Hypertension In Chronic Renal Failure Research Articles

Have rational therapeutic principles emerged in treating hypertension in chronic renal failure?

PA TIENTS with chronic renal insufficiency often suffer from hypertension, irrespective of the underlying renal disease. Like their hypertensive counterparts with normal renal function, treatment is indicated to prevent the damaging effects of the sustained high blood pressure on various target organs, and to reduce the relatively high rates of morbidity and mortality. Whereas not so long ago the choice of treatment was dictated by the antihypertensive efficacy of a certain drug, more emphasis has lately been put on the importance of individualizing the treatment. Such an individual approach appears also to be applicable to the group of hypertensive patients with chronic renal insufficiency. This particular group often suffers from symptoms that are the consequence of the renal disease, such as proteinuria and hyperfiltration of the remaining nephrons. One of the important consequences is the fact that these phenomena may cause a progressive loss of renal function over time. Although the cause of this progression is still debated, evidence is accumulating that certain antihypertensive drugs may reduce urinary protein excretion and attenuate the progression of renal function loss. In this report we will evaluate the potential effects of various antihypertensives on these two parameters. Of the variety of different antihypertensive drug modalities currently at our disposal we will particularly focus on: /1-blocking agents, angiotensin-converting enzyme (ACE) inhibitors, and calcium-channel-blocking (CCB) agents.

Hyperparathyroidism, platelet intracellular free calcium and hypertension in chronic renal failure

To investigate possible relationships between hyperparathyroidism, alterations in intracellular free calcium concentration ([Ca2+]i) and hypertension in chronic renal failure, serum concentrations of intact parathyroid hormone (PTH) were measured by two-site immunometric assay, and platelet ([Ca2+]i) was assessed using the fluorescent indicator fura-2. Thirty-six patients with chronic renal failure were studied, 10 with normal serum PTH concentrations (mean 8.0 +/- 0.6 pmol/liter), 17 with elevated serum PTH (35.0 +/- 7.2 pmol/liter) and 9 patients with elevated PTH (36.2 +/- 5.9 pmol/liter) who were receiving nifedipine. Platelet [Ca2+]i was increased in patients with elevated PTH, compared with those in whom PTH was normal (138 +/- 16 vs. 83 +/- 7 nmol/liter, P < 0.01). A linear relation was observed between serum PTH and platelet [Ca2+]i in these patients (r = 0.818, P < 0.001). In contrast, platelet [Ca2+]i was not elevated (84 +/- 9 nmol/liter) in the patients with elevated PTH who were receiving nifedipine. A linear relation was also present between both serum PTH (r = 0.616, P < 0.001) and platelet [Ca2+]i (r = 0.576, P < 0.005) and mean blood pressure. Nine patients with hyperparathyroidism were restudied after treatment with the vitamin D analogue alfacalcidol. This resulted in significant decreases in serum PTH (P < 0.01), platelet [Ca2+]i (P < 0.02), and mean blood pressure (P < 0.05). These studies indicate that [Ca2+]i may be increased early in renal failure, and that this increase occurs in association with both hyperparathyroidism and hypertension. Furthermore, treatment of hyperparathyroidism with alfacalcidol may result in reductions in both [Ca2+]i and blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of endothelial factors, cyclosporine, and erythropoietin in hypertension in chronic renal failure

Hypertension is commonly observed in patients with renal insufficiency. The pathogenesis of this condition is multifactorial and not clearly understood. Recently, a great deal of attention has been paid to the role of endothelial factors, such as endothelin and endothelial-derived relaxing factor, in the regulation of the microcirculation and in the pathogenesis of hypertension. The role of these factors in the pathogenesis of hypertension in patients with renal insufficiency is reviewed. In addition, cyclosporine and erythropoietin have recently been used to prevent rejection in renal transplant patients and to treat anemia in patients with renal insufficiency. We review the evidence that these agents may cause or aggravate hypertension in patients with renal failure.

Hypertension in Chronic Renal Failure

Hypertension in Chronic Renal Failure

Nocturnal hypertension in chronic renal failure. A chronobiological study

Nocturnal hypertension in chronic renal failure. A chronobiological study

Normalization of Increased Sodium Sensitivity by Maintenance Hemodialysis

Blood pressure (BP) becomes more sodium and body fluid sensitive as renal function deteriorates. Thus, hypertension in chronic renal failure is mostly of the sodium sensitive type. We studied whether the increased sodium sensitivity (SS) can be restored to normal on the maintenance phase of hemodialysis (HD) therapy. Body weight (BW) and BP (specifically, mean arterial pressure [MAP]) were measured after HD and before the next HD, and the body fluid sensitivity (BFS) was calculated as the ratio of changes in these factors on both introduction and maintenance phases in HD patients (n = 56) who were not taking any antihypertensive drugs (BFS = delta MAP/delta BW). In a preliminary study, the amount of interdialytic sodium intake (QNa+) was measured (n = 30), and SS was calculated as the ratio of the change in MAP to QNa+ (SS = delta MAP/QNa+). Interdialytic BW gain (3.1 +/- 0.1 kg) was correlated with the amount of sodium intake (136 +/- 17 mEq), resulting in a positive relationship between BFS and SS (r = 0.79, P less than .0001). Therefore, BFS was used as an index of SS. As a whole, BFS decreased from the introduction to the maintenance phase (6.5 +/- 1.0 to 3.5 +/- 0.6 mm Hg/L, P less than .01). This decrease was marked (6.2 +/- 1.1 to 2.9 +/- 0.6 mm Hg/L, P less than .01) in patients (n = 46) whose BP was normalized in the maintenance phase, while not significant (7.9 +/- 1.9 to 6.3 +/- 1.3 mm Hg/L) in patients (n = 10) whose BP was still high.(ABSTRACT TRUNCATED AT 250 WORDS)

Alteration of vascular thromboxane in rats with subtotal renal ablation

To assess the roles of vascular prostaglandins in the hypertension of chronic renal failure, the release of prostacyclin and thromboxane (TX) from aorta was evaluated in male Sprague-Dawley rats, the renal mass of which was reduced by removing one kidney and two-thirds of the contralateral kidney (“ 5 6 nephrectomy”). Five-sixths nephrectomy was followed by significant rises in serum creatinine to 0.55 ± 0.03 mg/dl and urea nitrogen to 42.9 ± 3.8 mg/dl, with a concomitant rise in mean blood pressure from 121.6 ± 1.6 mmHg to 155.3 ± 8.4 mmHg. In 5 6 nephrectomized rats, the release of TX A 2 from aorta, as measured by its stable metabolite TX B 2, increased by 60% (p < (p < 0.01) and prostacyclin, as measured by its stable metabolite 6-keto-prostaglandin F 1α (6-keto-PG F 1α) increased by 51% (p<0.05). The amounts of both TX B 2 and 6-keto-PG F 1α released from aorta were closely related to the height of mean blood pressure. These results suggest that the enhanced vasoconstrictor TX production in the vascular walls may be relevant to hypertension in rats with subtotal renal ablation. The adaptive increase in prostacyclin production in the vascular walls may compensate for the elevation of blood pressure due to chronic renal failure in this animal model.

Participation of the sympathetic nervous system in hypertension in rats with subtotal renal ablation.

To clarify the role of the sympathetic nervous system in the development of hypertension in chronic renal failure, plasma levels and urinary excretions of catecholamines were evaluated in male Sprague-Dawley rats. The renal mass of the rats was reduced by removing one kidney and two-thirds of the contralateral kidney (5/6 nephrectomy). Five-sixths nephrectomy was followed by significant increases in serum creatinine (to 0.55 +/- 0.03 mg/dl) and urea nitrogen (to 42.9 +/- 3.8 mg/dl). There was a concomitant increase in mean blood pressure, measured directly by an implanted aortic catheter, in comparison with control rats (155.3 +/- 8.3 versus 123.6 +/- 3.3 mmHg, P less than 0.01). Both plasma levels and urinary excretion of norepinephrine and epinephrine were elevated in the 5/6-nephrectomized rats compared with controls. Mean blood pressure correlated negatively with 24-h creatinine clearance (r = -0.66, P less than 0.05), and positively with plasma norepinephrine (r = 0.83, P less than 0.01) and urinary excretion of norepinephrine (r = 0.63, P less than 0.05). These results suggest that not only the decrease in renal function, but also hyperactivity of the sympathetic nervous system, may be involved in the pathogenesis of hypertension in rats with subtotal renal ablation.

Erythrocyte Sodium and Sodium Flux in Relation to Hypertension in Chronic Renal Failure

Erythrocyte sodium and sodium fluxes in plasma and in physiological buffer solution were studied in normotensive and hypertensive uraemic patients and normal subjects. Erythrocyte sodium was reduced in the uraemic patients due primarily to low sodium influx, further supported by low passive membrane permeability. These differences were much more marked in normotensive patients. There was no evidence for sodium pump inhibition in the erythrocytes. The low erythrocyte sodium influx in the uraemic patients appeared to be due to a plasma factor which could be reversed in young cells but not in old. However, erythrocyte sodium flux in both plasma and physiological buffer was lower in normotensive than in hypertensive uraemic patients. Therefore, a membrane change to compensate for the effects of the plasma factor on sodium influx may be related to the development of hypertension in the uraemic patients.

Immunohistochemical localization of renin in end-stage kidneys.

Hypertension in chronic renal failure is usually due to excessive accumulation of salt and water. In some cases, sodium and volume depletion by dialysis fail to reduce the high BP, and plasma renin activity tends to be higher. We performed a semiquantitative analysis of the immunohistochemical distribution of renin in the kidneys of ten patients with end-stage renal disease and hypertension using a specific antihuman renin antibody and a peroxidase-antiperoxidase technique on paraffin sections of nephrectomy and/or autopsy specimens. In five cases with severe, dialysis-resistant hypertension, the degree of immunoreactivity was most striking, exceeding that found in renovascular hypertension and present in arterioles at a distance from the glomeruli. Three cases of advanced diabetic glomerulosclerosis consistently showed minimal immunoreactivity. We conclude that renin often can be detected immunologically in the kidney of patients with chronic renal failure and hypertension, but its pathophysiological role will require further study.

Management of hypertension in chronic renal failure.

Management of hypertension in chronic renal failure.

Urinary kallikrein excretion in chronic renal failure: relationship to blood pressure and the acute effect of captopril.

Previous studies of the renal kallikrein-kinin system in chronic renal failure (CRF) have given conflicting results. We have assessed activity of this vasoactive hormone system in CRF and investigated a possible relationship to hypertension in patients with CRF: 24-hour urinary kallikrein excretion (UKa) was measured in 22 patients with CRF (9 normotensive and 13 hypertensive) and 11 healthy controls. Age, sex, urine volume, and urinary sodium excretion were similar in each group. Compared with controls, UKa was reduced in both normotensive and hypertensive patients with CRF, with no difference between CRF groups. The reduction in UKa in CRF was less than the reduction in glomerular filtration rate (GFR), as assessed by endogenous creatinine clearance (CCr). When UKa was divided by CCr, UKa/mL CCr was therefore increased, to a similar extent, in both normotensive and hypertensive patients with CRF. This suggests that release of renal kallikrein from functioning nephrons is increased in CRF. The results do not support a role for deficient kallikrein release in the genesis of hypertension in CRF, as previously suggested; however, these abnormalities could be relevant to other aspects of renal function in CRF. The converting-enzyme inhibitor, captopril, was given to 5 patients with CRF, hypertension, and low UKa. Introduction of captopril was followed by a further reduction in UKa in all subjects. Captopril is known to inhibit kininase II, the principal enzyme involved in degradation of kinins; this potentiating effect may be counteracted by a reduction in renal kallikrein release and hence in kinin generation.

Erythrocyte Sodium and Hypertension in Chronic Renal Failure

Erythrocyte Sodium and Hypertension in Chronic Renal Failure

Salt-induced hypertension in chronic renal failure: Evidence for a neurogenic mechanism

We investigated the possibility that blood pressure elevation induced by salt excess may be secondary to a neurogenic mechanism. The compound SK&F 64139 (50 mg/kg) known to inhibit central and peripheral phenylethanolamine N-methytransferase (PNMT) the enzyme necessary for the conversion of norepinephrine to epinephrine, was given by oral gavage to two groups of subtotally nephrectomized rats maintained for five days on either a high salt (HS) or low salt (LS) diet respectively. Blood urea nitrogen (BUN) and hematocrit were not different between the two groups, while body weight and serum Na were significantly higher in the HS animals. Baseline mean blood pressure (BP) was higher in the HS animals (HS 154 ± 4.7 vs LS 121 ± 3.7 mmHg, p<0.001) and decreased by 39 ± 6.9 mmHg one and one half hour post SK&F 64139 to normotensive levels in the HS as opposed to a decrease of 10 ± 1.8 mmHg in the LS group. Baseline heart rate (HR) was higher in the LS group (474 ± 17 beats/min) vs the HS group (408 ± 17, p<0.05), and decreased significantly after SK&F 64139 in both groups to the same extent (by 17.6% in the HS vs 13.3% in the LS). A third group of subtotally nephrectomized rats maintained for five days on a HS diet were given by oral gavage the compount SK&F 29661 (100 mg/kg), a PNMT inhibitor which does not cross the blood-brain barrier. Following SK&F 29661, there was no significant decrease in mean BP (153 ± 5 to 149 ± 4 mmHg) and a less than 2% decrease in HR. Baseline plasma norepinephrine (NE) was higher in the HS as compared to the LS group (1.50 ± 0.16 vs 0.904±0.15 ng/ml, respectively, p<0.05) and a significant correlation was found between plasma NE level and decrease in BP following SK&F 64139 (r=0.65, p<0.01). Not withstanding possible effects of some ancillary properties of SK&F 64139, these data support the hypothesis that a neurogenic component, possibly mediated via central epinephrine containing neurons, contributes to the BP elevation induced by salt excess.

Hypertension in chronic renal failure. Clinical presentation, prognosis, pathophysiology and treatment.

Hypertension in chronic renal failure. Clinical presentation, prognosis, pathophysiology and treatment.

Blood pressure in terminal renal failure. Fluid spaces and the renin-angiotensin-system.

Most of the 52 patients on maintenance dialysis investigated in this study suffered from arterial hypertension in spite of efforts to reduce 'dry weight'. In this situation we found that the majority of patients were underweight and that total body water, extracellular volume and blood volume were close to normal when related to reference systems consisting of height and age. Hypertensive patients were not volume expanded as compared to normotensive patients and controls. Plasma renin activity and angiotensin II were elevated in a few patients, with a trend to higher levels in the more hypertensive patients. Various approaches attempting to correlate blood pressure and the respective volume-renin factors did not prove to be conclusive in explaining the maintenance of hypertension in chronic renal failure on the basis of the sodium-renin feedback.

Lipid and carbohydrate metabolism in uraemia

Lipid and carbohydrate metabolism variables were studied in twenty-eight patients with chronic renal failure (mean GFR 7.7 +/- 2.5 ml/min) and uraemic symptoms. 71% of the patients had hypertriglyceridaemia (greater than or equal to 2.2 mmol/l). Total serum cholesterol was normal while VLDL cholesterol was high and alpha-lipoprotein cholesterol was low. The fractional elimination rate of Intralipid was low and inversely correlated to serum triglyceride levels. Intravenous glucose tolerance was reduced with normal or slightly increased fasting blood glucose and insulin values before and during the test. Serum triglycerides were correlated to plasma insulin but not to residual renal function or serum urea levels. The cause of hypertriglyceridaemia and lowering of alpha-Lp cholesterol is not unequivocally clear. Present evidence indicate that retarded catabloism of triglyceride-rich lipoproteins is important but accentuated release of triglyceride-rich lipoproteins may have occurred in a number of cases. The commonly used treatment with beta-blocking agents for hypertension in chronic renal failure may accentuate certain of the metabolic responses in uraemia.

Severe hypertension in chronic renal failure treated with minoxidil.

Twenty patients suffering from severe hypertension associated with renal failure have been treated with Minoxidil. Ten patients, not on RDT, had a residual Creatinine clearance between 7-71 ml/min; 10 were on hemo-dialytic treatment. Before starting on Minoxidil, all patients had been unsuccessfully treated with an association of traditional anti-hypertensive drugs (blood pressure 200.24/125.6 mmHg). Minoxidil administration dramatically lowered the blood pressure in all cases. After 1 week of treatment the mean decrease in DBP was 22.7%; after 1 month 28.1%, and after 3 months 32.9%. At 6, 12, and 18 months the results were substantially unaltered. Minoxidil dosage ranged from 5 to 50 mg/day over the initial phase; by the third month the daily dose was between 5 and 25 mg/day. Previous anti-hypertensive drugs were suspended in all cases and not subsequently resumed. Furosemide and Propranolol were the only exceptions to counteract the Minoxidil induced fluid retention and tachycardia. The main side effec...

The influence of different sodium loads on renin release in hypertensive and normotensive states of chronic renal failure.

The purpose of the present study was to examine the influence of different sodium loads on renin release in the hypertensive and normotensive state of chronic renal failure. Blood pressure (BP), plasma renin concentration (PRC) and exchangeable sodium (NaE) were measured in eighteen patients with advanced chronic renal failure, nine hypertensives and nine normotensives, and in seven normal subjects (a) 6 days after a fixed sodium intake of 10 mmol/day, and (b) 6 days after a fixed sodium intake of 150 mmol/day. Mean NaE was 14-19% higher in the hypertensives compared with the normotensives and values of NaE correlated significantly to values of mean BP. No significant differences were present in PRC between the groups of patients and controls on either of the sodium regimens and no correlation was found between BP and PRC. However, average decreases of PRC in the hypertensives on high sodium intake, 33-34%, were significantly lower than the corresponding values of 69-71% in the normotensive patients and controls, respectively. Furthermore, the percentage changes of PRC on high sodium intake correlated significantly to mean BP as well as to NaE. These results suggest that renin release is relatively unresponsive to different sodium intakes in hypertension following chronic renal failure. This alteration in renin release may contribute to the maintenance of hypertension in chronic renal failure, PRC being "inappropriately' increased in relationship to the sodium excess.

Nephrology: An Annotated Bibliography of Recent Literature

Nephrology: An Annotated Bibliography of Recent Literature