Publications by authors named "Pantelis Sarafidis"

238 Publications

Accuracy of Peridialytic, Intradialytic, and Scheduled Interdialytic Recordings in Detecting Elevated Ambulatory Blood Pressure in Hemodialysis Patients.

Authors:
Pantelis Sarafidis Marieta P Theodorakopoulou Charalampos Loutradis Fotini Iatridi Marilena Alexandrou Antonios Karpetas Georgios Koutroumpas Vassilios Raptis Charles J Ferro Aikaterini Papagianni

Am J Kidney Dis 2021 Apr 12. Epub 2021 Apr 12.

Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Greece.

Rationale And Objective: Current recommendations suggest the use of ambulatory-BP-monitoring (ABPM) as the gold-standard for hypertension diagnosis and management in hemodialysis patients. This study assesses the accuracy of peridialytic, intradialytic, and scheduled interdialytic recordings in detecting abnormally elevated 44-h interdialytic BP.

Study Design: Diagnostic test study.

Settings And Participants: 242 Greek hemodialysis patients who successfully underwent ABPM.

Tests Compared: Ambulatory BP was used as reference to evaluate the accuracy of following BP metrics: pre- and post-dialysis, intradialytic, intradialytic plus pre/post-dialysis, and scheduled interdialytic BP at off-dialysis day at 8:00 am, 8:00 pm, and their average.

Outcome: 44-h ambulatory SBP/DBP ≥130/80 mmHg.

Results: 44-h SBP/DBP levels differed significantly from pre- and post-dialysis BP, but showed no or minor differences compared to the other BP metrics. Bland-Altman plots showed absence of systematic bias for all metrics, but large between-method difference and wider 95% limits of agreement for pre- and post-dialysis BP compared to intradialytic, intradialytic plus pre/post-dialysis and averaged scheduled interdialytic BP. The sensitivity/specificity and κ-statistic for diagnosing 44-h SBP≥130 mmHg were low for pre-dialysis (86.5%/38.6%, κ-statistic=0.27) and post-dialysis BP (63.1%/73.3%, κ-statistic=0.35), but better for intradialytic (77.3%/76.2%, κ-statistic=0.53), intradialytic plus pre/post-dialysis (76.6%/72.3%, κ-statistic=0.49), and scheduled interdialytic BP (87.9%/77.2%, κ-statistic=0.66). In ROC-analyses, the Areas-Under-the-Curve (AUC) of pre-dialysis (AUC 0.723) and post-dialysis SBP (AUC 0.746) were significantly lower than that of intradialytic (AUC 0.850), intradialytic plus pre/post-dialysis (AUC 0.850) and scheduled interdialytic SBP (AUC 0.917) (z-test, p<0.001 for all pairwise comparisons). Similar observations were made for DBP.

Limitations: Typical home BP data were not obtained and no assessment was obtained of reproducibility of examined metrics over time.

Conclusions: Intradialytic, intradialytic plus pre/post-dialysis, and scheduled interdialytic BP measurements were more accurate in detecting elevated 44-h BP than pre- and post-dialysis BP. Averaged intradialytic BP recordings or scheduled readings at the off-dialysis day appear to be promising approaches to the diagnosis of elevated BP in hemodialysis.
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http://dx.doi.org/10.1053/j.ajkd.2021.01.022DOI Listing
April 2021

Sex differences in the progression of kidney injury and risk of death in CKD patients: is different ambulatory blood pressure control the underlying cause?

Authors:
Pantelis Sarafidis Michel Burnier

Nephrol Dial Transplant 2021 Apr 12. Epub 2021 Apr 12.

Service of Nephrology and Hypertension, Lausanne University Hospital, Lausanne, Switzerland.

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http://dx.doi.org/10.1093/ndt/gfab115DOI Listing
April 2021

Associations of serum sclerostin and Dickkopf-related protein-1 proteins with future cardiovascular events and mortality in haemodialysis patients: a prospective cohort study.

Authors:
Eirini Stavrinou Pantelis A Sarafidis Charalampos Loutradis Evangelos Memmos Danai Faitatzidou Panagiotis Giamalis Charalampos Koumaras Asterios Karagiannis Aikaterini Papagianni

Clin Kidney J 2021 Apr 31;14(4):1165-1172. Epub 2020 Aug 31.

Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Background: Sclerostin and Dickkopf-related protein-1 (Dkk-1) proteins are inhibitors of the canonical Wnt/β-catenin bone pathway. Sclerostin but not Dkk-1 is associated with increased arterial stiffness. This study examined the prognostic significance of sclerostin and Dkk-1 levels for cardiovascular outcomes and mortality in haemodialysis (HD) patients.

Methods: Serum sclerostin and Dkk-1 levels were measured with enzyme-linked immunosorbent assay in 80 HD patients that were followed-up for a median of 45 months. Factors that could interfere with the association of sclerostin and Dkk-1 with outcomes [including carotid-femoral pulse wave velocity (PWV), parathyroid hormone (PTH), calcium-phosphate product and others] were assessed at baseline. The primary endpoint was a combination of all-cause death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, hospitalization for decompensated heart failure and new-onset atrial fibrillation. Secondary endpoints included cardiovascular and all-cause mortality.

Results: Cumulative freedom from the primary endpoint was significantly lower for higher tertiles of sclerostin (77.8, 69.2 and 40.7%; Tertiles 1-3, respectively; log-rank P = 0.004). The risk for the primary outcome gradually increased for higher sclerostin tertiles [Tertile 3: hazard ratio (HR) = 3.847, 95% confidence interval (CI) 1.502-9.851]. No significant association was evident between sclerostin and all-cause mortality, whereas higher sclerostin levels presented a trend towards higher risk for cardiovascular mortality. Dkk-1 levels exhibited no association with the risk of the primary or secondary endpoints. In stepwise Cox regression modelled analysis, sclerostin levels were associated with the primary outcome, independently of PTH, calcium-phosphate product, serum albumin, C-reactive protein and PWV levels (HR = 2.921, 95% CI 1.401-6.090; P = 0.004).

Conclusions: High sclerostin levels are associated with lower cumulative freedom and higher risk for a composite endpoint of cardiovascular events and mortality. Dkk-1 exhibited no association with the future risk of adverse outcomes.
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http://dx.doi.org/10.1093/ckj/sfaa069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023195PMC
April 2021

Renal tubular transport protein regulation in primary aldosteronism: can large-scale proteomic analysis offer a new insight?

Authors:
Konstantinos Stavropoulos Efstratios Kassimatis Michael Doumas Pantelis Sarafidis

J Hum Hypertens 2021 Apr 9. Epub 2021 Apr 9.

Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

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http://dx.doi.org/10.1038/s41371-021-00537-0DOI Listing
April 2021

Opportunistic screening for hypertension: what does it say about the true epidemiology?

Authors:
Ariadni Menti Natasa Kalpourtzi Magda Gavana Apostolos Vantarakis Paraskevi V Voulgari Christos Hadjichristodoulou Eugenia Gkaliagkousi Michael Doumas Rigas G Kalaitzidis Manolis S Kallistratos Argiro Karakosta Vasiliki Katsi Xenophon Krokidis Efstathios Manios Maria Marketou Angeliki Ntineri John A Papadakis Dimitrios Papadopoulos Pantelis Sarafidis Grigoris Trypsianis Michail Chatzopoulos Grigoris Chlouverakis Yannis Alamanos Pantelis Zebekakis Giota Touloumi George S Stergiou

J Hum Hypertens 2021 Apr 9. Epub 2021 Apr 9.

Hypertension Center STRIDE-7, National and Kapodistrian University of Athens, School of Medicine, Third Department of Medicine, Sotiria Hospital, Athens, Greece.

This study aimed to assess the reliability of opportunistic screening programs in estimating the prevalence, treatment, and control rate of hypertension in the general population. Two recent epidemiological surveys obtained data on hypertension in the adult general population in Greece. The EMENO (2013-2016) applied a multi-stage stratified random sampling method to collect nationwide data. The MMM (2019) collected data through opportunistic (voluntary) screening in five large cities. Hypertension was defined as blood pressure (BP) ≥ 140/90 mmHg (single occasion; average of 2nd-3rd measurement; electronic devices) and/or use of antihypertensive drugs. Data from a total of 10,426 adults were analyzed (EMENO 4,699; MMM 5,727). Mean age (SD) was 49.2 (18.6)/52.7 (16.6) years (EMENO/MMM, p < 0.001), men 48.6/46.5% (p < 0.05) and body mass index 28.2 (5.7)/27.1 (5.0) kg/m (p < 0.001). The prevalence of hypertension in ΕΜΕΝΟ/MMM was 39.6/41.6% (p < 0.05) and was higher in men (42.7/50.9%, p < 0.001) than in women (36.5/33.6%, p < 0.05). Among hypertensive subjects, unaware were 31.8/21.3% (EMENO/MMM, p < 0.001), aware untreated 2.7/5.6% (p < 0.001), treated uncontrolled 35.1/24.8% (p < 0.001), and treated controlled 30.5/48.3% (p < 0.001). In conclusion, the prevalence of hypertension was similar with random sampling (EMENO) and opportunistic screening (MMM). However, opportunistic screening underestimated the prevalence of undiagnosed hypertension and overestimated the rate of hypertension treatment and control. Thus, random sampling national epidemiological studies are necessary for assessing the epidemiology of hypertension. Screening programs are useful for increasing awareness of hypertension in the general population, yet the generalization of such findings should be interpreted with caution.
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http://dx.doi.org/10.1038/s41371-021-00532-5DOI Listing
April 2021

Acute kidney injury is more common in men than women after accounting for socioeconomic status, ethnicity, alcohol intake and smoking history.

Authors:
Charalampos Loutradis Luke Pickup Jonathan P Law Indranil Dasgupta Jonathan N Townend Paul Cockwell Adnan Sharif Pantelis Sarafidis Charles J Ferro

Biol Sex Differ 2021 Apr 8;12(1):30. Epub 2021 Apr 8.

Department of Renal Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2GW, UK.

Background: The association of several comorbidities, including diabetes mellitus, hypertension, cardiovascular disease, heart failure and chronic kidney or liver disease, with acute kidney injury (AKI) is well established. Evidence on the effect of sex and socioeconomic factors are scarce. This study was designed to examine the association of sex and socioeconomic factors with AKI and AKI-related mortality and further to evaluate the additional relationship with other possible risk factors for AKI occurrence.

Methods: We included 3534 patients (1878 males with mean age 61.1 ± 17.7 and 1656 females 1656 with mean age 60.3 ± 20.0 years) admitted to Queen Elizabeth or Heartlands Hospitals, Birmingham, between October 2013 and January 2016. Patients were prospectively followed-up for a median 47.70 [IQR, 18.20] months. Study-endpoints were incidence of AKI, based on KDIGO-AKI Guidelines, and all-cause mortality. Data acquisition was automated, and information on mortality was collected from the Hospital Episode Statistics and Office of National Statistics. Socioeconomic status was evaluated with the Index of Multiple Deprivation (IMD).

Results: Incidence of AKI was higher in men compared to women (11.3% vs 7.1%; P < 0.001). Model regression analysis revealed significant association of male sex with higher AKI risk (OR, 1.659; 95% CI, 1.311-2.099; P < 0.001); this association remained significant after adjustment for age, eGFR, IMD, smoking, alcohol consumption, ethnicity, existing comorbidities and treatment (OR, 1.599; 95% CI, 1.215-2.103; P = 0.001). All-cause mortality was higher in patients with compared to those without AKI. Males with AKI had higher mortality rates in the first 6-month and 1-year periods after the index AKI event. The association of male sex with mortality was independent of socioeconomic factors but was not statistically significant after adjustment for existing comorbidities.

Conclusions: Men are at higher risk of AKI and this association is independent from existing risk factors for AKI. The association between male sex and AKI-related mortality was not independent from existing comorbidities. A better understanding of factors associated with AKI may help accurately identify high-risk patients.
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http://dx.doi.org/10.1186/s13293-021-00373-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034098PMC
April 2021

Vascular endothelial injury assessed with functional techniques in systemic sclerosis patients with pulmonary arterial hypertension versus systemic sclerosis patients without pulmonary arterial hypertension: a systematic review and meta-analysis.

Authors:
Marieta P Theodorakopoulou Ioanna Minopoulou Pantelis Sarafidis Vassilios Kamperidis Christodoulos Papadopoulos Theodoros Dimitroulas Afroditi K Boutou

Rheumatol Int 2021 Apr 8. Epub 2021 Apr 8.

Department of Respiratory Medicine, G. Papanikolaou Hospital, Thessaloniki, Greece.

Microvascular dysfunction is one of the hallmarks of systemic sclerosis (SSc). The presence of pulmonary-arterial-hypertension (PAH) in SSc-patients is associated with poor prognosis. This is a systematic review and meta-analysis of studies assessing microvascular and endothelial injury with functional techniques in SSc-patients with PAH (SSc-PAH) compared to those without PAH (SSc-non-PAH) (PROSPERO: CRD42021236212). Literature search involved PubMed, the-Cochrane-Library, Web-of-Science, Scopus and manual search of article references. Studies assessing microvascular function by all available functional methods were considered eligible. Preclinical studies and studies using structural nailfold-videocapillaroscopy or biomarkers were excluded. Newcastle-Ottawa-Scale (NOS) was applied to evaluate the quality of retrieved studies. From a total of 602 retrieved articles, four studies (n = 159 participants) were included in meta-analysis; three studies were of high quality (NOS ≥ 7). In pooled analysis, a marginally significant impaired microvascular function was observed in SSc-PAH compared to SSc-non-PAH patients [SMD - 0.71, 95% CI (- 1.53, 0.12)], with significant between-study heterogeneity (I = 80%, p = 0.002). Among the studies examining endothelium-dependent and -independent vasodilation with LDF-iontophoresis, SSc-PAH subjects had significantly impaired endothelium-dependent-vasodilation [Ach-stimulated %change WMD - 216.79, 95% CI (- 337.87, - 95.71), I = 0%, p = 0.40], but no significant differences in endothelium-independent-vasodilation [SNP-stimulated %change WMD 90.84, 95% CI (- 82.52, 264.19), I = 44%, p = 0.18] compared with SSc-non-PAH subjects. In sensitivity analysis including only studies where SSc-PAH patients were diagnosed by right-heart-catheterization, a borderline difference between the two groups was noted [SMD - 1.09, 95% CI (- 2.30, 0.13), I = 82%, p = 0.004]. SSc-PAH patients showed marginally impaired microvascular function in the pooled analysis, as well as impaired endothelium-dependent-vasodilation in subgroup analysis compared with SSc-non-PAH patients. Vascular endothelial dysfunction could be involved in high cardiovascular risk of patients with SSc and PAH.
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http://dx.doi.org/10.1007/s00296-021-04850-2DOI Listing
April 2021

Cardiopulmonary exercise testing (CPET) in patients with end-stage kidney disease (ESKD): principles, methodology and clinical applications of the optimal tool for exercise tolerance evaluation.

Authors:
Eva Pella Afroditi Boutou Aristi Boulmpou Christodoulos E Papadopoulos Aikaterini Papagianni Pantelis Sarafidis

Nephrol Dial Transplant 2021 Apr 6. Epub 2021 Apr 6.

Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Greece.

Chronic kidney disease (CKD), especially end-stage kidney disease (ESKD), is associated with increased risk for cardiovascular events and all-cause mortality. Exercise intolerance as well as reduced cardiovascular reserve are extremely common in patients with CKD. Cardiopulmonary exercise testing (CPET) is a non-invasive, dynamic technique that provides an integrative evaluation of cardiovascular, pulmonary, neuropsychological and metabolic function during maximal or submaximal exercise, allowing the evaluation of functional reserves of these systems. This assessment is based on the principle that system failure typically occurs when the system is under stress and, thus, CPET is currently considered to be the gold-standard for identifying exercise limitation and differentiating its causes. It has been widely used in several medical fields for risk stratification, clinical evaluation and other applications but its use in everyday practice for CKD patients is scarce. This article describes the basic principles and methodology of CPET and provides an overview of important studies that utilized CPET in patients with ESKD, in an effort to increase awareness of CPET capabilities among practicing nephrologists.
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http://dx.doi.org/10.1093/ndt/gfab150DOI Listing
April 2021

Cardiovascular Protection With Sodium-Glucose Cotransporter-2 Inhibitors and Mineralocorticoid Receptor Antagonists in Chronic Kidney Disease: A Milestone Achieved.

Authors:
Pantelis Sarafidis Christodoulos E Papadopoulos Vasilios Kamperidis George Giannakoulas Michael Doumas

Hypertension 2021 May 29;77(5):1442-1455. Epub 2021 Mar 29.

Second Propaedeutic Department of Internal Medicine (M.D.), Aristotle University of Thessaloniki, Greece.

Chronic kidney disease (CKD) and cardiovascular disease are intimately linked. They share major risk factors, including age, hypertension, and diabetes, and common pathogenetic mechanisms. Furthermore, reduced renal function and kidney injury documented with albuminuria are independent risk factors for cardiovascular events and mortality. In major renal outcome trials and subsequent meta-analyses in patients with CKD, ACE (angiotensin-converting enzyme) inhibitors and ARBs (angiotensin II receptor blockers) were shown to effectively retard CKD progression but not to significantly reduce cardiovascular events or mortality. Thus, a high residual risk for cardiovascular disease progression under standard-of-care treatment is still present for patients with CKD. In contrast to the above, several outcome trials with SGLT-2 (sodium-glucose cotransporter-2) inhibitors and MRAs (mineralocorticoid receptor antagonists) clearly suggest that these agents, apart from nephroprotection, offer important cardioprotection in this population. This article discusses existing evidence on the effects of SGLT-2 inhibitors and MRAs on cardiovascular outcomes in patients with CKD that open new roads in cardiovascular protection of this heavily burdened population.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17005DOI Listing
May 2021

Εndothelial and microvascular function in CKD: Evaluation methods and associations with outcomes.

Authors:
Marieta P Theodorakopoulou Konstantina Dipla Andreas Zafeiridis Pantelis Sarafidis

Eur J Clin Invest 2021 Mar 27:e13557. Epub 2021 Mar 27.

Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Background: Cardiovascular disease is the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Endothelial dysfunction, the hallmark of atherosclerosis, is suggested to be involved pathogenetically in cardiovascular and renal disease progression in these patients.

Methods: This is a narrative review presenting the techniques and markers used for assessment of microvascular and endothelial function in patients with CKD and discussing findings of the relevant studies on the associations of endothelial dysfunction with co-morbid conditions and outcomes in this population.

Results: Venous Occlusion Plethysmography was the first method to evaluate microvascular function; subsequently, several relevant techniques have been developed and used in patients with CKD, including brachial Flow-Mediated Dilatation, and more recently, Near-Infrared Spectroscopy and Laser Speckle Contrast Analysis. Furthermore, several circulating biomarkers are commonly used in clinical research. Studies assessing endothelial function using the above techniques and biomarkers suggest that endothelial dysfunction occurs early in CKD and contributes to the target organ damage, cardiovascular events, death and progression towards end-stage kidney disease.

Conclusions: Older and newer functional methods and several biomarkers have assessed endothelial dysfunction in CKD; accumulated evidence supports an association of endothelial dysfunction with outcomes. Future research with new, non-invasive and easily applicable methods could further delineate the role of endothelial dysfunction on cardiovascular and renal disease progression in patients with CKD.
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http://dx.doi.org/10.1111/eci.13557DOI Listing
March 2021

Blood pressure monitoring in kidney transplantation: a systematic review on hypertension and target organ damage.

Authors:
Anna Pisano Francesca Mallamaci Graziella D'Arrigo Davide Bolignano Gregoire Wuerzner Alberto Ortiz Michel Burnier Nada Kanaan Pantelis Sarafidis Alexandre Persu Charles J Ferro Charalampos Loutradis Ioannis N Boletis Gérard London Jean-Michel Halimi Bénédicte Sautenet Patrick Rossignol Liffert Vogt Carmine Zoccali

Nephrol Dial Transplant 2021 Mar 25. Epub 2021 Mar 25.

CNR-Institute of Clinical Physiology; Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Reggio Calabria, Italy.

Background: Sparse studies show that ambulatory blood pressure monitoring (ABPM) is superior to office BP (oBP) measurements to predict target organ damage and cardiovascular (CV) events in kidney transplant recipients (KTRs). We performed a systematic review aimed at determining the potential associations between BP recordings by different methods and renal and CV outcomes in this population.

Methods: Major medical databases were searched for studies enrolling adult KTRs undergoing 24h ABPM compared to office or home BP measurements. Main outcomes were: associations between different BP recordings and renal and CV outcomes. Additionally, any association between the circadian BP pattern (dipping/non-dipping status) and outcomes was assessed.

Results: Twenty-two studies (2078 participants) were reviewed. Amongst 12 studies collecting data on renal endpoints, ten studies found that BP assessed by ABPM was a stronger predictor of renal function decline, assessed by serum creatinine (SCr) and/or creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR), than traditional office measurements. Twelve studies analyzed the relation between different BP recordings and CV target organ damages and reported robust correlations between echocardiographic abnormalities [i.e. left ventricular mass index (LVM/LVMI)] and 24h ABPM, but not with office BPs. Furthermore, 24h ABPM correlated better than oBP with markers of vascular damage, such as carotid intima-media thickness (IMT), diffuse thickening, and endothelial dysfunction. Additionally, abnormal circadian BP pattern (non-dippers and reverse dippers) identified a group of kidney recipients at risk for kidney function loss and CV abnormalities.

Conclusions: In our systematic review, ABPM reflected target organ damage more closely than oBP in KTRs. Furthermore, altered circadian BP profile associated with renal and CV target organ damages.
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http://dx.doi.org/10.1093/ndt/gfab076DOI Listing
March 2021

Renin-angiotensin system blockade in patients with chronic kidney disease: benefits, problems in everyday clinical use, and open questions for advanced renal dysfunction.

Authors:
Charalampos Loutradis Anna Price Charles J Ferro Pantelis Sarafidis

J Hum Hypertens 2021 Mar 2. Epub 2021 Mar 2.

Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Management of hypertension and albuminuria are considered among the primary goals of treatment to slow the progression of chronic kidney disease (CKD). Renin-angiotensin system (RAS) blockers, i.e., angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are the main drugs to achieve these goals. Seminal studies have showed that RAS blockers present significant renoprotective effects in CKD patients with very high albuminuria. In post hoc analyses of such trials, these renoprotective effects appeared more robust in patients with more advanced CKD. However, randomized trials specifically addressing whether RAS blockers should be initiated or maintained in patients with advanced CKD are scarce and do not include subjects with normoalbuminuria, thus, many clinicians are unconvinced for the beneficial effects of RAS blockade in these patients. Further, the fear of hyperkalemia or acute renal decline is another factor due to which RAS blockers are usually underprescribed and are easily discontinued in patients with more advanced CKD; i.e., those in Stages 4 and 5. This review summarizes evidence from the literature regarding the use of RAS blockers in patients with advanced CKD.
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http://dx.doi.org/10.1038/s41371-021-00504-9DOI Listing
March 2021

The effect of admission and pre-admission serum creatinine as baseline to assess incidence and outcomes of acute kidney injury in acute medical admissions.

Authors:
Luke Pickup Charalampos Loutradis Jonathan P Law Julia J Arnold Indranil Dasgupta Pantelis Sarafidis Jonathan N Townend Paul Cockwell Charles J Ferro

Nephrol Dial Transplant 2021 Jan 17. Epub 2021 Jan 17.

Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, Birmingham, UK.

Background: Acute kidney injury (AKI) in hospital-admitted patients is a common complication associated with increased mortality. The diagnosis of AKI relies on the ascertainment of peak increase in serum creatinine (SCr). This study evaluated the incidence of AKI using the increase from mean 7-365 days pre-admission (AKIpre) and admission (AKIadm) SCr levels, and examined the associations of AKI and changes in SCr levels with all-cause mortality.

Methods: A total of 2436 patients admitted to a tertiary hospital were recruited and followed-up for a median of 47.70 (interquartile range 18.20) months. AKI incidence and severity were defined according to the Kidney Disease: Improving Global Outcomes-AKI Guidelines. Follow-up data were collected from the Hospital Episode Statistics and Office of National Statistics. Mortality was evaluated during a short- (30 days), mid- (1 year) and long-term (4 years) period.

Results: No difference in the AKI rates using AKIpre and AKIadm (12.5% versus 12.2%; P = 0.695) or in the AKI severity (P = 0.261) was evident. Agreement between the two definitions was modest (Kappa-statistic = 0.596, P < 0.001). Patients with AKIpre or AKIadm had increased all-cause mortality compared with those without AKI during all follow-up periods. In fully adjusted regression analysis, AKIpre [hazard ratio (HR) = 2.226, 95% confidence interval (CI) 1.140-4.347; P = 0.027] and AKIadm (HR = 2.105, 95% CI 1.090-4.064; P = 0.027) remained associated with 30-day mortality. Results for the 1- and 4-year periods were similar. Increases of >4.00 μmol/L and >6.06% from pre-admission or >6.00 μmol/L and >17.24% from admission SCr levels presented increased mortality risk during follow-up.

Conclusions: Use of admission or pre-admission SCr provides similar incidence rates, but they diagnose different sets of patients. Even minor increases in SCr, below those required for the classification of AKI, were associated with increased mortality. These findings can help the clinicians to identify patients at higher risk for adverse outcomes.
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http://dx.doi.org/10.1093/ndt/gfaa333DOI Listing
January 2021

Sodium--glucose co-transporter-2 inhibitors for patients with diabetic and nondiabetic chronic kidney disease: a new era has already begun.

Authors:
Pantelis Sarafidis Alberto Ortiz Charles J Ferro Jean-Michel Halimi Reinhold Kreutz Francesca Mallamaci Giuseppe Mancia Christoph Wanner

J Hypertens 2021 Jan 11. Epub 2021 Jan 11.

Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Greece IIS-Fundacion Jimenez Diaz, School of Medicine, University Autonoma of Madrid, FRIAT and REDINREN, Madrid, Spain Department of Renal Medicine, University Hospitals Birmingham, Edgbaston, Birmingham, UK Service de Nephrologie-HTA, dialyses, transplantation rénale, CHRU de Tours-Hospital Bretonneau, Tours, France Institute of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany CNR-Institute of Clinical Physiology, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Reggio Calabria Università Milano-Bicocca, Milan and Policlinico di Monza, Monza, Italy Division of Nephrology, Wuerzburg University Clinic, Würzburg, Germany.

Chronic kidney disease (CKD) is a major issue of public health. Hypertension control and use of renin--angiotensin system (RAS) blockers are the cornerstones of treatment for CKD of any cause. However, even under optimal RAS blockade, many individuals will progress towards more advanced CKD. Within the past few years, evidence from cardiovascular outcome trials with sodium--glucose co-transporter-2 (SGLT-2) inhibitors clearly suggested that these agents substantially delay CKD progression in patients with diabetes mellitus on top of standard-of-care treatment. The Canagliflozin-and-Renal-Events-in-Diabetes-with-Established-Nephropathy-Clinical-Evaluation (CREDENCE) study, showed that canagliflozin substantially reduced the risk of doubling of SCr, end-stage kidney disease (ESKD), or death from renal or cardiovascular causes in 4401 patients with diabetic CKD compared with placebo (hazard ratio 0.70; 95% CI 0.59-0.82). Recently, the Study-to-Evaluate-the-Effect-of-Dapagliflozin-on-Renal-Outcomes-and-Cardiovascular-Mortality-in-Patients-With-Chronic-Kidney-Disease (DAPA-CKD), including 2510 patients with diabetic and 1803 with nondiabetic CKD, also showed an impressive reduction in the risk of ≥50% decline in eGFR, ESKD, or death from renal or cardiovascular causes (HR 0.61; 95% CI 0.51-0.72). The benefit was similar for patients with diabetic and nondiabetic CKD, including patients with glomerulonephritides. Following this conclusive evidence, relevant guidelines should accommodate their recommendations to implement treatment with SGLT-2 inhibitors for patients with diabetic and nondiabetic CKD.
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http://dx.doi.org/10.1097/HJH.0000000000002776DOI Listing
January 2021

Effects of intradialytic exercise on physical performance and cardiopulmonary fitness: promises that need to be confirmed.

Authors:
Marieta P Theodorakopoulou Afroditi K Boutou Pantelis Sarafidis

Int Urol Nephrol 2021 Jan 1. Epub 2021 Jan 1.

Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

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http://dx.doi.org/10.1007/s11255-020-02764-9DOI Listing
January 2021

Can the assessment of ultrasound lung water in haemodialysis patients be simplified?

Authors:
Claudia Torino Rocco Tripepi Charalampos Loutradis Pantelis Sarafidis Giovanni Tripepi Francesca Mallamaci Carmine Zoccali

Nephrol Dial Transplant 2020 Dec 29. Epub 2020 Dec 29.

CNR-IFC, Clinical Epidemiology and Pathophysiology of Hypertension and Renal Diseases Unit, Ospedali Riuniti, Reggio Calabria, Italy.

Background: Lung ultrasound (US) reliably estimates lung water and it is increasingly applied in clinical practice in dialysis patients. A semi-quantitative US score summing up the US-B lines (an equivalent of B lines in the standard chest X-ray) at 28 sites in the intercostal spaces (Jambrik et al. Usefulness of ultrasound lung comets as a non-radiologic sign of extravascular lung water. Am J Cardiol 2004; 93: 1265-1270) is the most used score.

Methods: We compared the prognostic performance for death, and cardiovascular (CV) events of the 28-sites US score with a score restricted to eight sites in a cohort of 303 haemodialysis (HD) patients.

Results: The 8- and the 28-sites scores were highly inter-related (Spearman's ρ = 0.93, P < 0.001), and their concordance index was fairly good (k = 0.79, 95% confidence interval 0.74-0.84). During a mean follow-up of 3 years, 112 patients died, and 129 experienced a CV event. At univariate and multivariate analysis, both scores were associated with mortality (P ≤ 0.01) and CV events (P ≤ 0.05). The explained variances (R2) for death and CV events of the 28-sites score in multivariate models including major risk factors for these outcomes in the end-stage kidney disease (ESKD) population were 3.9 and 2.2%, and those of the 8-sites score were 3.1 and 2.4%, respectively. The median time needed to perform the examination was 3.05 min [interquartile range (IQR) 2.22-5.00 min] for the 28-sites score and 1.35 min (IQR 1.16-2.00 min) for the 8-sites score.

Conclusion: The 8-sites score is tightly related to the classical Jambrik 28-sites score and this score holds an almost identical predictive power to the reference score. Even though the 28-sites score can be completed just in ∼3 min, the 8-sites score requires only ∼1.30 min, and it is, therefore, better suited for application in everyday clinical practice in HD units.
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http://dx.doi.org/10.1093/ndt/gfaa285DOI Listing
December 2020

Nocturnal dipping profile in chronic kidney disease: Searching for underlying mechanisms in order to prevent adverse events.

Authors:
Marieta Theodorakopoulou Konstantina Dipla Andreas Zafeiridis Pantelis Sarafidis

Physiol Rep 2021 Jan;8(24):e14665

Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

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http://dx.doi.org/10.14814/phy2.14665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757368PMC
January 2021

Assessment of Endothelial and Microvascular Function in CKD: Older and Newer Techniques, Associated Risk Factors, and Relations with Outcomes.

Authors:
Marieta P Theodorakopoulou Maria Schoina Pantelis Sarafidis

Am J Nephrol 2020 11;51(12):931-949. Epub 2020 Dec 11.

Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece,

Background: Endothelium is the inner cellular lining of the vessels that modulates multiple biological processes including vasomotor tone, permeability, inflammatory responses, hemostasis, and angiogenesis. Endothelial dysfunction, the basis of atherosclerosis, is characterized by an imbalance between endothelium-derived relaxing factors and endothelium-derived contracting factors.

Summary: Starting from the semi-invasive venous occlusion plethysmography, several functional techniques have been developed to evaluate microvascular function and subsequently used in patients with CKD. Flow-mediated dilatation of the forearm is considered to be the "gold standard," while in the last years, novel, noninvasive methods such as laser speckle contrast imaging and near-infrared spectroscopy are scarcely used. Moreover, several circulating biomarkers of endothelial function have been used in studies in CKD patients. This review summarizes available functional methods and biochemical markers for the assessment of endothelial and microvascular function in CKD and discusses existing evidence on their associations with comorbid conditions and outcomes in this population. Key Messages: Accumulated evidence suggests that endothelial dysfunction occurs early in CKD and is associated with target organ damage, progression of renal injury, cardiovascular events, and mortality. Novel methods evaluating microvascular function can offer a detailed, real-time assessment of underlying phenomena and should be increasingly used to shed more light on the role of endothelial dysfunction on cardiovascular and renal disease progression in CKD.
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http://dx.doi.org/10.1159/000512263DOI Listing
December 2020

Dapagliflozin Does Not Affect Short-Term Blood Pressure Variability in Patients With Type 2 Diabetes Mellitus.

Authors:
Eirini Papadopoulou Marieta P Theodorakopoulou Charalampos Loutradis Georgios Tzanis Glykeria Tzatzagou Kalliopi Kotsa Ioanna Zografou Apostolos Tsapas Asterios Karagiannis Pantelis Sarafidis

Am J Hypertens 2021 Apr;34(4):404-413

Department of Nephrology, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece.

Background: Increased blood pressure variability (BPV) is associated with increased cardiovascular and all-cause mortality in patients with type-2 diabetes mellitus (T2DM). Sodium-glucose co-transporter 2 (SGLT-2) inhibitors decrease the incidence of cardiovascular events, renal events, and death in this population. This study aimed to evaluate the effect of dapagliflozin on short-term BPV in patients with T2DM.

Methods: This is a secondary analysis of a double-blind, randomized, placebo-controlled trial in 85 patients with T2DM. Subjects were randomized to dapagliflozin 10 mg/day or placebo for 12 weeks. All participants underwent 24-hour ambulatory blood pressure (BP) monitoring with Mobil-O-Graph-NG device at baseline and study-end. SD, weighted SD (wSD), coefficient of variation, average real variability (ARV), and variation independent of mean were calculated for the 24-hour, daytime and nighttime periods.

Results: Dapagliflozin reduced 24-hour brachial BP compared with placebo. From baseline to study-end 24-hour brachial BPV indexes did not change with dapagliflozin (SBP-ARV: 11.51 ± 3.45 vs. 11.05 ± 3.35; P = 0.326, SBP-wSD: 13.59 ± 3.60 vs. 13.48 ± 3.33; P = 0.811) or placebo (SBP-ARV: 11.47 ± 3.63 vs. 11.05 ± 3.00; P = 0.388, SBP-wSD: 13.85 ± 4.38 vs. 13.97 ± 3.87; P = 0.308). Similarly, no significant changes in BPV indexes for daytime and nighttime were observed in any group. At study-end, no between-group differences were observed for any BPV index. Deltas (Δ) of all indexes during follow-up were minimal and not different between groups (SBP-wSD: dapagliflozin: -0.11 ± 3.05 vs. placebo: 0.12 ± 4.20; P = 0.227).

Conclusions: This study is the first to evaluate the effects of an SGLT-2 inhibitor on short-term BPV in T2DM, showing no effect of dapagliflozin on all BPV indexes studied.

Clinical Trials Registration: Trial Number NCT02887677.
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http://dx.doi.org/10.1093/ajh/hpaa207DOI Listing
April 2021

Proton Pump Inhibitors, Histamine-2 Receptor Antagonists, and the Risk of Kidney Stones: Negligible or Not?

Authors:
Eva Pella Maria Chalkidou Pantelis Sarafidis

Clin Gastroenterol Hepatol 2021 Mar 26;19(3):624-625. Epub 2020 Nov 26.

Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

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http://dx.doi.org/10.1016/j.cgh.2020.04.079DOI Listing
March 2021

Serum Copeptin, NLPR3, and suPAR Levels among Patients with Autosomal-Dominant Polycystic Kidney Disease with and without Impaired Renal Function.

Authors:
Vasileios Raptis Charalampos Loutradis Afroditi K Boutou Danai Faitatzidou Athanasios Sioulis Charles J Ferro Aikaterini Papagianni Pantelis A Sarafidis

Cardiorenal Med 2020 17;10(6):440-451. Epub 2020 Nov 17.

Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece,

Background: The pathophysiology of renal disease progression in autosomal-dominant polycystic kidney disease (ADPKD) involves not only cystogenesis but also endothelial dysfunction, leading to the activation of inflammatory and fibrotic pathways. This study evaluated the levels of biomarkers related to osmoregulation, immune system activation, and tubular injury in ADPKD patients with impaired or preserved renal function.

Methods: This study included 26 ADPKD patients with modestly impaired renal function (estimated glomerular filtration rate [eGFR] 45-70 mL/min/1.73 m2; Group A), 26 age- and sex-matched ADPKD patients with relatively preserved renal function (eGFR >70 mL/min/1.73 m2; Group B), and 26 age- and sex-matched controls (Group C). Serum levels of copeptin, the inflammasome nucleotide-binding and oligomerization domain-like receptors pyrin domain-containing protein 3 (NLRP3), and soluble urokinase-type plasminogen activator receptor (suPAR) were measured with ELISA techniques.

Results: Patients in Group A had higher levels of copeptin (median [interquartile range]: 50.44 [334.85] pg/mL), NLRP3 (5.86 [3.89] ng/mL), and suPAR (390.05 [476.53] pg/mL) compared to patients in Group B (32.38 [58.33], p = 0.042; 2.42 [1.96], p < 0.001; and 313.78 [178.85], p = 0.035, respectively) and Group C (6.75 [6.43]; 1.09 [0.56]; and 198.30 [28.53], respectively; p < 0.001 for all comparisons). Levels of all studied markers were also significantly higher in Group B patients compared to controls (p < 0.001), despite having similar eGFR. In patients with ADPKD, all studied biomarkers were correlated positively with asymmetric-dimethylarginine (ADMA) and endocan levels, and negatively with eGFR. ADMA and endocan levels were the only parameters independently associated with increased copeptin levels.

Conclusions: This study showed that ADPKD patients with impaired and preserved renal function had higher copeptin, NLRP3, and suPAR levels than controls. Such findings support that cystogenesis and inflammation are associated with endothelial dysfunction, even in the early stages of ADKPD.
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http://dx.doi.org/10.1159/000510834DOI Listing
November 2020

Dapagliflozin decreases ambulatory central blood pressure and pulse wave velocity in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial.

Authors:
Eirini Papadopoulou Charalampos Loutradis Glykeria Tzatzagou Kalliopi Kotsa Ioanna Zografou Ioanna Minopoulou Marietta P Theodorakopoulou Apostolos Tsapas Asterios Karagiannis Pantelis Sarafidis

J Hypertens 2021 Apr;39(4):749-758

Department of Nephrology.

Objectives: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors reduce the incidence of heart failure and death in patients with type-2 diabetes mellitus. Arterial stiffness is a prominent risk factor for heart failure and overall mortality. The aim of this study was to evaluate the effects of dapagliflozin on ambulatory brachial and central blood pressure (BP) levels and arterial stiffness parameters in patients with type-2 diabetes mellitus.

Methods: This is a double-blind, randomized, placebo-controlled clinical trial including 85 adult patients with type-2 diabetes mellitus on monotherapy or combination therapy with two of: metformin, sulphonylurea, DPP-4 inhibitor, or insulin. Patients were randomized in a 1 : 1 ratio to oral dapagliflozin 10 mg per day or placebo for 12 weeks. Study participants underwent 24-h ambulatory BP monitoring with the Mobil-O-Graph NG monitor at baseline and study-end.

Results: Baseline demographic, clinical and laboratory parameters were similar in the two groups. During follow-up, 24-h brachial SBP/DBP (129.0 ± 12.6/77.3 ± 7.3 vs. 123.2 ± 12.4/75.1 ± 6.4 mmHg; P < 0.001/P = 0.008) and central SBP/DBP (117.4 ± 10.5/78.9 ± 7.3 vs. 113.3 ± 8.8/77.3 ± 6.5 mmHg; P = 0.002/P = 0.047) significantly decreased in dapagliflozin but not in the placebo group. Corresponding reductions of 24-h brachial SBP (-5.8 ± 9.5 vs. -0.1 ± 8.7, P = 0.005) and central SBP (-4.1 ± 8.0 vs. -0.7 ± 7.8; P = 0.046) were greater with dapagliflozin than placebo. Twenty-four-hour heart-rate adjusted augmentation index significantly decreased with dapagliflozin and insignificantly with placebo. Importantly, there was a significant difference in change of estimated 24-h PWV (-0.16 ± 0.32 vs. 0.02 ± 0.27; P = 0.007) favoring dapagliflozin. In generalized linear mixed models including 24-h brachial SBP as a random covariate, the adjusted marginal means of delta 24-h central SBP and delta 24-h PWV were not significantly different between-groups.

Conclusion: Treatment with dapagliflozin significantly reduces ambulatory brachial and central BP levels and PWV in patients with type-2 diabetes mellitus. Improvement in these parameters may substantially contribute to the cardiovascular benefits of SGLT-2 inhibitors.
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http://dx.doi.org/10.1097/HJH.0000000000002690DOI Listing
April 2021

Volume overload in hemodialysis: diagnosis, cardiovascular consequences, and management.

Authors:
Charalampos Loutradis Pantelis A Sarafidis Charles J Ferro Carmine Zoccali

Nephrol Dial Transplant 2020 Nov 13. Epub 2020 Nov 13.

CNR-IFC Clinical Epidemiology of Renal Diseases and Hypertension, Reggio Calabria, Italy.

Volume overload in haemodialysis (HD) patients associates with hypertension and cardiac dysfunction and is a major risk factor for all-cause and cardiovascular mortality in this population. The diagnosis of volume excess and estimation of dry weight is based largely on clinical criteria and has a notoriously poor diagnostic accuracy. The search for accurate and objective methods to evaluate dry weight and to diagnose subclinical volume overload has been intensively pursued over the last 3 decades. Most methods have not been tested in appropriate clinical trials and their usefulness in clinical practice remains uncertain, except for bioimpedance spectroscopy and lung ultrasound (US). Bioimpedance spectroscopy is possibly the most widely used method to subjectively quantify fluid distributions over body compartments and produces reliable and reproducible results. Lung US provides reliable estimates of extravascular water in the lung, a critical parameter of the central circulation that in large part reflects the left ventricular end-diastolic pressure. To maximize cardiovascular tolerance, fluid removal in volume-expanded HD patients should be gradual and distributed over a sufficiently long time window. This review summarizes current knowledge about the diagnosis, prognosis and treatment of volume overload in HD patients.
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http://dx.doi.org/10.1093/ndt/gfaa182DOI Listing
November 2020

Comparison of ambulatory central hemodynamics and arterial stiffness in patients with diabetic and non-diabetic CKD.

Authors:
Charalampos Loutradis Maria Schoina Theodoros Dimitroulas Michael Doumas Alexandros Garyfallos Asterios Karagiannis Aikaterini Papagianni Pantelis Sarafidis

J Clin Hypertens (Greenwich) 2020 12 30;22(12):2239-2249. Epub 2020 Oct 30.

Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Increased arterial stiffness is independently associated with renal function decline in patients with diabetes mellitus (DM). Whether DM has additional deleterious effects on central hemodynamics and arterial stiffness in chronic kidney disease (CKD) patients is yet unknown. This study aimed to compare ambulatory central BP, arterial stiffness parameters, and trajectories between patients with diabetic and non-diabetic CKD. This study examined 48 diabetic and 48 non-diabetic adult patients (>18 years) with CKD (eGFR: <90 and ≥15 ml/min/1.73 m ), matched in a 1:1 ratio for age, sex, and eGFR within CKD stages (2, 3a, 3b and 4). All patients underwent 24-h ABPM with the Mobil-O-Graph device. Parameters of central hemodynamics [central systolic (cSBP) and diastolic blood pressure (cDBP), pulse pressure (PP)], wave reflection [augmentation index (AIx), and pressure (AP)] and pulse wave velocity (PWV) were estimated from the 24-h recordings. Diabetic CKD patients had higher 24-h cSBP (118.57 ± 10.05 vs. 111.59 ± 9.46, P = .001) and 24-h cPP (41.48 ± 6.80 vs. 35.25 ± 6.98, P < .001) but similar 24-h cDBP (77.09 ± 8.14 vs. 76.34 ± 6.75 mmHg, P = .625) levels compared to patients with non-diabetic CKD. During day- and nighttime periods, cSBP and cPP levels were higher in diabetics compared to non-diabetics. 24-h PWV (10.10 ± 1.62 vs. 9.61 ± 1.80 m/s, P = .165) was numerically higher in patients with DM, but no between-group differences were noted in augmentation pressure and index. In multivariate analysis, DM, female gender, and peripheral SBP were independently associated with higher cPP levels. Patients with diabetic CKD have higher ambulatory cSBP and increased arterial stiffness, as indicated by higher ambulatory cPP. These finding suggest that DM is a factor independently contributing to the adverse macrocirculatory profile of CKD patients.
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http://dx.doi.org/10.1111/jch.14089DOI Listing
December 2020

SGLT2 inhibitors for non-diabetic kidney disease: drugs to treat CKD that also improve glycaemia.

Authors:
Beatriz Fernandez-Fernandez Pantelis Sarafidis Mehmet Kanbay Juan F Navarro-González María José Soler Jose Luis Górriz Alberto Ortiz

Clin Kidney J 2020 Oct 9;13(5):728-733. Epub 2020 Oct 9.

IIS-Fundacion Jimenez Diaz and School of Medicine, Universidad Autónoma de Madrid, Grupo Español de Estudio de la Nefropatia Diabetica, Madrid, Spain.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors decreased cardiovascular (CV) events and improved renal outcomes in CV safety studies in type 2 diabetes melitus (T2DM) patients at high CV risk. Canagliflozin also improved kidney outcomes in diabetic kidney disease in the Canagliflozin and Renal Events in Diabetes and Nephropathy Clinical Evaluationtrial. More recently, the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial showed that dapagliflozin improved CV outcomes in patients with HF with or without diabetes. Protection from HF in non-diabetics was confirmed for empagliflozin in the EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) trial. A meta-analysis of DAPA-HF and EMPEROR-Reduced confirmed reductions in all-cause and CV death and the combined risk of CV death or worsening HF, as well as in the composite renal endpoint {hazard ratio [HR] 0.62 [95% confidence interval (CI) 0.43-0.90]} without differences based on the presence of diabetes or baseline estimated glomerular filtration rate (eGFR). Moreover, the Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease (DAPA-CKD) showed that dapagliflozin as an add-on over renin-angiotensin system blockade in patients with chronic kidney disease (CKD; with or without T2DM) reduced the HR for the primary endpoint (time to the first occurrence of ≥50% eGFR decline, end-stage kidney disease or renal or CV death) to 0.61 (95% CI 0.51-0.72) and for the secondary endpoints of worsening renal function or death from kidney failure [HR 0.56 (95% CI 0.45-0.68)], hospitalization for HF or CV death [HR 0.71 (95% CI 0.55-0.92)] and all-cause mortality [HR 0.69 (95% CI 0.53-0.88)]. These beneficial effects were consistent in patients with and without T2DM. In conclusion, SGLT2 inhibitors offer CV and kidney protection in both diabetic and non-diabetic CKD and, additionally, improve glycaemic control in T2DM, making them first-line therapy for CKD independent from diabetic status.
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http://dx.doi.org/10.1093/ckj/sfaa198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577767PMC
October 2020

The presence of diabetes mellitus further impairs structural and functional capillary density in patients with chronic kidney disease.

Authors:
Maria Schoina Charalampos Loutradis Marieta Theodorakopoulou Theodoros Dimitroulas Eva Triantafillidou Michael Doumas Asterios Karagiannis Alexandros Garyfallos Aikaterini Papagianni Pantelis Sarafidis

Microcirculation 2021 02 30;28(2):e12665. Epub 2020 Oct 30.

Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Objective: Endothelial dysfunction has been associated with increased cardiovascular events and overall mortality. Microvascular damage is prevalent both in diabetes mellitus (DM) and chronic kidney disease (CKD). Our aim was to compare microcirculatory function parameters in diabetic and non-diabetic CKD patients via nailfold video-capillaroscopy.

Methods: We included 48 diabetic and 48 non-diabetic adult CKD patients. All participants underwent nailfold video-capillaroscopy, during which capillary density was measured at normal conditions (baseline), after a 4-minute arterial occlusion (postocclusive reactive hyperemia), and at the end of a 2-minute venous occlusion (congestion phase).

Results: Diabetic patients presented significantly lower capillary density during reactive hyperemia (36.3 ± 3.8 vs 38.3 ± 4.3 capillaries/mm , P = .022) and at venous congestion (37.8 ± 4.0 vs 39.8 ± 4.2 capillaries/mm , P = .015). When stratified according to CKD stages, only in stage 3b capillary density was significantly lower in diabetic compared to non-diabetic subjects at baseline, during postocclusive hyperemia (36.8 ± 2.7 vs 40.0 ± 4.3 capillaries/mm , P = .037) and venous congestion (38.3 ± 2.8 vs 41.5 ± 3.5 capillaries/mm , P = .022).

Conclusions: Capillary density during postocclusive hyperemia and after venous congestion is lower in diabetic compared to non-diabetic CKD patients, a finding indicative that diabetes is an additional factor contributing to microcirculatory structural and functional impairment in CKD. These differences are more prominent in CKD stage 3b.
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http://dx.doi.org/10.1111/micc.12665DOI Listing
February 2021

The Effects of Nebivolol and Irbesartan on Ambulatory Aortic Blood Pressure and Arterial Stiffness in Hemodialysis Patients with Intradialytic Hypertension.

Authors:
Marieta Theodorakopoulou Charalampos Loutradis Athanasios Bikos Elena Angeloudi Manina Schoina Vasileios Raptis Vassilios Liakopoulos Aikaterini Papagianni Pantelis Sarafidis

Blood Purif 2021 5;50(1):73-83. Epub 2020 Oct 5.

Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece,

Background: Intradialytic hypertension occurs in 5-15% of hemodialysis patients and is associated with increased cardiovascular risk, but the responsible mechanisms remain unknown. This study examined the effects of nebivolol and irbesartan on ambulatory central blood pressure (BP), arterial stiffness, and wave-reflection parameters in patients with intradialytic hypertension.

Methods: This is a prespecified analysis of a single-blind, randomized, cross-over study in 38 hemodialysis patients with intradialytic hypertension. Patients were randomized to nebivolol 5 mg followed byirbesartan 150 mg, or vice versa. In a non-randomized manner, the first half of the patients (n = 19) received a single drug dose 1 h prior to dialysis session and the remaining received the drugs for a whole week before the evaluation. Ambulatory central BP, arterial stiffness, and wave-reflection parameters were estimated with Mobil-O-Graph NG device, during a midweek dialysis day.

Results: Intake of a single dose of nebivolol or irbesartan resulted in lower postdialysis central systolic BP (c-SBP) (baseline: 140.9 ± 15.4; nebivolol: 130.3 ± 19.5, p = 0.009; irbesartan: 127.3 ± 24.4 mm Hg, p = 0.007). Single-dose nebivolol also produced marginally lower 24-h c-SBP (p = 0.064) and lower 24-h central diastolic BP (c-DBP) (p = 0.029). Weekly administration of both drugs reduced postdialysis c-SBP (baseline: 144.1 ± 15.3; nebivolol: 131.8 ± 14.1, p = 0.014; irbesartan: 126.4 ± 17.8, p = 0.001) and 24-h c-SBP and c-DBP (baseline: 135.5 ± 10.3/91.9 ± 9.2; nebivolol: 126.4 ± 8.4/86.6 ± 7.2, p < 0.001/p = 0.002; irbesartan: 128.7 ± 11.6/87.0 ± 9.4, p = 0.061/p = 0.051 mm Hg). Single-dose intake of both drugs did not affect heart rate-adjusted augmentation index [AIx(75)], but decreased postdialysis pulse wave velocity (PWV). Importantly, weekly administration of both drugs reduced 24-h PWV (baseline: 10.0 ± 2.5; nebivolol: 9.7 ± 2.5, p = 0.012; irbesartan: 9.7 ± 2.7, p = 0.041). In between drug-group comparisons, no significant differences were noted.

Conclusions: This is the first randomized evaluation on the effects of pharmacological interventions on central BP and PWV in patients with intradialytic hypertension. Weekly administration of both nebivolol and irbesartan reduced 24-h central BP and PWV, but not AIx(75).
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http://dx.doi.org/10.1159/000507913DOI Listing
October 2020

Hypertension Management in Patients With Autosomal Dominant Polycystic Kidney Disease: Time for a Paradigm Shift?

Authors:
Charalampos Loutradis Charles J Ferro Pantelis Sarafidis

Am J Kidney Dis 2020 11 18;76(5):743. Epub 2020 Sep 18.

Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

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http://dx.doi.org/10.1053/j.ajkd.2020.06.011DOI Listing
November 2020

Are endourological procedures for nephrolithiasis treatment associated with renal injury? A review of potential mechanisms and novel diagnostic indexes.

Authors:
Ioannis Mykoniatis Pantelis Sarafidis Dimitrios Memmos Anastasios Anastasiadis Georgios Dimitriadis Dimitrios Hatzichristou

Clin Kidney J 2020 Aug 22;13(4):531-541. Epub 2020 May 22.

First Department of Urology, G. Gennimatas Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Nephrolithiasis is one of the most common urological conditions with a huge socio-economic impact. About 50% of recurrent stone-formers have just one lifetime recurrence and >10% of patients present with a high recurrent disease requiring subsequent and sometimes multiple surgical interventions. The advent of new technology has made endourological procedures the pinnacle of stone treatment, including procedures like percutaneous nephrolithotomy (PCNL), retrograde intrarenal surgery and miniaturized PCNL procedures. Researchers have primarily focused on comparisons with respect to stone-free rates, procedure parameters and post-operative complications. However, the effect of these three procedures on renal function or indexes of renal injury has not been sufficiently examined. This was only reported in a few studies as a secondary objective with the use of common and not the appropriate and detailed renal parameters. This review presents current literature regarding the use of novel and highly predictive biomarkers for diagnosing acute kidney injury, discusses potential mechanisms through which endourological procedures for renal stone treatment may affect renal function and proposes areas with open questions where future research efforts in the field should focus.
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http://dx.doi.org/10.1093/ckj/sfaa020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467591PMC
August 2020

Heart Failure and Atrial Fibrillation Modify the Associations of Nocturnal Blood Pressure Dipping Pattern With Mortality in Hemodialysis Patients.

Authors:
Christopher C Mayer Christoph Schmaderer Charalampos Loutradis Julia Matschkal Marrieta Theodorakopoulou Georg Lorenz Antonios Karpetas Susanne Angermann Athanasios Bikos Matthias C Braunisch Vasilios Raptis Marcus Baumann Aikaterini Papagianni Uwe Heemann Siegfried Wassertheurer Pantelis A Sarafidis

Hypertension 2020 10 31;76(4):1231-1239. Epub 2020 Aug 31.

Department of Nephrology, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece (C.L., M.T., A.B., A.P., P.A.S.).

Heart failure (HF), hypertension, and abnormal nocturnal blood pressure dipping are highly prevalent in hemodialysis patients. Atrial fibrillation (AF) and HF might be important mediators for the association of abnormal dipping patterns with worse prognosis. Thus, the aim of this study is to investigate the association of dipping with mortality in hemodialysis patients and to assess the influence of AF and HF. In total, 525 hemodialysis patients underwent 24-hour ambulatory blood pressure monitoring. All-cause and cardiovascular mortality served as end points. Patients were categorized according to their systolic dipping pattern (dipper, nondipper, and reverse dipper). Cox regression analysis was performed to determine the association between dipping pattern and study end points with dipping as reference. Subgroup analysis was performed for patients with and without AF or HF. In total, 185 patients with AF or HF and 340 patients without AF or HF were included. During a median follow-up of 37.8 months, 177 patients died; 81 from cardiovascular causes. Nondipping and reverse dipping were significantly associated with all-cause mortality in the whole cohort (nondipper: hazard ratio, 1.95 [1.22-3.14]; =0.006; reverse dipper: hazard ratio, 2.31 [1.42-3.76]; <0.001) and in patients without AF or HF (nondipper: hazard ratio, 2.78 [1.16-6.66]; =0.02; reverse dipper: hazard ratio, 4.48 [1.87-10.71]; <0.001) but not in patients with AF or HF. For cardiovascular mortality, associations were again significant in patients without AF or HF and in the whole cohort. The observed associations remained significant after adjustment for possible confounders. This study provides well-powered evidence for the association between abnormal dipping patterns and mortality in hemodialysis patients and suggests that HF or AF modifies this association.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15420DOI Listing
October 2020