 episodes (156 patients) of peritonitis during the study periods: 77 episodes in group 1, 115 episodes in group 2 and 111 episodes in group 3. There was no difference in gram- positive, gram-negative or fungal rate of peritonitis among three groups. In group 3, 16.2% of the patients transferred to hemodialysis, while 3.9% and 7.0% of patients in group 1 and 2 transferred to hemodialysis (p<0.05). CONCLUSION: Patients maintained on PD for over three years are associated with higher rate of technique failure than patients maintained on PD for less than three years. PD duration may be considered as a factor for predicting prognosis of peritonitis. Peritonitis in patients on long-term PD needs special attention.

Causative organisms and patterns of antibiotics sensitivity of CAPD peritonitis in different dialysis centers / 대한내과학회지

BACKGROUND: The International Society for Peritoneal Dialysis (ISPD) changed their recommendations for empiric therapy of peritonitis to a first generation cephalosporin to substitute vancomycin and a ceftazidime or an aminoglycoside to cover Gram negative organisms. These guidelines have been recently challenged based on microbiologic evidence and practical considerations. We believe that the management of CAPD peritonitis should be adapted to the specific circumstances affecting the patient, geographic location, local epidemiology of causative bacteria and availability of specific antibiotics. METHODS: To evaluate causative microorganisms and patterns of antibiotics sensitivity of CAPD peritonitis in different dialysis centers, we performed retrospective analysis in three dialysis centers located at different geographic area : Kyungpook University Hospital (Center A), Samsung Seoul Hospital (Center B), Ilsan Hospital (Center C). Among a total of 642 patients on CAPD from January 2001 to December 2001, 113 patients who experienced peritonitis (157 episodes of peritonitis) were included. For microbiologic culture, dialysate effluent was plated in blood agar, thioglycollate broth and McConkey medium. The pattern of antibiotic sensitivity was assessed using broth dilution and disc diffusion method. RESULTS: The sex ratio and proportion of diabetic patients were not different among each center, but the age of center C was higher than that in center A (A: 56.2 13.6, C: 64.6 14.1, p<0.05). Distribution of the causative microorganisms was not different among each center but the pattern of antibiotic sensitivity was different. The incidence of methicillin-resistant staphylococcus species and aztreonam-resistant Gram negative organisms was significantly different among each center. Regimen of 2000 ISPD empiric treatment protocol was ineffective in about 23% of all peritonitis episodes. A treatment with cefazolin instead of vancomycin was associated with resistance in 32.1% of Gram positive organisms and with mobactam instead of ceftazidime was associated with resistance in 23.1% of Gram negative organisms. CONCLUSION: Individual centers should continue to monitor the epidemiology of CAPD peritonitis and the epidemiology of the causative organisms and their sensitivity patterns in order to adapt general guidelines into a center-tailored empirical treatment protocols.

A Case of Spontaneous Renal Artery Dissection with Renal Infarction in a Healthy Man Without Hypertension / 대한신장학회잡지

It is usually known that arterial dissection is associated with malignant hypertension, severe atherosclerosis or trauma. Marfan syndrome or Ehlers- Danlos syndrome may also be rare causes. However, as in this case, spontaneous arterial dissection without aortic dissection in normotensive men is rarely reported. A 39-year-old man presented with acute onset right flank pain with microscopic hematuria. Physical examination was unremarkable and his blood pressure was normal. Clinical impression was urolithiasis because he experienced two episodes of urolithiasis previously. IVP was not completed due to adverse reaction during study. Right renal infarction was diagnosed by contrast-enhanced computed tomography. To search for possible cardiac embolic disease, the patient underwent surface echocardiography, which was normal and a detailed evaluation for a thrombotic tendency was unremarkable. A renal arteriogram showed dissection of the main right renal artery with extension to renal artery branches and a wedge-shape perfusion defect in the distal part of the occluded artery. He received aorto-renal bypass surgery using his great saphenous vein. The patient developed hypertension 3 months later. To summary, we report a case of spontaneous renal artery dissection with renal infarction in a healthy man without hypertension.

Clinical Usefulness of Low Calcium Dialysate in CAPD Patients with High Risk of Low-turnover Bone Disease / 대한신장학회잡지

Hypercalcemia is a common complication in CAPD patients treated with calcium-containing phosphate binders and using the standard dialysate(Ca++ : 3.5 mEq/L). Furthermore, the high calcium concentration in standard dialysate may have a suppressive effect on parathyroid hormone(iPTH) level, contributing to the high prevalence of low-urnover bone disease. We studied the effect of low calcium dialysate(Ca++ : 2.5 mEq/L) for those patients with high risk of low- turnover bone disease. Among 386 patients(1996. 1.- 1999. 12.) who had been stable on CAPD for at least 3 months, 46 patients were included in this study. The patients were divided into 3 groups on the basis of the iPTH levels(10 mg/dL) before the conversion to low calcium dialysate. Group 1(n=29), iPTH 10 mg/dL; Group 2 (n=14), iPTH 150 pg/mL and Ca++ >10 mg/ dL. During a 2-month run-in period, those patients were treated with standard dialysate. After that, a 12-month therapy with low calcium dialysate was followed. Biochemical data including calcium, phosphorus, iPTH and alkaline phosphatase were measured regularly and daily phosphate binder and calcitriol intake(pill counting) were assessed during the run-in and therapy period. We obtained the following result: the prevalence of hypercalcemia(Ca++>10.5 mg/dL) was 5.7%(22/ 386 patients). Serum calcium levels decreased during the therapy period(12 months)(10.5+/-1.4 vs 9.4+/-1.3 mg/dL, p<0.05). Serum phosphorus levels remained unchanged. Mean serum alkaline phosphatase level increased(203.0+/-92.9 vs 257.2+/-103.4 U/L, p<0.05). Serum iPTH levels increased (92.7+/-128.8 vs 225.3+/-237.3 pg/mL,p<0.05). The mean intake of oral phosphate binders was not significantly different between run-in period and therapy period. But calcitriol doses increased 0.038+/-0.087 at run-in period to 0.158+/-0.288 tablets/person/day at therapy period(p<0.05). In the six patients, low calcium dialysate was converted to standard dialysate due to high iPTH level (n=3), symptomatic hypo calcemia(n=2), and uncontrolled edema(n=1). In conclusion, in the study of 46 patients over 12 month period, the usage of 2.5 mEq/L calcium dialysate resulted in a significant decrement in calcium levels and increased iPTH levels. Therefore, we propose that dialysis with a low calcium dialysate is an acceptable form of therapy for the patients with high risk of low-turnover bone disease showing hypercalcemia and low iPTH level. However, further study will be needed for evaluating the effect of low calcium dialysate in low-turnover bone disease.

Comparison between Osteopontin Expression and Renal Function in Spontaneous Renal Failure Model / 대한신장학회잡지

Tubuolointerstitial inflammation and tubular injury account for most types of glomerulonephritis. The injury is characterized by an infiltration of mononuclear cells with atrophy and dilation of tubules and increased deposition of collagen in the interstitium. Despite the fact that the degree of tubulointerstitial injury in glomerular diseases may be the best predictor of overall outcome, the pathogenic mechanism by which the tubular injury develops remains unknown. Osteopontin, a highly acidic, phosphorylated, secreted glycoprotein, is up-regulated in renal cortex in many experimental models of tubulointerstitial fibrosis. In this study, we examined the expression of osteopontin in tubulointerstitium in experimental renal failure mouse, FGS/KIST. Mice were assigned three groups and sacrificed at 1 month, 2 months, and 3 months, in each. Proteinuria, GFR, the degree of tubulointerstitial inflammation, tubular atrophy, glomerulosclerosis and osteopontin expression were measured. Three-month-old group showed severely decreased GFR and marked tubulointerstitial inflammation and glomerulosclerosis compared with other groups. The expression of osteopontin increased with the severity of tubulointerstitial injury. These data suggest that osteopontin may act as a chemotactic or adhesive factor in the recruitment of the monocyte/macrophages and have a role in the pathogenesis of the tubulointerstitial injury.

A Case of Gastritis Cystica Profunda with Long Pendulous Pedicle / 대한소화기내시경학회지

Gastritis cystica profunda (GCP) is a rare disease which is mainly observed at the site of gastroenterostomy. However, it may occur in the stomach without a previous history of surgery. Under histologic examination GCP shows hyperplastic and cystic dilatation of the pseudopyloric glands with submucosal invasion. GCP with sessile polypoid pro-trusion is most commonly found but, submucosal tumors, giant gastric mucosal folds and pedunculated forms are occasionally found. We present the case of GCP showing a large sized polyp (3 2.5 2.5 cm) with a long pendulous pedicle that had developed in the fundus of the stomach without previous surgical history. Endoscopic polypectomy was performed for confirmation.

A Case of Membranous Nephropathy Improved by Removal of Early Gastric Cancer / 대한신장학회잡지

The nephrotic syndrome in association with extrarenal malignancy is not an uncommon event. The membranous nephropathy is most frequently associated with various carcinomas of the lung, breast, stomach and colon. Though the exact causal relationship has not been determined completely, deposition of the immune complexes composed of antitumor antibody and tumor antigens in the subepithelium is most favorably accepted. We experienced a patient with previously diagnosed membranous nephropathy and subsequently demonstrated early gastric cancer during patient follow-up. After surgical resection proteinuria improved significantly. All physicians are strongly recommended to examine thoroughly and search carefully for possibility of concomitant occult malignancy when an aged patient, especially over 40 years old, is diagnosed as a nephrotic syndrome.

The Influence of Rotatory Movement on the Tissue Catecholamines in Rats

The present study was designed to examine the possible relationship between the function of the labyrinth and the role of the sympathetic nervous system In experimental motion sickness produced by rotatory movement(8O r.p.m.). The catecholamines in the brain, the heart and the adrenal gland of rats were rapidly reduced to one half of normal values following exposure to rotatory movement. The pretreatment with streptomycin and dramamine completely prevented the depletion by the rotatory movement of the catecholamines in the brain, the heart and the adrenal gland, but scopolamine did not prevent the decrease. Bretylium or chlorpromazine signifcantly inhibited reduction of the catechol-amines in both of the brain and the heart. However they did not influence the decrease in the adrenal gland. The reduction of the tissue catecholamines in rotatory movement is presumed to be caused largely by activation of the sympathetic nervous system mediated through labyrinthine stimulation.