Didactical characteristics of Dutch websites about kidney transplantation targeted for kidney patients and living donors: An exploratory study.

Objective: The aim was to explore the origin, content topics, teaching modes (instruction, interaction, and assessment), and corresponding social-epistemological dimensions (choices in knowledge transfer vs. knowledge building, and individual vs. group learning) of web-based information on kidney transplantation targeted for patients and living donors. Methods: Dutch websites on kidney transplantation were retrieved using the search engine Google.nl. From 24 websites, 250 webpages were examined on origin, content topics, teaching modes, and corresponding social-epistemological dimensions. Results: The majority of the websites had a professional organization as origin (20/24). The number and distribution of content topics varied among the websites. Of the 16 different teaching modes found, 11 were instructional, 4 were interactional, and 1 assessment mode was found. The websites offered almost exclusively teaching modes on individual and passive learning, whereas group learning and interactive knowledge building was hardly encountered. Conclusion: The diversity in teaching modes and social-epistemological dimensions of Dutch websites on kidney transplantation targeted for patients and living donors is limited. The websites only provided a partial view on kidney transplantation; information regarding contact with others, e.g. support, was limited. A more balanced availability of teaching approaches and content topics is desirable to fit with the didactical goals to make well-considered health decisions.

Concentration-controlled treatment of lupus nephritis with mycophenolate mofetil.

BACKGROUND: Mycophenolate mofetil (MMF) has recently been established as a potent drug in maintenance treatment for lupus nephritis. However, there is no consensus on the optimal dosing regimen because of a high inter-individual variability of mycophenolic acid (MPA), the active metabolite of MMF. This retrospective study aimed to investigate the effect of an individualized dosing regimen through concentration-controlled treatment on MPA exposure and renal outcome in patients with lupus nephritis. METHODS: Sixteen patients with lupus nephritis and treatment with low-dose intravenous cyclophosphamide followed by MMF were included. MPA area under the plasma concentration-time curve from 0 to 12 hours (MPA-AUC(0-12)) was assessed within a month after MMF initiation. After determination of MPA-AUC(0-12), MMF doses were titrated to achieve a target MPA-AUC(0-12) of 60-90 mg*h/l. After on average six months, MPA-AUC(0-12) measures were repeated to assess the effect of dose adjustment. RESULTS: One month after introducing MMF, MPA-AUC(0-12) was low and showed a high inter-individual variability. Dose adjustment with a target MPA-AUC(0-12) of 60-90 mg*h/l resulted in individualized MMF dosing, significantly higher MPA-AUC(0-12) levels, and a non-significant reduction in variability of MPA-AUC(0-12). Adverse effects were reported by 37.5% of patients, which resulted in a switch to azathioprine in two patients. There was no significant relationship between the occurrence of adverse effects and MPA-AUC(0-12). At 12 months of follow-up 87.5% of patients had achieved either partial (18.7%) or complete (68.8%) remission. CONCLUSION: Concentration-controlled dose adjustments with a target MPA-AUC(0-12) of 60-90 mg*h/l was associated with optimized MPA exposure and an excellent renal outcome at 12 months of follow-up in a small sample of SLE patients with lupus nephritis.

Human CD34+/KDR+ cells are generated from circulating CD34+ cells after immobilization on activated platelets.

OBJECTIVE: The presence of kinase-insert domain-containing receptor (KDR) on circulating CD34+ cells is assumed to be indicative for the potential of these cells to support vascular maintenance and repair. However, in bone marrow and in granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood, less than 0.5% of CD34+ cells co-express KDR. Therefore, we studied whether CD34+/KDR+ cells are generated in the peripheral circulation. METHODS AND RESULTS: Using an ex vivo flow model, we show that activated platelets enable CD34+ cells to home to sites of vascular injury and that upon immobilization, KDR is translocated from an endosomal compartment to the cell-surface within 15 minutes. In patients with diabetes mellitus type 2, the percentage of circulating CD34+ co-expressing KDR was significantly elevated compared to age-matched controls. When treated with aspirin, the patients showed a 49% reduction in the generation of CD34+/KDR+ cells, indicating that the level of circulating CD34+/KDR+ cells also relates to in vivo platelet activation. CONCLUSIONS: Circulating CD34+/KDR+ are not mobilized from bone marrow as a predestined endothelial progenitor cell population but are mostly generated from circulating multipotent CD34+ cells at sites of vascular injury. Therefore, the number of circulating CD34+/KDR+ cells may serve as a marker for vascular injury.

Office and ambulatory pulse pressure--association with clinical characteristics and cardiovascular risk factors in normoalbuminuric patients with type 2 diabetes (ROADMAP study).

To investigate the association of office and ambulatory 24-h pulse pressure (PP) with clinical characteristics and cardiovascular risk factors in normoalbuminuric type 2 diabetic patients enrolled to the Randomised Olmesartan and Diabetes Microalbuminuria Prevention study, 4449 patients (2054 male and 2395 female; mean age 57.7±8.7 years) with type 2 diabetes, normoalbuminuria and at least one additional cardiovascular risk factor were included into the analysis. After adjustment by age, there were significant correlations between office PP and presence of hypertension (r=0.24; P<0.001), presence of cardiac and vascular disorders (r=0.17; P<0.001), metabolic syndrome (r=0.10; P<0.001), duration of diabetes (r=0.09; P<0.001), fasting blood glucose (r=0.08; P<0.001), albumin/creatinine ratio (r=0.07; P<0.001), insulin treatment, glycosylated haemoglobin (HbA1c), male gender and current smoking. In the subgroup of 1234 patients with ambulatory blood pressure measurement performed, ambulatory PP adjusted for office PP correlated with fasting blood glucose (r=0.16; P<0.001), metabolic syndrome (r=0.14; P<0.001), albumin/creatinine ratio (r=0.11; P<0.001) and indices of glycemic control (HbA1c: r=0.11; P<0.001). In this group of normoalbuminuric type 2 diabetic patients, office and ambulatory PP were associated with duration of diabetes, indices of glycemic control and cardiovascular risk factors. There was relationship between office and ambulatory PP and albuminuria even within normal albuminuria range.

Determinants of urinary albumin excretion within the normal range in patients with type 2 diabetes: the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study.

AIMS/HYPOTHESIS: In contrast to microalbuminuric type 2 diabetic patients, the factors correlated with urinary albumin excretion are less well known in normoalbuminuric patients. This may be important because even within the normoalbuminuric range, higher rates of albuminuria are known to be associated with higher renal and cardiovascular risk. METHODS: At the time of screening for the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) Study, the urinary albumin/creatinine ratio (UACR) was 0.44 mg/mmol in 4,449 type 2 diabetic patients. The independent correlates of UACR were analysed. RESULTS: Independent correlates of UACR during baseline were (in descending order): night-time systolic BP (r(s) = 0.19); HbA(1c) (r(s) = 0.18); mean 24 h systolic BP (r(s) = 0.16); fasting blood glucose (r(s) = 0.16); night-time diastolic BP (r(s) = 0.12); office systolic BP, sitting (r(s) = 0.11), standing (r(s) = 0.10); estimated GFR (r(s) = 0.10); heart rate, sitting (r(s) = 0.10); haemoglobin (r(s) = -0.10); triacylglycerol (r(s) = 0.09); and uric acid (r(s) = -0.08; all p

Mannose binding lectin deficiency and triglyceride-rich lipoprotein metabolism in normolipidemic subjects.

Mannose binding lectin (MBL) is one of the three initiators of complement activation and is therefore closely linked to inflammation. MBL deficiency has been associated with the generation of atherosclerosis. Since atherosclerosis, the complement system and postprandial lipemia are linked to inflammation, we studied postprandial lipoprotein metabolism in MBL deficiency. An observational study was carried out in 107 volunteers (21% MBL deficient). Classical cardiovascular risk factors were not different between subjects with and without MBL deficiency. Oral fat loading tests in 8 MBL deficient and 14 MBL sufficient subjects showed similar postprandial triglyceride, free fatty acid, hydroxybutyric acid and complement component 3 concentrations. MBL deficient subjects had 2.4 times lower postprandial Sf>400 (chylomicron)-apoB48 concentrations, but in contrast a 2-3.5 times increased Sf 60-400 (VLDL1-TG) and Sf 60-400-apoB100 response. MBL activity was inversely related to the postprandial Sf 60-400-TG increase. Despite lower postprandial Sf>400-apoB48 concentrations, MBL deficient subjects show an accumulation of Sf 60-400 lipoproteins.

Influence of atherosclerosis on age-related changes in renal size and function.

BACKGROUND: Renal size and function reflect the health of the kidney. These parameters are associated with age, gender and body weight. The kidneys are also influenced by micro- and macrovascular diseases. Atherosclerotic markers and risk factors may influence the age-related changes of renal size and function. METHODS: Data of 1056 patients who entered the SMART-study (Second Manifestations of ARTerial disease) were used to assess the effect of atherosclerosis on the relationship between age and renal size and function and to study the effect of atherosclerosis on renal size and function. Patients who were newly referred to the hospital with manifestations of vascular disease were screened for asymptomatic atherosclerosis with noninvasive tests. The carotid intima-media thickness (IMT) and albuminuria were used as estimates for the atherosclerotic burden. Renal size was defined as the mean pole-to-pole length of both kidneys measured by ultrasonography. Renal function was represented by serum creatinine. RESULTS: Intima-media thickness was a significant effect modifier of the age-renal size relationship (P = 0.041). The increase of serum creatinine with age was more pronounced in the highest tertile of IMT (P = 0.048). Renal size decreased equally with age in patients with and without hypertension or diabetes mellitus (DM). The same held true for the age-renal function relationship. Albuminuria and DM were independent predictors of renal size and function. CONCLUSION: Atherosclerosis accelerates the decrease of renal size and the increase of serum creatinine with age. Renal size and function are determined by albuminuria and DM.

[Nobel prize in Medicine and Physiology 1998 for the discovery of the role of nitric oxide as a signalling molecule]. / Nobelprijs Geneeskunde en Fysiologie 1998 vanwege de betekenis van stikstofmonoxide als signaalmolecuul.

The Nobel Prize for Medicine and Physiology 1998 was awarded to three American pharmacologists: Robert F.Furchgott, Louis J. Ignarro and Ferrid Murad for their work on nitric oxide as a signalling molecule in the cardiovascular system. This discovery is a classical case of serendipity. NO is an endothelium-derived factor which mediates local vasodilation. It protects the vascular system against atherosclerosis by various effects on leukocytes and vascular permeability. NO appears to be a universal signalling molecule in the body, involved in the inflammatory response, apoptosis and neurotransmission. Its biochemistry is closely linked to that of oxygen radicals.

[Endothelins: possibly a new pharmacological approach in cardiovascular diseases, kidney diseases and oncological disorders]. / Endothelinen: mogelijk een nieuw farmacologisch aangrijpingspunt bij hart-en vaatziekten, nierziekten en oncologische aandoeningen.

Only 10 years ago, the vasoconstricting peptide endothelin was discovered; it is produced by endothelial cells. Different isoforms and receptors of endothelin have been identified. The effects of endothelin-I, the most important isoform, are mainly vasoconstriction and proliferation of cells. In the last few years endothelin receptor antagonists have become available, which can delineate the clinical importance of the endothelin system. Possible indications for endothelin receptor blockers are renal disease (acute and chronic renal failure) and cardiovascular disease (heart failure; restenosis after percutaneous transluminal coronary angioplasty (PTCA); pulmonary hypertension; systemic hypertension). There is also a possible role for endothelin receptor blockers in oncology (prostatic carcinoma). Currently clinical trials are being carried out to determine the efficacy of these compounds for the above-mentioned indications.

L-arginine does not prevent the renal effects of endothelin in humans.

The infusion of endothelin to obtain plasma levels as present in sodium-retaining conditions such as heart failure and hepatorenal syndrome has been shown to cause sodium retention and renal vasoconstriction. Whether these renal effects of endothelin could be modulated by the stimulation of nitric oxide production by the infusion of L-arginine was examined. Therefore, the renal and endocrine effects of the systemic administration of endothelin (2.5 ng/kg per minute for 90 min), L-arginine (5 mg/kg per minute for 90 min), or the combination of endothelin and L-arginine were studied in healthy subjects under clearance conditions. During endothelin infusion, plasma endothelin levels rose from 3.0 +/- 0.2 to 14.1 +/- 2.4 pmol/L (P < 0.01). Mean arterial pressure increased by 7 mm Hg (P < 0.01). The effects on renal function were disproportionately large: renal vascular resistance increased from 77.5 +/- 3.2 to 124.1 +/- 6.7 mm Hg/min per liter (P < 0.01), and sodium excretion fell from 178 +/- 30 to 83 +/- 11 mumol/min (P < 0.01). Endothelin had no effect on urinary nitrite excretion. L-Arginine caused a fall in blood pressure of 5 mm Hg (P < 0.01) and decreased renal vascular resistance by 12% (P < 0.05). Sodium excretion increased twofold. This was associated with an increase in urinary nitrite excretion from 112 +/- 36 to 465 +/- 190 nmol/min (P < 0.01), suggesting stimulation of renal nitric oxide production. During the combination of endothelin and L-arginine, urinary nitrite excretion increased similarly.(ABSTRACT TRUNCATED AT 250 WORDS)

Natriuretic and kaliuretic response to potassium load: modulation by sodium intake.

Potassium (K) loading is followed by a rapid increase in sodium (Na) and K excretion. To evaluate the influence of Na intake on this effect, we studied the acute natriuretic and kaliuretic response to a single oral K load (100 mmol) in six healthy volunteers equilibrated on a 10-, 100-, and 400-mmol Na intake. Compared to the 100-mmol Na intake, the 400-mmol Na intake greatly enhanced the natriuretic effect of the K load; during the 10-mmol Na intake no natriuresis but even some Na retention occurred. The kaliuretic effect was not significantly changed and occurred at similar values of plasma K. Plasma aldosterone was suppressed during the 400-mmol Na diet and stimulated during the 10-mmol Na diet, but the relative increments after the KCl load did not differ among the three diets. In conclusion, whereas the effect of a K load on kaliuresis is relatively independent of Na intake, its effect on Na excretion varies from marked natriuresis to slight Na retention. The Na retention is probably due to acute K-induced aldosterone stimulation, and the natriuresis to K-induced increase in distal Na delivery not utilized to promote K excretion. Apparently, the integration of renal Na and K handling after a K load is such that K balance is maintained at the cost of Na balance.

Response of urinary angiotensin to challenges of the renin-angiotensin system.

Angiotensin has an intrarenal action which may not parallel its action in the general circulation. We investigated whether the urinary excretion rates of angiotensin I and II (UV-AI, UV-AII) can be used as a marker of renal production. We therefore measured UV-AI, UV-AII, plasma angiotensin I and II (PAI, PAII), and plasma renin activity (PRA) in healthy subjects under conditions influencing the renin-angiotensin system: captopril injection (n = 7), enalapril treatment (n = 9), furosemide infusion on high and low sodium intake (n = 6), indomethacin treatment (n = 8), and head-out water immersion (three sodium intakes). After captopril (acute) and enalapril (chronic), PAI and PRA increased, PAII decreased, but neither UV-AI nor UV-AII changed. During furosemide infusion, PAI, PAII, PRA, as well as UV-AI and UV-AII increased. During indomethacin treatment, PAI, PAII, and PRA decreased, whereas UV-AI and UV-AII did not change consistently. Sodium restriction increased PAI, PAII, and PRA, but did not alter UV-AI and UV-AII. Head-out immersion decreased PAI, PAII, and PRA, but did not change UV-AI and UV-AII. The relative constancy of the urinary AI and AII excretion rates makes it doubtful whether urinary angiotensins reflect changes of renal angiotensin production.

Influence of indomethacin on extracellular calcium homeostasis.

Rheumatoid arthritis is associated with a generalised loss of bone mass. One of the factors that have been implicated in the pathogenesis of this bone loss is the chronic use of non-steroidal anti-inflammatory drugs (NSAIDs). These drugs are known to increase gastrointestinal permeability and may thus influence the absorption of calcium; they may also influence glomerular filtration rate and the renal excretion of calcium; in addition, NSAIDs may inhibit osteoblast function as well as osteoclastic bone resorption. Calcium homeostasis was studied in eight healthy volunteers during eight days' treatment with 150 mg indomethacin daily. No changes in serum concentration of calcium, phosphorus, parathyroid hormone, 25-hydroxyvitamin D3, and 1,25-dihydroxyvitamin D3 were found. The creatinine clearance and the urinary excretion of phosphorus and sodium did not change, but a decrease in calcium excretion was noted (mean (SEM) calcium/creatinine excretion 0.52 (0.05) v 0.28 (0.06)). This decrease is probably due to renal retention of calcium. Whether this decrease of urinary calcium excretion has a positive or a negative effect on bone is presently unknown.

Small intra- and large inter-individual variability in lithium clearance in humans.

We report the inter- and intra-individual variability in fractional lithium clearance (CLi), an alleged quantitative index of Na and water delivery from the proximal tubules, in humans (N = 91). The inter-individual variability was large, the variation coefficients at various Na excretion rates ranging between 11% and 19%. The intra-individual variability was small, the relative intra-individual standard deviation for duplicate measurements (N = 33) being 5%. These observations suggest large inter-individual differences in proximal tubular Na reabsorption. To confirm this, we also studied the inter- and intra-individual variability in the maximum urine flow during water diuresis (Vmax), an index of Na delivery to the diluting segment. They were found to be almost identical to the inter- and intra-individual variability in CLi, and fractional CLi and Vmax correlated strongly (r = 0.83, P less than 0.001). In addition, the inter-individual variability in the fractional clearance of uric acid (CUA), a directional marker of Na reabsorption in the proximal tubules, was large, but the intra-individual variability small. The correlation between fractional CUA and CLi, however, was relatively weak (r = 0.40, P less than 0.01). Although our results do not prove the exact, quantitative validity of the lithium clearance concept, we conclude that the variability in CLi reflects large inter-individual differences in Na handling in the proximal segments of the nephron. Our observations also have implications for the use of the lithium clearance method. The large inter-individual variability in CLi makes the method less suitable to detect subtle differences in CLi in small, unpaired groups of subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal response to infusion versus repeated bolus injections of atrial natriuretic factor in man.

In 7 healthy humans consuming a 170 mmol sodium diet the effect of the mode of administration of atrial natriuretic factor (human ANF 99-126) on renal function has been investigated, using conventional clearance studies during maximal water diuresis. ANF was administered as four repeated bolus (0.4 microgram/kg) injections and, after a 2-day interval, as a one-hour infusion (0.02 microgram/kg/min) preceded by a 0.4 microgram/kg bolus injection. In the two experiments ANF caused comparable elevations in glomerular filtration rate, free water clearance, and lithium excretion. No change in blood pressure or heart rate was observed in either study, and plasma renin activity and aldosterone fell by a similar extent. As expected, the time course of plasma ANF concentrations was markedly different during the two studies. It is concluded that with those doses of ANF the changes in renal haemodynamics and sodium handling were essentially similar after bolus injections and a constant infusion.

Indomethacin increases renal lithium reabsorption in man.

We examined the effect of semi-acute indomethacin (4 x 50 mg orally during the preceding 27 h) on renal function parameters, including fractional lithium reabsorption (FRLi) in seven healthy subjects during a 200 mmol and a 40 mmol sodium diet. Studies were carried out during maximal water diuresis. During the sodium-rich diet, indomethacin raised minimal urine osmolality from 61 +/- 1 to 72 +/- 2 mosm/kg (P less than 0.05), and during the sodium-restricted diet from 55 +/- 3 to 93 +/- 6 mosm/kg (P less than 0.01). Indomethacin reduced maximal free water clearance only during the low-sodium diet, and had no consistent effect on inulin clearance and the fractional excretions of sodium, phosphate and uric acid. Nevertheless, FRLi rose substantially, from 71 +/- 2% to 75 +/- 2% (P less than 0.01) and from 75 +/- 2% to 81 +/- 2% (P less than 0.01) during high- and low-sodium diets respectively. During either diet, indomethacin caused a significant reduction of 24-h urine PGE2 excretion. Since indomethacin is not supposed to influence proximal tubular sodium reabsorption, the rise in lithium reabsorption occurred beyond this nephron level, presumably in the loop of Henle. Clearly, the FRLi cannot be used as a quantitative marker of proximal tubular sodium reabsorption in humans in all conditions.

Effects of simvastatin and cholestyramine on lipoprotein profile in hyperlipidaemia of nephrotic syndrome.

The efficacy, safety, and tolerability of simvastatin (20 mg twice a day) in the treatment of hyperlipidaemia due to unremitting nephrotic syndrome was compared with that of cholestyramine (8 g twice a day) in a crossover trial in ten patients. Two patients were taken off the protocol, one because he could not tolerate cholestyramine and one because of non-compliance with the cholestyramine regimen. No clinical or laboratory adverse experiences were noticed during the study in the other eight patients. Simvastatin was significantly more effective than cholestyramine in reducing the hyperlipidaemia--it produced a 36% decrease in total cholesterol and a 39% decrease in low density (LDL)-cholesterol, whereas cholestyramine reduced total cholesterol by 8% and LDL-cholesterol by 19%. With simvastatin the apolipoprotein B level decreased by 30%, whereas the apolipoprotein A level increased by 10%.

Mineralocorticoid activity and the excretion of an oral potassium load in normal man.

In six healthy males on a fixed sodium/potassium (Na/K) intake, we studied the relation between plasma K and urine K and Na excretion after an oral K load. Studies were repeated during fludrocortisone (0.5 mg bid) or spironolactone (50 mg qid), that is, after escape from the Na-retaining and Na-excreting effects of these drugs. A steep positive relation between plasma K (ordinate) and urine K or Na (abscissa) was found, compatible with a strong influence of changes in plasma K on K and Na excretion. Fludrocortisone reset the relation to a lower level of plasma K. Spironolactone, on the other hand, had little effect on these relations, although a tendency towards a higher plasma K could be recognized. Paradoxically, the K load was excreted less efficiently during fludrocortisone, probably due to enhanced cellular K deposition. Prolonged kaliuresis relative to the transient rise in plasma K and natriuresis was found only without medication. Only in this situation aldosterone rose and fell parallel to plasma K. We conclude that: 1) chronic mineralocorticoid increase shifts the set point of both K and Na excretion following a K load to a lower plasma K, compatible with resetting of the positive influence of plasma K on distal solute delivery towards a lower plasma K; 2) total kaliuresis is paradoxically low due to enhanced cellular K uptake; 3) blockade of endogenous aldosterone action has relatively little influence on these relations between plasma K and urine K or Na; 4) the contribution of acute aldosterone stimulation to the excretion of a single oral K load can be recognized as a delayed kaliuresis extending beyond the peak in plasma K.