Robotic assisted living donor nephrectomy - the first in the Czech Republic.

INTRODUCTION: A kidney transplant is the best method for treating terminal kidney failure. Long-term results of kidney transplants from living donors are significantly better than transplants from dead donors. Living kidney donors are healthy people who undergo a major operation in order to improve the health of another person. Therefore, major emphasis is on safety, low level of invasiveness and a desirable cosmetic effect of the donor nephrectomy. Since 2012, the Department of Urology at the University Hospital in Olomouc has performed 12 kidney harvestings from living donors. The kidney harvesting was conducted using various techniques. CASE REPORT: The first robotic assisted kidney harvesting in the Czech Republic was performed in June 2022. The donor was a 57-year-old man who donated his kidney to his 32-year-old daughter. The left kidney was evaluated as suitable for kidney harvesting. The operation took 174 min. The kidney's warm ischemia was 145 s. Based on the Clavien Dindo classification, no 2nd degree or high post-operative complications were recorded. The donor's pre-operative glomerular filtration was 1.63 mL/s. Six months post-operation, it went down to 1.19 mL/s. This represents a 27% decrease. The kidney recipient did not require early dialysis. Six months post-operation, the recipient's glomerular filtration was 2.03 mL/s. CONCLUSION: In the hands of experienced professionals and transplantation centres, robotic assisted donor nephrectomy is a feasible and safe option for this operation. It not only provides all the advantages of a laparoscopic operation but it also adds other technical improvements and minimizes intraoperative stress on the surgeon. Currently, the global trend is moving towards increasing the ratio of robotic assisted donor nephrectomies.

The most common founder pathogenic variant c.868G > A (p.Val290Met) in the NPHS2 gene in a representative adult Czech cohort with focal segmental glomerulosclerosis is associated with a milder disease and its underdiagnosis in childhood.

Background: 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 NPHS2. In this study, we analyzed the spectrum of NPHS2 variants and their associated phenotype in Czech adult FSGS patients. Methods: 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 NPHS2 gene. The histological classification of FSGS followed the Columbia classification. Results: We detected seven (3%) cases bearing homozygous or compound heterozygous pathogenic NPHS2 variants. A single pathogenic variant c.868G > A (p.Val290Met) was found in the majority of NPHS2-positive cases (86%; 6 out of 7) in histologically confirmed instances of FSGS. Its allele frequency among unrelated NPHS2-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 NPHS2 in Central European FSGS populations. The phenotype of the p.Val290Met NPHS2-associated FSGS demonstrated a later onset and a much milder course of the disease compared to other NPHS2 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. Conclusions: We identified the most prevalent pathogenic variant, p.Val290Met, in the NPHS2 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 NPHS2-associated adult FSGS cases based on the Columbia classification. This might improve patient stratification and optimize their treatment.

Current Status, Prevention and Treatment of BK Virus Nephropathy.

All renal transplant recipients should undergo a regular screening for BK viral (BKV) viremia. Gradual reduction of immunosuppression is recommended in patients with persistent plasma BKV viremia for 3 weeks after the first detection, reflecting the presence of probable or suspected BKV-associated nephropathy. Reduction of immunosuppression is also a primary intervention in biopsy proven nephropathy associated with BKV (BKVN). Thus, allograft biopsy is not required to treat patients with BKV viremia with stabilized graft function. There is a lack of proper randomised clinical trials recommending treatment in the form of switching from tacrolimus to cyclosporin-A, from mycophenolate to mTOR inhibitors or leflunomide, or the additive use of intravenous immunoglobulins, leflunomide or cidofovir. Fluoroquinolones are not recommended for prophylaxis or therapy. There are on-going studies to evaluate the possibility of using a multi-epitope anti-BKV vaccine, administration of BKV-specific T cell immunotherapy, BKV-specific human monoclonal antibody and RNA antisense oligonucleotides. Retransplantation after allograft loss due to BKVN can be successful if BKV viremia is definitively removed, regardless of allograft nephrectomy.

Rejection-associated Phenotype of De Novo Thrombotic Microangiopathy Represents a Risk for Premature Graft Loss.

BACKGROUND: Thrombotic microangiopathy (TMA) significantly affects kidney graft survival, but its pathophysiology remains poorly understood. METHODS: 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. RESULTS: 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; P = 0.043) and higher peak pretransplant panel-reactive antibodies (odds ratio, 1.03; 95% CI, 1.01-1.06; P = 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; P < 0.0001). Concomitant rejection significantly affected graft prognosis at 5 y (HR, 6.36; 95% CI, 2.92-13.87; P < 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; P < 0.001) compared with other TMA. CONCLUSIONS: 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.

Nephrotoxicity of calcineurin inhibitors as a risk factor for BK polyomavirus replication after kidney transplantation.

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.

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.

Late Rupture of Lumbar Artery as an Unusual Complication after Renal Biopsy - Case Report.

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.

Clinical experience of conversion from cyclosporine to tacrolimus prolonged-release in stabilized kidney transplant patients.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Conversion from cyclosporine to tacrolimus PR was shown to be a safe therapeutic alternative with patient benefits.

Cutaneous bacillary angiomatosis due to Bartonella quintana in a renal transplant recipient.

Bacillary angiomatosis (BA) is a disorder of neovascular proliferation involving skin and other organs of immunosuppressed patients caused by Bartonella species. BA has been recognized in both immunocompetent and immunodeficient patients, mostly in human immunodeficiency virus (HIV)-infected persons, much more rare in those with other immunodeficiencies, including organ transplantation. Diagnosis is based on serologic analysis, culture and molecular biology [detection of Bartonella species deoxyribonucleic acid (DNA) in tissue biopsy extracts by real-time polymerase chain reaction (PCR)]. All immunosuppressed patients with BA should be treated with antibiotics because of potentially life-threatening course of the disease. We report the first case of cutaneous bacillary angiomatosis due to Bartonella quintana in renal transplant recipient. This presentation demonstrates that BA should be considered a differential diagnosis in immunocompromised patients presenting with fever and cutaneous angioma-like lesions.

[Bortezomib-based therapy in patients with light chain deposition disease]. / Lécba bortezomibem u pacientu s onemocnením z depozice lehkých retezcu imunoglobulinu.

Light chain deposition disease (LCDD) is a rare systemic condition caused by monoclonal proliferation of terminally differentiated B-lymphocytes with production of free light chains and their deposition in kidneys or other organs. The aim of our study is to show the pitfalls of the diagnostics, and to demonstrate the effect of bortezomib-based therapy on a series of 4 patients with LCDD, from the point of hematological and organ therapeutic response. We include that bortezomib based treatment provides rapid and effective hematological response. It is, however, often accompanied by adverse events, especially within intensive treatment schedules. The most serious adverse effects includes peripheral neuropathy, which might be dose or treatment-limiting. Less intensive regimens ("bortezomib weekly") suggest an alternative with expectation of lower incidence of adverse effects. Autologous stem cell transplantation is a recommended and relatively safe approach in convenient candidates. Organ response is significantly delayed after hematological response, and organ damage by light chain deposits might not be fully reversible.

Renal manifestations of rheumatic diseases. A review.

BACKGROUND: Renal manifestations of rheumatic diaseases are sometimes very discrete and mild. At others, they can present the leading symptomatology of a given disease. Systemic lupus erythematosus, systemic scleroderma, renal vasculitis, rheumatoid arthritis, mixed connective tissue disease, Sjögren's syndrome and gout can all manifest in or be accompanied by renal impairment. METHODS AND RESULTS: The authors reviewed the literature on renal manifestation of rheumatic diseases using the key words, lupus erythematosus, systemic autoimmune diseases, rheumatoid arthritis, vasculitis and gout. The review below is accompanied by their own histological findings. CONCLUSION: Diagnosis requires proper interpretation of the clinical situation, laboratory results and image analysis methods plus close interdisciplinary collaboration between nephrologist and clinical pathologist/nephropathologist.

Complement system in SLE as a target for antibodies.

SLE is characterized by overproduction of various types of autoantibodies. Under certain circumstances, antibodies targeting some of the neoepitopes of the complement system can be seen. The most studied among antibodies directed against a component of the complement system is anti-C1q. Anti-C1q antibodies are present in approximately one third of the patients with lupus, who often have high clinical disease activity and in particular renal involvement. In the presence of high titers of anti-C1q antibodies also the levels of C1q and C3 and C4 components of the complement system are also usually low. The presence of the anti-C1q antibodies is not limited or specific just for SLE or lupus nephritis. For the first time, they were described in HUVS (Hypocomplementemic Urticarial Vasculitis Sydrome), later in Felty´s syndrome, rheumatoid vasculitis, hepatitis C, poststreptococcal glomerulonephritis or aging population.

In vivo oxidized low-density lipoprotein (ox-LDL) aopp and tas after kidney transplantation: a prospective, randomized one year study comparing cyclosporine A and tacrolimus based regiments.

AIMS: Restoration of renal function after kidney transplantation (KT) is expected to improve oxidative stress (OS). However, little is known about the influence of calcineurin inhibitors on oxidized low-density lipoproteins (ox-LDL) after KT. The aim of this study was to evaluate ox-LDLs and related markers of OS, advanced oxidation protein products (AOPP) and total antioxidant status (TAS) in patients after KT on either cyclosporin A (CyA) or tacrolimus (Tac) treatment. METHODS: This was a prospective, randomized, single-center 12 month study evaluating time-dependent changes in biomarkers of OS before and after KT. Twenty nine patients (mean age 54.4 ± 11.1; 55% male and 45% female) were treated with CyA (Group A) and twenty four patients (mean age 52.9 ± 9.9; 75% male and 25% female) were treated with Tac (Group B). The ox-LDL, AOPP, TAS, lipid metabolism parameters, creatinine and glomerular filtration were assessed on day 1 before KT and on days 1 and 7, and in months 1, 3, 6 and 12 after KT. RESULTS: Over the 12 months, the ox-LDL for group A changed from 69.2±32.9 to 65.1±17.1 U/L (P=0.665), while AOPP significantly decreased from 233.0±159.6 to 156.5±90.1 µmol/L (P=0.025) and TAS from 1.87±0.31 to 1.68±0.20 mmol/L (P=0.030). For group B the ox-LDL changed from 62.9±29.7 to ± 61.4±14.6 U/L (P=0.168) and TAS from 1.87±0.51 to 1.68±0.20 mmol/L (P=0.168), while AOPP significantly decreased from 180.5±90.0 to 123.9±37.7 µmol/L (P=0.019). CONCLUSION: AOPP is more sensitive than ox-LDL for assessing OS after KT. TAS values appear to be insufficiently sensitive for monitoring OS in patients after KT.

Skin cancer incidence in renal transplant recipients - a single center study.

AIMS: To provide the first single-center study of a Czech renal transplant program that compares skin cancer risk estimates to the general population. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Merkel cell carcinoma of the gluteal region with ipsilateral metastasis into the pancreatic graft of a patient after combined kidney-pancreas transplantation.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare tumour of the skin that predominantly affects elderly or immunocompromised patients. The malignant transformation of Merkel cells is currently considered to be related to an infection with Merkel cell polyomavirus. CASE REPORT: We present the case of a 62-year-old man who developed a Merkel cell polyomavirus-positive MCC in a non-UV-exposed part of the right gluteal region 8 years after combined kidney-pancreas transplantation. Following excision and radical re-excision of the tumour, no adjuvant radiotherapy was indicated because of the risk of adjacent pancreatic graft failure. Despite adjustment of the immunosuppressive therapy with conversion to sirolimus, the tumour generalised and metastasised into the pancreatic graft, leading to its failure. Subsequent chemotherapy did not affect the course of the disease, and the patient died 9 months after diagnosis. CONCLUSIONS: To our knowledge, we present the first case of MCC associated with metastatic involvement of the transplanted pancreas followed by its subsequent failure. Given the highly aggressive course of the disease in patients after organ transplantation, MCC therapy should be sufficiently aggressive from the time of diagnosis and should not be influenced by attempts to preserve graft function.

Effect of different calcineurin inhibitors on AOPP and TAS after kidney transplantation.

OBJECTIVES: Little is known about the influence of calcineurin inhibitors on advanced oxidation protein products (AOPP) and total antioxidant status (TAS) after renal transplantation. DESIGN AND METHODS: 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). RESULTS: Over 6 months, the mean levels of AOPP in group A decreased from 205.9+/-125.7 to 140.9+/-78.9 micromol/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 micromol/L and TAS from 1.80+/-0.39 to 1.78+/-0.23 mmol/L. CONCLUSION: 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).

Calcineurin inhibitor-induced renal allograft nephrotoxicity.

BACKGROUND: The introduction of the calcineurin inhibitors (CI) cyclosporine and tacrolimus into immunosuppressive protocols initiated a new era in organ transplantation with excellent short-term graft survival. Nevertheless, the chronic nephrotoxicity of these drugs represents a significant adverse factor limiting their long-term use. Patients treated with a CI can be at risk for developing renal failure and this problem is especially pronounced in patients after renal transplantation. METHODS AND RESULTS: In a review paper we summarize the clinical aspects, histological manifestations and pitfalls of diagnostics of acute and chronic CI nephrotoxicity in patients after kidney transplantation. We look in detail at the disputed relationship between blood concentrations of cyclosporine and tacrolimus and histological manifestation of toxicity and summarize data showing that for toxic effects, local renal exposure to CI and their metabolites can play a more significant role than systemic exposure. We also include recent views on the pathophysiologic and molecular mechanisms underlying these changes; factors influencing local susceptibility to CI nephrotoxicity are discussed, including variability of expression and activity of P-glycoprotein and cytochrome P450. Last but not least we summarize our own experience with clinically manifest and subclinical forms of nephrotoxicity and their impact on the progression of chronic graft changes. CONCLUSIONS: Owing to their unique effects, CI remain the cornerstone of most immunosuppressive protocols for renal transplantation. Together with optimization of local kidney exposure to CI and their metabolites, efforts to reduce systemic levels as much as possible are the most important preventive measure for reducing toxic renal graft damage.

Subclinical toxicity of calcineurin inhibitors in repeated protocol biopsies: an independent risk factor for chronic kidney allograft damage.

The purpose of the prospective study was to determine the prevalence of subclinical toxicity of calcineurin inhibitors (CI) in repeated protocol renal allograft biopsies and to assess its impact on the development of chronic graft changes. A total of 424 biopsies were conducted in a cohort of 158 patients; of these biopsies, 158 were in the third week, 142 were in the third month and 124 were in the first year after transplantation. Histological signs of toxicity occurred in the third week in 33 (20.1%) patients, with persistence after CI dose reduction in the third month in 27 (19.0%) and in the first year in 23 (18.5%) patients. Of the toxic changes, 52% were clinically silent. At the end of the one-year follow-up, both subclinical and clinically manifest toxicity resulted in a similar progression of chronic changes quantified by Banff chronicity score and they significantly differed from the control group (P < 0.05). Subclinical toxicity affects a significant percentage of grafts; it occurs independently of dosage, blood level and type of applied CI. It is associated with the progression of chronic changes as early as in the first year after transplantation and represents an independent risk factor for chronic allograft damage. We report here our clinical approach to toxicity.

Improvement of cardiovascular risk factors and cosmetic side effects in kidney transplant recipients after conversion to tacrolimus.

AIMS: Tacrolimus and Cyclosporine A (CyA) are cornerstones in immunosuppressive therapy. Cyclosporine side eff ects include hypertension and hypercholesterolemia both of which may increase the risk of cardiovascular mortality, gingival hyperplasia and hirsutism are known to reduce quality of life. The aim of this prospective study was to evaluate changes in cardiovascular risk profile and cosmetic side eff ects after conversion from CyA to tacrolimus. METHODS: 25 stable kidney transplant recipients (9 male, 16 female) were converted from a CyA to a tacrolimus--based regimen. Mean age was 45.7 +/- 13.5 years. Time to switch following transplantation was 4.7+/-1.7 years. Reasons for conversion were multiple: arterial hypertension (9), hypertrichosis (3), gingival hyperplasia (3), hyperlipidemia (14). RESULTS: 19/25 patients completed the one year study period. One patient died, two returned to hemodialysis, two were switched back to CyA and one patient was lost to follow-up. There were statistically significant changes (p = < 0.05) in systolic and diastolic pressure and antihypertensive medication could be reduced in 13 patients. The dose of lipid-lowering agents could be reduced in the majority of the recipients and a complete withdrawal was achieved in 7 patients. Hypertrichosis and gingival hyperplasia resolved in all patients. Further, there was a significant improvement (p = <0.05) in urea and serum creatinine levels. Adverse events were consistent with the established safety profile for tacrolimus. CONCLUSIONS: Conversion to a tacrolimus-based regimen led to an improvement in the cardiovascular risk profile. Further, cosmetic side eff ects which may lead to non-compliance, resolved after the switch.

Sonographic findings in borderline changes and subclinical acute renal allograft rejection.

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.