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1.
Fundam Clin Pharmacol ; 32(2): 209-215, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29239015

ABSTRACT

Hepatic encephalopathy (HE) influences short-term and long-term prognoses. Recently, glycerol phenylbutyrate (PB), that lowers ammonia by providing an alternate pathway to urea for waste nitrogen excretion, has shown that it was effective in preventing the occurrence of HE in RCT. The aim was to assess the benefits of sodium PB in cirrhotic patients admitted to ICU for overt HE, in terms of ammonia levels decrease, neurological improvement, and survival. Cirrhotic patients who presented with overt HE, ammonia levels >100 µmol/L, and did not display any contra-indication were included. Sodium PB was administered at 200 mg/kg/day. Control group included historical controls treated by standard therapy, matched for age, sex, MELD score, and severity of HE. Eighteen patients were included and treated with sodium PB (age: 59 [45-68], male gender: 15 [83%], Child-Pugh B: 8 [44%], Child-Pugh C: 10 [56%], and MELD score: 16 [13-23]). Ammonia levels significantly decreased in the PB as compared to the control group from inclusion to 12 h and from inclusion to 48 h (P = 0.0201 and P = 0.0230, respectively). The proportion of patients displaying neurological improvement was only higher in the PB-treated group as compared to controls at ICU discharge (15 [83%] vs. 9 [50%], P = 0.0339). ICU discharge survival was significantly higher in patients treated with PB (17 [94%] vs. 9 [50%], P = 0.0017). In cirrhotic patients with overt HE, sodium PB could be effective in reducing ammonia levels and might be effective in improving neurological status and ICU discharge survival. More extensive data, especially a RCT, are mandatory.


Subject(s)
Hepatic Encephalopathy/drug therapy , Hyperammonemia/drug therapy , Intensive Care Units , Liver Cirrhosis/complications , Patient Admission , Phenylbutyrates/therapeutic use , Aged , Ammonia/blood , Biomarkers/blood , Case-Control Studies , Female , Hepatic Encephalopathy/blood , Hepatic Encephalopathy/etiology , Hepatic Encephalopathy/mortality , Hospital Mortality , Humans , Hyperammonemia/blood , Hyperammonemia/etiology , Hyperammonemia/mortality , Liver Cirrhosis/blood , Liver Cirrhosis/mortality , Male , Middle Aged , Patient Discharge , Phenylbutyrates/adverse effects , Preliminary Data , Prospective Studies , Time Factors , Treatment Outcome
2.
AIDS ; 27(8): 1295-302, 2013 May 15.
Article in English | MEDLINE | ID: mdl-23925378

ABSTRACT

OBJECTIVE: To assess the frequency of glomerular and tubular proteinuria in a cohort of HIV-infected patients, and to determine the factors associated with each type of injury. DESIGN: Cross-sectional study of 1210 consecutive HIV-infected adults followed in HIV outpatient unit (Montpellier/France). METHODS: Spot urine protein to creatinine (uPCR), albumin to creatinine (uACR) and albumin to protein (uAPR) ratios were assessed. Glomerular injury was defined as uACR at least 30 mg/g or uPCR at least 200 mg/g with uAPR at least 0.4. Tubular injury was defined as uPCR 200 mg/g or more with uAPR less than 0.4. Multivariate logistic regression identified independent factors of each type of proteinuria, in the 1158 patients with estimated glomerular filtration rate (eGFR) at least 60 ml/min per 1.73 m, using re-expressed modification of diet in renal disease equation. RESULTS: Frequency of proteinuria was 18.2% among patients with eGFR at least 60 ml/min per 1.73 m consisting in tubular proteinuria for 50.7% of them. Factors associated with glomerular proteinuria were age [OR 1.34/10-year increment (95%CI: 1.08-1.66)], diabetes [OR 3.37 (95%CI: 1.53-7.44)], and arterial hypertension [OR 2.52 (95%CI: 1.36-4.66)]. Factors associated with tubular proteinuria were age [OR 1.43 (95%CI: 1.14-1.79)], current tenofovir use [OR 3.52 (95%CI: 1.86-6.65)], hepatitis C co-infection [OR 1.62 (95%CI: 1.00-2.65)], AIDS stage [OR 1.83 (95%CI: 1.18-2.82)], CD4 cell count less than 200 per µl [OR 2.48 (95%CI: 1.31-4.70)]. CONCLUSION: This study distinguished risk factors for tubular injury, mainly related to HIV disease and its treatment (tenofovir), and glomerular injury, linked to non HIV-related variables (age, diabetes, hypertension). Measuring uPCR, uACR and uAPR may help with the detection and specific management of early chronic kidney disease in HIV-infected patients having normal or sub-normal eGFR.


Subject(s)
Glomerular Filtration Rate/physiology , HIV Infections/complications , Proteinuria/complications , Renal Insufficiency, Chronic/complications , Adenine/analogs & derivatives , Adenine/therapeutic use , Adult , Aged , Anti-HIV Agents/therapeutic use , Cross-Sectional Studies , Female , HIV Infections/drug therapy , HIV Infections/physiopathology , Humans , Kidney Glomerulus/physiology , Kidney Tubules/physiology , Male , Middle Aged , Organophosphonates/therapeutic use , Proteinuria/physiopathology , Regression Analysis , Renal Insufficiency, Chronic/physiopathology , Risk Factors , Tenofovir
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