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Blood Purif ; 44(3): 198-205, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28668963


BACKGROUND: Metformin-associated lactic acidosis (MALA) is a severe complication of drug administration with significant morbidity and mortality. So far no study in large population areas have examined the incidence, clinical profile and outcome of acute kidney injury (AKI)-MALA patients admitted in intensive care units (ICUs) and treated by renal replacement therapy (MALA-RRT). METHODS: Retrospective analysis over a 6-year period (2010-2015) in Piedmont and Aosta Valley regions (5,305,940 inhabitants, 141,174 diabetics treated with metformin) of all MALA-RRT cases. RESULTS: One hundred and seventeen cases of AKI-MALA-RRT were observed (12.04/100,000 metformin treated diabetics, 1.45% of all RRT-ICU patients). Survival rate was 78.3%. The average duration of RRT was 4.0 days at mean dialysis effluent of 977 mL/kg/day. At admission most patients were dehydrated, and experienced shock and oliguria. CONCLUSION: Our data showed that MALA-RRT is a common complication, needing more prevention. Adopted policy of early, extended, continuous and high efficiency dialysis could contribute to an observed high survival rate. Video Journal Club "Cappuccino with Claudio Ronco" at

Acidose Láctica , Cuidados Críticos , Unidades de Terapia Intensiva , Metformina/efeitos adversos , Terapia de Substituição Renal , Acidose Láctica/induzido quimicamente , Acidose Láctica/epidemiologia , Acidose Láctica/terapia , Idoso , Feminino , Humanos , Itália , Masculino , Metformina/administração & dosagem , Estudos Retrospectivos
Blood Coagul Fibrinolysis ; 26(2): 225-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25629417


Dabigatran is an oral direct inhibitor indicated for stroke prevention in patients with atrial fibrillation. Unlike warfarin, dabigatran's observed therapeutic window and minimal drug-to-drug interaction suggest that laboratory test and dose adjustments are not necessary; nevertheless, circumstances of excessive anticoagulation, decreased kidney function, and instances of significant bleeding and thrombosis require laboratory assessment. In order to gather experience in the management of global [activated partial thromboplastin time (APTT) and thrombin time (TT) with extended endpoint] and specific [ecarin chromogenic assay (ECA) and diluted thrombin time (dTT)] laboratory coagulation tests in patients receiving dabigatran with untoward effects, we describe a case in which hemodialysis was used in attempt to remove dabigatran in a patient with excessive anticoagulation, rectal bleeding, and severe anemia. Our experience confirmed that APTT is an unreliable method for the assessment of dabigatran in patients with acute complications because it was often normal in spite of the therapeutic drug plasma levels. Both ECA and dTT showed a linear correlation with dabigatran levels over a broad range, and identified therapeutic and supratherapeutic levels. TT assay, which is highly sensitive to dabigatran, correlated well and linearly not only with low drug levels, but also, because of the introduction of the extended endpoint (400 s), with high concentrations of the drug, and demonstrated to be a simple and reliable alternative to ECA and dTT to assess dabigatran in patients with acute complications.

Antitrombinas/envenenamento , Benzimidazóis/envenenamento , Coagulação Sanguínea/efeitos dos fármacos , Overdose de Drogas/terapia , Diálise Renal/métodos , beta-Alanina/análogos & derivados , Idoso de 80 Anos ou mais , Dabigatrana , Overdose de Drogas/sangue , Humanos , Masculino , beta-Alanina/envenenamento
G Ital Nefrol ; 31(2)2014.
Artigo em Italiano | MEDLINE | ID: mdl-24777926


A 85-year-old man, with CKD (e-GFR 35 mL/min), had been given Dabigatran (a direct thrombin inhibitor) at 110 mg daily dose because of atrial fibrillation. Due to intercurrent diarrhea and dehydration, renal function worsened (e-GFR 11 mL/min) and Dabigatran excretion decreased, thereby inducing drug overload. In this case, Dabigatran must be removed by dialysis, but the most appropriate schedule is still undefined. The effects of both continuous haemodiafiltration (CVVHDF) and intermittent haemodialysis (IHD) on plasma Dabigatran (Echarin Chromogenic Assay) were reported. Dialysis clearance of Dabigatran was reported as ratio to urea clearance (Dab/Urea(Cl)). Coagulation was assessed by both DOA-aPTTratio and Thrombin Time-ratio (TTratio). Dabigatran was elevated at 597 ng/mL predialysis (bleeding threshold being 30 ng/mL), and decreased to 96 ng/mL (-84%) after 20 hours of CVVHDF (Urea(Cl) = 67 mL/min). Dab/Urea(Cl) was 0.49. Three hours after dialysis, Dabigatran rebounded to 208 ng/mL. On IHD (Urea(Cl)=238 mL/min), predialysis Dabigatran was 52 ng/mL and decreased to 8 ng/mL (-85%) after 3.5 hours of treatment. Dab/Urea(Cl) was 0.47. Fourteen hours later, Dabigatran rebounded at 19 ng/mL. There was a positive correlation between Dabigatran and TTratio (r = 0.92; p<0.0001), whereas DOA-aPTT did not increase above 2.5 times the reference values, even in face of the highest values of Dabigatran. Therefore, TTratio is more reliable than DOA-aPTT in detecting Dabigatran overdose. Post-dialysis rebound of Dabigatran occurred also with CVVHDF, thereby suggesting that accurate monitoring of both Dabigatran levels and bleeding risk are mandatory, also after long-lasting dialysis sessions.

Antitrombinas/envenenamento , Benzimidazóis/envenenamento , Overdose de Drogas/terapia , Terapia de Substituição Renal , beta-Alanina/análogos & derivados , Idoso de 80 Anos ou mais , Dabigatrana , Humanos , Masculino , Diálise Renal , beta-Alanina/envenenamento
J Nephrol ; 26(1): 158-63, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22419236


BACKGROUND: Unfractionated heparin (UFH) is the standard anticoagulant in regular dialysis treatments (RDTs), despite the fact that it may induce thrombocytopenia, dyslipidemia, allergy and osteoporosis. Dermatan sulfate (DS) selectively inhibits thrombin, does not inhibit F-Xa and does not interfere with platelets (PLTS). Here we described an original protocol for the use of DS as anticoagulant in RDT and compared its effects with those of UFH. METHODS: In 102 patients, 7,254 RDTs were performed using DS for anticoagulation (DS-phase) and 5,707 with UFH (UFH-phase). DS was supplied as initial bolus (80 ± 12 mg) and continuous infusion (14 ± 7 mg/hour). With UFH, the initial bolus was 1,475 ± 141 IU and continuous infusion 576 ± 349 IU/hour. Activated partial thromboplastin time and its ratio were measured at least monthly, both before (pre-RDT APTT ratio) and after (post-RDT APTT ratio) RDT sessions. With 41 of 102 patients, both DS and UFH doses were not changed during study phases (stable patients). In this subset, the coefficient of variation (CV) of all pre-RDT APTT ratio and post-RDT APTT ratio values was calculated. RESULTS: In DS and UFH phases, post-RDT APTT ratio increased by 61% and 50%, respectively, by comparison with pre-RDT APTT ratio (p<0.001). PLTS count was lower in the UFH than in the DS phase (p<0.01). In stable patients, post-RDT APTT ratio CV was lower in the DS than in the UFH phase (p<0.001), which indicates a more predictable anticoagulant effect of DS compared with UFH. CONCLUSIONS: DS appeared as effective as UFH for anticoagulation in RDT. It can reliably be considered as an alternative approach especially in cases of thrombocytopenia or other adverse effects of UFH.

Anticoagulantes/administração & dosagem , Dermatan Sulfato/administração & dosagem , Heparina/administração & dosagem , Diálise Renal/métodos , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Intervalos de Confiança , Dermatan Sulfato/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Tempo de Tromboplastina Parcial , Contagem de Plaquetas , Diálise Renal/efeitos adversos , Estudos Retrospectivos
G Ital Nefrol ; 27(6): 639-48, 2010.
Artigo em Italiano | MEDLINE | ID: mdl-21132646


The treatment of membranous glomerulonephritis (MGN) is controversial, especially in cases of no response to first-line treatment or multiple relapses. The Clinical Nephrology Group of Piedmont carried out a multicenter analysis of the treatment of patients affected by MGN in 15 nephrology units in Piedmont. The first treatment is usually started after a waiting period of 3-6 months in case of proteinuria in the nephrotic range but normal or slightly impaired renal function. A history of cancer, the presence of infectious disease, and secondary forms of MGN are criteria for exclusion from treatment. As first-line treatment, Piedmont nephrologists prescribe corticosteroids alternated with immunosuppressive drugs, generally preferring cyclophosphamide to chlorambucil. Only one nephrology unit uses cyclosporin A (CyA) as the first choice. In case of no response to treatment, a second therapeutic approach is undertaken after 2-12 months. Second-line treatment consists of CyA if immunosuppressive drugs were given before, and corticosteroids/ immunosuppressive drugs if CyA was the first treatment. A further choice may be ACTH or rituximab. In case of multiple relapses the treatment options are the same but previous immunosuppressive treatment, patient age, and the duration of kidney disease with a greater probability of renal failure and progression towards sclerosis require careful attention. Concern has been expressed regarding the potentially severe side effects of ACTH including myopathy, cataract and diabetes. In conclusion, the applied therapeutic approaches in Piedmont reflect the difficulty reported in the literature in identifying simple recommendations. ACTH and rituximab are increasingly preferred for the treatment of MGN and there is a need for prospective studies to determine the best protocol for rituximab and the safety profile of ACTH.

Corticosteroides/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Fidelidade a Diretrizes/estatística & dados numéricos , Imunossupressores/uso terapêutico , Hormônio Adrenocorticotrópico/uso terapêutico , Anticorpos Monoclonais Murinos/administração & dosagem , Clorambucila/administração & dosagem , Ciclofosfamida/administração & dosagem , Ciclosporina/administração & dosagem , Progressão da Doença , Quimioterapia Combinada , Glomerulonefrite Membranosa/diagnóstico , Hormônios/uso terapêutico , Humanos , Itália , Guias de Prática Clínica como Assunto , Rituximab , Resultado do Tratamento
Am J Kidney Dis ; 45(3): 540-9, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15754276


BACKGROUND: Ascorbate supplementation for patients on regular dialysis treatment (RDT) is advised to obviate deficiency and improve epoetin response in those with functional iron deficiency. However, clear-cut safety concerns regarding hyperoxalemia are still poorly understood. This study tries to establish safety/efficacy profiles of ascorbate and oxalate during long-term intravenous ascorbate supplementation. METHODS: A prospective study was performed in 30 patients on RDT showing ascorbate deficiency (plasma ascorbate < 2.6 mg/L [<15 micromol/L]): 18 patients were administered intravenous ascorbate during 18 months (250 mg/wk, subsequently increased to 500 mg), and 12 patients were taken as reference untreated cases. Plasma ascorbate and oxalate assays and dialytic balance determinations were performed (ion chromatography and reverse-phase high-performance liquid chromatography, respectively) at baseline, during treatment, and 12 months after withdrawal. RESULTS: Plasma ascorbate levels increased dose dependently with supplementation (1.6 +/- 0.8 mg/L [9.1 +/- 4.6 mumol/L] at baseline, 2.8 +/- 1.8 mg/L [15.9 +/- 10.1 micromol/L]) with 250 mg of ascorbate, and 6.6 +/- 2.8 mg/L [37.5 +/- 16.0 micromol/L] with 500 mg/wk of ascorbate), but only normalized with greater dosages for several months in 94% of patients. Baseline plasma oxalate levels increased from 3.2 +/- 0.8 mg/L (35.8 +/- 8.8 micromol/L) to 3.6 +/- 0.8 mg/L (39.5 +/- 9.1 micromol/L) and 4.5 +/- 0.9 mg/L (50.3 +/- 10.4 micromol/L) with 250 and 500 mg, respectively ( P < 0.001). The calcium oxalate saturation threshold was exceeded by 7 of 18 patients (40%) during 6 months therapy with 500 mg/wk. Ascorbate dialysis removal increased from 37.8 +/- 23.2 mg (215 +/- 132 micromol) to 99.6 +/- 51.7 mg (566 +/- 294 micromol) during supplementation (P < 0.001), with corresponding increases in oxalate removal from 82.5 +/- 33.2 mg (917 +/- 369 micromol) to 111.2 +/- 32.6 mg/L (1,236 +/- 362 micromol; P < 0.01). Withdrawal reverted plasma levels and dialysis removal to initial values. Values for untreated patients did not change during 1 year of follow-up. CONCLUSION: Patients on RDT may resolve ascorbate deficiency with intravenous supplementation of 500 mg/wk, but this implies a significant risk for oxalate supersaturation. Oxalate measurements are strongly recommended during long-term ascorbate therapy.

Ácido Ascórbico/efeitos adversos , Oxalato de Cálcio/sangue , Falência Renal Crônica/terapia , Diálise Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/prevenção & controle , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/sangue , Ácido Ascórbico/farmacocinética , Ácido Ascórbico/uso terapêutico , Deficiência de Ácido Ascórbico/tratamento farmacológico , Deficiência de Ácido Ascórbico/etiologia , Resistência a Medicamentos , Eritropoetina/farmacocinética , Eritropoetina/uso terapêutico , Feminino , Humanos , Hiperoxalúria/induzido quimicamente , Hiperoxalúria/etiologia , Infusões Intravenosas , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos