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author:("colic, Adrian")
1.  A longitudinal study on illness perceptions in hemodialysis patients: changes over time 
Introduction
Self-regulatory theory explains how patients’ illness representations influence self-management behavior. The aim of this study was to examine the changes that occur in disease perceptions after 6 years in hemodialysis patients.
Material and methods
A total of 81 clinically stable patients (53.6% males, meanage 54 ±12.54 years, mean hemoglobin level 11 ±1.52 g/dl, mean Kt/V 1.49 ±0.21) who were treated with hemodialysis three times weekly completed questionnaires on illness representations in 2005, and then at follow-up, in December 2011, 47 patients. IPQ-R (Illness Perceptions Questionnaire-Revised) was used to assess patients’ illness perceptions.
Results
After a long period of years (6 years), patients had a stronger perception of a chronic course of the disease (timeline; p < 0.001), considered hemodialysis more efficient in controlling end stage renal disease (ESRD) (treatment control; p < 0.05), considered that their disease had less serious consequences for their life (consequences; p < 0.05), and also registered a less intense emotional response to their illness (emotional representation; p < 0.05). Two of the seven components of illness representations (personal control, cyclical symptoms) remained unchanged. Treatment control perceptions were also predictive of mortality after controlling for covariates (age, gender, dialysis vintage, blood hemoglobin level and Kt/V) (HR = 0.13, 95% CI: 0.02–0.75, p = 0.022).
Conclusions
Our results show that patients’ illness perceptions vary over a significantly long follow-up period, in the sense of having more optimistic views towards their illness perceptions.
doi:10.5114/aoms.2013.38678
PMCID: PMC3832830  PMID: 24273565
end-stage renal disease; hemodialysis; illness perceptions; Illness Perceptions Questionnaire-Revised
2.  Hyperphosphatemia in patients with ESRD: assessing the current evidence linking outcomes with treatment adherence 
BMC Nephrology  2013;14:153.
In recent years, the imbalance in phosphate homeostasis in patients with end-stage renal disease (ESRD) has been the subject of much research. It appears that, while hyperphosphatemia may be a tangible indicator of deteriorating kidney function, lack of phosphate homeostasis may also be associated with the increased risk of cardiovascular events and mortality that has become a hallmark of ESRD. The need to maintain phosphorus concentrations within a recommended range is reflected in evidence-based guidelines. However, these do not reflect serum phosphorus concentrations achieved by most patients in clinical practice. Given this discrepancy, it is important to consider ways in which dietary restriction of phosphorus intake and, in particular, use of phosphate binders in patients with ESRD can be made more effective. Poor adherence is common in patients with ESRD and has been associated with inadequate control of serum phosphorus concentrations. Studies indicate that, among other factors, major reasons for poor adherence to phosphate binder therapy include high pill burden and patients’ lack of understanding of their condition and its treatment. This review examines available evidence, seeking to understand fully the reasons underlying poor adherence in patients with ESRD and consider possible strategies for improving adherence in clinical practice.
doi:10.1186/1471-2369-14-153
PMCID: PMC3728082  PMID: 23865421
Adherence; Chronic kidney disease; Hyperphosphatemia; Phosphate binder; Pill burden
3.  Changes in the histological spectrum of glomerular diseases in the past 16 years in the North-Eastern region of Romania 
BMC Nephrology  2013;14:148.
Background
The aim of this study was to describe the findings of renal biopsies from a large nephrology center in Iasi, Romania, performed between 2005 and 2010. We compared these findings with our previous ones, from 1995 to 2004, as well as with similar reports.
Methods
We studied retrospectively 239 renal biopsies. The indications for renal biopsy were categorized into: nephrotic syndrome, acute nephritic syndrome, asymptomatic urinary abnormalities, acute kidney injury, and chronic kidney disease of unknown etiology.
Results
During the past 16 years, a gradual increase in the annual number of renal biopsies/per million population (p.m.p.)/year was observed, although this incidence remained lower than in other European countries. Nephrotic syndrome was the indication for renal biopsy in over 50% of cases. Glomerulonephritis (GN) was the main histological diagnosis in 91% of cases, of which 56% were primary GN and 35% were secondary GN. The frequency of various types of primary GN was: membranoproliferative GN (MPGN) - 29.3%, membranous nephropathy (MN) -27.5%, focal segmental glomerulosclerosis (FSGS) - 17.2%, mesangial GN (including IgAN) -13.7%, crescentic GN - 9.4%, and minimal change disease (MCD) - 2.5%. Compared to the previously reported period (1994–2004), we observed a significant decrease in the frequency of MPGN and significant increases in the frequency of FSGS and, particularly MN - which more than doubled.
Conclusion
We report significant changes in the histological spectrum of GN in North-Eastern Romania in 2005–2010, compared to the previously reported 10-yrs. These changes seem to be following a trend that has also been observed in Western countries a few decades ago, and which may have a socioeconomic explanation.
doi:10.1186/1471-2369-14-148
PMCID: PMC3716947  PMID: 23855530
Glomerular disease; Glomerulonephritis; Kidney disease; Tubulointerstitial disease
4.  Soluble TWEAK independently predicts atherosclerosis in renal transplant patients 
BMC Nephrology  2013;14:144.
Background
Cardiovascular risk is increased in the early stages of chronic kidney disease (CKD) and also found to be ongoing in renal transplant (Rtx) patients. As a sign of atherosclerosis, increased carotid intima-media thickness (CIMT) has been widely accepted as a strong predictor of cardiovascular disease (CVD) and mortality in CKD patients. A novel markers, soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and neutrophil-to-lymphocyte ratio (NLR) were introduced as potential markers in inflammatory disorders including CKD. The role of Rtx in terms of atherogenesis is still unclear. We aimed to investigate the relationship between sTWEAK, NLR and CIMT in Rtx patients without overt CVD and to compare these results with those obtained from healthy subjects.
Methods
Cross-sectional analysis in which CIMT measurements, NLR and serum TWEAK levels were assessed in 70 Rtx patients (29 females; mean age, 40.6 ± 12.4 years) and 25 healthy subjects (13 females, mean age; 37.4±8.8 years).
Results
sTWEAK levels were significantly decreased (p=0.01) and hs-CRP, NLR and CIMT levels of Rtx patients were significantly increased compared to healthy subjects (p<0.0001, p=0.001, p<0.0001, respectively). sTWEAK was also found to be decreased when eGFR was decreased (p=0.04 between all groups). CIMT was positively correlated with sTWEAK and NLR in Rtx patients (r=0.81, p<0.0001 and r=0.33, p=0.006, respectively). sTWEAK was also positively correlated with NLR (r=0.37, p=0.002). In the multivariate analysis only sTWEAK was found to be an independent variable of increased CIMT.
Conclusion
sTWEAK might have a role in the pathogenesis of ongoing atherosclerosis in Rtx patients.
doi:10.1186/1471-2369-14-144
PMCID: PMC3711729  PMID: 23849432
sTWEAK; Neutrophil-to-lymphocyte ratio; Carotid intima-media thickness; Renal transplantation
5.  A comparison of calcium acetate/magnesium carbonate and sevelamer-hydrochloride effects on fibroblast growth factor-23 and bone markers: post hoc evaluation from a controlled, randomized study 
Nephrology Dialysis Transplantation  2013;28(9):2383-2392.
Background
Different phosphate binders exert differing effects on bone mineral metabolism and levels of regulating hormones. The objective of this post hoc evaluation of the CALcium acetate MAGnesium carbonate (CALMAG) study was to compare the effects of calcium acetate/magnesium carbonate (CaMg) and a calcium-free phosphate binder, sevelamer-hydrochloride (HCl), on serum levels of fibroblast growth factor-23 (FGF-23) and markers of bone turnover.
Methods
This secondary analysis of the controlled, randomized CALMAG study, comparing the effect of CaMg and sevelamer-HCl on serum phosphorus (P), aimed to investigate the parameters described above. The analysis included 204 patients who completed the initial study per protocol (CaMg, n = 105; sevelamer-HCl, n = 99).
Results
The study showed that serum levels of FGF-23 were significantly reduced with CaMg and sevelamer-HCl, with no difference between groups at Week 25 [analysis of covariance (ANCOVA); log-intact FGF-23 (iFGF-23), P = 0.1573]. FGF-23 levels strongly correlated with serum P levels at all time points in both groups. The bone turnover parameters alkaline phosphatase (AP), bone AP (BAP), procollagen type 1 amino-terminal propeptide 1 (P1NP), osteoprotegerin (OPG), beta-crosslaps (β-CTX) and tartrate-resistant acid phosphatase 5b (TRAP 5b) increased significantly in the sevelamer-HCl group; they remained almost unchanged in the CaMg group, after the initial phase of P lowering (ANCOVA, P < 0.0001 for all except OPG, P = 0.1718).
Conclusions
CaMg and sevelamer-HCl comparably lower serum levels of iFGF-23. Changes in bone parameters were dependent on characteristics of the phosphate binder; in contrast with sevelamer-HCl, CaMg had no influence on bone turnover markers.
doi:10.1093/ndt/gft203
PMCID: PMC3769980  PMID: 23787550
bone markers; calcium acetate; fibroblast growth factor-23; haemodialysis; magnesium carbonate; phosphate binder
7.  Relationship between Uric Acid and Subtle Cognitive Dysfunction in Chronic Kidney Disease 
American Journal of Nephrology  2011;34(1):49-54.
Background
Elevated serum uric acid has been associated with cognitive dysfunction and vascular cognitive impairment in the elderly. Serum uric acid is also commonly elevated in chronic kidney disease (CKD), but its relationship with cognitive function in these patients has not been addressed.
Methods
Subjects with CKD (defined as eGFR <60/ml/min/1.73 m2) were evaluated for cognitive dysfunction using the validated Standardized Mini-Mental State Examination (SMMSE). Individuals with dementia, depression or other psychiatric disorders were excluded, as were subjects on uric acid-lowering therapy or with serious illnesses such as severe anemia or active or ongoing cardiovascular or cerebrovascular disease.
Results
247 subjects were enrolled. SMMSE scores showed stepwise deterioration with increasing quartile of serum uric acid (26.4; 26.1; 25.5; 25.3, score range 20–30, p = 0.019). Post-hoc analysis demonstrated that there was no linear trend and only groups 1 and 4 were different with respect to SMMSE scores (p = 0.025). Stepwise multivariate linear regression revealed that age, educational status, presence of cerebrovascular disease, and serum uric acid were independently related to SMMSE scores.
Conclusion
Serum uric acid levels are independently and inversely associated with mild cognitive dysfunction in subjects with CKD.
doi:10.1159/000329097
PMCID: PMC3121541  PMID: 21659739
Cognitive function; Chronic kidney disease; Uric acid
8.  Serum Uric Acid Level and Endothelial Dysfunction in Patients with Nondiabetic Chronic Kidney Disease 
American Journal of Nephrology  2011;33(4):298-304.
Background
An elevated serum uric acid level is strongly associated with endothelial dysfunction and inflammation, both of which are common in chronic kidney disease (CKD). We hypothesized that endothelial dysfunction in subjects with CKD would correlate with uric acid levels.
Materials and Methods
We evaluated the association between serum uric acid level and ultrasonographic flow-mediated dilatation (FMD) in 263 of 486 patients with recently diagnosed CKD (stage 3–5) (48% male, age 52 ± 12 years). To minimize confounding, 233 patients were excluded because they were diabetic, had established cardiovascular complications or were taking drugs (renin-angiotensin system blockers, statins) interfering with vascular function.
Results
Serum uric acid level was significantly increased in all stages of CKD and strongly correlated with estimated glomerular filtration rate (eGFR-MDRD); FMD was inversely associated with serum uric acid (r = −0.49, p < 0.001). The association of serum uric acid with FMD remained after adjustment for age, gender, smoking, LDL cholesterol, eGFR, high-sensitivity C-reactive protein, systolic blood pressure, proteinuria, and homeostatic model assessment index (β = −0.27, p < 0.001).
Conclusion
Increased serum uric acid is an independent predictor of endothelial dysfunction in subjects with CKD.
doi:10.1159/000324847
PMCID: PMC3064939  PMID: 21389694
Chronic kidney disease; Uric acid; Endothelial dysfunction
9.  Uric Acid and Pentraxin-3 Levels Are Independently Associated with Coronary Artery Disease Risk in Patients with Stage 2 and 3 Kidney Disease 
American Journal of Nephrology  2011;33(4):325-331.
Background and Objectives
Cardiovascular disease is prevalent in chronic kidney disease (CKD). Uric acid is increased in subjects with CKD and has been linked with cardiovascular mortality in this population. However, no study has evaluated the relationship of uric acid with angiographically proven coronary artery disease (CAD) in this population. We therefore investigated the link between serum uric acid (SUA) levels and (i) extent of CAD assessed by the Gensini score and (ii) inflammatory parameters, including C-reactive protein (CRP) and pentraxin-3, in patients with mild-to-moderate CKD.
Material and Methods
In an unselected population of 130 patients with estimated glomerular filtration rate (eGFR) between 90 and 30 ml/min/1.73 m2, we measured SUA, serum pentraxin-3, CRP, urinary protein-to-creatinine ratio, lipid parameters and the severity of CAD as assessed by coronary angiography and quantified by the Gensini lesion severity score.
Results
The mean serum values for SUA, pentraxin-3 and CRP in the entire study population were 5.5 ± 1.5 mg/dl, 6.4 ± 3.4 ng/ml and 3.5 ± 2.6 mg/dl, respectively. The Gensini scores significantly correlated in univariate analysis with gender (R = −0.379, p = 0.02), uric acid (R = 0.42, p = 0.001), pentraxin-3 (R = 0.54, p = 0.001), CRP (R = 0.29, p = 0.006) levels, eGFR (R = −0.33, p = 0.02), proteinuria (R = 0.21, p = 0.01), and presence of hypertension (R = 0.37, p = 0.001), but not with smoking status, diabetes mellitus, and lipid parameters. After adjustments for traditional cardiovascular risk factors, only uric acid (R = 0.21, p = 0.02) and pentraxin-3 (R = 0.28, p = 0.01) remained significant predictors of the Gensini score.
Conclusions
SUA and pentraxin-3 levels are independent determinants of severity of CAD in patients with mild-to-moderate CKD. We recommend a clinical trial to determine whether lowering uric acid could prevent progression of CAD in patients with CKD.
doi:10.1159/000324916
PMCID: PMC3064941  PMID: 21389698
Chronic kidney disease; Coronary artery disease; Uric acid; Pentraxin-3
10.  Consequences of Advanced Glycation End Products Accumulation in Chronic Kidney Disease and Clinical Usefulness of Their Assessment Using a Non-invasive Technique – Skin Autofluorescence 
Mædica  2011;6(4):298-307.
ABSTRACT
Accelerated formation and accumulation of advanced glycation end-products occur under circumstances of increased supply of substrates such as hyperglycaemic or oxidative stress and in age-related and chronic diseases like diabetes mellitus, chronic renal failure, neurodegenerative diseases, osteoarthritis and also non-diabetic atherosclerosis and chronic heart failure. Advanced glycation end-products accumulation occurs especially on long-lived proteins such as collagen in the skin and in vascular basement membranes leading to vascular damage. Adequate renal clearance capacity is an important factor in the effective removal of advanced glycation end-products. The Autofluorescence Reader was developed as a marker, representative for tissue advanced glycation end-products accumulation, easily applicable in a clinical setting, initially for predicting diabetes related complications. Studies have already shown a relationship between skin autofluorescence and diabetes complications, as well as its predictive value for total and cardiovascular mortality in type 2 diabetes. Moreover skin autofluorescence was demonstrated to be superior to Haemoglobin A1c and other conventional risk factors. Advanced glycation end-products have been proposed as a novel factor involved in the development and progression of chronic heart failure. Assessment of advanced glycation end-products accumulation in end-stage renal disease and undergoing renal replacement therapies patients has become of great importance. Cardiovascular and connective tissue disorders are very common in patients with end-stage renal disease, and the accumulation of advanced glycation end-products is significantly increased in these patients. Mortality is markedly increased in patients with decreased kidney function, particularly in patients with end-stage renal disease. Skin advanced glycation end-products levels are strong predictors of survival in haemodialysis patients independent of other established risk factors. The Autofluorescence Reader may be useful as a clinical tool for rapid assessment of risk for advanced glycation end-products related long-term complications, not only in diabetes, but in other conditions associated with advanced glycation end-products accumulation as well.
PMCID: PMC3391948  PMID: 22879845
advanced glycation end-products; skin autofluorescence; metabolic stess; chronic kidney disease
11.  Fluid Status in Peritoneal Dialysis Patients: The European Body Composition Monitoring (EuroBCM) Study Cohort 
PLoS ONE  2011;6(2):e17148.
Background
Euvolemia is an important adequacy parameter in peritoneal dialysis (PD) patients. However, accurate tools to evaluate volume status in clinical practice and data on volume status in PD patients as compared to healthy population, and the associated factors, have not been available so far.
Methods
We used a bio-impedance spectroscopy device, the Body Composition Monitor (BCM) to assess volume status in a cross-sectional cohort of prevalent PD patients in different European countries. The results were compared to an age and gender matched healthy population.
Results
Only 40% out of 639 patients from 28 centres in 6 countries were normovolemic. Severe fluid overload was present in 25.2%. There was a wide scatter in the relation between blood pressure and volume status. In a multivariate analysis in the subgroup of patients from countries with unrestricted availability of all PD modalities and fluid types, older age, male gender, lower serum albumin, lower BMI, diabetes, higher systolic blood pressure, and use of at least one exchange per day with the highest hypertonic glucose were associated with higher relative tissue hydration. Neither urinary output nor ultrafiltration, PD fluid type or PD modality were retained in the model (total R2 of the model = 0.57).
Conclusions
The EuroBCM study demonstrates some interesting issues regarding volume status in PD. As in HD patients, hypervolemia is a frequent condition in PD patients and blood pressure can be a misleading clinical tool to evaluate volume status. To monitor fluid balance, not only fluid output but also dietary input should be considered. Close monitoring of volume status, a correct dialysis prescription adapted to the needs of the patient and dietary measures seem to be warranted to avoid hypervolemia.
doi:10.1371/journal.pone.0017148
PMCID: PMC3044747  PMID: 21390320
12.  Evaluation of calcium acetate/magnesium carbonate as a phosphate binder compared with sevelamer hydrochloride in haemodialysis patients: a controlled randomized study (CALMAG study) assessing efficacy and tolerability 
Nephrology Dialysis Transplantation  2010;25(11):3707-3717.
Background. Phosphate binders are required to control serum phosphorus in dialysis patients. A phosphate binder combining calcium and magnesium offers an interesting therapeutic option.
Methods. This controlled randomized, investigator-masked, multicentre trial investigated the effect of calcium acetate/magnesium carbonate (CaMg) on serum phosphorus levels compared with sevelamer hydrochloride (HCl). The study aim was to show non-inferiority of CaMg in lowering serum phosphorus levels into Kidney Disease Outcome Quality Initiative (K/DOQI) target level range after 24 weeks. Three hundred and twenty-six patients from five European countries were included. After a phosphate binder washout period, 255 patients were randomized in a 1:1 fashion. Two hundred and four patients completed the study per protocol (CaMg, N = 105; dropouts N = 18; sevelamer-HCl, N = 99; dropouts N = 34). Patient baseline characteristics were similar in both groups.
Results. Serum phosphorus levels had decreased significantly with both drugs at week 25, and the study hypothesis of CaMg not being inferior to sevelamer-HCl was confirmed. The area under the curve for serum phosphorus (P = 0.0042) and the number of visits above K/DOQI (≤1.78 mmol/L, P = 0.0198) and Kidney disease: Improving global outcomes (KDIGO) targets (≤1.45 mmol/L, P = 0.0067) were significantly lower with CaMg. Ionized serum calcium did not differ between groups; total serum calcium increased in the CaMg group (treatment difference 0.0477 mmol/L; P = 0.0032) but was not associated with a higher risk of hypercalcaemia. An asymptomatic increase in serum magnesium occurred in CaMg-treated patients (treatment difference 0.2597 mmol/L, P < 0.0001). There was no difference in the number of patients with adverse events.
Conclusion. CaMg was non-inferior to the comparator at controlling serum phosphorus levels at Week 25. There was no change in ionized calcium; there was minimal increase in total serum calcium and a small increase in serum magnesium. It had a good tolerability profile and thus may represent an effective treatment of hyperphosphataemia.
doi:10.1093/ndt/gfq292
PMCID: PMC2957591  PMID: 20530499
calcium acetate; haemodialysis; magnesium carbonate; phosphate binder; safety parameters
13.  The safety and efficacy of intravenous ferric carboxymaltose in anaemic patients undergoing haemodialysis: a multi-centre, open-label, clinical study 
Nephrology Dialysis Transplantation  2010;25(8):2722-2730.
Background. Patients with chronic kidney disease (CKD) often present with iron depletion and iron deficiency anaemia (IDA) because of frequent blood (and iron) loss. Therapy consists of repletion of iron stores and intravenous (i.v.) iron has become the standard care in this setting. However, older i.v. iron preparations have their limitations. This study primarily investigated the safety, and also the efficacy, of ferric carboxymaltose (FCM), a next-generation i.v. iron formulation, given as a bolus–push injection in patients with CKD undergoing maintenance haemodialysis (HD).
Methods. Patients (aged 18–65 years) with IDA undergoing HD received 100–200 mg of iron as FCM via an i.v. bolus–push injection into the HD venous line, two to three times weekly for ≤6 weeks. Safety assessments included incidence of adverse events (AEs). Treatment responders were patients attaining ≥1.0 g/dl increase in haemoglobin (Hb) from baseline at any time during the study. Enrolled patients (safety population) receiving ≥1 dose of study medication were included in the efficacy analyses [intent-to-treat (ITT) population].
Results. Of 163 patients enrolled, 150 (92%) completed the study. The mean ± SD total cumulative dose of iron as FCM administered was 2133.3 ± 57.7 mg. In total, 193 AEs were reported in 89 out of 163 (54.6%) patients. Almost three-quarters of patients (73.6%) received erythropoiesis-stimulating agents (ESAs), but the dose remained stable during the study. Serious AEs occurred in 12 out of 163 (7.4%) patients and two patients died; none of these was considered by the investigator to be related to the study medication. Only five out of 163 (3.1%) patients discontinued study medication due to an AE. Overall, 100 out of 162 (61.7%; ITT population) patients were treatment responders, and mean Hb levels increased from 9.1 ± 1.30 g/dl at baseline to 10.3 ± 1.63 g/dl at follow-up.
Conclusions. FCM is well-tolerated and effective in the correction of Hb levels and iron stores in patients with IDA undergoing HD. As changes in anaemia treatment other than i.v. FCM (e.g. increased ESA doses) were not permitted during the study, the clinically relevant increase in Hb in the majority of patients can be solely attributed to efficient iron utilization. The incidence of AEs was as expected for this population.
doi:10.1093/ndt/gfq069
PMCID: PMC2905444  PMID: 20190247
clinical trial; efficacy; ferric carboxymaltose; haemodialysis; iron deficiency anaemia; safety
14.  Trace elements in end-stage renal disease – unfamiliar territory to be revealed 
BMC Nephrology  2009;10:12.
Although associated with unfavorable outcomes in the general population, abnormal blood levels of various trace elements have not been consistently studied in the end-stage renal disease population (with the notable exception of aluminum). This is surprising, as the uremic patient treated by chronic dialysis loses one major route of trace element excretion and is exposed systematically to a foreign environment (the dialysis fluid) possibly contaminated with significant amounts of potential deleterious trace elements. Moreover, some biological important trace elements may be lost through the dialysis membrane. Most studies to date demonstrated significantly altered blood levels of trace elements in ESRD patients compared to healthy controls. However, the biological impact of these abnormalities in renal disease is largely unknown and should be clarified by future studies. A further step would be the design of well-controlled randomized interventional studies, examining the potential therapeutic benefit of supplementing one or more trace elements in ESRD patients, a population characterized by an impressive mortality due to cardiovascular, infectious and neoplasic disease.
doi:10.1186/1471-2369-10-12
PMCID: PMC2698895  PMID: 19490615

Results 1-14 (14)