Living donor kidney transplantation in patients with donor-specific HLA antibodies enabled by anti-CD20 therapy and peritransplant apheresis

ObjectiveDue to increasing waiting times for deceased donor kidneys, living donor kidney transplantation is increasingly performed in the presence of donor-specific antibodies (DSA).MethodsTwenty-three patients with Luminex-detected DSA were successfully desensitized by anti-CD20 therapy and immunoadsorption (N = 19) or plasmapheresis (N = 4) and received a kidney transplant from a living donor. Twelve of the 23 patients (52%) had a positive CDC and/or ELISA crossmatch result before desensitization. Six patients were negative in CDC as well as ELISA screening but positive in Luminex for DSA.ResultsThe 23 patients received a median of 8 apheresis treatments before and 5 treatments after transplantation. Induction therapy was performed with either thymoglobulin (N = 11) or basiliximab (N = 12). The 2-year graft survival rate was 100%. At last follow up, a median of 12 months after transplantation, median serum creatinine was 1.42 mg/dL, median MDRD-GFR 59.5 mL/min/1.73 m², and median urinary protein-to-creatinine ratio 0.12. Ten out of fourteen patients (71%) who had completed the first year after transplantation by the time of analysis had no DSA by day 360. Acute T-cell mediated rejection was diagnosed in one patient (4%), and antibody-mediated changes were found in 5 patients (22%). Four out of these 5 patients showed evidence of persistent (N = 2) or reemerging plus/minus de novo DSA (N = 2) on day 360, and the 2 patients with persistent DSA lost their allograft subsequently on days 750 and 810, respectively. Infectious complications were infrequent.ConclusionsOur previously described treatment algorithm for desensitization of living donor kidney transplant recipients with DSA results in good graft outcomes with a low rate of side effects.     

Outcomes and complications following ABO‐incompatible kidney transplantation performed after desensitization by semi‐selective immunoadsorption ‐ a retrospective study

Because of the current organ shortage, ABO‐incompatible (ABOi) transplantations have been increasingly performed in recent years. The results seem comparable to those of compatible transplantations, but there have also been reports of increased side effects possibly because of the desensitization therapy. To address an increase in severe infectious complications, we compared the outcomes of 48 ABOi transplant recipients to outcomes of 96 matched ABO‐compatible (ABOc) controls transplanted at Heidelberg University Hospital from August 2005 to April 2018. Over a follow‐up period of 8 years, ABOi transplant recipients had comparable graft and patient survival as well as graft function compared with ABOc patients. T‐cell‐mediated and antibody‐mediated rejections were not different between groups. In ABOi transplant recipients, urosepsis (22.9% vs. 8.5%; P = 0.019) and pneumonia with opportunistic pathogens (8.3% vs. 1.0%, P = 0.025) appeared more frequently. As a consequence, a significantly higher number of deaths from infection have been observed after ABOi transplantations (6.3% vs. 0%, P = 0.010). High‐titer recipients (isoagglutinin titer of ≥1:256) showed a higher incidence of BK virus replication and postoperative bleeding complications. ABO‐incompatible transplantations can be performed with results that are not different from results after ABOc transplantations. However, an increased rate of serious infectious complications must be taken into account.     

Metabolic control improves long-term renal allograft and patient survival in type 1 diabetes

It is a matter of debate whether pancreas allografts independently contribute to renal allograft and patient survival in individuals who have type 1 diabetes and receive a simultaneous pancreas and kidney transplant (SPK). Using data from the Collaborative Transplant Study, we studied patients who had type 1 diabetes and were recipients of deceased-donor kidneys (DDK), living-donor kidneys (LDK), or SPK. We analyzed graft and patient survival rates with a maximum of 18 yr of follow-up. DDK recipients had inferior graft and patient survival compared with LDK and SPK recipients. LDK recipients had superior graft and patient survival rates initially, but SPK recipients demonstrated equal survival rates toward the end of follow-up. Multivariate analysis, adjusting for pretransplantation cardiovascular risk, showed that patient survival of SPK recipients was superior to that of LDK recipients beyond the 10th year after transplantation (hazard ratio 0.55; P = 0.005). In summary, the early survival advantage of LDK over SPK is lost during long-term follow-up, probably as a result of improved glycemic control in SPK recipients.     

Early Humoral Responses of Hemodialysis Patients after COVID-19 Vaccination with BNT162b2

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Transplantatnieren

Color Doppler sonography of the major transplant vessels and kidney parenchyma is a standard procedure in the perfusion diagnostics of kidney transplants. While conventional color Doppler sonography, e.g. in the diagnosis of arterial or venous transplant stenosis, is established as an essential technique which can be carried out quickly with high accuracy, the value of this method for perfusion is unfortunately very limited. Using contrast medium, a simple and rapid method is available which makes possible the early diagnosis of allograft nephropathy. The diagnosis of early vascular damage before the elevation of retention values offers the possibility of rapid therapeutic intervention and, thus, at least the possibility for improving transplant success.     

Pathogenesis of CNS involvement in disorders of amino and organic acid metabolism

Summary Inherited disorders of amino and organic acid metabolism have a high cumulative frequency, and despite heterogeneous aetiology and varying clinical presentation, the manifestation of neurological disease is common. It has been demonstrated for some of these diseases that accumulating pathological metabolites are directly involved in the manifestation of neurological disease. Various pathomechanisms have been suggested in different in vitro and in vivo models including an impairment of brain energy metabolism, an imbalance of excitatory and inhibitory neurotransmission, altered transport across the blood–brain barrier and between glial cells and neurons, impairment of myelination and disturbed neuronal efflux of metabolic water. This review summarizes recent knowledge on pathomechanisms involved in phenylketonuria, glutaric aciduria type I, succinic semialdehyde dehydrogenase deficiency and aspartoacylase deficiency with examples, highlighting general as well as disease-specific concepts and their putative impact on treatment. Competing interests: None declared References to electronic databases: Phenylketonuria: OMIM #261600. Glutaric aciduria type I: OMIM #231670. Succinic semialdehyde dehydrogenase deficiency: OMIM #271980. Aspartoacylase disease (Canavan–van Bogaert–Bertrand disease): OMIM #271900. Phenylalanine hydroxylase: EC 1.14.16.1. Glutaryl-CoA dehydrogenase: EC 1.3.99.7. Succinic semialdehyde dehydrogenase: EC 1.2.1.16. Aspartoacylase: EC 3.5.1.15. Presented at the Annual Symposium of the SSIEM, Hamburg, 4–7 September 2007     

The possible critical role of T‐cell help in DSA‐mediated graft loss

In this review, we discuss a possible central role of T‐cell help in severe forms of graft damage mediated by donor‐specific HLA antibodies (DSA). Some kidney transplant recipients with pretransplant DSA show a high graft failure rate, whereas in other patients DSA do not harm the transplanted kidney and in most cases, disappear shortly after transplantation. Analyzing 80 desensitized highly immunized kidney transplant recipients and another multicenter cohort of 385 patients with pretransplant HLA antibodies, we reported recently that an ongoing T‐cell help from an activated immune system, as measured by an increased level of soluble CD30 in serum, might be necessary for the DSA to exert a deleterious effect. Patients positive for both pretransplant DSA and sCD30 appear to require special measures, such as the elimination of DSA from the circulation, potent immunosuppression, good HLA‐matching, and intense post‐transplant monitoring, whereas exclusion of DSA‐positive patients from transplantation in the absence of high sCD30 may not be justified in all cases, even if the pretransplant DSA are strong and complement‐activating.     

Structure-function relationship of cytokine induction by lipoteichoic acid from Staphylococcus aureus

Lipoteichoic acids (LTAs) have been proposed as putative Gram-positive immunostimulatory counterparts to Gram-negative lipopolysaccharides. However, LTA from Staphylococcus aureus, the clinically most frequent Gram-positive pathogen, was inactive after purification. Here, a novel isolation procedure to prepare pure (>99%) biologically active LTA, allowing the first structural analysis by nuclear magnetic resonance and mass spectrometry, is described. A comparison with LTA purified by standard techniques revealed that alanine substituents are lost during standard purification, resulting in attenuated cytokine induction activity. In line with this finding, hydrolysis of alanine substituents of active LTA decimated cytokine induction. LTA represents a major immunostimulatory component of S. aureus.