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Background‘Coronavirus disease 2019 (COVID-19) is a rapidly changing disease. So, in this study, we evaluated the evolution of COVID-19 presentation and course in hemodialysis patients (HD).MethodsWe retrospectively compared clinical data and outcomes of HD patients affected by COVID-19 during the first pandemic waves of 2020 (from March to December 2020-Group 1) with patients diagnosed with COVID-19 from September 2021 to February 2022 (Group 2), after the full completion of vaccination. Then, we distinguished among them patients responsive (antibody levels > 13 binding antibody units/ml) and unresponsive to the vaccine. We collected data on COVID-19 clinical presentation, laboratory examinations, and outcomes.ResultsGroup 1 was constituted of 44 patients (69.3±14.6 years) and Group 2 of 55 patients (67.4±15.3 years). Among Group 2, fifty-two patients (95%) were vaccinated, 43 of them (83%) with three doses. Patients of Group 2, compared with Group 1, were more often asymptomatic (38 vs 10%, p=0.002), and reported less frequent fever and pulmonary involvement. At diagnosis, the Group 2 showed a significantly higher number of lymphocytes (0.97±0.45 vs 0.69±0.35 cells x109/L, p=0.008) and lower levels of circulating IL-6 (16±13.3 vs 41±39.4 pg/ml, p=0.002). Moreover, in Group 2, inflammatory parameters significantly improved after a few days from diagnosis. Patients of Group 2 presented a lower hospitalization rate (12.7 vs 38%, p=0.004), illness duration (18.8±7.7 vs 29.2±19.5 days, p=0.005), and mortality rate (5.4 vs 25%, p= 0.008). Finally, responders to the vaccination (80% of the vaccinated patients) compared with non-responders showed a reduction in infection duration and hospitalization (5 vs 40%, p=0.018).ConclusionsCOVID-19 presentation and course in HD patients have improved over time after the implementation of vaccine campaigns. However, due to the evolving nature of the disease, active surveillance is necessary.

Membranous nephropathy (MN) is one of the most common causes of adult-onset nephrotic syndrome. We describe the cases of 2 young women in their 20s presenting with nephrotic syndrome due to antiphospholipase A2 receptor (anti-PLA2R)–negative MN, that was found to be associated with benign tumors. Both women had no extrarenal symptoms of a connective tissue disease, infection, or malignancy. They both had been previously healthy and were not receiving treatment with any drugs. Both had MN on kidney biopsy. Biopsies were negative for PLA2R antigen, and their serum did not demonstrate the presence of anti-PLA2R antibodies. Both were investigated for a secondary cause on the basis of negative anti-PLA2R serology and biopsy features supportive of secondary MN and were found to have benign tumors on radioimaging: a uterine leiomyoma and mesenteric fibromatosis, respectively. In both instances, the nephrotic syndrome remitted following resection of the tumors. To our knowledge, uterine leiomyoma and mesenteric fibromatosis have not previously been described in association with MN. These cases highlight the importance of pursuing a secondary cause of MN in patients without anti-PLA2R antibodies in serum or PLA2R antigen on kidney biopsy.

There is no specific therapy for polyoma BK virus nephropathy (BKVN) in kidney transplant recipients, a condition associated with poor outcomes. Everolimus showed promising antiviral effects, but data from prospective studies are limited. Therefore, we converted ten consecutive kidney transplant recipients with biopsy-proven BKVN from standard exposure Calcineurin inhibitors and Mycophenolate to Everolimus and reduced exposure Calcineurin inhibitors. Ten patients not administered Everolimus, on reduced exposure Calcineurin inhibitor and halved MPA doses served as controls. All kidney transplant recipients continued steroid therapy. Each patient underwent kidney graft biopsy, BKV replication by PCR, and de novo DSA determination. During a 3-year follow-up no graft loss occurred in kidney transplant recipients on Everolimus but it was observed in 5/10 controls (P = 0.032). eGFR improved on Everolimus and worsened in controls (between group difference + 25.6 ml/min/1.73 m2, 95% CI 10.5–40.7, P = 0.002). BKV replication declined in the Everolimus group alone (from 6.4 ± 0.8 to 3.6 ± 1.6 Log 10 genomic copies, P = 0.0001), and we found a significant inverse relationship between eGFR and BKV genomic copy changes (P = 0.022). Average Calcineurin inhibitors trough levels did not differ between the two study groups during follow-up. By multivariable Cox regression analysis, Everolimus treatment resulted the only significant predictor of survival free of a combined endpoint of graft loss and 57% eGFR reduction (P = 0.02). Kidney transplant recipients on Everolimus had a higher survival free of adverse graft outcome (log-rank test, P = 0.009). In conclusion an Everolimus-based immunosuppressive protocol with minimization of Calcineurin inhibitors and antimetabolite discontinuation effectively treated BKVN in kidney transplant recipients.

Macrophage infiltration is associated with unfavorable kidney graft outcome in protocol biopsies, but few studies have evaluated its impact on clinical practice. We therefore prospectively evaluated 37 kidney transplant recipients (KTRs) who underwent kidney biopsy due to slight increases in serum creatinine, or mild proteinuria (>0.3 g/24 hr), in the first post-transplant year. Banff score, CD68+ count (score 0-3) by immunohistochemistry, and 1-year DSA were assessed. DGF was reported in 10 (27%) patients, 6 (16%) had normal biopsy, 7 (19%) borderline lesions, 13 (35%) IFTA, and 11 (30%) other lesions. Fifteen KTRs had grade 3 CD68+ infiltration, and 47% developed de novo DSA. During a 6.2 ± 2.7 year follow-up, four patients (11%) suffered from biopsy-proven T-cell rejection, 17 KTRs (46%) lost their graft (12 in the grade 3 CD68+ group). Graft survival was lower in KTRs with grade 3 CD68+ infiltration (P = 0.0074; log-rank test). Grade 3 CD68+ infiltrate was an independent predictor of graft loss (HR 5.41, 95% CI 1.74-16.8; P = 0.003), together with more severe graft dysfunction at biopsy (HR 6.41, 95% CI 2.57-16; P

The emerging role of humoral immunity in the pathogenesis of chronic allograft damage has prompted research aimed at assessing the role of anti-HLA antibody (Ab) monitoring as a tool to predict allograft outcome. Data on the natural history of allografts in children developing de novo Ab after transplantation are limited. Utilizing sera collected pretransplant, and serially posttransplant, we retrospectively evaluated 82 consecutive primary pediatric kidney recipients, without pretransplant donor-specific antibodies (DSA), for de novo Ab occurrence, and compared results with clinical-pathologic data. At 4.3-year follow up, 19 patients (23%) developed de novo DSA whereas 24 had de novo non-DSA (NDSA, 29%). DSA appeared at a median time of 24 months after transplantation and were mostly directed to HLA-DQ antigens. Among the 82 patients, eight developed late/chronic active C4d+ antibody-mediated rejection (AMR), and four C4d-negative AMR. Late AMR correlated with DSA (p < 0.01), whose development preceded AMR by 1-year median time. Patients with DSA had a median serum creatinine of 1.44 mg/dL at follow up, significantly higher than NDSA and Ab-negative patients (p < 0.005). In our pediatric cohort, DSA identify patients at risk of renal dysfunction, AMR and graft loss; treatment started at Ab emergence might prevent AMR occurrence and/or progression to graft failure.

Background Focal and segmental glomerulosclerosis (FSGS) accounts for more than 10% of all cases of renal diseases leading to renal failure in children. After renal transplantation, 20% to 40% of FSGS relapse, frequently leading to renal loss.Plasmapheresis is considered the first option to treat relapses by several authors but is often ineffective. The anti-CD20 monoclonal antibody rituximab has been proposed as a possible treatment. Methods We reviewed the effect of rituximab in seven children or young adults with pretransplant FSGS and relapse of proteinuria after transplantation who did not respond to intensive plasmapheresis. Results After treatment, urine protein disappeared in three patients, was reduced by 70% in one patient and by 50% in one patient. No response was observed in one patient who had a quick deterioration of renal function and reached end-stage renal failure after 3 months. One additional patient developed a severe reaction a few minutes after the start of the first rituximab infusion. Conclusion Rituximab is a possible option to treat some resistant cases of FSGS with relapsing proteinuria after transplantation. It is important that therapy is started early after evidence of failure of plasmapheresis, before sclerosis develops in the glomeruli. The response to treatment can occur after several months. During the follow-up period, CD19 cells should be monitored carefully, and additional rituximab infusions considered to maintain B-cell depletion.

Microalbuminuria, a powerful predictor of cardiovascular events, is thought to reflect widespread subclinical vascular abnormalities. To explore the pathogenesis of increased urinary albumin excretion in primary hypertension we evaluated systemic capillary permeability and ambulatory blood pressure (BP) measurement in two groups of matched untreated patients with (n = 11) and without (n = 29) microalbuminuria.Albuminuria was measured as the mean of albumin-to-creatinine ratio (ACR) in three nonconsecutive first morning urine samples. Systemic capillary permeability was evaluated by transcapillary escape rate of albumin (TERalb) (ie, the 1-h decline rate of intravenous (125)I-albumin). Twenty-four-hour ambulatory BP, renal hemodynamics, and hormones of the renin-angiotensin-aldosterone system (RAAS) were also assessed.Patients with microalbuminuria showed greater body mass index (BMI) (P.04), higher 24-h systolic and diastolic BP levels (P = .02), and higher capillary permeability to albumin (P.02) as compared to normoalbuminurics. Renal hemodynamics and RAAS hormones were similar in the two groups. Univariate analysis showed that urinary ACR was related to ambulatory pressure components (P.02), TERalb (r = 0.31, P.05), smoking habits (r = 0.36, P = .02), and left ventricular mass index (LVMI) (r = 0.57, P.001) among the whole study group. Logistic regression analysis showed that each 1% increment in TERalb or 10 mm Hg increase in systolic BP entailed an almost three times higher risk of having microalbuminuria.Microalbuminuria is associated with greater systemic BP load and increased vascular permeability in patients with primary hypertension.

Background Urinary albumin excretion and left ventricular mass are related to each other and to the risk of cardiovascular events in patients with primary hypertension. We aimed to identify a lower threshold for albuminuria that might improve detection of patients with left ventricular hypertrophy (LVH) and cost-effectiveness in cardiovascular risk assessment. Methods Albuminuria and left ventricular mass index were assessed in 448 untreated, nondiabetic patients with primary hypertension. The impact that lower albuminuria cut-off levels might have on detecting LVH was evaluated with regard to test cost and sensitivity. This was done by a diagnostic algorithm consisting of albuminuria evaluation followed by echocardiography in the presence of normoalbuminuria. Results The area under the ROC curve of albuminuria in predicting LVH was 0.73. Using a lower albumin to creatinine ratio threshold than what is recommended by the guidelines (ie, 11.5 mg/g), the sensitivity and specificity of albuminuria in identifying patients with LVH was 39% and 92%, respectively, which translated to positive and negative predictive values of 76% and 69%, respectively. When considering only patients without electrocardiographically detected LVH, routine screening for albuminuria, followed by echocardiography in the presence of albuminuria ≤11.5 mg/g, allowed us to decrease the number of echocardiograms by 23%. Conclusion Adopting a lower threshold to define microalbuminuria could prove to be cost-effective for assessing cardiovascular risk in hypertensive patients.

The role of serum uric acid as an independent risk factor for cardiovascular and renal morbidity is controversial. A better understanding of its relationship with preclinical organ damage may help clarify the mechanism(s) implicated in the development of early cardiovascular disease. We evaluated the association between uric acid and the presence and degree of target organ damage in 425 (265 males, 160 females) middle-aged, untreated patients with essential hypertension. Left ventricular mass index and carotid intima-media thickness were assessed by ultrasound scan. Albuminuria was measured as the albumin to creatinine ratio in 3 nonconsecutive first morning urine samples. Overall, patients with target organ damage had significantly higher levels of serum uric acid as compared with those without it (presence versus absence of left ventricular hypertrophy, P =0.04; carotid abnormalities, P P P P

Development of de novo donor-specific antibodies (dnDSA) is associated with late or chronic antibody-mediated rejection (CAMR) and poor graft outcome in low-risk kidney transplant recipients. High-level soluble B-cell activating factor (sBAFF) was observed in kidney recipients at higher risk of developing dnDSA.We longitudinally analyzed sBAFF levels in 81 consecutive primary pediatric kidney recipients monitored for de novo human leukocyte antigen (HLA) antibody (Ab) occurrence to gain insight into the events conditioning B-cell activation posttransplant and to analyze the usefulness of paired DSA-sBAFF monitoring in this clinical setting.At a median follow-up of 65 months, 23 patients (28%) developed dnDSA, with 13 of 23 developing CAMR. Irrespective of HLA Ab status, sBAFF levels progressively increased in all patients in the first posttransplant year, thereafter reaching a plateau. sBAFF levels were influenced by the degree of HLA class I antigen match and donor age. Despite higher levels of sBAFF in HLA Ab-positive patients (median and 95% confidence interval sBAFF in DSA+non-DSA patients: 568, 534-608 pg/mL vs. 502, 422-548 pg/mL in Ab-negative patients; P0.05), we found that sBAFF monitoring could not predict DSA development by a time to event longitudinal analysis. Moreover, sBAFF kinetics up to CAMR onset could not anticipate CAMR development in the DSA cohort.Our findings provide evidence of early posttransplant B-cell activation even in unsensitized recipients of first kidney allograft. The significance of this activation, likely induced by exposition to the allograft, is yet unclear.

The three yr results of a multicenter trial in de novo pediatric KT treated with a proliferative signal inhibitor and low dose CNI are presented. Thirty-seven children (9.1 ± 5 yr old) received basiliximab, cyclosporine A (CyA C2:1400 ng/mL), (MMF C0:1.5-3 μg/mL), and prednisone. Three wk later everolimus was started (C0:5-10 ng/mL), CyA was reduced (C2:600 ng/mL after 90 days 300 ng/mL), and MMF discontinued. During the three-yr period patient and graft survivals were 96%. One patient died for causes unrelated to the immunosuppression. Cumulative acute rejection rate including protocol and indication biopsies was 21.9%. None of the patients had signs of chronic humoral rejection. Incidence of dnDSA was 5%, 11%, and 22% at one, two, and three yr post-transplant, respectively. Mean glomerular filtration rate measured at one yr and three yr post-transplant was 105.5 ± 31 and 110.7 ± 27 mL/min/1.73 m(2), respectively. A growth velocity of 7.7 ± 6.7 cm/yr was achieved with positive catch-up growth. No malignancy or post-transplant lymphoproliferative diseases were diagnosed. In conclusion, the treatment based on basiliximab induction, everolimus, low-dose cyclosporine, and low-dose prednisone leads to good long-term efficacy in de novo pediatric KT recipients.

Microalbuminuria, i.e., abnormal urinary excretion of albumin, which is detectable by low cost and widely available tests, is a first-line tool for identifying hypertensive patients who are at higher cardiovascular (CV) risk. Numerous studies have provided evidence that microalbuminuria is a concomitant of cardiac and vascular damage as well as a strong, independent predictor of CV events. An important, emerging issue is that the risk for CV morbidity and mortality is linearly related to urinary albumin excretion and persists well below the currently used cutoff for defining microalbuminuria. Furthermore, late-breaking evidence suggests that a reduction of albuminuria under antihypertensive treatment is paralleled by changes in CV risk. The routine search for target organ damage by means of microalbuminuria could lead to a significant improvement in the evaluation and treatment of patients with primary hypertension.

Advances in immunosuppression have lowered the acute rejection rates in kidney transplant recipients but have impacted negatively on the viral infection rates. Polyomavirus-associated interstitial nephropathy (PyVA N) affects up to 10% of kidney transplant recipients and can progress to irreversible allograft failure in up to 45% of affected cases. Nowadays, thanks to increased awareness of PyVA N and improved diagnostic techniques, the rate of graft loss has decreased, most markedly in centers with active screening and intervention programs. The diagnosis of PyVA N is made by allograft histology. However, systematic screening by quantitative molecular-genetic techniques allows intervention in the early stages of the disease, before the occurrence of irreversible parenchymal changes. So far, the only proven measure affecting PyVA N progression and outcome is the reduction of immunosuppression. Other therapeutic approaches including cidofovir, leflunomide, fluoroquinolones and intravenous immunoglobulins have been explored, but there is no clinical evidence supporting their efficacy. It has been largely demonstrated that BKV-specific T-cell immunity plays a pivotal role in controlling viral replication and disease progression. For this reason viral-specific T-cell immunity can help in monitoring PyVA N. Protocols of adoptive T-cell transfer based on infusion of BKV-specific T cells are the object of many studies and should be considered an innovative treatment approach for PyVA N.

Sub-clinical organ damage is a strong independent predictor of cardiovascular mortality in primary hypertension, and its changes over time parallel those in risk of cardiovascular events. A better understanding of the pathogenetic mechanisms underlying the development of target organ damage may help us devise more effective therapeutic strategies. We therefore investigated the relationship between the presence of organ damage and some of its potential determinants, such as blood pressure severity and early atherosclerotic abnormalities. Thirty-seven untreated, non-diabetic hypertensive patients were enrolled. Target organ damage was assessed by albuminuria and left ventricular mass index; systemic vascular permeability was evaluated by transcapillary escape rate of albumin (TERalb); and blood pressure was measured by 24h ambulatory blood pressure monitoring. The albumin-to-creatinine ratio and left ventricular mass index were directly related to TERalb (r = 0.48, p = 0.003 and r = 0.39, p < 0.020, respectively) and 24-h systolic blood pressure values (r = 0.54, p < 0.001; r = 0.60, p < 0.001). The simultaneous occurrence of increased blood pressure load and TERalb was associated with higher left ventricular mass index values (p = 0.012) and entailed an increased risk of having at least one sign of damage (chi2 = 17.4; p < 0.001). Logistic regression analysis showed that the risk of presenting at least one sign of organ damage increased more than ten-fold when TERalb was above the median and more than five-fold with each 10 mmHg increase in 24-h systolic blood pressure. Blood pressure load and vascular permeability are potentially modifiable factors that are independently associated with the occurrence of sub-clinical signs of renal and cardiac damage in hypertensive patients.

Inappropriate left ventricular mass (LVM) and microalbuminuria predict cardiovascular events in hypertension. We attempted to evaluate the relationship between inappropriate LVM and albuminuria in hypertensive patients.Four hundred and two nondiabetic, untreated patients with primary hypertension were studied. The appropriateness of LVM to cardiac workload was calculated by the ratio of observed LVM to the predicted value using the reference equation. Albuminuria was evaluated by the urinary albumin to creatinine ratio.The deviation of LVM from the predicted value was positively related to albuminuria (P0.0001). Multiple regression analysis showed that albuminuria (0.0182), pulse pressure (P0.0001) and left ventricular hypertrophy (LVH) (P0.0001) were the only independent predictors of observed/predicted LVM. When subjects were divided into subgroups on the basis of the presence/absence of inappropriate LVM, patients with inappropriate LVM showed higher urinary albumin excretion (P0.0001), regardless of potential confounding factors, including LVH (analysis of covariance, P = 0.0453), and higher prevalence of microalbuminuria (P = 0.0024) compared to those without it. Analogous results were obtained by looking at the study patients on the basis of the presence of micro- or normoalbuminuria. Indeed, patients with microalbuminuria showed higher prevalence of inappropriate LVH compared to other left ventricular geometries (appropriate LVH and absence of LVH) (P0.0001). After adjusting for confounders, microalbuminuria entailed a three- and five-fold greater risk of having appropriate and inappropriate LVH, respectively.Inappropriate LVM is associated with albuminuria in hypertension. These data strengthen the role of microalbuminuria as an indicator of high cardiovascular risk.

Microalbuminuria and a reduction in creatinine clearance are well known, independent predictors of unfavourable cardiovascular prognosis. Our aim was to evaluate the impact of renal damage on global risk stratification in 459 non-diabetic, untreated hypertensive patients (64% men, mean age 47.3 years).Renal damage was defined as creatinine clearance60 ml/min per 1.73 m2 (Cockcroft-Gault formula) or the presence of microalbuminuria (albumin to creatinine ratio). Cardiac and vascular organ damage was assessed by ultrasound scan. We evaluated the impact of renal damage, left ventricular hypertrophy and carotid atherosclerosis on risk stratification as recommended by the 2007 European Society of Hypertension-European Society of Cardiology Guidelines.The prevalence of renal damage, microalbuminuria and creatinine clearance60 ml/min per 1.73 m2 was 24, 12 and 13%, respectively. There was no correlation between albuminuria and estimated creatinine clearance, and only 0.9% of patients showed microalbuminuria and reduced creatinine clearance simultaneously. The presence of renal damage entailed a 3.3 times higher risk of having cardiovascular abnormalities. Based on routine work-up, 58% of our study patients were classified as high-very high risk. The simultaneous evaluation of albuminuria and creatinine clearance resulted in a significant change in risk stratification, since 68% of patients were classified in the high-very high risk class. The search for left ventricular hypertrophy or carotid atherosclerosis by ultrasonography did not improve risk stratification significantly as compared to the assessment of renal damage.Our findings support the assessment of renal abnormalities as the first step when evaluating target organ damage for cardiovascular risk assessment in hypertensive patients.

High sensitivity C-reactive protein (hs-CRP) has been recognized as a risk factor for cardiovascular disease. Asymptomatic organ damage is known to precede cardiovascular events in hypertension. The aim of the present study was to investigate the relationship between hs-CRP and signs of organ damage, namely left ventricular mass index (LVMI), albuminuria, and carotid atherosclerosis in a group of hypertensive patients. One hundred and eighty-two untreated patients with primary hypertension were studied. HS-CRP was measured by immunonephelometry. LVMI was assessed by echocardiography, albuminuria was measured as albumin to creatinine ratio, and carotid atherosclerosis by ultrasonography. Patient stratification according to quartiles of hs-CRP showed a significant trend toward higher age, prevalence of left ventricular hypertrophy, and carotid plaques. Moreover, there was a significant correlation among hs-CRP quartiles and left ventricular mass index, carotid cross-sectional area, carotid plaques, and albuminuria. Multiple regression analysis showed that, after adjusting for established cardiovascular risk factors (ie, age, duration of hypertension, smoking habit, body mass index (BMI), 24-hour systolic and diastolic blood pressures, glucose, creatinine, uric acid, triglycerides, total and low-density lipoprotein cholesterol), hs-CRP remained a strong correlate of target organ damage. These results support the importance of chronic microinflammation in the development of atherosclerotic disease in hypertension.

Background Subclinical renal damage and hyperuricemia are not uncommon in patients with primary hypertension. Whether mild hyperuricemia reflects a subclinical impairment of renal function or contributes to its development is currently debated. We investigated the relationship between serum uric-acid levels and the occurrence of early signs of kidney damage. Methods Four hundred eighteen patients with primary hypertension were studied. Albuminuria was measured as the albumin-to-creatinine ratio, and creatinine clearance was estimated by the formula of Cockcroft and Gault. Interlobar resistive index and renal abnormalities, ie, the renal volume-to-resistive index ratio, were evaluated by renal Doppler and ultrasound. Results Uric acid was directly related to resistive index (P = .007) in women and to albuminuria (P = .04) in men, and was inversely related to the renal volume-to-resistive index ratio in both men (P = .005) and women (P = .02). Patients with uric-acid levels above the median showed a higher prevalence of microalbuminuria (14% v 7%, P = .012) and of renal abnormalities (41% v 33%, P = .007). Moreover, when creatinine clearance was taken as a covariate, patients with increased uric-acid levels showed higher albuminuria and resistive indices, and a lower renal volume-to-resistive index ratio. Even after adjustment for several risk factors, each standard deviation increase in serum uric acid entailed a 69% higher risk of microalbuminuria, and a 39% greater risk of ultrasound detectable renal abnormalities. Conclusions Mild hyperuricemia is associated with early signs of renal damage, ie, microalbuminuria and ultrasound-detectable abnormalities, regardless of the glomerular filtration rate in primary hypertension.

Increased arterial stiffness and the presence of metabolic syndrome (MS) have been shown to predict cardiovascular events in patients with primary hypertension. We investigated the relationship between a recently proposed index of arterial stiffness derived from ambulatory blood pressure (BP) monitoring and MS in 156 untreated, non-diabetic patients with primary hypertension. Ambulatory arterial stiffness index (AASI) was defined as 1 minus the regression slope of diastolic over systolic BP readings obtained from 24-h recordings. A modified National Cholesterol Education Program definition for MS was used, with body mass index replacing waist circumference. The prevalence of MS was 23%. Patients with MS were more frequently male (0.0291) and had increased serum uric acid (P=0.0005), high-sensitivity C-reactive protein (P=0.0259), as well as total and low-density lipoprotein (LDL)-cholesterol (P=0.0374 and P=0.0350, respectively) as compared to those without MS. After adjusting for these confounders, the association between AASI and the presence of MS was statistically significant (P=0.0257). Moreover, the prevalence of increased AASI (upper tertile, that isor=0.550) was greater in patients with MS (P=0.0156). After adjusting for age and 24-h mean BP, the presence of MS entailed a more than twofold greater risk for increased AASI (0.0280). MS is associated with increased AASI in non-diabetic patients with primary hypertension. These data support the role of this new index of arterial stiffness as a marker of risk and help to explain the high cardiovascular morbidity and mortality that is observed in hypertensive patients with MS.

Objective Arterial stiffness is a predictor of cardiovascular mortality in the general population as well as in hypertension and end-stage renal disease. We investigated the relationship between a recently proposed ambulatory blood pressure monitoring-derived index of arterial stiffness and early signs of renal damage in patients with primary hypertension. Design and setting A total of 168 untreated patients with sustained primary hypertension were studied. Ambulatory arterial stiffness index (AASI) was calculated based on 24-h ambulatory blood pressure readings. Albuminuria was measured as the albumin to creatinine ratio. Creatinine clearance was estimated using the Cockcroft-Gault formula, and the interlobar resistive index was evaluated by renal ultrasound and Doppler examination. Results AASI was positively related to urinary albumin excretion and resistive index, and was negatively related to estimated creatinine clearance and renal volume to the resistive index ratio. Patients with AASI above the median (i.e. > 0.51) showed a higher prevalence of microalbuminuria and a mild reduction in creatinine clearance. Moreover, patients with microalbuminuria or a mild reduction in creatinine clearance had significantly higher AASI values compared with those without, and the greater the renal involvement, the greater the AASI. After adjusting for several potentially confounding variables, we found that each standard deviation increase in AASI (i.e. 0.16) entails an almost twofold greater risk of renal involvement. Conclusion Increased AASI is independently associated with early signs of renal damage in patients with sustained primary hypertension. These results strengthen the usefulness of AASI and ambulatory blood pressure monitoring in cardiovascular risk assessment.

Increased arterial stiffness has been shown to predict cardiovascular mortality in patients with primary hypertension. Asymptomatic organ damage is known to precede cardiovascular events. We investigated the relationship between a recently proposed index of stiffness derived from ambulatory blood pressure (BP) and target organ damage in 188 untreated patients with primary hypertension. Ambulatory arterial stiffness index was defined as 1 minus the regression slope of diastolic over systolic BP readings obtained from 24-hour recordings. Albuminuria was measured as the albumin:creatinine ratio, left ventricular mass index was assessed by echocardiography, and carotid abnormalities were evaluated by ultrasonography. The prevalence of microalbuminuria, left ventricular hypertrophy (LVH), and carotid abnormalities was 12%, 38%, and 19%, respectively. Ambulatory arterial stiffness index was positively related to age, triglycerides, office and 24-hour systolic BP, 24-hour pulse pressure, urinary albumin excretion, and carotid intima-media thickness. Patients with microalbuminuria, carotid abnormalities, or LVH showed higher ambulatory arterial stiffness index as compared with those without it. After adjusting for confounding factors, each SD increase in ambulatory arterial stiffness index entails an &2 times higher risk of microalbuminuria, carotid abnormalities, and LVH and doubles the risk of the occurrence of ≥1 sign of organ damage. Ambulatory arterial stiffness index is associated with organ damage in patients with primary hypertension. These data strengthen the role of this index as a marker of risk and help to explain the high cardiovascular mortality reported in patients with high ambulatory arterial stiffness index.

The metabolic syndrome can be found in approximately one third of patients who do not have diabetes but have primary hypertension. Its presence has been associated with a wide range of traditional and nontraditional cardiovascular risk factors and early signs of cardiovascular and renal damage. Moreover, it was emphasized recently that the metabolic syndrome predicts an increased probability of sustaining a cardiovascular event or dying. In the clinical setting of insulin resistance, attention should be paid to the metabolic side effects of antihypertensive drugs; therefore, preference should be given to renin-angiotensin system inhibitors and calcium channel blockers rather than to beta blockers and diuretics.

Leoncini G, Ratto E, Viazzi F, Vaccaro V,Parodi D, Parodi A, Falqui V, Tomolillo C, DeferrariG, Pontremoli R (University of Genoa, Genoa, Italy).Metabolic syndrome is associated with early signs oforgan damage in nondiabetic, hypertensive patients.J Intern Med 2005; 257: 454–460.Objectives. Hypertensive patients with metabolicsyndrome (MS) are at greater risk for cardiovasculardisease. To get a better understanding of the patho-physiology underlying this association, we evaluatedthe relationship between MS and subclinical organdamage in essential hypertensive patients.Design and setting. A total of 354 untreated,nondiabetic patients with primary hypertensionwere included in the study. A modified ATP IIIdefinition for MS was used, with body mass indexreplacing waist circumference. Albuminuria wasmeasured as albumin to creatinine ratio, leftventricular mass index (LVMI) was assessed byechocardiography and carotid abnormalities byultrasonography.Results. The prevalence of MS was 25%. Patientswith MS were more likely to be smokers (P ¼ 0.004)and had higher serum uric acid levels (P ¼ 0.004).Moreover, they showed higher urinary albuminexcretion (P ¼ 0.0004) and LVMI (P ¼ 0.0006),increased intima-media thickness (P ¼ 0.045), aswell as higher prevalence of microalbuminuria(P ¼ 0.03) and left ventricular hypertrophy (LVH;P ¼ 0.003). After adjusting for age, gender andduration of hypertension, we found that thepresence of MS entails a twofold greater risk formicroalbuminuria (P ¼ 0.04), LVH (P ¼ 0.003)and carotid abnormalities (P < 0.05). Whenpatients were stratified according to the number ofcomponents of MS, albuminuria (P ¼ 0.002) andLVMI (P ¼ 0.005) increased progressively acrosscategories.Conclusions. Metabolic syndrome is associated withsubclinical organ damage in nondiabetic, essentialhypertensive patients. These data may, in part,explain the high cardiovascular morbidity andmortality that is observed in hypertensive patientswith MS.Keywords: hypertension, left ventricular hypertrophy,metabolic syndrome, microalbuminuria.

Accurate assessment of cardiovascular risk is a key step toward optimizing the treatment of hypertensive patients. We analyzed the impact and cost-effectiveness of routine, thorough assessment of target organ damage (TOD) in evaluating risk profile in hypertension. A total of 380 never-treated patients with essential hypertension underwent routine work-up plus evaluation of albuminuria and ultrasonography of cardiac and vascular structures. The impact of these tests on risk stratification, as indicated by European Society of Hypertension-European Society of Cardiology guidelines, was assessed in light of their cost and sensitivity. The combined use of all of these tests greatly improved the detection of TOD, therefore leading to the identification of a higher percentage of patients who were at high/very high risk, as compared with those who were detected by routine clinical work-up (73% instead of 42%; P < 0.0001). Different signs of TOD only partly cluster within the same subgroup of patients; thus, all three tests should be performed to maximize the sensitivity of the evaluation process. The diagnostic algorithm yielding the lowest cost per detected case of TOD is the search for microalbuminuria, followed by echocardiography and then carotid ultrasonography. Adopting lower cut-off values to define microalbuminuria allows us to optimize further the cost-effectiveness of diagnostic algorithms. In conclusion, because of its low cost and widespread availability, measuring albuminuria is an attractive and cost-effective screening test that is especially suitable as the first step in the large-scale diagnostic work-up of hypertensive patients.

Hypertension is an important modifiable risk factor for cardiovascular disease; its prevention and treatment currently represent major health concerns around the world, especially in western countries. Effective, well-tolerated drugs such as dihydropyridine calcium channel blockers, to be used either alone or in combination treatments, play a key role in reducing cardiovascular morbidity and mortality. The extended-release formulation of nifedipine given once daily provides a relatively constant concentration profile and has proved to be effective in reducing blood pressure values. In the International Nifedipine gastrointestinal therapeutic system Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) study, it was demonstrated that nifedipine confers cardiovascular protection as effectively as diuretics in high-risk patients, with a smaller incidence of adverse metabolic consequences. Furthermore, two INSIGHT substudies demonstrated that nifedipine prevents the progression of carotid atherosclerosis and reduces the worsening of coronary calcifications, supporting the use of calcium channel blockers in hypertensive patients--especially those at high cardiovascular risk. This review discusses the existing clinical evidence supporting the use of nifedipine in the treatment of hypertension.