Biomedical subjects

V Kliem

Publications and source records attributed to V Kliem.

At least 55 records · Page 3Linked to original sources

PubMed1997

Assessment of long-term risks for living related kidney donors by 24-h blood pressure monitoring and testing for microalbuminuria.

Our aim was to assess the long-term risks for kidney donors of developing arterial hypertension and hypertension-associated diseases or hyperfiltration injury of the remaining solitary kidney. We conducted a cross-sectional study in which 29 donors who were nephrectomized at our center between October 1973 and March 1990 were enrolled. At the time of evaluation median age was 54 (37-70) yr. Since kidney donation an average time interval of 11.1 +/- 3.8 yr had elapsed. Body weight, casual blood pressure, S-creatinine and proteinuria were recorded. In 28/29 donors 24-h blood pressure monitoring was performed; all 29 were tested for microalbuminuria (MAU). The patient history was checked for treatment with antihypertensives, coronary heart disease and diabetes mellitus. From all 29 kidney donors surveyed up to 19.8 yr none developed marked renal insufficiency: median S-creatinine was 1.0 mg/dl (range 0.7-1.6), only 3 donors had a S-creatinine > 1.3 mg/dl. Glomerular filtration rate (GFR) decreased in an age-dependent manner. While all donors had been normotensive without an antihypertensive treatment at time of nephrectomy, actually 29% proved to be hypertensive with average values > 130/80 mmHg in the 24-h assessment. 5/29 donors received antihypertensives, 3 of whom nevertheless were hypertensive. Day-night profile was lost in 2 patients. After donation one patient developed coronary heart disease. 7/29 donors (24%) displayed positive testing for MAU, furthermore one had proteinuria (approx. 300 mg/l). MAU was associated in one case with slightly elevated S-creatinine (1.3 mg/dl) and in 3 cases with arterial hypertension. In the long-term course living related kidney donors do not seem to be at risk for developing hypertensive disorders more often than the general population. The prevalence of MAU in the 29 cases studied was higher than so far described for healthy subjects. This may reflect subclinical hyperfiltration damage of the glomerulus. Progressive renal insufficiency with clinical relevant function loss of the remaining solitary organ, however, was not observed up to 19.8 yr after kidney donation.

Adult↗

PubMed1996

The long-term course of hepatitis C after kidney transplantation.

Patients with chronic hepatitis run the risk of developing progressive liver disease during immunosuppressive therapy after kidney transplantation. To determine the impact of chronic hepatitis C on morbidity and mortality we analyzed 162 anti-HCV positive of 1241 renal-grafted patients (prevalence 13.1%; 84.9% HCV RNA positive) regularly surveyed in our outpatient clinic between 1992 and 1994. The mean age at transplantation was 44.5 (6-69) years, and follow-up after grafting was 7.4 (0.1-23.9) years. The immunosuppressive regimen and frequency of rejection episodes in HCV-infected patients were comparable to the total population. Only 4.3% (5/117) of the anti-HCV positive, HBV negative patients living with functioning grafts developed a markedly compromised liver function. Fifteen (9.3%) of the HCV-infected patients died, but none suffered from posthepatitic cirrhosis. An additional retrospective analysis of causes of death after transplantation prior to 1992 revealed that liver disease had only been responsible for 2% of the deaths (7 of 324) in the HBsAg negative population (n= 1901). In contrast, the predominant cause of death in the HBsAg positive population (n=76) was posthepatitic cirrhosis in 58% (15 of 26). Thus, kidney transplantation in patients with replicative hepatitis C and normal liver function appears to be justified because of low early and late morbidity and mortality due to chronic liver disease. HBV infection and hemosiderosis substantially increase the risk of chronic liver disease in renal transplant recipients with hepatitis C.

Adolescent↗

PubMed1996

Incidence of Pneumocystis carinii pneumonia after renal transplantation. Impact of immunosuppression.

The incidence and potential risk factors of Pneumocystis carinii pneumonia (PCP) in our population of renal transplant recipients were analyzed retrospectively. Of 1427 patients who received transplants between January 1986 and June 1994, 1192 were evaluated. Four different immunosuppressive regimens were applied: (1) cyclosporine (CsA) + prednisolone (Pred), (2) CsA + azathioprine (Aza, 2 mg/kg/day) + Pred, (3) CsA + Aza + antithymocyte globulin, and (4) (after December 1, 1993, European multicenter trial) FK506 + Aza (1 mg/kg/day) + Pred. No prophylaxis against PCP was performed. Before December 1, 1993, three PCPs in 494 patients on protocol 2 or 3 occurred (0.6%). Afterward, seven PCPs in 77 patients occurred (9%): three in 38 patients on protocol 2 (7.8%) and four in 28 patients on protocol 4 (14.3%). Comparing patients with PCP on CsA and FK506, the mean Aza dose was 2.40 and 1.32 mg/kg/day, five and two patients received additional steroids, antibody treatment was used in three and no patients, and CMV infections occurred in five and two patients, respectively. The incidence of PCP with a moderate CsA-based immunosuppressive regimen is low and seems to occur only in cases of additional immunosuppressive cofactors. Despite a general increase of PCP, its incidence was highest in patients on FK506 with fewer immunosuppressive cofactors. Thus, prophylaxis against PCP after renal transplantation should be performed, if not in every renal transplant recipient, at least in case of treatment with additional steroids, antibodies, or FK506.

Adult↗

PubMed1996

How best to use tacrolimus (FK506) for treatment of steroid- and OKT3-resistant rejection after renal transplantation.

Nineteen patients with biopsy-confirmed ongoing acute rejection of renal allografts were converted from standard immunosuppression to FK506. Eight grafts showed vascular rejection and 11 had cellular rejection on biopsy. All patients had already received intravenous high-dose steroid treatment. Ten patients also had additional OKT3 rescue therapy. Initial FK506 doses were 0.13 +/- 0.06 mg/kg/day; the FK506 whole blood trough level after 3 days of treatment was 9.3 +/- 4.5 ng/ml. After conversion to FK506 all but four patients also received azathioprine, 1.5-2 mg/kg/day, and all patients received oral prednisolone. Concomitant with initiation of FK506, an anti-infective prophylaxis was prescribed, consisting of ganciclovir and trimethoprim/sulfamethoxazole. Sixteen out of 19 of the grafts (84%) were rescued successfully, including two grafts of patients already on hemodialysis at the time of conversion. Graft function of the responders improved from an average serum creatinine level of 364 +/- 109 mumol/L to 154 +/- 49 mumol/L. Of the patients receiving high-dose steroids alone prior to FK506 initiation, 8/9 responded to FK506 treatment, compared with 8/10 of those who had also received OKT3. During the mean follow-up of 35 weeks after conversion, no clinically apparent cytomegalovirus infection and no pneumonia were seen. Treatment with FK506 may successfully suppress ongoing acute rejection, even if antilymphocyte preparations have failed. FK506 can be used at a lower dose than so far recommended without impairing the antirejection potential. An additional anti-infective prophylaxis seems effective in preventing severe complications in the first months after rejection therapy.

Adult↗

PubMed1996

Hepatitis B virus envelope variation after transplantation with and without hepatitis B immune globulin prophylaxis.

Hepatitis B virus (HBV) replicates via an intermediate RNA step. High frequency of polymerase errors with additional selection pressure leads to mutations in the HBV genome. We investigated the number, type, and antigenic effects of mutations in the coding region of the HBV surface antigen in eight patients who underwent orthotopic liver transplantation (OLT) for HBV-related end-stage liver disease and were experiencing infection of the graft and who received hepatitis B surface antigen antibody (anti-HBs) prophylaxis (hepatitis B immune globulin [HBIG]) after OLT. Controls were chronic HBV patients who underwent kidney transplantation and received the same immunosuppressive regime but no HBIG. The S-gene was amplified from serum before and after transplantation, sequenced, and changes in the genome were analyzed. In the five patients who experienced reinfection while receiving anti-HBs, clear mutations occurred in the S-gene. In the patient who did not receive HBIG and those who experienced reinfection only after termination of HBIG, no mutations were found in the S-gene. In the kidney recipients, mutations in the S-gene occurred in only one of eight patients. Because the a determinant contains neutralizing epitopes, this region was chosen for antibody binding to quantify antigenic effects of the mutations. The two patients who selected mutations in the a determinant and became reinfected while receiving HBIG had reduced antibody binding after OLT. Our results suggest that HBIG after OLT imposes a selection pressure on the S-gene, and that mutations are one mechanism for reinfection while receiving HBIG.

Amino Acid Sequence↗

PubMed1996

High mortality from urothelial carcinoma despite regular tumor screening in patients with analgesic nephropathy after renal transplantation.

Patients with end-stage renal failure due to analgesic nephropathy have an increased risk of developing a urothelial carcinoma. To determine the impact of renal transplantation on the frequency of urothelial carcinomas, we analyzed 2072 patients who underwent 2371 renal transplantation between 1968 and 1993, including 78 (3.8%) with clinically proven analgesic nephropathy. Before and after transplantation a regular tumor screening was performed in patients with analgesic nephropathy by urine cytology and abdominal sonography. In 11 of the 78 patients with analgesic nephropathy (14.1%; age 51-66 years, 40-108 months after initiation of dialysis treatment, 5-77 months after transplantation), a urothelial carcinoma of the native urinary tract, especially the kidneys, was diagnosed. Therapy comprised nephroureterectomy (n = 6), transurethral resection (n = 6) and/or cystectomy (n = 2). Seven patients died due to tumor progression 16.3 (4-33) months postoperatively and one patient died due to a perioperative complication. Despite regular tumor screening after transplantation, the diagnosis of a urothelial carcinoma was made very late, leading to a high tumor-related mortality. As a consequence, we suggest that a bilateral nephroureterectomy should be performed prophylactically in patients with proven analgesic nephropathy. In addition, a cystoscopy with lavage cytology testing of the bladder should be performed twice a year.

Acetaminophen↗

PubMed1996

Mechanisms involved in the pathogenesis of tubulointerstitial fibrosis in 5/6-nephrectomized rats.

The 5/6 nephrectomy model is used to study pathogenetic mechanisms underlying chronic renal failure. We previously demonstrated that increased mesangial cell proliferation and glomerular PDGF B-chain expression precede glomerulosclerosis in this model. In the present study we have assessed the concomitant changes in the cortical tubulointerstitium. A wave of tubular and interstitial cell proliferation (as determined by immunostaining for PCNA) occurred at week 1 after 5/6 nephrectomy. This wave preceded the peak glomerular cell proliferation by one week. Tubulointerstitial cell proliferation decreased thereafter and reached control values by week 10. In situ hybridization and immunostaining for PDGF B-chain and beta-receptor in sham-operated controls showed labeling of distal tubules and collecting ducts, while no signal was present in the interstitium. PDGF B-chain mRNA and protein expression was markedly increased in tubules at weeks 2 and 4 after 5/6 nephrectomy and in the interstitium (particularly in areas of inflammatory infiltrates) at weeks 2 to 10. Similar changes occurred with PDGF receptor beta-subunit immunostaining. Interstitial expression of desmin and alpha-smooth muscle actin (markers of myofibroblasts) progressively increased after week 1. Interstitial influx of monocytes/macrophages with focal accentuation started at week 2. Counts of lymphocytes, neutrophils and platelets showed only minor changes. In parallel to the monocyte/macrophage influx, progressive interstitial accumulation of collagens I and IV, laminin, and fibronectin occurred. All of these changes were correlated with the increase in serum creatinine, proteinuria and an index of tubulointerstitial damage. We conclude that tubulointerstitial changes after 5/6 nephrectomy show similarities with those observed in the glomeruli. Tubular and interstitial overexpression of PDGF B-chain and its receptor may play a role in mediating fibroblast migration and/or proliferation in areas of tubulointerstitial injury.

Actins↗

PubMed1996

Diltiazem increases blood concentrations of cyclized cyclosporine metabolites resulting in different cyclosporine metabolite patterns in stable male and female renal allograft recipients.

1. Six male and six female stable renal allograft recipients under cyclosporine immunosuppression and without concomitant therapy with drugs known either to induce or inhibit CYP3A enzymes were included in the study and received 180 mg day-1 diltiazem for 1 week in a two-period cross-over fashion. Cyclosporine (352 +/- 56 mg day-1) was given in two daily oral doses. The daily doses were not changed during the study. Blood samples were collected for 12 h after receiving cyclosporine alone and after receiving diltiazem in addition for 1 week. Cyclosporine and nine of its metabolites were quantified using h.p.l.c. 2. Co-administration of diltiazem caused a 1.6 fold increase of the AUC (0, 12 h) of cyclosporine and a 1.7 fold increase of the AUC(0, 12 h) of its metabolites. Analysis of the metabolite patterns showed an over-proportional increase of the AUC(0, 12 h) of the cyclized metabolites AM1c (2.6 fold) and AM1c9 (2.2 fold). The AUC(0, 12 h) values of cyclosporine and the hydroxylated metabolites increased less than two fold. 3. Differences of the AUC(0, 12 h) values of cyclosporine with and without diltiazem were significantly higher in female than in male patients (P < 0.02). The differences in the AUC(0, 12 h) values of the metabolites, especially AM1c, tended to be higher in female patients as well. 4. It is concluded that coadministration of diltiazem not only increases the blood concentration of cyclosporine but also those of its metabolites, leads to a shift of the metabolite pattern towards cyclized metabolites, and that the pharmacokinetic changes under diltiazem administration are more prominent in female than in male patients.

Adult↗

PubMed1996

No significant influence of HLA determinants on susceptibility to hepatitis C virus infection in Caucasian patients with end-stage renal disease.

In hepatitis C, both susceptibility to infection and the course of disease may depend on differences in the immune response. As the major histocompatibility complex (MHC) plays a crucial role in antigen presentation, we investigated a possible relationship between susceptibility to hepatitis C virus (HCV) infection and human leucocyte antigen (HLA) alleles. Therefore, phenotype frequencies of HLA were compared in 186 anti-HCV positive patients with end-stage renal disease (ESRD) to 328 anti-HCV negative patients with ESRD. HLA class I alleles were determined serologically and HLA class II alleles (DRB1, DQA1, DQB1) by the polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) technique. Additionally, in anti-HCV positive patients we looked for a relationship between the activity of hepatitis C (indicated by elevation of transaminases or the presence of viremia) and HLA determinants. For the three criteria (antibody status, elevation of transaminases and viremia) a significant association to HLA alleles was not found in patients with ESRD. This suggests that neither susceptibility to HCV infection nor the biochemical activity of hepatitis and HCV-RNA positivity seem to be strongly related to HLA status in Caucasian patients with end-stage renal disease.

Adult↗

PubMed1996

Recurrence of membranoproliferative glomerulonephritis after renal transplantation in a patient with chronic hepatitis C.

Chronic hepatitis C (HCV) infection may be associated with membranoproliferative glomerulonephritis (MPGN) with or without concomitant cryoglobulinemia. We report on a patient with end-stage renal disease caused by MPGN I in association with replicative HCV infection. Two years after successful renal transplantation, this patient developed nephrotic syndrome caused by recurrence of MPGN I in the renal transplant. The recurrence of renal disease after transplantation in this patient with chronic replicative HCV further elucidates the role of the viral infection in the pathogenesis of MPGN and suggests anti-viral treatment as, e.g., with interferon.

Adult↗

PubMed1996

Relationship between human leukocyte antigen determinants and courses of hepatitis B virus infection in Caucasian patients with end-stage renal disease.

BACKGROUND: Divergent results have been reported with regard to the relationship between the course of hepatitis B virus (HBV) infection and the human leukocyte antigen (HLA) determinants. The aim of the present study was to investigate the phenotype frequencies of HLA class-I and -II alleles in Caucasians with and without HBV infection. METHODS: Fifty-eight patients with persistent HBV infection (group 1), 119 patients with resolved HBV infection (group 2), and 106 patients neither infected by HBV nor vaccinated against HBV (group 3) were analyzed. All patients had end-stage renal disease. HLA class-I antigens were serologically determined. For HLA class-II typing we performed DRB1, DQA1, and DQB1 genotyping using a polymerase chain reaction-sequence-specific oligonucleotide procedure. RESULTS: Compared with group 2, group 1 showed increased frequencies of HLA-B8, DR3 (P < 0.05), A30, DQA1*0501 (P < 0.01), and a decreased frequency of HLA-B12 (P < 0.05). Decreased frequencies of HLA-B27, B40, DR13, and DQ1*0604 (P < 0.05) and an increased frequency of HLA-B35 (P < 0.05) were found in groups 1 and 2 compared with controls (group 3). None of the differences detected in the phenotype frequencies of HLA alleles were statistically significant after correction. CONCLUSIONS: We conclude that the susceptibility to HBV infection and the different courses of HBV infection are not strongly related to HLA status in Caucasians.

Adult↗

PubMed1996

Interleukin-1 beta stimulates glucose uptake of human peritoneal mesothelial cells in vitro.

To investigate whether the glucose uptake (GU) of human peritoneal mesothelial cells (HPMC) is mediated by glucose transporters and whether this uptake is influenced by interleukin 1-beta (IL-1 beta), we measured 2-deoxy-(3H)-GU of HPMC in vitro, after exposing the cells for different times (two and 12 hours) to increasing concentrations (0.1, 1.0, and 2.0 ng/mL) of IL-1 beta. To exclude a noncarrier-mediated transport, GU was also tested in the presence of cytochalasin B. All experiments were performed in triplicate in the cells of two donors. Cytochalasin B inhibits GU of HPMC almost completely. GU of HPMC is not stimulated by insulin. GU is stimulated by IL-1 beta in a dose-dependent manner. These data indicate a GU of HPMC, which is mediated by a glucose transporter and stimulated by IL-1 beta. The increased uptake of glucose from the dialysate in patients with peritonitis may be mediated by a (cytokine-induced) increased activity of HPMC glucose transporters.

Blood Glucose↗

PubMed1996