Patients' representations of their end-stage renal disease: relation with mortality.

BACKGROUND: Self-regulation theory explains how patients' illness perceptions influence self-management behaviour (e.g. via adherence to treatment). Following these assumptions, we explored whether illness perceptions of ESRD-patients are related to mortality rates. METHODS: Illness perceptions of 182 patients participating in the NECOSAD-2 study in the period between December 2004 and June 2005 were assessed. Cox proportional hazard models were used to estimate whether subsequent all-cause mortality could be attributed to illness perception dimensions. RESULTS: One-third of the participants had died at the end of the follow-up. Mortality rates were higher among patients who believed that their treatment was less effective in controlling their disease (perceived treatment control; RR = 0.71, P = 0.028). This effect remained stable after adjusting for sociodemographic and clinical variables (RR = 0.65, P = 0.015). CONCLUSIONS: If we consider risk factors for mortality, we tend to rely on clinical parameters rather than on patients' representations of their illness. Nevertheless, results from the current exploration may suggest that addressing patients' personal beliefs regarding the effectiveness of treatment can provide a powerful tool for predicting and perhaps even enhancing survival.

Pelvic abscess caused by Arcanobacterium haemolyticum mimicking a soft tissue tumour.

Arcanobacterium haemolyticum has usually been isolated in cases of pharyngitis and wound infections. Rarely it has been reported to cause deep tissue infections. Here, a case of a 71-year-old-male, who developed a pelvic abscess due to A. haemolyticum that initially was thought to be a malignant tumour, is described.

A short-term antihypertensive treatment-induced fall in glomerular filtration rate predicts long-term stability of renal function.

In long-term intervention studies on renal function outcome an initial decline in the glomerular filtration rate (GFR) may occur after starting therapy. If this initial GFR decline is the result of a treatment-induced hemodynamic change reflecting a fall in intraglomerular pressure, it should be reversible after treatment withdrawal, even after long-term treatment. In fact, it could be beneficial for renal function in the long term. We therefore studied systemic and renal hemodynamics in 40 non-diabetic patients with impaired renal function before treatment, during four years treatment with either atenolol or enalapril, and after withdrawal of that treatment. The acute change in GFR 12 weeks after start of treatment varied widely from -11 to + 11 ml/min (mean +/- SD -1.0 +/- 4.1 ml/min, NS). After four years of treatment, withdrawal for 12 weeks resulted in a rise in GFR of +2.2 +/- 5.4 ml/min, P = 0.011, again with a wide range of +14 to -6 ml/min). The initial fall in GFR was related to the rise after withdrawal (r = 0.32, P < 0.05). Interestingly, the acute treatment induced change in GFR correlated with the long-term slope, such that a patient with a greater initial decline in GFR showed a more stable course during the follow up (r = -0.36, P < 0.05). The patients were arbitrarily divided in group A (N = 20), with the largest initial treatment-induced fall in GFR, and group B (N = 20), with the smallest initial fall in GFR. Group A had a significantly less steep slope than group B (-0.41 +/- 1.52 vs. -2.09 +/- 2.79 ml/min/year, P = 0.023) during the four year follow-up. In group A GFR increased again after withdrawal of treatment (+3.8 +/- 5.6 ml/min, P = 0.011) whereas it did not change in group B (+0.5 +/- 4.0 ml/min, NS). As a consequence, GFR post-treatment was not different compared to pre-treatment in group A (-2.5 +/- 7.2 ml/min, NS), whereas it was 5.9 +/- 12.1 ml/min lower in group B (P = 0.023). Patients treated with enalapril had a similar response as patients treated with atenolol. In conclusion, an initial fall in GFR after starting antihypertensive treatment in patients with a mild to moderate renal function impairment (GFR 30 to 90 ml/min) is reversible even after years of treatment, suggesting that this therapy-induced fall is of hemodynamic and not of structural origin. This initial GFR fall was associated with a subsequent stable renal function. These data lead to the hypothesis that the initial fall in GFR in response to antihypertensive therapy reflects renal protection.

Are angiotensin converting enzyme inhibitors superior to beta blockers in retarding progressive renal function decline?

We questioned the superiority of angiotensin converting enzyme (ACE) inhibitors to beta blocking drugs with regard to renal function outcome in patients with mild to moderate renal insufficiency and normal to moderately elevated blood pressure (BP). We therefore studied 89 patients in a prospective double-blind randomized trial comparing the effect of enalapril and atenolol on the slope of glomerular filtration rate (GFR). Mean baseline GFR was 53 +/- 20 ml/min, untreated BP 152 +/- 20 mm Hg systolic and 90 +/- 11 mm Hg diastolic and median proteinuria 0.6 g/24 hr (interquartile range 0.0 to 2.5). After a run-in period without antihypertensives, the test drug was titrated to lower diastolic BP to a predefined goal of 10 mm Hg below baseline and/or below 95 mm Hg. The median follow up was 3.9 years. Antihypertensive therapy resulted in a comparable decrease of BP in both study groups. Filtration fraction and proteinuria decreased in both groups. The slope of GFR over time was not different between both groups (-1.39 +/- 2.82 and -1.97 +/- 3.38 ml/min/year on atenolol and enalapril, respectively). In multiple regression analysis a higher baseline GFR, a greater decrease in GFR and in proteinuria during titration and a lower proteinuria during follow up were independently related to a better GFR slope. We conclude that the use of ACE inhibitors is not imperative in all patients with non-diabetic nephropathy.

Precision of glomerular filtration rate determinations for long-term slope calculations is improved by simultaneous infusion of 125I-iothalamate and 131I-hippuran.

In studies on the progression of chronic renal failure the measurement of GFR must be very reliable. Sequential determination of GFR using the renal clearances of exogenous tracers such as inulin or iothalamate is the most accepted method. However, because of inaccuracies in urine collection, intratest variation, and thus intertest variation, of these clearances is considerable. This has a negative impact on the precision of long-term slope estimations. A previously described method of GFR determination on the basis of simultaneous infusion of 131I-hippuran and 125I-iothalamate corrects for inaccurate urine collection. To study whether this correction method improves the precision of the GFR slope measurement, this study analyzed longitudinal GFR data obtained in 71 patients with renal disease during a follow-up of 84 to 180 wk (477 renal function studies). All GFR were calculated by using both the standard renal clearance method and the correction method. The intratest and intertest coefficient of variation was significantly smaller for the correction method compared with the standard method (1.93 +/- 0.20 versus 8.48 +/- 1.66% P < 0.0005; and 2.88 +/- 0.32 versus 5.12 +/- 0.66%, P < 0.005, respectively). As a result, the precision of the GFR slope estimation was significantly better with the correction method compared with the standard method (error of the slope, 1.63 +/- 1.09 versus 2.35 +/- 2.36 mL/min per yr, P < 0.01). This improvement in precision of the slope by using the correction method reduces the necessary sample size needed to detect a GFR slope difference between interventions to about 30% of that needed when using the standard method. It is concluded that the precision of GFR measurements is improved by using correction for inaccurate urine collection with concomitant 131I-hippuran clearance.

Association between angiotensin-converting-enzyme gene polymorphism and failure of renoprotective therapy.

BACKGROUND: Polymorphism in the gene for angiotensin-converting enzyme (ACE), especially the DD genotype, is associated with risk for cardiovascular disease. Glomerulosclerosis has similarities to atherosclerosis, and we looked at ACE gene polymorphism in patients with kidney disease who were in a trial of long-term therapy with an ACE inhibitor or a beta-blocker. METHODS: 81 patients with non-diabetic renal disease had been entered into a randomised comparison of oral atenolol or enalapril to prevent progressive decline in renal function. The dose was titrated to a goal diastolic blood pressure of 10 mm Hg below baseline and/or below 95 mm Hg. The mean (SE) age was 50 (1) years, and the group included 49 men. Their renal function had been monitored over 3-4 years. We have looked at their ACE genotype, which we assessed with PCR. FINDINGS: 27 patients had the II genotype, 37 were ID, and 17 were DD. 11 patients were lost to follow-up over 1-3 years. The decline of glomerular filtration rate over the years was significantly steeper in the DD group than in the ID and the II groups (p = 0.02; means -3.79, -1.37, and -1.12 mL/min per year, respectively). The DD patients treated with enalapril fared as equally a bad course as the DD patients treated with atenolol. Neither drug lowered the degree of proteinuria in the DD group. INTERPRETATION: Our data show that patients with the DD genotype are resistant to commonly advocated renoprotective therapy.

Discordant effects of enalapril and lisinopril on systemic and renal hemodynamics.

OBJECTIVE: To investigate whether there are quantitative differences between the angiotensin converting enzyme (ACE) inhibitors enalapril and lisinopril with respect to their influence on renal versus systemic hemodynamics in humans. METHODS: This was a 12-month, single-blind crossover study in which eight patients with essential hypertension were examined. The main outcome measures were blood pressure and renal hemodynamics during ACE inhibition and/or angiotensin II infusion. RESULTS: The decrease in blood pressure was dose dependent and not significantly different between both drugs. However, with the same blood pressure reduction effective renal plasma flow (ERPF) rose more and filtration fraction (FF) and renovascular resistance (RVR) decreased more after administration of enalapril (20 mg) than after administration of lisinopril (20 mg) (ERPF: 21.9% +/- 2.0% versus 4.4% +/- 2.5%, p = 0.018; FF: -16.7% +/- 2.8% versus -6.6% +/- 2.5%, p = 0.028; RVR: -28.1% +/- 3.1% versus -18.5% +/- 3.7%, p = 0.018). During angiotensin II infusion, with a similar increase in systemic blood pressure, the change in ERPF, FF, and RVR again was more pronounced during enalapril than during lisinopril (ERPF: -14.6% +/- 2.9% versus -7.8% +/- 3.3%, p = 0.018; FF: 18.3% +/- 5.9% versus 12.8% +/- 6.0%, p = 0.028; RVR: 36.7% +/- 8.1% versus 21.9% +/- 4.3%, p = 0.018). CONCLUSIONS: We conclude that in a situation of a comparable systemic blood pressure reduction, enalapril has greater effects on renal hemodynamics than lisinopril. This finding may have implications for the choice of a certain ACE inhibitor in specific disease conditions.

Management of chronic renal failure.

There is growing evidence that treatment of patients with renal function impairment will undergo a major shift within the next few years. Along with more or less successful attempts to alleviate the signs and symptoms of reduced renal function, new insights into renal pathophysiology as well as new therapeutic modalities have given rise to the notion that we may be able to retard the naturally occurring decline in renal function in patients with diabetic and nondiabetic nephropathy.

The antiproteinuric effects of blood pressure-lowering agents: differences between nondiabetics and diabetics.

The mechanism of the antiproteinuric effect of angiotensin-converting enzyme (ACE) inhibitors in diabetic and nondiabetic renal disease is as yet unknown. A meta-analysis of studies on the effects of ACE inhibitors and other antihypertensive drugs on proteinuria, blood pressure, and renal hemodynamics in nondiabetic renal disease revealed that ACE inhibitors lower proteinuria more than other antihypertensives. Moreover, a close correlation (p less than 0.01) between changes in urinary protein loss and in filtration fraction was found, whereas such a correlation could not be detected between changes in proteinuria and in blood pressure. This suggests that, at least in nondiabetic renal disease, the fall in proteinuria during ACE inhibition is the consequence of the intrarenal effect of the drug more than the systemic effect. Data on the mechanism of action of ACE inhibitors in diabetic microalbuminuria and in diabetic overt proteinuria are less consistent. A fall in proteinuria on antihypertensive drugs in these patients can be observed also without a significant fall in blood pressure, and without any change in filtration fraction. We therefore conclude that one should be cautious in extrapolating the data from studies in diabetic renal disease to patients with nondiabetic nephropathies. Moreover, we argue also that nonhemodynamic effects of ACE inhibitors also could be involved in the antiproteinuric effect of these drugs.

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.

Lisinopril in hypertensive patients with renal function impairment.

The antihypertensive and renal effects of the angiotensin-converting enzyme inhibitor lisinopril were studied in a group of patients with moderate-to-severe hypertension and impaired renal function. After 12 weeks of treatment, most patients had good blood pressure response to lisinopril monotherapy. During this period, correlations between antihypertensive effect, drug dose, and serum drug level were observed. These correlations were no longer evident after prolonged treatment. During a 1-year follow-up period, the drug dose was lowered gradually without losing antihypertensive effect. Hyperkalemia occurred in one third of the patients. During the 1-year follow-up, the glomerular filtration rate (GFR) decreased in two thirds of the patients and remained stable in the other third. In this latter group, the pretreatment GFR was higher, and the effective renal plasma flow had increased, whereas in the patients with a decreased GFR no renal vasodilation had occurred during lisinopril therapy. Thus, lisinopril is an effective antihypertensive drug for patients with impaired renal function. The dose should be adjusted to the pretreatment GFR, and a decrease in dosage should be considered with prolonged treatment.