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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

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]

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]

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]

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 (ePER_biopsy) 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 ePER_biopsy 1,672 vs. 356 vs. 268 mg/day/1.73m²; p < 0.001). Receiver operator characteristics (ROC) analyses demonstrated that ePER_–3m and ePER_biopsy 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]

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]

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]

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]

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]

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]

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]

Abstract

Clinical Nephrology, Vol. 92 – No. 6/2019 (287-292)

Estimation of glomerular filtration rate based on dry lean body mass in kidney transplant recipients 

Špela Borštnar¹#⁴, Jelka Lindič¹, Luka Ležaič², Aljaž Sočan², Uroš Godnov³, and Damjan Kovač¹

¹Department of Nephrology, ²Department of Nuclear Medicine, University Medical Center Ljubljana, Ljubljana, ³Department of Information Science, Faculty of Management, University of Primorska, Koper, and ⁴Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Aim: The use of glomerular filtration rate (GFR) estimating equations is not always reliable, especially in specific populations, such as patients with transplanted kidney. The purpose of this study was to improve the performance of GFR equations by taking into account dry lean body mass.
Materials and methods: A prospective clinical study included 100 patients with kidney graft. Estimated GFR (eGFR) with Chronic Kidney Disease Epidemiology Collaboration equations with serum creatinine concentration (CKD-EPI Cr), serum cystatin C concentration (CKD-EPI CysC), or both (CKD-EPI Cr-CysC) were compared with measured GFR with ⁵¹Cr-EDTA clearance (mGFR ⁵¹Cr-EDTA). Dry lean body mass (body mass without fat mass and water) was measured with bioimpedance analysis.
Results: All of the eGFRs overestimated mGFR ⁵¹Cr-EDTA by a significant degree (shown as bias ± SD in mL/min/1.73m² with 30% accuracy in parentheses): 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 (R = 0.241; p = 0.016) and all biases except the bias of CKD-EPI CysC. Considering the dry lean body mass and preexisting equations with creatinine, we developed two new equations with better performance and statistically insignificant bias: Corrected CKD-EPI Cr –1.43 ± 13.6 (67%) and Corrected CKD-EPI Cr-CysC –1.64 ± 13.4 (77%).
Conclusion: Dry lean body mass improves the performance of GFR equations in our kidney transplant cohort.Correspondence to:
 Špela Borštnar, MD, Msc,
Department of Nephrology
University Medical Center Ljubljana
Zaloška 7, 1000 Ljubljana, Slovenia
Email: spelaborstnar@ hotmail.com

Abstract

Clinical Nephrology, Vol. 96 – Suppl. 1/2021 (S16-S23)

Complement activation and cryoglobulinemia are common in monoclonal gammopathy of renal significance: Data from a case series

Andrej Škoberne¹,³, Matevž Škerget²,³, Nika Kojc⁴, Maja Frelih⁴, Andreja Aleš Rigler¹,³, Željka Večerić Haler¹,³, Špela Borštnar¹,³, Nuša Avguštin Rotar¹,³, Damjan Kovač¹,³, Jelka Lindič¹,³, and Samo Zver²,³

¹Department of Nephrology, ²Department of Hematology, University Medical Center Ljubljana, ³Faculty of Medicine, and ⁴Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Introduction: Monoclonal gammopathy of renal significance (MGRS) denotes kidney diseases caused by monoclonal immunoglobulins in patients who do not have an overt hematological malignancy. Treatment is primarily directed against the underlying clone. Complement activation and cryoglobulinemia are known factors that can contribute to tissue damage, however, the full extent of their involvement is not clear. Materials and methods: This was a retrospective study including all patients with MGRS referred for consultation to our hospital over a 3-year period. Results: We identified 17 patients, of which 12 had proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID). Treatment with anti-clonal or immunosuppressive therapy was successful in 60% of patients with PGNMID, and treatment success was more common in patients with λ chain (100%) compared to κ chain deposits (20%). Serum markers of complement involvement were identified in 41% of all patients (88% of tested samples), most commonly high serum C5b-9 values or anti-factor H autoantibodies (both 24%). Patients with complement involvement did not respond well to treatment, which was unsuccessful in all treated patients with anti-factor H autoantibodies and 75% of patients with high serum C5b-9 values. Cryoglobulinemia was identified in 29% of all patients (71% tested samples) and was monoclonal in 40% of positive cases and mixed in 60%. None of the patients with cryoglobulinemia had organized deposits, however, there was a trend toward more common intramembranous deposits. In patients with monoclonal cryoglobulinemia both anti-clonal and immunosuppressive treatment were unsuccessful. All patients with mixed cryoglobulinemia were treated successfully with immunosuppressive therapy. Conclusion: Treatment of patients with PGNMID was successful in most cases. Complement involvement as well as monoclonal and mixed cryoglobulinemia were relatively common in our cohort, with the first two generally associated with unsuccessful treatment and the latter with successful treatment.Correspondence to:
Andrej Škoberne, MD, PhD, Department of Nephrology, University Medical Centre Ljubljana, Zaloška cesta 7, 1000 Ljubljana, Slovenia
Email: [email protected]

Abstract

Clinical Nephrology, Vol. 96 – Suppl. 1/2021 (S24-S30)

Histomorphological and clinical characteristics of patients with thin glomerular basement membrane nephropathy

Aleksandra Pečovnik¹, Željka Večerić Haler²,³, Karmen Wechtersbach⁴, Jerica Pleško⁴, Maja Frelih⁴, Jelka Lindič²,³, and Nika Kojc⁴

¹Department of Pathology and Cytology, General Hospital Celje, Celje, ²Clinical Department of Nephrology, University Clinical Center Ljubljana, ³Faculty of Medicine, and ⁴Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Background: Thin basement membrane nephropathy (TBMN) is a disorder characterized by ultrastructural abnormalities of the glomerular basement membrane (GBM), representing a spectrum of genetic and clinical phenotypes ranging from benign hematuria to proteinuria and chronic kidney disease. Recent studies have shown that a significant percentage of patients who initially present with hematuria later develop proteinuria and worsening renal function. Materials and methods: We retrospectively analyzed records of patients diagnosed with TBMN, including their clinical, laboratory, and histological features, in Slovenia from 2015 to 2020. Results: TBMN was the main diagnosis at kidney biopsy in 34 (65%) of 52 included patients, while in 18 patients (35%) TBMN was diagnosed in addition to other renal diseases. In the isolated TBMN group, 29 of 34 patients had glomerulosclerosis (global, global and segmental, segmental only) accompanied by interstitial fibrosis/tubular atrophy of varying degrees. 13 patients with isolated TBMN had signs of advanced chronic kidney disease at the time of diagnosis, with estimated glomerular filtration rate < 60 mL/min/1.73m2. 29 patients had proteinuria, which exceeded 3 g/day in 4 patients. TBMN represents a proportion of patients with focal segmental glomerulosclerosis (FSGS) that have often been classified in the past as etiologically indeterminate FSGS. Conclusion: Ultrastructural examination showing diffuse thinning of the GBM is crucial for the TBMN diagnosis. TBMN was the main diagnosis of kidney biopsy in 2/3 of our patients, while it was accompanied by other renal diseases in 1/3. Up to 1/3 of patients with isolated TBMN had evidence of advanced chronic kidney disease at the time of diagnosis.Correspondence to:
Nika Kojc, MD, PhD, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia
Email: [email protected]

Abstract

Clinical Nephrology, Vol. 96 – Suppl. 1/2021 (S49-S55)

The predictive value of urinary erythrocyte morphology for proliferative glomerular kidney disease

Nuša Avguštin Rotar¹,³, Alexander Jerman¹,³, Andrej Škoberne¹,³, Špela Borštnar¹,³, Nika Kojc¹,²,³, and Jelka Lindič¹,³

¹Department of Nephrology, University Medical Center Ljubljana, ²Institute of Pathology, Faculty of Medicine, and ³Medical Faculty, University of Ljubljana, Ljubljana, Slovenia
Background and aim: Glomerular erythrocyturia (GlomEry) is usually associated with proliferative kidney diseases. In our retrospective cohort, we aimed to validate the predictive value of GlomEry criteria ≥ 40% dysmorphic erythrocytes (DysEry) or ≥ 5% acanthocytes (AcaEry) or at least 1 erythrocytic cast (CastEry) and of two new indices – the count of DysEry per high power field (HPF) and per microliter of urine (Stansfeld-Webb (SW)) method, for proliferative disease. Materials and methods: We included patients with erythrocyturia from 2015 to 2016. Based on renal histology, we divided them into a proliferative and a non-proliferative disease group. Urine erythrocyte count was done using SW and urinary sediment examination was carried out by skilled nephrologists. Sensitivity, specificity, and cutoff values were determined using ROC curves. Results: We included 90 patients (33% women), median age of 63 (IQR 51, 71) years. In the proliferative group, proteinuria was lower (2.4 vs. 6.6 g/day), and SW erythrocyturia was higher (174 (IQR 60, 353) vs. 44 (IQR 20, 67) × 106/L) than in the non-proliferative group. The threshold to differentiate between the proliferative and non-proliferative group was determined at ˃ 43% of DysEry (sensitivity 73%, specificity 79%, AUC 0.808) and at ˃ 2% AcaEry (sensitivity 71%, specificity 56%, AUC 0.647). No significant difference in CastEry was found between groups. Among tested parameters, the calculated number of DysEry/HPF > 6.7 (sensitivity 77%, specificity 92%, AUC 0.878), followed by DysEry/SW > 28 × 106/L (sensitivity 76%, specificity 86%, AUC 0.879), discriminated those two groups best. Conclusion: In concordance with known GlomEry criteria, > 43% of DysEry predicted proliferative kidney disease, whereas CastEry did not, and AcaEry predicted poorly. The best predictor of proliferative glomerular disease was DysEry/HPF, closely followed by DysEry/SW.Correspondence to:
Nuša Avguštin Rotar MD, Department of Nephrology, University Medical Center Ljubljana, Zaloška cesta 7, 1000 Ljubljana, Slovenia
Email: [email protected]

Abstract

Clinical Nephrology, Vol. 96 – Suppl. 1/2021 (S127-S132)

Glomerular and tubulointerstitial foscarnet nephropathy of kidney allograft with emphasis on ultrastructural findings: A case report

Jerica Pleško¹, Damjan Kovač²,³, Zoran Arsov⁴, Jelka Lindič²,³, Andrej Škoberne²,³, Dušan Ferluga¹, and Nika Kojc¹

¹Institute of Pathology, Faculty of Medicine, University of Ljubljana, ²Department of Nephrology, University Medical Center Ljubljana, ³Faculty of Medicine, University of Ljubljana, and ⁴Department of Condensed Matter Physics, Jozef Stefan Institute, Ljubljana, Slovenia
Introduction: Foscarnet (trisodium phosphonoformate hexahydrate) is standard treatment for ganciclovir-resistant cytomegalovirus (CMV) infections. In the kidney, foscarnet-induced injury may be attributed to reversible tubulointerstitial lesions, but foscarnet crystals have also been observed within glomerular capillaries, suggesting that foscarnet can lead to glomerular lesions such as crescentic glomerulonephritis. We present biopsy and autopsy findings of foscarnet induced nephropathy in a transplanted kidney, with a particular emphasis on the histopathology and electron micrographic peculiarities of drug crystal deposits. Case presentation: A 72-year-old Caucasian male patient with a deceased donor kidney was treated with several foscarnet applications due to ganciclovir-resistant CMV infection. Transplant kidney biopsy revealed massive glomerular crystalline precipitates, resulting in crescentic glomerulonephritis and tubular damage. The last foscarnet application was complicated with several infections and kidney graft failure. Autopsy revealed multi-organ damage due to foscarnet crystal precipitations associated with systemic CMV and fungal infection. On autopsy of kidney specimens, we succeeded in preserving the rectangular flat plate-like foscarnet crystals in stacks detected by transmission electron microscopy (TEM) after 100% alcohol fixation. The chemical composition of the crystals was confirmed by attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. Conclusion: Transplant kidney biopsy remains the gold standard in distinguishing between foscarnet crystalline glomerular and/or tubulointerstitial lesions, and various forms of rejection and other causes of impaired renal function in transplant kidney.Correspondence to:
Nika Kojc, MD, PhD, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia
Email: [email protected]

Abstract

Clinical Nephrology, Vol. 104 – Suppl. 1/2025 (S35-S40)

Impact of dietary counseling on Mediterranean diet principles on dietary fiber intake and serum uremic toxins in patients treated with peritoneal dialysis: A pilot study

Kaja Pajk¹, Nina Bremec¹, Aljoša Kuzmanovski², Jelka Lindič³,⁴, Jernej Pajek³,⁴ and Bojan Knap³,⁴

¹Department for food science, Biotechnical Faculty, University of Ljubljana, ²Dietetics and Nutrition Service, ³Department of Nephrology, University Medical Center Ljubljana, and ⁴Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Introduction: The Mediterranean diet (MD) offers numerous health benefits, including improvements in cardiovascular health, cognitive function, and reduced inflammation. Its role in patients with chronic kidney disease (CKD), particularly those undergoing peritoneal dialysis (PD), remains understudied, but attractive. This study evaluated achieved adherence to the MD, impact on dietary fiber intake, and serum uremic toxins in PD patients. Materials and methods: An interventional randomized pilot study was conducted on 21 PD patients, randomized into intervention (MD diet counseling) and control groups (standard diet). Dietary intake, fiber consumption, serum potassium, phosphate and serum uremic toxins (trimethylamine-N-oxide (TMAO), p-cresyl sulfate (pCS), and indoxyl sulfate (IS)) were measured before and after a 4-week intervention. Dietary adherence was assessed using the Mediterranean Diet Adherence Screener (MEDAS). Statistical analyses compared the changes between groups. Results: Adherence to the principles of MD significantly improved in the intervention group (MEDAS: 6.6 ± 1.0 to 8.8 ± 1.2, p < 0.001). Dietary fiber intake increased modestly but not significantly (16.7 ± 6.7 g/day to 19.8 ± 7.5 g/day, p = 0.374). Serum levels of uremic toxins showed no significant change, while potassium and phosphate levels remained stable. Conclusion: The MD counseling improved dietary adherence to the goals of MD without negatively affecting serum electrolyte and phosphate control in PD patients. No significant changes were observed in serum uremic toxin levels or dietary fiber intake. Correspondence to:
Assoc. Prof. Bojan Knap, MD, PhD, Department of Nephrology, University Medical Center Ljubljana, Zaloška 7, 1000 Ljubljana, Slovenia
Email: [email protected]

Abstract

Clinical Nephrology, Vol. 104 – Suppl. 1/2025 (S73-S84)

Clinical profile, treatment response, and outcomes in adult primary focal segmental glomerulosclerosis: A single-center experience 

Željka Večerić-Haler¹,², Andreja Aleš Rigler¹,², Andrej Škoberne¹,², Špela Borštnar¹,², Nuša Avguštin Rotar¹,², Damjan Kovač¹,², Ana Dovč¹,², Nika Kojc³, and Jelka Lindič¹,²

¹Department of Nephrology, University Medical Center Ljubljana, ²Department of Internal Medicine, Faculty of Medicine, and ³Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Objective: Primary focal segmental glomerulosclerosis (FSGS) is a major cause of nephrotic syndrome in adults. This study evaluates the clinical profile, treatment response, and outcomes of patients with primary FSGS at the University Medical Centre (UMC) Ljubljana, Slovenia. Materials and methods: Patients diagnosed and treated at UMC Ljubljana from 2008 to 2024 were included. Clinical, laboratory, histological, and treatment data were analyzed. Results: 56 patients were followed for a median of 71 months (range: 2 – 186). At diagnosis, 91.1% had nephrotic syndrome, with proteinuria of 10.2 ± 9.8 g/day, serum albumin of 23.7 ± 6.5 g/L, and estimated glomerular filtration (eGFR) of 66.7 ± 27.7 mL/min/1.73m². Histological subtypes included tip (37.5%), cellular (25%), collapsing (14.3%), not-otherwise specified (16.1%), while in 7.1% the variant was not defined. First-line therapy, mainly corticosteroids, led to remission in 67.3%, but 71% experienced relapses or steroid resistance. Calcineurin inhibitors (CNIs) and corticosteroids were used in 20 patients, achieving 60% remission, however the majority of patients experienced relaps following their discontinuation. Rituximab was given to 23 patients with refractory disease, with 78.2% achieving remission (56.5% complete, 21.7% partial) in 5.1 ± 4.9 months. Among initial rituximab responders, 30.4% experienced relapse. At the last follow-up, mean eGFR was 59.6 ± 33.2 mL/min/1.73m², 21.4% progressed to end-stage renal disease (ESRD), and 5.3% died. Four patients underwent kidney transplantation, with early recurrence in 3. Conclusion: Despite high steroid resistance, use of CNIs and rituximab improved remission rates. However, ESRD remains a significant concern, highlighting the need for early intervention and optimized treatment strategies. Correspondence to:
Željka Večerić-Haler, MD, PhD, Department of Nephrology, University Medical Center Ljubljana, Zaloška 7, 1000 Ljubljana, Slovenia
Email: [email protected]

Abstract

Clinical Nephrology, Vol. 104 – Suppl. 1/2025 (S123-S129)

Central obesity – the most common nutritional disorder in non-frail patients with chronic kidney disease

Aljoša Kuzmanovski¹, Bojan Knap²,³, Mojca Poljanec⁴, Tjaša Bonča⁴, Gašper Poljšak⁴, and Jelka Lindič²,³

¹Dietetics and Nutrition Service, ²Department of Nephrology, Division of Internal Medicine, University Medical Center Ljubljana, ³Faculty of Medicine, and ⁴Biotechnical Faculty, University of Ljubljana, Slovenia
Introduction: Patients with chronic kidney disease (CKD) often experience various nutritional disorders, leading to increased frailty, morbidity, and mortality. The aim of our study was to explore the impact of dietary habits and physical activity on body composition in non-dialysis CKD patients. Materials and methods: This cross-sectional study included 199 non-frail CKD patients (stages 1 – 5) from the University Medical Center Ljubljana. Participants completed a food frequency questionnaire, and anthropometric measurements were collected. Body composition was assessed using bioelectrical impedance analysis (BIA), and muscle strength was evaluated with handgrip dynamometry. Results: Central obesity was present in 79.9% of participants, and obesity based on body mass index (BMI) was found in 26.6%. Elevated fat mass was observed in 58.3% of patients. Sarcopenia was identified in 1%, and sarcopenic obesity in 0.5%. Based on the Global Leadership Initiative on Malnutrition (GLIM) criteria, 11.6% of patients were malnourished. Dietary analysis revealed too frequent intake of refined carbohydrates, red meat, and sweets, while intake of fruits and vegetables was not often enough. Dietary habits were suboptimal, with no significant differences between individuals with normal waist circumference and BMI and those with central obesity and elevated BMI. However, a significant difference was observed in physical activity, with those having central obesity engaging in less physical activity. Conclusion: Central obesity was the most prevalent nutritional disorder in non-frail CKD patients that was markedly more prevalent than obesity defined by BMI. Waist circumference was a more sensitive marker of increased fat mass determined with BIA than BMI. Inadequate dietary habits and insufficient physical activity were major contributing factors to the observed nutritional disorders in our CKD patients and call for long-term lifestyle modifications. Correspondence to:
Aljoša Kuzmanovski, MSc. in Nutrition, Dietetics and Nutrition Service, University Medical Center Ljubljana, Zaloška 7, Ljubljana, Slovenia
Email: [email protected]

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