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V Kliem

Publications and source records attributed to V Kliem.

At least 19 recordsLinked to original sources
PubMed2006

Low 1-year cyclosporine microemulsion doses are associated with better 5-year renal graft function: an insight from MOST, a multinational observational study.

BACKGROUND: In earlier registry analyses, cyclosporine at doses of < 3 mg/kg/d at 1 year post-renal transplantation has been associated with significant graft loss or reduction in renal function. Improvements in cyclosporine formulation with increased bioavailability, plus the use of more efficient comedications, may now confer better outcomes. To determine the effect of the 1-year cyclosporine microemulsion (CsA-ME) dose on renal allograft function at 5 years, we analyzed data collected from 2889 patients with documented graft survival to year 5 in a prospective, multinational, observational study-Neoral MOST. RESULTS: Glomerular filtration rate (GFR) at year 1 was 63 +/- 20 mL/min and 59 +/- 22 mL/min at year 5. The multivariate analysis including year 1 CsA-ME dose as factor and GFR at 1 year as covariate revealed the most significant factors affecting GFR at year 5 were 1-year GFR, donor age > 60 years, and CsA-ME dose at 1 year. Risk factors associated with reduction in 5-year GFR (<65 mL/min) included donor or recipient age >60 years, delayed graft function, cadaveric donor, previous graft, and acute rejection. CsA-ME dose <3 mg/kg/d was found to protect GFR. Analysis of GFR at each year posttransplantation (Wilcoxon model) found 1-year CsA-ME (cutoff 3 mg/kg/d) had a significant effect at each time point. CONCLUSIONS: Compared to higher doses, CsA-ME <3 mg/kg/d at year 1 posttransplantation is associated with increased preservation of renal allograft function at year 5.

Aged↗
PubMed2005

Cyclosporine-based immunosuppressive strategies for kidney recipients: interim analysis of German data from the Multinational Observational Study (MOST).

INTRODUCTION: We collected data from kidney recipients with a functioning graft at German kidney transplant centers in order to analyze the efficacy of various cyclosporine (CsA)-based immunosuppressive strategies, the effects of different perioperative and maintenance regimens, and the impact of donor source on clinical outcome. METHODS: As part of the ongoing prospective Multinational Observational Study in Transplantation (MOST), data for both prospective and retrospective analysis were collected from kidney recipients over 18 years bearing a functioning graft that was transplanted at 21 German kidney transplant centers between 1987 and 2002. RESULTS: Data from 1223 renal graft recipients, including their CsA-based immunosuppressive regimens, were stratified as: 402 de novo patients (median 6.8 months posttransplant) and 821 patients on maintenance therapy (median 71 months posttransplant). Triple regimens with CsA + mycophenolate mofetil (MMF) + steroids (Ste) currently comprise the major perioperative immunosuppressive strategies in Germany (de novo 65%). IL-2 receptor antagonist (IL-2Ra) use is increasing (de novo 18%, maintenance 4%), while mono and dual regimen use de novo is declining (de novo 4%, maintenance 20%). Among 689 patients transplanted between 1987 and 2002 with outcome data, the mean incidence of acute rejection during the first posttransplant year was 21.6%. Rejection rates on initial therapy with CsA + MMF + Ste +/- antibodies (n = 517) averaged 17.8%. CONCLUSIONS: Between 1987 and 2002, CsA-based immunosuppression combined with MMF and Ste became the most commonly used strategy for both initial and maintenance therapy after kidney transplantation in Germany, yielding the low acute rejection rates particularly when combined with IL-2Ra.

Adult↗
PubMed2003

One-year posttransplant renal function is a strong predictor of long-term kidney function: results from the Neoral-MOST Observational Study.

BACKGROUND: Peritransplant risk factors influence short-term and long-term graft survival, and 1-year serum creatinine is known to predict long-term graft survival. To examine interrelationships between risk factors, renal function at 1 year, and long-term graft function in patients maintained on cyclosporine, we analyzed data collected from 10,692 de novo or maintenance renal transplant recipients in an ongoing international, prospective, observational study--Neoral-MOST (Multinational Observational Study in renal Transplantation). The effect of donor age, delayed graft function, acute rejection, donor type, panel-reactive antibodies, and previous graft on 1- and 5-year renal function and their relationship to 1-year serum creatinine was assessed. RESULTS: Donor age, delayed graft function, acute rejection, and donor type significantly increased the risk for serum creatinine > 130 micromol/L at 1 year posttransplant, and 1-year serum creatinine was the strongest predictor of 5-year renal function. After adjustment for 1-year serum creatinine, an ongoing influence was observed for donor age, donor type, and previous graft. Delayed graft function and acute rejection had a significant effect on serum creatinine at year 1 but no additional impact on long-term graft function. CONCLUSIONS: Serum creatinine at 1 year is influenced by risk factors known to affect overall graft survival and is predictive of 5-year renal graft function. The effects of delayed graft function and acute rejection appear to be limited to their influence on serum creatinine at 1 year, whereas donor type and previous graft predominantly affect later stages of graft life.

Creatinine↗
PubMed2001

Low frequency of HLA-DRB1*11 in hepatitis C virus induced end stage liver disease.

Hepatitis C virus (HCV) infection becomes chronic in more than 70% of patients, leading to end stage liver disease in about 20-30% of these patients. Apart from the virus itself, host factors that modulate the immune response are likely to be involved in determining the outcome of HCV infection. Studies on the association of human leucocyte antigens (HLAs) and HCV infection have shown inconsistent results. Selection of patient subgroups may be crucial. However, any association relevant to HCV disease progression will become evident, especially in those patients with end stage liver disease. Therefore, we analysed the phenotype frequencies of HLA antigens in two groups of 69 and 39 patients with HCV induced liver cirrhosis who had received a transplant or were awaiting liver transplantation. The first group was typed serologically and compared with 331 blood and liver donors. The second group, prospectively HLA typed by a polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) procedure for HLA-DRB and DQB alleles, was compared with another 170 PCR-SSO typed and randomly selected blood donors. Decreased frequencies for HLA-DR5 and HLA-DQ3 were found in one group of patients with HCV induced liver cirrhosis compared with the control groups. In the second analysis comparing 39 patients with end stage liver cirrhosis with blood donors, we confirmed the significant decrease in HLA-DRB1*11 and HLA-DQB1*03, which corresponded to serological HLA-DR5 and HLA-DQ3 antigens, respectively. Our results show that the presence of HLA-DRB1*11 and HLA-DQB1*03 alleles is associated with a reduced risk for the development of HCV induced end stage liver disease.

Alleles↗
PubMed2000

Renal transplantation in older adults: is graft survival affected by age? A case control study.

BACKGROUND: The demand for kidney allografts in older patients is growing continually. Previously published data indicate that the higher rate of graft losses resulting from the age-related increased mortality in older transplant recipients is balanced by a significantly lower number of graft losses from immunological problems (acute and chronic rejection) in old patients. This single center study was performed to scrutinize these results with the methods of a case control analysis. METHODS: Ninety-one patients, 65 years and older (mean age 67), were included in the case group. Their data were compared with those obtained from two control groups, 40-55 and 18-35 years old, respectively (mean ages 48 and 29, respectively). Apart from age, the groups were matched with regard to HLA-mismatches and date of transplantation. RESULTS: The number of initially non-functioning grafts and donor age did not differ significantly between the case and the control groups. During the follow-up of 5 years, acute rejections were significantly more frequent in the older control group. In contrast to previous studies, however, graft losses caused by rejections were not significantly more frequent in younger patients than in transplant recipients over age 65 years. Thus, as a consequence of increased patient mortality, the total graft survival in the case group was significantly worse than in the control groups. CONCLUSIONS: In the presence of organ shortage, an indication for kidney transplantation in patients over 65 years has to be considered carefully because age did not prove to have a beneficial effect on graft survival. Nevertheless, patients of this age group should not be excluded from renal transplantation, because not only medical, but also ethical, issues are involved.

Acute Disease↗
PubMed2000

Native pyeloureterostomy after kidney transplantation: experience in 48 cases.

Necrosis and stenosis of the ureter are severe complications after kidney transplantation and occur with mean incidence of 2,9-13,4 %. Several surgical techniques like simple nephrostomy or complex urinary tract reconstruction have been applied for repair. In this study, our experience with native pyeloureterostomy (NPUS) using the native ureter is presented. Between March 1978 and June 1996, 2,592 kidney transplantations were performed in our institution. In 48 patients (1,9%), secondary urinary tract reconstruction by NPUS was necessary. These patients were evaluated retrospectively by review of the case notes. At the time of operation the mean age was 45 +/- 14 years. Indications for NPUS were distal ureteral stenosis (n = 29), necrosis (n = 17), bleeding (n = 1) or iatrogenic lesion of the ureter (n = 1). The mean time period between transplantation and urinary tract reconstruction was 20 +/- 23 days (range: 1-90 days) for necrosis and 404 +/- 637 days (range: 14-2,385 days) for stenosis. A pyeloureterostomy was technically feasible in all patients using the recipient's ipsilateral ureter. In 40 out of 48 patients the graft developed a normal function postoperatively (follow up: 39 +/- 48 months). A graft nephrectomy was necessary only in one patient, because of complete pyelonnecrosis 6 days after NPUS. Two grafts were lost due to acute rejection. Data of five patients were not available > 15 years after successful reconstruction. We can conclude that NPUS is a safe and simple rescue technique for the treatment of distal ureteral complications after kidney transplantation. Therefore, this technique should be the therapy of choice when secondary reconstruction by re-ureteroneocystostomy is not possible.

Female↗
PubMed2000

Free serum leptin but not bound leptin concentrations are elevated in patients with end-stage renal disease.

BACKGROUND: Leptin is a 16-kDa protein that is thought to be a regulator of food intake and body weight. Although total serum leptin levels have been reported to be elevated in obese and normal weight patients with end-stage renal disease (ESRD), it is not known whether serum-free leptin concentrations are also increased in patients with ESRD with no apparent nutritional problems. Furthermore, there are no data on how different dialysis modes (high-flux haemodiafiltration and low-flux dialysis) influence serum leptin subfractions. METHODS: We measured fasting serum free and bound leptin levels in three groups of male subjects: patients on haemodiafiltration with high flux dialysers (n=11), patients on haemodialysis with low-flux dialysers (n=17) and healthy age (61+/-8 years) and BMI (23.8+/-3.1 kg/m(2)) matched control subjects (n=28). Both leptin components were determined before and after a single dialysis session. RESULTS: Body mass indices were correlated with serum free leptin levels in both patients (r=0.69, P<0.001) and controls (r=0.77, P<0.001). Mean (SD) serum free leptin levels were significantly higher in ESRD patients than in control subjects (91+/-33 vs 41+/- 21 pmol/l; P<0.01). Bound leptin levels did not differ in both groups (0.67+/-0.12 vs 0.56+/-0.11 nmol/l, NS). Elevated serum-free leptin levels in ESRD patients could be reduced by haemodiafiltration with high-flux membranes, but not with low-flux haemodialysis membranes. The former led to a reduction of initial serum free leptin values to 76+/-17% (P<0.01), whereas bound leptin remained unaffected. CONCLUSION: Serum-free leptin levels are elevated in ESRD without any apparent effect on body weight. In contrast, serum bound leptin levels remain stable, thus central feedback regulation via the bound form of the hormone may serve as an alternative explanation in the regulation of food intake and energy expenditure in chronic patients on haemodialysis with no apparent nutritional problems.

Body Mass Index↗
PubMed2000

Extended daily veno-venous high-flux haemodialysis in patients with acute renal failure and multiple organ dysfunction syndrome using a single path batch dialysis system.

BACKGROUND: In the treatment of acute renal failure in patients with multiple organ dysfunction syndrome (MODS), continuous renal replacement therapies (CRRT) are increasingly used because of excellent volume control in the presence of improved cardiovascular stability. Patients with MODS, however, are frequently catabolic and have a high urea generation rate requiring either cost-intensive high-volume CRRT or additional intermittent haemodialysis to provide adequate clearance of small-molecular waste products. We tested the closed-loop batch haemodialysis system (called Genius((R))) for the treatment of acute renal failure in patients with MODS in the intensive care unit. METHODS: Blood flow and countercurrent dialysate flow were reduced to 70 ml/min. Thus the 75 l dialysate tank of the Genius((R)) system lasts for 18 h of extended single-path high-flux haemodialysis (18 h-HFD) using polysulphous F60 S((R)) dialysers. Blood pressure, body temperature, and venous blood temperature in the extracorporeal circuit (no heating of the dialysate), ultrafiltration rate, serum urea levels, dialyser urea clearance, and total urea removal were monitored. In addition we tested the bacteriological quality of the spent dialysate at the end of 18-h treatments. RESULTS: Twenty patients with acute renal failure and MODS were investigated. Averaged dialyser urea clearance was 59.8 ml/min (equal to 3.6 l/h or 64.8 l/day). Total removal of urea was 14.1+/-6.5 g/day keeping serum levels of urea below 13 mmol/l. Mean arterial pressure remained stable during the 18-h treatments with a mean ultrafiltration rate of 120 ml/h. The temperature in the venous blood tubing dropped by 5+/-0.5 degrees C during the 18-h treatment (0.28 degrees C/h) in the presence of unchanged core temperature in the patients. There was no bacterial growth in 2.5 l of spent dialysate (<0.0004 colony forming units/ml). CONCLUSIONS: Extended high-flux dialysis using the Genius((R)) system combines the benefits of CRRT (good cardiovascular stability, sterile dialysate) with the advantages of intermittent dialysis (high urea clearance, low treatment costs). High efficiency, simplicity and flexibility of the system offers the unique opportunity to use the same dialysis machine for extended time periods (18 h) as well as for shorter intermittent renal replacement therapy in critically ill patients.

Acute Kidney Injury↗
PubMed2000

Detection of significant renal artery stenosis with color Doppler sonography: combining extrarenal and intrarenal approaches to minimize technical failure.

BACKGROUND: Renal artery disease can cause both hypertension and renal failure, and color Doppler sonography (CDS) may be a good screening method to detect it. Presently reported techniques of Doppler sonography have either a high rate of technical failure (4-42%), or low sensitivity and specificity, or detect only stenoses greater than 70%, or exclude patients with renal failure from analysis. In previous studies Doppler detection of renal artery stenosis (RAS) was based either on increased intrastenotic velocity or on the detection of post-stenotic Doppler phenomena. In the present prospective study these two approaches were combined to detect RAS (> or = 50% diameter reduction) in 226 consecutive patients (144 with normal and 82 with impaired renal function). METHODS: Stenosis of 50% or more was diagnosed if the maximal systolic velocity in the main renal artery was more than 180 cm/sec and velocity in the distal renal artery less than one quarter of the maximum velocity. When these velocities could not be determined a diagnosis of RAS was made when the acceleration time in intrarenal segmental arteries exceeded 70 msec. All patients subsequently underwent arteriography as the gold standard for the detection of RAS. RESULTS: With this combined approach, the technical failure rate of CDS was 0% in both patients with normal and those with impaired renal function. The mean time required for the Doppler investigation was 17 minutes. The sensitivity and specificity for detection of a significant stenosis in a given vessel (including accessory arteries), as compared to angiography, were 96.7% and 98.0%. CONCLUSION: Color Doppler sonography, evaluating both main renal and intrarenal arteries is an ideal screening method for detection of RAS of 50% or more because it allows accurate and rapid detection of stenosis in all patients, irrespective of renal function.

Blood Flow Velocity↗
PubMed1999

Five cases of Kaposi's sarcoma in kidney graft recipients: possible influence of the immunosuppressive therapy.

BACKGROUND: Kaposi's sarcoma (KS) is an human herpesvirus 8-associated tumor, occurring in immunocompromised patients. We report here an increased incidence of KS among kidney graft recipients (KGRs) during the last 2 years, concomitant to the introduction of the immunosuppressant mycophenolate mofetil (MMF). METHODS: A total of 1835 KGRs, receiving organs between 1987 and 1997, were surveyed for the development of KS. A total of 371 patients received therapy including MMF (group A), whereas 1464 patients were treated with an MMF-free protocol (group B). RESULTS: 3/371 patients (0.8%) of group A versus 2/1464 patients (0.1%) of group B developed KS. In group A, KS became evident 7+/-2 months after initiation of MMF therapy. CONCLUSIONS: At our center, during the last 2 years, the incidence of KS has increased in KGRs, and it is not clear whether the introduction of MMF contributes to the phenomenon.

Drug Therapy, Combination↗
PubMed1999

Entry-into-human study with the novel immunosuppressant SDZ RAD in stable renal transplant recipients.

AIMS: To evaluate the tolerability of single oral SDZ RAD doses in stable renal transplant recipients and the pharmacokinetics of ascending SDZ RAD doses when coadministered with steady-state cyclosporin A microemulsion (Neoral). METHODS: This randomized, double-blind, placebo-controlled, sequential study involved 54 patients in six treatment groups; a different SDZ RAD dose (0.25, 0. 75, 2.5, 7.5, 15, 25 mg) was assessed in each group. Patients received a single oral dose of SDZ RAD (n=6) or placebo (n=3) with their usual Neoral dose. SDZ RAD and cyclosporin A pharmacokinetic parameters were determined. RESULTS: All SDZ RAD doses were well tolerated, with no discontinuations due to adverse events, serious adverse events, or deaths. Similar proportions of patients receiving SDZ RAD and placebo had at least one adverse event (44% and 50%, respectively). Mean changes in laboratory variables (baseline to endpoint) showed no clinically meaningful differences between SDZ RAD and placebo groups. SDZ RAD was absorbed rapidly and showed dose-proportional pharmacokinetics (dose: 2.5-25 mg), based on systemic exposure. Multiple postabsorptive phases in the pharmacokinetic profile indicate tissue distribution. The elimination half-life ranged from 24 to 35 h across the five highest dose groups. Pharmacokinetics were similar in men and women. Co-administration of escalating single oral SDZ RAD doses did not affect steady-state cyclosporin A pharmacokinetics. CONCLUSIONS: SDZ RAD was well tolerated; safety profiles of SDZ RAD and placebo were similar. SDZ RAD pharmacokinetics were dose-proportional across the range 2.5-25 mg in conjunction with cyclosporin A-based therapy, according to systemic exposure. Cyclosporin A pharmacokinetics were not affected by coadministration of single oral doses of 0.25-25 mg SDZ RAD.

Adolescent↗
PubMed1999

Short- and long-term effects of fish oil on proteinuria, morphology and renal hemodynamics in the Milan normotensive rat model of spontaneous glomerulosclerosis.

BACKGROUND/AIMS: A diet rich in polyunsaturated Omega3 fatty acids has been shown to modulate the course of several experimental models of renal disease. The short- and long-term effects of an 8% fish oil (FO) chow on proteinuria, renal blood flow and glomerular morphology were evaluated in Milan normotensive rats that spontaneously develop progressive glomerulosclerosis. METHODS: Eight rats each were pairfed FO- versus cholesterol-enriched or control diets for either 2 or 32 weeks. 4/48 animals died (2-week trial: 1 rat on the FO and 1 rat on the control diet; 32-week trial: 1 rat on the cholesterol and 1 rat on the control diet) and were excluded from all statistic analyses. RESULTS: After 2 weeks the renal blood flows were higher in the FO animals versus controls (8.75+/-2.19 vs. 6.87+/-1.91 ml/min/g, p<0.05), and the prostaglandin E2/thromboxane B2 ratio shifted towards the vasodilatative prostaglandin E2 (1. 76+/-0.18 vs. 0.91+/-0.19, p<0.05). During the long-term trial proteinuria in the FO animals progressed faster and to a higher level (176.5+/-32.2 vs. 82.7+/-36.7 mg/24 h at week 32, p<0.01). After 32 weeks the renal blood flow was significantly lower in th FO group 2.8+/-1.1 vs. 4.6+/-1.9 ml/min/g, (p<0.05), and the rats had an accelerated development of nephrosclerosis, with sclerotic lesions in 60.3+/-6.6% of the glomeruli as compared with 46.5+/-9.8% in the cholesterol and 39.8+/-5.9 in the control group (p<0.05). CONCLUSION: The short-time effects of FO on renal hemodynamics did not alleviate the progress of renal damage in Milan normotensive rats, but the morphologic and functional signs of injury were rather pronounced with FO feeding.

Animals↗
PubMed1999

CMV in kidney transplantation: a single center experience over 22 years.

Analysis of a historic renal transplant population for risks of developing CMV disease demonstrated a low mortality (0.2%) and morbidity. In our population of 1,959 patients, 411 (21%) developed subclinical CMV infection and 220 (11%) had CMV disease which was severe in 41 (2%). Important factors for infection were baseline immunosuppression, indicating that triple therapy with the proliferation inhibitors, azathioprine and MMF, had significantly higher infection numbers in comparison to dual, CsA-based immunosuppression. The cumulative dose of steroids correlated strongly with an increased number of CMV infections and disease, as did the addition of ALG/ATG or OKT3 for either steroid-resistant rejections or induction therapy. While CMV serology had an impact on infection in cases of seropositive donors to seronegative recipients, seropositive patients, in general, demonstrated increased infection rates most likely due to reactivation of the virus. Prophylaxis had no impact on the incidence of infection but reduced the severity.

Adult↗
PubMed1998

Pronounced renal vasoconstriction and systemic hypertension in renal transplant patients treated with cyclosporin A versus FK 506.

This prospective study investigated hypertension and renal vasoconstriction developing during the 1st year after renal transplantation in patients randomly allocated to treatment with FK 506 (n = 28) or CyA (n = 13). Starting doses were 0.2-0.3 mg/kg per day for FK 506 and 5-8 mg/kg per day for CyA: doses were subsequently adjusted to trough levels (5-15 ng/ml for FK 506 and 100-150 ng/ml for CyA). We compared 24-h ambulatory blood pressure measurement, antihypertensive treatment, serum creatinine, and resistance index (RI), measured by Doppler ultrasound at the level of the interlobar artery. Until month 2 of treatment, FK 506-treated patients had a significantly lower RI (8%) and better renal graft function, as evidenced by significantly lower serum creatinine values. Some 13% of FK 506-treated patients, compared to 70% of CyA-treated patients (P < 0.01), needed additional antihypertensive drugs after transplantation to keep blood pressure stable. FK 506 treatment, at the above-mentioned dosages, was associated with a significantly higher number of infections (urinary tract infection, pyelonephritis, and pneumonia). We conclude that CyA produces greater renal vasoconstriction and systemic hypertension than FK 506, as reflected in higher renal interlobar artery RI values and a greater need for antihypertensive treatment. After 2 months of treatment and a reduction in CyA trough levels, the renal effects (i.e., lower RI and lower creatinine values), but not the systemic hypertensive effects, disappear.

Adult↗