Irena Głowińska

Biomarkers of delayed graft function as a form of acute kidney injury in kidney transplantation

Renal transplantation ensures distinct advantages for patients with end-stage kidney disease. However, in some cases early complications can lead to allograft dysfunction and consequently graft loss. One of the most common early complications after kidney transplantation is delayed graft function (DGF). Unfortunately there is no effective treatment for DGF, however early diagnosis of DGF and therapeutic intervention (eg modification of immunosuppression) may improve outcome. Therefore, markers of acute kidney injury are required. Creatinine is a poor biomarker for kidney injury due principally to its inability to help diagnose early acute renal failure and complete inability to help differentiate among its various causes. Different urinary and serum proteins have been intensively investigated as possible biomarkers in this setting. There are promising candidate biomarkers with the ability to detect DGF. We focused on emerging biomarkers of DGF with NGAL is being the most studied followed by KIM-1, L-FABP, IL-18, and others. However, large randomized studies are needed to establish the value of new, promising biomarkers, in DGF diagnosis, prognosis and its cost-effectiveness.

Iron metabolism in hemodialyzed patients - a story half told?

Introduction All living organisms have evolved sophisticated mechanisms to maintain appropriate iron levels in their cells and within their body. Recently our understanding of iron metabolism has dramatically increased. Overt labile plasma iron (LPI) represents a component of non-transferrin bound iron (NTBI) that is both redox active and chelatable, capable of permeating into organs and inducing tissue iron overload. The LPI measures the iron-specific capacity of a given sample to produce reactive oxygen species. We studied for the first time NTBI correlations with markers of iron status and inflammation in prevalent hemodialyzed patients. Material and methods Complete blood count, urea, serum lipids, fasting glucose, creatinine, ferritin, serum iron, total iron binding capacity (TIBC) were studied by standard laboratory method. The NTBI was assessed commercially available kits from Aferrix Ltd in Tel Aviv, Israel. A test result of 0.6 units of LPI or more indicates a potential for iron-mediated production of reactive oxygen species in the sample. Results Patients with LPI units ≥ 0.6 had higher serum iron, erythropoiesis stimulating agents (ESA) dose, ferritin, high-sensitivity C-reactive protein (hsCRP), hepcidin and lower hemojuvelin. In hemodialyzed patients NTBI correlated with hsCRP (r = 0.37, p < 0.01), ferritin (r = 0.41, p < 0.001), IL-6 (r = 0.43, p < 0.001). In multivariate analysis predictors of NTBI were hemoglobin and alkaline phosphatase, explaining 58% of the variability Conclusions Elevated NTBI in HD may be due to disturbed iron metabolism. Anemia and liver function might also contribute to the presence of NTBI in this population.

GDF15 Is Related to Anemia and Hepcidin in Kidney Allograft Recipients

Anemia is more prevalent in renal transplant recipients than in GFR-matched chronic kidney disease patients. Hepcidin is a small defensin-like peptide whose production by hepatocytes is modulated in response to anemia, hypoxia or inflammation. Growth differentiation factor 15 (GDF15) was recently identified as a hepcidin-suppression factor that is expressed at high levels in patients with ineffective erythropoiesis. The aim of the study was to assess GDF15 levels with relation to iron parameters in 62 stable kidney allograft recipients maintained on triple immunosuppressive therapy. Methods: Complete blood count, urea, creatinine, and iron status were assessed by standard methods. We measured GDF15, hepcidin, hemojuvelin, IL-6 and NGAL with commercially available assays. Results: Mean levels of GDF15, NGAL, hepcidin and hemojuvelin were significantly higher in kidney allograft recipients when compared to the control group (p < 0.001 for all). GDF15 was significantly higher in patients with anemia according to the WHO definition when compared to their nonanemic counterparts (p < 0.05). GDF15 levels were not dependent on the type of immunosuppressive therapy. In univariate analysis GDF15 was related to kidney function (creatinine r = 0.39, p < 0.01, eGFR by MDRD r = -0.37, p < 0.01), urea (r = 0.39, p < 0.01), uric acid (r = 0.42, p < 0.01), hepcidin (r = -0.32, p < 0.01), IL-6 (r = 0.28, p < 0.05), hemoglobin (r = -0.32, p < 0.05), and NGAL (r = -0.35, p < 0.01). GDF15 was not related to serum iron, or ferritin. In multivariate analysis, hepcidin was found to be a predictor of GDF15. In conclusion, our preliminary data may suggest possible mutual relations between GDF15 and hepcidin in patients with kidney disease and that GDF15 might be involved in the pathogenesis of anemia in kidney allograft recipients. However, the role of inflammation should be also elucidated.

Basilic Vein Transposition in the Forearm for Secondary Arteriovenous Fistula

Radiocephalic (RC) fistulae remain the first choice access for hemodialysis. The antecubital fossa is recommended as the next site. However, for some patients a basilic vein can be used to create an arteriovenous (av) fistula. We report a series of patients where the forearm basilic vein served as an alternative conduit for secondary procedures. Over an 8-year period, 30 patients who had a failed RC fistula underwent a basilic vein transposition. The immediate results were satisfactory. All fistulas were successfully cannulated. Cumulative patency was 93% after 1 year, 78% after 2 years, and 55% after 3 years. No ischemic or infectious complications were noted during the study period. The use of the forearm basilic vein to create a native av fistula appears to be a good alternative to procedures in the antecubital fossa or upper arm, thus preserving more proximal veins for future use.

Use of short prosthesis segments for brachiocephalic arteriovenous fistulas in elderly hemodialysis population

Introduction The autogenous brachiocephalic fistula is a recognized secondary access for hemodialysis. However, veins in the antecubital fossa are often damaged, due to repeated venipunctures and subsequent scarring. Sometimes their anatomy does not enable successful arteriovenous fistula creation. In cases when the proximal part of the cephalic vein seemed patent, during ultrasound Doppler examination, we decided to use a short segment of 6 mm polytetrafluoroethylene graft to connect the vein with the brachial artery. We report our series of this procedure. Material and methods Over an 8-year period, 34 patients underwent such an operation. Grafts were anastomosed either to the end of the cephalic vein or to the side. The decision was made based on the vein condition: small-caliber veins were considered better for the end-to-side anastomosis. All procedures were performed under local anesthesia, and were well tolerated. Results Thirty-three fistulas were successfully cannulated at 2-8 weeks after the operation. Fistula patency rates were 84%, 73% and 55% at 12, 24 and 36 months. Comparison of two anastomosis types showed differences, 50% and 62.8% at 36 months, yet without statistical significance (p = 0.27, log-rank test). Fistula patency was not influenced by patients age, sex or comorbidities. Conclusions The described procedure provides satisfactory cumulative patency with an acceptable complication rate. It can enhance the number of cephalic veins used with its main advantages of simple surgical technique and low perioperative morbidity.