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.
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.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.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.Genotyping of the functional UGT1A9 SNP may be of practical use in kidney transplant recipients.
<b><i>Background:</i></b> 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. <b><i>Methods:</i></b> 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 <i>t</i> test, and ANOVA were performed. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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.
