Antihypertensive Treatment in Diabetic Kidney Disease: The Need for a Patient-Centered Approach

Diabetic kidney disease affects up to forty percent of patients with diabetes during their lifespan. Prevention and treatment of diabetic kidney disease is currently based on optimal glucose and blood pressure control. Renin-angiotensin aldosterone inhibitors are considered the mainstay treatment for hypertension in diabetic patients, especially in the presence of albuminuria. Whether strict blood pressure reduction entails a favorable renal outcome also in non-albuminuric patients is at present unclear. Results of several clinical trials suggest that an overly aggressive blood pressure reduction, especially in the context of profound pharmacologic inhibition of the renin-angiotensin-aldosterone system may result in a paradoxical worsening of renal function. On the basis of this evidence, it is proposed that blood pressure reduction should be tailored in each individual patient according to renal phenotype

Natural history and risk factors for diabetic kidney disease in patients with T2D: lessons from the AMD-annals

The Associazione Medici Diabetologi (AMD) annals initiative is an ongoing observational survey promoted by AMD. It is based on a public network of about 700 Italian diabetes clinics, run by specialists who provide diagnostic confirmation and prevention and treatment of diabetes and its complications. Over the last few years, analysis of the AMD annals dataset has contributed several important insights on the clinical features of type-2 diabetes kidney disease and their prognostic and therapeutic implications. First, non-albuminuric renal impairment is the predominant clinical phenotype. Even though associated to a lower risk of progression compared to overt albuminuria, it contributes significantly to the burden of end-stage renal disease morbidity. Second, optimal blood pressure control provides significant but incomplete renal protection. It reduces albuminuria but there may be a J curve phenomenon with eGFR at very low blood pressure values. Third, hyperuricemia and diabetic hyperlipidemia, namely elevated triglycerides and low HDL cholesterol, are strong independent predictors of chronic kidney disease (CKD) onset in diabetes, although the pathogenetic mechanisms underlying these associations remain uncertain. Fourth, the long-term intra-individual variability in HbA1c, lipid parameters, uric acid and blood pressure plays a greater role in the appearance and progression of CKD than the absolute value of each single variable. These data help clarify the natural history of CKD in patients with type 2 diabetes and provide important clues for designing future interventional studies

Serum Uric Acid and Kidney Disease Measures Independently Predict Cardiovascular and Total Mortality: The Uric Acid Right for Heart Health (URRAH) Project

Background: Serum uric acid predicts the onset and progression of kidney disease, and the occurrence of cardiovascular and all-cause mortality. Nevertheless, it is unclear which is the appropriate definition of hyperuricemia in presence of chronic kidney disease (CKD). Our goal was to study the independent impact of uric acid and CKD on mortality. Methods: We retrospectively investigated 21,963 patients from the URRAH study database. Hyperuricemia was defined on the basis of outcome specific cut-offs separately identified by ROC curves according to eGFR strata. The primary endpoints were cardiovascular and all-cause mortality. Results: After a mean follow-up of 9.8 year, there were 1,582 (7.20%) cardiovascular events and 3,130 (14.25%) deaths for all causes. The incidence of cardiovascular and all-cause mortality increased in parallel with reduction of eGFR strata and with progressively higher uric acid quartiles. During 215,618 person-years of follow-up, the incidence rate for cardiovascular mortality, stratified based on eGFR (>90, between 60 and 90 and <60 ml/min) was significantly higher in patients with hyperuricemia and albuminuria (3.8, 22.1 and 19.1, respectively) as compared to those with only one risk factor or none (0.4, 2.8 and 3.1, respectively). Serum uric acid and eGFR significantly interact in determining cardiovascular and all-cause mortality. For each SUA increase of 1 mg/dl the risk for mortality increased by 10% even after adjustment for potential confounding factors included eGFR and the presence of albuminuria. Conclusions: hyperuricemia is a risk factor for cardiovascular and all-cause mortality additively to eGFR strata and albuminuria, in patients at cardiovascular risk

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

BackgroundAlbuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 3 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 3 CKD in a large cohort of patients affected by T1DM.MethodsA total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 3 CKD (eGFR 30% from baseline was evaluated.ResultsThe mean estimated GFR was 9817mL/min/1.73m(2) and the proportion of patients with albuminuria was 15.3% (n=654) at baseline. About 8% (n=337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR 90ml/min/1.73m(2) and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60mL/min/1.73m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline.Conclusions Albuminuria and eGFR reduction represent independent risk factors for incident stage 3 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Prevalence of target organ damage in hypertensive subjects attending primary care: C.V.P.C. study (epidemiological cardio-vascular study in primary care)

<p>Abstract</p> <p>Background</p> <p>Except for the established risk factors, presence of target organ damage has an important role in the treatment of hypertensive subjects. The aim of the present study was to estimate the prevalence of target organ damage in primary care subjects.</p> <p>Methods</p> <p>This multi-centre, cross-sectional survey of 115 primary care physicians recruited 1095 consecutive subjects with hypertension: 611 men (55.8%); and 484 women (44.2%). A detailed history for the presence of cardiovascular disease and a thorough clinical examination was performed to each subject.</p> <p>Results</p> <p>Of the total study population, 44.5% (n = 487) had target organ damage (33.0% had left ventricular hypertrophy, 21.8% increased carotid intima media thickness, 11.0% elevated plasma creatinine levels and 14.6% microalbuminuria). Target organ damage was more prevalent in males than in females (P = 0.05). In addition, males had more often increased carotid intima media thickness than females (P = 0.009). On the contrary, females had more often microalbuminuria (P = 0.06) than males. No differences were observed between the two genders regarding left ventricular hypertrophy (P = 0.35) and elevated plasma creatinine levels (P = 0.21). Logistic regression analysis showed associations between target organ damage and dyslipidemia (P < 0.001), presence of metabolic syndrome (P = 0.005), diabetes (P < 0.001) and coronary artery disease (P < 0.001).</p> <p>Conclusion</p> <p>A significant proportion of hypertensive subjects in primary care had documented associated target organ damage, with left ventricular hypertrophy being the most prevalent target organ damage.</p

Relationship between Estimated Glomerular Filtration Rate (eGFR) and Metabolic Syndrome in Japanese

We investigated the link between renal function as evaluated by estimated glomerular filtration rate (eGFR) and metabolic syndrome in Japanese. A total of 11,711 Japanese subjects, aged 20-79 years, were recruited in a cross-sectional clinical investigation. From this group, we further investigated the data on 1,576 subjects. eGFR was calculated using serum creatinine (Cr), age and sex. The diagnosis of metabolic syndrome was based on the Japanese criteria. In the first analysis, 288 men (7.8%) and 498 women (6.2%) were diagnosed with reduced eGFR (<60ml/min). eGFR was not correlated with anthropometric, body composition parameters in either sex. In the second analysis, in subjects without medications, 132 men (20.8%) and 15 women (1.6%) were diagnosed with metabolic syndrome. eGFR was lower in men with abdominal obesity and in women with hypertension was than in those without. Among Japanese not taking medications, lower eGFR may be a characteristic of men with abdominal obesity and of women with hypertension

Diabetic kidney disease in the elderly: Prevalence and clinical correlates

Background: Diabetic kidney disease (DKD) is a major burden in elderly patients with type 2 diabetes (T2DM). Low estimated glomerular filtration rate (eGFR+, &lt; 60 mL/min/1.73 m2) and albuminuria (Alb+) are essential for the diagnosis of DKD, but their association with clinical variables and quality of care may be influenced by ageing. Methods: Here we investigated the association of clinical variables and quality of care measures with eGFR+ and Alb+ in 157,595 T2DM individuals participating to the Italian Association of Clinical Diabetologists (AMD) Annals Initiative, stratified by age. Results: The prevalence of eGFR+ and Alb+ increased with ageing, although this increment was more pronounced for low eGFR. Irrespective of age, both the eGFR+ and Alb + groups had the worst risk factors profile when compared to subjects without renal disease, showing a higher prevalence of out-of target values of HbA1c, BMI, triglycerides, HDL-C, blood pressure and more complex cardiovascular (CVD) and anti-diabetic therapies, including a larger use of insulin In all age groups, these associations differed according to the specific renal outcome examined: male sex and smoking were positively associated with Alb+ and negatively with eGFR+; age and anti-hypertensive therapies were more strongly associated with eGFR+, glucose control with Alb+, whereas BMI, and lipid-related variables with both abnormalities. All these associations were attenuated in the older (&gt; 75 years) as compared to the younger groups (&lt; 65 years; 65-75 years), and they were confirmed by multivariate analysis. Notably, Q-score values &lt; 15, indicating a low quality of care, were strongly associated with Alb+ (OR 8.54; P &lt; 0.001), but not with eGFR+. Conclusions: In T2DM patients, the prevalence of both eGFR and Albuminuria increase with age. DKD is associated with poor cardiovascular risk profile and a lower quality of care, although these associations are influenced by the type of renal abnormality and by ageing. These data indicate that clinical surveillance of DKD should not be unerestimated in old T2DM patients

The Role of Syzygium Polyanthum Leaf Extract in Reducing Renal Cell Damage with Potassium Oxonate-Induced Hyperuricemia

Background: Kidney is an organ that plays an important role in regulating homeostasis, excrete the foreign or toxic substances, and metabolism product such as uric acid, urea, and creatinine in the body through the urine. Syzygium polyanthum, has been used in lowering uric acid levels. The purpose of this research is to tested the effect of bay leaf extract on kidney histopathology of hyperuricemia induced mice model of potassium oxonate. Methods: This study is a laboratory experimental study with a post-test only control group design, and was divided into a control group, a hyperuricemia (PO) group, an PO group with 75 mg/kg bay leaf extract, an PO group with 150 bay leaf extract and an PO group with 300 mg/kgBW bay leaf extract.  The treatment was given for 14 days then histopathological examination of the kidneys was carried out with HE staining. Results: Histopathological inflammation occurred in all groups and necrosis was the most severe found in the positive control group where the administration of bay leaf extract significantly reduced inflammatory cells from the lowest to the highest dose with P < 0.001. Conclusion: Administration of Syzygium polyanthum affected renal histopathology in potassium oxonate-induced hyperuricemic mice

May Measurement Month 2019: an analysis of blood pressure screening results from Italy

: Cardiovascular (CV) diseases are burdened by high mortality and morbidity, being responsible for half of the deaths in Europe. Although hypertension is recognized as the most important CV risk factor, hypertension awareness, and blood pressure (BP) control are still unsatisfactory. In 2017 and 2018, respectively &gt;10&nbsp;000 and &gt;5000 individuals took part in the May Measurement Month (MMM) campaign in Italy, of whom 30.6% and 26.3% were found to have high BP, respectively. To raise public awareness on the importance of hypertension and to collect BP data on a nation-wide scale in Italy. In the frame of the MMM campaign, an opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2019. BP measurement, the definition of hypertension, and statistical analysis followed the standard MMM protocol. Screening was conducted in multiple sites by health personnel. Among the 10&nbsp;182 people screened (females: 52.3%, mean age 58 ± 16years) mean BP was 127/78 mmHg, and 3171 (31.1%) participants had arterial hypertension, of whom 62.1% were aware of being hypertensive. Diabetes, body mass index &gt;25 kg/m2 were associated with higher BP and previous myocardial infarction with lower BP. For the third consecutive year we collected a nation-wide snapshot of BP control in a large sample of individuals. The high participation, with some yearly fluctuations likely due to the limitations of the sampling technique, confirms the power of this kind of health campaign in reaching a significant number of people to raise awareness on health topics