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R A Koene

Publications and source records attributed to R A Koene.

At least 109 records · Page 6Linked to original sources
PubMed1992

Haemodynamic changes in human kidney allografts following administration of nifedipine: assessment with Doppler spectrum analysis.

Cyclosporin (CyA) has been demonstrated to increase the vascular resistance of renal allografts (RVR), whereas calcium channel blocking agents like nifedipine may counteract this effect. In this study RVR was calculated from renal blood flow (RBF), measured by the clearance of para-aminohippurate (PAH), and mean arterial pressure (MAP). Analysis of Doppler spectra obtained under ultrasonographic guidance was used as a non-invasive method of assessing renal haemodynamics. A comparison was made between these two methods to detect changes in renal haemodynamics which were caused by the administration of 10 mg nifedipine orally to 11 renal transplant recipients treated with CyA. RBF increased significantly (444 +/- 176 vs 559 +/- 192 ml/min per 1.73 m2; P < 0.05) despite a decrease in MAP (116 +/- 10 vs 101 +/- 11 mmHg; P < 0.05) after administration of nifedipine. Calculated RVR decreased from 0.31 +/- 0.17 to 0.20 +/- 0.07 mmHg x min/ml (P < 0.05). Results of Doppler spectrum analysis were in concordance with these observations. Resistance index (RI) in interlobar arteries decreased from 0.60 +/- 0.04 to 0.56 +/- 0.06 (P < 0.05) and acceleration time (Tmax) of the Doppler spectrum decreased from 133 +/- 32 to 98 +/- 32 ms (P < 0.05). Theoretically, a lower RI and decreased Tmax indicate a reduced vascular resistance and changes in vascular wall compliance, respectively. Analysis of Doppler spectra may thus become a useful device for non-invasive assessment of acute changes in RVR.

Adult↗
PubMed1992

Detection of interstitial increase in macrophages, characteristic of acute interstitial rejection, in routinely processed renal allograft biopsies using the monoclonal antibody KP1.

Acute interstitial rejection (AIR) of renal allografts is accompanied by a characteristic peritubular increase in macrophages, which can be identified with the CD14 monoclonal antibody (mAb) WT14 in cryostat sections. Since frozen tissue is not always available, we tested whether this increase can also be demonstrated in Bouin-fixed, paraffin-embedded biopsies, using the CD68 antimacrophage mAb KP1, which can also be applied to paraffin sections. Sections of 16 biopsies with AIR and 11 controls were stained with KP1. In 25 of the 27 biopsies, macrophages were strongly positive for KP1. Two AIR biopsies were completely negative, probably due to prolonged fixation. In the remaining 14 AIR biopsies, the number of KP1-positive cells was significantly higher than in the controls [1184 +/- 410 per mm2 (mean +/- SD) vs 112 +/- 126 per mm2]. We conclude that, especially in cases in which frozen tissue is not available, the demonstration of increased numbers of monocytes/macrophages with mAb KP1 can be a helpful adjunct in the histological diagnosis of AIR in routinely processed renal biopsies.

Antibodies, Monoclonal↗
PubMed1992

Evidence for renal vasodilation in pre-dialysis patients during correction of anemia by erythropoietin.

Results from animal experiments have suggested that treatment with recombinant human erythropoietin (rHuEPO) causes changes in renal hemodynamics which are detrimental to renal function. Therefore, the effects of correction of the anemia by rHuEPO on glomerular filtration rate (GFR; inulin clearance) and effective renal plasma flow (ERPF; PAH clearance) were studied in eight pre-dialysis patients. The studies were done before (Hct 0.24 +/- 0.05 liter/liter) and at 89 +/- 19 days after the start of rHuEPO therapy (Hct 0.39 +/- 0.03 liter/liter). To further evaluate the effects of ACE inhibition, 25 mg of captopril was given orally after baseline values had been obtained. Baseline GFR, renal blood flow (RBF) and filtration fraction (FF) did not change during rHuEPO therapy. At low hematocrit (Hct) captopril induced a significant increase in ERPF and RBF, and a decrease in MAP. After correction of the hematocrit the blood pressure lowering effect of captopril remained unchanged. However, captopril no longer induced changes in ERPF and RBF. We conclude that the increase in hematocrit had no adverse effects on GFR. The results suggest that changes in hematocrit may influence the effects of ACE inhibition on efferent vascular resistance. Therefore, the hematocrit should be taken into account when evaluating studies on the effects of ACE inhibition in the progression of chronic renal failure.

Adult↗
PubMed1992

Accessory function of endothelial cells in anti-CD3-induced T-cell proliferation: synergism with monocytes.

Monoclonal antibodies to CD3 can induce proliferation of resting T cells. In vitro this effect is dependent on the presence of monocytes. They serve as accessory cells providing a co-stimulatory signal after cross-linking of the antibody-coated TcR/CD3 complex by the Fc receptor on the monocytes. We have studied whether endothelial cells can replace monocytes with regard to this function. Highly purified T-cell preparations were cultured in the presence of anti-CD3 antibody, purified monocytes, and human umbilical vein endothelial cells. Anti-CD3 and endothelial cells alone were unable to support T-cell proliferation, due to lack of FcR expression. Addition, however, of as few as 1000 FcR+ monocytes (0.8% of the number of T cells present) to a coculture of T cells and endothelial cells (EC) in the presence of soluble anti-CD3 resulted in a strong proliferation of T cells. When anti-CD3 was presented in an immobilized form (coated to the culture well or to Sepharose beads), or when phytohaemagglutinin was added to the culture as a cross-linking agent, EC could support T-cell proliferation in the absence of any monocytes. We conclude that EC by themselves cannot support the proliferation of pure T cells induced by soluble anti-CD3, but are potent generators of the co-stimulatory signal(s). They provide a suitable starting material to further define this co-stimulatory activity.

Antigen-Presenting Cells↗
PubMed1992

Intraperitoneal administration of recombinant human erythropoietin.

OBJECTIVE: To determine the efficacy and safety of intraperitoneal administration of recombinant human erythropoietin (rHuEPO) in continuous ambulatory peritoneal dialysis (CAPD) patients compared to subcutaneous rHuEPO. DESIGN: Prospective analysis of an open, nonrandomized investigation. SETTING: Outpatient CAPD clinics in two university hospitals. PATIENTS: Nine adult CAPD patients receiving rHuEPO intraperitoneally and 8 patients receiving rHuEPO subcutaneously. INTERVENTION: One hundred units of rHuEPO per kilogram of body weight were administered three times a week for 8 weeks or until the target hematocrit of 35% was reached. Thereafter, dosages of rHuEPO were adjusted for response. Intraperitoneal rHuEPO was administered in 1 L of dialysis solution during the night. MEASUREMENTS: Efficacy was assessed by measuring the increase in hemoglobin. Tolerance was assessed by monitoring side effects. RESULTS: In the first 8 weeks of treatment hemoglobin concentration increased from 64.5 +/- 12.9 g/L to 98.3 +/- 16.1 g/L (p < 0.0005) in the intraperitoneally treated group. In the subcutaneously treated group hemoglobin increased significantly faster (p < 0.05) from 72.5 +/- 4.8 g/L to 119.2 +/- 11.3 g/L (p < 0.0005) in the same period. Antihypertensive medication had to be increased or instituted in most of the patients in both groups. The incidence of peritonitis in the intraperitoneally treated group was not increased when compared to the pretreatment incidence. CONCLUSIONS: Subcutaneously administered rHuEPO is superior to intraperitoneally administered rHuEPO with regard to the required dosages. However, the results of this study show that intraperitoneal administration of rHuEPO might be a convenient and safe alternative when subcutaneous administration is undesirable.

Adult↗
PubMed1992

Is natriuresis on felodipine due to reversal of the renal effects of angiotensin II?

Felodipine induces natriuresis, possibly by renal hemodynamic and/or tubular effects. Theoretically, reversal of the sodium-retaining effect of angiotensin II (Ang II) could be involved. Therefore, we administered felodipine during Ang II infusion and during suppression of endogenous Ang II production in two double-blind studies in healthy volunteers. First, a gradually increasing dose of Ang II was infused during felodipine or solvent infusion. Before starting Ang II, felodipine had lowered renal vascular resistance (RVR) and filtration fraction (FF), and simultaneously increased CNa. The Ang II induced rise of mean arterial pressure (MAP) and renal vasoconstriction was partly antagonized and the falls in glomerular filtration rate (GFR) and CNa completely abolished by felodipine. The combination of felodipine and 3.0 ng/kg/min Ang II even enhanced natriuresis. Second, felodipine or solvent was infused after one week of pretreatment with placebo or the angiotensin converting enzyme (ACE) inhibitor ramipril, which reduced MAP and induced renal vasodilatation. Ramipril pretreatment did not influence significantly the blood pressure reduction, renal vasodilatation, and natriuresis caused by felodipine. In conclusion, it seems unlikely that the natriuretic effect of felodipine is due to interference with renal effects of endogenous Ang II. The fact that felodipine reverses sodium retention on exogenous Ang II may be explained by interference with systemic and renal hemodynamic effects of exogenous Ang II.

Adult↗
PubMed1992

Acute renal effects of felodipine in hypertensive patients with kidney disease.

In contrast to other types of directly acting vasodilators, calcium antagonists promote sodium excretion. It is not well established, however, whether these drugs also induce natriuresis in hypertensive patients with renal disease. Therefore, we studied the acute effects of the dihydropyridine calcium antagonist felodipine in nine such patients (CCr 68 +/- 19 ml/min) and 12 healthy normotensive subjects. In both the hypertensive patients and the normotensive subjects total and fractional sodium excretion rose during the first 40 minutes of intravenous felodipine infusion; in the hypertensive patients this rise of sodium excretion was positively correlated to the initial glomerular filtration rate (GFR) (r = 0.87, P less than 0.01). In the patients, during ongoing felodipine infusion, natriuresis was attenuated in the setting of a large continuing decrease of blood pressure. In contrast, in the normotensive subjects, in whom blood pressure did not fall any further, a steady rise of sodium excretion was observed. In both the hypertensive patients and the normotensive subjects GFR remained unchanged and renal vascular resistance decreased, whereas renal plasma flow increased only in the latter group. Changes in sodium excretion were not correlated to changes in renal hemodynamic parameters. It is concluded, that also in hypertensive patients with diminished renal function felodipine exerts a potentially advantageous natriuretic effect. However, this natriuretic effect is possibly less at lower GFR and seems to be attenuated by blood pressure reduction. The mechanism of this natriuretic effect as well as its contribution to the antihypertensive effect of felodipine still has to be clarified.

Adult↗
PubMed1991

[Rhabdomyolysis].

Explore the source record for details and available documents.

Acute Kidney Injury↗
PubMed1991

Assessment of hemodynamic changes in human kidney grafts induced by cyclosporin infusion.

Cyclosporin A (CyA) nephrotoxicity is at least partly caused by the vasoconstrictive action of the drug. In this study we set out to assess this hemodynamic effect of CyA on Doppler spectra obtained in arteries of human renal allografts. Doppler spectra of renal arteries were obtained shortly before and after the start of CyA infusion in renal transplant recipients. Doppler spectrum analysis revealed a significant change in several spectrum-derived parameters. Tmax (acceleration time of the systolic frequency peak), in particular, showed a decrease after 4 h of CyA administration (106 +/- 58 ms vs 76 +/- 36 ms in segmental arteries; P less than 0.05). On day 2 the Tmax returned to its original value (117 +/- 57 ms). Thus, Doppler spectrum analysis enables one to detect temporary hemodynamic changes in the transplanted kidney following CyA administration. These observations may be useful in differentiating causes of renal dysfunction by Doppler spectrum analysis in clinical transplantation.

Cyclosporine↗
PubMed1991

Cyclosporin A blood levels during use of cyclosporin as oral solution or in capsules: comparison of pharmacokinetic parameters.

Recently cyclosporin A (CsA) capsules have been introduced to meet a number of disadvantages associated with the use of the oral solution. We compared the pharmacokinetics of the oral solution and the capsules in a group of nine renal transplant patients during the first 3 weeks after transplantation. After a morning dose of CsA, whole blood concentrations were measured at regular intervals for 12 h. Subsequently, a cross-over was made to the alternative form of administration, and 3 or 4 days later a second pharmacokinetic profile was obtained. Comparison of the trough level, the maximum concentration, the time to reach the maximal concentration and the area under the blood concentration curve, showed no significant differences. Our findings thus suggest a similar bioavailability of CsA administered as oral solution or in capsules in the early post-transplant period.

Administration, Oral↗
PubMed1991

Cimetidine improves the reliability of creatinine as a marker of glomerular filtration.

To investigate whether the administration of cimetidine can improve the reliability of creatinine as a marker of GFR, we compared the creatinine clearance (CCr) to the clearance of the true filtration markers 51Cr-EDTA (CEDTA) and inulin (CIn), after oral ingestion of cimetidine in 10 healthy men and 29 patients with varying degrees of renal dysfunction. After administration of cimetidine for three to six days, serum creatinine level rose in all participants, while CEDTA and CIn remained stable in a subgroup of 14 subjects in whom they were measured before as well as after the administration of cimetidine. The mean (+/- SD) ratios of CCr to CEDTA (N = 39) and of CCr to CIn (N = 19) after ingestion of cimetidine were 1.02 +/- 0.13 and 1.01 +/- 0.13, respectively, and did not differ significantly from unity. This high degree of accuracy of the cimetidine-aided CCr was present over the entire range of renal function in the study population. Our results also indicated an improved precision of the cimetidine-aided measurement of CCr, resulting in a variability that did not differ significantly from that of the measurement of CEDTA or CIn. We conclude that after oral administration of cimetidine, the creatinine clearance can be used as a reliable measure of GFR within a broad range of renal function.

Adult↗
PubMed1991

Detrimental effect of acute renal failure on the survival of renal allografts: influence of total ischaemia time and anastomosis time.

In a retrospective study the incidence and consequences of acute renal failure were evaluated in 324 renal transplantations performed in our centre. The overall incidence of acute renal failure was 31.2%. In recipients with acute renal failure, patient and graft survival were significantly worse than in those without acute renal failure (P less than 0.02 and P less than 0.0001 respectively). Acute renal failure also increased the morbidity during the first 3 months after transplantation. Three months after transplantation renal function as determined by serum creatinine and proteinuria, was less satisfactory. Factors influencing the incidence of acute renal failure appeared to be: match grade on the AB locus, percentage of antibodies, duration of dialysis, number of blood transfusions prior to transplantation, anastomosis time and total ischaemia time. Recipients transplanted for the first time were less likely to develop acute renal failure, but also for this group total ischaemia time was a prognostic factor for the development of acute renal failure. When recipients were allocated to different classes of total ischaemia time it appeared that the incidence of acute renal failure differed, especially between groups with total ischaemia time 32-36 h (27%) and 36-40 h (38%). The difference in acute renal failure between these groups was also reflected in a difference in graft survival for total ischaemia time less than 36 h and greater than 36 h. Thus, it appears that acute renal failure has a detrimental effect on graft survival and postoperative morbidity in renal transplantation. Total ischaemia time is one of the prognostic factors for the development of acute renal failure. To improve renal transplantation results it is worth attempting to shorten total ischaemia time.

Acute Kidney Injury↗
PubMed1991

The role of antibody isotype in IFN-gamma and IL-2 production during anti-CD3-induced T cell proliferation.

Murine anti-CD3 mAb of the IgG2a isotype are effective in the reversal of graft rejection. However, the first injection of these mAb causes a transient T cell activation in vivo, resulting in the release of cytokines that are held responsible for the sometimes severe febrile and adverse circulatory reactions associated with this therapy. Previously, we and others have reported that there is a polymorphism in the interaction of human Fc gamma R with mouse IgG1 and mouse IgG2b. This polymorphism implies that IgG1 and IgG2b mAb are mitogenic for T cells from respectively 70% and less than 5% of healthy individuals. By contrast, Fc gamma R interact with murine IgG2a and IgG3 mAb in virtually all individuals. We have now investigated the role of the isotype of the anti-CD3 mAb with respect to in vitro T cell proliferation and production of IFN-gamma and IL-2. IFN-gamma and IL-2 production always accompanied IgG2a- and IgG3-induced mitogenesis, whereas with IgG1 mAb the polymorphism in mitogenic effects completely correlated with IFN-gamma and IL-2 production. With IgG2a, IgG3, and IgG1 mAb, proliferation and IFN-gamma production were, at least in part, dependent on IL-2 production. On the other hand, IgG2b-induced proliferation was not accompanied by measurable IFN-gamma or IL-2 production. This suggests a fundamental difference in the way T cells are activated by IgG2b mAb. Given the role of IFN-gamma and IL-2 in the generation of adverse events during in vivo administration of anti-CD3 mAb, the use of IgG1 anti-CD3 or anti-TCR mAb offers a tool to further analyze the role of isotype in this respect. Moreover, the clinical use of IgG2b might result in immunosuppression without side effects.

Antibodies↗
PubMed1991

Immunocytology of urinary sediments as a method of differentiating acute rejection from other causes of declining renal graft function.

We have previously reported that during acute rejection of renal allografts T lymphocytosis and increased HLA-DR expression on tubular epithelial cells can be demonstrated in urinary sediments by incubating cytospin preparations with monoclonal antibodies against T cells and HLA-DR antigen in an indirect alkaline phosphatase technique. We now tested whether immunocytological analysis of urinary sediments can be used to differentiate acute rejection from other causes of declining graft function. For this we retrospectively selected, from a series of urinary samples that were taken either at random or as part of a longitudinal study in unselected graft recipients, those specimens that were taken at the time of increasing creatinine levels, and compared the original immunocytological diagnosis, made without knowledge of clinical data, with the final clinical one. In 44 of 74 evaluable cases an immunocytological diagnosis of rejection was made, which in 37 patients was consistent with the eventual clinical diagnosis. In 28 of 30 cases the diagnosis no rejection proved to be correct. This indicates a sensitivity of 95% and a specificity of 80% for the immunocytological diagnosis of rejection. Of 38 patients who underwent a renal core biopsy, the immunocytological diagnosis was consistent with the histological diagnosis in 36 cases (31 rejections, 5 no rejections). In this subgroup the sensitivity of the immunocytology was 97% and the specificity 83%. We conclude that immunocytological examination of urinary sediments in renal allograft recipients can be a valuable new tool in discriminating acute interstitial rejection from other causes of deteriorating graft function.

Biopsy↗