Quality System of Kidney Donation for Transplantation From Living Donors in Poland.

OBJECTIVE: The program aims to build and develop a high-quality donation system at the hospital and national level. Thirty coordinator posts for the transplantation of kidneys from living donors (LDs) were created. The coordinators' tasks were identified as determining or excluding the possibility of LD donation for kidney transplantation for every potential kidney recipient referred to the waiting list, qualifying potential LDs, supervising health monitoring for LDs and kidney recipients, and education and promotion of transplantation from LDs. METHODS: The coordinators' reports and verification of data in the national transplant register from June 1, 2018 to November 30, 2019 were analyzed. ETHICS: The study was conducted according to principles of the Declaration of Helsinki, and the Declaration of Istanbul participation was on a voluntary basis. RESULTS: Information on possible LDs was obtained from 707 (43%) of the 1630 potential recipients entered on the waiting list. In 373 cases there was no potential LD; 16 recipients did not give consent for kidney transplantation from a LD; for 318 recipients, 340 potential LDs were identified; 90 potential LDs were rejected at the initial stage for medical reasons; 60 potential donors were rejected at further stages of the qualification process; 3 persons resigned from donation; and 23 recipients were transplanted from deceased donors. Kidneys from 73 LDs were qualified and transplanted. On November 30, 2019, 91 potential donors were awaiting further qualification. As part of the program, 27 potential pairs for paired kidney exchange were reported to Poltransplant (17 pairs with positive HLA crossmatch, 10 with incompatible blood groups). CONCLUSIONS: The creation of posts for coordinators for LD kidney transplantation in centers that qualify for LD kidney transplantation enabled systematic monitoring of donation potential, which led to an increase in the number of LD kidney transplants in 2019. Making full use of donation potential should significantly increase these numbers in the coming years.

Therapeutic Problems and Pregnancy in a Patient With Infantile Nephropathic Cystinosis: A Case Report.

BACKGROUND: Cystinosis is a rare genetic disorder characterized by the abnormal accumulation of cystine in the lysosomes of various tissues and organs leading to their dysfunction. The most common type is the infantile nephropathic cystinosis which without treatment leads to renal failure and before the introduction of cysteamine was the cause of death before puberty. CASE PRESENTATION: A 27-year-old female patient with infantile cystinosis developed end-stage renal disease at the age of 10. The first kidney transplantation from patient's father was carried out at the age of 12. The recurrent urinary tract infections led to the graft failure after 6 years. Following the removal of right appendages due to the ovarian tumor, the patient underwent the second kidney transplantation from her mother at the age of 19. After the transplantation, the cysteamine treatment was irregular due to limited availability of the medicine. When it became regular in 2017 the patient did not tolerate full doses. Despite elevated blood levels of cystine and the removal of right appendages, the patient naturally became pregnant in August 2017. Except for recurrent urinary tract infections, the renal parameters remained normal throughout the entire pregnancy. However, in the 32nd week of gestation, due to preeclampsia a caesarean section was performed. A healthy daughter was born, 1400/41 and with a 9 point Apgar score. CONCLUSIONS: Due to the possibility of treatment with cysteamine and kidney transplantations, patients with cystinosis live longer and their quality of life improves. These female patients can even naturally become pregnant and give birth to healthy children.

Kidney Transplant Recipients With Rheumatic Diseases: Epidemiological Data From the Polish Transplant Registries 1998-2015.

Chronic kidney disease (CKD) is a common complication of rheumatic disorders. We analyzed the incidence of different rheumatic conditions as a primary diagnosis of end-stage renal disease (ESRD) in kidney transplant recipients in Poland. Data were received from the national waiting list for organ transplantation (Poltransplant) registries. Primary diagnosis leading to ESRD were analyzed in 15,984 patients who received kidney transplants between 1998 and 2015. There was no information about primary diagnosis in 4981 cases (31%) and in 1482 cases (9%) the diagnosis was described as unknown. Rheumatic diseases were specified in 566 (5.14%) kidney transplant recipients: lupus erythematosus, (systemic lupus erythematous nephritis) in 211 (1.92%), vasculitis in 176 (1.60%), amyloidosis AA in 82 (0.75%), hemolytic uremic syndrome in 59 (0.54%), secondary glomerulonephritis in 24 (0.22%), scleroderma in 9 (0.08%), rheumatoid arthritis in 4 (0.04%) and Sjögren syndrome in 1 (0.01%). Graft survival at 1 and 5 years were significantly better in the nonrheumatic versus rheumatic group (90 vs 87% and 76 vs 72% respectively, P = .04). Recipient survival at 5 years was significantly better in the nonrheumatic versus the rheumatic group (88 vs 84%, P = .02). Our study showed that systemic lupus erythematosus and systemic vasculitides are the major rheumatic causes of ESRD in the Polish population. Long-term graft and recipient survival were significantly better in the nonrheumatic versus the rheumatic group in the Poltransplant cohort.

Liver Donation and Transplantation in Poland: Numbers, Indicators, and Trends.

We aim to provide a panorama of liver donation and transplantation in Poland, where each year around 300 liver transplantations from deceased donors and 20 liver fragment transplantations from living donors are performed. This means about 9 transplantations per population of 1 million. Each year, the number of deceased donors reaches more than 500. In more than 50% of cases, livers are used. The law allows liver procurement from living donors. Until the end of 2013, liver fragments were recovered from 236 living donors and transplanted mainly to pediatric recipients (n = 232). A living-donor registry was created to monitor and assess the health condition of donors. The range of the national waiting list and allocation is nationwide. It is managed with the use of the Web tool www.rejestry.net. There are 2 modes of recipient referral: "urgent" and "elective." Allocation is either patient oriented and center oriented. Disease groups, which comprise the most frequent indications for transplantation in adults, include the cirrhosis group (48%), in which the highest number of procedures was performed for patients with hepatitis C virus (24%); alcohol-induced cirrhosis (14%); alcohol-induced hepatitis (8%), and hepatitis B virus cirrhosis (7%). Among pediatric recipients, the most frequent indications were congenital cholestatic diseases, which made up 38% of all transplantation indications. The results of liver transplantations are collected in the national transplant register. The 1-year graft and recipient survival with deceased donor transplantation are 81% and 84% and with living donor transplantation 86% and 89%. The 5-year graft and recipient survival in deceased donor transplantation are 69% and 73%, and in living donor transplantation are 80% and 83%.

Liver Transplant Registry in Poland: Web-Netted Quality Tool in Liver Transplantation From Deceased and Living Donors.

BACKGROUND: Poltransplant managed a national transplant registry with the use of the Web tool www.rejestry.net. It collects information about all organ transplantations in the country along with outcomes. This article presents a formal analysis of data collected in the registry for the years 1998 to 2014. MATERIALS AND METHODS: Results presented are actual, not extrapolated, numbers; these were calculated only for the events for which the observation was complete, meaning that a given term of follow-up had passed and the information on recipient's and graft survivals were available. RESULTS: All liver transplant procedures were registered from the years 1998 to 2014, with follow-up data completeness of 89% to 99%. Detailed statistical descriptions of liver transplant results were significantly better for transplants from living donors, in comparison to deceased donors, for pediatric recipients. Results for pediatric and adult recipients did not vary if the organ was from a deceased donor. Elective and primary transplantations have significantly better results in comparison to urgent and re-transplanted cases. Results depend on indications for transplantation. Significantly better results were obtained in the case of cholestatic diseases and cirrhosis other than hepatitis C virus. Significantly worse results were obtained in acute liver failure, independently of etiology. Results in the case of hepatitis C virus cirrhosis, metabolic diseases, and neoplasms do not vary significantly. CONCLUSIONS: The strength of these findings are based on the registry's reliability and completeness. The registry fulfills its aims related to collecting records and monitoring graft function, and recipient survival. The data are an important source of information, to be used by transplantation institutions and referred to in the literature.

Organ Donation From Elderly Deceased Donors and Transplantation to Elderly Recipients in Poland: Numbers and Outcomes.

The age of a donor and recipient is one medical criterion in the kidney allocation system. The number of elderly donors and recipients is steadily growing. The aim of the study was to retrospectively evaluate the 5-year results of kidney transplantation from donors over 65 years of age to recipients over 60 years of age. In the years 1998 to 2010, 8526 potential deceased donation after brain death organ donors and 8206 people (81%), who had been treated with transplantation of kidneys were referred to the Poltransplant. The actual number of deceased donors >65 years was 358 and <65 years was 7207. The actual 5-year survival of a kidney transplant from donors >65 years was 59.2% (55.3% of recipients >60 years and 60.7% of recipients <60 years of age; P < .0001) and from donors <65 years was 75.1% (67.5% of recipients >60 years and 75.7% of recipients <60 years; P < .0001). The actual 5-year survival of kidney recipients from all donors >65 years was 75.6% (79.5% younger recipients vs 65.9% elderly recipients; P < .0001). The 5-year survival of kidney recipients from all donors <65 years was 88.1% (P < .0001); 89% younger recipients and 74.3% elderly recipients (P < .0001). The above analysis of the material from the Polish registry displayed significantly worse results of kidney transplantation from donors >65 years, regardless of the age group of recipients.

National Transplants Registry in Poland: Early and Long-term Results of Organ Transplantations in the Years 1998 to 2014.

BACKGROUND: In 2006, the National Transplants Registry, administered by the national transplant organization, was introduced in Poland for monitoring the results of organ transplantations. Statistical analysis is published yearly in Poltransplant Bulletin and publicly available on the website and reported to European institutions. The Transplants Registry cooperates with another registers functioning on-line, based on the web-net tool www.rejestry.net. We present the formal analysis of data collected for the years 1998 to 2014. METHODS: Analysis covered the total number of organ transplantations in every transplant center; outcomes after 3 months and 1, 3, and 5 years; and if data were available after 10, 15, and 20 years from transplantation. Results presented are real, not extrapolated. RESULTS: Some examples are as follows. The total number of deceased kidney transplantations was 15,009; 1-year recipient survival was 95%, graft survival was 88% (data completeness of 81%), 5-year recipient survival was 87%, and graft survival was 74% (data completeness of 82%). The total number of deceased liver transplantations was 3143; 1-year recipient survival was 84%, graft survival was 81% (data completeness of 99%), 5-year recipient survival was 73%, and graft survival was 89% (data completeness of 99%). CONCLUSIONS: The National Transplant Registry is an important tool for quality and safety systems in the transplantation field on the national level. Nowadays, the Registry efficiently and effectively fulfills its tasks related to collecting records of all performed transplantations. Monitoring function for graft and recipient survival is also satisfied. Collected numbers are an important and unique source of information to be used by transplant institutions and referred to in the literature.

When less is more--case report of successful renal transplantation from a living unrelated donor to a high-risk female recipient.

Qualification for kidney transplantation for patients with a long history of renal replacement therapy and numerous medical complications requires individual analysis of all contraindications and limitations as well as advantages of the procedure. In this case report, we analyze the qualification process and posttransplantation course of a 28-year-old female patient with end-stage renal failure due to reflux nephropathy, treated with renal replacement therapy since early childhood, who received her second kidney transplant with glomerular filtration rate <40 mL/min/1.73 m(2) from a living, unrelated donor in 2009. Despite the high risk of immunological and surgical complications, transplanting organs of borderline excretory capacity, and no human leukocyte antigen matching, significant health benefits were achieved. Procurement of a kidney with borderline filtering function reduces the risk of potential negative consequences of impaired remnant filtration in the living donor. Following the principle of procuring a kidney with worse parameters from the living donors, it is necessary to perform an examination evaluating the function of each kidney. Procurement of a kidney with significantly worse parameters requires an individual assessment of benefits for the recipient.

Mutations in Pol gene of hepatitis B virus in patients with chronic hepatitis B before and after therapy with nucleoside/nucleotide analogues.

Chronic hepatitis B (CHB) is one of the most common infections worldwide. Currently approved treatments of CHB include nucleoside/nucleotide analogues (NAs). However, long-term NA therapy is associated with accumulation of resistant mutations within the hepatitis B virus (HBV) polymerase gene. The incidence of naturally occurring HBV mutations leading to primary antiviral resistance has not been fully elucidated yet. The objective of present study was to detect the frequency of mutations within the HBV polymerase gene in 263 patients naïve to nucleoside/nucleotide analogues. Prevalence of HBV Pol gene mutations secondary to NA treatment in patients without pre-existing antiviral resistance mutations was also examined. Retrospective analysis showed that HBV Pol gene mutations were present in 7 out of 263 patients prior to the treatment. Mutations observed in NA-naïve CHB patients were associated only with resistance to lamivudine and adefovir. Compensatory mutations were observed as well. In the course of antiviral treatment, HBV Pol gene mutations were identified in 65 out of the remaining 256 CHB patients (25.39%), while no mutations of any type were detected in 160 patients (62.5%). The profiles of detected mutations were comparable to those observed in other studies that focused on the analysis of clinically relevant NA-resistant mutations. In conclusion, we found out that antiviral resistance mutations may pre-exist in the overall viral population present in untreated patients, although the incidence of HBV Pol gene mutations in NA-naïve CHB patients was low and reached only up to 2.66%. However, possible circulation and transmission of NAs-resistant HBV mutants in human population should be taken into account.

Characteristics of potential living kidney donors and recipients: donor disqualification reasons--experience of a Polish center.

INTRODUCTION: Kidney transplantation is efficacious as a renal replacement, particularly pre-emptive living donation. In Poland, the rate of transplantation of living donor kidneys is only 3%. The aim of the study was to identify the most common reasons to disqualify a potential living kidney donor. METHODS: We evaluated 124 kidney donor candidates for 111 potential recipients at 1 medical center for genders and ages of donor and recipient; thus relation, donor disqualification reasons, number of potential donors for a particular recipient, prior transplantations, and kidney vasculature. RESULTS: The 111 recipients of ages 2-62 years had, 1, 2, or 3 potential donors were tested in 101, 1, and 7, cases respectively. We had 18.9% recipients referred for pre-emptive transplantation; 59.5% were on haemodialysis and 21.6% on peritoneal dialysis. In all, 89% recipients sought first kidney transplantations. Kidneys were procured from 49/124 (39.5%) of the initially evaluated donors. The full examination was completed by 92 potential donors with 68/124 donors disqualified early. Single and multiple renal arteries were detected in 56 and 36 potential donors, respectively. Donor disqualification was due to medical contraindications (39.7%), earlier transplantation from a deceased donor (25%), immunologic constraints (23.5%), donor consent withdrawn (6%) or psychological and social reasons (4.4%). CONCLUSIONS: A considerable number of donor candidates are disqualified for medical reasons.

PTPN22, PDCD1 and CYP27B1 polymorphisms and susceptibility to type 1 diabetes in Polish patients.

Type 1 diabetes (T1DM) is a common autoimmune disease with a complex genetic background. This study was aimed to investigate the association of PTPN22 G(-1123)C and C1858T, PDCD1 G7146A and CYP27B1 C(-1260)A polymorphisms with T1DM among Polish subjects. The PTPN22 gene encodes lymphoid tyrosine phosphatase, a potent negative regulator of T cell activation. PDCD1 gene gives rise to an inhibitory cell-surface receptor, expressed on activated lymphocytes. CYP27B1 encodes 1-alpha hydroxylase, responsible for conversion of the vitamin D(3) precursor into its active form, involved in the immune function. Polymorphic variants of these genes have previously been associated with various autoimmune disorders. The four polymorphisms were genotyped by PCR-restriction fragment assays in a case-control study comprising 215 T1DM patients and 236 healthy controls. The PTPN22 T1858 allele appeared significantly increased in T1DM compared to the control group (P=0.004), yielding an OR of 1.73 (95% CI 1.19-2.51). The difference in distribution of C1858T genotypes also demonstrated statistical significance (P=0.015). The frequencies of PTPN22 G(-1123)C alleles and genotypes did not differ between T1DM cases and controls, although the haplotype comprising both mutant PTPN22 alleles, C(-1123) and T1858, was significantly more frequent in affected individuals (P=0.003). G(-1123)C and C1858T were in linkage disequilibrium (D' = 0.98; r(2) =0.61 in T1DM and D' = 0.97; r(2) =0.41 in controls). No significant differences in the allele and genotype frequencies of PDCD1 and CYP27B1 polymorphisms were found between patients and controls. This study confirms the association of PTPN22 C1858T polymorphism with T1DM, whereas the effects of PTPN22 G(-1123)C, PDCD1 G7146A and CYP27B1 C(-1260)A seem unlikely, at least in the Polish population.

Association of the CYP27B1 C(-1260)A polymorphism with autoimmune Addison's disease.

Autoimmune Addison's disease (AAD) is a complex endocrine disorder with several susceptibility loci. This study was aimed to investigate the associations of CYP27B1 C(-1260)A and PDCD1 G7146A polymorphisms with AAD in a Polish cohort, comprising 101 AAD patients and 251 healthy controls. CYP27B1 encodes 1alpha-hydroxylase, responsible for conversion of the vitamin D (3) precursor into its active form, involved in the immune function. PDCD1 gene gives rise to an inhibitory immune receptor, expressed on activated lymphocytes. Polymorphic variants of these genes had previously been associated with various autoimmune disorders. Genotyping was performed by PCR-RFLP method. The CYP27B1 C(-1260) allele appeared significantly more frequent in AAD compared to controls ( P=0.020), yielding an OR of 1.53 (95% CI 1.07-2.19). The distribution of C(-1260)A genotypes also demonstrated significant difference ( P=0.003). Stratification according to the presence of concomitant autoimmune disorders revealed an association of the C(-1260) allele with the polyendocrine cases of AAD ( P=0.031), while no significance was found for the isolated ADD compared with healthy controls ( P=0.253). Overall, the association between AAD and C(-1260)A was confirmed in a meta-analysis of 325 AAD patients and 952 controls from three different European populations. Under a fixed-effect model, C(-1260) allele and CC genotype were associated with AAD susceptibility with a pooled OR of 1.44 (95% CI 1.18-1.75) and 1.88 (95% CI 1.42-2.36), respectively. No differences were observed for the PDCD1 G7146A between affected subjects and controls (p>0.05). In conclusion, this study confirms the association of the CYP27B1 C(-1260)A polymorphism with AAD, whereas the contribution of PDCD1 G7146A seems less likely.

Factors predisposing to urinary tract infections in adult kidney allograft recipients with lower urinary tract reconstruction.

OBJECTIVE: Urinary bladder augmentation or urinary diversion may be necessary for successful kidney transplantation in cases of serious urinary tract dysfunction. Patients with reconstructions of the urinary collecting system show noninferior graft survival, although urinary tract infections (UTI) may threaten kidney and recipient survivals. Herein we sought to identify risk factors for serious UTIs in cases of urinary collecting system reconstructions and to evaluate kidney survival and function. PATIENTS AND METHODS: This prospective, case-controlled study included 24 kidney allograft recipients with urinary tract reconstructions who were engrafted from 1999 to 2008. As controls we selected recipients of standard kidney transplants who were matched (1:3) for sex, age, donor type, procedure date, and immunosuppressive regimen. RESULTS: At posttransplantation 33.6 +/- 28 months follow-up, kidney allograft survival was 83% among the reconstructed and 97% among the control groups (P = NS). Kidney allograft function at 3 months in the reconstruction group showed estimated glomerular filtration rate (eGFR) calculated by the Cockcroft-Gault (C-G) equation of 70.4 +/- 20.8 vs 78.8 +/- 19.2 mL/1.73 m(2) in controls (P = .39), and at the end of follow-up, 66.3 +/- 18.1 vs 77.1 +/- 18.9 mL/1.73 m(2), respectively (P = .26). Urinary tract reconstruction patients experienced UTI in 91.7% of cases (n = 22) vs 45.6% in controls (n = 31; P < .0001). A necessity for in-hospital treatment was observed in 67% vs 28% of cases (P < .001). Urosepsis occurred in 4 study patients and 4 controls (P = NS). We observed an increased risk for serious UTI and a trend to diminished graft function (odds ratio [OR] = 1.6 per 10 ml/min of eGFr C-G; 95% confidence interval (CI) 0.97-2.77; P = .055; and OR = 14.7 per 1 mg/dL of serum creatinine; 95% CI 0.61-352.3; P = .097). Another predictor for UTI was cytomegalovirus disease (CMV). CONCLUSION: Kidney recipients requiring urinary tract reconstructions additionally benefit from obtaining the best quality allografts and CMV prophylaxis.

Dynamic behavior of Arabidopsis eIF4A-III, putative core protein of exon junction complex: fast relocation to nucleolus and splicing speckles under hypoxia.

Here, we identify the Arabidopsis thaliana ortholog of the mammalian DEAD box helicase, eIF4A-III, the putative anchor protein of exon junction complex (EJC) on mRNA. Arabidopsis eIF4A-III interacts with an ortholog of the core EJC component, ALY/Ref, and colocalizes with other EJC components, such as Mago, Y14, and RNPS1, suggesting a similar function in EJC assembly to animal eIF4A-III. A green fluorescent protein (GFP)-eIF4A-III fusion protein showed localization to several subnuclear domains: to the nucleoplasm during normal growth and to the nucleolus and splicing speckles in response to hypoxia. Treatment with the respiratory inhibitor sodium azide produced an identical response to the hypoxia stress. Treatment with the proteasome inhibitor MG132 led to accumulation of GFP-eIF4A-III mainly in the nucleolus, suggesting that transition of eIF4A-III between subnuclear domains and/or accumulation in nuclear speckles is controlled by proteolysis-labile factors. As revealed by fluorescence recovery after photobleaching analysis, the nucleoplasmic fraction was highly mobile, while the speckles were the least mobile fractions, and the nucleolar fraction had an intermediate mobility. Sequestration of eIF4A-III into nuclear pools with different mobility is likely to reflect the transcriptional and mRNA processing state of the cell.

IgA nephropathy in kidney allograft recipients-therapeutic perspective.

INTRODUCTION: A growing number of patients are losing their kidney allografts due to glomerulonephritis. Although posttransplant IgA nephropathy (IgAN) is regarded as benign, it may lead to late allograft loss in a substantial number of patients. The aim of this study was to evaluate the influence of posttransplant IgAN on long-term transplantation outcomes, risk factors for progression of graft dysfunction, and effectiveness of therapeutic interventions. PATIENTS AND METHODS: We evaluated, potential risk factors for accelerated graft loss among 27 kidney allograft recipients with posttransplant IgAN, comparing graft survival in a control group matched for population and transplantation-related parameters. We evaluated the effectiveness of therapeutic interventions regarding immunosuppressive regimen, and hypertension control including angiotensin converting enzyme inhibitor (ACEI) usage with Kaplan-Meier, Cox proportional hazard plots, and log-rank tests in statistical analyses. RESULTS: Compared with the control group, patients with IgAN experienced a 6.57 higher risk for dialysis dependence (P < .01, 95% CI 1.4 to 30.83). The risk for accelerated graft loss in the course of IgAN was associated with graft dysfunction (RR = 2.16 for additional 1 mg/dL of serum creatinine at glomerulonephritis presentation; P < .03, 95% CI 1.2 to 4.36) and intense proteinuria as evidenced by a RR = 4.67 for the presence of the nephrotic syndrome (P < .05, 95% CI 0.95 to 22.8). Immunosuppression enhancement resulted in a significantly decreased risk of dialysis dependence, namely, RR = 4.76 (95% CI 1.12 to 20, P < .04). With ACEI treatment there was a tendency for a 2.8-fold decreased risk of dialysis dependence, without reaching statistical significance (P = .14). CONCLUSIONS: Patients with posttransplant IgAN may benefit from intensifying maintenance immunosuppression, which slows progression to end-stage graft dysfunction.

Serum TGF-beta1 correlates with chronic histopathological lesions in protocol biopsies of kidney allograft recipients.

INTRODUCTION: Transforming growth factor-beta (TGF-beta) is a well-known profibrotic factor playing a role in chronic kidney allograft nephropathy. Cyclosporine (CsA)-sparing immunosuppressive regimens may improve long-term graft function. Our aim was to study the influence of immunosuppressive treatment with versus without calcineurin inhibitors on serum TGF-beta levels and histological changes in protocol biopsies of kidney allograft recipients. PATIENTS AND METHODS: In this prospective, randomized study of 42 low-rejection risk patients we randomized two groups: group A: mycophenolate mofetil (MMF), prednisone, daclizumab, and reduced CsA dose for 7 months (5 mg per kg per day) followed by complete withdrawal (n = 21); and group B: normal CsA dose (10 mg per kg per day adjusted according to C2 levels), MMF, prednisone, and no daclizumab (n = 21). METHODS: In both groups we performed histological assessments (Banff 97) and measured serum TFG-beta levels before as well as, at 3 and 12 months after transplantation. RESULTS: We found a relationship between immunosuppressive regimen and the TGF-beta concentration over 1 year of observation. Before transplant the TGF-beta1 levels did not differ between the groups (P = .29); at 3 months they were 33 +/- 9 vs 49 +/- 15 pg per mL, respectively, in groups A and B (P = .08), and at 12 months they were 39.5 +/- 4 versus 55.5 +/- 11 pg per mL, respectively, in groups A and B (P = .03). Protocol biopsies at 12 months in group B showed chronic tubular lesions more pronounced than in group A. TGF-beta1 concentrations were significantly higher among group B than A. We conclude that TGF-beta1 concentration may predict the development of kidney graft fibrosis; early CsA withdrawal may achieve a reduction in chronic tubular and interstitial injury of cadaveric kidney allografts.

36-month follow-up of 75 renal allograft recipients treated with steroids, tacrolimus, and azathioprine or mycophenolate mofetil.

OBJECTIVES: The aim of this retrospective study was to assess the incidence of acute rejection episodes (AR), diabetes mellitus (DM), and serum creatinine (SCr) among renal transplant recipients treated with tacrolimus (Tac), steroids (S), and mycophenolate mofetil (MMF) or azathioprine (Aza). METHODS: Seventy-five renal allograft recipients enrolled in the COSTAMP study were followed for a period of 3 years. Patients were randomized to receive either Tac and MMF (n = 41) or Tac and Aza (n = 34) concomitantly with steroids. Follow-up assessments were performed at 3, 6, 12, 24, and 36 months. RESULTS: Patient survival at month 36 was 91.18% in the Tac/Aza/S group and 97.56% in the Tac/MMF/S group. Graft survival at month 36 was 82.35% and 85.37%, respectively. During the study period, 22 cases of biopsy-proven AR were diagnosed in 17 patients (22.6%). After 36 months the total number of AR was 11 in the Aza-treated group (32.4%) and 11 in the MMF-treated group (26.8%). DM was diagnosed de novo in 17 individuals (22.6%). During 36 months, 10 patients from Aza-treated group (29.4%) and seven from MMF-treated group developed DM (17.1%). Serum creatinine values were not significantly different in both arms of the study. Comparison of arterial blood pressure and total cholesterol revealed no significant changes in any of the studied groups. CONCLUSIONS: We conclude that combinations of steroids, tacrolimus, and azathioprine or MMF provide good results with regard to renal function.

The role of the protocol biopsies in renal allograft recipients.

Subclinical rejection and long-term cyclosporine nephrotoxicity are well-known risk factors of chronic allograft nephropathy. In a prospective study 32 low-risk patients were randomized to either a reduced CsA dose (5 mg/kg/d) and daclizumab (group A, n = 16) for 7 months posttransplant with subsequent CsA tapering/withdrawal, or to a normal CsA dose (10 mg/kg/day) without daclizumab (group B, n = 16). Both groups received MMF and prednisone. Protocol biopsies were obtained at engraftment and 3 and 12 months after Tx. The number of rejection episodes was the primary endpoint. The secondary endpoints were: renal function, histological parameters related to CsA, and serum levels of TGF-beta and PDGF-BB. A low incidence of clinically suspected rejection episodes was observed (19% in group A and 12.4% in group B; P = NS). Although protocol biopsies showed 12 subclinical rejection episodes (six in group A, six in group B), serum creatinine levels were not different between the examined groups at 3 months. However, at 12 months, there was a statistically improved mean creatinine level in group A patients (1.2 mg/dL +/- 0.5 in group A vs 1.54 mg/dL in group B; P <.05). Chronic histopathologic changes were significant for biopsies at 3 and 12 months in both groups compared to the baseline findings for protocol biopsies (with no differences between groups, or between 3 and 12 months in both groups). Serum TGF-beta and PDGF-BB did not differ between the groups. Protocol biopsies may be useful to monitor safety and efficiency of new immunosuppressive protocols. Immunosuppressive regimens with low CsA doses followed by the drug's complete withdrawal seem to be efficient and safe in low-risk kidney allograft recipients.

Pneumonia in kidney allograft recipients.

Infectious complications, including pneumonia, remain one of the leading causes of morbidity and mortality in kidney allograft recipients. The aim of the study was to evaluate the relationship between pneumonia occurrence and treatment duration and recipient age, cause of native kidney insufficiency, dialysis duration, time between transplantation and onset, HLA matching, PRA immunosuppressive protocol, acute rejection incidence and treatment, kidney function at the pneumonia onset, as well as presence of comorbid conditions. One hundred and twenty pneumonia cases occurred in kidney allograft recipients transplanted between 1991 and 2000 with 12 to 120 months follow-up. Twenty five percentage of pneumonia episodes were diagnosed during the first posttransplant month, 25% between 2 and 6 months, and 25% at 0.5 to 3 years. Treatment duration measured from pneumonia onset to the study endpoint of recovery, which was defined as antibiotic withdrawal, show 50% of patient we cured after 15 days and 75% after 24 days of treatment. The risk of prolonged pneumonia treatment was associated with: second versus first kidney transplantation with RR = 2.3 (P <.02) and medians of treated time 28 versus 15 days; as well as serum creatinine level above 2 mg/dL (RR = 1.4; P <.098). Exposure to enhanced-potency immunosuppressive protocols including induction therapy with mono- or polyclonal antibodies increased the RR = 1.65 (P <.02), and lengthened the time to 18 versus 14 days. Maintenance immunosuppression with agents other than cyclosporine also enhanced the risk. (RR = 2.18; P <.068).