Caracterización clínica de la Nefropatía por Poliomavirus BK en pacientes trasplantados renales / Clinical characterization of Polyomavirus BK nephropathy in kidney transplanted patients

INTRODUCCIÓN. La nefropatía por poliomavirus BK resulta un problema emergente en el trasplante renal, pues contribuye a la pérdida temprana de los injertos renales. OBJETIVO. Caracterizar clínicamente a los pacientes trasplantados renales con nefropatía por poliomavirus BK. MATERIALES Y MÉTODOS. Estudio observacional, descriptivo, realizado en el Hospital de Especialidades Carlos Andrade Marín en el período 2013-2022, se obtuvo una base de datos anonimizada, 479 pacientes trasplantados renales, de estos se identificaron 37 pacientes que corresponde a un 7,7% con nefropatía por poliomavirus BK, se realizó un análisis con el programa estadístico SPSS v26®. RESULTADOS. La población estuvo caracterizada por pacientes del sexo masculino (56,8%), con una edad media de 48,2 años, el donante cadavérico fue el más frecuente (94,5%), la mayor parte del tratamiento de la nefropatía por poliomavirus BK consistió en cambio de micofenolato sódico a everolimus y se mantuvo con 50% de Tacrolimus y Prednisona (40,5%); al valorar el cambio de los valores de creatinina, los niveles más elevados fueros a los 12 meses cuando la pérdida renal fue temprana (p: 0,042), y de la misma manera a los 12 meses, fueron más elevados los niveles de creatinina cuando el diagnóstico histopatológico fue Nefropatía por Poliomavirus Clase 3 (p: 0,01). DISCUSIÓN. La prevalencia de la nefropatía se mantuvo por debajo del 10% reportado a nivel global, la creatinina empeoró en pacientes con pérdida temprana del injerto renal y con una clase patológica avanzada, hecho reportado en la fisiopatología de la enfermedad. CONCLUSIÓN. La pérdida del injerto renal temprano presentó una creatinina más alta que la tardía. Es recomendable un tamizaje adecuado para la detección temprana del virus BK siendo crucial para prevenir el deterioro de la función renal y limitar la posterior pérdida del injerto.

INTRODUCTION: BK polyomavirus nephropathy is emerging as a significant concern in kidney transplantation, as it contributes to the early loss of renal grafts. OBJECTIVE: The aim of this study was to clinically characterize renal transplant recipients with BK polyomavirus nephropathy. MATERIALS AND METHODS: An observational and descriptive study was conducted at Carlos Andrade Marín Specialties Hospital during the period of 2013 to 2022. An anonymized database comprising 479 renal transplant patients was utilized. Among these, 37 patients, constituting 7.7%, were identified with BK polyomavirus nephropathy. Data analysis was performed using the statistical program SPSS v26®. RESULTS: The study population was predominantly composed of male patients (56.8%) with a mean age of 48.2 years. Deceased donors accounted for the majority (94.5%) of cases. The primary approach for managing BK polyomavirus nephropathy involved transitioning from mycophenolate sodium to everolimus, alongside maintaining a regimen of 50% tacrolimus and 40.5% prednisone. When assessing changes in creatinine values, the highest levels were observed at 12 months, coinciding with early renal loss (p: 0.042). Similarly, at the 12-month mark, elevated creatinine levels were associated with a histopathological diagnosis of Polyomavirus nephropathy Class 3 (p: 0.01). DISCUSSION: The prevalence of nephropathy remained below the globally reported threshold of 10%. Creatinine levels worsened in patients experiencing early graft loss and an advanced pathological classification, aligning with established disease pathophysiology. CONCLUSION: Early renal graft loss was associated with higher creatinine levels compared to delayed loss. Adequate screening for early detection of BK virus is recommended, as it plays a crucial role in preventing renal function deterioration and limiting subsequent graft loss.

The role of mammalian target of rapamycin inhibitor in virus infection of organ transplant recipients / 器官移植

At present, mammalian target of rapamycin (mTOR) inhibitors are commonly-used immunosuppressive drugs after organ transplantation, including sirolimus (rapamycin) and everolimus. mTOR inhibitors not only exert an immunosuppressive effect by inhibiting T cell proliferation, but also possess multiple potential functions, such as antiaging, anti-tumor and anti-virus infection, etc. Virus infection is one of the most common complications after organ transplantation. Current anti-viral treatments are limited and yield poor efficacy. In this article, the role of mTOR pathway in virus infection, the mechanism of common mTOR inhibitors and the role of mTOR inhibitors in different types of virus infections were reviewed, aiming to provide reference for clinical application and subsequent research of mTOR inhibitors in organ 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.

Clinicopathological features and prognostic analysis of 44 patients with polyomavirus nephropathy after kidney transplantation / 器官移植

Objective To analyze the clinicopathological features and prognosis of polyomavirus nephropathy (PyVN) after kidney transplantation. Methods Clinical data of 44 patients who were diagnosed with PyVN after kidney transplantation were retrospectively analyzed. The causes of puncture and the time of pathological diagnosis were analyzed. Histological grading was carried out according to Banff 2018 classification. Clinical data and pathological characteristics of patients at all grades were statistically compared. BK viral DNA loads in the blood and urine were measured and renal allograft function were assessed. Clinical prognosis of all patients was compared among different groups and the risk factors affecting clinical prognosis were also analyzed. Results The time interval between pathological diagnosis of PyVN and kidney transplantation was 16(8, 29) months, and the increase of serum creatinine level was the main cause for puncture. Among 44 patients, 19 cases were classified as grade ⅠPyVN, 21 cases of grade Ⅱ PyVN and 4 cases of grade Ⅲ PyVN, respectively. Under optical microscope, there was no significant difference in the positive rate of virus inclusion bodies among different groups (P=0.148). Inflammatory cell infiltration, interstitial fibrosis and polyomavirus load in grade Ⅱ PyVN patients were all more or higher than those in grade Ⅰ counterparts. Inflammatory cell infiltration and polyomavirus load in grade Ⅲ patients were more or higher than those in grade Ⅰ counterparts. Polyomavirus load in grade Ⅲ patients was more or higher than that in grade Ⅱ counterparts. The differences were statistically significant (all P < 0.05/3). Upon diagnosis, BK viral DNA load was detected in the blood and urine of 39 patients. Among them, 38 patients were positive for BK virus in the urine and 30 patients were positive for BK virus in the blood. The serum creatinine level upon diagnosis was higher compared with that at postoperative 1 month. The serum creatinine level at the final follow-up was significantly higher than that upon diagnosis. The differences were statistically significant (P < 0.001, P=0.049). There was no significant difference in the serum creatinine level among patients with different grades of PyVN at postoperative 1 month (P=0.554). The serum creatinine level of patients with grade Ⅱ PyVN upon diagnosis was significantly higher than that of those with grade Ⅰ PyVN (P=0.007). The 1-, 3- and 5-year cumulative survival rates of renal allografts were 95%, 69% and 62%, respectively. The survival rates of renal allografts significantly differed among patients with different grades of PyVN. The higher the grade, the lower the survival rate (P=0.014). Univariate and multivariate Cox's regression analyses prompted that intrarenal polyomavirus load and serum creatinine level upon diagnosis were the independent risk factors for renal allograft dysfunction (all P < 0.05). Conclusions PyVN mainly occurs within 2 years after kidney transplantation. Clinical manifestations mainly consist of increased serum creatinine level, BK viremia and BK viruria. Postoperative routine monitoring of BK virus contributes to early diagnosis and protection of renal allografts. Banff 2018 classification may effectively predict the prognosis of renal allografts.

JCV viruria associates with suboptimal recovery of kidney function three years after living kidney donation / Virúria por JCV se associa a recuperação subótima da função renal três anos após doação renal de doador vivo

Abstract Introduction: Few studies have investigated pre-donation factors that could affect renal recovery after living kidney donation (LKD). We retrospectively investigated the role of John Cunningham virus (JCV) infection and other pre-donation factors on the magnitude of kidney function decline after LKD. Methods: Urine JCV viral loads, glomerular filtration rate, and blood pressure were evaluated in 60 consecutive LK donors before donation. Suboptimal compensatory hypertrophy was defined as an eGFR <60% of the pre-donation eGFR. Results: LKD (40% JCV infected) were followed for 3.2±1.6 years. No association was found between age, gender, and baseline hypertension with 1st, 2nd, 3rd, and 4th years post-donation eGFR <60% of the pre-donation eGFR. Mean eGFR recovery at the 3rd year after donation was lower in JCV infected donors vs non-infected donors (61.8% vs 71.0%, p=0.006). Conclusion: We hypothesized that JCV could shift glomeruli into a hyperfiltration state before nephrectomy, modulating the magnitude of compensatory hypertrophy after donation. Conversely, JCV might curtail the ability of the remaining kidney to promote hyperfiltration. Longer follow up is needed to determine whether JCV viruria ultimately leads to lower eGFR over time or if it is a protective factor for the remaining kidney.

Resumo Introdução Poucos estudos investigaram fatores anteriores à doação que poderiam afetar a recuperação renal após doação renal de doador vivo (LKD, do inglês Living Kidney Donation). Investigamos retrospectivamente o papel da infecção pelo vírus John Cunningham (JCV) e outros fatores de risco pré-doação na magnitude do declínio da função renal após LKD. Métodos: Cargas virais de JCV na urina, taxa de filtração glomerular e pressão arterial foram avaliadas consecutivamente em 60 doadores renais vivos antes da doação. Hipertrofia compensatória subótima foi definida como uma TFGe <60% da TFGe pré-doação. Resultados: LKD (40% infectados pelo JCV) foram acompanhados por 3,2±1,6 anos. Não foi encontrada nenhuma associação entre idade, sexo e hipertensão basal com a TFGe pós-doação no 1º, 2º, 3º e 4º anos <60% da TFGe pré-doação. A recuperação média da TFGe no 3º ano após a doação foi menor em doadores infectados pelo JCV vs doadores não infectados (61,8% vs 71,0%, p=0,006). Conclusão: Levantamos a hipótese de que o JCV pode levar os glomérulos a um estado de hiperfiltração antes da nefrectomia, modulando a magnitude da hipertrofia compensatória após a doação. Por outro lado, o JCV pode limitar a capacidade do rim remanescente de promover a hiperfiltração. É necessário um acompanhamento mais longo para determinar se a virúria por JCV leva, em última instância, a uma menor TFGe ao longo do tempo ou se é um fator de proteção para o rim remanescente.

Outpatient haploidentical hematopoietic stem cell transplant using post-transplant cyclophosphamide and incidence of hemorrhagic cystitis

Abstract Introduction Hemorrhagic cystitis (HC) is a common complication of haploidentical hematopoietic stem cell transplantation (haplo-HSCT), characterized by irritative symptoms of the urinary tract and a higher morbidity and mortality rate. The worldwide incidence is reported between 10% and 70%. The use of alkylating agents and BK viral infection are the most frequent etiologies. The aim of this study was to report the HC incidence in an outpatient haplo-HCST program with a reduced intensity-conditioning (RIC) regimen, cataloguing risk factors, complications and final outcomes. Methods The medical database of patients who received a haplo-HSCT between January 2012 and November 2017 was retrospectively analyzed. Demographic variables, general characteristics and HC incidence were included. Results One hundred and eleven patients were included, 30 (27%) of whom developed HC, most of them (70%) being grade II, with a 30-day (7-149) median time of post-transplant HC onset. The BK virus was detected in 71% of the urine samples analyzed. All HC patients responded to treatment, except two (6.6%), who died due to HC complications. Conclusions There was no difference in the HC incidence or severity, compared to that reported when performing haplo-HSCT in hospitalized patients, although the donor-recipient sex mismatch did relate to a higher HC incidence.

Molecular characterization of BK virus detected in renal transplant patients in Sri Lanka: a preliminary study

Background & objectives: BK virus (BKV) is a polyomavirus and cause of a common infection after renal transplantation which could be preceded to BKV-associated nephropathy. It has four main subtypes (I–IV). BKV subtypes II and III are rare, whereas subtype I shows a ubiquitous distribution. The objective of the present study was to investigate the prevailing BKV subtypes and subgroups in renal transplant patients in Sri Lanka. Methods: The presence of BKV in urine was tested through virus load quantification by real-time PCR from 227 renal transplant patients who were suspected to have BKV infection. Of these patients only 41 were found to be BKV infected (>103copies/ml) and those were subjected to conventional PCR amplification of VP1 gene followed by BKV genotyping via phylogenetic analysis based on DNA sequencing data. Results: Persistent BK viral loads varied from 1×103 to 3×108 copies/ml. Of the 41 patient samples, 25 gave positive results for PCR amplification of subtyping region of VP1 gene of BKV. BKV genotyping resulted in detecting subtype I in 18 (72%) and subtype II in seven (28%) patients. BKV subgroups of Ia, Ib-1 and Ib-11, and Ic were identified with frequencies of 6/18 (33.3%), 6/18 (33.3%), 5/18 (27.8%), and 1/18 (5.6%), respectively. Interpretation & conclusions: Findings from this preliminary study showed a high occurrence of subtype I, while the presence of subtype II, which is rare and less prevalent, was a novel finding for this Asian region. This emphasizes the need for further molecular and serological studies to determine the prevalence of different BKV subtypes in Sri Lanka

The correlation between the prognosis of renal transplant recipients infected with BK virus and peripheral blood related indexes / 中华泌尿外科杂志

Objective:To investigate the correlation between the prognosis of patients infected with BK virus after renal transplantation and their peripheral blood related indexes.Methods:131 patients from the Renal Transplantation Department of the Second Xiangya Hospital of Central South University who underwent renal transplantation and firstly infected with BK virus after the surgery during the period from August 2018 to August 2021 were retrospectively analyzed. 93 males (71.0%) and 38 females (29.0%). The average age was (37.5±11.3) years old. 109 cases underwent cadaveric kidney transplant (83.2%) and 22 cases underwent relatives kidney transplant (16.8%). The onset time of the first infection with BK virus after renal transplantation was (188.7±16.6) days, and the serum creatinine was (127.5±39.5) μmol/L. 25 patients (19.1%)infected with BK virus were positive in blood and urine at the same time, and 106 patients (80.9%)infected with BK virus were positive only in urine. Among 131 patients infected with BK virus, 70 patients were treated by lowering the blood concentration of tacrolimus to enhance immunity, 12 patients were treated by switching tacrolimus to cyclosporine, and 49 patients had incomplete follow-up data. The DNA load of BK virus in 25 patients [5.6(2.4, 12.3)×10 3copies/ml] positive in blood, white blood cell count(WBC)(5.8±2.0)×10 9/L, hemoglobin(Hb)(122.0±22.4)g/L, platelet count(PLT)(187.1±63.1)×10 9/L, neutrophil count(NEUT)(3.9±1.7)×10 9/L, lymphocyte count(LYM)(1.5±0.8)×10 9/L, monocyte count(MONO)(0.4±0.2)×10 9/L, neutrophil to lymphocyte ratio(NLR)2.2(1.7, 3.5), derived neutrophil to lymphocyte ratio(dNLR)1.7(1.3, 2.6), platelet to lymphocyte ratio(PLR)121.3(86.3, 227.3), monocyte to lymphocyte ratio(MLR)0.2(0.1, 0.4) and lymphocyte to monocyte ratio(LMR)4.7±2.6. The DNA load of BK virus in 106 patients [20.4(0.4, 2 570.0)×10 5copies/ml] positive in urine, WBC 6.6(4.8, 9.1)×10 9/L, Hb(129.0±24.5)g/L, PLT 188.0(147.3, 226.5)×10 9/L, NEUT 4.6(3.0, 6.6)×10 9/L, LYM(1.7±0.8)×10 9/L, MONO 0.4(0.3, 0.5)×10 9/L, NLR 2.8(1.9, 3.9), dNLR 2.1(1.5, 3.0), PLR 120.5(87.0, 163.2), MLR 0.2(0.1, 0.4), LMR 4.5(2.8, 6.7). 70 patients infected with BK virus treated by lowering the blood concentration of tacrolimus were divided into BK virus rise group and BK virus decline group according to the change of BK virus DNA load in blood and urine before and after treatment (the grouping principle of this study gives priority to the change of BK virus DNA load in blood, followed by the change of BK virus DNA load in urine). The WBC, Hb, PLT, NEUT, LYM, MONO, NLR, dNLR, PLR, MLR, LMR, tacrolimus blood concentration and change difference, blood creatinine and change difference were analysed between two groups. Results:The BK virus DNA load in 25 patients positive in blood was correlated with NLR and dNLR ( r=0.5062, P=0.0098; r=0.5738, P=0.0027), and there was no correlation between the BK virus DNA load in blood with the WBC ( r=-0.0185, P=0.9302), Hb ( r=0.0912, P=0.6646), PLT ( r=-0.3931, P=0.0519), NEUT ( r=0.2438, P=0.2401), LYM ( r=-0.3035, P=0.1402), MONO ( r=-0.3279, P=0.1096), PLR( r=0.1054, P=0.6161), MLR( r=0.0738, P=0.7257), LMR( r=-0.0738, P=0.7257). There was no correlation between the BK virus DNA load in 106 patients positive in urine and WBC( r=0.0222, P=0.8209), Hb( r=-0.0323, P=0.7423), PLT( r=0.0847, P=0.3881), NEUT( r=0.0417, P=0.6713), LYM( r=0.0010, P=0.9916), MONO( r=0.0224, P=0.8196, NLR( r=0.0170, P=0.8623), dNLR ( r=-0.0013, P=0.9892), PLR( r=0.0387, P=0.6934), MLR( r=-0.0070, P=0.9433)and LMR( r=0.0070, P=0.9433). As for 70 patients infected with BK virus, there were 37 patients in the BK virus rise group and 33 patients in the BK virus decline group. In the two groups, age [(38.4±12.0)years old and(39.0±9.0)years old], gender [male /female: (23/14) cases and(27/6)cases], blood type [A+ /B+ /AB+ : (22/13/20)cases and (26/6/1)cases], donation type [relatives donnation/cadaveric donation: (29/8)cases and (27/60)cases], blood creatinine(after treatment)[123.0(98.4, 140.5)μmol/L and 132.0(107.1, 162.4)μmol/L] and change difference before and after treatment [0(-15.7, 10.5)μmol/L and -2.0(-9.1, 15.0)μmol/L], tacrolimus blood concentration (after treatment)[(6.7±2.0)ng/ml and(6.5±1.5)ng /ml] and tacrolimus concentration change difference [-1.4(-3.8, 0.6)ng/ml and -1.2(-2.2, 1.3)ng/ml] had no significant difference( P<0.05). The MONO of the two groups was statistically different [0.3(0.2, 0.5)×10 9/L and 0.4(0.3, 0.6)×10 9/L, P=0.033], and there was no difference between the two groups in WBC[6.6(4.1, 8.8)×10 9/L and 6.8(5.4, 8.9)×10 9/L], Hb[(133.2±25.3)g/L and(131.6±20.6)g/L], PLT[185.0(151.0, 231.5)×10 9/L and 196.0(149.0, 234.0)×10 9/L], NEUT[4.3(2.4, 6.4)× 10 9/L and 4.2(3.1, 5.5)×10 9/L], LYM[1.7(1.1, 2.2)×10 9/L and 1.8(1.1, 2.3)×10 9/L], NLR[2.5(1.9, 3.8)and 2.4(1.9, 3.7)], dNLR [2.0(1.5, 2.8)and 1.9(1.4, 2.5)], PLR [114.9(85.1, 159.4)and 111.3(77.1, 159.6)], LMR(4.6±2.6 and 5.2±2.4), MLR[0.2(0.2, 0.4)and 0.2(0.2, 0.4)]( P<0.05). Conclusions:There is a positive correlation between the blood BK virus DNA load and NLR, dNLR in renal transplant recipients infected with BK virus. The rise of MONO correlates with good prognosis of BK virus.

Research progress and application of donor-derived cell-free DNA in diagnosis and treatment of kidney transplantation / 器官移植

Early diagnosis and treatment of rejection after kidney transplantation play a critical role in alleviating allograft injury. Detection of donor-derived cell-free DNA (dd-cfDNA) could be performed based on the next-generation sequencing and other techniques. The content of DNA fragments derived from necrotic and apoptotic donor kidney tissues in circulating body fluids could be determined by concentration and absolute quantitative methods, which has application potential in monitoring allograft injury in clinical practice. Compared with traditional serum creatinine and other indicators, dd-cfDNA detection may monitor allograft injury from several weeks to months in advance, providing a "time window" for clinical treatment and delaying graft failure. Along with deepening research of dd-cfDNA in recent years, dd-cfDNA has captivated widespread attention due to its non-invasiveness, high sensitivity and real-time evaluation of therapeutic effect. In this article, current study evidence and conclusions related to multidimensional application of dd-cfDNA detection in diagnosis and treatment of kidney transplantation were reviewed, and the future research and clinical application direction of dd-cfDNA were discussed, aiming to provide reference for widespread application of dd-cfDNA detection in clinical practice in China.

Risk factors of BK virus infection after kidney transplantation / 中华器官移植杂志

Objective:To retrospectively analyze the BKV infection of recipients after kidney transplantation(RT)and provide references for diagnosing and treating BK virus infection post-RT.Methods:From January 1, 2018 to December 31, 2020, clinical and follow-up data were reviewed for 561 RT recipients(cadaveric and living donor kidney)at First Hospital of Jilin University. DNA loading of BK virus in blood and urine was determined by quantitative polymerase chain reaction(qPCR)and kidney allograft biopsy performed. Based upon the results, they are divided into four groups of A (372 cases), high-level BK viruria(group B, 128 cases), BK viremia(group C, 52 cases)and BK virus nephropathy(BKVN)(group D, 9 cases). The variables related to BK virus infection were screened by univariate analysis. Meaningful variables( P<0.1)are incorporated into the multi-factor ordered Logistic regression model for examining the independent risk factors of postoperative BK virus infection. Results:The incidence of high-level BKV viruria is 33.69%(189/561)at 18 months post-RT. The average detection time is(4.2±3.8)months, the incidence of BK viremia 10.87%(61/561)and the average detection time(5.2±3.6)months post-RT. The incidence of BKVN is 1.78%(9/561)and the average detection time(7.0±4.0)months post-RT. Univariate analysis showed that gender, age, immunotherapeutic regimen, history of acute rejection and type of donor are correlated with BKV infection. Multivariate Logistic regression analysis indicated that male recipient( P=0.013), immune maintenance regimen( P<0.001)and history of acute rejection( P=0.002)were independent risk factors for developing postoperative BKV infection. Conclusions:There is a high incidence of BKV infection within 12 months post-RT. Male recipient, history of acute rejection and immune maintenance regimen are independent risk factors for BKV infection post-RT.

Association analysis of high level of BK virus viruria and HLA site after kidney transplantation / 中华器官移植杂志

Objective:To explore the temporal distribution of high level of BK virus(BKV) viruria after kidney transplantation(KT)and the association of high level of viruria with clinical factors and specific human leukocyte antigen(HLA)sites in donors and recipients.Methods:From January 1, 2017 to December 31, 2019, clinical data were retrospectively reviewed for 212 recipients of cadaveric KT.A high level of urinary BKV viruria was defined as urinary BKV-DNA quantification>10 7(copies/ml)after KT while 212 recipients with the same gender composition below the threshold during the same period were selected as low-level controls.Clinical data and HLA sites of two groups were statistically analyzed and risk factors for high level of viruria screened by univariate and multifactorial Logistic regressions. Results:The median time to initial high-level BKV infection in urine after RT was 125.5 days.Based upon univariate Logistic analysis, delayed graft function(DGF)and HLA-A24 of recipient were risk factors for high-level BKV infection in urine while HLA-DQ9 of donor acted as a protective factor.Through multivariate Logistic analysis, DGF( OR=2.18, 95% CI 1.18~4.01, P=0.012)and HLA-A24( OR=1.63, 95% CI 1.06~2.53, P=0.027)of recipient were independent risk factors for high-level BKV infection in urine.And HLA-DQ9 of donors( OR=0.58, 95% CI 0.36~0.91, P=0.019)was an independent protective factor. Conclusions:High level of BKV viruria after RT is associated with donor/recipient-specific HLA sites.Early risk factor stratification and protective factors of recipients can aid in tailoring postoperative immunosuppression and screening program and developing T cell-associated vaccines.

BK virus nephropathy in a heart transplant recipient / Nefropatia pelo vírus BK em um receptor de transplante cardíaco

Abstract BK virus nephropathy in kidney transplantation is widely recognized as an important cause of graft dysfunction and loss. In the case of transplants of organs other than kidney, BK virus nephropathy in native kidneys has been recognized as a cause of chronic kidney disease, which is related with immunosuppression; however, the diagnosis is usually late because the renal dysfunction is attributed to other causes, such as toxicity by anticalcineurinic drugs, interstitial nephritis due to medications, hemodynamic changes, diabetes, hypertension, etc. We report a case of BK virus nephropathy in a patient who underwent heart transplantation due to peripartum cardiomyopathy. The kidney biopsy reported active chronic tubulointerstitial nephritis associated with late stage polyomavirus nephritis and the blood viral load for BK virus was positive (logarithm 4.5). The immunosuppressive treatment was reduced, and after two years of follow-up, the patient had stable renal function with a serum creatinine of 2.5 mg/dL (GFR of 23.4 mL/min/1.73m2). We recommend that the BK virus be considered as a cause of renal dysfunction in heart transplant recipients, with the aim of detecting its replication in time to reduce immunosuppressive therapy before irreversible compromise of renal function may manifest.

Resumo A nefropatia pelo vírus BK no transplante renal é amplamente reconhecida como uma importante causa de disfunção e perda do enxerto. No caso de transplantes de órgãos que não sejam rins, a nefropatia pelo vírus BK em rins nativos tem sido reconhecida como uma causa de doença renal crônica, que está relacionada com imunossupressão; entretanto, o diagnóstico é geralmente tardio porque a disfunção renal é atribuída a outras causas, tais como toxicidade por drogas anticalcineurínicas, nefrite intersticial devido a medicamentos, alterações hemodinâmicas, diabetes, hipertensão, etc. Relatamos um caso de nefropatia pelo vírus BK em um paciente que foi submetido a transplante cardíaco devido à cardiomiopatia periparto. A biópsia renal relatou nefrite túbulo-intersticial crônica ativa associada à nefrite por poliomavírus em estágio avançado e a carga viral sanguínea para o vírus BK foi positiva (logaritmo 4,5). O tratamento imunossupressor foi reduzido, e após dois anos de acompanhamento, o paciente apresentava função renal estável com creatinina sérica de 2,5 mg/dL (TFG de 23,4 mL/min/1,73m2). Recomendamos que o vírus BK seja considerado como uma causa de disfunção renal em receptores de transplante cardíaco, com o objetivo de detectar sua replicação a tempo de reduzir a terapia imunossupressora antes que um comprometimento irreversível da função renal possa se manifestar.

Interpretation of latest literatures on renal transplantation in the third quarter of 2020 / 器官移植

How to improve the long-term prognosis of transplant kidney and solve the shortage of donor kidney are still two major problems that plague clinicians. Among them, ischemia-reperfusion injury (IRI), rejection, infection, and immunosuppressive therapy are important issues in the research field of renal transplantation. Therefore, strengthening the literature study in the field of renal transplantation and understanding the nature of transplant kidney related diseases and international frontier research hotspots, help to further improve the function and prolong the survival time of the transplant kidney in clinic. This article interpreted literatures on the research hotspots and new progress in the field of renal transplantation in the third quarter of 2020, combined with the meeting minutes of the 12th Lingnan Reading Club, and reviewed from the three aspects of IRI, rejection and infection.

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.

Analysis of risk factors of high-level BK viruria after renal transplantation / 器官移植

Objective To analyze the risk factors of high-level BK viruria after renal transplantation and the significance in preventing BK virus-associated nephropathy (BKVAN). Methods Clinical data of 262 renal transplant recipients with regular follow-up data were retrospectively analyzed. According to the DNA load of BK virus, all recipients were divided into the high-level BK viruria group (n=35) and non-high-level BK viruria group (n=227). The incidence of high-level BK viruria after renal transplantation was summarized. The risk factors of high-level BK viruria after renal transplantation were analyzed by univariate analysis and multivariate analysis. Survival curve was delineated by Kaplan-Meier method, and survival analysis of recipients was performed. Results Among 262 renal transplant recipients, 35 cases developed high-level BK viruria with an incidence of 13.4%. The median time of occurrence of high-level BK viruria was 181 (126, 315) d. The incidence was the highest within 6 months after renal transplantation, gradually decreased from 6 months to 2 years, and then increased after 2 years. Univariate analysis showed that the history of antithymocyte globulin (ATG) treatment, acute rejection (AR), donation type and delayed graft function (DGF) were the risk factors of high-level BK viruria after renal transplantation (all P < 0.05). Multivariate Cox regression analysis demonstrated that donation after brain death followed by cardiac death (DBCD), AR and DGF were the independent risk factors of high-level BK viruria after renal transplantation. The 1-, 3- and 5-year survival rates of recipients with ATG treatment history, AR, DGF and donation type of DBCD were significantly lower than those with non-ATG treatment history, non-AR, non-DGF and other donation types [donation after brain death (DBD), donation after cardiac death (DCD) and living organ donation] respectively (all P < 0.05). Conclusions DBCD, AR and DGF are the independent risk factors of high-level BK viruria after renal transplantation. Strengthening the postoperative monitoring of these recipients and delivering early intervention may effectively prevent BKVAN.

Research highlights of renal transplantation in 2020: voice from China / 器官移植

Renal transplantation is the optimal approach to improve the quality of life and restore normal life for patients with end-stage renal diseases.With the development of medical techniques and immunosuppressants, the shortterm survival of renal graft has been significantly prolonged, whereas the long-term survival remains to be urgently solved.Renal ischemia-reperfusion injury (IRI), acute rejection, chronic renal allograft dysfunction, renal fibrosis and other factors are still the major problems affecting the survival of renal graft.Relevant researches have always been hot spots in the field of renal transplantation.Meantime, 2020 is an extraordinary year.The novel coronavirus pneumonia (COVID-19) pandemic severely affects the development of all walks of life.Researches related to renal transplantation have also sprung up.In this article, the frontier hotspots of clinical and basic studies related to renal transplantation and the COVID-19 related researches in the field of renal transplantation in China were reviewed, aiming to provide novel therapeutic ideas and strategies.

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.

Cistitis hemorrágica por infección viral en receptores de trasplante hematopoyético haploidéntico: reporte de dos casos / Hemorrhagic cystitis due to viral infection in patients who received hematopoietic haploidentical transplantation: two case reports

Introducción: Las infecciones por virus o la reactivación de virus en estado latente son frecuentes durante el estado de inmunosupresión que sigue al trasplante de progenitores hematopoyéticos, y constituyen una causa importante de complicaciones, como la cistitis hemorrágica, que se caracteriza por disuria, polaquiuria, dolor abdominal y hematuria. La aparición precoz se asocia a la administración de citostáticos como la ciclofosfamida, y el comienzo tardío a la primoinfección o reactivación de virus como citomegalovirus, los adenovirus o los poliomavirus como el BK y el JC. Objetivo: Describir las características clínicas, la evolución y el manejo de la cistitis hemorrágica postrasplante. Casos clínicos: Se presentan dos pacientes con leucemia mieloide aguda que desarrollaron cistitis hemorrágica asociada a infección viral por virus BK y citomegalovirus después del trasplante haploidéntico con ciclofosfamida postrasplante. La cistitis hemorrágica de causa viral después del trasplante hematopoyético en estos pacientes estuvo asociada a una severa inmunosupresión, por lo que constituyó una complicación potencialmente letal. Los dos pacientes presentaron cistitis hemorrágica grado IV y fallecieron a pesar del tratamiento. Conclusiones: El trasplante haploidéntico con la administración de ciclofosfamida postrasplante incrementa la posibilidad de donantes de progenitores hematopoyéticos para los pacientes sin un hermano HLA idéntico pero el mayor nivel de inmunosupresión podría aumentar la incidencia de cistitis hemorrágica de causa viral(AU)

Introduction: Viral infections or latent-virus reactivation are frequent during the immunosuppressed cincition that follows hematopoietic stem-cell transplantation, and an important cause of complications, such as hemorrhagic cystitis, characterized by dysuria, urinary frequency, abdominal pain, and hematuria. The early appearance is associated with the administration of cytostatic drugs such as cyclophosphamide, and the late onset is associated with primary infection or reactivation of viruses such as cytomegalovirus, adenoviruses, or polyomaviruses such as BK and JC. Objective: To describe the clinical characteristics, evolution and management of post-transplant hemorrhagic cystitis. Clinical cases: The cases are presented of two patients with acute myeloid leukemia who developed hemorrhagic cystitis associated with viral infection by BK virus and cytomegalovirus after haploidentical transplantation with post-transplant cyclophosphamide. Viral hemorrhagic cystitis after hematopoietic transplantation in these patients was associated with severe immunosuppression, making it a potentially lethal complication. Both patients presented grade IV hemorrhagic cystitis and died despite treatment. Conclusions: Haploidentical transplantation with the of post-transplant cyclophosphamide administration increases the possibility for donors of hematopoietic progenitor cells to patients without an identical HLA match, but the higher level of immunosuppression could increase the incidence of viral hemorrhagic cystitis(AU)

Clinical manifestations of BK virus infection in pediatric kidney transplant patients / 소아과

BACKGROUND: Polyomavirus BK (BKV) infection is an important cause of graft loss in kidney transplant patients.PURPOSE: The purpose of this study was to evaluate clinical findings and risk factors for BKV in pediatric patients after kidney transplantation.METHODS: This retrospective single-center study included 31 pediatric kidney transplant recipients from January 2002 to December 2017. Two patients received 2 transplantations during the study period, and each transplant was analyzed independently. Total number of cases is 33 cases with 31 patients. BKV infection was confirmed from blood samples via periodic quantitative polymerase chain reaction.RESULTS: The mean age at kidney transplantation was 11.0±4.7 years, and the male-to-female ratio was 2.7:1. Three patients had a past medical history of high-dose chemotherapy and autologous stem-cell transplantation for solid tumors. Nine patients (27.3%) developed BKV infection. The median period from kidney transplantation to BKV detection in blood was 5.6 months. There was no statistically significant difference in estimated glomerular filtration rate between patients with and those without BKV infection. Among 9 patients with BKV viremia, 7 were treated by reducing their immunosuppressant dose, and BKV was cleared in 6 of these 7 patients. In the other 2 BKV-positive patients, viremia improved without immunosuppressant reduction.CONCLUSION: BKV infection is common in children with kidney transplantation and might not have affected short-term renal function in our patient sample due to early immunosuppressant reduction at the time of BKV detection.

Diagnosis and treatment of BK virus-associated nephropathy after renal transplantation / 中华器官移植杂志

Objective@#To explore the diagnosis and treatment of BKV nephropathy after renal transplantation.@*Methods@#A total of 62 patients with progressive creatinine elevation were routinely examined by blood and urine BKV-DNA. And 21 patients with positive results underwent graft biopsies for confirming a diagnosis.@*Results@#Among 21 cases of BKV infection, 20 cases received leflunomide in replacing mycophenolate mofetil (MMF) and a lower dose of tacrolimus. One case with urine (-) & blood (+ ) received sirolimus in replacing tacrolimus and a lower dose of MMF. Among 11 cases with urine (+ ) and blood (-), urinary BKV-DNA turned negative & creatinine decreased markedly (n=4), urinary BKV-DNA load decreased & creatinine stablized (n=4), death from pulmonary infection with hepatic & renal failure (n=1), urine BKV-DNA load decreased & creatine increased (n=1), BKV–DNA load was not re-examined in 1 case of acute rejection and hydronephrosis with elevated creatine; Among 9 cases with urine (+ ) & blood (+ ), blood BKV-DNA turned negative with urinary BKV-DNA load & creatine decreased (n=6), blood BKV-DNA load decreased & creatine stablized (n=2) and no re-examination with a stable level of creatine (n=1); One case with urine (-) & blood (+ ) was not timely treated and ultimately leading to graft loss after an onset of acute rejection.@*Conclusions@#BKV nephropathy may be effectively treated by decreasing immunosuppressive intensity. However, clinicians should stay on a high alert for acute rejection due to an excessive reduction of immunosuppressive agents.