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L Fricke

Publications and source records attributed to L Fricke.

At least 19 recordsLinked to original sources
PubMed2005

Cyclosporine C2 levels in de novo renal allograft recipients: a German multicenter prospective observational study.

This ongoing multicenter prospective observational study was undertaken in de novo renal allograft recipients managed with cyclosporine (CsA) trough (C0) and 2-hour postdose (C2) level monitoring at defined times so as to assess the risk for an acute rejection episode or allograft dysfunction. The renal transplant recipients (n = 159) were enrolled at 11 German centers. The 6-month posttransplant data from 138 patients were evaluable for this interim analysis. Mean C2 levels (ng/mL), which were measured by liquid chromatography-tandem mass spectrometry at a central laboratory, were: days 3 to 5: 873.1 +/- 391.9; days 7 to 10: 939.1 +/- 422.8; days 14 to 28: 1116.3 +/- 497.6; 3 months: 905.0 +/- 316.8; and after 6 months: 787.0 +/- 276.5. To identify patients at higher risk for acute rejection or allograft dysfunction, we calculated the relative CsA absorption capacity (C2 [ng/mL]/morning dose [mg/kg]; CsA-Abs), yielding mean values on days 3 to 5: 284.4 +/- 115.1; days 7 to 10: 306.7 +/- 134.8; days 14 to 28: 382.5 +/- 164.7; month 3: 501.5 +/- 168.8; month 6: 512.7 +/- 176.5. Three groups were distinguished by CsA-Abs at days 7 to 10: low absorbers (CsA-Abs < 200), normal absorbers (CsA-Abs 200 to 350), and high absorbers (CsA-Abs > 350). A between-group comparison of absorption level at 6 months posttransplant revealed the incidences of biopsy-proven acute rejection and Cockcroft-Gault formula-based mean glomerular filtration rates of 23.8% and 54.7 +/- 19.0 mL/min, 22.6% and 59.5 +/- 20.7 mL/min, and 17.6% and 67.7 +/- 23.5, respectively. In conclusion, mean C2 levels >1000 ng/mL are attained within 2 to 4 weeks, with CsA-Abs increasing continuously over the first 6 posttransplant months. High CsA absorbers show a propensity toward good allograft function and lower acute rejection rates at 6 months after renal transplantation.

Area Under Curve↗
PubMed2005

Relationship between donor factors, immunogenic up-regulation, and outcome after kidney transplantation.

Epidemiological data show that the cause of brain death as well as the condition of the organ donor have considerable influence on the outcome of kidney transplantation. An early immunogenic up-regulation, which already exists at the time of organ removal seems to be primarily responsible. So far it has remained unclear which donor factors cause this effect. In a prospective study of 37 organ donors a 0-hour biopsy was performed at the time of explantation to measure the expression of HLA-DR and endothelin-1 (ET-1) immunohistologically using the alkaline phosphatase anti-alkaline phosphatase (APAAP) method. The transplant outcome and the immunohistological results were correlated with various donor factors. Statistically significant correlations were seen with the following parameters: the donor serum creatinine prior to explantation correlated with the incidence of delayed graft function (DGF: 104 +/- 39 vs 78 +/- 35 micromol/L versus no DGF n = 37; P = .043). Early graft loss after transplantation correlated significantly with increased numbers of leukocytes as well as with decreased O2 saturation in the donor immediately before explantation (leucocytes: 16.7 +/- 6.8 vs 12.6 +/- 4.6/nL, n = 37; P = .036; O2 saturation: 94.1% +/- 6.9%, vs 97.7% +/- 2.3%, n = 37; P = .026). Further, donor-independent factors that correlated with acute rejections included cold ischemic time (P = .031), HLA mismatches (P = .028), and occurrence of DGF (P = .033). The degree of HLA-DR expression (range 0 to 2) correlated significantly with early graft loss (2.0 +/- 0.2 vs 1.33 +/- 0.9 for graft function, n = 37; P = .01) as well as the ET-1 expression with DGF (2.0 +/- 0.3 vs 1.5 +/- 0.7 versus no DGF, n = 37; P = .016). In summary, marginal donors should be seen as high immunological risk situations that need careful conditioning.

Biopsy↗
PubMed2002

Hemolytic anemia after kidney transplantation: case report and differential diagnosis.

A 58-year-old woman presented with hemolysis and thrombocytopenia 2 weeks after receiving a kidney graft. Hemolytic uremic syndrome was initially suspected, because in addition to hematological changes the graft function was missing. Unexpectedly, the results of the direct antiglobulin test became positive (4+), which is not normally observed in the hemolytic uremic syndrome. Differentiation of the eluted antibodies revealed anti-rhesus D specificity, which had to be interpreted either as an autoantibody of patient's origin or, hypothetically, as a "graft versus host" antibody of donor origin. Gm- and Km allotyping of these antibodies demonstrated a pattern which differed from the patient's but was identical to that of the kidney donor. Therefore hemolysis could be explained unambiguously by "graft versus host" antibodies. Whether the thrombocytopenia was also due to an immune process was not clear, although some evidence favors this hypothesis. Immunosuppressive treatment remained unchanged and several red blood cell transfusions were necessary before reactivity of the direct antiglobulin test diminished and became negative 7 weeks after kidney transplantation. The occurrence of hemolysis in the early posttransplantation period should thus draw attention to the possibility of "graft versus host" antibodies directed against red cells. Concomitant thrombocytopenia may occur. Donor screening for irregular erythrocyte antibodies should be performed whenever solid organ transplantation is intended.

Anemia, Hemolytic↗
PubMed2001

Laparoscopic fenestration of posttransplant lymphoceles.

BACKGROUND: A lymphocele is a common finding after renal transplantation and occurs in up to 20% of patients. The majority of patients are asymptomatic. However, once a lymphocele has become symptomatic (e.g., through transplant dysfunction) this condition has to be treated. We report our 9-year experience with laparoscopic lymphocele fenestration and discuss the current management options for posttransplant lymphoceles. METHODS: Since 1993, 19 patients (11 males and 8 females; median age 56 years, range 22-68 years) of a total of 31 patients with a symptomatic posttransplant lymphocele have undergone laparoscopic fenestration of their lymphocele at a median of 66 days (range, 19-111 days) following successful renal transplantation in our department. As a first-line treatment, a percutaneous pigtail drainage catheter was inserted in all patients. In case of failure in resolving the fluid collection, the next step included sclerotherapy by instillation of tetracycline or ethanol into the lymphocele cavity in some cases. In patients with a persistent lymphocele, a laparoscopic lymphocele fenestration via a transabdominal approach was undertaken to achieve adequate drainage. RESULTS: Primary laparoscopic lymphocele fenestration was successful in all except two patients, who required a conversion. The median operating time was 36 min (range, 20-70 min). Following the procedure, renal transplant function remained stable or returned to individually normal levels in all patients. Median duration of hospital stay was 4 days (range, 1-13 days). At median follow-up of 27 months, all patients were alive with a functioning transplant. CONCLUSIONS: Laparoscopic lymphocele fenestration is reserved for patients in whom temporary drainage with or without sclerotherapy failed to resolve the fluid collection. In these cases the laparoscopic approach offers obvious technical and clinical advantages compared to open operative techniques.

Adult↗
PubMed2001

A randomized, double-blind trial of basiliximab immunoprophylaxis plus triple therapy in kidney transplant recipients.

BACKGROUND: A double-blind, placebo-controlled, randomized study was performed to assess whether immunoprophylaxis with basiliximab (Simulect) could reduce the incidence of acute rejection in kidney transplant recipients treated with cyclosporine (Neoral), steroids, and azathioprine. METHODS: Three hundred forty patients received either placebo or basiliximab at a dose of 20 mg, given intravenously on days 0 and 4. All patients received cyclosporine, steroids, and azathioprine. The primary endpoint was the incidence of acute rejection at 6 months. Secondary endpoints included the safety and tolerability of basiliximab and placebo, 1-year patient and graft survival, and significant medical events up to 12 months. RESULTS: During the first 6 months posttransplantation, acute rejection occurred in 20.8% of patients given basiliximab versus 34.9% of patients administered placebo (P=0.005). Similarly, there was a reduction in biopsy-proven acute rejection at 6 months in the patients receiving basiliximab (P=0.023). One-year patient survival was 97.6% with basiliximab and 97.1% with placebo, graft survival was 91.5% versus 88.4%, respectively (NS). The adverse-events profile of patients treated with basiliximab was indistinguishable from that of patients treated with placebo. The number of patients with infections was similar (65.5% for basiliximab vs. 65.7% for placebo), including cytomegalovirus infections (17.3% vs. 14.5%, P=0.245). Nine neoplasms (three in the basiliximab group, six in the placebo arm) were recorded up to 1 year from transplantation. CONCLUSIONS: Basiliximab in combination with cyclosporine, steroids, and azathioprine triple therapy was highly effective in reducing the incidence of acute renal allograft rejection without increasing the incidence of infections and other side effects.

Adult↗
PubMed2001

Human thiopurine S-methyltransferase activity in uremia and after renal transplantation.

UNLABELLED: In addition to cyclosporin and steroids, azathioprine is frequently used for immunosuppression after renal transplantation. Thiopurine S-methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs. A genetic polymorphism was shown with 1 in 300 homozygous for a TPMT deficiency. These subjects carry the risk of severe myelosuppression when treated with azathioprine. OBJECTIVE: To investigate the influence of hemodialysis on TPMP activity in uremic patients and the effect of azathioprine treatment on enzyme activity. METHODS: The assay for measurement of TPMT activity in packed red blood cells is based on a non-radioactive conversion of 6-thioguanine to 6-methylthioguanine. In 251 patients, TPMT activity was determined before and after a 4-h period of hemodialysis. In 49 patients (26 on azathioprine, 23 on mycophenolate mofetil as control group), TPMT activity was regularly determined during the first 120 days after renal transplantation. RESULTS: TPMT activity is elevated in red blood cells of uremic patients before hemodialysis when compared with TPMT activity after hemodialysis. The latter is comparable to the activity in healthy subjects. In patients treated with azathioprine, the TPMT activity showed a slow increase that declined to pre-treatment values when azathioprine was withdrawn. This could not be observed in patients treated with mycophenolate mofetil. CONCLUSIONS: In uremic patients, TPMT activity is activated by some uremic factors that are removed by hemodialysis. In contrast to what has been observed before, dialysis shifted the TPMT activity close to that of a healthy control group. In patients treated with azathioprine after renal transplantation, the observed increase of TPMT activity could possibly be the result of enzyme induction.

Adult↗
PubMed2001

Laparoscopic nephroureterectomy to exclude upper urinary tract malignancy associated with analgesic nephropathy.

BACKGROUND AND PURPOSE: Analgesic abuse is a potential cause of end-stage renal disease. Such patients bear an elevated risk of developing malignancies, predominantly transitional-cell carcinoma. We report our experience with laparoscopic nephroureterectomy carried out in patients with analgesic nephropathy to exclude upper urinary tract malignancy. All patients were scheduled to be put on the waiting list for cadaveric renal transplantation. PATIENTS AND METHODS: Since 1996, nine women and two men with a long-term history of analgesic abuse have undergone laparoscopic nephroureterectomy at our hospital. The median age was 63 years (range 51-70 years). All patients had developed end-stage renal failure secondary to heavy analgesic abuse with a median duration of 14 years (range 7-40 years). The median interval from the beginning of hemodialysis to laparoscopic nephroureterectomy was 36 months (range 6-76 months). RESULTS: The median operative time was 99 minutes (range 55-170 minutes). There were no conversions to open surgery. Two complications occurred, and three patients required blood transfusions. The median hospital stay lasted 5 days (range 2-12 days), and the median convalescence was 20 days (range 6-44 days). In seven patients, histopathologic examination of the kidney revealed changes attributable to analgesic abuse. None of the patients had a transitional-cell carcinoma, but in two patients, a renal-cell carcinoma stage pT1cN0cM0 grade 2 was detected. CONCLUSION: Patients with analgesic nephropathy bear an elevated risk for the development of transitional-cell or renal-cell carcinoma. In these patients, laparoscopic nephroureterectomy combines minimally operative invasiveness with a maximum of diagnostic safety.

Aged↗
PubMed2001

The effect of HLA-C matching on acute renal transplant rejection.

BACKGROUND: The acute immunological rejection and long time survival of kidney allografts are correlated with the human leukocyte antigen (HLA) match status between donor and recipient. HLA-A, -B and -DR have all turned out to be relevant HLA loci in several studies. The role of HLA-C has not been studied before now. METHODS: In 104 consecutive patient/donor pairs from our transplantation unit, we retrospectively analysed whether acute graft rejection is influenced by HLA-C match status between donor and recipient. For typing HLA-C alleles, we used an allele-specific PCR protocol in combination with serology. RESULTS: By analysing groups of donor/recipient pairs with a homogeneous distribution of HLA-B mismatches in order to exclude an effect of the linkage disequilibrium between HLA-B/C, HLA-C mismatch turned out to be significantly correlated with acute transplant rejection in pairs with one additional mismatch on the B locus (P=0.004). Additional parameters that may hypothetically influence acute rejection episodes (HLA-A or DR mismatch, time of cold and warm ischaemia, previous transplantations, pre-existing HLA antibodies) were also analysed but cannot explain this finding. CONCLUSION: HLA-C matching of all kidney donors and recipients seems to be an option to reduce the probability of acute rejection episodes. Further studies of greater patient cohorts analysing organ rejection and organ survival are warranted.

Alleles↗
PubMed2001

Primary hyperoxaluria type 1 causing end-stage renal disease in a 45-year-old patient.

Primary hyperoxaluria type 1 (PH1) is caused by deficiency of peroxisomal alanine-glyoxylate aminotransferase which is in humans exclusively expressed in liver cells. The disease is inherited as an autosomal recessive trait, and initial symptoms usually occur in early childhood. Up to the age of 25 years, 90% of the patients are symptomatic, and many patients develop end-stage renal failure. Pronounced medical care is necessary in PH1 patients to prevent generalized oxalosis with complications due to bone disease and peripheral gangrene. The rather short survival of patients on hemodialysis is caused by sudden arrhythmias and heart block. As no dialysis procedure is able to remove the daily produced oxalate, early transplantation is mandatory. Our 45-year-old patient is remarkable on the basis of the late manifestations of PH1. The diagnosis was delayed by unspecific symptoms of nephrolithiasis with recurrent pyelonephritis. Clinical course and diagnostic cornerstones of primary hyperoxaluria are outlined. The principles of conservative treatment and experiences with dialysis and transplantation are discussed.

Acute Kidney Injury↗
PubMed2000

Monitoring of anti-HLA class I and II antibodies by flow cytometry in patients after first cadaveric kidney transplantation.

While the relevance of pre-formed anti-human leukocyte antigen (HLA) antibodies has been studied extensively, the role of anti-HLA class I and II antibodies produced after cadaveric kidney transplantation is still a matter of discussion. As it has been proposed that they are involved in a considerable number of cases, it should be investigated whether a post-transplant monitoring is a sensitive parameter for the early diagnosis of acute rejection episodes. Additionally, it has been suggested that antibodies are a major cause for chronic rejection; thus, it would be of interest to correlate antibody detection and graft survival. We retrospectively investigated 59 patients after a first cadaveric kidney transplantation without known anti-HLA antibodies (complement-dependent cytotoxicity [CDC] testing). The panel reactivity was determined with a new highly sensitive and specific flow-cytometric technique (Flow-PRA Screening Test, One Lambda, Canoga Park, USA) in sequentially collected serum samples pre- and post-transplant. In patients with acute rejection episodes during the clinical course, the last sample prior to rejection, and in patients without rejection, the last sample prior to discharge, was analyzed. Furthermore, we analyzed 3-yr graft survival and several clinical parameters such as cold ischemia time (CIT). Twenty-four of 59 patients (41%) experienced acute rejections during the clinical course. Five of 59 died with a functioning graft within the first 3 yr. Seven of 54 patients, still alive after 3 yr, lost their graft. Anti-HLA antibodies were detectable in only 7/59 patients and a correlation between antibody positivity and acute rejections (p = 0.32 and 0.54 for anti-HLA class I and II, respectively) could not be identified (sensitivity 12.5 and 8.3%). However, we found a significant correlation between the detection of anti-HLA class II and graft loss within 3 yr (p = 0.005, specificity 97.9%). Additionally, anti-HLA class II positive patients had significantly longer CIT (p = 0.003). Whether the detection of anti-HLA class II antibodies in the early post-transplant phase is of great value for the identification of patients at high risk for early graft loss needs additional investigation. However, we found that anti-HLA antibodies are detectable only in a minority of unsensitized patients and we conclude that flow-cytometric monitoring with Flow PRA is not a sensitive parameter for the early diagnosis of acute rejection episodes in patients after first cadaveric kidney transplantation.

Acute Disease↗
PubMed1999

The IL-4 receptor alpha-chain variant Q576R is strongly associated with decreased kidney allograft survival.

The involvement of the interleukin-4 (IL-4) pathway in B-lymphocyte activation and induction of a T helper 2 (Th2) cell response prompted us to investigate the influence of a recently described gain-of function mutation in the IL-4 receptor alpha-chain gene (IL-4R alpha; CD 124) on renal allograft survival. We developed a genotyping assay for the IL-4R alpha variant Q576R and investigated 203 renal transplant patients, all of whom underwent transplantation surgery at a single institution. The overall frequency of the IL-4R alpha variant Q576R in this group was 38.9% (79/203). The Kaplan-Meier method was used to estimate the graft survival of 156 patients with complete follow-up time of 24 months. Significantly higher graft survival rates (P=0.012, log-rank test) were found in patients with the wild-type IL-4 receptor (2-year graft survival 78.8%) as compared to patients with the IL-4R alpha variant Q576R (2-year graft survival 60.6%). Multifactorial cox regression analysis showed that this effect was independent of HLA matching, sex of donor and recipient, age of recipient, year of transplantation and preformed antibodies (P=0.017). These results indicate a strong association of the IL-4R alpha variant Q576R with kidney allograft loss. Genotyping of kidney allograft recipients for the IL-4R alpha variant may offer a simple method to identify high-risk patients in the post-transplantation period.

B-Lymphocytes↗
PubMed1998

Treatment of posttransplant hypertension by laparoscopic bilateral nephrectomy?

BACKGROUND: Hypertension is an important risk factor for the development of chronic graft failure and decreased graft and patient survival after renal transplantation. METHODS: Between September 1994 and August 1996, 14 patients underwent laparoscopic bilateral nephrectomy for treatment of drug-resistant hypertension after successful renal transplantation. Common causes of hypertension were largely excluded before bilateral nephrectomy. A scoring system was developed for comparison of different antihypertensive regimes. In this system, points were given according to type and dosage of each antihypertensive drug. RESULTS: At 6-month follow-up, all patients showed well-controlled blood pressure (median of mean arterial pressure: 104 vs. 130 mmHg preoperatively, P<0.001, n=14), and significantly fewer antihypertensive drugs were needed according to the scoring system (48.9+/-20.9 points vs. 105.9+/-23.5 points preoperatively, P<0.001, n=14). During laparoscopy, three conversions to open surgery were necessary. Postoperatively, four complications occurred. After laparoscopy, immunosuppression and other oral medication were given continuously. The hospital stay ranged between 3 and 6 days (median: 5 days). CONCLUSIONS: The results indicate that bilateral nephrectomy using the laparoscopic technique can be an effective alternative method for a selected group of patients with severe hypertension, which is unresponsive to conservative management after successful renal transplantation with regard to improving the long-term graft survival.

Adult↗
PubMed1998

Laparoscopic nephrectomy: comparison of dialysis and non-dialysis patients.

BACKGROUND: Laparoscopy is believed to result in possible clinical benefits for the patient. We report our experience with renal laparoscopy in dialysis patients and compare the results with those from non-dialysis patients. METHODS: Between December 1994 and April 1997, 19 dialysis patients underwent laparoscopic nephrectomy or nephroureterectomy at our hospital. The group consisted of 11 female and eight male patients (mean age 45 years). In nine patients the indication for nephrectomy was chronic pyelonephritis. Nephroureterectomy for vesicoureteral reflux with recurrent episodes of pyelonephritis or analgesic nephropathy for exclusion of transitional cell carcinoma of the upper urinary tract was considered in nine other patients. Laparoscopic bilateral nephrectomy for drug-resistant hypertension was performed in one patient. In comparison, a consecutive group of non-dialysis patients who had undergone renal laparoscopy was reviewed. RESULTS: In the dialysis group, one patient had to be converted to open nephrectomy due to bleeding. Six dialysis patients required blood transfusions compared with none in the non-dialysis group. There were four complications in the dialysis group and two in the non-dialysis group. Both groups had comparable results for operative times, analgesic consumption, postoperative start of oral intake and mobilization, and duration of hospitalization and convalescence. CONCLUSIONS: Laparoscopic nephrectomy in dialysis patients has acceptable results. The higher transfusion rate is probably due to a lower preoperative haemoglobin and is not aggravated by possible affects of the clotting system in patients with chronic uraemia.

Adult↗
PubMed1998

Comparison of laparoscopic and open nephroureterectomy for benign disease.

PURPOSE: We report our experience with laparoscopic nephroureterectomy for benign disease and compare the results to a contemporary group of patients undergoing open nephroureterectomy. MATERIALS AND METHODS: Between October 1994 and March 1997, 12 women and 4 men with a mean age of 50 years (range 22 to 70) underwent laparoscopic nephroureterectomy at our hospital. Indications for operation were nonfunctioning kidneys due to vesicoureteral reflux with recurrent episodes of pyelonephritis or analgesic nephropathy before a planned renal transplantation. In comparison 11 women and 4 men with a mean age of 40 years (range 18 to 64) underwent open nephroureterectomy for various benign diseases. RESULTS: Laparoscopic and open nephroureterectomy had no significant differences regarding operative times (100 versus 124 minutes) and complication rates (25 versus 20%). In the laparoscopy group conversion to open surgery was not necessary. Patients who underwent laparoscopic nephroureterectomy had significantly less consumption of morphine equivalent for postoperative pain control (12 versus 40 mg.), shorter time to achieve mobilization and oral intake (11 versus 39 hours), shorter hospital stay (6 versus 12.7 days) and faster return to normal activities (21 versus 39 days). CONCLUSIONS: Laparoscopic nephroureterectomy in patients with benign disease has similar operative results but obvious postoperative advantages compared to the open approach.

Adolescent↗
PubMed1997

[The angiography of kidney transplant arteries using carbon dioxide].

BACKGROUND AND OBJECTIVE: After renal transplantation hypertension occurs in 60-80% of patients, in 3-23% of them due to renal artery stenosis in the transplanted kidney. Angiographic assessment of the severity of the stenosis would best be done with a non-nephrotoxic contrast medium. We investigated the use of carbon dioxide, a bubble-forming contrast medium excreted via the lung, for its suitability in the angiography of the arterial system in the renal transplant. PATIENTS AND METHODS: In an uncontrolled series of observations on six patients with renal transplants and hypertension who were being treated with three or four antihypertensive drugs, the transplant's arteries were demonstrated with carbon dioxide, injected by Seldinger technique into the ipsilateral femoral artery, and the results recorded by subtraction angiography. RESULTS: The angiograms demonstrated postoperative kinked renal artery, a plaque in the external iliac artery, and a sharply angled origin of the external iliac artery in one case each, and three normal cases. CONCLUSIONS: Carbon dioxide is a suitable medium for demonstrating renal arteries in a transplanted kidney and is preferable to conventional contrast media for the angiographic diagnosis of possible renal artery stenosis.

Adult↗