CKD LAB METHODS, PROGRESSION & RISK FACTORS 1
FREQUENCY 3 4 11 12 21 22 30 32 33 35 37
0 Department of Nephrology-Dialysis-Transplantation, University of Lie?ge , CHU Sart Tilman, Lie?ge , Belgium
1 Department of Renal Physiology, Ho?pital Bichat, AP-HP and Denis Diderot University , Paris , France
2 Department of Clinical Chemistry, University of Lie?ge , Chu Sart Tilman, Lie?ge , Belgium
3 Markus Heisterkamp
4 Antoine Bouquegneau
5 Medical University of Gdansk , Gdansk , Poland
6 University Hospital of Bern , Bern , Switzerland
7 University Hospital of Lausanne , Lausanne , Switzerland
8 University Hospital of Lausanne (CHUV) , Lausanne , Switzerland
9 University Hospital of Gdansk , Gdansk , Poland
10 University Hospital of Bern (Inselspital) , Bern , Switzerland
11 Young Su Kim
12 Maciej Piskunowicz
13 Hallym University , Anyang , Republic of Korea
14 National Medical Center , Ilsan , Republic of Korea
15 Hallym University Sacred Heart Hospital , Chuncheon , Republic of Korea
16 Hallym University Sacred Heart Hospital , Anyang , Republic of Korea
17 AIB University Hospital , Bolu , Turkey
18 Abant Izzet Baysal University, Faculty of Medicine , Bolu , Turkey
19 Derince Education and Research Hospital , Kocaeli , Turkey
20 Victor Babes? National Institute for Research and Development In Pathology and Biomedical Sciences , Bucharest , Romania
21 Diana Zilisteanu
22 Hikmet Tekce
23 Odense University Hospital , Odense , Denmark
24 University of Potsdam , Potsdam , Germany
25 Odense University Hosptial , Odense , Denmark
26 University of Heidelberg , Mannheim , Germany
27 Synlab Academy , Mannheim , Germany
28 University Hospital Heidelberg , Heidelberg , Germany
29 University Medical Center Groningen , Groningen , Netherlands
30 Buket Kin Tekce
31 University Medical Center Groningen , Groningen , Germany
32 Alexandra Scholze
33 Graciela Delgado
34 University of Messina , Messina , Italy
35 Domenico Santoro
36 University of Torino , Torino , Italy
37 Roberta Clari
Introduction and Aims: Uric acid (UA) has been identified as a prognostic marker of
chronic kidney disease (CKD) progression. Preclinical studies also support an
independent pathophysiological role of UA in this process. Treatment of
hyperuricemia in CKD can be challenging as it requires dose reduction of the most
frequently used urate lowering therapy (ULT), the xanthineoxidase inhibitor
allopurinol. The aim of the current study was to analyze the prevalence of ULT in
patients with CKD stage 3. Further the dose adjustment of allopurinol was investigated
in the baseline data of the German Chronic Kidney Disease (GCKD) study cohort.
Methods: Baseline data and drug prescription pattern in a 1894 patient subset of the
GCKD study, on whom medication dosing information for allopurinol was available,
were evaluated. The GCKD study is a prospective observational national cohort study
that enrolled more than 5000 patients with CKD of various aetiologies, who are under
nephrological care, and currently follows them for up to 10 years. At the time of
enrolment, male and female patients had an estimated glomerular filtration rate
(eGFR) of 30-60 mL/min/1.73 m?.
Results: The mean age of the 1894 patients investigated was 62 ? 13 years. The average
urate level in the entire cohort was 7.2 mg/dl ?1.86 mg/dl. 532 (28.1%) of patients
received a UA lowering therapy. While patients without ULT had a urate level of 7.31 ?
1.9 mg/dl, patients being treated for high UA had a mean uric acid level of 6.9 ? 1.78
mg/dl. Among patients on ULT, 496 (93.2%) received allopurinol, 18 (3.4%) febuxostat
and 18 (3.4%) benzbromarone. The median allopurinol dose was 150 mg/d, which is in
line with the current recommendations at this GFR range. Nevertheless 30.2% of the
allopurinol treated patients received a dose of 300 mg/d [Figure]. Despite this excessive
dose these patients had a mean uric acid level of 6.31mg/dl ? 1.68 mg/dl. In the group
of patients on ULT, 365 (68.6%) were above the recommended urate level of 6 mg/dl.
Conclusions: Despite the fact that hyperurecemia is frequent in CKD 3, only a third of
patients are treated. Treatment largely fails to lower urate level below 6 mg/dl. While
the median dose was adequately adapted to GFR, a third of the patients received an
allopurinol dose that would be considered inadequately high. Our data indicate that the
treatment of hyperuricemia in CKD can be improved in both frequency of treatment
and dose adjustment.
ACCURACY OF COCKCROFT&GAULT AND CKD-EPI
EQUATIONS TO ESTIMATE GLOMERULAR FILTRATION RATE
IN OBESE POPULATION
Introduction and Aims: The prevalence of obesity is dramatically rising worldwide.
When drug dosing is considered, KDIGO recommends using estimated glomerular
filtration rate (eGFR), which is not adjusted to the body surface area (BSA). We have
tested the performances of two creatinine-based equations: Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI) ?de-indexed? by BSA, and Cockcroft&Gault
(CG) equation (non-indexed by BSA) with actual body weight or adjusted ideal body
weight (AIBW). We test the performance of these equations by comparing them with
measured GFR (mGFR) also expressed in mL/min.
Methods: Patients with body mass index (BMI) higher than 30 kg/m? were included.
The reference method for GFR measurement was plasma clearance of 51Cr-EDTA. We
have ?de-indexed? CKD-EPI, which is a BSA-adjusted value, by multiplying eGFR by
each individual?s body surface area and by dividing this intermediate result by 1.73 m2
(CKD-EPIdeindexed). We calculated bias (defined as the mean difference between
estimated and measured GFR), precision (defined as the SD around the bias) and
accuracy 30% (defined as the percentage of estimations within ? 30% of measured
Results: The population included 366 patients (185 women) from two different areas.
Mean age was 55 ? 14 years and mean BMI was 36 ? 7 kg/m2. Mean mGFR was
71 ? 35 mL/min. In the global population, bias of CG and CGAIBW was + 25 ?
39.8 mL/min and + 2.6 ? 21.7 mL/min, respectively. Accuracy 30% was 57% and
78%, respectively ( p=0.05). For the CKD-EPIdeindexed equation, the bias
was + 6.2 ? 19.7mL/min and the accuracy 30% was 76%.
Conclusions: CG is actually the equation used for drug dosing adaptation. Its accuracy
to estimate GFR is however not optimal in obese patients, as expected by the bias
induced by the actual body weight in the equation. Using adjusted ideal body weight in
CG avoids this inadequacy and significantly improves the performance of the CG. We
demonstrated that CKD-EPIdeindexed had globally the same performance as the
CGAIBW equation to estimate non-indexed mGFR. CKD-EPI could thus also be
recommended in this context of ?non-indexation?.
? The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
CIRCULATING ACE AND ACE2 IN PATIENTS WITH CHRONIC
KIDNEY DISEASE WITHOUT HISTORY OF CARDIOVASCULAR
Lidia Anguiano1, Marta Riera1, Julio Pascual1, Clara Barrios1, Angels Betriu2, Jose
M Valdivielso2, Elvira Fern?ndez2 and Mar?a Jos? Soler1
1Hospital del Mar-Institut Hospital del Mar d?Investigacions M?diques, Barcelona,
Spain, 2Hospital Arnau de Vilanova, Lleida, Spain
Introduction and Aims: Circulating angiotensin converting enzyme (ACE)2 activity is
increased in patients with cardiovascular(CV) disease. However, it has not been
Age (years) Gender (male/female)
Free water clearance
SP139 Table 1: Patient characteristics and circadian rhythms of renal functions
Cases: SCI + NP
previously studied in patients with Chronic Kidney Disease(CKD) without history of
Methods: Studied groups from NEFRONA: non-dialysis CKD stage 3-5 patients
(CKD3-5, n=1458), patients on dialysis(CKD5D, n=546) and 568 patients without
CKD were used as controls. Variables analyzed: gender, age; history of diabetes mellitus
(DM), dyslipidemia, hypertension; glycemic, renal, nutritional, lipid and anemia
profiles, vitamin D analogues treatment and antihypertensive treatments (ACEi and
ARBs). Circulating ACE2 and ACE activity was measured using a modified
fluorimetric assay for plasma samples. Paired case-control studies were performed.
Results: When matching samples for gender, DM, hypertension, dyslipidemia,
smoking, weight and age no differences for ACE2 activity between CKD3-5 and
CKD5D were found (44.6?2.22 RFU/?l/h vs 41.3?2.27). Control group showed higher
levels of ACE2 compared to CKD3-5 (57.9?2.3 vs 43.9?2.8) and CKD5D (56.4?2.8 vs
38.8?2.2). For ACE activity, control had lower levels compared to CKD3-5 (3712.2
?104.8 vs 4137?129.4) and CKD5D (3848.9?128.4 vs 4427.5?135.3). Statistical
differences between CKD3-5 and CKD5D were also found. ACE2 and ACE activity:
The bivariate analyses are showed in Figure 1 (*p<0.05). By multiple regression analysis
for ACE2, male gender, advanced age and DM were independent predictors of ACE2 in
CKD3-5 patients. Predictors in CKD5D patients were male gender, age, ARBs
treatments and colecalciferol treatment(Figure 2). By multiple regression analysis for
ACE, male gender, advanced age, DM, ACEi treatment and colecalciferol treatment
were independent predictors of ACE activity in CKD3-5 patients. Predictors in
CKD5D patients were ACEi and colecalciferol treatment(Figure 2).
Conclusions: In CKD3-5 patients without history of CV disease, old age and male
gender are significant predictors for elevated ACE2 and decreased ACE. DM was an
independent predictor for elevated ACE2 and ACE. In CKD5D, additional predictors
are ARBs treatment for ACE2 and ACEi treatment for ACE.
PATHOPHYSIOLOGY OF NOCTURNAL POLYURIA: CIRCADIAN
RHYTHMS OF RENAL FUNCTIONS
Marie-Astrid Denys1, Annick Viaene1,2, An-Sofie Goessaert1, Joris Delanghe1 and Karel Everaert1
1Ghent University Hospital, Ghent, Belgium, 2Ghent Univserity Hospital, Ghent,
Introduction and Aims: Nocturnal polyuria (NP) is a highly prevalent condition,
affecting up to 80% of nocturic patients. It can result in nocturia, which has an
important impact on quality of life, morbidity and mortality. NP can also lead to
overnight dilatation of the bladder in patients with a spinal cord injury (SCI) and
neurogenic bladder, resulting in various complications. The objective of this study was
to evaluate circadian rhythms of renal functions in an adult population.
Methods: A total of 97 adults <60 years were included: 26 cases with a SCI and NP, 30
able bodied controls with NP and 41 without NP. The ICS definition was used to define
NP: nocturnal urine production/24h-urine production >33%. All participants
performed a 24h-urinecollection (1sample/3h) to determine the voided volumes and
the levels of creatinine, osmolality, urea and sodium for each sample. The last 3
samples (12-2am, 3-5am, 6-8am) were considered as nighttime samples in the controls,
while the last 4 samples were considered as nighttime samples in the cases. A blood
sample was taken during the 24h-urinecollection.
Results: The median age in the 26 cases, 30 controls with NP and 41 controls without
NP was respectively 46 (21-59), 51 (21-59) and 42 (18-59) years (table 1). Controls
without NP (n=41) showed a significant circadian rhythm with a lower diuresis rate
( p<0,001), creatinine clearance ( p<0,05) and osmotic clearance ( p<0,001) during the
night. They showed no diurnal variation in free water clearance. In contrast, controls
with NP showed a significant increase in nocturnal free water clearance ( p<0,001),
pleading for a disturbance in vasopressin secretion. We observed no circadian rhythms
in renal functions in the cases. An episode of high diuresis rate and creatinine clearance
was observed early in the night (glomerular hyperfiltration, renal function capacity, ?)
Controls + no NP (n=41)
Conclusions: Different pathophysiological mechanisms can contribute to the
development of NP: disturbances in water diuresis, osmotic diuresis, and glomerular
filtration. Consequently, specific treatment is necessary in order to avoid the symptoms
and complications of NP.
DECREASED RENAL FUNCTION AS A RISK FACTOR FOR
POOR THREE-MONTH OUTCOMES IN PATIENTS WITH
ACUTE ISCHEMIC STROKE
Introduction and Aims: Chronic kidney disease (CKD) is an established risk factor for
cardiovascular disease including stroke. However, the effect of decreased estimated
glomerular filtration rate (eGFR) on stroke outcome remains controversial. In this
study, we evaluated the association between eGFR and 3-month stroke outcomes and
assessed whether CKD and its severity could affect clinical outcomes or not
Methods: In this prospective cohort study with a hospital-based stroke registry, 1,449
consecutive patients with ischemic stroke were enrolled. The eGFR was assessed using
CKD Epidemiology Collaboration (CKD-EPI) equations and divided as 4 groups
(eGFR ?60, 45-59, 30-44, and <30 mL/min/1.73m2). Composite endpoint included
all-cause mortality, stroke recurrence and coronary artery disease. Functional outcome
was measured using modified Rankin Scale (mRS) score, and a mRS score >2 was
defined as a poor functional outcome.
Results: Mean eGFR was 83.9 ? 21.1 (range, 5.0 to 152.0) mL/min/1.73m2 and the
distribution of baseline renal impairment was as follows: 1,274 with eGFR ?60 mL/
min/1.73m2, 94 with eGFR 45-59 mL/min/1.73m2, 43 with eGFR 30-44 mL/min/
1.73m2 and 38 with eGFR <30 mL/min/1.73m2. At 3-month of the stroke onset, 130
cases of composite endpoint were occurred. Patients with more advanced stages of
renal dysfunction had a higher incidence of all-cause mortality including fatal
cardiovascular events. The eGFR levels were also associated with the 3-month mRS
scores. Subjects with eGFR <30 mL/min/1.73m2 showed the highest rates of poor
functional outcome. In multivariate analysis, a baseline eGFR <30 mL/min/1.73m2
increased the risk of composite endpoint and poor functional outcome by 3.97- and
Conclusions: A low eGFR was closely associated with stroke outcome. In particular,
severely decreased renal function had a prognostic effect on 3-month all-cause
mortality and poor functional outcomes.
SIMPLE CYSTATIN C FORMULA COMPARED TO NEWER
CKD-EPI CYSTATIN C FORMULA FOR ESTIMATION OF
GLOMERULAR FILTRATION RATE IN PATIENTS WITH
CHRONIC KIDNEY DISEASE
Sebastjan Bevc1, Nina Hojs1, Radovan Hojs1, Robert Ekart1,
Maksimiljan Gorenjak1 and Ludvik Puklavec1
1University Clinical Center Maribor, Maribor, Slovenia
Introduction and Aims: Accurate assessment of glomerular filtration rate (GFR) is
essential for detecting and managing chronic kidney disease (CKD). Recently, serum
cystatin C-based formula (CKD-EPI cystatin formula) was proposed as a new GFR
marker. The aim of our study was to compare CKD-EPI cystatin formula and simple
cystatin C formula (100/serum cystatin C) against 51CrEDTA clearance in a large group
of CKD patients.
Methods: In this study 800 adult Caucasian patients (339 women, 461 men; mean age
58?15.5 years) with CKD were enrolled. In each patient serum cystatin C
(immunonephelometric method) was determined. GFR was calculated using the
CKD-EPI cystatin formula and simple cystatin C formula. GFR was also measured
using 51CrEDTA clearance, and the correlation, accuracy, bias and precision of both
equations were determined. Ability to correctly estimate patient's GFR with different
equations compared to 51CrEDTA clearance below and above 60 ml/min/1.73m2 was
Results: The mean 51CrEDTA clearance was 47.2?33.6 ml/min/1.73m2, mean serum
cystatin C was 2.53?1.53 mg/l. Statistically significant correlations between 51CrEDTA
clearance and both formulas were found (P<0.0001). The Receiver Operating
Characteristic (ROC) curve analysis (cut-off for GFR 60 ml/min/1.73m2) showed that
simple cystatin C formula (area under the ROC curve (AUC)=0.972)) had a higher
diagnostic accuracy than CKD-EPI cystatin formula (AUC=0.922) (P=0.0001). Bland
and Altman analysis for the same cut-off value showed that CKD-EPI cystatin formula
(bias: -10.8 ml/min/1.73m2) underestimated and simple cystatin C formula (bias: 9.4
ml/min/1.73m2) overestimated measured GFR. All equations lacked precision. It was
21.8 ml/min/1.73m2 for CKD-EPI cystatin formula and 15.4 ml/min/1.73m2 for simple
cystatin C formula. Analysis of ability to correctly predict GFR below and above 60 ml/
min/1.73m2 showed that simple cystatin C formula had higher prediction than
CKD-EPI cystatin formula (simple cystatin C formula 89.1% vs. CKD-EPI cystatin
formula 81.5%; P<0.0005).
Conclusions: Our results indicate that the simple cystatin C formula is a reliable
marker of GFR in CKD patients and comparable to the newer sophisticated CKD-EPI
ESTIMATION OF GLOMERULAR FILTRATION RATE IN
ELDERLY PATIENTS - EXTERNAL VALIDATION OF TWO
Sebastjan Bevc1, Nina Hojs1, Radovan Hojs1, Robert Ekart1,
Maksimiljan Gorenjak1 and Ludvik Puklavec1
1University Clinical Center Maribor, Maribor, Slovenia
Introduction and Aims: Estimation of glomerular filtration rate (GFR) is essential for
the evaluation of patients with chronic kidney disease (CKD). Recently, two novel
equations that use both serum creatinine and cystatin C concentration (The Chronic
Kidney Disease Epidemiology Collaboration formula (CKD-EPI creatinine & cystatin)
and Berlin Initiative Study (BIS2)) were proposed as new GFR markers. The aim of our
study was to perform external validation of both novel equations in our elderly CKD
Methods: 106 adult Caucasian patients, older than 65 years (58 women, 48 men; mean
age 72.5 years), were included. In each patient 51CrEDTA clearance, serum creatinine
(IDMS traceable method) and serum cystatin C (immunonephelometric method) were
determined. GFR was calculated using the CKD-EPI creatinine & cystatin formula and
Results: The mean 51CrEDTA clearance was 52.2?15.9 ml/min/1.73m2, mean serum
creatinine 141.4?41.5 ?mol/l, mean serum cystatin C 1.79?0.6 mg/l. Statistically
significant correlations between 51CrEDTA clearance and both formulas were found
(P<0.0001). In the ROC curve analysis (cut-off for GFR 45 ml/min/1.73m2) no
significant difference of diagnostic accuracy between CKD-EPI creatinine & cystatin
formula and BIS2 formula was found (P=0.843) (area under the ROC curve for both
formulas was 0.948). Bland and Altman analysis for the same cut-off value showed that
CKD-EPI creatinine & cystatin formula (bias: -18.3 ml/min/1.73m2) and BIS2 formula
(bias: -18 ml/min/1.73m2) underestimated measured GFR. All equations lacked
precision. It was 8.8 ml/min/1.73m2 for CKD-EPI creatinine & cystatin formula and
8.3 ml/min/1.73m2 for BIS2 formula. Analysis of ability to correctly predict patient?s
GFR below or above 45 ml/min/1.73m2 showed similar ability for both formulas
(CKD-EPI creatinine & cystatin formula (61.3%) versus BIS2 formula (63.2%)
Conclusions: Our external validation of novel formulas indicates that both
sophisticated formulas are equally accurate and reliable markers of GFR in Caucasian
elderly CKD patients.
A NEW TECHNIQUE WITH HIGH REPRODUCIBILITY TO
ESTIMATE RENAL OXYGENATION USING BOLD-MRI IN
CHRONIC KIDNEY DISEASE
Introduction and Aims: Animal studies suggest that renal tissue hypoxia plays an
important role in the pathogenesis of chronic kidney disease (CKD). Blood
oxygenation level-dependent MRI (BOLD-MRI) is a powerful technique to assess renal
tissue oxygenation non-invasively in humans. However, the acquisition and analysis of
MR images lacks standardization, and studies in CKD patients are sparse. The aim of
this study was to assess inter-observer variability of the classical ROI (region of
interest)-based technique, in comparison with a new method of analysis, called the
concentric objects (CO) technique, in healthy subjects and CKD patients.
iii??? | Abstracts
Methods: MR imaging (3.0 Tesla) was performed under standardized conditions
before and after furosemide in ten CKD patients and ten healthy volunteers, and R2*
maps determined on four coronal slices covering both kidneys. In the ROI technique,
the R2* values in medulla and cortex were based on the manual placement of circles
(ROIs), whereas in the CO technique, a semi-automatic procedure divided each kidney
in six equal layers based on the kidney contour (see figure). The mean R2* values (a
low R2* value indicating high oxygenation) as assessed by two independent
investigators were compared.
Results: With the ROI technique, inter-observer variability for mean cortical and
medullary R2* values was 3.6 and 6.8% in non-CKD, versus 4.7 and 12.5% in CKD
subjects; with the CO technique, inter-observer variability was between 0.7 and 1.9%
across all layers in non-CKD, and between 1.6 and 3.8% in CKD patients. Similar
results were seen after furosemide. There was a trend towards higher R2* values in
CKD patients than healthy controls with the CO technique, whereas opposite results
were obtained with the ROI technique.
Conclusions: The classical ROI-based technique is not a reliable way to estimate renal
tissue oxygenation in CKD patients. The CO technique offers a new, highly
reproducible alternative and suggests, in line with animal studies, that CKD is
characterized by chronic renal tissue hypoxia.
SERUM OSTEOPROTEGERIN IS A PREDICTOR OF DIASTOLIC
DYSFUNCTION AND VASCULAR STIFFNESS IN CHRONIC
KIDNEY DISEASE PATIENTS
Introduction and Aims: The aim of the present study is to evaluate the association
between osteoprotegerin (OPG) and fibroblast growth factor 23 (FGF23)
concentrations with respect to vascular stiffness and cardiac disease in chronic kidney
disease (CKD) patients.
Methods: We enrolled 54 subjects: 44 chronic kidney disease patients in pre-dialysis (8
patients with CKD stage 2, 24 patients with CKD stage 3, 12 patients with CKD stage
4), and 10 healthy controls. OPG, FGF23 intact parathyroid hormone (iPTH) were
measured using xMAP technology (Luminex? 200?). Arterial stiffness measurements
were performed with the SphygmoCor device. Echocardiographic evaluation was
performed in order to evaluate left ventricular function, including the transmitral early
tiastolic velocity/tissue Doppler mitral annular early diastolic velocity ratio (E/E?).
Statistical analysis was performed using IBM SPSS Statistics Version 21.
Results: Levels of OPG, FGF23 and iPTH were significantly higher ( p<0.05) in CKD
patients than in healthy controls. The levels of FGF23 inversely correlated with
estimated glomerular filtration rate. PWV mean value was significantly elevated in
CKD patients versus control group. Diastolic dysfunction was present in 89.3%
patients, left ventricular hypertrophy in 72.2%, and aortic valve calcifications were
present in 58.2% patients.OPG levels significantly correlated with left ventricular mass
index and E/E?( p<0.05). A stepwise multiple regression analysis showed that OPG and
iPTH levels positively reflected an increase of pulse wave velocity ( p<0.0001). We
didn?t find significant correlation between FGF23 and PWV. FGF23 correlated with
aortic valvular calcifications ( p=0.01).
Conclusions: Our results demonstrated that OPG is correlated with increased vascular
stiffness and diastolic dysfunction in CKD patients. Our data underscore that
cardiovascular disease appear even from early stages of CKD and mineral-bone disease
serology parametres could be used as surrogate biomarkers for cardiac complications
among patients with CKD.
This work was partially supported by a grant of the Romanian National Authority
for Scientific Research, CNDI- UEFISCDI, project number
CAROTID PLAQUES AND PROGRESSION OF RENAL
DYSFUNCTION IN PATIENTS WITH CHRONIC KIDNEY
Introduction and Aims: Carotid plaque is a surrogate marker of systemic
atherosclerosis and closely associated with adverse cardiovascular outcomes. However,
data regarding the predictive role of carotid plaque for progression of renal dysfunction
Methods: This is a longitudinal observational study with a cohort of 411 Stage 3 and 4
chronic kidney disease (CKD) patients. A carotid plaque was defined as a focal
structure encroaching into the arterial lumen of at least 0.5mm or 50% of the
surrounding carotid intima-media thickness (cIMT) or a thickness >1.5mm. Renal
function decline was measured by estimated glomerular filtration rate (eGFR) slope
and renal endpoint was defined as the start of dialysis.
Results: Baseline eGFR was 44.5?11.6 mL/min/1.73m2 and eGFR slope was -2.87
?3.76 min/1.73m2/yr. A carotid plaque was found in 282 (68.6%) patients, and these
patients had significantly faster rates of renal decline than those without plaque
(-3.64?3.84 vs. -1.20?2.85 mL/min/1.73m2/yr, p<0.001). According to multivariate
analysis, statistically significant variables determining eGFR slope were diabetes
(?=-0.77, p=0.033), increased pulse pressure (?=-0.02, p=0.015), proteinuria
(?=-0.50, p<0.001), cIMT (?=-4.36, p<0.001) and the presence of carotid plaques
(?=-1.48, p<0.001). During the 2.5-year follow-up, 47 (11.4%) of patients started
dialysis. Patients with carotid plaque had a poorer dialysis-free survival rate than
those without carotid plaque (hazard ratio 3.3: 95% confidence interval 1.01, 10.77).
Particularly, irregular plaque surface significantly increased the risk of dialysis by
Conclusions: Carotid plaque was closely associated with rapid decline of renal
function and progression to dialysis in stage 3 and 4 CKD patients.
DIALYSIS IN THE END-STAGE RENAL DISEASE: COMORBID
Momir Polenakovic1 and Nada Pop-Jordanova1
1Macedonian Academy of Sciences and Arts, Skopje, Macedonia, The Former
Yugoslav Republic of
Introduction and Aims: The haemodialysis as a treatment of choice for the end-stage
renal diseases disrupt a normal life-style and require considerable psychological and
social adaptation. Chronic stress related to the process of dialysis increases the level of
depression and leads to some personality changes like alexithymia construct. The
purpose of the study was a) to evaluate the level of depression in patients treated with
maintenance chronic haemodialysis and b) to assess the presence of the alexithymia
construct as a stable personality trait.
Methods: The evaluated sample comprises 230 patients; 110 were females (mean age
55.5 ? 13.5 years), and 120 males (mean age 54.5? 14.3 years). The mean duration of
maintenance dialysis was 8.3 ? 5.8 years (from 0.5 to 24 years). Patients were recruited
randomly from three dialysis centers in R. Macedonia.As a psychometric instruments
Beck Depression Inventory and TAS-20 was applied. Both are translated and validated
for Macedonian population.
Results: Obtained results showed that mild depression is most frequent in evaluated
patients (35.71%), but the percentage of severe depression is also very significant
(14.28%). Moderate depression was present in 17.85% and minimal in 21.43% of all
examinees. The depression was positively correlated with age and educational level and
negatively with the duration of dialysis.
Results for TAS-20 showed that 50% of patients obtained scores indicative of
alexithymia construct, 18% had possible alexithymia, and the rest of 32% were
non-alexithymic. The age and the duration of dialysis positively influenced the scores
for TAS-20. In addition, the duration of dialysis was significantly influenced by age.
Factors analysis in TAS-20 showed that F1 and F2 are not influenced by age or duration
of dialysis. Only factor F3 is very perceptible and influenced by the age and the
duration of dialysis. No significant differences in scores between males and females
were obtained. Only F1 is higher in males. We did not find correlation between
depression level and alexithymia scores.
Conclusions: The depression in dialyzed patients is frequently underdiagnozed. The
depression is influenced by age and educational level and negatively by the duration of
As a permanent personality trait alexithymia construct was confirmed in 50% of
patients as well as in 18% as possible alexithymia.It was concluded that the alexithymia
construct is related to neurobiological brain specifics. No correlation between
depression level and alexithymia scores was found.
Both, alexithymia construct and depression can influence the prognosis and outcome
of dialyzed patients. In any case, the psychological support for mediating these
comorbid characteristics should be included in the therapeutic protocols of all chronic
EFFECTS OF VOLUME OVERLOAD ON PROGRESSION
OF CHRONIC KIDNEY DISEASE
Szu-Chun Hung1 and Der-Cherng Tarng2
1Taipei Tzu Chi Hospital, New Taipei City, Taiwan, 2Taipei Veterans General
Hospital, Taipei, Taiwan
Introduction and Aims: Hypertension was an independent risk factor for renal disease
progression. However, no study has evaluated the association of volume dependent
hypertension versus non-volume dependent hypertension with renal outcomes. We
aim to evaluate the impact of baseline systolic blood pressure (SBP) and volume status,
according to relative overhydration levels (OH) determined by Body Composition
Monitor, on progression of chronic kidney disease (CKD).
Methods: 326 stage 3-5 CKD patients were classified according to baseline SBP
(categories: <140 or ?140 mmHg) and OH (categories: <7 or ?7%). Four different
groups can be identified: patients who are normohydrated and normotensive (32%,
Group A), who are hypertensive despite being normohydrated (17%, Group B,
non-volume dependent hypertension), who are normotensive despite being volume
overloaded (22%, Group C), and patients who are both volume overloaded and
hypertensive (29%, Group D, volume dependent hypertension). The main outcome
measure was decline of estimated glomerular filtration rate (eGFR) >50% or chronic
Results: After a median follow up of 596 days, there were 15 primary end-point events
in the Group A, 9 in the Group B, 18 in the Group C, and 43 in the Group D. Patients
with volume dependent hypertension (Group D) were at a higher risk of renal outcome
compared with patients in the other 3 groups (Groups A, B, and C, P<0.01). In a
multivariate Cox model, patients in the Group D had the highest hazard ratio (HR
1.93, 95% CI, 1.01-3.71, P=0.048) compared with patients in the Group A, when
adjusting for age, sex, cardiovascular disease, diabetes mellitus, use of
renin-angiotensin system blockade, eGFR, and proteinuria.
Conclusions: Volume dependent hypertension is associated with worse renal
outcomes than non-volume dependent hypertension in CKD patients. Further research
is warranted to clarify whether the correction of volume overload would improve renal
outcomes of CKD patients with volume dependent hypertension.
iii??? | Abstracts
ALLOPURINOL THERAPY FOR HYPERURICEMIA REDUCES
INFLAMMATION AND PROGRESSION OF RENAL DISEASE IN
MODERATE CHRONIC KIDNEY DISEASE
Liliana Tuta1 and Alina Stanigut1
1?Ovidius? University of Constanta, Faculty of Medicine, Constanta, Romania
Introduction and Aims: Hyperuricemia is a common finding in patients with
metabolic syndrome and in those with cardiovascular and renal disease. Moreover, the
elevation in uric acid levels observed after fructose ingestion, with a consequent
reduction in nitric oxide, may lead to a reduced glucose uptake in the skeletal muscle,
hyperinsulinemia, and insulin resistance. Clinical studies showed the beneficial effects
of lowering uric acid therapies on several markers of cardiovascular and renal disease.
To date, however, there is no evidence indicating that such therapies, that are not free
of risk, may reduce cardiovascular events. In the mean time, few data are available
regarding the effect of allopurinol in patients with chronic kidney disease.
Methods: We conducted a prospective, randomized trial of 125 patients with estimated
GFR (eGFR) 30-59 ml/min. Patients were randomly selected either to treatment with
allopurinol 100 mg/d (n= 52) or to continue the usual therapy (n =63). Clinical and
biochemical, including inflammatory parameters were followed at baseline and after 3,
6, and 12 months of therapy. The objectives of study were the monitoring of renal
disease progression (modifications of eGFR) and cardiovascular events that needed
Results: Serum uric acid, C-reactive protein levels and IL-6 were significantly decreased
in subjects treated with allopurinol. In the control group, eGFR decreased 2.2?1.2 ml/
min/1.73 m?, and in the allopurinol group, eGFR increased 1.7? 0.8 ml/min/1.73 m?
after 12 months. Allopurinol treatment slowed down renal disease progression
independently of age, gender, association with diabetes, levels of C-reactive protein,
IL-6, albuminuria, and renin-angiotensin system blockers use. After a mean follow-up
time of 12 months, 32 patients (24%) suffered a severe cardiovascular event that needed
hospitalization. Diabetes mellitus, previous coronary heart disease, and C-reactive
protein levels increased cardiovascular risk. Allopurinol treatment reduced risk of
cardiovascular events in 63% of cases, compared with standard therapy. Only in 6 cases
(4.8%) the allopurinol therapy was stopped because the occurrence of side effects.
Conclusions: Allopurinol decreases C-reactive protein and IL-6 levels and seems to
slow down the progression of renal disease in patients with moderate to severe chronic
kidney disease. In addition, allopurinol reduces serious cardiovascular events, need for
hospitalization and, consecutively, the medical costs in these subjects.
ACUTE RENAL INFARCTION: A SINGLE CENTRE
Paola Mesiano1, Cristiana Rollino1, Michela Ferro1, Giulietta Beltrame1,
Carlo Massara1, Giacomo Quattrocchio1, Marco Borca1, Mario Bazzan1 and Dario Roccatello1,2
1Ospedale San Giovanni Bosco, Turin, Italy, 2Universit? Di Torino, Turin, Italy
Introduction and Aims: acute renal infarction, due to an abrupt interruption of blood
flow in the renal artery, is frequently not recognized. Non specific clinical presentation,
mimicking other conditions (i.e., nephrolithiasis, pyelonephritis), may explain the
possible delay in diagnosis. Major causal factors include atrial fibrillation, valvular or
ischaemic heart disease, renal artery thrombosis/dissection, coagulopathies. Etiology
remains in many cases unknown. We describe the clinical characteristics and outcome
of 16 patients with acute renal infarction.
Methods: we retrospectively analysed the medical records of 16 patients (12 M and 4 F)
with renal infarction diagnosed by computed tomography (CT) or magnetic resonance
imaging (MRI) admitted to our Nephrology Department between 1999 and 2012 and
subsequently followed for 10 years as outpatients.
Results: mean age was 58.62 years (range 29-86 years); at the time of diagnosis, eleven
patients presented with lumbar pain, 3 with diffuse abdominal pain. Notably, in 2
patients renal infarction was painless. Associated symptoms included macroscopic
haematuria (3 patients), arterial hypertension (9), hyperthermia (4), oliguria (2) and
dysuria (1). Possible associated risk factors included obesity/overweight (6 patients),
current smoking (3), cocaine abuse (1), estroprogestinic therapy (2), atrial fibrillation
(4), and atrial mixoma (1 patient). Six out of 11 patients were found to have
antophospholipid antibodies at the diagnosis (anti-?2GPI antibodies in 3,
anticardiolipin antibodies in 2, LAC in 1), but only one had these antibodies still
detectable 12 weeks later. Systolic arterial pressure was 147.69?18.99 mmHg, diastolic
83?10 mmHg. Laboratory investigations at onset revealed leukocytosis in 10 patients,
elevated lactate dehydrogenase levels in 13 and augmented C-reactive protein in 10.
Mean serum creatinine was 1.4 ? 0.6 mg/dL (eGFR 65?30 mL/min/1.73 m2). Acute
kidney injury occurred in two patients at presentation. CT scan/MRI imaging showed
alterations of renal arteries in 9 cases (thrombosis in 5 patients, renal artery dissection
in 1, fibromuscular dysplasia in 2 and both thrombosis and dissection in 1). Thirteen
patients were treated with LMWH, 2 with aspirin alone; one patient did not receive
anticoagulant/antiplatelet treatment because of severe arterial hypertension. At the end
of follow-up (23.6?36 months in 9 patients), serum creatinine was 1.1 ? 0.2 mg/dL; one
patient remained on chronic hemodialysis. In 4/6 patients who underwent renal
scintigraphy after a median of 28 months (range 6-120), the contribution of the
affected kidney to total renal function was reduced.
Conclusions: 50% of our patients had an idiopathic renal infarction. Renal artery
abnormalities (fibromuscular dysplasia, renal artery dissection) were present in 25% of
patients, cardioembolic etiology in 25%. Clinical presentation was confirmed to be non
Further studies should focus on etiology and evolution of kidney function in patients
with acute renal infarction.
BIOMARKERS OF EARLY RENAL TUBULAR DAMAGE
IN PATIENTS WITH GOUT
Adelya Maksudova1, Lilya I Urasaeva1 and Tamila N Khalfina1
1Kazan State Medical University, Kazan, Russian Federation
Introduction and Aims: Many patients with gout can have CKD at a later stage, as
there are no clinical manifestations for a long time. In this connection it is important to
study biomarkers of kidney damage at the preclinical stage of CKD. The aim of the
study: to determine level of kidney damage markers in patients with gout without
clinical manifestations of CKD.
Methods: We examined 33 gouty patients with normal GFR, with normal
microalbuminuria level and kidney ultrasound, thus without any CKD evidence. The
average age of the patients was 52 ? 9.4 years, GFR 92,2 ml/min/1,73 m2 [85; 101,8] .
The control group consisted of 25 healthy volunteers. The average age of them was 47.9
? 5.6 years, GFR 91,2 ml/min/1,73 m2[88,7; 111,6]. The examination included the
detection by ELISA, VEGF, TGF-b1, KIM-1. Statistical analysis was carried out using a
standard package Statistics 6.0.
Results: The group of patients had significantly lower levels of a marker of
angiogenesis VEGF-A compared with healthy volunteers: 97pg/ml [64.6; 262.8] vs
193.3 pg/ml [113.8; 275.6], p <0.05. TGF-b1 as a marker of fibrosis in patients with
gout was significantly lower than in the control group 529.5 pg/ml [478.6, 546.5] vs
549.8 pg/ml [526; 621.5], p 0.05.
Conclusions: Patients with gout without clinical manifestations of CKD showed
decrease of the VEGF, TGF-b1 levels which can indicate the presence of early signs of
endothelial dysfunction and renal tubular fibrosis. At the same time a marker of acute
tubule injury in patients with gout did not change.
FIBROBLAST GROWTH FACTOR 23 CORRELATES WITH
AORTIC VALVE CALCIFICATIONS AND NON-DIPPER STATUS
IN CHRONIC KIDNEY DISEASE PATIENTS
Introduction and Aims: The aim of the present study is to evaluate the association
between fibroblast growth factor 23 (FGF-23) with respect to aortic valve calcifications,
arterial stiffness and dipping status in chronic kidney disease (CKD) patients.
Methods: We enrolled 54 subjects: 44 CKD patients in pre-dialysis (8 patients with
CKD stage 2, 24 patients with CKD stage 3 and 12 patients with CKD stage 4), and 10
healthy controls. FGF-23, IL-6, TNFalpha and intact parathyroid hormone (iPTH)
were evaluated using xMAP technology (Luminex? 200?). Echocardiography 2-D and
M-mode was used to assess the presence of aortic valve calcifications. Peripheral pulse
wave analysis and pulse wave velocity (PWV) was performed using SphygmoCor
device. All patients underwent 24 hour ambulatory blood pressure monitoring
(ABPM). Statistical analysis was performed using IBM SPSS Statistics Version 21.
Results: Levels of FGF-23, IL-6 and TNF-alpha and were significantly higher ( p<0.05)
in CKD patients compared to healthy controls. The levels of FGF-23, IL-6 and
TNF-alpha inversely correlated with estimated glomerular filtration rate. Aortic valve
calcifications were present in 58.2% patients, left ventricular hypertrophy in 72.2%, and
54.4% patients had non-dipper pattern. Mean values for stiffness parameters were:
PWV = 9.87 +/- 2.8 m/sec, left ventricular ejection duration index (ED) = 32.8 +/- 3.3
%, subendocardial viability ratio (SEVR) = 159.8 +/- 26.3 %. FGF-23 ( p=0.01),
TNF-alpha ( p=0.015) and eGFR ( p=0.008) significantly correlated with aortic valve
calcifications.FGF-23 significantly correlated with markers of inflammation and
mineral disturbances (TNF-alpha, p=0.01; IL-6, p=0.0001; iPTH, p=0.01), and
proteinuria ( p=0.008). Also, FGF-23 correlated with ED ( p=0.02), and SEVR
( p=0.019), but not with PWV. FGF-23 and IL-6 were significantly increased in CKD
patients with non-dipper versus dipper status ( p<0.05).
Conclusions: Our results demonstrated a link between FGF-23, aortic valve
calcifications, left venticular function (evaluated by ED and SEVR) and non-dipper
status in chronic kidney disease patients.
Acknowledgement: This work was partially supported by a grant of the Romanian
National Authority for Scientific Research, CNDI- UEFISCDI, project number
SERUM OMENTIN-1 LEVELS IN DIABETIC AND
NONDIABETIC PATIENTS WITH CHRONIC KIDNEY DISEASE
Introduction and Aims: Omentin-1, a novel adipokine identified in visceral adipose
tissue, is negatively correlated with different conditions such as diabetes, obesity and
inflammation. However, changes in serum Omentin levels associated with the degree of
the renal dysfunction and with metabolic risk factors in Chronic Kidney Disease
(CKD) patients has not yet been revealed. In the present study, we aimed to investigate
the level of Omentin-1 and related parameters in diabetic and nondiabetic CKD
Methods: Sixty-four (30 diabetic, 34 non-diabetic) CKD patients and 27 healthy
control subjects enrolled in this cross-sectional study. Patients with conditions that
possibly affect serum Omentin levels were excluded. Serum levels of albumin and
C-Reactive Protein (CRP) were used to determine malnutrition, and inflammation,
respectively, just as in studies evaluating high cardiovascular mortality and morbidity
in CKD patients. Malnutrition defined as serum albumin <3.5 mg/dL and
inflammation was defined as serum CRP level of > 10 mg/L (normal range, 0-5 mg/
L). The patients were classified as malnutrition-inflammation (MI)-0 (no
component), MI-1 (one component) and MI-2 (two components). Anthropometric
and laboratory assesment performed and malnutrition and inflammation
components evaluated. Serum concentrations of Omentin-1 and insulin were
measured by using ELISA.
Results: Serum Omentin-1 levels in CKD patients were significantly lower
compared to the healthy controls. Further analyse revealed that decrease in
omentin in CKD patients is due to the reduced omentin levels in diabetic
subgroup. There was a significant difference in serum Omentin-1 levels between
non-diabetic (324.2 ? 47.7 ng/mL) and diabetic (189.4 ? 31.2 ng/mL) CKD
subgroups ( p < 0.01). Omentin levels were lower in stage 2 and 3 CKD but not
stage 4 CKD patients compared to controls. An increase in inflammation and
malnutrition components were correlated with a decrease in the serum level of
Omentin. Omentin-1 measurements of the patients according to MI components
were shown in Table 1.
Conclusions: Diabetes mellitus and inflammation are responsible from the decrease
in serum levels of Omentin in CKD, however, this reduction resolves due to the
failure of degradation and excretion of omentin when creatinin clearance falls below
30 ml/dk (stage 4 CKD).
SP152 Table 1: Omentin-1 levels in malnutrition-inflammation (MI) subgroups
Number of MIcomponents
None One component Two components
Number of CKD
307.4 ? 172.2
191.3 ? 84.7a
145.8 ? 67.3b
One-way ANOVA test results was demonstrated in table 4. The ANOVA test p value was
0.019. CKD: Chronic kidney disease; MI: malnutrition, inflammation.
a Omentin-1 difference between one MI component versus no MI components, P =0.022.
bOmentin-1 difference between two MI components versus no MI components, P=0.013;
Omentin difference between two MI components versus one MI component, P=0.042.
THE FIRST MORNING URINE SAMPLE IS NOT APPROPRIATE
FOR THE EVALUATION OF PROTEINURIA
Jelka Lindic1, Darinka Purg1, Jasna Skamen1, Mladen Krsnik1, Andrej Skoberne1,
Jernej Pajek1, Radoslav Kveder1, Andrej Bren1 and Damjan Kovac1
1University Medical Centre Ljubljana, Ljubljana, Slovenia
Introduction and Aims: Proteinuria and albuminuria are early signs of chronic
renal disease and important risk factors for its progression. On the basis of the
results of epidemiological studies, the first morning urine sample analysis is
recommended for in patients with risk factors for chronic kidney disease. The aim
of this prospective study was to evaluate which urine sample is the most
appropriate for the evaluation of glomerular, tubular and total proteinuria, if
compared to 24-hour proteinuria.
Methods: We evaluated 20 patients with chronic glomerulonephritis, 7 women and
13 men, aged from 44.5 ? 11.3 years, with an estimated glomerular filtration rate of
85.2 ? 5.2 ml/min/1.73 m? and mild to nephrotic proteinuria (urinary protein to
creatinine 198.9 ? 45.8 g/mol, range 19.4-695.8 g/mol). They collected 24-hour
urine and on the same day the samples of the first and second morning urine, as
well as samples at 12 a.m., 3, 6 and 9 p.m. In the urinary samples and in the
24-hour urine, the ratios of albumin to creatinine, immunoglobulin G to creatinine,
alpha-1-microglobulin to creatinine, N-acetyl-?-D-glucosaminidase to creatinine
and protein to creatinine were determined.
Results: The second morning urine sample was the most appropriate for the
assessment of glomerular proteinuria - albuminuria (R = 0.989, p <0.001) and
immunoglobulin G excretion (R = 0.990, p <0.001), the sample taken at 3 p.m. for
N-acetyl-?-D-glucosaminidase (R = 0.897, p <0.001), the sample taken at 6 p.m. for
alpha-1-microglobulin (R = 0.921, p <0.001), and the sample taken at 9 p.m. for
total proteinuria (R = 0,997, p <0.001). Glomerular, tubular and total proteinuria
were underestimated in the first morning sample.
Conclusions: The second morning urine was superior for the detection of
glomerular proteinuria, and the late evening sample at 9 p.m. the most appropriate
one for the estimation of overall proteinuria. The first morning sample
underestimated glomerular, tubular and total proteinuria; therefore, its use for the
screening purposes or evaluation is questionable.
EVALUATION THE SERUM LEVELS OF KIDNEY
INJURY MOLECULE-1 IN PATIENTS WITH CHRONIC
KIDNEY DISEASE SECONDARY TO DIABETIC
Introduction and Aims: Early diagnosis of diabetic nephropathy is essential in
avoiding of end stage renal disease. Markers used for dianosis of renal damage in
diabetic patients have known handicaps, therefore, investigators search for new
biomarkers in diagnosis of renal damage. Kidney Injury Molecule-1 (KIM-1) is a
protein that increases in urine following tubular damage. We studied urinary KIM-1
levels according to the level of Chronic Kidney Disease (CKD) based from diabetic
Methods: We evaluated clinical and laboratory findings of 69 patients with diabetic
nephropathy who were followed by nephrology department of our institution and 18
healthy volunteers. Creatinine, albumin, total cholesterol, triglyceride, low density
lipoprotein cholesterol, high density lipoprotein cholesterol and HbA1c levels in blood
samples and albumin, creatinine and KIM-1 levels in urine samples assessed. KIM-1
levels adjusted for creatinine concentration to account for day-today variation in urine
volume. Glomerular filtration rate (GFR) calculated by Modification of Diet in Renal
Disease (MDRD) formula.
Results: Urinary KIM-1 /creatinine levels [( pg/ml)/(mg/dl)](uKIM-1) were
significantly increased in all stages of CKD patients (CKD stage 2-4) compared to
controls (2.8 ? 0.7 vs 1.4 ? 0.2, p<0.01). uKIM-1 were significantly higher in stage 2
CKD patients (3.7 ? 0.9), compared to both stage 3 (2.7 ? 0.8) and stage 4 (2.2 ? 0.6)
CKD patients. (all p <0.01). Although uKIM-1 of stage 4 CKD patients were higher
than control group, the difference did not reached statistically significance level
( p>0.05). In addition, uKIM-1 were not significantly different in subgroups (normo/
micro/macro-albuminuria) of diabetic nephropathy. uKIM-1 were not correlated
with albuminuria, however, positively correlated with the duration of diabetes
( p=0.027, r=0.322) and inversely and poorly correlated with GFR ( p=0.043, r=0.214).
Conclusions: We showed that urinary KIM-1 levels were increased in all three
diabetic nephropathy stages independent of the levels of urinary albumin excretion.
Therefore, we think that KIM-1 should be useful in early diagnosis of diabetic
nephropathy. In addition, elevated levels of KIM-1 in every 3 stages of diabetic
nephropathy indicates tubulary injury beside glomerular damage. We also showed
that urinary KIM-1 levels increase in early stages of CKD (stage 2) and decreases to
above normal levels as CKD progresses to stage 3 and 4. These findings suggest that
urinary KIM-1 levels should be useful in determining the progression of renal failure
due to diabetic damage.
GALECTIN?3 AND ADVERSE OUTCOMES IN CHRONIC
KIDNEY DISEASE ? RESULTS FROM THE LURIC AND THE
Introduction and Aims: Galectin-3 has been linked to incident renal disease,
experimental renal fibrosis and nephropathy. Our aim was to examine the association
between galectin-3, renal function and adverse outcomes in two large cohorts of
patients over a broad range of renal function.
Methods: We measured galectin-3 concentrations in baseline samples from the 4D
study (1168 dialysis patients with type 2 diabetes) and the LURIC study (2579 patients
with coronary angiograms). Patients were stratified in three groups with eGFR > 90 ml/
min/1.73m2 (CKD stages 0-1), eGFR 60-89 ml/min/1.73m2 (CKD stage 2) and eGFR
< 60 ml/min/1.73m2 (CKD stages 3-5). We correlated galectin-3 levels to demographic,
clinical and biochemical parameters. The association of galectin-3 with clinical
endpoints was assessed by Cox proportional hazards regression within 10 years
(LURIC) and 4 years of follow-up (4D), respectively.
Results: Mean galectin-3 concentrations were 12.8?4.0 ng/mL (CKD stage 0-1), 15.6
?5.4 ng/mL (stage 2), 23.1?9.9 ng/mL (stage 3-5), and 54.1?19.6 ng/mL (stage 5D),
respectively. Galectin-3 was significantly associated with clinical endpoints in
participants with impaired kidney function (CKD 2-5). Per standard deviation increase
in log-transformed galectin-3 concentration, the risks of all-cause mortality,
cardiovascular mortality and fatal infection increased significantly with HRs of 1.22
(1.05-1.41), 1.21(1.01-1.44) and 1.71(1.08-2.70), respectively. In CKD 5D patients,
galectin-3 was associated with the combined endpoint of cardiovascular events (HR
Conclusions: Galectin-3 concentrations increase with progressive renal impairment
and independently associate with CV endpoints, infectious and all-cause deaths. The
precise role of galectin-3 in the pathophysiology of renal disease warrants further study.
ROLE OF FIBROBLAST GROWTH FACTOR-23 AND SOLUBLE
ALPHA KLOTHO IN CHRONIC KIDNEY DISEASE
Introduction and Aims: The interplay of fibroblast growth factor-23 (FGF23) and
soluble-alpha klotho in chronic kidney disease is only partly known. Now we
investigated the hypothesis that FGF23 concentrations influence the relation of soluble
iii??? | Abstracts
alpha klotho levels and estimated glomerular filtration rate (eGFR).
Methods: We analyze plasma FGF23, plasma klotho, plasma bone-specific alkaline
phosphatase, and eGFR in 24 patients with chronic kidney disease stage 1 to 5.
Results: Median soluble alpha klotho concentration was 282 pg/mL in CKD stage 1/2,
223 pg/mL in CKD stage 3, and 203 pg/mL in CKD stage 4/5, respectively, showing no
significant differences ( p=0.484 by Kruskal-Wallis test). On the other hand, we
observed a highly significant association of soluble alpha klotho levels with eGFR in
patients showing FGF23 less than the median of 73pg/mL (Spearman r=0.75; p<0.005)
but not in patients showing FGF23 higher then the median (Spearman r=-0.05;
p=0.884). Patients with reduced soluble alpha klotho below 204pg/mL had significantly
lower bone-specific alkaline phosphatase compared to patients with higher soluble
alpha klotho levels (median 30.1U/L, IQR 29.7 to 32.3; vs. median 37.7U/L, IQR 34.1
to 48.8; p=0.012).
Conclusions: A positive association of soluble alpha klotho levels with kidney function
was observed only when FGF23 concentrations were in the normal range. These results
suggest that different mechanisms influence soluble alpha klotho at different stages of
chronic kidney diseases.
RENAL FUNCTION TRAJECTORY IN CHRONIC KIDNEY
DISEASE PATIENTS: RESULTS OF A REAL-LIFE STUDY
Elaine Amaral De Paula1, Chislene Pereira Vanelli1, Marcio Santos Caminhas1,
Bruna Caldas Soares1, Fernanda Anselmo Bassoli1, Darc?lia M.N. Da Costa1, Carla
M.M. Lanna1, Arise G.S. Galil1, Fernando A.B. Colugnati1, M?nica Barros Costa1,2,
Marcus Gomes Bastos1 and Rog?rio Baumgratz De Paula1
1Funda??o Instituto Mineiro de Ensino e Pesquisa em Nefrologia (IMEPEN), Juiz de
Fora, Brazil, 2Funda??o de Apoio A Pesquisa Fapemig, Belo Horizonte, Brazil
Introduction and Aims: The HIPERDIA Minas Center (CHDM/JF) is a secondary
prevention program established by the Health Secretary of the State of Minas Gerais,
Brazil runned by by the Nephrology Unit of the Federal University of Juiz de Fora. The
CHDM/JF offers free interdisciplinary care, medications and exams, for hypertensive
patients with high cardiovascular risk, diabetic patients (all type 1 and type 2 with poor
metabolic control) as well as patients with CKD stages 3b to 5 and/or with decline of
estimated glomerular filtration rate (eGFR) ?5 mL/min/year. Our aim was to
determine the renal function trajectory in CKD patients attending an interdisciplinary
prevention Program in Brazil.
Methods: We analysed the trajectory of eGFR of 934 patients with CKD referred to
CHDM/JF between August of 2010 and September of 2012. Clinic and laboratory data
were obtained from the electronic data base system. eGFR was estimated from
creatinine using the MDRD equation, and CKD was defined when eGFR was 60ml/
min/1.73m? in the presence of albuminuria for a minimum of 3-months. According to
eGFR trajectory over the follow up period, patients were stratified into non-progressors
(GFR did not decrease or even increased over the time); slow-progressors (GFR
decreased up to 4 ml/min/yr) and fast-progressors (GFR decreased >/ 4 ml/min/yr).
Linear regression with univariate analyses were carried out using SPSS v 15.0.
Results: Of the total of patients, 493 (52.8%) were men, and the average age was 65+14
years. Mean eGFR at the baseline period was 42.9+20.56 ml/ min/1.73m?. According to
eGFR trajectory, fast progressors (31.6%) had a median decline of eGFR of 15.8 + 15.6
ml/min/yr; slow progressors (58.3%), decreased 1.20 + 1.7 ml/min/yr, and
non-progressors (10.1%) increased eGFR on 16.8 + 17.7 ml/min/yr. Body surface area
(?=9.895 per g/m?; p=0.007; R?=0.012), proteinuria >150 mg/24h (?=4.711; p=0.009;
R?=0.013), baseline eGFR (?=0.224 per ml/min higher; p<0,001; R?=0.042), and ACE
inhibitor use (?=1.821; p=0.033; R?=0.007) were positively correlated with the rate of
Conclusions: Our finding in this real-life retrospective study revealed that two-third of
our patients presented a stable or slow decline of eGFR, suggesting the effectiveness of
the interdisciplinary team on the management of this high risk group of CKD patients
when free care is available.
COMPARISON OF FORMULAS TO ESTIMATE THE
GLOMERULAR FILTRATION RATE WITH THAT OF
SCINTIGRAPHY EVALUATION OF KIDNEY FUNCTION
IN HOSPITALIZED PATIENTS
Introduction and Aims: Accurate staging of chronic kidney disease (CKD) is very
important in order to properly stratify, establish therapeutic interventions, and predict
outcomes of patients with impaired renal function. The evaluation of GFR (Glomerular
Filtration Rate) can be obtained simply with creatinine serum dosage, resulting in
estimated GFR (eGFR), or through Gates method at 99mTc-DTPA renal scintigraphy.
We tried to identify difference in GFR evaluation between CKD-EPI and Gates method
and which variables are associated with these differences.
Methods: We retrospectively reviewed the records of 341 patients who underwent
dynamic renal scintigraphy in the last 5 years. Patients were categorized according to
KDIGO staging I to V, using the eGFR calculated with the CKD-EPI equation.
Secondarily, we stratified patients according to treatment with renin-angiotensin
Results: Gates method tends to underestimate GFR in CKD stage I (mean - 22.2 ml/
min) and II (mean - 12.5 ml/min), while it seems to overestimate in stages IV and
V. The division in quartiles of ages showed a progressive decline of renal function with
ageing and an underestimation of GFR only in the first quartile of age (< 50 years old).
Gates method underestimation of GFR was more pronounced in stage I patients treated
with RAS-inhibitors (mean - 34.6 ml/min). The same occurs in stage II, even though to
a lesser extent.
Conclusions: The assessment of GFR by the Gates method must be carefully
considered in the early stages of CKD, especially in younger patients. Moreover, the
difference is more pronounced in patients treated with RAS-inhibitors. Longitudinal
studies will prove which method better predict cardiovascular or renal events.
doi:10.1093/ndt/gfu145 | iii???
URINARY RETINOL BINDING PROTEIN IS A MARKER OF THE
EXTENT OF INTERSTITIAL KIDNEY FIBROSIS
Nicolas Pallet1, Sophie Chauvet1, Charlene Levi1, Vannary Meas-Yedid2,
Philippe Beaune1, Eric Thevet1 and Alexandre Karras1
1HEGP Hospital, Paris, France, 2Institut Pasteur, Paris, France
Introduction and Aims: Quantification of interstitial fibrosis (IF) on renal biopsy has
been shown to be correlated with the renal prognosis in most nephropathies. The aim
of our study was to evaluate the diagnostic performance of the measurement of urinary
low molecular weight (LMW) protein concentrations as a method to determine the
extent of IF.
Methods: The urines specimen from 162 consecutive patients who underwent a renal
biopsy in our center were prospectively analyzed. Computerized quantification, based
on the colorimetric analysis of fibrous areas, was used to assess the percentage of IF.
Total proteinuria, albuminuria, and the urinary levels of retinol binding protein (RBP),
alpha1-microglobulin (A1MG), beta 2-microglobulin (B2MG), transferrin, and IgG
immunoglobulins were measured for each specimen.
Results: There was a significant correlation between the degree of IF and the urinary
RBP/creatinine ratio (R2: 0.11, p25% of the parenchyma was 95% when using a
threshold of 20 mg/g creat.
Conclusions: RBP appears to be a useful quantitative non-invasive marker for the
independent prediction of the extent of kidney IF. As methods for the measurement of
urinary RBP are available in most clinical chemistry departments, RBP measurementis
appealing for implementation in the routine care of patients with chronic kidney
disease, in order to predict long-term renal outcome.
PREDICTON OF SIGNIFCANT EVENTS ON A CKD COHORT BY
GFR ESTIMATES BASED ON CREATININE OR CYSTATIN C
Sofia Santos1, Jorge Malheiro1, Andreia Campos1, Sofia Pedroso1,
Josefina Santos1 and Ant?nio Cabrita1
1Hospital Santo Ant?nio - CHP, Porto, Portugal
Introduction and Aims: Plasma cystatin C has been shown to be superior to plasma
creatinine for the estimation of adverse clinical outcomes, specifically cardiovascular
morbidity and mortality. So, the aim of the present study was to investigate eGFR using
formulas based in these renal function markers, and their relationship with end stage
renal disease (ESRD) and death prediction.
Methods: Cystatin C and creatinine were measured in 234 patients during the period of
1 May to 30 June of 2009 and they were followed for 50.6?17.7 months for the
occurrence of a predefined endpoint event: need for renal replacement therapy or
death. For each patient eGFR was calculated using Modification Diet Renal Disease-4
formula (MDRD) for creatinine, and using both Steven?s and Rule?s formulas based on
Cystatin C (Cyst_St and Cyst_Rule, respectively). Demographics, risk factors and
analytical data were compared between patients with (E) and without (NE) event.
Receiver operating characteristics (ROC) analyses and reclassification analysis were
performed to explore prediction ability for each marker for events evaluated.Patients
were divided according to each eGFR equations in 10 percentiles (P10) and 3 groups of
patients were created: those without reclassification, those reclassified for a higher
eGFR percentile by Cyst_St or Cyst_Rule vs MDRD and those reclassified for a lower
eGFR percentile by Cyst_St or Cyst_Rule vs MDRD. These 3 groups were compared by
the log-rank test for event occurrence (death or ESRD). Furthermore, patients
reclassification status as event predictor, considering patients without reclassification as
reference, were explored by Cox regression adjusted for sex, diabetes, hypertension,
proteinuria >0.3g/g and previous cardiovascular disease.
Results: 47 events were recorded: 27 deaths and 20 ERSD. Table1 shows baseline
characteristics. 75% of the population was classified in CKD 3-5, as calculated by
MDRD. ROC analyses for prediction of death showed Cyst_St having the highest area
under de curve (AUC 0.731; p<0.001), followed by Cyst_Rule (AUC 0.722; p<0.001)
and MDRD (AUC 0.657; p=0.008).
ROC analyses for prediction of ESRD showed MDRD having the highest AUC (0.824),
and both Cystatin based formulas with the same AUC (0.786), all with p<0.001. The
SP160 Table 1.
No event (NE) (n=187)
Event (E) (n=47)
iii??? | Abstracts
MDRD-4 = Cyst_Rule (N=88)
MDRD-4 > Cyst_Rule (N=73)
MDRD-4 < Cyst_Rule (N=73)
MDRD-4 = Cyst_St(N=79)
MDRD-4 > Cyst_St(N=76)
MDRD-4 < Cyst_St(N=79)
SP160 Table 2.
results of reclassification analysis for the death event are showed in table 2. For the
event ESRD there were not significantly differences between the three formulas.
Conclusions: Death prediction was improved with the reclassification of kidney
function by cystatin C formulas. ESRD prediction was similar between reclassification
groups. Although the link between cystatin C and mortality goes beyond kidney
function, it brings significant impute in the clinical risk stratification of an elderly CKD
population as ours.
LITHOGENIC RISK INDEXES IN LITHIASIC PATIENTS
AND THEIR POST TREATMENT PROGRESS
Maria Magdalena Mayor1, Roger Ayala1, Carlos Ramos1, Silvio Franco1 and Rosa Guill?n2
1Instituto de Previsi?n Social, Asunci?n, Paraguay, 2Instituto Ciencias de La Salud,
Introduction and Aims: Determine the lithogenic risk indexes including metabolic
factors and urine saturation in lithiasic patients that attend to the Social Previtional
Institute (IPS) hospitals and their post treatment variations
Methods: The temporal series experimental design work, included 29 adult lithiasic
patients of both sex that attended the urology and nephrology services of the IPS
hospitals during 2012 that were not receiving treatment for their renal lithiasis and
agreed to participate willingly. A metabolic screening was performed to determine the
urinary indexes of the patients using EQUIL software, besides that, a morphologic
study of the kidney stones was available. A customized treatment according to their
base results was prescribed and a six month follow up was done, after this period of
time each patient was re study with the same initial therapy scheme. The protocol was
approved by both the scientific and ethics committees of the IICS. The data gathered
was analyzed with the SPSS version11.5 software, employing the e Kolmogorov test to
verify the regular distribution of data, the Wilcoxon test and the paired samples
method to compare the pre and post treatment results of these patients.
Results: 18 kidney stones were analyzed of which 77,7% were of Calcium oxalate and
22,3% of uric acid. In the basal evaluation 65,5% presented hypocitraturia, 44,8%
hypercalciuria, 13,8% hyperoxaluria and 41,4% had a diuresis below 2L/day. The
saturation indexes indicated calcium oxalate crystallization risk, sodium urate,
hydroxyapatite and uric acid of 1, 2, 12 y 12 patients accordingly. After the treatment
and increase in the mean values of the diuresis, magnesiuria, citraturia and urinary pH,
as well as a decreased calciuria and the number of patients with urinary saturation for
calcium oxalate and uric acid. The statistical analysis of paired samples before and after
the treatment were studied showing a remarkable variation of the numbers in the
diuresis ( p 0,0001), urinary pH ( p 0,83) and urinary saturation for uric acid ( p 0,001),
sodium urate ( p 0,017) and potassium urate (0,012).
Conclusions: The lithogenic risk factors identification of each patient allowed taking
more specific therapeutical decisions. The use of software tools to create a risk for
crystallization calculus is an important introduction in Paraguay.
URINARY ARGININE VASOPRESSIN AND AQUAPORIN-2 ARE
USEFUL MARKERS IN EDEMA AND IDIOPATHIC EDEMA
Jae Seok Kim1, Jae Won Yang1, Byoung Geun Han1 and Seung Ok Choi1
1Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
Introduction and Aims: Edema is a common symptom that is encountered in clinic.
But, the causes of edema are various and complex. In addition, in case of idiopathic
edema, clinicians are often confused with whether the edema really exists because of
cyclic feature of swelling. Therefore, it is difficult to diagnose the exact etiology of
edema. Bioimpedance spectroscopy is a useful method to measure excessive body fluid
amounts for edema. However, other useful markers for edema have not been
investigated sufficiently. This study aims to investigate urine AVP (arginine
vasopressin) and AQP-2 (aquaporin-2) as a marker for edema.
Methods: The subjects included thirty-three patients complaining of edema who had
visited from Jan. 1. 2012 to Oct. 31. 2012. We measured OH (overhydration, liters)
values as excessive body fluid amounts with use of bioimpedance spectroscopy and the
serum level of hormones such as renin, aldosterone, thyroid hormone. In addition, we
collected 24-hr urine samples from patients, and measured the excretion amount of
AVP, AQP-2 in it. Lastly, for discriminating idiopathic edema patients, we made the
subjects to check their body weight at morning and evening in the nude.
Results: The results showed that urinary AVP excretion had the negative correlation
with OH value (r= - 0.438, p=0.020). In addition, apparent edema patients who had
OH value more than 1 liter showed more decreased excretion of urinary AVP than
inapparent edema patients (2.6?0.9 vs. 7.4?3.7 ng/day, p=0.018). In idiopathic edema
patients who were characterized by cyclic edema, bioimpedance spectroscopy showed
no finding of excessive body fluid (OH= - 0.28 liters), while urinary AVP excretion was
decreased (8.7 ng/day, reference value by Merkelbach U, 1975 : 34-70 ng/day) and
urinary AQP-2 were also decreased (0.9 ug/day, reference value by Rai T, 1997 : 11 ug/
day), which indicated edema status.
Conclusions: This study demonstrates that the measurement of urinary AVP excretion
is a useful in diagnosis of edema. In addition, the measurement of urinary AVP and
AQP-2 excretions is especially benefit to diagnosis of idiopathic edema which is
difficult to diagnose by physical exam and bioimpedance spectroscopy because of cyclic
feature of swelling.
AMBULATORY BLOOD PRESSURE MONITORING VERSUS
OFFICE BLOOD PRESSURE AND TARGET ORGAN DAMAGE
IN PATIENTS WITH HYPERTENSION AND CHRONIC KIDNEY
Mirela-Nicoleta Tudor1, Maria Francisca Navajas Martinez2, Cristina Vaduva1,
Daniela Teodora Maria1 and Eugen Mota1
1University of Medicine and Pharmacy of Craiova, Craiova, Romania, 2University
Campus Bio-Medico of Rome, Rome, Italy
Introduction and Aims: Hypertension is a major independent risk factor for the
progression of chronic kidney disease (CKD) and cardiovascular disease. In the
management of hypertension in patients with CKD, control of hypertension is very
important and depends on the technique of blood pressure (BP) measurement. Recent
evidence suggests that ambulatory blood pressure monitoring (ABPM) is a superior
prognostic marker of target organ damage compared to BP obtained in the clinic.The
aim of the study was to determine the superiority of BP values obtained using ABPM
compared to BP values obtained from standard clinical measurements and its
importance for documenting target organ damage in patients with CKD and
Methods: We performed a retrospective study that included 129 subjects from the
Nephrology-Hypertension Out-patient Department of the University Campus
Bio-Medico, Rome from January 2011 to April 2013. ABPM parameters, clinical BP,
creatinine, proteinuria/24h and left ventricular ejection fraction (LVEF) were collected.
Estimated glomerular filtration rate (eGFR) was calculated by The Chronic Kidney
Disease Epidemiology Collaboration (CKD-EPI) formula. Univariate and multivariate
analyses were used. P-values <0.05 were considered statistically significant.
Results: The mean age of the 129 patients CKD patients (stages 1 to 4) was 62.75 ?
12.3 years; 68.99% were men and 31.01% were women and the mean of eGFR/
CKD-EPI was 65.14 ? 24.38 ml/min/1.73m2. We found correlations between the
parameters of ABPM (especialy night/day ratio ambulatory SBP) and eGFR ( p=0.024)
and LVEF ( p=0.027). When we analyzed the correlation between office BP and GFR
and LVEF in the study group we did not find statistically a significant correlation
( p=0.287). Also we did not find statistically significant correlations between
proteinuria/24 hour and ABPM parameters or office BP.
Conclusions: The parameters of ABPM (especially nigt/day ratio ambulatory SBP)
were better correlated with target organ damage (eGFR and LVEF) versus office BP in
the study group.
NEPHROCALCINOSIS AND MICROCYTAEMIA: AN EMERGING
Introduction and Aims: Nephrocalcinosis is a clinical-pathological entity caused by
various hereditary or acquired diseases that lead to the deposition of calcium salts
within the kidney parenchyma. Epidemiological data are scant; the protean
presentation may explain the lack of data regarding its prevalence. The aim of this
study is to report the prevalence and main clinical features of the cases of
nephrocalcinosis diagnosed in a newly opened Nephrology Out-patient Unit with
particular regard for the cases related to mycrocythemia.
Methods: We carried out a retrospective analysis on the data we prospectively gathered
from the start of our activity in December 2007 until December 2013. Clinical and
laboratory data were collected from the medical records and from the general
laboratory; diagnosis was based upon imaging data (mainly ultrasounds) reviewed by
the same Radiologists.
Results: About 2.5% of the patients referred to our Unit were diagnosed with
nephrocalcinosis; the disease was associated with autoimmune disorders in 29% of
patients and with microcythemia in 23%, while positive family history was present in
23% of patients.Mycrocythemia patients were referred to us due to the presence of
kidney stones, electrolyte derangements, mild proteinuria or history of kidney urinary
tract infections or malformations. 17 patients are affected by beta thalassemia (10 males
and 7 females), while 4 patients are affected by sickle cell disease (all females). Median
age is low: 35 (22-46) for the subset with beta thalassemia and 35.5 (30-47) for the
other subset. Kidney function is preserved in both groups with median CRs of 0.73 mg/
dl (0.51-1.09 mg/dl) in thalassaemic patients and 0.63 mg/dl (0.51-0.76 mg/dl) in
patients with sickle cell disease.The biochemical profile of Beta thalassemiapatients is
homogeneous and is characterized by severe hypercaciuria which is often concomitant
with increased FePi. The four patients with sickle-cell disease do not display
hypercalciuria, in keeping with the different pathogenesis (calcifications on
parenchymal microinfarctions).(table )
Conclusions: Nephrocalcinosis is a rare, but not exceptional disease in the
Nephrological practice. Microcythemia appeared to be a major cause, probably also
better diagnosed on the account of the recent interest for a detailed analysis of kidney
function related to the surveillance of the new oral iron chelators. Better awareness of
this disease points to the need for an integrated approach involving various branches of
Internal Medicine and Radiology.
ABNORMAL LEFT VENTRICULAR MASS INDEX- A
SURROGATE END POINT IN VITAMIN D DEFICIENT CHRONIC
Pinaki Mukhopadhyay1, Kartik Patar1, Nandini Chaterjee1 and Kajal Ganguly1
1NRS Medical College, Kolkata, India
Introduction and Aims: Cardiovascular morbidity and mortality is prevalent in
established chronic kidney disease (CKD) with vitamin D deficiency.Aims of this study
was to evaluate the effect of vitamin D deficiency on cardiac structure and functions in
predialysis diabetic and non-diabetic CKD patients.
Methods: All diabetic and nondiabetic CKD stage 3onwards predialysispatients not on
any form of vit D therapy were included prospectively. Demographical, clinical and
laboratory data were analysed.Vit D was measured in all cases and echocardiogram was
done andall the parameters was examined.Left Ventricular Mass index (LVMI) was
calculated by Devereux?s(Penn) formula. More than 134 g/m2in men and 110 g/m2 in
female was considered abnormal.These were calculated using appropriate statistical tool.
Results: About 150 pts were enrolled in one year of them M:F were1.6:1.Mostly belonged
to the age group of 41-60yrs(58%). About 96(64%) were diabetic and rest of 54(36%)
were non diabetic. CKD III,IV,V comprises of 26%,14%,24% and 4%,12% and 20%
respectively. Diabetic CKD patients are more severely deficient of vitamin D than
non-diabetic CKD (38% vs 8%).Higher stages of CKD showed severe grade of Vit D
deficiency.AmongStage V CKD 14% were grade II and 28% were grade III vitamin D
deficient ( p=0.07). Among all CKD patients with severe vitamin D deficiency (stage III)
15 (10 %) had moderatelyabnormal(Group II) LVMI and 51(34%) had severely
abnormal (Group III) LVMI and among moderate vitamin D deficient (stage II) patients
36(24%) had group II LVMI and 21(14%) had group III LVMI. This correlation is
extremely significant ( p=0.0163).There is significant correlation between lowVitamin D
level and LVMI related inversely with standard error 6.08 with 95% CI (142.2-167.5).
Conclusions: Chronic kidney disease with vitamin D deficiency associated with
abnormal LVMI which results in widespread risk for cardiovascular disease in CKD.