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
Volume 88 (2017) p. 1 - 6
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
Volume 88 (2017) p. 7 - 9
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]
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
Volume 88 (2017) p. 78 - 82
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
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
Volume 88 (2017) p. 101 - 108
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]
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
Volume 88 (2017) p. 27 - 31
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]
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
Volume 88 (2017) p. 91 - 96
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]
Original
Estimation of glomerular filtration rate based on dry lean body mass in kidney transplant recipients
Špela Borštnar, Jelka Lindič, Luka Ležaič, Aljaž Sočan, Uroš Godnov, and Damjan Kovač
Price
42.00 $
Volume 92 (2019) p. 287 - 292
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
Characteristics of renal sarcoidosis and tubulointerstitial nephritis and uveitis syndrome in Slovenia: An analysis of the national renal biopsy registry and patient datasets in the last decade
Maja Frelih, Nejc Piko, Željka Večerić-Haler, Nika Kojc, and Špela Borštnar
Volume 96 (2021) p. 6 - 15
Abstract
Clinical Nephrology, Vol. 96 – Suppl 1/2021 (S6-S15)
Characteristics of renal sarcoidosis and tubulointerstitial nephritis and uveitis syndrome in Slovenia: An analysis of the national renal biopsy registry and patient datasets in the last decade
Maja Frelih1, Nejc Piko2, Željka Večerić-Haler3,4, Nika Kojc1, and Špela Borštnar3,4
1Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, 2Department of Dialysis, University Medical Center Maribor, Maribor, 3Department of Nephrology, University Medical Center Ljubljana, and 4Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Background: Sarcoidosis is characterized by granulomatous inflammation in multiple organs. Renal involvement is rare, and granulomatous tubulointerstitial nephritis (TIN) is the predominant histologic feature. TIN is also a hallmark of tubulointerstitial nephritis and uveitis (TINU) syndrome. Diagnoses of both sarcoidosis and TINU syndrome are usually made by exclusion and by combining clinical and histological findings, and often remain misdiagnosed. The aim of this retrospective study was to determine the characteristics of renal sarcoidosis and TINU syndrome in Slovenia in the last decade (2010 – 2020). Materials and methods: A thorough search of the national database of renal biopsies from January 2010 to December 2020 was performed. Inclusion criteria were TIN and a clinical history of either sarcoidosis or TINU syndrome. To compare the characteristics of our cohort with others, we also reviewed the global literature reported since 2010. Results: 13 patients (9 female, 4 male) were included in our study. Indications for kidney biopsy were acute kidney injury (n = 8), acute exacerbation of chronic kidney disease (n = 4), and proteinuria (n = 1). Seven patients had clinical and histological evidence of sarcoidosis, and 6 patients were classified as having TINU syndrome. All patients were treated with corticosteroids. Of the 13 patients, 11 had improved kidney function 6 months after treatment, and proteinuria decreased in 9 patients. One patient was on dialysis at the time of diagnosis and remained so thereafter. Conclusion: Renal sarcoidosis and TINU syndrome are rare but important causes of kidney injury, with a favorable long-term prognosis if properly diagnosed and treated in a timely manner.Correspondence to:
Špela Borštnar, MD, Msc, Department of Nephrology, University Medical Centre Ljubljana, Zaloška cesta 2, 1000 Ljubljana, Slovenia
Email: [email protected]
Complement activation and cryoglobulinemia are common in monoclonal gammopathy of renal significance: Data from a case series
Andrej Škoberne, Matevž Škerget, Nika Kojc, Maja Frelih, Andreja Aleš Rigler, Željka Večerić Haler, Špela Borštnar, Nuša Avguštin Rotar, Damjan Kovač, Jelka Lindič, and Samo Zver
Volume 96 (2021) p. 16 - 23
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]
The predictive value of urinary erythrocyte morphology for proliferative glomerular kidney disease
Nuša Avguštin Rotar, Alexander Jerman, Andrej Škoberne, Špela Borštnar, Nika Kojc, and Jelka Lindič
Volume 96 (2021) p. 49 - 55
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]
Supplement
Comparison of Torque teno virus viral load and QuantiFERON Monitor assay and their association with the degree of immunosuppression in kidney transplant patients
Špela Borštnar, Željka Večerić-Haler, Anja Ponikvar Ležaić, Neva Bezeljak, Miha Arnol, Mario Poljak, Maja M. Lunar, and Gregor Mlinšek
Volume 104 (2025) p. 10 - 19
Abstract
Clinical Nephrology, Vol. 104 – Suppl. 1/2025 (S10-S19)
Comparison of Torque teno virus viral load and QuantiFERON Monitor assay and their association with the degree of immunosuppression in kidney transplant patients
Špela Borštnar1,2, Željka Večerić-Haler1,2, Anja Ponikvar Ležaić1, Neva Bezeljak1,2, Miha Arnol1,2, Mario Poljak3, Maja M. Lunar3, and Gregor Mlinšek1,2
1Department of Nephrology, University Medical Center Ljubljana, 2Faculty of Medicine, and 3Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Introduction: Solid organ transplant patients require appropriate immunosuppression to sufficiently control the allorecognition of the graft. Two tests, the QuantiFERON Monitor (QFM) and the Torque teno virus load (TTVL) provide an option to monitor the strength of immunosuppression. Materials and methods: TTVL and QFM were simultaneously determined in kidney transplant patients. Clinical data, microbiological and histopathological findings were collected from the patients’ medical records. Results: 128 TTVL and QFM values were quantified in 107 patients. 69 patients (54%) had recurrent infections in the previous 6 months, 19 (15%) had malignancies, 47 (37%) had a recent kidney biopsy and among them 17 (36%) had histologically proven graft rejection. Results showed that there was no significant correlation between TTVL and QFM (ρ = –0.169, p = 0.061). In patients with histologically proven rejection, TTVL was significantly lower than in patients without rejection (3.64 ± 2.45 vs. 5.02 ± 1.67 log<sub>10</sub> copies/mL, p = 0.026), but there was no difference between the groups in QFM (1.63 ± 0.67 vs. 1.55 ± 0.80 log<sub>10</sub> IU/mL, p = 0.735). Patients with known malignancy had lower TTVL compared to patients without it (p = 0.041). No statistically significant difference was observed in TTVL and patients with or without infections (p = 0.278). QFM was not different in patients with or without infection or malignancy. Conclusion: TTVL as an immune marker was associated with transplant rejection. There were no clinically significant associations between QFM and rejection and TTVL or QFM with infections and malignancies. Further prospective studies should be performed to confirm these results.
Correspondence to:
Gregor Mlinšek, MD, PhD, Department of Nephrology, University Medical Center Ljubljana, Zaloška 7, 1000 Ljubljana, Slovenia
Email: [email protected]
Supplement
Fibrillary glomerulonephritis: A retrospective analysis of a case series from a tertiary center
Ana Dovč, Željka Večerić-Haler, Nika Kojc, Špela Borštnar, Andrej Škoberne, and Andreja Aleš Rigler
Volume 104 (2025) p. 66 - 72
Abstract
Clinical Nephrology, Vol. 104 – Suppl. 1/2025 (S66-S72)
Fibrillary glomerulonephritis: A retrospective analysis of a case series from a tertiary center
Ana Dovč1,2, Željka Večerić-Haler1,2, Nika Kojc3, Špela Borštnar1,2, Andrej Škoberne1,2, and Andreja Aleš Rigler1,2
1Department of Nephrology, Division of Internal Medicine, University Medical Center Ljubljana, 2Faculty of Medicine, and 3Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Introduction: Fibrillary glomerulonephritis is a rare diagnosis, and guidance on diagnosis and management is scant. We present a case series of patients with fibrillary glomerulonephritis from University Medical Center Ljubljana. Materials and methods: We conducted a retrospective analysis of patients with the diagnosis of fibrillary glomerulonephritis since 2006. We analyzed data on clinical presentation, treatment modalities, and kidney survival. For a subset of patients, data on DNAJB9 staining and markers of complement activation were also available. Results: We included 17 patients with fibrillary glomerulonephritis, 59% female, with a median age of 61 years (range 33 – 71). The most common clinical presentation was asymptomatic proteinuria with preserved kidney function (41%). Eight patients had complement activity testing performed, which revealed elevated serum C5b-9 at least at 1 time point in 5 patients (63%). One patient had positive anti-factor H antibodies, and 2 patients had positive anti-C1q antibodies. Nine patients had available staining results for DNAJB9, which was positive in all 9 cases. The median time of follow-up was 12 months. The most common form of treatment was with corticosteroids in 8 patients, followed by rituximab in 5 patients. Seven patients (41%) had at least partial remission with stabilization of kidney function, 8 patients (47%) reached end-stage kidney disease during follow-up. Due to the small number of patients, analysis of impact of treatment on kidney survival was not performed. Conclusion: Fibrillary glomerulonephritis is a heterogenous disease, and a significant number of patients present with a slowly progressive disease, warranting long-term treatment. New treatment strategies are necessary.
Correspondence to:
Ana Dovč, MD, Department of Nephrology, Division of Internal Medicine, University Medical Centre Ljubljana, Zaloška 7, 1000 Ljubljana, Slovenia
Email: [email protected]
Supplement
Clinical profile, treatment response, and outcomes in adult primary focal segmental glomerulosclerosis: A single-center experience
Željka Večerić-Haler, Andreja Aleš Rigler, Andrej Škoberne, Špela Borštnar, Nuša Avguštin Rotar, Damjan Kovač, Ana Dovč, Nika Kojc, and Jelka Lindič
Volume 104 (2025) p. 73 - 84
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]