Splenic Vessels as a Rescue for Pediatric Kidney Retransplantation in Children With Iliac-caval Agenesis or Thrombosis : Transplantation

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Original Clinical Science—General

Splenic Vessels as a Rescue for Pediatric Kidney Retransplantation in Children With Iliac-caval Agenesis or Thrombosis

Tandoi, Francesco MD, PhD, FEBS1,*; Peruzzi, Licia MD, PhD2,*; Lonardi, Pietro MD2; Cussa, Davide MD1; Catalano, Silvia MD1; Verri, Aldo MD3; Merlo, Maurizio MD3; Sedigh, Omidreza MD4; Gerocarni Nappo, Simona MD5; Melloni, Claudia MD3; Patrono, Damiano MD, PhD, FEBS1; Gianoglio, Bruno MD2; Romagnoli, Renato MD, FEBS1

Author Information
Transplantation 107(1):p 225-230, January 2023. | DOI: 10.1097/TP.0000000000004255

Abstract

INTRODUCTION

Management of chronic dialysis in small infants is challenging. Peritoneal dialysis (PD), generally preferred as the simpler and most effective treatment, can be complicated by peritonitis, ultrafiltration/depuration inefficiency, or catheter-related complications, whereas hemodialysis (HD), which requires a proper vascular access by the mean of comparatively large central venous catheters, may lead to endothelial damage, infection, and thrombosis and result in progressive venous depletion.1 Chronic dialysis, however, even if supplemented by optimized medical therapy, only partially substitutes renal function and might be associated with growth retardation, mineral bone disorders, loss of school time, and developmental delays, all of which can be overcome by transplantation. Therefore, kidney transplantation (KT) in infants is indicated as soon as they reach reasonable weight and height, even if thrombosis or vascular malformations of the iliac-caval system may require tailored solutions.2-4 Implantation of the kidney graft on the splenic vessels has been described as a rescue strategy in adults with unsuitable iliac-caval axis.5

We report our experience with 2 children who required a second KT using splenic vessels, representing original cases in the literature.

MATERIALS AND METHODS

Two children on chronic HD were managed in 2016 and 2021, respectively (Table 1). Both had a history of a previously failed KT, PD dropout for clinical indication, pending exhaustion of vascular accesses for dialysis, and unavailability of the iliac-caval system for implantation of a second kidney.

TABLE 1. - Clinical data of the 2 children undergoing kidney retransplantation on the splenic vessels
Patient 1 Patient 2
Recipient
 Sex Female Male
 Age, y 6 4
 Weight, kg 18 11
 Height, cm 102 87
 Body surface area, m2 0.71 0.51
 Waiting list time, d 88 18
 Blood type A A
 HLA-A1 1 2
 HLA-A2 26 (10) 26 (10)
 HLA-B1 44 (12) 7
 HLA-B2 57 (17) 44 (12)
 HLA-DR1 7 4
 HLA-DR2 15 (2)
Donor
 Age, y 12 10
 Sex Male Male
 Weight, kg 40 37
 Height, cm 151 151
 Body surface area, m2 1.31 1.27
 Cause of brain death Anoxia Trauma
 Blood type O A
 HLA-A1 2 1
 HLA-A2 2 68 (28)
 HLA-B1 50 (21) 8
 HLA-B2 51 (5) 44 (12)
 HLA-DR1 7 17 (3)
 HLA-DR2 11 (5) 11 (5)
Transplant surgery
 Kidney Left Left
 Long axis, cm 10.5 11.5
 Cold ischemia time, min 1126 916
 Warm ischemia time, min 48 25
Donor/recipient match
 Donor/recipient CMV Negative/positive Positive/positive
 Donor/recipient EBV Negative/positive Positive/negative
 Crossmatch Negative Negative
Posttransplant course
 IS induction Antithymocyte globulins (3.5 mg/kg) and steroids (20 mg/kg) Antithymocyte globulins (4.5 mg/kg) and steroids (20 mg/kg)
 IS maintenance Tacrolimus + MMF + steroids Tacrolimus + steroids
 Antithrombotic drugs Acetylsalicylate (3 mg/kg/d) None
 Anticoagulant drugs Sodium enoxaparin (50 IU/d) Sodium enoxaparin (50 IU/d)
 ICU stay, d 10 7
 Follow-up, mo 64 10
CMV, cytomegalovirus; EBV, Epstein-Barr virus; ICU, intensive care unit; IS, immunosuppression; MMF, mycophenolate mofetil.

RESULTS

The first patient was a 5-y-old girl, who was anuric since birth due to bilateral renal hypodysplasia, not genetically defined. She had been treated with PD until 12 mo of age, when she lost ultrafiltration capacity because of recurrent bouts of peritonitis and was switched to daily HD to allow proper feeding and calorie intake. In the absence of a related living donor, she was waitlisted for deceased donor KT as soon as she reached a suitable body size (10 kg of body weight and 85 cm of height) and transplanted at the age of 4 y. The kidney graft was implanted in the right iliac fossa on the iliac vessels with an extraperitoneal access. KT was complicated by venous thrombosis, and the graft was explanted. Despite a preoperative Doppler ultrasound assessment showing patent iliac veins, a subsequent computed tomography scan revealed inferior vena cava (IVC) agenesis also in the retrohepatic tract with multiple retroperitoneal collaterals and a hypertrophic azygous system, whereas the portal system was normal (Figure 1A, B). The portal circulation was identified as the only low-pressure venous district. Despite immunosuppression (IS) maintenance, the previous transplant and the repeated blood transfusions led to a hypersensitized state with panel reactive antibody (PRA) of 99%. The child was desensitized according to Vo et al6 15 mo before waitlisting. The protocol was based on two 2 g/kg (30 g) doses of intravenous immunoglobulin G at days 0 and 30, combined with a single 500 mg/m2 (350 mg) dose of rituximab at day 15. Because of the partial response, an additional dose of rituximab (350 mg) was administered 1 y later. At the time of waitlisting, PRA was reduced to 75%. Three months later, a compatible deceased brain-dead donor with negative crossmatch became available. The transplant began (Video S1, SDC, https://links.lww.com/TP/C536) by performing splenectomy with preservation of 2 accessory spleens; the distal pancreas was then mobilized to expose the splenic vein and artery. The kidney graft was implanted by the mean of a venous end-to-side and an arterial end-to-end anastomosis between renal and splenic vessels, obtaining proper vascular alignment (Figure 1C–E). Thanks to the favorable donor-to-recipient height mismatch, a tension-free ureterovesical anastomosis could be performed on a double J stent. IS induction was based on antithymocyte globulins (total, 3.5 mg/kg over 5 d), tacrolimus (target through level, 8–10 ng/mL), and steroids (cumulative dose, 20 mg/kg). Maintenance IS was based on tacrolimus (target through level, 6–8 ng/mL), mycophenolate mofetil (1200 mg/m2), and steroids (0.75 mg/kg/d), which were slowly tapered and finally discontinued at 24 mo. Aspirin (3 mg/kg/d) and sodium enoxaparin (targeting the anti-Xa factor level of 0.35–0.75 IU/mL) were administered as antithrombotic prophylaxis for 6 mo. Graft function recovered to a serum creatinine level of 0.4 mg/dL (35.2 µmol/L) and remained stable thereafter. At 5-y follow-up, she had not developed major viral and bacterial infections or posttransplant lymphoproliferative diseases. The catch-up growth has been so far satisfactory (both weight and stature above the 75th percentile), with normal pubertal progression, cognitive capacities, and school performances (Table S1, SDC, https://links.lww.com/TP/C488).

F1
FIGURE 1.:
Rationale and technical aspects of the kidney transplantation performed by replacing the spleen in patient 1. A, Inferior vena cava agenesis discovered on computed tomography (CT) at age 5. B, Splanchnic venous circulation (with insert) on enhanced volume rendering CT imaging at age 5: the hepatic veins are patent and converge directly into the right atrium; the portal vein and its main branches are normal. Note that the splenic vein is the largest portal branch, making its use preferable to the superior mesenteric vein. In the insert, an axial CT slice shows 2 accessory spleens (12 and 9 mm in diameter, respectively). C, Splenorenal arterial reconstruction (with insert) on CT slices 3 mo after transplant. End-to-end anastomosis (arrow) was performed close to the celiac trunk and resulted in proper vessel alignment. D, Splenorenal venous reconstruction (with insert) on CT slices 3 mo after transplant. No kinking or torsion is observed by virtue of the end-to-side anastomosis (arrow). Arrowheads indicate the distal portion of the recipient splenic vein (patent but thin due to the low flow inside) and an accessory spleen already having reached a 2.6-cm diameter. E, Three-dimensional reconstruction of the kidney transplanted on the splenic vessels and placed in the splenic fossa.

Ultrasound scan performed during follow-up has shown normal renal vascular resistances (resistance index, 0.6) and a normal portal flow and liver parenchyma.

The second patient was a boy affected by primary hyperoxaluria type 1 (homozygous mutation on AGXT p.lle244Thr), who developed end-stage kidney disease requiring renal replacement therapy at 2 mo of age for severe nephrocalcinosis. Considering the elevated oxalemia (pre/post-dialysis, 266/72 mmol/L) and the extreme difficulty to thrive, he was started on daily HD combined with PD to maximize oxalate removal. At the age of 15 mo, he underwent combined liver-KT and a right nephrectomy; KT was performed on the left iliac vessels with an extraperitoneal access. After an initial complete recovery of renal function, postoperative course was complicated by severe pneumonia with respiratory failure and fluid overload. Although liver function persisted as normal, he required continuous renal replacement therapy, which resulted in dramatic oliguria and oxalate accumulation, finally leading to the failure and the need to explant the kidney graft. The repeated cannulations were complicated by bilateral jugular, right subclavian, and diffuse IVC thrombosis up to the piggyback caval anastomosis of the previous liver transplant (Figure 2A, B). When he reached the age of 4 y, the possibility of KT on the splenic vessels was investigated. Liver graft biopsy showed no evidence of acute cellular rejection (rejection activity index, 0/9)7 and mild-moderate fibrosis (liver allograft fibrosis score, 5/9),8 whereas liver elastography was satisfactory (7.6 kPa; interquartile range, 26%). A hepatic venous pressure gradient of 6 mm Hg was directly measured by ultrasound-guided percutaneous transhepatic catheterization of the left portal branch and the middle hepatic vein. The child was waitlisted for re-KT, with pre- and postdialysis oxalemia of 80 and 7 mmol/L, respectively, and PRA <30%. At KT, after splenic vein isolation with a caudal approach to the body of pancreas, the graft renal vein was anastomosed end-to-side to the recipient splenic vein, and the renal artery was anastomosed end-to-side to the aorta (Figure 2C, D). Finally, as in patient 1, a tension-free ureteroneocystostomy on a double J stent was performed, thanks to the donor/recipient dimensional mismatch. IS induction was based on antithymocyte globulins (total, 4.5 mg/kg; over 5 d) and steroids (20 mg/kg cumulative dose). Tacrolimus dosage was increased targeting through levels of 9–12 ng/mL until 4 wk after transplant and 6–8 ng/mL thereafter. Steroids (0.75 mg/kg/d) were tapered and will be discontinued at 24 mo. Anticoagulation was based on sodium enoxaparin, targeting anti-Xa factor level of 0.35–0.75 IU/mL. Postoperative course was uneventful. Plasma oxalate immediately normalized (4 mmol/L), and urinary oxalate rapidly reached the normal range for the child’s age. At 10-mo follow-up, the child is alive and well, with normal renal and liver functions.

F2
FIGURE 2.:
Rationale and technical aspects of the kidney transplanted on the splenic vein following orthotopic liver transplantation in patient 2. A, Patency of the iliac-caval axis on computed tomography (CT) at 6 mo of age, before listing for combined liver-kidney transplantation. B, Venous anatomy on enhanced volume rendering CT imaging at age 4: the subhepatic inferior vena cava (IVC) is not visible because of thrombosis, whereas the hepatic veins are patent and converge into suprahepatic IVC through the piggyback anastomosis of the liver graft. The portal vein and its main branches are normal. C, Intraoperative image of the left kidney graft transplanted in orthotopic position on the recipient splenic vein (blue arrow) and aorta (white arrow); the ureter was anastomosed to the native bladder (yellow arrow). D, Lifting the body of the pancreas, the end-to-side anastomosis between the splenic vein and the graft renal vein is visible (blue arrow); white arrow: end-to-side anastomosis between the left renal artery and the aorta.

DISCUSSION

The use of splenic or mesenteric veins as sites for venous drainage during KT has been described in adults with IVC thrombosis since the 1980s2,9-13 but only rarely in children. Shapira et al14 reported a KT in a 6-y-old child with previous Wilm’s tumor, during which kidney vessels were anastomosed to the aorta and the splenic vein after splenectomy and the ureter on the native one. Using the same technique, Kumar et al15 described a KT in a 7-y-old child with IVC thrombosis; the ureter was reconstructed by ureteroneocystostomy. The splenic fossa as a site for graft implantation on splenic vessels was only recently reported in liver transplantation.16,17

Both patients in this series show significant peculiarities. To our knowledge, patient 1 represents the first pediatric recipient in whom the native spleen was replaced with a kidney graft. Implantation in the splenic fossa, which was necessary because of the size of the kidney graft (Table 1), prevented vascular kinking, also allowing an easy access for eventual biopsies. Although clear evidence is missing, previous reports have suggested an increased immunological tolerance in KT with portal venous drainage.18,19 KT on splenic vessels could be of interest in highly sensitized patients, because the combination of splenectomy20 with hepatic passage of the graft outflow21 might theoretically confer an immunological advantage in the long term. Patient 2 represents the first KT performed with portal venous drainage in a liver transplanted recipient; considering the young age and the frailty of the patient, the spleen was preserved to reduce the risk of bacterial infections and portal vein thrombosis. In both cases, the ureter of the kidney graft was preserved as long as possible and directly anastomosed on the native bladder.

Although PD represents the first option for chronic substitutive treatment in newborns and small infants, in some specific situations, HD is required to overcome the ultrafiltration problems due to repeated peritonitis or peritoneal fibrosis or, as in primary hyperoxaluria type I, to offer a more efficient depuration and avoid massive systemic deposition. Central veins repeated catheterization with the available devices, which are always disproportionately large, may cause residual thrombosis with progressive venous depletion.

Aberrant vascular anatomy and venous thrombosis may preclude long-term HD and contraindicate KT using traditional approaches. Because the splanchnic circulation is frequently patent and untouched in these patients, we suggest considering KT on splenic vessels as a safe and effective option to manage complex pediatric cases.

ACKNOWLEDGMENTS

Both patients were managed within the European Reference Network Transplant Child.

REFERENCES

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