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Biomedical subjects

H Kreis

Publications and source records attributed to H Kreis.

At least 55 records · Page 3Linked to original sources

Carotid atherosclerosis in renal transplant recipients.

BACKGROUND: Cardiovascular accidents are the major cause of morbidity and mortality in renal transplant recipients. However, there is little information concerning carotid atherosclerotic wall changes in renal transplant recipients, their relationship with cardiovascular accidents and their possible association with cardiovascular risk factors in such patients. METHODS: Between April 1991 and December 1997, we prospectively assessed cardiovascular accidents in 79 renal transplant recipients who had received a transplant at our institution before January 1, 1986. Carotid morphology by B-mode ultrasonography, relevant clinical and laboratory cardiovascular risk factors, including lipid abnormalities and total homocyst(e)ine, were determined at the start of the follow-up period. Seventeen healthy subjects matched for age and sex with renal transplant recipients served as controls who volunteered for ultrasonographic examination of carotid arteries. RESULTS: Nine patients experienced cardiovascular events during the period of follow-up. Compared with healthy, age- and sex-matched control subjects (n = 17), the frequency of carotid plaques was higher in renal transplant recipients with cardiovascular events (n = 9), but not in those without such events (n = 70). The frequency of cardiovascular accidents was related to the number of carotid plaques (4, 17 and 24% for no plaque, one plaque and > 1 plaque respectively, P < 0.04). However, by multivariate analysis, serum total cholesterol [odds ratio (OR) of 1.8 for each 1.0 mM, P < 0.07) and the presence of diabetes mellitus (OR of 28.4 for presence, P < 0.01) were the only predictors of cardiovascular events in such patients, whereas the presence of carotid plaques was not. Moreover, neither serum lipoprotein (a) nor total homocyst(e)ine concentrations could be identified as risk factors. CONCLUSIONS: This prospective study shows that although a close association exists between asymptomatic carotid atherosclerosis and cardiovascular accidents in renal transplant recipients with long-term follow-up and relatively good renal function, other potentially modifiable risk factors appear to be better predictors of cardiovascular events. Consequently, the assessment of carotid atherosclerosis may not be clinically useful for the systematic identification of renal transplant recipients with an increased risk of developing cardiovascular events.

Adult↗

Study of the in vitro effect on glomerular albumin permselectivity of serum before and after renal transplantation in focal segmental glomerulosclerosis.

BACKGROUND: The selective proteinuria observed in patients with focal segmental glomerulosclerosis (FSGS) suggests an abnormal loss of fixed anionic charges on the glomerular capillary wall. METHODS: In this article, we have studied the putative presence of such factor(s) by using a new in vitro assay to assess glomerular permselectivity by measuring glomerular volume variation (GVV) in isolated glomeruli after hypotonic stress. We randomly tested the serum GVV activity of 10 healthy donors and 143 patients before transplantation. Of the patients, 80 had FSGS, 26 membranous glomerulonephritis, 19 polycystic kidney disease, and 18 malformative uropathies. Moreover, we tested the pre- and posttransplantation serum of 14 patients with recurrence and 14 without recurrence. RESULTS: Serum GVV was significantly higher in patients with FSGS than in those with the other end-stage renal diseases studied (P<0.01) or in healthy donors (P<0.01). However, a wide distribution of serum GVV activity in patients with and without FSGS was observed. Statistically, pregraft GVV values were not predictive of the recurrence of FSGS after transplantation. Moreover, we observed a significant decrease in serum GVV activity after transplantation in patients without recurrence (P<0.01) compared to those who underwent a recurrence. CONCLUSIONS: These results reinforce the hypothesis of a circulating factor that alters glomerular albumin permselectivity in FSGS patients. However, the presence of this factor before transplantation did not appear to predict relapse of the disease after transplantation, as recently supported, although its activity seems to be down-regulated after transplantation in patients who do not experience recurrence of the disease.

Capillary Permeability↗

A pilot trial of recombinant human interleukin-10 in kidney transplant recipients receiving OKT3 induction therapy.

BACKGROUND: We conducted a randomized, double-blind, placebo-controlled, rising single-dose study to investigate the effects of recombinant human (rh) interleukin (IL) 10 in renal transplant patients who received OKT3 as induction therapy. METHODS: Patients received 0.1 (n=6), 1 (n=6), or 10 microg/kg (n=3) rhIL-10 or placebo (n=6) intravenously 30 min before the first injection of 5 mg of OKT3. We monitored IL-10 serum levels, the effect of rhIL-10 on OKT3-induced cytokine production, clinical toxicity, and the incidence of immunization against OKT3. RESULTS: Serum IL-10 levels in the three experimental groups reached 0.8+/-0.2, 7.9+/-1.3, and 118.6+/-7.3 ng/ml (mean+/-SEM), respectively, 30 min after rhIL-10 injection. Peak plasma levels of tumor necrosis factor-alpha (TNF-alpha) were reduced from 2953+/-1599 pg/ml in patients injected with OKT3 and placebo to 447+/-155, 703+/-246, and 459+/-246 pg/ml in patients injected with 0.1, 1, and 10 microg/kg rhIL-10, respectively. Values for 24-hr TNF-alpha area under the curve decreased from 8988+/-3551 pg x hr/ml in control patients to 2284+/-494, 3950+/-955, and 2420+/-931 pg x hr/ml for the 0.1, 1, and 10 microg/kg rhIL-10 dose groups, respectively (P=0.045). There was also a trend toward reduced plasma levels of IL-2, IL-8, and interferon-gamma in rhIL-10-pretreated patients. Although none of the patients who received placebo or 0.1 or 1 microg/kg rhIL-10 developed an IgM antibody response directed against OKT3 during the first 10 days, this occurred in all three patients who received the highest rhIL-10 dose. In two of these patients, neutralization of OKT3 was associated with a reversible acute rejection episode. CONCLUSIONS: Pretreatment with doses of up to 1 microg/kg rhIL-10 is safe and reduces the release of TNF-alpha induced by OKT3. However, higher doses might promote early sensitization to OKT3.

Adult↗

[Renal venous thrombosis: a forgotten complication of acute pyelonephritis].

BACKGROUND: Renal vein thrombosis, long recognized as a classical complication of acute pyelonephritis, has become exceptional since the advent of antibiotics. CASE REPORT: An 85-year-old woman was hospitalized for acute Escherichia coli nephritis. Computed tomography with contrast agent injection was performed due to clinical improvement after an 8-day course of antibiotics and demonstrated purulent urine collection on an obstructive calicial stone as well as homolateral thrombosis of the renal vein. Duplex Doppler confirmed the diagnosis. Pulmonary embolism was evidenced by pulmonary scintigraphy. The clinical course was satisfactory after urine drainage and efficacious antibiotics. CONCLUSION: Renal vein thrombosis remains a severe though uncommon complication of acute pyelonephritis. Computed tomography with iodine, contrast agent or duplex Doppler allows noninvasive diagnosis.

Acute Disease↗

Treatment and prognosis of post-transplant lymphoproliferative disease.

Post-transplant lymphoproliferative diseases (PTLDs) are a clinically and morphologically heterogeneous group of lymphoid proliferations. They represent a life-threatening complication of solid organ transplantation. The mechanisms of their pathogenesis are not yet fully understood. A combination of impaired immunity, oncogenic consequences of immunosuppressive therapy and EBV infection may play a role. Studies on incidence, treatment and prognosis are difficult because of the small number of cases occurring at each transplant center and the lack of reliable classification. Overall mortality remains high even though 25% of patients require no other measure than reduction in immunosuppression which must be the first step of treatment. Several treatments are currently used but more adequate classification as well as multicenter studies are urgently needed because many questions remain with regard to therapeutic strategy. Late-onset monoclonal tumors may be treated by conventional chemotherapy, while EBV-positive PTLDs may benefit from other approaches such as antiviral therapies or immunologic modulation of tumor functions.

Humans↗

The long-term virologic and pathologic impact of renal transplantation on chronic hepatitis B virus infection.

In an attempt to evaluate the long-term reciprocal impact of renal transplantation on hepatitis B virus infection, we analyzed the clinical, virologic, and pathologic features of 151 HBsAg-positive kidney transplant recipients. The spontaneous disappearance rates of HBsAg, HBeAg, and HBV DNA during a median follow-up of 125 months (range 1 to 320) were 3, 30.6, and 3%, respectively, figures lower than in the general population. A high rate of persistent viral replication (50%) and reactivation (30%) was noted. Noteworthy was the high frequency of histologic deterioration (85.3%), accompanied by cirrhosis in 28% and by hepatocellular carcinoma in 23% of the patients with cirrhosis. Co-infection by hepatitis C and B viruses was significantly associated with histologic worsening. Liver disease was the leading cause of death (36.6%), especially in patients with cirrhosis. Despite persistent viral replication, histopathologic deterioration, and liver-related overmortality, there were paradoxically no significant differences in the survival of these 151 HBsAg-positive compared with 1247 HBsAg-negative kidney recipients--however, allograft actuarial survival was better in the former than in the latter group (P=0.0006). Chronic hepatitis B infection is not a contraindication to renal transplantation in the absence of cirrhosis. The presence of cirrhosis should lead either to dialysis continuation or to a combined liver/kidney transplantation, in the absence of viral replication.

Adult↗

Azathioprine hepatitis in kidney transplant recipients. A predisposing role of chronic viral hepatitis.

Influence of viral liver diseases on the occurrence of azathioprine hepatitis was evaluated in 21 kidney transplant recipients. Diagnosis of azathioprine hepatitis was always based on jaundice, which disappeared after azathioprine withdrawal in 18 patients and after azathioprine dose reduction in 3 patients. Histopathological diagnosis of azathioprine toxicity was ascertained in 14 patients. Rechallenge with azathioprine performed in 4 patients, within 2-4 months after the first jaundice episode, resulted in relapse of jaundice in all cases. Viral hepatitis B virus and hepatitis C markers were present in all 20 tested patients (serum hepatitis B surface antigen in 6 patients and anti-HCV antibodies in 17 patients). Biopsy-proven chronic hepatitis was observed in 18 patients, including 14 chronic active hepatitis, 3 chronic persistent hepatitis and cirrhosis in 1. In kidney transplant recipients, azathioprine hepatitis seems to be facilitated or induced by hepatitis B virus or hepatitis C virus chronic hepatitis. Azathioprine reduction or withdrawal should therefore be combined with the diagnostic evaluation and the treatment of viral liver diseases.

Adult↗

The IgE humoral response in OKT3-treated patients. Incidence and fine specificity.

We recently described a case of anaphylaxis occurring at the time of retreatment with OKT3 of a renal allograft recipient in whom, for the first time, high anti-OKT3 IgE levels were documented. This led us to examine a large series of sera from 181 OKT3-treated patients to better define the frequency of IgE sensitization, its fine specificity (anti-isotypic and/or anti-idiotypic) and its relation to the appearance of IgG anti-OKT3 antibodies (Abs). Six patients out of the 181 assayed have developed anti-OKT3 IgE Abs as detected by ELISA. The earliest time of appearance of IgE anti-OKT3 Abs was 10 days after starting OKT3 (range, 10-25). The IgE response peaked by day 18 (range, 11-35) and had usually disappeared at 3 months after treatment. A more careful dissection of the fine specificity of the IgE response revealed that three of the four patients tested had developed an exclusive anti-idiotypic response. In the last patient, an anti-isotypic component was present since anti-OKT3 IgE Abs also reacted with control IgG2a, IgG2b, and IgG3 monoclonal antibodies. Importantly, anti-OKT3 IgE Abs were only detected in heavily sensitized patients also showing high titers of IgG specific Abs by ELISA (> or = 1/1000) as well as "blocking" anti-OKT3 antibodies, as assessed by immunofluorescence. We conclude that (1) exposure to OKT3 may lead to specific IgE sensitization that, however, only appears in about 38% of the patients; (2) IgE Abs mostly appear in patients also showing high levels of conventional IgG anti-OKT3 Abs including the presence of "blocking" anti-idiotypic Abs, and (3) IgE Abs may be directed to both idiotypic and isotypic determinants of the monoclonal antibody.

Animals↗