A 4-Variable Model to Predict Cardio-Kidney Events and Mortality in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (CRIC) Study.

INTRODUCTION: Current prognostic models for chronic kidney disease (CKD) are complex and were designed to predict a single outcome. We aimed to develop and validate a simple and parsimonious prognostic model to predict cardio-kidney events and mortality. METHODS: Patients from the CRIC Study (n = 3,718) were randomly divided into derivation (n = 2,478) and validation (n = 1,240) cohorts. Twenty-nine candidate variables were preselected. Multivariable Cox regression models were developed using stepwise selection for various cardio-kidney endpoints, namely, (i) the primary composite outcome of 50% decline in estimated glomerular filtration rate (eGFR) from baseline, end-stage renal disease, or cardiovascular (CV) mortality; (ii) hospitalization for heart failure (HHF) or CV mortality; (iii) 3-point major CV endpoints (3P-MACE); (iv) all-cause death. RESULTS: During a median follow-up of 9 years, the primary outcome occurred in 977 patients of the derivation cohort and 501 patients of the validation cohort. Log-transformed N-terminal pro-B-type natriuretic peptide (NT-proBNP), log-transformed high-sensitive cardiac troponin T (hs-cTnT), log-transformed albuminuria, and eGFR were the dominant predictors. The primary outcome risk score discriminated well (c-statistic = 0.83) with a proportion of events of 11.4% in the lowest tertile of risk and 91.5% in the highest tertile at 10 years. The risk model presented good discrimination for HHF or CV mortality, 3P-MACE, and all-cause death (c-statistics = 0.80, 0.75, and 0.75, respectively). The 4-variable risk model achieved similar c-statistics for all tested outcomes in the validation cohort. The discrimination of the 4-variable risk model was mostly superior to that of published models. CONCLUSION: The combination of NT-proBNP, hs-cTnT, albuminuria, and eGFR in a single 4-variable model provides a unique individual prognostic assessment of multiple cardio-kidney outcomes in CKD.

Association of combined fractional excretion of phosphate and FGF23 with heart failure and cardiovascular events in moderate and advanced renal disease.

BACKGROUND: High levels of FGF23 associate with adverse events in CKD. The urinary fractional excretion of phosphate (FePi) might modify this association, although data are limited in moderate and advanced CKD. We investigated the association of combined FePi and serum FGF23 with incident heart failure, cardiovascular events and mortality in patients with CKD stages 2-4. METHODS: Patients from the Chronic Renal Insufficiency Cohort were divided into four groups according to the median of FePi and FGF23: low-FePi/low-FGF23, reference group; high-FePi/low-FGF23; low-FePi/high-FGF23; high-FePi/high-FGF23. Primary outcomes were: the composite of cardiovascular death or hospitalization for heart failure; cardiovascular death; hospitalization for heart failure; and death from any cause. Survival analysis and adjusted regression analyses were performed. RESULTS: We analyzed 3684 patients with a mean age of 58 ± 11 years of whom 45% were male. Mean eGFR was 44 ± 15 ml/min/1.73 m2. The median time of follow-up was 12 (IQR 7-13) years. The risk of the composite of cardiovascular death or hospitalization for heart failure was increased in the low-FePi/high-FGF23 group (HR 1.35; 95%CI 1.09-1.67) and in the high-FePi/high-FGF23 group (HR 1.50; 95%CI 1.20-1.86), compared to the low-FePi/low-FGF23 group. Cardiovascular death and hospitalization for heart failure were also increased in both groups with high FGF23. Death from any cause was increased in the low-FePi/high-FGF23 group (HR 1.56 (95%CI 1.30-1.89) and in the high-FePi/high-FGF23 (HR 1.57 (95%CI 1.29-1.90)). CONCLUSIONS: High FGF23 was associated with heart failure and cardiovascular death in patients with low FePi and high FePi with moderate to advanced CKD. This contrasts with reports in mild CKD.

The Role of Vascular Lesions in Diabetes Across a Spectrum of Clinical Kidney Disease.

INTRODUCTION: The clinical-histologic correlation in diabetic nephropathy is not completely known. METHODS: We analyzed nephrectomy specimens from 90 patients with diabetes and diverse degrees of proteinuria and glomerular filtration rate (GFR). RESULTS: Thirty-six (40%) subjects had normoalbuminuria, 33 (37%) microalbuminuria, and 21 (23%) non-nephrotic proteinuria. Mean estimated GFR (eGFR) was 65±23 (40% <60 ml/min per 1.73 m2). About 170 glomeruli per patient were analyzed, and all samples included vascular tissue. Six subjects (7%) were classified in diabetic nephropathy class I, 61 (68%) in class II-a, 13 (14%) in class II-b, 9 (10%) class III, and 1 (1%) in class IV. Eighty percent to 90% of those with normoalbuminuria or microalbuminuria were classified in class II-a or II-b and <10% in class III; 52% of those with proteinuria were in class II-a, 15% in class II-b, and 19% in class III. Nodular sclerosis (57%) and mesangial expansion (15%) were more frequent in cases with proteinuria than in normoalbuminuria (28% and 8%; P = 0.028 and 0.017). About 20% to 30% of all cases, regardless the level of albuminuria or proteinuria or the histologic class had tubular atrophy, interstitial fibrosis, or inflammation in >10% to 20% of the sample. Moderate hyalinosis and arteriolar sclerosis were observed in 80% to 100% of cases with normoalbuminuria, microalbuminuria, proteinuria, as well as in class I, II, or III. CONCLUSIONS: Weak correspondence between analytical parameters and kidney histology was found. Thus, disease may progress undetected from the early clinical stages of the disease. Finally, vascular damage was a very common finding, which highlights the role of ischemic intrarenal disease in diabetes.

[Analysis of the Cochrane Review: Antiplatelet Agents for Preventing Pre-Eclampsia and Its Complications. Cochrane Database Syst Rev. 2019;10:CD004659.] / Análise da Revisão Cochrane: O Papel dos Antiagregantes Plaquetários para Prevenir a Pré-Eclâmpsia e as Suas Complicações. Cochrane Database Syst Rev. 2019;10:CD004659.

Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a vasoconstrictor and stimulant of platelet aggregation. These observations led to the hypotheses that antiplatelet agents, low-dose aspirin in particular, might prevent or delay development of pre-eclampsia. This Cochrane review aimed to assess the effectiveness and safety of antiplatelet agents, such as aspirin and dipyridamole, when given to women at risk of developing preeclampsia. A systematic review of literature was carried out by searching the following databases up to September 2019: Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP), and reference lists of retrieved studies. Seventy-seven trials were included, including 40 249 women at risk of developing pre-eclampsia. About 80% of these women were evaluated in nine of the 77 trials included, with eight of these nine trials providing individual data. Interventions were administration of an antiplatelet agent, and comparisons were either placebo or no antiplatelet. The present review provides high-quality evidence that administering low-dose aspirin (50 - 150 mg) to pregnant women led to small-to-moderate benefits, including reductions in the risk of pre-eclampsia, preterm birth, small-for-gestational age fetus, and fetal or neonatal death. Overall, administering antiplatelet agents to 1000 women led to 20 fewer pregnancies with serious adverse outcomes.

A pré-eclâmpsia está associada à produção intravascular deficiente de prostaciclina, um vasodilatador, e à produção excessiva de tromboxano, um vasoconstritor e estimulante da agregação plaquetária. Essas observações levaram à hipótese de os antiagregantes plaquetários, em particular o ácido acetilsalicílico, poderem, em dose reduzida, prevenir ou retardar o desenvolvimento da pré-eclâmpsia. Esta revisão da Cochrane teve como objetivo avaliar a eficácia e segurança de antiagregantes plaquetários comparativamente a placebo ou a ausência de tratamento, quando administrados a mulheres em risco de desenvolver pré-eclâmpsia. Foi realizada uma revisão sistemática da literatura até setembro de 2019, através de pesquisa nas seguintes bases de dados: Registo de Ensaios de Gravidez e Parto da Cochrane, ClinicalTrials.gov, Plataforma Internacional de Registo de Ensaios Clínicos da OMS (ICTRP) e listas de referência de estudos recuperados. Foram incluídos 77 ensaios clínicos aleatorizados, incluindo 40 249 mulheres grávidas em risco de desenvolver pré-eclâmpsia. Cerca de 80% destas mulheres foram avaliadas em nove dos 77 ensaios incluídos, sendo que oito destes nove ensaios disponibilizavam dados individuais. O ácido acetilsalicílico foi o antiagregante plaquetário avaliado na maioria dos ensaios, incluindo nos nove ensaios de maior dimensão. A presente revisão concluiu, com qualidade de evidência elevada, que a administração de ácido acetilsalicílico em dose reduzida (50 - 150 mg) a mulheres grávidas está associada a benefícios, considerados de magnitude pequena a moderada, na redução do risco de pré-eclâmpsia, parto prematuro, feto pequeno para a idade gestacional, e morte fetal ou neonatal. A administração de antiagregantes plaquetários a 1000 mulheres resultou em menos 20 gestações com desfechos adversos graves.

Association of Prediabetes With CKD Progression and Adverse Cardiovascular Outcomes: An Analysis of the CRIC Study.

PURPOSE: Despite our understanding of diabetes as an established risk factor for progressive kidney disease and cardiac complications, the prognostic significance of prediabetes in patients with chronic kidney disease (CKD) remains largely unknown. METHODS: Participants of the Chronic Renal Insufficiency Cohort (CRIC) were categorized as having normoglycemia, prediabetes, or diabetes according to fasting plasma glucose, glycated hemoglobin A1c (HbA1c), and treatment with antidiabetic drugs at baseline. Unadjusted and adjusted proportional hazards models were fit to estimate the association of prediabetes and diabetes (versus normoglycemia) with: (1) composite renal outcome (end-stage renal disease, 50% decline in estimated glomerular filtration rate to ≤ 15 mL/min/1.73 m2, or doubling of urine protein-to-creatinine ratio to ≥ 0.22 g/g creatinine); (2) composite cardiovascular (CV) outcome (congestive heart failure, myocardial infarction or stroke); and (3) all-cause mortality. RESULTS: Of the 3701 individuals analyzed, 945 were normoglycemic, 847 had prediabetes and 1909 had diabetes. The median follow-up was 7.5 years. Prediabetes was not associated with the composite renal outcome (adjusted hazard ratio [aHR] 1.13; 95% confidence interval [CI], 0.96-1.32; P = 0.14), but was associated with proteinuria progression (aHR 1.23; 95% CI, 1.03-1.47; P = 0.02). Prediabetes was associated with a higher risk of the composite CV outcome (aHR 1.38; 95% CI, 1.05-1.82; P = 0.02) and a trend towards all-cause mortality (aHR 1.28; 95% CI, 0.99-1.66; P = 0.07). Participants with diabetes had an increased risk of the composite renal outcome, the composite CV outcome, and all-cause mortality. CONCLUSIONS: In individuals with CKD, prediabetes was not associated with composite renal outcome, but was associated with an increased risk of proteinuria progression and adverse CV outcomes.

Intensive Blood Pressure Treatment Reduced Stroke Risk in Patients With Albuminuria in the SPRINT Trial.

Background and Purpose- Albuminuria is associated with stroke risk among individuals with diabetes. However, the association of albuminuria with incident stroke among nondiabetic patients is less clear. Methods- We performed a post hoc analysis of the SPRINT (Systolic Blood Pressure Intervention Trial), which examined the effect of higher versus lower intensity blood pressure management on mortality in 8913 participants without diabetes. We fit unadjusted and adjusted Cox proportional hazards models to estimate the association of baseline albuminuria (urinary albumin-to-creatinine ratio ≥30 mg/g versus<30 mg/g) with stroke risk. We also assessed effect modification according to treatment arms. Results- Mean age was 68±9 years, 35% were female, and 30% were black. Median follow-up was 3.2 years, and 19% patients had baseline albuminuria. Incident stroke occurred in 129 individuals during follow-up. Albuminuria was associated with increased stroke risk (unadjusted hazard ratio, 2.24; 95% CI, 1.55-3.23; adjusted hazard ratio 1.73; 95% CI, 1.17-2.56). The association of albuminuria with incident stroke differed according to the randomized treatment arm (P interaction=0.03). In the intensive treatment arm, the association of albuminuria and stroke was nonsignificant (unadjusted hazard ratio, 1.25; 95% CI, 0.69-2.28), whereas, in the standard treatment arm, it was significant (unadjusted hazard ratio, 3.44; 95% CI, 2.11-5.61). Conclusions- In a post hoc analysis of SPRINT, baseline albuminuria (versus not) was associated with a higher risk of incident stroke, but this relationship appeared to be restricted to those in the standard treatment arm. Further studies are required to conclusively determine if reduction of albuminuria in itself is beneficial in reducing stroke risk. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01206062.

Impaired Fasting Glucose and Chronic Kidney Disease, Albuminuria, or Worsening Kidney Function: A Secondary Analysis of SPRINT.

PURPOSE: Diabetes mellitus is a risk factor for the development and progression of chronic kidney disease (CKD). However, the association of prediabetes with adverse kidney outcomes is uncertain. METHODS: We performed a secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), including 9361 participants without diabetes at baseline. We categorized participants according to fasting glucose level as having impaired fasting glucose [≥100 mg/dL (≥5.6 mmol/L)] or normoglycemia [<100 mg/dL (<5.6 mmol/L)]. Unadjusted and adjusted proportional hazards models were fitted to estimate the association of impaired fasting glucose (vs normoglycemia) with a composite outcome of worsening kidney function [≥30% decrease in estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73 m2 in participants without baseline CKD; ≥50% decrease in eGFR or need for long-term dialysis/kidney transplantation in participants with CKD] or incident albuminuria (doubling of urinary albumin/creatinine ratio from <10 mg/g to >10 mg/g). These outcomes were also evaluated separately and according to CKD status at baseline. RESULTS: Participants' mean age was 67.9 ± 9.4 years, 35.5% were female, and 31.4% were black. The median follow-up was 3.3 years, and 41.8% had impaired fasting glucose. Impaired fasting glucose was not associated with higher rates of the composite outcome [hazard ratio (HR): 0.97; 95% CI: 0.8 to 1.16], worsening kidney function (HR: 1.02; 95% CI: 0.75 to 1.37), or albuminuria (HR: 0.98; 95% CI: 0.78 to 1.23). Similarly, there was no association of impaired fasting glucose with outcomes according to baseline CKD status. CONCLUSIONS: Impaired fasting glucose at baseline was not associated with the development of worsening kidney function or albuminuria in participants of SPRINT.

[Prescribing of Non-Steroidal Anti-Inflammatory Drugs to Patients with Diabetes Mellitus in Portugal]. / Prescrição de Anti-Inflamatórios Não Esteroides a Doentes com Diabetes Mellitus em Portugal.

INTRODUCTION: Portugal presents the highest incidence of stage 5 chronic kidney disease in Europe. It is speculated that a high consumption of non-steroidal anti-inflammatory drugs (NSAIDS) may contribute to this high incidence. Our aim was to characterize the prescription of non-steroidal anti-inflammatory drugs to patients with diabetes mellitus in Portugal. MATERIAL AND METHODS: We analyzed the national prescription database in triennium 2015 - 2017. In patients with diabetes mellitus, we evaluated the prescription of non-steroidal anti-inflammatory drugs according to age, gender and region of the patient and specialty of the prescribing physician. We evaluated the prescription of non-steroidal anti-inflammatory drugs in all patients with diabetes mellitus, in patients with presumed renal impairment, and in those with concomitant prescription of angiotensin converting enzyme inhibitors or angiotensin receptor antagonists. RESULTS: We analyzed 23 320 620 prescriptions, corresponding to 610 157 adults, including 104 306 patients with diabetes mellitus. The most prescribed non-steroidal anti-inflammatory drugs were ibuprofen (20.1%), metamizole (14.7%), and diclofenac (11.4%). The prescription of non-steroidal anti-inflammatory drugs was higher in females, in patients aged 51 - 70 years and in the Alentejo region. Non-steroidal anti-inflammatory drugs were prescribed to 70.6% of patients with diabetes mellitus, from which 10.6% were prescribed ≥ 10 packages during the three years. Among patients with diabetes mellitus on angiotensin converting enzyme inhibitors/angiotensin receptor antagonists and with presumed reduction in kidney function, 69.3% were prescribed non-steroidal anti-inflammatory drugs and 11.5% were prescribed ≥ 10 packages during the three years. DISCUSSION: The level of prescribing of non-steroidal anti-inflammatory drugs to patients with diabetes mellitus is high. The concern of reducing non-steroidal anti-inflammatory drugs prescription to patients already on angiotensin converting enzyme inhibitors/angiotensin receptor antagonists and/or decreased renal function does not seem to exist. CONCLUSION: In Portugal, the level of prescribing of non-steroidal anti-inflammatory drugs to patients with diabetes mellitus should be reduced, particularly in the subgroups identified with higher prescription and with higher risk of progression to stage 5 chronic kidney disease.

Introdução: Portugal apresenta a incidência mais elevada de doença renal crónica estádio 5 na Europa. Especula-se que o elevado consumo de anti-inflamatórios não esteroides possa contribuir para esta incidência. O objetivo do presente estudo foi caracterizar a prescrição de anti-inflamatórios não esteroides a doentes com diabetes mellitus em Portugal. Material e Métodos: Na Base de Dados Nacional de Prescrições do Ministério da Saúde, triénio 2015 - 2017, analisámos a prescrição de anti-inflamatórios não esteroides em doentes com diabetes mellitus, de acordo com a idade, género e região do doente e a especialidade do médico prescritor. Avaliámos a prescrição de anti-inflamatórios não esteroides no total de doentes com diabetes mellitus, em doentes com diminuição presumida da função renal e naqueles com prescrição concomitante de inibidores da enzima de conversão da angiotensina ou antagonistas dos recetores da angiotensina. Resultados: Analisámos 23 320 620 prescrições, correspondendo a 610 157 adultos, dos quais 104 306 doentes com diabetes mellitus. Os anti-inflamatórios não esteroides mais prescritos foram ibuprofeno (20,1%), metamizol (14,7%) e diclofenac (11,4%). A prescrição foi mais frequente nas mulheres, nos doentes com 51 - 70 anos e no Alentejo. Foram prescritos anti-inflamatórios não esteroides a 70,6% dos doentes com diabetes mellitus, dos quais 10,6% receberam prescrições de ≥ 10 embalagens durante os três anos. Dos doentes com diabetes mellitus medicados com inibidores da enzima de conversão da angiotensina ou antagonistas dos receptores da angiotensina e com diminuição presumida da taxa de filtração glomerular, 69,3% receberam prescrição de anti-inflamatórios não esteroides e 11,5% receberam ≥ 10 embalagens durante os três anos. Discussão: A prescrição de anti-inflamatórios não esteroides na diabetes mellitus é elevada. Não parece existir uma preocupação na menor utilização de anti-inflamatórios não esteroides em doentes simultaneamente medicados com inibidores da enzima de conversão da angiotensina ou antagonistas dos recetores da angiotensina e/ou com diminuição da função renal. Conclusão: A prescrição de anti-inflamatórios não esteroides em Portugal a doentes com diabetes mellitus deverá ser reduzida, particularmente nos subgrupos identificados com prescrição mais elevada e com maior risco de progressão para doença renal crónica estádio 5.

Lower free triiodothyronine levels within the reference range are associated with higher cardiovascular mortality: An analysis of the NHANES.

BACKGROUND: Thyroid hormones play a central role in cardiovascular homeostasis. Lower free triiodothyronine (FT3) levels have been associated with worse prognosis in several conditions. However, contrary to thyrotropin (TSH) and free thyroxine (FT4), the role of FT3 in morbidity and mortality in the general population remains uncertain. Our objective was to evaluate the association between within the normal range FT3 levels and mortality in the general population. METHODS: We evaluated 7116 adults in the National Health and Nutrition Examination Survey (NHANES) 2001-2002, 2007-2008, and 2009-2010 cycles with mortality evaluated as of December 2011. Exclusion criteria were: pregnancy; history of thyroid disease; use of thyroid-related drugs; and TSH, FT4, or FT3 level outside the reference range. RESULTS: During a median follow-up of 45 months, 357 participants died. In unadjusted analysis, lower FT3 levels were associated with higher all-cause (HR per 0.1 pg/mL increase in FT3: 0.82 [95% confidence interval, 0.78-0.87]), cardiovascular (HR 0.74 [0.66-0.83]), cancer-related (HR 0.88 [0.80-0.97]) and other cause-related mortality (HR 0.83 [0.77-0.90]). After adjustment with Cox proportional hazard models, lower FT3 levels remained significantly associated with higher cardiovascular mortality (HR 0.83 [0.75-0.93]), but not with all-cause (HR 0.97 [0.92-1.02]), cancer-related (HR 1.02 [0.89-1.17]), or other cause-related mortality (HR 1.00 [0.92-1.10]). CONCLUSIONS: Lower levels of FT3 within the reference range may independently predict higher cardiovascular mortality in the general population.

Caffeine consumption and mortality in chronic kidney disease: a nationally representative analysis.

BACKGROUND: An inverse relationship between coffee consumption and mortality has been reported in the general population. However, the association between caffeine consumption and mortality in patients with chronic kidney disease (CKD) remains uncertain. METHODS: We analysed 4863 non-institutionalized USA adults with CKD [defined by an estimated glomerular filtration rate (eGFR) of 15-60 mL/min/1.73 m2 and/or a urinary albumin:creatinine ratio >30 mg/g] in a nationwide study using the National Health and Nutrition Examination Survey (NHANES) 1999-2010. Caffeine consumption was evaluated by 24-h dietary recalls at baseline and all-cause, cardiovascular and cancer mortality were evaluated until 31 December 2011. We also performed an analysis of caffeine consumption according to its source (coffee, tea and soft drinks). Quartiles of caffeine consumption were <28.2 mg/day (Q1), 28.2-103.0 (Q2), 103.01-213.5 (Q3) and >213.5 (Q4). RESULTS: During a median follow-up of 60 months, 1283 participants died. Comparing with Q1 of caffeine consumption, the adjusted hazard ratio for all-cause mortality was 0.74 [95% confidence interval (CI) 0.60-0.91] for Q2, 0.74 (95% CI 0.62-0.89) for Q3 and 0.78 (95% CI 0.62-0.98) for Q4 (P = 0.02 for trend across quartiles). There were no significant interactions between caffeine consumption quartiles and CKD stages or urinary albumin:creatinine ratio categories regarding all-cause mortality. CONCLUSIONS: We detected an inverse association between caffeine consumption and all-cause mortality among participants with CKD.

Caffeine Consumption and Mortality in Diabetes: An Analysis of NHANES 1999-2010.

Aim: An inverse relationship between coffee consumption and mortality has been reported in the general population. However, the effect of coffee consumption in diabetes remains unclear. We aimed to evaluate the association of caffeine consumption and caffeine source with mortality among patients with diabetes. Methods: We examined the association of caffeine consumption with mortality among 1974 women and 1974 men with diabetes, using the National Health and Nutrition Examination Survey (NHANES) 1999-2010. Caffeine consumption was assessed at baseline using 24 h dietary recalls. Cox proportional hazard models were fitted to estimate hazard ratios (HR) for all-cause, cardiovascular, and cancer-related mortality according to caffeine consumption and its source, adjusting for potential confounders. Results: A dose-dependent inverse association between caffeine and all-cause mortality was observed in women with diabetes. Adjusted HR for death among women who consumed caffeine, as compared with non-consumers, were: 0.57 (95% CI, 0.40-0.82) for <100 mg of caffeine/day, 0.50 (95% CI, 0.32-0.78) for 100 to <200 mg of caffeine/day, and 0.39 (95% CI, 0.23-0.64) for ≥200 mg of caffeine/day (p = 0.005 for trend). This association was not observed in men. There was a significant interaction between sex and caffeine consumption (p = 0.015). No significant association between total caffeine consumption and cardiovascular or cancer mortality was observed. Women who consumed more caffeine from coffee had reduced risk of all-cause mortality (p = 0.004 for trend). Conclusion: Our study showed a dose-dependent protective effect of caffeine consumption on mortality among women with diabetes.

[Bacteriuria. Cochrane Database Syst Rev. 2015;4:CD009534.] / Análise da Revisão Cochrane: Antibióticos Destinados ao Tratamento da Bacteriúria Assintomática. Cochrane Database Syst Rev. 2015;4:CD009534.

Asymptomatic bacteriuria is frequently detected in women aged up to 60 years, patients with diabetes and elderly patients. The benefit of antibiotic treatment for this condition is controversial. The objective of this Cochrane systematic review was to assess the effectiveness and safety of antibiotic treatment for asymptomatic bacteriuria in adults. A systematic review of the literature up to 24 February 2015 was performed using the Cochrane Renal Group's Specialised Register. Randomised controlled trials (RCTs) and quasirandomised controlled trials comparing antibiotics to placebo or no treatment for asymptomatic bacteriuria in adults were included. The outcomes of interest were the development of symptomatic urinary tract infection, complications, death, adverse events, development of antibiotic resistance, bacteriological cure, and decline in kidney function. Nine studies (1614 participants) were included in this review. The incidence of symptomatic urinary tract infection, complications or death was similar between groups. Antibiotic use was significantly associated with bacteriological cure and an increase in minor adverse events. No decline in kidney function was observed with any one of the treatments. According to the results of the studies included in this revision, authors have concluded that there is no clinical benefit in treating asymptomatic bacteriuria in adults.

A bacteriúria assintomática é frequentemente detectada em mulheres com idade inferior a 60 anos, doentes com diabetes e doentes idosos. O benefício do seu tratamento com antibióticos é controverso. Esta revisão sistemática Cochrane teve como objetivo avaliar a eficácia e a segurança da utilização de antibióticos no tratamento de bacteriúria assintomática em adultos. Foi realizada revisão sistemática da literatura até 24 de fevereiro de 2015, através de pesquisa no Cochrane Renal Group´s Specialised Register. Foram incluídos ensaios aleatorizados controlados e quasi-aleatorizados nos quais doentes adultos tivessem sido tratados com antibiótico comparativamente com placebo ou ausência de tratamento. Foi avaliada a ocorrência de infeções do trato urinário sintomáticas, complicações, morte, qualquer efeito adverso, desenvolvimento de resistência a antibióticos, cura bacteriológica e declínio da função renal. Foram incluídos nove ensaios clínicos nesta revisão (1614 participantes). A ocorrência de infeções do trato urinário sintomáticas, complicações e morte foi semelhante entre grupos. A utilização de antibióticos encontrou-se significativamente associada a cura bacteriológica e a um número mais elevado de efeitos adversos, predominantemente ligeiros. Não se verificou agravamento da função renal com qualquer um dos tratamentos. De acordo com os ensaios clínicos incluídos nesta revisão, os autores concluem não existir benefício no tratamento da bacteriúria assintomática.

BP Reduction, Kidney Function Decline, and Cardiovascular Events in Patients without CKD.

BACKGROUND AND OBJECTIVES: In the Systolic Blood Pressure Intervention Trial (SPRINT), intensive systolic BP treatment (target <120 mm Hg) was associated with fewer cardiovascular events and higher incidence of kidney function decline compared with standard treatment (target <140 mm Hg). We evaluated the association between mean arterial pressure reduction, kidney function decline, and cardiovascular events in patients without CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We categorized patients in the intensive treatment group of the SPRINT according to mean arterial pressure reduction throughout follow-up: <20, 20 to <40, and ≥40 mm Hg. We defined the primary outcome as kidney function decline (≥30% reduction in eGFR to <60 ml/min per 1.73 m2 on two consecutive determinations at 3-month intervals), and we defined the secondary outcome as cardiovascular events. In a propensity score analysis, patients in each mean arterial pressure reduction category from the intensive treatment group were matched with patients from the standard treatment group to calculate the number needed to treat regarding cardiovascular events and the number needed to harm regarding kidney function decline. RESULTS: In the intensive treatment group, 1138 (34%) patients attained mean arterial pressure reduction <20 mm Hg, 1857 (56%) attained 20 to <40 mm Hg, and 309 (9%) attained ≥40 mm Hg. Adjusted hazard ratios for kidney function decline were 2.10 (95% confidence interval, 1.22 to 3.59) for mean arterial pressure reduction between 20 and 40 mm Hg and 6.22 (95% confidence interval, 2.75 to 14.08) for mean arterial pressure reduction ≥40 mm Hg. In propensity score analysis, mean arterial pressure reduction <20 mm Hg presented a number needed to treat of 44 and a number needed to harm of 65, reduction between 20 and <40 mm Hg presented a number needed to treat of 42 and a number needed to harm of 35, and reduction ≥40 mm Hg presented a number needed to treat of 95 and a number needed to harm of 16. CONCLUSIONS: In the intensive treatment group of SPRINT, larger declines in mean arterial pressure were associated with higher incidence of kidney function decline. Intensive treatment seemed to be less favorable when a larger reduction in mean arterial pressure was needed to attain the BP target.

[Analysis of the Cochrane Review: Pharmacotherapy for Hyperuricemia in Hypertensive Patients. Cochrane Database Syst Rev. 2017;4:CD008652.] / Análise da Revisão Cochrane: Terapêutica Farmacológica da Hiperuricemia em Doentes Hipertensos. Cochrane Database Syst Rev. 2017;4:CD008652.

Arterial hypertension is a public health problem that affects approximately 25% of the world's adult population. The association between hypertension and hyperuricemia has been shown on epidemiological and experimental studies. However, it is unclear whether lowering serum uric acid might lower blood pressure. This Cochrane systematic review - a revised edition of a previously published one - intended as primary objective to evaluate the effect of hypouricemic drugs in patients with primary hypertension or prehypertension. The secondary objectives were to evaluate the efficacy and safety of hypouricemic drugs. A systematic search until February 2016 on controlled, randomized or quasi-randomized trials comparing the effect of hypouricemic drug versus placebo in hypertensive or prehypertensive patients was performed on the following databases: The Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, The World Health Organization International Clinical Trials Registry Platform, e ClinicalTrials.gov. LILACS database up to March 2016 was also searched and the authors of relevant studies were contacted. There were 349 identified papers, 21 were preselected and three randomized clinical trials (211 patients) were included in the qualitative analysis and in the meta-analysis. Two of the trials were conducted exclusively on adolescents. The authors conclude that hypouricemic drugs are not effective in lowering blood pressure in patients with hyperuricemia and primary prehypertension or hypertension. However, this strategy might be more effective in the specific population of adolescents with prehypertension or mild primary hypertension recently diagnosed. Hypouricemic drugs effectively reduce serum uric acid level and withdrawals of therapy due to adverse effects were not superior in the treated group, comparing to placebo; however, one patient withdrew due to a severe cutaneous reaction.

A hipertensão arterial é um problema de saúde pública que afeta cerca de 25% da população adulta mundial. A associação entre hiperuricemia e hipertensão arterial tem sido demonstrada em estudos epidemiológicos e experimentais. No entanto, não é claro se a terapêutica hipouricemiante reduz os valores de pressão arterial. Esta revisão sistemática - uma versão atualizada de outra previamente publicada - teve como objetivo primário avaliar o efeito da terapêutica hipouricemiante nos valores de pressão arterial de doentes com pré-hipertensão ou hipertensão arterial primárias. Os objetivos secundários foram avaliar a eficácia da terapêutica na redução da uricemia e o perfil de segurança. Foram selecionados ensaios clínicos aleatorizados ou quasi-aleatorizados que comparassem o efeito nos valores de pressão arterial da terapêutica hipouricemiante versus placebo, em doentes com hiperuricemia e pré-hipertensão ou hipertensão arterial essencial. Foram pesquisadas as seguintes bases de dados até fevereiro de 2016: The Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, The World Health Organization International Clinical Trials Registry Platform, e ClinicalTrials.gov. Foi também pesquisada a LILACS até março de 2016 e contactados os autores dos estudos considerados relevantes. Dos 349 artigos identificados, foram pré-selecionados 21, tendo sido incluídos três ensaios clínicos aleatorizados (211 doentes) na análise qualitativa e na meta-análise. Dois destes ensaios incluíram exclusivamente adolescentes. Os autores concluem que a terapêutica hipouricemiante não é eficaz na redução da pressão arterial na população de doentes com hiperuricemia e pré-hipertensão ou hipertensão arterial essencial. No entanto, esta estratégia poderá ser mais eficaz na população específica dos adolescentes com pré-hipertensão ou hipertensão arterial ligeira diagnosticada recentemente. A terapêutica hipouricemiante é eficaz na redução do valor sérico de ácido úrico e a suspensão da terapêutica devido a efeitos adversos não foi superior nos grupos tratados comparativamente com placebo (embora um doente a tenha suspendido por reação cutânea grave).