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.

Orthorexia Nervosa with Hyponatremia, Subcutaneous Emphysema, Pneumomediastimum, Pneumothorax, and Pancytopenia

30-year-old male was admitted with general weakness and drowsy mental status. He had eaten only 3-4 spoons of brown rice and fresh vegetable without salt for 3 months to treat his tic disorder, and he had been in bed-ridden state. He has had weight loss of 14 kg in the last 3 months. We report a patient with orthorexia nervosa who developed hyponatremia, metabolic acidosis, subcutaneous emphysema, mediastinal emphysema, pneumothorax, and pancytopenia and we will review the literature. Also, we mention to prevent refeeding syndrome, and to start and maintain feeding in malnourished patients.

Serum Globotriaosylceramide Assay as a Screening Test for Fabry Disease in Patients with ESRD on Maintenance Dialysis in Korea

BACKGROUND/AIMS: Fabry disease is an X-linked recessive and progressive disease caused by alpha-galactosidase A (alpha-GaL A) deficiency. We sought to assess the prevalence of unrecognized Fabry disease in dialysis-dependent patients and the efficacy of serum globotriaosylceramide (GL3) screening. METHODS: A total of 480 patients of 1,230 patients among 17 clinics were enrolled. Serum GL3 levels were measured by tandem mass spectrometry. Additionally, we studied the association between increased GL3 levels and cardiovascular disease, cerebrovascular disease, or left ventricular hypertrophy. RESULTS: Twenty-nine patients had elevated serum GL3 levels. The alpha-GaL A activity was determined for the 26 patients with high GL3 levels. The mean alpha-GaL A activity was 64.6 nmol/hr/mg (reference range, 45 to 85), and no patient was identified with decreased alpha-GaL A activity. Among the group with high GL3 levels, 15 women had a alpha-GaL A genetics analysis. No point mutations were discovered among the women with high GL3 levels. No correlation was observed between serum GL3 levels and alpha-GaL A activity; the Pearson correlation coefficient was 0.01352 (p = 0.9478). No significant correlation was observed between increased GL3 levels and the frequency of cardiovascular disease or cerebrovascular disease. CONCLUSIONS: Fabry disease is very rare disease in patients with end-stage renal disease. Serum GL3 measurements as a screening method for Fabry disease showed a high false-positive rate. Thus, serum GL3 levels determined by tandem mass spectrometry may not be useful as a screening method for Fabry disease in patients with end stage renal disease.

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.

Aldosterone Synthase Gene (CYP11B2) Polymorphism in Korean End-Stage Renal Disease Patients on Hemodialysis

Aldosterone synthase gene (CYP11B2) -344C/T polymorphism has been reported to be associated with serum aldosterone level, urinary aldosterone excretion, blood pressure, and left ventricular size and mass. The aim of this study was to evaluate the relation between CYP11B2 polymorphism and end-stage renal disease (ESRD) in the Korean population and the association with CYP11B2 polymorphism and cardiovascular morbidity in ESRD patients on hemodialysis. Genotyping was performed in 134 control subjects and 271 ESRD patients for CYP11B2 polymorphism using polymerase chain reaction through subsequent cleavage with restriction enzyme. Also current blood pressure, demographic, anthropometric and biochemical variables were investigated. The genotype distribution did not differ between ESRD patients and controls and there were no significant differences in blood pressure, use of antihypertensive medication, left ventricular hypertrophy and cardiovascular disease among the three genotypes in ESRD patients on hemodialysis. Our findings do not support the hypothesis that CYP11B2 polymorphism may be associated with prevalence of ESRD and suggest that CYP11B2 polymorphism may not be a genetic marker for cardiovascular morbidity in Korean ESRD patients.

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.

Asymptomatic Cryptococcus and Subsequent Symptomatic Tuberculosis Infection in a Renal Transplant Patient / 대한이식학회지

Cryptococcus is an important opportunistic pathogen of fungal infection after organ transplantation. And, tuberculosis is also a major cause of infection in immunocompromised patients. We experienced a case of asymptomatic cryptococcal pulmonary infection detected by routine chest X-ray in a renal transplant patient, and a subsequent development of symptomatic multi-drug resistant pulmonary tuberculosis during oral fluconazole treatment. For the appropriate infection control, we should make the thorough evaluation in immunocompromised organ-transplant patients.

Serum Cystatin C Compared with Other Markers for Glomerular Filtration Rate / 대한신장학회잡지

BACKGROUND: Serum cystatin C has been suggested to be a better marker for GFR than creatinine because believed to be produced at a constant rate by most nucleated cells, and eliminated exclusively by glomerular filtration We compared serum cystatin C with creatinine-based estimates, especially in patients with old age or extreme protein composition to investigate the utility of cystatin C and to identify factors that influence on cystatin C other than renal function. METHODS: A total of 446 patients, admitted to department of nephrology of Korea University Anam Hospital From September 2003 to March 2004, had their glomerular filtration rate (GFR) estimated by DTPA scintigraphy, clearance of creatinine, and calculated from Cockcroft-Gault and Modification of Diet in Renal Disease (MDRD) formula. A body composition, the serum creatinine and cystatin C levels were also measured. RESULTS: Serum cystatin C showed similar correlation with DTPA GFR to serum creatinine. The formula, GFR (mL/min/1.73m2) = 61.84 x cystatin C(-0.8135), was derived with better precision than either Cockcroft-Gault or MDRD. The diagnostic accuracy of cystatin C was not better than creatinine in older patients as well as those with overweight, or an extreme protein composition. The addition of age, body surface area, and gender increased the R2 for both serum creatinine and cystatin C. CONCLUSION: Serum cystatin C is a good marker for GFR, but not superior to serum creatinine even in patients with old age, overweight, or an extreme protein composition, and affected by age, body surface area, and gender independent on renal function.

Association of IL-10 genotypes with cardiovascular risk factors in patients with hemodialysis / 대한내과학회지

BACKGROUND: Chronic systemic inflammation in ESRD patients due to uremia and hemodialysis procedure itself comes into notice as a main factor for premature mortality secondary to rapid progressing atherosclerosis. Various pro-inflammatory cytokine, known to mediate these reaction of malnutrition, inflammation and atherosclerosis, are regulated by anti-inflammatory cytokine, such as IL-10. Quantitative production of IL-10 shows interindividual variability determined genetically by polymorphisms of promotor gene. The aim of this study was to measure the degree of IL-10 synthesis in ESRD patients treated with hemodialysis and evaluate the association with genotypes and cardiovascular risk factors. METHODS: The IL-10 genotypes for polymorphic bases at position at -1082 was determined in 66 chronic hemodialysis patients and 98 healthy subjects using highly specific PCR and the lipopolysaccharide (LPS)-stimulated IL-10 (sIL-10) release from whole blood were measured by ELISA. RESULTS: The distribution of the IL-10 genotypes in hemodialysis patients were similar to the general population, but the proportion of A allele in hemodialysis group was significantly higher (72.3% vs 59.8%, p=0.05). sIL-10 concentration were lower in hemodialysis patients compared with normal control (21.1 pg/mg vs 36.1 pg/mg, p=0.001) and both groups showed same relationship of sIL-10 with genotypes, that AA type was low producer. In multiple regression analysis, sIL-10 of normal group correlated negatively with age, creatinine, uric acid and existence LVH, and positively with albumin, hemoglobin. On the other hand, lower albumin, lower ejection fraction on echocardiography and existence of left ventricular hypertrophy were associated with higher sIL-10 in hemodialysis group. CONCLUSION: Polymorphisms by IL-10 genotypes were associated with production of IL-10 by endotoxin stimulation, and sIL-10 was lower in hemodialysis patients than in normal control. According to relation of sIL-10 with cardiovascular risk factors such as existence LVH, ejection fraction and malnutrition, it could be suggested that sIL-10 is useful marker in evaluating the risk of cardiovascular events.

Changes of CA125 and PIIINP (Procollagen-3-N-terminal Peptide) in Peritoneal Dialysis Patients with Low GDP Solution / 대한신장학회잡지

BACKGROUND: The bioincompatability of the conventional peritoneal dialysis can be partly attributed to the presence of GDPs, which are generated during the heat sterilization. Formation of GDPs can be significantly reduced by the use of multi-chamber bag systems because high concentrated glucose is separated from alkaline lactate. In order to investigate whether multi-chamber bag system can improve the in vivo biocompatibility, we performed a randomized, prospective study comparing the multi-chamber bag system with the conventional PD system, measuring CA125 and PIIINP levels in the effluent dialysates as well as the other clinical and biochemical parameters. METHODS: Forty five patients who were stable on CAPD were enrolled randomly assigned to experiment group (n=27), and control group (n=18). Overnight effluent was collected for measurement of CA125 and PIIINP and the other clinical, biochemical parameters were compared including the number of peritonitis, the ultrafiltration volume. RESULTS: In patients treated with the multiple chamber bag system, there were significantly higher levels of CA125 and PIIINP from 1 month. No clinical and biochemical parameters influenced on their levels. The incidence of peritonitis or ultrafiltration volume did not differ between the two groups. CONCLUSION: Using the low GDP solution resulted in a better preservation of peritoneal mesothelial mass and an improvement of local peritoneal homeostasis, which are supposed to contribute to the biocompatibility of peritoneal dialysis fluid.

Chemical Pleurodesis as a Treatment for Hydrothorax Complicating Peritoneal Dialysis / 대한신장학회잡지

Hydrothorax complicating continuous ambulatory peritoneal dialysis (CAPD) occurs approximately 2% of continuous ambulatory peritoneal dialysis. Management might begin with interruption of peritoneal dialysis for 2-6 weeks. But, approximately half of the patients failed to respond to the conservative approach, as thus some authors advocated the combined use of intrapleural sclerosing agents and discontinuation of CAPD. As a rule of thumb, a 10-day wait is recommended after pleurodesis before resuming CAPD. As opposed to closed pleurodesis, the diaphragmatic defects can be identified and repaired under direct vision with surgical approach. But, limited eligibility of dialysis patients for open thoracostomy or video-assisted thoracostomy has been a major impediment for this definitive treatment of choice. From 1999 to 2003, among patients undergoing CAPD in Korea University Hospital, hydrothorax developed in four patients. Discontinuation of CAPD and conventional pleurodesis were performed. Three patients were treated successfully. A patient who interrupted peritoneal dialysis only for four days recurred after resuming CAPD. In conclusion, when pleural effusion complicates in a CAPD patient, chemical pleurodesis and cessation of CAPD during at least 10 days might be an initial tratement of choice.

A Case of Scleroderma Renal Crisis without Malignant Hypertension after Steroid Treatment / 대한신장학회잡지

Scleroderma renal crisis is defined as rapidly progressive renal failure and/or new onset of malignant hypertension during the course of systemic sclerosis. Most patients show clinical features of malignant hypertension, but there have been several reports of normotensive renal crisis. We have experienced a 63 year old female patients with acute renal failure due to scleroderma renal crisis who did not show the clinical features of malignant hypertension. She had taken steroid for the treatment of degenerative osteoarthritis and gradually developed shortness of breath and edema. Her blood pressure on admission was 150/90 mmHg and easily controlled by diuretics. Renal biopsy showed onion-skin appearance in the interlobular arteries with varying degree of tubulointerstitial changes. Her renal function rapidly deteriorated despite ACE inhibitor therapy and cytotoxic therapy had to be initiated because of progressive interstitial pneumonitis and myocarditis. We describe a patient with scleroderma renal crisis who did not show the clinical features of malignant hypertension following steroid treatment.

A Case of lambda-type Light Chain Deposition Disease Manifested as Acute Renal Failure and Multiple Organ Dysfunction by Embolic Events / 대한신장학회잡지

Light chain deposition disease is caused by systemic paraprotein deposition resulting from monoclonal plasma cell dyscrasia. It is usually characterized rapidly progressive renal failure and multiple organ dysfunctions. Besides deposition of light chain, it can lead to multiple organ dysfunctions due to hyperviscosity syndrome. We experienced a case of 54-year-old man who presented as an acute renal failure, and elevation of liver enzyme. Radiologically, there was no abnormal finding except enlargement of both kidney in abdominal sonogram. Globulinuria was noticed on 24 hrs-urine study. The histologic findings of kidney showed lambda chain deposits in basement membrane of tubules and glomeruli, interstitium, and vessel walls. On 10th day of hospitalization, he developed sudden hypoxia that was not corrected by oxygen supplementation, and focal neurologic signs accompanied with a change of consciousness. We report a case of light chain deposition disease manifested as an acute renal failure and liver enzyme elevation with suspicious multiple organ embolic events later.

Responsiveness of Recombinant Human Erythropoietin in Chronic Renal Failure Patients Undergoing Maintenance Hemodialysis / 대한신장학회잡지

BACKGROUND: Hyporesponsiveness to erythropoietin is an important issue in the treatment of the anemia of chronic renal failure. We tried to identify the factors of erythropoietin responsiveness in chronic renal failure patients undergoing maintenance hemodialysis for the effective treatment of anemia. METHODS: Seventy hemodialysis patients with hemoglobin increment over 2.0 g/dL during erythropoietin treatment were divided into two groups by median erythropoietin dose, 120 IU/kg/week (the low-dose group vs. the high-dose group). We compared age, gender, cause of renal failure, duration of hemodialyis, use of angiotensin-converting enzyme inhibitor, hemoglobin, hematocrit, serum iron, TIBC, transferrin saturation, ferritin, albumin, cholesterol, parathyroid hormone (iPTH), CRP, CO2 content, BUN, creatinine and Kt/V between the two groups. RESULTS: The low-dose group had significantly shorter duration of hemodialysis (40.9 months vs. 66.1 months, p=0.036), higher serum albumin level (3.93 g/dL vs. 3.72 g/dL, p=0.011) and lower iPTH level (94.97 pg/mL vs. 218.52 pg/mL, p=0.013) compared with the high-dose group. Serum creatinine level and Kt/V showed a tendency to be higher in the low-dose group but there were no significant differences (10.53 mg/dL vs. 9.40 mg/dL, p=0.053 and 1.69 vs. 1.38, p=0.080). Other clinical and laboratory parameters were not different between the two groups. CONCLUSION: Adequate nutritional support and prevention of secondary hyperparathyroidism may be helpful to enhance the responsiveness of erythropoietin in chronic renal failure patients undergoing maintenance hemodialysis.

Efficacy of Protocol-based Erythropoietin Administration in Chronic Hemodialysis Patients / 대한신장학회잡지

BACKGROUND: Anemia is a major contributor to morbidity and mortality in chronic renal failure patients. The benefits of anemia correction using recombinant human erythropoietin (Epo) are well established but because of high cost, several studies increasing the efficacy of it were described. The objective of this study was to evaluate the efficacy of an anemia management protocol using subcutaneous Epo and intravenous iron therapy. METHODS: We enrolled seventy-eight maintenance hemodialysis patients for at least 3 months from January 2000 to November 2002. They received a practice of anemia correction in two other settings. One (control) group performed an irregular administration of Epo and iron, the other (protocol) group performed a regular administration according to anemia management protocol. Clinical and laboratory parameters were analyzed. Dosage of Epo and IV iron were compared. RESULTS: Thirty-one patients in control group and forty-seven patients in protocol group were enrolled. There were no significant differences between two groups in age, gender, existence of diabetic mellitus, vintage of hemodialysis, use of angiotensin-converting enzyme inhibitor, BUN, prealbumin, parathyroid hormone and Kt/Vurea. Mean arterial pressure, creatinine and albumin were significantly lower and hematocrit was significantly higher and well-maintained on the target level in protocol group. There were no significant differences in serum iron, transferrin saturation, ferritin but total iron binding capacity was significantly lower in protocol group. Doses of erythropoietin and IV iron showed no significant differences between two groups. CONCLUSION: The protocol based erythropoietin administration was more efficient in achieving target hematocrit without increment of dosage of erythropoietin and intravenous iron and side effect of hypertension.