Unexpected severe hypocalcemia during continuous venovenous hemodialysis with regional citrate anticoagulation

Citrate is known to induce acute hypocalcemia in patients undergoing liver transplantation during the anhepatic phase. We describe the case of a 71-year-old woman with fulminant hepatic failure secondary to hepatitis A, who was started on continuous venovenous hemodialysis (CVVHD) for acute renal failure. Because anticoagulation with heparin was untenable, regional anticoagulation was accomplished by trisodium citrate (46.7%) infusion. Unfortunately, severe hypocalcemia developed when citrate accumulated because of impaired hepatic metabolism. Because of chelation by citrate, the ionized calcium concentration declined to values as low as 2.72 mg/dL (normal, 4.5 to 5.6 mg/dL), whereas the total calcium concentration remained in the normal range. With an unusually high calcium chloride infusion rate via a central line (up to 140 mL/h of 10 mEq/dL CaCl₂ ) and additional boli of CaCl₂ (for a total of 190 mEq), the ionized calcium concentration could be maintained at target levels. Nevertheless, the ionized calcium concentration was maintained in the normal range, and the total calcium concentration increased to a value as high as 15 mg/dL. Thus, the total to ionized calcium ratio was 3.5:1. After 24 hours of treatment, trisodium citrate infusion was gradually reduced from 15 mL/h to 7 mL/h, and the calcium chloride infusion was decreased to 50 mL/h. Nevertheless, persistence of the elevated total to ionized calcium ratio (3:1) indicated citrate accumulation likely secondary to decreased hepatic metabolism. Using this approach, the patient was successfully maintained on CVVHD with regional citrate anticoagulation for a total of 11 days without any additional complications. We conclude that CVVHD with regional citrate anticoagulation can be used in patients with acute hepatic failure if increased CaCl₂ requirements are anticipated and if citrate is infused at a lower rate compatible with decreased citrate metabolism. Citrate accumulation should be suspected in patients with an elevated total to ionized Ca⁺⁺ ratio during CVVHD with citrate anticoagulation.     

Cyclosporine-associated microangiopathic hemolytic anemia in a renal transplant recipient

A case of microangiopathic hemolytic anemia (MHA) associated with the immunosuppressive agent, cyclosporine, is reported herein. The patient manifested anemia with red blood cell fragmentation, hypertension, thrombocytopenia, elevation of serum LDH levels and glomerular capillary thromboses within a few days of his transplantation. Extensive treatments with urokinase and heparin proved ineffective and graftectomy was performed 7 days after his transplantation. Immunofluorescent staining failed to show immunoglobulin (IgG or IgM) or complement (C₃) deposition within the glomeruli, which discriminated MHA from acute humoralvascular rejection.     

Enoxaparin versus unfractioned heparin as anticoagulant for continuous venovenous hemodialysis: a randomized open-label trial

Aim: In this study we aimed to compare the efficacy and safety of enoxaparin with unfractioned heparin (UFH) as anticoagulant for continuous venovenous hemodialysis (CVVHD). Methods: An open-label randomized controlled trial was carried out in an intensive care unit (ICU) where 40 patients with acute renal failure (ARF) who needed continuous renal replacement therapy were randomized to receive UFH (n = 21) or enoxaparin (n = 19). Coagulation parameters were evaluated, and antithrombotic activity of UFH was measured by activated partial thromboplastin time (aPTT) and for enoxaparin by anti-factor Xa activity. Primary outcomes were thrombosis of the extracorporeal circuit and bleeding, classified as major or minor. Results: Minor bleeding episodes were observed only in patients anticoagulated with enoxaparin (26 vs. 0%, p = 0.018). Comparing patients with or without bleeding after 24 hours of therapy, the level of anticoagulation tended to be higher (anti-factor Xa: 1.62 vs. 1.13 IU/mL, p = 0.09) and the platelet count to be lower [107 ± 53 vs. 229 ± 84 (×10³/μL), p = 0.09] in patients who bled, but without statistical difference. Filter life span of enoxaparin and UFH groups was similar (43 ± 15 vs. 52 ± 18 hr, p = 0.10), as well as the proportion of circuit clotting. Conclusion: Weight-unadjusted enoxaparin in patients with ARF in CVVHD was associated with an increased rate of bleeding, a finding that addresses the need to adjust drug dose and to monitor anti-factor Xa activity during dialysis. No benefit to prolong dialysis circuit survival was found with enoxaparin. In patients who do not present contraindication for systemic anticoagulation, UFH remains an effective and low-cost option.     

维持性血液透析患者贫血及相关因素分析

目的探讨维持性血液透析(maintenance hemodialysis,MHD)患者血红蛋白(hemoglobin,Hb)达标情况及其相关影响因素。方法选择2014年1月1日至2015年1月1日间在我院血液透析中心规律行血液透析3个月以上的终末期肾脏疾病患者作为研究对象,收集患者的基本资料(年龄、性别、原发病、体质量、透析时间、透析频率、药物使用情况等)和实验室指标(Hb、铁蛋白、血白蛋白、尿素氮、血肌酐等)以及促红细胞生成素(erythropoietin,EPO)及铁剂使用情况;统计本中心患者Hb达标情况,再根据Hb水平进行分组,采用χ~2检验比较各组间Hb达标情况及EPO、铁剂的使用情况,并对EPO剂量采用Pearson线性相关分析,铁剂的使用采用秩相关分析。结果①本次研究共纳入的257例MHD患者中,按Hb≥110 g/L为达标Hb进行统计,达标患者123例(占46.70%),未达标患者134例(占53.3%)。Hb达标率与国内研究相比基本相似,较国际发达国家水平低。将患者按原发病发病率分组,发病率前五位的分别为高血压肾病92例(占35.80%),慢性肾小球肾炎82例(占31.91%),糖尿病肾脏疾病40例(占15.56%),多囊肾病7例(占2.72%),痛风6例(占2.33%);不同原发病之间贫血患病率的差异具有统计学意义(P0.05)。②将患者按Hb值分组,未达标组的EPO使用量较达标组的EPO使用量低[(60.54±50.41)IU·Kg~(-1)·W~(-1)比(136.51±36.32)IU·Kg~(-1)·W~(-1),P0.001],未达标组静脉铁剂使用量比达标组低[(139.01±52.08)mg比(150.00±78.59)mg,P0.001],2组的年龄、体质量、透析时间、铁蛋白、血白蛋白、尿素氮、血肌酐的差异均无统计学意义(P0.05)。根据患者使用铁剂的情况分组,静脉铁剂组和口服铁剂组间Hb水平的差异均无统计学意义(P0.05)。③通过相关分析显示,Hb与EPO剂量呈正相关(r=0.849,P0.01),而与铁剂的使用呈正相关(r=0.196,P0.01)。结论①本血液透析中心MHD患者的贫血治疗达标率为46.7%,与国内研究相比基本相似,较国际发达国家水平低;②使用EPO治疗的MHD患者有着更高的Hb水平和Hb达标率;③使用铁剂的MHD患者中,Hb达标例数比未使用铁剂组高,但使用静脉铁剂组与口服铁剂组间Hb水平差异无统计学意义;④通过相关性分析显示,Hb与EPO剂量呈强正相关,与铁剂的使用呈弱正相关。     

腹膜透析与血液透析患者肾性贫血治疗效果比较

目的比较腹膜透析（peritoneal dialysis,PD）与血液透析（hemodialysis,HD）患者肾性贫血的治疗效果。方法选择尿毒症行肾脏替代治疗患者90例,其中腹膜透析患者41例,血液透析患者49例。患者入组前1个月内均未行肾脏替代治疗、未使用促红细胞生成素（erythropoietin,EPO）、无失血;在肾脏替代治疗开始时加用EPO,比较腹膜透析组（PD组）和血液透析组（HD组）患者治疗前、治疗后第1、2、3个月血红蛋白（hemoglobin,Hb）的变化,以及PD组与HD组治疗后3个月超敏C反应蛋白（high sensitivity C reactive protein,hs—CRP）、血白蛋白（albumin,Alb）、尿素清除指数（Kt／V）的差异。结果治疗前2组的Hb值无统计学差异（P〉O．05或P〉0．01）,治疗后第3个月2组的hs-CRP、Alb、Kt／V值无统计学差异（P〉0．05或P〉0．01）。透析治疗前后比较,PD组治疗后第1、2、3个月的Hb值均较治疗前升高（P〈0．05或P〈0．01）,且治疗后第3个月〉第2个月〉第1个月;HD组治疗后第1、2、3个月的Hb值均较治疗前升高（P〈0．05或P〈0．01）,且治疗后第3个月〉第2个月〉第1个月。PD组治疗后第1、2、3个月EPO的Hb值分别高于HD组,差异具有显著性（P〈0．01）。结论肾脏替代治疗、使用EPO可有效纠正尿毒症患者的肾I生贫血,PD患者使用EP0更有利于肾陛贫血的纠正。     

Hemodiafiltration for vancomycin overdose in a neonate with end-stage renal failure

 We describe continuous venovenous hemodiafiltration (CVVHD) with a high-flux membrane as a novel treatment modality for vancomycin overdose associated with renal insufficiency. CVVHD was used in a 6-day-old male with a solitary hypodysplastic kidney, suspected sepsis, and anuric renal failure who subsequently received an accidental tenfold overdose of vancomycin. We furthermore present evidence for the importance of countercurrent dialysis in addition to continuous hemofiltration for optimal vancomycin removal. Received: 12 June 1998 / Revised: 5 October 1998 / Accepted: 6 October 1998     

Successful management of thrombocytopenia, microangiopathic anemia, and acute renal failure by plasmapheresis

We report on the outcome of six consecutive adult patients who presented with microangiopathic anemia and thrombocytopenia. Clinical parameters on admission included platelet counts less than 45,000/mm3, microangiopathic red blood cell morphology, mental status abnormalities, and in three, rapidly progressive azotemia requiring dialysis. All patients underwent plasma exchange therapy as part of their treatments. Patients with renal failure underwent plasma exchange with a hollow fiber plasma separator, while those without renal failure were treated with a cytocentrifuge. All received fresh frozen plasma as replacement solution and were treated with glucocorticoids as well. For all six patients, plasmapheresis and conventional drug therapy resulted in remission that has lasted for 16 +/- 5 months (range 8 to 24 months). Early cessation of plasmapheresis in two patients resulted in rapid relapse. Patients who required dialysis now have a mean creatinine of 2.0 +/- 0.9 mg/dL (range 1.2 to 3.5). With similar volumes of exchange, and the same number of treatments, less fresh frozen plasma was used in the three patients treated with the hollow fiber separator than in patients treated with the cytocentrifuge (6.3 +/- 3.7 v 14.8 +/- 4.3 U/exchange, P less than 0.05). We conclude that plasmapheresis is a useful therapeutic modality for the treatment of thrombocytopenia and microangiopathic hemolytic anemia. In addition the use of a hollow fiber plasma separator for plasmapheresis is safe and efficient, particularly when concurrent dialysis is required.     

Treatment of acute renal failure in an infant by continuous arteriovenous hemodialysis

Continuous arteriovenous hemodialysis (CAVHD) was performed in a critically ill, oliguric infant with progressive uremia using a miniature Amicon hemofilter. Modification was made in the filter system by circulating 2.5% Dianeal peritoneal dialysis fluid into the second port of the ultrafiltrate compartment to enable the filter to function by dialysis too (CAVHD). In comparison with continuous arteriovenous hemofiltration (CAVH), CAVHD provided superior urea clearance and adequate fluid removal, allowing the simultaneous administration of parenteral nutrition. The higher solute clearances in CAVHD make the technique superior to CAVH for renal replacement therapy in critically ill infants.     

不同血液净化方式对维持性血液透析患者贫血治疗的影响

目的比较单纯血液透析与血液透析联合血液灌流治疗对维持性血液透析（maintenance hemodialysis,MHD）患者贫血治疗的影响。方法选择2013年4月至11月在我院血液净化中心MHD患者40例,入组前患者均每周3次行单纯血液透析治疗,并使用促红细胞生成素刺激剂（eryhropoises stimulating agent,ESA）纠正贫血。按照随机数表法将MHD患者40例分为单纯血液透析（hemodialysis,HD）治疗组（HD组）和血液透析联合血液灌流（hemoperfusion,HP）治疗组（HD＋HP组）,每组20例。HD组仍每周3次均行HD治疗;HD＋HP组每周行2次HD治疗,1次HD＋HP治疗,仍继续使用ESA;治疗12周。记录2组患者治疗前、后血红蛋白（hemoglobin,Hb）,ESA用量,计算ESA抵抗指数（ESA resistant index,ESARI）评价ESA治疗的反应,同时检测2组治疗前、后血清铁、白蛋白（albumin,Alb）、C反应蛋白（c-reactiveprotein,CRP）、全段甲状旁腺素（intact parathyroidism hormone,iPTH）水平及透析治疗的单室模型尿素清除指数（singlepool Kt／V,spKt／V）。结果40例患者均随访至第12周末。第12周时,HD＋HP组患者Hb水平较基线时显著升高[（119．27±12．16）g／L比（106．59±6．51）g／L,（P〈0．01）],而ESA剂量低于基线时水平[（76．99±16．6）IU·W^-1·kg^-l比（128．96±33．47）IU·w^-1·kg^-1（P〈0．05）],ESARI亦低于基线时水平[（0．56±0．20）比（1．30±0．47）,（P〈0．01）]。第12周时HD＋HP组患者的iPTH水平较基线时显著降低[（161．09±63．70）ng／L比（256．23±56．77）ng／L,（P〈0．01）],CRP水平较基线时降低[（4．65±1．32）mg／L比（7．55±3．23）mg／L,（P〈0．05）];而第12周时HD组患者的Hb水平、ESA用量、ES—ARI值及iPTH、CRP水平与基线时比较无统计学差异（P〉0．05）。结论HD联合HP治疗较单纯HD治疗能更有效清除CRP、iPTH,提高MHD患者对ESA治疗的反应性,减少ESA使用剂量,改善MHD患者纠正贫血治疗的效果。     

Complete factor H deficiency-associated atypical hemolytic uremic syndrome in a neonate

Recent advances have shown that atypical hemolytic uremic syndrome (aHUS) is a disease of complement dysregulation. Almost 50% of cases are associated with mutations in the three complement regulatory genes, factor H (HF1), membrane co-factor protein (MCP) and factor I (IF). The corresponding gene products act in concert and affect the same enzyme, alternative pathway convertase C3bBb, which initiates the alternative pathway and amplification of the complement system. Factor H (FH) deficiency-associated aHUS usually occurs in infants to middle-aged adults and only rarely in neonates. Moreover, the vast majority of patients are heterozygous for the HF1 gene mutations. We report on a case of neonatal-onset aHUS associated with complete FH deficiency due to novel compound heterozygous mutations in the HF1 gene. A 22-day-old baby girl developed acute renal failure and a remarkably low serum complement C3 level, which was rapidly followed by the development of micro-angiopathic hemolytic anemia. Western blot analysis revealed nearly zero plasma FH levels, and an HF1 gene study showed compound heterozygous mutations, C1077W/Q1139X. Renal pathology findings were compatible with glomerular involvement in HUS. The baby recovered completely after the repetitive infusion of fresh frozen plasma. During follow-up (until she was 20 months old) after the initial plasma therapy, the disease recurred three times; twice after the tapering off of plasma therapy, and once during a weekly plasma infusion. All recurrence episodes were preceded by an upper respiratory tract infection, and were successfully managed by restarting or increasing the frequency of plasma therapy.     

Effect of peritoneal dialysis versus hemodialysis on renal anemia in renal in end-stage disease patients: a meta-analysis

The aim of this meta-analysis was to evaluate the effect of peritoneal dialysis (PD) and hemodialysis (HD) on renal anemia (RA) in renal disease patients by a meta-analysis. Relevant studies published before June 2015 were searched. Pooled odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the effect of HD and PD on RA based on five indexes: hemoglobin, ferritin, transferrin saturation index, serum albumin, and parathyroid hormone. Sensitivity analysis and publication bias assessment were conducted to evaluate the stability and reliability of our results. A total of fourteen eligible studies with 1103 cases underwent HD and 625 cases underwent PD were used for this meta-analysis. There were no significant difference for levels of hemoglobin (SMD?=??0.23, 95% CI: ?0.74 to 0.28), ferritin (SMD?=?0.01, 95% CI: ?0.59 to 0.62), parathyroid hormone (SMD?=?0.11, 95% CI: ?1.53 to 1.75) and transferrin saturation index (SMD?=??0.06, 95% CI: ?0.67 to 0.56) between HD and PD group. However, the content of serum albumin in HD group was much more than that in PD group (SMD?=?1.58, 95% CI: 0.35 to 2.81). Neither of the included studies could reverse the pooled side effect and Egger’s test demonstrated no publication bias. Both of the two dialysis strategies have a similar effect on RA in renal disease patients.     

Intravenous iron treatment of renal anemia in children on hemodialysis

Treatment of anemia in children with end-stage renal disease (ESRD) has been greatly facilitated by the introduction of recombinant human erythropoietin (rHuEPO). A major limiting factor in the treatment of renal anemia is sufficient iron supplementation. Eight children (aged 10–17 years) receiving hemodialysis were treated with intravenous iron (1 mg/kg per week) for 3 months. Hemoglobin (Hb), hematocrit (Hct), and serum ferritin levels were measured regularly. The mean Hct increased from 25% to 30%, the mean Hb increased from 7.8 g/dl to 9.2 g/dl, and the mean ferritin level from 200 to 395 mg/dl. The mean EPO dosage could be tapered from 6,500 IU to 6,150 IU. No adverse side-effects were noted. Hence, in this uncontrolled study intravenous iron was an effective treatment for iron deficiency during rHuEPO therapy in children with ESRD on hemodialysis. Received: 30 October 1997 / Revised: 17 November 1998 / Accepted: 18 November 1998     

Prognosis in critically ill children requiring continuous renal replacement therapy

We performed an observational prospective study in 53 critically ill children to analyze the prognostic factors of children requiring continuous renal replacement therapy. Pediatric index of mortality (PIM), pediatric risk of mortality score (PRISM), multi-organ failure score, serum lactate levels, blood pressure, vasoactive drugs, renal function and characteristics of renal replacement therapy were analyzed. The mortality was 32.1%, with multi-organ failure being the most frequent cause of death (59%). The children who died presented a significantly lower blood pressure and required more doses of vasoactive drugs, dopamine and epinephrine than did the survivors. The PRISM and PIM scores and the serum lactate levels and the number of organs suffering failure were significantly higher in the patients who died than in the survivors. However, the PRISM and PIM scores underestimated the risk of mortality. The age, sex, urea and creatinine levels, type of pump and volume of ultrafiltrate did not affect the prognosis. The association of a mean BP<55 mmHg and epinephrine dose >0.6 g/kg/min was predictive of mortality in 76% of the patients. We conclude that the prognosis in children requiring renal replacement therapy depends on the severity of the clinical state at the time of starting therapy, principally on the hemodynamic situation.     

生血宁治疗维持性血液透析患者肾性贫血及改善铁代谢的临床观察

目的观察生血宁治疗尿毒症维持性血液透析患者肾性贫血的临床疗效。方法采用随机对照方法将维持性血液透析合并肾性贫血患者50例随机分为治疗组和对照组,其中治疗组25例,对照组25例。对照组予常规治疗,治疗组在常规治疗的基础上加用生血宁0.5 g,一天3次,疗程3个月,并于观察结束时分别检测血红蛋白、红细胞计数、红细胞压积、血清铁、血清铁蛋白水平。2组治疗期间均使用重组人促红细胞生成素50~100 IU/kg,每周2~3次。结果治疗前治疗组与对照组在血红蛋白、红细胞计数、红细胞压积、血清铁、血清铁蛋白上比较,无统计学差异(P0.05),具有可比性。治疗后2组在血红蛋白、红细胞计数、红细胞压积方面比较,治疗组平均水平均略高于对照组,但组间比较无统计学差异(P0.05),可能与2组患者均使用促红细胞生成素治疗、改善了维持性血液透析患者的贫血状况所致。治疗组在血清铁蛋白、血清铁上升的平均水平高于对照组,比较有统计学差异(P0.05)。结论生血宁能够改善维持性血液透析患者缺铁性贫血状态,提高患者红蛋白、红细胞计数、红细胞压积,促进铁转运及利用,增加储备铁,降低铁耗竭,改善铁代谢。     

Systemic lupus erythematosus complicated with microangiopathic hemolytic anemia, acute renal failure, and central nervous system disorder, treated successfully with corticosteroids and plasmapheresis

We report on a 15-year-old girl who had systemic lupus erythematosus (SLE), hemolytic anemia, thrombocytopenia, acute renal failure, and central nervous system disorder including an episode of convulsions. Red cell fragmentation was observed in the peripheral blood, but only a slight abnormality was noted in the coagulative/fibrinolytic system. She was treated with corticosteroid pulse therapy, hemodialysis, and plasmapheresis and anticoagulants. The severe anemia and thrombocytopenia responded to immunoadsorption. The renal biopsy specimen showed a thickening of the small arteries with a narrowing of the lumens, and an immunofluorescent study revealed deposits of fibrinogen in the renal blood vessels. A provisional diagnosis of SLE with thrombotic thrombocytopenic purpura was made. A magnetic resonance image of the brain obtained at the time of a convulsion showed multiple, scattered high-intensity areas on the rim of the cerebral cortex; these disappeared after treatment. These findings were strikingly similar to those observed in central nervous system lupus. We describe a case of SLE with microangiopathic hemolytic anemia that provides an insight into the mechanisms of thrombotic thrombocytopenic purpura and SLE that affect the central nervous system. A summary of this report was presented at the 21st meeting of the Western Branch of the Japanese Society of Nophrology.     

Progressive anemia following combination therapy with interferon-α and interleukin-2 in a patient with metastatic renal cell carcinoma

Various toxicities have been observed during the treatment of advanced renal cell carcinoma with interferon-alpha (IFN-alpha) and/or interleukin-2 (IL-2). We report a case of severe anemia, which responded well to steroid therapy, in a patient receiving IL-2 plus IFN-alpha for metastatic renal cell carcinoma.     

Aortic and renal artery thrombosis in a neonate: recovery with thrombolytic therapy

 This report describes a neonate with acute renal failure associated with extensive aortic and bilateral renal artery thrombosis attributed to inadequate breastfeeding and severe dehydration. Dialytic and general supportive care, together with concurrent anticoagulation, and continuous aggressive intrathrombic instillation of urokinase for 5 days resulted in near-complete thrombolysis. Renal functional recovery began 11 days after the onset of anuria. Despite ischemic atrophy of the left kidney, renal function and blood pressure were normal on follow-up. Thus, in neonates thrombolytic therapy may positively impact survival and recovery of renal function even in the setting of prolonged ischemic renal injury. Received November 7, 1996; received in revised form and accepted February 25, 1997     

Imaging the kidneys and urinary tract in the neonate with acute renal failure

Transitional nephrology seriously affects the manner in which radiological investigations and other forms of imaging are undertaken in the neonate. When this is complicated by acute renal failure then caution must be exerted in taking care of the neonate. The use of ultrasound and micturating cystourethrography are well described and form the baseline for all imaging of the renal tract. The physiological handling of TC_99m DTPA and the contrasts used for IVU are described as well as the normal appearances of these techniques in the neonate. TC_99m DMSA is also included, as are other modalities of imaging.