Muscle Oxygenation and Microvascular Reactivity Across Different Stages of CKD: A Near-Infrared Spectroscopy Study.

RATIONALE & OBJECTIVE: Previous studies in chronic kidney disease (CKD) showed that vascular dysfunction in different circulatory beds progressively deteriorates with worsening CKD severity. This study evaluated muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with different stages of CKD versus controls. STUDY DESIGN: Observational controlled study. SETTING & PARTICIPANTS: 90 participants (18 per CKD stage 2, 3a, 3b, and 4, as well as 18 controls). PREDICTOR: CKD stage. OUTCOME: The primary outcome was muscle oxygenation at rest. Secondary outcomes were muscle oxygenation during occlusion-reperfusion and exercise, and muscle microvascular reactivity (hyperemic response). ANALYTICAL APPROACH: Continuous measurement of muscle oxygenation [tissue saturation index (TSI)] using near-infrared spectroscopy at rest, during occlusion-reperfusion, and during a 3-minute handgrip exercise (at 35% of maximal voluntary contraction). Aortic pulse wave velocity and carotid intima-media thickness were also recorded. RESULTS: Resting muscle oxygenation did not differ across the study groups (controls: 64.3% ± 2.9%; CKD stage 2: 63.8% ± 4.2%; CKD stage 3a: 64.1% ± 4.1%; CKD stage 3b: 62.3% ± 3.3%; CKD stage 4: 62.7% ± 4.3%; P=0.6). During occlusion, no significant differences among groups were detected in the TSI occlusion magnitude and TSI occlusion slope. However, during reperfusion the maximum TSI value was significantly lower in groups of patients with more advanced CKD stages compared with controls, as was the hyperemic response (controls: 11.2%±3.7%; CKD stage 2: 8.3%±4.6%; CKD stage 3: 7.8%±5.5%; CKD stage 3b: 7.3%±4.4%; CKD stage 4: 7.2%±3.3%; P=0.04). During the handgrip exercise, the average decline in TSI was marginally lower in patients with CKD than controls, but no significant differences were detected across CKD stages. LIMITATIONS: Moderate sample size, cross-sectional evaluation. CONCLUSIONS: Although no differences were observed in muscle oxygenation at rest or during occlusion, the microvascular hyperemic response during reperfusion was significantly impaired in CKD and was most prominent in more advanced CKD stages. This impaired ability of microvasculature to respond to stimuli may be a crucial component of the adverse vascular profile of patients with CKD and may contribute to exercise intolerance. PLAIN-LANGUAGE SUMMARY: Previous studies in chronic kidney disease (CKD) have shown that vascular dysfunction in different circulatory beds progressively deteriorates with CKD severity. This study evaluated muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with nondialysis CKD versus controls, as well as across different CKD stages. It showed that the microvascular hyperemic response after an arterial occlusion was significantly impaired in CKD and was worst in patients with more advanced CKD. No significant differences were detected in skeletal muscle oxygenation or muscle oxidative capacity at rest or during the handgrip exercise when comparing patients with CKD with controls or comparing across CKD stages. The impaired ability of microvasculature to respond to stimuli may be a component of the adverse vascular profile of patients with CKD and may contribute to exercise intolerance.

Meta-analysis addressing the impact of cardiovascular-acting medication on peak oxygen uptake of patients with HFpEF.

As our therapeutic armamentarium for HFpEF is insufficient, research has been focusing on the potential beneficial effect of existing pharmaceutical regimens on this specific patient population. A series of RCTs have recently examined the impact of various pharmaceutical treatments with proven benefit in HFrEF, on the improvement of symptoms of HFpEF patients. This systematic review and meta-analysis comprised studies of adult patients with HFpEF and evaluated the impact of different cardiovascular acting medication on cardiorespiratory fitness, reflected by peak VO2 values measured during CPET. The primary outcome was difference between groups in the change of peak VO2 (ΔpeakVO2). Literature search involved PubMed/MEDLINE, Scopus and Web of Science databases. Our search identified 3634 records and 19 studies were included in qualitative analysis; 12 studies with 1341 patients were finally included in primary outcome analysis. ΔpeakVO2 between baseline and study-end did not significantly change after treatment with spironolactone, ivabradine, sildenafil, or oral inorganic nitrate and neither did difference in 6MWT distance after treatment with spironolactone. Spironolactone led to statistically significant reduction in E/E' ratio study-end values (WMD - 1.64, 95%CI - 2.42 to - 0.86, I2 = 87%, p < 0.0001), as well as to a significant increase in MLHFQ values (WMD 0.75, 95%CI 0.02 to 1.48, I2 = 0%, p = 0.65), indicating deterioration in HRQoL among HFpEF patients. A series of established cardiovascular acting medication in HFrEF seems not to confer significant benefit in peak VO2 and 6MWT distance in HFpEF. Spironolactone is associated with improvements in diastolic function and with a significant deterioration in HRQoL of this population.

Ambulatory central BP and arterial stiffness in patients with and without intradialytic hypertension.

BACKGROUND: Increased arterial stiffness is suggested to be involved in the pathogenesis of intradialytic-hypertension (IDH). Ambulatory pulse-wave-velocity (PWV) is an independent predictor for all-cause-mortality in haemodialysis and its prognostic power is better than office PWV. This is the first study examining ambulatory central blood pressure (BP) and arterial stiffness parameters in patients with and without IDH. METHODS: This study examined 45 patients with IDH (SBP rise ≥10 mmHg from pre- to post-dialysis and post-dialysis SBP ≥150 mmHg) in comparison with 197 patients without IDH. All participants underwent 48-h ABPM with Mobil-O-Graph-NG; parameters of central haemodynamics, wave reflection and PWV were estimated. RESULTS: Age, dialysis vintage and interdialytic weight gain did not differ between-groups. IDH patients had higher 48-h cSBP (131.7 ± 16.2 vs. 119.2 ± 15.2 mmHg, p < 0.001), 48-h cDBP (86.7 ± 12.7 vs. 79.6 ± 11.5 mmHg, p < 0.001) and 48-h cPP (45.5 ± 10.4 vs. 39.8 ± 10.0 mmHg, p = 0.001) compared to patients without IDH. Similarly, during day- and nighttime periods, cSBP/cDBP and cPP levels were higher in IDH-patients compared to non-IDH. Forty-eight-hour augmentation pressure and index, but not AIx(75) were higher in IDH patients; 48-h PWV (10.0 ± 2.0 vs. 9.2 ± 2.1 m/s, p = 0.017) was significantly higher in patients with IDH. The two study groups displayed different trajectories in central BP and PWV over the course of the recording; IDH patients had steadily high values of the above variables during the 2 days of the interdialytic-interval, whereas non-IDH patients showed a gradual elevation, with significant increases from the 1st to 2nd 24 h. CONCLUSIONS: IDH patients have significantly higher levels of ambulatory central BP and arterial stiffness parameters and a different course over the 48-h period compared with non-IDH patients. Increased arterial stiffness could be a prominent factor associated with the high burden of cardiovascular disease in this population.

Hemodialysis Effects on Autonomic Function: Results of Linear and Nonlinear Analysis of Heart Rate Variability at Rest and in Response to Physical and Mental Stress Tests.

INTRODUCTION: Cardiac arrhythmias are the most common cause of death in hemodialysis. Autonomic dysfunction plays a central role in this arrhythmogenic background. Previous studies on hemodialysis-related changes in heart rate variability (HRV) give contradictory results. This study investigated HRV indices both at rest and in response to physical and mental stimulation maneuvers at multiple time-points around and during the hemodialysis procedure. METHODS: Autonomic function was assessed by linear and nonlinear HRV indices at predialysis, during dialysis (3 equal time-periods), postdialysis, and on the nondialysis day in 36 hemodialysis patients. Continuous measurement of beat-by-beat heart rate was recorded with Finometer-PRO (The Netherlands) at rest and after orthostatic, sit-to-stand, handgrip, and mental-arithmetic test. RESULTS: The RMSSD, SD1, and SD2 indices significantly increased during dialysis (early-HD, mid-HD, late-HD periods) compared with the predialysis levels (p < 0.05) and returned to baseline postdialysis (RMSSD: 54.39 ± 83.73 vs. 137.98 ± 109.53* vs. 119.85 ± 97.34* vs. 144.47 ± 88.74* vs. 85.82 ± 121.43msec, *p < 0.05 vs. predialysis and postdialysis). No differences were detected in the above indices between the predialysis and nondialysis day. However, postdialysis, the HRV responses to orthostatic and sit-to-stand tests were more exaggerated than in the predialysis measurements (p < 0.05). The HRV responses both at resting and physical tests in the nondialysis day were similar to the predialysis levels. HRV indices in the mental arithmetic test during hemodialysis were much higher than at the nondialysis day (RMSSD: 77.05 [180.41] versus 19.75 [105.47] msec; p = 0.031). CONCLUSIONS: Hemodialysis causes marked changes in the autonomic function. Resting HRV indices return to baseline postdialysis, but HRV responses to physical stress remain exaggerated and return to baseline on the nondialysis day. Detecting patients with significant autonomic dysfunction may help towards reduction of arrhythmia risk through individualized approaches.

Lung Ultrasound as a Tool to Evaluate Fluid Accumulation in Dialysis Patients.

BACKGROUND: Volume overload is the main mechanism of BP elevation in end-stage kidney disease (ESKD) patients undergoing hemodialysis or peritoneal dialysis and has been linked to adverse outcomes and increased mortality in this population. SUMMARY: This review discusses current knowledge on lung ultrasound as a tool for detection of extracellular volume overload through evaluation of extravascular lung water content. We describe the principles of lung US, the main protocols to apply it in clinical practice, and accumulated data evidence regarding its associations with cardiovascular events and mortality. We also summarize available evidence on the effect of lung ultrasound-guided -volume management strategies on BP control, echocardiographic parameters, and major outcomes in patients undergoing dialysis. KEY MESSAGES: Among interventions attempting to reduce the burden of cardiovascular disease in ESKD, effective management of volume overload represents an unmet clinical need. Assessment of hydration status by lung ultrasound is a cheap, easy to employ, and real-time technique that can offer accurate dry weight assessment leading to several clinical benefits.

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

RATIONALE & OBJECTIVE: Current recommendations suggest the use of ambulatory blood pressure 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-hour interdialytic blood pressure (BP). STUDY DESIGN: Diagnostic test study. SETTINGS & PARTICIPANTS: 242 Greek hemodialysis patients who successfully underwent ABPM. TESTS COMPARED: Ambulatory BP was used as the reference method to evaluate the accuracy of the following BP metrics: predialysis and postdialysis BP, intradialytic BP, intradialytic plus pre/postdialysis BP, and scheduled interdialytic BP (on an off-dialysis day at 8:00 am, 8:00 pm, and their average). OUTCOME: 44-hour ambulatory systolic BP/diastolic BP (SBP/DBP) ≥ 130/80 mm Hg. RESULTS: The 44-hour SBP/DBP levels differed significantly from predialysis and postdialysis BP but showed no or minor differences compared with the other BP metrics. Bland-Altman plots showed an absence of systematic bias for all metrics but large between-method difference and wider 95% limits of agreement for predialysis and postdialysis BP compared with intradialytic, intradialytic plus pre/postdialysis, and averaged scheduled interdialytic BP. The sensitivity/specificity and κ-statistic for diagnosing 44-hour SBP ≥ 130 mm Hg were low for predialysis (86.5%/38.6%, κ-statistic = 0.27) and postdialysis BP (63.1%/73.3%, κ-statistic = 0.35), but better for intradialytic BP (77.3%/76.2%, κ-statistic = 0.53), intradialytic plus pre/postdialysis BP (76.6%/72.3%, κ-statistic = 0.49), and scheduled interdialytic BP (87.9%/77.2%, κ-statistic = 0.66). In receiver operating characteristic (ROC) analyses, the areas under the curve (AUC) of predialysis SBP (AUC = 0.723) and postdialysis SBP (AUC = 0.746) were significantly lower than that of intradialytic SBP (AUC = 0.850), intradialytic plus pre/postdialysis SBP (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 the reproducibility of the examined metrics over time. CONCLUSIONS: Intradialytic, intradialytic plus pre/postdialysis, and scheduled interdialytic BP measurements were more accurate in detecting elevated 44-hour BP than predialysis and postdialysis 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.

Diagnostic Performance of Office versus Ambulatory Blood Pressure in Kidney Transplant Recipients.

INTRODUCTION: Hypertension is the most prominent risk factor in kidney transplant recipients (KTRs). No study so far assessed in parallel the prevalence, control, and phenotypes of blood pressure (BP) or the accuracy of currently recommended office BP diagnostic thresholds in diagnosing elevated ambulatory BP in KTRs. METHODS: 205 stable KTRs underwent office BP measurements and 24-h ambulatory BP monitoring (ABPM). Hypertension was defined as follows: (1) office BP ≥140/90 mm Hg or use of antihypertensive agents following the current European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines, (2) office BP ≥130/80 mm Hg or use of antihypertensive agents following the current American College of Cardiology/American Heart Association (ACC/AHA) guidelines, (3) ABPM ≥130/80 mm Hg or use of antihypertensive agents, and (4) ABPM ≥125/75 mm Hg or use of antihypertensive agents. RESULTS: Hypertension prevalence by office BP was 88.3% with ESC/ESH and 92.7% with ACC/AHA definitions compared to 94.1 and 98.5% at relevant ABPM thresholds. Control rates among hypertensive patients were 69.6 and 43.7% with office BP compared to 38.3 and 21.3% with ABPM, respectively. Both for prevalence (κ-statistics = 0.52, p < 0.001 and 0.32, and p < 0.001) and control rates (κ-statistics = 0.21, p < 0.001 and 0.22, and p < 0.001, respectively), there was moderate or fair agreement of the 2 techniques. White-coat and masked hypertension were diagnosed in 6.7 and 39.5% of patients at the 140/90 threshold and 5.9 and 31.7% of patients at the 130/80 threshold. An office BP ≥140/90 mm Hg had 35.3% sensitivity and 84.9% specificity for the diagnosis of 24-h BP ≥130/80 mm Hg. An office BP ≥130/80 mm Hg had 59.7% sensitivity and 73.9% specificity for the diagnosis of 24-h BP ≥125/75 mm Hg. Receiver operating curve analyses confirmed this poor diagnostic performance. CONCLUSIONS: At both corresponding thresholds studied, ABPM revealed particularly high hypertension prevalence and poor BP control in KTRs. Misclassification of KTRs by office BP is substantial, due to particularly high rates of masked hypertension. The diagnostic accuracy of office BP for identifying elevated ambulatory BP is poor. These findings call for a wider use of ABPM in KTRs.

Cardiorespiratory fitness in kidney transplant recipients compared to patients with kidney failure: a systematic review and meta-analysis.

Patients with kidney failure often present with reduced cardiovascular functional reserve and exercise tolerance. Previous studies on cardiorespiratory fitness examined with cardiopulmonary exercise testing (CPET) in kidney transplant recipients (KTR) had variable results. This is a systematic review and meta-analysis of studies examining cardiovascular functional reserve with CPET in KTR in comparison with patients with kidney failure (CKD-Stage-5 before dialysis, hemodialysis or peritoneal dialysis), as well as before and after kidney transplantation. Literature search involved PubMed, Web-of-Science and Scopus databases, manual search of article references and grey literature. From a total of 4,944 identified records, eight studies (with 461 participants) were included in quantitative analysis for the primary question. Across these studies, KTR had significantly higher oxygen consumption at peak/max exercise (VO2 peak/VO2 max) compared to patients with kidney failure (SMD = 0.70, 95% CI [0.31, 1.10], I2  = 70%, P = 0.002). In subgroup analyses, similar differences were evident among seven studies comparing KTR and hemodialysis patients (SMD = 0.64, 95% CI [0.16, 1.12], I2  = 65%, P = 0.009) and two studies comparing KTR with peritoneal dialysis subjects (SMD = 1.14, 95% CI [0.19, 2.09], I2  = 50%, P = 0.16). Across four studies with relevant data, oxygen consumption during peak/max exercise showed significant improvement after kidney transplantation compared to pretransplantation values (WMD = 2.43, 95% CI [0.01, 4.85], I2  = 68%, P = 0.02). In conclusion, KTR exhibit significantly higher cardiovascular functional reserve during CPET compared to patients with kidney failure. Cardiovascular reserve is significantly improved after kidney transplantation in relation to presurgery levels.

Cardiorespiratory fitness assessed by cardiopulmonary exercise testing between different stages of pre-dialysis chronic kidney disease: A systematic review and meta-analysis.

AIM: The burden of several cardiovascular risk factors increases in parallel to renal function decline. Exercise intolerance is common in patients with chronic kidney disease (CKD) and has been associated with increased risk of adverse outcomes. Whether indices of cardiorespiratory capacity deteriorate with advancing CKD stages is unknown. METHODS: We conducted a systematic review and meta-analysis of studies assessing cardiorespiratory capacity in adult patients with pre-dialysis CKD using cardiopulmonary exercise testing (CPET) and reporting data for different stages. Our primary outcome was differences in peak oxygen uptake (VO2 peak) between patients with CKD Stages 2-3a and those with Stages 3b-5(pre-dialysis). Literature search was undertaken in PubMed, Web of Science and Scopus databases, and abstract books of relevant meetings. Quality assessment was undertaken with Newcastle-Ottawa-Scale. RESULTS: From 4944 records initially retrieved, six studies with 512 participants fulfilling our inclusion criteria were included in the primary meta-analysis. Peak oxygen uptake (VO2 peak) was significantly higher in patients with CKD Stages 2-3a versus those with Stages 3b-5(pre-dialysis) [weighted-mean-difference, WMD: 2.46, 95% CI (1.15, 3.78)]. Oxygen consumption at ventilatory threshold (VO2 VT) was higher in Stages 2-3a compared with those in Stages 3b-5(pre-dialysis) [standardized-mean-difference, SMD: 0.59, 95% CI (0.06, 1.1)], while no differences were observed for maximum workload and respiratory-exchange-ratio. A secondary analysis comparing patients with CKD Stages 2-3b and Stages 4-5(pre-dialysis), yielded similar results [WMD: 1.78, 95% CI (1.34, 2.22)]. Sensitivity analysis confirmed the robustness of these findings. CONCLUSION: VO2 peak and VO2 VT assessed with CPET are significantly lower in patients in CKD Stages 3b-5 compared with Stages 2-3a. Reduced cardiorespiratory fitness may be another factor contributing to cardiovascular risk increase with advancing CKD.

Endothelial Dysfunction during Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

Chronic obstructive pulmonary disease (COPD) is characterized by high cardiovascular risk, which is further amplified during acute COPD exacerbations (AECOPD). Endothelial dysfunction has been previously suggested as one of the potential pathogenetic mechanisms. In order to study the effects of AECOPD on endothelial function assessed by available functional methods, we performed a literature search involving Pubmed and Scopus databases. Eligible studies were those that included adult patients with COPD and evaluated endothelial damage via semi-invasive or noninvasive functional methods, during AECOPD and after recovery or in stable condition. Newcastle-Ottawa Scale was applied to evaluate the quality of retrieved studies. Endothelial function was significantly impaired during AECOPD compared to recovery/stable condition (SMD: -0.87, 95%CI [-1.19, -0.55]). Patients during AECOPD presented a significantly worse response in endothelium-dependent (flow-mediated dilatation WMD: -2.59, 95%CI [-3.75, -1.42]) and independent vasodilation (nitroglycerine-mediated dilatation WMD: -3.13, 95%CI [-5.18, -1.09]) compared to recovery. Sensitivity analyses confirmed the above results. In conclusion, endothelium-dependent and independent vasodilation is worse during AECOPD compared to the stable condition. Endothelial dysfunction could play a role in the high cardiovascular risk during AECOPD.

Assessment of Hydration Status in Peritoneal Dialysis Patients: Validity, Prognostic Value, Strengths, and Limitations of Available Techniques.

BACKGROUND: The majority of patients undergoing peritoneal dialysis (PD) suffer from volume overload and this overhydration is associated with increased mortality. Thus, optimal assessment of volume status in PD is an issue of paramount importance. Patient symptoms and physical signs are often unreliable indexes of true hydration status. SUMMARY: Over the past decades, a quest for a valid, reproducible, and easily applicable technique to assess hydration status is taking place. Among existing techniques, inferior vena cava diameter measurements with echocardiography and natriuretic peptides such as brain natriuretic peptide and N-terminal pro-B-type natriuretic peptide were not extensively examined in PD populations; while having certain advantages, their interpretation are complicated by the underlying cardiac status and are not widely available. Bioelectrical impedance analysis (BIA) techniques are the most studied tool assessing volume overload in PD. Volume overload assessed with BIA has been associated with technique failure and increased mortality in observational studies, but the results of randomized trials on the value of BIA-based strategies to improve volume-related outcomes are contradictory. Lung ultrasound (US) is a recent technique with the ability to identify volume excess in the critical lung area. Preliminary evidence in PD showed that B-lines from lung US correlate with echocardiographic parameters but not with BIA measurements. This review presents the methods currently used to assess fluid status in PD patients and discusses existing data on their validity, applicability, limitations, and associations with intermediate and hard outcomes in this population. Key Message: No method has proved its value as an intervening tool affecting cardiovascular events, technique, and overall survival in PD patients. As BIA and lung US estimate fluid overload in different compartments of the body, they can be complementary tools for volume status assessment.

The effect of dry-weight reduction guided by lung ultrasound on ambulatory blood pressure in hemodialysis patients: a randomized controlled trial.

Approximately 85% of hemodialysis patients are hypertensive, but less than 30% achieve adequate blood pressure (BP) control. Reduction of volume overload is fundamental for BP control, but clinical criteria to estimate dry-weight are inaccurate. In the present study we examined the effect of dry-weight reduction with a lung-ultrasound-guided strategy on ambulatory BP in 71 clinically euvolemic hemodialysis patients with hypertension. Patients were equally randomized into an active group, following a strategy for dry-weight reduction guided by pre-hemodialysis lung ultrasound, and a control group with standard-of-care treatment. All patients underwent 48-hour ambulatory BP monitoring (ABPM) at baseline and after eight weeks. Overall, more patients in the active than in the control group had dry weight reduction, 54.3% compared to 13.9%, respectively. The ultrasonographic-B line change during follow-up was significantly different (-5.3±12.5 in active versus +2.2±7.6 in control group), which corresponded to significant differences in dry weight changes between the groups. The magnitude of reductions in 48-hour systolic BP (-6.61±9.57 vs. -0.67±13.07) and diastolic BP (-3.85±6.34 vs. -0.55±8.28) was significantly greater in the active group. Similarly, intradialytic BP, 44-hour BP, and daytime or night-time systolic/diastolic BP during both days of the interdialytic interval were significantly reduced in the active group but remained unchanged in the control group. The percentage of patients experiencing one or more intradialytic hypotensive episodes was marginally lower in the active group (34.3% vs. 55.6%). Thus, a lung-ultrasound-guided strategy for dry-weight reduction can effectively and safely reduce ambulatory BP levels in hemodialysis patients. Clinical implementation of this simple technique can help increase BP control in this population.

Changes in right ventricular dimensions, function, and pulmonary circulation loading according to the degree of interdialytic weight gain in maintenance hemodialysis patients.

INTRODUCTION: The aim of this study was to investigate changes in echocardiographic right ventricular (RV) indices in relation to the degree of fluid accumulation between hemodialysis sessions, evaluated according to the recommended threshold of interdialytic-weight-gain corrected for dry weight (IDWG%). METHODS: A post-hoc analysis was performed using data from 41 maintenance hemodialysis patients. Patients were divided into a higher (>4.5%) and a lower (<4.5%) IDWG% group and underwent an echocardiographic assessment at the start and the end of the 3-day and the 2-day interdialytic interval. RESULTS: RV systolic pressure (RVSP) increments were more pronounced in the higher compared to the lower IDWG% group (16.43 ± 5.37 vs. 14.11 ± 13.38 mm Hg respectively, p = 0.015) over the 3-day interval, while changes in RV filling pressures, did not differ significantly between the groups (p = 0.84). CONCLUSIONS: During the 3-day interdialytic interval, pulmonary circulation is particularly overloaded in patients with fluid accumulation higher than the recommended thresholds, as evidenced by higher RVSP elevations.

Effects of sodium-glucose co-transporter 2 inhibitors on heart failure events in chronic kidney disease: a systematic review and meta-analysis.

AIMS: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors significantly reduce the risk for hospitalizations for heart failure (HF) in patients with diabetes, and HF; findings in patients with chronic kidney disease (CKD) are not uniform. We aimed to perform a meta-analysis exploring the effect of SGLT-2 inhibitors on HF events in patients with CKD and across subgroups defined by baseline kidney function. METHODS AND RESULTS: A systematic search in major electronic databases was performed. Randomized controlled trials (RCTs) providing data on the effect of SGLT-2 inhibitors on the primary outcome, time to hospitalization or urgent visit for worsening HF in patients with prevalent CKD at baseline or across subgroups stratified by baseline estimated glomerular-filtration-rate (eGFR) were included. Twelve studies (n = 89,191 participants) were included in the meta-analysis. In patients with CKD, treatment with SGLT-2 inhibitors reduced the risk for HF events by 32% compared to placebo [hazard ratio (HR) 0.68; 95% confidence interval (CI) 0.63-0.73]. Reduction in HF events with SGLT-2 inhibitors was more prominent in patients with eGFR <60 ml/min/1.73 m2 (HR 0.68; 95% CI 0.62-0.74) than in those with eGFR ≥60 ml/min/1.73 m2 (HR 0.76; 95% CI 0.69-0.83). Subgroup analysis according to type of SGLT-2 inhibitor showed a consistent treatment effect across all studied agents (p-subgroup-analysis = 0.44). Sensitivity analysis including data from studies including only diabetic patients showed an even more pronounced effect in eGFR subgroup <60 ml/min/1.73 m2 (HR 0.62; 95% CI 0.54-0.70). CONCLUSION: Treatment with SGLT-2 inhibitors led to a significant reduction in HF events in patients with CKD. Such findings may change the landscape of prevention of HF events in patients with advanced CKD. PROSPERO Registration number CRD42022382857.

Advanced chronic kidney disease with life-threatening hypokalemia due to undiagnosed Gitelman syndrome.

We report a case of a 58-year-old woman presenting with symptoms of oliguria, fatigue, anorexia, constipation, hypovolemic signs, and laboratory tests showing severe hypokalemia (1.7 mEq/L), hyponatremia (120 mEq/L), high serum creatinine (SCr, 6.46 mg/dL) and urea (352 mg/dL). The patient had previously been diagnosed with chronic kidney disease (CKD), with SCr up to 2.58 mg/dL 1 year prior, and had in all her previous laboratory tests shown hypokalemia, which was treated with conservative measures and eplerenone despite low-normal blood pressure and normal heart function. A set of coordinated measures were applied to restore the potassium deficit, revert hypovolemic hyponatremia, and support renal function (including 4 dialysis sessions). In addition, a careful diagnostic approach revealed inappropriately high urine sodium and potassium losses, hypocalciuria, and hyperreninemic hyperaldosteronism leading to the diagnosis of Gitelman syndrome and hypokalemia-associated chronic tubulointerstitial nephropathy. Importantly, compliance with a simple set of instructions on high potassium and liberal sodium diet enabled the patient not only to remain euvolemic, free of symptoms, and with normal electrolytes, but also to recover a significant part of renal function and stabilize at an earlier CKD stage. Gitelman syndrome is a rare disorder that can be easily diagnosed and treated following simple measures; its early diagnosis is necessary to avoid life-threatening complications.

Effect of kidney transplantation on indices of cardiorespiratory fitness assessed with cardiopulmonary exercise testing: a systematic review and meta-analysis.

BACKGROUND: Patients with kidney failure often present with reduced cardiovascular reserve. Kidney transplantation (KT) is the optimal treatment for patients with end-stage kidney disease as it is associated with longer survival and improved quality of life compared to dialysis. METHODS: This is a systematic review and meta-analysis of studies using cardiopulmonary-exercise-testing to examine the cardiorespiratory fitness of patients with kidney failure before and after KT. The primary outcome was difference in pre- and post-transplantation values of peak oxygen uptake (VO2peak). Literature search involved three databases (PubMed-Web of Science-Scopus), manual search, and grey literature. RESULTS: From 379 records initially retrieved, six studies were included in final meta-analysis. A marginal, but not significant, improvement was observed in VO2peak after KT compared to pre-transplantation values (SMD: 0.32, 95%CI -0.02; 0.67). Oxygen consumption at anaerobic threshold was significantly improved after KT (WMD: 2.30 ml/kg/min, 95%CI 0.50; 4.09). Consistent results were shown between preemptive and after-dialysis-initiation transplantation and a trend for improvement in VO2peak was observed at least 3 months post-transplantation, but not earlier. CONCLUSION: Several major indices of cardiorespiratory fitness tend to improve after KT. This finding may represent another modifiable factor contributing to better survival rates of kidney transplant recipients compared to patients undergoing dialysis.

Effect of patient gender on short-term blood pressure variability in hemodialysis patients.

Increased blood pressure variability (BPV) is strongly associated with cardiovascular events in end-stage kidney disease patients. Male hemodialysis patients present higher cardiovascular risk compared with females. The aim of this study is to investigate sex differences in short-term BPV in hemodialysis patients. 129 male and 91 female hemodialysis patients that underwent 48-h ABPM were included in this analysis. Standard deviation (SD), weighted SD (wSD), coefficient of variation (CV), and average real variability (ARV) of SBP and DBP were calculated with validated formulas. Age, dialysis vintage and history of major comorbidities did not differ between men and women. 48-h SBP/DBP (137.2 ± 17.4/81.9 ± 12.1 mmHg vs 132.2 ± 19.2/75.9 ± 11.7 mmHg, p = 0.045/<0.001) was significantly higher in men than women. During the 48-h period, all systolic BPV indices were similar between men and women (48-h SBP-ARV: 12.0 ± 2.9 vs 12.1 ± 3.2 mmHg, p = 0.683); 48-h DBP-SD, DBP-wSD and DBP-ARV (9.1 ± 1.6 vs 8.4 ± 1.8 mmHg, p = 0.005) were higher in men. In conclusion, short-term diastolic BPV indices are higher in male than female hemodialysis patients. Increased BPV may impact on the higher incidence of cardiovascular events observed in male hemodialysis patients.

Peridialytic and intradialytic blood pressure metrics are not valid estimates of 44-h ambulatory blood pressure in patients with intradialytic hypertension.

PURPOSE: In contrast to peridialytic blood pressure (BP), intradialytic and home BP measurements are accurate metrics of ambulatory BP load in hemodialysis patients. This study assessed the agreement of peridialytic, intradialytic, and scheduled interdialytic recordings with 44-h BP in a distinct hemodialysis population, patients with intradialytic hypertension (IDH). METHODS: This study included 45 IDH patients with valid 48-h ABPM and 197 without IDH. With 44-h BP used as reference method, we tested the accuracy of the following BP metrics: Pre- and post-dialysis, mean and median intradialytic, mean intradialytic plus pre/post-dialysis, and scheduled interdialytic BP (out-of-dialysis day: mean of 8:00am/8:00 pm readings). RESULTS: In IDH patients, peridialytic and intradialytic BP metrics showed at best moderate correlations, while averaged interdialytic SBP/DBP exhibited strong correlation (r = 0.882/r = 0.855) with 44-h SBP/DBP. Bland-Altman plots showed large between-method-difference for peri- and intradialytic-BP, but only + 0.7 mmHg between-method difference and good 95% limits of agreement for averaged interdialytic SBP. The sensitivity/specificity and κ-statistic for diagnosing 44-h SBP ≥ 130 mmHg were low for pre-dialysis (72.5/40.0%, κ-statistic = 0.074) and post-dialysis (90.0/0.0%, κ-statistic = - 0.110), mean intradialytic (85.0/40.0%, κ-statistic = 0.198), median intradialytic (85.0/60.0%, κ-statistic = 0.333), and intradialytic plus pre/post-dialysis SBP (85.0/20.0%, κ-statistic = 0.043). Averaged interdialytic SBP showed high sensitivity/specificity (97.5/80.0%) and strong agreement (κ-statistic = 0.775). In ROC analyses, scheduled interdialytic SBP/DBP had the highest AUC (0.967/0.951), sensitivity (90.0/88.0%), and specificity (100.0/90.0%). CONCLUSION: In IDH patients, only averaged scheduled interdialytic but not pre- and post-dialysis, nor intradialytic BP recordings show reasonable agreement with ABPM. Interdialytic BP recordings only could be used for hypertension diagnosis and management in these subjects.

The effect of standard percutaneous nephrolithotomy, miniaturized percutaneous nephrolithotomy and retrograde intrarenal surgery on biomarkers of renal injury: a randomized clinical trial.

Background: Observational studies on the association of endourological procedures with renal parenchymal damage are lacking. This randomized trial examined the effect of standard percutaneous nephrolithotomy (sPCNL) in comparison with miniaturized-PCNL (mini-PCNL) and retrograde intrarenal surgery (RIRS) for nephrolithiasis treatment on novel biomarkers of renal injury. Methods: Seventy-five patients were randomized in a 1:1:1 ratio to receive sPCNL, mini-PCNL and RIRS for nephrolithiasis. The ratios of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and interleukin-18 (IL-18) normalized for urinary creatinine (Cr) were calculated from urine samples collected at baseline (2-h preoperatively) and at 2-, 6-, 24- and 48-h postoperatively. Two-way mixed analysis of variance (ANOVA) for repeated measurements was used to evaluate the effects of type of procedure and time on studied biomarkers. Results: Between baseline and 2-h postoperatively, no significant differences were observed in NGAL/Cr changes between sPCNL [median (interquartile range) 9.46 (4.82-14.9)], mini-PCNL [12.78 (1.69-25.24)] and RIRS [6.42 (2.61-23.90)] (P = .902). Similarly, no between-group differences were observed for KIM-1/Cr (P = .853) and IL-18 (P = .980) at 2 h, and all biomarkers at any time-point postoperatively. Within-groups, significant increases from baseline were noted for NGAL/Cr (sPCNL, P < .001; mini-PCNL, P < .001; RIRS, P = .001), KIM-1/Cr and IL-18/Cr at 2 h; progressively lower increases from baseline were noted in all groups for KIM-1/Cr and IL-18/Cr at 6-, 24- and 48-h postoperatively. As such, a significant effect of time but not of type of procedure was evidenced with two-way mixed ANOVA. No significant between-group differences were observed in acute kidney injury incidence and complications. Conclusions: The endourological procedures under study are associated with similar patterns of early tubular injury, detected by novel biomarkers, which is largely reduced within 48 h and no changes in glomerular function.

Mineralocorticoid receptor antagonist use in chronic kidney disease with type 2 diabetes: a clinical practice document by the European Renal Best Practice (ERBP) board of the European Renal Association (ERA).

Chronic kidney disease (CKD) in individuals with type 2 diabetes (T2D) represents a major public health issue; it develops in about 30%-40% of patients with diabetes mellitus and is the most common cause of CKD worldwide. Patients with CKD and T2D are at high risk of both developing kidney failure and of cardiovascular events. Renin-angiotensin system (RAS) blockers were considered the cornerstone of treatment of albuminuric CKD in T2D for more than 20 years. However, the residual risk of progression to more advanced CKD stages under RAS blockade remains high, while in major studies with these agents in patients with CKD and T2D no significant reductions in cardiovascular events and mortality were evident. Steroidal mineralocorticoid receptor antagonists (MRAs) are known to reduce albuminuria in individuals on RAS monotherapy, but their wide clinical use has been curtailed by the significant risk of hyperkalemia and absence of trials with hard renal outcomes. In recent years, non-steroidal MRAs have received increasing interest due to their better pharmacologic profile. Finerenone, the first compound of this class, was shown to effectively reduce the progression of kidney disease and of cardiovascular outcomes in participants with T2D in phase 3 trials. This clinical practice document prepared from a task force of the European Renal Best Practice board summarizes current knowledge on the role of MRAs in the treatment of CKD in T2D aiming to support clinicians in decision-making and everyday management of patients with this condition.