Surgical site infections after simultaneous pancreas kidney and pancreas transplantation in the Swiss Transplant Cohort Study.

BACKGROUND: Among hospital-acquired infections, surgical site infections (SSIs) are frequent. SSI in the early post-transplant course poses a relevant threat to transplant recipients. AIM: To determine incidence, risk factors for SSI and its association with post-transplant outcomes and pancreas transplant (P-Tx) recipients. METHODS: Adult simultaneous kidney-pancreas transplantation (SPK-T) and P-Tx recipients with a follow-up of at least 90 days were identified in the Swiss Transplant Cohort Study (STCS) dataset. Except for the categorization of SSIs according to Centers for Disease Control and Prevention (CDC) criteria, all other data were prospectively collected. Risk factors for SSI were investigated with logistic regression. A Weibull accelerated failure-time model was applied to address the impact of SSI on length of stay, correcting for transplant-related complications and delayed graft function. FINDINGS: Of 130 transplant recipients, 108 SPK-Tx and 22 P-Tx, 18 (14%) individuals developed SSI within the first 90 days after transplantation. Deep incisional (seven, 38.9%) and organ/space infections (eight, 44.4%) predominated. In the majority of SSIs (11, 61.1%; two SSIs with simultaneous identification of fungal pathogens) bacteria were detected with Enterococcus spp. being most frequent. The median duration of hospitalization after transplantation was significantly longer in recipients with SSI (median: 26 days; interquartile range (IQR): 19-44) than in patients without SSI (median: 17 days; IQR: 12-25; P = 0.002). In multivariate analysis, SSI was significantly associated with increased length of stay and prolonged the duration of hospitalization by 36% (95% confidence interval: 4-79). CONCLUSION: SSI after SPK-Tx and P-Tx occurred at a frequency of 14%. Among pathogens, Enterococcus spp. predominated. SSI was independently associated with a longer hospitalization after transplantation.

Donor Specificity but Not Broadness of Sensitization Is Associated With Antibody-Mediated Rejection and Graft Loss in Renal Allograft Recipients.

Panel-reactive antibodies are widely regarded as an important immunological risk factor for rejection and graft loss. The broadness of sensitization against HLA is most appropriately measured by the "calculated population-reactive antibodies" (cPRA) value. In this study, we investigated whether cPRA represent an immunological risk in times of sensitive and accurate determination of pretransplantation donor-specific HLA antibodies (DSA). Five hundred twenty-seven consecutive transplantations were divided into four groups: cPRA 0% (n = 250), cPRA 1-50% (n = 129), cPRA 51-100% (n = 43), and DSA (n = 105). Patients without DSA were considered as normal risk and received standard immunosuppression without T cell-depleting induction. Patients with DSA received an enhanced induction therapy and maintenance immunosuppression. Surveillance biopsies were performed at 3 and 6 months. Median follow-up was 5.7 years. Among the three cPRA groups, there were no differences regarding the 1-year incidence of ABMR (p = 0.16) and TCMR (p = 0.75). The 5-year allograft survival rates were similar and around 87% (p = 0.28). The estimated glomerular filtration rate at last follow-up was 50-53 mL/min (p = 0.45). On multivariable Cox proportional hazard analysis, the strongest independent predictor for ABMR and (death-censored) graft survival was pretransplantation DSA. cPRA were not predictive for ABMR, TCMR, or (death-censored) graft survival. We conclude that with current DSA assignment, the broadness of sensitization measured by cPRA does not imply an immunological risk.

A Comparison of Two Types of Rabbit Antithymocyte Globulin Induction Therapy in Immunological High-Risk Kidney Recipients: A Prospective Randomized Control Study.

BACKGROUND: Induction treatment with rabbit polyclonal antithymocyte globulins (ATGs) is frequent used in kidney transplant recipients with donorspecific HLA antibodies and shows acceptable outcomes. The two commonly used ATGs, Thymoglobulin and ATG-F have slightly different antigen profile and antibody concentrations. The two compounds have never been directly compared in a prospective trial in immunological high-risk recipients. Therefore we performed a prospective randomized controlled study comparing the two compounds in immunological high-risk kidney recipients in terms of safety and efficacy. METHODS: Immunological high-risk kidney recipients, defined as the presence of HLA DSA but negative CDC-B and T-cell crossmatches were randomized 1:1 to receive ATG-F or Thymoglobulin. Maintenance immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil and steroids. RESULTS: The per-protocol analysis included 35 patients. There was no immediate infusion reaction observed with both compounds. No PTLD or malignancy occurred during the follow-up in both groups. The incidence of viral and bacterial infections was similar in both groups (p = 0.62). The cumulative incidence of clinical and subclinical antibody mediated allograft rejection as well as T-cell mediated allograft rejection during the first year between ATG-F and Thymoglobulin was similar (35% versus 19%; p = 0.30 and 11% versus 18%; 0.54 respectively). The two-year graft function was similar with a median eGFR of 56 ml/min/1.73m2 (range 21-128) (ATG-F-group) and 51 ml/min/1.73m2 (range 22-132) (Thymo-group) (p = 0.69). CONCLUSION: We found no significant differences between the compared study drugs for induction treatment in immunological high-risk patients regarding safety and efficacy during follow-up with good allograft function at 2 years after transplantation.

Mechanism of Platelet Activation and Hypercoagulability by Antithymocyte Globulins (ATG).

T cell depletion with antithymocyte globulins (ATG) can be complicated by thrombopenia and hypercoagulability. The underlying mechanism is still unclear. We found that binding of ATG to platelets caused platelet aggregation, α-granule release, membrane phosphatidylserine exposure and the rapid release of procoagulant platelet microvesicles (MV). Platelet activation and MV release were complement-dependent and required membrane insertion of C5b-8 but not stable lytic pore formation by C5b-9. ATG also activated platelets via binding to the low-affinity Fc gamma receptor FcγRII. However, only complement inhibition but not blockade of FcγRII prevented MV release and subsequent thrombin activation in plasma. In 19 hematopoietic stem cell and kidney transplant patients, ATG treatment resulted in thrombopenia and increased plasma levels of d-dimer and thrombin-antithrombin complexes. Flow cytometric analysis of complement fragments on platelet MV in patient plasma confirmed dose-dependent complement activation by ATG. However, the rapid rise in MV numbers observed in vitro was not seen during ATG treatment. In vitro experiments suggested that this was due to adherence of C3b-tagged MV to red blood cells via complement receptor CR1. These data suggest a clinically relevant link between complement activation and thrombin generation and offer a potential mechanism underlying ATG-induced hypercoagulability.

High incidence of rejection episodes and poor tolerance of sirolimus in a protocol with early steroid withdrawal and calcineurin inhibitor-free maintenance therapy in renal transplantation: experiences of a randomized prospective single-center study.

Immunosuppressive maintenance therapy after kidney transplantation leads to various undesired side effects such as calcineurin inhibitor (CNI)-associated nephrotoxicity or elevated cardiovascular risk due to posttransplantation diabetes and hypertension. These effects show negative impacts on long-term allograft function as well as patient morbidity and mortality. Therefore, we used an immunosuppressive regimen with early corticosteroid withdrawal (ESW), maintenance therapy containing tacrolimus, sirolimus (SRL), and mycophenolate sodium for 3 months followed by a prospective randomized trial comparing a CNI free versus a low-dose CNI therapy. The primary endpoint was 6-month graft function. Among 75 patients, ESW was performed after 4 days in 65 patients. Over the following 3 months before randomization to CNI-free maintenance therapy, we experienced a high number (25%) of SRL discontinuations due to adverse events, including leukopenia, anemia, arthritis, and pneumonitis. In addition there were significantly more allograft rejection episodes in the CNI-free group (P = .017) during the study period leading to a switch from SRL to a CNI. Despite the higher rate of rejection episodes in the CNI-free groups, glomerular filtration rates (GFR) at 6 months were comparable between the study groups (P = .25). After 1 year only 9.2% (6/65) of all patients treated with SRL remained on this drug. Conclusion, there was an unacceptably high rate of SRL intolerance using an ESW and CNI-free immunosuppressive regimen combined with a significantly higher rate of rejection episodes.

[Fever, coughing and dyspnea in a 38-year-old female kidney transplant recipient]. / Fieber, Husten und Dyspnoe bei einer nierentransplantierten 38-jährigen Patientin.

This article reports on a 38-year-old kidney transplant patient who presented with fever, coughing and dypnea. The patient was immunosuppressed with mycophenolate and prednisone. Due to the suspicion of community acquired pneumonia antibiotic treatment was initiated and the patient was admitted to the intensive care unit. Despite antibiotic treatment the condition did not improve and in the subsequently performed bronchioalveolar lavage parainfluenza virus was diagnosed.Infections with respiratory viruses can be fatal in immunosuppressed patients. Human parainfluenza virus is the third most common pathogen of viral pneumonia. Molecular genetic detection methods allow fast and sensitive diagnosis of respiratory materials. As the treatment options are limited for these infections prophylactic measurements are important.

Detection of clinical and subclinical tubulo-interstitial inflammation by the urinary CXCL10 chemokine in a real-life setting.

Urinary CXCL10 is a promising noninvasive biomarker for tubulo-interstitial allograft inflammation, but its diagnostic characteristics have not been assessed in a real-life setting. We investigated urinary CXCL10 in 213 consecutive renal allograft recipients having 362 surveillance biopsies at 3/6 months and 80 indication biopsies within the first year posttransplant. Allograft histology results were classified as (i) acute Banff score zero, (ii) interstitial infiltrates only, (iii) tubulitis t1, (iv) tubulitis t2-3 and (v) isolated vascular compartment inflammation. For clinical and subclinical pathologies, urinary CXCL10 correlated well with the extent of tubulo-interstitial inflammation. To determine diagnostic characteristics of urinary CXCL10, histological groups were separated into two categories: no relevant inflammation (i.e. acute Banff score zero and interstitial infiltrates only) versus all other pathologies (i.e. tubulitis t1-3 and isolated vascular compartment inflammation). For subclinical pathologies, AUC was 0.69 (sensitivity 61%, specificity 72%); for clinical pathologies, AUC was 0.74 (sensitivity 63%, specificity 80%). A urinary CXCL10-guided biopsy strategy would have reduced performance of surveillance and indication biopsies by 61% and 64%, respectively. Missed (sub)clinical pathologies were mostly tubulitis t1 and isolated vascular compartment lesions. In real life, urinary CXCL10 had clinically useful diagnostic properties making it a candidate biomarker to guide allograft biopsies.

[Management of renal anemia in patients with chronic kidney disease: the role of the general practitioner]. / Prise en charge de l'anémie chez les patients atteints de maladie renale chronique: rôle du médecin gênéraliste.

The prevalence of chronic kidney disease (CKD) is high and diabetic nephropathy is a leading cause of CKD. One of the most common complications of CKD is anemia, the frequency and severity of which increase as kidney failure progresses. Renal anemia is primarily caused by reduced renal erythropoietin production. It can also be associated with iron deficiency caused by reduced iron absorption, occult blood loss and impaired iron mobilization. This work provides an overview of the management of renal anemia with focus on intravenous iron therapy, which is more effective than oral iron administration in CKD due to reduced iron absorption.

Is monitoring of FOXP3 Treg cells in renal transplants during acute cellular rejection episodes useful?

BACKGROUND: The FOXP3 (forkhead Box p3) transcription factor is a marker for T regulatory cells (Treg). During cellular immune responses, Treg are expected to increase in number to ultimately control and limit this response. In renal transplants massive infiltration by T cells is often seen during rejection crises. This prompted us to examine changes in the numbers of FOXP3 positive T cells accompanying acute cellular rejection events. METHODS: A total of 32 transplant biopsies from 23 patients were studied retrospectively, these 16 protocol biopsies and 16 biopsies taken during rejection episodes included 9 serial pairs (protocol-rejection). To quantify FOXP3 positive T cells, frozen sections were double immunostained with anti-CD3 and anti-FOXP3 antibodies. Areas revealing T cell infiltrates were measured morphometrically and the number of FOXP3 positive cells per 1,000 µm2 of CD3 positive cells was taken as an FOXP3 index. RESULTS: This index was 0.46 (median, range 0.00-1.00) in the 16 protocol biopsies and 0.48 (median, range 0.16-2.31) in rejection episode biopsies. The highest values were seen during rejection crises, exceeding 1.00 in 6/16 biopsies, whereas no protocol biopsies had values greater than 1.00 (0/16) (difference significant p<0.02). In serial biopsies no consistent behavior was observed; the FOXP3 index remained unchanged, fell slightly or rose to a maximum of 13 fold. Expression levels of FOXP3 could vary within weeks. No correlations were found between donor type, initial therapy, therapy at biopsy, serum creatinine at the time of biopsy, at 3 months or 1 year later, and any of the morphometric parameters (CD3 and FOXP3) studied. CONCLUSIONS: During rejection of renal allografts the fraction of FOXP3+ Treg cells within the infiltrating T-cell population can increase transiently. This phenomenon was not consistently seen in acute cellular rejection and the information does not appear to be of value for individual patient management in such cases.

Reducing immunosuppression preserves allograft function in presumptive and definitive polyomavirus-associated nephropathy.

Early detection of polyomavirus BK (BKV) viremia and reduction of immunosuppression is recommended for preventing polyomavirus-associated nephropathy (PyVAN), but systematic histological evaluations were not performed in previous studies. We routinely screen for decoy cells and, if positive, measure plasma BKV-loads. In a cohort of 203 consecutive renal transplantations performed from 2005-2008, 38 patients (19%) developed BKV-viremia and were treated with reduction of immunosuppression. Based on subsequent allograft biopsy results and peak BKV-viremia, patients were assigned to three groups: (i) definitive PyVAN (n = 13), (ii) presumptive PyVAN defined by plasma BKV-loads of ≥ 4 log(10) copies/ml (n = 17) and (iii) low BKV-viremia (n = 8). Clearance of BKV-viremia was achieved in 35/38 patients (92%) and subsequent clinical rejection occurred in 3/35 patients (8.6%), both without any difference among the groups. Patients with definitive PyVAN had higher peak plasma BKV-loads and required longer time for clearance (8.8 vs. 4.6 vs. 2.9 months; p = 0.001). However, allograft function remained stable from baseline to last follow-up at 34 months (range 18-60) in all three groups with median serum creatinine of 1.6 mg/dl, 1.6 mg/dl and 1.3 mg/dl, respectively. We conclude that screening for BKV-replication and reduction of immunosuppression is an effective strategy to preserve medium-term allograft function even in patients developing definitive PyVAN.

Parameters for successful monthly extended dosing of darbepoetin-alpha in patients undergoing hemodialysis.

AIM: To document the feasibility and report the results of dosing darbepoetin-alpha at extended intervals up to once monthly (QM) in a large dialysis patient population. MATERIAL: 175 adult patients treated, at 23 Swiss hemodialysis centres, with stable doses of any erythropoiesis-stimulating agent who were switched by their physicians to darbepoetin-alpha treatment at prolonged dosing intervals (every 2 weeks [Q2W] or QM). METHOD: Multicentre, prospective, observational study. Patients' hemoglobin (Hb) levels and other data were recorded 1 month before conversion (baseline) to an extended darbepoetin-alpha dosing interval, at the time of conversion, and once monthly thereafter up to the evaluation point (maximum of 12 months or until loss to follow-up). RESULTS: Data for 161 evaluable patients from 23 sites were included in the final analysis. At 1 month prior to conversion, 73% of these patients were receiving darbepoetin-alpha weekly (QW) and 27% of the patients biweekly (Q2W). After a mean follow-up of 9.5 months, 34% received a monthly (QM) dosing regimen, 52% of the patients were receiving darbepoetin-alpha Q2W, and 14% QW. The mean (SD) Hb concentration at baseline was 12.3 +/- 1.2 g/dl, compared to 11.9 +/- 1.2 g/dl at the evaluation point. The corresponding mean weekly darbepoetin-alpha dose was 44.3 +/- 33.4 microg at baseline and 37.7 +/- 30.8 microg at the evaluation point. CONCLUSIONS: Conversion to extended darbepoetin-alpha dosing intervals of up to QM, with maintenance of initial Hb concentrations, was successful for the majority of stable dialysis patients.

Reluctance over right-sided retroperitoneoscopic living donor nephrectomy: justified or not?

UNLABELLED: We retrospectively compared perioperative donor outcomes and early complication rate of right- and left-sided retroperitoneoscopic living donor nephrectomy (RLDN). METHODS: From November 2001 to April 2006, we performed 118 RLDN. Including 24% (n = 28) right-sided RLDN and 76% (n = 90) left-sided RLDN. Perioperative results and the rate of adverse events were compared for both sides. RESULTS: We observed no significant difference in operation time, blood loss, warm ischemia time, or postoperative creatinine levels between right- and left-sided kidney donors. RLDN was successfully performed in 116 of 118 donors. One donor in each group had to be converted to an open approach. We observed one graft loss due to renal artery kinking in one recipient after left-sided RLDN. Two right donations needed a saphenous venous patch due to a short right renal vein (<2 cm). Overall, intraoperative and postoperative complications were comparable between the two donor groups. CONCLUSION: Right-sided RLDN provides comparable perioperative and postoperative results to those of left-sided RLDN. Our results demonstrated that groups with significant experience in RLDN can perform right living donor nephrectomy safely and efficiently with minimal invasiveness.

Efficient haemodialysis despite complete central venous thrombosis.

Two cases with a fully functional haemodialysis access, in spite of complete thrombotic occlusion of the ipsilateral subclavian and/or brachiocephalic vein are reported. The coincidentally detected complete venous occlusions may indicate that occult venous stenosis or thrombosis is more frequent than generally assumed. In order to avoid deterioration of the haemodynamic situation interventions may be withheld unless clinical problems related to a diminished outflow occur.

The fate of C4d positive kidney allografts lacking histological signs of acute rejection.

BACKGROUND: C4d deposits in renal transplants are known to be an independent risk factor of graft failure. The current analysis evaluates the impact of C4d deposits on graft function and survival in renal transplants without morphological signs of rejection. METHODS: We retrospectively analyzed diagnostic transplant biopsies performed due to allograft dysfunction from June 1994 to June 2001 at the University Hospital in Basel. STUDY GROUP: Grafts/patients with focal or diffuse positivity of C4d along peritubular capillaries; absence of morphological signs of acute cellular and/or humoral rejection; up to 3 year follow-up analysis post index biopsy. Patients treated with anti-rejection therapy or an increase in maintenance immunosuppression post biopsy (intervention group = IG) were compared to patients with unaltered immunosuppression (standard group = SG). RESULTS: Study group: 22 biopsies/patients out of 400 biopsies (5%) were included into the study, 17 in the SG and 5 in the IG. Patient survival (1-/3-years): SG: 100/94%, IG: 80/80%; graft survival censored for death (1-/3-years): SG: 82.5/68.8%, IG: 100/100%; serum creatinine (micromol/l) at index biopsy/1-year/3-years: SG: 221 +/- 70/231 +/- 103/245 +/- 124, IG: 217 +/- 100/143 +/- 28/177 +/- 55; acute rejection episodes within 1 year post index biopsy: SG: 4 (4 patients), IG: 1 (1 patient); all differences not significant. Lowest serum creatinine within 4 weeks post index biopsy (IG vs. SG): 108 +/- 25 vs. 181 +/- 61, p = 0.02. CONCLUSIONS: C4d positivity in kidney transplants lacking histological evidence of acute rejection is not associated with rapid functional graft deterioration, even in untreated cases. However, anti-rejection therapy results in the improvement of kidney function. Thus, even in grafts with normal histology, the detection of C4d in diagnostic biopsies can be interpreted as a sign of "smoldering" rejection that benefits from therapy.

Surgical management of renal cell carcinoma during the second trimester of pregnancy.

Renal cell carcinoma is rarely diagnosed during pregnancy and its management represents a real challenge. Pregnancy demands special consideration in terms of diagnostic evaluation and management, particularly during the second trimester. We report a patient undergoing left radical nephrectomy using a thoracoretroperitoneal approach at 22 weeks' gestation. Histological analysis revealed a pT2R0G2 chromophobic renal cell carcinoma. Furthermore, we review the sparse literature available.

[Kidney transplantation]. / Nierentransplantation.

Since its introduction into clinical medicine in the 1950ties kidney transplantation has become the preferred renal replacement therapy. This article provides a review about indications, evaluations, results, clinical course, and complications of kidney transplantation. The possibility of living kidney donation is emphasized. The careful consulting and follow up by the unique Swiss Organ Living Donor Health Registry (SOL-DHR) are discussed.

Retroperitoneoscopic living donor nephrectomy: a comparison with the open approach in respect of early postoperative pain management.

INTRODUCTION: We retrospectively compared perioperative donor outcomes and early postoperative pain control after retroperitoneoscopic (RLDN) and standard open (OLDN) living donor nephrectomy. METHODS: One hundred donors included fifty after RLDN (37 women/13 men) and 50 after OLDN (35 women/15 men) were retrospectively analyzed for basic analgesics, for opioid consumption, and for visual analog scale (VAS) to verify the experienced pain. The donors were questioned in the morning and evening of the first through fifth postoperative days. RESULTS: The mean age of both groups was equal. The mean operating time was 149.7 +/- 48.2 minutes (60 to 270) for RLDN and 164.1 +/- 30.3 minutes (60 to 240) for OLDN (P = NS). The mean warm ischemia time was 120 +/- 36 seconds (50 to 240) and 114 +/- 31 seconds (60 to 190) for the RLDN and OLDN groups, respectively (P = NS). The mean evening VAS for RLDN versus OLDN on postoperative days 1 to 5 was: 2.1 versus 2.2 (P = NS), 0.9 versus 1.8 (P = .009), 0.5 versus 1.3 (P = .016), 0.1 versus 0.7 (P = .013), and 0.1 versus 0.7 (P = .013), respectively. In both groups there was a tendency toward a higher VAS score in the morning than in the evening. RLDN donors showed significantly earlier period free of pain (VAS = 0) than those after OLDN. There was a significant difference of being free from any opiate between both groups after surgery. CONCLUSIONS: After RLDN donors experienced less postoperative pain than after OLDN over the early postoperative days. Therefore, postoperative regional anesthesia is not necessary for donors operated by a retroperitoneoscopic approach.