Yoji Hyodo

Outcomes of Pediatric ABO-Incompatible Kidney Transplantations Are Equivalent to ABO-Compatible Controls

BACKGROUND Due to the profound shortage of suitable deceased allografts, much effort has been made to investigate whether successful kidney transplantation (KT) is possible across the ABO blood group barrier even for pediatric recipients. METHODS We reviewed 52 consecutive ABO incompatible (ABOic) transplantation performed between September 1989 and March 2011. The mean age at transplantation was 10.6 ± 3.9 years (range, 4.4-19.7), with 35 boys and 17 girls. The donor-to-recipient ABO blood antigen incompatibility was as follows: A1/O (n = 17); B/O (n = 13); A1/B (n = 6); B/A1 (n = 1); A1B/B (n = 9); and A1B/A (n = 6). As a control group, data were collected from 271 pediatric ABO compatible (ABOc) living donor KT in the same period. RESULTS Overall acute rejection episodes (ARE) among the ABOic group were significantly higher than those of the ABOc group (44% vs 26%; P < .02). However, there was no difference in glomerular filtration rate (GFR) at 1 year after transplantation: 86 ± 31 mL/min for ABOic vs 99 ± 37 mL/min for ABOic, respectively. The 1-y, 5-y, and 10-year patient survival rates were 98%, 92%, and 92% in the ABOic group, respectively, and 99%, 98%, and 97% in the ABOc group, respectively (P = not significant [NS]). The overall 1-, 5-, 10-, and 15-year graft survival rates were 94%, 88%, 86%, and 86% in the ABOic group, respectively, and 95%, 92%, 88%, and 78% in the ABOc group, respectively. CONCLUSION ABOic KT provided long-term allograft and patient survivals equivalent to ABOc live donor transplantations.

The New Desensitization Porotocol for ABO Incompatible Living Donor Kidney Transplantation Using Low Dose Rituximab without Plasmapheresis

Purpose We have demonstrated that the long-term outcome of ABO incompatible living donor kidney transplantation (ABOiKT) was comparable to those of ABO compatible KT(ABOcKT). Since 2010, new protocol using low dose rituximab (RIT) without plasmapheresis(PP) was administered to recipients with low titer anti-donor blood group antibody titer (ABGAb) was less than x64. The purpose of this study was to evaluate the efficacy of this new protocol for ABOiKTx. Method 279 recipients underwent kidney transplantation between September 2010 and August 2017. 43 patients who received PP before kidney transplantation because of positivity of donor specific antibody, high titer ABGAb or a recurrence prevention of original disease were excluded. Consequently, 236 recipients were enrolled in this study. The patients were divided into two groups: ABOiKT (n=41) and ABOcKT (n=195). No recipient received splenectomy before kidney transplantation. As a standard protocol, all patients received quadruple immunosuppressive therapy including calcineurin inhibitor, methylprednisolone and mycophenolate mofetil. In addition, as a desentization protocol for ABOiKT, RIT was administered twice on day -10 and -1 day before transplantation at a dose of 100 mg/body. To evaluate the efficacy and safety of this new protocol for ABOiKT, graft survival, clinical acute rejection rate, late-onset neutropenia (LON) and infectious complication were compared between the two groups. Results Median baseline titers of ABGAb in ABOiKT was x16 (0-x64). Overall 1-,3- and 5-year graft survival rates were 98.3%, 96.8% and 96.8% in ABOcKT and 97.1%, 97.1% and 97.1% in ABOiKT, respectively (p=0.950). There was no significant difference in the clinical T cell mediated acute rejection rates (17 (8.7%) in ABOcKT vs. 3 (7.3%) in ABOiKT (p=0.770)) nor antibody mediated acute rejection rates (3 (1.5%) in ABOcKT vs. o (0%) in ABOiKT (p=0.424)). Ocurrence rates of LON were significantly higher in ABOiKT (18 (43.9%)) than in ABOcKT (11 (5.6%)) (p<0.0001). However, the rates of infectious complication that needed inpatient hospital care or modification of immunosuppression were no significantly different between two groups (p=0.256). Conclusion Our current desensitization protocol using low dose RIT without splenectomy was safe and effective for ABOiKTx. Though infectious complication did not increase, we had to pay attention to LON after ABOiKT. Moreover, pretransplant antibody removal would not be prerequisite for ABOiKTx with low titer ABGAb.

Interlobular hyaline arteriopathy reflects severe arteriolopathy in renal allografts: Interlobular hyaline arteriopathy

The present study was performed to examine the clinicopathological significance of hyaline deposits in the smooth muscle of the interlobular artery (interlobular hyaline arteriopathy [IHA]) in renal allografts.

Novel technique for repair of arteriovenous fistula with aneurysm

Aneurysm of autogenous arteriovenous fistula is a common complication in patients receiving hemodialysis. We present a novel method for repair of a case of aneurysm of arteriovenous fistula resulting from stenosis. A 52-year-old woman presented with aneurysm formation of the left upper arm arteriovenous fistula, with related numbness in the left hand. Clinical examination revealed a tense, pulsatile aneurysm above the brachiocephalic anastomosis. Ultrasound examination revealed an aneurysm (50 mm × 25 mm) with proximal stenosis and an arteriovenous fistula flow rate above 1200 mL/min. An incision was made lateral to the aneurysm from the brachiocephalic anastomosis to the proximal stenosis through the antecubital fossa. After exposure of the entire aneurysmal arteriovenous fistula, the narrowed segment, and the proximal cephalic vein, the aneurysm outflow was ligated and the narrowed segment was removed. A U-shaped incision was made on the aneurysm to create an aneurysmal flap (75 mm × 20 mm). The flap was tubularized after calibration of the lumen with a 14-Fr cannula. End-to-end anastomosis was performed between the distal tubularized flap and the proximal cephalic vein. Intra- and postoperative arteriovenous fistula flow rates were below 900 mL/min. After surgery, the remodeled arteriovenous fistula was immediately usable for hemodialysis with normal arteriovenous fistula flow in the upper arm. The repair technique achieved not only aneurysmorrhaphy but also created an autologous vascular graft as the bypass after removal of the narrowed segment. Moreover, this technique achieved reduced arterial inflow and is suitable for patients with conditions similar to those of this case.

Pharmacokinetic Profile of Twice- and Once-daily Tacrolimus in Pediatric Kidney Transplant Recipients

BACKGROUND The aim of this study was to assess the differences in pharmacokinetic (PK) profiles after the 1:1 ratio-based conversion from a twice-daily to a once-daily tacrolimus formulation (TD-TAC and OD-TAC, respectively) in pediatric recipients of kidney transplants. METHODS TD-TAC was initially administered to 29 pediatric patients who underwent kidney transplantations between April 2010 and September 2015 and were then subsequently switched to OD-TAC. The switch dose ratio was 1:1, and the 24-hour complete PK parameter assessment was performed before and after the regimen was changed from TD-TAC to OD-TAC. RESULTS The mean total daily dose at baseline was 5.5 ± 2.9 mg (0.18 ± 0.10 mg/kg body weight). Consecutive PK studies revealed no significant difference in the mean time to achieve maximum concentrations and the area under the concentration-time curve from 0 to 24 hours (AUC0-24) of both drug formulations. However, the mean trough concentration (Cmin) and the maximum concentration of OD-TAC were 22% and 6% lower and higher, respectively, than those of TD-TAC. Therefore, a better correlation was observed between the AUC0-24 and Cmin of OD-TAC than between those of TD-TAC. CONCLUSIONS After the change from TD-TAC to OD-TAC, the AUC0-24 values were equivalent despite a 22% reduction in Cmin. Cmin may therefore be an excellent predictor in the therapeutic drug monitoring of OD-TAC because of its superior correlation with AUC0-24.

Urinary reconstruction in vertebral, anorectal, cardiac, trachea‐esophageal, renal abnormalities and limb defects association with chronic renal failure and penile duplication

Various urological complications in VATER association require careful management. A 15‐year‐old boy with VATER association, including a hypoplastic lower urinary tract and diphallia, presented with chronic kidney disease and incontinence after a right loop ureterostomy. In order to acquire urinary continence without renal function impairment, an ileocecal reservoir with umbilical catheterizable stoma was created as a urinary reconstruction. The ectopic posterior penis was resected for cosmetic reasons, and the stump of the hypoplastic urethra was opened at the perineal skin. Clean intermittent self‐catheterization through the umbilicus using disabled bilateral limbs was then achieved. This report describes the management of VATER association in a patient with complicated urological anomalies.

Evaluation of blood group antibodies in ABO-incompatible living-donor kidney transplantation

To assess changes in anti‐blood type antibody titers and postoperative outcomes (graft survival and rejection rates) at our center with the use of the immunosuppressant, rituximab, in ABO‐incompatible kidney transplants from living donors. Confirming anti‐donor blood group antibodies is important for avoiding humoral rejection in ABO‐incompatible kidney transplants. Splenectomy has been carried out in our hospital according to Alexandres policy in order to suppress the production of anti‐donor blood group antibodies. However, splenectomy has recently been avoided due to the administration of the immunosuppressant rituximab, which gives satisfactory outcomes. Thus, pre‐ and postoperative anti‐donor blood group antibodies were measured, and the outcomes achieved with rituximab were examined.