Volume 88 (2017), No. 7/2017(Supplement 1)
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6th Slovenian Congress of Nephrology
The whole issue as pdf-file
Editors of the Proceedings: Damjan Kovač, Radoslav Kveder, and Andrej Škoberne
Page No. 0
Abstract
The whole issue as pdf-file
Editors of the Proceedings: Damjan Kovač, Radoslav Kveder, and Andrej Škoberne
Clinical Nephrology
Tubular urinary indexes reliably distinguish between primary tubulointerstitial and primary glomerular diseases in patients referred for kidney biopsy
Andrej Škoberne, Špela Borštnar, Nuša Avguštin, Damjan Kovač, Andreja Aleš Rigler, Željka Večerić-Haler, Jernej Pajek, Mladen Krsnik, Nika Kojc, Dušan Ferluga, and Jelka Lindič
Page No. 1
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S1-S6)
Tubular urinary indexes reliably distinguish between primary tubulointerstitial and primary glomerular diseases in patients referred for kidney biopsy
Andrej Škoberne1, Špela Borštnar1, Nuša Avguštin1, Damjan Kovač1, Andreja Aleš Rigler1, Željka Večerić-Haler1, Jernej Pajek1, Mladen Krsnik2, Nika Kojc3, Dušan Ferluga3, and Jelka Lindič1
1Department of Nephrology and 2Institute of Clinical Chemistry and Biochemistry, University Medical Center Ljubljana, and 3Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Aims: Kidney biopsy remains the gold standard for accurately diagnosing renal diseases. Urinalysis and assessment of renal function are the cornerstones for assessment of patients prior to biopsy. There is significant overlap in the results of routine urine parameters (proteinuria, erythrocyturia, leukocyturia) among different kidney diseases, which hinders the possibility of adequately estimating disease etiology prior to the biopsy. The aim of our study was to assess whether diverse markers of glomerular and tubular proteinuria – urinary albumin, IgG, α-1-microglobulin (α-1-m) and N-acetyl-β-D-glucosaminidase (NAG) – are capable of distinguishing between patients with primary tubulointerstitial (TID) and primary glomerular disease (GLOM). Methods: Our study is a retrospective, single-center, consecutive case series of patients referred for kidney biopsy. We analyzed routine urinalysis results performed on a second morning urine sample immediately prior to the biopsy. Results: Patients with TID had significantly higher values of α-1-m and NAG, with lower values of albumin and IgG in the urine compared to patients with GLOM. Three tubular urinary indexes had high sensitivity and specificity for distinguishing TID from GLOM: NAG/albumin, α-1-m/proteinuria, and α-1-m/albumin, with the highest values in the latter index (96.6% and 98.2%, respectively, cut-off point ≥ 0.33). Conclusions: Prior to kidney biopsy, tubular urinary indexes may present a valuable tool in distinguishing patients with TID from patients with GLOM.
Correspondence to:
Andrej Škoberne, MD, PhD
Department of Nephrology
University Medical Centre Ljubljana
Zaloška 7, 1000 Ljubljana, Slovenia
Email: andrej.skoberne@
gmx.net
Clinical Nephrology
Determination of red blood cells in urinary sediment: Do pH and specific gravity of urine matter?
Nuša Avguštin, Alexander Jerman, Žiga Rotar, Špela Borštnar, Andrej Škoberne, and Jelka Lindič
Page No. 7
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S7-S9)
Determination of red blood cells in urinary sediment: Do pH and specific gravity of urine matter?
Nuša Avguštin1, Alexander Jerman1, Žiga Rotar2, Špela Borštnar1, Andrej Škoberne1, and Jelka Lindič1
1Department of Nephrology and 2Department of Rheumatology,
University Medical Centre Ljubljana, Ljubljana, Slovenia
Introduction: It has been postulated that erythrocyte cell lysis in urine is common in the case of low urine specific gravity and high urine pH. We aimed to verify the influence of urine dipstick pH and specific gravity on erythrocyturia in the urine sediment in the case of positive dipstick hemoglobinuria. Methods: We retrospectively collected data on dipstick specific gravity, pH, and urine sediment analysis done by nephrologists in the clinical and research urine laboratory at the Department of Nephrology, University Medical Center Ljubljana. Results: During the 6-year observation period, we analyzed 843 second morning midstream urine samples with positive dipstick hemoglobinuria. Erythrocyturia in urinary sediment was detected significantly less often in urine samples with concomitant hemoglobinuria 1+ and pH < 6.0, (odds ratio (OR) 0.40; 95% confidence interval (CI) 0.21 – 0.76, p = 0.005). The difference was maintained in multivariate analysis including patient age, gender, and specific gravity (OR 0.32; 95% CI 0.15 – 0.65, p = 0.002). In samples with higher grade of hemoglobinuria (≥ 2+), the impact of cell lysis in the case of low pH was negligible. Specific gravity did not have any influence on erythrocyte detection in urinary sediment. Conclusions: Urinary pH < 6.0 impaired the detection of erythrocytes in urinary sediment, while the dipstick measured urine specific gravity did not have any impact on it. Urine samples with low-grade hemoglobinuria and low pH without erythrocyte detection in urinary sediment should be evaluated again to avoid false-negative results.
Correspondence to:
Assist. Prof. Jelka Lindič, MD, PhD
Department of Nephrology
University Medical Centre Ljubljana
Zaloška cesta 7, 1000 Ljubljana, Slovenia
Email: [email protected]
Clinical Nephrology
The predictive value of urinary vascular endothelial growth factor (VEGF) on worsening kidney function in proteinuric chronic kidney disease
Nuša Avguštin, Žiga Rotar, Jernej Pajek, Damjan Kovač, Joško Osredkar, and Jelka Lindič
Page No. 10
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S10-S13)
The predictive value of urinary vascular endothelial growth factor (VEGF) on worsening kidney function in proteinuric chronic kidney disease
Nuša Avguštin1, Žiga Rotar2, Jernej Pajek1, Damjan Kovač1, Joško Osredkar3, and Jelka Lindič1
1Department of Nephrology, 2Department of Rheumatology, and 3Clinical Institute of Clinical Chemistry and Biochemistry, University Medical Center Ljubljana, Ljubljana, Slovenia
Objectives: To evaluate the role of urinary vascular endothelial growth factor (VEGF) as an early predictor of chronic kidney disease (CKD) progression in patients with glomerular diseases. Methods: We prospectively included patients with proteinuria and CKD grade 1 – 5 due to glomerular disease at the time of kidney biopsy. At baseline, we collected demographics, comorbidities, smoking history, serum creatinine (sCr), proteinuria, and urinary VEGF in collected 24-hour urine. The primary outcome was a 50% increase in sCr at last follow-up. Binary regression was used to explore the impact of urinary biomarkers adjusted for baseline patient characteristics on the outcome. Results: From July 2011 to September 2012 we included 49 patients aged 45.2 ± 14.8 years, 43% female, with different glomerular diseases. We followed them for 29 ± 11 months. Twelve out of 49 (22%) patients met the primary outcome. The patients with a 50% increase in sCr at last follow-up had a significantly higher baseline sCr (193 ± 101 vs. 127 ± 84; p = 0.014) and higher urinary VEGF/creatinine in 24-hour urine (7.7 ± 6.4 vs. 3.0 ± 4.0; p = 0.005). When we added both sCr and urinary VEGF/creatinine to the binary regression model, the correlation with baseline sCr was not significant (OR 1.01; 95% CI 1.00 – 1.01; p = 0.184), while urinary VEGF/creatinine remained significant (OR 1.18; 95% CI 1.04 – 1.35; p = 0.008). Baseline patient characteristics, such as age, gender, body mass index, sCr, proteinuria, smoking status, histopathologic diagnosis, concomitant arterial hypertension, and time to last follow-up did not influence the primary outcome. Conclusions: The urinary VEGF/creatinine ratio in 24-hour urine seems to independently predict worsening of chronic kidney disease in patients with glomerular diseases.
Correspondence to:
Asist. Prof. Jelka Lindič, MD, PhD
Department of Nephrology
University Medical Center Ljubljana
Zaloška cesta 7, 1000 Ljubljana, Slovenia
Email: [email protected]
Clinical Nephrology
Measurement of breath ammonia for detection of patients with chronic kidney disease
Sebastjan Bevc, Eva Mohorko, Mitja Kolar, Polona Brglez, Andrej Holobar, Daniela Kniepeiss, Matej Podbregar, Nejc Piko, Nina Hojs, Maša Knehtl, Robert Ekart, and Radovan Hojs
Page No. 14
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S14-S17)
Measurement of breath ammonia for detection of patients with chronic kidney disease
Sebastjan Bevc1#2, Eva Mohorko3, Mitja Kolar3, Polona Brglez4, Andrej Holobar4, Daniela Kniepeiss5, Matej Podbregar6#7, Nejc Piko1, Nina Hojs1#2, Maša Knehtl1#2, Robert Ekart2#8, and Radovan Hojs1#2
1Department of Nephrology, Clinic for Internal Medicine, University Clinical Center Maribor, 2Faculty of Medicine, University of Maribor, 3Faculty of Chemistry and Chemical Engineering, University of Maribor, Maribor, 4ECHO d.o.o., Slovenske Konjice, Slovenia, 5Medical University of Graz, Graz, Austria, 6Clinical Department for Anesthesiology and Intensive Care, University Medical Center Ljubljana, 7Faculty of Medicine, University of Ljubljana, Ljubljana, and 8Department of Dialysis, Clinic for Internal Medicine, University Clinical Center Maribor, Slovenia
Background: In a healthy individual, ammonia is converted to urea in the liver. Urea is then transported through the bloodstream and then excreted into the urine by the kidneys. In patients with chronic kidney disease (CKD), the accumulated urea is degraded by salivary urease into ammonia, which is then excreted by breathing. Breath ammonia can therefore be used for detecting the increased nitrogen-bearing wastes. In our pilot study, an electrochemical sensor was used to measure and analyze breath ammonia in healthy volunteers and patients with CKD. Patients and methods: In our study, 8 patients with CKD (stages 4 and 5) and 6 healthy volunteers were enrolled. All participants were nonsmokers and without pulmonary or liver disease. One controlled breath sample was collected from each participant. Immediately after the sample was collected, a gas analyzer was used for measuring breath ammonia in our participants. Results: Mean creatinine value of CKD patients was 455.2 ± 294.1 µmol/L and 62.1 ± 7.5 µmol/L for healthy volunteers. Breath ammonia levels (3.32 ± 2.19 ppm vs. 0.49 ± 0.08 ppm; p = 0.003) and measured electric current (4.33 ± 0.25 mA vs. 4.01 ± 0.01 mA; p = 0.003) were significantly higher in the CKD group. Conclusions: The results of our pilot study show that breath monitoring of ammonia can be a simple, useful, fast, and noninvasive tool for detection of advanced kidney impairment.
Correspondence to:
Piko Nejc, MD
University Clinical Center Maribor
Clinic for Internal Medicine
Department of Nephrology
Ljubljanska ulica 5, 2000 Maribor, Slovenia
Email: [email protected]
Clinical Nephrology
Acute kidney injury in critically-ill adult patients with seasonal influenza infection
Ana Dovč, Vladimir Premru, Blaž Pečavar, and Rafael Ponikvar
Page No. 18
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S18-S21)
Acute kidney injury in critically-ill adult patients with seasonal influenza infection
Ana Dovč1, Vladimir Premru1, Blaž Pečavar2, and Rafael Ponikvar1
1Department of Nephrology and 2Department of Infectious Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia
Background: Acute kidney injury (AKI) occurs in 22.4 – 100% of critically-ill hospitalized patients with influenza infection. In up to 2/3, it is severe enough to necessitate renal replacement therapy. We aimed to document the incidence of AKI among patients with influenza-related critical illness and its relation to clinical outcomes. Methods: We conducted a retrospective observational study of all adult patients with acute respiratory illness and laboratory-confirmed influenza infection admitted to non-surgical intensive care units at the University Medical Centre Ljubljana between January 1, 2016, and March 31, 2016. Result: Our sample consisted of 28 adult patients with mean age in years of 57.5 ± 20.2. Incidence of AKI was 71.4%. Mortality was 28.6% (35% in patients with AKI and 41.6% in patients who required renal replacement therapy). Conclusions: Influenza-related critical illness is rare but can cause AKI in a large proportion of affected patients. In this setting, requirement for renal replacement therapy could be associated with increased mortality risk.
Correspondence to:
Ana Dovč, MD
Department of Nephrology
University Medical Centre Ljubljana
Zaloška 7, 1000 Ljubljana, Slovenia
Email: [email protected]
Clinical Nephrology
Relationship between subendocardial viability ratio and hemoglobin in patients with chronic kidney disease
Robert Ekart, Sebastjan Bevc, Nina Hojs, Tina Stropnik Galuf, Martin Hren, Benjamin Dvoršak, Maša Knehtl, Eva Jakopin, Igor Krajnc, and Radovan Hojs
Page No. 22
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S22-S26)
Relationship between subendocardial viability ratio and hemoglobin in patients with chronic kidney disease
Robert Ekart1#2, Sebastjan Bevc2#3, Nina Hojs1#2, Tina Stropnik Galuf1, Martin Hren1, Benjamin Dvoršak3, Maša Knehtl3, Eva Jakopin3, Igor Krajnc4, and Radovan Hojs2#3
1Department of Dialysis, Clinic for Internal Medicine, University Medical Center Maribor, 2Faculty of Medicine, University of Maribor, 3Department of Nephrology, and 4Department of Cardiology, Clinic for Internal Medicine, University Medical Center Maribor, Maribor, Slovenia
Aims: Pulse wave analysis (PWA) uses the technique of applanation tonometry to obtain a peripheral pulse pressure waveform from which central hemodynamic information is derived. Using PWA, subendocardial viability ratio (SEVR) can be measured. SEVR represents a noninvasive measure of myocardial perfusion. It is related to the work of the heart, the oxygen consumption, and the energy supply of the heart. Anemia is a common complication of chronic kidney disease (CKD). A complex relationship exists between CKD, cardiovascular disease (CVD), and anemia. The aim of our study was to assess the relationship between SEVR and hemoglobin in nondialysis CKD patients. Material and methods: We examined the associations between PWA hemodynamic parameters, 24-hour ambulatory blood pressure (BP) measurements, and laboratory variables including hemoglobin, cardiac biomarkers troponin I, NT-proBNP, and hs-CRP in a cohort of 91 nondialysis CKD patients. PWA was assessed by radial applanation tonometry (SphygmoCor, Atcor, Sydney, Australia). The patients were divided into two groups according to the median value of hemoglobin. Results: Mean age of included patients was 60.2 years, 67% were men, 44% were smokers, 25.3% had diabetes. A significant correlation between hemoglobin and SEVR was found (r = 0.26; p = 0.012). With multivariate regression analysis, SEVR as dependent variable turned out to be statistically significantly associated with hemoglobin (β = 0.344, p = 0.013) and with troponin I (β = –0.217, p = 0.037). Patients in the group with lower hemoglobin had statistically-significantly higher serum creatinine, cystatin C, NT-proBNP, and 24-hour ambulatory systolic BP and lower e-GFR, SEVR, and office diastolic BP. Conclusions: Results of our study show that SEVR is independently associated with hemoglobin in nondialysis CKD patients. CKD patients with lower hemoglobin have lower SEVR.
Correspondence to:
Assoc. Prof. Robert Ekart, MD, PhD
University Medical Center Maribor
Clinic for Internal Medicine, Department of Dialysis
Ljubljanska 5, 2000 Maribor, Slovenia
Email: robert.ekart2@
guest.arnes.si
Clinical Nephrology
Rituximab for the treatment of membranous nephropathy: a single-center experience
Andreja Aleš Rigler, Alexander Jerman, Aleša Orsag, Nika Kojc, Damjan Kovač, Andrej Škoberne, Špela Borštnar, Željka Večerić Haler, Nuša Avguštin, Radoslav Kveder, Dušan Ferluga, Alenka Vizjak, and Jelka Lindič
Page No. 27
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S27-S31)
Rituximab for the treatment of membranous nephropathy: a single-center experience
Andreja Aleš Rigler1, Alexander Jerman1, Aleša Orsag1, Nika Kojc2, Damjan Kovač1, Andrej Škoberne1, Špela Borštnar1, Željka Večerić Haler1, Nuša Avguštin1, Radoslav Kveder1, Dušan Ferluga2, Alenka Vizjak2, and Jelka Lindič1
1Department of Nephrology, University Medical Center Ljubljana, and
2Institute of Pathology, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia
Background: Treatment of idiopathic membranous nephropathy with rituximab was introduced more than a decade ago following experimental data that suggested involvement of B-cell-mediated reactions in its pathogenesis. It was a logical step towards a more selective therapy with less severe side effects as compared to the recommended first-line immunosuppressive therapy with corticosteroids and different immunosuppressant drugs. Methods: We retrospectively analyzed the anonymous data of patients who were treated with rituximab for idiopathic membranous nephropathy at our institution from January 2006 to July 2016. Daily proteinuria and serum creatinine were analyzed 3, 6, 9, and 12 months after rituximab application. The patients were divided into 4 groups according to proteinuria. We separately analyzed remission rates in the whole group and in groups with different quantity of daily proteinuria. Other history data and laboratory parameters were also compared within different groups of patients. Results: The study involved 29 rituximab treatments in 26 patients: 7 (26.9%) female and 19 (73.1%) male patients. In 16 out of 29 treatment cases (55.1%), patients had been previously treated with cyclophosphamide and steroids, or cyclosporine with low dose of steroids, or both. In 72.4% of patients, antiphospholipase A2 receptor antibodies were present. In 2 cases of treatment (6.9%), patients received rituximab 375 mg/m2 of body surface area in 3 and 4 weekly doses, respectively. In all other cases, repeated rituximab applications were given as needed according to the levels of circulating CD-20 B-cells. The total remission rate in our cohort of patients was 37.9% (11 out of 29 cases). The average serum creatinine in the group of patients who achieved remission was significantly lower than in the group without remission (86.5 vs. 155.5 µmol/L, p = 0.003). There was no difference in the duration of the disease prior to treatment with rituximab between the groups (53.6 and 56.4 months, respectively). The remission rate was highest in the group with daily proteinuria less than 4 g per day (83.3%). There were no remissions in the group of patients with daily proteinuria more than 12 g per day. Conclusion: The remission rate after rituximab treatment in our cohort of patients with idiopathic membranous nephropathy was lower than in other studies. The reason for this is possibly the application of a single dose of rituximab in the majority of patients, which might have been insufficient in patients with higher proteinuria.
Correspondence to:
Andreja Aleš Rigler, MD, PhD
Department of Nephrology
University Medical Center Ljubljana
Zaloška 7, 1000 Ljubljana, Slovenia
Email: [email protected]
Clinical Nephrology
Rhabdomyolysis and interferon-β: case report and short review
Alexander Jerman, Damjan Kovač, Željka Večerić-Haler, Alojzija Hočevar, Ajda Ota, Sanela Banović, and Jelka Lindič
Page No. 32
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S32-S34)
Rhabdomyolysis and interferon-β: case report and short review
Alexander Jerman1, Damjan Kovač1,2, Željka Večerić-Haler1,2, Alojzija Hočevar2,3, Ajda Ota4, Sanela Banović1, and Jelka Lindič1,2
1Department of Nephrology, University Medical Center Ljubljana, 2Medical Faculty, University of Ljubljana, 3Department of Rheumatology, University Medical Center Ljubljana, and 4Department of Food Science and Technology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia
Background: We present a case of acute rhabdomyolysis in the setting of interferon-β treatment and concomitant pomelo juice ingestion, with concern of possible pharmacological interaction, which has not yet been described in the literature. Case presentation: A young Caucasian female with multiple sclerosis on chronic therapy with interferon-β presented with acute rhabdomyolysis after mild exercise and concomitant ingestion of pomelo extract. After stopping the suspected drugs, the signs of rhabdomyolysis diminished, the subsequent course was favorable. Conclusions: The most probable cause of rhabdomyolysis in our patient could have been the combination of interferon effect, which down-regulates P450 expression, with inhibition of the P450 activity by furanocoumarin derivatives from pomelo juice. Therefore, patients treated with drugs that have a possible interaction with inhibitors of cytochrome P450 should be warned against pomelo ingestion.
Correspondence to:
Jelka Lindič, MD
University Medical Center Ljubljana
Zaloška cesta 7, 1000 Ljubljana, Slovenia
Email: [email protected]
Clinical Nephrology
Subendocardial viability ratio and ejection duration as parameters of early cardiovascular risk in children
Nataša Marčun-Varda, Sara Nikolic, and Mirjam Močnik
Page No. 35
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S35-S38)
Subendocardial viability ratio and ejection duration as parameters of early cardiovascular risk in children
Nataša Marčun-Varda1,2, Sara Nikolic2, and Mirjam Močnik2
1Department of Pediatrics and 2University Medical Center Maribor, Maribor, Slovenia
Aim: The purpose of this study was to investigate subendocardial viability ratio (SEVR) and ejection duration (ED) in children and adolescents with common cardiovascular risk factors such as arterial hypertension, obesity, and hypercholesterolemia. Methods: Four groups of pediatric patients were analyzed: 31 children and adolescents had hypertension, 36 were overweight, 49 were overweight and had hypertension, and 70 had hypercholesterolemia. The patients were compared to a control group of 50 healthy individuals. Subjects were sampled by opportunity sampling at the Department of Pediatrics Maribor, Slovenia. In each patient, blood pressure, anthropometrical parameters, and pulse wave analysis (PWA) measurements using applanation tonometry technique were performed and calculated. Results: The results show a statistically-significant difference in ED (p = 0.013) but not in SEVR (p = 0.074) in the hypercholesterolemia group in comparison to the control group. In other research groups, no statistically-significant differences were found. In all study groups, SEVR correlated significantly with age (positive, moderate) and heart rate (negative, strong) as well as with central mean pressure (CMP). Conclusions: Our study does not show a significant role of SEVR and ED in early cardiovascular risk determination in children. However, some results do indicate a potential role of both, at least in hypercholesterolemia, and should be further investigated.
Correspondence to:
Sara Nikolic
University Medical Center Maribor
Ljubljanska 5, 2000 Maribor, Slovenia
Email: [email protected]
Clinical Nephrology
Bone mineral disturbances in patients with chronic kidney disease stage 5 not yet on dialysis
Andreja Marn Pernat and Matej Zrimšek
Page No. 39
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S39-S43)
Bone mineral disturbances in patients with chronic kidney disease stage 5 not yet on dialysis
Andreja Marn Pernat and Matej Zrimšek
Department of Nephrology, University Medical Center Ljubljana, Ljubljana, Slovenia
Aims: This retrospective study evaluates the success of a treatment strategy for secondary hyperparathyroidism in our cohort of patients with chronic kidney disease stage 5 who were not yet on dialysis. Materials and methods: 81 predialysis patients from the outpatient clinic of the Department of Nephrology, University Medical Center Ljubljana were reviewed. We focused on serum markers for bone mineral metabolism including intact parathyroid hormone (PTH), phosphate, corrected calcium, and the usage of phosphate-binding agents and vitamin D analogs. Results of intact PTH and phosphorus and calcium concentrations were related to treatment options for secondary hyperparathyroidism. Results: The average intact PTH concentration was 198.8 ± 162.5 ng/L, serum phosphate was 1.52 ± 0.35 mmol/L, and corrected calcium was 2.23 ± 0.2 mmol/L. Phosphate-binding agents were prescribed in 62% patients, 44% of these patients were on calcium-containing phosphate binders. Active vitamin D or synthetic vitamin D analogs were given to 65% of patients, and 48% of all received a combination of active vitamin D derivate and inactive vitamin D supplementation. Serum intact PTH was between 150 and 300 ng/L in 30%, under 150 ng/L in 46%, and over 300 ng/L in 24% of patients, respectively. Conclusions: Our data show that 76% of our patients with CKD stage 5 not yet on dialysis achieved adequate control of secondary hyperparathyroidism. Marked reduction of intact PTH levels in a significant proportion of our patients prompt us to assess the administration of excessive amounts of calcium and/or vitamin D supplements to prevent over-suppression of PTH, which can induce adynamic bone disease.
Correspondence to:
Andreja Marn Pernat, MD, PhD
Department of Nephrology
University Medical Center Ljubljana
Zaloška 7, 1000 Ljubljana, Slovenia
Email: [email protected]
Clinical Nephrology
Fabry disease: diagnostic methods in nephrology practice
Bojan Vujkovac
Page No. 44
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S44-S47)
Fabry disease: diagnostic methods in nephrology practice
Bojan Vujkovac
Department of Internal Medicine, General Hospital Slovenj Gradec, Slovenj Gradec, Slovenia
Fabry disease (FD; OMIM 301500) is a rare X-linked systemic disease caused by a mutation of the GLA gene. Consequently, there is very low, or even absent, activity of the lysosomal enzyme α-galactosidase A (α-Gal A), resulting in the progressive accumulation of glycosphingolipids (predominantly, globotriaosylceramide (GL-3)) in various cells of different organs. Chronic progressive proteinuric kidney disease is one of the hallmarks of this disease, and it constitutes an important component of this condition’s clinical picture. Many patients with FD develop advanced chronic kidney disease, and half of them progress to end-stage renal disease. Most male patients die before the age of 60 years. Specific treatment with enzyme replacement therapy (ERT) has been shown to be effective when treatment is started early enough, before irreversible changes can occur. Therefore, the early diagnosis of FD has become very important. However, in nephrology practice, too many patients are still being diagnosed in late and very advanced stages of the disease. Also, the number of diagnosed patients varies among different countries and regions. The reasons for this are numerous and diverse, and they mostly depend on the knowledge, awareness, and availability of diagnostic procedures.
Correspondence to:
Bojan Vujkovac, MD
General Hospital Slovenj Gradec
2380 Slovenj Gradec, Slovenia
Email: [email protected]
Dialysis
Physical function and 25-hydroxyvitamin D in dialysis patients – lessons learned from the Slovenian DIAGIB study
Maja Bučar Pajek, Ivan Čuk, Gregor Mlinšek, Joško Osredkar, and Jernej Pajek
Page No. 48
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S48-S52)
Physical function and 25-hydroxyvitamin D in dialysis patients – lessons learned from the Slovenian DIAGIB study
Maja Bučar Pajek1, Ivan Čuk1, Gregor Mlinšek2, Joško Osredkar3, and Jernej Pajek2
1Faculty of Sport, University of Ljubljana, 2Department of Nephrology, and 3Institute for Clinical Chemistry and Biochemistry, University Medical Center Ljubljana, Ljubljana, Slovenia
Aims: Vitamin D stores in dialysis patients may be associated with their muscle function and physical performance. We analyzed associations of 25-hydroxyvitamin D levels with functional test results in prevalent hemodialysis patients and healthy controls. Methods: Study sample included 54 dialysis patients and 81 healthy controls who performed a 6-minute walk test, sit-to-stand test, handgrip strength measurement, and self-rated habitual adjusted activity score with Human Activity Profile questionnaire. Adjusted general linear models were used to analyze association of 25-hydroxyvitamin D levels with test results. Results: Serum 25-hydroxyvitamin D concentration was 73.1 ± 35.4 nmol/L in dialysis patients and 64.6 ± 22 nmol/L in controls (p = 0.12). When adjusted for age, sex, body height, spontaneous gait speed, and dialysis dependence, 25-hydroxyitamin D was significantly positively associated with 6-minute walk test result, explaining 5% of variability in walked distance (B = 0.6 m/nmol/L, p = 0.008) and 12% of variability in adjusted activity score (B = 0.1 point/nmol/L, p < 0.001). There was no significant association with handgrip strength or sit-to-stand performance in adjusted models. Conclusions: Serum 25-hydroxyvitamin D levels are significantly positively associated with submaximal aerobic physical performance and habitual activity level in dialysis patients.
Correspondence to:
Assoc. Prof. Jernej Pajek, MD, PhD
Department of Nephrology
University Medical Center Ljubljana
Zaloška 2, 1525 Ljubljana, Slovenia
Email: [email protected]
Dialysis
Anticoagulation assessment methods in plasma exchange with regional citrate anticoagulation: evaluation of post-filter and filtered plasma ionized calcium
Manja Antonič, Jakob Gubenšek, Jadranka Buturović-Ponikvar, and Rafael Ponikvar
Page No. 53
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S53-S56)
Anticoagulation assessment methods in plasma exchange with regional citrate anticoagulation: evaluation of post-filter and filtered plasma ionized calcium
Manja Antonič1, Jakob Gubenšek2,3, Jadranka Buturović-Ponikvar2,3, and Rafael Ponikvar2
1Department of Nephrology and Dialysis, General Hospital Celje, Celje, 2Department of Nephrology, University Medical Center Ljubljana, and 3Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Aim: To assess the possibility of using filtered plasma instead of postfilter ionized calcium (iCa) for the assessment of anticoagulation in plasma exchange (PE) with citrate anticoagulation. Methods: 140 PE treatments were performed using either 4% or 15% citrate at a comparable dose. Paired samples of postfilter blood and filtered plasma were taken for iCa measurements with a point-of-care analyzer. Anticoagulation was also assessed with a bedside clotting time and visual assessment of the circuit after procedures. Results: In 490 paired samples, mean postfilter iCa was 0.39 ± 0.14 mmol/L, and filtered plasma iCa was 0.33 ± 0.11 mmol/L. Mean bedside clotting time was 18 ± 7 minutes. Neither the postfilter (r = 0.03, p = 0.73) nor the filtered plasma iCa (r = 0.09, p = 0.25) correlated significantly with bedside clotting time. Bland-Altman analysis showed a modest agreement between filtered plasma and postfilter iCa values (mean difference –0.07 mmol/L, upper and lower 95% limits of agreement 0.10 and –0.23 mmol/L). Median visual assessment score was excellent at all three checkpoints. Conclusions: A modest agreement between filtered plasma and postfilter iCa values could be acceptable if only a confirmation of anticoagulant effect is required. Measuring filtered plasma instead of postfilter iCa would reduce blood loss with sampling, which could be important in some settings.
Correspondence to:
Prof. Rafael Ponikvar, MD, PhD
Department of Nephrology
University Medica Center Ljubljana
Zaloška 7, 1000 Ljubljana, Slovenia
Email: [email protected]
Dialysis
Hemodialysis treatment of cardiorenal syndrome
Boštjan Leskovar, Tjaša Furlan, Simona Poznič, Maja Potisek, and Anton Adamlje
Page No. 57
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S57-S60)
Hemodialysis treatment of cardiorenal syndrome
Boštjan Leskovar, Tjaša Furlan, Simona Poznič, Maja Potisek, and Anton Adamlje
Trbovlje General Hospital, Trbovlje, Slovenia
Aims: We evaluated the impact of hemodialysis on mortality and hospital readmission in patients with cardiorenal syndrome. Methods: All patients were NYHA IV functional class and underwent laboratory testing, echocardiography, and cardiac functional testing. Hemodialysis was indicated in patients with progressive decline of kidney function and consequent failure to titrate heart failure medication as well as in patients with hypervolemia that was resistant to conservative treatment with more than 4 annual hospitalizations due to heart failure and/or concomitant chronic kidney disease stage III – IV. Patients were treated with low-efficacy bicarbonate hemodialysis with permanent central venous catheter used as vascular access. Results: Since 2004, 67 patients were started on hemodialysis because of cardiorenal syndrome. Hospital readmission rate due to heart failure decreased (1 year before dialysis vs. 1 year after dialysis: 0.79 ± 1.32 vs. 0.22 ± 0.65 hospitalizations per year, p = 0.001) together with the duration of annual hospital stay (11.4 ± 21.4 vs. 3.7 ± 10.4 days, p = 0.011). 1-, 2-, 3-, 4- and 5-year survival for our patients was 81%, 61%, 52%, 47%, and 39%, respectively. Conclusions: Chronic renal replacement therapy with hemodialysis and strict uremic, electrolyte, and volume control may be more beneficial for patients with advanced heart failure with preserved or reduced LVEF than ultrafiltration alone. We have observed better survival of terminal cardiorenal patients treated with hemodialysis than in the general NYHA IV population, with lower hospital readmission rate and less hospitalized days for heart failure.
Correspondence to:
Boštjan Leskovar, MD
Trbovlje General Hospital
Rudarska cesta 9, 1420 Trbovlje, Slovenia
Email: [email protected]
Dialysis
Ultrasound-guided percutaneous endovascular treatment of arteriovenous fistula/graft
Boštjan Leskovar, Tjaša Furlan, Simona Poznič, Maja Potisek, Anton Adamlje, and Tomaž Ključevšek
Page No. 61
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S61-S64)
Ultrasound-guided percutaneous endovascular treatment of arteriovenous fistula/graft
Boštjan Leskovar1, Tjaša Furlan1, Simona Poznič1, Maja Potisek1, Anton Adamlje1, and Tomaž Ključevšek2
1Trbovlje General Hospital, Trbovlje, and 2Institute of Radiology, University Medical Center Ljubljana, Ljubljana, Slovenia
Background: Ultrasound-guided percutaneous endovascular treatment of arteriovenous fistula (AVF) or graft failure is an alternative to radiologically-guided angioplastic methods. Its main advantages are that it can be used with open or percutaneous access, using no contrast media and no radiation. The aim of this study was to analyze the results of ultrasound-guided endovascular treatment of arteriovenous access failure. Material and methods: Preoperative ultrasound was used to determine the degree of stenosis and the size of balloon used in angioplasty. Angioplasty was performed as open procedure or by using a 4 – 6 French percutaneous sheath. Indications for angioplasty were significant stenosis of native vein or polytetrafluoroethylene (PTFE) graft with or without AVF thrombosis. Stenosis was considered significant if it narrowed the lumen of AVF for more than 50% and changed the shape of the flow curve. Balloon inflation was controlled by ultrasound. Procedural success was assessed with repeated postprocedural ultrasound. Results: In the period from August 2012 until August 2016, 228 ultrasound-guided open or percutaneous transluminal angioplasties (PTA) were performed (61% men, mean age 66.6 ± 12.0 years), success rate was 93%. In 19 (8%) cases, ultrasound-guided PTA was used in conjunction with surgical reconstruction of arteriovenous fistula/graft and in 27 (12%) cases with thromboendarterectomy. Main complications were recoil, phlebitic vein rupture, and guidewire false route in thrombotic vessels. The main cause of access failure was perianastomotic stenosis (25%). 46% of patients required repeated PTA after the first one (after a mean time of 20.8 ± 22.8 weeks, mean number of repeated PTA 2.1 ± 1.7). Repeated PTA was done intentionally as stepped dilatation or because of rethrombosis/restenosis. Ultrasound-guided stent placement was done in 8% of PTA. Conclusions: Ultrasound-guided endovascular treatment of arteriovenous fistula or graft is a feasible and safe method of reestablishing or maintaining a functional vascular access.
Correspondence to:
Boštjan Leskovar, MD
Trbovlje General Hospital
Rudarska cesta 9, 1240 Trbovlje, Slovenia
Email: [email protected]
Dialysis
Impact of short-term nutritional supplementation on surrogate markers of undernutrition in hemodialysis patients – prospective real-life interventional study
Andreja Ocepek, Sebastjan Bevc, and Robert Ekart
Page No. 65
Abstract
Clinical Nephrology, Vol. 88 – Suppl 1/2017 (S65-S68)
Impact of short-term nutritional supplementation on surrogate markers of undernutrition in hemodialysis patients – prospective real-life interventional study
Andreja Ocepek1, Sebastjan Bevc2,3, and Robert Ekart3,4
1Department of Gastroenterology and Endoscopy, 2Department of Nephrology, Division of Internal Medicine, University Medical Center Maribor, 3Faculty of Medicine, University of Maribor, and 4Department of Dialysis, Division of Internal Medicine, University Medical Center Maribor, Maribor, Slovenia
Introduction: Hemodialysis (HD) patients are at increased risk for undernutrition, especially protein wasting. We present the results of a prospective study in HD patients after 4 months of intervention with oral nutritional supplements (ONS). Methods: After a 3-month wash-out period, 92 HD patients were enrolled in the study. Patients were tested for undernutrition with composite parameters, laboratory tests, bioelectrical impedance analysis (BIA), and hand-grip strength test (HGS). All patients fulfilling criteria for, or at high risk of, undernutrition were given ONS in addition to their regular diet. The impact of short-term ONS on surrogate markers of undernutrition was statistically analyzed. Results: Data for 84 patients, 45 (53.6%) male, average age 63.3 years, were available for analysis after 4 months. Patients were divided into three groups: group A (n = 28), patients with normal nutritional status (NUS) at baseline not necessitating ONS; group B (n = 43), patients entitled to receive ONS; group C (n = 13), patients entitled to receive but refused to take ONS. In group B patients, received on average 4.1 bottles of ONS (902 mL; 1,623.6 kcal; 73.06 g protein) per week. Baseline results showed statistically-significant differences between groups in serum albumin levels and phase angle (PhA) but not in HGS. After 4 months of ONS, we noticed stagnation of observed markers in group B. Interestingly, in group A, significant deterioration of serum albumin and PhA was observed, but HGS improved. There was a trend towards worsening of serum albumin levels and HGS in group C not reaching statistical significance. Conclusions: In undernourished HD patients after ONS we did not find statistically-significant improvement of NUS evaluating surrogate markers. Nevertheless, in undernourished patients not receiving ONS, serum albumin and HGS showed a trend towards worsening, and even in well-nourished patients, nutritional markers (serum albumin and PhA) declined. We speculate that a certain positive effect of ONS on nutritional status in undernourished HD patients could be observed already after short-term supplementation.
Correspondence to:
Andreja Ocepek, MD
Department of Gastroenterology and Endoscopy
Division of Internal Medicine
University Medical Center Maribor
Ljubljanska ulica 5, 2000 Maribor, Slovenia
Email: [email protected]
Dialysis
Hyperuricemia and long-term survival in patients with chronic kidney disease undergoing hemodialysis
Tadej Petreski, Sebastjan Bevc, Robert Ekart, and Radovan Hojs
Page No. 69
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S69-S72)
Hyperuricemia and long-term survival in patients with chronic kidney disease undergoing hemodialysis
Tadej Petreski1, Sebastjan Bevc1#2, Robert Ekart1#3, and Radovan Hojs1#2
1Faculty of Medicine, University of Maribor, 2Department of Nephrology, Clinic of Internal Medicine, and 3Department of Dialysis, Clinic of Internal Medicine, University Medical Center Maribor, Maribor, Slovenia
Introduction: Uric acid (UA), a breakdown product of purines, has been associated with mortality in different populations. Less is known about associations between hyperuricemia and mortality in chronic kidney disease (CKD) patients, later undergoing hemodialysis (HD), during a long observation period. The aim of this study was to determine the impact of elevated UA levels on long-term (19.5 years) survival of CKD patients. Methods: 120 CKD patients (49 female, 71 male) enrolled in our study were observed from their first visit at the patients’ nephrology outpatient clinic (NOC). All patients later started HD and were followed until their death or January 1, 2016. UA was measured regularly from venous sampling during NOC visits and HD sessions. Patients with mean UA below 420 µmol/L were defined as normouricemic, patients with mean UA above 420 µmol/L as hyperuricemic. No patients were treated for hyperuricemia. Survival rates were analyzed using Kaplan-Meier survival curves. Cox regression model was used to assess the influence of UA, age, arterial hypertension, diabetes mellitus, total cholesterol, triglycerides, smoking, and body mass index on the survival of our patients. Results: Mean UA was 383.6 ± 83, range 220 to 710 µmol/L. 86 (71.7%) patients were normouricemic, and 34 (28.3%) hyperuricemic. 43 (50.0%) normouricemic and 28 (82.4%) hyperuricemic patients died. Kaplan-Meier survival analysis showed the risk of death to be higher for hyperuricemic patients (log-rank test; p < 0.0001). With Cox multivariable regression model, the mean UA still remained a predictor of mortality in our patients (p < 0.0001). Conclusions: The results indicate an association between UA and long-term survival of CKD patients and show that hyperuricemia was directly associated with higher mortality among our patients.
Correspondence to:
Tadej Petreski, MS
Department of Nephrology
Clinic of Internal Medicine
University Medical Centre Maribor
Ljubljanska ulica 5, 2000 Maribor, Slovenia
Email: [email protected]
Dialysis
The impact of gene polymorphisms in angiotensin receptor 1 and aldosterone synthase in peritoneal dialysis patients
Alijana Trošt Rupnik, Damjan Kovač, Jernej Pajek, Joško Osredkar, Janja Marc, and Jelka Lindič
Page No. 73
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S73-S77)
The impact of gene polymorphisms in angiotensin receptor 1 and aldosterone synthase in peritoneal dialysis patients
Alijana Trošt Rupnik1, Damjan Kovač2, Jernej Pajek2, Joško Osredkar3, Janja Marc4, and Jelka Lindič2
1Department of Nephrology, General Hospital Nova Gorica, Šempeter pri Gorici, 2Department of Nephrology, 3Institute of Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana, and 4Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
Aim: Longevity of peritoneal membrane is an important issue in patients treated with peritoneal dialysis (PD). In our study, we studied the impact of angiotensin receptor 1 (AGT R1) and aldosterone synthase (CYP11B2) gene polymorphism on peritoneal concentrations of interleukin-6 (PI-IL-6), vascular endothelial growth factor (PI-VEGF), plasminogen activator inhibitor-1 (PI-PAI-1), transforming growth factor-β (PI-TGF-β), and cancer antigen-125 (PI-CA-125) as known markers of peritoneal fibrosis. The single nucleotide polymorphism rs5186 (A1166C) in AGT R1 gene is located in 3’ untranslated region (UTR) of the gene, while polymorphism rs1799998 (T -344 C) in CYP11B2 gene is located in the promoter region of the gene. Methods: We compared marker concentrations in patients with genotype DD vs. Dd and dd for AGT R1 and patients with genotype HH vs. Hh and hh for CYP11B2. Results: The results show that polymorphism of CYP11B2 gene is associated with serum concentration of aldosterone. Patients with genotype HH had statistically significantly lower serum concentration of aldosterone (p = 0.04). These patients also showed a trend to a lower rate of production of I-IL-6 (p = 0.07), which correlated with lower concentrations of PAI-1 (p = 0.002) and VEGF (p = 0.005). AGT R1 gene polymorphism did not show any association with studied variables. Conclusions: Our findings suggest the possibility of genetic predisposition for development of peritoneal fibrosis that could be important for identification of patients with an “unfavorable” genotype, which could lead to customized prescription of appropriate therapy and personalized patient management.
Correspondence to:
Assist. Prof. Jelka Lindič, MD, PhD
University Medical Centre Ljubljana
Department of Nephrology
Zaloška 7, 1525 Ljubljana, Slovenia
Email: [email protected]
Kidney Transplantation
Role of dry lean body mass for estimation of glomerular filtration rate in kidney transplant recipients
Špela Borštnar, Jelka Lindič, Andrej Škoberne, Luka Ležaič, Aljaž Sočan, Aljoša Kandus, and Damjan Kovač
Page No. 78
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S78-S82)
Role of dry lean body mass for estimation of glomerular filtration rate in kidney transplant recipients
Špela Borštnar1,2, Jelka Lindič1, Andrej Škoberne1, Luka Ležaič3, Aljaž Sočan3, Aljoša Kandus1, and Damjan Kovač1
1Department of Nephrology, University Medical Centre Ljubljana, Ljubljana, 2Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 3Department of Nuclear Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia
Background: The use of equations that predict glomerular filtration rate (GFR) in patients with a kidney graft is still a matter of debate. The purpose of this study was to determine the level of accuracy of GFR equations and the relevance of dry lean body mass in the assessment of GFR. Methods: In a prospective clinical study, 100 patients with a kidney graft were included. Estimated GFR with Modification of Diet in Renal Disease equation (MDRD), Chronic Kidney Disease Epidemiology Collaboration equation (CKD EPI) with serum creatinine concentration (CKD EPI Cr), serum cystatin C concentration (CKD EPI CysC) or both (CKD EPI Cr-CysC), and creatinine clearance calculated with Cockcroft-Gault equation (CG) was compared with GFR measured by 51Cr-EDTA clearance (mGFR 51Cr-EDTA). Dry lean body mass (body mass without fat mass and body water) was measured with bioimpedance analysis. Results: All of the estimating equations overestimated mGFR 51Cr-EDTA by a significant degree (bias ± SD in mL/min/1.73m2, 30% accuracy in brackets): CG 16.8 ± 14.1 (44%), MDRD 12.5 ± 15.3 (54%), CKD EPI Cr 15.1 ± 15.3 (50%), CKD EPI CysC 8.0 ± 16.6 (56%), CKD EPI Cr-CysC 10.3 ± 13.4 (55%). Dry lean body mass significantly correlated with mGFR 51Cr-EDTA, but not with estimated GFRs. Conclusion: The estimating GFR equations are neither accurate nor precise in renal transplant recipients. Dry lean body mass is an important parameter that could potentially improve the GFR estimation in this population.
Correspondence to:
Špela Borštnar
Department of Nephrology
University Medical Center Ljubljana
Zaloška 7, 1000 Ljubljana, Slovenia
Email: [email protected]
Kidney Transplantation
Increase in spot urine protein excretion is associated with late kidney graft rejection and predicts rejection phenotype
Miha Arnol, Manca Oblak, Gregor Mlinšek, Jelka Lindič, Aljoša Kandus, Dušan Ferluga, Nika Kojc, and Jadranka Buturović-Ponikvar
Page No. 83
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S83-S90)
Increase in spot urine protein excretion is associated with late kidney graft rejection and predicts rejection phenotype
Miha Arnol1#2, Manca Oblak1, Gregor Mlinšek1, Jelka Lindič1, Aljoša Kandus1, Dušan Ferluga3, Nika Kojc3, and Jadranka Buturović-Ponikvar1#2
1Department of Nephrology, University Medical Center Ljubljana, 2Faculty of Medicine, and 3Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Aims: A noninvasive test that foretells kidney graft rejection before loss of kidney function would be desirable. We hypothesized that an increase in estimated protein excretion rate (ePER) from spot urine samples is associated with graft rejection and predicts rejection phenotype. Methods: 151 patients who had undergone first-indication kidney biopsy due to graft dysfunction beyond 3 months after transplant were identified from a national cohort of 616 transplant recipients between 2000 and 2012 (25%). ePER were calculated from spot urine protein-to-creatinine ratios at baseline, 3 months before biopsy (ePER–3m), and at the time of biopsy (ePERbiopsy) and were correlated with histologic biopsy findings. Results: Levels of ePER 3 months before biopsy and at the time of biopsy were greater in 32 patients with antibody-mediated rejection (ABMR) than in 77 patients with T-cell-mediated rejection (TCMR) and 42 patients with other findings (median ePER–3m 912 vs. 320 vs. 232 mg/day/1.73m2; and median ePERbiopsy 1,672 vs. 356 vs. 268 mg/day/1.73m2; p < 0.001). Receiver operator characteristics (ROC) analyses demonstrated that ePER–3m and ePERbiopsy had good diagnostic accuracy to discriminate between biopsy specimens showing ABMR vs. those showing TCMR or other histologic findings (area under the ROC curve 0.84, 95% CI 0.75 – 0.93 and 0.89, 95% CI 0.82 – 0.97, respectively; p < 0.001). Conclusions: An increase in ePER before kidney graft dysfunction appears to be associated with graft rejection and predicts ABMR phenotype.
Correspondence to:
Miha Arnol, MD, PhD
Department of Nephrology
Center for Kidney Transplantation
University Medical Center Ljubljana
Zaloska 7, Ljubljana 1000, Slovenia
Email: [email protected]
Kidney Transplantation
Treatment of antibody-mediated rejection of kidney grafts with bortezomib and/or rituximab compared to standard regimen: experience of Slovene National Center
Teja Oblak, Jelka Lindič, Jakob Gubenšek, Radoslav Kveder, Andreja Aleš Rigler, Andrej Škoberne, Željka Večerić Haler, Špela Borštnar, Nuša Avguštin, Rafael Ponikvar, Gregor Mlinšek, Dušan Ferluga, Nika Kojc, Uroš Godnov, and Damjan Kovač
Page No. 91
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S91-S96)
Treatment of antibody-mediated rejection of kidney grafts with bortezomib and/or rituximab compared to standard regimen: experience of Slovene National Center
Teja Oblak1, Jelka Lindič1, Jakob Gubenšek1#2, Radoslav Kveder1, Andreja Aleš Rigler1, Andrej Škoberne1, Željka Večerić Haler1, Špela Borštnar1, Nuša Avguštin1, Rafael Ponikvar1#2, Gregor Mlinšek1, Dušan Ferluga2#3, Nika Kojc2#3, Uroš Godnov4, and Damjan Kovač1
1Department of Nephrology, University Medical Center Ljubljana, 2Faculty of Medicine, 3Insititute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, and 4Faculty of Management, University of Primorska, Koper, Slovenia
Background: The aim of our study was to determine outcomes of standard treatment of antibody-mediated rejection (ABMR) of kidney grafts as compared to the addition of bortezomib or rituximab. Methods: The cohort of this retrospective study included patients treated for ABMR of kidney grafts at our national center in the period of 2005 – 2017, divided into two groups: standard (ST) group treated standardly with plasmapheresis or immunoadsorption, intravenous immunoglobulins, and corticosteroids, and BR group treated with the addition of bortezomib and/or rituximab. Patient and graft survival at 2 years was analyzed by Kaplan-Meier method, and predictors of graft survival were analyzed by Cox regression. Results: There were 78 patients with ABMR (48 in the ST group, 30 in the BR group), 41 (53%) were men, mean age 49.5 ± 13.8 years. In ST and BR, respectively, mean serum creatinine was 267 ± 164 and 208 ± 112 µmol/L (p = 0.088), donor-specific antibodies (DSA) were positive in 75% and 97% (p = 0.022), and ABMR was acute in 50% and 33% (p = 0.149). Patient survival at 2 years was 89% in the ST and 100% in the BR group (p = 0.125). Cumulative proportion of kidney graft survival at 1 and 2 years was 67% and 53% in the ST group and 73% and 48% in the BR group, respectively, (p = 0.641). Chronic ABMR (HR 5.22, p = 0.004) was significant, while dialysis dependency at biopsy (HR 3.28, p = 0.072), serum creatinine at kidney biopsy (HR 1.003, p = 0.082), and presence of DQ-DSA (HR 3.37, p = 0.062) were borderline significant predictors of worse graft outcome. Infections were relatively common in both groups, with a trend towards more rehospitalizations due to infections in the first 6 months after treatment in the BR group (p = 0.066). In 5 patients (17%), treatment with bortezomib was discontinued prematurely due to cytopenia. Conclusions: Bortezomib or rituximab, added to standard treatment, did not significantly improve kidney graft survival and was also not associated with significant side effects, except cytopenia in some cases. Treatment of acute ABMR resulted in better graft survival than chronic ABMR.
Correspondence to:
Assoc. Prof. Damjan, Kovač, MD, PhD
Department of Nephrology
University Medica Centre Ljubljana
Zaloška cesta 7, 1525 Ljubljana, Slovenia
Email: [email protected]
Kidney Transplantation
Acute granulomatous interstitial nephritis and acute rejection in a kidney transplant recipient after zoledronic acid therapy – a case report and review of the literature
Nuša Avguštin, Damjan Kovač, Nika Kojc, Gregor Mlinšek, and Jelka Lindič
Page No. 97
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S97-S100)
Acute granulomatous interstitial nephritis and acute rejection in a kidney transplant recipient after zoledronic acid therapy – a case report and review of the literature
Nuša Avguštin1, Damjan Kovač1, Nika Kojc2, Gregor Mlinšek2, and Jelka Lindič1
1Department of Nephrology, University Medical Center Ljubljana, and 2Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Background: Acute granulomatous interstitial nephritis (AGIN) in native kidneys is most commonly linked to drugs. In allografts, it is a rare complication, and it occurs mostly with infections. Case presentation: Our case report presents AGIN with simultaneous acute cellular rejections and acute tubular necrosis in a kidney transplant patient 2 weeks after intravenous application of zoledronic acid. A kidney biopsy showed signs of destructive AGIN with acute cellular rejection. After treatment with methylprednisolone pulses and immunosuppressive therapy modification, rebiopsy confirmed complete regression of AGIN with less intense persistent acute cellular rejection and acute tubular necrosis. Kidney function improved after glucocorticoid and intravenous immunoglobulin G therapy. Conclusion: To our knowledge, this is the first case of AGIN related to bisphosphonate zoledronate in a kidney transplant patient with consequent acute cellular rejection. In using intravenous zoledronate infusion in a kidney transplant recipient, we should be aware that it could potentially induce acute granulomatous tubulointerstitial nephritis and acute rejection.
Correspondence to:
Jelka Lindič, MD, PhD
Department of Nephrology
University Medical Center Ljubljana
Zaloška cesta 7, 1000 Ljubljana, Slovenia
Email: [email protected]
Kidney Transplantation
Prevalence and risk factors for nonvertebral bone fractures in kidney transplant recipients – a single-center retrospective analysis
Alexander Jerman, Jelka Lindič, Andrej Škoberne, Špela Borštnar, Maja Martinuč Bergoč, Uroš Godnov, and Damjan Kovač
Page No. 101
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S101-S108)
Prevalence and risk factors for nonvertebral bone fractures in kidney transplant recipients – a single-center retrospective analysis
Alexander Jerman1, Jelka Lindič1, Andrej Škoberne1, Špela Borštnar1, Maja Martinuč Bergoč2, Uroš Godnov3, and Damjan Kovač1
1University Medical Center Ljubljana, Department of Nephrology, Ljubljana, 2General Hospital of Nova Gorica, Department of Nephrology, Šempeter, and 3Faculty of Management, University of Primorska, Koper, Slovenia
Background: Complex and longstanding bone disease superimposed by harmful influences of immunosuppression is the reason for increased risk of bone fracture in kidney transplant recipients. The aim of our study was to analyze the incidence and prevalence of nonvertebral bone fractures and early (in the first post-transplant year) clinical and laboratory risk factors for suffering bone fracture in the long-term post-transplant period. Methods: Clinical and laboratory data as well as bone mineral density (BMD) measurements of 507 first kidney transplant recipients who were transplanted in the period from 1976 to 2011 were analyzed. Results: The mean age of included patients was 54.3 ± 12.0 years, there were 45% females, and mean time on renal replacement treatment prior to transplantation was 63.4 ± 43.6 months. The average observation time post-transplant was 9.7 years (1.4 – 36.3 years). Post-transplant, 64 (12.6%) patients suffered 89 nonvertebral fractures (44 patients suffered 1 fracture, 15 patients 2 fractures, and 5 patients 3 fractures). Patients with fractures had significantly lower late BMD of femoral neck in the period of 1 – 10 years post-transplant, had osteopenia and osteoporosis more frequently in the same time period, and higher serum alkaline phosphatase in the first year post-transplant. 13 patients (13/64, 20.3%) had major fractures. Patients with major fractures were significantly older than patients with no major fractures and had lower serum albumin. Frequency of treatment with bisphosphonate, calcium, or phosphate did not differ between the groups. Vitamin D supplement (active form in 98% of cases) was prescribed more frequently in the group without fractures, but this was not statistically significant. Conclusion: Fracture rate in our transplant patient population was comparable to that reported in the literature. Except for a higher level of serum total alkaline phosphatase in the fracture group, we found no other early laboratory risk factors for bone fractures. BMD at the femoral region 1 – 10 years after kidney transplantation but not BMD at the time of transplantation was a risk factor for nonvertebral fractures. Osteopenia and osteoporosis in the post-transplant period were found to be a fracture risk factor.
Correspondence to:
Assoc. Prof. Damjan Kovač, MD, PhD, University Medical Centre Ljubljana, Zaloška cesta 7, 1000 Ljubljana, Slovenia
Email: [email protected]
Kidney Transplantation
Outcome of polyomavirus nephropathy in renal transplant patients: a single-center experience
Nika Kojc, Andreja Aleš Rigler, Gregor Mlinšek, Damjan Kovač, Dušan Ferluga, and Miha Arnol
Page No. 109
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S109-S114)
Outcome of polyomavirus nephropathy in renal transplant patients: a single-center experience
Nika Kojc1#2, Andreja Aleš Rigler3, Gregor Mlinšek3, Damjan Kovač3, Dušan Ferluga1, and Miha Arnol2#3
1Institute of Pathology, 2Medical Faculty, University of Ljubljana, and 3Department of Nephrology, University Medical Center Ljubljana, Ljubljana, Slovenia
Background: Reduction of immunosuppression is a common therapeutic strategy in patients with polyomavirus nephropathy (PVN) but may be associated with acute rejection. This study aimed to evaluate the morphology of PVN in renal biopsies after reduction of immunosuppression. Methods: Eight of 241 patients who received a kidney transplant between January 2012 and December 2015 presented with BK viremia and biopsy-proven PVN. Morphological evaluation according to Banff criteria and correlation with viremia and kidney function after immunosuppression reduction was performed. Results: PVN grades A and B were diagnosed on average 4.7 months post-transplant in 1 and 7 patients, respectively. Indication biopsies after immunosuppression reduction showed an increase in tubulitis and interstitial inflammation score compared to those at the time of the PVN diagnosis. Surveillance biopsies 1 year after transplantation revealed resolution of interstitial inflammation and tubulitis accompanied by clearance of BK viremia in 4 patients (50%), including 1 patient with rejection. One patient showed residual interstitial inflammation after viral clearance. In these patients, renal function returned to baseline. One patient with persisting low BK virus (BKV) in serum and kidney showed a decrease of tubulointerstitial inflammation but scarring was seen. Rejection occurred in 3 patients (38%). Conclusion: PVN-associated interstitial inflammation and tubulitis cannot be differentiated morphologically from T-cell-mediated tubulointerstitial rejection. Significant interstitial inflammation and tubulitis in PVN under low-dose immunosuppression might represent immune reconstitution injury, which is reduced after successful BKV clearance from the serum and kidney. Concomitant rejection in PVN patients on low immunosuppression might be efficiently treated with transient pulse immunosuppressive therapy.
Correspondence to:
Nika Kojc, MD, PhD
Institute of Pathology, Medical Faculty
University of Ljubljana
Korytkova 2, 1000 Ljubljana, Slovenia
Email: [email protected]
Kidney Transplantation
The role of single nucleotide polymorphisms of CYP3A and ABCB1 on tacrolimus predose concentration in kidney transplant recipients
Gregor Mlinšek, Vita Dolžan, Katja Goričar, Jadranka Buturović-Ponikvar, and Miha Arnol
Page No. 115
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S115-S118)
The role of single nucleotide polymorphisms of CYP3A and ABCB1 on tacrolimus predose concentration in kidney transplant recipients
Gregor Mlinšek1, Vita Dolžan2, Katja Goričar2, Jadranka Buturović-Ponikvar1#3, and Miha Arnol1#3
1Department of Nephrology, University Medical Centre Ljubljana, 2Institute of Biochemistry, Pharmacogenetics Laboratory, Faculty of Medicine, and 3Department of Internal Medicine, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenja
Background: Tacrolimus has a narrow therapeutic drug window but high inter- and intrapatient variability. Our aim is to construct a model able to predict optimal maintenance tacrolimus predose concentration (C0) in kidney transplant patients. Here we present our study design and genotype and variant allele frequencies for the selected single nucleotide polymorphisms of genes involved in tacrolimus metabolism in our national cohort of kidney transplant recipients. Methods: In the observational part of the study, we intend to determine allelic variants of CYP3A4, CYP3A5, and ABCB1 gene in a national cohort of 700 kidney transplants recipients. Clinical and laboratory data of this historic cohort will be added to assess patient’s immunologic risk. Based on these data, a prediction model will be constructed that will be validated in a prospective randomized study in 60 de-novo kidney transplant recipients. Results: Our interim cross-sectional observational results show higher variability of ABCB1 genotypes when compared to CYP3A genes, with more than two thirds of the population carrying at least one polymorphic allele. On the other hand, less than 1% of our transplant recipients possess the CYP3A genotype, which requires high daily tacrolimus dose. Conclusions: Due to high inter- and intrapatient tacrolimus variability, a patient-tailored approach to define the optimal maintenance tacrolimus C0 for each individual patient is needed. Our model will rely on individual pharmacogenomic and clinical data to cover different patient-specific risk factors for adverse outcomes.
Correspondence to:
Assist. Prof. Gregor Mlinšek, MD, PhD
Department of Nephrology
University Medical Center Ljubljana
Zaloška 7, 1000 Ljubljana, Slovenia
Email: [email protected]
Kidney Transplantation
Effects of paricalcitol on biomarkers of inflammation and fibrosis in kidney transplant recipients: results of a randomized controlled trial
Manca Oblak, Gregor Mlinšek, Aljoša Kandus, Jadranka Buturović-Ponikvar, and Miha Arnol
Page No. 119
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S119-S125)
Effects of paricalcitol on biomarkers of inflammation and fibrosis in kidney transplant recipients: results of a randomized controlled trial
Manca Oblak1, Gregor Mlinšek1, Aljoša Kandus1, Jadranka Buturović-Ponikvar1#2, and Miha Arnol1#2
1Department of Nephrology, University Medical Center Ljubljana, and
2Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Aims: Paricalcitol, a selective vitamin D activator, decreases proteinuria and may reduce graft failure risk in kidney transplant recipients. In this study, we evaluated the effect of paricalcitol on renin-angiotensin system (RAS) activity as well as interleukin (IL)-6 and transforming growth factor (TGF)-β plasma concentrations as biomarkers of inflammation and fibrosis. Methods: This placebo-controlled, double-blind trial enrolled a national cohort of kidney transplant recipients with urinary protein-to-creatinine ratio (UPCR) ≥ 20 mg/mmol despite optimization of the RAS blockade. Patients were randomly assigned to receive 24 weeks of treatment with 2 µg/day paricalcitol or placebo. The primary endpoint was the percent change in geometric mean UPCR. In this secondary analysis, we examined the effect of paricalcitol on plasma renin activity (PRA) and aldosterone levels as well as IL-6 and TGF-β plasma concentrations from baseline to last measurement during treatment. Results: Of the 168 patients with UPCR ≥ 20 mg/mmol who consented to undergoing randomization, 83 were allocated to paricalcitol and 85 to placebo. Baseline patient demographics, clinical characteristics, PRA, and aldosterone levels were similar between groups. Mean change in IL-6 was –29% (from 2.53 to 2.02 pg/mL) in the paricalcitol group and 23% (from 2.07 to 2.54 pg/mL) in the placebo group (p < 0.001). Mean change in TGF-β was –12% (from 8,011 to 6,935 pg/mL) in the paricalcitol group and 21% (from 7,418 to 8,992 pg/mL) in the placebo group (p < 0.001). Conclusion: In kidney transplant recipients, the addition of 2 µg/day paricalcitol to RAS inhibition lowers IL-6 and TGF-β concentrations, which may be beneficial for reducing graft inflammation and fibrosis.
Correspondence to:
Miha Arnol, MD, PhD
Department of Nephrology
Center for Kidney Transplantation
University Medical Center Ljubljana
Zaloska 7, Ljubljana 1000, Slovenia
Email: [email protected]
Kidney Transplantation
Expanded valganciclovir prophylaxis in kidney transplant recipients is associated with lower incidence of cytomegalovirus infection
Željka Večerić-Haler, Boštjan Bizjak, Karmen Romozi, and Miha Arnol
Page No. 126
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S126-S130)
Expanded valganciclovir prophylaxis in kidney transplant recipients is associated with lower incidence of cytomegalovirus infection
Željka Večerić-Haler1, Boštjan Bizjak1, Karmen Romozi1, and Miha Arnol1#2
1Department of Nephrology, University Medical Center Ljubljana, and 2Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Aims: The aim of this study was to compare the efficacy and safety of two subsequent CMV prophylaxis regimens for prevention of cytomegalovirus (CMV) infection and disease in our kidney transplant recipients (KTRs). Methods: In an historic-cohort of KTRs, two CMV prophylaxis protocols were compared: short protocol in which CMV IgG seronegative recipients (R–) of CMV IgG seropositive donors (D+) received valganciclovir for 3 months post-transplant (group 1: 2005 – 2010); and expanded protocol in which prophylaxis for high-risk recipients was extended to 6 months, and a 3-month prophylaxis for D+/R+ and D–/R+ was introduced (group 2: 2011 – 2016). Incidences of CMV viremia, disease, and adverse events were assessed 12 months after transplant. Results: Of 457 KTRs, 167 received short (group 1) and 290 expanded (group 2) CMV prophylaxis. The incidence of CMV viremia was significantly lower in group 2 than in group 1: 17.6% vs. 29.2%, respectively (p = 0.001). The incidence of CMV disease was 5.2% in group 2 vs. 10.2% in group 1 (p = 0.04). After comparing group 2 and group 1 according to the risk of CMV infection, incidences of CMV viremia were 50% vs. 47.4% in D+/R– (p = 0.79), 3.1% vs. 5.7% in D–/R+ (p = 0.05), and 9.7% vs. 23.6% in D+/R+ (p = 0.0004). The incidence of neutropenia was 41.7% in group 2 and 33.5% in group 1 (p = 0.09). Conclusions: The results show a significant reduction of CMV viremia in D+/R+ and D–/R+ KTRs after introduction of 3-month prophylaxis with valganciclovir. Extension of CMV prophylaxis to 6 months in D+/R– was not associated with reduction in CMV viremia at 12 months after transplant.
Correspondence to:
Željka Večerić-Haler, MD, PhD
University Medical Center Ljubljana
Department of Nephrology
Zaloska 7, Ljubljana 1000, Slovenia
Email: [email protected]
