Optimal hemoglobin level for anemia treatment in a cohort of hemodialysis patients

BACKGROUND: Anemia is a major risk factor that contributes to mortality in patients with chronic kidney disease. There is controversy over the optimal hemoglobin (Hb) target in these patients. This study investigated the association between Hb level and mortality in a cohort of hemodialysis (HD) patients in Korea. METHODS: This study was a multicenter prospective observational study of maintenance HD patients that was performed for 5 years in western Seoul, Korea. Three hundred and sixty-two participants were enrolled. Laboratory values and mortality were accessed every 6 months. Repeated measures of laboratory values in each interval were averaged to obtain one semiannual mean value. The Hb values were divided into six groups: (1) Hb or =13 g/dL. We analyzed the odds ratio for all-cause mortality, based on the Hb group, and adjusted for demographics and various laboratory values. Statistics were performed with SAS, version 9.1 software (SAS Institute Inc., Cary, NC, USA). RESULTS: Mortality odds ratios relative to the reference group (10-11 g/dL) in the fully adjusted model were 3.61 for or =13 g/dL (* indicates P<0.05). CONCLUSION: In this study, a Hb level of 10-11 g/dL was associated with the lowest mortality among the groups with Hb level<13 g/dL. Larger interventional trials are warranted to determine the optimal Hb target for Korean HD patients.

Maxillofacial Enlargement in Secondary Hyperparathyroidism Successfully Treated by Limited Parathyroidectomy and Paricalcitol / 대한신장학회지

Maxillary enlargement is a rare complication of secondary hyperparathyroidism (SHPT). A 35-year-old Korean man undergoing chronic hemodialysis presented with a painless enlargement involving the maxilla and mandible. Plain radiography and CT scan showed bony expansion at the maxilla and mandible with multiple radiolucency. Serum intact parathyroid hormone (iPTH) was >1,600 pg/mL. Tc-99m sestamibi (MIBI) parathyroid scan and neck sonogram were compatible with SHPT. He underwent limited parathyroidectomy and commenced a course of paricalcitol. Fifteen months after surgery, maxillary enlargement and bony resorptions involving both hands markedly improved. Thirty-six months after the surgery, the serum iPTH level was 109.3 pg/mL. This is the first report in Korea documenting a patient with maxillary enlargement in SHPT who was successfully treated with limited parathyroidectomy and paricalcitol.

Mandibular Enlargement, Metastatic Pulmonary Calcification and Gastric Mucosal Calcinosis in a Patient with Chronic Kidney Disease-mineral Bone Disorder / 대한신장학회지

Secondary hyperparathyroidism is one of the most common complications of patients with chronic kidney disease (CKD). Mandibular enlargement, metastatic pulmonary calcification, and gastric mucosal calcinosis are rare complications in these patients. The defect of calcium and phosphorus metabolism may precipitate pathologic calcification at diverse organs and soft tissue, and change bone architecture. In case of involving periarticular area, patients usually present with localized swelling, pain, and reduced mobility in affected sites. However, in case of organ involvement, except in an advanced stage of disease, there are no specific symptoms. Among these patients, treatment strategies include tight control of calcium and phosphate levels, parathyroidectomy for hyperparathyroidism, renal transplantation, and local excision of calcific lesions. We report a case of mandibular enlargement, metastatic pulmonary calcification, and gastric mucosal calcinosis due to CKD with improvement 3 months after medical and surgical treatment.

Supernumerary Parathyroid Gland Diagnosed with Contrast-enhanced MDCT after Total Parathyroidectomy / 대한신장학회지

We report a case of a 25-year old man with chronic kidney disease with secondary hyperparathyroidism who had persistent elevation of serum parathyroid hormone level after the immediate total parathyroidectomy and autotransplantation. To localize supernumerary (ectopic) parathyroid gland, we checked Tc-99m MIBI scintigraphy, MDCT and PET-CT. Contrast-enhanced MDCT showed a small strong enhancing lesion over left bracheocephalic vein, and PET-CT showed multiple brown tumors. We removed the supernumerary parathyroid gland and got a rapid drop of parathyroid hormone level.

Peritonitis due to Aspergillus niger in Two Continuous Ambulatory Peritoneal Dialysis Patients / 대한신장학회지

Aspergillus peritonitis is a rare but serious cause of peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients. We report 2 cases of peritonitis caused by Aspergillus niger in CAPD which were treated successfully with voriconazole and caspofungin, respectively, and catheter removal. Both patients initially received amphotericin B; however, they were not cured with the agent. We briefly discuss the proper selection of antifungal agent and the treatment duration. Previously reported cases of the CAPD peritonitis caused by A. Niger are also reviewed in this article.

25-Hydroxyvitamin D Status in Patients with Chronic Kidney Disease in a Single Center / 대한신장학회지

PURPOSE: We checked the levels of serum 25-hydroxyvitmain D (25OHD) in the patients with chronic kidney disease (CKD) to survey the status of vitamin D levels, to see the seasonal variations of 25OHD, and to evaluate the relationships among the levels of intact PTH, corrected calcium, and phosphorus. METHODS: We defined vitamin D insufficiency and vitamin D deficiency as serum 25-hydroxyvitamin D levels between 20 and 30 ng/mL and below 20 ng/mL, respectively. 185 patients in a single center were enlisted who categorized into 3 groups, CKD2-3, CKD4, and CKD5 by eGFR using MDRD7 equation. To see the seasonal differences of the levels of 25OHD, we collected laboratory data two times per each patient during summer division (April to September) and winter division (October to March). RESULTS: Prevalences of hypovitaminosis D were 42.8% (CKD2-3), 66.1% (CKD4), 92.8% (CKD5) in summer division and 48.7% (CKD2-3), 73.1% (CKD4), 92.8% (CKD5) in winter division. Seasonal difference of the levels of 25OHD was evident only in CKD stage 2-3 (p=0.018). Negative correlations were recognized between 25OHD and intact PTH (r=-0.2048, p<0.001), phosphorus (r=-0.1711, p=0.0011). CONCLUSION: Hypovitaminosis D is prevalent even in patients with early stages of CKD. The levels of 25OHD decreased significantly in winter division in patients with CKD stages 2-3. The levels of 25OHD were inversely correlated with those of intact PTH, phosphorus, respectively.

Erythropoietin (EPO) Attenuates Renal Injury in an Experimental Model of Cisplatin-induced Nephrotoxicity in Rats / 대한신장학회지

PURPOSE:In addition to its hematopoietic effects, EPO has protective effects in vivo in several animal models of acute renal injury. We examined whether EPO also attenuated renal injury in a rat model of cisplatin-induced nephrotoxicity via anti-apoptotic and anti-inflammatory actions. METHODS:Male SpragueDawley rats were divided into four groups: control rats, EPO+control rats, cisplatin rats, and EPO+cisplatin rats. EPO treatment was started 24 h prior to cisplatin administration. Then, 96 h after cisplatin administration, all experimental animals were killed. And renal molecular, functional and structural parameters were measured. RESULTS:The serum levels of BUN and creatinine in the 96 h after cisplatin administration were significantly lower than in cisplatin rats. On microscopic examination, the magnitude of renal tubular epithelial damage in the EPO+cisplatin rats was also significantly less than that of cisplatin rats. Renal expression of TNF-alpha Fas, MCP-1 and TGF-betain the cisplatin rats was significantly higher than those of control rats and EPO+control rats. The levels of TNF-alpha Fas, MCP-1 and TGF-betagene expression in EPO+cisplatin rats were significantly lower than those of cisplatin rats. The Bcl-2 mRNA level in EPO+cisplatin rats was significantly higher than in cisplatin rats. EPO+cisplatin rats had significantly fewer TUNEL-positive cells. CONCLUSION:These results suggest that EPO has a protective effect against experimental cisplatin- induced renal injury and that the anti-inflammatory and anti-apoptotic properties of EPO may be involved.

A Case of Small Bowel Bleeding Treated by Single Balloon Enteroscopy in a Patient on Maintenance Hemodialysis / 대한신장학회지

Anemia is a common complication of hemodialysis. It reduces the quality of life and is recognized as adverse risk factor. The cause of anemia in CKD (chronic kidney disease) include lack of erythropoietin, gastrointestinal (GI) bleeding, hypothyroidism, hidden infection, and blood loss in hemodialysis. GI bleeding is not unusual complication in patient on maintenance hemodialysis, caused by uremia, medicine (NSAIDS, antiplatelet agents, anticoagulants), angiodysplasia, and ulcer. In CKD patients, GI bleeding is found in various sites over the whole bowel. Small bowel bleeding is one of the most common causes of obscure GI bleeding and constitutes 2-10% of all GI bleeding. Regarding the small bowel bleeding, diagnosis and treatment are much improved recently with the help of wireless capsule endoscopy and double or single balloon enteroscopy. We report a case of GI bleeding due to erosion of small bowel, which was diagnosed and treated with the single-balloon enteroscopy in patients on maintenance hemodialysis.

Acute Renal Failure Complicated by Valaciclovir in a Patient with IgA Nephropathy / 대한신장학회지

Valaciclovir is L-valyl ester of acyclovir which has the antiviral effect against herpes zoster virus and Cytomegalovirus. Its adverse effects were reported as nephrotoxicity and neurotoxicity. Although the mechanism of nephrotoxicity of valaciclovir is indeterminate, several hypotheses such as obstructive uropathy and interstitial nephritis have been suggested. We experienced a 54-year-old female patient with IgA nephropathy who developed acute renal failure after taking valaciclovir. She did not develop either central neuropathy or respiratory muscle weakness. The serum creatinine was normalized after 6 days by withdrawal of valaciclovir and hydration. When we use valaciclovir in the elderly or patients with preexisting renal disease, we should monitor the renal function carefully.

Clinical outcomes of renal patients treated with therapeutic plasma exchange / 대한내과학회지

BACKGROUND: Therapeutic plasma exchange (TPE) is a procedure by which plasma is removed from whole blood and this can be used in the treatment of some renal diseases. METHODS: We reviewed the medical records for the chief complaints, underlying diseases, clinical courses and treatment outcomes of 23 patients who had been treated with TPE at the Renal Division of Chungnam National University Hospital from January 1995 to June 2005. RESULTS: Patients with thrombotic thrombocytopenic purpura (TTP), microcopic polyangitis, lupus nephritis, hyperacute humoral rejection after kidney trasnplantation and rapidly progressive glomerulonephritis (RPGN) secondary to subacute bacterial endocarditis were included in this study. Among the 11 patients with TTP, six patients improved and two patients progressed to end-stage renal disease (ESRD). Three patients with TTP died. Seven patients with microscopic polyangitis and two patients with lupus nephritis had pulmonary hemorrhage at the time of TPE. Eight of the 11 TTP patients showed improvement of their pulmonary hemorrhage after TPE. One of the two patients with hyperacute humoral rejection after kidney transplantation and one patient with secondary RPGN were improved after TPE. Hypotension (three cases) was the most common adverse effect of TPE, followed by two cases of itching sensation and one case of fever with chills. CONCLUSIONS: Therapeutic plasma exchange was an effective treatment for patients with TTP, microscopic polyangitis, lupus nephritis with pulmonary hemorrhage and hyperacute humoral rejection after kidney transplantation.

A Case of Cystadenocarcinoma of the Pancreas in a Patient with Autosomal Dominant Polycystic Kidney Disease / 대한신장학회지

Polycystic kidney disease is an autosomal dominant disease that may be associated with liver and pancretic cysts. Mitral valve prolapse and intracranial berry aneurysms are also well-known manifestations of autosomal dominant polycystic kidney disease (ADPKD). Cystadenocarcinoma of the pancreas is uncommon and accounts for only 1% of primary pancreatic malignancies. Few cases were reported to have an association of ADPKD and pancreatic malignancies. We report a 63-year-old man with ADPKD who was admitted to our hospital with anorexia and severe weight loss. After abdominal CT and histologic examination, he was diagnosed as pancreatic cystadenocarcinoma with lung, spleen, and liver metastasis. To prolong the life of the patient, we tried gemcitabine and cisplatin combination chemotherapy. But the patient died 2 months after diagnosis due to the disease progression.

The Effect of Cobalt Chloride Pre-treatment on Experimental Ischemia-Reperfusion Renal Injury / 대한신장학회잡지

BACKGOUND: Cobalt chloride (COCL) has hypoxia-mimetic effects by inhibiting degradation of HIF-1alpha, which is a master regulator of genes activated by low oxygen tension. Heme oxygenase-1 (HO-1), an inducible heat shock protein, is known to have cytoprotective effects against ischemic injury. This study evaluated the efficacy of COCL in a bilateral renal ischemia-reperfusion (I-R) injury model of male Sprague-Dawley rats. METHODS: I-R renal injury was induced by 45 min clamping of both renal arteries. Rats in the sham (n=6) and I-R control groups (n=8) had been drinking tap water, whereas rats in the COCL treated sham (n=6) and COCL treated I-R groups (n=9) had been drinking water containing 2 mM COCL from day -10 to day 1. RESULTS: The serum level of creatinine 24 hrs after surgery was 2.6+/-1.1 (mean+/-SD) mg/dL in I-R COCL treated group, significantly lower than that in I-R control group (4.8+/-1.6 mg/dL, p<0.05). The renal HO-1 gene expression and protein signal were significantly upregulated in the COCL treated sham group compared to sham operated control rats (all, p<0.05). The expressions of TGF-beta MCP-1, TNF-alpha endothelin-1 and Fas genes in COCL treated I-R rats were significantly lower than those of I-R control rats (all, p<0.05). The level of Bcl-2 gene expression of COCL treated I-R rats was significantly higher than the level of I-R control rats (p<0.05). CONCLUSION: It is speculated that the pretreatment of COCL in I-R rat model attenuates ischemic renal injury and at least in part, upregulation of renal HO-1 is involved in this mechanism.

Allopurinol Induced DRESS Syndrome in Patients with Chronic Kidney Disease / 대한신장학회잡지

Allopurinol decreases serum uric acid levels in hyperuricemic patients and may slow the progression of renal diseases, Allopurinol-induced Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome, which was called allopurinol hypersensitivity syndrome previously, is very rare and can be associated with serious complications characterized by fever, skin rash, acute hepatocelluar injury, renal insufficiency, leukocytosis, and eosinophilia. We report four cases of allopurinol-induced DRESS syndrome in patients with chronic kidney disease who had been taking allopurinol as a dose of 100 mg daily for 5 to 10 weeks. They presented with skin rash and eosinophilia. Blood chemistry showed acute aggravation of renal dysfunction. All of the patients recovered from DRESS syndrome and renal function of them were returned to the basal levels in several weeks.

A case of systemic lupus erythematosus associated with Hashimoto's thyroiditis and aplastic anemia / 대한내과학회지

We report a 45-year-old female who presented with azotemia, pancytopenia, pericardial effusion, hypothyroidism, decreased complement and positive ANA and was diagnosed as systemic lupus erythematosus (SLE). She referred to our hospital for the evaluation of azotemia. Bone marrow findings were compatible with aplastic anemia and Hashimoto's thyroiditis was diagnosed. After 3 days of methylprednisolone pulse therapy, the aplastic anemia responded and started to improve. She is visiting our clinic on a regular interval and showing good response to maintenance therapy. Hashimoto's thyroiditis is not rare in SLE, and aplastic anemia is relatively rare in SLE but, SLE that is combined with Hashimoto's thyroiditis and aplastic anemia simultaneously, has not been reported as far as our knowledge concerned. So, we report a case of successful treatment of SLE combined with Hashimoto's thyroiditis and aplastic anemia by steroid and thyroxine.

Efficacy of erythropoietin in renal function of pre-dialysis patients with chronic renal failure / 대한내과학회지

BACKGROUND: Anemia is one of the most important risk factors for cardiovascular morbidity and mortality in patients with chronic renal failure. The most effective treatment modality for anemia is erythropoietin injection. Besides erythropoietic effect, erythropoietin has multiple beneficial effects such as anti-oxidant, anti-hypoxic, anti-apoptotic and vasculogenetic effects, and prevents tubular lesions and interstitial fibrosis. Despite lots of advantages of erythropoietin therapy, the number of patients treated with this agent is modest, particularly during the pre-dialysis chronic renal failure. We conducted a clinical trial to evaluate the effects of erythropoietin on renal function in the anemic pre-dialysis patients with chronic renal failure. METHODS: Data of 23 pre-dialysis patients with chronic renal failure were analyzed retrospectively 6 months prior, and prospectively 6 months after the initiation of erythropoietin therapy. Erythropoietin was admitted at a dose of 3000 IU weekly with supplementary iron. RESULTS: The average hematocrit and hemoglobin rose from 22.1+/-2.5%, 7.4+/-0.8 g/dL to 28.4+/-4.2%, 9.6+/-1.5 g/dL, respectively. When linear regression analysis was applied to pre- and post-erythropoietin glomerular filtration rate and 1/Cr, mean rate of decline of glomerular filtration rate were significantly delayed (p=0.039) but that of 1/Cr had a tendency to be delayed but was not statistically meaningful (p=0.099). CONCLUSIONS: Treatment of the anemia with low dose erythropoietin in pre-dialysis patients with chronic renal failure is relatively safe and may slow the rate of renal function deterioration.

A Case of Trimethoprim-Sulfamethoxazole and Omeprazole Induced Acute Interstitial Nephritis in a Patient with Renal Transplantation / 대한신장학회잡지

A 44-year-old woman diagnosed with idiopathic chronic kidney disease was subjected to living related renal transplantation from her brother. Immunosuppressant consisted of cyclosporine, mycophenolate mofetil, and prednisolone. On the day 2 after transplantation, her serum level of BUN and creatinine (Cr) were normalized to 13.4 mg/dL and 1.06 mg/dL respectively. Urine output was also well maintained. On day 9, her body temperature was 39degrees C, serum level of BUN and Cr were increased to 20.8 mg/dL and 1.54 mg/dL respectively and urine output was decreased with weight gain. Her serum cyclosporine trough level was 118 ng/dL. DTPA renal scan and Doppler sonography suggested acute rejection. So, antirejection treatment was started with methylprednisolone pulse therapy under the cover of empirical broad spectrum antibiotics. On day 11, graft biopsy was done and the biopsy was compatible with acute interstitial nephritis. The relationship between the time of renal dysfunction and drug medication was analyzed; trimethoprim-sulfamethoxazole (TMP-SMZ) and omeparzole were suspected as causative drugs. So, TMP-SMZ and omeprazole were discontinued. Her serum Cr was slowly increased to 2.32 mg/dL until day 15. And afterward, her serum Cr decreased and normalized We suggest that acute interstitial nephritis should be considered among the many causes of early renal allograft dysfunction when using TMP- SMZ and omeprazole.

3 Cases of Fenoverine-Induced Rhabdomyolysis / 대한신장학회잡지

Fenoverine is a spasmolytic drug. It has been reported as a causative drug for rhabdomyolysis in France and also in Korea. Well known risk factors for fenoverine induced rhabdomyolysis are hepatic dysfunction, renal dysfunction, concomitant use of lipid lowering drug, mitochondrial myopathy, lipid storage myopathy or malignant hyperthermia. We describe the clinical findings of 3 cases of fenoverine-induced rhabdomyolysis. (Case 1) A 78 year-old male patient complained of generalized myalgia after 7 days medication of fenoverine 300 mg, daily. (Case 2) A 72 year-old female who had been on statin medication for 4 years, complained of generalized myalgia and weakness after 1 day medication of 300 mg of fenoverine. (Case 3) A 57 year-old female who was diagnosed with liver cirrhosis, complained of generalized myalgia, after 4 days medication of 300mg of fenoverine. Laboratory and Tc-99m MDP bone scan findings were compatible with rhabdomyolysis in all 3 patients: ARF was complicated in case 2 and 3. The renal function improved with supportive care. As far as our knowledge concerned, case 1 is the first report of fenoverine-induced rhabdomyolysis without previously known risk factors. So we suggest when physicians are prescribing fenoverine, careful monitoring of symptoms and signs of rhabdomyolysis should be taken to all patients.

A Case of Idiopathic Light Chain Deposition Disease / 대한신장학회잡지

Light chain deposition disease (LCDD) is a systemic disorder characterized by the deposition of monoclonal immunoglobulin light chains (LCs) in various organs. As LCs are overproduced by an abnormal clone of B cells, LCDD is usually described in the course of plasma cell dyscrasias or other lymphoproliferative disorders. However, it can occur in the absence of any detectable hematological disorder even during prolonged follow-up. We experienced a case of 62-year-woman who presented generalized edema, massive proteinuria and renal insufficiency. The histologic findings showed nodular glomerular mesangial expansion and prominent ribbon like immunohistochemical staining for kappa-light chain in the glomerular capillary wall. There was no evidence of multiple myeloma in bone marrow biopsy specimen. Because she refused the intensive chemothrapy, low dose of prednisolone and cyclophosphamide were prescribed for 6 months. Her renal function was maintained relatively well without renal replacement therapy for 7 months. We report a case of idiopathic LCDD not associated with multiple myeloma or other plasma cell dysclasia.

A Case of Tuberous Sclerosis with Spontaneous Rupture of Renal Angiomyolipoma / 대한신장학회잡지

Tuberous sclerosis is an autosomal dominant disorder characterized by seizures, mental retardation and hamartomatous tumors in multiple organs, including subependymal giant cell astrocytomas, cortical tubers, cardiac rhabdomyoma, pulmonary lymphangiomyomatosis and renal angiomyolipomas. However, these clinical features are not always present. The following is a report concerning a 30-year-old woman with tuberous sclerosis who suffered a spontaneous hemorrhage into the angiomyolipoma of the kidney and underwent curative selective renal embolization. The patient had a medical history of focal seizures. Moreover, brain magnetic resonance imaging revealed typical signs of tuberous sclerosis, and a high resolution computerized tomography of the chest showed bilateral nodules with irregular margins and multiple thin-walled cystic lesions. There was no family history of renal disease or of tuberous sclerosis. As such, this case exhibited rare clinical manifestations of tuberous sclerosis involving multiple organs.

The clinical impact of the referral pattern to nephrologist in patients with chronic renal failure / 대한내과학회지

BACKGROUND: It has been speculated that many factors including age, hemoglobin serum albumin level and socioeconomic factors are closely related with the mortality and morbidity of patients with end-stage renal disease (ESRD). Optimal management of the patients with pre-dialysis chronic kidney disease has been thought to be very important for the prognosis of end-stage renal disease patients on dialysis. METHODS: In order to evaluate the clinical impact of referral pattern of chronic renal failure patients to nephrologist, 217 patients (male 129, female 88) who initiated hemodialysis from Jan. 1998 to Jul. 2002 in Chungnam National University Hospital were included in this retrospective analysis. Patients were defined as early referral (n=129) when hemodialysis was initiated at least 90 days after the first visit to nephrologist and as late referral (n=88) when hemodialysis was performed within 90 days after the first visit to nephrologist. RESULTS: Male gender and medical aid coverage were significantly more prevalent in late referral than early referral group (p<0.05, p<0.05, respectively). Late referral group had more combined medical problems than those of early referral group (p<0.05). Serum albumin level of early referral group was significantly higher than that of late referral group at the initiation of hemodialysis (p<0.001). At the initiation of hemodialysis, temporary central catheter for the blood access was needed in 85.2 % of late referral group. However, only 41.6% of early referral group needed such temporary catheter (p<0.001). One year after initiation of hemodialysis treatment, early referral group showed significantly lower mortality rate than that of late referral group (p<0.001). CONCLUSION: The early referral of chronic renal failure patients to nephrologist has beneficial effects including higher one-year survival after beginning of hemodialysis.