tretinoin and Acute-Kidney-Injury

Differentiation Syndrome (DS) has been identified in a subset of patients undergoing treatment with novel classes of differentiating therapies for acute myeloid leukemia (AML) such as IDH and FLT3 inhibitors. While DS is a well-known treatment-related complication in acute promyelocytic leukemia (APL), efforts are still ongoing to standardize diagnostic and treatment parameters for DS in AML. Though the rates of incidence vary, many of the signs and symptoms of DS are common between APL and AML. So, DS can lead to fatal complications in AML, but prompt management is usually effective and rarely necessitates interruption or discontinuation of AML therapy.

Topics: Acute Kidney Injury; Adrenal Cortex Hormones; Antineoplastic Agents; Arsenic Trioxide; Cell Differentiation; Clinical Trials as Topic; Cytokine Release Syndrome; Edema; Enzyme Inhibitors; Epigenesis, Genetic; Fever; fms-Like Tyrosine Kinase 3; Humans; Hypotension; Isocitrate Dehydrogenase; Leukemia, Myeloid, Acute; Molecular Targeted Therapy; Myelopoiesis; Neoplasm Proteins; Pleural Effusion; Respiration Disorders; Tretinoin

Acute promyelocytic leukaemia differentiation syndrome (APL DS) is seen when patients with APL are treated with all-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO). Presenting symptoms are varied but frequently include dyspnoea, unexplained fever, weight gain >5 kg, unexplained hypotension, acute renal failure and a chest radiograph demonstrating pulmonary infiltrates or pleural or pericardial effusion. Immediate treatment with steroids at the first clinical suspicion is recommended and ATRA/ATO should be stopped in severe cases or if there is no response to treatment. The utility of steroid prophylaxis in order to prevent APL DS is less certain. Here we provide a detailed review of the pathogenesis, clinical signs and symptoms as well as management and prophylaxis strategies of APL DS.

Topics: Acute Kidney Injury; Arsenic Trioxide; Cell Differentiation; Humans; Hypotension; Leukemia, Promyelocytic, Acute; Pulmonary Edema; Steroids; Syndrome; Tretinoin

Kidney is a target organ for heavy metals. They accumulate in several segments of the nephron and cause profound alterations in morphology and function. Acute intoxication frequently causes acute renal failure. The effects of chronic exposure have not been fully disclosed. In recent years increasing awareness of the consequences of their presence in the kidney has evolved. In this review we focus on the alterations induced by heavy metals on the intercellular junctions of the kidney. We describe that in addition to the proximal tubule, which has been recognized as the main site of accumulation and injury, other segments of the nephron, such as glomeruli, vessels, and distal nephron, show also deleterious effects. We also emphasize the participation of oxidative stress as a relevant component of the renal damage induced by heavy metals and the beneficial effect that some antioxidant drugs, such as vitamin A (all-trans-retinoic acid) and vitamin E ( α -tocopherol), depict on the morphological and functional alterations induced by heavy metals.

Topics: Acute Kidney Injury; Antioxidants; Humans; Kidney; Kidney Glomerulus; Kidney Tubules, Proximal; Metals, Heavy; Nephrons; Oxidative Stress; Tight Junction Proteins; Tretinoin

All trans-retinoic acid (ATRA) syndrome is a life-threatening complication of uncertain pathogenesis that can occur during the treatment of acute promyelocytic leukemia (APL) by ATRA. Since its initial description, however, no large series of ATRA syndrome has been reported in detail. We analyzed cases of ATRA syndrome observed in an ongoing European trial of treatment of newly diagnosed APL. In this trial, patients 65 years of age or less with an initial white blood cell count (WBC) less than 5,000/microL were initially randomized between ATRA followed by chemotherapy (CT) (ATRA-->CT group) or ATRA with CT started on day 3; patients with WBC greater than 5,000/microL received ATRA and CT from day 1; patients aged 66 to 75 received ATRA-->CT. In patients with initial WBC less than 5, 000/microL and allocated to ATRA-->CT, CT was rapidly added if WBC was greater than 6,000, 10,000, 15,000/microL by days 5, 10, and 15 of ATRA treatment. A total of 64 (15%) of the 413 patients included in this trial experienced ATRA syndrome during induction treatment. Clinical signs developed after a median of 7 days (range, 0 to 35 days). In two of them, they were in fact present before the onset of ATRA. In 11 patients, they occurred upon recovery from the phase of aplasia due to the addition of CT. Respiratory distress (89% of the patients), fever (81%), pulmonary infiltrates (81%), weight gain (50%), pleural effusion (47%), renal failure (39%), pericardial effusion (19%), cardiac failure (17%), and hypotension (12%) were the main clinical signs, and 63 of the 64 patients had at least three of them. Thirteen patients required mechanical ventilation and two dialysis. A total of 60 patients received CT in addition to ATRA as per protocol or based on increasing WBC; 58 also received high dose dexamethasone (DXM); ATRA was stopped when clinical signs developed in 30 patients. A total of 55 patients (86%) who experienced ATRA syndrome achieved complete remission (CR), as compared with 94% of patients who had no ATRA syndrome (P = .07) and nine (14%) died of ATRA syndrome (5 cases), sepsis (2 cases), leukemic resistance (1 patient), and central nervous system (CNS) bleeding (1 patient). None of the patients who achieved CR and received ATRA for maintenance had ATRA syndrome recurrence. No significant predictive factors of ATRA syndrome, including pretreatment WBC, could be found. Kaplan Meier estimates of relapse, event-free survival (EFS), and survival at 2 years were 32% +/-

Topics: Acute Kidney Injury; Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cardiovascular Diseases; Cytarabine; Dexamethasone; Disease-Free Survival; Female; Humans; Incidence; Leukemia, Promyelocytic, Acute; Leukocyte Count; Life Tables; Male; Middle Aged; Pericardial Effusion; Pleural Effusion; Proportional Hazards Models; Remission Induction; Respiration Disorders; Survival Rate; Syndrome; Treatment Outcome; Tretinoin

All-trans retinoic acid (ATRA) is used as standard induction therapy for acute promyelocytic leukemia (APL), but it is contraindicated for patients on hemodialysis. We present a case of a patient with APL on hemodialysis, intubated, and with marked disseminated intravascular coagulation (DIC) who was successfully treated with ATRA. A 49-year-old man was transferred to our hospital and admitted into the intensive care unit due to renal dysfunction, DIC, and pneumonia. Promyelocytes were noted in the peripheral blood, and he was diagnosed with APL after bone-marrow examination. Because of renal dysfunction, only Ara-C was used but with a reduced dose. The patient's condition improved, and he was extubated and withdrawn from dialysis on the 5

Topics: Acute Kidney Injury; Antineoplastic Combined Chemotherapy Protocols; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Remission Induction; Renal Dialysis; Tretinoin

Retinoic acid receptor (RAR) signaling is essential for mammalian kidney development but, in the adult kidney, is restricted to occasional collecting duct epithelial cells. We now show that there is widespread reactivation of RAR signaling in proximal tubular epithelial cells (PTECs) in human sepsis-associated acute kidney injury (AKI) and in mouse models of AKI. Genetic inhibition of RAR signaling in PTECs protected against experimental AKI but was unexpectedly associated with increased expression of the PTEC injury marker Kim1. However, the protective effects of inhibiting PTEC RAR signaling were associated with increased Kim1-dependent apoptotic cell clearance, or efferocytosis, and this was associated with dedifferentiation, proliferation, and metabolic reprogramming of PTECs. These data demonstrate the functional role that reactivation of RAR signaling plays in regulating PTEC differentiation and function in human and experimental AKI.

Topics: Acute Kidney Injury; Animals; Epithelial Cells; Humans; Kidney; Kidney Tubules, Proximal; Mammals; Mice; Tretinoin

Although arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) are well-tolerated and effective treatments for Acute Promyelocytic Leukemia (APL), Differentiation Syndrome (DS) is a lethal side effect in some patients. The pathogenesis of DS is complex and not well understood; however, it is considered as an inflammatory response due to cytokines release of differentiated cells. Moreover, adhesion molecules that are widely expressed on the surface of differentiated cells and gene expression changes of transglutaminase2 (TGM2) are mechanisms involved in the development of DS. The purpose of this study was to assess the association of single nucleotide polymorphisms (SNP) of Intercellular Adhesion Molecule-1 (ICAM-1), chemokine (C-C motif) ligand 2 (CCL2) and TGM2 as inflammatory factors with differentiation syndrome susceptibility.. DNA was extracted from 133 APL patients and 100 normal controls. Assessment according to the PETHEMA criteria revealed that 13.5% of these patients experienced differentiation syndrome. Tetra-ARMS PCR and PCR-RFLP were done to amplify DNA fragments in APL patients with and without DS. Then DNA sequencing was done to validate the results. SNPStats, SPSS and Finch TV were used to analyze the results.. A significant correlation was found between rs4811528 in the TGM2 gene and differentiation syndrome susceptibility (P = 0.002, 95% CI = 1.74-18.81, OR = 5.72) while rs5498 in ICAM-1, rs1024611 in CCL2, and rs7270785 in TGM2 genes showed no correlation with differentiation syndrome. The G allele of rs7270785 and rs4811528 showed a haplotypic association with differentiation syndrome (P = 0.03, 95% CI = 1.13-13.86, OR = 3.96).. AA genotype of the TGM2 SNP (rs4811528) may be a risk factor for development of DS in patients with APL following the use of ATRA/ATO.

Topics: Acute Kidney Injury; Adult; Antineoplastic Agents; Biomarkers, Tumor; Case-Control Studies; Cell Differentiation; Chemokine CCL2; Female; Follow-Up Studies; GTP-Binding Proteins; Humans; Intercellular Adhesion Molecule-1; Leukemia, Promyelocytic, Acute; Lung Diseases; Male; Polymorphism, Genetic; Prognosis; Protein Glutamine gamma Glutamyltransferase 2; Survival Rate; Syndrome; Systemic Inflammatory Response Syndrome; Transglutaminases; Tretinoin

Topics: Abdomen; Acute Kidney Injury; Aged, 80 and over; Anaplasma phagocytophilum; Antineoplastic Agents; Bone Marrow Examination; Diagnosis, Differential; Ehrlichiosis; Fibrin Fibrinogen Degradation Products; Humans; L-Lactate Dehydrogenase; Leukemia, Promyelocytic, Acute; Male; Pancytopenia; Thorax; Tomography, X-Ray Computed; Tretinoin

Contrast-induced acute kidney injury (CI-AKI) has been the third leading cause of hospital-acquired AKI. Retinoic acid (RA), the main derivative of vitamin A, has preventative and therapeutic effects in ischemia-reperfusion-AKI and UUO models, but little is known about its effects on CI-AKI. This study aimed to explore the effects of RA on CI-AKI as well as the underlying mechanisms.. We established a new miniature pig model of CI-AKI by catheterizing the external jugular vein and injecting a single dose of iohexol after dehydration. Bun, Scr, serum and urinary RBP and β-MG levels were measured. Renal histological, TEM examination, LDH assays, TUNEL assays, GFP-LC3 plasmid transfection and western blotting were performed.. The levels of Bun, Scr, serum and urinary RBP and β-MG were increased after CI-AKI and decreased by RA pretreatment. The renal histology showed foamy degeneration and dilated tubules after CI-AKI, and the tissue damage was alleviated significantly by RA pretreatment. RA mitigated renal fibrosis after CI-AKI. In vitro, RA protected proximal TECs against iohexol-induced injury. RA inhibited TECs apoptosis and activated autophagy in vivo and in vitro.. RA alleviates CI-AKI and mitigates renal fibrosis after CI-AKI. Autophagy activation and apoptosis inhibition are involved in the protective effect of RA on CI-AKI. RA may be a new agent for the prevention and therapeutic treatment of CI-AKI in the future.

Topics: Acute Kidney Injury; Animals; Apoptosis; Contrast Media; Disease Models, Animal; Humans; Protective Agents; Swine; Swine, Miniature; Tretinoin

Acute kidney injury (AKI) is a serious disorder for which there are limited treatment options. Following injury, native nephrons display limited regenerative capabilities, relying on the dedifferentiation and proliferation of renal tubular epithelial cells (RTECs) that survive the insult. Previously, we identified 4-(phenylthio)butanoic acid (PTBA), a histone deacetylase inhibitor (HDI), as an enhancer of renal recovery, and showed that PTBA treatment increased RTEC proliferation and reduced renal fibrosis. Here, we investigated the regenerative mechanisms of PTBA in zebrafish models of larval renal injury and adult cardiac injury. With respect to renal injury, we showed that delivery of PTBA using an esterified prodrug (UPHD25) increases the reactivation of the renal progenitor gene

Topics: Acute Kidney Injury; Animals; Animals, Genetically Modified; Butyrates; Cell Dedifferentiation; Cell Proliferation; Epithelial Cells; Immune System; Kidney Tubules; Macrophages; Neutrophils; PAX2 Transcription Factor; Prodrugs; Regeneration; Signal Transduction; Sulfides; Tretinoin; Zebrafish; Zebrafish Proteins

Differentiation syndrome (DS), previously known as retinoic acid syndrome or ATRA (all-trans retinoic acid) or ATO (arsenic trioxide) syndrome, is a life-threatening complication of the therapy with differentiating agents in patients with acute promyelocytic leukemia (APL). The latter is a rare subtype of acute myeloid leukemia and represents a hematological emergency. The clinical manifestations of DS, after induction therapy with differentiating agents, include unexplained fever, acute respiratory distress with interstitial pulmonary infiltrates, unexplained hypotension, peripheral edema, congestive heart failure and acute renal failure. The therapy is based on early intravenous administration of high-dose dexamethasone, in order to counteract the cytokine storm responsible for the DS. Among the supportive measures for the management of DS, furosemide (in 87% of patients) and dialysis (12% of patients) are used to manage acute renal failure, peripheral and pulmonary edema. We describe a case of acute renal failure, treated with haemodialysis, in a young patient with APL and an early and severe DS after induction therapy. This is a rare condition, not well known among nephrologists, where early recognition and treatment are crucial for the prognosis.

Topics: Acute Kidney Injury; Adult; Antineoplastic Agents; Arsenic Trioxide; Dexamethasone; Edema; Fever of Unknown Origin; Humans; Hypotension; Induction Chemotherapy; Leukemia, Promyelocytic, Acute; Male; Renal Dialysis; Respiratory Distress Syndrome; Syndrome; Tretinoin

Retinoic acid (RA) has been used therapeutically to reduce injury and fibrosis in models of AKI, but little is known about the regulation of this pathway and what role it has in regulating injury and repair after AKI. In these studies, we show that RA signaling is activated in mouse and zebrafish models of AKI, and that these responses limit the extent of injury and promote normal repair. These effects were mediated through a novel mechanism by which RA signaling coordinated the dynamic equilibrium of inflammatory M1 spectrum versus alternatively activated M2 spectrum macrophages. Our data suggest that locally synthesized RA represses proinflammatory macrophages, thereby reducing macrophage-dependent injury post-AKI, and activates RA signaling in injured tubular epithelium, which in turn promotes alternatively activated M2 spectrum macrophages. Because RA signaling has an essential role in kidney development but is repressed in the adult, these findings provide evidence of an embryonic signaling pathway that is reactivated after AKI and involved in reducing injury and enhancing repair.

Topics: Acute Kidney Injury; Animals; Macrophages; Male; Mice; Mice, Inbred BALB C; Signal Transduction; Tretinoin

All-trans retinoic acid (ATRA) is routinely associated with chemotherapy for the treatment of acute promyelocytic leukemia (APL). Several reports of scrotal ulceration induced by this agent have been made in the recent years.. The aim of this article was to report the first case of a lingual ulceration associated with retinoic acid syndrome (RAS).. We presented a 32-year-old man with a diagnosis of acute promyelocytic leukemia who received treatment with ATRA. He presented with febrile neutropenia and a lingual ulcer that did not respond to antibiotic and antifungal regimens. He developed weight gain, lower limb edema, polyserositis, and acute renal failure. Retinoic acid syndrome syndrome was diagnosed.. An exhaustive attempt to exclude infectious causes was made performing repeated cultures, histologic examinations, and direct immunofluorescence for HSV. No causative agent was identified. Re-epithelialization of the ulcer was achieved with ATRA cessation and treatment with systemic steroids.. As far as we are concerned, we report the first case of a lingual ulceration associated with RAS.. It is important for dermatologists to recognize this cutaneous complication of ATRA as it poses many differential diagnoses in neutropenic patients.

Topics: Acute Kidney Injury; Adult; Antineoplastic Combined Chemotherapy Protocols; Febrile Neutropenia; Humans; Idarubicin; Leukemia, Promyelocytic, Acute; Male; Oral Ulcer; Syndrome; Tongue Diseases; Tretinoin

Differentiation syndrome is a life-threatening complication of therapy that is carried out with agents used for acute promyelocytic leukemia. Its physiopathology comprehends the production of inflammatory mediators by differentiating granulocytes, endothelial and alveolar cells due to stimulation by all-trans retinoic acid and leading to sustained systemic inflammation.. Treatment with high cut-off continuous veno-venous hemodialysis (HCO-CVVHD) was performed to reduce the circulating mediators of systemic inflammation.. After 52 h of treatment, an important reduction was observed in inflammatory mediators (IL-1β: from 10 to 2 pg/ml; IL-8: from 57 to 40 pg/ml; TNF-α: from 200 to 105 pg/ml; IL-6: from 263 to 91 pg/ml), as well as in anti-inflammatory mediators (IL-10: from 349 to 216 pg/ml).. HCO-CVVHD should be explored as a part of treatment in systemic inflammation states other than sepsis (e.g., differentiation syndrome). Furthermore, its immunomodulatory effects could be particularly useful in immunocompromised patient treated with corticosteroids.

Topics: Acute Kidney Injury; Adult; Anticoagulants; Antineoplastic Combined Chemotherapy Protocols; Calcium Citrate; Capillary Leak Syndrome; Cell Differentiation; Disseminated Intravascular Coagulation; Fatal Outcome; Hemofiltration; Humans; Idarubicin; Immunomodulation; Inflammation; Inflammation Mediators; Leukemia, Promyelocytic, Acute; Male; Membranes, Artificial; Molecular Weight; Permeability; Prednisolone; Respiratory Insufficiency; Serum Albumin; Syndrome; Tretinoin

Ginsenoside Rb1 (RB1), the most clinically effective constituent of ginseng, possesses a variety of biological activities. The objectives of this study were to investigate the protective effects of RB1 and its underlying mechanism on renal injury induced by intestinal ischemia-reperfusion (IIR) in mice. RB1 was administered prior to inducing IIR achieved by occluding the superior mesenteric artery for 45 min followed by 120 min of reperfusion. All-trans-retinoic acid (ATRA) was used as an inhibitor of NF-E2-related factor-2 (Nrf2) signaling. Adult male C57BL/6J mice were randomly divided into six groups: (1) sham group, (2) IIR group, (3) RB1 group, (4) sham + ATRA group, (5) IIR + ATRA group, and (6) RB1 + ATRA group. Intestinal histology and pathological injury score were observed. Intestinal mucosal injury was also evaluated by measuring serum diamine oxidase (DAO). Renal injury induced by IIR was characterized by increased levels of histological severity score, blood urea nitrogen (BUN), serum creatinine (Scr) and neutrophil gelatinase-associated lipocalin (NGAL), which was accompanied with elevated renal TUNEL-positive cells and the Bcl-2/Bax expression ratio. RB1 significantly reduced renal injury and apoptosis as compared with IIR group, which was reversed by ATRA treatment. Immunohistochemistry and Western blot analysis demonstrated that RB1 significantly upregulated the protein expression of heme oxygenase-1 (HO-1) and Nrf2, which were attenuated by ATRA treatment. Taken together, these results suggest that the protective effects of RB1 pretreatment against renal injury induced by IIR are associated with activation of the Nrf2/ anti-oxidant response element (ARE) pathway.

Topics: Acute Kidney Injury; Acute-Phase Proteins; Amine Oxidase (Copper-Containing); Animals; Antioxidants; bcl-2 Homologous Antagonist-Killer Protein; bcl-2-Associated X Protein; Blood Urea Nitrogen; Creatinine; Gene Expression Regulation; Ginsenosides; Intestinal Mucosa; Intestines; Kidney; Lipocalin-2; Lipocalins; Male; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; Oncogene Proteins; Oxidative Stress; Reperfusion Injury; Signal Transduction; Tretinoin

All-trans retinoic acid (ATRA) is a vitamin A derivative that is used in combination with chemotherapy to treat acute promyelocytic leukemia (APL). A serious complication of ATRA is retinoic acid syndrome (RAS), which is characterized by an inflammatory reaction with capillary leakage and myeloid cell tissue invasion that presents with cardiopulmonary symptoms and occasionally acute kidney injury.. We report the case of a 3-year-old child with APL who developed transient nephrotic-range proteinuria (max urine protein:creatinine ratio 8.6) during two episodes of RAS while on ATRA therapy. ATRA was temporarily discontinued and the patient was treated with a 3-day course of dexamethasone during each episode. He maintained normal renal function throughout and the proteinuria completely resolved.. This is the first reported occurrence of nephrotic-range proteinuria in a child treated with ATRA. Nephrologists should be aware that RAS is a serious complication of ATRA that may lead to proteinuria.

Topics: Acute Kidney Injury; Antineoplastic Agents; Child, Preschool; Humans; Leukemia, Promyelocytic, Acute; Male; Proteinuria; Tretinoin

Nur77 and its family members Nurr1 and Nor-1 are inducible orphan nuclear receptors that orchestrate cellular responses to diverse extracellular signals. In epithelia, Nur77 can act as a potent proapoptotic molecule in response to cellular stress, suggesting a possible role for this nuclear receptor in the tissue response to injury. Here, we found that Nur77 promotes epithelial cell apoptosis after AKI. Injury of proximal tubular epithelial cells rapidly and strongly induced Nur77, Nor-1, and Nurr1 both in vitro and in vivo. After renal ischemia-reperfusion, Nurr77-deficient mice exhibited less apoptosis of tubular epithelial cells and better renal function than wild-type mice. Nur77-mediated renal injury involved a conformational change of Bcl2 and an increase in the protein levels of proapoptotic Bcl-xS. Ligand-activated retinoic acid receptors repressed Nur77 induction and function. Pretreatment of wild-type mice with retinoic acid before renal ischemia-reperfusion blunted the induction of Nur77, conferred protection of renal function, attenuated renal histologic injury, and reduced the expression of epithelial-derived proinflammatory cytokines. Retinoic acid also inhibited hypoxia-mediated induction of proinflammatory cytokines in cultured renal epithelial cells. Results obtained from proximal tubule cultures derived from Nur77-deficient mice suggested that the inhibition of Nur77 expression mediated the renoprotective effects of retinoic acid. In summary, Nur77 promotes epithelial apoptosis after ischemia-reperfusion injury, and retinoic acid-mediated inhibition of Nur77 expression is a promising therapeutic strategy for the prevention of AKI.

Topics: Acute Kidney Injury; Animals; Apoptosis; Cells, Cultured; Dimethyl Sulfoxide; Disease Models, Animal; DNA-Binding Proteins; Epithelial Cells; In Situ Hybridization; Kidney Function Tests; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nuclear Receptor Subfamily 4, Group A, Member 1; Random Allocation; Reference Values; Reperfusion Injury; Severity of Illness Index; Tretinoin

All-trans-retinoic acid (ATRA), which is used in acute promyelocytic leukemia, is usually well tolerated, but some side effects can be observed. Retinoic acid syndrome is the most severe side effect. Triazole derivatives such as fluconazole inhibit the NADPH-dependent cytochrome P-450-mediated catabolism of ATRA and are increased plasma levels of ATRA. Here, the authors report a case of APL who developed acute renal failure during ATRA and concurrent use of fluconazole.

Topics: Acute Kidney Injury; Adolescent; Antifungal Agents; Antineoplastic Agents; Female; Fluconazole; Humans; Leukemia, Promyelocytic, Acute; Tretinoin

The all-trans retinoic acid (ATRA) is the treatment of first line of acute promyelocytic leukemia (APL). ATRA is usually well tolerated, but a few major side effects can be observed, ATRA syndrome (RAS) being the most important of them, potentially fatal. The manifestations of this Syndrome are fever, weight gain, pulmonary infiltrates, pleural or pericardial effusions, hypotension, liver dysfunction and renal failure.. We studied to the 29 patients diagnosed in (January of 2002 - December of 2004) of acute promyelocytic leukemia (APL), which were treated with ATRA, all received the 45 dose of mg/m(2)/d . The diagnosis of the leukemia was made by citomorphologist analysis. The criterion of renal insufficiency, it was an increase of the creatinina superior to 20% of the basal level. The definition of the transretinoico acid Syndrome was based on the clinical criteria of Frankel.. Fourteen patients presented the Transretinoico Syndrome (48.3%), 11 of which (37.9%) died. The fundamental differences between the patients with or without ATRA were: fever (14 vs. 9, p=0,017), gain of weight (14 vs 0, p=0,000), pleural effusion (14 vs 2, p=0.000), pulmonary infiltrates (13 vs 1, p=0,000), cardiac failure (12 versus 2, p=0,000), respiratory distress (12 versus 4, p=0,003), presence of renal failure (10 vs 4, p=0,02), necessity of substitute renal treatment (6 vs 0, p=0,006) and arterial hypotension (12 vs. 3, p=0,001). The acute renal failure appeared in 10 of the 14 patients with SAR (71.4%), to 12+/-5 (1-25) days of the beginning of the treatment and their duration it was of 14+/-5 (1-46) days. Six (60%) needed substitute renal treatment and 5 (50%) died. Of the patients who survived, only a patient continues in dialysis. In both patient in that renal biopsy was made, the study showed signs of cortical necrosis.. The appearance of acute renal failure in the course of the SAR is frequent, being observed deterioration of the renal function that needs substitute renal treatment in more than half the cases. The association of RAS with renal failure entails the high mortality (50%). The diagnosis and the precocious restoration of suitable the preventive measures and therapeutic are very important to avoid in possible the this serious complication of the treatment with ATRA.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Child; Female; Humans; Male; Middle Aged; Prevalence; Syndrome; Tretinoin

Retinoic acid syndrome (RAS) is the clinical syndrome that occurs after treatment of acute promyelocytic leukemia with all-trans-retinoic acid (ATRA). The patients experience fever, dyspnea, hypotension, respiratory distress, edema and weight gain. Chest x-ray will show pulmonary infiltrates and pleuropericardial effusion. The onset of this syndrome is usually 5-21 days after ATRA treatment when white blood cell counts are rising more than 10,000/cu.mm. The authors have reported a case of RAS. The patient was a 29-year-old man who had been working in a battery manufacturing factory for 7 years. He presented with easily bruising for one month. The initial blood test showed hematocrit of 36.2%, white blood cells count of 3,200/cu.mm with 28% neutrophils, 20% lymphocytes, 2% eosinophils and 50% promyelocytes and platelet of 20,000/cu.mm. Peripheral blood smear revealed numerous fragmented red blood cells. Bone marrow examination showed hypercellularity with abnormal promyelocytes of 95% and bone marrow cytogenetics was translocation of chromosome 15 and 17 [t (15;17)(q22;q12)]. The diagnosis was acute promyelocytic leukemia and the patient was treated with ATRA 45 mg/m2/day per oral starting on day 1 and intravenous idarubicin 10 mg/n2 on day 4, 5 and 6. On day 13, he had a body temperature of 39 degrees C and a dry cough. The white blood cells were rising to 7,400/cu.mm with 16% neutrophils. On day 18, he had oliguria, high grade fever, hypotension, cough with chest pain and white blood cells rose to 21,300/cu.mm with 65% neutrophils and rising of blood urea nitrogen and creatinine. Chest x-ray showed enlarged cardiac shadow with pleural effusion. Echocardiogram revealed moderate amount of pericardial effusion. The diagnosis of RAS was made and ATRA was withdrawn. Intravenous dexamethasone 4 mg every 6 hours and hemodialysis was started. The patient's symptoms improved dramatically and bone marrow examination was in complete remission. He was subsequently given cytarabine and idarubicin as consolidation. This patient had clinical manifestation consistent with RAS, which improved after prompt treatment.

Topics: Acute Kidney Injury; Adult; Dexamethasone; Glucocorticoids; Humans; Leukemia, Promyelocytic, Acute; Male; Respiration Disorders; Syndrome; Tretinoin

Retinoic acid (RA) exerts beneficial effects on vascular remodelling and experimental nephritis, and plays a role in kidney development. Pathological changes caused by acute renal failure (ARF) result in high mortality. We determined whether RA ameliorates ARF-induced pathology caused by potassium dichromate (PD).. Adult Wistar female rats (210-250 g) were randomly allocated to four groups: (i) an ARF group that received PD [15 mg/kg body weight (bw), single dose subcutaneously]; (ii) a group that received PD plus RA (1 mg/kg bw) beginning at 5 days before PD and that continued for 14 additional days; (iii) a group that received PD plus thyroxine (T(4); 8 micro g/100 g bw) with RA; and (iv) a group that received only the vehicle for PD (saline solution). We evaluated functional, biochemical and morphological characteristics of the kidneys.. PD-induced alterations in serum creatinine, creatinine clearance (C(cr)) and fractional excretion of sodium (FeNa) were less severe when rats received RA. PD increased lipoperoxidation and this alteration was partially blocked by RA. Animals undergoing ARF showed severe histological injury (brush border loss, acidophilia, oedema, pyknosis, karyorhexis, cell detachment and disruption of the basement membrane). These alterations were less severe in RA-treated rats, indicating a protective effect on functional and morphological alterations. Alterations in urinary sediment were reduced by RA. The simultaneous administration of T(4) with RA did not produce additional protection.. RA exerted beneficial effects on the duration and severity of renal damage induced by PD in a model of renal failure resembling ARF in humans. The protective effect of RA may be mediated by diminished lipoperoxidative damage.

Topics: Acute Kidney Injury; Animals; Creatinine; Diuresis; Drug Combinations; Drug Synergism; Female; Lipid Peroxidation; Natriuresis; Potassium Dichromate; Rats; Rats, Wistar; Severity of Illness Index; Thyroxine; Tretinoin; Weight Loss

Topics: Acute Kidney Injury; Adult; Antifibrinolytic Agents; Antineoplastic Agents; Female; Humans; Kidney Cortex; Leukemia, Promyelocytic, Acute; Necrosis; Renal Artery; Thrombosis; Tomography, X-Ray Computed; Tranexamic Acid; Tretinoin

Topics: Acute Kidney Injury; Antineoplastic Agents; Dexamethasone; Humans; Hypertension; Incidence; Leukemia, Promyelocytic, Acute; Leukocyte Count; Leukocytosis; Leukostasis; Mortality; Premedication; Respiratory Distress Syndrome; Risk Factors; Syndrome; Tretinoin

A case of acute renal failure, due to occlusion of renal vessels in a patient with acute promyelocytic leukemia (APL) treated with all-trans-retinoic acid (ATRA) and tranexamic acid has been described recently. We report a case of acute renal failure in an APL patient treated with ATRA alone. This case further supports the concern about thromboembolic complications associated with ATRA therapy in APL patients. The patients, a 43-year-old man, presented all the signs and symptoms of APL and was included in a treatment protocol with ATRA. After 10 days of treatment, he developed acute renal failure that was completely reversible after complete remission of APL was achieved and therapy discontinued. We conclude that ATRA is a valid therapeutic choice for patients with APL, although the procoagulant tendency is not completely corrected. Thrombotic events, however, could be avoided by using low-dose heparin.

Topics: Acute Kidney Injury; Adult; Anticoagulants; Antineoplastic Agents; Blood Coagulation Factors; Disseminated Intravascular Coagulation; Fibrinolysis; Hemorrhage; Heparin; Humans; Kidney Glomerulus; Leukemia, Promyelocytic, Acute; Male; Thrombosis; Tretinoin

Topics: Acute Kidney Injury; Administration, Oral; Anemia, Hemolytic; Antineoplastic Agents; Australia; Dose-Response Relationship, Drug; Fatal Outcome; Hemolysis; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Tretinoin

All-trans-retinoic acid is an effective agent to induce remission in patients with acute promyelocytic leukemia (APL). Unlike conventional chemotherapy, this drug exerts its effect by inducing differentiation of immature leukemic cells. A distinctive clinical syndrome characterized by fever, dyspnea, effusions, weight gain, and organ failure (the "retinoic acid syndrome") can occur during treatment with this drug. Postmortem studies have shown extensive organ infiltration by leukemic cells, and the early administration of corticosteroids can result in prompt resolution of symptoms. We describe a patient with APL in whom acute renal failure developed during treatment with all-trans-retinoic acid. Transient renal enlargement during a period of leukocytosis and a beneficial response to treatment with dexamethasone suggest that renal failure in this patient was probably related to the retinoic acid syndrome.

Topics: Acute Kidney Injury; Dyspnea; Fever; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Pericardial Effusion; Pleural Effusion; Syndrome; Tretinoin

Topics: Acute Kidney Injury; Adult; Antineoplastic Combined Chemotherapy Protocols; Cerebral Hemorrhage; Combined Modality Therapy; Cytarabine; Daunorubicin; Dexamethasone; Disease Progression; Fatal Outcome; Female; Humans; Leukemia, Promyelocytic, Acute; Leukocytosis; Renal Dialysis; Respiration, Artificial; Respiratory Insufficiency; Syndrome; Tretinoin

In contrast to patients with disseminated intravascular coagulation (DIC) due to other causes, patients with acute promyelocytic leukemia (APL) receiving standard cytotoxic chemotherapy can be treated safely with antifibrinolytic drugs for prophylaxis of hemorrhage, without the occurrence of thromboembolic complications. However, such drugs should be used cautiously in APL patients who are receiving all-trans retinoic acid (ATRA) differentiation therapy. We report here a patient with APL who had fatal thromboembolism after receiving ATRA and tranexamic acid therapy.

Topics: Acute Kidney Injury; Antifibrinolytic Agents; Drug Interactions; Fatal Outcome; Female; Hemorrhage; Humans; Leukemia, Promyelocytic, Acute; Middle Aged; Thromboembolism; Tretinoin

We recently demonstrated a rapid up-regulation of serum retinol-retinol binding protein-transthyretin concentration in rats with short-term acute renal failure. We examine the effect of retinoic acid and apo-retinol binding protein (apo-RBP) on the up-regulation of serum retinol in renal failure. Injection of retinoic acid (10 micrograms) into rats with acute renal failure or sham-operated rats increased circulatory retinoic acid concentration 29-fold within 2 h but did not influence serum retinol concentration in either group. Injection of a large dose of retinoic acid (100 micrograms) decreased serum retinol concentration in rats with acute renal failure (19%) and sham-operated rats (29%). These results suggest that changes in serum retinoic acid concentration within the near-physiological range have no effect on regulation of hepatic retinol release. Injection of a large dose of retinoic acid may depress serum retinol indirectly via a retinol sparing effect in target tissues. In rats with renal failure the serum retinol concentration, elevated 44-52% above that of sham-operated controls, was also increased to 70-164% above controls by the injection of 52-63 micrograms of apo-RBP. This suggests that circulatory apo-RBP can up-regulate serum retinol. Circulatory apo-RBP may be a positive physiological feedback signal from peripheral tissues for hepatic release of retinol.

Topics: Acute Kidney Injury; Animals; Apoproteins; Liver; Male; Rats; Rats, Inbred Strains; Retinol-Binding Proteins; Retinol-Binding Proteins, Plasma; Tretinoin; Vitamin A