Changing Donor Source Pattern for Kidney Transplantation over 40 Years: A Single-Center Experience

BACKGROUND/AIMS: Kidney transplantations at our center rely mainly on living donors. The purpose of this study was to suggest future donor supply directions by reviewing changing trends in donor type. METHODS: During the past 40 years, 1,690 kidney transplantations were performed at our center. We divided the follow-up period into four decades and the donor population into three groups: living related, living unrelated, and deceased. We analyzed changing trends in donors from each group for each decade. Patients receiving overseas transplantation were also included. RESULTS: The proportion of living related donors decreased from 84% (54/64) in the 1970s to 61% (281/458) in the 2000s. Living unrelated donors showed a sustained proportion of around 20% after 1990. However, among living unrelated donors, the proportion of spouse donors increased from 4.6% (17/369) in the 1980s to 8.5% (39/458) in the 2000s. Transplants from deceased donors were only 3.3% (12/369) in the 1980s. However the proportion of deceased donors increased gradually, reaching 13.2% (105/799) in the 1990s and 19.9% (91/458) after 2000. Overseas transplantations increased after 2000 and reached 20% of all cases treated in our center during the 2000s. Such transplantations peaked in 2006 and decreased markedly thereafter. CONCLUSIONS: The proportion of each donor type has continuously changed, and the changes were associated with changes in the social structure and system. We expect that this study could be an important reference for other countries to estimate future changes of donor type.

Improved Gastrointestinal Symptoms and Quality of Life after Conversion from Mycophenolate Mofetil to Enteric-Coated Mycophenolate Sodium in Renal Transplant Patients Receiving Tacrolimus

It is reported that a conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) relieves gastrointestinal (GI) symptom burden and improves health-related quality of life (HRQoL). However, it is unclear whether renal transplant recipients using tacrolimus receive the same benefit from the conversion. In this prospective, multi-center, open-label trial, patients were categorized into two groups by their GI symptom screening. Equimolar EC-MPS (n=175) was prescribed for patients with GI burdens; those with no complaints remained on MMF (n=83). Gastrointestinal Symptom Rating Scale (GSRS) and Gastrointestinal Quality of Life Index (GIQLI) were evaluated at baseline and after one month. Patients and physicians completed Overall Treatment Effect (OTE) at one month. EC-MPS-converted patients had worse GSRS and GIQLI scores at baseline than MMF-continued patients (all P<0.001). Significant improvements in GSRS and GIQLI scores were observed for EC-MPS-converted patients at one month, but MMF-continued patients showed worsened GSRS scores (all P<0.05). OTE scale indicated that EC-MPS patients improved in overall GI symptoms and HRQoL more than MMF patients did (P<0.001). In tacrolimus-treated renal transplant recipients with GI burdens, a conversion from MMF to EC-MPS improves GI-related symptoms and HRQoL.

Specimen Adequacy and Safety of Percutaneous Ultrasound-Guided Native Kidney Biopsies Performed by Short-Term Trained Nephrology Fellows / 대한신장학회지

PURPOSE: Specimen adequacy and safety of percutaneous ultrasound-guided native kidney biopsies performed by short-term trained nephrology fellows were evaluated. METHODS: The differences in specimen adequacy and safety between nephrology fellow-performed (NP, n=67) and radiologist-performed (RP, n=82) percutaneous ultrasound-guided native kidney biopsies were retrospectively evaluated. RESULTS: The mean age of the patients was 35+/-15 years old, and the M:F ratio was 1.2:1. There were no differences in age, sex, anemia, platelet count and glomerular filtration rate between NP and RP patients. The mean glomerular count was 15.9+/-8.4 in light microscopy and 9.9+/-7.2 in immunofluorescent microscopy. Ninety five percent of biopsy specimens were adequate for pathological diagnosis. Between NP and RP kidney biopsies, there were no differences in the glomerular count in light and immunofluorescent microscopy, percentage of presence of glomeruli in electron microscopy, and the specimen adequacy for the pathological diagnosis. The rates of major and minor complications were 1.5% and 6%, respectively, in NP kidney biopsies. On the other hand, the rate of major complications was 9.8% in RP kidney biopsies, which was significantly higher than that in NP kidney biopsies. The rate of decrease in hemoglobin and hematocrit levels after biopsies was significantly higher in RP biopsies than in NP biopsies. CONCLUSION: Short-term trained nephrology fellows perform percutaneous ultrasound-guided kidney biopsy at a level equal to or superior to radiologists.

Successful Renal Transplantation with Desensitization in Highly Sensitized Patients: A Single Center Experience

Intravenous immunoglobulin (IVIG) and/or plasmapheresis (PP) are effective in preventing antibody-mediated rejection (AMR) of kidney allografts, but AMR is still a problem. This study reports our experience in living donor renal transplantation in highly sensitized patients. Ten patients with positive crossmatch tests or high levels of panel-reactive antibody (PRA) were included. Eight patients were desensitized with pretransplant PP and low dose IVIG, and two were additionally treated with rituximab. Allograft function, number of acute rejection (AR) episodes, protocol biopsy findings, and the presence of donor-specific antibody (DSA) were evaluated. With PP/IVIG, six out of eight patients showed good graft function without AR episodes. Protocol biopsies revealed no evidence of tissue injury or C4d deposits. Of two patients with AR, one was successfully treated with PP/IVIG, but the other lost graft function due to de novo production of DSA. Thereafter, rituximab was added to PP/IVIG in two cases. Rituximab gradually decreased PRA levels and the percentage of peripheral CD20+ cells. DSA was undetectable and protocol biopsy showed no C4d deposits. The graft function was stable and there were no AR episodes. Conclusively, desensitization using PP/IVIG with or without rituximab increases the likelihood of successful living donor renal transplantation in sensitized recipients.

The Efficacy and Safety of Ezetimibe and Low-Dose Simvastatin as a Primary Treatment for Dyslipidemia in Renal Transplant Recipients

BACKGROUND/AIMS: The efficacy and safety of a combination of ezetimibe and low-dose statin as primary treatment for dyslipidemia in renal transplant patients were evaluated prospectively. METHODS: The study enrolled 77 renal transplant recipients with dyslipidemia. They were given ezetimibe (10 mg) and simvastatin (10 mg) for 6 months as the initial treatment for dyslipidemia. Efficacy and safety were evaluated using lipid profiles, trough calcineurin inhibitor levels, allograft function, and adverse effects. The effects on proteinuria and high sensitivity C-reactive protein (hsCRP) levels were also evaluated. RESULTS: Ezetimibe and low-dose simvastatin significantly decreased the levels of total cholesterol (34.6%), triglyceride (16.0%), and low-density lipoprotein cholesterol (LDL-C) (47.6%), and 82.5% of the patients reached the target LDL-C level of <100 mg/dL. No significant change in the trough calcineurin inhibitor levels or allograft function occurred, and no serious adverse effects were observed. Fourteen patients (18.2%) discontinued treatment; eight patients (11.7%) developed muscle pain or weakness without an increase in creatinine kinase levels, and two patients (2.6%) developed elevated liver transaminase levels. The proteinuria and hsCRP levels did not change significantly. CONCLUSIONS: Ezetimibe and low-dose statin treatment is safe and effective as a primary treatment for dyslipidemia in renal transplant patients.

A Case of Primary Aldosteronism after Renal Transplantation / 대한신장학회지

After renal transplantation, we are more likely to encounter hyperkalemia rather than hypokalemia. We report a case of kidney transplantation recipient with hypokalemia and hypertension secondary to primary aldosteronism. A 48 year-old woman was presented with fatigue and weight loss that had lasted for 3 months. She was diagnosed as autosomal dominant polycystic kidney disease that ultimately progressed to end-stage renal disease. She was operated for renal transplantation before 6 months. She had hypokalemia and hypertension at that time. The ratio of plasma aldosterone over plasma renin activity was 851.7. The computed tomography (CT) revealed 2.4x1.7 cm sized adrenal mass on the right side. The pre-transplantation CT also showed that there had been adrenal mass in the same location even before the transplantation. Right adrenalectomy was performed. After she got discharged, she was again presented with nausea and vomiting. She developed hyperkalemia and was diagnosed as hyporeninemic hypoaldosteronism. She was prescribed with fludrocortisones and recovered from the disease, and resumed the state of normokalemia and normotension.

Spontaneous Subcapsular Hematoma of the Liver in a Patient on Maintenance Hemodialysis / 대한신장학회지

Spontaneous bleeding in various parts of the body has been reported in patients receiving maintenance hemodialysis, but reports on spontaneous subcapsular hematoma of the liver are scarce. We present a case of spontaneous subcapsular hematoma of the liver which developed in a 53-year-old man with maintenance hemodialysis. He was admitted to our hospital with epigastric pain and abnormal liver function test. On abdominal computed tomographic (CT) scan, a large, well-defined subcapsular mass of the liver with a density consistent with blood was observed. We performed embolization of the bleeding vessel and percutaneous drainage of the hematoma. Five months later, follow up abdominal CT scan revealed a moderate reduction of the subcapsular hematoma. In conclusion, the possibility of spontaneous hematoma of the liver should be considered in hemodialysis patients with epigastric pain, unexplained anemia and abnormal liver function.

Spontaneous Cauda Equina Syndrome in a Renal Transplant Patient with Long-term Azathioprine Treatment / 대한이식학회지

Azathioprine is a conventional immunosuppressant in renal transplantation but long-term administration may lead to hematologic complications. We here report a cauda equina syndrome caused by spontaneous epidural hematoma in a renal transplant recipient who had undergone long-term azathioprine treatment. A 34 year-old male was admitted to our hospital with complaints of numbness of the lower extremities and back pain. He had received renal transplantation 14 years ago and had been on sole therapy with azathioprine for 11 years. Three months before admission, the patient developed pancytopenia, and a subsequent bone marrow biopsy revealed hypocellularity. Azathioprine was replaced by tacrolimus and steroids thereafter. After a three months discontinuation of azathioprine, an epidural hematoma developed and resulted in cauda equina syndrome. Regular follow-up of complete blood count and change of immunosuppressants with less bone marrow toxicity should be considered in patients receiving azathioprine for long-term period.

Expression and Function of Calcineurin in Inflammatory Arthritis

BACKGROUND: Calcineurin plays a crucial role in T cell activation, cell growth, apoptosis, and angiogenesis, and its over-expression has been implicated in the pathogenesis of cardiomyopathy and stroke. However, the expression and function of calcineurin in the pathologic lesion of chronic inflammatory diseases, like rheumatoid synovium, remain to be defined. This study was aimed to determine the role of calcineurin in inflammatory arthritis and investigate the expression and function of calcineurin in the rheumatoid synovium and synoviocytes, the actual site of chronic inflammation. METHODS: Immunohistochemical staining using specific antibody to calcineurin was perfomed in the synovium of rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLS) from RA and osteoarthritis (OA) patients were isolated from RA and OA patients, and cultured with IL-1beta and TNF-alpha in the presence or absence of cyclosporin A, a calcineurin inhibitor. The calcineurin expression was assessed by phosphatase assay and Western blotting analysis. IL-6, -10, -17, matrix metalloproteinase (MMP)-1, -2, -3, and -9 released into the culture supernatants were measured by ELISA. After transfection with GFP-Cabin 1 gene into synoviocytes, the levels of IL-6 and MMPs were measured by ELISA. RESULTS: Calcineurin was highly expressed in the lining layer of synovium and cultured synoviocytes of RA patients. The elevated calcineurin activity in the rheumatoid synoviocytes was triggered by proinflammatory cytokines such as IL-1beta and TNF-alpha. In contrast, IL-10, an anti-inflammatory cytokine, failed to increase the calcineurin activity. The targeted inhibition of calcineurin by the over-expression of Cabin 1, a natural calcineurin antagonist, inhibited the production of IL-6 and MMP-2 by rheumatoid synoviocytes in a similar manner to the calcineurin inhibitor, cyclosporin A. CONCLUSION: These data suggest that abnormal activation of calcineurin in the synoviocytes may contribute to the pathogenesis of chronic arthritis, and thus provide a potential target for controlling inflammatory arthritis.

A Case of Patient with Coincident Lung Cancer and Rheumatoid Arthritis Treated with Docetaxel-Cisplatin Chemotherapy / 대한류마티스학회지

A 54-year-old male was admitted due to lung cancer and polyarthralgia involving wrist, hand, shoulder, and ankle joints. Five months ago, he had been diagnosed as adenocarcinoma of the lung, and treated with three cycles of chemotherapy using gemcitabine and cisplatin. In the course of chemotherapy, he had complained symmetrical polyarthralgia of hand and shoulder joints, resembling rheumatoid arthritis (RA). After treatment with chemotherapeutic agents, he still had severe polyarthritis refractory to anti-rheumatic drugs, including prednisolone, hydroxychloroquine, and methotrexate, and thus referred to our hospital. We changed the previous anti-cancer regimens to cisplatin plus docetaxel, a semisyntheic taxane molecule, which is known to suppress experimental polyarthritis. With additional three cycles of cisplatin plus docetaxel, RA disease activity as well as polyarthralgia was nearly completely resolved, and the extent of lung cancer was not aggravated. Although RA patients have an increased risk of malignancy, the outbreak of RA was very rare in lung cancer patients. Here we report a case of coincident lung cancer and rheumatoid arthritis, which was successfully treated by docetaxel plus cisplatin chemotherapy.

Four Cases of Verapamil Deleterious Effects in Chronic Renal Failure / 대한신장학회잡지

Four hypertensive patients with chronic renal insufficiency who were treated with sustained release verapamil hydrochloride subsequently developed acute toxic effects. All four patients developed marked bradycardia, hypotension, hyperkalemia and metabolic aciodosis and were treated with atropine, fluid therapy, potasium lowing measure, dialysis, and temporary pacemaker, and were restored to the renal function and sinus rhythm after 12-24 hr. Patients with renal impairement who are treated with sustained release verapamil may accumulate verapamil or its metabolites and develop toxic side effects. We conclude that sustained release verapamil should be used with caution in chronic renal failure and that patients should be closely monitored for adverse cardiovascular, metaboic, and hepatic side effects.

A Case of Pulmonary Cryptococcosis in an Immunocompetent Patient / 결핵및호흡기질환

We experienced a case of pulmonary cryptococcosis in an immunocompetent patient who presented with uncommon radiological findings. He complained of a dry cough for 3 weeks. The chest X-ray and CT showed multiple, variable sized, and irregular patch consolidations with cavities combined with some ground glass opacities in both lower lung fields. The diagnosis was made histologically via a thoracoscopic lung biopsy. The patient was administered oral fluconazole has since been well.

The anti-inflammatory effects of angiotensin II blockade in animal model of cyclosporine-induced nephropathy / 대한내과학회지

BACKGROUND: Long-term treatment of immunosuppresant CsA causes interstitial inflammation and fibrosis in the kidney. Renin-angiotensin system (RAS) plays the most important role in the pathogenesis CsA-induced renal injury. Accordingly we evaluated the anti-inflammatory effect of angiotensin II blockades using losartan (LSRT) in a rat model of chronic CsA nephropathy. METHODS: Male Sprague-Dawley rats, initially weighing 225 to 250 g, were used. After 1 week of a low-salt diet (0.05% sodium), the rats were randomized into four groups and treated for 4 weeks. The Vehicle (VH) group was treated with olive oil. The VH+LSRT group was treated with olive oil and LSRT. The CsA group received CsA. The CsA+LSRT group was simultaneously treated with CsA and LSRT. The anti-inflammatory effect of LSRT was evaluated with C-reactive protein (CRP) expression, osteopontin (OPN) mRNA and protein expression, and ED-1 infiltration RESULTS: The CsA treatment caused an increase in serum creatinine and a decrease in creatinine clearance compared with that of the VH group. Intrarenal CRP positive cells were significantly decreased in the CsA+LSRT group compared with the CsA group (38.0 +/- 2.1 vs. 65.0 +/- 5.1, p<0.01). In the CsA group, the degree of OPN mRNA expression was increased compared with that of the VH group. But, OPN mRNA expression was decreased in the CsA+LSRT group (387.5 +/- 56.6% vs. 719.8 +/- 58.5%, p<0.05). In the degree of ED-1 infiltration, we had a similar results such as CRP and OPN mRNA expression (CsA group 30.5 +/- 8.0 vs. CsA+LSRT 86.0 +/- 11.0, p<0.01). CONCLUSION: We concluded that the anti-inflammatory effects of angiotensin II blockade has a potential protective effect against CsA-induced renal injury.