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Background. A large proportion of potential organ donors are not utilized for kidney transplantation out of risk of early allograft loss because of donor-related characteristics. These can be summarized using kidney donor profile index (KDPI). Because KDPI affects the choice of the recipient, the predictive ability of KDPI is tied to recipient attributes. These have been questioned to explain most of the predictive ability of KDPI. This study aims to quantify the effect of the donor on early graft loss (EGL) by accounting for nonrandom allocation. Methods. This study included patients undergoing kidney transplantation from deceased donors between 2014 and 2020 from the Scientific Registry of Transplantation Recipients. EGL, defined as a return to dialysis or retransplantation during the first posttransplant year, was the primary endpoint. Nonrandom allocation and donor–recipient matching by KDPI necessitated the use of inverse probability treatment weighting, which served to assess the effect of KDPI and mitigate selection bias in a weighted Cox regression model. Results. The study comprised 89 290 transplantations in 88 720 individual patients. Inverse probability treatment weighting resulted in a good balance of recipient covariates across values of continuous KDPI. Weighted analysis showed KDPI to be a significant predictor for short-term outcomes. A comparable (in terms of age, time on dialysis, previous transplants, gender, diabetes status, computed panel-reactive antibodies, and HLA mismatches) average recipient, receiving a kidney from a donor with KDPI 40–60 had a 3.5% risk of EGL increased to a risk of 7.5% if received a kidney from a KDPI >95 donor (hazard ratio, 2.3; 95% confidence interval, 1.9-2.7). However, for all-cause survival KDPI was less influential. Conclusions. The predictive ability of KDPI does not stem from recipient confounding alone. In this large sample-sized study, modeling methods accounting for nonindependence of recipient selection verify graft quality to effectively predict short-term transplantation outcomes.

Background. The clinical significance of kidney transplant protocol biopsies has been debated. We studied the frequency of borderline changes and T cell–mediated rejection (TCMR) in 1-y protocol biopsies in standard risk kidney transplant recipients. Methods. Consecutive non-HLA-sensitized recipients of kidney transplants between 2006 and 2017, who underwent a protocol biopsy at 1 y in 2 national transplant centers were studied retrospectively (N = 1546). Donor-specific HLA antibodies (DSAs), graft function (plasma creatinine), and proteinuria were measured at the time of 1-y protocol biopsy. The occurrence of subclinical acute TCMR (i2t2v0 or higher) or borderline changes suspicious of TCMR (i1t1v0 or higher) in the protocol biopsy was studied, together with frequency of findings causing changes in the composite score iBox. Results. Subclinical acute TCMR was detected in 30 of 1546 (1.9%) of the protocol biopsies, and borderline or TCMR in 179 of 1546 (12%). Among patients with no history of acute rejection, and no proteinuria or DSA, TCMR was detected in only 1 of 974 (0.1%) and borderline or TCMR in only 48 of 974 (4.9%) patients at 1 y. In the absence of proteinuria (

Cytomegalovirus (CMV) infections remain a common problem after solid-organ transplantation. We characterized the burden of CMV infections, and adverse events of CMV prophylaxis after simultaneous pancreas-kidney transplantation (SPK). We included all SPK patients (n = 236) since 2010 in our country. Immunosuppression was ATG, tacrolimus, mycophenolate, and steroids. Valganciclovir prophylaxis was given to all CMV D+/R− patients for six months, and to seropositive SPK patients for three months since February 2019. CMV DNAemia was monitored with quantitative PCR from plasma. Among D+/R− SPK recipients, post prophylaxis CMV infection was detected in 41/60 (68%) during follow-up. In seropositive SPK recipients with no prophylaxis, CMV infection was detected in 53/95 (56%), vs. 28/78 (36%) in those who received 3 months of prophylaxis (P = 0.01). CMV was symptomatic in 35 (15%) patients, of which 10 required hospitalization. Mean duration of viremia was 28 days (IQR 21–41). Leukopenia was detected in 63 (46%) of the 138 patients with valganciclovir prophylaxis. 7/122 (6%) of the CMV infections detected were defined as refractory to treatment, and three patients had confirmed ganciclovir resistance. SPK recipients experience a high burden of CMV infections despite CMV prophylaxis. Leukopenia is common during valganciclovir prophylaxis.

Delayed graft function (DGF) after kidney transplantation is common and associated with worse graft outcomes. However, little is known about factors affecting graft survival post-DGF. We studied the association of cold ischemia time (CIT) and Kidney Donor Profile Index (KDPI) with the long-term outcomes of deceased brain-dead donor kidneys with and without DGF. Data from Finland (n = 2,637) and from the US Scientific Registry of Transplant Recipients (SRTR) registry (n = 61,405) was used. The association of KDPI and CIT with the graft survival of kidneys with or without DGF was studied using multivariable models. 849 (32%) kidneys had DGF in the Finnish cohort. DGF and KDPI were independent risk factors for graft loss, [HR 1.32 (95% CI 1.14–1.53), p < 0.001, and HR 1.01 per one point (95% CI 1.01–1.01), p < 0.001, respectively], but CIT was not, [HR 1.00 per CIT hour (95% CI 0.99–1.02), p = 0.84]. The association of DGF remained similar regardless of CIT and KDPI. The US cohort had similar results, but the association of DGF was stronger with higher KDPI. In conclusion, DGF and KDPI, but not CIT, are independently associated with graft survival. The association of DGF with worse graft survival is consistent across different CITs but stronger among marginal donors.

The total burden of infections after transplantation has not been compared in detail between recipients of simultaneous pancreas-kidney transplantation (SPK) and kidney transplantation alone (KTA). We compared infection-related hospitalizations and bacteremias after transplantation during 1- and 5-year follow-up among 162 patients undergoing SPK. The control group consisted of 153 type 1 diabetics undergoing KTA with the inclusion criteria of donor and recipient age < 60, and BMI < 30. During the first year, SPK patients had more infection-related hospitalizations (0.54 vs. 0.31 PPY, IRR 1.76, p =

Abstract Background Acute Kidney Injury (AKI) is a common clinical complication. Plasma/serum neutrophil gelatinase-associated lipocalin (NGAL) has been proposed as a rapid marker of AKI. However, NGAL is not kidney-specific. It exists in three isoforms (monomeric, homo-dimeric and hetero-dimeric). Only the monomeric isoform is produced by renal tubular cells and plasma NGAL levels are confounded by the release of all NGAL isoforms from neutrophils. Our aim was to investigate whether NGAL is released into blood from injured renal tubules. Methods Kidney transplantation (n = 28) served as a clinical model of renal ischaemic injury. We used ELISA to measure NGAL concentrations at 2 minutes after kidney graft reperfusion in simultaneously taken samples of renal arterial and renal venous blood. Trans-renal gradients (venous–arterial) of NGAL were calculated. We performed Western blotting to distinguish between renal and non-renal NGAL isoforms. Liver-type fatty acid binding protein (LFABP) and heart-type fatty acid binding protein (HFABP) served as positive controls of proximal and distal tubular damage. Results Significant renal release of LFABP [trans-renal gradient 8.4 (1.7–30.0) ng/ml, p = 0.005] and HFABP [trans-renal gradient 3.7 (1.1–5.0) ng/ml, p = 0.003] at 2 minutes after renal graft reperfusion indicated proximal and distal tubular damage. NGAL concentrations were comparable in renal venous and renal arterial blood. Thus, there was no trans-renal gradient of NGAL. Western blotting revealed that the renal NGAL isoform represented only 6% of the total NGAL in renal venous blood. Conclusions Ischaemic proximal and distal tubular damage occurs in kidney transplantation without concomitant NGAL washout from the kidney graft into blood. Plasma/serum NGAL levels are confounded by the release of NGAL from neutrophils. Present results do not support the interpretation that increase in plasma NGAL is caused by release from the renal tubules.

Introduction Remote ischaemic preconditioning (RIPC) using a non-invasive pneumatic tourniquet is a potential method for reducing ischaemia-reperfusion injury. RIPC has been extensively studied in animal models and cardiac surgery, but scarcely in solid organ transplantation. RIPC could be an inexpensive and simple method to improve function of transplanted organs. Accordingly, we aim to study whether RIPC performed in brain-dead organ donors improves function and longevity of transplanted organs.Methods and analyses RIPTRANS is a multicentre, sham-controlled, parallel group, randomised superiority trial comparing RIPC intervention versus sham-intervention in brain-dead organ donors scheduled to donate at least one kidney. Recipients of the organs (kidney, liver, pancreas, heart, lungs) from a randomised donor will be included provided that they give written informed consent. The RIPC intervention is performed by inflating a thigh tourniquet to 300 mm Hg 4 times for 5 min. The intervention is done two times: first right after the declaration of brain death and second immediately before transferring the donor to the operating theatre. The sham group receives the tourniquet, but it is not inflated. The primary endpoint is delayed graft function (DGF) in kidney allografts. Secondary endpoints include short-term functional outcomes of transplanted organs, rejections and graft survival in various time points up to 20 years. We aim to show that RIPC reduces the incidence of DGF from 25% to 15%. According to this, the sample size is set to 500 kidney transplant recipients.Ethics and dissemination This study has been approved by Helsinki University Hospital Ethics Committee and Helsinki University Hospital’s Institutional Review Board. The study protocol was be presented at the European Society of Organ Transplantation congress in Copenhagen 14−15 September 2019. The study results will be submitted to an international peer-reviewed scientific journal for publication.Trial registration number NCT03855722.

Background: Effective digestive enzymes are crucial for successful islet isolation. Supplemental proteases are essential because they synergize with collagenase for effective pancreatic digestion. The activity of these enzymes is critically dependent on the presence of Ca 2+ ions at a concentration of 5–10 mM. The present study aimed to determine the Ca 2+ concentration during human islet isolation and to ascertain whether the addition of supplementary Ca 2+ is required to maintain an optimal Ca 2+ concentration during the various phases of the islet isolation process. Methods: Human islets were isolated according to standard methods and isolation parameters. Islet quality control and the number of isolations fulfilling standard transplantation criteria were evaluated. Ca 2+ was determined by using standard clinical chemistry routines. Islet isolation was performed with or without addition of supplementary Ca 2+ to reach a Ca 2+ of 5 mM. Results: Ca 2+ concentration was markedly reduced in bicarbonate-based buffers, especially if additional bicarbonate was used to adjust the pH as recommended by the Clinical Islet Transplantation Consortium. A major reduction in Ca 2+ concentration was also observed during pancreatic enzyme perfusion, digestion, and harvest. Additional Ca 2+ supplementation of media used for dissolving the enzymes and during digestion, perfusion, and harvest was necessary in order to obtain the concentration recommended for optimal enzyme activity and efficient liberation of a large number of islets from the human pancreas. Conclusions: Ca 2+ is to a large extent consumed during clinical islet isolation, and in the absence of supplementation, the concentration fell below that recommended for optimal enzyme activity. Ca 2+ supplementation of the media used during human pancreas digestion is necessary to maintain the concentration recommended for optimal enzyme activity. Addition of Ca 2+ to the enzyme blend has been implemented in the standard isolation protocols in the Nordic Network for Clinical Islet Transplantation.

Liver metastases of colorectal cancer can be operated with a curative intent in selected cases. However, more than half of the patients have a recurrence. The aim of this study was to evaluate the prognostic and predictive value of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), human chorionic gonadotropin β (hCGβ) and tumour-associated trypsin-inhibitor (TATI) in colorectal cancer patients before and 3 months after resection of liver metastases. Marker concentrations were determined in blood samples from 168 colorectal cancer patients, who underwent liver resection between the years 1998 and 2007 at Helsinki University Hospital, Finland. The samples were taken before and 3 months after curative resection. Increased concentrations of CEA (>5 µg/L) and hCGβ (>1 pmol/L) 3 months after liver resection correlated with recurrence and impaired overall survival and increased CA19-9 (>26 kU/L) with impaired overall survival, but postoperative TATI was not prognostic. Preoperatively elevated CEA and CA19-9 correlated with impaired overall survival, but not with recurrence. Neither preoperative hCGβ nor TATI was prognostic. In conclusion, CEA is a useful prognostic marker, when measured 3 months after resection of colorectal liver metastases. CA19-9 also has prognostic significance and may have additional value.

This study aimed to evaluate a 50:50 mix of perfluorohexyloctane/polydimethylsiloxane 5 (F6H8S5) preservation of pancreases in a clinical setting compared with standard solutions for 1) cold ischemia time (CIT) 20 h. Procured clinical-grade pancreases were shipped in either F6H8S5 or in standard preservation solutions, that is, University of Wisconsin (UW) or Custodiol. F6H5S5 was preoxygenated for at least 15 min. Included clinical-grade pancreases were procured in UW or Custodiol. Upon arrival at the islet isolation laboratory, the duodenum was removed followed by rough trimming while F6H8S5 was oxygenated for 15-20 min. Trimmed pancreases were immersed into oxygenated F6H8S5 and stored at 4°C overnight followed by subsequent islet isolation. Pancreas preservation using F6H8S5 proved as effective as UW and Custadiol when used within CIT up to 10 h, in terms of both isolation outcome and islet functionality. Preservation in F6H8S5 of pancreases with extended CIT gave results similar to controls with CIT