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Biomedical subjects

R A Koene

Publications and source records attributed to R A Koene.

At least 55 records · Page 3Linked to original sources
PubMed1996

Organ distribution of aminopeptidase A and dipeptidyl peptidase IV in normal mice.

The hydrolases aminopeptidase A and dipeptidyl peptidase IV, both present in the kidney on the brush borders of the proximal tubule epithelial cells and podocytes, are involved in the induction of experimental membranous glomerulonephritis in the mouse. However, little is known about their (co)distribution in other tissues and their function in health and disease. A detailed insight into the localization of these two enzymes is a prerequisite to elucidation of their function. Therefore, we investigated the presence and co-distribution of aminopeptidase A and dipeptidyl peptidase IV by immunohistology with two different rat monoclonal antibodies, the specificity of which was determined by an immunodepletion technique. In addition, the molecular weight of the hydrolases; was analyzed by SDS-PAGE after isolation by solid-phase immunoprecipitation from glomeruli, renal brush borders, and thymus. Both hydrolases showed different molecular weights in renal corpuscle, renal brush borders, and thymic cells. A widespread organ distribution of the two hydrolases was observed, with co-localization in kidney, liver, small intestine, thymus, brain, spleen, and lymph nodes, either on the same cells or on different cells in the same organ. This distribution and partial co-localization suggests that the two hydrolases, acting either alone or in concert, have a role in many diverse biological processes.

Aminopeptidases↗
PubMed1996

Detailed study of changes in renal function after conversion from cyclosporine to azathioprine.

The renal dysfunction induced by cyclosporine (CsA) has been demonstrated to be at least partially reversible after cessation of CsA therapy. The time course and magnitude of changes in various parameters of renal function after CsA withdrawal have not been studied in detail. We examined 12 renal transplant patients immediately before and 1, 2, and 4 weeks after replacement of CsA by azathioprine at 3 months after transplantation. Nine patients in whom CsA was continued during this period served as a control group. A significant increase in glomerular filtration rate ([GFR] 15 + or - 17%, p <0.01) occurred already in the first week after discontinuation of CsA. From 1 to 4 weeks after conversion, GFR did not significantly increase any further. A fall in serum creatinine (-7 + or - 9%, Ns) paralleled the rise in GFR (r = -0.76, p <0.01), but there was a further decrease of creatinine in the second to fourth week after conversion. Withdrawal of CsA induced a rise in serum magnesium in all patients (0.73 + or - 0.13 vs 0.86 + or - 0.12 mmol/l, p <0.001) as well as a marked decrease in the serum level of urate (0.39 + or - 0.09 vs 0.33 + or - 0.07 mmol/l, p <0.01) within one week. None of the observed changes took place in the control group. In conclusion, a major improvement of GFR occurs within one week after cessation of CsA therapy. Changes in the serum levels of magnesium and urate appear to be the most responsive markers of the renal effects of CsA.

Adult↗
PubMed1996

Oedema formation with the vasodilators nifedipine and diazoxide: direct local effect or sodium retention?

OBJECTIVE: To determine whether the common side effect of ankle oedema with arteriolar vasodilators such as the calcium entry blocker (CEB) nifedipine and the potassium channel opener (PCO) diazoxide is the direct result of peripheral vasodilation or merely a consequence of renal sodium retention. DESIGN: In 12 healthy sitting volunteers we studied for 3 h the effects of 20 mg nifedipine, 150 mg diazoxide intravenously, 25 mg captopril and placebo on oedema formation and sodium excretion. CONCLUSIONS: Foot swelling was determined with a new accurate device (coefficient of variation 0.30%), which uses Archimedes principle to measure water displacement induced by immersion of the foot. Blood pressures were recorded with a Hawksley random-zero sphygmomanometer. RESULTS: All of the active drugs decreased diastolic blood pressure (captopril by 9 +/- 2%, nifedipine by 4 +/- 3% and diazoxide by 2 +/- 2%, compared with an increase of 5 +/- 2% with placebo). Foot volume increased acutely after administration of nifedipine (by 2.6 +/- 0.4%), whereas it remained stable with placebo and the other drugs. Administration of captopril and nifedipine induced increases of fractional sodium excretion (by 20 +/- 9% and 40 +/- 20%, respectively) in contrast to the decreases with placebo and diazoxide (by 13 +/- 11% and 24 +/- 10%, respectively). Only administration of nifedipine induced significant, albeit small, increases in haemoglobin and serum albumin levels. CONCLUSIONS: Administration of nifedipine increased foot volume and natriuresis simultaneously, thereby supporting the hypothesis that development of ankle oedema with CEB is a local phenomenon at the site of vasodilation. The absence of a similar increase in foot volume with diazoxide administration should be interpreted with caution because of the rather minor effect of this dose of diazoxide on blood pressure. However, it could be indicative of a different mechanism of oedema formation with PCO.

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

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

Familial glomerulonephritis characterized by massive deposits of fibronectin.

In recent years more than 150 cases of glomerulonephritis characterized by deposits of irregularly arranged fibrils have been documented. In the majority of these cases immunoglobulins and complement are the prime constituents of these deposits. We recently made a diagnosis of fibrillary glomerulonephritis without immunoglobulin deposition in two members of a family, a father and a son. In the father, proteinuria was first discovered 18 years ago. In 1985 he was referred to our outpatient clinic because of hypertension and increasing proteinuria. From that time onward he was regularly seen for blood pressure control. Nephrotic-range proteinuria persisted, without hardly any evidence of deterioration of renal function. Renal biopsies were performed in 1985 and 1993. His son underwent a renal biopsy in 1993 because of moderate proteinuria. The biopsies of both patients disclosed a distinct form of fibrillary glomerulonephritis that was characterized by massive deposits of a homogeneous, eosinophilic material in the mesangial and subendothelial areas. Staining for amyloid was negative. Immunofluorescence revealed that the biopsy specimens only stained faintly for immunoglobulins, complement factors C1q and C3, the extracellular matrix proteins, collagen IV, and laminin. However, they strongly stained for fibronectin. Using monoclonal antibodies specific for cell-derived fibronectin (IST-9) and plasma- and cell-derived fibronectin (IST-4), in the biopsy of the son we demonstrated that the fibronectin deposited in the glomeruli was mainly derived from the plasma, and to a lesser extent from resident glomerular cells. In addition, a moderate staining for amyloid P and vitronectin also was present. No or minor enhanced staining for collagen I, III, or V, heparan sulfate proteoglycan or its glycosaminoglycan side chains, tenascin, or thrombospondin could be observed. By electron microscopy the deposits in the mesangium and the subendothelial spaces appeared focally to be composed of irregularly arranged fibrils or microtubules 10 to 12 nm in diameter. Fibrillary glomerulonephritis with massive deposits of fibronectin represents a rare form of familial glomerulonephritis. In our patients the glomerulonephritis has an indolent course with hardly any deterioration of renal function.

Adult↗
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

Urinary excretion of beta 2-microglobulin predicts renal outcome in patients with idiopathic membranous nephropathy.

In patients with membranous nephropathy, treatment should be limited to those at risk for disease progression. Urinary beta 2-microglobulin excretion was measured in 30 patients with membranous nephropathy, a nephrotic syndrome, and normal renal function (endogenous creatinine clearance > 80 mL/min), who were subsequently monitored for a median of 48 months. Renal function deteriorated in 11 of the 14 patients with a beta 2-microglobulin excretion > 500 ng/min and in only 2 of the 16 patients with a beta 2-microglobulin excretion < or = 500 ng/min (P < 0.001). The measurement of urinary beta 2-microglobulin excretion thus contributes to the identification of patients with membranous nephropathy at high risk for developing renal insufficiency and may provide guidance for early immunosuppressive treatment.

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↗
PubMed1995

The use of epoetin beta in anemic predialysis patients with chronic renal failure.

UNLABELLED: Two clinical studies were conducted to investigate the efficacy and safety of epoetin beta in 266 [corrected] anemic predialysis patients. Epoetin beta was administered subcutaneously either daily or thrice weekly. Mean duration of treatment was 211 days (interquartile range: 105 to 350 days). RESULTS: Renal anemia could be corrected and the regular transfusion need could be eliminated in all patients. There was no difference in the dose requirement per week between daily and thrice weekly administration of epoetin beta. Regarding the entire study population, there was no acceleration of the progression of renal failure during epoetin beta treatment nor were there any notable changes in laboratory values other than retention values. Epoetin beta was safe and well tolerated; the most important adverse event was the development or aggravation of hypertension.

Adult↗