[Vaccinations and medical recommendations for patients traveling after organ transplantation].
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Bacterial Vaccines↗
Biomedical subjects
U Heemann
Publications and source records attributed to U Heemann.
[Dosage and monitoring of tacrolimus after kidney transplantation].
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Dose-Response Relationship, Drug↗
Cyclosporine A and azathioprine are equipotent in chronic kidney allograft rejection.
Chronic rejection is the major cause of graft loss after kidney transplantation. Various immunosuppressive protocols have been used to ameliorate this process. We investigated whether cyclosporin A- (CyA) or azathioprine- (Aza) based immunosuppression is better able to slow the progression of chronic rejection. Fisher kidneys were transplanted into bilaterally nephrectomized Lewis rats. Recipients received CyA (1.5 mg/kg/day, s.c.) for 10 days, and were treated from day 11 with either CyA (1.5 mg/kg)+pred (0.15 mg/kg) (C+P),Aza (2 mg/kg)+pred (A+P), vehicle+pred (P), or vehicle alone (controls) (n = 8/group). Proteinuria was regularly assessed and grafts were harvested for morphological, immunohistological, and molecular biological analysis at week 24. By week 12 proteinuria had increased to significant levels. At week 24, proteinuria was significantly lower and creatinine clearance was significantly higher in C+P and A+P, than in P or controls. Morphological analysis supported these functional results: at week 24, glomerulopathy, tubular atrophy and intimal proliferation (as assessed according to the BANFF score) were less pronounced in C+P and A+P, as compared with P or controls. These morphological parameters were accompanied by a reduced infiltration of ED-1+ macrophages and CD-5+ T lymphocytes. In P or controls the synthesis of IL-2Ralpha mRNA was markedly elevated at this time. In parallel to the reduced cellular infiltration, IL-2Ralpha mRNA expression was markedly inhibited, both, in C+P and A+P. There were no significant differences between C+P and A+P regarding the parameters studied. In conclusion, both C+P and A+P reduced the infiltration of activated T lymphocytes, and the pace of chronic kidney allograft rejection. The outcome of C+P and A+P based therapy did not differ significantly.
Animals↗
SDZ-RAD prevents manifestation of chronic rejection in rat renal allografts.
BACKGROUND: Chronic rejection remains the most frequent cause of renal graft loss over the long term. However, effective treatment of this process is not yet available. SDZ-RAD (40-O-[2-hydroxyethyl]-rapamycin) is a new, orally active rapamycin derivative with potent immunosuppressive activity. We have examined the effects of SDZ-RAD in a well-established model of chronic renal allograft rejection in rats. METHODS: Kidneys of Fisher (F334) rats were orthotopically transplanted into bilaterally nephrectomized Lewis recipients. To suppress an initial episode of acute rejection, rats were briefly treated with low doses of cyclosporine for the first 10 days. Thereafter they received either SDZ-RAD (0.5 mg/kg(day) or vehicle. At 24 weeks, functional evaluations were performed, kidneys were harvested, and histological, immunohistological, and reverse transcription-polymerase chain reaction evaluations were performed. RESULTS: Animals treated with SDZ-RAD developed lower proteinuria and less glomerulosclerosis as compared with controls. Additionally SDZ-RAD reduced the infiltration of macrophages and lymphocytes and the expression of intercellular adhesion molecule-1, laminin, and fibronectin. Furthermore, we observed a reduced expression of growth factor mRNA (transforming growth factor-beta and platelet-derived growth factor-AA) in these animals. CONCLUSION: Our results demonstrated that SDZ-RAD effectively ameliorates chronic renal allograft rejection in rats, probably mediated by suppression of growth factors.
Animals↗
Conversion from cyclosporine A to tacrolimus after kidney transplantation due to hyperlipidemia.
As more than 90% of renal grafts retain their function 1 year after renal transplantation, side effects of immunosuppressive therapy gain more and more importance. In a randomised prospective study, we investigated the effects of conversion from cyclosporine A to tacrolimus due to hyperlipidemia in recipients of renal allografts. Fifty-seven patients with stable graft function treated with cyclosporine were randomly assigned to conversion to tacrolimus or continuation of their current therapy and followed for 1 year. Twenty-seven patients were switched and 30 patients remained on cyclosporine A. Cholesterol levels decreased significantly in the tacrolimus group as compared to controls in the intent to treat analysis. When only those patients were evaluated who received cyclosporine or tacrolimus during the whole study, statistical significance was even more pronounced. Triglyceride levels decreased in the tacrolimus group, whereas they increased in controls. Creatinine levels remained stable and no acute rejection was observed. A switch to tacrolimus is a safe alternative in cases of hyperlipidemia after renal transplantation.
Adult↗
Cystatin C--an accurate marker of glomerular filtration rate after renal transplantation?
The performance of serum cystatin C as a screening marker of reduced creatinine clearance in renal transplantation was evaluated and compared to serum creatinine. In addition we studied whether cystatin C accurately reflects creatinine clearance over the entire range of transplant function. Serum cystatin C, serum creatinine, and creatinine clearance were measured in 110 adult renal transplant recipients. Cystatin C detected reduced creatinine clearance with the high sensitivity of 95%. Serum cystatin C and serum creatinine did not differ regarding 90 and 95% sensitivity, derived from the receiver-operating characteristics plot. We demonstrated a strong correlation and linear association between 1/cystatin C and creatinine clearance over the entire range of transplant function, equivalent to that of 1/creatinine. In summary, serum cystatin C accurately reflects creatinine clearance over the entire range of transplant function and is as efficacious as serum creatinine to detect reduced creatinine clearance in renal transplant recipients.
Adult↗
Lipopolysaccharide pretreatment protects from renal ischemia/reperfusion injury : possible connection to an interleukin-6-dependent pathway.
In vivo administration of low doses of lipopolysaccharide (LPS) to rodents can protect these animals from subsequently administrated, usually lethal doses of endotoxin or LPS. In this study we tested the effects of LPS pretreatment on ischemia/reperfusion injury in the kidney. Male C57/B1 mice were pretreated with different doses of LPS or phosphate-buffered saline on days -4 and -3. The right kidney was removed, and the vessels of the left kidney were clamped for 30 or 45 minutes on day 0. Creatinine levels and survival of animals were monitored. To test the involvement of cytokines, additional animals were harvested before ("time 0") and 15 minutes, 1, 2, 8, and 16 hours after reperfusion for histology, immunohistochemistry, terminal deoxynucleotidyltransferase-mediated UTP end-labeling assay, and reverse transcriptase-polymerase chain reaction analysis (including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, inducible nitric oxide synthase (iNOS), and interferon (IFN)-gamma messenger RNA (mRNA)). In controls, renal ischemia of 30 minutes was nonlethal, whereas 73% of the animals died within 48 +/- 18 hours, after 45 minutes of ischemia. All different doses of LPS protected the animals from lethal renal ischemia/reperfusion injury. Starting at similar levels, serum creatinine increased significantly in controls but not in LPS-pretreated animals over time. As early as 2 hours after reperfusion, tubular cell damage was significantly more pronounced in controls than in LPS-treated mice. In controls, tubules deteriorated progressively until 8 hours of reperfusion. At this time, more than 50% of tubular cells were destroyed. This destruction was accompanied by a pronounced leukocytic infiltration, predominantly by macrophages. In contrast, LPS pretreatment prevented the destruction of kidney tissue and infiltration by leukocytes. The terminal deoxynucleotidyltransferase-mediated UTP end-labeling assay revealed significantly more apoptotic cells in controls compared with LPS-pretreated animals. IL-1, IFN-gamma, and iNOS mRNA expression did not differ between the groups throughout the time points examined. However, the expression of TNF-alpha mRNA was significantly increased at 2 hours and IL-6 mRNA was significantly down-regulated before ischemia and shortly after reperfusion in the LPS-pretreated kidneys. Therefore, we found that sublethal doses of LPS induced cross-tolerance to renal ischemia/reperfusion injury. Our data suggest that increased TNF-alpha and reduced IL-6 mRNA expression might be responsible. However, more studies are needed to decipher the exact mechanism.
Animals↗
Male gender predisposes to development of endotoxic shock in the rat.
OBJECTIVE: After intravenous (i.v.) injection of lipopolysaccharide (LPS) macrophages release nitric oxide (NO) due to the expression of the inducible NO synthase (iNOS). After LPS NO is abundantly produced also in the cardiovascular system and may contribute to the development of hypotension and shock. Since the immune response, the synthesis of NO and the regulation of blood pressure (BP) differ between males and females, in the present study the effect of LPS on BP, renal function, the plasma and urinary concentration of the metabolites of NO as well as the splenic and aortic expression of the iNOS gene were compared between male and female rats. METHODS: BP and renal function were measured in anesthetized rats following the i.v. injection of LPS (E. coli, 4 mg/kg). The NO2- and NO3- (metabolites of NO=NOx) concentration was measured by the Griess reaction. The iNOS gene expression was studied by RT-PCR. RESULTS: Four hours after LPS, BP of males (n=9) was reduced by 63+/-12 mmHg versus 10+/-4 in females (n=7, P<0.005). Aminoguanidine, a selective inhibitor of iNOS, prevented the reduction of BP in males. The plasma concentration of NOx (P(NOx)), microM) was lower in hypotensive males (128+/-20) than in normotensive females (235+/-29, P<0.005). Males also exhibited lower urinary NOx excretion (U(NOx)V) after LPS (P<0.001 vs. females). Prior castration of males provided protection against hypotension (fall of BP: -4+/-4 mmHg, n=6, P<0.02 versus males) and resulted in higher P(NOx) as well as U(NOx)V (both P<0.001 versus males and not different from females). Prior ovariectomy (n=5) had no influence on the hemodynamic and NOx response to LPS. Male rats displayed enhanced aortic iNOS/beta-actin ratio relative to females after LPS (n=3 in each group, P<0.05). CONCLUSIONS: (1) Male gender may sensitize to LPS-induced shock and (2) sensitivity of males to endotoxin is associated with an attenuated, not exaggerated total rate of NO synthesis.
Animals↗
The Whitaker test, a useful tool in renal grafts?
OBJECTIVES: To evaluate the Whitaker test, a pressure flow examination, for its prognostic value in dilated renal transplants because urologic complications, such as ureteral stenosis, are significant problems after kidney transplantation. METHODS: Twenty-five patients with obstruction of the renal transplant and subsequent percutaneous nephrostomy were evaluated with a urodynamic pressure flow test (Whitaker test) in combination with antegrade pyeloureterography. The results of the Whitaker test were related to the serum creatinine values. RESULTS: The Whitaker test demonstrated normal pressure flow (less than 15 cm H(2)O) in 7 patients, pressure flow between 15 and 25 cm H(2)O in 10, and pathologic results (greater than 25 cm H(2)O) in 8 patients. After percutaneous nephrostomy, the serum creatinine level decreased in 22 of 25 patients, although the urodynamic pressure flow revealed a significant obstruction (Whitaker test greater than 25 cm H(2)O) in only 8 patients. The sensitivity of the Whitaker test to indicate the relevance of post-renal transplant stenosis in comparison to the declining serum creatinine level after successful percutaneous nephrostomy was 79%; the specificity was 50%. CONCLUSIONS: The results of our study indicate that a decreasing creatinine level in correlation with radiologic results is the leading finding in dilation of transplanted kidneys without rejection. The Whitaker test, as a pressure flow examination, provided no additional information.
Adolescent↗
Effect of angiotensin-converting enzyme inhibition on growth factor mRNA in chronic renal allograft rejection in the rat.
BACKGROUND: Despite considerable progress in immunosuppression, the incidence of chronic renal allograft rejection has not decreased. Recent studies have revealed that angiotensin-converting enzyme (ACE) inhibition ameliorates graft arteriosclerosis, glomerulosclerosis, and tubular atrophy. Moreover, it decreases systemic and glomerular capillary hydrostatic pressure in a rat kidney allograft model. We evaluated the effects of the ACE inhibitor enalapril on cytokine and growth factor expression in chronically rejecting rat kidney allografts. METHODS: Kidneys of Fisher (F344) rats were orthotopically transplanted into Lewis (Lew) rats. To prevent acute rejection, cyclosporine A (1.5 mg/kg/day) was given to all recipients during the first 10 days after transplantation. Enalapril (60 mg/L) or vehicle was added to the drinking water 10 days after transplantation. Animals were harvested 20 weeks after transplantation for histologic and immunohistologic studies, as well as for evaluation of cytokine and growth factor mRNA by semiquantitative polymerase chain reaction. RESULTS: Controls developed severe signs of chronic rejection, such as glomerular and vascular lesions, associated with a large number of infiltrating leukocytes. Enalapril-treated animals developed less proteinuria and other signs of chronic rejection. The mRNA levels of transforming growth factor-beta 1 (TGF-beta 1), platelet-derived growth factor A and B chain (PDGF A and B), insulin-like growth factor-I (IGF-I), interleukin-1 (IL-1), and monocyte chemoattractant protein-1 (MCP-1) were significantly reduced in the enalapril group and were most pronounced for IL-1 and PDGF A. In addition, we found an increased level of renal angiotensinogen mRNA after treatment with enalapril. CONCLUSIONS: Treatment with enalapril attenuated the development of proteinuria, ameliorated morphological damage, decreased leukocyte infiltration, and prevented a rise in renal mRNA levels of growth factors and cytokines in kidney grafts in a rat model of chronic renal allograft rejection.
Angiotensin-Converting Enzyme Inhibitors↗
[Hepatitis G virus infection in hemodialyzed children and adults following kidney transplantation].
Recently, a new human virus hepatitis G virus was identified. The aim of the present study was to use a combination of the reverse transcription-polymerase chain reaction and a new test for antibodies to the viral envelope protein E2 to assess the prevalence of hepatitis G virus infection in sera of children and adults treated with hemodialysis or peritoneal dialysis as well as in sera of those who underwent renal transplantation. Hepatitis G virus RNA prevalence was higher in the shole group of patients with renal failure than in control group. The difference between hepatitis RNA prevalence in transplanted group and in control group was found to be significant. Anti-E2, which are is considered as an indicator of a past hepatitis G virus infection, were detected in the similar rate in the treated and control subjects. Time on hemodialysis was significantly longer in hepatitis G virus infected patients as compared to uninfected patients and all patients with hepatitis G virus RNA have a history of blood transfusions. Patients with renal failure treated with dialysis or subjected to renal transplantation are at increased risk of acquiring the hepatitis G virus infection. Higher rates of the hepatitis G virus RNA and similar prevalence of anti-E2 in patients with renal failure as compared to controls suggest that the rate of hepatitis G virus infection resolution in immunosuppressed patients with renal failure might be lower than in immunocompetent subjects.
Adolescent↗
In vivo migration of lymphocytes in chronically rejecting rat kidney allografts.
Histological analyses have identified lymphocytes and macrophages as the predominant leukocyte populations that infiltrate organs undergoing chronic rejection. In order to define the time frame of this infiltration, we investigated the in vivo migration pattern of lymphocytes in a well-established rat model of chronic kidney allograft rejection. F344 kidneys were orthotopically transplanted into bilaterally nephrectomized Lewis rats. Recipients were treated with cyclosporin A (1.5 mg/kg/per day) for the first 10 days. After anti-CD18 or vehicle pretreatment, peripheral blood lymphocytes obtained from naive Lewis rats and labeled with 3H-uridine were injected into transplanted rats 12 and 16 weeks after transplantation. Organs were harvested 4, 8, and 12 h thereafter. After 12 weeks, proteinuria developed, accompanied by all signs of chronic rejection including glomerular sclerosis. Labeled lymphocytes rapidly infiltrated grafted kidneys 4 h after injection. Even more lymphocytes had accumulated in the grafts 12 h after injection. After 16 weeks, few lymphocytes had emigrated into the graft at 4 h, while infiltration was most pronounced by 12 h. Pretreatment with anti-CD18 inhibited the influx of lymphocytes. There was no difference between the patterns of lymphocytes derived from naive and transplanted rats. Our results emphasize the importance of endothelial cells in chronically rejecting kidneys for the control of leukocyte influx. Beta2-integrins may play a central role in determining the transendothelial migration during this process.
Animals↗
Conversion from cyclosporine to tacrolimus in renal transplant recipients with gum hyperplasia.
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Cyclosporine↗
Quality of life in end-stage renal disease patients after successful kidney transplantation: development of the ESRD symptom checklist - transplantation module.
The End-Stage Renal Disease Symptom Checklist - Transplantation Module (ESRD-SCL((R))) was developed to assess the specific physical and psychological quality of life of renal transplant recipients, with a special focus on side effects of immune system suppression therapy. A list of potentially relevant items was administered to 458 transplant recipients. The symptoms present in >20% of patients were chosen, and factor analysis was used to create the final questionnaire which consists of 43 items in six dimensions: (1) limited physical capacity (10 items; internal consistency: Cronbach's alpha = 0.85); (2) limited cognitive capacity (8 items, alpha = 0.82); (3) cardiac and renal dysfunction (7 items, alpha = 0. 76); (4) side effects of corticosteroids (5 items, alpha = 0.77); (5) increased growth of gum and hair (5 items, alpha = 0.78), and (6) transplantation-associated psychological distress (8 items, alpha = 0.80). All questions are scored on a five-point Likert scale. Validity was demonstrated in correlation with corresponding SF-36 scales and in a stepwise hierarchical regression model predicting the subscales of the ESRD-SCL by sociodemographic and medical data. The ESRD-SCL was found to have adequate reliability, test-retest correlations in a subsample of 88 stable patients after 1 year, and construct validity.
Adolescent↗
[Quality of life following transplantation. The impact ofa new immunosuppressive substance].
The improvement of quality of life is one of the major goals in the treatment of patients after renal transplantation. While immunosuppressive therapy is present in almost all of these patients, little is known about the effects of newer immunosuppressive agents. We therefore investigated the impact of tacrolimus on life quality. From November 1997 to January 1998, a questionnaire was handed out which focussed on physical and mental problems as well as sexual capacity and the attitudes towards graft, donor and transplant related side effects. 50 kidney graft recipients treated with tacrolimus were matched to 50 patients with a cyclosporine-based immunosuppression (= controls). Values are given as mean +/- standard deviation. Tacrolimus treated patients had a mean creatinine of 1.8 +/- 0.8 mg/dl, as compared to 1.6 +/- 0.7 mg/dl in controls. The overall status of health was assessed to be good in 82% of the tacrolimus group (controls: 80%). 38% were working full-time (controls: 20%). Only 14% of patients described their physical condition as poor (16% in controls). Sexual function was good in 66% (controls: 74%) and poor in 10% (controls: 12%). Mental function was assessed to be good in 92% (controls: 82%). The majority of patients felt comfortable with their physical, sexual and mental capabilities. This was independent from the immunosuppressive regimen.
Cyclosporine↗
Continuous venovenous hemodialysis treatment in critically ill patients after liver transplantation.
BACKGROUND: Acute renal failure (ARF) in critically ill patients is associated with a high mortality rate. Continuous renal replacement therapy (CRRT) is now widely used for the treatment of ARF in these critically ill patients. We retrospectively analyzed the role of CRRT as a prognostic parameter in patients receiving a cadaveric liver graft in 1998. METHODS: We reviewed the patient records of all adult recipients of a cadaveric liver graft (N = 54) in 1998 and compared those who underwent CRRT treatment (N = 19) to those without CRRT treatment (N = 35). RESULTS: Mortality was high in the continuous venovenous hemodialysis (CVVHD) group (58%). At the time of transplantation, creatinine (1.7+/-0.4 vs. 1.0+/-0.1 mg/dl), blood urea nitrogen (40+/-13 vs. 22+/-3 mg/dl), aspartate aminotransferase (ASAT; 585+/-420 vs. 242+/-97 U/liter), and bilirubin (11.6+/-4.1 vs. 6.5+/-1.9 mg/dl) were higher in the CVVHD group than in controls, whereas hemoglobin (10.3+/-0.6 vs. 10.8+/-0.4 g/dl), white blood cells (6.3+/-0.6 vs. 7.0+/-0.8/nl), and thrombocytes (110+/-18 vs. 90+/-10/nl) were similar. After transplantation, liver graft function was impaired in the CVVHD group as compared with controls. CONCLUSIONS: The necessity for CRRT in patients after liver transplantation correlates with a high risk of death. Thus, more efforts have to be made to prevent renal failure in patients after liver transplantation.
Acute Kidney Injury↗
Coinhibition of immune and renin-angiotensin systems reduces the pace of glomerulosclerosis in the rat remnant kidney.
The development of progressive glomerulosclerosis (GS) has been attributed to a number of humoral and hemodynamic factors, however, neither the exact pathomechanism nor the prevention and treatment have been clearly established. Renin-angiotensin system (RAS), interleukin-2 (IL-2)-activated T cells, systemic BP, and serum lipid levels all have been recognized as pathogenetic factors. According to our working hypothesis, a combination therapy with the inhibition of RAS and IL-2 system may be more potent in the prevention of the progression of GS than a monotherapy. After 5/6 subtotal nephrectomy, rats were treated with either the angiotensin-converting enzyme-blocker enalapril (E), the angiotensin II AT1 receptor blocker candesartan cilexetil (CA), the IL-2 synthesis inhibitor tacrolimus (T), or a combination of these agents. Proteinuria, as a functional hallmark of GS, was determined regularly, and at week 16, systolic BP, plasma total cholesterol, and triglyceride (TG) levels were measured and kidneys were harvested for morphologic and immunohistochemical analysis. Combination therapy was more effective (proteinuria: CA + T: 29.3+/-12.8 mg/24 h, E + T: 31.3+/-13.0 mg/24 h; GS: CA + T: 10.7+/-4.1%, E + T: 8.3+/-4.6%, P < 0.01) than monotherapy (proteinuria: T: 49.3+/-17.3 mg/24 h, CA: 53.2+/-18.1 mg/24 h, E: 51.1+/-26.6 mg/24 h; GS: T: 10.9+/-4.4%, CA: 23.8+/-4%, E: 14.2+/-5.3%, P < 0.05, with control values of proteinuria: 77.6+/-27.1 mg/24 h and GS: 28+/-2.9%). The number of infiltrating ED-1 (rat macrophage marker) macrophages (T: 161.5+/-51.2 cells/field of view, CA: 203.6+/-102.3, E: 178.6+/-35.3, CA + T: 140.2+/-63.2, E + T:128.2+/-75.6), and CD-5+ (rat T cell marker) T lymphocytes (CA + T: 261.5+/-103.6, E + T: 236+/-94.8) was significantly reduced by the treatment protocols (controls: ED-1: 356+/-100, CD-5: 482.9+/-154.5). These results indicate that an inhibition of RAS either with angiotensin-converting enzyme or AT1 receptor blockade, together with the inhibition of IL-2 synthesis, is more effective in the prevention of GS than a single treatment alone.
Animals↗
[Diagnostic procedure in renal artery stenosis].
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Captopril↗