The role of kidney dysfunction in COVID-19 and the influence of age.

COVID-19 is strongly influenced by age and comorbidities. Acute kidney injury (AKI) is a frequent finding in COVID-19 patients and seems to be associated to mortality and severity. On the other hand, the role of kidney dysfunction in COVID-19 is still debated. We performed a retrospective study in a cohort of 174 hospitalized COVID-19 patients in Italy from March 3rd to May 21st 2020, to investigate the role of kidney dysfunction on COVID-19 severity and mortality. Moreover, we examined in depth the relationship between kidney function, age, and progression of COVID-19, also using different equations to estimate the glomerular filtration rate (GFR). We performed logistic regressions, while a predictive analysis was made through a machine learning approach. AKI and death occurred respectively in 10.2% and 19.5%, in our population. The major risk factors for mortality in our cohort were age [adjusted HR, 6.2; 95% confidence interval (CI) 1.8-21.4] and AKI [3.36 (1.44-7.87)], while, in these relationships, GFR at baseline mitigated the role of age. The occurrence of AKI was influenced by baseline kidney function, D-dimer, procalcitonin and hypertension. Our predictive analysis for AKI and mortality reached an accuracy of ≥ 94% and ≥ 91%, respectively. Our study scales down the role of kidney function impairment on hospital admission , especially in elderly patients. BIS-1 formula demonstrated a worse performance to predict the outcomes in COVID-19 patients when compared with MDRD and CKD-EPI.

Renal dysfunction in cardiovascular diseases and its consequences.

It is well known that the heart and kidney and their synergy is essential for hemodynamic homeostasis. Since the early XIX century it has been recognized that cardiovascular and renal diseases frequently coexist. In the nephrological field, while it is well accepted that renal diseases favor the occurrence of cardiovascular diseases, it is not always realized that cardiovascular diseases induce or aggravate renal dysfunctions, in this way further deteriorating cardiac function and creating a vicious circle. In the same clinical field, the role of venous congestion in the pathogenesis of renal dysfunction is at times overlooked. This review carefully quantifies the prevalence of chronic and acute kidney abnormalities in cardiovascular diseases, mainly heart failure, regardless of ejection fraction, and the consequences of renal abnormalities on both organs, making cardiovascular diseases a major risk factor for kidney diseases. In addition, with regard to pathophysiological aspects, we attempt to substantiate the major role of fluid overload and venous congestion, including renal venous hypertension, in the pathogenesis of acute and chronic renal dysfunction occurring in heart failure. Furthermore, we describe therapeutic principles to counteract the major pathophysiological abnormalities in heart failure complicated by renal dysfunction. Finally, we underline that the mild transient worsening of renal function after decongestive therapy is not usually associated with adverse prognosis. Accordingly, the coexistence of cardiovascular and renal diseases inevitably means mediating between preserving renal function and improving cardiac activity to reach a better outcome.

Volatile Anesthetics versus Propofol for Cardiac Surgery with Cardiopulmonary Bypass: Meta-analysis of Randomized Trials.

BACKGROUND: The aim of this systematic review and meta-analysis was to assess the effect of anesthesia maintenance with volatile agents compared with propofol on both short- and long-term mortality (primary outcomes) and major clinical events in adults undergoing cardiac surgery with cardiopulmonary bypass. METHODS: Randomized clinical trials on the effects of current volatile anesthetics versus propofol in adults undergoing cardiac surgery with cardiopulmonary bypass were searched (1965 to September 30, 2019) in PubMed, the Cochrane Library, and article reference lists. A random effect model on standardized mean difference for continuous outcomes and odds ratio for dichotomous outcomes were used to meta-analyze data. RESULTS: In total, 37 full-text articles (42 studies, 8,197 participants) were included. The class of volatile anesthetics compared with propofol was associated with lower 1-yr mortality (5.5 vs. 6.8%; odds ratio, 0.76 [95% CI, 0.60 to 0.96]; P = 0.023), myocardial infarction (odds ratio, 0.60 [95% CI, 0.39 to 0.92]; P = 0.023), cardiac troponin release (standardized mean difference, -0.39 [95% CI, -0.59 to -0.18], P = 0.0002), need for inotropic medications (odds ratio, 0.40 [95% CI, 0.24 to 0.67]; P = 0.0004), extubation time (standardized mean difference, -0.35 [95% CI, -0.68 to -0.02]; P = 0.038), and with higher cardiac index/output (standardized mean difference, 0.70 [95% CI, 0.37 to 1.04]; P < 0.0001). The class of volatile anesthetics was not associated with changes in short-term mortality (1.63 vs. 1.65%; odds ratio, 1.04 [95% CI, 0.73 to 1.49]; P = 0.820) and acute kidney injury (odds ratio, 1.25 [95% CI, 0.77 to 2.03]; P = 0.358). CONCLUSIONS: In adults undergoing cardiac surgery with cardiopulmonary bypass, the class of volatile anesthetics was superior to propofol with regard to long-term mortality, as well as to many secondary outcomes indicating myocardial protection.

Remote ischaemic preconditioning for renal and cardiac protection in adult patients undergoing cardiac surgery with cardiopulmonary bypass: systematic review and meta-analysis of randomized controlled trials.

Background: The main aim of this systematic review was to assess whether remote ischaemic preconditioning (RIPC) protects kidneys and the heart in cardiac surgery with cardiopulmonary bypass (CPB) and to investigate a possible role of anaesthetic agents. Methods: Randomized clinical trials (RCTs) on the effects of RIPC through limb ischaemia in adult patients undergoing cardiac surgery with CPB were searched (1965-October 2016) in PubMed, Cochrane Library and article reference lists. A random effects model on standardized mean difference (SMD) for continuous outcomes and the Peto odds ratio (OR) for dichotomous outcomes were used to meta-analyse data. Subgroup analyses to evaluate the effects of different anaesthetic regimens were pre-planned. Results: Thirty-three RCTs (5999 participants) were included. In the whole group, RIPC did not significantly reduce the incidence of acute kidney injury (AKI), acute myocardial infarction, atrial fibrillation, mortality or length of intensive care unit (ICU) and hospital stays. On the contrary, RIPC significantly reduced the area under the curve for myocardial injury biomarkers (MIBs) {SMD -0.37 [95% confidence interval (CI) -0.53 to - 0.21]} and the composite endpoint incidence [OR 0.85 (95% CI 0.74-0.97)]. In the volatile anaesthetic group, RIPC significantly reduced AKI incidence [OR 0.57 (95% CI 0.41-0.79)] and marginally reduced ICU stay. Conversely, except for MIBs, RIPC had fewer non-significant effects under propofol with or without volatile anaesthetics. Conclusions: RIPC did not consistently reduce morbidity and mortality in adults undergoing cardiac surgery with CPB. In the subgroup on volatile anaesthetics only, RIPC markedly and significantly reduced the incidence of AKI and composite endpoint as well as myocardial injury.

High performance of a risk calculator that includes renal function in predicting mortality of hypertensive patients in clinical application.

OBJECTIVE: The aim of this study was to assess the accuracy of a risk calculator that includes renal function as compared with that of the traditional Framingham Risk Score (FRS) in predicting the risk of mortality of hypertensive individuals managed in primary care. METHODS: From the databases of British and Italian General Practitioners, we retrieved demographic and clinical data for 35 101 UK and 27 818 Italian individuals aged 35-74 years with a diagnosis of hypertension. Then, the 5-year incidence of cardiovascular events as well as all-cause and cardiovascular mortality were recorded for both samples. A comparison analysis of the performance of the Individual Data Analysis of Antihypertensive Intervention Trials (INDANA) calculator with that of FRS in predicting 5-year all-cause and cardiovascular mortality risk was made. RESULTS: The INDANA calculator was more accurate than the FRS in predicting all-cause [Δc 0.038, 95% confidence interval (CI) 0.026-0.051 for United Kingdom, and 0.018, 95% CI 0.010-0.027 for Italy, both P < 0.0001] and cardiovascular mortality (Δc 0.050, 95% CI 0.027-0.074 for United Kingdom, and 0.080, 95% CI 0.059-0.101 for Italy, both P < 0.0001). By using the INDANA calculator, 20% of the UK and 10% of the Italian patients were reclassified to higher risk classes for all-cause mortality, and 25 and 28%, respectively were reclassified when cardiovascular mortality was assessed (P < 0.0001 for all). CONCLUSION: The INDANA calculator proved to be more accurate than the FRS in predicting the risk of mortality in hypertensive patients and should be considered for systematic adoption for risk stratification of hypertensive individuals managed in primary care.

Left-ventricular hypertrophy and renal outcome in hypertensive patients in primary-care.

BACKGROUND: Subclinical cardiac damage has recently emerged as a potential predictor of adverse renal outcome. We therefore retrospectively evaluated the effect of left-ventricular hypertrophy (LVH), diagnosed electrocardiographically, on the renal outcome of hypertensive patients managed in primary care. METHODS: From a historical cohort of 39,525 hypertensive individuals evaluated in 2005, we retrieved 5-year data of the 18,510 surviving subjects for whom renal follow-up was available. RESULTS: The baseline prevalences of chronic kidney disease (CKD) and LVH in the study cohort were 25.6% and 5.6%, respectively. During the 5-year follow-up, 1.4% of patients with LVH and 0.5% of those without LVH progressed to end-stage renal disease (ESRD) requiring dialysis (P < 0.01). Moreover, 25.6% of patients with LVH and 17% without LVH progressed from each stage of CKD to a more advanced stage (P < 0.01), whereas 0.9% of patients with LVH and 0.4% without LVH reached stage 5 CKD (P < 0.01). Multivariate Cox regression analysis showed that besides estimated glomerular filtration rate (eGFR) and male gender, LVH was the most significant modifiable predictor of progression to dialysis (hazard ratio (HR), 1.82; 95% CI, 1.05-3.17; P = 0.03). Multivariate logistic regression analysis also revealed LVH as a significant predictor of the risk of progression from each stage of CKD to a more advanced stage (OR, 1.24; 95% CI, 1.07-1.45; P < 0.01), as well as of progression to stage 5 CKD (OR, 1.86; 95% CI, 1.17-2.95; P < 0.01). CONCLUSIONS: Left-ventricular hypertrophy proved to be a significant predictor of adverse renal outcome in hypertensive patients managed with primary care, and systematic screening for LVH should be adopted for assessing renal risk in these patients.

Sex differences in hypertension-related renal and cardiovascular diseases in Italy: the I-DEMAND study.

AIM: The aim of this study is to evaluate the differences in the prevalence of chronic kidney disease (CKD) and of cardiovascular risk factors and diseases between men and women participating in the Italy Developing Education and awareness on MicroAlbuminuria in patients with hyperteNsive Disease (I-DEMAND) study. METHODS: This is an observational, cross-sectional, multicenter study aimed at assessing prevalence and correlates of CKD among Italian hypertensive patients attending out-patient referral clinics. CKD was defined as glomerular filtration rate (GFR) less than 60 ml/min per 1.73 m(2) [Modification of Diet in Renal Disease (MDRD) study equation and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation] and/or urine albumin-to-creatinine ratio of at least 2.5 mg/mmol in men and of at least 3.5 mg/mmol in women or both. Left-ventricular hypertrophy (LVH) was diagnosed by either ECG or echocardiography. RESULTS: A total of 3558 study patients with renal data available were considered for this analysis: mean age was 61 ± 4 years and 37% had diabetes mellitus. Female patients (n = 1636, 46%) were older, with a greater prevalence of obesity and lower prevalence of smoking. The prevalence of concomitant coronary artery and peripheral artery diseases, but not of hypertension, diabetes mellitus, or heart failure, was lower in women than in men. The overall prevalence of albuminuria (21 vs. 32%; P = 0.001) and of microalbuminuria (16 vs. 23%; P = 0.001) was lower in women than in men. In women the prevalence of a reduced GFR estimated by both MDRD (33 vs. 21%; P = 0.001) and CKD-EPI equations (32 vs. 23%; P = 0.001) was higher than in men. CKD prevalence was similar in women and men (44 vs. 41%; P = 0.095 and 43 vs. 43%; P = 0.475, respectively, when MDRD and CKD-EPI eGFR estimations were used). The prevalence of LVH (diagnosed by either ECG or echocardiography) was similar in men and women (18 vs. 20%; P = 0.12).The main independent determinants of CKD were age, glycemia, uricemia, pulse pressure, hypertension duration, and previous cardiovascular diseases in men, and increasing age, glycemia, uricemia, pulse pressure, and a lower BMI in women. CONCLUSION: Renal abnormalities are present in a significant number of female hypertensive patients attending hypertension clinics. Prevalence of reduced eGFR and of microalbuminuria, associated risk factors, and clinical conditions are different between men and women, suggesting the need to develop specific therapeutic strategies to prevent renal dysfunction and reduce associated morbidity and mortality.

Metabolic syndrome and chronic kidney disease in high-risk Italian hypertensive patients: the I-DEMAND study.

BACKGROUND: Metabolic syndrome (MS) and chronic kidney disease (CKD) are well-known, independent predictors of increased cardiovascular risk. Both conditions are fairly prevalent in the general population. The aim of this study was to assess the relationship between MS or its individual components and CKD in an Italian population of hypertensive patients with normal or mildly to moderately impaired renal function under specialist care. METHODS: A total of 2,916 patients (mean age 62 ± 11 years) among those enrolled in the I-DEMAND study were taken into consideration for this analysis. MS was defined according to the NCEP-ATP III criteria. CKD was defined as an estimated GFR (abbreviated MDRD equation) <60 ml/min/1.73m2 or as the presence of microalbuminuria (mean albumin-to-creatinine ratio =2.5 mg/mmol in men and =3.5 mg/mmol in women). RESULTS: MS was present in 59% of our study patients. The prevalence of microalbuminuria, reduced GFR and CKD was 26%, 25%, and 41%, respectively. Patients with MS had higher urinary albumin excretion (p<0.0001), lower GFR (p=0.0077), and a greater prevalence of CKD (p<0.0001), even after adjusting for age and gender. Multivariate logistic regression analysis revealed that MS was significantly associated with CKD, even after adjusting for several potential confounders including its individual components (OR 1.33, 95%CI 1.03-1.71, p=0.0268). The association between MS and CKD was stronger in nondiabetic patients. CONCLUSIONS: Renal abnormalities and MS are frequently associated in hypertensive patients under specialist care. This relationship is independent of several potential confounding factors including the components of MS.

Combined use of urinary neutrophil gelatinase-associated lipocalin (uNGAL) and albumin as markers of early cardiac damage in primary hypertension.

BACKGROUND: Neutrophil Gelatinase-Associated Lipocalin (NGAL) is an early and specific marker of acute kidney dysfunction. Recent evidences suggest that NGAL may also be involved in chronic vascular remodeling during the development of atherosclerosis. Albuminuria, a powerful predictor of cardiovascular events, is thought to reflect widespread subclinical vascular abnormalities. We investigated the relationship between urinary NGAL (uNGAL), albuminuria and left ventricular mass (LVM) in patients with primary hypertension. METHODS: A total of 120 untreated, non diabetic patients with primary hypertension (mean age 47 ± 9 years) were studied. uNGAL was measured by a chemiluminescent microparticle method, optimized on a fully automated analytical platform (ARCHITECT, Abbott Diagnostics Inc, Rome, IT). Albuminuria was measured by immunonephelometry on an Immage Immunochemistry System (Beckman Coulter, Inc., Fullerton, California, USA) and expressed as albumin/creatinine ratio (ACR). LVM was assessed by echocardiography and indexed to body surface area (LVM/BSA). RESULTS: No significant correlation was found between uNGAL and ACR; however, both variables were directly related to clinic systolic blood pressure (rho=0.241, p=0.0085 and rho=0.248, p=0.0068 respectively), left ventricular relative wall thickness (rho=0.251, p=0.0156 and rho=0.263, p=0.0013 respectively), and LVM/BSA (rho=0.285, p=0.0062 and rho=0.213, p=0.0410 respectively). The uNGAL and ACR simultaneous increase above their respective median values was associated with higher LVM/BSA values (p=0.0109) and with a higher prevalence of left ventricular hypertrophy (LVH) (p=0.0017). Furthermore, logistic regression analysis showed that the risk of presenting LVH increased more than 4-fold when uNGAL and ACR were both above the median value, even after adjustment for age, gender and blood pressure values. CONCLUSIONS: The simultaneous increase in uNGAL and ACR excretion is significantly associated with the increase of LVM in low risk patients with primary hypertension. This association is clinically significant for the early assessment of cardiac damage in hypertension.

Chronic kidney disease in the hypertensive patient: an overview of the I-DEMAND study.

The kidney has been recognized as a sensor of cardiovascular risk. However, evaluation of urinary albumin excretion and estimated glomerular filtration rate is still too often overlooked in clinical practice. The I-DEMAND (Italy-Developing Education and awareness on MicroAlbuminuria in patients with hyperteNsive Disease) study was designed to assess the prevalence of microalbuminuria and its clinical correlates among Italian hypertensive patients. A total of 4151 patients from 87 specialized care centres were included in the study. Overall, this study demonstrated that approximately one-half of the enrolled patients had chronic kidney disease, with albuminuria being present in one-quarter of the individuals. The presence of renal abnormalities was more prevalent in patients with concomitant cardiovascular risk factors. This article discusses the main results of the study and its potential implications in clinical practice.

Serum uric acid levels predict new-onset type 2 diabetes in hospitalized patients with primary hypertension: the MAGIC study.

OBJECTIVE: Recent studies suggest that uric acid may predict the development of diabetes in the general population. Whether this association holds true in primary hypertension and is independent of renal function and metabolic syndrome is not clear at present. RESEARCH DESIGN AND METHODS: In a prospective, observational study, 758 untreated hypertensive patients were evaluated at baseline and followed-up for 11 years. RESULTS: A total of 8,332 person-years of follow-up revealed that slightly elevated uric acid levels (i.e., ≥318 µmol/l for women and ≥420 µmol/l for men) at baseline were associated with a significantly higher risk of developing diabetes (hazard ratio 3.65 [95% CI 1.99-6.69], P < 0.0001), even after adjustment for several confounding factors such as metabolic syndrome (2.78 [1.35-5.70], P = 0.0054). CONCLUSIONS: Uric acid is an independent predictor of diabetes in primary hypertension.

CKD awareness and blood pressure control in the primary care hypertensive population.

BACKGROUND: Chronic kidney disease (CKD) is associated with poor renal and cardiovascular outcomes, and early identification largely depends on general practitioners' (GPs') awareness of it. To date, no study has evaluated CKD prevalence in patients with hypertension in primary care. STUDY DESIGN: Cross-sectional evaluation of the Italian GPs' database. SETTING & PARTICIPANTS: 39,525 patients with hypertension representative of the Italian hypertensive population followed up by GPs in 2005. FACTOR: Estimated glomerular filtration rate (eGFR); eGFR <60 mL/min/1.73 m² was defined as CKD. OUTCOMES: GPs' awareness of CKD assessed using International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes for CKD, and blood pressure (BP) control. MEASUREMENTS: Data concerning serum creatinine levels, BPs, and antihypertensive medications were obtained for each patient from the GPs' database; eGFR was calculated according to the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation. RESULTS: CKD prevalence was 23%, but kidney disease was diagnosed by GPs in only 3.9% of patients. BP control was inadequate in patients with CKD and those with eGFR >60 mL/min/1.73 m², with only 44% of patients reaching a BP target <140/90 mm Hg and 11% achieving <130/80 mm Hg. Patients with eGFR <60 mL/min/1.73 m² whose GPs were aware of CKD were more likely to reach recommended BP target values (OR, 1.35; 95% CI, 1.15-1.59; P < 0.001). LIMITATIONS: The prevalence of decreased eGFR may be overestimated because of the lack of creatinine calibration. Proteinuria data were not available. CONCLUSIONS: Awareness of CKD by GPs is critical for achieving the recommended guideline BP targets. However, awareness of CKD by GPs is still far too low, highlighting the need to systematically adopt eGFR for more accurate identification of CKD in high-risk populations.

Microalbuminuria is a predictor of chronic renal insufficiency in patients without diabetes and with hypertension: the MAGIC study.

BACKGROUND AND OBJECTIVES: Increased urinary albumin excretion is a known risk factor for cardiovascular events and clinical nephropathy in patients with diabetes. Whether microalbuminuria predicts long-term development of chronic renal insufficiency (CRI) in patients without diabetes and with primary hypertension remains to be documented. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted an 11.8-year follow-up of 917 patients who did not have diabetes and had hypertension and were enrolled in the Microalbuminuria: A Genoa Investigation on Complications (MAGIC) cohort between 1993 and 1997. Urinary albumin-to-creatinine ratio (ACR) was assessed at baseline in untreated patients in a core laboratory. Microalbuminuria was defined as ACR > or =22 mg/g in men and ACR > or =31 mg/g in women. RESULTS: A total of 10,268 person-years of follow-up revealed that baseline microalbuminuria was associated with an increased risk for developing CRI (relative risk [RR] 7.61; 95% confidence interval [CI] 3.19 to 8.16; P < 0.0001), cardiovascular events (composite of fatal and nonfatal cardiac and cerebrovascular events; RR 2.11; 95% CI 1.08 to 4.13; P < 0.028), and cardiorenal events (composite of former end points; RR 3.21; 95% CI 1.86 to 5.53; P < 0.0001). Microalbuminuria remained significantly related to CRI (RR 12.75; 95% CI 3.62 to 44.92; P < 0.0001) and cardiorenal events (RR 2.58; 95% CI 1.32 to 5.05; P = 0.0056) even after adjustment for several baseline covariates. CONCLUSIONS: Microalbuminuria is an independent predictor of renal and cardiovascular complications in patients without diabetes and with primary hypertension.

Combined effect of albuminuria and estimated glomerular filtration rate on cardiovascular events and all-cause mortality in uncomplicated hypertensive patients.

OBJECTIVES: Decreased glomerular filtration rate (GFR) and microalbuminuria predict cardiovascular events and mortality in the general population and in high-risk patients. Their combined prognostic power in low-risk patients has never been reported. We assessed the prognostic role of GFR and albuminuria for cardiovascular disease and all-cause mortality in nondiabetic patients with primary hypertension. METHODS: We conducted an 11.2-year follow-up of 837 uncomplicated hypertensive patients enrolled in the Microalbuminuria: A Genoa Investigation on Complications (MAGIC) cohort between 1993 and 1997. Urinary albumin-to-creatinine ratio (ACR) and estimated GFR (eGFR) were assessed in untreated patients at baseline. Renal dysfunction was defined as the inclusion in the most unfavorable sex-specific decile of eGFR or of ACR. The primary endpoints were the occurrence of fatal and nonfatal cerebrovascular and cardiac events (CVEs), composite of nonfatal cerebrovascular and cardiac events (CVD) and all-cause death (CEP), and composite of CVD and chronic renal insufficiency (CRE). RESULTS: During 9374 person-years of follow-up, the incidence rate for CVE, CRE, and all-cause mortality was 6.3, 7.8, and 3.1 /1000 person-years, respectively. Renal dysfunction was associated with increased risk for CVE [relative risk (RR) 2.13, 95% confidence interval (CI) 1.15-3.93, P = 0.011], CEP (RR 1.78, 95% CI 1.02-3.08, P = 0.027), and CRE (RR 2.47, 95% CI 1.45-4.29, P < 0.001), even after adjusting for several baseline covariates such as sex, duration and severity of blood pressure, and total cholesterol. CONCLUSION: Renal dysfunction is a risk factor for cardiorenal events and all-cause mortality, regardless of traditional confounders, in uncomplicated patients with primary hypertension.

Chronic kidney disease in hypertension under specialist care: the I-DEMAND study.

OBJECTIVE AND METHODS: Italy Developing Education and awareness on MicroAlbuminuria in patients with hyperteNsive Disease is an observational, cross-sectional, multicenter study aimed at determining prevalence and correlates of chronic kidney disease (CKD) among Italian hypertensive patients attending out-patient referral clinics. CKD was defined as glomerular filtration rate (GFR) less than 60 ml/min per 1.73 m (Modification of Diet in Renal Disease equation) or urine albumin to creatinine ratio of at least 2.5 mg/mmol in men and of at least 3.5 mg/mmol in women or both. RESULTS: Among 3534 study patients (mean age 61 years, 54% male patients, 37% diabetic patients), the prevalence of microalbuminuria, reduced GFR, and CKD was 27, 26, and 42%, respectively. Only 11% of patients had concomitant microalbuminuria and reduced GFR. Sex, smoking, systolic blood pressure, glucose, and GFR were the independent predictors of albumin to creatinine ratio, whereas sex, age, history of cardiovascular diseases, uric acid, abdominal obesity, and albumin to creatinine ratio were more closely related to GFR. The presence of CKD was associated with older age, smoking, higher systolic and pulse pressure levels, impaired fasting glucose, hyperuricemia, and previous cardiovascular disease. Furthermore, CKD was not only associated with a greater use of renin-angiotensin system-inhibiting, lipid-lowering and antiplatelet drugs but also with inadequate blood pressure control. CONCLUSION: Renal abnormalities are found in a significant number of hypertensive patients. CKD occurs more often in older patients and in those with associated metabolic risk factors or clinical conditions. These results suggest the need to improve awareness of the role of renal damage as a component of global risk and to develop appropriate therapeutic strategies to reduce morbidity and mortality in this specific subgroup of patients.

Association of renal damage with cardiovascular diseases is independent of individual cardiovascular risk profile in hypertension: data from the Italy - Developing Education and awareness on MicroAlbuminuria in patients with hypertensive Disease study.

OBJECTIVES: In the past years, several risk charts have been created to increase the accuracy of cardiovascular risk stratification. The most widely used and validated algorithms do not included target organ damage as risk prediction. The aim of the present study was to evaluate whether preclinical renal damage is associated with cardiovascular diseases independently of individual risk profile assessed by risk charts. METHODS: The study population was that of Italy-Developing Education and awareness on MicroAlbuminuria in patients with hypertensive Disease, a large observational study conducted on hypertensive patients in Italy. The Framingham Risk Score (FRS), Systematic COronary Risk Estimation (SCORE) and Progetto Cuore Risk Score (Progetto Cuore RS) were computed in each eligible patient. Chronic kidney disease was defined by the presence of albuminuria or by a reduction of glomerular filtration rate. RESULTS: Study participants were categorized to have low, medium and high risk according to the tertiles of the three charts. Prevalence of total cardiovascular diseases progressively and significantly increased according to the degrees of risk assessed by the three charts, the highest prevalence being in participants with a high-risk profile (both high and medium vs. low risk <0.01 for FRS, SCORE and Progetto Cuore RS). The presence of chronic kidney disease was associated with total cardiovascular diseases, independently of FRS (odds ratio 1.64, 95% confidence interval 1.33-2.02, P < 0.001), SCORE (odds ratio 1.55, 95% confidence interval 1.21-1.98, P < 0.001) and Progetto Cuore RS (odds ratio 1.59, 95% confidence interval 1.22-2.07, P < 0.001). Moreover, inclusion of renal damage in the logistic model significantly increased the accuracy of the FRS (P < 0.05), SCORE (P < 0.01) and Progetto Cuore RS (P < 0.01) to identify patients with overt cardiovascular diseases. CONCLUSION: Identification of patients with preclinical renal damage should be encouraged in the hypertension cardiovascular risk stratification setting in order to achieve a more accurate individual risk computation. The presence of renal damage could improve cardiovascular risk prediction over the widely used risk stratification charts.

Androgen-mediated apoptosis of kidney tubule cells: role of c-Jun amino terminal kinase.

The incidence and the rate of progression of chronic kidney diseases (CKD) are for most diseases greater in men than in age-matched women. We have previously shown that testosterone (T) promotes the apoptosis of proximal tubule kidney cells. To better understand the downstream signaling process associated with T-induced apoptosis, we examined the involvement of c-Jun amino terminal kinase (JNK) in a human proximal tubule cell line (HK-2) exposed to T: JNK and its downstream effector c-Jun were rapidly phosphorylated. By blocking androgen receptor, JNK phosphorylation was reduced and 17beta-Estradiol treatment had no effect on it. Similarly, pre-treatment with the JNK inhibitor SP600125 prevented the T-induced apoptosis, the phosphorylation of c-Jun and the upregulation of the Fas/FADD pathway. These data show that the JNK/c-Jun pathway is directly regulated by androgens in vitro and highlight a potential mechanism explaining the reported gender differences in the progression of renal diseases.

Effect of the monocyte chemoattractant protein-1/CC chemokine receptor 2 system on nephrin expression in streptozotocin-treated mice and human cultured podocytes.

OBJECTIVE: Monocyte chemoattractant protein-1 (MCP-1), a chemokine binding to the CC chemokine receptor 2 (CCR2) and promoting monocyte infiltration, has been implicated in the pathogenesis of diabetic nephropathy. To assess the potential relevance of the MCP-1/CCR2 system in the pathogenesis of diabetic proteinuria, we studied in vitro if MCP-1 binding to the CCR2 receptor modulates nephrin expression in cultured podocytes. Moreover, we investigated in vivo if glomerular CCR2 expression is altered in kidney biopsies from patients with diabetic nephropathy and whether lack of MCP-1 affects proteinuria and expression of nephrin in experimental diabetes. RESEARCH DESIGN AND METHODS: Expression of nephrin was assessed in human podocytes exposed to rh-MCP-1 by immunofluorescence and real-time PCR. Glomerular CCR2 expression was studied in 10 kidney sections from patients with overt nephropathy and eight control subjects by immunohistochemistry. Both wild-type and MCP-1 knockout mice were made diabetic with streptozotocin. Ten weeks after the onset of diabetes, albuminuria and expression of nephrin, synaptopodin, and zonula occludens-1 were examined by immunofluorescence and immunoblotting. RESULTS: In human podocytes, MCP-1 binding to the CCR2 receptor induced a significant reduction in nephrin both mRNA and protein expression via a Rho-dependent mechanism. The MCP-1 receptor, CCR2, was overexpressed in the glomerular podocytes of patients with overt nephropathy. In experimental diabetes, MCP-1 was overexpressed within the glomeruli and the absence of MCP-1 reduced both albuminuria and downregulation of nephrin and synaptopodin. CONCLUSIONS: These findings suggest that the MCP-1/CCR2 system may be relevant in the pathogenesis of proteinuria in diabetes.