Impact of G-CSF Therapy on Leukopenia and Acute Rejection Following Kidney Transplantation.

BACKGROUND: Leukopenia is a common problem after kidney transplantation. The therapeutic approach typically includes a reduction of the immunosuppressive therapy, which is associated with an increased risk of rejection and allograft loss. Granulocyte colony-stimulating factor (G-CSF) is used as a therapeutic option to raise the leukocyte blood count; however, the effect on acute rejections is controversial. OBJECTIVE: The goal of this study is to examine the incidence of acute rejections following G-CSF therapy. METHODS: We retrospectively evaluated patients with leukopenia following kidney transplantation and GCSF therapy between January 2007 and December 2017 at our center compared to controls with matched minimal leucocyte blood count in a matched pair analysis. RESULTS: We identified 12 patients, who received G-CSF therapy with a cumulative dose of 10.74 µg/kg body weight over a time frame of 4.3 days. G-CSF therapy resulted in a significantly shorter time period with leucocytes <3,000/µL (9.5 vs. 16.6 days), but also trended towards an increased risk of rejection within the next 30 days with three patients in the G-CSF group and no patient in the control group (p=0.06) developing an acute biopsy-proven rejection. Infection and mortality rate in the subsequent year were not different between groups. CONCLUSION: G-CSF therapy decreases the duration of leukopenia post-kidney transplantation, but may also increase the risk of an acute rejection.

Consensus on definition and severity grading of lymphatic complications after kidney transplantation.

BACKGROUND: The incidence of lymphatic complications after kidney transplantation varies considerably in the literature. This is partly because a universally accepted definition has not been established. This study aimed to propose an acceptable definition and severity grading system for lymphatic complications based on their management strategy. METHODS: Relevant literature published in MEDLINE and Web of Science was searched systematically. A consensus for definition and a severity grading was then sought between 20 high-volume transplant centres. RESULTS: Lymphorrhoea/lymphocele was defined in 32 of 87 included studies. Sixty-three articles explained how lymphatic complications were managed, but none graded their severity. The proposed definition of lymphorrhoea was leakage of more than 50 ml fluid (not urine, blood or pus) per day from the drain, or the drain site after removal of the drain, for more than 1 week after kidney transplantation. The proposed definition of lymphocele was a fluid collection of any size near to the transplanted kidney, after urinoma, haematoma and abscess have been excluded. Grade A lymphatic complications have a minor and/or non-invasive impact on the clinical management of the patient; grade B complications require non-surgical intervention; and grade C complications require invasive surgical intervention. CONCLUSION: A clear definition and severity grading for lymphatic complications after kidney transplantation was agreed. The proposed definitions should allow better comparisons between studies.

ANTECEDENTES: La incidencia de complicaciones linfáticas tras el trasplante renal (post-kidney-transplantation lymphatic, PKTL) varía considerablemente en la literatura. Esto se debe en parte a que no se ha establecido una definición universalmente aceptada. Este estudio tuvo como objetivo proponer una definición aceptable para las complicaciones PKTL y un sistema de clasificación de la gravedad basado en la estrategia de tratamiento. MÉTODOS: Se realizó una búsqueda sistemática de la literatura relevante en MEDLINE y Web of Science. Se logró un consenso para la definición y la clasificación de gravedad de las PKTL entre veinte centros de trasplante de alto volumen. RESULTADOS: En 32 de los 87 estudios incluidos se definía la linforrea/linfocele. Sesenta y tres artículos describían como se trataban las PKTL, pero ninguno calificó la gravedad de las mismas. La definición propuesta para la linforrea fue la de un débito diario superior a 50 ml de líquido (no orina, sangre o pus) a través del drenaje o del orificio cutáneo tras su retirada, más allá del 7º día postoperatorio del trasplante renal. La definición propuesta para linfocele fue la de una colección de líquido de tamaño variable adyacente al riñón trasplantado, tras haber descartado un urinoma, hematoma o absceso. Las PKTL de grado A fueron aquellas con escaso impacto o que no requirieron tratamiento invasivo; las PKTL de grado B fueron aquellas que precisaron intervención no quirúrgica y las PKTL de grado C aquellas en que fue necesaria la reintervención quirúrgica. CONCLUSIÓN: Se propone una definición clara y una clasificación de gravedad basada en la estrategia de tratamiento de las PKTLs. La definición propuesta y el sistema de calificación en 3 grados son razonables, sencillos y fáciles de comprender, y servirán para estandarizar los resultados de las PKTL y facilitar las comparaciones entre los diferentes estudios.

Magnetic Ureteral Stents Are Feasible in Kidney Transplant Recipients: A Single-Center Experience.

BACKGROUND: Insertion of ureteral catheters is a common procedure in kidney transplantation. The stent is usually removed by cystoscope. Magnetic ureteral stents may be an alternative to conventional stents. OBJECTIVE: To assess the functional efficacy and feasibility of magnetic double J (DJ) stents in kidney transplant recipients. METHODS: We used 6 Fr (diameter), 22 cm (length) magnetic DJs. We examined 7 cases of exclusively AB0-identical living donations. Stent were removed 10-12 days after transplantation. Ureteral Stent Symptoms Questionnaire (USSQ) and visual analog scale (VAS) were used to determine quality of life and pain of the recipients. The total removal time was recorded and cost reduction was calculated. RESULTS: Removal of the magnetic DJ was successful in all cases. The mean±SD duration of the removal was 3.4±1.6 min. The mean±SD overall pain score on the VAS during the procedure was 2.6±1.1. Using this technique was associated with a cost reduction of € 130. CONCLUSION: Using magnetic ureteral stents is a feasible option for living donation AB0-identical kidney transplant recipients.

Telemedically Supported Case Management of Living-Donor Renal Transplant Recipients to Optimize Routine Evidence-Based Aftercare: A Single-Center Randomized Controlled Trial.

Improving mid-term and long-term outcomes after solid organ transplantation is imperative, and requires both state-of-the-art transplant surgery and optimization of routine, evidence-based aftercare. This randomized, controlled trial assessed the effectiveness of standard aftercare versus telemedically supported case management, an innovative aftercare model, in 46 living-donor renal transplant recipients during the first posttransplant year. The model includes three components: (i) chronic care case management initiated after discharge, (ii) case management initiated in emerging acute care situations, and (iii) a telemedically equipped team comprising a transplant nurse case manager and two senior transplant physicians (nephrologist, surgeon). Analyses revealed a reduction of unplanned inpatient acute care, with considerable cost reductions, in the intervention group. The prevalence of nonadherence over the 1-year study period was 17.4% in the intervention group versus 56.5% in the standard aftercare group (p = 0.013). Only the intervention group achieved their pre-agreed levels of adherence, disease-specific quality of life, and return to employment. This comparative effectiveness study provides the basis for multicenter study testing of telemedically supported case management with the aim of optimizing posttransplant aftercare. The trial was registered with the German Clinical Trials Register (www.DRKS.de), DKRS00007634.

Analyzing the success of T-matrix diagrammatic theories in representing a modified Hubbard model.

We present a systematic study of various forms of renormalization that can be applied in the calculation of the self-energy of the Hubbard model within the T-matrix approximation. We compare the exact solutions of the attractive and repulsive Hubbard models, for linear chains of lengths up to eight sites, with all possible taxonomies of the T-matrix approximation. For the attractive Hubbard model, the success of a minimally self-consistent theory found earlier in the atomic limit (Verga et al 2005 Phys. Rev. B 71 155111) is not maintained for finite clusters unless one is in the very strong correlation limit. For the repulsive model, in the weak correlation limit at low electronic densities-that is, where one would expect a self-consistent T-matrix theory to be adequate-we find the fully renormalized theory to be most successful. In our studies we employ a modified Hubbard interaction that eliminates all Hartree diagrams, an idea which was proposed earlier (Zlatic et al 2000 Phys. Rev. B 63 035104).

Rapidly progressive hepatic alveolar echinococcosis in an ABO-incompatible renal transplant recipient.

We report on the case of an ABO-incompatible renal re-transplant recipient maintained on an intensified immunosuppressive regimen for recurrent cellular rejection episodes and transplant glomerulopathy who presented with rapidly growing hepatic tumors, radiologically suggestive of hemangiosarcoma. Upon resection and pathological work-up, the lesions revealed alveolar echinococcosis, a rare but potentially life-threatening parasitosis. Usually infection with Echinococcus multilocularis remains asymptomatic for extended periods of time and can go unrecognized for years. In the case presented, we observed an atypically rapid growth pattern of E. multilocularis that might have been due to the extent of the immunosuppressive regimen, which included repetitive anti-CD20 treatments. Retrospectively performed serological studies with enzyme-linked immunosorbent assays known to provide high sensitivity and specificity for the detection of echinococcosis in the general population, yielded ambiguous results in our immunocompromised host, which could be, in part, explained by B-cell depletion and its effects on antibody production and indirect actions on cellular immunity. In conclusion, this is the first report to our knowledge of hepatic alveolar echinococcosis in a renal transplant recipient. This case documents an altered clinical course of the parasitosis and the challenge of serological diagnostic tools under an intensified regimen of immunosuppressive agents, including rituximab.

ABO-incompatible kidney transplantation with antigen-specific immunoadsorption and rituximab - insights and uncertainties.

Several protocols have been developed to effectively overcome the blood group barrier in renal transplantation. In the evolution of these protocols, one of the latest steps was the combination of anti-CD20 treatment with antigen-specific immunoadsorptions. Over the last years we have learned that these relatively new protocols carry very promising short-term and intermediate-term results which compare favorably to the outcome of ABO-compatible living donor transplantations. Latest reports suggest that combining immunoadsorptions with rituximab does not result in an increased risk of infectious complications or tumors in the first years after transplantation compared to ABO-compatible living donor transplantations. We recently demonstrated that a majority of patients with isoagglutinin titers >1:128 can be safely transplanted using rituximab and immunoadsorptions without an added risk of early antibody-mediated rejections. We have also shown that a cost saving 'on-demand strategy' of postoperative immunoadsorptions based on careful titer monitoring can be used as an alternative to preemptively scheduled immunoadsorptions. Although rituximab and antigen-specific immunoadsorptions are significantly less invasive than splenectomy and plasma-pheresis, long-term follow-up of patients treated with a combination of anti-CD20 antibody and antigen-specific immunoadsorption will be needed to benchmark this therapeutic option in relation to more established protocols.

Immunosuppression in pancreas transplantation: the Euro SPK trials and beyond.

The Immunosuppression in Pancreas Transplantation was historically based on the fact that the pancreas is an extremely immunogenic organ. Quadruple drug therapy with polyclonal or monoclonal antibodies induction was the mainstay therapy since the introduction of Cyclosporine A. In the modern era of Immunosuppression, Mycophenolate Mofetil replaced Azathioprine while Tacrolimus-another potent calcineurin inhibitor-had-and still has-a difficult challenge to replaced Cyclosporine A, due to its potential diabetogenic effect. Thanks to the first two EuroSPK studies which prospectively tried to answer several questions in that field. But, the future challenge will be in understanding the impact of innate immunity and ischemic reperfusion injuries on the long-term graft function. Hopefully, new drugs will be available and tested to block unspecific deleterious reactions to attenuate the proinflammatory response. It will be the aim of the third Euro SPK Study.

[Kidney transplantation with simultaneous nephrectomy: inappropriate or sensible?]. / Krankes Organ entfernen oder nicht?

In conventional single kidney transplantation, the patient's kidneys are left in place. However, in certain patient collectives, the removal of the kidney may be indicated under some circumstances. This applies especially to patients whose own kidney may be a source of infection, bleeding, severe proteinuria and physical impairment due to a considerable increase in the kidney volume (cystic kidneys). Up until now, the procedure planned for either a bilateral nephrectomy after inclusion on the waiting list or a sequential procedure, which involves nephrectomy of one kidney and the removal of the other after kidney transplantation (sandwich technique). The concept presented here, kidney transplantation with concomitant ipsilateral nephrectomy is a safe procedure that leads to neither a significant increase in the incidence of surgical complications nor to a decrease in patient-and transplant survival. The major advantage of this method, in addition to a high measure of patient satisfaction, is the definitive surgical restoration of the kidney transplant recipient on the transplanted side with only one surgical intervention.

Reduced-exposure cyclosporine is safe and efficacious in de novo renal transplant recipients treated with enteric-coated mycophenolic acid and basiliximab.

BACKGROUND: The lower limit of exposure to calcineurin inhibitors has not yet been established in de novo renal transplant patients receiving mycophenolic acid therapy with basiliximab. METHODS: A 12-month, multicenter, randomized, open-label trial was carried out in which de novo renal transplant patients received enteric-coated mycophenolate sodium, cyclosporine microemulsion, steroids and basiliximab. Patients were randomized to receive standard-exposure (n = 45) or reduced-exposure (n = 44) cyclosporine, based on differing C2 target ranges, after the first month post-transplant. RESULTS: Cyclosporine exposure gradually increased over the first month and was lower than previously recommended. Mean calculated creatinine clearance (primary end-point) was similar in the standard-exposure and reduced-exposure groups at month 6 (55.3+/-3.2 ml/min and 61.5+/-3.7 ml/min respectively, n.s.). There were 4 deaths but no death-censored graft losses, resulting in 95.5% patient and graft survival at one year in both groups. At 6 and 12 months, the incidence of biopsy-proven acute rejection was 17.8% and 17.8% in the standard-exposure group, and 13.6% and 15.9% in the reduced-exposure group. Adverse events were similar between treatment groups. Exploratory analyses could not identify a lower limit for the optimal CsA exposure range, but results suggested that high exposure at one year was associated with deteriorating renal function. CONCLUSIONS: These results indicate that enteric-coated mycophenolate sodium with reduced-exposure cyclosporine, steroids and basiliximab induction has an excellent therapeutic effect and is safe in de novo kidney transplant recipients. Lower C2 targets than previously recommended, particularly early post-transplant, do not appear to be associated with compromised efficacy.

Cure of ventriculitis and central nervous system shunt infection by Staphylococcus epidermidis with vancomycin by intraventricular injection in a liver transplant recipient.

A 19-year-old female underwent orthotopic liver transplantation for acute hepatic failure because of fulminant Wilson's disease. Three months post transplantation she developed systemic fungal meningoencephalitis and obstructive hydrocephalus that required cerebrospinal fluid (CSF) shunting by a ventriculo-atrial shunt. Subsequently, she contracted Staphylococcus epidermidis bacteremia, ventriculitis, and shunt infection. Treatment with vancomycin either by conventional intravenous (i.v.) or continuous i.v. injection proved ineffective because of insufficient drug concentrations in the CSF. Eradication of S. epidermidis from CSF and cure of chronic ventriculitis and shunt infection was readily achieved by delivering vancomycin by intraventricular injection (5 mg/24 h) via an extraventricular drain together with continuous i.v. infusion (4 g/24 h) over a period of 18 days. This treatment was well tolerated and free of untoward side effects despite the patient's chronic immunosuppression subsequent to liver transplantation. Intraventricular injection of vancomycin is an effective and safe procedure to eradicate S. epidermidis from the central nervous system when i.v. vancomycin treatment fails.

Successful transplantation of kidneys from a donor with myoglobinuric acute renal failure.

The shortage of donor organs is reflected in the growing number of patients on the waiting list for kidney transplantation worldwide. It seems to be sensible to expand the scarce donor pool by the cautious use of extended donor criteria. Kidneys from a 21-year-old deceased donor road traffic accident victim who suffered acute renal failure (ARF) due to myolysis were transplanted. Both transplantations were successful after an initial period of delayed graft function. Therefore, kidneys from deceased donors with ARF should not be excluded for transplantation in general.

Careful clinical monitoring in comparison to sequential Doppler sonography for the detection of acute rejection in the early phase after renal transplantation.

Acute rejection is the most frequent cause of early graft failure. There is unanimity that Doppler sonography is a helpful method for the detection of complications after kidney transplantation. In the past, the indication for renal biopsy relied mainly on clinical assessment, although this assessment has not been standardised. Therefore, we conducted this prospective study to compare the value of sequential Doppler measurements with a standardised clinical rejection score, based on renal function, weight gain, graft swelling and tenderness. Fifty-eight patients (37 males, 21 females, mean age 46 +/- 12 years) after kidney transplantation were consecutively enrolled into the study. Doppler investigations were obtained within the first 24 h after transplantation, followed by an interval of 48-72 h. At the same time, a clinical examination was scored by a transplant physician blinded to the Doppler results. Clinical score and Doppler results, both were referred to the histological results of renal biopsy. In 24 out of 58 patients 25 acute rejections occurred. In seven patients, acute rejection was superimposed on primary graft failure. The cut-off levels for rejection were set at RI > or = 0.80 and PI > or = 1.70 based on receiver-operator curves using data from 663 Doppler examinations. Sensitivity and specificity was 72% for RI, and 72% and 74% for PI, respectively. The calculation of the intraindividual increase (deltaRI > or = 3%, deltaPI > or = 10%) did not improve these values. The clinical score revealed a sensitivity and specificity of 82% and 87%, respectively. The combined analysis of Doppler indices and clinical score showed a sensitivity of 96% with a specificity of 66%. Careful clinical monitoring alone using a clinical score is an appropriate procedure with which to decide about renal biopsy. Our data show that Doppler sonography should be performed within the first 24 h after transplantation to evaluate graft perfusion and baseline values. Afterwards, it should be used when clinical signs of rejection occur to underline the decision for renal biopsy even in borderline cases.

[Kidney donation by living donors. Surgical procedure]. / Die Nierenlebendspende. Chirurgische Vorgehen.

The living donation of kidneys is gaining importance as a possible way to give a transplant to patients with terminal renal insufficiency. However we do not yet have experience with all the possibilities arising from this method. In particular, there is caution caused by the risks of the donor operation. In this context, the method is discussed according to the literature and our own experience of 89 living kidney donations. In our own practice with living donations, we have a success rate with 96% after 4 years and 82% after 16 years. We observed complications including wound infections (10.7%), haemorrhage, hernia and neurological complications (each 2.7%). When performed by specialists, the donor operation is safe and is a responsible alternative to the transplantation of cadaver kidneys, which opens up new possibilities in these times of organ shortage.

Unusual cause of early graft dysfunction after kidney transplantation.

BACKGROUND/AIMS: Transplant renal artery stenosis usually develops in the later period after renal transplantation and is usually due to atherosclerosis and fibrosis at the anastomosis. A kinking renal artery stenosis, however, is a rare cause of early graft dysfunction. METHODS: In a 34-year-old-man early graft failure developed within 1 week after kidney transplantation. In the presence of histologically proven ischemic damage an arterial kinking stenosis was diagnosed by color Doppler sonography. Selective arteriography confirmed the sharp kinking of the transplant renal artery; however, a significant stenosis could not be visualized by arteriography. RESULTS: Due to progressive loss of renal function surgical resection of scar tissue in the kink of the transplant artery and nephropexy was performed. Immediately thereafter graft function and blood pressure significantly improved so that the successful clinical outcome of this unusual case of early graft failure confirmed the relevance of the arterial kinking stenosis. CONCLUSIONS: In this unusual case of early graft dysfunction relevant kinking renal artery stenosis could not be adequately visualized by arteriography, although color Doppler sonography clearly demonstrated the stenosis. Therefore, both methods should be considered if parenchymal causes of graft dysfunction are excluded by biopsy and a kinking renal artery stenosis is suspected.