Objective:To explore the characteristic pathological manifestations of non-HLA antibodies after kidney transplantation (KT) and examine the differences of MFT values of non-HLA antibodies in different pathological manifestations.Methods:The study was conducted on KT recipients at the First Affiliated Hospital of Zhengzhou University from February 2021 to June 2023 with unexplained elevated serum creatinine. Patients undergoing pathological puncture and concurrent HLA antibody testing were included, focusing on those with DSA (MFI>4 000) and non-HLA antibody negativity. According to the detection results of non-HLA and HLA antibodies, they were assigned into two groups of non-HLA antibody positive (45 cases) and HLA-DSA positive (28 cases). Both non-HLA and HLA antibodies were detected by luminex single antigen microbeads, χ2, t or Mann-Whitney U nonparametric tests were utilized for examining the inter-group differences in pathological manifestations. The recipients with positive non-HLA antibodies were grouped according to the differential pathological features[microvascular inflammation group (22 cases) and non-microvascular inflammation group (23 cases), interstitial fibrosis group (39 cases) and non-interstitial fibrosis (9 cases) ]. MFI values of non-HLA antibodies were standardized and heat map was generated with R language ComplexHeatmap package. The differences of response values of non-HLA antibodies with different pathological manifestations were examined by rank-sum test. Results:The positive rates of microvascular inflammation were 48.9% (22/45) and 82.1% (23/28) in HLA-DSA positive and non-HLA antibody positive groups with statistical significance ( χ2=8.073, P=0.006). The positive rates of interstitial fibrosis in two groups were 80.8% (36/45) and 53.6% (15/28) and the difference was statistically significant ( χ2=5.726, P=0.021). The relative levels of anti-arachnotoxin receptor 1 (Latrophilin 1, LPHN1), keratin 8 (KRT8), keratin 18 (KRT18) and Sjogren's syndrome antigen B (SSB) were higher in microvascular inflammation group than those in non-microvascular inflammation group. The differences were statistically significant [559.50 (262.00, 801.25) vs 285.00 (183.00, 460.00), P=0.024; 504.50 (369.5, 725.25) vs 317.00 (231.50, 458.00), P=0.014; 672.50 (454.50, 969.50) vs 399.00 (246.50, 772.50), P=0.030; 967.50 (482.00, 2 066.50) vs 399.00 (246.50, 772.50), P=0.033]. The relative levels of anti-cyclic citrullinate peptide (CCP), colony-stimulating factor 2 (CSF2), intercellular adhesion molecule 1 (ICAM1) and collagen Ⅳ antibody were higher in interstitial fibrosis group than those in non-interstitial fibrosis group with statistical significance [100.00 (79.88, 167.50) vs 64.50 (37.00, 89.00), P=0.016; 146.25 (93.38, 244.75) vs 87.00 (66.00, 105.00), P=0.041; 132.50 (106.38, 229.50) vs 95.00 (55.00, 125.00), P=0.037; 432.50 (280.75, 653.75) vs 208.00 (192.00, 301.00), P=0.028]. Conclusions:As compared with HLA-DSA, the characteristic pathological manifestations of non-HLA antibodies post-KT include a lower incidence of microvascular inflammation and a higher incidence of interstitial fibrosis. For non-HLA antibody response values of characteristic pathological manifestations, the expressions of different non-HLA antibodies vary statistically.

Objective:To explore the efficacy and safety of low-dose rabbit anti-human thymocyte globulin (rATG) for induction therapy of kidney transplantation (KT) in children.Methods:From October 2018 to May 2021, clinical data were reviewed retrospectively for 77 pediatric KT recipients on a low-dose rATG induction protocol.Recipient/graft survival rate, renal function recovery, acute rejection (AR) and adverse reactions were observed at 1 year post-operation.The postoperative changes of renal function were examined by Friedman’s test; According to the preoperative baseline data, Pearson’s Chi-square or Fisher's exact test was utilized for examining the influencing factors of postoperative AR.Results:A total of 16(20.78%) recipients had AR within the first 6 months post-operation.The incidence of delayed graft function (DGF) was 14.29%(11/77); The incidence of severe infection post-transplantation 18.18%(14/77), the infection rate of BK virus 25.97%(20/77) and the incidence of neutropenia 32.47%(25/77).The recipient/graft survival rate at 1 year post-operation was 97.40%(75/77) and 94.81%(73/77) respectively.Chi-square test indicated that the incidence of postoperative infection in children with body weight ≤30 kg and height ≤138 cm was 28.95%(11/38) and 27.50%(11/40) respectively, Both were higher than 7.69%(3/39) and 8.11%(3/37) of children with body weight >30 kg and height>138 cm.The difference between groups was statistically significant ( P=0.016 and 0.028). Conclusions:Low-dose rATG is generally excellent in preventing AR in pediatric KT recipients.And the risk of related AR may be lower.The infection rate of recipients with decent preoperative development is low.

Objective:To explore the clinical efficacy of vascular interventional therapy in children with transplantation renal artery stenosis(TRAS).Methods:From January 2013 to September 2021, retrospective analysis was performed for clinical data of 238 TRAS children.Peak systolic velocity(PSV)of transplant renal artery, interlobular artery PSV, transplant renal artery PSV/ interlobular artery PSV(post PSV ratio)and serum creatinine level before and after vascular interventional therapy and at the last follow-up were compared.Results:Six pediatric kidney transplantation recipients were diagnosed as TRAS.The median operative age was 12(9-17)years, the median postoperative time to diagnosing TRAS 4(1.7-18.0)months and the median follow-up period 6.6(2.5-8.0)years.All of them received vascular interventional therapy of percutaneous transluminal angioplasty(PTA, n=5)and stent angioplasty( n=1). The serum creatinine pre-treatment with vascular interventional therapy was significantly higher than baseline serum creatinine level at discharge(200.8±88.5)vs(75.2±27.9)μmol/L, P=0.025 and decreased to(103.8±44.7)μmol/L at Month 1 post-treatment( P=0.196)and(98.7±30.2)μmol/L at the last follow-up( P=0.115). Comparing with internal diameter of grafted renal artery anastomosis site(2.6±0.6 mm)pre-treatment with vascular interventional therapy, significant changes occurred at 24 h post-treatment(3.8±0.5 mm)and at the last follow-up(4.1±0.8 mm)(all P=0.027). In addition, PSV and post PSV ratio of transplanted renal artery at 24 h post-treatment(163±45.0 cm/s, 6.5±2.2)and at the last follow-up(184.7±80.8 cm/s, 5.4±2.0)were significantly lower than that before vascular interventional therapy(356.5±77.9 cm/s, 18.0±5.8)and interlobular artery PSV was significantly higher than that before vascular interventional therapy( P=0.024, P=0.032, respectively). During follow-ups, no restenosis or thrombosis occurred in transplanted renal arteries. Conclusions:PTA or stent angioplasty for TRAS children is technically feasible with low restenosis rate and relatively satisfactory mid/long-term outcomes.

Objective:To retrospectively analyze clinical data of infant donors with body weight ≤15 kg into children recipients, and to investigate the efficacy and complications under the strategy of pediatric donor to pediatric recipient (PTP) of pediatric kidney transplantation allocation.Methods:Clinical data of kidney transplantation for children with infant donors performed in the First Affiliated Hospital of Zhengzhou University from August 2010 to December 2019 were collected.Clinical data of donors and recipients, postoperative adverse events, postoperative renal recovery, and human and renal survival were analyzed.Results:A total of 50 infant donors and 93 pediatric recipients were enrolled in this study.Recipients included 89 patients with single kidney transplantation (SKT) and 4 with en-bloc kidney transplantation (EBKT). The major perioperative complications were delayed graft function (DGF) (5 cases, 5.4%) and vascular thrombosis (VT) (3 cases, 3.2%), followed by recurrence of primary nephropathy (3 cases, 3.2%), respiratory tract infection (3 cases, 3.2%), and acute rejection (AR) (2 cases, 2.2%). During the follow-up period, the main cause of death was respiratory tract infection (4 cases, 4.3%). Except for the cause of death, the main causes of graft loss were rejection (2 cases, 2.2%) and recurrence of primary kidney disease (2 cases, 2.2%). Serum creatinine decreased progressively from (824.77±150.24) μmol/L preoperatively to (90.73±47.24) μmol/L 1 month postoperatively.In SKT group, the median follow-up time was 31 months (3-74 months), and the survival rates of recipients and transplanted kidneys at 1, 3 and 5 years postoperatively were 97.5%/94.2%, 96%/88.8% and 93.1%/86.1%, respectively.In EBKT group, the median follow-up time was 50 months (13-65 months), and the survival rates of recipients and transplanted kidneys at 1, 3 and 5 years postoperatively were all 100.0%.During the fo-llow-up period, there was no significant difference in the human/kidney survival rate between groups (all P>0.05), and well acceptable transplantation outcomes were obtained. Conclusions:Single/double kidney transplantation for children and adolescent recipients from infant donors in the First Affiliated Hospital of Zhengzhou University has achieved acceptable outcomes.Adopted by the PTP strategy, the incidence of complications after kidney transplantation does not increase, indicating its safety and reliability.

Objective:To compare the efficacy of single kidney transplantation for children from pediatric donors between body weight ≤15 kg and >15 kg.Methods:A retrospective review in 156 children with single donor kidney transplantation from August 2010 to December 2019 in the Kidney Transplantation Department of the First Affiliated Hospital of Zhengzhou University was conducted. The patients were classified into the small kidney group (pediatric donor body weight ≤15 kg) and the big kidney group (pediatric donor body weight >15 kg). In this study, 89 cases were concluded in the small kidney group and 67 cases were concluded in the big kidney group. The donor kidneys were obtained from 46 cases of small weight (≤15 kg) pediatric donors and 48 cases of large weight (>15 kg) pediatric donors. There were significant differences in age [1.00 (0.02 - 4.00) years vs. 10.00 (3.00-18.00) years], body weight [10.0 (3.4 - 15.0) kg vs. 35.0 (16.2- 35.0) kg], height [76 (50- 113) cm vs. 144 (67-172) cm], GFR [(31.50±7.46)ml/min vs. (36.79±7.00) ml/min], and renal length to diameter [(5.91±0.48) cm vs. (8.71±1.88) cm] between the small kidney group and the big kidney group ( P < 0.01). There was no significant difference between the two groups of donors in gender, cold/warm ischemia time and cause of death ( P>0.05). There were significant differences in age [(11.28±3.89) years vs. (13.86±3.56) years], body weight [(31.83±10.45)kg vs. (35.13±9.15) kg], and height [(130.02±28.56) cm vs. (143.97±16.59) cm] between recipients of the small kidney group and big kidney group ( P < 0.05). While there were no significant differences in preoperative serum creatinine level [(822.65 ± 135.04) μmol/L vs. (777.31 ± 165.40) μmol/L], HLA mismatch [(3.4 ± 1.4) site vs. (3.2±1.3) site], and primary disease between the two groups ( P > 0.05). The recovery of renal function, postoperative adverse events, postoperative children, and graft survival were compared between the two groups. Results:The renal function of the two groups of recipients returned to normal 3 months after operation. The perioperative complications in the small kidney group and the big kidney group mainly included renal delayed recovery [5.6% (5/89) vs. 7.5% (5/67), P=0.89], renal vascular embolization [3.4% (3/89) vs. 0, P=0.35], and acute rejection [2.2% (2/89) vs. 4.3% (3/67) , P=0.75]. The main cause of recipient death during the follow-up period was pulmonary infection [4.5% (4/89) vs. 6.0% (4/67) , P=0.68]. The postoperative small kidney group was followed up for an average of 30 (3-74) months. The survival rates of children in the small kidney group at the 1, 3 and 5 years after surgery were 96.6% (86/89), 91.0% (81/89) and 91.0%(81/89), while the transplanted renal survival rates were 92.1% (82/89), 86.5% (77/89) and 84.2% (75/89), respectively. The postoperative big kidney group was followed up for an average of 32 (4-89 ) months. The survival rates of children in the big kidney group were 95.5% (64/67), 94.0% (63/67) and 91.0%(61/67) in the first 1, 3 and 5 years postoperatively, while the graft survival rates were 92.5% (62/67), 83.6% (56/67) and 83.6% (56/67), respectively. The postoperative kidneys of two groups were fast-growing, and there was no significant difference between the small kidney group and the big kidney group in graft length to diameter [(9.63±0.31) cm vs. (9.75±0.71) cm] after 1 year ( P>0.05). Conclusions:The effect of single pediatric kidney transplantation for pediatric donor with body weight ≤15 kg is equivalent to that for pediatric donor with body weight >15 kg , which can be carried out clinically.

Objective:To evaluate the effect of unilateral pediatric kidney donation for adult kidney transplantation.Methods:Retrospective analysis was conducted on the cases of children who donated unilateral donor kidney for adult kidney transplantation recipients in our hospital, and those who were followed up for more than three years were included in this study. The body weight of the recipients in group A was ≤50 kg, and the body weight of the recipients in group B was ≤70 kg.The recipients were divided into 0-5 year old donor group (group A) and 6-17 year old donor group (B group). Clinical data, recipient/kidney survival, graft function and growth, and complications of the recipient were analyzed.Results:A total of 45 adult recipients were enrolled, including 12 in group A and 33 in group B. The renal survival rate at 3 years after operation was (100%, 96.9%)/(91.6%, 93.9%). One week after the operation, the early postoperative recovery of renal function in group B was better than that in group A, and the difference of serum creatinine was statistically significant ( P<0.05), while the difference of serum creatinine in other postoperative follow-up time points was not statistically significant ( P>0.05). Within a year, both groups of grafts continued to grow, reaching adult levels in one year. There was no statistical significance in the incidence of complications between the two groups ( P>0.05). The incidence of protein in the two groups was 33.3% and 6.1%, respectively, 1 case in each group still had proteinuria at 1 year after surgery, and only 1 case in the infant donor kidney recipient in group A had proteinuria at 3 years after surgery. Conclusions:Unilateral donor kidney transplantation from children can provide good results for adult patients with uremia by selecting suitable donors according to the weight of the recipient.

Objective:To explore whether hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) preconditioning can relieve inflammation, reduce cell apoptosis and alleviate renal ischemia-reperfusion injury in mice.Methods:Male C57BL/6 mice were randomly divided into three groups of sham operation (sham), ischemia reperfusion injury (IRI) and IRI+ HIF-PHI ( n=6 each). In IRI+ HIF-PHI group, mice received an intragastric dose of roxadustat (20 mg/kg) every other day one week before. After renal IRI modeling, serum creatinine (SCr) level was monitored and hematoxylin-eosin (HE) staining employed for observing the pathological changes of renal tissue and scoring injury degree. Apoptosis of renal tubular epithelial cells was assessed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). Reverse transcription-polymerase chain reaction (RT-PCR) was utilized for detecting the mRNA expressions of HIF-1α, TNF-α and IL-1β in renal tissues. Immunofluorescence and immunohistochemistry were employed for detecting the expressions of hypoxia-inducing factor 1α (HIF-1α), inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Results:As compared with IRI group, SCr level declined markedly in IRI+ HIF-PHI group ( P<0.01), renal tissue injury improved markedly, semi-quantitative score of renal tubule injury dropped ( P<0.01), apoptotic cells decreased ( P<0.01) and the expression levels of TNF-α and IL-1β declined ( P<0.05). Compared with sham group, the mRNA expression of HIF-1α was not significantly elevated in IRI group ( P>0.05). Immunofluorescence showed that the expression of HIF-1α in medulla of renal tissues was up-regulated in IRI group, but not markedly in cortex. While the mRNA expression of HIF-1α was markedly up-regulated after a pretreatment of HIF-PHI ( P<0.05), the expression spiked markedly in renal cortex, but was weaker in medulla than that in IRI group. Conclusions:HIF-PHI can boost the expression level of HIF-1α, reduce the expression of inflammatory factors, relieve the inflammatory response, reduce cell apoptosis, improve renal function and alleviate renal ischemia reperfusion injury.

Objective:To explore the efficacies of single-center pediatric transplantations and discuss the current problems.Methods:From July 2007 to September 2019, the clinical data of 202 children (aged ≤17 years) undergoing renal transplantation were reviewed. And their perioperative complications, transplantation outcomes and patient/kidney survival were analyzed.Results:The most common perioperative complication was delayed graft function (DGF)( n=24, 11.9%), recurrence of renopathy ( n=8, 4.0%) and acute rejection ( n=21, 10.4%). The major causes of death and graft failure were lung infection ( n=9, 4.5%) and rejection ( n=11, 5.4%). Perioperative serum creatinine decreased progressively from (816.1±303.1) μmol/L preoperatively to (62.7±20.6) μmol/L at Month 3 post-operation. The value of eGFR were (166.8±37.3), (135.1±29.0) and (109.9±31.1) ml/(min·1.73 m 2) at Year 1/3/5 post-operation respectively. The survival rates were 96.7%, 96.3%, 94.1%, 93.5%, 94.1% and 90.7% at Year 1/3/5 post-operation respectively. No difference existed in human/kidney survival rate between LD and DD groups at Year 1/3/5 post-operation ( P>0.05) and transplantation outcomes were excellent. Conclusions:Effective and successful outcomes have been achieved at our center. And further optimizations are required for resolving various problems.

Objective To compare the therapeutic efficacy of plasmapheresis (PP ) and intravenous immunoglobulin (IVIG) plus Rituximab for antibody-mediated rejection (AMR) after kidney transplantation .Methods From May 2015 to November 2018 ,a single-center retrospective cohort study was conducted for 540 recipients with high-resolution HLA undergoing kidney transplantation .According to the criteria of diagnosing AMR and patient selection ,20 patients were selected for PP+IVIG (group A ,n=12) ,PP+ IVIG+ Rituximab (group B ,n=8) .The efficacies and outcomes of two groups were compared .Results During a follow-up period of (12 .0 ± 5 .8 ) months ,no significant inter-group differences existed in basic profiles (P> 0 .05) .After AMR treatment ,serum creatinine levels decreased significantly from 283 .4 to 226 .4 μmol/L in group A (P=0 .001) and from 289 .4 to 166 .6 μmol/L in group B (P=0 .049) .And the magnitude of decline was more marked in group B (P=0 .023) .Meanwhile ,antibody MFI (log10) decreased from 3 .73 to 3 .62 in group A (P=0 .012) and from 3 .57 to 3 .02 in group B (P=0 .043) .At months 3 and 6 , serum creatinine level was lower in group B than that in group A (125 .0 vs .166 .1 μmol/L , P=0 .03 ;127 .0 vs .169 .0μmol/L ,P=0 .048) .The serum creatinine levels of AMR patients were 249 .8 and 233 .8 μmol/L respectively ( P= 0 .182 ) .Serum creatinine levels were 176 .1 and 120 .3 μmol/L ( P=0 .045) and 180 .2 and 114 .8 μmol/L at months 3 and 6 (P=0 .044) respectively .Serum creatinine levels were 202 .8 and 122 .5μmol/L (P=0 .049) in group A and 142 .7 and 107 .0μmol/L (P=0 .046) in group B respectively .Four recipients developed allograft failure .At month 6 post-operation ,AMR occurred in group A (n=3 ,25％ ) and group B (n=1 ,12 .5％ ) .And the incidence of leucopenia was 37 .5％ and 0 (P=0 .049) in groups A and B respectively .Conclusions PP and IVIG plus rituximab is more efficacious for AMR .The earlier occurring time ,the better prognosis .

Objective To explore the significance of time-zero renal biopsy on evaluating renal function and postoperative complications after transplantation from donation in old age donors.Methods Clinical and pathological data of 112 transplantations with time-zero renal biopsy which performed in the First Affiliated Hospital of Zhengzhou Hospital from August 2016 to April 2017 were collected.Based on donor age and Remuzzi score,112 transplantations were divided into four groups:Group A (donor age ＜50 years and Remuzzi score is 0 to 3) with 58 recipients,Group B (donor age ＜50 years and score is 4 to 6) with 9 recipients,Group C (donor age≥50 years and score is 0 to 3) with 35 recipients,and Group D (donor age≥50 years and score is 4 to 60) with 10 recipients.Renal function and postoperative complications of recipients in each group were recorded and compared among groups.Results The estimated glomerular filtration rate (eGFR) at 6th month after operation was significantly negatively correlated with glomerular sclerosis (r=-0.398,P=0.05),arteriolar hyaline degeneration (r=-0.416,P＜0.05) and arterial intimal fibrosis (r=-0.242,P＜0.05).Arteriolar hyaline degeneration (β=-0.249,P＜0.05) and arterial intimal fibrosis (β=-0.246,P=0.020) were the independent correlated factors of eGFR at 6th month after operation.The levels of serum creatinine of group D were higher than those in the other three groups at each time after operation(all P＜0.05);Moreover,in group D the eGFR values at each time were lower than those in the other three groups(P＜0.05).Additionally,the incidences of acute rejection within 6 months after operation in group C and D were higher than those in group A and B (all P＜0.05),but the incidences of delayed graft function,hematuria,proteinuria among four groups were not significantly different (all P＞ 0.05).Conclusions Patients who accepted older kidney with moderate histological lesions show worse renal function and higher incidence of acute rejection after transplantation.Recipient selection and postoperative immunosuppressive treatment should be more cautious for those renal donors.