Nurse practitioners improve quality of care in chronic kidney disease: two-year results of a randomised study.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased cardiovascular risk. Here we evaluate whether strict implementation of guidelines aimed at multiple targets with the aid of nurse practitioners (NP) improves management in patients with CKD. METHODS: MASTER PLAN is a randomised controlled clinical trial, performed in nine Dutch hospitals. Patients with CKD (estimated glomerular filtration rate (eGFR) 20-70 ml÷min) were randomised to receive NP support (intervention group (IG)) or physician care (control group (CG)). Patients were followed for a median of five years. Presented data are an interim analysis on risk factor control at two-year follow-up. RESULTS: We included 788 patients (532 M, 256 F), (393 CG, 395 IG), mean (±SD ) age 59 (±13) years, eGFR 38 (±15) ml÷min÷1.73m(2), blood pressure (BP) 138 (±21)÷80 (±11) mmHg. At two years 698 patients (352 IG, 346 CG) could be analysed. IG as compared with CG had lower systolic (133 vs 135 mmHg; p= 0.04) and diastolic BP (77 vs 80 mmHg; p=0.007), LDL cholesterol (2.30 vs 2.45 mmol(-l); p= 0.03), and increased use of ACE inhibitors, statins, aspirin and vitamin D. The intervention had no effect on smoking cessation, body weight, physical activity or sodium excretion. CONCLUSION: In both groups, risk factor management improved. However, changes in BP control, lipid management and medication use were more pronounced in IG than in CG. Lifestyle interventions were not effective. Coaching by NPs thus benefits everyday care of CKD patients. Whether these changes translate into improvement in clinical endpoints remains to be established.

Hospital specific factors affect quality of blood pressure treatment in chronic kidney disease.

BACKGROUND: Blood pressure (BP) is the most important modifiable risk factor for cardiovascular (CV) disease and progression of kidney dysfunction in patients with chronic kidney disease. Despite extensive antihypertensive treatment possibilities, adequate control is notoriously hard to achieve. Several determinants have been identified which affect BP control. In the current analysis we evaluated differences in achieved BP and achievement of the BP goal between hospitals and explored possible explanations. METHODS: At baseline, BP was measured in a supine position with an oscillometric device in 788 patients participating in the MASTER PLAN study. We also retrieved the last measured office BP from the patient records. Additional baseline characteristics were derived from the study database. Univariate and multivariate analyses were performed with general linear modelling using hospital as a random factor. RESULTS: In univariate analysis, hospital was a determinant of the level of systolic and diastolic BP at baseline. Adjustment for patient, kidney disease, treatment or hospital characteristics affected the relation. Yet, in a fully adjusted model, differences between centres persisted with a range of 15 mmHg for systolic BP and 11 mmHg for diastolic BP. CONCLUSION: Despite extensive adjustments, a clinically relevant, statistically significant difference between hospitals was found in standardised BP measurements at baseline of a randomised controlled study. We hypothesise that differences in the approach towards BP control exist at the physician level and that these explain the differences between hospitals.

Orthostatic proteinuria: a harmless variant of protein loss?

A 28-year-old young woman was referred to our department of Internal Medicine for analysis of unintentional weight loss. At initial analysis, a persistent proteinuria was found with no evident relation to her weight loss. Anamnestic as well as additional studies showed no evidence of a primary kidney disease. After this exclusion, orthostatic proteinuria was confirmed by simple urine analysis. Since the weight loss had not yet been explained, an analysis followed at the Department of Gastointestinal and Liver Diseases where inflammatory bowel disease (IBD) was found. Literature study shows that proteinuria may be associated with IBD. This concerns mainly selective tubular protein loss, without a distinctive change in protein loss with a change in position. Orthostatic proteinuria, therefore, remained the most likely diagnosis. In this case, the patient was advised to check both urine and kidney function annually.

[The portfolio will increase the quality of specialist education]. / Het portfolio zal de kwaliteit van de speciajistenopleiding vergroten.

The portfolio gives the doctor who is undergoing training to become a specialist (Dutch abbreviation aios) a tool to help describe his or her own progress and the future targets in the training programme, and assists the trainer to obtain a more detailed insight into the educational goals that should receive more emphasis. The self-critical attitude of the aios that this helps to develop is a good guarantee for society of the thoroughness of medical specialist training.

A thyrotropin-secreting pituitary adenoma as a cause of thyrotoxic periodic paralysis.

We describe a patient with thyrotoxic periodic paralysis (TPP) caused by a thyrotropin-secreting pituitary adenoma. The diagnosis TPP was based on the combination of episodes of reversible hypokalaemic paralysis, hyperthyroidism and electrophysiological findings. A thyrotropin-secreting pituitary adenoma was diagnosed on the basis of endocrinological function tests and MRI of the pituitary gland. Before transsphenoidal resection of the adenoma, treatment with octreotide restored euthyroidism both clinically and biochemically. Immunocytochemistry of the pituitary adenoma was positive for TSH exclusively. Incubation with octreotide or quinagolide induced decreased TSH and alpha-subunit production by the cultured adenoma cells, in agreement with the pre-operative in vivo data. This paper is the first to describe in vivo and in vitro characteristics of a thyrotropin-secreting pituitary adenoma in a patient presenting with periodic paralysis.

Influence of uraemia on the determination of blood glycohaemoglobin by HPLC, electrophoresis and affinity chromatography in diabetic and non-diabetic patients.

Glycohaemoglobin in human blood can be determined by several methods. We investigated three methods used in daily practice, viz. affinity chromatography, HPLC and electrophoresis. We examined the influence of uraemia in diabetic and non-diabetic patients on the results obtained with HPLC and electrophoresis and compared these with the results obtained with affinity chromatography. Our current method (electrophoresis) proved to be very sensitive to uraemia giving falsely elevated levels of HbA1. HPLC was not disturbed by uraemia.

Quality-of-life in a long-term multicentre trial in chronic nonspecific lung disease: assessment at baseline. The Dutch CNSLD Study Group.

Quality-of-life (QOL) in patients with respiratory illness is a topic of increasing interest to clinicians and researchers. In a multicentre trial, which studies the long-term effects of three medication regimens (beta-agonist plus either placebo, anticholinergic agent or corticosteroid, all by inhalation) in patients with chronic nonspecific lung disease ((CNSLD): asthma and chronic obstructive pulmonary disease (COPD)), quality-of-life was included as an additional outcome measure. We wanted to provide a baseline assessment of quality-of-life in 274 adult patients with a mild to moderate degree of CNSLD. Quality-of-life was measured using a set of six standardized tests: Anxiety, Depression and Sleep Disorders, Optimism and Stigma, and Activities of Daily Living were assessed via scales with adequate validity and reliability, as established in previous work in Dutch patients with CNSLD. We found that quality-of-life was mildly impaired in these patients. Although differences with a reference group were present throughout, these were not significant, probably due to selection of relatively young, clinically stable, and highly motivated patients for our study. Quality-of-life scores showed higher correlation coefficients (0.20 < r < 0.38) to symptom scores than did results of pulmonary function tests (r < 0.015). In logistic regression models, absence from work and hospitalizations due to CNSLD were partly determined by quality-of-life scores.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of in vivo prednisolone on increased in vitro O2- generation by neutrophils in emphysema.

Evidence is accumulating that neutrophil-derived oxidants substantially contribute to the development of emphysema, especially in smoking individuals. It is not clear, however, why not all smokers develop emphysema. We tested the hypothesis that an abnormality in the oxidative metabolism of polymorphonuclear leucocytes (PMNs) might contribute to the development of emphysema. We investigated in vitro O2- production by peripheral PMNs in patients with stable emphysema and in healthy controls. In addition, we investigated whether in vivo prednisolone may modulate in vitro O2- production by PMNs in patients with emphysema during a stable phase of the disease. Spontaneous O2- production by PMNs was not significantly different in patients and controls. After stimulation with submaximal concentrations of calcium ionophore A23187 and phorbol myristate acetate, however, PMNs from patients with stable emphysema produced more O2- than those from healthy controls, especially in smoking subjects. Moreover, in vitro O2- generation by PMNs significantly decreased after in vivo prednisolone treatment in patients with emphysema. We suggest that our findings reflect an abnormality of PMNs, acting as one of the factors that contribute to the development of emphysema. This abnormality may, at least partially, be dampened by in vivo prednisolone treatment. These findings may provide new insights into the pathogenesis and treatment of pulmonary emphysema. Further studies on pulmonary PMNs are necessary to extend our findings.

A comparison of bronchodilator therapy with or without inhaled corticosteroid therapy for obstructive airways disease. Dutch Chronic Non-Specific Lung Disease Study Group.

BACKGROUND: The morbidity from obstructive airways disease (asthma and chronic obstructive pulmonary disease) is considerable, and the mortality rate is rising in several countries. It has been hypothesized that long-term improvement in prognosis might result from vigorous bronchodilator or antiinflammatory therapy. METHODS: In a multicenter trial we compared three inhalation regimens in which a beta 2-agonist (terbutaline, 2000 micrograms daily) was combined with a corticosteroid (beclomethasone, 800 micrograms daily), an anticholinergic bronchodilator (ipratropium bromide, 160 micrograms daily), or placebo. Patients with airways hyperresponsiveness and obstruction who were 18 to 60 years old were followed for 2 1/2 years. RESULTS: Of the 274 patients enrolled, 56 percent had allergies. The mean forced expiratory volume in one second (FEV1) was 64 percent of the predicted value. The mean PC20 (the concentration of inhaled histamine causing a 20 percent decrease in FEV1, a measure of hyperresponsiveness) was 0.26 mg per milliliter. Withdrawal from the study, due mainly to pulmonary symptoms, was less frequent in the corticosteroid group (12 of 91 patients) than in the anticholinergic-drug group (45 of 92 patients) or the placebo group (44 of 91 patients; P < 0.001). The mean FEV1 (+/- SE) increased by 10.3 +/- 1.3 percent of the predicted value in the corticosteroid group within three months and remained stable thereafter, whereas it did not change in the other two groups (P < 0.001). The PC20 increased by 2.0 doubling concentrations in the corticosteroid group but did not change in the other groups (P < 0.001). In the corticosteroid group, patients who did not smoke, who had allergies, or who were less than 40 years old benefited more from their treatment than did those who smoked, did not have allergies, or were over 40, but all subgroups of the corticosteroid group had improvement as compared with the anticholinergic-drug or placebo group. CONCLUSIONS: The addition of an inhaled corticosteroid--but not an inhaled anticholinergic agent--to maintenance treatment with a beta 2-agonist (terbutaline) substantially reduced morbidity, hyperresponsiveness, and airways obstruction in patients with a spectrum of obstructive airways disease.

Interpretation of bronchodilator response in patients with obstructive airways disease. The Dutch Chronic Non-Specific Lung Disease (CNSLD) Study Group.

BACKGROUND: There is no agreement on how a bronchodilator response should be expressed. Ideally, the index used should be able to distinguish asthma from chronic obstructive lung disease and be independent of initial FEV1. METHODS: Two hundred and seventy four adults (aged 18-60 years) outpatients with obstructive airways disease were studied. Patients were divided into syndrome groups on the basis of a standardised history: asthma (n = 99), asthmatic bronchitis (n = 88), and chronic obstructive lung disease (n = 51); 36 subjects could not be attributed to any subgroup. FEV1 was measured before and 20 minutes after inhalation of 1000 micrograms terbutaline. Different expressions of bronchodilator response (delta FEV1) were compared with respect to their dependence on initial FEV1 and their efficacy in separating subjects with asthma from those with chronic obstructive lung disease. delta FEV1 was expressed as a percentage of initial FEV1 (delta FEV1%init), absolute value (delta FEV1[1]), percentage of predicted FEV1 (delta FEV1%pred), standardised residual (delta SR-FEV1), and percentage of maximal possible increase (delta FEV1%[pred-init]). RESULTS: delta FEV1%init was more dependent on initial FEV1 (p = -0.405) than delta FEV1[1] (r = -0.145), delta FEV1%pred (r = -0.166), and delta SR-FEV1 (r = -0.127). delta FEV1%[pred-init] reached infinity when initial FEV1 approached predicted levels. delta FEV1%pred had a higher likelihood ratio (1.71) for separating patients with asthma from those with chronic obstructive lung disease than other expressions of bronchodilator response. Asthmatic patients had larger mean bronchodilator responses than patients in other subgroups; this difference was largest for delta SR-FEV1 (F = 9.19) and delta FEV1%pred (F = 9.03); it was much smaller for delta FEV1%init (F = 5.89). Despite significant differences in mean response, there was a large overlap of individual responses between diagnostic subgroups. The bronchodilator response was continuously and unimodally distributed for all expressions. CONCLUSIONS: delta FEV1%pred appears to be the most useful method of expressing bronchodilator response, both for clinical and for research purposes. Reversibility of airways obstruction in response to a bronchodilator is a continuous variable and not a dichotomous triat. Any cut off level of a "positive" bronchodilator response is therefore arbitrary.

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.

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.

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.

Long-term multicentre trial in chronic nonspecific lung disease: methodology and baseline assessment in adult patients. Dutch CNSLD Study Group.

Airways obstruction and airways hyperresponsiveness are two dominant features in patients with chronic nonspecific lung disease (asthma and chronic obstructive pulmonary disease (COPD)). We set up a study to determine whether long-term (3 yrs) therapeutic intervention directed at airways obstruction and hyperresponsiveness is superior to one directed at airways obstruction alone. Patients were selected on functional criteria (age, baseline forced expiratory volume in one second (FEV1), and airways hyperresponsiveness) and, furthermore, extensively characterized by history, smoking habits, allergy, reversibility of airways obstruction and quality of life. The methodology and practical problems of setting up this large multicentre study are outlined, together with an analysis of baseline data. Standardization of methods and techniques and recruitment of patients required much effort, recruitment taking about twice as long as expected. A 3 month feasibility study allowed us to eliminate minor problems in the protocol. Over a 16 month period, 274 adult patients (18-60 yrs) from the out-patient clinics of six university centres entered the study; 99 met the diagnostic criteria for asthma, 51 for COPD, 88 for asthmatic bronchitis, and 36 could not be classified. Their mean (SD) FEV1% pred was 65.1 (15.2)%. Their geometric mean provoking concentration of histamine producing a 20% fall in FEV1 (PC20 histamine) was 0.28 mg.ml-1. In a multiple regression analysis, more severe airways hyperresponsiveness was associated with lower prechallenge FEV1% pred (p less than 0.0001), higher pack-years of smoking (p = 0.0099), blood eosinophil count (p = 0.0004), skin test reactivity (p = 0.0047) and with female sex (p = 0.0302). We conclude that setting up long-term multicentre trials in chronic nonspecific lung disease (CNSLD) is feasible and that these may offer valuable information on treatment and outcome of the disease.

In vitro release of neutrophil elastase, myeloperoxidase and beta-glucuronidase in patients with emphysema and healthy subjects.

Evidence is accumulating that cigarette smoking plays an important role in the protease-antiprotease imbalance in alpha 1-antitrypsin-sufficient emphysema. Since most smokers, however, do not develop emphysema, it has to be presumed that other factors in addition to smoking contribute to the origin of the imbalance. The major source of proteases is the polymorphonuclear leucocyte (PMN). We tested the hypothesis that an abnormality in the releasability of PMN might predispose for the development of emphysema. Therefore, the release of elastase, myeloperoxidase, and beta-glucuronidase from PMN was investigated in patients with emphysema and healthy controls, matched for sex, age, and smoking habits. PMN were isolated from peripheral blood and stimulated with calcium-ionophore A23187, formyl-methionyl-leucyl-phenylalanine (FMLP), and serum-treated zymosan (STZ). Total enzyme content of PMN was measured after cell lysis with Triton X-100. Total elastase, myeloperoxidase, and beta-glucuronidase content of PMN were not significantly different in healthy subjects and patients with emphysema. In vitro release of elastase and myeloperoxidase from both stimulated and unstimulated PMN was not significantly different in healthy subjects and emphysematous patients. Moreover, no differences were found between smoking and ex-smoking individuals. Beta-glucuronidase release tended to be lower in patients with emphysema than in healthy controls. We conclude that an abnormality in the releasability of peripheral PMN is unlikely to be a pathogenetic factor in emphysema.

Differential effects of enalapril and atenolol on proteinuria and renal haemodynamics in non-diabetic renal disease.

OBJECTIVE: To compare the antihypertensive, renal haemodynamic and antiproteinuric effect of enalapril and atenolol in patients with proteinuria of non-diabetic origin. DESIGN: Prospective, double blind, randomised 16 week study after a pretreatment period of at least three weeks. SETTING: Outpatient nephrology and hypertension unit. PATIENTS: 27 patients with proteinuria (greater than 300 mg protein/day) of non-diabetic origin, moderately impaired renal function (creatinine clearance 30-90 ml/min), and a pretreatment diastolic blood pressure of greater than 80 mm Hg. INTERVENTIONS: Treatment with enalapril (10 mg/day, adjusted between 5 and 40 mg, if necessary) or atenolol (50 mg/day, adjusted between 25 and 100 mg if necessary) titrated against a target fall in diastolic blood pressure to less than 95 mm Hg or of greater than 10 mm Hg, or both. MAIN OUTCOME MEASURES: Blood pressure, renal haemodynamics, and urinary protein excretion. RESULTS: No differences were detected between the two groups before treatment. The falls in systolic and diastolic blood pressures during treatment were not significantly different between both groups. Proteinuria fell slightly with atenolol but significantly more with enalapril (mean change -0.38 (95% confidence interval -0.78 to 0.03) v -1.2 (-1.70 to -0.69) g/day respectively, p less than 0.02) as did filtration fraction (mean change -1.8 (-2.9 to -0.7) v -3.8 (-4.9 to -2.8)% respectively. Serum potassium concentration increased with enalapril (mean change 0.63 (SD 0.51) v 0.19 (0.47) mmol/l, p less than 0.05). CONCLUSIONS: Enalapril lowers proteinuria more than atenolol in patients with non-diabetic renal disease despite a similar blood pressure lowering effect of both drugs, and its antiproteinuric effect seems to be associated with the characteristic renal haemodynamic effect of angiotensin converting enzyme inhibitors.

Clinical signs in severe Guillain-Barré syndrome: analysis of 63 patients.

Clinical data are presented of 63 artificially ventilated Guillain-Barré patients. About half of them had an antecedent event. In 57% the disease was heralded by sensory symptoms. The mean progressive phase lasted 12 days, the plateau 12 days and the recovery phase 568 days. In all patients one or more cranial nerves were involved, most often leading to facial palsy or difficulties in swallowing. Three-quarters of the patients had sensory signs, proprioceptive more often than superficial. Autonomic disturbances were common, especially hypertension and tachycardia. Twenty-two percent of the patients were severely confused in the first weeks of the disease. Laboratory examination showed atypical lymphocytes in the blood of 37% of patients and disturbed hepatic function tests in 79%. CSF protein level was elevated in all patients, with a mean value of 1.5 g/l.