The Use of the Implantable Doppler Probe as a Blood Flow Monitoring Device in Clinical Settings: A Narrative Review of the Evidence.

OBJECTIVES: In the past decade, the implantable Doppler probe has been studied widely as a blood flow-monitoring device in reconstructive and transplant surgical specialities. Its utility as an effective postoperative monitoring technique is still debatable, with no clear guidelines in clinical practice. Here, we mapped the current evidence on the usefulness of the implantable Doppler probe as a blood flow-monitoring device. The objective was to present an up-to-date assessment of the benefits and limitations of using implantable Doppler probes in clinical and experimental clinical settings. MATERIALS AND METHODS: We conducted a literature search using the Cochrane Library and Healthcare Databases Advanced Search and using implantable Doppler probe, transplant, graft, and flap as key words. The search yielded 184 studies, with 73 studies included after exclusions. We evaluated, synthesized, and summarized the evidence from the studies in tabular form. RESULTS: There is clinical equipoise regarding the effectiveness of implantable Doppler probe as a flow sensing technique. The main reason is the lack of information and gaps in the evidence regarding the benefits and limitations of using implantable Doppler probes in clinical practice. CONCLUSIONS: The implantable Doppler probe has the potentialto be used as an adjunctpostoperativeblood flow-monitoring device. However, keeping in view of technical limitations, its signals should be interpreted alongside traditional clinical assessment techniques to determine the patency of microvascular anastomosis. Although evidence in this review will inform clinical practice in transplant and reconstructive surgical specialties, a prospective randomized controlled study with a larger patient cohort is required to evaluate the effectiveness of this probe in clinical settings.

Prolonged warm ischemia time leads to severe renal dysfunction of donation-after-cardiac death kidney grafts.

Kidney transplantation with grafts procured after donation-after-cardiac death (DCD) has led to an increase in incidence of delayed graft function (DGF). It is thought that the warm ischemic (WI) insult encountered during DCD procurement is the cause of this finding, although few studies have been designed to definitely demonstrate this causation in a transplantation setting. Here, we use a large animal renal transplantation model to study the effects of prolonged WI during procurement on post-transplantation renal function. Kidneys from 30 kg-Yorkshire pigs were procured following increasing WI times of 0 min (Heart-Beating Donor), 30 min, 60 min, 90 min, and 120 min (n = 3-6 per group) to mimic DCD. Following 8 h of static cold storage and autotransplantation, animals were followed for 7-days. Significant renal dysfunction (SRD), resembling clinical DGF, was defined as the development of oliguria < 500 mL in 24 h from POD3-4 along with POD4 serum potassium > 6.0 mmol/L. Increasing WI times resulted in incremental elevation of post-operative serum creatinine that peaked later. DCD120min grafts had the highest and latest elevation of serum creatinine compared to all groups (POD5: 19.0 ± 1.1 mg/dL, p < 0.05). All surviving animals in this group had POD4 24 h urine output < 500 cc (mean 235 ± 172 mL) and elevated serum potassium (7.2 ± 1.1 mmol/L). Only animals in the DCD120min group fulfilled our criteria of SRD (p = 0.003), and their renal function improved by POD7 with 24 h urine output > 500 mL and POD7 serum potassium < 6.0 mmol/L distinguishing this state from primary non-function. In a transplantation survival model, this work demonstrates that prolonging WI time similar to that which occurs in DCD conditions contributes to the development of SRD that resembles clinical DGF.

Evaluation of Early and Late Complications of Pediatric Liver Transplantation with Multi-slice Computed Tomography: A High-Volume Transplant Single-Center Study.

BACKGROUND: To present abdominal multi-slice computed tomography (MSCT) results following transplantation in pediatric patients with a liver transplantation (LT), and to create awareness of early (<3 months) and late (>3 months) complications that may occur. METHODS: This retrospective study included 119 children with an LT performed in our hospital from 2014 to 2017. The descriptive statistics relating to patients' age, gender, transplantation indications, transplantation technique, and MSCT findings were calculated, and are presented as numbers and percentages. The complications were divided into 4 groups: vascular, biliary, parenchymal, and extraparenchymal. RESULTS: The LT procedures were performed with organs from living donors for 83 patients, and from deceased donors for 36 patients. Hepatic artery and portal vein complications were mostly seen in the early period (n = 18), and hepatic vein complications were also observed in the late period (n = 6). The most commonly encountered biliary complications were stenosis/stricture (n = 13) and bile leak/ bilioma (n = 9). Stenosis/stricture frequently occurred in the late period. The most common parenchymal complications were ischemic infarct (n = 8) in the early period, and abscess (n = 4) and recurrent hepatoblastoma (n = 2) in the late period. Hematoma (n = 7), intestinal perforation (n = 3), and focal spleen infarct (n = 3) were among the most commonly observed extraparenchymal abdominal complications. CONCLUSION: The complications occurring after pediatric LT varied according to the time after surgery and the transplantation technique used. Using MSCT, different abdominal complications can be assessed simultaneously, greatly contributing to diagnosis and treatment.

Early Transplant Arteriopathy in Kidney Transplantation.

BACKGROUND: Early dysfunction of renal allografts may be associated with vascular injury, which raises the specter of active rejection processes that require medical intervention. In our practice, we have encountered patients who present with delayed graft function and demonstrate a unique pattern of endothelial cell injury that raises concern for rejection in their biopsy. Therefore, we sought to systematically determine the biopsy characteristics and outcome of these patients. METHODS: During a 17-year period at the University of Washington in Seattle, United States, we identified 24 cases of a distinct arterial vasculopathy presenting in the first year posttransplantation. This early transplant arteriopathy (ETA) is characterized by endothelial cell swelling and intimal edema but without the intimal arteritis that defines vascular rejection. RESULTS: Approximately 1% of transplant biopsies during the study period showed ETA, almost all of which were in deceased donor organs (96%), and most presented with delayed graft function (54%) or increased serum creatinine (38%) soon after transplantation (median 13 days; range, 5-139). In this study, 77% of patients were managed expectantly, with only 2 patients (7.6%) subsequently developing acute vascular rejection. Except for 1 patient who died, all patients had functioning allografts at 1 year follow-up. CONCLUSION: Recognizing ETA and distinguishing it from vascular rejection is important to prevent over-treatment because most patients appear to recover allograft function rapidly with expectant management.

Clinical Significance of Isolated V1 Arteritis in Renal Transplantation.

BACKGROUND: The presence of intimal arteritis (v) in renal allograft biopsy specimens establishes the presence of acute T-cell mediated rejection (TCMR), Grade IIa-III, according to the Banff classification of rejection. The clinical significance of isolated v1 lesions (v1), characterized by arteritis alone, compared with lesions of arteritis with tubulointerstitial inflammation (i-t-v) has been controversial. METHODS: We performed a retrospective review of 280 patients undergoing renal transplantation between 2005 and 2015 who received a "for cause" transplant biopsy using the Banff 2013 classification. Patients with TCMR grade IIa (n = 83) were subdivided into groups with isolated v1 arteritis and i-t-v. Pre- and postoperative renal function, graft survival, and overall survival were evaluated in all patients. RESULTS: Donor and recipient demographics were similar between groups. One month following treatment of rejection, patients with v1 disease had superior recovery of glomerular filtration rate vs patients with i-t-v (P < .002). At a median follow-up of 41 months from transplant, death-censored graft survival was 92% vs 79% (P = .04), and overall survival was 98% vs 79% (P < .004) in the isolated v1 and i-t-v groups, respectively. CONCLUSION: Despite having identical Banff classification of TCMR IIa, our results indicate that graft survival in patients with isolated v1 rejection is superior to those with i-t-v. Following corroboration with data from other centers, modification of the Banff classification scheme should be considered.

Hypothermic Machine Perfusion of Kidneys Compensates for Extended Storage Time: A Single Intervention With a Significant Impact.

INTRODUCTION: Delayed graft function (DGF) adversely affects graft survival and function. Machine perfusion (MP) improves DGF rate and may compensate for extended storage time. MATERIAL AND METHODS: In this single-center cohort study, we included 193 consecutive kidney transplantations. MP was used in 78 kidneys (36%) and static cold storage (CS) in 115 kidneys (64%). CS kidneys were transplanted first followed by MP kidneys if stored differently. Pairs of kidneys from the same donor were subjected for subgroup analysis and included 58 pairs. The primary endpoints were the rate of DGF and 1- and 5-year graft survival. The secondary endpoints were the rate of the primary nonfunction, mortality, acute rejection, duration of DGF, and 5-year estimated glomerular filtration rate. RESULTS: Median cold ischemia time (CIT) was significantly different between the MP and CS groups (24 vs 20 hours, P < .05). MP significantly reduced the rate of DGF (MP vs CS: 21.8% vs 42.6%, P < .05, odds ratio 0.34, 95% confidence interval 0.17-0.67) with no impact on overall 1- and 5-year survival rates. Storage method did not affect the duration of DGF, mortality rate, acute rejection, or the 5-year estimated glomerular filtration rate. CONCLUSIONS: Hypothermic pulsatile MP significantly reduced the rate of DGF in kidneys transplanted with CIT equal to or longer than 12 hours. It is safe and may compensate for longer storage time.

NK cells in antibody-mediated rejection - Key effector cells in microvascular graft damage.

Antibody-mediated rejection (ABMR) stands as the major limitation to long-term transplant outcome. The immunologic understanding of ABMR continues to progress and has identified natural killer (NK) cells as key effector cells promoting and coordinating the immune attack on the graft microvascular endothelium. This review discusses the current concepts outlining the different ways that allow for NK cell recognition of graft endothelial cells which includes antibody-dependent as well as independent processes.

Transplantation Using Renal Grafts With Multiple Renal Arteries: A Putative Study on the Impact of Arterial Reconstruction Technique and Site of Implantation on Outcomes.

BACKGROUND: In the present retrospective study, we analyzed the outcomes of patients transplanted with grafts with multiple renal arteries (MRAs). PATIENTS AND METHODS: In total, 89 patients were transplanted with renal grafts with MRAs from 2003 to 2018. Demographic characteristics; type of donor; warm and cold ischemia times; arterial anastomosis technique; complications; graft function at first month, first year, and last outpatient clinic visit; and patient and graft survival were all retrospectively evaluated. RESULTS: The mean age of the patients was 40.4 ± 13.3 years. Fifty-six patients (62.9%) were male. In total, 42 patients (47.2%) received renal grafts from living related donors. In group A (n = 24; 27%), anastomosis was performed separately to the recipient external or internal iliac arteries; in group B (n = 38; 42.7%), the secondary artery was anastomosed to the main artery in a side-to-side fashion to form a single common orifice; in group C (n = 27; 30.3%), secondary arteries were anastomosed to the main renal artery in an end-to-side fashion. Creatinine clearance at the first month was significantly lower for deceased-donor grafts compared to living-donor renal grafts (P < .05). Creatinine clearance in the first postoperative month was significantly lower in group A and creatinine clearance in the first year was significantly lower in group C (P < .05). The best survival was found for anastomosis to the internal iliac artery (P < .05). CONCLUSION: MRAs can be safely used and the reconstruction technique does not matter if the graft kidney's arterial supply is preserved and the internal iliac artery is chosen for anastomosis.

Successful Endovascular Treatment for Very-Late-Onset and Acute Progressive Multiple Transplant Renal Segmental Artery Stenoses: A Case Report.

PURPOSE: To report the endovascular treatment for acute progressive and very-late-onset multiple segmental small-artery stenoses in transplanted kidney parenchyma presenting with rapidly deteriorating renal function and refractory hypertension in a 65-year-old man. CASE REPORT: Nineteen years ago, the patient received a living renal transplant via end-to-end anastomosis of the right internal iliac artery for kidney failure caused by chronic glomerulonephritis. His transplant renal function (creatinine: 0.9 mg/dL) and blood pressure were stable for 18 years. Then rapid worsening of renal function (creatinine: 2.5 mg/dL) and refractory hypertension occurred. Magnetic resonance angiography and renal angiography showed multiple small segmental artery stenoses in the transplanted kidney. At the 1-month follow-up consultation, total occlusion of 2 branches traversing the inferior pole of the kidney was observed, revealing acute progression of artery stenosis. Balloon angioplasty was successfully performed on those branches; renal function improved (creatinine: 1.3 mg/dL), and blood pressure was sufficiently controlled. CONCLUSIONS: This is a rare case that revealed very-late-onset multiple segmental renal artery stenoses with acute progression in the transplant kidney. Even multiple small segmental artery stenoses can reduce transplant renal function in the chronic phase and progress rapidly. Early percutaneous transluminal angioplasty may thus be feasible and important for preventing graft loss.

Undiagnosed fibromuscular dysplasia in a deceased donor kidney transplant successfully treated with angioplasty.

A 41-year-old man with end-stage renal disease received a deceased donor kidney transplant without complication. Maintenance immunosuppression consisted of tacrolimus, mycophenolate and prednisone. Two months after transplantation, his creatinine did not improve beyond 2-2.3 mg/dL, which prompted allograft biopsy. His biopsy showed tubular epithelial injury without rejection, and given concern for possible calcineurin-inhibitor toxicity, his tacrolimus was changed to sirolimus. Renal function improved, but 1 month later he presented to the hospital with seizure activity, severe hypertension, acute kidney injury and MRI findings suggestive of posterior reversible encephalopathy syndrome. Blood pressure was difficult to control, which had not been the case in the immediate posttransplant period, and addition of lisinopril worsened his renal function. Transplant renal artery stenosis was suspected, and allograft ultrasound with doppler confirmed our suspicion. The patient underwent an angiogram, showing 60% stenosis of the mid-distal transplanted renal artery. Interventional radiology successfully stented this lesion, with subsequent improvement in allograft function and blood pressure control. He did not require further intervention in follow-up.

Living-donor liver transplantation: Right versus left.

A dilemma of graft selection between right or left livers occurs during the planning of living-donor liver transplantation (LDLT) as well as splitting a whole liver graft into full right/full left grafts in deceased-donor liver transplantation. The right liver's relation to the whole liver could be considered as the trunk of a tree; it has a larger volume, the main axis of bile ducts, and the inferior vena cava mainly belongs to the right liver. Therefore, it was considered as the standard graft in LDLTs. Whether to procure the middle hepatic vein (MHV) with a right liver graft or to leave it attached to the left-liver remnant largely depends on the transplant institute. Recently, most transplant institutes tend to leave the MHV with the left liver for the sake of donor safety. Unlike hepatectomy for liver tumors, it is vital to preserve inflow and outflow for both the resected as well as the remaining livers. While procuring any graft type, the most important is to procure a liver graft with reconstructable portal veins, hepatic arteries, hepatic veins, and bile ducts, which should be well preoperatively planned using 3D-computed tomography with considerations given to graft volume and potential congestion areas.

Double Single-Side Kidney Transplants With Bench Vascular Reconstruction: A Further Challenge Beyond the Marginality Without Future Preclusions.

BACKGROUND: Double kidney transplantation allows the use of marginal kidneys with a significant improvement in the recovery of renal function expected after transplantation, although with a greater anesthesiologic and surgical risk. One-sided positioning, more cautious in the event of functional exhaustion, can be complex due to vascular anomalies. MATERIALS AND METHODS: We report the case of 2 double unilateral kidney transplants with vascular reconstructions. The first is a double kidney transplant from a 83-year-old donor. Both kidneys (score 5) had 2 arteries and the arterial patch was not usable. A cryopreserved arterial graft was used for the packaging of an arterial axis with which a single T-L anastomosis was performed; the 2 veins were also joined with the packaging of a single anastomosis. The second case is a double kidney transplant from a cadaveric donor performed on a recipient suffering from severe diffuse atheromasia. The right kidney had 2 arteries and the left kidney had 3 arteries (both score 5). The aortic patches and veins of the 2 kidneys were joined together and a single arterial and venous anastomosis was performed. RESULTS: The course has been uneventful. In both cases there were no perioperative vascular complications. CONCLUSIONS: The use of marginal organs is an increasingly common reality. Bench vascular reconstructions can further increase donation resources, safely enhancing the transplantation of already marginal organs that would otherwise not be usable and allowing the contralateral vascular axis to be kept intact.

Clinicopathologic Analyses of Chronic Vascular Rejection After Kidney Transplantation.

AIM: We discuss the clinicopathologic analyses of cases of biopsy specimens (BS) after renal transplantation and clarify the mechanisms underlying the development and prognostic significance of chronic vascular rejection (CVR). PATIENTS: CVR was diagnosed in 30 renal allograft BS obtained from 23 renal transplant patients being followed up at the Department of Urology and Transplant Surgery, Toda Chuo General Hospital, between January 2010 and August 2017. RESULTS: CVR was diagnosed at a median of 33.1 months post-transplantation. Among the 23 patients, 14 had a history of rejection. Among the 30 BS showing evidence of CVR, the CVR was mild (cv1 on Banff's classification) in 19, moderate (cv2) in 6, and severe (cv3) in 5. We then classified the 30 BS showing evidence of CVR by their overall histopathologic features as follows: cv alone was seen in 9 (30%), cv + antibody-mediated rejection (AMR) in 11 (37%), and cv + T-cell-mediated rejection (TCMR) in 8 (27%). Loss of the renal allograft occurred during the observation period in 2 patients (9%). Of the remaining patients with functioning grafts, deterioration of the renal allograft function after the biopsies occurred in 6 (26%). CONCLUSIONS: Our study results suggest that AMR contributes to CVR in 30% to 40% of cases, TCMR in 20% to 30% of cases, isolated v lesions in 10% of cases, and cv lesions alone in 30%. The prognosis of the graft exhibiting CVR was not too poor even under the present immunosuppressive protocol.

Tissue Factor and Risk of Complications After Kidney Transplantation.

OBJECTIVE: Tissue factor (TF) is a membrane component of many cells and a strong activator of blood coagulation. Damage to the cells induces an increase in its expression and concentration in blood plasma. The injury and breakdown of the cells is inseparably connected with the harvesting and preservation of the kidney. PURPOSE: The aim of the study was an analysis of TF in the renal vein after of restoration of circulation in the transplanted kidney. An additional goal was to investigate the impact of warm ischemia on TF. MATERIALS AND METHODS: The examined group included 61 kidney recipients. Blood was taken from the renal vein in the first minute during reperfusion. Simultaneously, blood from a peripheral vein was also drawn. Apart from tissue factor (TF), I also examined thrombin/antithrombin complexes and fragments 1+2 of prothrombin. RESULTS: In blood from renal veins, I noticed higher level of TF, thrombin/antithrombin complexes and fragments 1+2 of prothrombin in comparison with blood from peripheral veins (P < .0048, P < .016, P < .046, respectively). The 29 recipients (47% of the total) with postoperative complications had much higher concentrations of TF than others (P < .019). TF showed a strong positive correlation with the time of warm ischemia (r = 0.53864, P < .05). CONCLUSIONS: The donor kidney appeared to be one of the main sources of TF in the blood of recipients. Warm ischemia significantly increased its concentration in renal vein blood. This concentration of TF may be associated with damage to the kidney. TF significantly increased the risk of postoperative complications.

Arterial reconstruction using the donor's gonadal vein in living renal transplantation with multiple renal arteries: a case report and a literature review.

BACKGROUND: Arterial reconstruction is one of the paramount procedures in kidney transplantation (KT) and greatly important if the procured kidney has multiple renal arteries (MRA). Despite various established techniques for arterial reconstruction, sometimes, the surgeon finds performing arterial anastomoses challenging in case of MRA. In our case, the donor's gonadal vein and recipient's internal iliac artery graft were used for arterial anastomoses, and 3 years after KT, the allograft did not present vascular complications. CASE PRESENTATION: A 34-year-old man underwent ABO-incompatible preemptive living KT. The allograft had three renal arteries and four renal veins. After donor nephrectomy, arterial reconstruction was performed on a back table. These arteries were reconstructed into one piece using the recipient's internal iliac artery graft. The two arteries at the middle of the renal hilum were reconstructed using the conjoined method. As the superior renal artery was too short to anastomose, the donor's gonadal vein was used for extension. The internal iliac artery graft was anastomosed to the original internal iliac artery. Intraoperative Doppler ultrasonography revealed that the blood flow in each renal artery was adequate, resulting in sufficient blood flow throughout the allograft. The allograft function was maintained with a serum creatinine level of approximately 0.9 mg/dL without vascular complications 3 years after KT. CONCLUSIONS: The donor's gonadal vein can be a candidate for extension of the renal artery in the allograft with MRA. Further follow-up is needed for the assessment of long-term outcomes.

Endovascular Treatment of Pseudoaneurysm After Simultaneous Pancreas-Kidney Transplant: A Case Report.

Pseudoaneurysm is a rare vascular complication in pancreas transplantation that can lead into life-threatening situations. A 44-year-old male patient after simultaneous pancreas-kidney transplant was admitted to the hospital for routine tests 3 months after surgery. A computed tomography scan and ultrasound examination were done, and a diagnosis of pseudoaneurysm was made. The patient was qualified for endovascular treatment. The pseudoaneurysm was closed using coils, and kidney and pancreas grafts stayed in proper condition. Endovascular interventions in patients after pancreas transplantation are safe and preferable in managing postoperative complications.

Predictive Value of Intraoperative Doppler Flowmetry for Delayed Graft Function in Kidney Transplantation: A Pilot Study.

BACKGROUND: The delayed graft function (DGF) in kidney transplantation (KT) is a risk factor for long-term poor graft survival. The pathogenesis is multifactorial but mainly related to an ischemia-reperfusion injury. However, the graft hemodynamics have been recently identified as a key aspect for early DGF risk assessment and potential therapeutic intervention. METHODS: A pilot study on 20 single kidney grafts from donor after brain death with intraoperative measurement of graft arterial flowmetry, 30 minutes after reperfusion. Exclusion criteria were grafts with multiple arteries or severe atherosclerosis of the recipient's external iliac artery. RESULTS: KT recipients with DGF (n = 4, 20%) were homogenous with controls (n = 16) in terms of cold ischemia time, donor age, recipients' hemodynamic parameters, renal artery, and recipients' external iliac artery diameters. Nonetheless, at transplant, the kidney grafts that developed DGF were characterized by a significantly higher renal artery resistive index (DGF vs no-DGF 0.96 ± 0.04 vs 0.77 ± 0.13, P = .02), as well as lower flow extraction rate (24.8% ± 11.8 vs 59.2% ± 21.1, P < .01). CONCLUSIONS: Intraoperative arterial graft flowmetry seems to be an effective tool to identify grafts at high risk of DGF.