Search PubMed⌕ Search

Biomedical subjects

R A Koene

Publications and source records attributed to R A Koene.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1994

Doppler spectrum analysis to diagnose rejection during posttransplant acute renal failure.

During posttransplant acute renal failure (ARF), the diagnosis of allograft rejection constitutes a major problem. We evaluated the value of Doppler ultrasonography in identifying grafts at risk of rejection during ARF. In 184 recipients of a renal allograft, Doppler examinations were performed on the first and fifth postoperative day. Doppler spectra were quantitatively analyzed with a user-written computer program. Doppler findings were not used in clinical decision making. ARF was defined as a diuresis < 400 ml/24 hr and/or the necessity for dialysis. Doppler spectra obtained on the first day after transplantation showed a resistance index (RI) of 0.59 +/- 0.09 in recipients with immediately functioning cadaveric grafts (n = 123), while living related donor grafts (n = 20) showed a lower RI (0.55 +/- 0.07; P < 0.05). Grafts with ARF (n = 41) showed a considerably higher RI (0.67 +/- 0.13; P < 0.05). When grafts with a duration of ARF < or = 4 days (n = 17) were compared with ARF > 4 days (n = 24), RI was not significantly different (0.63 +/- 0.07 vs. 0.68 +/- 0.15; NS). However, the acceleration time of the systolic deflection of the spectrum waveform (Tmax) was shorter in grafts with ARF > 4 days (86 +/- 47 msec vs. 128 +/- 39 msec; P < 0.05). On the fifth day after transplantation, Doppler spectra in grafts with ARF > 4 days (n = 24) showed a Tmax < 90 msec in 9 patients, 8 of whom experienced rejection during ARF (positive predictive value, 8/9 = 89%). In the 15 patients with Tmax > or = 90 msec, only 2 rejections occurred (negative predictive value, 13/15 = 87%). For the RI (> 0.85), positive predictive value was 4/5 = 80% and negative predictive value (RI < or = 0.85) was 13/19 = 68%. In conclusion, a short acceleration time of the Doppler waveform on the first day after transplantation is associated with a longer duration of ARF. Quantitative analysis of Doppler spectra can be helpful in the identification of patients at risk for rejection and in the timing of allograft biopsy during ARF. Persistently short Tmax values on the fifth day after transplantation perform better in identifying grafts at risk of rejection than high RI values.

Acute Kidney Injury↗
PubMed1994

Preserving renal function in patients with membranous nephropathy: daily oral chlorambucil compared with intermittent monthly pulses of cyclophosphamide.

OBJECTIVE: To compare oral chlorambucil and intravenous cyclophosphamide-based drug regimens in the treatment of patients with membranous nephropathy and deteriorating renal function. DESIGN: Randomized study. SETTING: University hospital and teaching hospitals. PATIENTS: 18 patients with membranous nephropathy, a nephrotic syndrome, and deteriorating renal function. INTERVENTION: Chlorambucil (0.15 mg/kg body weight per day orally in months 2, 4, and 6) and prednisone (three intravenous pulses of 1 g of methylprednisolone followed by oral prednisone at 0.5 mg/kg per day in months 1, 3, and 5) or intravenous cyclophosphamide (750 mg/m2 body surface area once every month for 6 months) and methylprednisolone (three intravenous 1-g pulses in months 1, 3, and 5). MEASUREMENTS: Serum creatinine, serum cholesterol, serum albumin, and urinary protein levels. RESULTS: Before treatment, no statistical differences were found between the treatment groups. Six months after treatment was started, serum creatinine levels had decreased in the group treated with chlorambucil, methylprednisolone, and prednisone from a mean of 260 +/- 112 mumol/L to 186 +/- 74 mumol/L (P = 0.003) and had increased in the group treated with intravenous cyclophosphamide and methylprednisolone from 218 +/- 85 mumol/L to 297 +/- 143 mumol/L (P = 0.02; difference between both groups, P < 0.001). Serum albumin levels increased in both groups by 9 and 6 g/L, respectively, and the urinary protein/creatinine ratio decreased by 2.6 and 3.1 g/10 mmol, respectively. At the end of follow-up (median, 15 months; range, 6 to 36 months), one patient in the chlorambucil group and four patients in the cyclophosphamide group had reached end-stage renal failure after 36, 12, 12, 18, and 18 months of therapy, respectively. One patient in the intravenous cyclophosphamide group died after 6 months of therapy. CONCLUSIONS: Thus far, both oral chlorambucil and oral cyclophosphamide have been shown to be effective in the treatment of patients with membranous nephropathy and deteriorating renal function. Our study shows that intermittent monthly pulses of low-dose cyclophosphamide are ineffective in preserving renal function in such patients.

Administration, Oral↗
PubMed1994

[Dysmorphic erythrocytes in urinary sediment in differentiating urological from nephrological causes of hematuria].

OBJECTIVE: To determine the significance of dysmorphic erythrocytes in the urinary sediment for discrimination between urological and nephrological causes of haematuria. DESIGN: Evaluation of diagnostic test. SETTING: Departments of Nephrology and Pathology, University Hospital Nijmegen. METHOD: Of 107 patients with haematuria in whom renal parenchymal or urological disease was diagnosed, the percentage of dysmorphic erythrocytes was estimated in the unstained urinary sediment with normal light microscopy. By using a Receiver Operating Characteristic curve the cutoff point that provided the highest diagnostic value of the erythrocyte morphology was determined. In addition, the inter-observer variation was estimated in a separate series of 26 urinary sediments. RESULTS: At a cutoff value of 40% dysmorphic erythrocytes the sensitivity for urological pathology was 100% and the specificity 66.7%. When presence of erythrocyte, haemoglobin or fatty casts was also considered as a criterion for a nephrological diagnosis, the specificity for urological pathology rose to 88.1%. The inter-observer variation showed a correlation coefficient of 0.90 (kappa: 0.77). CONCLUSION: Evaluation of the erythrocyte morphology in the urinary sediment is a reliable aid in determining the strategy to be followed in patients with haematuria. It is important, however, that strict criteria for establishing erythrocyte dysmorphism are applied.

Adolescent↗
PubMed1994

Acute effects of nifedipine in renal transplant recipients treated with cyclosporine or azathioprine.

Cyclosporine (CsA) impairs renal function, probably by preglomerular vasoconstriction. Vasodilating substances may therefore be of benefit to ameliorate CsA-induced renal dysfunction. We studied the acute effects on blood pressure and renal function of the dihydropyridine calcium antagonist nifedipine (10 mg orally) in 20 CsA-treated renal transplant patients. In addition, we compared the effects of nifedipine when given immediately before and 4 weeks after elective conversion from CsA to azathioprine. Compared with placebo (n = 14), administration of nifedipine led to a significant decrease in blood pressure and a strong natriuretic and diuretic response. Despite the reduction in blood pressure, glomerular filtration rate improved from 60 +/- 20 (mean +/- SD) to 69 +/- 24 mL/min/1.73 m2 (P < 0.001) and renal plasma flow (RPF) increased from 260 +/- 87 to 338 +/- 120 mL/min/1.73 m2 (P < 0.001). The combination of a decreased blood pressure with an increased RPF was reflected in a sharp decrease in renal vascular resistance (0.34 +/- 0.18 units v 0.23 +/- 0.10 units; P < 0.001). The conversion from CsA to azathioprine by itself led to significant increases in glomerular filtration rate (62 +/- 15 mL/min/1.73 m2 v 76 +/- 18 mL/min/1.73 m2; P < 0.05) and RPF (280 +/- 86 mL/min/1.73 m2 v 334 +/- 66 mL/min/1.73 m2; P < 0.05). During treatment with azathioprine an effect of nifedipine on glomerular filtration rate and RPF was no longer observed, although the natriuretic effect was similar on both occasions. The decrease in renal vascular resistance was larger during treatment with CsA than during treatment with azathioprine (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Azathioprine↗
PubMed1994

Exogenous aldosterone antagonizes distal tubular effects of calcium entry blocker felodipine.

Calcium entry blockers, such as felodipine, increase natriuresis without increasing kaliuresis. Since these drugs acutely increase plasma renin activity without a concomitant change of aldosterone, inhibition of such stimulated aldosterone release might explain the absence of kaliuresis. In a randomized crossover study in 12 male volunteers, we compared the effects of simultaneously administered exogenous aldosterone and felodipine with the effects of either felodipine or aldosterone alone. Felodipine infusion decreased blood pressure, increased renal plasma flow, and induced natriuresis without kaliuresis. Aldosterone alone reduced sodium excretion and increased potassium excretion without influencing hemodynamics. Addition of aldosterone to felodipine attenuated its natriuretic effect and induced a kaliuresis, which clearly exceeded the rise of potassium excretion during aldosterone alone [delta% fractional excretion of K+ +42 +/- 12 with felodipine+aldosterone and +7 +/- 8% with aldosterone alone; means +/- SE, P < 0.02]. Our data suggest that felodipine-mediated inhibition of stimulated aldosterone release is essential for the absence of kaliuresis with felodipine. In addition, the pronounced kaliuresis with aldosterone during felodipine is in keeping with increased distal sodium delivery due to a proximal tubular action of felodipine.

Adult↗
PubMed1994

Metoclopramide stimulates kaliuresis during felodipine without affecting its natriuresis.

Calcium entry blockers such as felodipine induce natriuresis without a parallel rise of potassium excretion. Previous studies with exogenous aldosterone and felodipine have suggested that the absence of kaliuresis might be explained by a felodipine-induced inhibition of aldosterone release. The natriuresis with calcium entry blockers could not be attributed to a similar mechanism but might be due to the stimulation of intrarenal natriuretic systems such as the dopaminergic system. We studied whether the aselective dopamine antagonist metoclopramide prevents the natriuresis with low and therapeutic felodipine doses and whether metoclopramide-induced aldosterone release promotes kaliuresis with felodipine. Twelve healthy male volunteers participated in a randomized, placebo-controlled, crossover study comparing felodipine infusion during metoclopramide with felodipine alone. Metoclopramide had no significant influence on the pronounced and dose-dependent increases of renal plasma flow and urinary sodium excretion with felodipine. Metoclopramide increased plasma aldosterone concentration from 0.17 +/- 0.03 to 0.60 +/- 0.14 nmol/L, and subsequent felodipine infusion clearly increased urinary potassium excretion by 23 +/- 6 and 35 +/- 8 mumol/min (low and therapeutic doses, respectively). In contrast, potassium excretion remained stable with felodipine alone (+5 +/- 4 and +7 +/- 5 mumol/min, respectively). In conclusion, the natriuretic action of calcium entry blockers cannot be blocked by the aselective dopamine antagonist metoclopramide. This natriuresis is accompanied by kaliuresis only in the presence of elevated endogenous aldosterone concentrations. The ability of calcium entry blockers to prevent a rise of plasma aldosterone thus seems essential for the prevention of urinary potassium losses.

Adult↗
PubMed1994

Characterization of a 43 kD protein associated to aminopeptidase A from murine kidney.

SDS-PAGE of affinity-purified APA under reducing conditions showed in addition to the specific APA band of M(r) 130 kD, a second band of M(r) 43 kD. Internal amino acid sequencing of three tryptic peptides from this second band, that was cut out of the polyacrylamide gel, matched the actin sequence. The identity of the 43 kD band was also confirmed by Western blotting.

Actins↗
PubMed1994

Analysis of the efficacy of measures to reduce pain after subcutaneous administration of epoetin alfa.

Pain at the injection site with subcutaneous administration of epoetin alfa preparations is a common adverse event, and sometimes precludes self-administration. The pain is caused mainly by the vehicle. The present studies were designed to assess whether pain after subcutaneous administration of the vehicle can be influenced by making the solution iso-osmotic, or by diluting the vehicle by the bacteriostatic agent benzyl alcohol saline (BAS). The volumes injected were 1 ml. We also determined whether reduction of the injected volume of 1 ml to 0.33 ml or to 0.1 ml could be of clinical importance. One millilitre of normal saline served as a placebo control. The studies were done in a double-blind, placebo-controlled, randomized order, cross-over fashion in healthy volunteers. Pain scores were obtained from visual analogue pain scales with no divisions and from 5-point verbal descriptive pain scales. Dilution of the vehicle with BAS resulted in significantly less pain (P < 0.0001) after subcutaneous injection, comparable to levels obtained with normal saline. Making the vehicle iso-osmotic had no effects. Injection of smaller volumes of the vehicle was beneficial with 0.1 ml (P < 0.0001), but the reduction to 0.33 ml was not statistically significant.

Adult↗
PubMed1993

High incidence of arteriovenous fistula after biopsy of kidney allografts.

Arteriovenous fistula (AVF) is a well known but rarely diagnosed complication of percutaneous biopsy of kidney allografts. In the past diagnosis was usually made when clinical signs of an AVF occurred but Doppler ultrasonography has now enabled non-invasive diagnosis. Doppler examination of kidney allografts was performed after 100 biopsies. A total of ten AVFs were diagnosed within 2 weeks of biopsy. On repeated examination 2 months later, no additional fistula was detected. All fistulas were detected by abnormal colour shading of the artery and vein of the fistula caused by high blood velocity. Quantification in the artery supplying the fistula showed a higher systolic velocity compared with that in a normal artery of comparable size and location in the graft (mean (range) 64 (25-150) versus 36 (20-65) cm/s, P < 0.05). Diastolic velocity was also higher in the artery supplying the fistula than in a normal artery (mean (range) 34 (9-72) versus 7 (0-13) cm/s, P < 0.05). In the group with an AVF the proportion with a prolonged bleeding time (> 3 min) was higher (80 versus 47 per cent, P < 0.05), as was the prevalence of a platelet count < 200 x 10(9)/l (60 versus 22 per cent, P < 0.05). After detection of the fistula, four of the grafts were lost because of rejection and two patients died from sepsis during antirejection treatment. During follow-up of the remaining four AVFs, three disappeared spontaneously and one persisted. None of the fistulas has had an impact on renal function requiring intervention. In conclusion, AVF is a complication observed frequently after kidney allograft biopsy that can be detected and monitored by Doppler ultrasonography.

Arteriovenous Fistula↗
PubMed1993

Renal allograft artery stenosis: results of medical treatment and intervention. A retrospective analysis.

In a retrospective analysis of 1165 renal transplantations in our center, 65 cases of renal allograft artery stenosis were diagnosed angiographically (prevalence 5.5%). Hypertension was present in all cases; a bruit over the allograft and an increase in serum creatinine level were additional reasons for angiography. Shortly after diagnosis of the stenosis, two patients died and two others lost their grafts due to thrombosis. In 24 patients the decision was made not to correct the stenosis. One of these grafts was lost because the stenosis could not be corrected. Medical management of hypertension in these patients resulted in a decrease in diastolic blood pressure from 109 +/- 22 to 96 +/- 12 mm Hg (P < 0.01) 3 months after diagnosis with the use of almost twice as many antihypertensive drugs as at the time of diagnosis (P < 0.01). The stenosis was corrected if the angiography showed it to be so severe that it jeopardized renal allograft function or caused uncontrollable hypertension. Only three of nine percutaneous transluminal angioplasty (PTA) procedures resulted in a definitive correction of the stenosis. Surgical intervention was performed in 30 patients, including two patients whose PTAs had proved unsuccessful. Surgery led to graft loss due to thrombosis in 6 of 30 operations (20%), whereas restenosis occurred twice (7%). In three other cases (10%), the correction was not successful due to local anatomical variations or concomitant rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗
PubMed1993

The proliferative response of human T cells to allogeneic IFN-gamma-treated endothelial cells is mediated via both CD2/LFA-3 and LFA-1/ICAM-1 and -2 adhesion pathways.

We studied the proliferative response of purified human peripheral blood T lymphocytes (contaminated with less than 0.1% monocytes) to allogeneic MHC class II molecules expressed by endothelial cells (EC) or fibroblasts (FB). In vitro expression of MHC class II molecules was induced by gamma-interferon (IFN-gamma) treatment. The MHC class II expression levels after IFN-gamma treatment on both cell types were comparable. No T cell proliferation was found in the presence of either untreated or IFN-gamma-treated FB, and a marginal proliferation in the presence of untreated EC. IFN-gamma-treated EC, however, were able to induce significant T cell growth. The previously established role of MHC class II molecules in allogeneic T cell proliferation was confirmed in inhibition experiments with monoclonal antibody (mAb) against MHC class II or CD4. In this model, we tested the involvement of a number of adhesion molecules by adding mAbs to cocultures of T cells and IFN-gamma-treated EC. Monoclonal antibodies directed against CD31, CD26, B7/BB1, E-selectin, CD44, VLA-4 alpha-chain and VCAM-1 had no effect, whereas moderate inhibition was observed with anti-VLA-beta-chain and anti-LFA-3. A distinct inhibition of T cell proliferation was observed with mAbs directed against LFA-1, CD2, or a combination of anti-ICAM-1 and -2. Combinations of mAbs directed against T cell adhesion molecules (LFA-1, CD2, VLA-4) or EC adhesion molecules (ICAM-1, and -2, LFA-3, VCAM-1) were able to block T cell proliferation for 100 and 80% respectively. We conclude that CD2/LFA-3 and LFA-1/ICAM interactions are crucially involved in allogeneic T cell/EC interactions.

Antibodies, Monoclonal↗
PubMed1993

Identification of the component part in an epoetin alfa preparation that causes pain after subcutaneous injection.

The subcutaneous administration of epoetin alfa preparations may cause pain at the injection site. To identify the pain-causing substance in these formulations we performed two double-blind, placebo-controlled, randomized order, cross-over studies. Differences in pain experienced after subcutaneous injection of an epoetin alfa solution and its vehicle were assessed in 36 patients. The vehicle and its component parts, albumin and citrate, were compared in 36 volunteers. Normal saline served as a placebo control in both studies. Pain scores were obtained from visual analogue pain scales with no divisions and from five point verbal descriptive pain scales. Both the epoetin alfa solution and its vehicle caused significantly more pain than normal saline (P < 0.0001) in the patients studied. In volunteers the pain scores with the vehicle or its citrate component were significantly higher (P < 0.0001) when compared with normal saline or with the albumin component of the vehicle. In conclusion, the local pain experienced after subcutaneous administration of epoetin alfa preparations is mainly caused by the citrate component of the buffered solution. Epoetin alfa and the albumin component of the preparation do not play a role in this phenomenon.

Adolescent↗