RESUMEN
INTRODUCTION: The risk of polyomavirusassociated nephropathy (PyVAN) currently ranges from 1% to 10%, and the risk of graft loss is 10% to 50% within 2 years postdiagnosis. There is currently no specific antiviral therapy against BK polyomavirus (BKPyV), and no therapeutic approach has been proven superior. Natural killer cells play a key role in the defense against viral infections. OBJECTIVES: A retrospective, singlecenter cohort study was performed to investigate the association between the kidney transplant recipients' killercell immunoglobulinlike receptor (KIR) genotype and PyVAN. We also evaluated other possible risk factors for the occurrence of PyVAN in a population of kidney transplant recipients. PATIENTS AND METHODS: DNA samples from 134 kidney transplant recipients were identified for the presence or absence of variable KIR genes and their HLA ligands using polymerase chain reaction with sequencespecific primers. RESULTS: The analysis revealed that the presence of the inhibitory KIR2DL3 (P = 0.03) was a risk factor for posttransplant PyVAN. We also found that the presence of acute rejection before PyVAN (P = 0.02), male sex (P = 0.04), and the lack of antiviral prophylaxis (P = 0.01) were additional risk factors for posttransplant PyVAN. CONCLUSIONS: Our findings confirm that the KIR/HLA genotype plays a significant role in the development of PyVAN and suggest the contribution of both environmental and genetic factors to the incidence of BKPyV infection after kidney transplantation.
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Virus BK , Trasplante de Riñón , Nefritis Intersticial , Infecciones por Polyomavirus , Humanos , Masculino , Antivirales , Virus BK/genética , Trasplante de Riñón/efectos adversos , Infecciones por Polyomavirus/diagnóstico , Infecciones por Polyomavirus/etiología , Receptores KIR , Receptores KIR2DL3 , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Data on serum biochemistry markers as a component of the first-trimester screening test in pregnant kidney graft recipients are limited. In the absence of a separate validated algorithm, biochemical testing is commonly used in the first-trimester screening in kidney transplant recipients. Therefore, the study aimed to analyze first-trimester serum biochemical markers and the first trimester combined screening results in pregnant kidney graft recipients. A retrospective study was carried out in pregnant women who underwent the first-trimester combined screening test performed per the Fetal Medicine Foundation (FMF) protocol in 2009−2020. The study group included 27 pregnancies in kidney graft transplant recipients, and the control group was 110 patients with normal kidney function, matched according to age, body mass index (BMI), and gestational age. The biochemical serum markers (free beta-human chorionic gonadotropin [beta-hCG] and pregnancy-associated plasma protein A [PAPP-A]) were evaluated using the FMF-approved Roche Elecsys® assay and exhibited as multiples of the median (MoM) values. Data on first-trimester screening test results, perinatal outcomes, and graft function (assessed using serum creatinine concentrations) were analyzed. The analysis of first-trimester screening parameters revealed no difference in nuchal translucency (NT) measurements and uterine artery flow. However, free beta-hCG MoM and PAPP-A values were higher in posttransplant pregnancies than in controls: 3.47 ± 2.08 vs. 1.38 ± 0.85 (p = 0.035) and 1.46 ± 0.81 vs. 0.98 ± 0.57 (p = 0.007), respectively. The false positive rate of trisomy 21 (T21) screening in graft recipients was 25.9% vs. 3% in the controls. The free ß-hCG MoM values positively correlated with serum creatinine levels before (r = 0.653; p < 0.001), during (r = 0.619; p = 0.001), and after pregnancy (r = 0.697; p < 0.001). There was a statistically significant negative correlation for PAPP-A MoM values for postpartum serum creatinine concentration (r = −0.424, p = 0.035). Our results show significantly higher serum concentrations of free beta-hCG and PAPP-A in posttransplant pregnancies than in healthy controls, confirmed when exhibited as MoM values and their association with graft function was assessed by serum creatinine concentration. Taking those changes into account would reduce the high number of false positive test results in this group. The validated first-trimester screening algorithm that considers altered kidney function in pregnant kidney graft recipients remains to be developed.
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Trasplante de Riñón , Femenino , Humanos , Embarazo , Primer Trimestre del Embarazo , Creatinina , Estudios Retrospectivos , Gonadotropina Coriónica Humana de Subunidad beta , BiomarcadoresRESUMEN
BACKGROUND: Despite its established association with chronic kidney disease (CKD) the role of myosin-9 (MYH9) gene variation on transplanted kidney function remains unknown. This study aimed at evaluating the effect of donor MYH9 nephrogenic variants on renal allograft function within the first post transplantation year. METHODS: In the longitudinal kidney transplant study 207 deceased donors were genotyped for previously known risk MYH9 single nucleotide polymorphisms (SNPs). The predictor was MYH9 high-risk variants status. The primary outcome was mean eGFR found in low vs. high risk MYH9 genotypes between third and twelfth post-transplant month, the secondary outcome was the risk of proteinuria. RESULTS: Distribution of genotypes remained in Hardy-Weinberg equilibrium. The T allele of rs3752462 (dominant model, TT or TC vs. CC) was associated with higher filtration rate (P = 0.05) in a multivariate analysis after adjusting for delayed graft function and donor sex. Two G alleles of rs136211 (recessive model, GG vs. GA or AA) resulted in doubling the risk of proteinuria (OR = 2.22; 95% CI = 1.18-4.37, P = 0.017) after adjusting for donor and recipient sex. CONCLUSION: Deceased donor kidneys of European descent harboring MYH9 SNPs rs3752462 T allele show significantly superior estimated filtration rate while those of rs136211 GG genotype excessive risk of proteinuria. These findings, if replicated, may further inform and improve individualization of allocation and treatment policies.
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Tasa de Filtración Glomerular , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Cadenas Pesadas de Miosina/genética , Complicaciones Posoperatorias/genética , Proteinuria/genética , Insuficiencia Renal/genética , Adolescente , Adulto , Anciano , Cadáver , Femenino , Genotipo , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Complicaciones Posoperatorias/epidemiología , Proteinuria/epidemiología , Insuficiencia Renal/epidemiología , Donantes de Tejidos , Adulto JovenRESUMEN
RMND1 (required for meiotic nuclear division 1 homolog) pathogenic variants are known to cause combined oxidative phosphorylation deficiency (COXPD11), a severe multisystem disorder. In one patient, a homozygous RMND1 pathogenic variant, with an established role in COXPD11, was associated with a Perrault-like syndrome. We performed a thorough clinical investigation and applied a targeted multigene hearing loss panel to reveal the cause of hearing loss, ovarian dysfunction (two cardinal features of Perrault syndrome) and chronic kidney disease in two adult female siblings. Two compound heterozygous missense variants, c.583G>A (p.Gly195Arg) and c.818A>C (p.Tyr273Ser), not previously associated with disease, were identified in RMND1 in both patients, and their segregation with disease was confirmed in family members. The patients have no neurological or intellectual impairment, and nephrological evaluation predicts a benign course of kidney disease. Our study presents the mildest, so far reported, RMND1-related phenotype and delivers the first independent confirmation that RMND1 is causally involved in the development of Perrault syndrome with renal involvement. This highlights the importance of including RMND1 to the list of Perrault syndrome causative factors and provides new insight into the clinical manifestation of RMND1 deficiency.
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Proteínas de Ciclo Celular/genética , Disgenesia Gonadal 46 XX/etiología , Pérdida Auditiva Sensorineural/etiología , Enfermedades Renales/fisiopatología , Mutación , Adulto , Femenino , Disgenesia Gonadal 46 XX/patología , Pérdida Auditiva Sensorineural/patología , Homocigoto , Humanos , Masculino , Linaje , FenotipoRESUMEN
BACKGROUND: The outcomes of pregnancy in women with renal diseases remain controversial. The purpose of the study was to report fetal and maternal outcomes among women with glomerular disease in comparison with healthy pregnant women and a review of the current literature on this issue. METHODS: Retrospective analysis included 72 pregnancies in 62 women with biopsy-proven glomerulonephritis (GN) (in 65.3% of cases, immunoglobulin A nephropathy was found). The control group consisted of 315 healthy pregnant women. We assessed fetal (prematurity, low birth weight, hypotrophy, fetal malformation, or intrauterine death) and maternal (gestational hypertension, preeclampsia, deterioration in kidney function, and maternal death) outcomes. Descriptive data analysis, Fisher's exact test, unpaired Student's t test, and ANOVA were performed. RESULTS: Hypertension prevalence among the GN group and controls was 76.4 and 10.2%, respectively. Preeclampsia complicated 29.2% of pregnancies among women with GN and 2.9% of controls. In 8.3% of patients, at least a 50% decrease in GFR during pregnancy was observed. Preterm delivery prevalence in the GN group and controls was 74.7 and 12.7%, respectively. Hypotrophy was diagnosed in 12.5% of cases from the GN group and 5.4% of controls. The analysis showed that low estimated glomerular filtration rate, hypertension, and proteinuria were risk factors of adverse neonatal outcomes. CONCLUSION: Women with GN are a risk factor of adverse pregnancy outcomes. As pregnancy complications are more prevalent across all the CKD stages, even in patients with near-normal kidney function, they require specialized care. It might be advisable to screen pregnant women for the presence of CKD, as especially in the early stage, it is often asymptomatic. Both hypertension and proteinuria are risk factors for neonatal and maternal complications.
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Anomalías Congénitas/epidemiología , Muerte Fetal , Glomerulonefritis/complicaciones , Hipertensión Inducida en el Embarazo/epidemiología , Muerte Perinatal , Nacimiento Prematuro/epidemiología , Adulto , Puntaje de Apgar , Biopsia , Estudios de Casos y Controles , Anomalías Congénitas/etiología , Femenino , Edad Gestacional , Tasa de Filtración Glomerular , Glomerulonefritis/patología , Glomerulonefritis/fisiopatología , Humanos , Hipertensión Inducida en el Embarazo/etiología , Recién Nacido de Bajo Peso , Recién Nacido , Glomérulos Renales/patología , Glomérulos Renales/fisiopatología , Edad Materna , Embarazo , Nacimiento Prematuro/etiología , Prevalencia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: The Klotho protein, encoded by the KL (Klotho) gene, exerts antiaging and antifibrotic effects. The KL-VS genotype diminishes Klotho expression and correlates with cardiovascular death, heart failure, and chronic kidney disease progression. The aim of this study was to analyze the contribution of donor Klotho rs9536314 and rs9527025 polymorphisms (KL-VS genotype) to renal allograft morphology and function in the early post-transplant period. METHODS: Clinical data and biopsy reports of 170 deceased donor transplantations were retrieved from standard medical files. Donor DNA was genotyped for rs9527025 and rs9536314 SNPs using custom TaqMan assays. RESULTS: As rs9527025 remained in full linkage with rs9536314, we report results for the latter. The analyses were performed for G dominant model (GG+GT vs TT). We found an association between reported SNP alleles, morphologic changes in the peritransplant biopsy, and kidney function 3 months after engraftment. A chronic glomerulopathy score of >0 was found in 12.2% of GG+GT cases and in 3.2% of TT cases (P = .023). For G allele carriers, the third month's median estimated glomerular filtration rate value was 35.0 (range, 20.4-76.6 mL/min), while for TT haplotype, the value was 46.3 (range, 15.5-96.8 mL/min), P = .001. At the third post-transplant month, proteinuria incidence was higher for organs with G allele than with TT haplotype (24.4% vs 9.5%; P = .030; odds ratio 3.09; 95% confidence interval 1.22-7.69). CONCLUSION: Deceased donor KL-VS polymorphism, altering protein dimerization and coreceptor function, predicts early renal transplant glomerular lesions and function. Further analyses for mentioned effect durability are necessary. ETHICS STATEMENT: This study complies with the Helsinki Congress and the Istanbul Declaration regarding donor source. Donors were not prisoners, and were not paid or coerced.
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Glomerulonefritis/genética , Glucuronidasa/genética , Trasplante de Riñón , Complicaciones Posoperatorias/genética , Donantes de Tejidos/estadística & datos numéricos , Adulto , Alelos , Femenino , Genotipo , Tasa de Filtración Glomerular/genética , Haplotipos , Humanos , Riñón/metabolismo , Proteínas Klotho , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Valor Predictivo de las Pruebas , Trasplantes/metabolismo , Resultado del TratamientoRESUMEN
Membranous nephropathy is a common form of glomerulonephritis typically presenting between 30 to 50 years of age with nephrotic range proteinuria, with one third of patients undergoing spontaneous remission, one third experiencing non-progressive CKD (Chronic Kidney Disease) while the remaining third progressing to ESRD (end stage renal disease). CASE REPORT: A 21-year old pregnant female developed massive proteinuria and hypoalbuminemia during first weeks of pregnancy and required intensive nephrological evaluation and treatment. Renal biopsy was performed, microscopic examination was consistent with Membranous Nephropathy and as anti-PLA2R antibodies tested positive, active disease was confirmed. The patient received an immunosuppressive treatment consisting of prednizone and cyclosporine A, enoxaparine was also implemented. In the follow up proteinuria and hypoalbuminemia decreased significantly, stable eGFR and anti-PLA2R (M-type phospholipaseA2 receptor) depletion were observed. C-section was performed at 31 weeks of gestational age due to premature rupture of membranes. The baby developed correctly, showed no signs of nephrotic syndrome. After delivery the mother's immunosuppressive treatment was continued. CONCLUSIONS: Diagnostic algorithm of adult patients with nephrotic syndrome suggests that in cases positive for anti PLA2R antibodies one can diagnose idiopathic membranous nephritis (IMN) based on serological testing and desist kidney biopsy. An early immunosupressive treatment applied in described case confirms proper procedure.
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Glomerulonefritis Membranosa , Glomerulonefritis , Síndrome Nefrótico , Adulto , Autoanticuerpos , Femenino , Humanos , Inmunosupresores , Persona de Mediana Edad , Embarazo , Receptores de Fosfolipasa A2 , Adulto JovenRESUMEN
INTRODUCTION: Transplantation is not only the best method for treating end-stage failure of many organs but also the way to improve the quality of life of patients. For women of childbearing age, an organ transplant often brings a restoration of regular reproductive functions, which means, among other things, the possibility of having biological offspring. OBJECTIVES: The aim of the study was to analyze the medical records and assess the impact of a liver transplant on the course of pregnancy and labor. MATERIALS AND METHODS: The research was carried out from March to May 2019 in the Nephrology and Transplant Clinic Medical University of Warsaw. The study group consisted of 19 women after liver transplantation. Medical records were analyzed, and laboratory test results routinely performed on patients were also used for the study. RESULTS: The mean age of conception of the patients following transplantation was 30 ± 4 years old. In the analyzed period, 6 patients gave birth to 2 children each, and 8 patients to 1 child each. Only 3 patients experienced premature birth. Twelve patients gave birth by caesarean delivery. Fourteen patients took tacrolimus. CONCLUSIONS: Pregnancy is possible in patients following a liver transplant and does not appear to have a damaging effect on liver functionality. There is an increased risk of pre-eclampsia, intensified hypertension, and premature birth among patients following a transplant, which is why it is essential for these patients to remain under the care of a specialistic therapeutic team.
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Trasplante de Hígado/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones del Embarazo/etiología , Adulto , Femenino , Humanos , Hipertensión/etiología , Preeclampsia/etiología , Embarazo , Resultado del Embarazo , Nacimiento Prematuro/etiología , Calidad de Vida , Tacrolimus/uso terapéutico , Resultado del TratamientoRESUMEN
Infection with cytomegalovirus (CMV) remains a major problem in kidney transplant recipients, resulting in serious infectious complications and occasionally mortality. Accumulating evidence indicates that natural killer cell immunoglobulin-like receptors (KIRs) and their ligands affect the susceptibility to various diseases, including viral infections (e.g., CMV infection). We investigated whether KIR genes and their ligands affect the occurrence of CMV infection in a group of 138 kidney transplant recipients who were observed for 720 days posttransplantation. We typed the recipients for the presence of KIR genes (human leukocyte antigen C1 [HLA-C1], HLA-C2, HLA-A, HLA-B, and HLA-DR1) by polymerase chain reaction with sequence-specific primers. The multivariate analysis revealed that the lack of KIR2DS2 (p = 0.035), the presence of KIR2DL3 (p = 0.075), and the presence of KIR2DL2â»HLA-C1 (p = 0.044) were risk factors for posttransplant CMV infection. We also found that a lower estimated glomerular filtration rate (p = 0.036), an earlier time of antiviral prophylaxis initiation (p = 0.025), lymphocytopenia (p = 0.012), and pretransplant serostatus (donor-positive/recipient-negative; p = 0.042) were independent risk factors for posttransplant CMV infection. In conclusion, our findings confirm that the KIR/HLA genotype plays a significant role in anti-CMV immunity and suggest the contribution of both environmental and genetic factors to the incidence of CMV infection after kidney transplantation.
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Infecciones por Citomegalovirus/genética , Antígenos HLA-C/metabolismo , Trasplante de Riñón , Receptores KIR/metabolismo , Adulto , Anciano , Femenino , Frecuencia de los Genes , Marcadores Genéticos , Genotipo , Haplotipos/genética , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Successful spontaneous pregnancy in a kidney graft recipient is regarded as a sign of full recovery. The crucial factors determining positive outcome are optimizing time of conception and multidisciplinary team care. However, there are only a few reports dealing with in vitro fertilization (IVF) outcomes in organ recipients. CASE REPORT: A 34-year-old living donor kidney recipient with primary infertility due to bilateral tubal obstruction was referred to our clinic. Transfer of 2 embryos was conducted after a long stimulation protocol with GnRH and rFSH, and a viable singleton pregnancy was confirmed by subsequent ultrasound examination. Pregnancy complications were: chronic hypertension, fetal intrauterine growth restriction, and severe anemia requiring blood transfusions and erythropoietin treatment. In the 34th week of gestation the patient presented with worsening of blood pressure control. A male newborn, 1810 grams weight and 10 points Apgar score was delivered by cesarean section. Although our patient was qualified for the IVF program with signs of suboptimal graft function, it was stable during the ovarian stimulation protocol. Fortunately, in the second half of the pregnancy only mild creatinine rise and proteinuria <1 g/day were observed. CONCLUSIONS: IVF may be a good treatment option in female kidney graft recipients. It does not necessarily lead to graft function deterioration and it provides multidisciplinary specialized care, allowing for delivery of a healthy newborn.
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Fertilización In Vitro/métodos , Infertilidad Femenina/terapia , Trasplante de Riñón , Resultado del Embarazo , Receptores de Trasplantes , Adulto , Femenino , Retardo del Crecimiento Fetal/diagnóstico , Humanos , Hipertensión Inducida en el Embarazo/diagnóstico , EmbarazoRESUMEN
BACKGROUND: The influence of pregnancy on graft function in patients after solid organ transplantation is still uncertain. MATERIAL AND METHODS: Our study is based on a group of 78 cases after liver (LTR) and/or renal transplantation (RTR) with 91 deliveries in the past 12 years in the 1st Department of Obstetrics and Gynecology, Warsaw Medical University. We compared duration of pregnancy, mode of delivery, weight of neonates, and graft function. RESULTS: Rate of preterm delivery was very high (74% RTR and 43% LTR). The average duration of pregnancy was shorter in the RTR than in the LTR group (34.7 vs. 36.8 p<0.001) with a high rate of cesarean sections (81.4% in RTR and 68.1% in LTR). Birth weight in LTR (2898 g) was higher than in RTR (2248 g) (p<0.0001). Currently, 29 RTR and 38 LTR have preserved graft function. Thus, graft survival in the study group is longer than in the general RTR or LTR population. CONCLUSIONS: Pregnancy after kidney or liver transplantation does not seem to increase the risk of graft loss, but is associated with a higher risk of maternal and fetal complications. In our data these complications occur more often in the RTR group.
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Peso al Nacer , Supervivencia de Injerto , Trasplante de Riñón , Trasplante de Hígado , Resultado del Embarazo , Embarazo de Alto Riesgo , Adolescente , Adulto , Cesárea/estadística & datos numéricos , Femenino , Humanos , Recién Nacido , Estimación de Kaplan-Meier , Embarazo , Complicaciones del Embarazo/etiología , Adulto JovenRESUMEN
BACKGROUND: Cytisine, a partial agonist that binds with high affinity to the α(4)ß(2) nicotinic acetylcholine receptor, is a low-cost treatment that may be effective in aiding smoking cessation. This study assessed the efficacy and safety of cytisine as compared with placebo. METHODS: We conducted a single-center, randomized, double-blind, placebo-controlled trial. Participants were randomly assigned to receive cytisine or matching placebo for 25 days; participants in both groups received a minimal amount of counseling during the study. The primary outcome measure was sustained, biochemically verified smoking abstinence for 12 months after the end of treatment. Of 1542 adult smokers screened, 740 were enrolled and 370 were randomly assigned to each study group. RESULTS: The rate of sustained 12-month abstinence was 8.4% (31 participants) in the cytisine group as compared with 2.4% (9 participants) in the placebo group (difference, 6.0 percentage points; 95% confidence interval [CI], 2.7 to 9.2; P=0.001). The 7-day point prevalence for abstinence at the 12-month follow-up was 13.2% in the cytisine group versus 7.3% in the placebo group (P=0.01). Gastrointestinal adverse events were reported more frequently in the cytisine group (difference, 5.7 percentage points; 95% CI, 1.2 to 10.2). CONCLUSIONS: In this single-center study, cytisine was more effective than placebo for smoking cessation. The lower price of cytisine as compared with that of other pharmacotherapies for smoking cessation may make it an affordable treatment to advance smoking cessation globally.
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Cistina/uso terapéutico , Cese del Hábito de Fumar/métodos , Adulto , Cistina/administración & dosificación , Cistina/efectos adversos , Método Doble Ciego , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Placebos , Resultado del TratamientoRESUMEN
BACKGROUND: UDP-glucuronosyltransferases (UGTs) are a group of enzymes involved in the detoxification and excretion of xeno- and endobiotics. Polymorphic variants of the UGT1A9 gene were shown to influence exposition to mycophenolate mophetil (MMF), a common immunosuppressive drug used in kidney allograft recipients. Therefore, the aim of this study was to evaluate an association between key clinical features of kidney post-transplant course in patients receiving MMF therapy and UGT1A9-2152C>T and -275 T>A SNPs, known to induce UGT1A9 gene expression and UGT1A9 98T>C, resulting in reduced enzyme activity. MATERIAL/METHODS: DNA was isolated from peripheral blood of kidney allograft recipients (n=103) and a control group representing the background population of Poland (n=450). Presence of the analyzed SNP was detected using the PCR restriction fragment length polymorphism (RFLP) method. Accuracy of the applied method was confirmed by DNA sequencing. RESULTS: In patients carrying the UGT1A9-2152T and -275A minor alleles we observed a trend of increased risk of acute allograft rejection within 3 months after transplantation, but this difference was at the border of significance. However, the UGT1A9 98C allele was found to be associated with diminished estimated glomerular filtration rate (eGFR) during the first year after engraftment and transient proteinuria in the first and second month post-transplantation. This association was not observed for UGT1A9-2152C>T and -275 T>A. Our data show that transplanted kidney function may be affected in patients carrying UGT1A9 98C allele and receiving MMF. CONCLUSIONS: Genotyping of the functional UGT1A9 SNP may be of practical use in kidney transplant recipients.
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Glucuronosiltransferasa/genética , Trasplante de Riñón/fisiología , Polimorfismo de Nucleótido Simple , Enfermedad Aguda , Adulto , Secuencia de Bases , Cartilla de ADN/genética , Femenino , Estudios de Asociación Genética , Rechazo de Injerto/enzimología , Rechazo de Injerto/etiología , Rechazo de Injerto/genética , Humanos , Inmunosupresores/farmacocinética , Inmunosupresores/uso terapéutico , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/inmunología , Masculino , Persona de Mediana Edad , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/farmacocinética , Ácido Micofenólico/uso terapéutico , Farmacogenética , Trasplante Homólogo , UDP Glucuronosiltransferasa 1A9RESUMEN
BACKGROUND: Novel immunosuppressives neither prevent nor attenuate post-transplant glomerulonephritis, third common cause of late allograft loss. Data addressing influence of ACEI/ARA and statins on kidney transplants survival is contradictory. The aim of this study was to evaluate efficacy of therapeutic interventions undertaken in post-transplant glomerulonephritis. MATERIAL/METHODS: In 75 individuals with biopsy-confirmed post-transplant glomerulonephritis, engrafted in Warsaw Transplantation Institute, graft survival from index biopsy to permanent dialysis need, in regard to numerous therapeutic interventions was analysed. Evaluation of graft survival was performed using Kaplan-Meier estimator, log-rank and Wilcoxon tests. Relations between introduced treatment and time to graft loss was expressed with hazard ratio (HR), results regarded significant at p<0.05. RESULTS: Glomerulonephritis diagnosis was established 50.2+/-39.5 months after engraftment. Maintenance immunosuppression modifications included: methylprednisolone infusions (n=28), cyclofosfamide/ chlorambucil introduction (n=10), mycophenolate mofetil addition to maintenance treatment (n=23). Immunosuppression modifications did not result in graft survival prolongation. Statins (n=20) and renin-angiotensin-system blockers (n=49) substantially diminished the risk of graft loss (respectively: HR=0.37 (95% CI 0.15-0.88), p<0.02. and HR=0.39 (95% CI 0.16-0.98; p<0.05). The effect persisted after adjustment for presentation with nephrotic syndrome, graft dysfunction, mean arterial pressure, immunosuppression enhancement with mycophenoalte mofetil. Best result was obtained with combined RAASB and statin treatment (HR=0.24; 95% CI 0.69-0.09, p=0.008). CONCLUSIONS: According to our data statins and renal renin-angiotensin system blockers prolong graft survival in patients with posttransplant glomerulonephritis. We feel that these relatively safe agents, bringing also other pro fi ts, should be routinely applied in patients with post transplant glomerulonephritis.
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Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Glomerulonefritis/tratamiento farmacológico , Supervivencia de Injerto/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Trasplante de Riñón/efectos adversos , Adulto , Quimioterapia Combinada , Femenino , Glomerulonefritis/etiología , Rechazo de Injerto/epidemiología , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Masculino , Persona de Mediana Edad , Análisis de SupervivenciaRESUMEN
We describe the case of 24-years old man, smoking up to 60 cigarettes daily, with rapidly progressive crescentic glomerulonephritis in the course of Goodpasture's syndrome. The disease was initially presented with recurrent diffuse pulmonary hemorrhage with normal renal function and moderate proteinuria and haematuria on urinalysis lasting 2 months. Immunologic tests for ANCA and anti-GBM Ab were negative until the patient's renal function rapidly deteriorated during next 3 weeks. At the time of the diagnosis patient presented with renal insufficiency with oliguria requiring hemodialysis but without pulmonary hemorrhage. Renal biopsy showed cellular crescents in all glomeruli with linear deposition of IgG along the GBM. Repeated testing showed anti-GBM Ab. The patient received pulse cyclophosphamide, and pulse methylprednisolone continued by oral prednisone, and consecutive plasma exchange treatment but remained oliguric after 3 weeks of the treatment. The case confirm that in Goodpasture's syndrome even several days' delay in diagnosis and treatment has a strongly negative impact on outcome.
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Enfermedad por Anticuerpos Antimembrana Basal Glomerular/diagnóstico , Hemorragia/diagnóstico , Enfermedades Pulmonares/diagnóstico , Adulto , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/complicaciones , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/tratamiento farmacológico , Antiinflamatorios/administración & dosificación , Hemorragia/etiología , Humanos , Enfermedades Pulmonares/etiología , Masculino , Alveolos Pulmonares/diagnóstico por imagen , Radiografía , Insuficiencia Renal/etiología , Fumar/efectos adversosRESUMEN
Long-term cyclosporine nephrotoxicity, subclinical rejections are risk factors of chronic allograft nephropathy. In a prospective, randomized study 44 pts. were randomized either to a reduced dose of CyA and daclizumab (group A, n = 22) or to a normal dose of CyA without daclizumab (group B, n = 22). Both groups were treated with MMF and prednisone. Number of rejection episodes was the primary endpoint. The secondary endpoints were renal function; histological parameters related to CyA; serum level of TGF-beta, PDGF-BB, blockade of CD25 molecule and surface expression of CD3, CD4, CD8, CD69, CD11a, CD49d, CD28, CD152 molecules in the subpopulations of T cells in the peripheral blood. A low incidence of clinically suspected rejection episodes were observed (19% in group A and 12.4% in group B; NS). The protocol biopsies at 3 month emerged 7 subclinical rejection episodes (4 in group A and 3 in group B). Serum creatinine level did not differ between examined groups. Chronic histopathologic changes related to CyA progressed significantly at the 3 month biopsies in both groups (with no differences between groups). Serum TGF-beta, PDGF did not differ between groups. Expression of CD25, CD152 molecule was significantly lower in group A than in group B. Immunosuppression regiment with low CyA dose with daclizumab, MMF, prednisone seems to be efficient and safe in low-risk rejection kidney allograft recipients.
Asunto(s)
Citocinas/sangre , Sustancias de Crecimiento/sangre , Trasplante de Riñón , Ciclosporina/uso terapéutico , Ensayo de Inmunoadsorción Enzimática , Femenino , Rechazo de Injerto/prevención & control , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Trasplante Homólogo/fisiologíaRESUMEN
The aim of this study was to evaluate efficacy and safety of lamivudine therapy in renal allograft recipients with chronic hepatitis B infection. Twenty-four patients with chronic hepatitis B after renal transplantation were observed. We obtained HBV replication blockage in 95% of patients, in half of them also ALT normalisation was observed. Delayed HBV replication blockage was observed in patients with prolonged duration of haemodialysotherapy or HBV infection and HCV coinfection, although listed parameters did not influence overall treatment efficacy. After lamivudine discontinuation HBV replication relapsed, in part of patients with ALT activity elevation. We did not observed any serious adverse reactions under lamivudine therapy.