Activity and chronicity of kidney involvement in ANCA-associated vasculitis (AAV) can be currently reliably evaluated only by kidney biopsy. In this study, we measured a panel of serum and urinary ...biomarkers collected at the time of kidney biopsy and hypothesized that they could reflect specific histopathological parameters in the biopsy and help to predict prognosis.
We examined a cohort of 45 patients with AAV and 10 healthy controls. Biomarker levels (DKK-3, CD163, EGF, PRO-C6 and C3M) were measured in this study by ELISA. Biopsies were scored with a scoring system for AAV (focal x crescentic x sclerotic x mixed class) and interstitial fibrosis was quantified.
Levels of urinary DKK-3, CD163, EGF, PRO-C6 and C3M significantly differed among biopsy classes in AAV, with urinary DKK-3 and PRO-C6 levels being highest in the sclerotic class and lowest in the focal class, urinary CD163 levels highest in the crescentic class and urinary C3M levels highest in the focal class. Moreover, the urinary biomarkers were able to discriminate focal biopsy class from the other classes. Urinary DKK-3, EGF, PRO-C6 and C3M levels measured at the time of biopsy were also significantly related to the extent of fibrosis and to the final kidney function at the end of follow-up.
This small pilot study suggests that selected urinary biomarkers of fibrosis and inflammation may reflect changes in the kidney biopsy and be prognostic of kidney outcome in patients with AAV.
Aims
High‐flow arteriovenous fistula (AVF) for haemodialysis leads to profound haemodynamic changes and sometimes to heart failure (HF). Cardiac output (CO) is divided between the AVF and body ...tissues. The term effective CO (COef) represents the difference between CO and AVF flow volume (Qa) and better characterizes the altered haemodynamics that may result in organ hypoxia. We investigated the effects of Qa reduction on systemic haemodynamics and on brain oxygenation.
Methods and results
This is a single‐centre interventional study. Twenty‐six patients on chronic haemodialysis with high Qa (>1500 mL/min) were indicated for surgical Qa reduction for HF symptoms and/or signs of structural heart disease on echocardiography. The included patients underwent three sets of examinations: at 4 months and then 2 days prior and 6 weeks post‐surgical procedure. Clinical status, echocardiographical haemodynamic assessment, Qa, and brain oximetry were recorded. All parameters remained stable from selection to inclusion. After the procedure, Qa decreased from 3.0 ± 1.4 to 1.3 ± 0.5 L/min, P < 0.00001, CO from 7.8 ± 1.9 to 6.6 ± 1.5 L/min, P = 0.0002, but COef increased from 4.6 ± 1.4 to 5.3 ± 1.4 L/min, P = 0.036. Brain tissue oxygen saturation increased from 56 ± 11% to 60 ± 9%, P = 0.001.
Conclusions
Qa reduction led to increased COef. This was explained by a decreased proportion of CO running through the AVF in patients with Qa > 2.0 L/min. These observations were mirrored by higher brain oxygenation and might explain HF symptoms and improved haemodynamics even in asymptomatic high Qa patients.
Heart failure (HF) is a serious complication of end-stage kidney disease (ESKD). However, most data come from retrospective studies that included patients on chronic hemodialysis at the time of its ...initiation. These patients are frequently overhydrated, which significantly influences the echocardiogram findings. The primary aim of this study was to analyze the prevalence of heart failure and its phenotypes. The secondary aims were (1) to describe the potential of N-terminal pro-brain natriuretic peptide (NTproBNP) for HF diagnosis in ESKD patients on hemodialysis, (2) to analyze the frequency of abnormal left ventricular geometry, and (3) to describe the differences between various HF phenotypes in this population.
We included all patients on chronic hemodialysis for at least 3 months from five hemodialysis units who were willing to participate, had no living kidney transplant donor, and had a life expectancy longer than 6 months at the time of inclusion. Detailed echocardiography together with hemodynamic calculations, dialysis arteriovenous fistula flow volume calculation, and basic lab analysis were performed in conditions of clinical stability. Excess of severe overhydration was excluded by clinical examination and by employing bioimpedance.
A total of 214 patients aged 66.4 ± 14.6 years were included. HF was diagnosed in 57% of them. Among patients with HF, HF with preserved ejection fraction (HFpEF) was, by far, the most common phenotype and occurred in 35%, while HF with reduced ejection fraction (HFrEF) occurred only in 7%, HF with mildly reduced ejection fraction (HFmrEF) in 7%, and high-output HF in 9%. Patients with HFpEF differed from patients with no HF significantly in the following: they were older (62 ± 14 vs. 70 ± 14,
= 0.002) and had a higher left ventricular mass index 96(36) vs. 108(45),
= 0.015, higher left atrial index 33(12) vs. 44(16),
< 0.0001, and higher estimated central venous pressure 5(4) vs. 6(8),
= 0.004 and pulmonary artery systolic pressure 31(9) vs. 40(23),
= 0.006 but slightly lower tricuspid annular plane systolic excursion (TAPSE): 22 ± 5 vs. 24 ± 5,
= 0.04. NTproBNP had low sensitivity and specificity for diagnosing HF or HFpEF: with the use of the cutoff value of 8,296 ng/L, the sensitivity of HF diagnosis was only 52% while the specificity was 79%. However, NTproBNP levels were significantly related to echocardiographic variables, most significantly to the indexed left atrial volume (
= 0.56,
< 10
) and to the estimated systolic pulmonary arterial pressure (
= 0.50,
< 10
).
HFpEF was by far the most common heart failure phenotype in patients on chronic hemodialysis and was followed by high-output HF. Patients suffering from HFpEF were older and had not only typical echocardiographic changes but also higher hydration that mirrored increased filling pressures of both ventricles than in those of patients without HF.
Vast majority of chronic kidney disease patients die from cardiovascular complications. Echocardiography is a fundamental method, which reveals many of them. They include especially dilatation and ...systolic dysfunction of the left ventricle and atrium, left ventricular hypertrophy, diastolic dysfunction of the left ventricle, heart calcification, which could lead up to the development of stenotic valvular disease, right ventricular dysfunction and pulmonary hypertension. Patients with chronic kidney failure differ from the general population by cyclic changes of hydration and by the presence of a low resistant arteriovenous shunt (hemodialysis access). These factors significantly affect the actual echocardiographic finding.
Background:
Heart failure (HF) is a frequent cause of morbidity and mortality of end-stage kidney disease (ESKD) patients on hemodialysis. It is not easy to distinguish HF from water overload. The ...traditional HF definition has low sensitivity and specificity in this population. Moreover, many patients on hemodialysis have exercise limitations unrelated to HF. Therefore, we postulated two new HF definitions ((1) Modified definition of the Acute Dialysis Quality Improvement working group; (2) Hemodynamic definition based on the calculation of the effective cardiac output). We hypothesize that the newer definitions will better identify patients with higher number of endpoints and with more advanced structural heart disease.
Methods:
Cohort, observational, longitudinal study with recording predefined endpoints. Patients (n = 300) treated by hemodialysis in six collaborating centers will be examined centrally in a tertiary cardiovascular center every 6–12 months lifelong or till kidney transplantation by detailed expert echocardiography with the calculation of cardiac output, arteriovenous dialysis fistula flow volume calculation, bio-impedance, and basic laboratory analysis including NTproBNP. Effective cardiac output will be measured as the difference between measured total cardiac output and arteriovenous fistula flow volume and systemic vascular resistance will be also assessed non-invasively. In case of water overload during examination, dry weight adjustment will be recommended, and the patient invited for another examination within 6 weeks. A composite major endpoint will consist of (1) Cardiovascular death; (2) HF worsening/new diagnosis of; (3) Non-fatal myocardial infarction or stroke. The two newer HF definitions will be compared with the traditional one in terms of time to major endpoint analysis.
Discussion:
This trial will differ from others by: (1) detailed repeated hemodynamic assessment including arteriovenous access flow and (2) by careful assessment of adequate hydration to avoid confusion between HF and water overload.
Purpose
Data on the anti-Xa efficacy of fondaparinux in dialysis-dependent chronic kidney disease (DD-CKD) patients are scarce. This study characterizes the pharmacokinetics (PK) and pharmacodynamics ...(PD) of fondaparinux in DD-CKD patients undergoing renal replacement therapy (RRT), to assess dosing strategies.
Methods
A retrospective, observational study was conducted using data on anti-Xa activity (112 samples) from 12 (3 male and 9 female) DD-CKD patients (median (IQR) age 71 years (63–88), weight 73 kg (59–98.5)). Eleven patients underwent high-flux or low-flux hemodialysis (HD) and one patient underwent peritoneal dialysis. Three patients were also treated with therapeutic plasma exchange (TPE). A non-linear mixed effects analysis was performed using NONMEM 7.3.0.
Results
The lab-specific slope of the relationship between fondaparinux concentration and anti-Xa levels was 1.18 IU/µg. In a one-compartment model, clearance (CL) and volume of distribution (Vd) were 0.05289 L/h and 5.55 L, respectively. High-flux HD was found to increase the CL of fondaparinux 2.26 times. TPE also considerably increased CL, but the fold-change could not be accurately estimated. Low-flux HD and peritoneal dialysis did not impact PK parameters.
Conclusions
Model-based simulations showed that standard dosing (2.5 mg three times weekly before HD) results in a median anti-Xa activity of 0.55 IU/mL and 0.98 IU/mL, pre- and post-low-flux HD, respectively. In patients undergoing high-flux HD, these values are approximately 27% lower. Additional caution is warranted with TPE, as this treatment can reduce anti-Xa activity even further.
Vancomycin is frequently used in haemodialysis (HD) patients but generally accepted target serum ranges and dosing strategy are still lacking in this group. Based on retrospective analysis of data ...from 118 HD patients treated with vancomycin the interdialytic elimination constant (K
e
), apparent volume of distribution (Vd) and dialysis efficacy were calculated. The influence of possible clinical variables on the pharmacokinetic parameters of vancomycin have been tested. The median of K
e
in interdialytic periods, corresponding half-life and Vd were 0.0073 h
−1
, 95.0 h and 0.87 L/kg, respectively. We found significant positive correlation between time in dialysis program and K
e
. The Vd correlated best with lean body mass (LBM). For high- and low flux membrane HD of 4 hours duration the decline in vancomycin levels was 20.88% and 12.86%, respectively. Based on these data loading dose for vancomycin in HD patient should be calculated as 24.483 × LBM (kg) + 455 mg. The utility of this equation for entire HD population should be also verified prospectively.
Peritonitis is a limiting complication of peritoneal dialysis, which is treated by intraperitoneal administration of antibiotics. Various dosing strategies are recommended for intraperitoneally ...administered vancomycin, which leads to large differences in intraperitoneal vancomycin exposure. Based on data from therapeutic drug monitoring, we developed the first-ever population pharmacokinetic model for intraperitoneally administered vancomycin to evaluate intraperitoneal and plasma exposure after dosing schedules recommended by the International Society for Peritoneal Dialysis. According to our model, currently recommended dosing schedules lead to possible underdosing of a large proportion of patients. To prevent this, we suggest avoiding intermittent intraperitoneal vancomycin administration, and for the continuous dosing regimen, we suggest a loading dose of 20 mg/kg followed by maintenance doses of 50 mg/L in each dwell to improve the intraperitoneal exposure. Vancomycin plasma level measurement on the fifth day of treatment with subsequent dose adjustment would prevent it from reaching toxic levels in the few patients who are susceptible to overdose.
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