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1.
Clin Case Rep ; 12(7): e9028, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38911919

ABSTRACT

Key Clinical Message: In addition to post-transplant lymphoproliferative disorders, it is necessary to be alert to the drug-resistant bacteria or fungal infection, especially Talaromyces marneffei, in kidney transplant patients who have failed antibiotic treatment and whose PET-CT indicates high metabolic mass in the transplanted kidney with a large number of other organs and lymph nodes. Abstract: Talaromyces marneffei (TM) is a rare pathogenic fungus that primarily affects individuals with compromised immune systems. Post-transplant lymphoproliferative disorders (PTLD) are serious complications that can occur after solid organ and cell transplantation. Both TM infection and PTLD can invade the monocyte-macrophage system and often manifest as extranodal masses. This case report describes a kidney transplant patient who presented with symptoms of frequent, urgent, and painful urination over 6 months. Pulmonary CT scans revealed multiple nodules, and PET-CT demonstrated enlarged lymph nodes in the lungs and the transplanted kidney. The clinical manifestations closely mimicked those of PTLD. The confirmation of TM was achieved through pathogen metagenomic next-generation sequencing and renal biopsy. Unfortunately, despite receiving treatment with antifungal agents, anti-infective therapy, the patient's condition did not respond favorably, ultimately resulting in their unfortunate demise due to COVID-19.

2.
Kidney Int Rep ; 9(1): 96-107, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38312778

ABSTRACT

Introduction: Biopsy findings often lead to the discard of many donor kidneys although their clinical value is not fully understood. We investigated the predictive value of postreperfusion biopsy on long-term allograft outcome after single-kidney transplantation. Methods: We retrospectively evaluated the significance of histologic findings, read by experienced renal pathologists, in 461 postreperfusion biopsy specimens collected from 2010 to 2017 after deceased donor renal transplant; and performed time-to-event analyses to determine the association between histology and hazard of death-censored graft failure. Recipients were followed-up with over a median time of 6.8 (range, 0.2-11.9) years. We assessed specimens using the Remuzzi score (scale of 0-12) and categorized them into low-score (≤3) and high-score (>3) groups. Kappa coefficients were calculated to assess agreement in procurement versus reperfusion biopsies. Results: High Remuzzi score kidneys came from older donors with a higher incidence of hypertension, higher final creatinine, death from cerebrovascular disease, expanded criteria donor, and a higher kidney donor risk index (KDRI) (all P < 0.001). In adjusted analyses, Remuzzi score was independently associated with death-censored graft failure (hazard ratio [HR] 1.389 for each 1 score rise in Remuzzi score, 95% confidence interval 1.181-1.633, P < 0.001). Overall histologic agreement (procurement biopsy versus reperfusion biopsy) was kappa = 0.137. Conclusion: Our findings suggest that postreperfusion biopsy is associated with long-time graft outcomes after transplant from a deceased donor. Agreement between procurement and reperfusion biopsy was found to be low. Prospective trials are necessary to optimize procurement biopsy practices.

3.
BMC Infect Dis ; 23(1): 888, 2023 Dec 19.
Article in English | MEDLINE | ID: mdl-38114917

ABSTRACT

BACKGROUND: Lymphomas involving the gastrointestinal tract may be manifested as anti-inflammatory tract bleeding, abdominal lymph node enlargement, or even perforation of the gastrointestinal tract. After organ transplantation, the likelihood of post-transplant lymphoproliferative disorders increases, and some rare infections may also appear. CASE PRESENTATION: Herein, we report a living transplant patient with talaromycosis marneffei (TSM) or Talaromyces marneffei (TM) infection with gastrointestinal hemorrhage and systemic lymph node enlargement, which presented clinically as lymphoma. CONCLUSION: This case is TSM in a kidney transplant patient, confirmed by lymph node biopsy and blood culture. The patient discharged from hospital successfully under the treatment of antifungal therapy and immunosuppressive therapy. Physicians should be aware that TSM can mimic lymphoma, and early diagnosis and treatment can benefit the outcomes.


Subject(s)
Kidney Transplantation , Lymphadenopathy , Lymphoma , Humans , Antifungal Agents/therapeutic use , Kidney Transplantation/adverse effects , Diagnosis, Differential , Lymphoma/diagnosis , Lymphadenopathy/drug therapy
4.
Microorganisms ; 11(11)2023 Nov 10.
Article in English | MEDLINE | ID: mdl-38004758

ABSTRACT

The composition of the gut microbiome is profoundly influenced by the accumulation of toxins in end-stage renal disease (ESRD) and specific medical treatments during kidney transplantation (KT). However, variations in results may arise due to factors such as genetics, dietary habits, and the strategy of anti-rejection therapy. Therefore, we conducted a 16S rRNA sequencing study to characterize intestinal microbiomes by using 75 fecal specimens obtained from 25 paired Chinese living donors (LDs) of kidneys and recipients before and after KT. Surprisingly, similar enterotypes were observed between healthy LDs and ESRD recipients. Nonetheless, following KT, the fecal communities of recipients exhibited distinct clustering, which was primarily characterized by Escherichia-Shigella and Streptococcus at the genus level, along with a reduction in the diversity of microbiota. To further explore the characteristics of gut microorganisms in early rejection episodes, two recipients with biopsy-proven borderline changes during follow-up were enrolled in a preliminary sub-cohort study. Our findings reveal a comparable construction of gut microbiota between ESRD patients and their healthy relatives while also highlighting the significant impact of KT on gut microbial composition.

5.
Kidney Dis (Basel) ; 9(5): 326-341, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37901712

ABSTRACT

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) were initially developed as glucose-lowering agents in patients with type-2 diabetes. However, available data from clinical trials and meta-analyses suggest that SGLT2i have pleiotropic benefits in reducing mortality and delaying the progression of chronic kidney disease (CKD) in both diabetic and nondiabetic patients. Thus, we herein review the current evidence regarding the efficacy and safety of SGLT2i in patients with nondiabetic CKD and appraise the recently reported clinical trials that might facilitate the management of CKD in routine clinical practice. Summary: The benefits of SGLT2i on nondiabetic CKD are multifactorial and are mediated by a combination of mechanisms. The landmark DAPA-CKD trial revealed that dapagliflozin administered with renin-angiotensin system blockade drugs reduced the risk of a sustained decline (at least 50%) in the estimated glomerular filtration rate, end-stage kidney disease, or death from cardiorenal causes. The recent EMPA-KIDNEY trial showed that empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes. These benefits were consistent in patients with and without diabetes. Moreover, a meta-analysis of DAPA-HF and EMPEROR-Reduced trials confirmed reductions in the combined risk of cardiovascular death or worsening heart failure including composite renal endpoint. Key Messages: Considering the robust data available from DAPA-CKD, EMPA-KIDNEY, and other trials such as EMPEROR-Preserved, DIAMOND that included nondiabetic patients, it may be necessary to update current guidelines to include SGLT2i as a first-line therapy for CKD and reevaluate current CKD therapeutic approaches.

6.
ACS Appl Mater Interfaces ; 15(29): 34588-34606, 2023 Jul 26.
Article in English | MEDLINE | ID: mdl-37459593

ABSTRACT

Disturbance of single-cell transcriptional heterogeneity is an inevitable consequence of persistent donor-specific antibody (DSA) production and allosensitization. However, identifying and efficiently clearing allospecific antibody repertoires to restore single-cell transcriptional profiles remain challenging. Here, inspired by the high affinity of natural bacterial proteins for antibodies, a genetic engineered membrane-coated nanoparticle termed as DSA trapper by the engineering chimeric gene of protein A/G with phosphatidylserine ligands for macrophage phagocytosis was reported. It has been shown that DSA trappers adsorbed alloreactive antibodies with high saturation and activated the heterophagic clearance of antibody complexes, alleviating IgG deposition and complement activation. Remarkably, DSA trappers increased the endothelial protective lineages by 8.39-fold, reversed the highly biased cytotoxicity, and promoted the proliferative profiles of Treg cells, directly providing an obligate immune tolerant niche for single-cell heterogeneity restoration. In the mice of allogeneic transplantation, the DSA trapper spared endothelial from inflammatory degenerative rosette, improved the glomerular filtration rate, and prolonged the survival of allogeneic mice from 23.6 to 78.3 days. In general, by identifying the lineage characteristics of rejection-related antibodies, the chimeric engineered DSA trapper realized immunoadsorption and further phagocytosis of alloantibody complexes to restore the single-cell genetic architecture of the allograft, offering a promising prospect for the treatment of alloantibody-mediated immune injury.


Subject(s)
Kidney Transplantation , Mice , Animals , Transplantation, Homologous , Isoantibodies , Complement Activation , Allografts
7.
J Zhejiang Univ Sci B ; 24(6): 524-529, 2023 Apr 15.
Article in English, Chinese | MEDLINE | ID: mdl-37309043

ABSTRACT

There is currently a huge worldwide demand for donor kidneys for organ transplantation. Consequently, numerous marginal donor kidneys, such as kidneys with microthrombi, are used to save patients' lives. While some studies have shown an association between the presence of microthrombi in donor kidneys and an increased risk for delayed graft function (DGF) (McCall et al., 2003; Gao et al., 2019), other studies have demonstrated that microthrombi negatively impact the rate of DGF (Batra et al., 2016; Hansen et al., 2018), but not graft survival rate (McCall et al., 2003; Batra et al., 2016; Gao et al., 2019). In contrast, Hansen et al. (2018) concluded that fibrin thrombi were not only associated with reduced graft function six months post-transplantation but also with increased graft loss within the first year of transplantation. On the other hand, Batra et al. (2016) found no significant differences in the DGF rate or one-year graft function between recipients in diffuse and focal microthrombi groups. To date, however, the overall influence of donor kidney microthrombi and the degree of influence on prognosis remain controversial, necessitating further research.


Subject(s)
Thrombotic Microangiopathies , Humans , Transplantation, Homologous , Tissue Donors , Kidney , Allografts
8.
Int Urol Nephrol ; 55(12): 3217-3224, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37093441

ABSTRACT

INTRODUCTION: Pretransplant osteoporosis and vascular calcification probably increase the risk of fractures and cardiovascular events after kidney transplantation. In the present study, we investigated the related risk factors of osteoporosis and vascular calcification among end-stage renal disease (ESRD) patients awaiting kidney transplantation. METHODS: A total of 221 ESRD patients (age, 43.4 ± 14.3 years; 125 males and 96 females; median dialysis duration, 61.0 m) awaiting kidney transplantation were enrolled in this cross-sectional study. Serum levels of bone turnover markers and intact parathyroid hormone (iPTH) were analyzed from fasting morning blood samples. Dual-energy X-ray absorptiometry was used to measure bone mineral density (BMD). Vascular calcification was evaluated by lateral abdominal radiography and plain radiographic films of the pelvis and hands. RESULTS: The osteoporosis prevalence was 27.6% in this cohort of kidney transplantation candidates, and the prevalence of vascular calcification was 51.1%. The related factors for osteoporosis and vascular calcification were similar and included older age, longer dialysis duration, parathyroid hyperplasia, and higher levels of iPTH and bone turnover markers. In the multivariable regression model, age and iPTH were independent risk predictors of both vascular calcification and osteoporosis. There were strong, positive correlations between iPTH and all bone turnover markers. The moderate and severe hyperparathyroidism (iPTH 600-1499 pg/ml and iPTH 1500 pg/ml) were related to reduced serum albumin and hemoglobin levels. CONCLUSION: The involvement of high iPTH levels in vascular calcification, osteoporosis, and malnutrition indicated the need of treating hyperparathyroidism early in patients awaiting kidney transplantation. Prospective studies are needed to further examine the utility of bone turnover markers.


Subject(s)
Hyperparathyroidism , Kidney Failure, Chronic , Kidney Transplantation , Osteoporosis , Vascular Calcification , Male , Female , Humans , Adult , Middle Aged , Kidney Transplantation/adverse effects , Cross-Sectional Studies , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Bone Density , Osteoporosis/etiology , Osteoporosis/complications , Vascular Calcification/diagnostic imaging , Vascular Calcification/epidemiology , Vascular Calcification/etiology , Parathyroid Hormone
9.
Adv Sci (Weinh) ; 9(31): e2202633, 2022 11.
Article in English | MEDLINE | ID: mdl-36073846

ABSTRACT

Direct contact of membrane molecules and cytokine interactions orchestrate immune homeostasis. However, overcoming the threshold of distance and velocity barriers, and achieving adhesion mediated immune interaction remain difficult. Here, inspired by the natural chemotaxis of regulatory T cells, multifunctionalized FOXP3 genetic engineered extracellular vesicles, termed Foe-TEVs, are designed, which display with adhesive molecules, regulatory cytokines, and coinhibitory contact molecules involving CTLA-4 and PD-1, by limited exogenous gene transduction. Foe-TEVs effectively adhere to the tubular, endothelial, and glomerular regions of allogeneic injury in the renal allograft, mitigating cell death in situ and chronic fibrosis transition. Remarkably, transcript engineering reverses the tracking velocity of vesicles to a retained phenotype and enhanced arrest coefficient by a factor of 2.16, directly interacting and attenuating excessive allosensitization kinetics in adaptive lymphoid organs. In murine allogeneic transplantation, immune adhesive Foe-TEVs alleviate pathological responses, restore renal function with well ordered ultrastructure and improved glomerular filtration rate, and prolong the survival period of the recipient from 30.16 to 92.81 days, demonstrating that the delivery of extracellular vesicles, genetically engineered for immune adhesive, is a promising strategy for the treatment of graft rejection.


Subject(s)
Extracellular Vesicles , Kidney Transplantation , Mice , Animals , Graft Rejection/prevention & control , Graft Rejection/genetics , Transplantation, Homologous , T-Lymphocytes, Regulatory/metabolism
10.
Ann Palliat Med ; 10(11): 11859-11867, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34872310

ABSTRACT

BACKGROUND: To observe the efficacy and safety of roxadustat, an inhibitor of proline hydroxylase, in renal allograft anemia patients. METHODS: This prospective study collected the clinical data of renal transplant patients treated with roxadustat for anemia at the Kidney Disease Center of the First Affiliated Hospital of Zhejiang University from April to August 2020. The patients were followed up every 2 weeks, and the changes in their hemoglobin index and any adverse reactions were recorded during 10 weeks of treatment. The efficacy of roxadustat for treatment of anemia after kidney transplantation was analyzed by comparing the change and increase in average hemoglobin levels before and after treatment. Rates of treatment response and achievement of the standard hemoglobin level were statistically analyzed. In addition, any potential adverse events and the glomerular filtration rate were recorded for 10 weeks to assess the safety of roxadustat in renal allograft anemia patients. RESULTS: After 10 weeks of roxadustat treatment, the mean hemoglobin level was 10.4±3.9 g/dL, which was significantly higher than at baseline. Over the entire period, treatment was observed to have a therapeutic effect at weeks 2-4, with mean hemoglobin levels increasing as treatment time increased. At the 10-week endpoint, the percentage of patients reaching the standard hemoglobin level and exhibiting a response to treatment was 52.4% and 71.4%, respectively. During the treatment, there was no rejection, and the glomerular filtration rate was stable. Only one person showed symptoms of fatigue, and there were no other obvious adverse reactions reported. CONCLUSIONS: Roxadustat significantly improves hemoglobin levels and can be safely used in renal transplant anemia patients.


Subject(s)
Anemia , Kidney Transplantation , Renal Insufficiency, Chronic , Allografts , Anemia/chemically induced , Anemia/drug therapy , Glycine/analogs & derivatives , Humans , Hypoxia-Inducible Factor-Proline Dioxygenases , Isoquinolines , Prospective Studies
11.
Ann Transplant ; 26: e931059, 2021 Jun 08.
Article in English | MEDLINE | ID: mdl-34099614

ABSTRACT

BACKGROUND Pneumocystis jirovecii pneumonia (PJP) is one of the common opportunistic infections diagnosed in kidney transplantation recipients. It is difficult to identify early by use of classic tools such as Grocott-Gomori stains and polymerase chain reaction (PCR). Metagenomic next-generation sequencing (mNGS) is accurate, unbiased, and sensitive, and is promising in PJP diagnosis. MATERIAL AND METHODS Data on kidney transplantation patients diagnosed with PJP were retrospectively analyzed. The sensitivity and specificity of different tools such as mNGS, laboratory tests, and Grocott-Gomori stains for PJP diagnosis were compared. All recipients were treated with trimethoprim-sulfamethoxazole (TMP-SMX). RESULTS There were a total of 12 kidney transplantation recipients diagnosed with PJP based on mNGS in our center from January 01, 2020 to October 27, 2020. Highly variable numbers of sequence reads for P. jiroveci (19 to 1041285) showed diagnostic significance. Bronchoalveolar lavage fluid (BALF) samples were tested by Grocott-Gomori staining, with only 6 of 11 (54.5%) positive. Other routine laboratory tests like routine blood tests, blood biochemistry, procalcitonin (PCT), immune function, (1,3)-ß-d-glucan (BG), serum galactomannan (GM), and C-reactive protein (CRP) showed even lower efficacy. TMP-SMX appeared to be the ideal therapy for kidney transplantation recipients with PJP. CONCLUSIONS mNGS has utility in the diagnosis of PJP and mixed infections in kidney transplantation recipients, and TMP-SMX could be the ideal therapeutic drug for kidney transplantation recipients suffering from PJP.


Subject(s)
High-Throughput Nucleotide Sequencing , Kidney Transplantation , Pneumonia, Pneumocystis , Adult , Female , Humans , Kidney Transplantation/adverse effects , Male , Middle Aged , Pneumocystis carinii/genetics , Pneumonia, Pneumocystis/diagnosis , Retrospective Studies
12.
Front Pharmacol ; 11: 563967, 2020.
Article in English | MEDLINE | ID: mdl-33117163

ABSTRACT

BACKGROUND: Depending on the renal function of patients and many other influencing factors, studies on vancomycin pharmacokinetics show significant inter- and intra-individual variability. The present study was conducted using a population pharmacokinetics method to investigate the pharmacokinetic parameters and identified their influencing covariates for intravenous vancomycin in adult kidney transplant recipients. METHODS: The drug monitoring data included 56 adult renal transplant recipients who received intravenous vancomycin as prophylactic medication. The analysis was performed by a population approach with NONMEM. Data were collected mainly during the first week after transplantation. Monitoring of vancomycin trough concentration in blood was initiated mainly 3-5 days after the initial administration. RESULTS: The one-compartment open model was optimal and adequately described the data. Body weight (WT) and estimated glomerular filtration rate (GFR) were identified as significant covariates of the pharmacokinetic parameters CL and V of intravenous vancomycin in the kidney transplant patients. The typical values of vancomycin CL and V were 2.08 L h-1 and 63.2 L, respectively. A dosage strategy scheme according to model results was also designed. CONCLUSION: Both WT and GFR of the kidney transplant patients positively influence the pharmacokinetic parameters CL and V for intravenous vancomycin. Our population pharmacokinetic model provides a reference for vancomycin dosage adjustment in kidney transplant recipients.

13.
Aging (Albany NY) ; 12(18): 18396-18414, 2020 Sep 29.
Article in English | MEDLINE | ID: mdl-32991326

ABSTRACT

Allograft rejection after renal transplantation remains a challenge to overcome. Interleukin (IL)-21, a cytokine with pleiotropic effects, maintains immune homeostasis post-transplantation. Here, we report higher levels of IL-21 in kidney transplant recipients with non-rejection (NR) than in recipients with T cell-mediated rejection (TCMR, P < 0.001) and antibody-mediated rejection (ABMR, P = 0.005). We observed a negative correlation between IL-21 and creatinine (Cr) levels (P = 0.016). The receiving operating characteristic (ROC) curve showed a promising diagnostic value of IL-21 to identify acute rejection with an area under the curve (AUC) of 0.822 (P < 0.001). In contrast, exogenous administration of IL-21 accelerated acute rejection in a comparative translational kidney transplant (KT) mouse model. Reduced IL-21 levels in the peripheral blood were observed in KT mice after IL-21 injection. Further analysis revealed that increased IL-21 levels in the spleen induced proliferation of CD4+ T cells and CD19+ B cells after IL-21 treatment. Our findings suggest a critical function of IL-21 in kidney transplantation and the potential involvement of the IL-21/IL-21R pathway in acute rejection management.

14.
Clin Transplant ; 34(10): e14053, 2020 10.
Article in English | MEDLINE | ID: mdl-32735352

ABSTRACT

Donor-derived cell-free DNA (dd-cfDNA) is a promising biomarker for monitoring allograft status. However, whether dd-cfDNA can reflect real-time anti-rejection treatment effects remains unclear. We prospectively recruited 28 patients with acute renal rejection, including 5 with ABMR, 12 with type IA or type IB rejection, and 11 with type IIA or IIB rejection. dd-cfDNA levels in peripheral blood were measured using human single nucleotide polymorphism (SNP) locus capture hybridization. The percentage of dd-cfDNA (dd-cfDNA%) declined significantly from 2.566 ± 0.549% to 0.773 ± 0.116% (P < .001) after anti-rejection therapy. The dd-cfDNA% decreased steadily over the course of 3 days with daily methylprednisolone injections, but no significant difference in the dd-cfDNA% was observed between the end of anti-rejection therapy and 2 weeks later. Changes in the dd-cfDNA% (∆dd-cfDNA%) demonstrated a positive correlation with estimated glomerular filtration rates at 1 month (ρ = 2.570, P = .022), 3 months (ρ = 3.210, P = .027), and 6 months (ρ = 2.860, P = .019) after therapy. Thus, the dd-cfDNA assay shows prognostic capabilities in therapy outcome and allograft recovery; however, its ability is inhibited by methylprednisolone regardless of the types of rejection. Additionally, a reassessment of frequency intervals for testing is required.


Subject(s)
Cell-Free Nucleic Acids , Kidney Transplantation , Graft Rejection/diagnosis , Graft Rejection/drug therapy , Graft Rejection/etiology , Humans , Prognosis , Prospective Studies
15.
Ann Transl Med ; 8(11): 683, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32617303

ABSTRACT

BACKGROUND: Chronic refractory dialysis hypotension (CRDH) is a serious issue in dialysis patients waiting for transplants. It leads to fatal clinical outcomes and disqualification from kidney transplantation. Kidney transplantation from pediatric donor to adult patient with lower blood pressure (BP) may be an option. No related study has been reported and we conducted this study to first evaluate the effect of pediatric donor kidney transplantation in CRDH recipients. METHODS: Ten single-kidney transplantations from small pediatric donors after cardiac death in our center between August 2016 and April 2018 were described. Half were CRDH recipients (group A) with intradialytic and interdialytic systolic blood pressure (SBP) below 100 mmHg. Each was paired with no-CRDH recipient (control, group B) from the same donor. The operation method of vascular anastomosis and ureterocystoneostomy was the same as that of adult donors. Clinical characteristics, post-operative treatment and outcomes of all recipients were retrieved. Postoperative BP, graft function and size were compared between two groups. The follow-up time was up to April 2019. RESULTS: There was no acute rejection (AR), graft loss or death in all recipients after transplantation. Their renal function was recovered despite three transient delayed graft function (DGF). There was no significant difference in serum creatinine (SCr) or graft size (P=0.84, 0.94) after transplantation between two groups. For all CRDH recipients, the postoperative SBP was above 100 mmHg (except one, 90-130 mmHg). The BP one year after transplantation was maintained at 110-125/70-85 mmHg. CONCLUSIONS: kidney transplantation from small pediatric donors may be feasible to CRDH recipients and their BP may return to normal after transplantation.

16.
Ann Transl Med ; 8(6): 330, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32355774

ABSTRACT

BACKGROUND: Hereditary renal hypouricemia (HRH) is a genetically heterogenetic disease. Patients with HRH are almost asymptomatic; but some may experience exercise-induced acute kidney injury (EAKI) and nephrolithiasis which may bring concerns regarding the risk-benefit ratio as marginal kidney donors. This study examined the pathogenic mutations of hypouricemia in two recipients after receiving kidney transplantation, providing preliminary evidence for the mechanism of hypouricemia. METHODS: Two participants underwent detailed biochemical examinations. DNA and RNA were extracted from transplant specimens for sequencing. The whole-genome sequencing and polymerase chain reaction (PCR) amplification were performed to confirm the pathogenic genes. Functional effects of mutant proteins were verified by bioinformatics analysis. RNA-sequencing (RNA-seq) was used to study the transcriptome of hypouricemia. RESULTS: Both of the recipients had the low serum uric acid (UA) (45-65 µmol/l), high fraction excretion of UA (44% and 75%) and an increase in the UA clearance (35.9 and 73.3 mL/min) with a functioning graft. The sequencing analyses revealed 7 kinds of potential mutational genes in this case, two novel mutations p.R89H and p.L181V in SLC22A12 gene which were revealed by bioinformatics could be pathogenic in nature. CONCLUSIONS: Two novel mutations of SLC22A12 were identified. Preliminary functional analysis revealed a potential deleterious effect of these mutations in the grafts derived from the donor and sequencing analysis expand the molecular mechanisms of renal hypouricemia.

17.
Kidney Blood Press Res ; 43(6): 1813-1821, 2018.
Article in English | MEDLINE | ID: mdl-30504705

ABSTRACT

BACKGROUND/AIMS: Hemodialysis (HD) or peritoneal dialysis (PD) is an important renal replacement method in patients with delayed graft function (DGF) after kidney transplantation; however, it is not clear which dialysis modality is superior. This study determined the impact of different dialysis modalities on patients with DGF. METHODS: It was a single-center, retrospective and descriptive study. We performed 673 kidney transplants from donors after cardiac death (DCD) between January 2010 and December 2016 at our center and 138 (20.5%) recipients developed DGF after transplantation. We classified the recipients into two groups according to post-transplant dialysis: DGF-HD (n=96) and DGF-PD (n=42). We analyzed the outcomes of the different dialysis modalities 30 days and 1 year post-transplantation. RESULTS: There were no differences in baseline factors between patients with post-transplant HD (n = 96) or PD (n = 42). There were 10 patients with conversion from PD to HD during DGF. The DGF-PD patients had a higher rate of treatment failure than the DGF-HD patients (23.8% vs. 0%, p < 0.001), peritonitis (7.1% vs. 0%, p = 0.027), and longer duration of dialysis dependence (10.5 vs. 9 days, p = 0.003). There was no statistically significant difference between both groups with respect to acute rejection, hemorrhage, and patient and graft survival at 1 year. CONCLUSION: In renal transplant recipients with DGF, post-transplant PD led to increased treatment failure. PD did not result in rapid recovery of transplanted renal function, and had a high probability of peritonitis.


Subject(s)
Delayed Graft Function/therapy , Kidney Transplantation/adverse effects , Peritoneal Dialysis/standards , Renal Dialysis/standards , Adult , Delayed Graft Function/etiology , Humans , Peritoneal Dialysis/adverse effects , Peritonitis , Retrospective Studies , Treatment Failure , Young Adult
18.
Exp Clin Transplant ; 13(3): 239-42, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26086834

ABSTRACT

OBJECTIVES: This study was conducted to evaluate the outcomes of single kidney transplant from pediatric donors in China younger than 5 years old after cardiac death. MATERIALS AND METHODS: We retrospectively reviewed single renal transplants from pediatric donors of cardiac death between January 2012 and June 2013 at the First Affiliated Hospital of Zhejiang University, China. RESULTS: Eleven recipients received single kidney transplant from 6 pediatric donors of cardiac death donors at our center (aged, < 5 years). The median donor age was 39 months (range, 17-56 mo). The median donor weight was 14.5 kg (range, 11-20 kg). While the median recipient age was 35 years (range, 12-55 y). The median recipient weight was 42.5 kg (range, 21-55 kg). The recipient serum creatinine level gradually decreased and the 1-year serum creatinine was 77.7 ± 17.6 µmol/L. Delayed graft function occurred in 5 recipients (45.5%), and all of them recovered within 1 month after transplant. No episodes of acute rejection occurred. No vascular thrombosis or stenosis after ureteroneocystostomy was seen. One patient had urine leakage on the eighth day after transplant, and was cured through a ureter reimplantation. The graft size increased significantly the first month after transplant compared with that recorded immediately after reperfusion (P = .011). The 1-year patient/graft survival was 100%. CONCLUSIONS: Use of single kidney from pediatric donors after cardiac death (aged, < 5 y) is a safe and effective procedure and can greatly expand the donor pool.


Subject(s)
Heart Diseases/mortality , Kidney Transplantation/methods , Tissue Donors/supply & distribution , Adolescent , Adult , Age Factors , Biomarkers/blood , Cause of Death , Child , Child, Preschool , China , Creatinine/blood , Delayed Graft Function/blood , Delayed Graft Function/diagnosis , Delayed Graft Function/etiology , Female , Hospitals, University , Humans , Infant , Kidney Transplantation/adverse effects , Male , Middle Aged , Organ Size , Recovery of Function , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Young Adult
19.
Basic Clin Pharmacol Toxicol ; 117(3): 186-94, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25625413

ABSTRACT

Despite advancements in modern medicine, the treatment of acute heart failure (AHF) after acute myocardial infarction (AMI) remains challenging. Milrinone is effective in the treatment of chronic congestive heart failure, but its safety and efficacy in patients with AHF after AMI have not been systematically evaluated. This meta-analysis was performed to assess the safety and efficacy of milrinone in patients with AHF after AMI. We used a pre-designed protocol to search electronic databases for randomized trials assessing milrinone for the treatment of AHF after AMI. Data were abstracted from relevant studies. Heterogeneity was assessed qualitatively using a Q test and quantified using the I(2) statistic. Pooled risk estimates with 95% confidence intervals (CIs) were obtained using fixed-effects models unless substantial heterogeneity was observed (I(2) ≥ 50% and heterogeneity p ≤ 0.1). Four randomized trials met the inclusion criteria. However, there were no significant differences in deaths, blood pressure, premature ventricular contractions, gastrointestinal reactions, or ventricular tachycardia or fibrillation (all p > 0.05) between control group and milrinone treatment group. Pooled estimates showed that milrinone significantly increased the left ventricular ejection fraction (MD 5.69; 95% CI 4.27 to 7.10; p < 0.00001) and cardiac output (MD 0.35, 95% CI: 0.13 to 0.56; p = 0.002, I(2) = 24%). While studies to date are few and limited by small sample sizes and poor quality, they suggest that treatment with milrinone may be safe and effective for patients with AHF after AMI. However, this meta-analysis did not show that milrinone could improve prognosis or the survival rate.


Subject(s)
Cardiotonic Agents/therapeutic use , Heart Failure/drug therapy , Milrinone/therapeutic use , Myocardial Infarction/drug therapy , Heart Failure/etiology , Humans , Myocardial Infarction/complications
20.
Exp Clin Transplant ; 12(6): 515-21, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25019250

ABSTRACT

OBJECTIVES: The purpose of this study was to evaluate the effect of donor-recipient body surface area ratio on donor age and donor glomerular filtration rate in living-donor kidney transplant. MATERIALS AND METHODS: This retrospective study included 254 rejection-free patients who underwent their first living-donor kidney transplant at our center between April 2007 and April 2011. We performed multivariate linear regression and receiver operating characteristic curve analyses to determine independent associations and the cumulative effects on posttransplant graft function and outcomes in persons in China who had a living-donor kidney transplant. RESULTS: In multivariate linear regression, donor age, donor estimated glomerular filtration rate, and donor-recipient body surface area ratio were independent predictors of 1-year graft function. Linear regression showed that correcting donor age by donor-recipient body surface area ratio increased the strength of the correlation between donor age and 1-year graft function. In the older group (donor age ≥ 45 y), the effect of donor-recipient body surface area ratio on graft function was stronger. By considering the 1-year donor estimated glomerular filtration rate in 2 groups (< 60 or ≥ 60 mL/min/1.73 m(2)), the cutoff values for corrected donor age was 55 years and donor estimated glomerular filtration rate before surgery was 113 mL/min/1.73 m(2). CONCLUSIONS: By correcting for donor-recipient body surface area ratio, donor age accurately predicted and correlated better with 1 year graft function. During preoperative evaluation donor and recipient body surface area matching may be useful.


Subject(s)
Body Surface Area , Glomerular Filtration Rate , Kidney Failure, Chronic/surgery , Kidney Transplantation/methods , Kidney/surgery , Living Donors , Transplant Recipients , Adult , Age Factors , Aged , Area Under Curve , Asian People , China , Female , Graft Rejection/diagnosis , Graft Rejection/etiology , Humans , Kidney/physiopathology , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/ethnology , Kidney Failure, Chronic/physiopathology , Kidney Transplantation/adverse effects , Linear Models , Male , Middle Aged , Multivariate Analysis , Predictive Value of Tests , ROC Curve , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Young Adult
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