AB0 incompatible kidney transplantation using unspecific immunoadsorption.

BACKGROUND: A protocol for ABO-incompatible kidney transplantation with antigen specific immunoadsorption, rituximab and conventional immunosuppression has been successfully implemented in many European centers. We report an alternative method for the elimination of isoagglutinins with a number of advantages - large amount of treatable plasma, parallel removal of other rejection-inducing antibodies, long operating life, favorable cost-benefit ratio. METHOD: We report our first successfully treated case of an ABO-incompatible living donor kidney transplantation using Immunoadsorption with Ig-TheraSorb. We performed 5 sessions preoperatively and one after transplantation. Per treatment session twice the calculated plasma volume (4400 ml in this patient) was treated. RESULTS: Per treatment session the IgM- isoagglutinin-titers were reduced from 1:16 to 1:1 and the IgG- isoagglutinin-titers from 1:32 to 1:2. There were no side effects and the procedure was well tolerated with good renal function 500 days post transplantation. CONCLUSION: Ig-TheraSorb-Immunoadsorption is an alternative method of elimination of harmful antibodies and it enables successful integration of ABO-incompatible transplantation into regular transplantation programs.

Analysis of α-klotho, fibroblast growth factor-, vitamin-D and calcium-sensing receptor in 70 patients with secondary hyperparathyroidism.

BACKGROUND/AIMS: Secondary hyperparathyroidism (sHPT) is known as a very common complication in patients with chronic kidney disease, and G-protein-coupled calcium-sensing receptor (CaSR), Vitamin D receptor (VDR) and Fibroblast growth factor receptor (FGFR)/Klotho complexes seem to be involved in its development. METHODS: Hyperplastic parathyroid glands from 70 sHPT patients and normal parathyroid tissue from 7 patients were obtained during parathyroidectomy. Conventional morphological and immunohistochemical analysis of parathyroid glands was performed after dividing each slide in a 3x3 array. RESULTS: The presence of lipocytes in the normal parathyroid gland and tissue architecture (nodal in patients with sHPT) allows for discrimination between normal parathyroid glands and parathyroid glands of patients with sHPT. Protein expression of Klotho, FGFR, CaSR and VDR was higher in the normal parathyroid glands compared to the sHPT group (p<0.001, p=0.07, p =0.01 and p=0.001). The variability of each protein expression within each tissue slide was high. Therefore correlations between the different immunohistochemical variables were analyzed for each of the nine fields and than analyzed for all patients. Using this analysis, a highly significant positive correlation could be found between the expression of FGFR and VDR (p=0.0004). Interestingly, in terms of VDR we found a shift to a more mixed nuclear/cytoplasmic staining in the HPT group compared to normal parathyroid gland cells, which showed solitary nuclear staining for VDR (p>0.05). CONCLUSIONS: CaSR, VDR and an impaired Klotho-FGFR-axis seem to be the major players in the development of sHPT. Whether the detected correlation between FGFR and VDR and the shift to a more mixed nuclear/cytoplasmic staining of VDR will yield new insights into the pathogenesis of the disease has to be evaluated in further studies.

Involvement of α-klotho, fibroblast growth factor-, vitamin-D- and calcium-sensing receptor in 53 patients with primary hyperparathyroidism.

The presentation of patients with primary hyperparathyroidism is often atypical and ranges from normocalcemic, primary hyperparathyroidism to severe, symptomatic hypercalcemia. G-protein-coupled, calcium-sensing receptor (CaSR), vitamin D receptor (VDR), and fibroblast growth factor receptor (FGFR)/klotho complexes seem to be involved in the development of pHPT. Parathyroid glands from 53 patients with pHPT and normal parathyroid tissue from 7 patients were obtained during parathyroidectomy. Conventional detailed morphological and immunohistochemical analyses of parathyroid glands were performed after dividing each slide in a 3 × 3 array. From morphology, the number of lipocytes was significantly lower in parathyroid tissue glands in the pHPT group (p < 0.001). Protein expressions of klotho, CaSR, and VDR were significantly reduced in the pHPT compared with the control group (p = 0.004, p = 0.007, p < 0.001). No differences were seen between the two groups (p = 0.35) regarding expression of FGFR. Correlations between expression showed significant positively correlations between klotho and CaSR and FGFR and VDR. No correlations between klotho expression and serum calcium levels could be detected (R = -0.13, p = 0.66), but there were positive correlations between expressions of CaSR/serum phosphate and klotho/serum phosphate. Impaired protein expression of CaSR and VDR seem to be involved in the development of pHPT. The role of the FGFR/klotho-axis remains still unclear. Correlations between protein expression of CaSR and serum phosphate and klotho and serum phosphate levels could be detected. Whether these findings give new insights into the pathogenesis of the disease is yet unknown and has to be elucidated.

Inhibitory effects of human and porcine alpha-amylase on CCK-8-stimulated lipase secretion of isolated rat pancreatic acini.

Previously we have demonstrated inhibitory effects of the plant lectin wheat germ agglutinin (WGA) on (125)I-CCK-8 binding to pancreatic AR42J cells as well as on CCK-8-stimulated Ca(2+) release and alpha-amylase secretion of rat pancreatic acini or acinar cells. Therefore, it is entirely conceivable that alpha-amylase having several lectin-like carbohydrate recognition domains can modulate the CCK-8 stimulated lipase secretion. Human alpha-amylase, purified from pancreatic juice by affinity chromatography to homogeneity, and commercial porcine pancreatic alpha-amylase inhibit CCK-8-stimulated lipase secretion of rat pancreatic acini in a concentration-dependent manner. Acarbose, a specific inhibitor of alpha-amylase, was without effect on CCK-8-induced cellular lipase secretion. The data presented here provide evidence for a regulatory function of alpha-amylase in CCK-8-stimulated pancreatic secretion.