T. Steiner

Post-transplant diabetes mellitus: risk factors, frequency of transplant rejections, and long-term prognosis

BackgroundEstimates of the incidence of new-onset diabetes after renal transplantation vary between 2% and 54%. It was the aim of the present trial to study the prevalence of post-transplant diabetes mellitus (DM), the risk factors, the frequency of transplant rejections, and the long-term prognosis.MethodsWe studied all consecutive patients with endstage renal disease, but without DM who received kidney transplantation at our center since 1992 (n = 253; age, 52.2 ± 12.6 years; body mass index, 22.0 ± 7.9u2009kg/m2). Follow up was 3.3 ± 1.6 years (range, 0.1–17.7) years.ResultsIn total, 43/253 patients (17%) developed new-onset DM after transplantation. Patients with new-onset diabetes were significantly older (58.3 ± 11.4 vs 50.9 ± 12.5 years; P < 0.01) and had a tendency to a higher body mass index (24.0 ± 8.5 vs 21.6 ± 7.8u2009kg/m2; P = 0.077). There were no differences between the groups in respect of blood pressure control (137.7 ± 19.0/81.8 ± 14.2 vs 137.1 ± 21.9/83.9 ± 13.1u2009mmHg; P = 0.89/0.39), glomerular filtration rate (58.0 ± 28.1 vs 64.1 ± 22.1u2009ml/min per 1.73u2009m2; P = 0.13), steroid dosage (4.5 ± 1.2 [n = 21] vs 4.6 ± 2.2 [n = 135] mg/day; P = 0.13), or the frequency and dosage of immunosuppressive drugs such as cyclosporine, tacrolimus, and sirolimus during the follow up. However, more patients with post-transplant diabetes received steroids (83.7% vs 64.3%; P = 0.021) and azathioprine (41.9% vs 24.3%; P = 0.030). Patients with new-onset diabetes had higher serum creatinine values (163.4 ± 67.9 vs 138.7 ± 59.5u2009µmol/l; P = 0.017). The mean hemoglobin (Hb)A1c in patients with DM was 6.28 ± 1.29% (Tosho HPLC; mean normal, 5.15%). In 18 patients (7.1%) transplant rejections occurred (16 patients without DM [7.6%] vs 2 patients with new-onset DM [4.7%]; P = 0.39). On performing multivariate analysis, the only parameter found to be associated with new-onset DM was the body mass index (R2 = 0.05; β = 0.23; P = 0.02), and the only factor associated with transplant rejection was fasting blood glucose (R2 = 0.07; β = 0.28; P = 0.02). None of the other parameters included in the models (age, duration after transplantation, diabetes duration, immunosuppressive therapy, HbA1c, HLA mismatches) showed any associations.ConclusionsThe prevalence of new-onset DM after renal transplantation was 17%. The most important parameter associated with new-onset diabetes was a higher body mass index, and the most important parameter associated with transplant rejection was an elevated fasting blood glucose level. To prevent transplant rejections and to improve patients’ outcome, in addition to providing optimal immunosuppressive therapy and HLA matching, good blood pressure control and HbA1c, but also near normal fasting blood glucose levels, should be achieved.

Anemia After Renal Transplantation: An Underestimated Problem

In end-stage renal disease patients anemia is known to be an independent risk factor for cardiovascular disease and death. In a monocenter retrospective analysis, we investigated 207 stable patients (68 women/139 men) who underwent a first renal transplantation. Immunosuppressive therapy was performed with either cyclosporine plus mycophenolate mofetil, tacrolimus plus mycophenolate mofetil, or rapamycin plus mycophenolate mofetil; 43.5% of the patients were treated with steroids. Seventy-eight patients (37.7%) displayed anemia, including 8.7% with a severe disorder displaying an average hemoglobin (Hb) level of <6.8 mmo/L in men and <6.2 mmol/L in women. In 8.2% of the cases, we observed moderate anemia (Hb 6.8-7.4 mmol/L in men and 6.2-6.8 mmol/L in women), and in 20.8% (29 men and 14 women), mild anemia (Hb <8.06 mmol/L in men and <7.45 mmol/L in women). Erythropoietin was administered in 55.5% of patients with severe anemia, 53% with moderate anemia, and 11.6% with mild anemia. Serum creatinine level was a significant predictor of anemia (B -0.004; SE 0.001; P < .01). Among patients with creatinine >200 micromol/L, 63% were anemic compared with 22% of those with a serum creatinine level <200 micromol/L (P < .05). No correlation was observed with immunosuppressive medication or treatment with angiotensin-converting enzyme inhibitors/angiotensin-II receptor antagonists. During a 3-year follow-up, both mortality and graft failure rates were significantly greater among anemic patients nonanemic patients (mortality 3.3% vs 0.5%, P < .001; graft failure 4.3% vs 0%, P < .001). We found an unexpectedly high incidence of anemia in patients with well-functioning grafts. Anemia as a risk factor for mortality and graft failure should be treated more intensively among renal transplant patients.

Multi-colour FISH on preoperative renal tumour biopsies to confirm the diagnosis of uncertain renal masses

PurposeIn some cases with uncertain renal tumour lesions, it would be helpful to perform biopsies for the preoperative differential diagnosis. In our study, we evaluated the benefit of multi-colour interphase fluorescence in situ hybridization (M-FISH) on fine-needle core biopsies in uncertain renal masses.MethodsWe prospectively performed three ultrasound-guided percutaneous biopsies in 25 patients with indeterminate renal masses preoperatively. Histopathology was performed on two remaining cores samples. M-FISH was performed on one core for chromosomes 1, 2, 6, 9, 7, 17, the loci 3p24pter, and 3p13p14. After interphase FISH evaluation, we classified tumours and compared the results with histopathological findings.Results16 were classified as renal malignancies: 14 (56%) clear cell renal cell carcinomas (RCCs), 1 papillary RCCs (4%), and 1 “adenocarcinoma” (4%). Seven patients (28%) had a benign tumour, i.e. 6 (24%) were oncocytomas and 1 was classified as leiomyoma (4%). In two cases (8%), no renal neoplasms were found. In 19 out of 21 cases (90.5%), the preoperative diagnostic fine-needle biopsy matched the final histological findings. The combination of histopathological examination and M-FISH leads to a higher (95.5 vs. 90.5%) diagnostic fidelity as histology alone.ConclusionsUltrasound-guided percutaneous renal tumour biopsy is an accurate and safety method for the histopathologic evaluation of uncertain renal masses. The M-FISH represents a new highly sensitive and specific method to confirm histopathological classification in less than 24xa0h which can be used in routine laboratory diagnosis.

BCG strain S4-Jena: An early BCG strain is capable to reduce the proliferation of bladder cancer cells by induction of apoptosis.

BackgroundIntravesical immunotherapy with Mycobacterium bovis bacillus Calmette-Guérin has been established as the most effective adjuvant treatment for high risk non-muscle-invasive bladder cancer (NMIBC). We investigated the differences between the S4-Jena BCG strain and commercially available BCG strains. We tested the genotypic varieties between S4-Jena and other BCG strains and analysed the effect of the BCG strains TICE and S4-Jena on two bladder cancer cell lines.ResultsIn contrast to commercially available BCG strains the S4-Jena strain shows genotypic differences. Spoligotyping verifies the S4-Jena strain as a BCG strain. Infection with viable S4-Jena or TICE decreased proliferation in the T24 cell line. Additionally, hallmarks of apoptosis were detectable. In contrast, Cal29 cells showed only a slightly decreased proliferation with TICE. Cal29 cells infected with S4-Jena, though, showed a significantly decreased proliferation in contrast to TICE. Concordantly with these results, infection with TICE had no effect on the morphology and hallmarks of apoptosis of Cal29 cells. However, S4-Jena strain led to clearly visible morphological changes and caspases 3/7 activation and PS flip.ConclusionsS4-Jena strain has a direct influence on bladder cancer cell lines as shown by inhibition of cell proliferation and induction of apoptosis. The data implicate that the T24 cells are responder for S4-Jena and TICE BCG. However, the Cal29 cells are only responder for S4-Jena and they are non-responder for TICE BCG. S4-Jena strain may represent an effective therapeutic agent for NMIBC.

Renal Retransplantation: A Retrospective Monocentric Study

Approximately 10% to 20% of all annual renal transplantations are retransplantations and up to 20% of patients on waiting lists need a repeat kidney because of previous graft failure. The immunological risk is much greater among retransplanted patients than first-time kidney recipients. It is likely that retransplantation will become even more prevalent in the future. However, clinical studies or retrospective data are rare in this patient population. We retrospectively investigated 50 recipients after second or third renal transplantations in our center since 2001. Immunosuppression was performed with corticosteroids, mycophenolate mofetil (MMF), tacrolimus, and induction therapy with either thymoglobulin (2.5 mg/kg body weight; n = 27) or 20 mg basiliximab on days 0 and 4 (n = 22) after renal transplantation; 1 patient was treated with antithymoglobulin Fresenius after combined liver-kidney transplantation. Acute rejection occurred in 12 recipients (44.4%) after thymoglobulin and in 7 recipients (31.8%) after basiliximab induction therapy (P < .05). In 4 (14.8%) thymoglobulin- and 5 (22.7%) basiliximab-treated recipients, vascular rejections were observed (P = NS). Patients with basiliximab treatment showed improved renal function at 1 year after transplantation: serum creatinine 134.3 mumol/L versus 199.6 mumol/L in the thymoglobulin group (P < .05). Over the observation period the renal function remained stable or improved in both groups if rejection treatment was successful. However, allograft failure was higher in the basiliximab-treated group, namely, 18.1% versus 14.8% in thymoglobulin-treated patients, but the difference did not reach statistical significance. In 3 (11.1%) thymoglobulin- and 4 (18.2%) basiliximab-treated patients cytomegalovirus (CMV) infections complicated the follow-up (P = NS). In the follow-up period of 5 years, no malignant diseases were seen in either group. Three basiliximab-treated recipients died in the first year due to sepsis or cardiovascular complications. Two thymoglobulin-treated patients developed BK virus nephropathy in the follow-up period. In conclusion, we observed a high immunological risk and rejection risk among retransplanted kidney recipients in our center. Particularly, severe vascular rejections with a harmful long-term impact on allograft function were observed in this population. Induction treatment seems to be successful to reduce risk and achieve better results. Single-shot thymoglobulin may be preferable to reduce severe vascular rejection and prevent allograft failure than basiliximab with the same infection rate.

Presence of Cardiovascular Disease in Patients on a Waiting List for Renal Transplantation and in Patients After Kidney Transplantation in a Single Center

BACKGROUNDnCardiovascular risk in hemodialysis patients is enhanced, resulting in a higher mortality rate compared with the general population, yet the average wait time for renal transplantation in Germany is 5-7 years. The age of wait-listed patients has risen progressively. The aim of this study was to evaluate the prevalence of cardiovascular disease in patients on the waiting list in our center before and after renal transplantation as well as the extent to which invasive treatment was required in these patients.nnnMETHODSnThe study investigated 2 groups: 350 patients on the renal transplantation waiting list at our center in 2008 and 324 patients who underwent renal transplantation at the same center in the years 2003-2007.nnnRESULTSnIn 2008, 141 women and 209 men with a mean age of 48.6 years (range 13-71 years) were on the waiting list. In the years 2003-2007, 98 women and 226 men with a mean age of 54.3 years (range 16-78 years) received renal transplants. One hundred six patients on the waiting list for renal transplantation had to undergo coronary angiography. There is no upper age limit for donors or recipients in our program. Mean age at admission on the waiting list was 48.6 years (range 13-71 years). Mean age at transplantation was 54.3 years (range 16-78 years) in our center. Most of these patients were asymptomatic but presented a risk profile that included diabetes mellitus, severe general atherosclerosis, a pathologic ergometric test, or abnormal myocardial scintigraphy. Only in 1 case could coronary heart disease be excluded. Seventy patients (20%) suffered from mild to moderate coronary heart disease without the need for intervention. In 5 patients (1.4%) coronary bypass surgery was necessary due to severe 3-vessel coronary heart disease. In 2 cases (0.6%) replacement of the aortic valve was performed because of aortic valvular stenosis. Coronary angioplasty without implantation of stents was done in 2 patients (0.6%). Twenty-two patients (6.8%) were treated with implantation of bare metal stents and 6 patients (1.7%) with drug-eluting stents. After renal transplantation, 22 patients (6.8%) suffered from peripheral arterial occlusive disease. In 58 patients, coronary heart disease was documented by angiography. 16 patients (4.9%) had 1-vessel disease, 23 patients (7%) 2-vessel disease, and 19 patients (5.8%) 3-vessel disease. Myocardial infarction was documented in 18 patients (5.5%) before and in 5 patients (1.5%) after renal transplantation. Bare metal stent implantation was performed in 6 patients (1.8%) after transplantation. One patient received a drug-eluting stent after renal transplantation. In the years 2003-2007, 22 patients underwent coronary bypass surgery before kidney transplantation.nnnCONCLUSIONnThe prevalence of coronary heart disease is high in patients on the waiting list and after renal transplantation. The majority of these patients are clinically asymptomatic. One-third of the patients with coronary heart disease had to be treated invasively. Nevertheless, many diabetic patients are very sick from multiple complications after the waiting time, making theme unsuitable for transplantation.

Impact of immunologic and nonimmunologic variables on long-term outcome after kidney transplantation.

OBJECTIVEnTo assess the effect of longer cold ischemia time and other parameters on outcomes after kidney transplantation, where both organs were taken from the same donor and transplanted in the same clinic.nnnMETHODSnRetrospective analysis of renal transplants at our center.nnnRESULTSnFrom December 1990 to June 2006, we identified 166 transplant patients who received one organ from a pair. Median donor age was 52.4 years, median follow-up of recipients was 56 months (range = 0-156). Cold ischemia time of the group who underwent first transplantation (receiving the first kidney of a pair from one donor, designated group 1) was 644 minutes; for the second transplantation (group 2), 917 minutes (P < .0001). No difference was observed in warm ischemia times (40.8 +/- 12.9 vs 42.5 +/- 12.7 minutes, P = .4) or number of mismatches (MM; 3.4 vs 3.5, P = .7). The 5-year graft survival of the whole group was 66% with a death-censored value of 75%. Group 1 patients tended to show better primary graft function rates (80% vs 72%; P = .1). No significant differences were observed in 1-year graft survival rates for the two groups (81% vs 78%, P = .7) or in long-term graft survival (log-rank: P = .7). There was no influence of the number of MM on delayed graft function rates, but it was significant for long-term graft survival (log-rank: P [uncensored for death] = .023 for 0-3 MM vs 4-6 MM).nnnCONCLUSIONSnNonimmunologic parameters have less influence on the outcome of kidney transplantation than immunologic factors.