Katrin Ivens

Restenosis after elective coronary balloon angioplasty in patients with end stage renal disease: a case-control study using quantitative coronary angiography

Objective To assess the rate of angiographic restenosis in patients with end stage renal disease after elective coronary angioplasty. Design A retrospective case-control study of 20 patients with end stage renal disease and 20 sex and age matched controls without renal disease, who had undergone primarily successful coronary angioplasty. Control coronary angiography was performed regardless of worsening or renewed incidence of anginal symptoms. Main outcome measures Group comparison of coronary morphology, as evaluated by quantitative coronary angiography, and of cardiovascular risk factors. Results The rate of angiographic restenosis was 60% in patients with renal disease and 35% in controls. In patients with end stage renal disease the following differences (mean (SD) were found versus controls: raised plasma fibrinogen (483 (101)v 326 (62) mg/dl, p < 0.001); raised plasma triglyceride (269 (163) v 207 (176) mg/dl, p < 0.01); smaller diameter of the coronary reference segment (2.59 (0.87) v 2.90 (0.55) mm, p < 0.10); smaller minimum luminal diameter of the dilated stenosis (0.77 (0.46)v 0.97 (0.27) mm, p < 0.05). Discriminant analysis showed that minimum luminal diameter before angioplasty (r = −0.79) and fibrinogen (r = +0.34) had the highest statistical association with restenosis. Conclusions The high rate of angiographic restenosis in patients with end stage renal disease seems to be related to the size of the vessel dilated and to an increased prothrombotic risk, as indicated by higher fibrinogen concentrations.

CARDIOVASCULAR RISK FACTORS AND DISEASES AFTER RENAL TRANSPLANTATION

Cardiovascular disease is a leading cause of death after renal tranpslantation (tpx), and the incidence is considerably higher than in the general population.ObjectiveTo evaluate the incidence of atherosclerotic cardiovascular complications after tpx, the prevalence of cardiovascular risk factors, prior to and following tpx, and the association between the risk factors and complications.Patients and methodsAnalysis of atherosclerotic cardiovascular diseases (coronary artery disease, cerebral and peripheral vascular disease) and cardiovascular risk factors before and after transplantation in 427 renal transplant recipients between 1987 and 1992 (mean age at transplantation 45±12 years, 58% male, 7% diabetics) with a mean post-transplant follow-up of 29±20 months.ResultsFollowing tpx 11.7% developed atherosclerotic cardiovascular diseases, the majority coronary artery disease (9.8%). The comparison of risk factors 12 months before and 24 months following transplantation showed: prevalence of systemic hypertension (from 73% to 85%), diabetes mellitus (from 7% to 16%) and obesity with a body mass index >25 kg/m2 (from 26% to 48%) had increased significantly whereas the number of smokers halved to 20%. Triglycerides decreased significantly (from235 mg/dl to 217 mg/dl). Totaland HDL cholesterol rose significantly (from 232 mg/dl to 273 mg/dl and from 47 mg/dl to 56 mg/dl, respectively). LDL cholesterol increase was significant (from 180 mg/dl to 189 mg/dl). In the univariate analysis, cardiovascular diseases were significantly associated with male gender, age over 50 years, diabetes mellitus (DM), smoking, total cholesterol ≥200 mg/dl, LDL cholesterol>180 mg/dl, HDL cholesterol ≤55 mg/dl, fibrinogen ≥350 mg/dl, body mass index>25 kg/m2, serum uric acid >6.5 mg/dl and with more than two antihypertensive agents per day. The Cox proportional hazards model revealed DM with a relative risk (RR) of 4.3, age>50 years (RR=2.7), body mass index>25kg/m2 (RR=2.6), smoking (RR=2.5), LDL cholesterol>180 mg/dl (RR=2.3) and uric acid>6.5 mg/dl as independent risk factors.ConclusionsThe high incidence of cardiovascular disease following renal transplantation is mianly due to a high prevalence and accumulation of classical risk factors before and following transplantation. Future prospective studies should evaluate the success of treatment regarding reduction of cardiovascular morbidity and mortality in this high risk population.

A cell‐based approach to the minimization of immunosuppression in renal transplantation

Five renal transplant recipients were preoperatively treated with transplant acceptance‐inducing cells (TAICs) in a Phase‐I safety study of TAICs as an adjunct immune‐conditioning therapy in living‐donor kidney transplantation. Initially, patients received anti‐thymocyte globulin induction therapy in combination with tacrolimus and steroid immunosuppression. Over the course of 12 weeks, steroids were withdrawn and tacrolimus therapy was minimized. Three of the five patients were able to tolerate low‐dose tacrolimus monotherapy and one patient was withdrawn from all immunosuppression for over 8 months. No acute or delayed adverse events were associated with the infusion of TAICs. Monitoring of the recipient anti‐donor reactivity of TAIC‐treated patients in mixed lymphocyte cultures demonstrated that, during periods of clinically stable graft function, recipient T‐cell proliferation and cytokine secretion in response to stimulation with donor alloantigen was relatively suppressed. Therefore, although the TAIC‐II trial did not provide conclusive evidence of a beneficial effect of preoperative TAIC treatment, the results were encouraging because they suggest that TAICs promote a state of alloantigen‐specific unresponsiveness, which might allow safe minimization of pharmacological immunosuppression.

The use of different buffers during continuous hemofiltration in critically ill patients with acute renal failure

Objective: To determine the impact of different hemofiltration (HF) replacement fluids on the acid-base status and cardiovascular hemodynamics in patients with acute renal failure (ARF) and continuous veno-venous hemofiltration (CVVH).¶Design: Prospective, cohort study.¶Setting: Intensive Care Unit of the Heinrich Heine University Hospital, Düsseldorf, Germany.¶Subject and methods: One hundred and thirty-two critically ill patients with acute renal failure and continuous veno-venous HF were studied. Fifty-two patients were subjected to lactate-based (group 1), and 32 to acetate-based hemofiltration (group 2)while 48 (group 3) were treated with bicarbonate-based buffer hemofiltration fluid. Fifty-seven had a septic, and 75 a cardiovascular, origin of the ARF. Creatinine, blood urea nitrogen (BUN), serum bicarbonate, arterial pH, lactate and Apache II scores were noted daily.¶Main results: The mean CVVH duration was 9.8 ± 8.1 days, mortality was 65 %. No difference was present between the groups under investigation with regard to the main clinical parameters. Lactate- and bicarbonate-based hemofiltration led to significantly higher serum bicarbonate and arterial pH values as compared to the acetate-based hemofiltration. Serum bicarbonate values at 48 h after the initiation of CVVH treatment were 25.7 ± 3.8 mmol/l (p < 0.001) in group 1, 20.6 ± 3.1 mmol/l in group 2 and 23.3 ± 3.9 mmol/l (p < 0.001) in group 3. While a lack of increase in serum bicarbonate and arterial pH was correlated to poor prognosis in lactate- and bicarbonate-based hemofiltration, no such observation was made in acetate-based hemofiltration. Cardiovascular hemodynamics were superior in patients treated with lactate- and bicarbonate-based buffer solution as compared to those treated with acetate-based buffer solution.¶Conclusions: The degree of correction of acidosis during hemofiltration was determined by patient outcome in patients treated with lactate- and bicarbonate-based buffer solutions, but not in patients receiving acetate-buffered solution. Bicarbonate and lactate-based buffer solutions were found to be superior to acetate-based replacement fluid.

Influence of Genetic Polymorphisms of the Renin-Angiotensin System on IgA Nephropathy

Background: We evaluated the impact of the three major genetic polymorphisms of the renin-angiotensin system [angiotensinogen (AGT) gene M235T, angiotensin-converting enzyme (ACE) gene-I/D and angiotensin II-type 1 receptor (AT1R) gene A1166C polymorphisms] as risk factors in IgA nephropathy. Methods: The clinical course of 107 patients with biopsy proven IgA nephropathy followed up for 6.6 ± 5.8 years was examined. The genetic polymorphisms were determined by PCR amplification. Results: The allele frequencies of the polymorphisms studied were similar in patients and control subjects. AGT-M235T genotype was associated with the presence of nephrotic syndrome (p < 0.05), correlated to the number of antihypertensive drugs agents taken (p < 0.01) and influenced the rate of deterioration of renal function (p < 0.05). Combined analysis of AGT-M235T and ACE-I/D polymorphisms detected an interaction on affecting progression (p < 0.05). ACE-inhibition had a more pronounced effect in certain AGT-M235T and ACE-I/D genotypes (p < 0.05) and their combined analysis showed a synergistic effect (p < 0.01). No association between AT1R-A1166C polymorphism and any of the parameters studied was observed. Conclusions: Our results suggest that angiotensinogen-M235T polymorphism is an important marker of progression in IgA nephropathy in Caucasian patients, especially when analyzed in combination with ACE-I/D polymorphism.

Kidney transplantation in the elderly: age-matching as compared to HLA-matching: a single center experience.

Background. We report the short-term outcome of our patients participating within the Eurotransplant age-matching program, where kidneys from donors >65 years are transplanted to recipients >65 years regardless of human leukocyte antigen (HLA) compatibility but with short cold ischemia times, in comparison with patients >60 years transplanted with HLA-matching. Methods. Twenty-five patients (66.7±2.6 years) (donors 69±4.3 years) participated in this program (group A). The control group consisted of 21 patients (63±2.6 years) (group B) (donors 47.6±17.3 years). Results. Despite significant differences in donor age, cold ischemia time (12.3±4.6 hr in A, 22.8±4.8 hr in B, P <0.001) and a mean of 4.4±1.4 vs. 2.3±1.6 HLA-mismatches (P <0.001), there was no difference regarding the incidence of delayed graft function (64 vs. 57%), rejections (52 vs. 66.7%), infections (56 vs. 52.4%), and other complications (80 vs. 71.4%). Mean serum creatinine after 6 months was 1.94±0.49 and 1.83±0.67 mg/dl (NS). Conclusion. The short-term results of the age-matching program are promising and comparable with results from patients of similar age with HLA-matching.

Myocardial revascularization in patients with end-stage renal disease: Comparison of percutaneous transluminal coronary angioplasty and coronary artery bypass grafting

Background: Ischemic heart disease is the major cause of death inpatients with end-stage renal disease. The high prevalence of coronary artery disease results in a rising number of dialysis patients requiring myocardial revascularisation. Objective: The objective of this study was to compare the outcomes of recurrent angina, myocardial infarction, rate of reinterventions and cardiovascular death following percutaneous coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) inpatients with end-stage renal disease. Patients and methods: In a retrospective investigation 40 patients with chronic renal failure undergoing primarily PTCA and 65 patients undergoing CABG were included. Both groups were comparable for gender, duration on dialysis and the number of cardiovascular risk factors per patient. Patients undergoing PTCA were younger (53 ± 12 years vs. 57 ± 8 years; p < 0.05) and more often diabetics (30% vs. 14%; p < 0.05). Results: Most patients in both groups had a multi-vessel disease (95% in the CABG group vs. 74% in the PTCA group), in the CABG group there were significantly more patients with a triple-vessel disease (62% with vs. 40%in the PTCA group; p < 0.01), PTCA was primarily successful in 95% of the patients while complete revascularization was achieved in 88% of patients undergoing CABG. The perioperative mortality after CABG was 4.8% as compared to none after interventional revascularisation. The cumulative freedom of angina after 6, 12 and 24 months after intervention was significantly lower after PTCA (54%, 40%, 29%) than after bypass grafting (97%, 94%, 90%, p < 0.001). The frequency of reinterventions following PTCA was significantly higher compared to patients following CABG (p < 0.001). After PTCA 15 patients needed further revascularisations, 8 of them underwent CABG, whereas after CABG only two patients required additional myocardial revascularisation. There was no significant difference in the overall mortality between both groups; the survival rate after 12 and 24 months was 95% and 82% after PTCA and 93% and 86% after CABG, respectively. Condition: Although patients receiving CABG had a more severe coronary artery disease the overall mortality was comparable and clinical and functional outcome was improved compared to patients after coronary angioplasty.

Eurotransplant Senior Program ‘old for old’: results from 10 patients

More frequently there is the need for renal transplantation of older patients. Against the background of an increasing number of old donors and recipients, Eurotransplant Leiden started the Eurotransplant Senior Program (ESP) ‘old for old’ in 1999. The ESP works with donors and recipients both over 65 yr. The kidneys are transplanted with short cold ischaemia time regardless of the human leukocyte antigen (HLA) compatibility. Compatibility of blood groups, negative crossmatch and less than 5% cytotoxic antibodies are required. First experiences from 10 patients at Heinrich Heine University hospital are reported here. The course of 10 transplanted patients is described from January 1999 until November 1999 (28.4±15.8 wk). Age of donor and recipient, cause of dialysis and concomitant diseases from recipients, function of the transplanted kidney and complications are analysed. Immunosuppression consisted initially of cyclosporin A, mycophenolic acid and steroids. The results of these 10 patients were compared to 14 patients who were transplanted according to the ordinary Eurotransplant criteria (Eurotransplant Kidney Allocation System) in the same period of time. Kidneys from six donors (70.5±3.3 yr) were transplanted to 10 different recipients (66.9±2.2 yr). The control group consisted of 14 patients (47.6±14.4 yr) who received kidneys from 14 donors (48.3±10.1 yr). One double kidney transplantation was performed in the senior group, i.e. two kidneys from a marginal donor were transplanted to one recipient (‘two in one’). In the ESP group, cold ischaemia time was reduced by 5 h and mean of HLA mismatches was more than doubled. Mean length of hospitalisation of ESP and control groups was 47.2±28.2 and 34.2±11.6 d, respectively. Intraoperatively, no complications were seen, post‐operative care was performed on a normal ward. ESP patients suffered more often from delayed graft function, which led to further need for haemodialysis for 11.2 d. Finally, 9 of 10 patients acquired a satisfactory renal graft function. A total of 13 biopsies were performed in eight cases. Altogether seven acute rejections in 6 patients were found (four interstitial, one vascular, one interstitial+vascular, one clinical). The 9 patients with sufficient renal graft function were discharged with a mean serum creatinine level of 2.3±0.5 mg/dL (control: 1.9±0.8 mg/dL). Comparing these 10 recipients to a control group consisting of 14 patients, the results are comparable and encouraging. In conclusion, the short‐term results of the ESP are promising. Nevertheless, the post‐operative care requires more attention due to several complications. Though the HLA compatibility was not considered, all rejections were coped with effectively. Quality of life was improved.

Tumor Necrosis Factor-α Gene G-308A Polymorphism Is a Risk Factor for the Development of Membranous Glomerulonephritis

Background: Tumor necrosis factor-α (TNF-α) is a major pro-inflammatory cytokine. Recently, the G-308A polymorphism of the TNF-α gene has been associated with modified gene expression and increased TNF-α production in the -308A allele. We evaluated its influence on the incidence and clinical course of membranous glomerulonephritis. Methods: We studied 53 patients with biopsy-proven primary membranous glomerulonephritis followed up for 5.7 ± 4.9 years. 100 volunteers were analyzed as controls. According to the slope of the curve of reciprocal serum creatinine against time, group A (slow progressors, n = 35) and group B (fast progressors, n = 18) were defined. TNF-α G-308A polymorphism was determined by polymerase chain reaction amplification. Results: The frequency of the A-allele (associated with higher TNF-α levels) was significantly higher in patients than control subjects (patients: G-allele: 0.66, A-allele: 0.34; controls: G-allele 0.85, A-allele 0.15, p < 0.001). Similarly, the genotype distribution differed significantly between our study and control populations (patients: GG-genotype: 41.5%, GA: 49.1%, AA 9.4%; controls: GG: 71%, GA: 27%, AA 2%, p = 0.001). Age, renal function, proteinuria and blood pressure were similar at the time of renal biopsy between patients with different genotypes (NS). There was also a tendency towards an overpresentation of the A-allele in group B indicating a possible impact on the progression of membranous nephropathy, but a significance was not reached. Furthermore, no impact on renal survival in the Kaplan- Meier analysis was detected (NS). Conclusion: Our results suggest that TNF-α gene G-308A polymorphism is a risk factor for the development of membranous glomerulonephritis.

Influence of cytokine genes polymorphisms on long-term outcome in renal transplantation

Abstract:  Background:  Recently, polymorphisms of cytokine genes have been associated with modified gene expression and increased cytokine production. We evaluated the influence of interleukin‐10 (IL‐10) gene G‐1082A, tumour necrosis factor alpha (TNFα) gene G‐308A and IL‐6 gene G‐174C polymorphisms on the rejection rate, renal function and long‐term outcome in renal transplantation.