Charalampos Loutradis

Ambulatory Pulse Wave Velocity Is a Stronger Predictor of Cardiovascular Events and All-Cause Mortality Than Office and Ambulatory Blood Pressure in Hemodialysis Patients.

Arterial stiffness and augmentation of aortic blood pressure (BP) measured in office are known cardiovascular risk factors in hemodialysis patients. This study examines the prognostic significance of ambulatory brachial BP, central BP, pulse wave velocity (PWV), and heart rate–adjusted augmentation index [AIx(75)] in this population. A total of 170 hemodialysis patients underwent 48-hour ambulatory monitoring with Mobil-O-Graph-NG during a standard interdialytic interval and followed-up for 28.1±11.2 months. The primary end point was a combination of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. Secondary end points included: (1) all-cause mortality; (2) cardiovascular mortality; and (3) a combination of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, coronary revascularization, or hospitalization for heart failure. During follow-up, 37(21.8%) patients died and 46(27.1%) had cardiovascular events. Cumulative freedom from primary end point was similar for quartiles of predialysis-systolic BP (SBP), 48-hour peripheral-SBP, and central-SBP, but was progressively longer for increasing quartiles for 48-hour peripheral-diastolic BP and central-diastolic BP and shorter for increasing quartiles of 48-hour central pulse pressure (83.7%, 71.4%, 69.0%, 62.8% [log-rank P=0.024]), PWV (93.0%, 81.0%, 57.1%, 55.8% [log-rank P<0.001]), and AIx(75) (88.4%, 66.7%, 69.0%, 62.8% [log-rank P=0.014]). The hazard ratios for all-cause mortality, cardiovascular mortality, and the combined outcome were similar for quartiles of predialysis-SBP, 48-hour peripheral-SBP, and central-SBP, but were increasing with higher ambulatory PWV and AIx(75). In multivariate analysis, 48-hour PWV was the only vascular parameter independently associated with the primary end point (hazard ratios, 1.579; 95% confidence intervals, 1.187–2.102). Ambulatory PWV, AIx(75), and central pulse pressure are associated with increased risk of cardiovascular events and mortality, whereas office and ambulatory SBP are not. These findings further support that arterial stiffness is the prominent cardiovascular risk factor in hemodialysis.

Prevalence of Hyperkalemia in Diabetic and Non-Diabetic Patients with Chronic Kidney Disease: A Nested Case-Control Study.

Background: Hyperkalemia is a potentially life-threatening disorder, usually complicating chronic kidney disease (CKD). Factors superimposed to reduced renal function are further elevating hyperkalemia risk, but their contribution is not fully elucidated. This study aimed to compare the prevalence of hyperkalemia in diabetic and non-diabetic patients with CKD. Methods: This is a nested case-control study of 180 type-2 diabetic and 180 non-diabetic patients with CKD followed in a Nephrology outpatient clinic, matched for gender, age and estimated glomerular filtration rate. Type-1 diabetes or end-stage renal disease patients were excluded. Prevalence of hyperkalemia was defined as potassium >5 mEq/l or use of sodium polystyrene sulfonate, and further by potassium >5, ≥5.2 and ≥5.5 mEq/l. It was calculated in both groups in whole and CKD stages separately. Univariate and multivariate logistic regression analysis were conducted to identify factors associated with hyperkalemia. Results: The prevalence of hyperkalemia was higher in diabetic CKD patients (27.2 vs. 20%, p = 0.107) and remained around 30% higher with all secondary definitions used, but never reached statistical significance. In Stage 2, no difference was noted (8.7 vs. 17.4%, p = 0.665); in Stage 3, it was significantly higher in diabetics (28.6 vs. 17.5%, p = 0.036); and in Stage 4, it was equally high in both groups (35.5 vs. 32.3%, p = 0.788). In multivariate analysis, Stage 4 CKD (OR 4.535, 95% CI 1.561-13.173), use of angiotensin-converting enzyme inhibitors (ACEIs; OR 2.228, 95% CI 1.254-3.958) and smoking (OR 2.254, 95% CI 1.218-4.171) were independently associated with hyperkalemia. Conclusions: Diabetes mellitus was found to elevate the prevalence of hyperkalemia only in CKD Stage 3 patients (moderately impaired renal function). Advanced CKD at Stage 4 and ACEIs are major determinants of hyperkalemia occurrence.

Diabetes mellitus increases the prevalence of anemia in patients with chronic kidney disease: A nested case-control study

AIM To compare anemia prevalence between matched chronic kidney disease (CKD) patients with and without diabetes mellitus (DM) and to assess factors associated with anemia development. METHODS This is a nested case-control study of 184 type-2 diabetic and 184 non-diabetic CKD patients from a prospectively assembled database of a Nephrology outpatient clinic, matched for gender, age and estimated glomerular filtration rate (eGFR). Prevalence of anemia (hemoglobin: Men: < 13 g/dL, women: < 12 g/dL and/or use of recombinant erythropoietin) was examined in comparison, in the total population and by CKD Stage. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with anemia. RESULTS The total prevalence of anemia was higher in diabetics (47.8% vs 33.2%, P = 0.004). Accordingly, prevalence was higher in diabetics in CKD Stage 3 (53.5% vs 33.1%, P < 0.001) and particularly in Stage 3a (60.4% vs 26.4%, P < 0.001), whereas it was non-significantly higher in Stage 4 (61.3% vs 48.4%; P = 0.307). Serum ferritin was higher in diabetics in total and in CKD stages, while serum iron was similar between groups. In multivariate analyses, DM (OR = 2.206, 95%CI: 1.196-4.069), CKD Stages 3a, 3b, 4 (Stage 4: OR = 12.169, 95%CI: 3.783-39.147) and serum iron (OR = 0.976, 95%CI: 0.968-0.985 per mg/dL increase) were independently associated with anemia. CONCLUSION Prevalence of anemia progressively increases with advancing stages of CKD and is higher in diabetic than matched non-diabetic CKD patients and diabetes is independently associated with anemia occurrence. Detection and treatment of anemia in diabetic CKD patients should be performed earlier than non-diabetic counterparts.

Blood pressure variability increases with advancing chronic kidney disease stage: a cross-sectional analysis of 16 546 hypertensive patients

Objective: Increased BP-variability predicts cardiovascular morbidity and mortality in hypertensives. This study aimed to examine short-term BP-variability according to renal function stage. Methods: We included 16 546 patients [10 270 (62.1%) without/6276 (38.9%) with CKD Stage 1–5] from the Spanish Ambulatory-Blood-Pressure Monitoring (ABPM) Registry. Stages of CKD were defined according to K/DIGO criteria, based on estimated glomerular filtration rate calculated with the CKD-EPI equation and albumin-to-creatine ratio. BP-variability was assessed with standard deviation (SD), weighted SD (wSD), coefficient of variation (CV), and average real variability (ARV). Results: Compared with those without CKD, a lower proportion of CKD patients were dippers (51.9 versus 39.6%; P < 0.001). Across CKD stages, a progressive decrease in dipper (from 39.1 to 20.4%; P < 0.001) and increase in riser proportion (from 12.3 to 36.7%; P < 0.001) were noted. Patients with CKD had significantly higher SBP SD, wSD, CV and ARV and lower DBP SD compared with those without CKD (P < 0.001). Within CKD Stages, an increasing trend from Stage 1 towards Stage 5 was observed for SBP SD (from 13.8 ± 3.7 to 15.6 ± 5.4 mmHg), wSD (from 12.0 ± 3.2 to 13.9 ± 5.1 mmHg), CV (from 10.4 ± 2.7 to 11.5 ± 4.1%), ARV (from 9.9 ± 2.3 to 11.4 ± 3.2 mmHg); P < 0.001 for all comparisons. DBP SD (P < 0.001), wSD and ARV (P = 0.002) were slightly decreasing, whereas DBP CV increased from Stage 1 to Stage 4 (P < 0.001). In multivariate analysis, male gender, older age, abdominal obesity, diabetes, number of antihypertensive medications, and clinic SBP were independent factors for higher SBP 24-h ARV in CKD. Conclusion: An increase in short-term SBP-variability was present with advancing CKD stages in a large cohort. This increased SBP-variability may be involved in the sharp elevation of cardiovascular risk with worsening renal function.

Echocardiographic Parameters During Long and Short Interdialytic Intervals in Hemodialysis Patients

BACKGROUND The long interdialytic interval in thrice-weekly hemodialysis is associated with excess cardiovascular risk. However, the mechanisms behind these adverse consequences are not fully understood. This study investigated the interdialytic changes in right and left ventricular function during the 2- and 3-day intervals. STUDY DESIGN Observational study with 2 random crossover sequences of recordings: 3-day followed by 2-day interval or vice versa. SETTINGS & PARTICIPANTS 41 stable patients with end-stage renal disease on standard thrice-weekly hemodialysis therapy. PREDICTOR 3-day (long) versus 2-day (short) interdialytic interval. OUTCOME Interdialytic change in echocardiographic indexes of left and right ventricular function. MEASUREMENTS 2-dimensional echocardiographic and tissue Doppler imaging studies were performed with a Vivid 7 cardiac ultrasound system at the start and end of the 3- and 2-day interdialytic intervals. RESULTS During both intervals studied, elevations in cardiac output, stroke volume, left ventricular mass index, and peak early diastolic velocities of the left ventricle were evident. Interdialytic weight gain (3.0±1.7 vs 2.4±1.3 [SD] kg) and inferior vena cava diameter increase (0.54±0.3 vs 0.25±0.3) were higher during the 3-day versus the 2-day interval (P<0.001). Left ventricular systolic and diastolic function indexes were generally no different between interdialytic intervals. In contrast, interdialytic increases in left and right atrial volume, right ventricular systolic pressure (RVSP; 15.3±10.2 vs 4.7±5.2mmHg; P<0.001), and tricuspid regurgitation maximum velocity (0.46±0.45 vs 0.14±0.33m/s; P=0.001) were significantly greater during the 3- versus the 2-day interval. Multivariable analysis suggested that changes in interdialytic weight gain, right ventricle diastolic function, and pulmonary vascular resistance were determinants of the change in RVSP. LIMITATIONS Observational study design. CONCLUSIONS Excess volume accumulation over the long interdialytic interval in hemodialysis patients results in higher left and right atrial enlargement and RVSP elevation, which clinically corresponds to pulmonary circulation overload, providing one plausible pathway for the excess mortality risk during this period.

Renal injury progression in autosomal dominant polycystic kidney disease: a look beyond the cysts

Hypertension and progressive decline of renal function are among the common clinical manifestations in autosomal dominant polycystic kidney disease (ADPKD). At present, cyst formation in ADPKD patients is still considered the main pathogenic mechanism for the onset of these manifestations. However, the presence of polycystins in the vessels and the cilia of the endothelial cells and vascular smooth muscle cells, as well as development of hypertension prior to renal function decline and its prognostic role for the latter, indicate that polycystins may have an important role for endothelial damage in several vascular beds. Pathological polycystins induce intracellular calcium abnormalities, which affect various cellular organelles and functions and possibly lead not only to several abnormal biochemical reactions within endothelial cells, but also to an imbalance between oxidant and antioxidant capacity. Among the consequences of this process is accumulation of asymmetric-dimethylarginine, which not only participates in the induction and progression of renal damage, but also interferes with the normal vascular response due to nitric oxide (NO) inhibition. Reduced NO bioavailability would result in the long-run in relative vasoconstriction, impaired renal blood flow and vascular remodelling. This review summarizes the existing data from studies supporting that mechanisms other than cyst formation also contribute to the pathogenesis of hypertension and renal function decline in ADPKD.

Blood pressure variability is increasing from the first to the second day of the interdialytic interval in hemodialysis patients

Objectives: Patients with end-stage renal-disease under hemodialysis have increased cardiovascular risk and experience severe blood pressure (BP) fluctuations during the dialysis session and the subsequent interdialytic period. BP variability (BPV) may be an additional risk factor for cardiovascular events and preliminary data suggest increased BPV with advancing stages of chronic kidney disease. This is the first study to examine BPV during the whole intradialytic and interdialytic period in hemodialysis patients with ambulatory BP monitoring. Methods: A total of 160 patients receiving maintenance hemodialysis had 48-h ambulatory BP monitoring with the Mobil-O-Graph device during a regular dialysis session and the subsequent interdialytic interval. Brachial and aortic BPV were calculated with validated formulas and were compared between Days 1 and 2 of the interdialytic period (44-h), Days 1 and 2 of the total 48-h interval (including the dialysis session), and between the two respective daytime periods and night-time periods. Results: All brachial SBPV indices [SD: 14.75 ± 4.38 vs. 15.91 ± 4.41, P = 0.001; weighted SD: 13.80 ± 4.00 vs. 14.89 ± 3.90, P < 0.001; coefficient of variation (CV): 11.34 ± 2.91 vs. 11.93 ± 2.94, P = 0.011; average real variability (ARV): 11.38 ± 3.44 vs. 12.32 ± 3.65, P < 0.001)] were increasing from Days 1 to 2 of the 44-h interdialytic period. Similarly, all indexes of DBPV were significantly increased in Day 2, except for CV. Aortic SBPV and DBPV indices displayed a similar pattern. Furthermore, all studied brachial SBPV and DBPV indexes were also lower during daytimes 1 than 2 (systolic ARV 11.56 ± 3.98 vs. 12.44 ± 4.03, P = 0.002); systolic ARV was lower in night-time 1 compared with night-time 2 (11.20 ± 5.09 vs. 12.18 ± 4.66, P = 0.045). In multivariate regression analysis prehemodialysis SBP, age and diabetes were independently associated with increased SBP ARV. Conclusion: BPV is increased in interdialytic Day 2 compared with Day 1 in hemodialysis patients; this could be another mechanism involved in the complex cardiovascular pathophysiology and increased cardiovascular mortality of these individuals.

The association of interdialytic blood pressure variability with cardiovascular events and all-cause mortality in haemodialysis patients

BACKGROUND Long-term pre-dialysis blood pressure variability (BPV) in haemodialysis patients is associated with increased cardiovascular risk. The association of the main haemodynamic culprit in dialysis, that is, short-term BPV, with outcomes has not been investigated. We examine the prognostic role of short-term BPV for mortality and cardiovascular events in this population. METHODS A total of 227 haemodialysis patients underwent 44-h ambulatory monitoring during a standard interval and were followed-up for 30.17 ± 17.70 months. We calculated SD, weighted SD (wSD), coefficient of variation (CV) and average real variability (ARV) of BP with validated formulas. The primary endpoint was first occurrence of all-cause death, non-fatal myocardial infarction or non-fatal stroke. Secondary endpoints were: (i) all-cause mortality, (ii) cardiovascular mortality and (iii) a combination of cardiovascular events. RESULTS Cumulative freedom from the primary endpoint was similar for quartiles of pre-dialysis and 44-h systolic BP (SBP), but was progressively longer for increasing quartiles of 44-h SBP-SD (P = 0.014), wSD (P = 0.007), CV (P = 0.031) and ARV (83.9, 71.9, 70.2 and 43.9% for quartiles 1-4; P < 0.001). Higher quartiles of 44-h SBP-ARV were associated with higher risk of all studied outcomes. Among diastolic BPV indices, 44-h diastolic BP (DBP)-CV and 44-h DBP-ARV were associated with increased risk for the composite cardiovascular outcome. In Cox regression analysis, SBP-BPV was related to the primary endpoint, independently of SBP levels and interdialytic weight gain [ARV: hazard ratio (HR) 1.115, 95% confidence interval (95% CI) 1.048-1.185]. This association become insignificant after adjustment for pulse wave velocity (PWV; HR 1.061, 95% CI 0.989-1.137), and further attenuated after additional adjustment for age, dialysis vintage, gender, comorbidities and prevalent cardiovascular disease (HR 1.031, 95% CI 0.946-1.122). CONCLUSIONS Increased BPV during the interdialytic interval is associated with higher risk of death and cardiovascular events, whereas ambulatory BP levels are not. This association was not independent after adjustment for PWV, other risk factors and prevalent cardiovascular disease. Short-term BPV could be a mediator promoting the adverse cardiovascular profile of haemodialysis patients.

Levels of Endocan, Angiopoietin-2, and Hypoxia-Inducible Factor-1a in Patients with Autosomal Dominant Polycystic Kidney Disease and Different Levels of Renal Function

Background: Endothelial dysfunction leading to unbalanced vasoconstriction and ischemia of renal parenchyma is increasingly proposed as an alternative pathway of renal damage in autosomal dominant polycystic kidney disease (ADPKD). However, human studies investigating the evolution of such phenomena are limited. This study investigated the levels of emerging biomarkers of endothelial function, angiogenesis and hypoxia, in ADPKD patients with different renal function. Methods: The study population consisted of three groups: 26 ADPKD patients with impaired renal function (Group A; estimated glomerular filtration rate [eGFR] 45–70 mL/min/1.73 m2), 26 ADPKD patients with preserved renal function (Group B; eGFR >70 mL/min/1.73 m2), and 26 age- and sex-matched controls with no history of renal disease. Circulating levels of endocan (endothelial cell-specific molecule-1) angiopoietin-2, and hypoxia-inducible factor-1a (HIF-1a) were determined by enzyme-linked immunosorbent assay techniques. Results: Patients in Group A had significantly higher levels of endocan (7.17 ± 0.43 ng/mL), angiopoietin-2 (5,595.43 ± 3,390), and HIF-1a (163.68 ± 37.84 pg/mL) compared to patients in Group B (6.86 ± 0.59 ng/mL, p = 0.017, 3,854.41 ± 3,014.30, p = 0.018, 136.84 ± 42.10 pg/mL, p = 0.019 respectively) or controls (4.83 ± 0.69 ng/mL, 1,069 ± 427.88 pg/mL, 70.20 ± 17.49 pg/mL, p < 0.001 for all comparisons). Of note, patients in Group B had also higher levels of all markers compared to controls (p < 0.001) despite having similar renal function. In correlation analyses within ADPKD patients, we noted strong correlations of all studied markers with asymmetric dimethylarginine (ADMA; endocan r = 0.908, p < 0.001, angiopoietin-2 r = 0.983, p < 0.001 and HIF-1a r = 0.998, p < 0.001), and only weak or modest correlations with eGFR. Conclusions: This study suggests that endothelial dysfunction causing microcirculatory changes, linked to angiogenesis and hypoxia, may come early in the course of ADPKD and could be a key regulator of renal injury progression.

To intervene or not? A man with multidrug-resistant hypertension, endovascular abdominal aneurysm repair, bilateral renal artery stenosis and end-stage renal disease salvaged with renal artery stenting.

Abstract We report the case of a 69-year-old man with uncontrolled multidrug-resistant secondary hypertension following a 10 year history of endovascular abdominal aortic aneurysm repair, with suprarenal fixation and concurrent angioplasty with stenting of the left renal artery for atherosclerotic renal disease, and progressive chronic kidney disease. Renal scintigraphy revealed complete loss of the right kidney’s and severe reduction of the left kidney’s perfusion and function. Following recent evidence and consultation with vascular surgeons regarding the technical difficulties of any procedure, escalation of antihypertensive treatment was initially chosen. Careful drug adjustments significantly improved but did not fully control blood pressure (BP); further, the patient experienced an acute ischaemic stroke and renal function deterioration towards end-stage renal disease within a few months. At this point, revascularization of the left renal artery coupled with three haemodialysis sessions to remove contrast media was justified as rescue therapy against permanent renal replacement therapy. Successful intervention achieved an immediate BP reduction, with BP fully controlled, despite a  > 70% decrease in antihypertensive treatment, while renal function improved at 6 months from 11.5 to 22 ml/min/1.73 m2. Renal angioplasty confers undisputed benefits in BP control and nephroprotection, and should be offered without delay to patients with renovascular hypertension and/or ischaemic nephropathy.