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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.

Sarcopenia is a clinical condition that comprises declined skeletal muscle (SM) mass and SM strength, and is a risk factor for physical disability, impaired quality of life, and advanced morbidity and mortality in patients on hemodialysis (HD). The existing difficulty in evaluating SM mass and consequently of sarcopenia, with affordable and practical methods in clinical practice, is well established. The purpose of this study is to examine the creatinine index (CrI), a surrogate of SM mass, as a potential predictive marker of sarcopenia. In this cross-sectional study, we included 130 patients on HD with a mean age of 66.17 ± 12.47 years. SM mass and SM strength were evaluated with CrI and hand grip strength, respectively. Anthropometric, adiposity, nutritional, and biochemical assessments were also performed. Partial correlation and multivariate regression analyses were applied to investigate the association between CrI and SM strength. Correlation analysis showed that mid-arm circumference, calf circumference, Geriatric nutritional index, and albumin-to-total protein ratio were positively associated with SM strength. Multivariate model indicated that CrI (β = 2.05, p

Cardiac valve calcification (CVC) is a predictor of cardiovascular disease and all-cause mortality in end stage kidney disease (ESKD) patients. Several risk factors are related to CVC in patients with ESKD including traditional ones as well as inflammation, bone mineral disease and malnutrition. Adiposity is associated with dyslipidemia and proinflammatory activity which could predispose for CVC. Sarcopenia or dynapenia is a state common in patients with ESKD. This study aimed to investigate the relationship of adiposity, sarcopenia and malnutrition-inflammation markers with CVC in patients on maintenance hemodialysis.CVC in aortic (AVC), mitral valves (MVC) and systolic and diastolic dysfunction (DD) were assessed by using two-dimensional echocardiography. Nutritional, adiposity and anthropometric assessments were made using several indices respectively. Creatinine index and muscle strength measurements were also performed. Biochemical parameters such as total proteins, albumin, calcium, phosphate, plasma lipoproteins, C-Reactive Protein and parathyroid hormone were also measured.Adiposity, nutritional, and sarcopenia parameters did not show any difference between patients with or without CVC. Age ≥ 65 years [PR: 1.47 p = 0.012], DD [PR: 2.31, p = 0.005], high CRP/albumin ratio [PR: 1.46, p = 0.01], mid arm circumference (MAC) 26 cm [PR: 1.37, p = 0.03] were associated with increased prevalence of AVC, while DD [PR: 1.97 p = 0.02], high CRP/albumin ratio [PR: 1.56, p = 0.02], and MAC26 cm [PR: 1.52, p = 0.01], showed positive correlation with MVC. Age ≥ 65 years [PR: 1.33, p = 0.028], DD [PR: 1.72, p = 0.01], high CRP/albumin ratio [PR: 1.53, p = 0.003], and MAC26 cm [PR: 1.4, p = 0.006], related to greater prevalence of calcification at any valve.Ageing, diastolic dysfunction, MAC and increased CRP/albumin ratio were powerful predictors of CVC in patients on hemodialysis.

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.

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.

Purpose A retrospective longitudinal analysis was performed to evaluate the outcome of consecutive treatments with drug-coated balloons (DCBs) in dysfunctional arteriovenous (AV) dialysis access (fistulae and grafts). Materials and Methods From January 2015 to December 2017, 339 DCBs were used in 257 procedures in 165 patients with dysfunctional accesses. Of these, 38 patients had ≥ 2 procedures and were included in the analysis. A total of 112 procedures were performed with 133 devices (22 patients treated twice, 4 treated 3 times, 7 treated 4 times, 2 treated 5 times, and 3 treated 6 times). Mean balloon diameter was 8.13 mm (min-max range, 3–12 mm) and length was 63.16 mm (min-max range, 40–150 mm). Primary outcome measures were safety and effectiveness based on the noninferiority hypothesis that the second treatment would be as effective as the first regarding postintervention primary patency (PIPP). Secondary outcome measures included independent factors that may influence outcomes. Results Mean lesion follow-up was 617 d (range, 175–1,100 d). Median PIPP durations were 216.5 d for the first intervention and 280 d for the second (P = .37; hazard ratio, 1.271; 95% confidence interval, 0.75–2.16). There was a significant difference in PIPP in favor of the second intervention when patients with only 2 interventions (22 of 38; 57.9%) were included (first intervention, 269 d; second intervention, 520 d; P = .03; hazard ratio, 2.354; 95% confidence interval, 1.087–5.098). Conclusions There was no significant difference in PIPP between the first and second DCB procedures. Results suggest consistency in PIPP with the use of DCBs regardless of aging AV access.

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 Cardiac valve calcification (CVC) is a common disorder in patients with end stage kidney disease (ESKD) and is a predictor of cardiovascular disease and all-cause mortality. Several risk factors are related to CVC in patients with ESKD which include higher age, dyslipidemia, hypertension and diabetes as well as inflammation, bone mineral disease and malnutrition. Moreover, visceral adiposity is associated with disturbed lipid metabolism and proinflammatory activity which could predispose for CVC. Furthermore, sarcopenia and dynapenia is a state common in patients with ESKD. Thus, the aim of this cross-sectional study is to investigate the relationship of adiposity, components of sarcopenia and malnutrition with cardiac valves calcification in patients on chronic hemodialysis. Method Adult patients that were on maintenance hemodialysis were eligible for entering the study. Recruitment took place from March 2019 to September 2020. Exclusion criteria included, patients with less than 6 months on hemodialysis, patients with cancer, inflammatory bowel disease, severe infection, cardiac valve disease prior to dialysis initiation, history of parathyroidectomy and intravenous albumin administration 3 months prior to nutritional assessment. Calcification of heart valves and systolic and diastolic function was assessed by using two-dimensional echocardiography. Nutritional assessment was made using the Geriatric Nutritional Risk Index. Conicity Index, Waist to Height Ratio, the Visceral Adiposity Index, the Lipid Accumulation Product, the Height to Waist Phenotype were also calculated. Waist, calf and mid arm circumference measurement was performed in the end of a midweek dialysis session. Muscle strength was based on a measurement of hand grip strength using a hydraulic hand dynamometer in the non-fistula hand prior to dialysis session. Dynapenia was considered for values < 16 kg in females and < 27kg in males. Serum biochemistry parameters such as total protein, albumin, calcium, phosphate, total cholesterol, triglycerides, HDL, LDL, CRP and iPTH were also measured. Results Overall, 130 patients were included in the study with a mean age of 66±12.47 years (68.5% males) and an average dialysis duration of 4.37±4.95 years. No cardiac valve calcification was found in 34.6%, while both aortic and mitral valve calcification was found in 41.5% of patients. Calcification only of the aortic (AVC) or mitral (MVC) valve was found in 14.6% and 9.2% respectively. Compared to non AVC group, AVC group had significantly higher age, higher prevalence of diastolic dysfunction, CRP values and CRP/albumin ratio and lower albumin to total proteins ratio. Patients with MVC showed significantly higher prevalence of diastolic dysfunction, higher levels of iPTH, CRP/albumin ratio and lower albumin to total proteins ratio. Adiposity, nutritional, anthropometric indices and sarcopenia parameters such as creatinine index, muscle power and physical performance status did not show any difference between all CVC groups. Increased age [OR (95%CI):1.06 (1.00-1.12) p=0.05], diastolic dysfunction [OR (95%CI): 3.07 (1.05-8.92); p=0.04], CRP/albumin ratio were associated with increased risk of AVC, whereas the CRP/albumin ratio appeared as the most powerful risk factor for mitral and for any CVC [OR (95%CI): 3.41 (1.40-8.28); p=0.007, OR (95%CI): 7.98 (2.62-24.98) p Conclusion Adiposity, nutritional, anthropometric indices and sarcopenia did not show to correlate with CVC in patients with ESKD on hemodialysis. Factors, such as diastolic dysfunction and notably increased CRP/albumin ratio were strong predictors of CVC.

Background Arteriovenous fistulas (AVFs) for hemodialysis are inconstantly used primarily due to problems with maturation and early thrombosis. An endovascular approach -without open surgery- for fistula creation offers another option for establishing a reliable vascular access. By this procedure, a arteriovenous fistula is created in the area of the cubital fossa in the deep vascular system, either between the ulnar artery and the accompanying vein or the radial artery and radial vein and uses the perforating vein at the level of the elbow to transfer blood to the superficial network of the arm. Aim To evaluate the safety, success and maturation rates of percutaneous arteriovenous fistula creation. Materials and Methods From February 2018 to June 2020 (28 months), 30 percutaneous arteriovenous fistulas (pAVF) using the WavelinQ device were created in 30 patients (male: 100%) with end stage kidney disease. Outcome measures were safety, defined as adverse events occurring within the first month of creation, success, defined as the ability to create an anastomosis between the vessels of interest and maturation rates, defined as the ability to perform at least one successful dialysis with the AVF. Secondary outcome measures included procedural complications, secondary procedures, time to cannulation, and AVF survival. Results All cases were performed as day procedures. 23 out of 30 patients (70%) were already on hemodialysis carrying a permanent central venous catheter. Main comorbidities were hypertension (21/30; 70%), diabetes (15/30; 50%) while 11/30 (30.5%) were smokers. Success was 100% (30/30). Mean follow-up was 547 days (range: 14-1071 days). In one case a pseudoaneurysm of the brachial artery was created immediately after sheath removal and in another case, an aneurysm of the AVF anastomosis was observed 17 days post-procedure and AVF was legated with a covered stent placed in the arterial part. In all, 26/30 AVFs (86.6%) were successfully cannulated. Mean time to cannulation was 61.3 days. Another one failed after maturation during the follow-up period. In total, 15 interventions were needed to achieve maturation (15/26; 0.58 procedures per AVF). 5 maintenance endovascular interventions were performed during the follow-up period (5/26; 19.2%). Mean time from cannulation to the end of follow up was 566.2 days (range: 135-1041 days). Conclusion Current analysis suggests that percutaneous AVF creation is safe, successfully performed with high maturation rates. Large scale prospective studies are needed to validate results.

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.

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.

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.

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.

There is amassed evidence regarding the use of endovascular procedures for the treatment of vascular access stenosis and thrombosis. A review was conducted based on available randomized trials, cohort studies and retrospective analyses published after 2000 on endovascular treatment of dysfunctional and thrombosed vascular access, with an aim to illustrate the available device and procedural options. The use of paclitaxel-coated balloons, cutting balloons and covered stents is described in the field of vascular access stenosis. The broad spectrum of available devices and endovascular declotting procedures ranging from thrombolysis to thrombectomy is also discussed. Overall, in this review we demonstrate the increasing role of endovascular procedures in vascular access treatment and the improved patency outcomes provided by the implementation of novel endovascular devices. Moreover, the improvement of post-intervention primary patency rates after endovascular declotting procedures and the shift to more thrombectomy-dependent procedures over time is also highlighted. In conclusion, endovascular treatment of dialysis access stenosis and thrombosis has an established role, owing to the implementation of sophisticated devices, allowing, when needed, the simultaneous treatment of thrombosis and the underlying stenosis.

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.

AIM To investigate the incidence and the determinants of cardiovascular morbidity in Greek renal transplant recipients (RTRs) expressed as major advance cardiac event (MACE) rate. METHODS Two hundred and forty-two adult patients with a functioning graft for at least three months and available data that were followed up on the August 31, 2015 at two transplant centers of Western Greece were included in this study. Baseline recipients’ data elements included demographics, clinical characteristics, history of comorbid conditions and laboratory parameters. Follow-up data regarding MACE occurrence were collected retrospectively from the patients’ records and MACE risk score was calculated for each patient. RESULTS The mean age was 53 years (63.6% males) and 47 patients (19.4%) had a pre-existing cardiovascular disease (CVD) before transplantation. The mean estimated glomerular filtration rate was 52 ± 17 mL/min per 1.73 m2. During follow-up 36 patients (14.9%) suffered a MACE with a median time to MACE 5 years (interquartile range: 2.2-10 years). Recipients with a MACE compared to recipients without a MACE had a significantly higher mean age (59 years vs 52 years, P < 0.001) and a higher prevalence of pre-existing CVD (44.4% vs 15%, P < 0.001). The 7-year predicted mean risk for MACE was 14.6% ± 12.5% overall. In RTRs who experienced a MACE, the predicted risk was 22.3% ± 17.1% and was significantly higher than in RTRs without an event 13.3% ± 11.1% (P = 0.003). The discrimination ability of the model in the Greek database of RTRs was good with an area under the receiver operating characteristics curve of 0.68 (95%CI: 0.58-0.78). CONCLUSION In this Greek cohort of RTRs, MACE occurred in 14.9% of the patients, pre-existing CVD was the main risk factor, while MACE risk model was proved a dependable utility in predicting CVD post RT.

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.

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.

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.

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.

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.

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.