Background: Ciclosporin A (CsA) has been widely used in the treatment of patients with nephrotic syndrome over the last 10 years. Objective: Review of the accumulated knowledge from the use of CsA in ...patients with nephrotic syndrome due to idiopathic membranous nephropathy (IMN). Methods: The most important articles concerning the use of CsA in IMN patients have been reviewed. Results/conclusion: CsA, a potentially nephrotoxic drug, induces remission of nephrotic syndrome in > 80% of IMN patients. Relapses occur after its withdrawal and long-term treatment is necessary. Repeat renal biopsies show no signs of CsA nephrotoxicity, but show deterioration of chronic histological lesions with time, even in cases with remission. Thus, CsA is effective in IMN patients, but its long-term use should be examined with caution.
Abstract
Urinary tract infections (UTIs) represent the most common cause of bacterial infection in renal allograft recipients. The purpose of this study was to estimate the predisposing factors and ...the impact of UTIs in the long-term graft function. We studied 122 patients (75 males and 47 females), aged 44 ± 12 years. UTIs occurring during the first month, during the first year, and through the entire follow-up period were analyzed. Diabetes mellitus (DM), delayed graft function, acute rejection episodes, and urinary tract obstruction were evaluated as potential predisposing factors. UTI episodes (n = 316) were recorded in 74 of 122 patients (60.7%). The most common pathogen was Escherichia coli. Most patients (81%) who developed infection during the first month had a new episode in the first year. Hospitalization was necessary in 141 of the 316 UTI episodes whereas 87 were hospital acquired. A strong correlation between female gender and UTI occurrence was found (p = 0.01). Urinary tract obstruction was also related to the UTI occurrence during the first year after transplantation (p = 0.001). Patients' age, DM, delayed graft function, and acute rejection episodes did not correlate with UTI. Long-term renal graft function was not found to be affected by UTI occurrence. UTIs are common infectious complications in renal transplant recipients and often relapse and require hospitalization. The long-term graft function is not affected by the occurrence of UTIs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. Transglutaminase type 2 (TG2) contributes to renal scarring through altering extracellular matrix homeostasis. In ...this study we hypothesized that immunosuppressive treatment would downregulate TG2 expression leading to reduced fibrosis, and subsequently TG2 would have value as a biomarker of progression of MN.
TG2 expression was studied by immunofluorescence in kidney biopsy sections from 32 patients with MN and was compared to control biopsies. All patients were subsequently treated by a combination of cyclosporine and prednisolone for at least 24 months with a repeat biopsy taken in 14 patients.
Twenty-two out of 32 patients showed stable renal function, whereas 10 showed doubling of baseline serum creatinine and 5 of them reached end-stage renal disease during the 5-year follow-up. At the end of the follow-up, 22 out of 32 patients were in remission of nephrotic syndrome. TG2 immunostaining was increased in sections from patients with MN compared to healthy controls (p = 0.0002). TG2 at diagnosis was more intense in patients with severer interstitial fibrosis and advanced glomerular sclerosis. TG2 significantly increased in most patients in the repeat biopsies after treatment (p < 0.0001), whereas patients who showed a marked increase in interstitial fibrosis in the repeat biopsy had significantly more TG2 expression in the first biopsy (p = 0.02).
TG2 expression is increased in MN patients and continues to increase despite immunosuppressive treatment. However, early detection of TG2 might be of value in MN since increased TG2 production seems to precede extensive interstitial fibrosis.
ABSTRACT
Aim: Idiopathic membranous nephropathy (IMN), the most common cause of nephrotic syndrome in adults, is usually treated by cyclosporin A (CsA). Estimation of the effectiveness of long‐term ...use of CsA in the remission and relapse rate of nephrotic syndrome along with histological changes in repeat renal biopsies was the aim of the study.
Methods: Thirty‐two nephrotic patients with well‐preserved renal function treated by prednisolone and CsA were studied. A repeat biopsy was performed in 18 patients with remission of nephrotic syndrome, after 24 months of treatment, to estimate the activity of the disease and features of CsA toxicity.
Results: Complete remission of nephrotic syndrome was observed in 18 (56%) and partial remission in 10 patients (31%) after 12 months of treatment (total 87%). Relapses were observed in 39% and 60% of patients with complete and partial remission, respectively, and multiple relapses in 25% of patients, who showed gradual unresponsiveness to CsA and decline of renal function. Progression of stage of the disease and more severe glomerulosclerosis and tubulointerstitial injury were recognized in 55% and 61% of patients respectively. Features of CsA nephrotoxicity were not observed. The severity of histological changes was related to the time elapsed from the first biopsy (r = 0.452, P < 0.05).
Conclusion: Low doses of CsA with prednisolone induce remission of nephrotic syndrome in most idiopathic membranous nephropathy patients. Although typical features of CsA nephrotoxicity are not observed, significant deterioration of histological lesions occurs with time, even in patients with remission. Long‐term use of CsA should be examined with caution.
Small doses of cyclosporine A with prednisolone was found effective in inducing the remission of nephrotic syndrome in this study. However, significant deterioration of histological lesions is observed in repeat renal biopsies even in patients having remission of nephrotic syndrome, suggesting its long‐term use should be examined very cautiously.
Abstract
Background
Natural history, predisposing factors to an unfavourable outcome and the effect of various therapeutic regimens were evaluated in a cohort of 457 patients with immunoglobulin A ...nephropathy (IgAN) and follow-up of at least 12 months.
Methods
Patients with normal renal function and proteinuria <1 g/24 h as well as those with serum creatinine (SCr) >2.5 mg/dL and/or severe glomerulosclerosis received no treatment. Patients with normal or impaired renal function and proteinuria >1 g/24 h for >6 months received daily oral prednisolone or a 3-day course of intravenous (IV) methylprednisolone followed by oral prednisolone per os every other day or a combination of prednisolone and azathioprine. The clinical outcome was estimated using the primary endpoints of end-stage renal disease and/or doubling of baseline SCr.
Results
The overall 10-year renal survival was 90.8%, while end-stage renal disease and doubling of baseline SCr developed in 9.2% and 14.7% of patients, respectively. Risk factors related to the primary endpoints were elevated baseline SCr, arterial hypertension, persistent proteinuria >0.5 g/24 h and severity of tubulointerstial fibrosis. There was no difference in the clinical outcome of patients treated by the two regimens of corticosteroids; nevertheless, remission of proteinuria was more frequent in patients who received IV methylprednisolone (P = 0.000). The combination of prednisolone with azathioprine was not superior to IV methylprednisolone followed by oral prednisolone. Side effects related to immunossuppressive drugs were observed in 12.8% of patients.
Conclusion
The clinical outcome of patients with IgAN was related to the severity of clinical and histological involvement. The addition of azathioprine to a corticosteroid-based regimen for IgAN does not improve renal outcome.
Neutropenia after kidney transplant is an adverse event usually treated with a dosage reduction of mycophenolic acid. We evaluated the efficacy and safety of substituting mycophenolic acid with ...everolimus in patients with persistent neutropenia after kidney transplant.
This study was a retrospective analysis. A total of 17 patients who were initially treated with mycophenolic acid (1912 ± 196 mg/d), calcineurin inhibitors, and methylprednisolone for kidney transplant were included.
In 15 patients, neutropenia occurred within the first 3 months (during valganciclovir administration), and in 2 patients between the fourth and sixth month after transplant. One hundred eighteen episodes of neutropenia were recorded, originally treated by reducing the dosage of mycophenolic acid (765 ± 390 mg/d) and administering granulocyte colony-stimulating factor. Three patients experienced acute rejection 5 to 10 days after reducing the dosage of mycophenolic acid, and they were successfully treated with pulse steroids. Five patients developed cytomegalovirus infection 108 ± 65 days after the onset of neutropenia. After replacing mycophenolic acid with everolimus, episodes of neutropenia were observed in 6 patients. In 1 patient, discontinuing everolimus was necessary after 1.5 months of treatment. In 5 patients with cytomegalovirus infection, neutropenia subsided after termination of valganciclovir treatment. In the remaining 11 patients, no episodes of neutropenia were observed. No episodes of acute rejection occurred, and renal function remained stable during a followup of 47 ± 30 months (estimated glomerular filtration rate eGFRMDRD6: 45 ± 14 mL/min/1.73 m2→47 ± 22 mL/min/1.73 m2.
Replacing mycophenolic acid with everolimus appears to be a safe and effective alternative treatment in neutropenic renal transplant recipients.
It is unclear if brachio-basilic vein fistula should be performed as a primary or staged procedure, particularly for smaller basilic veins. Our aim was to report on a randomized controlled trial ...comparing these two techniques.
Sixteen patients with a basilic vein ≥2.5 mm were randomized into primary transposed brachio-basilic vein (TBBV) fistula (n = 9) and staged TBBV fistula (n = 7). Patients with basilic veins enlarged by previous arteriovenous fistulas were excluded. Baseline characteristics of the two study groups, including vein size, were comparable (median basilic vein diameter 3.5 mm, range 2.8-4.1 mm). The staged group had a brachio-basilic vein fistula performed first followed by the transposition procedure performed at least 6 weeks later to allow the basilic vein to enlarge. TBBV fistula maturation at 10 weeks, primary, assisted-primary, and secondary patency were the primary outcome measures. Early failures were included in the calculation of patency rates.
Transposed brachio-basilic vein fistula maturation rate after primary procedures (3/9, 33%) was lower compared to maturation rate after staged procedures (7/7, 100%, P = 0.011, Fisher's exact test), which led to premature termination of the trial. Time to hemodialysis median (interquartile range) of primary and staged procedures was 54 (51.5-113.5) days and 97 (93-126) days, respectively (P = 0.16). One-year primary and assisted-primary patency rates of primary and staged procedures were equivalent (44 vs 57%, P = 0.76 and 44 vs 71%, P = 0.29, respectively); however, there was a trend toward a better 1-year secondary patency after staged procedures (86 vs 44% for primary procedures, P = 0.09).
Among candidates for TBBV fistula with a small basilic vein, staged transposition achieves higher maturation rates compared to primary procedures, a difference reflected in long-term secondary patency.
www.ClinicalTrials.gov, identifier NCT01274117.
Atherosclerosis is a significant factor affecting long-term outcome in renal transplant recipients. Studies have been conducted to determine the pharmacogenomic pathways involved in statin efficacy, ...efficiency, and adverse effect likelihood. However, little is known about the influence of statins on tacrolimus kinetics. The aim of this study was to investigate possible pharmacological interactions between tacrolimus and statins in CYP3A5 non-expressors, renal transplant recipients.
Twenty-four patients, treated with tacrolimus (n=24), methylprednisolone (n=24), and mycophenolate mofetil (n=19)/azathioprine (n=1)/everolimus (n=4), participated in the study. After an observation time of 112±36 days, statins, namely, atorvastatin (n=12), simvastatin (n=8), pravastatin (n=2), or fluvastatin (n=2), were administered for additional 101±34 days. DNA was extracted from whole blood sample and polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for CYP3A5 genotyping. Student's t-test and Mann-Whitney test were used to test the significance of difference in variables that passed or did not pass Kolmogorov's normality test, respectively.
No statistically significant difference was observed in tacrolimus daily dose, concentration, concentration/dose ratio, and volume of distribution before and during the administration of statins. Statistically significant decrease in serum cholesterol was observed after initiation of statins. Renal and hepatic function remained unchanged and no skeletal muscle abnormalities were reported.
The results of this study show that tacrolimus and statins do not interact in terms of efficacy, efficiency, and adverse effect likelihood. No significant clinical interaction or effect was observed, even with the use of atorvastatin or simvastatin, which are metabolized by CYP3A4 such as tacrolimus.
There is currently debate if brachio-basilic vein fistula (BBVF) should be performed as a one-stage or two-stage procedure. The aim of the present study was to perform a systematic review and ...meta-analysis on BBVF staging.
On February 25, 2016, a search for randomized-controlled trials (RCTs) on BBVF procedures was performed in MEDLINE and Scopus databases. Meta-analyses were performed with fixed-effect or random-effects models as appropriate with risk ratios (RRs). The primary efficacy and safety outcome measures were BBVF maturation and development of complications, respectively. Specific types of complications, including loss of functional secondary patency and long-term complications were all secondary outcome measures.
We identified three RCTs reporting on 126 patients. Maturation failure of two-stage BBVFs (3/47, 6.4%) was less frequent than one-stage BBVFs (16/79, 20.3%; RR, 0.27; P=0.02). Complication rates of two-stage and one-stage BBVFs were similar (RR, 0.80; P=0.54), but on sensitivity analysis these were less likely to occur with two-stage BBVFs (37% vs. 69% for one-stage BBVFs; RR, 0.57; P=0.03). Two-stage BBVFs were less likely to lose their functional secondary patency (21.3% vs. 31.6% for one-stage BBVFs; RR, 0.61; P=0.11). This non-significant trend became significant (RR, 0.36; P=0.02) on sensitivity analysis. There was no difference in specific complication rates of the two study groups.
Among candidates for BBVF fistula, there is evidence to suggest that two-stage BBVFs achieve higher maturation rates compared to one-stage BBVFs. The evidence for difference in long-term secondary patency is less robust, calling for further research.
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