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Biomedical subjects

Markus Giessing

Publications and source records attributed to Markus Giessing.

14 recordsLinked to original sources

Improved diagnosis of early kidney allograft dysfunction by ultrasound with echo enhancer--a new method for the diagnosis of renal perfusion.

BACKGROUND: Conventional ultrasound parameters such as the resistance index (RI) are only of limited use in the diagnosis of early allograft dysfunction. We, therefore, performed a prospective study to compare the value of ultrasound contrast media (USCM) with conventional US in the diagnosis of early allograft dysfunction. METHODS: A total of 48 consecutive kidney recipients underwent US examination after USCM administration 4-10 days after transplantation. Arterial inflow was determined in the interlobar artery and renal cortex using time-intensity curve (TIC) software. The difference in time-to-peak intensity between these two vascular territories was determined, and a perfusion quotient (PQ) was defined as the ratio of TIC increase of interlobar artery to renal cortex. Three patients with segmental loss of renal perfusion demonstrated by Doppler US were excluded. RESULTS: Nineteen patients had an uneventful clinical course (control group); PQ was 1.2 +/- 0.4. Seven patients with a large perirenal haematoma, without rejection had an increased PQ (P < 0.05) and a prolonged time difference (P < 0.05). Based on clinical and histological criteria, the remaining patients were classified as acute tubular necrosis (ATN) (n = 7), non-vascular rejection (n = 7) or vascular rejection (n = 5). RI determination could not discriminate these groups. Patients with ATN (PQ = 1.6 +/- 0.7) or non-vascular rejection (PQ = 1.1 +/- 0.6) had a lower PQ than patients with vascular rejection (PQ = 2.2 +/- 0.8, P < 0.05). The time difference in all three subgroups was longer compared with controls. CONCLUSIONS: USCM might be superior in the diagnosis of early kidney allograft dysfunction compared with conventional US by means of RI determination. Perirenal haematoma, ATN and vascular rejection are associated with characteristic changes of the TIC.

Adolescent↗

Ureteral complications in the renal transplant recipient after laparoscopic living donor nephrectomy.

OBJECTIVES: We report on ureteral and surgical complications in our first 110 consecutive recipients of kidneys procured with laparoscopic living donor nephrectomy (LLDN). METHODS: The records of all living donor transplants with LLDN performed between February 1999 and December 2004, including 10 pediatric transplants, were reviewed retrospectively. Three urologists performed LLDN using a pure laparoscopic non-hand-assisted transperitoneal technique. Kidney transplantation was performed in a standard fashion. For ureteroneocystostomy, the intravesical Politano-Leadbetter (P-L) technique was used. RESULTS: Two-year patient and graft survival was 99% and 98%, respectively. Serum creatinine at 12 months was 1.36+/-0.1mg/dl in adult and 0.99+/-0.23 mg/dl in pediatric recipients. Nineteen right donor kidneys were transplanted into adult recipients. Surgical complications included three symptomatic lymphoceles, one peritransplant haematoma and one kinking of a lower pole artery. All five (4.5%) ureteral complications occurred in adult recipients with a mean age of 33.2+/-2.8 years. The incidence of ureteral complications was not clustered around the early phase of our LLDN experience. Of the three (2.7%) patients diagnosed with ureteral obstruction, two required ureteral reimplantation, and one was managed conservatively. Another two patients (1.8%) with a urinary leak received a double J stent and a cystostomy catheter for 3 and 5 months, respectively. Of the five patients with a ureteral complication, three had received a donor kidney with more than one renal artery. CONCLUSIONS: LLDN combined with the intravesical (P-L) ureteral implantation technique provides excellent graft outcomes with low recipient morbidity. Renal artery multiplicity may increase the risk of ureteral complications.

Adolescent↗

Limitations of C2 monitoring in renal transplant recipients.

BACKGROUND: Recent developments have proposed the cyclosporin (CsA) concentration at 2 h post-dose (C(2)) as the best single time-point predictor of the extent of CsA exposure and as the optimal basis for monitoring immunosuppressive therapy in renal transplant patients. The present study sought to validate the cornerstones of the current concept of C(2) monitoring. METHODS: We assessed the predictive value, dose proportionality and intrapatient variability of C(2) levels in 41 de novo renal transplant recipients treated with CsA microemulsion, steroids, mycophenolate sodium and basiliximab. RESULTS: Patients with rejection and patients with CsA nephrotoxicity had lower C(2) (P = NS) and absorption (P<0.05 for toxicity), while C(0) did not show any significant difference. Receiver operating characteristic analysis did not detect discriminative C(2) values as a predictor of rejection or toxicity. In a substantial number of patients (29%) we observed poor and/or slow absorption, with C(0) >300 ng/ml and C(2) levels <800 ng/ml during the first month and a high rate of complications in these patients (18% rejection, 64% toxicity). Absorption increased over the first month post-transplant. Analysis of dose changes indicated that C(2) levels are not dose-proportional. Intrapatient variability of C(2) was as high as that of C(0). CONCLUSIONS: C(2) levels do not predict rejection or toxicity. C(2) monitoring alone does not detect toxicity in poor and/or slow absorbers, who constitute a significant proportion of patients. Changes in absorption over time, high intrapatient variability and lack of dose proportionality constitute further limitations of the C(2) monitoring concept in the early post-transplant phase.

Adult↗

Laparoscopy for living donor nephrectomy--particularities of the currently applied techniques.

Today, laparoscopic donor nephrectomy (LDN) in many centers features the standard approach for kidney retrieval in living donors. More than 60% of the centers in the USA currently perform LDN and numbers are rising in Europe as well. Today's variety of laparoscopic approaches reflects the evolution in the field of LDN. Multiple modifications have been made for the laparoscopic approach, with consequences for intraoperative handling of the kidney, operating and ischemic times and with impact on donor, organ, and recipient. We reviewed the literature from 1995 to 2004 and critically evaluated the different technical modifications, their specific advantages and disadvantages and their impact for the operation. The article aims to help the surgeon choose the technique he feels most safe with for performing laparoscopic kidney retrieval safely and with good results for donor and recipient.

Humans↗

Quality of life of living kidney donors in Germany: a survey with the Validated Short Form-36 and Giessen Subjective Complaints List-24 questionnaires.

BACKGROUND: Most studies evaluating the impact of kidney donation on donors' quality of life (QOL) have limitations such as small cohort size, unmatched references, use of nonstandardized and nonvalidated questionnaires, or low response rates. METHODS: We performed a study on donors' QOL that was designed to avoid these limitations. All available living renal donors in our department in the last 18 years were included in the study. QOL was assessed with two validated, standardized questionnaires (Short Form-36, Giessen Subjective Complaints List [Giessener Beschwerdebogen]-24) and compared with gender- and age-matched references. In addition, specific questions relating to kidney donation were asked. RESULTS: The response rate (89.8%) is one of the highest reported for studies on QOL of living kidney donors. Most donors had an equal or better QOL than the healthy population. Donors' willingness to donate again (93.4%) or recommend living-donor kidney transplantation (92.4%) was high, irrespective of complications. A small number of donors experienced financial drawbacks or occupational disadvantages. Donors aged 31 to 40 years were found to be at risk of QOL deterioration after organ donation. Donor and recipient complications had a significant impact on donors' QOL. One third of the donors found that the psychologic care preceding and after kidney donation was insufficient. CONCLUSIONS: Our findings support the practice of living-donor kidney transplantation as a good means to meet the persisting organ shortage. Further effort must be put into minimizing donor and recipient complications. The specific demands of younger donors should be further elucidated. In addition to medical follow-up, living kidney donors should also be offered lifelong psychologic counseling.

Adolescent↗

Laparoscopic living-donor nephrectomy.

BACKGROUND: In order to increase the number of renal donors, laparoscopic live-donor nephrectomy (LLDN) was first performed 8 years ago. Today, LLDN is a routine procedure in many centres worldwide. We reviewed the literature with regard to extend the use of this method, the feasibility and safety for donor, graft and recipient. Laparoscopic and open-donor nephrectomy are compared, and the impact of LLDN on donors' willingness is evaluated. METHODS: Literature search (PubMed, DIMDI, Medline) for the period from 1995 to 2003. RESULTS: More than 200 centres worldwide perform LLDN. It is a feasible and safe surgical procedure. For the donor, LLDN has numerous advantages, while graft and recipient outcome are the same as with the open approach. The learning curve on the way to performing this operation safely is long, and surgeons planning to integrate LLDN into their programme must be trained thoroughly. There are some indications that with LLDN the number of donors willing to donate a kidney can be increased. CONCLUSIONS: LLDN is widely used and will spread further. It is of the utmost importance to undergo thorough laparoscopic training in general urology prior to performing this procedure.

Clinical Competence↗

Glucose-mediated transforming growth factor-beta1 release in human mesothelial cells is endothelin independent.

Glucose and mechanical forces have been shown to be potent stimuli for mesothelial endothelin-1 release promoting profibrotic processes during peritoneal dialysis. We studied the osmolarity-induced and physical stress-induced effects on transforming growth factor-beta1 (TGF-beta1) release in human peritoneal mesothelial cells (HPMC), and analyzed whether a combined endothelin-A/endothelin-B receptor antagonist is able to mitigate HPMC TGF-beta1 release. D-Glucose and glycerol were used to analyze the impact of osmolarity on HPMC TGF-beta1 release. A cellular model of non-laminar fluid shear stress and cellular stretch was used to analyze the effects of physical forces. To neutralize the endothelin effects, a combined endothelin-A/endothelin-B receptor antagonist (LU 302 872) was chosen. Glucose, but not glycerol, increased mesothelial TGF-beta1 release in a concentration-dependent and time-dependent manner (P < 0.05 versus controls). Mechanical forces alone had no effect on mesothelial TGF-beta release. Combining fluid shear stress with high glucose medium led to a 30% increase (P = 0.019), and cellular stretch to a 34% increase (P = 0.075) in TGF-beta release compared with glucose stress alone. The combined endothelin-A/endothelin-B receptor antagonist had no impact on the mesothelial TGF-beta release. In conclusion, HPMC TGF-beta1 release by glucose and mechanical stress seems not to be related to the activity of the peritoneal endothelin system - at least in our in vitro model.

Cells, Cultured↗

Pre-transplant inosine monophosphate dehydrogenase activity is associated with clinical outcome after renal transplantation.

UNLABELLED: Mycophenolate mofetil (MMF), an inhibitor of inosine monophosphate dehydrogenase (IMPDH) activity, is usually administered as a standard dose of 1 g b.i.d. after renal transplantation. Because MMF dose reductions are associated with inferior outcome, we investigated pre-transplant IMPDH activity, MMF dose reductions and outcome. IMPDH activity was determined in isolated peripheral mononuclear cells immediately prior to renal transplantation. We observed considerable inter-individual variability in pre-transplant IMPDH activity (9.35 +/- 4.22 nmol/mg/h). Thirty of 48 patients (62.5%) with standard MMF dose (1 g b.i.d.) had dose reductions within 3 years post-transplant; these patients also had significantly lower IMPDH activity. The area under the receiver-operating characteristics curve (AUC-ROC) for prediction of dose reduction within 6 months post-transplant was 0.75 (95% CI, 0.61-0.89; p < 0.004). IMPDH activity above the cut-off value, MMF dose reduction and age of recipient were significant contributors for the occurrence of acute rejection in the multivariate logistic regression. Patients with high IMPDH activity and MMF dose reduction had the highest rejection rate (81.8% vs. 36.4%; p < 0.01). CONCLUSION: Patients with low IMPDH activity experienced more complications of MMF therapy. High pre-transplant IMPDH activity and MMF dose reductions were associated with rejection. Determination of IMPDH activity prior to transplantation may help to improve MMF therapy after renal transplantation.

Area Under Curve↗

Gadolinium-enhanced three-dimensional magnetic resonance angiography versus conventional digital subtraction angiography: which modality is superior in evaluating living kidney donors?

This study evaluates the correlation of magnetic resonance angiography (MRA) and digital subtraction angiography (DSA) with the operative vessel findings in living kidney donors. The intraoperative vessel findings of 52 living renal donors were compared with the preoperative diagnoses of each imaging technique. Sixty-seven arteries were found during explantation. Forty kidneys showed a single arterial blood supply, and 12 kidneys showed a multiple arterial blood supply. No advantage of either imaging method was found for arterial imaging. There were 55 veins identified during organ harvesting. MRA could not determine the venous system in one donor (1.9%) and failed to detect one small pole vein in another. DSA did not yield a venous diagnosis in seven patients (13.5%) and yielded misdiagnoses in four patients. The correct diagnosis of renal donor veins differed significantly in favor of MRA (kappa 0.79 vs. 0.45; P=0.008). MRA is superior to DSA in assessing the renal vasculature in living kidney donors.

Angiography↗

"Old-for-old" cadaveric renal transplantation: surgical findings, perioperative complications and outcome.

OBJECTIVE: To evaluate the surgical findings and outcome of locally allocated, blood-group-compatible but HLA-unmatched cadaveric kidneys in first renal transplantation of donor/recipient pairs aged 65 years and above (Eurotransplant Senior Program=ESP). METHODS: 26 patients of the study group (donor age 70.4 +/- 3.6/recipient age 67.7 +/- 2.8) were compared to 30 controls aged 60 and above (mean recipient age 62.6 +/- 2.3/mean donor age 43.8 +/- 15.3). For controls kidney allocation included HLA matching. RESULTS: Cold ischemic time (ESP vs. controls 501 vs. 883 min; p<0.05) and mean number of HLA mismatches (4.2 +/- 1.36 vs. 1.6 +/- 1.62; p<0.05) differed significantly. Delayed graft function was lower in the study group (12% vs. 43%; p<0.05), rejection episodes in the ESP group were numerous but did not differ significantly from the controls (46% vs. 30%; p=0.21). More intraoperative complications and a higher incidence of donor organ arteriosclerosis (p<0.05) were seen in the ESP group. Three-year graft survival uncensored and censored for death with functioning graft did not differ, even though mean creatinine and creatinine clearance differed significantly beginning at month three. Three-year patient survival (55% vs. 81%) differed in favour of the control group, even though the difference was not significant due to small number of patients. CONCLUSION: "Old-for-old" kidney transplantation with local allocation yields graft survival rates comparable to HLA-matched young grafts and is a good approach to extend the donor and recipient pool. Careful patient selection is advised.

Age Factors↗

Combined ETA/ETB receptor blockade of human peritoneal mesothelial cells inhibits collagen I RNA synthesis.

BACKGROUND: Peritoneal fibrosis is a serious complication of peritoneal dialysis; however, the mechanisms are poorly understood. We studied osmolarity and physical stress-induced effects on collagen I RNA synthesis in human peritoneal mesothelial cells (HPMCs) and focused on endothelin as a possible mediator. METHODS: HPMCs were grown in a medium containing either d-glucose or glycerol to analyze the impact of osmolarity on mesothelial endothelin-1 (ET-1) release and on collagen I RNA synthesis [reverse transcription-polymerase chain reaction (RT-PCR)]. A cellular model of nonlaminar fluid shear stress and cellular stretch was used to analyze the effects of physical forces. To neutralize the endothelin effects, a combined ETA/ETB receptor antagonist (LU 302 872) was chosen. RESULTS: Glucose, but not glycerol, increased mesothelial ET-1 release in a concentration and time-dependent manner (P < 0.05 vs. controls). Collagen I RNA synthesis was significantly higher in glucose-challenged cell cultures (P < 0.05 vs. controls). The glucose-mediated collagen I RNA synthesis was completely inhibited by adding the combined ETA/ETB receptor antagonist to the medium. Fluid shear stress, but not cellular stretch, led to a significant increase in the mesothelial ET-1 release (P < 0.005 vs. controls) and collagen I RNA synthesis (P < 0.05 vs. controls). LU 302 872 completely inhibited these effects. CONCLUSION: We found that glucose and fluid shear stress are potent stimuli for ET-1 release and collagen I RNA synthesis in a model cellular system. Although our system is highly artificial, our findings raise the hypothesis that similar effects may occur in the peritoneal membranes of peritoneal dialysis patients and suggest that endothelin might be involved.

Cells, Cultured↗

Old-for-old kidney allocation allows successful expansion of the donor and recipient pool.

Allocation of kidneys from donors older than 64 years to recipients older than 64 years was started in 1999 to improve use of older donor kidneys. Kidneys are allocated locally without HLA-matching to keep cold ischemia short. We compared survival and rejection rates in elderly patients allocated in the old-for-old program (ESP) to patients aged 60 years and older based on HLA-matching, expected ischemia and waiting time (ETKAS). The 69 ESP patients were older (67.9 +/- 2.5 vs. 63.9 +/- 2.9 years), had older donors (71.2 +/- 3.9 vs. 44.6 +/- 14.5 years) and more HLA-mismatches (4.2 +/- 1.2 vs. 1.6 +/- 1.7) than the 71 ETKAS patients, while ischemia was shorter (7.8 +/- 3.4 vs. 14.2 +/- 5.5 h). ESP and ETKAS had similar graft (1-year: 83.6% vs. 86.9%) and patient survival (85.2% vs. 89.5%). With the introduction of ESP, use of older recipients and donors rose from less than 2% to 16% and 11%, respectively. Incidence of acute rejections was significantly higher in the ESP group (1 year: 43.2% vs. 27.4%) and significantly correlated with the degree of HLA-matching. Introduction of old-for-old allocation allows successful expansion of the donor and recipient pool without affecting patient and graft survival. HLA-matching should not be ignored, as the risk of acute rejection in elderly patients is substantial.

Age Factors↗