Primary hyperoxaluria type II and organ transplantation / 器官移植

Primary hyperoxaluria type Ⅱ (PH2) is an inherited disorder of the glyoxylate metabolism caused by the gene mutation of glyoxylate reductase/hydroxypyruvate reductase (GRHPR). PH2 is characterized by recurrent nephrolithiasis and nephrocalcinosis, which may even progress into end-stage renal disease. Currently, organ transplantation is the only treatment option for PH2, which mainly includes two strategies: kidney transplantation and combined liver and kidney transplantation. Kidney transplantation yields a high risk of recurrence of oxalate nephropathy, which may cause early graft dysfunction. Combined liver and kidney transplantation could mitigate the deficiency of oxalate metabolism, whereas it yields a high risk of graft complications. PH2 is an extremely rare disorder. No consensus has been reached on the indications, surgical selection and perioperative management of organ transplantation for PH2 patients. In this article, the pathogenesis, diagnosis, monitoring and organ transplantation experience of PH2 were reviewed, aiming to divert clinicians' attention to PH2 and provide reference for determining diagnosis and treatment regimens, especially transplantation strategy for PH2 patients.

Management of diarrhea after kidney transplantation / 器官移植

Diarrhea is a frequent complication after kidney transplantation, which is a common clinical manifestation of prevalent diseases following multiple types of organ transplantation. The common causes of diarrhea after kidney transplantation include adverse reactions of immunosuppressants, infectious diseases and de novo postoperative inflammatory bowel disease, etc. Diarrhea could seriously affect the quality of life of kidney transplant recipients, and may lead to allograft dysfunction or even death of recipients. Because the causes of diarrhea after kidney transplantation are complicated and probably overlap with each other, along with individual differences among recipients, the etiological diagnosis and targeted treatment of diarrhea after kidney transplantation should follow the principles of gradual and phased treatment. In this article, the epidemiology and harm, common causes and management strategies of diarrhea after kidney transplantation were summarized, aiming to deepen the clinicians' understanding and enhance the diagnosis and treatment levels of diarrhea after kidney transplantation, thereby improving the quality of life and prognosis of kidney transplant recipients.

Application of ureteral stent in kidney transplantation / 器官移植

Ureteral stricture, urine leakage and other urinary complications are likely to occur after kidney transplantation, which severely affect the function of renal allograft and even lead to renal allograft loss. Ureteral stent plays a critical role in kidney transplantation, which could promote the urine flow from kidney to bladder after kidney transplantation, lower the pressure within the ureter and reduce the risk of early urinary complications. However, it may also cause urinary tract infection, stent-related complications and BK virus infection, etc. Therefore, clinicians should flexibly grasp the indications for ureteral stent removal. In this article, the application, potential adverse reactions and the timing of removal of ureteral stent in the field of kidney transplantation were reviewed, aiming to provide reference for clinical decision-making related to ureteral stent after kidney transplantation.

Research progress on the role of macrophages in post-transplantation chronic rejection / 器官移植

Organ transplantation is the optimal treatment for end-stage organ failure. Nevertheless, rejection remains an important factor affecting the allograft survival. At present, acute rejection may be effectively treated, whereas no effective interventions are available for post-transplantation chronic rejection. Long-term chronic rejection may lead to graft failure and severely affect long-term survival rate of allografts. In recent years, the role of macrophages in post-transplantation chronic rejection has gradually captivated increasing attention. In this article, main pathological changes of chronic rejection, the diversity and functional differences of macrophages involved in chronic rejection, and the role and mechanism of macrophages in chronic rejection were reviewed, and research progresses on macrophage-related treatment for chronic rejection were summarized, aiming to provide reference for the study of macrophages in post-transplantation chronic rejection.

Research progress on the role of macrophages in renal allograft fibrosis / 器官移植

Ischemia-reperfusion injury, rejection, nephrotoxicity caused by calcineurin inhibitors and other factors cause excessive accumulation of renal extracellular matrix after kidney transplantation, which gradually induce renal fibrosis and eventually lead to renal failure. In recent years, the mechanism of macrophages in renal allograft fibrosis has gradually captivated widespread attention. Studies have shown that some drugs like mammalian target of rapamycin inhibitors may mitigate renal allograft fibrosis through the macrophage. In this article, the main pathogenesis and pathophysiological mechanism of renal allograft fibrosis, the role of different macrophages in the progression of renal allograft fibrosis, the infiltration of peripherally-recruited macrophages and renal resident macrophages into renal injury areas, the induction of myofibroblasts by macrophages and potential treatment regimens of macrophage-associated renal allograft fibrosis were reviewed, aiming to provide reference for investigating the role of macrophages in renal allograft fibrosis.

Mitofusin 2 and ischemia-reperfusion injury / 器官移植

Mitochondria is one of the important organelles, which is composed of outer mitochondrial membrane and inner mitochondrial membrane. Mitochondrial structure and function are regulated by mitochondrial dynamics. Mitochondrial fusion- and fission-related proteins may participate in the process of mitochondrial fusion and fission, mediate mitochondrial dynamics, thereby regulating cell structure, function and energy metabolism. Mitofusin (MFN) 2, a protein located on the outer mitochondrial membrane of mammalian, has guanosine triphosphatase activity, which may mediate mitochondrial fusion, participate in mitophagy, formation of mitochondria-associated endoplasmic reticulum membrane and apoptosis, and significantly affect the incidence and development of ischemia-reperfusion injury (IRI). In this article, the structure, regulation, function of MFN2 and its role in IRI were reviewed, and the relationship between MFN2 and IRI and underlying mechanism were investigated, aiming to provide novel targets and ideas for the prevention and treatment of IRI.

Research progress on application of shear wave elastography in kidney transplantation / 器官移植

Early detection of renal allograft dysfunction plays a critical role in the management of immunosuppression and the survival of renal allograft. However, early detection of renal allograft dysfunction still has certain challenges because no significant changes could be observed in clinical manifestations and biochemical parameters during the early stage. As a novel ultrasound examination tool in recent years, shear wave elastography has been successfully applied in the detection of thyroid, breast, liver and alternative organs. In addition, it also has promising application prospect in the examination of renal allograft due to multiple advantages of real-time, dynamic, accuracy and repeatability. In this article, the classification, principle, advantages, influencing factors of shear wave elastography and its application in the field of kidney transplantation were reviewed, aiming to provide reference for clinicians to make accurate decisions in the prevention and monitoring of renal allograft diseases.

The latest progress on JC virus infection after renal transplantation / 器官移植

JC virus (JCV) is a member of polyomaviridae family that infects approximately 70% of the population worldwide. JCV constantly stays in a latent state after the primary infection. In immunosuppressed individuals, especially under the circumstances of low cellular immune function, JCV may be reactivated and lead to severe clinical manifestations. In recent years, the correlation between JCV and complications after renal transplantation has captivated widespread attention. JCV-associated nephropathy (JCVAN) has been reported. Here, latest research progresses on the epidemiology, molecular biology, in vivo infection process, JCV and complications after renal transplantation, and the relationship between JCV and BKV were reviewed, aiming to provide reference for the adjustment of immunosuppressive regimen following renal transplantation.

Mechanism of intravenous immunoglobulin and its application in renal transplantation / 器官移植

Intravenous immunoglobulin (IVIG) is an immunoglobulin (Ig) isolated from the plasma of healthy human, and its main component is IgG. The mechanism of IVIG is complex, which may play a role via multiple pathways. For example, the combination of Fc fragment of IgG with various Fc gamma receptor (FcγR) regulates inflammatory response and autoantibody metabolism, and Fab fragment of IgG neutralizes multiple antigens and other molecules. IVIG may also inhibit complement activation and affect the balance of anti-inflammation and proinflammation among immune cells. In the treatment of diseases, IVIG constantly plays a role through multiple mechanisms simultaneously, primarily via one certain mechanism in different diseases. IVIG is commonly applied in the desensitization treatment of sensitized patients, ABO incompatible renal transplantation, antibody-mediated rejection and several infectious diseases. In this article, the mechanism of IVIG and its application in renal transplantation were reviewed.

Multi-disciplinary team on renal allograft dysfunction induced by recurrence of primary hyperoxaluria type I after renal transplantation / 器官移植

Objective To investigate the clinical characteristics and the experience of multi-disciplinary team (MDT) on recurrence of primary hyperoxaluria (PH) type I after renal transplantation. Methods One case presenting with unexplained rapid decline of renal allograft function after allogeneic renal transplantation was discussed by MDT. The role of MDT in diagnosing rare hereditary diseases and improving the long-term survival of renal transplant recipients was summarized. Results After MDT consultation, the patient was diagnosed with recurrence of PH type I. Routine immunosuppressive regimen was initiated after the exclusion of rejection. The patient was instructed to drink a large quantity of water, and given with high-quality protein and low-phosphorus diet, vitamin B6, calcium and other conservative therapies to actively prevent and treat postoperative complications. The deterioration of renal graft function was delayed. Nevertheless, regular hemodialysis was resumed at 5 months after renal transplantation until the submission date of this manuscript. Conclusions Recurrence of PH type I after renal transplantation is relatively rare. The main clinical manifestations are recurrent kidney stones and decreased renal function with multiple complications and poor prognosis. The condition of the patient is consulted by MDT for confirming the diagnosis, determining the optimal treatment scheme, delaying the progression and improving the clinical prognosis.

Clinical characteristics of infection-induced central nervous system complications in renal transplant recipients / 中华器官移植杂志

Objective:To summarize the clinical characteristics of central nerve system (CNS) infection and grasp the necessity and possibility of early diagnosis and precise intervention of CNS infection after renal transplantation.Methods:This retrospective study enrolled consecutive recipients of renal transplantation with CNS infection after transplant between January 2000 and December 2020. Correlative factors for CNS infection after renal transplant were determined by comparing the clinical data between recipients with and without CNS infection. After screening 3, 199 consecutive renal transplant recipients, 12 patients with CNS infection post-transplant were identified and recruited. The median age-of-onset was 48.5 (23-65) years. And the median time to disease onset after transplant was 50.5(1-204) months. The most common symptoms of CNS infection after renal transplant included fever (75.00%), consciousness disorder (58.33%), headache (58.33%) and neck rigidity (41.67%).Results:Hepatitis B virus carrier and pulmonary infection were correlated with CNS infection after transplantation ( P<0.05). Nine patients failed to identify the pathogen and only received empirical anti-infective regimen. The outcomes were curing ( n=3) and death ( n=6). Metagenomic sequencing was performed for identifying the pathogen in three recipients and actively adjusting the anti-infective regimen. As a result, 2 were cured and 1 died. The overall mortality was 58.33%. The median time to death or curing from disease onset were 20(2-19) and 25(16-35) days respectively in surviving and non-surviving recipients. Conclusions:The progress of CNS infection after transplantation is rapid with a high mortality. HBV carrier and pulmonary infection are possible risk factors of CNS infection after renal transplantation. Early pathogenic identification and precise etiological intervention are vital for better clinical outcomes.

Intracapsular infection of polycystic kidney disease and renal transplantation / 器官移植

Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenic hereditary kidney disease, which can progress into end-stage renal disease (ESRD). Patients with ADPKD constantly suffer from recurrent intracapsular infection. The drug resistance caused by antibiotic treatment is becoming increasingly prominent. The pattern of renal transplantation should be selected according to the infection of polycystic kidney disease. In this article, the origin of renal cyst, classification and source of cystic fluid, type and drug resistance of bacteria in the cystic fluid, and intracapsular infection of patients with renal transplantation- associated ADPKD were reviewed, aiming to provide reference for the diagnosis and treatment of intracapsular infection of patients with ADPKD.

Application of immunosuppressants in patients with autosomal dominant polycystic kidney disease after kidney transplantation / 南方医科大学学报

OBJECTIVE@#To investigate the optimal dose range of immunosuppressants in patients with autosomal dominant polycystic kidney disease (ADPKD) after renal transplantation.@*METHODS@#A cohort of 68 patients with ADPKD who received their first renal transplantation between March, 2000 and January, 2018 in our institute were retrospectively analyzed, with 68 non-ADPKD renal transplant recipients matched for gender, age and date of transplant as the control group. We analyzed the differences in patient and renal survival rates, postoperative complications and concentrations of immunosuppressive agents between the two groups at different time points within 1 year after kidney transplantation. The concentrations of the immunosuppressants were also compared between the ADPKD patients with urinary tract infections (UTI) and those without UTI after the transplantation.@*RESULTS@#The recipients with ADPKD and the control recipients showed no significantly difference in the overall 1-, 5-, and 10- year patient survival rates (96.6% 96.0%, 94.1% 93.9%, and 90.6% 93.9%, respectively; > 0.05), 1-, 5-, and 10-year graft survival rates (95.2% 96.0%, 90.8% 87.2%, and 79.0% 82.3%, respectively; > 0.05), or the incidences of other post- transplant complications including acute rejection, gastrointestinal symptoms, cardiovascular events, pneumonia, and neoplasms ( > 0.05). The plasma concentrations of both tacrolimus and mycophenolate mofetil (MPA) in ADPKD group were significantly lower than those in the control group at 9 months after operation ( < 0.05). The incidence of UTI was significantly higher in ADPKD patients than in the control group ( < 0.05). In patients with ADPKD, those with UTI after transplantation had a significantly higher MPA plasma concentration ( < 0.05).@*CONCLUSIONS@#In patients with ADPKD after renal transplant, a higher dose of MPA is associated with a increased risk of UTI, and their plasma concentrations of immunosuppressants for long-term maintenance of immunosuppression regimen can be lower than those in other kidney transplantation recipients.

De novo malignant tumor after renal transplantation: single-center trial / 器官移植

Objective To analyze the incidence and risk factors of de novo malignant tumors in renal transplant recipients. Methods Clinical data of 1 549 renal transplant recipients were retrospectively analyzed, including the basic status, pathological type and incidence rate of patients with de novo malignant tumors after renal transplantation. The survival situation of these patiensts was assessed. And the risk factors of de novo malignant tumors after renal transplantation were identified. Results The incidence rate of de novo malignant tumors in renal transplant recipients was 3.03%(47/1 549). The 47 recipients were (48±12) years old when undergoing renal transplantation, and they were (55±12) years old when diagnosed malignant tumors. The time interval between transplantation and diagnosis was 66 (36, 100) months. Among the de novo malignant tumors, colorectal cancer was the most common, with a cumulative incidence rate (CIR) of 0.58%. The survival time of 47 recipients with de novo malignant tumors after renal transplantation was 59 (2, 135) months, and the 5-year survival rate was 50%. The recipients with the age > 45 years old when undergoing renal transplantation was a risk factor for de novo malignant tumors after renal transplantation (P < 0.05). Conclusions The incidence rate of de novo malignant tumors is relatively high in renal transplant recipients. The recipients with the age > 45 years old when undergoing renal transplantation is a risk factor for de novo malignant tumors.

Delayed series casting after botulinum toxin injection is more effective for equinus children with spastic cerebral palsy / 中华物理医学与康复杂志

Objective:To compare the efficacy of series casting with different timings after botulinum toxin injection among equinus children with spastic cerebral palsy.Methods:Sixty-three equinus children with spastic cerebral palsy were randomly divided into a control group and an experimental group. After being injected with botulinum toxin type A, 4 weeks of series casting was applied immediately in the control group, while in the experimental group it was applied 2 weeks later. Both groups were given basic rehabilitation therapy including heel walking, kicking balls, single-leg standing, standing platform training and balance training. The modified Tardieu scale, three-dimensional gait analysis, gross motor function measure 88 (GMFM-88) and a self-made questionnaire were used to evaluate muscle tone, spasticity, gait parameters, standing and walking before the treatment and 2 and 6 months afterward.Results:Immediately after the treatment there was a significant improvement in both groups′ average MTS scores (R1, R2, R1-R2 with knee extension and flexion), dorsiflexion at initial contact, peak dorsiflexion in the stance and swing phases, and dimension D (standing), and also in their average GMFM-88 (walking) scores. Two and six months later the experimental group′s average MTS scores, peak dorsiflexion in the stance phase, and dimension D (standing) score in the GMFM-88 (walking) had improved significantly compared with the control group′s averages. However, no significant differences were observed between the two groups in any of the other measurements after the treatment.Conclusion:Delaying series casting after botulinum toxin A injection can significantly reduce tone and spasticity in the plantarflexors, improve the range of motion and functioning of the ankle, and alleviate the discomfort and pain caused by series casting.

Clinical values of 16S rRNA and ITS gene sequencing for pathogenic identification of renal transplant recipients with urinary tract infection / 中华器官移植杂志

Objective:Objective To explore the clinical values of next-generation sequencing (NGS) in bacterial 16S rRNA region and fungal ITS region for diagnosing and treating urinary tract infection (UTI) in renal transplant recipients.Methods:A total of 90 mid-stream clean-catch urine samples were collected from renal transplant recipients who were diagnosed with UTI at Hospital from January 2017 to December 2019. Each sample was equally divided and tested via NGS method and traditional urine culture separately. The results of pathogen test and detection rate were analyzed and compared.Results:And 21/90 sample were considered to be contaminated due to the identification of three or more kinds of microorganisms by culture. And among the remaining 69 samples, 36 (52.17%) cases tested positive by 16S rRNA sequencing, 25 (36.23%) positive by urine bacterial culture; meanwhile, 34(49.28%) tested positive by ITS sequencing and 4(5.80%) positive by urine fungal culture.Conclusions:The detection rate of both bacteria and fungi in NGS microorganism testing is higher than that in traditional urine culture ( P< 0.05). For renal transplant recipients with UTI, NGS microorganism testing is an effective supplement for traditional urine culture. Improving the detection rate and accuracy of etiology may enable an optimization of individualized treatment.

Characteristics of BK polymavirus infection in kidney transplant recipients / 南方医科大学学报

OBJECTIVE@#To analyze the characteristics of BK polymavirus (BKV) infection and the optimal time window for intervention in kidney transplant recipients (KTRs).@*METHODS@#We retrospectively analyzed the clinical data and treatment regimens in 226 KTRs in our center between January, 2013 and January, 2018. Among the recipients, 157 had a urine BKV load ≥1.0×10 copy/mL after transplantation, and 69 had a urine BKV load below 1.0×10 copy/mL (control group).@*RESULTS@#Among the 157 KTRs, 60 (38.2%) recipients were positive for urine BKV, 66 (42.0%) had BKV viruria, and 31(19.7%) had BKV viremia. The incidence of positive urine occult blood was significantly higher in BKV-positive recipients than in the control group ( < 0.05). The change of urine BKV load was linearly related to that of Tacrolimus trough blood level (=0.351, < 0.05). In urine BKV positive group, the average estimated glomerular filtration rate (eGFR) was below the baseline level (60 mL·min·1.73 m) upon diagnosis of BKV infection reactivation, and recovered the normal level after intervention. In patients with BKV viruria and viremia, the average eGFR failed to return to the baseline level in spite of improvement of the renal function after intervention.@*CONCLUSIONS@#Positive urine occult blood after transplantation may be associated with BKV infection reactivation in some of the KTRs. BKV infection is sensitive to changes of plasma concentration of immunosuppressive agents. Early intervention of BKV replication in KTRs with appropriate dose reduction for immunosuppression can help to control virus replication and stabilize the allograft function.

Progress on lipidomics analytical methods and their applications in studies of traditional Chinese medicines / 中国中药杂志

Lipids have been documented to play comprehensive and significant role in many biological processes. As a branch of metabolomics,lipidomics research mainly involves the analysis of the variation of lipid metabolism profiles under different physiologic,pathologic conditions or drug intervention,the discovery of key lipid biomarkers of a disease in lipid metabolic networks,and the study of the mechanism of action of lipid metabolic regulation during disease onset and progression,and drug treatment. Traditional Chinese medicines( TCMs)are characterized with integrated effects by multi-components,multi-targets and integrated effects. It is urgent to develop methods suitable for the study of complex TCMs to reveal the active constituents and integrated mechanism of action. Systems biology such as lipidomics provides valuable strategy and approach to illustrate the complex mechanisms of TCMs. In this paper,in order to provide technical references for TCMs,we have reviewed the analytical techniques applied in lipidomics and the applications of lipidomics in TCMs researches.

Clinical Observation on Modified Huqianwan in Treatment of Rheumatoid Arthritis Liver-kidney Yin Deficiency Syndrome / 中国实验方剂学杂志

Objective: To explore the clinical efficacy and safety of modified Huqianwan in treatment of rheumatoid arthritis (RA) liver-kidney Yin deficiency syndrome, and investigate its possible mechanism. Method: A total of 184 patients with RA liver-kidney Yin deficiency syndrome were randomly divided into Chinese medicine group (62 cases), western medicine group (57 cases) and integrated Chinese and western medicine group (65 cases) according to the digital table method. The patients in Chinese medicine group were treated with Huqianwan; the patients in western medicine group were treated with methotrexate tablets and leflunomide tablets; and the patients in integrated Chinese and western medicine group received Huqianwan+methotrexate tablets and leflunomide tablets,with a treatment course of 12 weeks in all groups. The pain visual analog scale (VAS), swelling and tenderness scores of 28 joints (DAS28), average hands grip strength, morning stiffness time and liver-kidney Yin deficiency syndrome differentiation of traditional Chinese medicine (TCM) syndrome score were compared between groups before and after treatment. The changes of erythrocyte sedimentation rate (ESR), C reactive protein (CRP), immunoglobulin (Ig) G, tumor necrosis factor-alpha (TNF-α) and rheumatoid factor (RF) were detected in all groups after treatment. Clinical efficacy, and incidence of adverse reactions such as gastrointestinal response, liver injury, leukopenia, serum glutamate oxaloacetic aminotransferase (GOT) and platelet (PLT) level changes were compared between the groups, so as to investigate the efficiency and safety of the different medicines. Result: After 12 weeks of treatment, the total clinical effective rate was 79.0%, 80.7%, and 92.3% respectively in Chinese medicine group, western medicine group, and integrated Chinese and western medicine group; the integrated Chinese and western medicine group was significantly better than the Chinese medicine group and western medicine group (PPPPConclusion: The efficacy in treating RA liver and kidney Yin deficiency syndrome shows no significant difference between modified Huqianwan and methotrexate tablets+leflunomide tablets. In the treatment of RA liver and kidney Yin deficiency syndrome, Huqianwan has fewer adverse reactions. Huqianwan combined with methotrexate tablets+leflunomide tablets is superior to that in methotrexate tablets+leflunomide tablets in treatment of RA liver-kidney Yin deficiency syndrome.

Cimicifuga heracleifolia is therapeutically similar to black cohosh in relieving menopausal symptoms: evidence from pharmacological and metabolomics studies / 中国天然药物

In the market of botanical dietary supplements, Cimicifuga heracleifolia (CH) has always been considered as an adulterated species of Cimicifuga racemosa (CR), a conventional American herb with promising benefits to counteract troubles arising from the menopause. However, the detailed comparison of their therapeutic effects is lacking. In present study, the pharmacological and metabolomics studies were comparatively conducted between CH and CR in ovariectomized (OVX) female rats. Specifically, estrogen-like, anti-hyperlipidemia and anti-osteoporosis effects were evaluated through measuring serum biochemical parameters, histopathological examination and micro computed tomography (Micro-CT) scanning. At the same time, a gas chromatography-mass spectrometry (GC-MS)-based serum metabolomics method was employed to profile the metabolite compositional changes. As a result, both CR and CH displayed anti-osteoporosis and anti-hyperlipemia on menopause syndrome. Meanwhile, their potentials in improving the OVX-induced metabolic disorders were discovered. In conclusion, these results demonstrated that CH is therapeutically similar to CR in relieving menopausal symptoms and CH could be considered as a promising alternative to CR instead of an adulterant in the market of botanical dietary supplements.