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D de Zeeuw

Publications and source records attributed to D de Zeeuw.

At least 91 records · Page 5Linked to original sources
PubMed1997

Pharmacokinetics of candesartan cilexetil in patients with renal or hepatic impairment.

Five clinical studies were conducted to investigate the pharmacokinetic profile and safety of candesartan cilexetil in patients with either normal or impaired renal or hepatic function. Participants in these open-label, single- or parallel-group prospective studies were administered candesartan cilexetil 8 or 12 mg as a single oral dose and then, in all but one study, as a repeated once-daily oral dose regimen. A total of 94 patients of either gender aged between 18 and 75 years with normal or mild to moderate hepatic dysfunction (Study 1) and normal or mild to moderate/severe renal dysfunction (Studies 2-5) were included. Subjects recruited to all studies evaluating the effect of renal impairment also had some degree of hypertension. Patients with mild to moderate hepatic impairment showed no significant differences in the key plasma pharmacokinetic parameters or plasma protein binding profile of candesartan compared with healthy volunteers. In patients with mild to moderate or severe renal impairment there were significant increases in the maximum plasma concentration, area under the plasma drug concentration-time curve and elimination half-life of candesartan and its inactive metabolite (CV-15959) when compared to volunteers with normal renal function following repeated administration of candesartan cilexetil 8 or 12 mg. However, there was no evidence of accumulation following treatment with the 8 mg dose apart from those with severe disease requiring dialysis. Nevertheless, dialysis itself did not appear to affect the pharmacokinetic profile of candesartan or that of CV-15959. Candesartan cilexetil was found to have a good safety profile and to be well tolerated by patients with hepatic or renal impairment. There were no clinically relevant changes detected in vital signs, laboratory safety parameters or in ECG readings. The most common adverse events were headache and dizziness. This series of studies show that candesartan cilexetil 8 mg once daily is suitable for administration to patients with mild to moderate renal or hepatic impairment with no need for additional dose adjustment. A lower starting dose may be appropriate in patients with severe renal impairment including those requiring dialysis.

Adolescent↗
PubMed1997

Angiotensin converting enzyme insertion/deletion polymorphism and short-term renal response to ACE inhibition: role of sodium status.

Angiotensin converting enzyme (ACEi) inhibition retards renal function loss, but the therapeutic benefit varies between individuals. Renoprotection is poor in patients with the ACE DD genotype. ACE genotype is reported to affect short-term antiproteinuric response to ACEi, a predictor of long-term renoprotection, in some studies but not in others. Short-term responses to ACEi are enhanced by stimulating the renin-angiotensin system, that is, sodium restriction. We hypothesized that the ACE genotype influences sodium dependency of the response to ACEi. Therefore, we performed a cross sectional analysis of short-term responses to ACEi (enalapril or lisinopril) in 88 patients with stable non-diabetic proteinuria (> 1.0 g/day) and variable sodium intake. ACE genotype distribution was: DD, N = 25; ID, N = 40; II, N = 23. Baseline proteinuria (5.9 +/- 0.7; 5.8 +/- 0.07; 4.8 +/- 0.8 g/day, respectively) and mean arterial pressure (108 +/- 3; 106 +/- 2; 107 +/- 2 mm Hg, respectively) were similar for the three genotypes. ACEi similarly reduced proteinuria (-49 +/- 5; -55 +/- 4, -48 +/- 6%, respectively) and blood pressure (-12 +/- 3; -14 +/- 1 and -12 +/- 2%, respectively) in the three groups. Interestingly, the responses to ACEi of proteinuria (r = 0.42, P < 0.05) and blood pressure (r = 0.41, P < 0.05) correlated with urinary sodium excretion in DD genotype but not in the ID (r = 0.05 and 0.17, resp) or II genotype (r = 0.09 and 0.08, respectively). Thus, in the DD group, individuals with a high sodium excretion had a less effective response to ACEi. We conclude that differences in sodium status could account for disparities between studies on the relationship between ACE genotype and response to ACEi, and that sodium restriction might be a strategy to circumvent treatment resistance in the DD genotype.

Adolescent↗
PubMed1997

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.

Adolescent↗
PubMed1997

Renal hemodynamic effects of candesartan in normal and impaired renal function in humans.

The effects of angiotensin II type I receptor antagonist candesartan cilexitil, 8 mg once daily, were studied after single dose and after five days treatment in 17 hypertensive patients [median mean arterial pressure (MAP) 118 mm Hg, range 84 to 134] with renal function impairment of different severity [glomerular filtration rate (GFR) 60 ml/min, range 11 to 161]. The MAP fell by -8% (-14 to -5) and -11 (-16 to -5)% after single and multiple dose, respectively (both P < 0.02). Effective renal plasma flow (ERPF) increased by 13% (7 to 19) and 10% (3 to 14) after single and multiple dose, respectively (both P < 0.02), while the GFR did not change. Filtration fraction (FF) fell by -11% (-14 to -5) and -12% (-13 to -4) after single and multiple doses, respectively (both P < 0.02). After a single dose the % change in ERPF (r = 0.58) and FF (r = -0.52, both P < 0.05) positively correlated with pretreatment GFR, indicating a more pronounced response in patients with normal GFR. After five days of treatment these correlations were absent, indicating similar renal vasodilation in patients with normal and impaired renal function. Thus, multiple dose candesartan cilexitil had a favorable renal hemodynamic profile, irrespective of pretreatment renal function. Further studies are needed to establish whether this provides long-term renoprotection as well.

Angiotensin Receptor Antagonists↗
PubMed1996

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.

Adrenergic beta-Antagonists↗
PubMed1996

ACE inhibitors and proteinuria.

This review discusses the clinical consequences of urinary protein loss and the effects of inhibitors of the angiotensin converting enzyme (ACE) on this clinical finding. Proteinuria appears to be an important risk factor for renal function deterioration and for cardiovascular mortality. ACE inhibitors have been shown to reduce proteinuria more effectively than other antihypertensives. Their antiproteinuric effect seems to be independent of the underlying renal disease, and is mediated by a specific, not yet fully elucidated mechanism. Urinary protein loss related phenomena, such as hypoalbuminemia and aberrant lipoprotein profile, tend to improve also during ACE inhibitor treatment. Furthermore, ACE inhibition has been shown to prevent the renal function deterioration that is frequently observed in patients with renal disease. Interestingly, it has recently been shown that in proteinuric patients with renal disease the initial proteinuria lowering response to ACE inhibition predicts long-term renal function outcome during this treatment the more proteinuna is lowered during the first months, the better renal function will be preserved over the following years. Because of these favorable effects ACE inhibitors have become a widely used class of agents in nephrology. They are not only prescribed for lowering blood pressure in the hypertensive renal patient, but also as symptomatic treatment of patients with proteinuria, and to prevent renal function loss in patients with both diabetic and non-diabetic renal disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

The serum lathosterol to cholesterol ratio, an index of cholesterol synthesis, is not elevated in patients with glomerular proteinuria and is not associated with improvement of hyperlipidemia in response to antiproteinuric treatment.

The hypothesis that increased cholesterol synthesis provides a mechanism that contributes to nephrotic syndrome-associated hyperlipidemia is mainly based on experimental evidence. The serum level of the cholesterol precursor, lathosterol (expressed per millimole cholesterol), is a reliable marker of whole-body cholesterol synthesis in normocholesterolemia and primary hypercholesterolemia. Serum lathosterol and lipoprotein levels were measured in 11 moderately hyperlipidemic patients with nephrotic-range proteinuria and 22 matched controls. The proteinuric patients were evaluated before and during three antiproteinuric treatment periods with angiotensin-converting enzyme (ACE) inhibition therapy (n = 6) or a low-protein diet (n = 5) alone, in combination, and again as a single treatment. In untreated patients, serum total cholesterol, very-low-density (VLDL) and low-density (LDL) lipoprotein cholesterol, apolipoprotein B (apo B), and lipoprotein (a) [Lp(a)] levels were higher than in controls (P < .01 to P < .001), but the lathosterol to cholesterol ratio tended to be lower in patients (0.99 +/- 0.43 micromol/mmol) as compared with controls (1.29 +/- 0.41 micromol/mmol, P < .10). During combined antiproteinuric treatment, total and VLDL + LDL cholesterol, apo B, and Lp(a) decreased (P < .02 to P < .01), but remained higher than levels in controls. Yet the serum lathosterol to cholesterol ratio changed little and was even lower (P < .05) in treated patients than in controls. Serum total cholesterol (r = -.82, P < .01) and apo B (r = -.84, P < .01) were inversely correlated with serum albumin in untreated patients, whereas the serum lathosterol to cholesterol ratio was not (r = -.01, NS). In the patient group, multiple regression analysis showed that changes in the lathosterol to cholesterol ratio during the study were only related to changes in the dietary polyunsaturated to saturated fatty acids ratio (P:S) coinciding with the low-protein diet (P < .01). In contrast, the decrease of VLDL + LDL cholesterol, apo B, and Lp(a) was independently related to reduction of proteinuria (P < .02 to P < .001), but not to changes in the lathosterol to cholesterol ratio. In conclusion, the present data, based on the serum lathosterol to cholesterol ratio, do not support the concept that increased cholesterol synthesis plays an important role in the maintenance of human nephrotic syndrome-associated hypercholesterolemia. Moreover, it appears unlikely that the decrease of apo B-containing lipoproteins with antiproteinuric treatment is attributable to inhibition of cholesterogenesis. These findings warrant further documentation of cholesterol synthesis in human nephrotic syndrome by direct methods.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Blood pressure reduction initiates the antiproteinuric effect of ACE inhibition.

Several observations question the role of blood pressure and renal hemodynamic changes in the long-term antiproteinuric effect of ACE inhibition. To differentiate blood pressure and renal effects in the initial antiproteinuric response, the placebo-controlled acute effects of the ACE inhibitor enalaprilat (10 mg i.v.) on blood pressure, renal hemodynamics, and proteinuria were compared with those of nitroprusside in nine patient with non-diabetic proteinuria. In addition, we studied whether an exogenous angiotensin II infusion reverse the initial enalaprilat-induced antiproteinuric response. Enalaprilat and nitroprusside reduced MAP by -11.3 +/- 2.4% and -14.1 +/- 2.3%, respectively, whereas only enalaprilat showed renal hemodynamic effects, reflected by an increase in ERPF of 18.4 +/- 5.4% and a decrease in FF of -17.1 +/- 2.6%. Despite the contrasting renal hemodynamic profiles, enalaprilat (-10.6 +/- 4.8%) and nitroprusside (-12.8 +/- 5.1% equally decreased proteinuria. Exogenous infusion of angiotensin II completely reversed the blood pressure reduction and renal efferent vasodilatation induced by enalaprilat. proteinuria also increased by 13.1 +/- 7.8% to placebo level, albeit statistically non-significant. We conclude that the initial antiproteinuric effect of ACE inhibition appears to be mediated by blood pressure reduction and does not require its specific renal hemodynamic effect. Further studies should clarify whether the renal efferent vasodilatation during ACE inhibition is required to gradually induce renal structural changes that prevent the abundant passage of proteins.

Adult↗
PubMed1996

Does the renin-angiotensin system determine the renal and systemic hemodynamic response to sodium in patients with essential hypertension?

Many patients with essential hypertension respond to a high dietary sodium intake with a rise in blood pressure. Experimental evidence suggests that the renal hemodynamic response to sodium determines, at least partially, this rise in blood pressure. Our aim was to clarify the role of the renin-angiotensin system in the renal and systemic adaptation to a change in dietary sodium. We studied changes in mean arterial pressure (MAP) (millimeters of mercury), effective renal plasma flow (ERPF), body weight, and immunoreactive renin in 17 patients with essential hypertension and 15 normotensive control subjects, randomly crossing over between a 3-week sodium-restricted (50 mmol/24 h) and a sodium-replete (200 mmol/24 h) diet period. In addition, the effects of renin inhibition by remikiren (600 mg, single oral dose) were studied during the high sodium period. In normotensive control subjects, high sodium intake had no effect on MAP or body weight, whereas ERPF increased (490 +/- 19 to 535 +/- 21 mL/min, P < .05) and immunoreactive renin decreased (32 +/- 6 to 14 +/- 1 pg/mL). In hypertensive subjects, high sodium intake induced a heterogeneous response of MAP (median change, 2.6 mm Hg; range, -4.7 to +21.2; P = NS) and ERPF (median change, 21 mL/min; range, -33 to +98; P = NS). Body weight increased from 81.3 +/- 1.9 to 82.5 +/- 2.0 kg (P < .05), and immunoreactive renin decreased from 18 +/- 3 to 10 +/- 1 pg/mL (P < .05). Interestingly, the patients with a distinct rise in MAP showed a blunted ERPF response to high sodium intake (r = -.70, P < .01) and an increase in body weight (r = .76, P < .001). Moreover, the increase of ERPF was more pronounced in patients with a larger fall in immunoreactive renin (r = .77, P < .001). After administration of remikiren, a heterogeneous response in ERPF was observed: the patients with the blunted ERPF response to high sodium intake showed the largest ERPF rise (r = .70, P < .01). The remikiren-induced rise in ERPF correlated (r = .68, P < .01) with the fall in MAP (114 +/- 2 to 110 +/- 2 mm Hg). In conclusion, in patients with essential hypertension a rise in blood pressure in response to high sodium intake appears to partially be the result of insufficient renal vasodilatation. This seems to be due to an inadequate (intrarenal?) renin-angiotensin system response to increased sodium intake.

Adult↗
PubMed1996

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.

Disease Progression↗
PubMed1996

ACE inhibitors and the kidney. A risk-benefit assessment.

ACE inhibitors effectively reduce systemic vascular resistance in patients with hypertension, heart failure or chronic renal disease. This antihypertensive efficacy probably accounts for an important part of their long term renoprotective effects in patients with diabetic and non-diabetic renal disease. The renal mechanisms underlying the renal adverse effects of ACE inhibitors--intrarenal efferent vasodilation with a consequent fall in filtration pressure--are held to be involved in their renoprotective effects as well. The fall in filtration pressure presumably contributes to the antiproteinuric effect as well as to long term renoprotection. The former is suggested by the positive correlation between the fall in filtration fraction and the reduction in proteinuria found during ACE inhibition. The latter is suggested by the correlation between the (slight) reduction in glomerular filtration rate at onset of therapy and a more favourable course of renal function in the long term. Such a fall in filtration rate at the onset of ACE inhibitor treatment is reversible after withdrawal, and can be considered the trade-off for long term renal protection in patients with diabetic and nondiabetic chronic renal disease. In conditions in which glomerular filtration is critically dependent on angiotensin II-mediated efferent vascular tone (such as a post-stenotic kidney, or patients with heart failure and severe depletion of circulating volume), ACE inhibition can induce acute renal failure, which is reversible after withdrawal of the drug. Systemic and renal haemodynamic effects of ACE inhibition, both beneficial and adverse, are potentiated by sodium depletion. Consequently, sodium repletion contributes to the restoration of renal function in patients with ACE inhibitor-induced acute renal failure. Our the other hand, co-treatment with diuretics and sodium restriction can improve therapeutic efficacy in patients in whom the therapeutic response of blood pressure or proteinuria is insufficient. Patients at the greatest risk for renal adverse effects (those with heart failure, diabetes mellitus and/or chronic renal failure) also can expect the greatest benefit. Therefore, ACE inhibitors should not be withheld in these patients, but dosages should be carefully titrated, with monitoring of renal function and serum potassium levels.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Angiotensin-converting enzyme inhibition-induced changes in hippurate renography and renal function in renovascular hypertension.

UNLABELLED: We studied the mechanism of angiotensin-converting enzyme (ACE) inhibition-induced changes in hippurate renography of the poststenotic kidney. METHODS: Ten male mongrel dogs, six with unilateral and four with bilateral renal artery stenosis, were equipped with renal artery blood flow probes and catheters in the aorta, atrium and both renal veins. RESULTS: Enalaprilat (10 mg intravenously) in conscious dogs with renal artery stenoses produced changes in all stenotic (n = 11) but not in nonstenotic kidney 123I-hippurate renograms (n = 6). Renographic changes correlated significantly with initiation of intrarenal 131I-hippurate retention, a decrease in mean arterial pressure (MAP), renal extraction of 131I-hippurate and 125I-iothalamate (r = 0.68, r = 0.62, r = 0.84, r = 0.83, respectively) but not with renal blood flow changes (r = 0.34). Furthermore, renal uptake of 131I-hippurate and 125I-iothalamate decreased in stenotic kidneys with a grade II renogram (-52 +/- 11% and -79 +/- 6%, respectively). Iodine-125-hippurate autoradiograms of stenotic kidneys during ACE inhibition showed tracer retention mainly in the proximal tubular cells. Results during osmotic diuresis supported our findings. CONCLUSION: Angiotensin-converting enzyme inhibition-induced hippurate retention curves of poststenotic kidneys appear to result from a sequence of events. A decrease in MAP combined with efferent vasodilation leads to a decrease in intraglomerular capillary pressure. This decrease in pressure causes a decrease in glomerular filtration rate and proximal tubular urine flow. This decrease in turn hampers tubular hippurate transit and transport across the luminal membrane, leading to intrarenal hippurate retention and, in more severe cases, decreased renal hippurate uptake.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Prognostic value of the short-term antiproteinuric response to ACE inhibition for prediction of GFR decline in patients with nondiabetic renal disease.

In chronic renal disease, the severity of proteinuria is associated with the rate of renal function loss. Proteinuria, therefore, was postulated to play a role in the final common pathway of chronic renal function loss. If so, reduction of proteinuria would improve long-term renal outcome. Improvement of long-term renal function outcome has been obtained in several intervention trials; in these studies; regimens providing better renoprotection were associated with more effective reduction of poteinuria than control regimens. As the reduction of proteinuria is mostly associated with a fall in blood pressure, however, it is difficult to delineate the respective roles of the lowering of blood pressure and of proteinuria. Interestingly, the initial reduction of proteinuria (but not of blood pressure) by antihypertensive treatment appears to predict long-term renal outcome in man as well as in experimental renal disease. This suggests that an intervention strategy aimed not only at the normalization of blood pressure, but also specifically at elimination of proteinuria, might be able to improve long-term renal outcome in proteinuric patients. If so, this would provide further evidence in support of the hypothesis that proteinuria is causally involved in the progression of long-term renal function loss.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Titrating for antiproteinuric effect: the clue to renoprotection?

Proteinuria may be involved in the final common pathway of progressive renal function loss. If so, intervention treatment that reduces proteinuria might prevent or retard long-term renal function loss. In renal patients and in experimental renal disease the severity of proteinuria is associated with the rate of long-term renal function loss. Several large trials on the prevention of long-term renal function loss by antihypertensive treatment with ACE inhibitors (ACEi), were recently completed in diabetic and in non-diabetic renal disease. In those studies long-term renal function loss could indeed be retarded by ACEi; these ACEi regimens were associated with a more effective reduction of proteinuria than control regimens. In studies with a single treatment regimen (drug treatment or a protein restricted diet) a more effective reduction of proteinuria is associated with a more favourable long-term course of renal function as well. As reduction of proteinuria is mostly associated with a lower blood pressure (BP) the respective contributions of the fall in BP and in proteinuria are hard to dissect. Remarkably, however, the efficacy of the reduction of proteinuria (but not of BP) at onset of antihypertensive treatment is predictive of long-term renal outcome. Albeit consistent with a causal role of proteinuria reduction in renoprotection these data cannot distinguish between proteinuria as a marker or a mediator of renal damage. In view of the consistent association of antiproteinuric efficacy with long-term renal outcome we suggest that it would be worthwhile to attempt to improve long-term renoprotection by a strategy aimed at enhancing antiproteinuric efficacy. This approach is feasible as antiproteinuric efficacy of ACEi can be enhanced in several ways, ie, by dietary sodium and protein restriction and by adding a diuretic or indomethacin. Such a strategy would require that titration for adequate BP control is followed by titration for a maximal antiproteinuric effect. If this treatment strategy would improve long-term renal outcome, it would not only be a step forward in the clinical treatment of chronic renal failure, but it would also provide compelling evidence for a causal role of proteinuria in the progression of renal disease.

Humans↗
PubMed1996

Hypertension and renal disease: role of microalbuminuria.

RISKS ASSOCIATED WITH HYPERTENSION: Hypertension is a risk factor for cardiovascular and possibly renal organ damage. Microalbuminuria is a newly recognized cardiovascular and renal risk factor in diabetic and non-diabetic subjects. The prevalence of microalbuminuria is enhanced in hypertensive subjects, in particular in those with blood pressure characteristics that are associated with enhanced cardiovascular risk, such as salt-sensitivity and an abnormal diurnal blood pressure rhythm. NEED FOR FURTHER TRIALS: Although microalbuminuria is more prevalent in hypertensives and is shown to be a strong and independent risk factor, the relation between microalbuminuria and hypertensive complications is unknown. Even more intriguing is the finding of elevated levels of microalbuminuria in normotensive children with one or two parents with hypertension. This suggests that microalbuminuria is linked to the pathogenesis of hypertension. However, the role and the cause(s) of microalbuminuria are uncertain. Microalbuminuria seems to link renal and cardiovascular organ damage. Microalbuminuria might be the consequence of (renal) organ damage induced by hypertension. Alternatively, microalbuminuria might be an independent marker of some process that occurs separately from diabetes, hypertension or dyslipidemia. Endothelial dysfunction has been suggested to underlie renal and/or cardiovascular organ damage in these diseases. More knowledge should be obtained on the cause and the natural course of microalbuminuria. CONCLUSION: Microalbuminuria possibly identifies at an early stage hypertensive patients with an enhanced risk of developing the well-known renal and cardiovascular hypertensive complications. For the patients at particular risk therapeutic measures than can be developed. If microalbuminuria identifies a specific underlying pathogenetic mechanism, these measures may intervene with such a mechanism. Alternatively, if microalbuminuria identifies enhanced risk then standard antihypertensive therapy can be intensified, since such measures also lower microalbuminuria.

Albuminuria↗
PubMed1995

Proteinuria: a risk factor for pregnancy-related renal function decline in primary glomerular disease?

Pregnancy may be followed by a postpartum acceleration of renal function loss in patients with renal disease. We retrospectively analyzed the effects of pregnancy on progressive renal function decline, and the risk factors for an acceleration, in a group of 19 renal disease patients with 30 pregnancies and a group of 31 patients who did not become pregnant after onset of glomerular disease. The rate of renal function loss was calculated for each patient by linear regression on reciprocal serum creatinine values over 11 years' follow-up. Multiple regression analysis showed that both pregnancy (P = 0.03) and initial proteinuria (P = 0.005) were independently related with the rate of renal function loss. Such a relation could not be observed with histologic diagnosis, and initial age, renal function, blood pressure, and serum albumin. Further analysis showed that 10 of 30 pregnancies are followed by a predefined acceleration of renal function loss. These pregnancies were preceded and complicated by a higher proteinuria (4.1 v 1.7 g/d, P < 0.005; and 3.6 v 2.1 g/d, P < 0.05, respectively) compared with the other 20 pregnancies that are not followed by such an acceleration. In conclusion, patients with primary glomerular disease complicated by substantial proteinuria are at risk for acceleration of renal function decline after pregnancy.

Adolescent↗