Comparison of two iron gluconate treatment modalities in chronic hemodialysis patients: results of a randomized trial

BACKGROUND: Iron supplementation in chronic hemodialyzed patients is not yet completely defined concerning the dosing regimen. This study aimed to evaluate the effects of the same iron load administered in different regimens on anemia, iron status and the reticulocyte (Ret) subpopulation patterns in stable patients on chronic hemodialysis (HD). Patients and methods: Seventeen patients undergoing thrice-weekly chronic HD and receiving stable alphaerythropoietin therapy with absolute iron deficiency (transferrin saturation (TSAT) <20%, ferritin (Frt) <100 ng/mL) were randomly divided into two groups: group A (n=9) received 20.8 mg of sodium iron gluconate at the end of each dialysis session; group B (n=8) 62.5 mg only at the end of the 1st dialysis session of the week. The treatment period lasted 3 months (period 1) and was followed by 3 months of observation (period 2). Results: Both treatments increased hemoglobin (Hb) levels by an average of 0.90 g/dL in period 1, with a progressive decline in period 2 (p=ns between groups), peaking at 11.2 g/dL in group A and 10.8 g/dL in group B. The effects on mean red blood cell volume and Hb concentrations were similar. Frt levels more than doubled during period 1 and early in period 2 in both groups (172 microg/L in group A; 149 microg/L in group B, and progressively decreased in period 2 (p=ns between groups). The TSAT index increased progressively peaking to 28.7% in group A and 24.3% in group B. Hypochromic red blood cells (hypocRBC) decreased early from 5.6-2.2% in group A, and from 5.5-2.1% in group B, and persisted in period 2; the between-period differences for the combined groups were statistically significant (p=0.0051). High fluorescence reticulocytes (HFR) increased from period 1 to period 2 only in group B (from 0.8-1.7%, p=0.012). CONCLUSIONS: Both regimens replenished iron stores and improved anemia. The HFR increase in group B could be due to soluble transferring receptor (STnfR) gene upregulation; alternatively it could indicate the prevalence of immature Ret release from bone marrow.     

右旋糖酐铁治疗24例长期透析患者不宁腿综合征

不安腿综合征（RKS）是终末期肾脏疾病（ESRD）患者在长期接受透析治疗中的常见症状，表现为肢体感觉异常、不自主运动，休息时加重和失眠。我们通过安慰剂对照试验研究，一次性大剂量静脉使用右旋糖酐铁治疗RLS取得了较好效果。     

Erythropoietin-producing renal cell carcinoma in chronic hemodialysis patients: A report of two cases

Erythropoietin (EPO)-producing renal cell carcinomas in two hemodialysis patients are reported. Despite deteriorated kidney function, these patients did not manifest anemia at diagnosis and their elevated serum EPO levels rapidly returned to within the normal range after nephrectomy. Immunohistochemical staining of the resected specimens showed production of erythropoietin in the tumor cells in one case and in the lining cells of the cyst wall in the other case. Renal cell carcinoma could cause an increase of blood hematocrit level in dialysis patients.     

Controlled trial of calcitriol in hemodialysis patients

We report on a 5-year, prospective, double-blind trial of 1,25 dihydroxycholecalciferol (calcitriol) versus placebo in 76 hemodialysis patients without biochemical or radiological evidence of bone disease. Calcitriol, 1 microgram daily, regularly induced hypercalcemia. Doses of 0.25 microgram daily or less proved satisfactory in most patients. During calcitriol treatment, plasma calcium concentration was significantly higher and serum parathyroid hormone concentration significantly lower than on placebo. There was no difference in the rates of development or of progression of vascular calcification in the two groups. Significantly more patients on placebo (17 vs. 6, p less than 0.05) developed a sustained elevation of plasma alkaline phosphatase concentration. Calcitriol appeared to protect against the development of histological evidence of osteitis fibrosa but not of osteomalacia, but accumulation of aluminum in bone occurred during the study. We conclude that calcitriol delays and may prevent the development of osteitis fibrosa in patients receiving regular hemodialysis and may reasonably be prescribed routinely in hemodialysis patients without biochemical or radiological abnormality, unless there is a substantial prospect of early renal transplantation.     

Uremic pruritus in chronic hemodialysis patients

Skin itching (pruritus) affects 50%-90% of patients undergoing peritoneal dialysis or hemodialysis and the symptoms range from localized and mild to generalized and severe. Among the dermatological abnormalities associated with end-stage renal disease, pruritus is the most prevalent. Of all systemic disorders, uremia is the most important cause of pruritus. The mechanism underlying uremic pruritus is poorly understood: secondary hyperparathyroidism, divalent-ion abnormalities, histamine, allergic sensitization, proliferation of skin mast cells, iron-deficiency anemia, neuropathy and neurological changes, or a combination of these have been hypothesized. Severe pruritus not only affects the quality of life but is also associated with poor outcome in chronic hemodialysis patients. No specific, effective treatment is currently available for uremic pruritus. Further studies are necessary to evaluate the long-term efficacy and safety of a novel kappa-opioid agonist, nalfurafine. Early diagnosis and treatment of uremic pruritus focusing on general strategies that include the optimization of dialysis dose, erythropoiesis-stimulating agents, and management of secondary hyperparathyroidism is recommended.     

Abdominal surgery in chronic hemodialysis patients

The number of patients with end-stage renal disease who benefit from chronic dialysis is steadily increasing. This study was designed to assess abdominal surgery in chronic hemodialysis (CHD) patients. A 7-year retrospective study was conducted including all the patients on CHD who underwent abdominal surgery in our unit. These patients were separated into an elective and an emergency surgery group. Forty-three patients underwent surgery. In the elective surgery group (18 patients), the most common diseases were colorectal cancer, symptomatic gallbladder stones, and hernia. There was no death related to surgery in this group, and only one patient developed a complication (5%). In the emergency surgery group (25 patients), the most common diseases were mesenteric ischemia and gastrointestinal bleeding from angiodysplasia. Complications occurred in 10 patients (total morbidity rate, 40%), and 6 of them died (mortality rate, 24%). Gastrointestinal elective surgery in patients on CHD can be performed with low morbidity and mortality rates. The emergency group was differentiated by the high prevalence of bleeding from angiodysplasia and mesenteric infarction, as well as its high surgical mortality rate.     

Verapamil-digoxin interaction in chronic hemodialysis patients

Verapamil increases the serum-digoxin concentration (SDC) in digoxin treated normals due to a compromised renal and extrarenal clearance. In chronic hemodialysis patients (CHD-patients) treated with digoxin where the renal elimination is diminished, verapamil has been shown to cause substantial increases of SDC with risk of digoxin intoxication. The effect of verapamil treatment on SDC in 8 nearly anephric (Uvol less than 1 l/d) CHD-patients on digoxin treatment was assessed. The patients were continuously treated with verapamil for two periods of two weeks at two dosage levels, 120 mg/d and 240 mg/d, whereafter verapamil was withdrawn. SDC and serum-verapamil were measured weekly. The SDC increased from 1.1 mmol/l to 1.7 mmol/l (p less than 0.05, N = 7) during the first two weeks. Increasing the dose of verapamil to 240 mg/d did not cause a further increment in SDC; on the contrary, the mean SDC decreased. The SDC increments varied between 0 and 200% of baseline values. We conclude that verapamil treatment decreases digoxin clearance in CHD-patients and that the influence of verapamil on SDC in CHD-patients shows great interindividual variation with no close dose dependency and decreases to pretreatment level in 2-3 weeks.     

Extrapulmonary tuberculosis in chronic hemodialysis patients

BACKGROUND: The incidence of extrapulmonary tuberculosis is higher in dialysis than general population. The aim of the study was to characterize clinical picture in dialysis patients, who developed extrapulmonary tuberculosis. METHODS: We retrospectively investigated the hemodialysis patients with extrapulmonary tuberculosis. 2208 hemodialysis patients were reviewed for extrapulmonary tuberculosis from October 1986 to January 2001. RESULTS: Seventeen patients (10 male, 7 female) were enrolled. The mean age was 57.4 +/- 12.4 years. The sites for extrapulmonary tuberculosis were peritoneum (35.3%, 6/17), cervical lymph node (17.6%. 3/17), bone marrow (5.9%, 1/17), spine (5.9%, 1/17), knee (5.9%, 1/17), brain (5.9%, 1/17), pericardium (5.9%, 1/17), cutaneous tissue (5.9%, 1/17) and genitourinary system (5.9%, 1/17). Fourteen of 15 tissue-biopsy specimens from suspicious sites revealed granulomatous inflammation. There were low yield in mycobacteria culture (11.1%, 1/9) and PCR (33.3%, 2/6). Three patients died during the treatment of the disease. CONCLUSION: Extrapulmonary tuberculosis constitutes a major part of tuberculosis in dialysis patients. Tissue biopsy with invasive procedures, such as laparoscopy or laparotomy, may be necessary if clinical presentations are suspicious.     

Urinalysis in patients on chronic hemodialysis

To determine what urinalysis findings are normal in patients maintained on chronic hemodialysis, we have studied the urine in 25 such patients. In end stage renal disease correlation with the original disease is lost, and the urine characteristically contains many white blood cells and frequent white blood cell casts; microscopic hematuria is unusual even in patients whose original disease was a proliferative nephritis.     

Esophageal dysfunction in chronic hemodialysis patients

Esophageal motility was studied in 16 asymptomatic hemodialysis patients and 38 normal volunteers. The incidence of triphasic tertiary and biphasic contractions was significantly higher in the patients than in the control subjects (25 vs. 0% and 87.5 vs. 39.5%, respectively). The above abnormalities were recorded in the lower two thirds of the esophageal body. We suggest that manometric evidence of esophageal dysfunction is very common in such patients. Although the pathogenesis is unclear, uremic neuropathy of the vagus nerve and/or smooth muscle myopathy due to chronic uremia could be the causative factors.     

Extra-renal abscess in chronic hemodialysis patients

AIM: Infectious disease represents one of the major causes of morbidity and mortality in hemodialysis patients. Extra-renal abscess constitutes a specific form of infection. The aim of this study was to evaluate and analyze the clinical characteristics of extra-renal abscess in chronic hemodialysis patients. METHODS: We retrospectively studied the extra-renal abscess among chronic hemodialysis patients in Chang Gung Memorial Hospital at Kaohsiung, Taiwan. The records of 2,168 chronic hemodialysis patients from October 1986 to January 2000, were studied. The clinical features were reviewed and analyzed. RESULTS: Sixteen patients who were enrolled during the study period developed extra-renal abscess. Ten of them were male. The mean age was 59.2 +/- 11.8 years old. More than half of the patients had diabetes (53.6%, 9/16). The locations of extra-renal abscess in these patients were liver (8/16), lung (5/16), spleen (1/16), perianal region (1/16), psoas muscle (1/16), and prostate (1/16). One patient had concurrent liver and spleen abscesses. All patients presented with fever and chills. Laboratory studies revealed leukocytosis and thrombocytopenia in 2/3 of the patients. The patients were associated with malnutrition status with lower serum albumin level (2.94 +/- 0.55 gm/dL) and lower nPCR (normalized protein catabolism rate; 0.84 +/- 0.11 gm/Kg/day) comparing to the other hemodialysis patients (albumin: 4.05 +/- 0.47 gm/dL; nPCR: 1.14 +/- 0.31gm/kg/day). There was no significant difference in kt/V between the patients with (1.28 +/- 0.34) or without abscess formation (1.47 +/- 0.36). The major causative pathogen was Klebsiella pnewnoniae. Parenteral antibiotic treatment is sufficient to treat most of the diseases, except 2 patients who needed surgical intervention. Twelve patients recovered after 2-3 weeks of treatment. Conclusions: The study indicated that extra-renal abscess is rare in chronic hemodialysis patients. The abscesses occurred mostly in liver. Diabetes mellitus and poor nutrition status were the important predisposing factors. Gram-negative bacilli, K. pneumoniae, were the major pathogen. Most of the patients responded to parenteral antibiotics and surgical draining.     

Adverse events in chronic hemodialysis patients receiving intravenous iron dextran--a comparison of two products

BACKGROUND: Parenteral iron therapy is required in a majority of chronic dialysis patients who are receiving recombinant human erythropoietin (r-HuEPO) in order to provide adequate iron for erythropoiesis. At this time, there are only two formulations of parenteral iron dextran available for clinical use in the USA. These two preparations of iron dextran have different physical and chemical characteristics that might affect the adverse events experienced by dialysis patients receiving iron dextran. METHODS: We performed a retrospective analysis of all 665 courses of parenteral iron dextran which were administered in our hemodialysis unit from June 1992 through July 1997. An adverse event (AE) was defined as any event which led to interruption of the prescribed course of iron therapy or precluded subsequent administration of parenteral iron in the presence of documented iron deficiency. Database elements included patient age, gender, cause of renal failure, and prior history of drug allergy. The average hemoglobin value and serum iron parameters (iron, total iron binding capacity (TIBC), percent saturation of TIBC, and ferritin) were recorded both pre- and post-iron administration, when available. A course of parenteral iron dextran consisted of a 25-mg test dose, followed by four or five doses of 300 mg each. Iron dextran was infused into the venous limb of the hemodialysis blood circuit over the last 30-60 min of a dialysis treatment. The two forms of iron dextran were designated as Iron A (molecular weight = 165,000) and Iron B (molecular weight = 267,000). RESULTS: Fifty-seven percent of our patients were male, 92% were of white race, and diabetes was the most common cause of renal failure (34%). Sixty-four percent of the patients were 60 years of age or older, and 39% had a history of allergy to one or more drugs. We observed 33 AEs during the administration of parenteral iron dextran, and these AEs occurred in 21 courses of parenteral iron dextran administration. Eighteen of the AEs were gastrointestinal in nature; 7 AEs were cutaneous in nature, 6 AEs had systemic manifestations, while only 2 AEs caused respiratory problems. Two of the AEs were felt to be anaphylactoid in nature. Female gender (p = 0.06) and iron dextran product (p = 0.02) were identified as potential risk factors for the development of an AE. There were 468 courses of Iron A administered, 10 of these courses were complicated by 15 AEs (one or more AE per course). One hundred and ninety-seven courses of Iron B were administered and 11 (5.6%) courses were complicated by the development of 18 AEs (9.1 AEs per 100 courses). Serum iron rose by 22 microg/dl and TIBC saturation increased by 14% after the administration of parenteral iron. The average serum ferritin level rose by 430 microg/l and hemoglobin values rose by an average of 0.8 g/dl. There were no significant differences in the changes of iron parameters or hemoglobin levels between the two iron dextran preparations. CONCLUSIONS: The administration of parenteral iron dextran to chronic hemodialysis patients has a relatively high degree of safety. Both iron products were equally efficacious in increasing serum iron parameters and hemoglobin levels. Even when corrected for other factors, there was a significant difference in the observed AEs between the two formulations of parenteral iron dextran. Our observations, if true, may have important implications for the management of anemia in chronic hemodialysis patients. If a significant number of AEs prohibit the administration of a specific iron dextran product to a large number of chronic hemodialysis patients, then anemia management may become suboptimal. In the future, newer iron products may provide even safer alternatives for the administration of parenteral iron to chronic hemodialysis patients.     

左旋卡尼汀治疗维持性血液透析患者肉碱缺乏症的临床研究

目的研究静脉注射左旋卡尼汀对维持血液透析（ＨＤ）患者肉碱缺乏症的治疗作用。方法采用多中心、双盲、随机、对照的研究方法,选择ＨＤ患者１９７例,分为治疗组、对照组和开放组,每次透析结束后,治疗组和开放组静脉注射左旋卡尼汀１ｇ,对照组注射生理盐水,为期３个月。结果治疗组和开放组体力、精神状态、食欲、恶心、呕吐、透析耐受性、透析中肌痉挛或低血压等症状的改善十分显著,血浆肉碱浓度明显升高（治疗前比治疗后：２８８２±１２５８ｖｓ．１８１３１±７４５７,Ｐ＜００１）,对照组以上各项均无变化,治疗组与对照组相比变化差异十分显著（Ｐ＜００１）;治疗组及开放组血浆总蛋白、白蛋白、前白蛋白和转铁蛋白等营养参数也明显升高。左旋卡尼汀治疗主要不良反应为转氨酶轻度升高和血小板降低,发生率分别为５．３％和２．３％,停药即可恢复正常。结论左旋卡尼汀能安全有效地治疗维持ＨＤ患者肉碱缺乏症。     

A randomized trial of iron deficiency testing strategies in hemodialysis patients.

BACKGROUND: Diagnosis of iron deficiency in hemodialysis patients is limited by the inaccuracy of commonly used tests. Reticulocyte hemoglobin content (CHr) is a test that has shown promise for improved diagnosis in preliminary studies. The purpose of this study was to compare iron management guided by serum ferritin and transferrin saturation to management guided by CHr. METHODS: A total of 157 hemodialysis patients from three centers were randomized to iron management based on (group 1) serum ferritin and transferrin saturation, or (group 2) CHr. Patients were followed for six months. Treatment with intravenous iron dextran, 100 mg for 10 consecutive treatments was initiated if (group 1) serum ferritin <100 ng/mL or transferrin saturation <20%, or (group 2) CHr <29 pg. RESULTS: There was no significant difference between groups in the final mean hematocrit or epoetin dose. The mean weekly dose of iron dextran was 47.7 +/- 35.5 mg in group 1 compared to 22.9 +/- 20.5 mg in group 2 (P = 0.02). The final mean serum ferritin was 399.5 +/- 247.6 ng/mL in group 1 compared to 304.7 +/- 290.6 ng/mL in group 2 (P < 0.05). There was no significant difference in final TSAT or CHr. Coefficient of variation was significantly lower for CHr than serum ferritin and transferrin saturation (3.4% vs. 43.6% and 39.5%, respectively). CONCLUSIONS: CHr is a markedly more stable analyte than serum ferritin or transferrin saturation, and iron management based on CHr results in similar hematocrit and epoetin dosing while significantly reducing IV iron exposure.     

Iron sucrose in hemodialysis patients: safety of replacement and maintenance regimens

BACKGROUND: Parenteral iron replacement and maintenance are frequently required in hemodialysis patients. However, serious adverse events have been reported after single doses of some intravenous iron products. This multicenter phase IV clinical trial examined the safety of iron sucrose for the treatment of iron deficiency and for the maintenance of iron sufficiency in hemodialysis patients. METHODS: In this safety study, iron sucrose was given in two dosing regimens. Iron deficient patients were treated with intravenous iron sucrose, 100 mg, during 10 consecutive hemodialysis sessions (replacement regimen). Iron replete patients were given iron sucrose, 100 mg intravenous (iv) over 5 minutes, weekly for 10 weeks (maintenance regimen). At the end of each 10-dose cycle, iron status was reassessed, and dosing during the subsequent cycle was based on the adequacy of iron stores as per Dialysis Outcome Quality Initiative (K/DOQI) Guidelines. With each dosing regimen, adverse events, if any, were recorded and described. RESULTS: Six hundred and sixty-five hemodialysis patients, including 80 who had experienced previous intolerance to other parenteral iron preparations, received a total of 8583 doses of iron sucrose. One hundred eighty-eight patients received more than one iv iron cycle (replacement, maintenance, or both). There were no serious or life-threatening drug-related adverse events. CONCLUSION: Iron sucrose is safe when given as treatment for iron deficiency or for maintenance of iron stores.