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1.
Niger J Clin Pract ; 23(10): 1387-1394, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33047695

RESUMO

Background: Chronic kidney disease (CKD) is a common late complication in liver-transplanted patients who have received long-term therapy with calcineurin inhibitors (CNIs). Aims: To analyze kidney disease progression after liver transplantation. Methods: We analysed the clinical data of adult single-organ liver transplant recipients performed at our centre between October 2003 and September 2009. The patients with the estimated glomerular filtration rate (eGFR) greater than 60 ml/min/1.73 m2 before surgery were included in the study. Results: 69 patients with complete follow-up data were analysed. We found that eGFR at 1 or 2 years after liver transplantation correlated well with eGFR at 5 years. In addition, our results showed that patients whose eGFR declined below 60 at 2 years after liver transplantation would develop an irreversible renal injury in the following years. At 2 years, 12 patients had an eGFR less than 60, which were maintained in 11 patients at 5 years (Sensitivity = 11/12, 91.67%; Specificity = 57/58, 98.28%, Youden's index = 89.95%). The annual rate of eGFR reduction of the tacrolimus group was greater than that of the tacrolimus sparing group based on the value-time variation curve in our study. Moreover, the tacrolimus concentration influenced the CKD progression at 1 and 2 years with an under the ROC curve of 0.73 and 0.78 when Youden's index was at its maximum and the tacrolimus concentrations were 8.55 and 5.96 ng/ml, respectively. Conclusion: We confirmed that eGFR at 2 years after liver transplantation is useful for observing a meaningful change in eGFR and renal damage. Obtaining the appropriate serum concentration of an early decrease of the dose of CNIs and transforming non-nephrotoxic immunosuppressants would help improve renal function to prevent CKD progression and end-stage renal disease (ESRD).


Assuntos
Inibidores de Calcineurina/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacos , Imunossupressores/uso terapêutico , Rim/efeitos dos fármacos , Transplante de Fígado/efeitos adversos , Insuficiência Renal Crônica/complicações , Tacrolimo/uso terapêutico , Proteínas Adaptadoras de Transdução de Sinal , Adolescente , Adulto , Inibidores de Calcineurina/uso terapêutico , Progressão da Doença , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Fatores de Risco
2.
Lancet Diabetes Endocrinol ; 8(11): 880-893, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32971040

RESUMO

BACKGROUND: Patients with type 2 diabetes have a high risk of developing chronic kidney disease. We examined the effects of semaglutide on kidney function and safety in a large, broad type 2 diabetes population. METHODS: We did a post-hoc analysis of 8416 patients with type 2 diabetes enrolled in the SUSTAIN 1-5 and SUSTAIN 7 randomised controlled trials, and the SUSTAIN 6 cardiovascular outcomes trial, to examine the effects of once-weekly subcutaneous semaglutide 0·5 mg and 1·0 mg versus comparators (active treatments or placebo) on estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), and kidney adverse events. Data from SUSTAIN 1-5 and SUSTAIN 7 were pooled. eGFR and UACR were also analysed by kidney function and albuminuria status. FINDINGS: In SUSTAIN 1-5 and SUSTAIN 7, eGFR decreased from baseline to week 12 with all active treatments; estimated treatment differences (ETDs) versus placebo were -2·15 (95% CI -3·47 to -0·83) mL/min per 1·73 m2 with semaglutide 0·5 mg and -3·00 (-4·31 to -1·68) mL/min per 1·73 m2 with semaglutide 1·0 mg; after week 12, eGFR plateaued. In SUSTAIN 1-5 and SUSTAIN 7, from baseline to end of treatment the decline in eGFR was greater with semaglutide than with placebo (ETD -1·58 [95% CI -2·92 to -0·25] mL/min per 1·73 m2 with semaglutide 0·5 mg and -2·02 [-3·35 to -0·68] mL/min per 1·73 m2 with semaglutide 1·0 mg). In SUSTAIN 6, the decline in eGFR was greater with semaglutide than with placebo from baseline to week 16 (ETD -1·29 [95% CI -2·07 to -0·51] mL/min per 1·73 m2 with semaglutide 0·5 mg and -1·56 [-2·33 to -0·78] mL/min per 1·73 m2 with semaglutide 1·0 mg), but not from week 16 to week 104 (1·29 [0·30 to 2·28] mL/min per 1·73 m2 with semaglutide 0·5 mg and 2·44 [1·45 to 3·44] mL/min per 1·73 m2 with semaglutide 1·0 mg). Overall (ie, from baseline to week 104), the eGFR decline in SUSTAIN 6 was similar between semaglutide and placebo (ETD 0·07 [95% CI -0·92 to 1·07] mL/min per 1·73 m2 with semaglutide 0·5 mg and 0·97 [-0·03 to 1·97] mL/min per 1·73 m2 with semaglutide 1·0 mg). In SUSTAIN 1-5, UACR ratios at end of treatment to baseline were 0·917 with semaglutide 0·5 mg, 0·836 with semaglutide 1·0 mg, and 1·239 with placebo; at end of treatment, greater reductions in UACR were observed with semaglutide versus placebo (estimated treatment ratios 0·74 [95% CI 0·64 to 0·85] for semaglutide 0·5 mg and 0·68 [0·59 to 0·78] for semaglutide 1·0 mg). In SUSTAIN 6, UACR ratios at end of treatment (week 104) to baseline were 0·973 with semaglutide 0·5 mg, 0·858 with semaglutide 1·0 mg, and 1·302 with placebo; at week 104, greater reductions in UACR were observed with semaglutide versus placebo (estimated treatment ratios 0·75 [95% CI 0·66 to 0·85] for semaglutide 0·5 mg and 0·66 [0·58 to 0·75] for semaglutide 1·0 mg). In SUSTAIN 1-7, eGFR initially declined in patients with normal kidney function (and in those with mild kidney impairment with semaglutide 1·0 mg in SUSTAIN 6), but overall (ie, by week 30 for SUSTAIN 1-5 and SUSTAIN 7, and week 104 for SUSTAIN 6), eGFR did not differ between semaglutide and placebo. In SUSTAIN 1-6, UACR decreased in patients with pre-existing microalbuminuria or macroalbuminuria at baseline; it did not change or increased in those with normoalbuminuria at baseline. Kidney adverse events were balanced between treatment groups. INTERPRETATION: Across the SUSTAIN 1-7 trials, semaglutide was associated with initial reductions in eGFR that plateaued, and marked reductions in UACR. This post-hoc analysis suggests no increase in the risk of kidney adverse events with semaglutide versus the active comparators used across SUSTAIN 1-7. FUNDING: Novo Nordisk.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Taxa de Filtração Glomerular/efeitos dos fármacos , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Rim/efeitos dos fármacos , Adulto , Idoso , Diabetes Mellitus Tipo 2/urina , Esquema de Medicação , Feminino , Taxa de Filtração Glomerular/fisiologia , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Humanos , Injeções Subcutâneas , Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
3.
N Engl J Med ; 383(15): 1436-1446, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-32970396

RESUMO

BACKGROUND: Patients with chronic kidney disease have a high risk of adverse kidney and cardiovascular outcomes. The effect of dapagliflozin in patients with chronic kidney disease, with or without type 2 diabetes, is not known. METHODS: We randomly assigned 4304 participants with an estimated glomerular filtration rate (GFR) of 25 to 75 ml per minute per 1.73 m2 of body-surface area and a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 200 to 5000 to receive dapagliflozin (10 mg once daily) or placebo. The primary outcome was a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes. RESULTS: The independent data monitoring committee recommended stopping the trial because of efficacy. Over a median of 2.4 years, a primary outcome event occurred in 197 of 2152 participants (9.2%) in the dapagliflozin group and 312 of 2152 participants (14.5%) in the placebo group (hazard ratio, 0.61; 95% confidence interval [CI], 0.51 to 0.72; P<0.001; number needed to treat to prevent one primary outcome event, 19 [95% CI, 15 to 27]). The hazard ratio for the composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal causes was 0.56 (95% CI, 0.45 to 0.68; P<0.001), and the hazard ratio for the composite of death from cardiovascular causes or hospitalization for heart failure was 0.71 (95% CI, 0.55 to 0.92; P = 0.009). Death occurred in 101 participants (4.7%) in the dapagliflozin group and 146 participants (6.8%) in the placebo group (hazard ratio, 0.69; 95% CI, 0.53 to 0.88; P = 0.004). The effects of dapagliflozin were similar in participants with type 2 diabetes and in those without type 2 diabetes. The known safety profile of dapagliflozin was confirmed. CONCLUSIONS: Among patients with chronic kidney disease, regardless of the presence or absence of diabetes, the risk of a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes was significantly lower with dapagliflozin than with placebo. (Funded by AstraZeneca; DAPA-CKD ClinicalTrials.gov number, NCT03036150.).


Assuntos
Compostos Benzidrílicos/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Glucosídeos/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Idoso , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/farmacologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Feminino , Glucosídeos/efeitos adversos , Glucosídeos/farmacologia , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Insuficiência Renal Crônica/complicações , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
4.
Lancet ; 396(10254): 819-829, 2020 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-32877652

RESUMO

BACKGROUND: Both DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin) trials showed that sodium-glucose co-transporter-2 (SGLT2) inhibition reduced the combined risk of cardiovascular death or hospitalisation for heart failure in patients with heart failure with reduced ejection fraction (HFrEF) with or without diabetes. However, neither trial was powered to assess effects on cardiovascular death or all-cause death or to characterise effects in clinically important subgroups. Using study-level published data from DAPA-HF and patient-level data from EMPEROR-Reduced, we aimed to estimate the effect of SGLT2 inhibition on fatal and non-fatal heart failure events and renal outcomes in all randomly assigned patients with HFrEF and in relevant subgroups from DAPA-HF and EMPEROR-Reduced trials. METHODS: We did a prespecified meta-analysis of the two single large-scale trials assessing the effects of SGLT2 inhibitors on cardiovascular outcomes in patients with HFrEF with or without diabetes: DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin). The primary endpoint was time to all-cause death. Additionally, we assessed the effects of treatment in prespecified subgroups on the combined risk of cardiovascular death or hospitalisation for heart failure. These subgroups were based on type 2 diabetes status, age, sex, angiotensin receptor neprilysin inhibitor (ARNI) treatment, New York Heart Association (NYHA) functional class, race, history of hospitalisation for heart failure, estimated glomerular filtration rate (eGFR), body-mass index, and region (post-hoc). We used hazard ratios (HRs) derived from Cox proportional hazard models for time-to-first event endpoints and Cochran's Q test for treatment interactions; the analysis of recurrent events was based on rate ratios derived from the Lin-Wei-Yang-Ying model. FINDINGS: Among 8474 patients combined from both trials, the estimated treatment effect was a 13% reduction in all-cause death (pooled HR 0·87, 95% CI 0·77-0·98; p=0·018) and 14% reduction in cardiovascular death (0·86, 0·76-0·98; p=0·027). SGLT2 inhibition was accompanied by a 26% relative reduction in the combined risk of cardiovascular death or first hospitalisation for heart failure (0·74, 0·68-0·82; p<0·0001), and by a 25% decrease in the composite of recurrent hospitalisations for heart failure or cardiovascular death (0·75, 0·68-0·84; p<0·0001). The risk of the composite renal endpoint was also reduced (0·62, 0·43-0·90; p=0·013). All tests for heterogeneity of effect size between trials were not significant. The pooled treatment effects showed consistent benefits for subgroups based on age, sex, diabetes, treatment with an ARNI and baseline eGFR, but suggested treatment-by-subgroup interactions for subgroups based on NYHA functional class and race. INTERPRETATION: The effects of empagliflozin and dapagliflozin on hospitalisations for heart failure were consistent in the two independent trials and suggest that these agents also improve renal outcomes and reduce all-cause and cardiovascular death in patients with HFrEF. FUNDING: Boehringer Ingelheim.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Glucosídeos/efeitos adversos , Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Volume Sistólico/efeitos dos fármacos , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos Benzidrílicos/uso terapêutico , Índice de Massa Corporal , Estudos de Casos e Controles , Causas de Morte/tendências , Ensaios Clínicos como Assunto , Morte , Diabetes Mellitus Tipo 2/complicações , Quimioterapia Combinada , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Taxa de Filtração Glomerular/fisiologia , Glucosídeos/uso terapêutico , Insuficiência Cardíaca/classificação , Insuficiência Cardíaca/fisiopatologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Neprilisina/antagonistas & inibidores , Avaliação de Resultados da Assistência ao Paciente , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
5.
PLoS One ; 15(8): e0237665, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32866166

RESUMO

AIMS: Inflammation plays a pivotal role in atherothrombosis. Colchicine is an anti-inflammatory drug that may attenuate this process. Cardiovascular protective effects of anti-inflammatory drugs, however, seem to be limited to patients with a biochemical response. We therefore investigated whether short-term exposure to colchicine reduced inflammatory markers and whether additional laboratory changes occur in patients with chronic coronary artery disease. METHODS & RESULTS: In 138 consecutive patients with chronic coronary artery disease and a high sensitivity C-reactive Protein (hs-CRP) ≥ 2 mg/L, inflammatory markers, lipids, haematologic parameters and renal function were measured at baseline and after 30 days exposure to colchicine 0.5mg once daily. Hs-CRP decreased from baseline 4.40 mg/L (interquartile range [IQR] 2.83-6.99 mg/L) to 2.33 mg/L (IQR 1.41-4.17, median of the differences -1.66 mg/L, 95% confidence interval [CI] -2.17 - -1.22 mg/L, p-value <0.01), corresponding to a median change from baseline of -40%. Interleukin-6 decreased from 2.51 ng/L (IQR 1.59-4.32 ng/L) to 2.22 ng/L (median of the differences -0.36 ng/L, 95%CI -0.70 - -0.01 ng/L, p-value 0.04), corresponding to a median change from baseline of -16%. No clinically relevant changes in lipid fractions were observed. Both leukocyte and thrombocyte count decreased (median change from baseline -7% and -4% respectively). Estimated glomerular filtration rate decreased with a mean change from baseline of -2%. CONCLUSION: In patients with chronic coronary artery disease and elevated hs-CRP, one-month exposure to colchicine 0.5 mg once daily was associated with a reduction of inflammatory markers. A small effect was seen on white blood cell count and platelet count, as well as a small decrease in estimated glomerular filtration rate.


Assuntos
Proteína C-Reativa/análise , Colchicina/administração & dosagem , Doença da Artéria Coronariana/tratamento farmacológico , Inflamação/tratamento farmacológico , Idoso , Biomarcadores/sangue , Doença Crônica/tratamento farmacológico , Colchicina/efeitos adversos , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/imunologia , Esquema de Medicação , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/imunologia , Contagem de Leucócitos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Prospectivos , Resultado do Tratamento
6.
N Engl J Med ; 383(15): 1413-1424, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-32865377

RESUMO

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure in patients regardless of the presence or absence of diabetes. More evidence is needed regarding the effects of these drugs in patients across the broad spectrum of heart failure, including those with a markedly reduced ejection fraction. METHODS: In this double-blind trial, we randomly assigned 3730 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive empagliflozin (10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of cardiovascular death or hospitalization for worsening heart failure. RESULTS: During a median of 16 months, a primary outcome event occurred in 361 of 1863 patients (19.4%) in the empagliflozin group and in 462 of 1867 patients (24.7%) in the placebo group (hazard ratio for cardiovascular death or hospitalization for heart failure, 0.75; 95% confidence interval [CI], 0.65 to 0.86; P<0.001). The effect of empagliflozin on the primary outcome was consistent in patients regardless of the presence or absence of diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.70; 95% CI, 0.58 to 0.85; P<0.001). The annual rate of decline in the estimated glomerular filtration rate was slower in the empagliflozin group than in the placebo group (-0.55 vs. -2.28 ml per minute per 1.73 m2 of body-surface area per year, P<0.001), and empagliflozin-treated patients had a lower risk of serious renal outcomes. Uncomplicated genital tract infection was reported more frequently with empagliflozin. CONCLUSIONS: Among patients receiving recommended therapy for heart failure, those in the empagliflozin group had a lower risk of cardiovascular death or hospitalization for heart failure than those in the placebo group, regardless of the presence or absence of diabetes. (Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Reduced ClinicalTrials.gov number, NCT03057977.).


Assuntos
Compostos Benzidrílicos/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Glucosídeos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Hospitalização/estatística & dados numéricos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Idoso , Compostos Benzidrílicos/efeitos adversos , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/complicações , Progressão da Doença , Método Duplo-Cego , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Glucosídeos/efeitos adversos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/complicações , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Volume Sistólico
7.
PLoS One ; 15(9): e0239300, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32956418

RESUMO

BACKGROUND: Recent reports from small studies in West Africa suggest that Black children may have high rate of steroid sensitivity nephrotic syndrome (SSNS) contrary to long held knowledge. Herein, we determined the proportion of children with idiopathic nephrotic syndrome (INS) who achieved complete remission with steroid therapy and identified factors associated with complete remission. METHODS: We reviewed the medical records of 241 children with INS in two centres in Lagos from 2010 to 2019. We extracted demographic data, clinical features, laboratory values at the time of diagnosis, and receipt and response to steroids and other immunosuppressants. RESULTS: The median (interquartile range) age at diagnosis of INS was 5.1 (3.0-8.7) years and boys were 60.2% of the study population. Children with SSNS made up 85.9% (n = 207) of the study cohort. Among those aged 0-5 years, 92.6%were SSNS compared with 69.2% in those aged 11-17 years at the time of diagnosis. In addition, the proportion of children with SSNS increased from 73.8% between year 2010 and 2012 to 88.4% afterwards. Also, children with SSNS had lower serum creatinine (0.44 vs 0.70; p<0.001) and higher estimated glomerular filtration rate (101 vs 74.3 ml/min/1.73 m2; p = 0.008) at the time of diagnosis than those with steroid resistant nephrotic syndrome (SRNS). CONCLUSION: Among Black children in Lagos, the proportion with SSNS is comparable to proportions described in children of Asian and European descent. Furthermore, children with SSNS had lower serum creatinine and higher glomerular filtration rate than those with SRNS.


Assuntos
Síndrome Nefrótica/tratamento farmacológico , Esteroides/efeitos adversos , Adolescente , África Ocidental/epidemiologia , Grupo com Ancestrais do Continente Africano/genética , Criança , Pré-Escolar , Estudos Transversais , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Masculino , Homens , Síndrome Nefrótica/epidemiologia , Síndrome Nefrótica/genética , Síndrome Nefrótica/patologia , Nigéria/epidemiologia , Esteroides/uso terapêutico
8.
BMC Infect Dis ; 20(1): 582, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32762646

RESUMO

BACKGROUND: Limited data are available on the effect of antiretroviral treatment (ART) or Tenofovir disoproxil fumarate (TDF) on renal function in Ethiopians. We aimed to assess factors associated with renal function changes during the first year of ART with special focus on TDF. METHODS: HIV positive persons who were ≥ 18 years of age and eligible for ART initiation were recruited. Creatinine measurement to estimate glomerular filtration rate (eGFR) and spot urine analyses were performed at baseline and after 3, 6 and 12 months of ART. Univariate and multivariate linear regression and univariate logistic regression were used to determine factors associated with eGFR as continuous and categorical variable respectively. A linear mixed model was used to assess 12 month eGFR difference in TDF and non-TDF based regimen. RESULT: Of 340 ART-naïve HIV patients with baseline renal function tests, 82.3% (279/339) were initiated on a TDF based ART regimen. All patients were on non-nucleoside reverse transcriptase inhibitors (NNRTI) based ART regimen. The median (IQR) change in eGFR with 12 months of ART was 0.8 (- 11.1; 10.0) ml/min/1.73m2. About 41 and 26.9% of HIV patients had a drop of greater than 3 and 10 mL/min/1.73 m2 in eGFR at 12 month, respectively. However, none of the HIV patients declined to < 60 ml/min/1.73m2 within 12 months. Moreover, none of the HIV patients had persistent proteinuria or glycosuria. Older HIV patients especially age > 45 years and those with unsuppressed viral load at 6 month of ART had a significantly lower eGFR at 12 months of ART initiation. However, there was no difference in 12 month eGFR between HIV patients initiated on TDF based regimen and non-TDF based regimen. CONCLUSION: Renal function remained stable with no difference between HIV patients treated with TDF or non-TDF NNRTI based ART regimen over 12 months. However, older HIV patients and those with unsuppressed viral load deserve special focus on renal monitoring. Data on long-term safety of TDF (> 1 year) is still warranted in this population.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Rim/efeitos dos fármacos , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico , Adolescente , Adulto , Creatinina/sangue , Etiópia/epidemiologia , Feminino , Seguimentos , Taxa de Filtração Glomerular/efeitos dos fármacos , Infecções por HIV/sangue , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteinúria , Fatores de Risco , Carga Viral , Adulto Jovem
9.
PLoS One ; 15(8): e0237586, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785260

RESUMO

This study investigated the kinetics of estimated glomerular filtration rate (eGFR) and quantitative hepatitis B surface antigen (qHBsAg) in telbivudine (LdT)-treated chronic hepatitis B (CHB) patients whose treatment was subsequently adjusted with the adding on adefovir or by switching to tenofovir disoproxil fumarate (TDF) as rescue. Of 295 CHB patients initially treated with LdT, 102 of them who subsequently receiving either adding-on adefovir (group A, n = 58) or switching to TDF (group B, n = 44) for more than 24 months were enrolled. Serial eGFR and qHBsAg levels (3 to 6 monthly) in both LdT monotherapy and rescue therapy periods were analyzed retrospectively. Subsequent decline of qHBsAg especially in rescue therapy period were noted (p<0.001 and p = 0.068 in group A and B). However, patients in group B achieved a significant increase of eGFR (p = 0.010) in LdT monotherapy period but had a significant decline of eGFR (p<0.001) in rescue therapy period. In contrast, patients in group A maintained eGFR levels in both periods. Meanwhile, switch to TDF (hazard ratio: 3.036; 95% confidence interval: 1.040-8.861; p = 0.042) was the sole factor related to the decrease of eGFR>20% from baseline. Both rescue therapies achieved subsequent declines of qHBsAg over time but caused different changes in eGFR. LdT-based rescue therapy maintained eGFR but TDF switching therapy descended eGFR. Therefore, it is essential to monitor patient's renal function intensively when switching from LdT to TDF as a rescue strategy.


Assuntos
Antivirais/farmacologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Antígenos de Superfície da Hepatite B/metabolismo , Vírus da Hepatite B/metabolismo , Hepatite B/patologia , Telbivudina/farmacologia , Feminino , Seguimentos , Hepatite B/metabolismo , Hepatite B/virologia , Vírus da Hepatite B/efeitos dos fármacos , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
10.
Medicine (Baltimore) ; 99(26): e21000, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590815

RESUMO

IgA Nephropathy (IgAN) is characterized by mesangial deposition of dominant, polymeric, galactose-deficient IgA1 molecules of gut-associated lymphoid tissue origin. We sought to evaluate the efficacy of targeting the mucosal immune system dysregulation underlying IgAN pathogenesis with a pH-modified formulation of budesonide with a maximum release of active compound in the distal ileum and proximal colon.We did a retrospective study evaluating the efficacy of budesonide (Budenofalk) in the treatment of IgAN. From a retrospective cohort of 143 patients with IgAN followed in our department we identified 21 patients that received treatment with budesonide. These patients received budesonide at a dose of 9 mg/d in the first 12 months, followed by a dose reduction to 3 mg/d for the subsequent period. Only patients that received a 24-month treatment with budesonide were included in the analysis (n = 18). We matched the budesonide-treated cohort to 18 patients with IgAN treated with systemic steroids from the same retrospective cohort. Efficacy was measured as change in proteinuria, hematuria and estimated glomerular filtration rate over a 24-month period.Treatment with budesonide was associated with a 24-month renal function decline of -0.22 (95%CI, -8.2 to 7.8) ml/min/1.73m, compared to -5.89 (95%CI, -12.2 to 0.4) ml/min/1.73m in the corticosteroid treatment group (p = 0.44, for between group difference). The median reduction in proteinuria at 24-month was 45% (interquartile range [IQR]: -79%; -22%) in the budesonide group and 11% (IQR: -39%; 43%) in the corticosteroid group, respectively (P = .009, for between group difference). The median reduction in hematuria at 24-month was 72% (IQR: -90%; -45%) in the budesonide group and 73% (IQR: -85%; 18%) in the corticosteroid group, respectively (P = .22, for between group difference). Treatment with budesonide was well tolerated with minimal side effects.Budesonide (Budenofalk) was effective in the treatment of patients with IgAN at high-risk of progression in terms of reducing proteinuria, hematuria and preserving renal function over 24 months of therapy.


Assuntos
Corticosteroides/normas , Budesonida/normas , Glomerulonefrite por IGA/tratamento farmacológico , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Adulto , Budesonida/efeitos adversos , Budesonida/uso terapêutico , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Hematúria/tratamento farmacológico , Hematúria/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Proteinúria/tratamento farmacológico , Proteinúria/prevenção & controle , Estudos Retrospectivos
11.
Medicine (Baltimore) ; 99(25): e20831, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569232

RESUMO

The objective was to investigate the association of different hydration doses and its effect on renal function in patients with primary osteoporosis treated with zoledronic acid.The subjects with primary osteoporosis treated with zoledronic acid at the First Affiliated Hospital of Chongqing Medical University, China, from January 2015 to December 2018 were included in this study. The subjects were classified according to different hydration doses. Renal function indexes before and after treatment were collected and adverse reactions recorded to analyze the changes in renal function associated with different hydration doses.The choice of the hydration dose treated with zoledronic acid deserves attention. The lower hydration dose is, the greater impact on renal function can be caused.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Rim/fisiopatologia , Osteoporose/tratamento farmacológico , Soluções para Reidratação/uso terapêutico , Ácido Zoledrônico/uso terapêutico , Idoso , Conservadores da Densidade Óssea/efeitos adversos , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Masculino , Osteoporose/fisiopatologia , Soluções para Reidratação/administração & dosagem , Estudos Retrospectivos , Ácido Zoledrônico/efeitos adversos
12.
N Engl J Med ; 382(26): 2504-2513, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32579811

RESUMO

BACKGROUND: Elevated serum urate levels are associated with progression of chronic kidney disease. Whether urate-lowering treatment with allopurinol can attenuate the decline of the estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease who are at risk for progression is not known. METHODS: In this randomized, controlled trial, we randomly assigned adults with stage 3 or 4 chronic kidney disease and no history of gout who had a urinary albumin:creatinine ratio of 265 or higher (with albumin measured in milligrams and creatinine in grams) or an eGFR decrease of at least 3.0 ml per minute per 1.73 m2 of body-surface area in the preceding year to receive allopurinol (100 to 300 mg daily) or placebo. The primary outcome was the change in eGFR from randomization to week 104, calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. RESULTS: Enrollment was stopped because of slow recruitment after 369 of 620 intended patients were randomly assigned to receive allopurinol (185 patients) or placebo (184 patients). Three patients per group withdrew immediately after randomization. The remaining 363 patients (mean eGFR, 31.7 ml per minute per 1.73 m2; median urine albumin:creatinine ratio, 716.9; mean serum urate level, 8.2 mg per deciliter) were included in the assessment of the primary outcome. The change in eGFR did not differ significantly between the allopurinol group and the placebo group (-3.33 ml per minute per 1.73 m2 per year [95% confidence interval {CI}, -4.11 to -2.55] and -3.23 ml per minute per 1.73 m2 per year [95% CI, -3.98 to -2.47], respectively; mean difference, -0.10 ml per minute per 1.73 m2 per year [95% CI, -1.18 to 0.97]; P = 0.85). Serious adverse events were reported in 84 of 182 patients (46%) in the allopurinol group and in 79 of 181 patients (44%) in the placebo group. CONCLUSIONS: In patients with chronic kidney disease and a high risk of progression, urate-lowering treatment with allopurinol did not slow the decline in eGFR as compared with placebo. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; CKD-FIX Australian New Zealand Clinical Trials Registry number, ACTRN12611000791932.).


Assuntos
Alopurinol/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Supressores da Gota/uso terapêutico , Ácido Úrico/sangue , Xantina Oxidase/antagonistas & inibidores , Idoso , Alopurinol/efeitos adversos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Método Duplo-Cego , Inibidores Enzimáticos/efeitos adversos , Feminino , Supressores da Gota/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/fisiopatologia , Sistema Renina-Angiotensina , Falha de Tratamento
13.
Medicine (Baltimore) ; 99(22): e20436, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481445

RESUMO

HCV infection is associated with chronic kidney disease due to several mechanisms. Patients treated with interferon-based regimens demonstrate improved renal function and reduced incidence of chronic kidney disease. There is scarce evidence on the effect of direct acting antiviral regimens (DAAs) on renal function.We evaluated serial measures of renal function in a cohort of HCV-infected participants following completion of DAA-based treatment regimens.Measures of glomerular filtration rate (GFR) were estimated by the CKD-EPI equation. Data was recorded at end of treatment, and at 6-12 months, 12-24 months, and greater than 24 months following treatment completion. Group-based trajectory modeling was used to determine distinct GFR trajectories. Predictors of group membership were determined by multinomial regression analysis.Six trajectories were identified. One trajectory comprising 27% of the cohort demonstrated declining renal function and the others demonstrated no change in renal function over time. Baseline GFR did not predict SVR. Diabetes was associated with lower post-treatment GFR but patients with diabetes did not demonstrate a decrease in GFR over the period of evaluation. Cirrhosis and SVR were not significant predictors of GFR or GFR trajectory.There is no clinically relevant change in renal function among the majority of HCV-infected patients following completion of DAA-based treatments. Renal function does not influence the efficacy of DAA-based regimens. No consistent effect of DAA treatment and/or SVR on renal function was observed over a 2-year period following treatment completion.


Assuntos
Antivirais/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Estudos de Coortes , Feminino , Hepatite C/fisiopatologia , Humanos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
14.
N Engl J Med ; 382(26): 2493-2503, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32579810

RESUMO

BACKGROUND: Higher serum urate levels are associated with an increased risk of diabetic kidney disease. Lowering of the serum urate level with allopurinol may slow the decrease in the glomerular filtration rate (GFR) in persons with type 1 diabetes and early-to-moderate diabetic kidney disease. METHODS: In a double-blind trial, we randomly assigned participants with type 1 diabetes, a serum urate level of at least 4.5 mg per deciliter, an estimated GFR of 40.0 to 99.9 ml per minute per 1.73 m2 of body-surface area, and evidence of diabetic kidney disease to receive allopurinol or placebo. The primary outcome was the baseline-adjusted GFR, as measured with iohexol, after 3 years plus a 2-month washout period. Secondary outcomes included the decrease in the iohexol-based GFR per year and the urinary albumin excretion rate after washout. Safety was also assessed. RESULTS: A total of 267 patients were assigned to receive allopurinol and 263 to receive placebo. The mean age was 51.1 years, the mean duration of diabetes 34.6 years, and the mean glycated hemoglobin level 8.2%. The mean baseline iohexol-based GFR was 68.7 ml per minute per 1.73 m2 in the allopurinol group and 67.3 ml per minute per 1.73 m2 in the placebo group. During the intervention period, the mean serum urate level decreased from 6.1 to 3.9 mg per deciliter with allopurinol and remained at 6.1 mg per deciliter with placebo. After washout, the between-group difference in the mean iohexol-based GFR was 0.001 ml per minute per 1.73 m2 (95% confidence interval [CI], -1.9 to 1.9; P = 0.99). The mean decrease in the iohexol-based GFR was -3.0 ml per minute per 1.73 m2 per year with allopurinol and -2.5 ml per minute per 1.73 m2 per year with placebo (between-group difference, -0.6 ml per minute per 1.73 m2 per year; 95% CI, -1.5 to 0.4). The mean urinary albumin excretion rate after washout was 40% (95% CI, 0 to 80) higher with allopurinol than with placebo. The frequency of serious adverse events was similar in the two groups. CONCLUSIONS: We found no evidence of clinically meaningful benefits of serum urate reduction with allopurinol on kidney outcomes among patients with type 1 diabetes and early-to-moderate diabetic kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; PERL ClinicalTrials.gov number, NCT02017171.).


Assuntos
Alopurinol/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Inibidores Enzimáticos/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Ácido Úrico/sangue , Xantina Oxidase/antagonistas & inibidores , Adulto , Idoso , Alopurinol/efeitos adversos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Método Duplo-Cego , Inibidores Enzimáticos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Renina-Angiotensina , Falha de Tratamento
15.
Int J STD AIDS ; 31(7): 689-693, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32538332

RESUMO

Renal monitoring is recommended for Pre-Exposure Prophylaxis (PrEP) users. We aimed to explore follow-up and outcomes among PrEP users with renal impairment (defined as estimated glomerular filtration rate <65 mL/min/1.73 m2) attending Sydney Sexual Health Centre. Time to follow-up was analysed for impairment results over a 12-month period (January-December 2018); 48/2504 (1.9%) tests among 1700 attendees showed impairment. Follow-up occurred in 39/48 (81.3%) impairment results after a median of 42 days. PrEP was ceased in 3/6 cases of non-resolving/persisting impairment, with one case of subsequent human immunodeficiency virus infection. Maintaining engagement and follow-up of those with renal impairment are important aspects of PrEP service provision.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Rim/fisiopatologia , Profilaxia Pré-Exposição/métodos , Insuficiência Renal/epidemiologia , Adulto , Fatores Etários , Idoso , Instituições de Assistência Ambulatorial , Fármacos Anti-HIV/administração & dosagem , Austrália/epidemiologia , Feminino , Seguimentos , Taxa de Filtração Glomerular/efeitos dos fármacos , Infecções por HIV/prevenção & controle , Humanos , Rim/efeitos dos fármacos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/fisiopatologia , Fatores de Risco , Resultado do Tratamento
18.
Drug Discov Ther ; 14(2): 84-88, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32378650

RESUMO

Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. A number of new therapies have been developed based on the pathogenic factors of diabetic nephropathy such as intensive glycemic control, precise hypertension control, lifestyle modifications including exercise and an energy-restricted diet, and numerous novel agents. The utilization of traditional Chinese medicine for patients with diabetic nephropathy has also received increasing attention due to its wide availability, weak side-effects, and proven therapeutic mechanisms and benefits. In this paper, we report the case of patients with diabetic nephropathy, stage 2 or 3. Kangen-karyu extract (7.5 g/day) was administered three times per day for 6 months. The estimated glomerular filtration rate was increased at the 6-month follow-up. The serum creatinine level decreased following administration. At that time, somatic and subjective symptoms had partially disappeared. Here, we present evidence that Kangen-karyu exerts a renoprotective effect against the development of diabetic nephropathy.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Idoso , Creatina/sangue , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/fisiopatologia , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
19.
Circ Heart Fail ; 13(5): e006758, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32362166

RESUMO

BACKGROUND: The FIGHT (Functional Impact of GLP-1 [glucagon-like peptide-1] for Heart Failure Treatment) trial randomized 300 patients with heart failure with reduced ejection fraction (HFrEF) and a recent hospitalization for heart failure to liraglutide versus placebo. While there was no difference in the primary outcome (rank score of time to death, time to rehospitalization for heart failure, and change in NT-proBNP [N-terminal pro-B-type natriuretic peptide]), there was a significant increase in cystatin C among patients randomized to liraglutide raising concern of adverse renal outcomes. We performed a post hoc analysis of FIGHT to investigate whether liraglutide was associated with worsening renal function (WRF). METHODS: The relationship between randomization to liraglutide and WRF was evaluated using logistic regression models. Two hundred seventy-four patients (91%) had complete data to assess for WRF defined as: increase in SCr ≥0.3 mg/dL, or ≥25% decrease in estimated glomerular filtration rate, or an increase in cystatin C ≥0.3 mg/L from baseline to 180-days. RESULTS: Patients with WRF (n=113, 41%), compared with those without, were older, had more comorbidities, and lower utilization of guideline-directed medical treatment. Logistic regression models showed that age and baseline cystatin C levels were associated with WRF. In adjusted models, liraglutide was not associated with excess risk of WRF compared with placebo (odds ratio, 1.02 [95% CI, 0.62-1.67]). There was also no difference in the rank score when WRF was added as a fourth-tier outcome. CONCLUSIONS: Liraglutide was not associated with WRF among patients with HFrEF and a recent hospitalization for heart failure. These data support the relative renal safety profile of liraglutide among patients with HFrEF. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01800968.


Assuntos
Taxa de Filtração Glomerular/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Incretinas/uso terapêutico , Rim/efeitos dos fármacos , Liraglutida/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Método Duplo-Cego , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Hospitalização , Humanos , Incretinas/efeitos adversos , Rim/fisiopatologia , Liraglutida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Resultado do Tratamento
20.
PLoS One ; 15(4): e0231102, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32287280

RESUMO

BACKGROUND: Our preliminary data showed a slight decrease of estimated glomerular filtration rate (eGFR) after direct-acting antivirals (DAAs) treatment in chronic hepatitis C (CHC). However, long-term outcome of renal evolution after DAAs has not been well documented. AIM: To assess the renal function under DAAs treatment in CHC patients of an Asian population at 6 months and 1 year after complete treatment. METHODS: A cohort of 1536 CHC patients who received therapies with DAAs were analyzed. Serial eGFR levels at 24 weeks after treatment (SVR24) and 48 weeks after treatment (SVR48) were evaluated. We compared eGFR at baseline, SVR12, SVR24 and SVR48, and defined renal function deterioration as decrease of eGFR >25% from baseline to SVR24 and SVR48. RESULTS: Overall, there was decline of eGFR from SVR12 to SVR48 in all patients (84.30 ± 27.00 -> 73.20 ± 28.67 mL/min/1.73m2, p<0.001). This trend of decline was similar in all groups. Multivariate analysis for deterioration in renal function from baseline to SVR24 showed liver transplantation, hypertension and baseline eGFR < 60 mL/min/1.73m2 were independent risk factors. Multivariate analysis for persistent deterioration in renal function from baseline to SVR48 showed liver transplantation, baseline eGFR < 60 mL/min/1.73m2 and DCV/ASV use were independent predictive factors. CONCLUSIONS: There is a trend of decline in eGFR at 1-year after DAAs treatment regardless of baseline renal function or DAAs. Liver transplantation and baseline eGFR < 60 mL/min/1.73m2 were independent predictive factors of persistent deterioration in renal function from baseline to SVR48. Close monitoring renal function in these patients was suggested.


Assuntos
Antivirais/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacos , Hepatite C Crônica/terapia , Rim/efeitos dos fármacos , Transplante de Fígado/efeitos adversos , Idoso , Quimioterapia Combinada/efeitos adversos , Feminino , Seguimentos , Taxa de Filtração Glomerular/fisiologia , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resposta Viral Sustentada , Taiwan , Fatores de Tempo
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