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.

Background. Chronic kidney disease is a risk factor for cardiovascular diseases. After renal transplant, some traditional and chronic kidney disease-specific risk factors vanish, but new risk factors emerge. This retrospective study aimed to define the long-term impact of renal transplant and diabetes mellitus on arterial stiffness, evaluated by measuring pulse wave velocity (PWV) and augmentation index (AI) and on myocardial perfusion, evaluated by subendocardial viability ratio (SEVR). Methods. PWV, AI, and SEVR were evaluated noninvasively by applanation tonometry using SphygmoCor in the first 4 weeks after kidney transplant and 4 to 5 years thereafter. Results. A total of 48 graft recipients (18 women, 30 men; mean +/- standard deviation age, 47.9 +/- 11.8 years) were included. The follow-up period was 57.4 +/- 8.0 months. PWV did not change significantly during the follow-up period (9.1 +/- 1.8m/s and 8.7 +/- 1.8m/s, respectively; P = .137). In the subgroup of patients without diabetes mellitus, we observed a trend of PWV reduction, whereas in the subgroup of patients with diabetes we observed the trend of PWV increase. The duration of smoking before transplant correlated significantly with PWV (P = .012). AI in the whole group increased significantly during the study period (from 18.3% +/- 10.3% to 25.9% +/- 9.4%; P < .01) as well as SEVR (from 134.9 +/- 23.1 to 155.4 +/- 28.6; P = .001). Conclusions. PWV, reflecting the central vessel stiffness, did not change significantly in the whole group during the follow-up period. The AI, which indicates systemic stiffness, increased significantly within 5 years after transplant, indicating the progression of vascular processes of elastic and muscular arteries. Significant increases in the SEVR values in both diabetics and non-diabetics indicate the long-term favorable effect of kidney transplant on myocardial perfusion.

Background. Pregnancy after kidney transplantation is an uncommon event. In addition to the risk to the child and the mother, pregnancy has a certain risk for the transplanted kidney. Methods. We made a retrospective analysis of pregnancy and kidney function over a 49year period in women with transplanted kidneys monitored at the National Transplant Centre, University Medical Centre Ljubljana, Ljubljana, Slovenia. Results. We analyzed 22 pregnancies in 18 women (26-39 years old) 78 ? 37 months after transplantation. Serum creatinine before conception was 92 ? 26 mmol/L; 3 years after delivery, it was 117 ? 67 mmol/L. There were no rejections during pregnancy. Three rejections occurred in the first 9 months after delivery. The median duration of pregnancies was 37 weeks. Preeclampsia occurred in 4 women and severe eclampsia occurred in 2 women. In 19 cases, delivery was by caesarean section. One child was born with trisomy of chromosome 21 and 3 children were born with minor congenital anomalies. Conclusions. Renal function and proteinuria did not deteriorate 3 years after pregnancy, even after 2 pregnancies. Rejections in the early post-pregnancy period were common. Preeclampsia was more frequent than in the average population. The incidence of major congenital anomalies was comparable to that seen in pregnant women without immunosuppression.

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.

Immunoglobulin A (IgA) nephropathy (IgAN) is the most common glomerulonephritis worldwide, characterized by IgA deposits in the glomerular mesangium. It has a progressive nature and can eventually lead to end-stage kidney failure. It can occur as a potential side effect of treatment with tumor necrosis factor alpha antagonist that has been used for numerous chronic inflammatory conditions, such as Crohn’s disease. In this study, the case of a 33-year-old man with renal dysfunction, nephrotic proteinuria, and erythrocyturia is described. He had had a history of Crohn’s disease for 8 years and had been treated with adalimumab for the past 7 years. The diagnosis of IgAN was confirmed by kidney biopsy. After discontinuance of adalimumab and the induction of corticosteroid therapy, he made a remarkable recovery. Four years after the first presentation of IgAN and discontinuation of adalimumab, his renal function was normal with no proteinuria and only mild erythrocyturia.

Uromodulin and microRNAs (miRNAs) have recently been investigated as potential biomarkers for kidney graft associated pathology and outcome, with a special focus on biomarkers indicating specific disease processes and kidney graft survival. The study's aim was to determine whether expression of serum uromodulin concentration and selected miRNAs might be related to renal function in kidney transplant recipients (KTRs). The uromodulin concentration and expression of six selected miRNAs (miR-29c, miR-126, miR-146a, miR-150, miR-155, and miR-223) were determined in the serum of 100 KTRs with stable graft function and chronic kidney disease of all five stages. Kidney graft function was estimated with routine parameters (creatinine, urea, cystatin C, and Chronic Kidney Disease Epidemiology Collaboration study equations) and precisely measured using chromium-51 labelled ethylenediaminetetraacetic-acid clearance. The selected miRNAs were shown to be independent of kidney graft function, indicating their potential as biomarkers of associated kidney graft disease processes. In contrast, the serum uromodulin level depended entirely on kidney graft function and thus reflected functioning tubules rather than any specific kidney graft injury. However, decreased concentrations of serum uromodulin can be observed in the early course of tubulointerstitial injury, thereby suggesting its useful role as an accurate, noninvasive biomarker of early (subclinical) kidney graft injury.

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.
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Introduction Chronic kidney disease (CKD) is a risk factor for cardiovascular diseases leading to rapid progression of arteriosclerosis. After renal transplantation some of the traditional and CKD-specific risk factors disappear, however, new risk factors emerge, such as metabolic effects of immunosuppression therapy and new onset diabetes mellitus (NODAT). Arterial properties can be evaluated by measuring pulse wave velocity (PWV) and augmentation index (AI). The aim of the study was to define the long-term impact of renal transplantation on arterial stiffness. Another goal of the study was to evaluate effects of diabetes mellitus on PWV and AI. Materials and Methods The study was conducted on renal graft recipients, who had successful kidney transplantation in the years between 2011 and 2013. PWV and AI were evaluated noninvasively by applanation tonometry using SphygmoCor™ (AtCor Medical Pty. Ltd., Sydney, Australia) immediately after transplantation and four to five years thereafter. Clinical and biochemical data were obtained from the hospital's database. Results and Discussion 44 graft recipients (17 women, 27 men, age 49.1±11.5 years) were included in the study. The average follow-up period between the first and the second measurement was 55.7±6.9 months. PWV did not change significantly during the follow-up period (9.1±1.8m/s vs. 8.7±1.8m/s; p=0.137). PWV in the group of non-diabetic patients decreased in the follow-up period by 0.62±1.23 m/s, while it increased for 0.43±2.1m/s in the group of diabetic patients. However, the difference between the two was not significant (p=0.057). At the second measurement the difference in PWV between diabetic and nondiabetic patients was significant (10.2±1.8 vs. 8.3±1.23m/s; p=0.02). Duration of smoking before transplantation correlated significantly with PWV (p=0.012). AI in the whole group increased significantly (from 18.3±10.3% to 25.9±9.4%; p<0.01), whereas a significant difference in AI between diabetic and nondiabetic patients was not found. Conclusion PWV of the whole group did not change significantly during the follow-up period, possibly due to stabilization of the process of arteriosclerosis after renal transplantation. In the subgroup of patients without diabetes we observed a trend of PWV reduction, whereas in the subgroup of patients with diabetes we observed the opposite. Diabetes mellitus and duration of smoking before transplantation are important risk factors for arteriosclerosis progression after renal transplantation.

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.
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INTRODUCTION AND AIMS:Recent studies have shown that exposure to polluted air is remarkably associated with increasing incidence of membranous nephropathy, coronary heart disease and chronic obstructive pulmonary disease.Patients with endstage renal disease (ESRD) are of higher risk of cardiovascular events and mortality than general population.Whether air pollution negatively impacts the prognosis of ESRD patients remains unclear.Therefore, a systematic review was conducted to evaluate the evidences from observational studies to address this issue.METHODS: Observational studies that contained ESRD population and addressed the relation between long-term exposure to air pollutants and mortality were included.CENTRAL, EMBASE, MEDLINE, PUBMED, and WEB OF SCIENCE were searched up to January 2017.Study screening, data extraction and quality assessment (Newcastle-Ottawa Scale) were performed independently by two researchers.RESULTS: The search identified 252 studies and 3 cohort studies were eligible.All of the included studies reached the maximum score of the Newcastle-Ottawa Scale.Due to the clinical heterogeneity of study population and exposure types, quantitative synthesis was inapplicable.One study included 32,239 adult kidney transplant recipients showed that the risk of fatal coronary heart disease (CHD) increased by 34% (relative risk [RR], 1.34; 95% CI, 1.03-1.76)for each 10-ppb increase in ozone after 7-year follow-up.Another study included 160 peritoneal dialysis patients and followed up for 2 years.It showed that exposure to high concentration of environmental nitrogen dioxide (NO 2 ) were associated with higher risk of mortality (hazard ratio [HR], 3.776; 95% CI,).The last study included 256 hemodialysis patients and categorized based on living environments, which found the risk of mortality increased in the high air pollution (particulate matter <2.5 lm [PM2.5] in diameter, carbon monoxide [CO] and NO 2 ) exposure group (HR, 1.762; 95% CI, 1.054-2.947)with a 2 years follow-up.CONCLUSIONS: In the ESRD patients who receiving RRT, long-term exposure to air pollutants is associated with higher risk of mortality.Appropriate precautions may be needed for this subgroup of patients.

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.
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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.
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OBJECTIVESTo 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.METHODSWe 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.RESULTSFrom 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.CONCLUSIONSThe urinary VEGF/creatinine ratio in 24-hour urine seems to independently predict worsening of chronic kidney disease in patients with glomerular diseases.
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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.
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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.
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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.
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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.
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