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Biomedical subjects

A J Hoitsma

Publications and source records attributed to A J Hoitsma.

At least 37 records · Page 2Linked to original sources
PubMed1996

Comparison of Sandimmun with a new cyclosporin derivative (IMM 125) in renal transplant patients with stable renal function. IMM 125 Multicentre Study Group.

A double-blind switch-over study was carried out on 70 renal transplant patients to assess the value of a new cyclosporin derivative, IMM 125. Preclinical in vitro and in vivo studies indicated that IMM 125 was as equally immunosuppressive as Sandimmun, but that its therapeutic index should be superior. The duration of the treatment was 24 weeks. The assumption that the dosage of IMM 125 could be 2.5 times lower than Sandimmun proved to be false; three patients suffered acute rejection episodes, probably as a consequence of the low dosage, and dosage adjustments had to be made for all patients receiving IMM 125 after only a few weeks. Although IMM 125 is an effective immunosuppressive agent, it does not appear to offer advantages over Sandimmun with regard to renal function. In addition, IMM 125 causes some disturbances in liver function.

Adolescent↗
PubMed1996

Costs of drugs used after renal transplantation.

There are no detailed data on the relative contributions to overall health care costs of the various drugs that are commonly used in renal transplant patients. We performed a cost analysis in 122 patients, using the medical records and our hospital administration service as data sources, for all health care-related costs during the first year after renal transplantation. During the first 3 months all patients were on cyclosporine (CsA) and prednisone. Subsequently, they were randomly allocated to CsA monotherapy or to conversion from CsA to azathioprine. Cost of drugs comprised about 25% of total health care expenses. In CsA-treated patients, the following costs per patient per year were calculated: CsA, DFL 9929 (1 DFL is about US$0.60; 67.5% of total drug costs); antilymphocyte agents, DFL 2613 (17.8%); other immunosuppressive drugs, DFL 455 (3.1%); antimicrobial agents, DFL 687 (4.7%); antihypertensive drugs, DFL 467 (3.2%); remaining drugs, DFL 554 (3.8%). Conversion from CsA to azathioprine resulted in a decrease in mean drug costs for the remainder of the first posttransplant year of DFL 4597 (P < 0.01). Although the incidence of acute rejections tended to be higher after steroid withdrawal than after conversion (39% versus 26%, not significant), the costs of anti-rejection therapy, hospitalization, and laboratory services did not differ. We conclude that CsA is the main determinant of overall drug costs. When compared to CsA monotherapy, conversion from CsA to azathioprine at 3 months after transplantation may result in subsequent cost savings of about DFL 5000 per patient per year without a higher incidence of rejection or graft loss.

Adolescent↗
PubMed1996

Cyclosporin does not inhibit the tubular secretion of creatinine.

BACKGROUND: The immunosuppressive drug cyclosporin is known to impair renal function. The degree of renal dysfunction is usually estimated from the clearance of creatinine (CCr). Theoretically however, a fall in CCr can be caused by a decrease of GFR, an inhibition of the tubular secretion of creatinine, or the combination of both. CsA has convincingly been shown to decrease GFR, but detailed information on the effects of CsA on tubular secretion of creatinine is lacking. METHODS: We performed two studies to investigate the influence of CsA on tubular creatinine secretion. In study A we simultaneously measured CCr and GFR (using inulin) immediately before and 4 weeks after cessation of CsA therapy in 17 renal transplant patients. In study B, the rise in serum creatinine after administration of cimetidine, which blocks the tubular secretion of creatinine, was compared in renal transplant patients treated with either CsA (in whom secretion might already be inhibited) or azathioprine. RESULTS: Study A: After cessation of CsA there was an increase of GFR (54+/-15 vs 63+/-16 ml/min/1.73 m2, PCr (71+/-21 vs 82+/-23 ml/min/1.73 m2; PCr and GFR (a measure of the relative contribution of tubular secretion to the clearance of creatinine) did not change significantly (1.33+/-0.21 vs 1. 32+/-0.30). Study B: In nine couples of patients matched for GFR the relative rises in serum creatinine after administration of cimetidine were 26+/-21% and 22+/-7% for CsA and azathioprine treated patients respectively (NS). CONCLUSION: CsA does not substantially inhibit the tubular secretion of creatinine. A rise in serum creatinine after administration of CsA can thus be attributed completely to a fall in GFR.

Adult↗
PubMed1996

Increased incidence of renal allograft thrombosis after continuous ambulatory peritoneal dialysis.

Allograft thrombosis occurred in 44 cases (4.8%) among 915 consecutive cadaveric renal transplantations performed in a single center over a 13-year period. Multiple logistic regression analysis of risk factors revealed that continuous ambulatory peritoneal dialysis (CAPD) was the only independent variable associated with renal allograft thrombosis. When CAPD was used for prior renal replacement therapy graft thrombosis occurred in 7.3% (22/303), whereas hemodialysis was associated with 3.6% (22/612) of graft thromboses (p < 0.02). No differences in transplant characteristics, including hemodynamics, hematological parameters, immunosuppressive therapy, graft anatomy and preservation, were observed between the cases with graft thrombosis and a matched control group (n = 88). CAPD treatment appears to be a risk factor in the development of renal allograft thrombosis that requires further perioperative coagulation studies in order to design an effective prophylaxis.

Adult↗
PubMed1996

Doppler spectrum analysis in the differential diagnosis of renal transplant dysfunction.

Cyclosporin A (CyA) nephrotoxicity and rejection of a renal allograft each demands a specific therapy. This study was designed to establish the capability of Doppler spectrum analysis to diagnose either one of these causes during renal dysfunction. Between October 1989 and October 1991 we performed echo-Doppler examinations in 209 renal transplant recipients on a routine basis during the first three months after transplantation. Echo-Doppler examinations during periods of renal dysfunction were analyzed. A total of 93 periods of renal dysfunction, retrospectively due to rejection (n = 40) or CyA toxicity (n = 53), occurred in 70 patients during the study period. A control group consisted of 82 patients with normal functioning grafts. When compared to the control group, the Doppler features (in segmental arteries) of the rejection group showed significant lower frequency shifts [Fmax (Hz) 1637 +/- 423 vs. 1436 +/- 465; p < 0.05; Fdia (Hz) 582 +/- 180 vs. 458 +/- 225; p < 0.05], a shorter deceleration time of the Doppler spectrum [Tdown (ms) 340 +/- 100 vs. 276 +/- 102; p < 0.05], and a higher Resistance Index (RI 0.64 +/- 0.08 vs. 0.68 +/- 0.13; p < 0.05). Doppler spectra during CyA toxicity showed only a significantly longer acceleration time [Tmax (ms) 123 +/- 36 vs. 139 +/- 40; p < 0.05]. The capability of differentiation between the two causes was assessed with ROC analysis of single Doppler features, stepwise regression and canonic discriminant analysis on a set of Doppler features and with manual selection of several features with extreme values. ROC analysis yielded maximum sensitivity and specificity for the diagnosis of rejection using Tdown (sensitivity 65%; specificity 68%). Stepwise regression and canonic discriminant analysis of a set of features rendered a sensitivity and specificity of 73% and 64%, respectively. Explorative selection of extreme Doppler feature values showed that 18 of the 40 grafts with rejection had values that were only seen in 2 cases with CyA toxicity (positive predictive value 90%; sensitivity 45%; specificity 96%). In half of these cases Doppler features preceded the clinical diagnosis of rejection by a median of 4 d. In conclusion, Doppler spectra are influenced by rejection and CyA toxicity in specific ways. The Doppler features, however do not enable definite differentiation between rejection and CyA toxicity in all cases. Some changes in Doppler spectra are only seen in cases of rejection and thus enable positive identification of grafts with rejection, often earlier than clinical signs indicate rejection. A normal Doppler spectrum does not exclude rejection as the cause of renal dysfunction.

Blood Flow Velocity↗
PubMed1995

Medication compliance after renal transplantation.

Noncompliance is known to be an important cause of late graft failure after renal transplantation. We investigated prospectively the degree of compliance with immunosuppressive and antihypertensive drugs during the first year after renal transplantation by monthly pill counts. In addition, we examined whether noncompliance was related to a number of demographic and clinical variables or to the occurrence of rejections. The study population consisted of 127 patients who were involved in a randomized trial comparing cyclosporine monotherapy with azathioprine-prednisone treatment. Average compliance rates approximated 100%, although considerable variability within and between subjects was observed. Using an arbitrary limit to classify patients as compliers or noncompliers, the following frequencies of noncompliance were observed during the study year: cyclosporine, 23%; azathioprine, 13%; prednisone, 23%; atenolol, 36%; and nifedipine, 32%. Average compliance scores for all immunosuppressive drugs were superior to those of antihypertensive medication (P < 0.001). Except for a better compliance for prednisone in men as compared with women, we found no consistent relationship between compliance on the one hand and several demographic variables, graft function, or quality of life on the other hand. Patients who developed one or more acute rejection episodes showed a higher degree of undercompliance, especially for prednisone, than patients without rejections (P < 0.01). Following the occurrence of a rejection episode, compliance scores improved significantly. Keeping in mind the limitations of the pill count method, we conclude that noncompliance with immunosuppressive drugs is not a huge problem during the first year after renal transplantation. However, it is likely that noncompliance contributes to a certain number of acute rejection episodes.

Adult↗
PubMed1995

Ling Zhi-8: studies of a new immunomodulating agent.

Ling Zhi-8 (LZ-8) is a protein derived from the fungus Ganoderma lucidum and has immunomodulatory capacities. It was shown to be mitogenic toward mouse splenocytes in vitro and immunosuppressive in vivo by reducing antigen-induced antibody formation and by preventing completely the incidence of autoimmune diabetes in nonobese diabetic mice. In this study, the mitogenic effects of LZ-8 on human mononuclear cells are reported. In accordance to its mitogenic effect on mouse splenocytes, LZ-8 proved to be mitogenic for human PBMC. This mitogenic effect of LZ-8 apparently required the presence of monocytes. We also demonstrated it to be immunosuppressive in vitro in a human MLC performed in the absence of monocytes, using purified T cells and EBV-transformed allogeneic B cells. Furthermore, we tested LZ-8 for its possible suppressive effects in 2 different models of allogeneic tissue transplantation. LZ-8 proved to have a significant effect on cellular immunity, since its administration in an allografted mouse skin model resulted in an increased survival time. In a model of transplanted allogeneic pancreatic rat islets, LZ-8 was effective in delaying the rejection process of allografted islets. More frequent or continuous administration resulted in a further prolongation of survival time. No serious side effects of LZ-8 could be discerned in these experiments.

Adjuvants, Immunologic↗
PubMed1995

The effect of immunosuppressive drugs on quality of life after renal transplantation.

This prospective, randomized study investigates the effect of two immunosuppressive treatment regimens on quality of life after renal transplantation. At 3 months after transplantation, patients treated with cyclosporine (CsA) and prednisone (Pred) were allocated to either withdrawal of Pred (n = 60) or to conversion of CsA to azathioprine (Aza) (Aza-Pred, n = 60). Quality of life was evaluated just before randomization, and at 6 and 12 months after transplantation using the Sickness Impact Profile (SIP), the Affect Balance Scale (ABS), the Center for Epidemiological Studies Depression Scale (CES-D), measures of satisfaction with several domains of life experience, and a population-specific physical symptoms questionnaire. In both groups, the overall SIP score as well as the scores on its physical and psychosocial dimensions improved continuously after transplantation, reaching levels that are comparable to those found in the general population. The occurrence of acute or chronic rejection had a significantly negative effect on SIP and CES-D scores. Intention-to-treat analysis showed no differences between groups for scores on SIP, ABS, CES-D, and satisfaction measures. Exclusion of 41 patients who did not strictly adhere to their originally designated therapy showed a tendency for better psychosocial SIP scores in CsA patients (P = 0.05), which mainly resulted from a difference on the category of social interaction (P = 0.01). This difference occurred despite a similar rejection rate and worse renal function in CsA-treated patients. Shortly after steroid withdrawal, a high proportion of CsA patients complained of stiff or painful muscles (CsA: 74%, Aza-Pred: 36%; P = 0.002). Our data indicate that if successfully completed, CsA monotherapy from 3 months after transplantation may lead to a higher degree of psychosocial well-being as compared with conversion from CsA-Pred to Aza-Pred. It seems likely that this advantage is related to the withdrawal of Pred.

Adult↗
PubMed1995

Soluble tumor necrosis factor-receptors are not a useful marker of acute allograft rejection: a study in patients with renal or cardiac allografts.

In this study, we investigated soluble tumor necrosis factor receptor (sTNF-R) levels in plasma of patients with either a kidney or cardiac allograft when clinical suspicion of acute rejection was raised. In plasma of patients with acute renal graft rejection, the sTNF-R levels were strongly enhanced (20-150 ng/ml) as compared to plasma of patients with stable renal function. Following successful treatment of the rejection, a gradual decline in sTNF-R levels occurred with improving renal function, and an inverse correlation between creatinine clearance and sTNF-R was found. To determine whether the increase was caused by an accumulation of constitutively released sTNF-R and lack of clearance by the kidney, or whether the immunological process of the rejection caused the enhancement, we measured sTNF-R in patients suffering from acute cardiac graft rejection but with predominantly stable kidney function. Rejection of a cardiac graft did not lead to a significant enhancement of sTNF-R levels. However, treatment with ATG or OKT3 did cause enhanced sTNF-R levels, followed by a decline that reached starting values after 7 days. These results provide evidence that the immune reaction that occurs during rejection of a graft does not per se induce discernible changes in sTNF-R levels, whereas that induced by ATG or OKT3 does. Thus, sTNF-R levels are not reliable marker in transplant recipient monitoring.

Acute Disease↗
PubMed1995

Renal transplant thrombosis in children.

Data concerning 100 consecutive renal transplantations in children were analyzed to determine factors enhancing the risk of renal transplant thrombosis. The incidence of renal transplant thrombosis was high, at 12%. It is concluded that in addition to young age and low body weight of recipient and young age of the donor, also a high preoperative urine production contributes to the occurrence of thrombosis. Children with hypoplastic or dysplastic kidneys are at greater risk for thrombosis. Considering the influence of high urine production of the native kidneys, it may be possible to prevent thrombosis by albumin and ample fluid administration.

Age Factors↗
PubMed1995

The effects of cyclosporine and prednisone on serum lipid and (apo)lipoprotein levels in renal transplant recipients.

Disturbances of lipid metabolism are frequently encountered after renal transplantation and have been ascribed to the use of cyclosporine (CsA) and corticosteroids, but the individual contribution of each of these drugs remains uncertain. The individual effects of CsA and prednisone (Pred) on serum lipid and (apo)lipoprotein levels were compared in a prospective randomized trial. All patients received CsA and Pred during the first 3 months after transplantation. Subsequently, they were allocated to either withdrawal of Pred or conversion from CsA to azathioprine (Aza). Serum lipids and (apo)lipoproteins, including lipoprotein(a) (Lp(a)), were measured at regular intervals during the first year after renal transplantation. Analysis of variance for repeated measures of the first year results showed higher values for serum triglycerides (P < 0.001) and lower high-density lipoprotein (HDL) cholesterol levels (P < 0.05) in the CsA monotherapy group (N = 59) as compared with the AzaPred group (N = 63). At 1 yr after transplantation, CsA-treated patients had significantly higher Lp(a) levels (CsA: median, 105 (interquartile range 42 to 340) mg/L; Aza-Pred: 46 (25 to 176) mg/L; P < 0.05). The withdrawal of Pred in the CsA group resulted in a large fall in HDL cholesterol (27 +/- 30% at 5 months after transplantation) and an increase in triglycerides (49 +/- 73% at 6 months). A reversion of these changes was observed in patients who were retreated with Pred. Multiple linear regression analysis showed an independent correlation between the use of Pred and HDL cholesterol level, whereas the use of CsA was independently associated with the concentration of Lp(a).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Pneumocystis carinii pneumonia in renal transplant recipients.

In 1991 and 1992 Pneumocystis carinii pneumonia (PCP) was diagnosed in 28 renal transplant recipients. The incidence of PCP in our renal transplant centre was remarkably increased from 1.1% before 1991 to 11.5% in 1991-1992. We compared 28 PCP patients with a control group of 27 renal transplant recipients, matched for transplantation day and without an episode of PCP. The mean age was significantly higher in the PCP group (50 +/- 13 versus 38 +/- 13 years). We observed no differences in basic immunosuppressive and rejection treatment nor in antibiotic consumption, number of hospitalization days, and incidence of CMV infection. In March 1993 we introduced PCP prophylaxis. More than 140 renal transplant recipients received co-trimoxazole, starting 1 day after transplantation and continued for a period of 4 months. To the time of writing no one in this group had developed PCP.

Adult↗
PubMed1995

Echo-Doppler diagnosis of renal allograft artery stenosis.

For the diagnosis of allograft artery stenosis in recipients of a renal transplant with hypertension a noninvasive investigation such as echo-Doppler is preferable to invasive methods such as angiography. Therefore we analyzed our experience with echo-Doppler diagnosis of renal allograft artery stenosis. In 131 renal transplant recipients with hypertension echo-Doppler examinations were performed. During the examinations several features indicative of stenosis were measured, and intrarenal Doppler spectra were quantitatively analyzed with a user-written program. Four patients showed signs of iliac artery stenosis. In 12 patients a renal allograft artery stenosis was suspected on echo-Doppler examination. In 8 of these 12 patients angiography was performed. All these showed a stenosis, 6 of which had more than > 75% stenosis. In 8 patients with normal echo-Doppler findings angiography was performed because of highly suggestive clinical signs of stenosis. In 7 of these no stenosis was found and in one a 50% stenosis was found. Comparison of quantitative Doppler spectrum features from patients with (n = 6) and without severe (> 75%) stenosis on angiography (n = 10) showed significant differences in several Doppler parameters. Subsequently an analysis of the best differentiation between these to groups on the basis of quantitative Doppler criteria was performed. In conclusion, echo-Doppler examinations with quantitative analysis of Doppler spectra enables reliable identification of renal allograft artery stenosis.

Angiography↗
PubMed1994

The extent of peritubular CD14 staining in renal allografts as an independent immunohistological marker for acute rejection.

Previously, we demonstrated that in acute interstitial rejection, immunohistological staining of renal allograft biopsies with the CD14 mAb WT14, reacting with human monocytes/macrophages, shows a characteristic peritubular increase of positive cells. To test the diagnostic value of this CD14 positivity, we compared, in 154 unselected renal allograft biopsies, the extent of peritubular WT14 staining with (a) the original histological diagnosis, made with knowledge of clinical data, (b) the retrospectively and blindly scored histological diagnosis according to the criteria of the Banff classification, and (c) the eventual clinical diagnosis, which included evaluation of the response to therapy. The extent of peritubular WT14 positivity, blindly scored on cryostat sections of the frozen part of the biopsies, correlated positively with the probability of acute rejection (AR). When using a cutoff of 70% WT14 positivity for the diagnosis of AR, as extracted from a receiver operating characteristic curve, the WT14 diagnosis had a positive predictive value of 91% and a negative predictive value of 56%, compared with the original histological diagnosis. Compared with the Banff diagnosis of AR (grade I-III), these values were 95% and 47%, and compared with the clinical diagnosis, 84% and 63%, respectively. The WT14 diagnosis essentially corrected the original histological diagnosis in 7 cases, and was consistent with the eventual diagnosis in 5 equivocal cases. We conclude that the extent of peritubular CD14 positivity can be used as a marker for AR and can serve as a valuable additional criterion for AR in the histological examination of renal allograft biopsies.

Acute Disease↗