Renal Graft Dysfunction Research Articles

The impact of pulmonary hypertension on the risk of early graft dysfunction in related kidney transplantation

Introduction. Pulmonary hypertension is a common complication among patients with end-stage renal disease and has a significant impact on the outcome of kidney transplantation, including during kidney transplantation from a living related donor.Objective. To study the prevalence of pulmonary hypertension among patients with end-stage renal disease and to determine its impact on the development of early renal graft dysfunction.Material and methods. The study was based on the analysis of treatment results in 650 patients who underwent kidney transplantation from a living related donor. Depending on the graft function, 2 groups of patients were identified: group I consisting of patients with early renal graft dysfunction (n=82); group II (n=79) that included the patients with a primary graft function who were selected by demographic and clinical laboratory data statistically comparable to patients of group I (p>0.5). This allowed us to equalize the chances of achieving the study endpoint (early graft dysfunction). Transthoracic echocardiography was performed in all patients, with the calculation of the mean pulmonary artery pressure. The relative risk of early renal graft dysfunction was calculated depending on the presence of pulmonary hypertension and its severity.Results. Among group I patients, pulmonary hypertension was detected in 97.56% of cases (mean pulmonary artery pressure 48.26±18.63 mmHg), versus 86.08% in patients with a primary graft function (mean pulmonary artery pressure 31.92±16.11 mmHg) (p<0.001). The presence of mild pulmonary hypertension increased the relative risk of early graft dysfunction by 2.58 times (95% CI [0.698-9.547]; p=0.174), moderate by 3.18 times (95% CI [0.860-11.764]; p=0.064), severe by 5.91 times (95% CI [1.644-21.241]; p<0.001) compared with patients without pulmonary hypertension.Conclusions. When performing kidney transplantation from a living donor, the presence of severe pulmonary hypertension in the recipient is associated with an increased risk of early graft dysfunction. This suggests that pulmonary hypertension may be one of the modifiable risk factors for this complication.

Application value of ultrasonic contrast imaging and ultrasonic parameters in post-transplant renal surgery.

Utilize VUEBOX quantitative analysis software to perform quantitative analysis dynamic ultrasound contrast images of post-transplant renal patients were assessed quantitatively five parameters of ultrasonic contrast and two-dimensional ultrasound are examined to explore their six value in Diagnosing Renal Graft Dysfunction. A retrospective analysis was conducted on 73 post-transplant renal patients who underwent ultrasound contrast examinations at Yiyang Central Hospital from July 2022 to December 2023, They were diagnosed clinically and pathologically. Based on pathological and clinical diagnostic results, the patients were divided into three groups: 47 cases in the stable renal function group, 18 cases in the acute rejection (AR) group, and 8 cases in the delayed graft function (DGF) group. All patients underwent routine ultrasound and ultrasound contrast examinations post-transplantation. By comprehensively assessing renal function test results, clinical course, and pathological findings, differences in ultrasonic contrast quantitative parameters were analyzed. Additionally, ROC curves were constructed to evaluate the diagnostic efficacy of ultrasound contrast in discriminating between transplant renal rejection reactions and delayed renal function recovery. Statistically significant differences in characteristics, such as renal segmental artery resistance index, were observed among the stable renal function group, AR group, and DGF group (all P < 0.05), while peak systolic velocity showed no statistical significance (P > 0.05). Differences in cortical time to peak (TTP), medullary time to peak(TTP), main renal artery rise time (RT), main renal artery(TTP), and main renal artery fall time (FT) were statistically significant among the stable renal function group, AR group, and DGF group (P < 0.05). ROC curve analysis demonstrated that the accuracy of quantitative parameters for the DGF group and AR group was as follows: Renal artery TTP = Renal artery RT > Renal artery FT > Medulla TTP > Cortex TTP (with respective area under the curve values of 0.828, 0.828, 0.758, 0.742, 0.719). Among these, Renal artery TTP and Renal artery RT exhibited larger AUC values, with sensitivities of 87.5% each and specificities of 81.2 and 87.5%, respectively. There are discernible differences in VUEBOX quantitative parameters between post-transplant AR and DGF cases, thereby providing imaging references for diagnosing of acute rejection and functional impairment following renal transplantation.

#2323 Sodium-glucose cotransporter 2 inhibitors in kidney transplant recipients—effectiveness and safety

Abstract Background and Aims Given the increasing incidence of posttransplant diabetes and the heightened cardiovascular burden among transplant recipients, the use of SGLT2 inhibitors (SGLT2i) in this population is attractive due to their cardiovascular and renoprotective advantages. However, evidence for diabetic kidney transplant recipients (DKTRs) is limited, primarily due to concerns regarding potential worsening of renal graft dysfunction and adverse effects. Method This retrospective study was conducted to evaluate the effectiveness and safety of SGLT2 inhibitors in kidney transplant recipients (KTRs). Individuals with type 1 diabetes (n = 2) and individuals submitted to a double kidney and pancreas transplant (n = 5) were excluded from the study to avoid diabetes type bias . The primary focus was on assessing SGLT2 inhibitors effect on parameters such as hemoglobin A1c levels, body mass index (BMI), lipid panel, hemoglobin levels, renal allograft function (estimated glomerular filtration rate), and urinary protein-to-creatinine ratio. Demographic, clinical, and laboratory data were collected and subjected to analysis using descriptive statistics with SPSS Statistics software. The data were presented as means ± standard error, and comparisons were conducted using the paired sample t-test. A significance level below 0.05 (P &amp;lt; 0.05) was considered statistically relevant. Results A total of 104 renal transplant patients were included. The study spanned a median observation period of 14 (2.0–71.0) months. Mean HbA1c decreased from 7.3 to 6.9% (P = 0.001). A significant improvement in BMI (27.6 to 27.0 kg/m2; P = 0.008), total and LDL-Cholesterol(P &amp;lt; 0.001 and P = 0.004, respectively) were also observed. Mean haemoglobin rate at baseline was 13.3 g/dL and also improved at end of follow-up to 13.5 g/dL (P = 0.065). Mean estimated glomerular filtration rate at baseline was 60.1 (26–120) mL/min/1.73 m2 and decreased to 54.8 throughout the follow-up (P = 0.007), while mean serum cystatin increased from 1.7 to 2.0 mg/L (P &amp;lt; 0.001). Regarding urinary protein:creatinine ratio, levels slightly but not significantly rose [+0.33 g/g]. Urinary tract infections occurred in 10% of the recipients. No other side effects were observed during the treatment course or neither the patients needed to discontinue the medication. Conclusion This study establishes that the use of SGLT2 inhibitors is both feasible and well-tolerated in kidney transplant recipients (KTRs), with no significant observed side effects. Further studies are required to clarify the impact of SGLT2 inhibitors on long-term patient and allograft survival.

Preexisting renal graft dysfunction as a major risk factor for SARS-CoV-2 Omicron variant pneumonia: A postinfection cross-sectional study of 312 immunosuppressed renal transplant recipients

ObjectivesSARS-CoV-2 pneumonia poses significant challenges to health systems worldwide, particularly, in severe and critical cases. Immunosuppressed renal transplant recipients appear to be at a particularly high risk for severe or critical COVID-19 illness. However, few studies elucidated the risk factors of SARS-CoV-2 pneumonia in renal transplant recipients with COVID-19. MethodsA postinfection cross-sectional survey was conducted in 312 renal transplant recipients and 503 age- and sex-matched controls to explore risk factors for SARS-CoV-2 pneumonia in immunosuppressed renal transplant recipients. ResultsThe results showed that renal transplant recipients had a much higher incidence of SARS-CoV-2 pneumonia (48.1%) after infection with the SARS-CoV-2 Omicron variant than controls (5.6%). The multivariate binary logistic regression analysis identified older age, lower creatinine clearance before infection, and higher dose of prednisone before infection as risk factors for SARS-CoV-2 pneumonia in renal transplant recipients. Preexisting renal dysfunction was a major risk factor for SARS-CoV-2 pneumonia, with an odds ratio of 3.27 (1.01-10.61). ConclusionsPreexisting renal graft dysfunction was a major risk factor for SARS-CoV-2 Omicron variant pneumonia. It is suggested that high-risk renal transplant recipients should undergo computed tomography scanning within 14 days after infection with SARS-CoV-2.

Histopathological diagnoses revealed by indication-based renal allograft biopsies: a retrospective analysis

Objectives: Although there have been several advances in post-solid organ transplantation immunosuppression medications over the last two decades, the long-term survival of renal allografts did not significantly improve. Renal allograft biopsy is a helpful tool for determining the cause of graft dysfunction and adjusting patient management. Methods: Patients who received kidney transplantation and underwent allograft biopsy in Istinye University Hospital between January 2017 and January 2023 constituted the target population of this study. Demographic parameters, clinical data and biopsy indications, and histopathological assessment results of the patients were retrospectively analyzed. Results: Overall, 74 patients were included. The histopathology results included acute T-Cell mediated rejection (TCMR) (n = 15, 20%), tubular atrophy/chronic allograft nephropathy (IFTA) (n = 11, 15%), calcineurin inhibitor (CNI) toxicity (n = 2, 3%), chronic antibody-mediated rejection (ABMR) (n = 2, 3%), borderline pathology (n = 10, 13.5%), normal histology (n = 5, 6.5%), transplant glomerulopathy (TG) (n = 5, 6.5%), acute ABMR (n = 4, 5%), acute tubular necrosis (n = 7, 9%), polyomavirus nephropathy (n = 3, 4%) and non-specific changes (n = 10, 13.5%). The C4d was positive in 12% (n = 9) of the graft biopsies. In 73% (n = 54) of cases, the treatment strategy was changed based on biopsy results. Among all patients, 19 (25.6%) lost their grafts during follow-up. Conclusions: According to the histopathological analysis results, acute TCMR, IFTA, and borderline pathology were the most common causes of renal graft dysfunction. Renal allograft biopsy led to a remarkable change in treatment strategies in a significant number of cases.

Adenovirus Infection in a Kidney–Pancreatic Transplant Recipient: Case Report

Adenovirus infection in transplant recipients may present from asymptomatic viremia to multisystemic involvement. Most frequently, it occurs in the first year after a kidney transplant, and it is secondary to the reactivation of latent disease. However, primary infection may occur, and disseminated disease is more common when related to primary infection. Kidney involvement may be confirmed by biopsy, although diagnosis may be presumptive. Reduction of immunosuppression and supportive care are important components of therapy. CASE DESCRIPTION: A 41-year-old female renal-pancreatic recipient 12 years before with chronic renal graft dysfunction and a functional pancreatic graft had a history of cytomegalovirus and polyoma virus infection 2 years after transplantation. She was taking tacrolimus, mycophenolate mofetil, and prednisolone. The patient was admitted after persistent uncharacteristic diarrhea 3 weeks before hospitalization without any relevant epidemiologic context. She was dehydrated, and the lab results showed worsened kidney function and leucocytosis. The viral culture revealed adenovirus. Vigorous hydration was implemented, and the mycophenolate mofetil dose was reduced. The patient was discharged, and renal function returned to previous values. DISCUSSION AND CONCLUSION: Adenovirus infection has a wide clinical presentation, and multisystemic involvement may occur in transplant recipients. Supportive care is paramount. The clinical features and viral culture confirm the diagnosis, although tissue samples and quantitative polymerase chain reaction may be required in more severe cases.

Immediate and long-term results of the use of balloon angioplasty with stenting in the treatment of renal graft arterial stenosis

Aim. To assess the safety and efficacy of percutaneous transluminal balloon angioplasty with stenting for renal graft artery stenosis. Material and methods. From June 2018 to December 2022, 344 kidney transplants from a deceased donor were performed at the surgical clinic of City Clinical Hospital n.a. S.P. Botkin. The study group consisted of 220 men (63.9%) and 124 women (36.1%). The mean age was 46.46±11.74 (19–73) years. With a mean follow-up period of 20.05 (1-54) months, stenosis of the renal graft artery was diagnosed in 4 patients (1.16%). The mean time from transplantation to the diagnosis of stenosis was 4 (1–9) months. In addition, we diagnosed the development of this complication in 4 kidney transplant recipients operated in other centers. The mean time from transplantation to the diagnosis of stenosis in these patients was 103.25 (12–221) months. Thus, we have the experience in the treatment of renal transplant arterial strictures in 8 recipients: 4 men (50%) and 4 women (50%). The mean age was 48.25±11.97 (27–60) years. Stenosis was manifested by renal graft dysfunction with a progressive increase in urea and creatinine in 6 patients (75%), by arterial hypertension in 2 patients (25%). The mean, level of creatinine at the time of diagnosing stenosis was 290.75 (157–494) µmol/L, glomerular filtration rate was 22.87±12.19 (8–41) ml/min/1.73m2 . Results. In the early postoperative period, 1 complication was recorded in the form of pulsating hematoma of the common femoral artery, which required surgical intervention (complication class IIIA according to Clavien-Dindo). The mean hospital postoperative bed-days made 5.22 (4-8). The mean follow-up time was 22.75±7.4 (14–33) months. All recipients were alive throughout the whole follow-up period. In 7 of 8 recipients (87.5%), the graft was functioning, in 1 patient a progressive graft dysfunction was noted, for which chronic hemodialysis was started. Mean creatinine in recipients with a functioning graft was 156.71±33.4 (123–200) µmol/L; mean glomerular filtration rate was 41.57 ml/min/1.73m2 . Conclusions. Percutaneous transluminal balloon angioplasty with stenting is a safe and effective minimally invasive technique and should be considered as the operation of choice in the development of renal graft artery stenosis.

Clinicopathological Results of Percutaneous Transplant Kidney Biopsies: Single Center Nine Years' Experience

Background: Based on clinical criteria alone, the cause of graft dysfunction cannot be accurately predicted in 40-70% of cases. Therefore, renal allograft biopsy is still the gold standard for accurate diagnosis. We performed this study to evaluate the causes of renal graft dysfunction detected in renal allograft biopsies in our center.&#x0D; Methods: The results of 90 patients who underwent renal allograft biopsy between May 2013 and June 2022 from kidney transplant patients were evaluated retrospectively.&#x0D; Results: It was determined that 92 biopsies were performed from 90 patients and all were ‘cause’’ biopsies. The mean age was 40.03±14.29 years. 82 of the kidney transplants were from living donors. 21 patients had preemptive transplantation. The type of renal replacement therapy before transplantation was hemodialysis in 52 patients, PD in 3 patients, PD and HD in 3 patients. The reason for biopsy was high creatinine in 67 patients, proteinuria in 23 patients, and BKV viremia in 2 patients. The mean discharge creatinine value was 1.64±1.11mg/dl, and the mean creatinine before biopsy was 3.06±2.07mg/dl. Although there was kidney tissue in one of the allograft biopsies, there was no glomeruli. The mean number of cores taken was 2.94±0.61, and the number of glomeruli was 21.33±11.64. In one of the 92 biopsies performed, bleeding requiring transfusion developed. No other biopsy-related complications were observed. Graft loss was observed in 46 of 90 patients during the follow-up period.&#x0D; Conclusions: Evaluation of serum creatinine and urinalysis may be useful in predicting histological graft diagnosis, but an allograft biopsy is necessary for definitive diagnosis.

Transplant renal artery stenosis: utilization of machine learning to identify ancillary sonographic and doppler parameters to predict stenosis in patients with graft dysfunction

To determine if ancillary sonographic and Doppler parameters can be used to predict transplant renal artery stenosis in patients with renal graft dysfunction. IRB-approved, HIPAA-compliant retrospective study included 80 renal transplant patients who had renal US followed by renal angiogram between January 2018 and December 2019. A consensus read of two radiologists recorded these parameters: peak systolic velocity, persistence of elevated velocity, grayscale narrowing, parvus tardus, delayed systolic upstroke, angle of the systolic peak (SP angle), and aliasing. Univariate analysis using t-test or chi-square was performed to determine differences between patients with and without stenosis. P values under 0.05 were deemed statistically significant. We used machine learning algorithms to determine parameters that could better predict the presence of stenosis. The algorithms included logistic regression, random forest, imbalanced random forest, boosting, and CART. All 80 cases were split between training and testing using stratified sampling using a 75:25 split. We found a statistically significant difference in grayscale narrowing (p=0.0010), delayed systolic upstroke (p=0.0002), SP angle (p=0.0005), and aliasing (p =0.0024) between the two groups. No significant difference was found for an elevated peak systolic velocity (p =0.1684). The imbalanced random forest (IRF) model was selected for improved accuracy, sensitivity, and specificity. Specificity, sensitivity, AUC, and normalized Brier score for the IRF model using all parameters were 73%, 81%, 0.82, and 69 in the training set, and 78%, 58%, 0.78, and 80 in the testing set. VIMP assessment showed that the combination of variables that resulted in the most significant change of the training set performance was that of grayscale narrowing and SP angle. Elevated peak systolic velocity did not discriminate between patients with and without TRAS. Adding ancillary parameters into the machine learning algorithm improved specificity and sensitivity similarly in the training and testing sets. The algorithm identified the combination of lumen narrowing coupled with the angle of the systolic peak as better predictor of TRAS. This model may improve the accuracy of ultrasound for transplant renal artery stenosis.

Medical complications after live donor kidney transplantation: An experience from tertiary care hospital of south Punjab, Pakistan.

Objective: To determine the frequency of medical complications after renal transplantation in recipients. Study Design: Prospective Cohort study. Setting: Nephrology Unit, Bahawal Victoria Hospital, Bahawalpur. Period: December 2018 to March 2022. Material &amp; Methods: All patients undergoing renal transplant during the study period were included. Patients unwilling to be part of this study or losing follow-ups were excluded. At the time of enrollment, all patients underwent pre-transplant work-up and routine investigations. Baseline characteristics of renal transplant recipients and donors were noted while frequency of post renal transplant medical complications was also noted. Results: In a total of 39 renal transplant recipients, 32 (82.1%) were male while the mean age was 30.31±7.21 years. Mean duration of dialysis before transplantation was 6.81±5.15 months (ranging between 0-24 months). Mean age of the live donors was 35.90±9.36 years. Mean duration of follow up was 26.15±11.62 months. Renal graft dysfunction was reported in 10 (25.6%) patients. Most common medical complications reported in post-transplantation period were sepsis 19 (48.7%), anemia 19(48.7%), secondary polycythemia 10 (25.6%), CMV infection 4 (10.3%) and new onset diabetes mellitus 3 (7.7%). Mortality was reported in 2 (5.1%) renal transplant recipients and the cause of mortality in both those patients was sepsis. Conclusion: Medical complications are common after renal transplantation. Sepsis being more common in 1st6-months post-transplant period. Early recognition and management of these complications is essential for decreasing mortality and morbidity of patients.

Dynamic changes of neutrophil-to-lymphocyte ratio in brain-dead donors and delayed graft function in kidney transplant recipients

Objectives Neutrophil-to-lymphocyte ratio (NLR) is a simple parameter implying the inflammatory status. We aimed to explore the association of brain-dead donor NLR change with delayed graft function (DGF) in kidney transplant recipients. Methods We retrospectively analyzed the data on 102 adult brain-dead donors and their corresponding 199 kidney transplant recipients (2018 − 2021). We calculated ΔNLR by subtracting the NLR before evaluating brain death from the preoperative NLR. Increasing donor NLR was defined as ΔNLR > 0. Results Forty-four (22%) recipients developed DGF after transplantation. Increasing donor NLR was significantly associated with the development of DGF in recipients (OR 2.8, 95% CI 1.2 − 6.6; p = .018), and remained significant (OR 2.6, 95% CI 1.0 − 6.4; p = .040) after adjustment of confounders including BMI, hypertension, diabetes, and the occurrence of cardiac arrest. When acute kidney injury (AKI) was included in the multivariable analysis, increasing donor NLR lost its independent correlation with DGF, while AKI remained an independent risk factor of recipient DGF (OR 4.5, 95% CI 2.7 − 7.6; p < .001). The area under the curve of combined increasing NLR and AKI in donors (0.873) for predicting DGF was superior to increasing donor NLR (0.625, p = .015) and AKI alone (0.859, p < .001). Conclusions Dynamic changes of donor NLR are promising in predicting post-transplant DGF. It will assist clinicians in the early recognition and management of renal graft dysfunction. Validation of this new biomarker in a large study is needed.

Bariatric Surgery Outcomes in Patients with Kidney Transplantation.

Obesity and kidney transplantation (KTx) are closely related. Obesity increases the risk of chronic kidney disease and can be a relative contraindication for KTx. Besides, KTx recipients are predisposed to obesity and its comorbidities. Consequently, bariatric surgery (BS) emerges as a powerful therapeutic tool either before or after KTx. Since evidence regarding the best approach is still scarce, we aimed to describe renal and metabolic outcomes in a single centre with more than 15-year experience in both surgeries. Methods: A retrospective study including patients who had received a KTx either before or after BS. Usual metabolic and renal outcomes, but also new variables (as renal graft dysfunction) were collected for a minimum follow-up of 1-year post-BS. Results: A total of 11 patients were included: n = 6 (BS-post-KTx) and n = 5 (BS-pre-KTx). One patient was assessed in both groups. No differences in the main outcomes were identified, but BS-post-KTx group tended to gain more weight during the follow-up. The incidence of renal graft dysfunction was comparable (4/6 for BS-post-KTx, 3/5 for BS-pre-KTx) between groups. Conclusions: BS in patients with KTx appears to be safe and effective attending to metabolic and renal outcomes. These results seem irrespective of the time course, except for weight regain, which appears to be a common pattern in the BS-post-KTx group.

Identifying stable reference genes in polyethene glycol precipitated urinary extracellular vesicles for RT-qPCR-based gene expression studies in renal graft dysfunction patients

BackgroundUrinary extracellular vesicles (UEVs) hold RNA in their cargo and are potential sources of biomarkers for gene expression studies. The most used technique for gene-expression studies is quantitative polymerase chain reaction (qPCR). It is critical to use stable reference genes (RGs) as internal controls for normalising gene expression data, which aren't currently available for UEVs. MethodsUEVs were precipitated from urine of graft dysfunction patients and healthy controls by Polyethylene glycol, Mn6000 (PEG6K). Vesicular characterisation confirmed the presence of UEVs. Gene expression levels of five commonly used RGs, i.e., Beta-2-Microglobulin (B2M), ribosomal-protein-L13a (RPL13A), Peptidylprolyl-Isomerase-A (PPIA), hydroxymethylbilane synthase (HMBS), and glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) were quantified, and their stability was established through the RefFinder. The stability of identified RGs was validated by quantification of Perforin and granzyme B, signature molecules of renal graft dysfunction. ResultsUrine precipitated with 12% 6 K PEG yielded round and double-membraned UEVs of size ranging from 30 to 100 nm, as confirmed through transmission electron microscopy. Nanoparticle tracking analysis (59 ± 22 nm) and Dynamic-light-scattering (78 ± 56.5 nm) confirmed their size profile. Semi-quantitative Exocheck antibody array demonstrated the presence of EV protein markers in UEV. Using the comparative ΔCт method and RefFinder analysis, B2M (1.6) and RPL13A (1.8) genes emerged as the most stable reference genes. Validation of target gene expression in renal graft dysfunction patients confirmed the efficiency of B2M and RPL13A through significant upregulation compared to other RGs. ConclusionsOur study identified and validated B2M and RPL13A as optimal RGs for mRNA quantification studies in the UEVs of patients with renal graft dysfunction.

Clinical significance of copeptin as an early predictor of renal graft dysfunction in renal transplant recipients

Background: Copeptin is the carboxyl-terminal part of the vasopressin precursor protein, and its concentration is an independent predictor of the onset of chronic kidney disease and a rapid decline in the glomerular filtration rate. The glomerular filtration rate is regarded as the best indicator of kidney transplant function and is a predictor of graft and patient survival. We investigated the clinical significance of copeptin as an early predictor of renal graft dysfunction in renal transplant recipients.Methods: We measured serum creatinine, cystatin C, and copeptin concentrations in renal transplant recipients on the day of their operation, as well as on postoperative days 3, 7, 30, and 365. Acute rejection was defined as a sudden decrease in renal function accompanied by histological changes.Results: Eight renal transplant recipients were enrolled in the study from July 2018 to December 2019. Four patients experienced histologically confirmed transplant rejection. All four cases involved acute T-cell rejection. No significant correlation was found between the copeptin level and the presence or absence of rejection at any time point. In subgroup analyses, changes in creatinine, the estimated glomerular filtration rate, cystatin, and copeptin did not show statistical significance.Conclusions: We anticipated that copeptin would be useful to identify individuals at high risk of transplant rejection; however, our study failed to show an association. Further research will be needed to overcome the limitations of this study.

P8.031: Outcome of Simultaneous Pancreas Kidney Transplantation A Single Center Experience

Introduction: Simultaneous simultaneous pancreas-kidney (SPK) transplantation is one of the treatment options for type 1 diabetes mellitus (T1DM) patients with chronic kidney disease stage 5. The SPKT outcomes are reported to be excellent with a 5 year patient, kidney and pancreas graft survival of 88%, 77% and 69% respectively. Here, we present data regarding outcome of the SPKT done at our institution. Method: We studied patients who underwent SPKT in our institution. 11 T1DM patients who were CKD-5 underwent SPKT from 2014 to 2022. Their graft function and complications were analysed. Results: A total of 12 patients were studied. 50 % were males and 50% were females. Mean age at diagnosis was 14 ± 4 years. Mean age at transplantation was 32 ± 6 years. Mean hemodialysis (HD) vintage was 22 ± 14 months. Mean age of donor was 31 ± 10 years. Induction was with Basiliximab in 1 patient, Alemtuzumab in 5 patients and ATG in 6 patients. Maintenance immunosuppression was tacrolimus and mycophenolate in 8 patients; and, tacrolimus, mycophenolate and everolimus in 2 patients Mean duration of hospital stay was 30 ± 18 days. Mean graft kidney function at 1 month was 1.38 ± 0.48 mg/dl. Mean graft kidney function at 6 months was 1.30 ± 0.47 mg/dl. At 1 year, one patient had severe renal graft dysfunction requiring HD. Among the other 10 patients who completed one year, mean kidney graft function at 1 year was 1.25 ± 0.23 mg/dl. Three (25%) patients had renal allograft loss with need for initiation of HD after 30, 21 and 6 months. Two patients with renal allograft loss required insulin after 19 and 25 months. Three (25%) patients had delayed graft function. Five (41.7%) patients had renal allograft rejection at 1 month. Among the five, three had another episode of rejection at 17, 11 and 4 months. Three (25%) patients had suspected pancreatic graft rejection at POD 13, 13 and 14, which resolved with intravenous steroids. Eight (66.6%) patients had infections in the first year following transplant which included urosepsis, LRTI, tuberculosis, varicella, CMV, cellulitis, periodontal abscess, dental caries and esophagial candidiasis. Seven (58.3%) had surgical complications including pseudo aneurysm of graft pancreas, urinoma, perinephric hematoma, abdominal bleed and DIC, jejujno-jejunal anastomotic site bleed, kinked renal vein requiring re-exploration, graft pancreas fat necrosis with impending GB rupture and peritonitis, and splenic vein thrombosis requiring re-exploration. Other complications noted were incisional hernia, subacute intestinal obstruction, bilateral femoral head avascular necrosis and acute myeloid leukemia. Conclusion: The graft survival and outcomes in our institution is comparable to that of international standards. Surgical complications were noted to be higher compared to renal transplantation. SPK remains to be treatment of choice in T1DM patients with ESRD.

Correlation of Different Serum Biomarkers with Prediction of Early Pancreatic Graft Dysfunction Following Simultaneous Pancreas and Kidney Transplantation.

Background: Despite recent advances and refinements in perioperative management of simultaneous pancreas–kidney transplantation (SPKT) early pancreatic graft dysfunction (ePGD) remains a critical problem with serious impairment of early and long-term graft function and outcome. Hence, we evaluated a panel of classical blood serum markers for their value in predicting early graft dysfunction in patients undergoing SPKT. Methods: From a prospectively collected database medical data of 105 patients undergoing SPKT between 1998 and 2018 at our center were retrospectively analyzed. The primary study outcome was the detection of occurrence of early pancreatic graft dysfunction (ePGD), the secondary study outcome was early renal graft dysfunction (eRGD) as well as all other outcome parameters associated with the graft function. In this context, ePGD was defined as pancreas graft-related complications including graft pancreatitis, pancreatic abscess/peritonitis, delayed graft function, graft thrombosis, bleeding, rejection and the consecutive need for re-laparotomy due to graft-related complications within 3 months. With regard to analyzing ePGD, serum levels of white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), pancreatic lipase as well as neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) were measured preoperatively and at postoperative days (POD) 1, 2, 3 and 5. Further, peak serum levels of CRP and lipase during the first 72 h were evaluated. Receiver operating characteristics (ROC) curves were performed to assess their predictive value for ePGD and eRGD. Cut-off levels were calculated with the Youden index. Significant diagnostic biochemical cut-offs as well as other prognostic clinical factors were tested in a multivariate logistic regression model. Results: Of the 105 patients included, 43 patients (41%) and 28 patients (27%) developed ePGD and eRGD following SPKT, respectively. The mean WBC, PCT, NLR, PLR, CRP and lipase levels were significantly higher on most PODs in the ePGD group compared to the non-ePGD group. ROC analysis indicated that peak lipase (AUC: 0.82) and peak CRP levels (AUC: 0.89) were highly predictive for ePGD after SPKT. The combination of both achieved the highest AUC (0.92; p < 0.01) in predicting ePGD. Concerning eRGD, predictive accuracy of all analyzed serological markers was moderate (all AUC < 0.8). Additionally, multivariable analysis identified previous dialysis/no preemptive transplantation (OR 2.4 (95% CI: 1.41–4.01), p = 0.021), donor age (OR 1.07 (95% CI: 1.03–1.14), p < 0.010), donor body mass index (OR 1.32 (95% CI: 1.01–1.072), p = 0.04), donors cerebrovascular cause of death (OR 7.8 (95% CI: 2.21–26.9), p < 0.010), donor length of ICU stay (OR 1.27 (95% CI: 1.08–1.49), p < 0.010), as well as CIT pancreas (OR 1.07 (95% CI: 1.03–1.14), p < 0.010) as clinical relevant prognostic predictors for ePGD. Further, a peak of lipase (OR 1.04 (95% CI: 1.02–1.07), p < 0.010), peak of CRP levels (OR 1.12 (95% CI: 1.02–1.23), p < 0.010), pancreatic serum lipase concentration on POD 2 > 150 IU/L (OR 2.9 (95% CI: 1.2–7.13), p = 0.021) and CRP levels of ≥ 180 ng/mL on POD 2 (OR 3.6 (95% CI: 1.54–8.34), p < 0.01) and CRP levels > 150 ng/mL on POD 3 (OR 4.5 (95% CI: 1.7–11.4), p < 0.01) were revealed as independent biochemical predictive variables for ePGD after transplantation. Conclusions: In the current study, the combination of peak lipase and CRP levels were highly effective in predicting early pancreatic graft dysfunction development following SPKT. In contrast, for early renal graft dysfunction the predictive value of this parameter was less sensitive. Intensified monitoring of these parameters may be helpful for identifying patients at a higher risk of pancreatic ischemia reperfusion injury and various IRI- associated postoperative complications leading to ePGD and thus deteriorated outcome.

Successful surgical repair of inguinal hernia causing positional obstructive uropathy: A rare cause of renal graft dysfunction - Case report

Bladder herniation with obstructive uropathy is a relatively rare occurrence, however, urinary bladder herniation along with ureteroneocystostomy and leading to positional obstructive uropathy of the graft is an unusual presentation. This is a unique case of a 38-year-old male who presented with inguinal hernia with raised serum creatinine who had undergone renal transplant 10 years back in 2011. Magnetic resonance urogram revealed herniation of urinary bladder and hydroureteronephrosis of transplant kidney. Patient is managed by surgical exploration through inguinal incision and reduction of ureteroneocystostomy herniation after ureterolysis and hernioplasty was performed. The cause of obstructive uropathy was herniation of the bladder along with ureteroneocystostomy, and the patient has an insidious onset of symptoms, immediate exploration, and repair of hernia done without any need for percutaneous nephrostomy. Importance of this case report is that sliding herniation of the bladder with ureteroneocystostomy should be considered a diagnosis and investigated if the patient presents with positional obstructive uropathy with inguinal hernia, leading to early identification and salvaging the graft function.

Proximal Tubule p53 in Cold Storage/Transplantation-Associated Kidney Injury and Renal Graft Dysfunction.

Kidney injury associated with cold storage/transplantation is a primary factor for delayed graft function and poor outcome of renal transplants. p53 contributes to both ischemic and nephrotoxic kidney injury, but its involvement in kidney cold storage/transplantation is unclear. Here, we report that p53 in kidney proximal tubules plays a critical role in cold storage/transplantation kidney injury and inhibition of p53 can effectively improve the histology and function of transplanted kidneys. In a mouse kidney cold storage/transplantation model, we detected p53 accumulation in proximal tubules in a cold storage time-dependent manner, which correlated with tubular injury and cell death. Pifithrin-α, a pharmacologic p53 inhibitor, could reduce acute tubular injury, apoptosis and inflammation at 24 h after cold storage/transplantation. Similar effects were shown by the ablation of p53 from proximal tubule cells. Notably, pifithrin-α also ameliorated kidney injury and improved the function of transplanted kidneys in 6 days when it became the sole life-supporting kidney in recipient mice. in vitro, cold storage followed by rewarming induced cell death in cultured proximal tubule cells, which was accompanied by p53 activation and suppressed by pifithrin-α and dominant-negative p53. Together, these results support a pathogenic role of p53 in cold storage/transplantation kidney injury and demonstrate the therapeutic potential of p53 inhibitors.

Endogenous Interleukin-33 Acts as an Alarmin in Liver Ischemia-Reperfusion and Is Associated With Injury After Human Liver Transplantation.

Ischemia and reperfusion injury is an early inflammatory process during liver transplantation that impacts on graft function and clinical outcomes. Interleukin (IL)-33 is a danger-associated molecular pattern involved in kidney ischemia/reperfusion injury and several liver diseases. The aims were to assess whether IL-33 was released as an alarmin responsible for ischemia/reperfusion injury in a mouse model of warm hepatic ischemia, and whether this hypothesis could also apply in the setting of human liver transplantation. First, a model of warm hepatic ischemia/reperfusion was used in wild-type and IL-33–deficient mice. Severity of ischemia/reperfusion injury was assessed with ALT and histological analysis. Then, serum IL-33 was measured in a pilot cohort of 40 liver transplant patients. Hemodynamic postreperfusion syndrome, graft dysfunction (assessed by model for early allograft scoring >6), renal failure, and tissue lesions on time-zero biopsies were assessed. In the mouse model, IL-33 was constitutively expressed in the nucleus of endothelial cells, immediately released in response to hepatic pedicle clamping without neosynthesis, and participated in the recruitment of neutrophils and tissue injury on site. The kinetics of IL-33 in liver transplant patients strikingly matched the ones in the animal model, as attested by serum levels reaching a peak immediately after reperfusion, which correlated to clinical outcomes including postreperfusion syndrome, posttransplant renal failure, graft dysfunction, and histological lesions of ischemia/reperfusion injury. IL-33 was an independent factor of graft dysfunction with a cutoff of IL-33 at 73 pg/ml after reperfusion (73% sensitivity, area under the curve of 0.76). Taken together, these findings establish the immediate implication of IL-33 acting as an alarmin in liver I/R injury and provide evidence of its close association with cardinal features of early liver injury-associated disorders in LT patients.

Prevalence and causes of graft dysfunction in first 3 months after kidney transplantation in Erbil transplant center

Graft dysfunction after kidney transplantation occur due to different causes. Diagnosis of graft dysfunction is a key component in the management of kidney transplant recipients. The aim of this study was to identify the causes of graft dysfunction in the first 3 months after kidney transplant by kidney biopsy for better graft survival. A total number of 250 patients who underwent renal transplantation at the Erbil teaching center from January 2020 to December 2020 were considered for this study. 50 biopsies were performed due to renal graft dysfunction in the first 3 months post-transplant. Descriptive statistics were analyzed using IBM SPSS Statistics software version 22.0. The biopsy results showed that acute cellular rejection (ACR) was observed in 21 patients (42%), acute interstitial nephritis (AIN) was found in 16 patients (32%), acute tubular necrosis (ATN) was occurred in 9 patients (18%), calcineurin inhibitor toxicity (CNI) was observed in 2 patients (4%), acute humoral rejection (AHR) was found in 1 patient (2%) and thrombotic microangiopathy (TMA) was occurred in 1 patient (2%). As a conclusion, the most important causes of graft dysfunction were ACR, AIN and ATN, respectively. Also, glomerulonephritis, diabetes and hypertension are the most risk factor for ESRD. In addition, the results of this study showed that Anti-HLA cross match can be used as an indicator for predicting the result of transplantation. Keywords: graft dysfunction, Kidney transplantation, acute cellular rejection, acute interstitial nephritis