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Introduction Normal saline (N/S) and Ringer’s-Lactate (L/R), are administered in everyday clinical practice. Despite that, N/S increases the risk of sodium overload and hyperchloremic metabolic acidosis. In contrast, L/R has lower sodium content, significantly less chloride and contains lactates. In this study we compare the efficacy of L/R versus N/S administration in patients with prerenal acute kidney injury (AKI) and pre-established chronic kidney disease (CKD). Methods In this prospective open-label study we included patients with prerenal AKI and previously known CKD stage III-V without need for dialysis. Patients with other forms of AKI, hypervolemia or hyperkalemia were excluded. Patients received either N/S or L/R intravenously at a dose of 20 ml/kg body-weight/day. We studied kidney function at discharge and at 30 days, duration of hospitalization, acid-base balance and the need for dialysis. Results We studied 38 patients and 20 were treated with N/S. Kidney function improvement during hospitalization and at 30 days after discharge, was similar between the two groups. Duration of hospitalization was also similar. Anion-gap improvement as expressed with Δanion-gap between discharge and admission day was higher in those patients that received L/R in comparison to those that received N/S and pH increase (ΔpH) was slightly higher in the L/R group. No patient required dialysis. Conclusions Administration of L/R or N/S to patients with prerenal AKI and pre-established CKD had no significant difference in short or long term kidney function but L/R showed a better profile in acid-base balance improvement and Cl− overload in comparison to N/S.

PURPOSE To retrospectively assess the safety and efficacy of percutaneous arteriovenous fistula (pAVF) creation with the WavelinQ 4-F EndoAVF System. MATERIALS AND METHODS From February 2018 to June 2020, 30 pAVFs were created in 30 consecutive patients (men; age, 55.3 years ± 13.6). Of the 30 patients, 21 (70%) were already on hemodialysis using a central venous catheter. The primary outcome measures were technical success, complications, and cannulation rate. The secondary outcome measures included the number of secondary procedures needed for cannulation, maintenance time to cannulation, and pAVF survival. RESULTS Technical success was 100%. The adverse event rate was 6.7% (2/30), including a pseudoaneurysm of the brachial artery that developed immediately after sheath removal and an aneurysm of the anastomosis 17 days after the procedure, which was treated with a covered stent placed in the arterial side. The mean follow-up was 547 days ± 315.7 (range, 14-1,071 days). The cannulation rate was 86.7% (26/30). The mean time to cannulation was 61.3 days ± 32.5 (range, 15-135 days). The mean follow-up after cannulation was 566.2 days ± 252.7 (range, 35-1,041 days). Four pAVFs were thrombosed after cannulation, with 2 of them successfully declotted. Sixteen interventions were needed to achieve cannulation after the index procedure in 15 patients (overall, 0.53 procedures/patient). Seven maintenance endovascular interventions (following cannulation) were performed during the follow-up period in 6 patients (overall, 0.27 procedures/patient, 0.17 procedures/patient-years). For the pAVFs that were cannulated, patency was 96% at 1 year, and 82% at 2 and 3 years, according to the Kaplan-Meier survival analysis. CONCLUSIONS This initial experience suggests that pAVF creation is safe and can be successfully performed with high maturation and long-term patency rates. Larger-scale prospective studies are needed to validate the results.

Medical societies have a social responsibility to disseminate knowledge and inform health authorities on threats to public health posed by various diseases. Advocacy for health protection programmes and for medical research funding is now embedded into the missions of most scientific societies. To promote kidney research funding in Europe, the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA), rather than acting as an individual society advocating for the fight against kidney disease, has actively helped to create an alliance of national associations centred on kidney diseases, the European Kidney Health Alliance (EKHA), and joined the Biomedical Alliance (BMA). The ERA-EDTA is fully committed to supporting its working groups (WGs) and consortia of its members to allow them to produce valuable kidney research. The framing and formalization of projects, and the regulatory issues related to submission to the European Commission, are complex. To help WGs to gain expert advice from agencies with specific know-how, the ERA-EDTA has adopted a competitive approach. The best research projects proposed by WGs and consortia of other European investigators will receive seed funding to cover the costs of consultancy by expert agencies. Via its broader platforms, the EKHA and the BMA, the ERA-EDTA will strive towards broader recognition of kidney disease and related clusters of non-communicable diseases, by European and national agencies, as major threats to the qualities of life of their populations and their economies.

In the last decades several important advances have taken place in the understanding of the pathogenesis underlying membranous nephropathy, which have sparked renewed interest in its management. Four landmark trials in membranous nephropathy, and a fifth clinical trial-which was a pilot study-, have been published in the last years. The results from some of these trials have had a significant impact in the recommendations included in the 2021 Kidney Disease: Improving Global Outcomes (KDIGO) Guideline for the Management of Glomerular Diseases, which represent a significant step forward compared to the previous guideline in several aspects such as diagnosis, disease monitoring and treatment strategies. However, considering the rapidly evolving advances in the knowledge of membranous nephropathy and the recent publication of the STARMEN and RI-CYCLO trials, several recommendations contained in the guideline warrant updates. This manuscript provides a perspective of the Immunonephrology Working Group of the European Renal Association (ERA) regarding the management of membranous nephropathy in native kidneys of adult patients.

The traditional chronic kidney disease (CKD) biomarkers (eGFR based on serum creatinine, sex and age and albuminuria) cannot predict a patient’s individual risk for developing progressive CKD. For this reason, it is necessary to identify novel CKD biomarkers that will be able to predict which patients are prone to develop progressive disease and discriminate between disease processes in different parts of the nephron (glomeruli or tubules). A good biomarker should change before or simultaneously with lesion development and its changes should correlate strongly with lesion development. Also, there should be a close relationship between severity of injury and amount of detectable biomarker and its levels should decrease with diminishing injury. Among the large number of molecules under investigation, we have reviewed the most promising ones: NGAL and KIM-1, MCP-1, MMP-9, clusterin, MMP-9, TIMP-1, Procollagen I alpha 1 and suPAR. All these, have been studied as biomarkers for prediction of CKD progression in cohorts of patients with chronic kidney disease of different stages and various aetiologies (proteinuric and non-proteinuric, glomerulonephritides, diabetic, hypertensive and polycystic kidney disease). There is evidence that these molecules could be useful as biomarkers for progressive chronic kidney disease, however, the available data are not enough to draw final conclusions. Further studies with large cohorts and long follow-up are required to identify appropriate biomarkers, that will be able to accurately and reliably define the risk for progressive chronic kidney disease.

Coronavirus disease 2019 (COVID-19) vaccine platforms are becoming available and are the most promising strategy to curb the spread of severe acute respiratory syndrome coronavirus 2 infections. However, numerous uncertainties exist regarding the pros and cons of vaccination, especially in patients with (immune-mediated) kidney diseases on immunosuppressive drugs. Here, members of the Immunonephrology Working Group of the European Renal Association–European Dialysis and Transplant Association discuss 13 frequently asked questions regarding the safety and efficacy of the most promising vaccine candidates. Post-marketing surveillance should be performed to estimate the rate of vaccine response (humoral and cellular) of different vaccine platforms and disease activity following the administration of COVID-19 vaccines. Some of the candidates induce signalling pathways, which also promote autoimmune kidney diseases, e.g. type I interferons in systemic lupus erythematosus. Efficacy estimates would thus far favour the use of selected COVID-19 vaccines, such as BNT162b2, mRNA-1273 or Gam-COVID-Vac. Humoral immune response after vaccination should be monitored using appropriate assays. Even in the absence of neutralizing antibodies, patients might be protected by a sufficient cellular immune response capable of reducing the severity of COVID-19. A reduced vaccine response after the use of CD20-depleting agents is anticipated and it is particularly important to discuss strategies to improve vaccine response with these patients. Distancing and shielding measures remain important, as not all vaccines fully protect from coronavirus infection. In-depth information about the most pressing vaccine questions is essential to reduce vaccine hesitancy of patients.

Objectives The appearance of new onset diabetes is common after kidney transplant. Treatment options are limited because of renal function-related contraindications, interactions with immunosuppressive drugs, and side effects. We investigated the long-term safety and efficacy of dipeptidyl peptidase IV inhibitors in renal transplant recipients with new onset diabetes. Materials and methods We treated 12 patients with dipeptidyl peptidase IV inhibitors, and 5 patients received insulin monotherapy as initial treatment of new onset diabetes after kidney transplant. All patients were followed for 12 months after diagnosis. Glycosylated hemoglobin A1c, estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration equation), plasma immunosuppressive trough levels, serum lipids, blood pressure, and body weight were measured during outpatient visits. Effects of dipeptidyl peptidase IV inhibitors and insulin on the aforementioned parameters were measured to compare values at time of diagnosis versus mean values of the last 6 months of follow-up. Results Patients were treated with linagliptin (4 patients), sitagliptin (4 patients), vildagliptin (2 patients), and alogliptin (2 patients). Patients had a mean age of 59.4 ± 12 years and a mean glycosylated hemoglobin A1c of 6.6% at diagnosis, which was decreased to 6.1% (P = .03) at 1 year of follow-up. Renal function remained stable, and plasma tacrolimus levels did not appear to be affected. No significant differences were shown in serum total, low-density lipoprotein, and high-density lipoprotein cholesterol levels aftertreatment. Nevertheless,triglyceride levels were significantly reduced (from 214.4 to 174.9 mg/dL; P = .0039). A decrease in body weight was also observed. Finally, patients treated with dipeptidyl peptidase V inhibitors achieved better glycosylated hemoglobin A1c levels than those treated with insulin. Conclusions Dipeptidyl peptidase IV inhibitors appear to be a safe, effective, and hypoglycemia-free option fortreatment of new onset diabetes in renaltransplant recipients and possibly provide better diabetes control than insulin therapy.

Background and Aims Following kidney transplantation despite improvement of kidney function, calcium and phosphate turnover and vitamin D metabolism, the risk of fractures is high. Moreover, most kidney transplant recipients (KTRs) have preexisting CKD mineral bone disease and osteopenia or osteoporosis are prevalent complications aggravated by immunosuppressive therapy, especially glucocorticoids and cyclosporine, which negatively affect KTRs risk of fractures and mortality. Treatment with bisphosphonates has been suggested to improve bone mineral density (BMD) in KTRs, nevertheless the evidence of such a therapeutic approach are scarce. The aim of this study is to evaluate the effectiveness of bisphosphonates treatment in post kidney transplantation BMD. Method We conducted a single center retrospective analysis on the effect of bisphosphonate treatment on bone mineral density in patients after kidney transplantation. Patients eligible for entering the study were adult (>18 years) KTRs with two valid BMD measurements either by hip or spine dual energy X-ray (DEXA). The primary BMD measurement was performed before the initiation of bisphosphonate treatment. We also evaluated the BMD course in KTRs who had two valid measurements after operation but received no treatment (control group). Patients that received other forms or treatment (calcitriol or vitamin D analogs) were excluded from the study. BMD was evaluated using the average t-score at the examined site of interest. Kidney function was evaluated with eGFR, using the CKD-EPI formula. Results Overall, out of 185 KTRs actively monitored, 26 met the aforementioned criteria and were included in the study. Bisphosphonate treatment was administered in 16 patients (10 men) with a mean age of 53.4±10.2 years while 10 patients (6 men) received no treatment (mean age 45.2±14.3 years, p=ns). There were no differences in baseline kidney function (eGFR), BMD, body mass index, or other baseline clinical characteristics between those patients that received treatment and the control group. Treatment was initiated 1.1±2.4 years after kidney transplantation, while in 9 patients was initiated in the early post transplant period (one month after operation) and overall it was administered for a period of 3.9±2.3 years. Bisphosphonates were administered in all patients as per os treatment (10 patients received risedronate sodium, 4 ibandronic acid and 2 alendronate sodium). Bone density was improved significantly in all but 2 patients that received treatment (BMD from -1.91±1.3 to -1.3±1.4, p=0.0114). Those that received no treatment showed an overall minor non significant bone density improvement (BMD from -1.53±1.2 to -1.3±0.8, p=ns) after 4.2±1.4 years of follow up. ΔBMD was also found higher in treated patients (0.66±0.86 vs. 0.23±0.85, p=ns). Kidney function was not affected by treatment (eGFR before vs. after treatment, 65.3±14.4 vs. 65.5±15.2 ml/min/1.73 m2, p=ns, respectively) and remained unchanged in those that received no treatment as well. Conclusion Treatment with bisphosphonates is a safe and effective treatment option that significantly improves BMD after kidney transplantation.

Aims Diagnosis of primary membranous nephropathy (PMN) is mainly based on immunofluorescence/immunohistochemistry findings. However, assessment of specific features on optical microscopy can help to estimate the severity of the disease, guide treatment and predict the response. The aim of this study was to identify, classify and grade the precise histological findings in PMN to predict renal function outcome and guide treatment. Methods and results Histological parameters, including focal segmental sclerosis (FSGS), tubular atrophy (TA), interstitial fibrosis (IF) and vascular hyalinosis (VH), were re‐evaluated in 752 patients with PMN. Their predictive value was estimated separately, and also in a combination score (FSTIV) graded from 0 to 4. Finally, the impact of histology was assessed in the response to immunosuppressive treatment. Mean age of patients was 53.3 (15–85) years and most presented with nephrotic syndrome. FSGS was present in 32% and VH in 51% of the patients, while TA and IF were graded as stage ≥1 in 52% and 51.4%, respectively. The follow‐up period was 122.3 (112–376) months. FSGS, TA and IF and VH were associated with impaired renal function at diagnosis (P = 0.02, P 50% eGFR reduction, FSGS (P = 0.001) and TA (P = 0.02). Also, patients presented with FSGS, IF, VH and/or with FSTIV > 1 could benefit from immunosuppression, regardless of clinical presentation. Conclusions The presence and degree of four histological indices, FSGS, VH, TA and IF, assessed separately or in combination, and FSTIV score not only predict renal function outcome after long‐term follow‐up, but can also help in the choice of appropriate treatment. Decisions concerning immunosuppressive treatment can be guided by pathology regardless of clinical findings.

Introduction . Circulating autoantibodies against phospholipase A2 receptor (anti-PLA2R) are recognized as key elements in the pathogenesis of idiopathic membranous nephropathy. In current clinical practice, they are increasingly gaining attention as novel tools for diagnosis and disease monitoring. We investigated the diagnostic and prognostic utility of anti-PLA2R antibody measurements in Greek patients with biopsy-proven membranous nephropathy. Methods . Anti-PLA2R levels were measured in serum samples from 33 patients at diagnosis using ELISA and were associated with treatment outcome. Moreover, serial anti-PLA2R measurements were performed in 15 patients under different clinical conditions and level alterations were correlated with disease activity. Results . Positive anti-PLA2R antibodies at diagnosis were found in 16 of 33 patients (48.5%). Anti-PLA2R levels were independently associated with the achievement of complete remission of nephrotic syndrome after immunosuppressive treatment compared to partial remission (p = 0.02, R2 = 0.265, 95%CI -0.019 to -0.0003). Higher detectable antibody levels at diagnosis were correlated with higher proteinuria levels (r = 0.813, p = 0.0001, 95%CI 0.532 to 0.933) and lower eGFR at the end of follow-up (r = -0.634, p = 0.0083, 95%CI -0.86 to -0.202). Serial antibody measurements during follow-up showed that anti-PLA2R titers were significantly reduced at the end of treatment after complete remission was achieved, remained low under sustained clinical remission, and increased during relapse. Conclusions . Our findings confirm the usefulness of anti-PLA2R measurements in the diagnosis of idiopathic membranous nephropathy. Low levels of anti-PLA2R antibodies at diagnosis are predictive of complete remission of nephrotic syndrome following immunosuppressive treatment. Serial anti-PLA2R measurements correlate well with clinical status throughout the follow-up period and could be used routinely for monitoring of disease activity and treatment planning.

Dyslipidemia is common in kidney transplant recipients owing to the disturbance of lipid metabolism caused by chronic kidney disease and the effect of immunosuppression on lipid metabolism. Patients receiving treatment with mammalian target of rapamycin inhibitors show more prominent lipid disorders, which are attributed mainly, but not only, to adipocyte lipid uptake disruption, lipolysis promotion and lipogenic gene expression enhancement. Dyslipidemias in kidney transplant recipients predispose these patients to an increased risk of developing cardiovascular disease; thus, current guidelines recommend treatment initiation with a statin, regardless of low-density lipoprotein cholesterol (LDL-C) concentration, with ezetimibe as a secondary option for patients who do not tolerate such therapy or for those with inadequate response. Treatment with pro-protein convertase subtilisin/kexin type 9 inhibitors such as alirocumab, although effectively reducing LDL-C in patients with chronic kidney disease, has not been evaluated in kidney transplant recipients. In this case report, we present a case of a female kidney transplant recipient who developed substantial dyslipidemia after everolimus initiation. This case was resistant to treatment with simvastatin/ezetimibe combination, and the patient subsequently received alirocumab. Our patient showed a mean reduction of 46.6% in LDL-C during an 18-month period after alirocumab initiation, which is comparable to the results of studies on patients with or without renal impairment. Furthermore, treatment with alirocumab proved to be well tolerated without adverse effects or interactions with the immunosuppression regimen.

Lupus nephritis in the context of Systemic Lupus Erythematosus (SLE) is characterized by an unpredicted course with remissions and flare-ups. Among others, it remains a significant cause of end-stage kidney disease (ESKD) in relatively young patients. Therapeutic regimens with newer immunosuppressive agents have been introduced in order to control SLE clinical manifestations more efficiently and limit organ damage induced by immune complex formation and sustained inflammation. Treatment is usually long-term, and the cumulative impact of immunosuppression is expressed through the increased frequency of infections and neoplasms. However, if the observed immunity dysregulation is secondary and pharmaceutically induced or there is a pre-existing, primary immunodeficiency that shares common pathogenetic pathways with SLE's autoimmunity is not always clear. Herein, we present the case of a 39-year-old woman, that reached ESKD due to lupus nephritis. After an upper respiratory cytomegalovirus (CMV) infection and concomitant CMV reactivations the investigation revealed significant immunodeficiency. Not long after the initiation of intravenous immunoglobulin (IVIG) administration, patient received a cadaveric kidney transplant. IVIG was continued along with standard immunosuppression so that both recurrent infections and allograft rejection are avoided. Patient is closely monitored, and her post-transplant course is remarkably satisfying so far. ESKD patients with immunodeficiency syndromes should not be excluded by definition from kidney transplantation.

Background: Patients with refractory to optimal pharmacological treatment heart failure (HF) require frequent hospitalization. Peritoneal dialysis (PD) has been part of the management of such patients mainly for promoting ultrafiltration and management of overhydration independently of kidney function. The aim of this study was to evaluate the efficacy of PD, especially the use of icodextrin solutions and intermittent PD, in the hospitalization rate and cardiac functional status of patients with HF. Methods: We conducted a retrospective study involving patients with New York Heart Association (NYHA) class IV HF and preserved renal function (estimated glomerular filtration rate (eGFR) > 25 ml/min), who were refractory to conservative treatment. Clinical data on weight loss, hospitalization rate before and after PD initiation, cardiac functional status, and technique complications during a 6-month observational period were analyzed. Results: PD treatment was performed in 32 patients with a mean age of 63.8 ± 11.9 years and a follow-up of 20.78 ± 14.24 months. Hospitalizations were significantly reduced from 20.7 ± 13.7 to 7.7 ± 8.9 days/patients at 6 months. All patients showed improvement in NYHA class as well as in left ventricular ejection fraction. Overall, eGFR showed a significant decrease but only six patients reached end-stage renal disease. Complications included 18 cases of peritonitis. PD was well tolerated and no patient dropped out of the method. Survival rate reached 72% at 12 months but mortality rate was high with 23 patients dying at 16.65 ± 12.3 months after the initiation of treatment. Patients survival was not influenced by the type of PD modality or weight reduction achieved. Conclusions: PD showed to be a viable option for the treatment of patients with refractory HF leading to a better cardiac functional status and diminishing the number of hospital admissions.

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Background and Aims Crystalline solutions, such as normal saline 0.9% (N/S 0.9%) and Ringer's Lactate (L/R), are readily administered for increasing plasma volume. Despite the utility of administering N/S 0.9% to hypovolemic patients, the dose of 154 mmol of sodium (Na) contained in 1 L exceeds the recommended daily dose increasing the risk of sodium overload and hyperchloremic metabolic acidosis. In contrast, L/R solution has the advantage of lower Na content, significantly less chlorine and contains lactates which may be advantageous in patients with significant acidemia such as patients with acute kidney injury (AKI) and chronic kidney disease (CKD). The aim of the present study is to investigate the safety and efficacy of administration of L/R versus N/S 0.9% in patients with prerenal AKI and established CKD. Method The study included adult patients with known CKD stage II to V without need for dialysis, with prerenal AKI (AKIN Stage I to III Criteria). Patients with other forms of AKI as well as hypervolemia, heart congestion or hyperkalemia (serum K>5.5 meq/l) were excluded from the study. Patients were randomized in 1:1 ratio to receive intravenously either N/S 0.9% or L/R solution at a dose of 20 ml/kg body weight/day. We studied kidney function (eGFR: CKD-EPI) and response to treatment at discharge and at 30 days after discharge, duration of hospitalization, improvement in serum bicarbonate levels (HCO3), acid-base balance, serum potassium levels and the need for dialysis. Results The study included 26 patients (17 males) with a mean age of 59.1 ± 16.1 years. Thirteen patients received treatment with N/S 0.9% and the rest with L/R solution. Baseline demographic and clinical characteristics at hospital admission and historical data did not show any significant differences in both groups of patients. Renal function at the onset of AKI did not show significant differences between the two groups (16.4 ± 5.8 vs 16.9 ± 5.7 ml/min/1.73 m2, p=ns, treatment with N/S and L/R respectively). The mean volume of solutions received by the two groups (N/S 0.9% 1119 ± 374 vs L/R 1338 ± 364 ml/day, p=ns) as well as the mean total volume of liquids received per day, did not differ significantly (2888 ± 821 vs 3069 ± 728 ml/d, p=ns). Patients treated with L/R were discharged 1 day earlier than patients treated with N/S (5.2 ± 3.2 vs 6.2 ± 4.9 days of hospitalization, p=ns). Renal function improvement during hospitalization and 30 days after discharge did not differ significantly between the two groups. Patients that received L/R showed a higher increase in plasma HCO3 (ΔHCO3) concentration at discharge than those that received N/S 0.9% (4.9 ± 4.1 vs 2.46 ± 3.7 meq/l, p=ns) and pH increase (ΔpH) was slightly higher in those that received L/R solution (0.052 ± 0.066 vs 0.023 ± 0.071, p=ns). Patients treated with N/S 0.9% showed a greater decrease in serum potassium (ΔK) at discharge compared to those treated with L/R (-0.39 ± 1.03 vs -0.17 ± 0.43 meq/l, p=ns, respectively). No patient received acute dialysis treatment. Conclusion Administration of L/R solution as a hydration treatment to patients with prerenal AKI and established CKD is not inferior concerning safety and efficacy to N/S 0.9% solution. In addition, L/R administration seems to marginally improve acid-base balance in this specific group of patients.

The coronavirus disease 2019 (COVID-19) pandemic has created major challenges for all countries around the globe. Retrospective studies have identified hypertension, cardiovascular disease, diabetes and older age as risk factors for high morbidity and mortality from COVID-19. There is a general concern that patients with immune-mediated kidney diseases, namely those on immunosuppressive therapies and/or those with more advanced kidney failure, could particularly be at risk for adverse outcomes due to a compromised antiviral immunity. Uncertainties exist on how management routines should be reorganized to minimize the risk of severe acute respiratory syndrome coronavirus 2 infection and what measures are necessary for infected patients. The aim of the present review of the Immunonephrology Working Group of the European Renal Association–European Dialysis and Transplant Association is to provide recommendations for the management of patients with immune-mediated kidney diseases based on the available evidence, similar circumstances with other infectious organisms and expert opinions from across Europe. Such recommendations may help to minimize the risk of encountering COVID-19 or developing complications during COVID-19 in patients with immune-mediated kidney disease.

Background and Aims New onset diabetes (NODAT) is a common complication after kidney transplantation. The available treatment options in this patient population have limitations due to reduced renal function, possible interactions with immunosuppressive drugs and side effects such as hypoglycemic events. The aim of this study was to investigate the long term safety and efficacy profile of dipeptidyl peptidase-IV (DDP-4 inhibitors) administration in renal transplant recipients with NODAT. Method The study included 12 patients treated with DPP-IV inhibitors monotherapy as well as 5 patients receiving insulin monotherapy as initial treatment immediately after NODAT diagnosis. All patients were monitored at every scheduled outpatient visit and for 12 months after diagnosis by measuring glycosylated hemoglobin (HbA1c), serum creatinine (eGFR calculation with CKD-EPI formula), plasma immunosuppressive trough levels, serum lipids, blood pressure, and body weight. The mean values of the aforementioned parameters for the last six months of follow up were compared to the ones at diagnosis. Results Patients receiving DPP-IV inhibitors were treated with either linagliptin (4 patients), sitagliptin (4 patients), vildagliptin (2 patients) or halogliptin (2 patients). These patients had a mean age of 59.4 ± 12 years, a mean HbA1c of 6.6% and a mean fasting glucose of 114.5 mg/dl at diagnosis. The mean HbA1c the last 6 months of one year of follow up after initiation of treatment, decreased to 6.1% (p=0.03). Renal function remained stable (mean eGFR from 58.8 to 61.7 ml/min/1.73m2, p=ns) while plasma tacrolimus levels did not appear to be affected (from 6.2 to 5.5 ng/dl, p=ns). Patients received a slightly reduced mean dose of tacrolimus during the last six months of follow up in comparison to the one at initiation of treatment (from 2.9 to 2.6 mg/24h, p=ns). No significant difference was shown in serum total, LDL, and HDL cholesterol before and after treatment, nevertheless, triglyceride levels were significantly reduced (from 214.4 to 174.9 mg/dl, p=0.0039). A decrease in body weight was observed (from 79.9 to 77.9 kg, p=ns) which was however not statistically significant. Finally, achieving the goal of lowering HbA1c levels was better in patients treated with DPP-IV inhibitors than in those treated with insulin (6.1% vs 7.1%, respectively, p=0.01). Conclusion Administration of DPP-IV inhibitors appears to be a safe and effective option for the treatment of NODAT in renal transplant recipients with the benefit of avoiding hypoglycemic episodes and possibly better diabetes control than with insulin therapy.

Cardiac valve calcification (CVC) is a significant risk factor for cardiovascular morbidity and mortality in patients with chronic kidney disease on maintenance hemodialysis. The aim of this study was to investigate the association of several risk factors and particularly of malnutrition on CVC. In this cross-sectional cohort study, we included stable adult patients on maintenance hemodialysis. Calcification of cardiac valves was evaluated using two-dimensional echocardiography. Nutritional assessment and body composition measurements were performed using the MQSGA clinical tool and bioelectrical impedance analysis, respectively. Biochemical parameters such as serum calcium, phosphorus, iPTH, 1.25 hydroxy-vitamin-D, triglycerides, total cholesterol, HDL-C, LDL-C, total proteins, albumin, creatinine and CRP were assessed as potentially risk factors. The receiver operating characteristic (ROC) curve analysis was used to evaluate the prognostic ability of the aforementioned variables on severe degree CVC. Binary logistic regression analysis was also performed to identify independent variables of severe CVC. Overall, 42 patients were included in the study with half of them exhibiting mitral calcification, 38% aortic valve calcification, and 16.7% calcification in both valves. ROC analysis indicated that aging (p = 0.011), increased CRP (p = 0.038) and decreased value of serum albumin to total proteins ratio (p = 0.012) were positive prognostic factors for moderate to severe degree cardiac valve calcification. Low phase angle was also associated with CVC, although with moderate specificity. Aging, inflammation, low serum albumin to total proteins ratio and low phase angle values as indicators of malnutrition are predictors of severe CVC in end-stage renal disease patients on hemodialysis.

Purpose: There is currently debate if brachio-basilic vein fistula (BBVF) should be performed as a one-stage or two-stage procedure. The aim of the present study was to perform a systematic review and meta-analysis on BBVF staging. Materials and Methods: On February 25, 2016, a search for randomized-controlled trials (RCTs) on BBVF procedures was performed in MEDLINE and Scopus databases. Meta-analyses were performed with fixed-effect or random-effects models as appropriate with risk ratios (RRs). The primary efficacy and safety outcome measures were BBVF maturation and development of complications, respectively. Specific types of complications, including loss of functional secondary patency and long-term complications were all secondary outcome measures. Results: We identified three RCTs reporting on 126 patients. Maturation failure of two-stage BBVFs (3/47, 6.4%) was less frequent than one-stage BBVFs (16/79, 20.3%; RR, 0.27; P=0.02). Complication rates of two-stage and one-stage BBVFs were similar (RR, 0.80; P=0.54), but on sensitivity analysis these were less likely to occur with two-stage BBVFs (37% vs. 69% for one-stage BBVFs; RR, 0.57; P=0.03). Two-stage BBVFs were less likely to lose their functional secondary patency (21.3% vs. 31.6% for one-stage BBVFs; RR, 0.61; P=0.11). This non-significant trend became significant (RR, 0.36; P=0.02) on sensitivity analysis. There was no difference in specific complication rates of the two study groups. Conclusion : Among candidates for BBVF fistula, there is evidence to suggest that two-stage BBVFs achieve higher maturation rates compared to one-stage BBVFs. The evidence for difference in long-term secondary patency is less robust, calling for further research.

Background Natural history, predisposing factors to an unfavourable outcome and the effect of various therapeutic regimens were evaluated in a cohort of 457 patients with immunoglobulin A nephropathy (IgAN) and follow-up of at least 12 months. Methods Patients with normal renal function and proteinuria 2.5 mg/dL and/or severe glomerulosclerosis received no treatment. Patients with normal or impaired renal function and proteinuria >1 g/24 h for >6 months received daily oral prednisolone or a 3-day course of intravenous (IV) methylprednisolone followed by oral prednisolone per os every other day or a combination of prednisolone and azathioprine. The clinical outcome was estimated using the primary endpoints of end-stage renal disease and/or doubling of baseline SCr. Results The overall 10-year renal survival was 90.8%, while end-stage renal disease and doubling of baseline SCr developed in 9.2% and 14.7% of patients, respectively. Risk factors related to the primary endpoints were elevated baseline SCr, arterial hypertension, persistent proteinuria >0.5 g/24 h and severity of tubulointerstial fibrosis. There was no difference in the clinical outcome of patients treated by the two regimens of corticosteroids; nevertheless, remission of proteinuria was more frequent in patients who received IV methylprednisolone (P = 0.000). The combination of prednisolone with azathioprine was not superior to IV methylprednisolone followed by oral prednisolone. Side effects related to immunossuppressive drugs were observed in 12.8% of patients. Conclusion The clinical outcome of patients with IgAN was related to the severity of clinical and histological involvement. The addition of azathioprine to a corticosteroid-based regimen for IgAN does not improve renal outcome.

Evidence-based cinical practice guidelines improve delivery of uniform care to patients with and at risk of developing kidney disease, thereby reducing disease burden and improving outcomes. These guidelines are not well-integrated into care delivery systems in most low- and middle-income countries (LMICs). The KDIGO Controversies Conference on Implementation Strategies in LMIC reviewed the current state of knowledge in order to define a road map to improve the implementation of guideline-based kidney care in LMICs. An international group of multidisciplinary experts in nephrology, epidemiology, health economics, implementation science, health systems, policy, and research identified key issues related to guideline implementation. The issues examined included the current kidney disease burden in the context of health systems in LMIC, arguments for developing policies to implement guideline-based care, innovations to improve kidney care, and the process of guideline adaptation to suit local needs. This executive summary serves as a resource to guide future work, including a pathway for adapting existing guidelines in different geographical regions.

The incidence of chronic kidney disease (CKD) in patients with chronic heart failure (CHF) is high as CKD and CHF share underlying risk factors such as arterial hypertension, diabetes mellitus and atherosclerosis. Cardiac failure leads to renal hypoperfusion and dysfunction and then fluid overload and need for aggressive diuretic therapy. However, development of diuretic resistance represents a significant problem in the management of these patients. The role of Renal Replacement Therapy (RRT) is important for patients who do not response to conservative management of fluid overload facilitating the failing heart to restore function. According to the guidelines, venovenous isolated Ultrafiltration (UF) is indicated for patients with refractory congestion not responding to medical therapy with loop diuretics and infusion of dopamine. A systematic review of randomized controlled trials on the effect of UF vs. IV furosemide for decompensated heart failure showed a benefit of UF on total body weight loss and on readmissions due to heart failure in patients with decompensated heart failure and CKD. Peritoneal dialysis (PD) can provide efficient ultrafiltration and sodium extraction in volume overloaded patients followed by decline of hospitalization days, decrease of body weight and improvement of LVEF in patients with refractory heart failure. The continuous draw of ultrafiltrate is followed by a lesser risk of abrupt hypotension and better preservation of the residual kidney function. This represents a significant advantage of PD over intermittent UF by dialysis. In conclusion, application of UF by dialysis and PD is followed by significant total body weight loss, reduced need for hospital readmissions and better quality of life. PD has a higher probability of preservation of residual kidney function and can be used by patients at home.

In January 2019, the ERA-EDTA surveyed nephrologists with questions on kidney care and kidney research designed to explore comprehension of the impact of alterations to organization of renal care and of advancements in technology and knowledge of kidney disease. Eight hundred and twenty-five ERA-EDTA members, ∼13% of the whole ERA-EDTA membership, replied to an ad hoc questionnaire. More than half of the respondents argued that kidney centres will be increasingly owned by large dialysis providers, nearly a quarter of respondents felt that many medical aspects of dialysis will be increasingly overseen by non-nephrologists and a quarter (24%) also believed that the care and long-term follow-up of kidney transplant patients will be increasingly under the responsibility of transplant physicians caring for patients with any organ transplant. Nearly half of the participants (45%, n = 367) use fully electronic clinical files integrating the clinical ward, the outpatient clinics, the haemodialysis and peritoneal dialysis units, as well as transplantation. Smartphone-based self-management programmes for the care of chronic kidney disease (CKD) patients are scarcely applied (only 11% of surveyed nephrologists), but a substantial proportion of respondents (74%) are eager to know more about the potential usefulness of these apps. Finally, European nephrologists expressed a cautious optimism about the application of omic sciences to nephrology and on wearable and implantable kidneys, but their expectations for the medium term are limited.

OBJECTIVES The effect of a functioning arteriovenous fistula on cardiac function in kidney transplant recipients has not been thoroughly investigated. MATERIALS AND METHODS We retrospectively evaluated cardiac function in 99 renal transplant recipients using transthoracic echocardiography, with available follow-up at baseline and 2 and 5 years posttransplant. Patients were divided into 2 groups: a control group (n = 47) with no functioning arteriovenous fistula immediately after transplant and an arteriovenous fistula group (n = 52) with a functioning arteriovenous fistula for at least 5 years after transplant. Left ventricular ejection fraction, diastolic thickness of the interventricular septum, and left ventricular end-diastolic diameter were assessed. RESULTS In our study, patients (62.6% men, 7.1% with diabetes, mean age of 55.6 ± 11.5 years), we observed no significant differences with respect to baseline left ventricular ejection fraction and interventricular septum; however, in the arteriovenous fistula group, baseline left ventricular end-diastolic diameter was marginally higher than that shown in the control group (50.6 ± 5.4 vs 48.6 ± 4.4 mm; P = .054). In multivariate analysis, functioning fistula and peripheral arterial disease were negatively associated with left ventricular ejection fraction at 5 years posttransplant, whereas baseline left ventricular ejection fraction had a minimal positive effect: B (95% confidence interval) of -2.186 (-4.312 to -0.061) (P = .044), -5.304 (-9.686 to -0.922) (P = .018), and 0.247 (0.047 to 0.446) (P = .016), respectively. Functioning fistula also emerged as associated with larger left ventricular end-diastolic diameter at 2 and 5 years posttransplant: B (95% confidence interval) of 3.047 (1.470-4.625) (P < .001) and 2.122 (0.406-3.838) (P = .016), respectively. CONCLUSIONS Maintenance of a functioning fistula in kidney transplant recipients may be associated with adverse long-term effects on left ventricular ejection fraction and left ventricular end-diastolic diameter.

Management of the Primary Membranous Nephropathy (PMN) usually involves administration of immunosuppressives. Cyclophosphamide (Cyclo) and Calcineurin Inhibitors (CNIs) are both widely used but only limited data exist to compare their efficacy in long term follow-up.Aimof the present study was to estimate and compare long term effects of Cyclo and CNIs in patients with PMN.Patients-MethodsClinical data, histologic findings and long term outcome were retrospectively studied. The response to treatment and rate of relapse was compared between patients treated with CNIs or Cyclo based immunosuppressive regimens.ResultsTwenty three centers participated in the study, with 752 PMN patients (Mean age 53.4(14-87)yrs, M/F 467/285), followed for 10.1±5.7 years. All patients were initially treated with Renin Angiotensin Aldosterone System inhibitors (RAASi) for at least 6 months. Based on their response and tolerance to initial treatment, patients were divided into 3 groups, group I with spontaneous remission, who had no further treatment, group II, continued on RAASi only, and group III on RAASi+immunosuppression. Immunosuppressive regimes were mainly based on CNIs or Cyclo. Frequent relapses and failure to treatment were more common between patients who had started on CNIs (n=381) compared to those initially treated with Cyclo (n=110), relapse rate: 25.2% vs. 6.4%, pConclusionsLong term follow up showed that administration of Cyclo in PMN is followed by better preservation of renal function, increased response rate and less frequent relapses, compared to CNIs.

Chronic kidney disease (CKD) is now seen as a systemic disease involving also the central nervous system [1], but the link between the kidney and different organ systems and disease went unnoticed for a long time. The king of Poland, Stephen Bathory (1533-86), suffered from CKD due to polycystic kidney disease and depression [2]. Similarly, Wolfgang Amadeus Mozart was also thought to have had CKD [3] and depression [4]. A list of 'Famous People Who Have Died from Kidney Disease' [5] includes many who suffered from both CKD and depression or other signs of mental illness. Is this a coincidence or actually evidence of a link between kidney disease and brain dysfunction? This is not merely an academic question because all forms of mental illness can seriously impair an individual's quality of life, and are frequently associated with progression of diseases and premature mortality, so it is worth the effort of trying to answer it. Europe and much of the industrialized countries are experiencing growing numbers of patients with CKD within their ageing populations [6]. CKD is complex and potentially fatal: (i) all organs are affected, sooner or later; (ii) the balance of plasma volume, electrolytes, acid-base and minerals, metabolites, hormones and proteins is disturbed; and (iii) patients often need a multidisciplinary team approach managing complex comorbidities, drug regimens and special diets. Although the prognosis of patients with CKD remains poor, their increasing life expectancy has shifted medical attention from life-threatening emergencies to long-term complications and sequelae, and how to improve quality of life [7]. Indeed, kidney failure has detrimental effects on health-related quality of life (HRQoL), reaching levels similar to those seen in patients with metastatic cancer [8]. This might be due to psychological factors, both kidney disease and cancer being chronic diseases with a bad prognosis. However, although the effect of CKD on quality of life is more evident in advanced stages (stage G4P) and in older patients [9, 10], a large study has shown a significant decrease in HRQoL as early as CKD stage G2 [11]. Notably, neurological and cognitive impairments [12], and depression [13] are among the most debilitating consequences of CKD contributing to the significantly reduced HRQoL [14].

IntroductionManagement of the Primary Membranous Nephropathy (PMN) usually involves administration of immunosuppressives. Cyclophosphamide (Cyclo) and Calcineurin Inhibitors (CNIs) are both widely used but only limited data exist to compare their efficacy in long term follow-up.AimThe aim of the present study was to estimate and compare long term effects of Cyclo and CNIs in patients with PMN.Patients-methodsClinical data, histologic findings and long term outcome were retrospectively studied. The response to treatment and rate of relapse was compared between patients treated with CNIs or Cyclo based immunosuppressive regimens.ResultsTwenty three centers participated in the study, with 752 PMN patients (Mean age 53.4(14-87) yrs, M/F 467/285), followed for 10.1±5.7 years. All patients were initially treated with Renin Angiotensin Aldosterone System inhibitors (RAASi) for at least 6 months. Based on their response and tolerance to initial treatment, patients were divided into 3 groups, group I with spontaneous remission, who had no further treatment, group II, continued on RAASi only, and group III on RAASi+immunosuppression. Immunosuppressive regimes were mainly based on CNIs or Cyclo. Frequent relapses and failure to treatment were more common between patients who had started on CNIs (n = 381) compared to those initially treated with Cyclo (n = 110), relapse rate: 25.2% vs. 6.4%, pConclusionsLong term follow up showed that administration of Cyclo in PMN is followed by better preservation of renal function, increased response rate and less frequent relapses, compared to CNIs.

The strengths and the limitations of research activities currently present in Europe are explored in order to outline how to proceed in the near future. Epidemiological and clinical research and public policy in Europe are generally considered to be comprehensive and successful, and the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) is playing a key role in the field of nephrology research. The Nephrology and Public Policy Committee (NPPC) aims to improve the current situation and translation into public policy by planning eight research topics to be supported in the coming 5 years by ERA-EDTA.

The exclusion of chronic kidney disease (CKD) patients from clinical trials—particularly cardiovascular trials—remains a long-standing, unsolved problem, which prevents the optimization of clinical care in these patients. The situation recalls the insufficient recruitment of women in cardiovascular trials until the 1980s, a problem that was only resolved following regulatory interventions. Regulatory agencies are in a unique position to promote recruitment of CKD patients in clinical trials. The main stakeholders, namely patients’ associations and scientific societies, should make major lobbying efforts to persuade these agencies that the issue is an absolute public health priority.

Objective Management of patients with type 2 diabetes (T2DM) and stage 3 to 5 chronic kidney disease (CKD) is challenging. The aim of the 'LEARN' study was to describe treatment patterns employed in this population and to record comorbidities, glycemic control and hypoglycemia episodes in routine clinical practice in Greece. Research design and methods 'LEARN' was a non-interventional, multicenter, cross-sectional study conducted in Greece between 15 February 2013 and 4 July 2013. A total of 120 adult patients were enrolled from four hospital sites in different geographic regions of Greece. Results Participants had a mean age of 69.1 ± 10.3 years and a male:female ratio of 2:1. Nearly all patients (99.2%) suffered from at least one comorbidity, with hypertension (95.8%) and hyperlipidemia/dyslipidemia (78.3%) being the most prevalent. Of the overall study population, 57.5% was managed with insulin therapy only, 30.8% with oral antidiabetics only and 11.7% with a combination of insulin and oral antidiabetics. The overall rate of glycemic control, defined as glycated hemoglobin (HbA1c) ≤ 7.0% during the most recent assessment, was 55.0%. This rate was significantly higher among those receiving oral antidiabetics only (73.0%) compared to insulin only (47.8%) or a combination of both types of treatment (42.9%) (p = 0.03). Moreover, patients receiving oral antidiabetics only had experienced fewer hypoglycemia episodes over the last 7 days prior to the study visit (0.1 ± 0.4) compared to patients receiving insulin only (0.9 ± 1.7) (p = 0.03). Conclusions Although this is an observational study, it seems that oral antidiabetic therapy might be advantageous for heavily burdened T2DM patients with moderate or severe CKD in terms of glycemic control and hypoglycemia episodes. More data preferably from randomized trials is needed in order to validate this hypothesis.

Background Glomerulonephritides (GNs) represent common causes of chronic kidney disease associated with a wide spectrum of clinical and histological features. Various factors that activate the inflammatory cascade are involved in the development of kidney injury. The aim of this study was to estimate the urinary excretion of pro-inflammatory (IL-2, INF-γ, TNF-α, IL-6, IL-17) and anti-inflammatory (IL-4, IL-10, TGF-β1) cytokines, as well as the chemokine MCP-1 in patients with various types of GN treated by immunosuppressive drugs and to identify any prognostic value of excreted cytokines for future renal function. Patients and methods Ninety-seven patients (62 M/35 F, age 53.1 ± 15.6 years) with primary glomerulonephritis and 32 healthy controls were studied. The original diagnoses were membranous nephropathy (MN, n = 36), IgA nephropathy (IgAN, n = 31) and minimal changes disease or focal segmental glomerulosclerosis (MCD/FSGS, n = 30). All patients had been treated with immunosuppressive drugs and, at the time of measurement of urinary cytokine excretion, were either in clinical remission or still had active disease with persistent proteinuria. Results GN patients had significantly higher levels of all cytokines and MCP-1 compared to healthy controls. A strong positive correlation between TGF-β1 and MCP-1 concentrations was observed in all GN patients. Increased urinary excretion of all tested cytokines apart from TNF-α and TGF-β1 was observed even in patients with clinical remission. The main difference between patients with proteinuria and those in clinical remission was the level of MCP-1 urinary excretion. The urinary excretion of MCP-1 and TGF-β1 was significantly higher in patients with MN who showed deterioration of renal function over a follow-up period of five years. Conclusions Increased levels of cytokines are observed in the urine of patients with different types of glomerulonephritis, even after the achievement of clinical remission with the administration of immunosuppressive drugs. Urinary excretion of MCP-1 and TGF-β1 indicates the ongoing inflammatory and fibrotic processes in the kidney and is probably related to unfavourable outcomes.

Brucellosis is the most common zoonotic disease in Greece, with an endemic distribution and can affect any organ. Infiltration of the renal parenchyma causes acute and chronic interstitial nephritis with granulomas, whereas renal glomeruli are rarely affected. The disease has been sporadically reported, and it causes various histopathologic patterns. Herein, we describe the case of a 39-year-old stock breeder with a history of recurrent episodes of bacteremia caused by Brucella melitensis over a period of 3 years. Two months after the last episode of bacteremia, he presented with mild renal insufficiency, nephrotic range proteinuria, and microscopic hematuria. A renal biopsy revealed membranoproliferative glomerulonephritis with a pattern of focal-segmental nodular sclerosis and moderate tubulointerstitial fibrosis. The patient received antimicrobial and corticosteroid therapy with partial remission of the nephrotic syndrome.

Chronic kidney disease, the end result of most renal and some systemic diseases, is a common condition where renal function is compromised due to fibrosis. During renal fibrosis, calreticulin, a multifunctional chaperone of the endoplasmic reticulum (ER) is up‐regulated in tubular epithelial cells (TECs) both in vitro and in vivo. Proteomic analysis of cultured TECs overexpressing calreticulin led to the identification of the family of 14‐3‐3 proteins as key proteins overexpressed as well. Furthermore, an increased expression in the majority of 14‐3‐3 family members was observed in 3 different animal models of renal pathologies: the unilateral ureteric obstruction, the nephrotoxic serum administration and the ischaemia‐reperfusion. In all these models, the 14‐3‐3σ isoform (also known as stratifin) was predominantly overexpressed. As in all these models ischaemia is a common denominator, we showed that the ischaemia‐induced transcription factor HIF1α is specifically associated with the promoter region of the 14‐3‐3σ gene. Finally, we evaluated the expression of the family of 14‐3‐3 proteins and specifically 14‐3‐3σ in biopsies from IgA nephropathy and membranous nephropathy patients. These results propose an involvement of 14‐3‐3σ in renal pathology and provide evidence for the first time that hypoxia may be responsible for its altered expression.

Persistent secondary hyperparathyroidism is common after successful kidney transplant, with concomitant hypercalcemia and hypophosphatemia potentially leading to reduced graft survival and increased cardiovascular risk. Cinacalcet, a calcimimetic agent that activates the calcium-sensing receptors in parathyroid glands, is a therapeutic option. In this study, we assessed the long-term treatment effects of cinacalcet for a period of up to 5 years in a cohort of kidney transplant recipients.Forty-seven patients with secondary hyperparathyroidism (intact parathyroid hormone level70 pg/mL or 7.43 pmol/L) and hypercalcemia (corrected calcium10.4 mg/dL or 2.6 mmol/L) were considered eligible for treatment with cinacalcet and were included in the analysis. Data were recorded at initiation of treatment and every 6 months up to a maximum follow-up of 60 months. A control group of patients treated with placebo, conventional treatment, or surgical treatment was not available for this study.Mean follow-up time was 45 ± 16 months. Treatment with cinacalcet was initiated at a median of 25 months after renal transplant. Serum calcium decreased by 0.21 mmol/L (2.69 vs 2.48 mmol/L; 95% confidence interval, 0.08-0.345; P.001) during the first 6 months, and this reduction was sustained during follow-up. Intact parathyroid hormone level decreased by 7.68 pmol/L (32.96 ± 36.4 vs 25.28 ± 19.5 pmol/L; 95% confidence interval, -6.42 to 21.75; P = not significant) at 6 months, whereas at the end of follow-up intact parathyroid hormone level decreased further by 20.07 pmol/L (32.96 ± 36.4 vs 12.89 ± 5.73 pmol/L; 95% confidence interval, 2.02-38.1; P.01). Mean starting dose of cinacalcet was 33.5 ± 10 mg/day. According to the therapeutic response, cinacalcet dose increased steadily and reached 51.1 ± 33 mg/day at the end of the observation period. Mean serum phosphorus increased significantly, whereas estimated glomerular filtration rate remained virtually stable throughout follow-up. Adverse reactions were observed in 4 patients, comprising mild gastro-intestinal complaints.Long-term treatment with cinacalcet in kidney transplant recipients with secondary hyperparathyroidism is effective in controlling hypercalcemia and correcting hypophosphatemia, without affecting graft function while being well-tolerated.

The urothelium represents "the tightest and most impermeable barrier in the body." We investigated the distribution of paclitaxel (PTX) in the ureteral wall after the inflation of a paclitaxel-eluting balloon (PEB) in an attempt to elucidate the possibility of clinical application of PEBs in the ureter.Nine domestic pigs were used. Nine PEBs and nine conventional percutaneous angioplasty balloons (CB) were inflated in the right and left ureter of each animal, respectively. The ureter treated by CB was the control for the contralateral ureter. Specimens were removed: Immediately after inflation (group A), after 12 hours (group B), and after 24 hours (group C). Two samples were obtained from each ureter of groups A, B and C. One sample was investigated by nuclear magnetic resonance spectroscopy (NMR), the other by histology and immunohistochemistry (IHC) using a specific for PTX polyclonal antibody.Reduced inflammation was observed in the group B and C samples in comparison with their controls. PTX was distributed mostly in the urothelium and submucosal layer in group A (IHC). The agent was present in the urothelial, submucosal, and muscle layer in groups B and C. The concentration of PTX (NMR) has been reduced in group C compared with the tissue extracts of group B.The distribution of PTX includes the urothelial, submucosal, and smooth muscle layers. Inflammation was reduced in the case of drug-eluting balloons.

As chronic kidney disease (CKD) progresses to the terminal stage, proper actions must be taken to prepare the patient for the initiation of the renal replacement therapy (RRT). If hemodialysis is an option for RRT, decisions should be made about the right vascular access for each individual patient. The available options for vascular access include the use of native arteriovenous fistulas (AVF), synthetic arteriovenous grafts (AVG) and double lumen dialysis catheters. With the help of ultrasound mapping, chances for choosing a right access are today very high. For hemodialysis patients the selection of the proper vascular access is of vital issue in regard of preventing complications and unnecessary procedures. Planning, creation and monitoring of the vascular access in dialysis patients should involve not only the nephrologist, but also the vascular surgeon and the interventional radiologist. Thus, multidisciplinary approach should be taken, in order to choose the way that has the most advantages and the least damage for the patient. That is the proper mode for hemodialysis patients to have longer and better quality of life.

Gastrointestinal disorders (GDs) are common in renal transplant recipients. The main cause of GDs seems to be the use of immunosuppressive medications, especially mycophenolic acid in the form of mycophenolate mofetil (MMF).The aim of this study was to estimate the frequency and severity of GDs in renal allograft recipients with the use of the Gastrointestinal Symptom Rating Scale (GSRS).Eighty-five renal allograft recipients, 50 ± 12 years old, treated with methylprednisolone, calcineurin inhibitor (cyclosporine [CsA], n = 42; tacrolimus (TAC), n = 43), and MMF were studied.At the time of completion of the GSRS questionnaire, 38 of the 85 patients (45%) already had their MMF dose reduced because of GDs. Only 15 patients (18%) were totally free from GDs. The most frequent and severe GDs recorded were indigestion and diarrhea who were significantly more frequent in women (P = .045). GDs were recorded in patients receiving both standard and reduced dose of MMF. MMF dose was significantly associated only with diarrhea. Although TAC-treated patients had the highest mean GSRS scores, no statistically significant differences were observed compared with CsA-treated patients. In 31 patients, MMF was replaced by enteric-coated mycophenolate sodium (EC-MPS) and new questionnaires were completed 1 month later. Significant improvement in total and all subscores of GSRS was demonstrated (P.001). Although EC-MPS dose tolerated by the patients was higher than MMF dose, the difference was not statistically significant.Female sex and the use of MMF, especially in combination with TAC, are related to the occurrence of severe gastrointestinal symptoms. Substitution of MMF with EC-MPS significantly reduces the severity of symptoms and permits the use of higher doses.