D. Lewandowska

Lamivudine therapy for chronic hepatitis B in renal transplant recipients.

HBV infection has adverse effect on patient and graft survival in renal allograft recipients.Lamivudine therapy is effective in serological and virological response in renal allograft recipients.Tolerance to lamivudine is very good.Lamivudine is the drug of choice for treatment and prophylaxis of hepatitis B after kidney transplantation.Resistance to lamivudine during prolonged therapy is associated with the emergence of lamivudine resistant strains due to mutations in the YMDD locus of the HBV polymerase gene.New nucleoside analogues (adefovir, entecavir) are promising agents in the treatment of a flare-up of hepatitis B associated with emergence of lamivudine resistant HBV mutants. Chronic liver disease due to hepatitis B virus (HBV) infection remains a significant cause of morbidity and mortality after renal transplantation. Administration of immunosuppressive drugs facilitates viral replication and may lead to increased frequency of progressive chronic hepatitis, cirrhosis and hepatocellular carcinoma. Chronic HBV infection adversely affects both patient and graft survival. Because of increased risk of death HBV-seropositive renal graft recipients require prophylaxis and treatment of hepatitis B. Interferon due to its immunomodulating effects, risk of activation of rejection is not recommended for transplant recipients. Lamivudine seems to be efficacious and useful for treating hepatitis B in renal transplant recipients. The main disadvantages of lamivudine are relapse after withdrawal of the agent and emergence of lamivudine resistant strains due to mutations in the YMDD locus of the HBV polymerase gene during prolonged lamivudine therapy. Optimal lamivudine treatment regimen for HBsAg-positive renal transplant recipients should be defined. It seems better to initiate lamivudine therapy before or immediately after transplantation to prevent viral replication. The clinical course of hepatitis in most patients with lamivudine resistant HBV mutants seems relatively benign and long-term resistance was well tolerated. Discontinuation of lamivudine in order to minimize the emergence of drug resistant HBV mutants is safe in selected groups of patients. Lamivudine therapy has become the treatment of choice in HBV positive renal transplant recipients and improves prognosis and outcome of infected patients.

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 drugs 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).

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.

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.

Identification of patients with increased immunological risk among potential kidney recipients in the Polish population

Pretransplant identification of allosensitized patients is possible thanks to new technologies, which allow for accurate detection of clinically relevant alloantibodies. Implementation of these methods in the screening of patients awaiting transplantation increased their chance for successful donor-recipient matching. Here, 1460 patients reported to the Polish National Waiting List were screened with the Luminex Screen (LS) solid phase test for anti-HLA antibodies. The patients with detected anti-HLA antibodies were assayed with the Luminex Single Antigen (LSA) tests in order to establish defined antigen specificity of the alloantibodies. The results were compared with data on the immunization assessed with the routine complement-dependent-cytotoxicity panel-reactive-antibody assay (PRA CDC). The study showed significantly higher sensitivity of the LS method when compared with PRA CDC. It has been shown that LSA test is a useful technique identifying the specificities of alloantibodies. In particular, LSA allowed to assess donor specific antibodies (DSA) to previous mismatches (MM) and to determine acceptable HLA mismatches of the potential donors. The introduction of solid phase tests in routine pretransplant diagnostics allowed for faster and more accurate assessment of the immunological risk of the recipients and optimal donor-recipient matching. Hence, the presented algorithm of solid phase assays has become a new standard for the identification of allosensitized patients awaiting kidney transplantation in Poland.

Hand-assisted laparoscopic donor nephrectomy: a single centre experience

Introduction The advantages of a minimally invasive nephrectomy are a faster recovery and better quality of life for the donors. Until recently, the majority of donor nephrectomies in Poland were done by open surgery. Aim To present a single centre experience in hand-assisted laparoscopic donor nephrectomy (HALDN). Material and methods The first videoscopic left donor nephrectomy in Poland was performed in our department in 2003 using a hand-assisted retroperitoneal approach. From 2011, we changed the method to a transperitoneal approach and started to harvest also right kidneys. Since then, it has become the method of choice for donor nephrectomy and has been performed in 59 cases. Preoperatively, kidneys were assessed by scintigraphy and by angio-computed tomography. We harvested 32 left and 27 right kidneys. There were double renal arteries in 2 cases and triple renal arteries in 1 case. The warm ischaemia time (WIT) was 80–420 s (average 176.13 s); operative time was 85–210 min (average 140 min). Results All procedures were uncomplicated, and all donors were discharged after 2–8 days with normal creatinine levels. The average follow-up period lasted 23 months (1–51 months). Out of all of the cases, 1 case had two minor complications, while all others were uneventful. None of the donors were lost to follow-up. All of the kidneys were transplanted. There were 2 cases of delayed graft function (DGF) and 2 cases of ureter necrosis. One of those kidneys was lost in the third postoperative week. Conclusions Our limited experience shows that HALDN is a safe method and should be used routinely instead of open surgery.

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.

Prevalence of the coronary artery disease risk factors and 10-year risk of cardiovascular mortality based on HeartScore in people qualified for kidney donation

BACKGROUND The living kidney donor is exposed to the renal function impairment as a result of kidney donation, which may increase the risk of cardiovascular diseases. It seems justified to identify cardiovascular risk factors prior to kidney donation. MATERIAL AND METHODS We analyzed data of 50 consecutive potential kidney donors. All individuals underwent clinical examination and lipid profile. For each subject we calculated atherogenic index. To calculate the 10-year risk of cardiovascular death, the HeartScore calculator was used. RESULTS The most frequent risk factors were obesity, lipid disorders, and smoking. In 72% of subjects, at least 1 of the risk factors was detected. Atherogenic index values considered to indicate high risk of atherosclerosis were found in 16% of subjects. More than 40% of subjects had more than 1 coronary risk factor, and most had 2. In 58% of subjects, the calculated HeartScore risk value was consistent with risk estimated for age, and in 26% it exceeded this value by 1-9% (mean, 3.1%). CONCLUSIONS The prevalence of coronary risk factors is high in potential kidney donors. HeartScore seems to be a useful method to evaluate the risk of cardiovascular mortality in these individuals, and is a simple tool to use in controlling the influence of the modification of risk factors on the global risk in follow-up. Comparison with the value of risk acceptable according to age and sex may oblige the physician to take action to reduce it.