Mineral disorders in pediatric pre-emptive kidney transplantation.

BACKGROUND: Pre-emptive kidney transplantation (PEKT) is beneficial for patients, improves graft survival and minimizes the complications associated with chronic kidney disease. Reports on pediatric PEKT, however, are limited, and little is known about the parathyroid hormone (PTH) abnormalities and calcium-phosphorus disorders (CPD) in this condition. This study was the first to report on mineral disorders in pediatric PEKT patients during a 1 year period. METHODS: We conducted a comparative examination of the abnormalities in calcium, phosphorus, calcium-phosphorus products and PTH before and 1 year after living donor kidney transplantation in PEKT and non-PEKT patients. RESULTS: Thirty-one patients were included. The patients were divided into two groups: PEKT (n = 11; 5 months in CKD stage 4-5) and non-PEKT (n = 20; 31.5 months in dialysis). Mean age at transplantation was 9.4 ± 5.0 years. Hypercalcemia and hyperphosphatemia were observed before and after transplantation in the PEKT and non-PEKT groups, and >15% of patients in each group had bone disorder and ectopic calcification associated with mineral disorder. Mineral disorder was present for approximately 3 months after transplantation in both treatment groups. CONCLUSIONS: No significant differences in PTH or CPD were noted between PEKT and non-PEKT groups; moreover, normalization of abnormal values did not differ between the PEKT and non-PEKT groups. Compared with non-PEKT, PEKT did not improve the course of mineral metabolism disorders. Mineral and bone disorder treatment was likely insufficiently provided to pediatric PEKT patients. To obtain the maximum advantage of PEKT, calcium and phosphorus levels should be strictly controlled before kidney transplantation.

Living-Donor Kidney Transplant With Preformed Donor-Specific Antibodies.

OBJECTIVES: We investigated outcomes in living-donor kidney transplant recipients with preformed donor-specific antibodies (detected with flow cytometry and specified with the LABScreen single antigen test) under desensitization pretransplant and immunosuppression posttransplant. MATERIALS AND METHODS: Of 15 recipients included, 8 had ABO-incompatible kidney transplant. Six patients had sensitization caused by pregnancy, 8 by blood transfusion, 5 by previous transplants, and 1 by unknown cause. Desensitization was initiated using calcineurin inhibitors, methylprednisolone, and mycophenolate mofetil 30 days pretransplant, with rituximab administered 1 and 10 days pretransplant. Patients underwent plasmapheresis 1, 3, and 5 days pretransplant. Antithymocyte globulin was admi nistered for 5 days posttransplant as induction therapy. At 3 and 12 months posttransplant, all recipients underwent protocol renal allograft biopsies, with donor-specific antibodies simultaneously measured with the single antigen test. RESULTS: T-cell complement-dependent cytotoxicity crossmatch was negative in all 15 recipients, but T-cell and B-cell flow cytometry was positive in 8 and 14 recipients, respectively. Anti-HLA class I antibodies became negative, except in 1 recipient 3 months posttransplant. Class II antibodies remained positive in 8 recipients 3 months posttransplant. No clinical or subclinical T-cell-mediated rejection occurred, but 1 recipient experienced clinical acute antibody-mediated rejection. At 3 and 12 months posttransplant, 8 and 5 recipients had subclinical acute antibody-mediated rejection. Cytomegalovirus test showed positivity in 14 recipients, but none developed cytomegalovirus disease. BK viremia was detected in 2 recipients, with 1 developing BK virus nephropathy, which was reversed by reducing immunosuppression. CONCLUSIONS: Transplant patients with preformed donor-specific antibodies showed good outcomes in terms of desensitization and immunosuppression. However, most anti-HLA class II donor-specific antibodies remained, and microvascular inflammation score could indicate long-term risk of renal allograft dysfunction.

Efficacy of 2 Doses of Rituximab on B-Cell and Antidonor Antibody and Outcomes of ABO-Incompatible Living-Donor Pediatric Kidney Transplant.

OBJECTIVES: Rituximab treatment strategies vary in ABOincompatible pediatric kidney transplant recipients. Here, we present the efficacy of 2 doses of rituximab and subsequent outcomes in ABO-incompatible pediatric kidney transplant patients. MATERIALS AND METHODS: Our study of ABO-incompatible pediatric kidney transplant recipients included 21 who were pretreated with desensitization that included 2 doses of 100 mg rituximab (rituximab group) at 10 and 1 day pretransplant and 14 who received splenectomy without rituximab (splenectomy group). Both groups received immunosuppression. Basiliximab was administered during transplant and 4 days posttransplant. Double-filtration plasmapheresis and/or plasma exchange procedures were performed pretransplant in those with higher antidonor antibody titers. CD19-positive and CD20-positive B cells were measured sequentially in the rituximab group. Maximum titers of antidonor antibody pre- and posttransplant, patient and graft survival, biopsy-proven rejection, and complications/infections were compared between groups. RESULTS: In the rituximab group, CD19- and CD20-positive B cells were depleted on transplant, persistently depleted at 3 months, and under 5% until 1 year posttransplant. Maximum titers of antidonor antibodies decreased significantly posttranplant in the rituximab (P < .001) but not in the splenectomy group (P = .174), with maximum titers posttransplant significantly lower than shown in the splenectomy group (P < .001). No rituximab patients had clinical rejection, but 5 splenectomy group patients had clinical T-cell-mediated rejection, with 2 also having antibody-mediated rejection. Six in the rituximab group had cytomegalovirus viremia but no cytomegalovirus disease; however, 5 splenectomy group recipients had cytomegalovirus disease and viremia. In the rituximab group, 3 had late-onset neutropenia. One child died of hypertrophic cardio myopathy with a functioning graft; all others survived with no failed grafts. All splenectomy group children survived, although 2 had deteriorated graft function. CONCLUSIONS: Two doses of rituximab were effective in long-term B-cell depletion to suppress antidonor antibodies. The possibility of late-onset neutropenia must be considered.

Impact of Transplant Nephrectomy for Patient Survival Over the Past 15 Years: A Single-Center Study.

OBJECTIVES: How transplant nephrectomy affects patient survival after return to dialysis is unclear. Here, we compared patient survival after graft loss between patients with and without transplant nephrectomy. MATERIALS AND METHODS: We divided 171 patients who received transplant between 2000 and 2015 and had graft loss into 3 groups: 64 had graft failure left in situ (without nephrectomy), 51 had nephrectomy < 3 months posttransplant (early nephrectomy), and 56 patients had nephrectomy > 3 months posttransplant (late nephrectomy). The primary endpoint was patient survival. Risk factors for patient death were also analyzed. Secondary endpoints included relisting for transplant and immunosuppressive agent status. RESULTS: Patient survival rates at 1, 3, and 5 years posttransplant in those without nephrectomy, early nephrectomy, and late nephrectomy were 92.1% /90.5%/86.6%, 96.0%/89.7%/80.4%, and 100.0% /97.9%/ 95.6%, respectively. Rates in patients with early nephrectomy differed significantly from those with late nephrectomy (P = .005). On multivariate analysis, patient survival was affected by relisting for transplant (hazard ratio 0.17; 95% confidence interval, 0.06-0.41; P < .001) and graft survival duration (hazard ratio 0.36, 95% confidence interval, 0.13-0.93; P = .036). Relisting for transplant occurred in 46.9% of patients without nephrectomy, 56.9% of patients with early nephrectomy, and 51.8% of patients with late nephrectomy. Those with late nephrectomy took 14.7 months after graft loss to relist for transplant, with 7.8 months for those without nephrectomy (P = .039) and 6.3 months for those with early nephrectomy (P = .051). Only 10.9% of those without nephrectomy were immunosuppressive free, which was in contrast to 94.1% and 78.6% of those with early and late nephrectomy, respectively. CONCLUSIONS: After graft failure, patients without nephrectomy did not have inferior survival versus patients who received early or late nephrectomy. Graft survival time and relisting for transplant were associated with patient survival regardless of having transplant nephrectomy.

Outcomes of Pediatric ABO-incompatible Living Kidney Transplantations From 2002 to 2015: An Analysis of the Japanese Kidney Transplant Registry.

BACKGROUND: Extensive data have been accumulated for adults who have undergone ABO-incompatible (ABOi)-living kidney transplantation (LKT). In contrast, available published data on pediatric recipients who underwent ABOi-LKT from the early to middle 2000s is very limited. Thus, pediatric ABOi-LKT has remained relatively rare, and there is a lack of large, multicenter data. METHODS: We analyzed data from the Japanese Kidney Transplant Registry to clarify the patient and graft outcomes of pediatric recipients who underwent ABOi-LKT from 2002 to 2015. A total of 102 ABOi and 788 ABO-compatible (ABOc) recipients were identified in this study. All recipients had received basiliximab and a triple immunosuppressive protocol comprising calcineurin inhibitors, mycophenolate mofetil, and steroids. The ABOi recipients also received preconditioning therapies including B-cell depletion by a splenectomy or rituximab treatment and therapeutic apheresis. RESULTS: Death rates for ABOi and ABOc recipients were 0.17 versus 0.17 deaths per 100 patient-years. Graft loss rates for ABOi and ABOc recipients were 1.58 versus 1.45 events per 100 patient-years. No particular causes of death or graft loss predominantly affected ABOi or ABOc recipients. CONCLUSIONS: The results of this registry analysis suggest that pediatric ABOi-LKT can be performed efficiently. Although further studies are clearly required to perform pediatric ABOi-LKT more safely and less invasively, ABOi-LKT is now an acceptable treatment for pediatric patients with end-stage renal disease.

Impact of Allograft Nephrectomy on Second Renal Transplant Outcome.

OBJECTIVES: The impact of allograft nephrectomy on the outcome of a subsequent renal transplant is unclear. This study was conducted to assess the effects of the first allograft nephrectomy on outcomes of a second transplant. MATERIALS AND METHODS: This study included 118 patients who received a second transplant between 1994 and 2015. Before the second transplant, 59 patients did not undergo a first allograft nephrectomy (group A). Group B comprised 59 patients who had undergone a first allograft nephrectomy. We compared sensitization, acute rejection, and survival of the second graft between groups. The risk factors of a second graft loss were assessed. RESULTS: The first graft survival was significantly longer in group A than in group B (100.6 vs 3.7 months; P < .001). Prevalence of preformed donor-specific antibodies before the second allograft was similar between both groups (28.8% vs 39.0% for group A vs group B; P = .243). Numerically higher acute rejection rates occurred in group B than in group A (23.7% vs 15.3%; P = .245). In group A, graft survival rates at 1, 3, and 5 years were 93.0%, 87.0%, and 82.3% and were significantly higher than for group B (76.7%, 69.1%, and 62.5%; P ⟨ .05). On multivariate analysis, survival of the second graft was affected by acute rejection (hazard ratio = 2.24; 95% confidence interval, 1.10-4.45; P = .027) and the interval from first graft loss to second transplant (hazard ratio = 1.11; 95% confidence interval, 1.02-1.19; P = .008). CONCLUSIONS: A first allograft nephrectomy was associated with inferior second graft survival. We recommend that recipients of second transplants should be considered as high risk if they had undergone prior allograft nephrectomy.

Surgical Challenge in Pediatric Kidney Transplant Vascular Anastomosis.

During pediatric kidney transplant, surgical challenges occasionally occur. In particular, vascular anastomosis should be considered for children with small body weight < 12 kg, multiple renal arteries, vascular anomaly, and inferior vena cava occlusion. In pediatric patients, a living-donor renal graft is usually donated from a parent. Therefore, the renal artery and vein are too large to be anastomosed with the recipient's internal iliac artery and external iliac vein. In children who are > 12 kg, the renal artery and vein could be anastomosed with the external iliac artery and the external iliac vein. In children who are < 10 kg, the renal artery and vein should be anastomosed directly with the aorta and inferior vena cava. A pediatric transplant surgeon should consider arterial and venous anastomosis sites before transplant surgery. In small children with partial or total inferior vena cava occlusion, the venous anastomosis site should be evaluated. If the graft is placed on the left side, a venous graft must be used as a bridge between the renal vein and inferior vena cava. In 13 kidney transplants in children with inferior vena cava occlusion, 7 were on the left and 6 were on the right side. A patent segment of the inferior vena cava, the left original renal vein, an ascending lumbar vein, an azygos vein, the first graft renal vein, and a portal vein were used for venous anastomosis in 6, 2, 2, 1, 1 and 1 recipient, respectively. One child had graft loss due to renal vein thrombosis and one died of hemorrhage immediately posttransplant. Three had grafts with relatively long-term function, but these were lost due to chronic allograft nephropathy 100, 122, and 137 months posttransplant. However, the other 8 recipients have so far maintained graft function from 6 to 138 months since transplant.

Surgical Challenge in Pediatric Kidney Transplant: Lower Urinary Tract Abnormality.

Lower urinary tract abnormalities are difficult to resolve in pediatric kidney transplant patients. Measure of residual urine, voiding cystourethrography, retrograde urethrography, cystometry, electromyography of urethral external sphincter muscle, urethrometry, and uroflowmetry are the primary methods for evaluation of lower urinary tract abnormalities. Endoscopic resection or ablation of urethral valves is required in children with posterior urethral valve to treat obstruction, but bladder function does not always recover and may deteriorate to end-stage renal failure even after the obstruction is released. This bladder dysfunction in posterior urethral valve defines valve bladder syndrome. Vesicoureteral reflux caused by high vesical pressure can cause even worse renal graft function posttransplant. In our patient group, urinary diversion occurred with Mitrofanoff conduit using an appendix in 6 children, a Yang-Monti channel conduit using ileum in 1 patient, with cystostomy in 3 children, and with augmented cystoplasty in 9 children before or simultaneously with kidney transplant. These procedures should be selected based on the type of lower urinary tract abnormality including bladder function. Recently, we have preferred a continent diversion for self-catheterization in children with lower urinary tract abnormalities. We have conducted 9 augmented cystoplasty procedures using a portion of the sigmoid colon or ileum. Seventeen children retained their own bladders when the transplant ureter was implanted. Most patients needed clean intermittent catheterization, depending on the residual urine volume and a bladder function. Ten-year graft survival rate in kidney transplant in our department is 98% in 36 children with lower urinary tract abnormalities. Lower urinary tract abnormality is not always a risk factor for pediatric kidney transplant; however, a preoperative evaluation is important to choose the best option for urinary diversion.

Successful Desensitization of T cell Flow Cytometry Crossmatch Positive Renal Transplant Recipients Using Plasmapheresis and Super High-Dose Intravenous Immunoglobulin.

BACKGROUND: High-dose IVIG (2 g/kg) alone or low-dose IVIG (100 mg/kg) in conjunction with plasma exchange is typically administered as a renal transplantation desensitization therapy. Herein, we monitored changes in T cell and B cell flow cytometry crossmatch (FCXM) to assess the effects of short-term super high-dose IVIG (4 g/kg) administration with plasmapheresis before living-donor renal transplantation. METHODS: Seventeen patients, each showing positive T cell FCXM (median ratio, ≥ 1.4) after 2 rounds of double-filtration plasmapheresis, received 4-day regimens of IVIG (1 g/kg per day) over 1-week periods. T cell and B cell FCXM determinations were obtained after every IVIG dose and again up to 4 weeks after initiating IVIG to ascertain negative conversion of T cell FCXM (median ratio < 1.4). The primary study endpoint was the percentage of patients achieving T cell FCXM-negative status after the 4-dose IVIG regimen. RESULTS: Upon completion (4 g/kg total) or discontinuation of IVIG administration, 8 (47.1%) of 17 patients displayed negative T cell FCXM. Based on Kaplan-Meier estimates, the cumulative T cell FCXM-negative conversion rate 4 weeks after IVIG administration initiation was 60.3%. The T cell FCXM-negative conversion rates after cumulative doses of 1, 2, 3, and 4 g/kg IVIG were 29.4%, 35.3%, 56.3%, and 46.7%, respectively. CONCLUSIONS: Desensitization of donor-specific antibody-positive renal transplant recipients seems achievable in only a subset of recipients through IVIG dosing (1 g/kg × 4) within 1 week after double-filtration plasmapheresis. The T cell FCXM-negative conversion rate resulting from a cumulative IVIG dose of 3 g/kg or greater surpassed that attained via conventional single-dose IVIG (2 g/kg) protocol. This short-term high-dose IVIG desensitization protocol may be an alternative to conventional protocols for recipients with donor-specific antibody.

Successful third renal transplantation in a child with an occluded inferior vena cava: A novel technique to use the venous interposition between the transplant renal vein and the infrahepatic inferior vena cava.

A girl aged 11 years and 3 months with occlusion of the inferior vena cava had experienced two renal transplant graft failures since birth. The third renal transplant from a live donor was carried out. Preoperative evaluation showed that the arteries from the right common to the right external iliac artery were absent, and the ilio-caval vein was occluded below the level of the renal vein. The donor's renal artery was anastomosed to the aorta. The donor's ovarian and large saphenous veins were used to extend the transplant renal vein to the recipient's patent inferior vena cava. The present report concludes that the extension of a short donor renal vein using other donor veins is a viable therapeutic option for pediatric patients with vascular occlusions.

Results of a multicenter prospective clinical study in Japan for evaluating efficacy and safety of desensitization protocol based on rituximab in ABO-incompatible kidney transplantation.

BACKGROUND: Deceased organ donations are rare in Japan, with most kidney transplants performed from a limited number of living donors. Researchers have thus developed highly successful ABO-incompatible transplantation procedures, emphasizing preoperative desensitization and postoperative immunosuppression. A recent open-label, single-arm, multicenter clinical study prospectively examined the efficacy and safety of rituximab/mycophenolate mofetil desensitization in ABO-incompatible kidney transplantation without splenectomy. METHODS: Mycophenolate mofetil and low dose steroid were started 28 days pretransplant, followed by two doses of rituximab 375 mg/m2 at day -14 and day -1, and postoperative immunosuppression with tacrolimus or ciclosporin and basiliximab. The primary endpoint was the non-occurrence rate of acute antibody-mediated rejection. Patient survival and graft survival were monitored for 1 year posttransplant. RESULTS: Eighteen patients received rituximab and underwent ABO-incompatible kidney transplantation. CD19-positive peripheral B cell count decreased rapidly after the first rituximab infusion and recovered gradually after week 36. The desensitization protocol was tolerable, and most rituximab-related infusion reactions were mild. No anti-A/B antibody-mediated rejection occurred with this series. One patient developed anti-HLA antibody-mediated rejection (Banff 07 type II) on day 2, which was successfully managed. Patient and graft survival were both 100 % after 1 year. CONCLUSION: Our desensitization protocol was confirmed to be clinically effective and with acceptable toxicities for ABO-I-KTx (University Hospital Medical Information Network Registration Number: UMIN000006635).

Association between Low Dietary Protein Intake and Geriatric Nutrition Risk Index in Patients with Chronic Kidney Disease: A Retrospective Single-Center Cohort Study.

Reduced dietary protein intake in malnourished patients with chronic kidney disease (CKD) may be associated with adverse clinical outcomes, which may mask any efficacy of a low-protein diet. The study included 126 patients with CKD who attended a dedicated dietary counseling clinic in 2005-2009 and were systematically followed until January 2015. Of these patients, 20 (15.9%) had moderate or severe nutrition-related risk of geriatric nutritional risk index (GNRI) < 92; these patients were more likely to be older, have a greater proteinuria, and have lower body mass index and serum albumin concentration. Dietary protein intake was significantly lower in older patients (r = -0.33, p < 0.001) and those with lower glomerular filtration rate (r = 0.47, p < 0.001). The non-protein to nitrogen calorie ratio was independently associated with GNRI. Reduced GNRI was significantly associated with mortality (hazard ratio (HR) = 4.94; 95% confidence interval (CI) = 1.61-15.42, p = 0.012) and cardiovascular events (HR = 9.37; 95% CI = 2.49-37.34, p = 0.006), but not with adverse renal outcomes. Restricting protein intake may be harmful to patients with any nutrition-related risk, suggesting that improvement of nutritional status should be a high priority.

Brain Natriuretic Peptide and Body Fluid Composition in Patients with Chronic Kidney Disease: A Cross-Sectional Study to Evaluate the Relationship between Volume Overload and Malnutrition.

BACKGROUND/AIM: Fluid volume overload occurs in chronic kidney disease (CKD), leading to the compensatory release of natriuretic peptides. However, the elevated cardiac peptides may also be associated with malnutrition as well as volume overload. METHODS: Body fluid composition was measured in 147 patients with CKD between 2009 and 2015, and its relationship to brain natriuretic peptide (BNP) levels was examined. Body fluid composition was separated into three components: (a) a water-free mass consisting of muscle, fat, and minerals; (b) intracellular water (ICW) content, and (c) extracellular water (ECW) content. Excess fluid mass was calculated using Chamney's formula. RESULTS: The measured BNP levels in the tertile groups were 10.9 ± 5.4, 36.3 ± 12.5, and 393 ± 542 pg/ml, respectively. Patients in a higher log-transformed BNP level tertile were more likely to be older, to have a higher frequency of cardiac comorbidities, pulse pressure, C-reactive protein levels, and proteinuria, and to have lower serum sodium, kidney function, and serum albumin (p < 0.05). In body fluid composition, decreased body mass was significantly associated with the ECW-to-ICW ratio in relation to the downward ICW slope (r = -0.235, p = 0.004) and was strongly correlated with excess fluid mass (r = -0.701, p < 0.001). The ECW-to-ICW ratio and excess fluid mass was independently associated with the BNP levels. CONCLUSION: Fluid volume imbalance between intra- and extracellular water regulated by decreased cell mass was independently associated with BNP levels, which may explain the reserve capacity for fluid accumulation in patients with CKD.

Successful Kidney Transplantation in Children With a Compromised Inferior Vena Cava.

BACKGROUND: Children with a compromised inferior vena cava (IVC) were previously considered unsuitable for kidney transplantation because of the technical difficulties and the increased risk of graft thrombosis secondary to inadequate renal venous outflow. METHODS: We conducted a retrospective study of 11 transplants in 9 patients with end-stage renal disease and thrombosed IVCs who received adult kidney allografts between 2000 and 2015. The mean age at transplantation was 7.5 ± 3.5 years. A pretransplant diagnosis of the IVC thrombosis was made in 7 patients by magnetic resonance imaging and computerized tomography, whereas there were 2 instances of intraoperative discovery of the IVC thrombosis. RESULTS: In the early cases, a kidney was placed intraperitoneally at the right iliac fossa with a venous anastomosis to the patent segment of the suprarenal IVC. After 2008, however, 6 adult-sized kidneys were subsequently placed in the left orthotopic position. Venous drainage was attained to the infrahepatic IVC (n = 3), left native renal vein (n = 2), and ascending lumbar vein (n = 1). Moreover, a venous bypass was created between the graft and the splenic vein in 2 children who showed high return pressure after the vessel was declamped. The mean glomerular filtration rate of the functioning 8 grafts 1 year posttransplant was 73.4 ± 20.4 mL/min per 1.73 m(2). Of note, 6 of the grafts have been functioning well, with a mean follow-up of 66 months. Both 1- and 5-year graft survival were 81.8%. CONCLUSIONS: Transplantation into the left orthotopic position and the revascularization methods are an effective set of surgical techniques that could potentially be adopted as safe and reliable transplant approaches in children with IVC thrombosis.

[Test-retest reliability of the Implicit Association Test for measuring shyness: Inclusion of malleability of implicit shyness].

The Implicit Association Test of Shyness (Shyness IAT: Aikawa & Fujii, 2011) provides an indirect assessment of shyness by measuring associations of self (vs. other) with shyness-related (vs sociability-related) words. In this study we examined the test-retest reliability of the Shyness IAT. Thirty-five participants responded twice to the Shyness IAT with a time lag of one month. The correlation coefficient between the two time points was .54 (p = .001), confirming an adequate level of test-retest reliability. Indeed, changes in explicit and implicit shyness between the two time points were not related to sociable behavior during the one month period. Implications of the results for the assessment of personalities using IATs as well as relevant future directions are discussed.

Comparing the efficacy of continuous erythropoietin receptor activator and darbepoetin Alfa treatments in Japanese patients with chronic kidney disease during the predialysis period: A propensity-matched analysis.

AIM: Erythropoiesis-stimulating agent (ESA) treatment during the predialysis period can be a strategy to reduce cardiac mortality soon after initiation of dialysis. In this study, we compared the efficacy of continuous erythropoietin receptor activator (CERA) and darbepoetin alfa (DA) in patients with chronic kidney disease (CKD) over 6 months prior to initiation of dialysis. METHODS: This study was a retrospective propensity score-matched study conducted at a single center in Japan that analyzed the effects of CERA and DA therapy on haemoglobin (Hb) changes, ESA resistance index (ERI) changes, and interval of ESA administration during a 6-month observation period prior to initiation of dialysis. Propensity scores were used for matching the patients included in the CERA and DA groups. RESULTS: Among 680 screened, 74 pairs of patients (one in each group) were included in the present analysis after propensity score matching. Mean Hb significantly decreased over 6 months in the DA group compared to that in the CERA group (-0.70 ± 0.23 vs. -0.33 ± 0.22). In the DA group, mean ERI was significantly increased at 4, 3, 2, and 1 month before dialysis and initiation of dialysis, while in the CERA group, mean ERI was significantly increased only at 1 month before dialysis and initiation of dialysis. Moreover, patients administered CERA were required to visit the hospital significantly less frequently for ESA administration than those administered DA. CONCLUSION: Our study showed that CERA may be more effective than DA for management of anaemia during the predialysis period in CKD patients.

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

OBJECTIVE: 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 Alexandre's 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. METHODS: A total of 134 cases of ABO-incompatible kidney transplants were carried out at Toho University Omori Medical Center between March 1989 and February 2013. These cases were classified as follows: azathioprine group (n = 62 patients); mycophenolate mofetil group (n = 33 patients); rituximab group (n = 39 patients). The anti-donor blood group antibodies levels (immunoglobulin G and immunoglobulin M) were measured in all groups before antibody removal, immediately before surgery, and 1, 2, 4 weeks and 3 months after surgery, and then compared. RESULTS: Rates of antibody-mediated rejection, including hyperacute rejection, in the azathioprine, mycophenolate mofetil, and rituximab groups were 32.2%, 18.1% and 7.6%, respectively. Graft survival rates were higher in the mycophenolate mofetil and rituximab groups than in the azathioprine group, but were lower in patients with higher preoperative antibody titers (≥128-fold higher immunoglobulin G) than in those with lower titers (<128-fold higher immunoglobulin G). In addition, postoperative anti-blood type antibody titers were significantly suppressed in the rituximab group. CONCLUSIONS: Administration of rituximab results in better antibody control than previous protocols including splenectomy, even in the postoperative period during which humoral rejection often occurs. This protocol eliminates the physical invasiveness of pre-transplant splenectomy, and is expected to provide better outcomes in chronic renal failure patients who undergo kidney transplants.

Trends in ABO-incompatible kidney transplantation.

The ABO-incompatible living-donor kidney transplantation was developed in Japan in 1989. Currently, most transplant physicians and surgeons have noted that outcomes are unexpectedly excellent, and no hyperacute rejections have been reported since 2001. In the registry of the Japanese ABO-Incompatible Kidney Transplantation Committee, the data of 2434 ABO-incompatible living-donor kidney transplants were collected from 120 Japanese kidney transplant centers. Overall patient and graft survival rates were 97% and 94% at 1 year, 93% and 86% at 5 years, 90% and 71% at 10 years, and 73% and 52% at 20 years. The patient survival and graft rates in 2001 to 2012 were 93% and 81%, which were significantly better than 83% and 55% reported in 1989 to 2000. The addition of novel immunosuppressive treatments has improved results. Azathioprine has been replaced by mycophenolate mofetil since 2000 to 2001, and basiliximab and rituximab were introduced in 2002 and 2004. The titer of antidonor blood group antibody before transplantation was not correlated with graft survival in 2001 to 2012. De novo antibodies against vascular endothelium of peritubular and glomerular capillaries seemed to be more important than natural antibodies against red blood cells. Therefore, recipients with antidonor blood group antibody titers < 1:128 did not require antibody-removal procedures such as plasmapheresis or immunoadsorption. In particular, children (regard less of their peritoneal dialysis status) do not need to be catheterized for plasmapheresis or immunoadsorption. It is better to avoid the risks of catheterization and antibody removal procedures in children with end-stage renal failure.

Renal complications in 6p duplication syndrome: microarray-based investigation of the candidate gene(s) for the development of congenital anomalies of the kidney and urinary tract (CAKUT) and focal segmental glomerular sclerosis (FSGS).

6p duplication syndrome is a rare chromosomal disorder that frequently manifests renal complications, including proteinuria, hypoplastic kidney, and hydronephrosis. We report a girl with the syndrome, manifesting left hydronephrosis, proteinuria/hematuria, and focal segmental glomerular sclerosis (FSGS) resulting in chronic end-stage renal failure, successfully treated with renal transplantation. Microarray comparative genomic hybridization showed the derivative chromosome 6 to have a 6.4-Mb duplication at 6p25.3-p25.1 with 32 protein-coding genes and a 220-Kb deletion at 6p25.3 with two genes of no possible relation to the renal pathology. Review of the literature shows that variation of renal complications in the syndrome is compatible with congenital anomalies of the kidney and urinary tract (CAKUT). FSGS, observed in another patient with 6p duplication syndrome, could be a non-coincidental complication. FOXC1, located within the 6.4-Mb duplicated region at 6p25.3-p25.2, could be a candidate gene for CAKUT, but its single gene duplication effect would not be sufficient. FSGS would be a primary defect associated with duplicated gene(s) albeit no candidate could be proposed, or might occur in association with CAKUT.