BK polyomavirus‐associated nephropathy (PyVAN) is responsible for a significant percentage of transplanted kidneys prematurely terminating their function. Its occurrence is closely related to the ...intensity of immunosuppressive therapy. In a group of 161 newly transplanted patients, we prospectively evaluated 457 protocol renal biopsies performed within the first year after transplantation. Using the calcineurin inhibitors (CI) nephrotoxicity score, the incidence of nephrotoxicity was monitored as a manifestation of excessive immunosuppression. Findings were correlated with clinical evidence of active BK polyomavirus (BKPyV) replication and PyVAN. Compared to the normal histology, nephrotoxicity was associated with more frequent BKPyV viremia and viruria (p = .01 and p < .01, respectively) and more common occurrence of PyVAN. The persistence of toxicity in the subsequent biopsy proved to be a negative risk factor of viremia and viruria (p = .03 and p < .01, respectively), independently of the initial BKPyV status. Toxicity could also be used as a predictor of viremia and viruria (p = .04 and p < .01, respectively) even in the absence of viral replication at the time of initial biopsy. The early histological manifestation of CI nephrotoxicity was associated with significant BKPyV reactivation in the risky first posttransplant year.
BK virus-induced renal allograft nephropathy Krejci, Karel; Tichy, Tomas; Bednarikova, Jana ...
Biomedical papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
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BK virus nephropathy (BKVN) is a serious opportunistic infection threatening renal function especially during the first year after transplantation. Its incidence is now on the rise and is closely ...related to the level of the recipient's immune system inhibition. This is more intensive with current trends in transplantation medicine, where more potent immunosuppressive protocols are used and more aggressive antirejection therapy is applied. In the absence of BK virus (BKV) specific therapy and limited treatment options for advanced BKVN, active screening of BKV replication and subsequent preemptive adjustment of immunosuppression are essential measures to prevent BKVN. However, it remains unclear how to modify immunosuppressive protocols as well as how to address initial stages of BKV replication. This comprehensive review summarizes the currently applied and not completely uniform procedures for the detection, prophylaxis and therapy of BKV replication and BKVN. The pitfalls brought by reduced immunosuppression, as a typical response to a significant viral replication or a developed BKVN, are also mentioned, particularly in the form of graft rejection. The paper also outlines the authors' experiences, and lists currently ongoing studies on the subject. The perspectives of new, especially immune-based, procedures in the treatment of complications associated with BKV infections are highlighted. Different views on the management of patients indicated for kidney re-transplantation whose previous graft failed because of BKVN are also discussed.
Genetic focal segmental glomerulosclerosis (FSGS) is caused by pathogenic variants in a broad spectrum of genes that have a variable representation based on subjects' ethnicity and/or age. The most ...frequently mutated autosomal recessive gene in FSGS is
. In this study, we analyzed the spectrum of
variants and their associated phenotype in Czech adult FSGS patients.
A representative cohort of 234 adult patients with FSGS, derived from 225 families originating from all regions of Czechia, was analyzed by massively parallel sequencing. In this study, we focused on the comprehensive analysis of the
gene. The histological classification of FSGS followed the Columbia classification.
We detected seven (3%) cases bearing homozygous or compound heterozygous pathogenic
variants. A single pathogenic variant c.868G > A (p.Val290Met) was found in the majority of
-positive cases (86%; 6 out of 7) in histologically confirmed instances of FSGS. Its allele frequency among unrelated
-associated FSGS patients was 50% (6/12), and Haplotype analysis predicted its origin to be a result of a founder effect. There is an identical V290M-related haplotype on all V290M alleles spanning a 0,7 Mb region flanking
in Central European FSGS populations. The phenotype of the p.Val290Met
-associated FSGS demonstrated a later onset and a much milder course of the disease compared to other
pathogenic variants associated with FSGS. The mean age of the FSGS diagnosis based on kidney biopsy evaluation was 31.2 ± 7.46 years. In 50% of all cases, the initial disease manifestation of proteinuria occurred only in adulthood, with 83% of these cases not presenting with edemas. One-third (33%) of the studied subjects progressed to ESRD (2 out of 6) at the mean age of 35.0 ± 2.82 years.
We identified the most prevalent pathogenic variant, p.Val290Met, in the
gene among Czech adult FSGS patients, which has arisen due to a founder effect in Central Europe. The documented milder course of the disease associated with this variant leads to the underdiagnosis in childhood. We established the histopathological features of the
-associated adult FSGS cases based on the Columbia classification. This might improve patient stratification and optimize their treatment.
The most serious complication of renal biopsy is vascular damage with subsequent haemorrhage. To our knowledge, we present a first ever case of lumbar artery (LA) rupture accompanied by massive ...retroperitoneal bleeding, which developed after a significant amount of time following the biopsy itself. In a 63-year-old Caucasian female patient, a percutaneous left kidney biopsy was performed under continuous ultrasound guidance. On the fourteenth day after the procedure, she was examined for a sudden onset of left lumbar region pain. Computed tomography angiography showed a large retroperitoneal hematoma with active bleeding from the fourth left LA. Successful endovascular superselective embolization was performed immediately. The predisposing factor for the late haemorrhage could have been anticoagulation therapy, renal insufficiency and older age. Our case report highlights the need for caution, especially when performing kidney biopsy in a group of high-risk patients, particularly if they are indicated for subsequent anticoagulant therapy.
Thrombotic microangiopathy (TMA) significantly affects kidney graft survival, but its pathophysiology remains poorly understood.
In this multicenter, retrospective, case-control paired study designed ...to control for donor-associated risks, we assessed the recipients' risk factors for de novo TMA development and its effects on graft survival. The study group consists of patients with TMA found in case biopsies from 2000 to 2019 (n = 93), and the control group consists of recipients of paired kidney grafts (n = 93). Graft follow-up was initiated at the time of TMA diagnosis and at the same time in the corresponding paired kidney graft.
The TMA group displayed higher peak panel-reactive antibodies, more frequent retransplantation status, and longer cold ischemia time in univariable analysis. In the multivariable regression model, longer cold ischemia times (odds ratio, 1.18; 95% confidence interval CI, 1.01-1.39;
= 0.043) and higher peak pretransplant panel-reactive antibodies (odds ratio, 1.03; 95% CI, 1.01-1.06;
= 0.005) were found to be associated with increased risk of de novo TMA. The risk of graft failure was higher in the TMA group at 5 y (hazard ratio HR, 3.99; 95% CI, 2.04-7.84;
< 0.0001). Concomitant rejection significantly affected graft prognosis at 5 y (HR, 6.36; 95% CI, 2.92-13.87;
< 0.001). De novo TMA associated with the active antibody-mediated rejection was associated with higher risk of graft failure at 5 y (HR, 3.43; 95% CI, 1.69-6.98;
< 0.001) compared with other TMA.
Longer cold ischemia and allosensitization play a role in de novo TMA development, whereas TMA as a part of active antibody-mediated rejection was associated with the highest risk for premature graft loss.
The CONCERTO study results showing the beneficial effects of conversion from cyclosporine to tacrolimus prolonged-release (tacrolimus PR) in stabilised patients after kidney transplantation, were ...first published in 2011. This communication describes our first experience of conversion from cyclosporine to tacrolimus PR in stabilised kidney transplant patients. The aim was to determine whether it could be used in routine clinical practice in the Czech and Slovak Republics.
Evaluation was carried out at five transplantation centres in the Czech Republic and Slovakia. In all participating Centres, the drug conversion was conducted according to the ICH/GCP guidelines. A total of 104 patients stabilised after kidney transplantation were converted from maintenance therapy with cyclosporine to treatment with tacrolimus PR. The data were collected 26 weeks after the switch. The primary endpoint was change in kidney graft function measured from the estimated glomerular filtration rate (GFR). The effect of conversion on blood pressure, metabolic parameters and cosmetic changes was also recorded. Special attention was paid to the safety and tolerability of treatment with tacrolimus PR.
GFR increased after six months by 10 % (P = 0.040). In addition a significant decrease in serum creatinine and triglycerides level was found together with major reduction in the incidence and severity of gingival hyperplasia and hirsutism. 3% of patients developed new onset of diabetes mellitus. Otherwise, the switch was very well-tolerated, without serious adverse events or acute rejections.
Conversion from cyclosporine to tacrolimus PR was shown to be a safe therapeutic alternative with patient benefits.
To provide the first single-center study of a Czech renal transplant program that compares skin cancer risk estimates to the general population.
We studied a total of 603 patients undergoing renal ...transplantation at the University Hospital Olomouc Transplant Center between January 1984 and December 2009. The mean time of follow-up was 5.5 years. Three patients were excluded for skin cancer diagnosis before transplant. The cohort was linked with the National Cancer Registry of the Czech Republic. For non-melanoma skin cancer (NMSC), the observed number of cancers were compared to the expected numbers of NMSC based on national cancer incidence rates stratified by age. The standartized incidence ratio (SIR) was calculated as observed-to-expected ratios.
We found a total of 127 cases of skin cancers in 55 patients. 52/55 (94.5%) were patients with non-melanoma skin cancers, 2/55 (3.6%) patients had malignant melanoma, and we uncovered one case of merkel cell carcinoma of the skin (1.8%). There were no cases of Kaposi's sarcoma, cutaneous lymphoma or malignant fibrous histiocytoma. For NMSC, the overall SIR was 7.39 (95% confidence interval 5.52-9.70). Thus, skin cancer was the most common malignant condition, representing 64.1% of all malignant tumours detected in study population.
We confirmed that skin cancer is a major complication in renal transplant recipients. Therefore it is important to increase the intensity of surveillence for these lesions in transplant patients.
Abstract Purpose A clinically manifested acute rejection is associated with graft dysfunction and with some ultrasound findings. The aim of our study was to determine the potential of ultrasound ...evaluation in the detection of subclinical acute rejective changes diagnosed in stable grafts by protocol biopsy. Methods Gray-scale evaluation, color Doppler imaging (CDI) and power Doppler imaging (PDI) was performed before each of 184 protocol graft biopsies in 77 patients in the third week, third month and first year after transplantation. The group was divided into four subgroups—normal histological finding, borderline changes, subclinical acute rejection of IA grade, and a clinically manifested acute rejection of IA grade. The sonographic findings were compared with individual groups. Results Detection of parenchymal edema using gray-scale imaging significantly differentiated borderline changes and subclinical acute rejection of IA grade from normal histological findings in the third week and in the third month ( P = 0.013, P = 0.002 and P = 0.024, P < 0.001), respectively. A similar finding could be recorded in the latter group in the first year after transplantation ( P = 0.024). The presence of edema and reduced peripheral parenchymal perfusion in PDI significantly more often indicated a clinically manifested acute IA rejection ( P = 0.019, P = 0.004, P = 0.044). Parenchymal CDI hyperperfusion had a high specificity (89.5%) but a low sensitivity (60%) in the detection of the subclinical form of acute IA rejection. Conclusion A composite gray-scale, PDI and CDI evaluation provide a significant differentiation of groups with borderline changes and subclinical acute rejection and groups with normal histological finding and clinically manifested acute rejection.
Little is known about the influence of calcineurin inhibitors on advanced oxidation protein products (AOPP) and total antioxidant status (TAS) after renal transplantation.
AOPP and TAS were evaluated ...in transplanted patients on different calcineurin inhibitors. Thirty-five patients were treated with cyclosporine A (group A) and 33 with tacrolimus (group B).
Over 6 months, the mean levels of AOPP in group A decreased from 205.9
±
125.7 to 140.9
±
78.9 µmol/L and TAS from 1.89
±
0.30 to 1.75
±
0.27 mmol/L. In group B, the mean levels of AOPP decreased from 196.5
±
123.9 to 129.6
±
63.8 µmol/L and TAS from 1.80
±
0.39 to 1.78
±
0.23 mmol/L.
No significant differences in AOPP and TAS were found with respect to treatment. The only exception was the higher mean concentration of AOPP at month 1 in group A (
p
=
0.026).
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