De Novo Metabolic Syndrome 1 Year after Liver Transplantation and Its Association with Mid- and Long-Term Morbidity and Mortality in Liver Recipients.

Background: Metabolic syndrome (MS) constitutes an important source of cardiovascular- and cancer-related morbidity and mortality in the general population. Limited information is available on whether these findings can be directly extrapolated to liver recipients. This study aimed to investigate the impact of post-transplant MS present 1 year after liver transplantation on survival rates, risk of major cardiovascular events (CVEs), and de novo malignancies. Methods: Adult deceased-liver-donor recipients who underwent transplantation in our centre between 2010 and 2019 and reached at least 1 year of post-transplantation follow-up were eligible. Results: Of 259 enrolled patients, 20% developed post-transplant MS 1 year after the procedure. The presence of post-transplant MS at 1 year did not affect all-cause mortality (p = 0.144) and risk of de novo malignancies (p = 0.198) in liver recipients. However, it was associated with an overall and time-dependent increase in the risk of major CVEs (p < 0.001). MASH aetiology of liver disease, pre-existing major CVEs, and development of de novo malignancy were independent predictors of all-cause mortality in liver recipients. Conclusions: New onset MS exerts a wide-ranging effect on the post-transplant prognosis of liver recipients. Obtaining optimal control over all modifiable metabolic risk factors is central to improving long-term outcomes in this population.

MASH Continues as a Significant Burden on Metabolic Health of Liver Recipients.

BACKGROUND: Metabolic complications are a recognized health concern in liver transplant recipients that result in inferior patient-reported outcomes. Patients with MASH are known to be disproportionately affected by metabolic diseases compared to other indications for transplantation. PURPOSE: The aim of this study was to investigate the incidence of metabolic abnormalities in liver recipients with specific focus on differences between patients transplanted for MASH and non-MASH-causes. PATIENTS AND METHODS: An observational, monocentric, and retrospective analysis was performed. Patients who received a cadaveric-donor-liver transplant between 2010 and 2019 were eligible. RESULTS: 282 patients were enrolled with a median age of 52 years (66.7% males). Metabolic dysfunction-associated steatohepatitis (MASH) led to liver transplant in 8.2% of cases. De-novo metabolic syndrome was diagnosed in 36% of the study population. Patients that underwent transplant owing to MASH showed significantly higher incidence of metabolic complications in both pre- and post-transplant period. Considerable differences were noted in the pattern of weight gain between patients transplanted for MASH and non-MASH patients. The MASH etiology (OR: 5.5; 95% CI: 1.624-22.868; P = .010), higher BMI at 1-year post-transplant (OR: 1.321; 95% CI: 1.214-1.449; P = <.001), and older age at transplant (OR: 1.038; 95% CI: 1.006-1.074; P = .022) were independently associated with new-onset metabolic syndrome in liver recipients. CONCLUSION: Metabolic complications were prevalent in liver recipients. Liver recipients with underlying MASH significantly surpassed patients transplanted for other indications in terms of metabolic complications incidence and demonstrated an unfavorable trajectory of weight gain post-transplant.

Evaluation of Long-Term Outcomes of Direct Acting Antiviral Agents in Chronic Kidney Disease Subjects: A Single Center Cohort Study.

BACKGROUND: The chronic kidney disease (CKD) population, including kidney transplant recipients (KTRs) and subjects on renal replacement therapy, is particularly vulnerable to unfavorable outcomes from chronic hepatitis C (CHC). Currently, there are oral direct-acting antiviral agents (DAAs) available to eradicate the virus with favorable short-term outcomes; however, their long-term effects are lacking. The aim of the study is to assess the long-term efficacy and safety of DAA therapy in the CKD population. METHODS: An observational, cohort single-center study was performed. Fifty-nine CHC subjects with CKD, treated with DAAs between 2016 and 2018, were enrolled in the study. Safety and efficacy profiles were assessed, including sustained virologic response (SVR), occult hepatitis C infection (OCI) incidence, and liver fibrosis. RESULTS: SVR was achieved in 96% of cases (n = 57). OCI was diagnosed only in one subject following SVR. Significant liver stiffness regression was observed 4 years after SVR compared to baseline values (Mdn = 6.1 kPa, IQR = 3.75 kPa; 4.9 kPa, IQR = 2.9 kPa), p < 0.001. The most common adverse events were anemia, weakness, and urinary tract infection. CONCLUSION: DAAs provide a safe and effective cure for CHC in both CKD patients and KTRs with a favorable safety profile in the long-term follow-up.

Are We on the Right Track for HCV Micro-Elimination? HCV Management Practices in Dialysis Centers in Poland-A National Cross-Sectional Survey.

Chronic hepatitis C (CHC) is prevalent in the hemodialysis-dependent population. Currently, all patients with CHC should be considered for treatment; however, many hemodialysis-dependent patients are still left untreated. Following HCV cure, accurate surveillance is mandatory to reduce liver-related mortality and prevent reinfection. We aimed to establish HCV management practices and barriers to HCV elimination in dialysis centers in Poland. Polish dialysis centers were surveyed via email. The HCV management strategies were investigated. Representatives of 112 dialysis centers responded, representing 43.1% of all dialysis centers in Poland and 43.4% of hemodialysis-dependent patients' volume. Most respondents were Heads of hemodialysis centers and board-certified nephrologists. The study demonstrated that in the vast majority of hemodialysis centers (91.6%), subjects are considered for antiviral treatment (AVT); however, many obstacles preventing patients from being prescribed AVT were identified; patients' reluctance to undergo AVT was most reported (60%). The majority of dialysis units neither evaluate patients with CHC for liver fibrosis (60.4%) nor screen them for hepatocellular carcinoma (53.5%). In conclusion, the presented study demonstrates that HCV management practices across Polish dialysis centers vary substantially. There is a need to optimize and streamline the HCV management infrastructure in the hemodialysis population in Poland.

Real-life comparison of efficacy and safety profiles of two prolonged-release tacrolimus formulations in de novo kidney transplant recipients: 24 months of follow-up.

INTRODUCTION: Calcineurin inhibitors constitute a cornerstone of immunosuppressive therapy in kidney transplant recipients. There are two main formulations of tacrolimus (Tac) which exhibit a prolonged-release mode of action: Advagraf® (MR-4) and Envarsus® (LCPT). However, they are not bioequivalent. Data comparing both once-daily prolonged-release formulations of Tac are insufficient. OBJECTIVE: The aim of the study was to compare safety and efficacy profiles of once-daily LCPT and MR-4 formulations of tacrolimus in adult kidney transplant recipients. PATIENTS AND METHODS: An observational, cohort single-center study was performed. One hundred fifteen kidney transplant recipients transplanted between 2016 and 2019 were enrolled to the study (59 vs 56, Envarsus® vs Advagraf®, respectively). Safety and efficacy profiles were assessed. RESULTS: Patient and graft survival at 12 and 24 months did not differ between the groups. There were no significant differences in serum creatinine at any timepoint. C/D ratio in the LCPT group was significantly higher at 12 and 24 months. Sepsis occurrence was more frequent in MR-4 group at 12 months. CONCLUSION: Both prolonged-release formulations of tacrolimus are safe and effective in immunosuppressive therapy in kidney transplant recipients.

Noninvasive Diagnostic Methods for the Assessment of Hepatic Fibrosis in Liver Transplant Recipients.

BACKGROUND: Hepatic fibrosis in liver transplant recipients is the main predictive factor for graft function. Diagnostic methods for hepatic fibrosis staging should be available, reproducible, and noninvasive, if possible. We aimed to compare diagnostic methods for the assessment of hepatic fibrosis in transplant recipients: liver biopsy as a reference method, dynamic elastography, and direct and indirect blood markers (the ELF test [Enhanced Liver Fibrosis] test and the FibroTest). We sought to set a cutoff value for each method in order to assess significant liver fibrosis (F ≥2). METHODS: The study involved 62 patients after liver transplantation. Fibrosis was assessed in biopsy specimens using the METAVIR Score System (F0-F4). To identify clinically significant cutoff values of hepatic fibrosis (F ≥2, F ≥3, F = 4) for each method compared, a receiver-operating characteristic (ROC) curve analysis was used. RESULTS: Area under ROC for the prediction of significant fibrosis (F ≥2), advanced fibrosis (F ≥3), and cirrhosis (F = 4) for the study group was 0.5938, 0.8952, and 0.9583 for dynamic elastography; 0.7295, 0.7072, and 0.8409 for the ELF test; and 0.4863, 0.8049, and 0.8723 for the FibroTest. The cutoff value for F ≥2 for dynamic elastography was 4.65 kPa; for the ELF test, 9.27; and for the FibroTest, 0.72. CONCLUSIONS: The sensitivity and specificity of the tests studied, as compared with biopsy results, increase with increasing severity of hepatic fibrosis. The noninvasive diagnostic methods are of limited value in the diagnosis of early fibrosis stages. In the diagnostic assessment of hepatic fibrosis in its advanced stages, dynamic elastography can be used in conjunction with ELF test as a noninvasive alternative to liver biopsy.

Utilization of HCV viremic donors in kidney transplantation: a chance or a threat?

Kidney transplantation is the treatment of choice in end-stage renal disease. The main issue which does not allow to utilize it fully is the number of organs available for transplant. Introduction of highly effective oral direct-acting antivirals (DAAs) to the treatment of chronic hepatitis C virus infection (HCV) enabled transplantation of HCV viremic organs to naive recipients. Despite an increasing number of reports on the satisfying effects of using HCV viremic organs, including kidneys, they are more often rejected than those from HCV negative donors. The main reason is the presence of HCV viremia and not the quality of the organ. The current state of knowledge points to the fact that a kidney transplant from an HCV nucleic acid testing positive (NAT+) donor to naive recipients is an effective and safe solution to the problem of the insufficient number of organs available for transplantation. It does not, however, allow to draw conclusions as to the long-term consequence of such an approach. This review analyzes the possibilities and limitations of the usage of HCV NAT + donor organs. Abbreviations: DAA: direct-acting antivirals; HCV: hepatitis C virus; NAT: nucleic acid testing; OPTN: Organ Procurement and Transplantation Network; KDIGO: Kidney Disease: Improving Global Outcomes; Ab: antigen; eGFR: estimated glomerular filtration rate; D: donor; R: recipient; CMV: cytomegalovirus; HBV: hepatitis B virus; UNOS: United Network for Organ Sharing; PHS: Public Health Service; EBR/GZR: elbasvir/grazoprevir; SVR: sustained virologic response; RAS: resistance-associated substitutions; SOF: soforbuvir; GLE/PIB: glecaprevir/pibrentasvir; ACR: acute cellular rejection; AR: acute rejection; DSA: donor-specific antibodies; KTR: kidney transplant recipients; AASLD: American Association for the Study of Liver Disease; IDSA: Infectious Diseases Society of America; PPI: proton pump inhibitors; CKD: chronic kidney disease; GN: glomerulonephritis; KAS: The Kidney Allocation system.

Multidirectional facets of obesity management in the metabolic syndrome population after liver transplantation.

The obesity pandemic has resulted in an increasing demand for liver transplantation and has significantly altered the profile of liver transplant candidates in addition to affecting posttransplantation outcomes. In this review, we discuss a broad range of clinical approaches that warrant attention to provide comprehensive and patient-centred medical care to liver transplant recipients, and to be prepared to confront the rapidly changing clinical challenges and ensuing dilemmas. Adipose tissue is a complex and metabolically active organ. Visceral fat deposition is a key predictor of overall obesity-related morbidity and mortality. Limited pharmacological options are available for the treatment of obesity in the liver transplant population. Bariatric surgery may be an alternative in eligible patients. The rapidly increasing prevalence of nonalcoholic fatty liver disease (NAFLD) is a global concern; NAFLD affects both pre- and posttransplantation outcomes. Numerous studies have investigated pharmacological and nonpharmacological management of NAFLD and some of these have shown promising results. Liver transplant recipients are constantly exposed to numerous factors that result in intestinal microbiota alterations, which were linked to the development of obesity, diabetes type 2, metabolic syndrome (MS), NAFLD, and hepatocellular cancer. Microbiota modifications with probiotics and prebiotics bring gratifying results in the management of metabolic complications. Fecal microbiota transplantation (FMT) is successfully performed in many medical indications. However, the safety and efficacy profiles of FMT in immunocompromised patients remain unclear. Obesity together with immunosuppressive treatment, may affect the pharmacokinetic and/or pharmacodynamic properties of coadministered medications. Individualized immunosuppressive regimens are recommended following liver transplantation to address possible metabolic concerns. Effective and comprehensive management of metabolic complications is shown to yield multiple beneficial results in the liver transplant population and may bring gratifying results in improving long-term survival rates.

Kidney and Liver Tissue Tacrolimus Concentrations in Adult Transplant Recipients-The Influence of the Whole Blood and Tissue Concentrations on Efficiency of Treatment during Immunosuppressive Therapy.

Tacrolimus (TAC) has a narrow therapeutic index and highly variable pharmacokinetic characteristics. Close monitoring of the TAC concentrations is required in order to avoid the risk of acute rejection or adverse drug reaction. The results in some studies indicate that inter-tissue TAC concentrations can be a better predictor with regards to acute rejection episode than TAC concentration in whole blood. Therefore, the aim of the study was to assess the correlation between dosage, blood, hepatic and kidney tissue concentration of TAC measured by a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) and clinical outcomes in a larger cohort of 100 liver and renal adult transplant recipients. Dried biopsies were weighed, mechanically homogenized and then the samples were treated with a mixture of zinc sulfate-acetonitrile to perform protein precipitation. After centrifugation, the extraction with tert-butyl methyl ether was performed. The analytical range was proven for TAC tissue concentrations of 10-400 pg/mg. The accuracy and precision fell within the acceptance criteria for intraday as well as interday assay. There was no correlation between dosage, blood (C0) and tissue TAC concentrations. TAC concentrations determined in liver and kidney biopsies ranged from 8.5 pg/mg up to 160.0 pg/mg and from 7.1 pg/mg up to 215.7 pg/mg, respectively. To the best of our knowledge, this is the first LC-MS/MS method for kidney and liver tissue TAC monitoring using Tac13C,D2 as the internal standard, which permits measuring tissue TAC concentrations as low as 10 pg/mg.

Outcomes of COVID­19 in hospitalized kidney and liver transplant recipients: a single­center experience.

Introduction: Solid organ transplant recipients seem to be more susceptible to severe COVID-19. Objectives: Our study aimed to assess the clinical outcomes of COVID-19 in kidney (KTRs) and liver transplant recipients (LTRs). Patients and methods: In this single-center study, the medical records of KTRs and LTRs with PCR-confirmed COVID-19 admitted between November 9, 2020 and February 26, 2021 were retrospectively reviewed. Results: Overall, 41 patients, including 32 KTRs (78%), one kidney-pancreas transplant recipient (2.4%), and 8 LTRs (19.5%) were included. Seven patients (17%) experienced COVID-19 in the first month after transplantation. Among the KTRs, 72% were male and the median (interquartile range) age was 54 (47­62) years. During a median (interquartile range) of 12 (8­18) days of hospital stay, 72.7% of the KTRs experienced acute kidney injury, 45.5% developed acute respiratory distress syndrome (ARDS), and 30.3% died. Baseline estimated glomerular filtration rate, respiratory rate on admission, and diabetes mellitus constituted independent risk factors for in-hospital mortality in the KTRs. The LTRs experienced relatively mild COVID-19: only 2 patients (25%) required oxygen supplementation and a single patient (12.5%) died of severe ARDS. Conclusion: In summary, hospitalized KTRs with COVID-19 are at a high risk of acute kidney injury, ARDS, and death.

Different Relevance of Peripheral, Central or Nighttime Blood Pressure Measurements in the Prediction of Chronic Kidney Disease Progression in Patients with Mild or No-Proteinuria.

BACKGROUND/AIMS: Arterial hypertension is one of the leading factors aggravating the course of chronic kidney disease (CKD). It seems that the novel parameters used in the assessment of the blood pressure (BP) load (i.e. central blood pressure, nighttime blood pressure) may be more precise in predicting the cardiovascular risk and the progression of CKD in comparison with the traditional peripheral blood pressure measurements in the office conditions. The aim of the study was to assess the impact of the central, or nighttime blood pressure on the progression of CKD in patients with mild or no-proteinuria (autosomal, dominant polycystic kidney disease or IgA nephropathy). METHODS: In each of the enrolled 46 patients with CKD stage 3 or 4, serum creatinine concentration was assessed, eGFR (MDRD) was calculated, also central blood pressure and pulse wave velocity (PWV) was assessed and the 24-hour ambulatory blood pressure monitoring (ABPM) was conducted at the beginning of the study and then repeated after one-year observation period. RESULTS: During the observation period mean eGFR decreased from 44.1 (33.2-50.6) mL/min to 36.7 (29.7-46.3) mL/min. No significant differences were observed in the peripheral blood pressure or central blood pressure parameters. After one-year observation period the values of diastolic blood pressure dipping during the night significantly decreased from 16 (13-19) mmHg to 12 (10-15) mmHg; p< 0.05. The values of systolic dipping during the night or the mean BP values recorded in ABPM did not change significantly. Additionally, no significant differences in the PWV values were found. In the multivariate regression model the change of serum creatinine concentration was explained by the initial diastolic dipping values. CONCLUSION: 1. In patients with CKD stages 3 or 4 and mild or no- proteinuria, peripheral and central blood pressure did not change significantly during a one-year observation period despite the significant decline of eGFR and seems not to participate in the CKD progression. 2. Reduced magnitude of the diastolic dipping, which reflects the increase of diastolic blood pressure load during the nighttime, may play an important role in the pathogenesis of deterioration of kidney function in these patients.

Fatal Acute Respiratory Distress Syndrome Due to Influenza A (H1N1) Infection in Patients After Kidney Transplantation: A Report of Five Cases.

BACKGROUND In the general population, swine influenza is a self-limited infection. Patients after kidney transplantation, however, are at increased risk for complications and mortality from influenza A (H1N1). Acute respiratory distress syndrome (ARDS) complicates up to 55% of influenza-related pneumonia in hospitalized patients and carries a mortality of 40-46%. We describe our experience in intensive care of kidney transplant patients with ARDS complicating influenza A (H1N1) pneumonia during a flu outbreak. CASE REPORT Five adult post kidney transplantation patients with progressive respiratory failure admitted to the ICU between February 2016 and April 2016 were included in this retrospectively analysis. All patients had influenza A (H1N1) viral pneumonia (confirmed with RT-PCR) complicated by ARDS and septic shock with multiple organ dysfunction syndrome. None of the patients received seasonal influenza vaccines. All patients had negative rapid influenza bedside tests, which resulted in delay of administration of antiviral therapy prior to admission to the ICU. All patients were managed with a lung protective ventilation strategy (average days of mechanical ventilation, 17.6±15.3). Three patients required additional therapies for refractory hypoxemia, including high positive end-expiratory pressure and prone positioning. Extracorporeal membrane oxygenation was not implemented. Treatment with oseltamivir was added to a broad-spectrum antibiotic on the first to the fifth day of intensive care. Despite these measures, all patients eventually died. CONCLUSIONS Despite great progress in the management of ARDS, based mostly on advanced mechanical ventilation, early antiviral treatment of pneumonia caused by influenza A (H1N1) and annual vaccinations seem essential in prevention and management of influenza A (H1N1) infection among kidney transplant recipients.

Development and validation of limited sampling strategies for the estimation of mycophenolic acid area under the curve in adult kidney and liver transplant recipients receiving concomitant enteric-coated mycophenolate sodium and tacrolimus.

BACKGROUND: Mycophenolic acid (MPA) is widely used in solid organ transplantation. MPA absorption from enteric-coated mycophenolate sodium (EC-MPS) is delayed, which results in a delayed enterohepatic recirculation and subsequently higher and more variable MPA 12-hour trough concentration and tmax values. Therefore, MPA trough level monitoring cannot be used to monitor MPA exposure in patients who are given EC-MPS. The aim of the study was to develop and validate a limited sampling strategy (LSS) for accurate prediction of the 12-hour area under the concentration-time curve (AUC0-12h) for MPA in patients who receive concomitant EC-MPS and Tacrolimus (Prograf or Advagraf) within 196 months posttransplantation. According to our knowledge, the LSS for MPA AUC estimation using high-performance liquid chromatography to determine MPA concentrations in plasma samples of kidney and liver transplant patients receiving EC-MPS and Tacrolimus (Advagraf) has not been previously evaluated. METHODS: Seventy-four renal and liver transplant patients receiving EC-MPS and concomitant tacrolimus (either Prograf or Advagraf) provided a total of 74 pharmacokinetic profiles. MPA concentrations were measured using a validated high-performance liquid chromatography method for 9 plasma samples collected at predose and at 0.5, 1, 2, 3, 4, 6, 9, and 12 hours after the morning dose of EC-MPS after an overnight fast. LSS were developed and validated by stepwise multiple regression analysis with the use of a 2-group method (test, n = 37; and validation, n = 37). RESULTS: The 3 and 4 time point equations using C1h, C3h, C9h and C1h, C2h, C3h, C6h, respectively, were found to be superior to all other models tested. When these LSS models were tested in the validation group, the results were acceptable [for 3 time points equation: r = 0.824, percentage of prediction error: 6.32 ± 25.75, 95% confidence interval (CI): -40.71 to 79.76; percentage of absolute prediction error: 27.45 ± 29.89, 95% CI: 0.04-199.92, predictive performance, 71% of estimated AUCs comprised within 85%-115% of the measured full MPA AUC, natural logarithmic residuals (ln) mean ± SD: -0.03 ± 0.24; for 4 time points equation: r = 0.898, percentage of prediction error: 3.32 ± 18.26, 95% CI: -49.35 to 51.06; percentage of absolute prediction error: 14.05 ± 11.89, 95% CI 0.13-49.86, percentage of predictive performance, 83% of estimated AUCs comprised within 85%-115% of the measured full MPA AUC, natural logarithmic residuals (ln) mean ± SD: -0.01 ± 0.19]. CONCLUSIONS: LSS equations using concentrations at 1, 3, and 9 hours or 1, 2, 3, and 6 hours time points provided the most reliable and accurate estimations of the MPA AUC in stable renal and liver transplant recipients treated with EC-MPS and tacrolimus. Further studies on independent groups of patients are required to confirm clinical utility of the presented LSS models.

Calcineurin inhibitor sparing immunosuppressive regimens in kidney allograft recipients.

Calcineurin inhibitors (CNI), cyclosporine and tacrolimus, have had a potent impact on the success of organ transplantation. However, the nephrotoxicity associated with CNI can cause renal dysfunction, which is an independent risk factor for graft loss and mortality after kidney transplantation (KTx). Thus, the search for an optimal immunosuppressive therapy continues to be crucial in KTx. Strategies to limit CNI exposure include CNI minimization, avoidance, and withdrawal. We conducted a literature review (PubMed, Medline) on this issue. Maximum reduction in CNI is associated with a modest improvement in renal function; however, the kidney damage is observed as long as CNIs are maintained. Avoidance of CNI is associated with high acute rejection rates. CNI withdrawal may be the optimal strategy because it reduces early immunologic graft injury after KTx, particularly when CNI withdrawal is initiated before irreversible renal damage. These strategies seem feasible with mycophenolate acid, sirolimus and induction therapy with interleukin-2 receptor antibodies as concurrent immunosuppressants.

Renin-Angiotensin-Aldosterone system inhibitors and statins prolong graft survival in post-transplant glomerulonephritis.

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.

[Recurrent alveolar hemorrhage in the course of Goodpasture's syndrome]. / Nawracajace krwawienia do pecherzyków plucnych w przebiegu zespolu Goodpasture'a.

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.

[Immunossupresive drugs in renal transplantation]. / Leki immunosupresyjne w transplantologii.

Modem immunosupressive agents have greatly reduced incidence and severity of acute renal allograft rejection. One-year graft survival rate of 95% can be easily achieved with optimal immunosuppressive regimens. However, long-term kidney transplant survival has improved poorly. At present, chronic allograft nephropathy (CAN) and recipients death (mainly due to circulatory complications, neoplasms and infections) are most common reasons of graft loss in the second and subsequent years after transplantation. Moreover adverse effects of immunosuppressive drugs (nephrotoxicity, arterial hypertension, dyslipidaemia, post-transplant diabetes mellitus) can account for development of CAN. Regimens with combination of at least two drugs are administered to recipients, as it allows for using minimal effective doses and reduces the risk of adverse effects. Narrow therapeutic window of most immunosuppressive agents forces clinicians to adequately monitor serum concentration of the drug or its metabolite. Early postransplant period requires higher doses, which then are reduced. Immunosuppressive regimen is individualized, to minimize the risk of acute rejection, but also to avoid overimmunosuppression and its complications. Presently there are two trends in immunosuppressive schemes: first one to withdraw glycocorticosteroids and the other one to reduce dose or withdraw calcineurin inhibitors, mostly because of their nephrotoxicity.

[Cytokines and growth factors serum level and renal allograft function (preliminary report)]. / Cytokiny i czynniki wzrostu w surowicy u biorców nerki allogenicznej a losy przeszczepu (doniesienie wstepne).

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.

[The usefulness of tubular and glomerular proteinuria measurement in non-invasive diagnosis of vascular changes accompanying chronic allograft nephropathy]. / Ocena przydatnosci oznaczania bialek wydalanych z moczem w rozpoznawaniu stopnia zaawansowania zmian naczyniowych towarzyszacych przewleklej nefropatii alloprzeszczepu nerkowego.

Chronic allograft nephropathy (CAN) is the most important cause of late renal allograft loss. The standard diagnosis of CAN is based on pathological examinations according to Banff'97 scheme. The aim of the study was to evaluate the usefulness of tubular and glomerular proteinuria in non-invasive recognition of vascular changes accompanying CAN (AH--arteriolar hyaline thickening, CV--vascular fibrous intimal thickening). beta 2- and alpha 2-microglobulin (beta 2-m and alpha 2-m), albumin (alb), immunoglobulin G (IgG), total protein (tp) and creatinine (cr) concentration were measured in the second time urine specimen in 66 renal allograft recipients. Then the subsequent renal biopsies were done. The aim of statistical analysis (MANOVA, Stepwise Discriminant Analysis, SDA) was to diagnose CV and AH changes based on results of urine analysis listed above and the patient's age, time after transplantation and serum creatinine level (scr). Results obtained with statistical analysis were in 90.91% and 87.69% identical with CV and AH pathological diagnoses, respectively.