Bone Metabolism Parameters in Hemodialysis Patients With Chronic Kidney Disease and in Patients After Kidney Transplantation.

Chronic kidney disease adversely affects the structure and metabolism of bone tissue, which may be a result of disturbed biochemical processes in adipose tissue. Renal replacement therapy is a life-saving therapy but it does not restore all metabolic functions and sometimes even escalates some disturbances. The study included 126 subjects: 47 hemodialysis patients (HD), 56 patients after renal transplantation (Tx) and 23 healthy controls (K). Bone density at the femoral neck (FN) and lumbar spine (LS), as well as body composition (adipose tissue content and lean body mass) were measured in each patient using the DXA method. In addition, serum concentrations of glucose, calcium, phosphorus, parathormone, FGF23, Klotho, osteocalcin, leptin, adiponectin and 1,25-dihydroxyvitamin D3 were measured. We observed significantly higher concentrations of leptin, FGF23 and Klotho proteins in the HD patients (77.2±48.1 ng/ml, 54.7±12.4 pg/ml, 420.6±303.8 ng/ml, respectively) and the Tx group (33.2±26.5 ng/ml; 179.8±383.9 pg/ml; 585.4±565.7, respectively) compared to the control group (24.4±24.6 ng/ml, 43.3±37.3 pg/ml, 280.5±376.0 ng/ml). Significantly lower bone density at FN was observed in the HD and Tx patients in comparison to the controls and in the HD patients compared to the Tx group. There were no significant differences in body mass composition between the studied groups. The results of this study indicate that both hemodialysis and transplantation are associated with increased serum concentrations of leptin, FGF23 and Klotho proteins, as well as lower bone density at femoral neck.

Anti-human leukocyte antigen antibodies are present in blood of blood donors: is therapy with blood preparations safe for graft recipients?

BACKGROUND: Blood products infusions are often administrated to graft recipients. Post-transfusion reactions of anti-human leukocyte antigen antibodies (anti-HLA) are responsible for transfusion-related acute lung injury, but cases of graft rejection after blood product infusions were recently also proven. METHODS: The aim of this study was to assess, with the use of the very sensitive Luminex technology and traditional lymphocytotoxic test, the prevalence and cytotoxic activity of anti-HLA in blood donors with different medical histories to evaluate a potential risk of post-transfusion immune complications. Data were analyzed according to different normalized background cutoffs (1.5, 2.2; and the high cutoffs-10.8 for I class and 6.9 for II class anti-HLA). RESULTS: We observed that anti-HLA may be present in 36% of donors, and even in up to 73.6% of risk groups. Significant risk factors included female sex (23.9% to 64.2% for different cutoffs) and pregnancy history (30% to 72.5%), regardless of the cutoff used in analysis, whereas sera from female donors showed lower cytotoxicity (panel reactive antibodies). Anti-HLA were also detected in men (3.7% to 37%), in donors after a transfusion (0% to 62.5%), and even with no known risk factors (3.8% to 26.9%). CONCLUSIONS: Luminex technology is a sensitive tool in anti-HLA detection, but consensus in measurement interpretation for blood donors is needed. Selection of blood products on the basis of medical history can be a useful alternative for routine testing of blood donors. The clinical significance of treatment of graft recipients with blood products requires further study; until then, more attention should be paid to possible complications.

Analysis of specificity of anti-human leukocyte antigen antibodies in kidney recipients in reference to clinical outcome.

BACKGROUND: Anti-human leukocyte antigens antibodies (HLA) are not always the main cause of graft injury but can be a marker of immune response to the graft. The aim of this study was to analyze anti-HLA specificities with the use of the most sensitive detection method (Luminex) in reference to clinical condition. METHODS: Sera of 65 kidney recipients (n = 443) were screened with the use of the mixed LABScreen kit, and, for 47 recipients, sera with maximal normalized background ratio (NBG) were subjected to specificity testing. NBG, numbers of specificities, donor-specific antibodies (DSA), and normalized mean fluorescence index (nMFI) of DSA and maximal anti-HLA were analyzed in reference to clinical (acute rejection [AR] diagnosis, immunosuppression), histopathological (C4d staining, chronic allograft nephropathy, AR type), and laboratory parameters (creatinine). RESULTS: We observed 1 to 51 specificities, class I DSA in 26.7%, class II in 10%, and estimated DQ-DSA in 63.3% of tested patients. Patients with AR and humoral AR had significantly higher NBG, number of anti-HLA class I, DQ and DQ-DSA types, and more frequently had anti-HLA and class II DSA-positive sera (P < .052). C4d staining was associated with higher anti-HLA class I (P = .053) and class I DSA (P = .002) type numbers, and maximal anti-HLA nMFI (P = .036) and was more frequent in AR (P = .048) and class II DSA positive patients (P = .046). Patients with chronic allograft nephropathy showed higher DQ-DSA-nMFI (P = .036). DQ-DSA-nMFI and maximal anti-HLA-nMFI correlated with creatinine increase (Spearman range [SR] = 0.64, SR = 0.41). Together with NBG, maximal class I and class II anti-HLA-nMFI correlated with the number of transplantation and maximal panel-reactive antibodies ratio (SR = 0.19-0.40). CONCLUSIONS: Anti-HLA detection allows for humoral AR diagnosis but also for identification of patients with risk of any rejection. However, clear rules of anti-HLA interpretation and studies on their clinical impact are needed.