Atypical Hemolytic Uremic Syndrome in a Patient with Acute Promyelocytic Leukemia: A Case Report

Introduction: Acute Promyelocytic Leukemia (APL) is highly associated with hemostasis alterations. The atypical hemolytic uremic syndrome (aHUS) is a rare type of Thrombotic Microangiopathy (TMA) due to an overactivation of the alternative complement pathway. Case Presentation: A 48-years-old woman was diagnosed with APL and achieved molecular remission after induction therapy. During the second consolidation cycle she presented with TMA. She began treatment with plasma exchange plus corticotherapy but due to aggravation of symptoms Eculizumab was initiated. Thrombotic thrombocytopenic purpura, infections and drug toxicity causes were ruled out. There was no evidence of relapse of the APL. Genetic studies of the hereditary anomalies of the alternative complement pathway were negative and the decision of stopping Eculizumab was made. During maintenance therapy for the APL she presented a severe relapse of the aHUS, requiring dialysis. She re-started treatment with Eculizumab with a progressive hematologic recovery and improvement of renal function. She completed APL treatment without relapse of the leukemia for the moment and continues to be treated with Eculizumab. Conclusion: This is the first published case of coexisting aHUS and APL successfully treated with Eculizumab.

溶血性尿毒综合征(Hemalytic—Uremic Syndrome, HUS)的治疗

溶血性尿毒综合征,其主需临床表现是:微血管病性溶血性贫血、血小板减少和急性肾病。主要见于婴幼儿,也可见于成人。病理改变是双侧肾皮质坏死,肾小球弥漫性或限局性坏死伴有输入小动脉内纤维蛋白沉积:肾小球毛细血管丛栓塞;肾小球内毛细血管及小动脉内皮细胞和上皮细胞肿胀增生。此外有25%的病例存在着透明血栓。本病主要发生于婴幼儿,也见于青少年。典型者在胃肠炎或上呼吸道感染后数天到二周突然发病,出现贫血、溶血、皮肤和粘膜出血、急性肾功衰竭,血象中出现畸形和碎片红细胞。本病的治疗,虽然不甚满意,但由于应用下列方法,取得了明显进步:一、抗血小板药物本病的主要病理改变是在微小血管中血小板血栓形成,因此,是应用抗血小板药物的适应症。常用阿斯匹林和潘生丁。

Role of β2-microglobulin in uremic patients may be greater than originally suspected

The role of beta2-microglobulin(β2M) in dialysisrelated amyloidosis as a specific amyloid precursor was defined in the 1980 s. Studies in those years were largely related to β2M amyloidosis. In 2005, for what was probably the first time in the available literature, we provided data about the association betweenβ2M and early-onset atherosclerosis in hemodialysis patients without co-morbidities. In recent years, the role of uremic toxins in uremic atherosclerosis and the interest in β2M as a marker of cardiovascular(CV) and/or mortality risk have grown. In the current literature,clinical studies suggest that β2M is an independent, significant predictor of mortality, not only in dialysis patients, but also in predialysis patients and in the highrisk portion of the general population, and it seems to be a factor strongly linked to the presence and severity of CV disease. It is still unknown whether β2M is only a uremic toxin marker or if it also has an active role in vascular damage, but data support that it may reflect an increased burden of systemic atherosclerosis in a setting of underlying chronic kidney disease. Thus, although there have been some inconsistencies among the various analyses relating to β2M, it promises to be a novel risk marker of kidney function in the awareness and detection of high-risk patients. However, more research is required to establish the pathophysiological relationships between retained uremic toxins and further biochemical modifications in the uremic milieu to get answers to the questions of why and how. In this review, the recent literature about the changing role of β2M in uremic patients will be examined.

Update on hemolytic uremic syndrome:Diagnostic and therapeutic recommendations

Hemolytic uremic syndrome （HUS） is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and patho-genetic classifications. New findings in genetics and, in particular, mutations of genes that encode the complement-regulatory proteins have improved our understanding of atypical HUS. Similarly, the comple-ment proteins are clearly involved in all types of thrombotic microangiopathy： typical HUS, atypical HUS and thrombotic thrombocytopenic purpura （TTP）. Fur-thermore, several secondary HUS appear to be related to abnormalities in complement genes in predisposed patients. The authors highlight the therapeutic as-pects of this rare disease, examining both “traditional therapy” （including plasma therapy, kidney and kidney-liver transplantation） and “new therapies”. The latter include anti-Shiga-toxin antibodies and anti-C5 mono-clonal antibody “eculizumab”. Eculizumab has been recently launched for the treatment of the atypical HUS, but it appears to be effective in the treatment of typical HUS and in TTP. Future therapies are in phases Ⅰ and Ⅱ. They include anti-C5 antibodies, which are more purifed, less immunogenic and absorbed orally and, anti-C3 antibodies, which are more powerful, but potentially less safe. Additionally, infusions of recombinant complement-regulatory proteins are a potential future therapy.

Role of narrow band ultra violet radiation as an add-on therapy in peritoneal dialysis patients with refractory uremic pruritus

AIM To assess the role of narrow band ultraviolet B(UVB) as a treatment option in peritoneal dialysis patients with refractory uremic pruritus.METHODS In this retrospective study, 29 adult patients with end stage renal failure on peritoneal dialysis, and who had refractory uremic pruritus, were given narrow band UVB radiation as an add-on therapy to standard care for a duration of 12 wk. The response to the pruritus was assessed both weekly and at the end of the study period using a visual analogue score(VAS).RESULTS The average VAS score at the end of the study was 3.14 ± 1.59, which was significant compared to the baseline value of 7.75 ± 1.02(P < 0.05). Improvements in symptoms were noted in 19 out of 21(90.4%) patients. However, relapse occurred in six out of the 19 patients who responded. The dropout rate was high during the study period(33.3%).CONCLUSION Narrow band UVB is effective as an add-on therapy in peritoneal dialysis patients with refractory uremic pruritus. However, the present regime is cumbersome and patient compliance is poor.

Percutaneous approach to treatment of coronary disease in a patient with uremic cardiomyopathy

Uremic cardiomyopathy is chronic ischemic left ventricular dysfunction characterized by heart failure, myocardial ischemia, hypotension in dialysis and arrhythmia. This nosologic entity represents a leading cause of morbidity and mortality among patients with endstage renal disease receiving long-term hemodialysis. It is intuitive that revascularization in the presence of coronary artery disease in these patients represents an effective option for improving their prognosis. Although the surgical option seems to be followed by the best clinical outcome, some patients refuse this option and others are not good candidates for surgery. The present report describes the case of a patient affected by uremic cardiomyopathy and severe coronary artery disease in whom revascularization with percutaneous coronary angioplasty was followed by a significant improvement in quality of life.

Gastrointestinal infection-related disseminated intravascular coagulation mimicking Shiga toxin-mediated hemolytic uremic syndrome-implications of classical clinical indexes in making the diagnosis:A case report and literature review

BACKGROUND Thrombocytopenia associated with acute kidney injury is a challenging disorder. Thrombotic microangiopathy (TMA) is a potentially life- or organ-threatening syndrome that can be induced by several disorders or medical interventions. There is overlap between the clinical presentation and pathophysiology of thrombotic thrombocytopenia purpura and hemolytic uremic syndrome (HUS), and to a lesser extent, disseminated intravascular coagulation (DIC). We describe a case to illustrate the potential diagnostic difficulty, especially at initial presentation. CASE SUMMARY We reported a case of a 44-year-old woman that presented with diarrhea, thrombocytopenia, schistocytes, elevated serum lactate dehydrogenase (LDH) level and acute kidney injury. While the clinical presentation resembled that of Shiga toxin–induced HUS, the disease course was more consistent with gastrointestinal infection-related DIC. To aid in the accurate diagnosis of TMA and other associated disorders, we have undertaken a review and provided a clear interpretation of some typical biomarkers including schistocytes, LDH and platelet count, coagulation profile and more specific indexes of ADAMTS13, complement profile, and the isolation of Shiga toxin-producing Escherichia coli (commonly referred to as STEC). CONCLUSION The use and correct interpretation of classical indexes of schistocyte, LDH, and platelet count is vital in diagnosing TMA and associated disorders. Understanding the characteristics of these biomarkers in the context of thrombocytopenia purpura, HUS and DIC will facilitate the accurate diagnosis and early initiation of appropriate treatment.

Hemolytic uremic syndrome in children:some predictive findings on the disease outcome

Objective:To decrease or delay the major un-wanted clinical consequences to improve the quality of life in the involved patients.Methods:A retrospective case series study has been made on the forty five pediatric patients admitted to nephrology department of Ali-Asghar Hospital during a period of nearly 10 years.The patients have been divided into two groups of good and poor prognoses according to their clinical outcomes.The routine laboratory records and clinical manifestations extracted and statistically analyzed as independent variables both by univariate and multivariate methods.Results:Forty three patients have been managed successfully with only two deaths occurred.According to clinical findings,nineteen patients were classified as poor prognosis and the rest were categorized as good prognosis.Multivariate statistical analyses showed that lesser age at the time of admission(age【46 months,P【0.015) and the higher initial WBC count(count】15 000,P【0.226) were well-interrelated to ominous clinical consequences like convulsion,coma and peritonitis and statistically different between the two groups of patients.Conclusion:Despite the importance of predictive variables in the course of Hemolytic uremic syndrome(HUS) in children and their critical influence on the clinical outcome,many aspects of these parameters have been remained to be elucidated comprehensively.Our study showed that simultaneous low age of child at the time of admission with simultaneous high WBC count will result in the poorer prognoses of the patients.This may warn the clinicians to provide more supportive cares for this group of patients.

Gemcitabine-induced haemolytic uremic syndrome,although infrequent,can it be prevented:A case report and review of literature

Gemcitabine is an antineoplastic used to treat several malignancies including pancreatic cancer. Its toxicity profile is well known with myelotoxicity, increased vascular permeability and peripheral oedema as most frequent adverse events. However, several cases of acute renal failure have been reported and haemolytic uremic syndrome(HUS) seems to be the underlying process. The cause of HUS remains unknown but its consequences can be lethal. Therefore, a high grade of suspicion is crucial to diagnose it and promptly treat it. This hopefully will reduce its morbidity. HUS is characterized by progressive renal failure associated with microangiopathic haemolytic anaemia and thrombocytopenia. The primary event is damage to endothelial cells and thrombotic microangiopathy(TMA) is the histopathological lesion. TMA affects mainly renal microvasculature. However, some cases evolve with central nervous or cardiovascular systems involvement. We present here a case of gemcitabine-induced HUS, with renal and cardiovascular system affected at the time of diagnosis which to our knowledge this is the first time of such case to be reported.

Streptococcal pneumonia-associated hemolytic uremic syndrome treated by T-antibody-negative plasma exchange in children: Two case reports

BACKGROUND The occurrence of Streptococcus pneumoniae-associated hemolytic uremic syndrome(SP-HUS)is increasing.Thomsen-Friedenreich antigen activation is highly involved in the pathogenesis of SP-HUS,and T-antibody-negative plasma exchange(PE)may be effective in the treatment of severe cases of SP-HUS.CASE SUMMARY We retrospectively reviewed two pediatric patients with SP-HUS.Both clinical features and laboratory examination results of the children were described.Tantibody-negative PE was performed in both cases.Both children made a full recovery after repeated PE and remained well at a 2 year follow-up.CONCLUSION Streptococcal pneumonia continues to be an uncommon but important cause of HUS.The successful treatment of the presented cases suggests that T-antibodynegative PE may benefit patients with SP-HUS.

Are potassium levels in children with hemolytic uremic syndrome predictive of outcome?

Objective: To ascertain the role of serum potassium levels in predicting clinical outcomes in diarrhea-associated hemolytic uremic syndrome (HUS D+). Methods: We reviewed clinical and laboratory data from HUS D+ patients at our tertiary care institution from 2001 to 2008. Serum potassium concentration at presentation and during the acute phase of acute renal failure were recorded and related to laboratory parameters and clinical outcomes. Results: 15 HUS D+ cases were identified. E. coli 0157:H7 was found in 9/15 cases (70%). Potassium levels were not predictive of clinical outcomes. Normal serum potassium levels were found in the majority of patients. Potassium levels <3.6 mmol/L were evident at presentation in 3/15 patients (23%), and no patient manifested hyperkalemia even when creatinine levels were concurrently increase. Conclusions: This study suggests the presence of vigorous compensatory mechanisms in the homoestasis of serum potassium levels during HUS D+ disease since neither the increase stool volumes associated with diarrhea nor the presence of renal failure resulted in clinically significant changes in serum potassium levels.

Hemolytic uremic syndrome in adults: A case report

Thrombotic microangiopathies(TMA) are microvascular occlusive disorders characterized by platelet aggregation and mechanical damage to erythrocytes, clinically characterized by microangiopatic haemolytic anemia, thrombocytopenia and organ injury. We are reporting a case of a woman patient with severe hemolytic uremic syndrome associated to infectious diarrhoea caused by Shiga toxin-producing pathogen, who were admitted to our intensive care unit. The patient described developed as organ injury, neurological failure and acute renal failure, with need of haemodialysis technique. Due to the severity of the case and the delay in the results of the additional test that help us to the final diagnose, we treated her based on a syndromic approach of TMA with plasma exchange, with favourable clinical evolution with complete recovery of organ failures. We focus on the syndromic approach of these diseases, because thrombotic thrombocytopenic purpura, one of the disorders that are included in the syndromes of TMA, is considered a haematological urgency given their high mortality without treatment; and also review the TMA in adults: Their pathogenesis, management and outcomes.

Calcific Uremic Arteriolopathy or Calciphylaxis in a Hemodialysis Patient: Case Study and Review of the Literature

Calcific uremic arteriolopathy (CUA) is a rare pathology affecting 5% of dialysis patients but with a poor prognosis. It is characterized by calcification and thrombotic lesions of the microcirculation leading to hyperalgesic ischemic skin lesions. Several risk factors have been identified, mainly warfarin treatment, mineral and bone disorders (MBD), inflammation and malnutrition. In the evocative forms, the diagnosis is made based upon the physical examination finding of classic painful ulcerated lesions that are covered by a black eschar. Skin biopsy, due to the risk of aggravation and delayed healing, is only performed in case of doubt diagnosis. The therapeutic attitude due to the lack of solid randomized studies is based on expert consensus and requires a multidisciplinary approach. We report here the case of a patient with CUA revealed in the form of multiple ulcerative-necrotic skin lesions associated with pressure sores and arterial wounds.

Uremic clearance granule combined with Alprostadil in the treatment of chronic renal failure: A systematic review and meta-analysis

Objective: To evaluate whether the combination of Uremic clearance granule with Alprostadil is superior to Alprostadil alone for CRF. Methods: Relevant RCTs were searched through March 2019. Data were analyzed by Stata 15.0. Results: Nine articles involving 726 patients were enrolled in this study. Meta-analysis showed that the total effective rate [OR = 3.68 (2.44, 5.55), P < 0.001], Scr [SMD =-2.34 (-3.49,-1.19), P < 0.001], BUN [SMD =-1.80 (-2.73,-0.87), P < 0.001], Ccr [SMD = 0.71 (0.44, 0.97), P < 0.001] were better in the experimental group. But there were no significant difference in UA, CysC, 24h-Upro and incidence of adverse reactions (all P > 0.05) between two groups. No serious adverse reactions were found. Conclusions: The effect of the integrated medicine on CRF was better than Alprostadil alone. Uremic clearance granule is safe and has no obvious adverse reactions.

Research progress of uremic myopenia in traditional Chinese and western medicine

Uremia,as a serious disease endangering human life and health,is often accompanied by many complications,and sarcopenia is one of the most common complications in uremic patients.In recent years,with the increase of the prevalence of uremic sarcopenia,the quality of life of patients has been greatly affected,increasing the mortality of patients.Therefore,how to prevent and treat uremic sarcopenia has become the main research direction to improve the quality of life of patients and reduce mortality.Modern medicine believes that mitochondria play a leading role in the occurrence and development of uremic sarcopenia.At the same time,the author found that uremic sarcopenia was closely related to the spleen of traditional Chinese medicine through reading ancient medical literature,and spleen dysfunction,spleen disease and kidney were the key factors for uremic sarcopenia.This article will analyze and summarize the pathogenesis and research of the disease from the perspective of traditional Chinese and western medicine,so as to provide basis for clinical prevention and treatment of uremic sarcopenia.

Effect of desensitization treatment for highly sensitized uremic patients before kidney transplantation

Objective To explore the feasibility and efficacy of desensitization protocol for highly sensitized renal transplant patients ( HSP ) . Methods Thirty - five HSPs ( HLA class - I panel reactive antibody 2〉50 % ) , including 27 patients with a positive T and/or B cell cy-

Berberine ameliorates chronic kidney disease through inhibiting the production of gut-derived uremic toxins in the gut microbiota

At present,clinical interventions for chronic kidney disease are very limited,and most patients rely on dialysis to sustain their lives for a long time.However,studies on the gut—kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease.This study showed that berberine,a natural drug with low oral availability,significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins,including p-cresol.Furthermore,berberine reduced the content of pcresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine—p-cresol pathway of the intestinal flora.Meanwhile,berberine increased the butyric acid producing bacteria and the butyric acid content in feces,while decreased the renal toxic trimethylamine N-oxide.These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut—kidney axis.

Study on the occurrence and influencing factors of gastrointestinal symptoms in hemodialysis patients with uremia

BACKGROUND Gastrointestinal symptoms are common in patients with uremia undergoing hemodialysis,and these symptoms seriously affect patients'prognosis.AIM To assess the occurrence and factors influencing gastrointestinal symptoms in patients with uremia undergoing hemodialysis.METHODS We retrospectively selected 98 patients with uremia who underwent regular hemo-dialysis treatment in the blood purification center of our hospital from December 2022 to December 2023.The gastrointestinal symptoms and scores of each dimension were evaluated using the Gastrointestinal Symptom Grading Scale(GSRS).Patients were divided into gastrointestinal symptoms and no gastrointestinal symptom groups according to whether they had gastrointestinal symptoms.The factors that may affect gastrointestinal symptoms were identified by single-factor analysis.Multiple logistic regression analysis was performed to identify independent risk factors for gastrointestinal symptoms.RESULTS Gastrointestinal symptoms included indigestion,constipation,reflux,diarrhea,abdominal pain,and eating disorders,and the total average GSRS score was 1.35±0.47.This study showed that age,number of tablets,dialysis time,glucocorticoid,parathyroid hormone(PTH),combined diabetes mellitus and C-reactive protein(CRP)were independent risk factors for gastrointestinal symptoms in patients with uremia undergoing hemodialysis,whereas body mass index(BMI),hemoglobin(Hb),and urea clearance index were independent protective factors(P<0.05).CONCLUSION Gastrointestinal symptoms are mostly mild in patients with uremia undergoing hemodialysis,most commonly including dyspepsia,eating disorders,and gastroesophageal reflux.The independent influencing factors mainly include the BMI,age,number of pills taken,dialysis time,urea clearance index,Hb,use of glucocorticoids,and thyroid hormone level.PTH,CRP,and diabetes are clinically related factors influencing the occurrence of gastrointestinal symptoms,and targeted prevention can be performed.

Inhibition of the Tubular Epithelial-to-Mesenchymal Transition in vivo and in vitro by the Uremic Clearance Granule(尿毒清颗粒)

Objective： To investigate the effect of the Uremic Clearance Granule （UCG, 尿毒清颗粒）, a Chinese patent medicine, on tubular epithelial-to-mesenchymal transition （EMT） in a unilateral ureteral obstruction （UUO） model in vivo and transforming growth factor （TGF）- 131 induced EMT of HK-2 cells in vitro. Methods： In vivo study, 50 Sprague Dawley rats were divided into three groups： a sham operation group （n=10）, a UUO group （n=20）, and a UUO with UCG treatment group （n=20）. The UCG was given at a dose of 4.5 g/kg body weight per day by gavage after surgery. In vitro study, HK-2 cells were cultured in 10% fetal bovine serum （FBS）, 10% healthy rat serum, 10% FBS and TGF-13 1 （10 ng/mL）, 10% healthy rat serum and TGF-13 1, or 10% rat serum containing the uremic clearance granule and TGF-13 1. The expression of the epithelial marker E-cadherin and the mesenchymal markers vimentin and e^-smooth muscle actin （ot-SMA） in kidney tissues and HK-2 cells were investigated by Western blot analysis and immunofluorescence staining. Results： The rats of the UUO group showed obvious tubulointerstitial fibrosis, compared with the sham operation group rats. Tubulointerstitial fibrosis score was reduced by 17.5%± 1.1% at day 7 and by 20.0%_＋ 1.2% at day 14 in the UCG-treated group, compared with the UUO group. The UCG could maintained expression of E-cadherin and suppressed expression of vimentin and α-SMA in kidney tissues of UUO rats at days 7 and 14, as determined by Western blot analysis and immunofluorescence staining. Rat serum containing the UCG partially inhibited TGF- β 1-induced fibroblast phenotype of HK-2 cells and maintained the epithelial morphology of HK-2 cells in vitro. This occurred partially through a reduction of vimentin expression and an increase of E-cadherin expression. Conclusion： These results suggest that the UCG prevents tubular EMT and may be a promising agent for treating tubulointerstitial fibrosis.

Understanding and Therapeutic Strategies of Chinese Medicine on Gut-Derived Uremic Toxins in Chronic Kidney Disease

Chronic kidney disease （CKD） is a major disease that threatens human health. With the progression of CKD, the risk of cardiovascular death increases, which is associated with the elevated levels of uremic toxins （UTs）. Representative toxins such as indoxyl sulfate and p-cresyl sulfate are involed in CKD progression and cardiovascular events inseparable from the key role of endothelial dysfunction. The therapeutic strategies of UTs are aimed at signaling pathways that target the levels and damage of toxins in modem medicine. There is a certain relevance between toxins and ＂turbid toxin＂ in the theory of Chinese medicine （CM）. CM treatments have been demonstrated to reduce the damage of gut-derived toxins to the heart, kidney and blood vessels. Modern medicine still lacks evidence-based therapies, so it is necessary to explore the treatments of CM.