Management of diabetes mellitus in individuals with chronic kidney disease: therapeutic perspectives and glycemic control

The purpose of this study was to evaluate the therapeutic options for diabetes treatment and their potential side effects, in addition to analyzing the risks and benefits of tight glycemic control in patients with diabetic kidney disease. For this review, a search was performed using several pre-defined keyword combinations and their equivalents: “diabetes kidney disease” and “renal failure” in combination with “diabetes treatment” and “oral antidiabetic drugs” or “oral hypoglycemic agents.” The search was performed in PubMed, Endocrine Abstracts and the Cochrane Library from January 1980 up to January 2015. Diabetes treatment in patients with diabetic kidney disease is challenging, in part because of progression of renal failure-related changes in insulin signaling, glucose transport and metabolism, favoring both hyperglycemic peaks and hypoglycemia. Additionally, the decline in renal function impairs the clearance and metabolism of antidiabetic agents and insulin, frequently requiring reassessment of prescriptions. The management of hyperglycemia in patients with diabetic kidney disease is even more difficult, requiring adjustment of antidiabetic agents and insulin doses. The health team responsible for the follow-up of these patients should be vigilant and prepared to make such changes; however, unfortunately, there are few guidelines addressing the nuances of the management of this specific population

Phosphorus Is Associated with Coronary Artery Disease in Patients with Preserved Renal Function

High serum phosphorus levels have been associated with mortality and cardiovascular events in patients with chronic kidney disease and in the general population. In addition, high phosphorus levels have been shown to induce vascular calcification and endothelial dysfunction in vitro. The aim of this study was to evaluate the relation of phosphorus and coronary calcification and atherosclerosis in the setting of normal renal function. This was a cross-sectional study involving 290 patients with suspected coronary artery disease and undergoing elective coronary angiography, with a creatinine clearance >60 ml/min/1.73 m2. Coronary artery obstruction was assessed by the Friesinger score and coronary artery calcification by multislice computed tomography. Serum phosphorus was higher in patients with an Agatston score >10 than in those with an Agatston score ≤10 (3.63±0.55 versus 3.49±0.52 mg/dl; p = 0.02). In the patients with Friesinger scores >4, serum phosphorus was higher (3.6±0.5 versus 3.5±0.6 mg/dl, p = 0.04) and median intact fibroblast growth factor 23 was lower (40.3 pg/ml versus 45.7 pg/ml, p = 0.01). Each 0.1-mg/dl higher serum phosphate was associated with a 7.4% higher odds of having a Friesinger score >4 (p = 0.03) and a 6.1% greater risk of having an Agatston score >10 (p = 0.01). Fibroblast growth factor 23 was a negative predictor of Friesinger score (p = 0.002). In conclusion, phosphorus is positively associated with coronary artery calcification and obstruction in patients with suspected coronary artery disease and preserved renal function

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

The effect of enalapril and losartan association therapy on proteinuria and inflammatory biomarkers in diabetic nephropathy: clinical trial on type 2 DM

O tratamento combinado com IECA e BRA foi proposto como alternativa para o tratamento da ND. Nosso objetivo foi avaliar se o tratamento IECA+BRA era superior ao tratamento com IECA em termos de proteinúria e excreção urinária de marcadores inflamatórios. Cinqüenta e seis pacientes com ND iniciaram o uso de enalapril. Após 4 meses, os pacientes passaram a receber losartan (Grupo E+L) ou placebo (Grupo E). As incidências de hipercalemia (HK) e deterioração aguda da função renal (DAFR) foram avaliadas. A análise de ANOVA de medidas repetidas não revelou diferença entre os grupos, mas, após ajustes, a progressão da proteinúria foi pior no Grupo E+L. A proteinúria final mostrou-se significativamente maior no Grupo E+L (proteinúria final estimada de 1,2 vs 2,6 g/d/1.73m2, p= 0.03). Os resultados foram confirmados nos modelos de regressão logística. Ocorreram 7 eventos de HK (12,6%) e 9 de DAFR (16,1%). Nossos dados sugerem que, em ND avançada, o tratamento combinado IECA+BRA não seja superior ao tratamento com IECA isoladamente em relação à proteinúria e marcadores inflamatórios.Combined treatment with an ACE inhibitor (ACEI) and an angiotensin II receptor blocker (ARB) has been proposed for diabetic nephropathy (DN) treatment. In this study we compared the effect of association therapy versus ACEI on proteinuria progression and on urinary inflammatory biomarkers in DN. Fifty-six patients with DN were started on enalapril. After 4 months, losartan (Group E+L) or placebo (Group E) treatment was started. Incidences of hyperkalemia (HK) and acute kidney function deterioration (AKFD) were monitored. Unadjusted repeated measures ANOVA revealed no difference between groups. After adjustment, proteinuria progression was significantly higher in the E+L Group. In addition, final proteinuria was significantly higher in the E+L Group (predicted adjusted final proteinuria 1,2 vs 2,6 g/d/1,73m2, p=0,03). Finally, logistic regression models showed the same results. We observed 7 HK events (12,6%) and 9 AKFD events (16,1%). These results suggest that, at least in advanced DN, association therapy is not superior to ACEI monotherapy in terms of proteinuria and inflammatory biomarkers

Urinary Retinol-Binding Protein: Relationship to Renal Function and Cardiovascular Risk Factors in Chronic Kidney Disease.

The role of urinary retinol-binding protein (RBP) as a biomarker of CKD in proximal tubular diseases, glomerulopathies and in transplantation is well established. However, whether urinary RBP is also a biomarker of renal damage and CKD progression in general CKD is not known. In this study, we evaluated the association of urinary RBP with renal function and cardiovascular risk factors in the baseline data of the Progredir Study, a CKD cohort in Sao Paulo, Brazil, comprising 454 participants with stages 3 and 4 CKD. In univariate analysis, urinary RBP was inversely related to estimated glomerular filtration rate (CKD-EPI eGFR) and several cardiovascular risk factors. After adjustments, however, only CKD-EPI eGFR, albuminuria, systolic blood pressure, anemia, acidosis, and left atrium diameter remained significantly related to urinary RBP. The inverse relationship of eGFR to urinary RBP (β-0.02 ± 95CI -0.02; -0.01, p<0.0001 for adjusted model) remained in all strata of albuminuria, even after adjustments: in normoalbuminuria (β-0.008 ± 95CI (-0.02; -0.001, p = 0.03), in microalbuminuria (β-0.02 ± 95CI (-0.03; -0.02, p<0,0001) and in macroalbuminuria (β-0.02 ± 95CI (-0.03; -0.01, p<0,0001). Lastly, urinary RBP was able to significantly increase the accuracy of a logistic regression model (adjusted for sex, age, SBP, diabetes and albuminuria) in diagnosing eGFR<35 ml/min/1.73m2 (AUC 0,77, 95%CI 0,72-0,81 versus AUC 0,71, 95%CI 0,65-0,75, respectively; p = 0,05). Our results suggest that urinary RBP is significantly associated to renal function in CKD in general, a finding that expands the interest in this biomarker beyond the context of proximal tubulopathies, glomerulopathies or transplantation. Urinary RBP should be further explored as a predictive marker of CKD progression

Chronic kidney disease - determinants of progression and cardiovascular risk. PROGREDIR cohort study: design and methods

ABSTRACT CONTEXT AND OBJECTIVE: Chronic kidney disease (CKD) has become an important public health issue. The socioeconomic burden of renal replacement therapy (RRT) is very high, as is CKD-related cardiovascular mortality and morbidity. Preventive and therapeutic measures only have modest impact and more research is needed. Few cohort studies have been conducted on populations with CKD. Our aim was to establish a cohort that would include more advanced forms of CKD (stages 3 and 4). Data collection was focused on renal and cardiovascular parameters. DESIGN AND SETTING: Prospective cohort study; São Paulo, Brazil. METHODS: Recruitment took place in Hospital das Clínicas, São Paulo, from March 2012 to December 2013. Data relating to medical history, food-frequency questionnaire, anthropometry, laboratory work-up, calcium score, echocardiography, carotid intimal-medial thickness, pulse-wave velocity, retinography and heart rate variability were collected. A biobank including serum, plasma, post-oral glucose tolerance test serum and plasma, urine (morning and 24-hour urine) and DNA was established. RESULTS: 454 participants (60% men and 50% diabetics) of mean age 68 years were enrolled. Their mean estimated glomerular filtration rate-CKD Epidemiology Collaboration was 38 ml/min/1.73 m2. Follow-up is ongoing and the main outcomes are the start of RRT, cardiovascular events and death. CONCLUSIONS: The PROGREDIR cohort is a promising prospective study that will allow better understanding of CKD determinants and validation of candidate biomarkers for the risks of CKD progression and mortality

Vitamin D status in a sunny country: Where has the sun gone?

Background & aims: Hypovitaminosis D [serum 25 vitamin D < 30 ng/ml] is related to the development of metabolic bone disease and greater risk of chronic illnesses. However, it is frequently under-diagnosed, mainly in countries where UV radiation is abundant. We prospectively determined the prevalence and the predictors of serum 25 vitamin D (s25(OH)D) in a healthy Brazilian population after the winter and after the summer. Methods: 603 (118M and 485F) healthy Brazilian volunteers aged 18-90 years from a universitary hospital were selected after the winter of 2006. From the initial sample, 209 volunteers (31M and 178F) accepted to participate in a second health check after the subsequent summer. Results: After the winter, median s25(OH)D was 21.4 ng/mL and 77.4% of the population presented hypovitaminosis D. s25(OH)D was significantly related to age, BMI, PTH and race. In multivariate linear regression analysis, s25(OH)D was significantly and independently dependent on age, glycemia and skin color. Significant increase in s25(OH)D was verified after summer [10.6 (3.7-19.3 ng/ml); p < 0.001] and this improvement was dependent on age. We also observed a significant decrease in hyperparathyroidism prevalence (20.8% vs. 4.9%; P < 0.0001). Conclusion: In Sao Paulo, at the end of winter, we observed a high prevalence of hypovitaminosis D and secondary hyperparathyroidism in healthy adults. s25(OH)D was dependent on age and skin color. After summer, we observed a decrease in the prevalence of hypovitaminosis D. This unexpected finding emphasizes the need for a strong recommendation to monitor s25(OH)D, even in a sunny country such as Brazil. (C) 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.Fundacao de Auxilio a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq