Late renal allograft torsion in a pediatric transplant recipient.

2021

e14210

2021 Dec 15

1399-3046

<p><strong>BACKGROUND: </strong>Kidney allograft torsion is a rare complication of kidney transplant that can lead to allograft loss from prolonged ischemia if not quickly corrected with detorsion and nephropexy. We report a case of late intraperitoneal renal allograft torsion in a pediatric transplant recipient.</p>

<p><strong>CASE REPORT: </strong>The patient is a 7-year-old male with a history of end-stage renal disease secondary to renal dysplasia in the setting of bilateral high-grade vesicoureteral reflux. He underwent bilateral native nephrectomies for recurrent pyelonephritis and right ureteral kink with urinary tract obstruction. Torsion occurred 3&nbsp;years after transplant in the setting of one day of emesis, loose stool, severe abdominal pain, and decreased urine output. Diagnosis of transplant torsion was suspected on non-contrast CT scan done after transplant Doppler ultrasound showed no flow to the allograft. The CT scan showed that the kidney had been medialized and renal hilum was flipped from the expected orientation. The patient required a transplant nephrectomy.</p>

<p><strong>CONCLUSIONS: </strong>Renal transplant torsion is a rare event but should be suspected in any renal transplant recipient with acute onset of abdominal pain, acute kidney injury, and decreased urine output, regardless of length of time from transplantation. Patients suspected to have renal torsion should be evaluated emergently with a transplant ultrasound Doppler.</p>

10.1111/petr.14210

Pediatr Transplant

34907635

Tissue metabolic profiling shows that saccharopine accumulates during renal ischemic-reperfusion injury, while kynurenine and itaconate accumulate in renal allograft rejection.

2020

65

2020 May 04

1573-3890

<p>To examine metabolic differences between renal allograft acute cellular rejection (ACR) and ischemic-reperfusion injury (IRI), we transplanted MHC-mismatched kidneys and induced 28&nbsp;min warm-IRI, and collected the ACR and IRI kidneys as well as their respective native and collateral control kidneys. We extracted metabolites from the kidney tissues and found the lysine catabolite saccharopine 12.5-fold enriched in IRI kidneys, as well as the immunometabolites itaconate and kynurenine in ACR kidneys. Saccharopine accumulation is known to be toxic to mitochondria and may contribute to IRI pathophysiology, while itaconate and kynurenine may be reflective of counterregulatory responses to immune activation in ACR.</p>

10.1007/s11306-020-01682-2

Metabolomics

32367163

Invited Letter Re: The kidney allocation system and its implications for pediatric recipients.

2018

1825

2018 07

1600-6143

10.1111/ajt.14882

Am. J. Transplant.

29673056

Use of public health service increased risk kidneys in pediatric renal transplant recipients.

2019

e13405

2019 Aug

1399-3046

<p>With the opioid epidemic and expansion of "IR" classification, 25% of deceased donors are categorized PHS-IR. Studies have assessed utilization of PHS-IR organs among adults, but little is known about pediatric recipients. This retrospective cohort study from 2004-2016 (IR period) aimed to: (a) assess IR kidney utilization patterns between adults and children; (b) identify recipient factors associated with transplant from IR donors among pediatric kidney recipients; and (c) determine geography's role in IR kidney utilization for children. The proportion of pediatric recipients receiving IR kidneys was significantly lower than adults (P&nbsp;&lt;&nbsp;0.001), even when stratified by donor mechanism of death (non-overdose/overdose) and era. In mixed effects models accounting for clustering within centers and regions, older recipient age, later era (post-PHS-IR expansion), and blood type were associated with significantly higher odds of receiving an IR kidney (17&nbsp;years era 5: OR 5.16 [CI 2.05-13.1] P&nbsp;&lt;&nbsp;0.001; 18-21&nbsp;years era 5: OR 2.72 [CI 1.05-7.06] P&nbsp;=&nbsp;0.04; blood type O: OR 1.32 [CI 1.06-1.64] P&nbsp;=&nbsp;0.013). The median odds ratio for center within region was 1.77 indicating that when comparing two patients in a region, the odds of receiving an IR kidney were 77% higher for a patient from a center with higher likelihood of receiving an IR kidney. Utilization of PHS-IR kidneys is significantly lower among pediatric recipients versus adult counterparts. More work is needed to understand the reasons for these differences in children in order to continue their access to this life-prolonging therapy.</p>

10.1111/petr.13405

Pediatr Transplant

31271263

18-month outcomes of heterologous bilateral hand transplantation in a child: a case report.

2017

35-44

2017 Sep

2352-4650

<p><strong>BACKGROUND: </strong>Although heterologous vascular composite allotransplantation has become a burgeoning treatment option for adult amputees, there have been no successful cases previously reported in children. Here, we describe the surgical, immunological, and neurorehabilitation details with functional outcomes 18 months after heterologous bilateral hand and forearm transplantation in an 8-year-old child with quadrimembral amputations and a previous kidney transplant.</p>

<p><strong>METHODS: </strong>2 years of extensive preparation by medical and surgical teams preceded the hand-forearm transplantation of this child. The initial immunosuppressive protocol included thymoglobulin, tacrolimus, prednisone, and mycophenolate mofetil. In July, 2015, our vascularised composite allotransplantation team did the first bilateral hand and forearm transplantation in a child, an 8-year-old boy with previous living-related kidney transplantation. The surgery included four teams working simultaneously on the donor and recipient limbs, aided by customised cutting guides that aimed to reduce ischaemia time. Following an extended length of time in hospital, skin biopsies and close monitoring of renal function and drug concentrations occurred weekly for the first 3 months and were slowly tapered to monthly, and then quarterly. Skin biopsies were also done when tissue rejection was suspected. Paediatric-specific rehabilitation techniques were applied to promote patient engagement during rehabilitation. Progress was assessed by monthly sensory and motor function tests during routine clinic visits and with serial functional brain imaging studies, including structural brain MRI, magnetoencephalography and transcranial magnetic stimulation.</p>

<p><strong>FINDINGS: </strong>The surgery lasted 10 h and 40 min. Vascular revision of the ulnar artery was required a few hours postoperatively. There were no further immediate postsurgical complications. Rejection episodes occurred throughout the first year but were reversed. An increase in serum creatinine led to the addition of sirolimus at 3 months after transplantation with concomitant reduction in tacrolimus targets. Sensibility to light touch was present by 6 months after transplantation. Intrinsic hand muscle innervation was present by 7-10 months after transplantation. At 18 months, the child had exceeded his previous adapted abilities. As of 18 months after transplantation surgery he is able to write and feed, toilet, and dress himself more independently and efficiently than he could do before transplantation. He remains on four immunosuppressive medications and functional neuroimaging studies have shown motor and somatosensory cortical reorganisation.</p>

<p><strong>INTERPRETATION: </strong>Hand transplantation in a child can be surgically, medically, and functionally successful under carefully considered circumstances. Long-term data on the functional trajectory, neurological recovery, psychological sequelae, and the potential late effect of immunosuppression are still needed to support broader implementation of paediatric vascular composite allotransplantation.</p>

<p><strong>FUNDING: </strong>The Children's Hospital of Philadelphia.</p>

10.1016/S2352-4642(17)30012-3

Lancet Child Adolesc Health

30169225

The Effects of Tacrolimus on T-Cell Proliferation Are Short-Lived: A Pilot Analysis of Immune Function Testing.

2017

e199

2017 Aug

2373-8731

<p><strong>BACKGROUND: </strong>Optimal immunosuppression after organ transplant should balance the risks of rejection, infection, and malignancy while minimizing barriers to adherence including frequent or time-sensitive dosing. There is currently no reliable immune function assay to directly measure the degree of immunosuppression after transplantation.</p>

<p><strong>METHODS: </strong>We developed an immune function assay to mea//sure T-cell proliferation after exposure to immunosuppression in vivo. We tested the assay in mice, and then piloted the approach using single time point samples, 11 pediatric kidney transplant recipients prescribed tacrolimus, mycophenolate, and prednisone 6 months to 5 years posttransplant, with no history of rejection, opportunistic infection, or cancer. Twelve healthy adults were controls.</p>

<p><strong>RESULTS: </strong>We demonstrated that our assay can quantify suppression of murine T-cell proliferation after tacrolimus treatment in vivo. In humans, we found a mean 25% reduction in CD4 and CD8 T-cell proliferation in pediatric renal transplant recipients on triple immunosuppression compared with adult healthy controls, but the pilot results were not statistically significant nor correlated with serum tacrolimus levels. We observed that cell processing and washing reduced the effects of tacrolimus on T-cell proliferation, as did discontinuation of tacrolimus treatment shortly before sampling.</p>

<p><strong>CONCLUSIONS: </strong>T-cell proliferation is currently not suitable to measure immunosuppression because sample processing diminishes observable effects. Future immune function testing should focus on fresh samples with minimal washing steps. Our results also emphasize the importance of adherence to immunosuppressive treatment, because T-cell proliferation recovered substantially after even brief discontinuation of tacrolimus.</p>

10.1097/TXD.0000000000000715

Transplant Direct

28795150