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V Kliem

Publications and source records attributed to V Kliem.

At least 37 records · Page 2Linked to original sources
PubMed1998

Pharmacokinetics of pantoprazole in patients with end-stage renal failure.

BACKGROUND: Pantoprazole is a selective inhibitor of the gastric H+/K+-ATPase with a low potential to interact with the cytochrome P450 enzyme system. Since pantoprazole is metabolized in the liver to metabolites which are mainly cleared by the renal route, it was the aim of this study to investigate its pharmacokinetics in patients with end-stage renal failure undergoing regular haemodialysis. METHODS: Eight patients with end-stage renal failure (creatinine clearance < 5 ml/min, age 45-65 years) on regular haemodialysis (duration of haemodialysis 4-5 h, cuprophan-dialyser Hemoflow E3, surface 1.3 m2) were given single i.v. doses of 40 mg pantoprazole one day before haemodialysis (A) and on a haemodialysis day immediately before the start of the haemodialysis (B). Concentrations of pantoprazole and metabolite M2 were determined in plasma and urine over 24 h and in timed samples of the dialysis fluid by HPLC. The protein binding was determined using equilibrium dialysis. RESULTS: The pharmacokinetic characteristics of pantoprazole AUC, t(1/2), CL and V(d area) (geometric means) were 2.4 mgxh/l, 0.63 h, 0.227 l/h/kg and 0.206 l/kg on day A (without dialysis) and 2.3 mgxh/l, 0.8 h, 0.237 l/h/kg and 0.273 l/kg on day B (with dialysis), respectively. The protein binding was 96%. Pantoprazole was found in small amounts in the dialysis fluid (max. 2.1% of the dose) but not in the urine. Pantoprazole was well tolerated. In particular, there were no clinically relevant changes in blood count, electrolytes or liver enzymes. CONCLUSIONS: Haemodialysis has no influence on the pharmacokinetic characteristics of pantoprazole. Thus, pantoprazole is not dialysed to any relevant degree, and therefore no dose-adjustment is required for patients with end-stage renal failure undergoing regular haemodialysis treatment.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Procalcitonin in the early phase after renal transplantation--will it add to diagnostic accuracy?

The determination of serum procalcitonin (PCT) was tested for its utility in detecting invasive bacterial infection and acute rejection during the first 6 wk after kidney transplantation. Fifty-seven kidney graft recipients were prospectively included in the study. In 13/57 patients, 16 episodes of acute biopsy-proven rejection occurred and were treated with high-dose steroids (n = 14) or with OKT3 (n = 2). Seventeen out of 57 patients experienced 19 invasive bacterial infections; 2/57 had partial graft necrosis due to malperfusion. Twenty-five out of 57 graft recipients experienced an uncomplicated postoperative course. A total of 116 samples were analyzed and the following data obtained: PCT, C-reactive protein (CRP), white blood cell (WBC) count, corresponding body temperature and serum creatinine. Procalcitonin values for patients with rejection did not differ significantly from those of the healthy transplant recipients (p = 0.47). In contrast, PCT was clearly elevated with invasive bacterial infection or partial graft necrosis (p < 0.01). OKT3 treatment of rejection led to a more than 10-fold increase in PCT. C-reactive protein, unlike PCT, was elevated to a variable extent in patients with graft rejection, though CRP values were significantly more elevated in patients with infection than in those with rejection (p < 0.01). The specifity for detection of invasive bacterial infection was 0.7 for PCT and 0.43 for CRP, whereas sensitivity was 0.87 for PCT and 1.0 for CRP. There was no correlation between PCT and serum creatinine (r = 0.06). Haemodialysis did not lower PCT serum concentrations. Procalcitonin values rose postoperatively to peak levels on the first and second days and mostly declined to normals within 1 wk. In conclusion PCT, not being influenced by acute kidney graft rejection but serving as a specific indicator of systemic bacterial infection, could help to discriminate between both types of inflammation.

Bacterial Infections↗
PubMed1998

Antiproteinuric efficacy of fosinopril after renal transplantation is determined by the extent of vascular and tubulointerstitial damage.

BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors have been successfully used for treatment of proteinuria after renal transplantation (RTx). Factors possibly responsible for the great inter-patient variance of the antiproteinuric effect (APE) have not yet been investigated in renal-transplanted patients. METHODS: 28 patients after RTx with a persistent proteinuria of more than 1.25 g/d were treated prospectively with does of fosinopril (10-15 mg/d) which were not effective on systemic arterial blood pressure. Prior to initiation of fosinopril, renal graft biopsy was performed in all patients and renal graft artery stenosis was excluded by duplex ultrasound. Serum creatinine and proteinuria were measured prior to, as well as 3 and 8 months after initiation of ACE inhibition, mean arterial pressure was controlled via 24-h measurement and repeated spot measurements. Reduction of proteinuria was correlated with renal histology, serum creatinine, creatinine clearance, mean arterial blood pressure, sodium excretion before therapy and the relative changes of these parameters during therapy respectively. RESULTS: Therapy had to be stopped in 8/28 patients due to side effects including rise of serum creatinine (n = 4). Three patients were excluded due to non-compliance. In the remaining patients (n = 17) proteinuria was reduced from 2.94 +/- 1.66 to 1.82 +/- 1.39 and 2.48 +/- 3.05 g/d after 3 and 8 months respectively, in the mean +/- SD. There was a significant inverse correlation between the APE and the extent of benign nephrosclerosis, interstitial fibrosis and tubular atrophy. No correlation of the APE to any of the other parameters could be demonstrated. CONCLUSIONS: Fosinopril can be administered effectively in a subgroup of proteinuric renal transplant recipients. However, because of a high proportion of patients developing side effects, careful monitoring is obligatory. Our results show that the lesser the degree of chronic morphological injury, the greater is the antiproteinuric effect. Thus, the degree of pre-existing histologically proven damage of the graft may serve as an indicator for the antiproteinuric efficacy of ACE inhibitor therapy after RTx.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Recurrent immunoglobulin A nephropathy after renal transplantation: a significant contributor to graft loss.

BACKGROUND: Although most transplanted patients with underlying IgA nephropathy (IgAN) develop histological recurrence, its clinical relevance is considered low. METHODS: We performed a single-center analysis of 61 renal transplant patients with IgAN. RESULTS: Forty-four percent of the patients showed a stable graft function. Progressive graft dysfunction apparently due to recurrent IgAN occurred in 23% of the patients (16% required dialysis). Five patients were retransplanted, and three again developed dialysis-dependent renal failure apparently due to recurrent IgAN. In 20% of the patients, chronic transplant dysfunction was due to other reasons, whereas no reason was identified in 13% of the patients. Neither findings before transplantation, the ACE genotype, the type of immunosuppression, nor the course after transplantation predicted transplant dysfunction due to recurrent IgAN. Follow-up after transplantation was longer in the group with dysfunction due to recurrent disease than in the group with dysfunction due to chronic rejection or in the stable group. CONCLUSION: Recurrent IgAN is a clinically relevant problem in renal transplant patients. Its importance may have been underestimated in the past due to inadequate lengths of follow-up.

Adult↗
PubMed1997

Renal transplantation for patients with autoimmune diseases: single-center experience with 42 patients.

BACKGROUND: In patients with autoimmune diseases such as vasculitis or systemic lupus erythematosus (SLE), end-stage renal disease develops in a high percentage of patients, and kidney transplantation has become a therapeutic option. However, only limited data about the prognosis and outcome after kidney transplantation are available. METHODS: Long-term graft survival and graft function of renal transplant recipients with SLE, Wegener's granulomatosis, microscopic polyangiitis, Goodpasture's syndrome, and Henoch-Schonlein purpura were evaluated in a single center. In addition, the incidence of renal and extrarenal relapses and the impact of the immunosuppressive therapy on the course of the autoimmune disease were studied. RESULTS: Renal transplant recipients with autoimmune diseases such as vasculitis and SLE had a patient survival rate (94% after 5 years) and a graft survival rate (65% after 5 years) comparable to those of patients with other causes of end-stage renal disease (patient survival 88% and graft survival 71% after 5 years). Graft losses due to the underlying disease were rare. Extrarenal relapses occurred in three patients with Wegener's granulomatosis, one patient with microscopic polyangiitis, and three patients with SLE, but were less frequent compared with the period with chronic dialysis therapy. Autoantibody levels in patients with SLE, Wegener's granulomatosis, or microscopic polyangiitis did not seem to influence the outcome. CONCLUSIONS: Renal transplantation should be offered to patients with autoimmune diseases. Follow-up should include the short-term control of renal and extrarenal disease activity.

Adult↗
PubMed1997

Usefulness of procalcitonin for differentiation between activity of systemic autoimmune disease (systemic lupus erythematosus/systemic antineutrophil cytoplasmic antibody-associated vasculitis) and invasive bacterial infection.

OBJECTIVE: To investigate whether the determination of serum procalcitonin (PCT) in systemic autoimmune disease will help to discriminate invasive infection from highly active underlying disease. METHODS: Three hundred ninety-seven serum samples, from 18 patients with systemic lupus erythematosus (SLE) and 35 patients with systemic antineutrophil cytoplasmic antibody-associated vasculitis (AAV), were analyzed. Clinical disease activity was assessed by the Systemic Lupus Activity Measure in SLE patients and by the Birmingham Vasculitis Activity Score in AAV patients. Procalcitonin concentrations were determined in parallel with concentrations of neopterin, interleukin-6 (IL-6), and C-reactive protein (CRP). Additionally, serum creatinine values were obtained. RESULTS: In 321 of the 324 samples from the 42 patients with autoimmune disease but without systemic infection, serum PCT levels were within the normal range (i.e., <0.5 ng/ml), whereas the values for neopterin, IL-6, and CRP were elevated in patients with active underlying disease. All 16 systemic infections occurred in 11 patients with AAV, and were associated with PCT levels that were markedly elevated, to a mean +/- SD of 1.93 +/- 1.19 ng/ml. No correlation between the degree of renal impairment and PCT concentrations was seen. CONCLUSION: PCT may serve as a useful marker for the detection of systemic bacterial infection in patients with systemic autoimmune disease.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1997

Open heart operations after renal transplantation.

BACKGROUND: Because of the increasing number of renal transplantations performed, secondary cardiac operations in these patients are discussed concerning their impact on patient and graft survival. METHODS: We reviewed our experience in 45 patients (33 male and 12 female) who underwent open heart operations after previous renal transplantation. Thirty-one patients (group I) received coronary artery bypass grafting and 14 (group II) underwent valve replacement. Mean age at the time of operation was 55 +/- 9 years. The interval between renal transplantation and cardiac operation was 57 +/- 39 months (range, 5 days to 174 months). All patients had functioning renal allografts with preoperative serum creatinine levels ranging from 100 to 338 mol/mL (mean +/- standard deviation, 195 +/- 86). RESULTS: Overall early operative mortality (30 days) was 8.8% (group I, 1 patient; group II, 3 patients). Underlying causes of death were septic endocarditis (n = 2, group II), necrotizing enterocolitis (n = 1, group I), and myocardial infarction (n = 1, group II). One further patient in group II also died of septic endocarditis after 69 days (in-hospital death). The mean follow-up of the 40 surviving patients was 44 +/- 31 months. There was another late death (24 months postoperatively) caused by coagulopathy. Four patients had returned to hemodialysis at intervals of 27 to 83 months (mean, 51 months) because of renal transplant failure. In all patients, the function of the renal allograft was not impaired by open heart operation. CONCLUSIONS: Open heart operations in renal transplant recipients have acceptable mortality and morbidity rates. In almost all patients, function of the transplanted organ can be maintained at the preoperative level.

Coronary Artery Bypass↗
PubMed1997

Accumulation of lovastatin, but not pravastatin, in the blood of cyclosporine-treated kidney graft patients after multiple doses.

OBJECTIVES: To study pravastatin and lovastatin pharmacokinetic and pharmacodynamic effects and their interactions with cydosporine (INN, ciclosporin) in kidney transplant patients after single and multiple doses. SUBJECTS AND METHODS: The pharmacokinetic and pharmacodynamic effects of administration of 20 mg/day oral pravastatin and lovastatin for 28 days and their interactions with cyclosporine (2 to 6 mg/kg/day) were studied in a double-blind, double-dummy, randomized, parallel-group multicenter trial in 44 stable kidney graft recipients. RESULTS: The median area under the curve [AUC(0-24)] of pravastatin was 249 microg x hr/L (range, 104 to 1026 microg x hr/L) after a single dose (day 1) and 241 microg x hr/L (114 to 969 microg x hr/L) after multiple doses (day 28) and was fivefold higher than values reported in the absence of cyclosporine. The median AUC(0-24) of lovastatin was 243 microg x hr/L (105 to 858 microg x hr/L) on day 1 and 459 microg x hr/L (140 to 1508 microg x hr/L) on day 28. Besides a significant accumulation during the study period (p < 0.001), the lovastatin AUC(0-24) values were twentyfold higher than values reported without cyclosporine. Coadministration of pravastatin or lovastatin did not alter cyclosporine pharmacokinetics. In this study, 20 mg/day doses of both drugs resulted in a significant improvement of the lipid profile and were well tolerated. CONCLUSIONS: In contrast to lovastatin, pravastatin did not accumulate over the study period, which is probably one of the reasons rhabdomyolysis has been reported in lovastatin-treated but not pravastatin-treated transplant patients receiving cyclosporine immunosuppression.

Adult↗
PubMed1997

Age-related glomerulosclerosis and interstitial fibrosis in Milan normotensive rats: a podocyte disease.

In Milan normotensive (MNS) rats glomerulosclerosis and interstitial fibrosis develop spontaneously in the absence of hypertension. Renal changes were sequentially assessed in these rats between 2 and 10 months of age. At 10 months, rats were characterized by heavy proteinuria, increased serum creatinine, focal or global glomerulosclerosis in 51 +/- 12% of the glomeruli as well as tubulointerstitial injury involving > 25% of the section area. Cell injury in podocytes (evidenced as increased expression of desmin and by electron microscopy) and interstitial fibroblasts (increased expression of alpha-smooth muscle actin) and mild glomerular hypertrophy were witnessed as early as three to four months of age and preceded glomerulosclerosis and interstitial fibrosis. Only minor evidence of mesangial cell activation (as assessed by glomerular (de novo alpha-smooth muscle actin or type I collagen expression or increased cell proliferation) was noted throughout the observation period. Later stages of the disease were characterized by glomerular and/or tubulointerstitial macrophage influx and osteopontin expression (a chemoattractant), mild accumulation of lymphocytes, platelets, fibrinogen, as well as by a progressive accumulation of various matrix proteins. Progressive renal disease in MNS rats is thus noteworthy for the relative lack of mesangial cell activation. Rather, early podocyte damage, induced by yet unknown mechanisms, may underlie the development of glomerulosclerosis and subsequent interstitial fibrosis.

Actins↗
PubMed1997

Risk of renal cell carcinoma after kidney transplantation.

Between December 1968 and July 1995, 2372 renal transplant recipients were seen regularly in our outpatient clinic. 154 patients (6.5%) of these subsequently developed a malignant tumor. One of the most frequently observed malignancies was a renal cell carcinoma in the native kidneys, found in 12 patients (7.8%; i.e. 0.5% of the total population), two of them with analgesic nephropathy and one with adult polycystic kidney disease. So-called acquired cystic kidney disease of the native kidneys was found in 73% of the patients with renal cell carcinoma. In the patients with renal cell carcinoma the median age at transplantation was 43.9 (39-55) yr. The median time from onset of end-stage renal failure and from transplantation to the appearance of the tumor amounted to 117.3 (43-206) and 75.8 (5-164) months, respectively. Despite nephrectomy, four patients died of the cancer (6-57 months). As a consequence we suggest a regular sonographic screening of the native kidneys twice a year in all renal transplant patients. As in dialysis patients, the main risk factors for the development of renal cell carcinoma seem to be so-called acquired cystic disease of the native kidneys and the underlying renal disease, such as analgesic nephropathy, and obviously not the immunosuppressive regimen after transplantation.

Adult↗
PubMed1997

Gene-polymorphisms of angiotensin converting enzyme and endothelial nitric oxide synthase in patients with primary glomerulonephritis.

UNLABELLED: The ACE D- and the ecNOS a-allele have been associated with an adverse prognosis in patients with glomerulonephritis (GN). Using genomic DNA we investigated by RT-PCR whether the two polymorphisms are useful prognostic markers in GN patients. In patients with primary GN (IgA-GN n = 70, membranous GN n = 23, FSGS n = 17, MPGN n = 6) neither the whole group nor disease-specific subgroups exhibited any alterations from the normal ACE genotype distribution. No significant associations were detected between the ACE genotype and the development of hypertension, antihypertensive therapy required, progression rate of the disease, age of diagnosis and the antiproteinuric response to ACE-inhibition. In 40 IgA-GN patients with ESRD no increased prevalence of the D-allele was noted. The distribution of the ecNOS-alleles in the above patients (a-allele 22%, b-allele 78%) was comparable to that of the normal controls. No association with any of the parameters mentioned above were detected in the case of the ecNOS-alleles. CONCLUSIONS: In our Caucasian patients neither the determination of the ACE nor the ecNOS genotype offered any diagnostic or prognostic help.

Adult↗