• Childhood Kidney Diseases
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• v.17 no.1
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• pp.6-12
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• 2013

Thrombotic microangiopathy (TMA) is a microvascular thrombotic lesion caused by endothelial injury and subsequent formation of platelet rich thrombus. TMA is first described as a classical pathologic feature of HUS/TTP. Renal biopsy finding of TMA represents kidney involvement of HUS/TTP as well as other diseases such as malignant hypertension, drug toxicity, eclampsia, pre-eclampsia, and several systemic infections. Autoimmune diseases and transplant kidney sometime also have TMA. It is needed to consider a complete autoimmune work-up of patients presenting with TMA including tests for ANA, ANCA, and ADAMTS13 inhibitory antibodies, because there are several reports of association with TMA in patients of SLE, anti-phospholipid syndrome, and ANCA-associated vasculitis.

• Journal of Yeungnam Medical Science
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• v.37 no.2
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• pp.122-127
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• 2020

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but fatal complication of cancer and causes pulmonary hypertension and acute/subacute right heart failure. PTTM is most commonly associated with gastric cancer and more rarely associated with pancreatic cancer. We report a case of progressive right heart failure associated with clinically diagnosed pancreatic cancer, suggesting PTTM.

• Journal of Gastric Cancer
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• v.14 no.2
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• pp.142-146
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• 2014

Pulmonary tumor thrombotic microangiopathy (PTTM) causing fatal pulmonary hypertension is a rare presentation of malignancy. In general, patients with PTTM rapidly succumb to death due to severe hypoxia. To date, very few cases of PTTM have been reported in the literature; and most of these cases were from gastric cancer and were diagnosed on post mortem autopsy, as it is extremely challenging to make an ante mortem diagnosis. We here report on a case of undiagnosed diffuse gastric cancer, presenting as worsening hypoxia. The clinical, radiographic, and echocardiographic features, and laboratory and pathological results were consistent with PTTM from gastric cancer. The patient was started on anticoagulation therapy, corticosteroids, and high-flow oxygen. However, her hypoxia worsened to the extent that she required ventilator support, and she died soon after intubation due to cardiac arrest. Since diffuse gastric cancer is associated with hereditary diffuse gastric cancer syndrome, cadherin 1 gene mutation analysis was performed to estimate the risk to her daughters. The test came back negative.

• Childhood Kidney Diseases
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• v.17 no.2
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• pp.149-153
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• 2013

We report the case of a 14-year-old girl, diagnosed with atypical thrombotic microangiopathy (TMA). The patient presented with persistent fever, nausea, and newly developed peripheral edema. Her laboratory findings indicated chronic anemia with no evidence of hemolysis, thrombocytopenia, or elevated serum creatinine level. A few days after hospitalization, acute renal failure and fever worsened, and proteinuria developed. On day 40 of hospitalization, she experienced a generalized tonic seizure for 5 min, accompanied by renal hypertension. Brain magnetic resonance imaging revealed posterior reversible leukoencephalopathy syndrome. After steroid pulse therapy, a renal biopsy was performed because of delayed recovery from thrombocytopenia. The biopsy findings showed features of thrombotic microangiopathic hemolysis with fibrinoid change restricted. Current diagnostic criteria for TMA have focused on thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, and diagnosis is based on the clinical presentation and etiology, with the consequence that idiopathic and atypical forms of TMA can be overlooked. Developing effective tools to diagnose TMA, such as studying levels of ADAMTS13 or testing for abnormalities in the complement system, will be the first step to improving patient outcomes.

• Childhood Kidney Diseases
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• v.23 no.1
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• pp.43-47
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• 2019

Atypical hemolytic uremic syndrome (aHUS), a rare form of thrombotic microangiopathy, is distinguished from the typical form by the absence of a preceding verotoxin-producing Escherichia coli infection. Notably, aHUS occurs in association with genetic or acquired disorders causing dysregulation of the alternative complement pathway. Patients with aHUS may show the presence of anti-complement factor H (CFH) autoantibodies. This acquired form of aHUS (antiCFH-aHUS) primarily affects children aged 9-13 years. We report a case of a 13-year-old Lao girl with clinical features of aHUS (most likely anti-CFH-aHUS). The initial presentation of the patient met the classical clinical triad of thrombotic microangiopathy (microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury) without preceding diarrheal illness. Low serum levels of complement 3 and normal levels of complement 4 indicated abnormal activation of the alternative complement pathway. Plasma infusion and high-dose corticosteroid therapy resulted in improvement of the renal function and hematological profile, although the patient subsequently died of infectious complications. This is the first case report that describes aHUS (possibly anti-CFH-aHUS) in Laos.

• Childhood Kidney Diseases
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• v.2 no.2
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• pp.138-144
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• 1998

Purpose : The use of cyclosporine and mitomycin in various immunologic or neoplastic disorders has been known to cause wide-ranged nephrotoxic effects including thrombotic microangiopathy. However, the mechanism of nephrotoxicity of these drugs has not been studied adequately, so that present experimental study has been undertaken to find out whether these drugs can cause direct damage to the kidney and to clarify the pathogenetic mechanism of nephrotoxic effect of these drugs. Materials and methods : Sprague-Dawley rats weighing 250-300 gm were used for experimental animals and unilateral renal perfusion technique, modified from the method described by Hoyer et al was used. Isolation of left kidney from systemic circulation was made by clamping aorta and left renal vein and a hole was punctured in the anterior wall of the left renal vein. Cyclosporine (2.5 mg in 4 ml solution) and mitomycin (1.6 mg in 4ml solution) were infused through left renal artery and normal saline was used in control rats. Forty-eight hours after infusion of the drugs, animals were sacrificed and left kidney removed and processed for histologic examination. Total ischemic time of left kidney was less than 15 minutes: Results : Cyclosporine-perfused group showed severe swelling of glomerular endothelial ceil along with swelling of glomerular epithelial cell and interstitial vascular endothelial cell. Mitomycin-perfused group also showed severe swelling of glomerular endothelial and epithelial cells. And in addition to these findings, they demonstrated platelets aggregation, swelling and degranulation of platelets and fibrin accumulation in some of the capillaries, indicating occurrance of thrombotic microangiopathy. Conclusion : present experiment indicates that cyclosporine and mitomycin can cause direct toxic injury to renal endothelial cell. And this direct toxic damage to endothelial cell seems to be an important initiating event for the development of thrombotic microangiopathy.

• Biomolecules & Therapeutics
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• v.20 no.3
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• pp.268-272
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• 2012

Nephrotoxicity occurs when kidney-specific detoxification and excretion do not work properly due to the damage or destruction of kidney function by exogenous or endogenous toxicants. Exposure to drugs often results in toxicity in kidney which represents the major control system maintaining homeostasis of body and thus is especially susceptible to xenobiotics. Understanding the toxic mechanisms for nephrotoxicity provides useful information on the development of drugs with therapeutic benefits with reduced side effects. Mechanisms for drug-induced nephrotoxicity include changes in glomerular hemodynamics, tubular cell toxicity, inflammation, crystal nephropathy, rhabdomyolysis, and thrombotic microangiopathy. Biomarkers have been identified for the assessment of nephrotoxicity. The discovery and development of novel biomarkers that can diagnose kidney damage earlier and more accurately are needed for effective prevention of drug-induced nephrotoxicity. Although some of them fail to confer specificity and sensitivity, several promising candidates of biomarkers were recently proved for assessment of nephrotoxicity. In this review, we summarize mechanisms of drug-induced nephrotoxicity and present the list of drugs that cause nephrotoxicity and biomarkers that can be used for early assessment of nephrotoxicity.

• Clinical and Experimental Pediatrics
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• v.53 no.3
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• pp.428-431
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• 2010

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy characterized by endothelial cell damage, resulting in microangiopathic hemolytic anemia, thrombocytopenia, and various degrees of neurological and renal impairment caused by microvascular thrombi. It is rare in children and frequently follows a fatal course. TTP is divided into 2 types: one is inherited and associated with ADAMTS-13 gene mutations and the other is acquired and associated with anti-ADAMTS-13 autoantibodies. The measurement of ADAMTS-13 activity in plasma, identification of ADAMTS-13 circulating inhibitor, anti-ADAMTS-13 IgG, and ADAMTS-13 gene sequencing are crucial to the diagnosis of TTP. Plasma exchanges are the first-line treatment for acquired TTP, combined with steroids and immunosuppressive drugs. Here, we describe the case of an adolescent patient with TTP, confirmed by decreased level of ADAMTS-13 activity and an increased level of ADAMTS-13 inhibitor, who was successfully treated by plasma exchanges.

• Journal of Trauma and Injury
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• v.34 no.4
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• pp.299-304
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• 2021

Atypical hemolytic uremic syndrome (aHUS) is a rare, progressive, life-threatening condition of thrombotic microangiopathy characterized by thrombocytopenia, microangiopathic hemolytic anemia, and renal impairment. The mechanisms underlying aHUS remain unclear. Herein, we present the first case in the literature of aHUS after a traumatic injury. A 55-year-old male visited the emergency department after a traumatic injury caused by a tree limb. Abdominal computed tomography revealed a rectal wall defect with significant air density in the perirectal space and preperitoneum, implying rectal perforation. Due to the absence of intraperitoneal intestinal perforation, we performed diverting sigmoid loop colostomy. An additional intermittent simple repair was performed due to perianal and anal injuries. One day postoperatively, his urine output abruptly decreased and serum creatinine level increased. His platelet level decreased, and a spiking fever occurred after 2 days. The patient was diagnosed with acute renal failure secondary to aHUS and was treated with fresh frozen plasma replacement. Continuous renal replacement therapy (CRRT) was also started for oliguria and uremic symptoms. The patient received CRRT for 3 days and intermittent hemodialysis thereafter. After hemodialysis and subsequent supportive treatment, his urine output and renal function improved. The hemolytic anemia and thrombocytopenia also gradually improved. Dialysis was terminated on day 22 of admission and the patient was discharged after recovery. This case suggests that that a traumatic event can trigger aHUS, which should be considered in patients who have thrombocytopenia and acute renal failure with microangiopathic hemolytic anemia. Early diagnosis and appropriate management are critical for favorable outcomes.