Felix S. Seibert

Impact of Atrial Fibrillation on the Accuracy of Oscillometric Blood Pressure Monitoring

The introduction of automated oscillometric blood pressure monitors was the basis for today’s widespread use of blood pressure self-measurement. However, in atrial fibrillation, there is a controversial debate on the use of oscillometry because there is a high variability of heart rate and stroke volume. To date, the accuracy of oscillometric blood pressure monitoring in atrial fibrillation has only been investigated using auscultatory sphygmomanometry as reference method, which may be biased by arrhythmia as well. We performed a cross-sectional study in 102 patients (52 sinus rhythm, 50 atrial fibrillation) assessing the accuracy of an automated and validated oscillometric upper arm (M5 Professional, Omron) and wrist device (R5 Professional, Omron) to invasively assessed arterial pressure. Blood pressure values were calculated as the mean of 3 consecutive measurements. Systolic and diastolic blood pressure did not significantly differ in patients with sinus rhythm and atrial fibrillation, independent of the method of measurement (P>0.05 each). The within-subject variability of the oscillometric measurements was higher in patients with atrial fibrillation compared with sinus rhythm (P<0.01 each). The biases of systolic and diastolic blood pressure, however, did not significantly differ in presence or absence of atrial fibrillation in Bland-Altmann analysis (P>0.05 each). In conclusion, atrial fibrillation did not significantly affect the accuracy of oscillometric measurements, if 3 repeated measurements were performed.

Attended Versus Unattended Blood Pressure Measurement in a Real Life Setting

The debate on the generalizability of the SPRINT (Systolic Blood Pressure Intervention Trial) findings raised considerable interest in the technique of unattended office blood pressure (BP) measurement. It remains elusive, however, whether unattended BP measurement yields lower values than conventional measurements in a real world setting with subjects consulting their personal general practitioner in a familiar office. We performed a cross-sectional study in 158 patients in 4 general practitioners’ offices and compared conventional auscultatory office BP to unattended automated office BP in 107 subjects (group 1) and unattended to attended automated office BP in another 51 subjects (group 2). Unattended BP was calculated as the mean of 3 automated measurements performed in a separate room after 5 minutes of rest. Additionally, patients documented home BP for 7 days after the consultation. Mean auscultatory office, unattended office and home BP were 144.6/81.0, 144.1/79.9, and 135.5/78.3 mm Hg in group 1; unattended and attended automated office BP were 134.2/80.6 and 135.7/80.6 mm Hg in group 2. Systolic attended and unattended office BP values were significantly higher than home BP (P<0.001, P<0.01, respectively). Attended and unattended office BP, however, did neither show a significant difference in group 1 nor in group 2 (P>0.05 each). Bland–Altman analysis revealed a bias of 0.5 mm Hg systolic and 1.1 mm Hg diastolic in group 1 and −1.5 mm Hg systolic and 0 mm Hg diastolic in group 2. In conclusion, the present findings show that unattended and attended office BP measurements achieve comparable results, if measurements take place at a familiar general practitioner’s office.

Urinary calprotectin and posttransplant renal allograft injury

Objective Current methods do not predict the acute renal allograft injury immediately after kidney transplantation. We evaluated the diagnostic performance of urinary calprotectin for predicting immediate posttransplant allograft injury. Methods In a multicenter, prospective-cohort study of 144 incipient renal transplant recipients, we postoperatively measured urinary calprotectin using an enzyme-linked immunosorbent assay and estimated glomerular filtration rate (eGFR) after 4 weeks, 6 months, and 12 months. Results We observed a significant inverse association of urinary calprotectin concentrations and eGFR 4 weeks after transplantation (Spearman r = −0.33; P<0.001). Compared to the lowest quartile, patients in the highest quartile of urinary calprotectin had an increased risk for an eGFR less than 30 mL/min/1.73 m2 four weeks after transplantation (relative risk, 4.3; P<0.001; sensitivity, 0.92; 95% CI, 0.77 to 0.98; specificity, 0.48; 95% CI, 0.31 to 0.66). Higher urinary calprotectin concentrations predicted impaired kidney function 4 weeks after transplantation, as well as 6 months and 12 months after transplantation. When data were analyzed using the urinary calprotectin/creatinine-ratio similar results were obtained. Urinary calprotectin was superior to current use of absolute change of plasma creatinine to predict allograft function 12 months after transplantation. Urinary calprotectin predicted an increased risk both in transplants from living and deceased donors. Multivariate linear regression showed that higher urinary calprotectin concentrations and older donor age predicted lower eGFR four weeks, 6 months, and 12 months after transplantation. Conclusions Urinary calprotectin is an early, noninvasive predictor of immediate renal allograft injury after kidney transplantation.

Dynamics of Urinary Calprotectin after Renal Ischaemia.

Background: Urinary calprotectin has been identified as a promising biomarker for acute kidney injury. To date, however, the time-dependent changes of this parameter during acute kidney injury remain elusive. The aim of the present work was to define the time-course of urinary calprotectin secretion after ischaemia/reperfusion-induced kidney injury in comparison to neutrophil gelatinase—associated lipocalin, thereby monitoring the extent of tubular damage in nephron sparing surgery for kidney tumours. Methods: The study population consisted of 42 patients. Thirty-two patients underwent either open or endoscopic nephron sparing surgery for kidney tumours. During the surgery, the renal arterial pedicle was clamped with a median ischaemic time of 13 minutes (interquartile range, 4.5–20.3 minutes) in 26 patients. Ten retro-peritoneoscopic living donor nephrectomy patients and 6 nephron sparing surgery patients in whom the renal artery was not clamped served as controls. Urinary calprotectin and neutrophil gelatinase—associated lipocalin concentrations were repeatedly measured by enzyme-linked immunosorbent assay and assessed according to renal function parameters. Results: Urinary concentrations of calprotectin and neutrophil gelatinase—associated lipocalin increased significantly after ischaemia/reperfusion injury, whereas concentrations remained unchanged after nephron sparing surgery without ischaemia/reperfusion injury and after kidney donation. Calprotectin and neutrophil gelatinase—associated lipocalin levels were significantly increased 2 and 8 hours, respectively, post-ischaemia. Both proteins reached maximal concentrations after 48 hours, followed by a subsequent persistent decrease. Maximal neutrophil gelatinase—associated lipocalin and calprotectin concentrations were 9-fold and 69-fold higher than their respective baseline values. The glomerular filtration rate was only transiently impaired at the first post-operative day after ischaemia/reperfusion injury (p = 0.049). Conclusion: Calprotectin and neutrophil gelatinase—associated lipocalin can be used to monitor clinical and sub-clinical tubular damage after nephron sparing surgery for kidney tumours. Urinary calprotectin concentrations start rising within 2 hours after ischaemia/reperfusion-induced kidney injury.

Effects of Treatment of Asymptomatic Hyperuricemia on Graft Survival and Mortality in Kidney Transplant Recipients.

BACKGROUND Hyperuricemia is very common after renal transplantation. It is associated with an increased risk of cardiovascular events and graft loss. To date, however, treatment is only recommended in symptomatic disease. MATERIAL AND METHODS We included 503 adult patients who underwent kidney transplantation at the Charité-Universitätsmedizin Berlin in this retrospective study. Patients were followed up for up to 120 months. All-cause mortality, graft survival, changes in level of serum uric acid (SUA), and estimated glomerular filtration rate (eGFR) were analyzed. RESULTS At 12 months post-transplantation, 225 patients had a serum uric acid (SUA) level >7 mg/dl: 52 patients were treated with allopurinol, 37 with benzbromarone, and 136 patients received no medication for hyperuricemia (control). At 12 months, eGFR did not differ between groups (p=0.15) but treated patients had higher SUA levels (p<0.001) compared to the control group. SUA-lowering treatment was associated with a lower risk of all-cause mortality (p=0.013) and graft loss (p=0.014) compared to controls. At 120 months, patients in the treatment group had lower SUA levels (p=0.001) and higher eGFR (p<0.001) compared to the control group. CONCLUSIONS Treatment of asymptomatic hyperuricemia was associated with a substantial benefit in patient and graft survival.

Urinary Calprotectin Differentiates Between Prerenal and Intrinsic Acute Renal Allograft Failure.

BackgroundUrinary calprotectin has recently been identified as a promising biomarker for the differentiation between prerenal and intrinsic acute kidney injury (AKI) in the nontransplant population. The present study investigates whether calprotectin is able to differentiate between these 2 entities in transplant recipients as well. MethodsUrinary calprotectin was assessed by enzyme-linked immunosorbent assay in 328 subjects including 125 cases of intrinsic acute allograft failure, 27 prerenal graft failures, 118 patients with stable graft function, and 58 healthy controls. Acute graft failure was defined as AKI stages 1 to 3 (Acute Kidney Injury Network criteria), exclusion criteria were obstructive uropathy, urothelial carcinoma, and metastatic cancer. The clinical differentiation of prerenal and intrinsic graft failure was performed either by biopsy or by a clinical algorithm including response to fluid repletion, history, physical examination, and urine dipstick examination. ResultsReasons for intrinsic graft failure comprised rejection, acute tubular necrosis, urinary tract infection/pyelonephritis, viral nephritis, and interstitial nephritis. Calprotectin concentrations of patients with stable graft function (50.4 ng/mL) were comparable to healthy controls (54.8 ng/mL, P = 0.70) and prerenal graft failure (53.8 ng/mL, P = 0.62). Median urinary calprotectin was 36 times higher in intrinsic AKI (1955 ng/mL) than in prerenal AKI (P < 0.001). Receiver-operating characteristic curve analysis revealed a high accuracy of calprotectin (area under the curve, 0.94) in the differentiation of intrinsic versus prerenal AKI. A cutoff level of 134.5 ng/mL provided a sensitivity of 90.4% and a specificity of 74.1%. Immunohistochemical stainings for calprotectin in renal allograft biopsy specimens confirmed the serological results. ConclusionsUrinary calprotectin is a promising biomarker for the differentiation of prerenal and intrinsic acute renal allograft failure.

[OP.4A.07] THE IMPACT OF BLOOD PRESSURE VARIABILITY ON ADVERSE OUTCOMES AFTER KIDNEY TRANSPLANTATION.

Objective: Elevated long-term blood pressure variability has been shown to be predictive of adverse outcomes in patients with chronic kidney disease. In kidney transplant recipients a negative correlation between endothelial function and short-term variability has been found. No data exist, however, for associations of visit-to-visit variability (long-term variability) and outcomes after kidney transplantation. Design and method: 877 patients who underwent kidney transplantation at the Charité-Universitätsmedizin Berlin and at the Universitätsklinikum Knappschaftskrankenhaus Bochum, Germany were included in this retrospective study. Patients were followed up for at least 12 months (up to 266 months) after transplantation. Visit-to-visit blood pressure variability over the first 12 months after transplantation (3 visits) and during the first 120 months after transplantation (7 visits) was calculated as the coefficient of variation (CV) = standard deviation (SD)/ mean blood pressure. Results: Patients were categorized to those with low vs. high level of systolic CV at 12 months, defined by the median value (CV < 5.6 and CV> = 5.6%). After adjustment for gender, age and mean creatinine over the first 12 months the combined endpoint of death or graft loss did not differ between the two groups (HR (95% CI) = 1.1 (0.82 – 1.56), p = 0.44). No association was also found between patients with low and high systolic CV over 120 months (p = 0.15). Only primary graft function was associated with better outcomes after transplantation (p < 0.001). Conclusions: Visit-to-visit blood pressure variability is not associated with mortality or graft loss after kidney transplantation in this retrospective analysis. The presence of primary graft function was predictive of better long-term outcomes after transplantation. Figure. No caption available.

Prognostic Value of Urinary Calprotectin, NGAL and KIM-1 in Chronic Kidney Disease

Background/Aims: Urinary biomarkers like neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) do not only allow an early diagnosis of acute kidney injury, but also provide prognostic information in this setting. The present prospective study investigates, whether the urinary biomarkers NGAL, KIM-1 and calprotectin have prognostic information in chronic kidney disease (CKD) as well. Methods: Urinary calprotectin, NGAL and KIM-1 concentrations were assessed in a study population of 143 patients with stable CKD comprising diabetic and hypertensive nephropathy, glomerulonephritis/vasculitis, and autosomal dominant polycystic kidney disease. An eGFR fluctuation > 5ml/min/1.73m2 in the past 12 months was defined as an exclusion criterion in order to exclude cases with acute on chronic kidney injury. Renal function was monitored for a median follow-up of 37 months. Results: In the overall study population, all the three biomarkers failed to predict DeGFR and DACR from baseline to follow-up in linear regression analysis adjusted for age, gender, and baseline eGFR. Contrarily, baseline ACR was significantly associated with DeGFR (p< 0.001). In the subgroup of patients with vasculitis and glomerulonephritis, all the three biomarkers were significantly associated with DeGFR, with calprotectin having the highest regression coefficient. Conclusion: In contrast to the traditional biomarker “albuminuria”, neither the inflammatory biomarker calprotectin, nor the tubular biomarkers NGAL and KIM-1, provide robust prognostic information on the loss or renal function in a heterogeneous CKD population. All of them, however, are candidate prognostic biomarkers in primarily inflammatory renal diseases.

Urinary Biomarkers in the Prediction of Prognosis and Treatment Response in IgA Nephropathy

Background/Aims: The addition of immunosuppression to supportive care reduces proteinuria in a subset of patients with IgA nephropathy (IgAN) but is associated with an increased rate of adverse events. The present work investigates whether urinary biomarkers are able to identify subjects who benefit from immunosuppression and to predict the progression of disease in a sub-cohort of the STOP-IgAN trial. Methods: Urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), calprotectin, and the product of tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 (TIMP2•IGFBP7) were measured in all available urine samples obtained at the time point of enrollment in the STOP-IgAN trial (n=113). Results: Biomarker concentrations in both the overall study population and the subgroup with additional immunosuppression did not differ in subjects reaching vs. not reaching full clinical remission, eGFR loss ≥ 15, or 30 ml/min/1.73 m2 over the 3-year trial phase (p> 0.05 each). Receiver-operating characteristic curves showed a poor predictive accuracy of each biomarker for the above-mentioned parameters in the overall study population (areas under the curve ≤0.611). Accordingly, there was neither a significant correlation of any biomarker and adverse outcome in linear regression analysis, nor between biomarker concentrations at enrollment and change in the eGFR over the 3-year observation period. Conclusion: NGAL, KIM-1, calprotectin, and [TIMP-2]•[IGFBP7] had neither a prognostic value for the progression of IgAN, nor for the response to immunosuppression in the present sub-cohort of the STOP-IgAN trial. The search for appropriate biomarkers for an individualized treatment strategy in IgAN continues.

THE EFFECT OF MICROGRAVITY ON CENTRAL AORTIC BLOOD PRESSURE

Objective: BACKGROUND: Blood pressure has been traditionally measured at peripheral arteries. In the past decade evidence has grown, that central aortic blood pressure may be a more powerful predictor for cardiovascular events, but data on its regulation are rare. The present works examines the impact of microgravity on central blood pressure for the first time. Methods: We performed seven parabolic flights with 22 seconds of weightlessness in each parabola. Hemodynamic parameters including central systolic blood pressure were measured non-invasively in a free-floating position in 20 healthy subjects (19–43 years of age). Results: Arterial elasticity at rest was normal in all participants (augmentation index 14% [interquartile range IQR 10–22], pulse wave velocity 5.2 m/s [IQR 5.0–5.4]). Transition of 1 g to 0 g led to a significant increase of central systolic blood pressure from 124 (IQR 118–133) to 127 (IQR 119–133) mmHg (p = 0.017). Cardiac index propelled significantly from 2.5 (IQR 2.2–2.8) to 2.7 (IQR 2.3–3.0) l/min/m2 (p < 0.001), whilst peripheral vascular resistance showed a decrease from 1.30 (IQR 1.14–1.48) to 1.25 (IQR 1.15–1.40) s*mmHg/ml (p = 0.037). Peripheral systolic blood pressure did not change significantly (p > 0.05). Conclusion: Whereas there is a multitude of studies on the effects of microgravity on peripheral blood pressure, this study provides first data on central aortic blood pressure. An acute loss of gravity leads to a central blood volume shift with an augmentation of cardiac output. In healthy subjects with normal arterial stiffness the compensatory decrease of peripheral resistance does not outweigh this effect resulting in an increase of central blood pressure.