Rejection quantity in kidney transplant recipients is associated with increasing intracellular interleukin-2 in CD8+ T-cells.

BACKGROUND: CD8+ T-cells and interleukin-2 play an important role during organ rejection in kidney transplant recipients. Numerous studies showed increased interleukin-2 levels during acute rejection. The aim of our study is to show an association between intracellular interleukin-2 in CD8+ T-cells and the incidence of those who underwent organ rejection in kidney transplant recipients. METHODS: 407 transplant recipients were included into this study. The rejection incidence was investigated from the patient records. White blood cells from recipients were separated using a ficoll gradient. The cells were double-gated (CD3+ and CD8+) for the analysis of cellular percentage for intracellular interleukin-2 with a flow cytometer. RESULTS: The percentage of CD8+ cells with detectable intracellular interleukin-2 was significantly higher in renal transplant recipients with a documented rejection compared to recipients without any history of rejection (9.06±0.50, N=133 vs. 4.28±0.24, N=274, p<0.0001, t-test). Further, there was a significant increase in patients with one (8.02±0.54, N=80, p<0.0001, t-test), two (10.40±1.17, N=33, p<0.0001, t-test) or three (11.82±1.58, N=18, p<0.0001, t-test) rejection events. CONCLUSIONS: Past studies showed, that during acute organ rejection intracellular interleukin-2 is increased in cytotoxic T-cells, supposed to be a marker for this event. We were able to show, that intracellular interleukin-2 in CD8+ T-cells is also increased after organ rejection. Furthermore it seems to depend on the quantity of rejection events. Further studies in recipients with increased intracellular interleukin-2 in cytotoxic CD8+ T-cells and documented history of organ rejection are needed to identify this as a possible risk factor for further rejection events.

Transitional cell carcinoma of the native urinary tract after kidney transplantation: recommendations following a long-term retrospective analysis.

INTRODUCTION: The aim of the current study was to explore the clinico-oncological characteristics, and the therapeutic and survival parameters, of renal transplant recipients who developed de novo transitional cell carcinoma (TCC) over a 30-year period at the authors' center. METHODS: Retrospective analysis of records from all registered patients who underwent kidney transplantation at the center between November 1979 and January 2010 who developed de novo TCC of the urinary tract. RESULTS: From all 2001 patients analyzed during the study period, 21 recipients developed 19 TCCs of the bladder and 6 TCCs of the upper urinary tract. Among bladder TCCs, 13 (68.4%) cases were confined to mucosa (pTa or carcinoma in situ, n = 7) or submucosa (pT1, n = 6) and 6 others (31.6%) infiltrated the detrusor muscle (≥p T2); the grading distribution was 5 cases of G1, 6 of G2 and 8 of G3. All recurrent cases (n = 8) revealed local or systemic progression. The overall and tumor-specific patient survival rates were 80.2%, 54.0% and 30.0% and 84.9%, 67.4% and 58.9% for 1, 5 and 10 years, respectively. CONCLUSIONS: In the light of the observed increased aggressiveness of TCC in renal transplant recipients, more frequent examinations and possibly more invasive follow-up protocols should be considered for patients with 1 or more risk factors for development of TCC. Urine cytology (including ureteral wash cytology) may be used as a reliable diagnostic tool in these patients. Prophylactic contralateral nephroureterectomy might be an option in patients at high risk.

De novo renal cell carcinoma of native and graft kidneys in renal transplant recipients.

OBJECTIVE: • To access the epidemiological, clinical and survival features of renal transplant patients with de novo renal cell carcinoma of native and graft kidneys. PATIENTS AND METHODS: • We performed a retrospective examination of the data of 2001 consecutive renal transplant recipients at our centre between November 1979 and January 2010. RESULTS: • In the patient cohort examined, 30 renal cell carcinomas were observed in 26 individuals (incidence 1.5%) with 25 tumours in the native and five in allograft kidneys. Mean tumour size in surgical specimens was 44 ± 36 mm. The rate of papillary cancer was 37.5%. • After a mean follow-up of 58.6 ± 62.3 months, 15.4% of the patients died from cancer and 57.7% were in complete remission. • Overall and tumour-specific survival rates at 1, 5 and 10 years were 86.1%, 75.1% and 43.8%, and 90.4%, 83.5% and 66.8%, respectively. CONCLUSIONS: • Due to increasingly improved survival after renal transplantation, de novo malignancies might soon become the main cause of intermediate- or long-term mortality. • Current data support an increased risk of renal cell carcinoma in renal transplant recipients in a particularly aggressive way, but low tendency for metachronous contralateral evolution. • With continuous radiological follow-ups, acceptable oncological outcome can be achieved. Graft tumours may have a favourable prognosis.

Development of urological cancers in renal transplant recipients: 30-year experience at the Frankfurt Transplant Center.

Fatal post-transplant malignancies with a high proportion of genitourinary neoplasms represent a serious long-term challenge. With continuous improvement of the allograft and patient survival, cancer development after renal transplantation may soon turn to the leading morbidity cause. In a retrospective single-center study of 1990 renal transplant recipients between November 1979 and November 2009, records of patients with urological neoplasms including epidemiological, clinical and survival parameters were accessed. Sixty-six de novo urological malignancies in 58 recipients were recorded in the study period, being most common after skin cancers (15.6% of enregistered tumors). From these, 29 were renal cell cancers, including five neoplasms of transplanted kidney, 24 transitional cell carcinomas, 11 prostate carcinomas, and two germ cell carcinomas with incidence rates of 1.5%, 1.2%, 0.9% and 0.2%, respectively. The patient follow up was virtually complete. Tumor-related death was found in 44% of cases. By multivariate analysis, no influence of either duration of dialysis, mode or duration of immunosuppression, gender or age at transplantation on overall patient survival could be demonstrated. This study, documenting a 30-year single center experience, emphasizes the increased risk for urological neoplasms occuring after renal transplantation. Screening strategies for urological cancers should be optimized.

Reactivation of hepatitis B two years after rituximab therapy in a renal transplant patient with recurrent focal segmental glomerulosclerosis: a note of caution.

We report on the reactivation of hepatitis B in a renal transplant patient who had been treated with rituximab for recurrent focal segmental glomerulosclerosis two and a half yr previously. He lost his anti-hepatitis B surface antigens and anti-hepatitis B core antigen antibodies and developed hepatitis B virus (HBV)-DNA positive hepatitis. Hepatitis C, which had been successfully treated by alpha interferon 10 yr before, remained quiescent. We suggest regular controls of HBV-DNA, anti-HBV antibodies and transaminases for prolonged periods in patients with status post-hepatitis B treated with rituximab. Prophylactic therapy with lamivudine and/or hepatitis B hyperimmune globulin may be considered in patients with a decrease in anti-HBV antibodies.

Abrogation of nephrotic proteinuria by rituximab treatment in a renal transplant patient with relapsed focal segmental glomerulosclerosis.

Relapse of focal segmental glomerulosclerosis (FSGS) after renal transplantation is 20-40%. Recurrence after a first relapse is 80%. The only current treatment is plasmapheresis and/or cyclophosphamide. We report successful treatment of a second relapse in a 48-year-old patient. At age 33, FSGS was diagnosed. The patient began hemodialysis 1 year later. In her first renal transplant, she developed recurrent FSGS and reached terminal transplant failure 3 years later. Eight years later, a second transplant was performed. Immunosuppressive regimen: steroids, mycophenolate mofetil (MMF), tacrolimus (TAC), and rabbit anti-thymocyte globulin. Proteinuria of 2-6 g/day was detected and a biopsy showed recurrent FSGS. Plasmapheresis was started without success. Another biopsy still showed FSGS. The patient received two doses of rituximab (375 mg/m2 each) i.v. Three weeks later, proteinuria was 350 mg/day (serum-creatinine 1.6 mg/dl). Twelve months later, proteinuria was at 90 mg/day. Rituximab might be an option for recurrent FSGS after renal transplantation.

Long-term consequences of live kidney donation follow-up in 93% of living kidney donors in a single transplant center.

Live kidney donation is increasing rapidly. Increases of blood pressure and proteinuria but no accelerated loss of renal function in kidney donors have been described. The credibility of this research is hampered by retrieval rates of only 50-70% of donors. We studied renal function, blood pressure, proteinuria, parathyroid hormone, 1,25(OH)2 cholecalciferol and calcium and phosphate excretion in a live kidney donor cohort with a 93% retrieval rate. A comprehensive physical and laboratory examination including 24-h urine collection was conducted. None of the 152 donors had renal failure. Mean time after uninephrectomy was 11 +/- 7 (range: 1-28) years. GFR had declined by 25%. Blood pressure had increased from 125 +/- 15/79 +/- 11 to 134 +/- 19/81 +/- 9 mmHg (p < 0.01) but remained significantly below normal. Fifty six percent of donors developed proteinuria (>150 mg/day), but only 10% had albuminuria. Nineteen percent had increased PTH, 30% had a decreased tubular reabsorption rate of phosphate. Regarding risk factors for a higher loss of GFR, greater increases in blood pressure or proteinuria no consistent picture emerged. Because of the high incidence of proteinuria and possible changes in bone metabolism inclusion of kidney donors in registries appears worthwhile.

Living kidney donors' long-term psychological status and health behavior after nephrectomy - a retrospective study.

BACKGROUND: The aim of the study was a comprehensive psychological evaluation of living kidney donors. Existing studies indicate a high donor satisfaction with the decision to donate and good donor quality of life in short-term, as well as in long-term follow-up periods. In many studies, questionnaires with only a few items have been used to assess psychological health or well-being; however, most studies exclusively measured quality of life. Therefore, our retrospective single center study applied a broad assessment of psychological variables. We evaluated whether standardized, differentiated and specific psychological research instruments confirmed the positive, long-term condition of kidney donors as reported in the scientific literature, albeit based on a limited set of variables. METHODS: From 1973 to 2001, 152 nephrectomies were performed in Frankfurt. In the context of a detailed medical follow-up examination, a psychological study was implemented using a semi-structured interview and a set of four standardized, well-established questionnaires. Overall, data from 145 donors was included in the medical follow-up and 112 donors participated in the psychological investigation. RESULTS: The mean age of donors was 55.9 (+/- 10.7) yrs at follow-up, and the time-since-donation was 11.2 (+/- 7.5) yrs. Donors scored better on a wide range of the psychological scales such as psychological symptoms, health behavior and health consciousness that was to be expected in comparison with data from representative German population samples. Nearly all donors (97%) would choose to donate again, and 91% remain entirely satisfied with their decision. CONCLUSION: The study demonstrates that existing results, reporting positive long-term psychological donor well-being, could be confirmed by a set of comprehensive, standardized and multi-methodological psychological instruments.