Nocturnal blood pressure and 24-hour pulse pressure are potent indicators of mortality in hemodialysis patients.

BACKGROUND: Cardiovascular (CV) complications are the leading cause of mortality in hemodialysis patients. The role of arterial hypertension on the prognosis of CV in hemodialysis patients is not as clear as in the general population. The purpose of this study was to investigate the prognostic role of ambulatory blood pressure (BP) on CV mortality in treated hypertensive hemodialysis patients. METHODS: Fifty-seven treated hypertensive hemodialysis patients (56.87 +/- 16.22 years, 30 men) were prospectively studied. All patients initially underwent an ambulatory BP monitoring between two dialysis sessions. The outcome event studied was CV death; kidney transplantation and deaths not related to CV disease were censored. RESULTS: The duration of follow-up was 34.4 +/- 20.39 months, during which 10 CV and 8 non-CV fatal events occurred. In the 10 patients who died from CV complications, age, previous CV events, ambulatory systolic BP, ambulatory pulse pressure (PP), and life-long smoking level were significantly higher, and the office diastolic BP was lower at the time of inclusion than in those who did not die from CV complications (N = 47). Based on Cox analysis and after adjustment for age, sex, and previous CV events, a low office diastolic BP [relative risk (RR) 0.49, 95% CI, 0.25 to 0.93, P = 0.03], an elevated 24-hour PP (RR 1.85, 95% CI, 1.28 to 2.65, P = 0.009), and an elevated nocturnal systolic BP (RR 1.41, 95% CI, 1.08 to 1.84, P = 0.01) were predictors of CV mortality (RR associated with a 10 mm Hg increase in BP and in PP). CONCLUSION: This study demonstrates that nocturnal BP and 24-hour PP are independent predictors of CV mortality in treated hypertensive hemodialysis patients. Randomized trials are needed to investigate whether nocturnal BP and 24-hour PP are superior to office BP as targets for antihypertensive therapy in this high-risk group.

Influence of nycthemeral blood pressure pattern in treated hypertensive patients on hemodialysis.

Arterial hypertension in end-stage renal disease (ESRD) patients is characterized by an altered nycthemeral blood pressure (BP) rhythm and an increased pulse pressure, and it could be suggested that this association of risk factors plays a major role in the cardiovascular prognosis of this population. The aim of this study was to determine the influence of nycthemeral BP pattern on arterial distensibility and pulsatile components of BP in treated hypertensive patients on regular hemodialysis. Forty-two hypertensive patients were included, and all underwent ambulatory BP and pulse wave velocity (PWV) measurements between the femoral and carotid arteries. The patients were divided into two groups according to the magnitude of the nocturnal fall in BP: dippers and non-dippers. The groups were similar in gender, age, duration of hemodialysis, body mass index, body size, history of cardiovascular complications, class and number of antihypertensive drugs used per patient. PWV was significantly higher in non-dippers. For the whole population, a stepwise regression analysis showed that PWV and erythropoietin therapy were independently related to the impaired nycthemeral BP pattern. In addition to its pressor effect, erythropoietin could have a deleterious influence on the ambulatory BP profile of treated hypertensive patients in ESRD. Arterial distensibility and nycthemeral BP impairment are linked, and these cardiovascular risk factors should be taken into account together for the management of hypertensive hemodialysis patients.

Sustained effect of angiotensin II on tyrosine phosphorylation of annexin I in glomerular mesangial cells.

By means of selective extraction in a Ca(2+)-chelating medium and immunoblotting, four annexins (I, II, V, and VI) were identified in both isolated rat renal glomeruli and rat glomerular mesangial cells. Upon 32P labeling of these cells in culture, annexin I was immunoprecipitated using a specific polyclonal antibody and was found to incorporate radioactivity in a constitutive manner. However, as with epidermal growth factor (200 ng/ml), addition of angiotensin II (10(-7) M), arginine-vasopressin (10(-7) M), or endothelin I (10(-7) M) resulted in a 2-3-fold stimulation of annexin I phosphorylation. The basal phosphorylation as well as the stimulating effect of angiotensin II were also detected by immunoblotting annexin extracts using an antiphosphotyrosine antibody. In addition, among various phosphotyrosyl proteins isolated from EGTA extracts by adsorption onto an anti-phosphotyrosine antibody, annexin I was specifically recognized by Western blotting using a monoclonal anti-annexin I antibody, and displayed the same increase upon cell stimulation with angiotensin II. Moreover, thin layer chromatographic analysis of phosphoamino acids present in immunoprecipitated [32P]annexin I showed an exclusive labeling of phosphotyrosine residue(s). Finally, the effect of angiotensin II was detectable after 10 min, maximal at 6 h, and present until 12 h of incubation. Using 12-h stimulation, tyrosine phosphorylation of annexin I displayed a maximum at 10(-7) to 10(-6) M angiotensin II. These data report for the first time the stimulation of annexin I tyrosine phosphorylation by biologically active peptides acting via receptors belonging to the superfamily of seven hydrophobic domain, G-protein-linked receptors, which lack an intrinsic protein tyrosine kinase. This suggests a possible role of annexin I in the mitogenic effect of angiotensin II, arginine-vasopressin, and endothelin I, which was previously observed on rat glomerular mesangial cells as well as on other cells.

Effect of renal function on the pharmacokinetics and pharmacodynamics of trandolapril.

1. The pharmacokinetics and pharmacodynamics of a single dose of trandolapril, an angiotensin converting enzyme (ACE) inhibitor with an active metabolite, trandolaprilat, which is in part further metabolised prior to renal elimination, were evaluated in 31 subjects with a wide range of renal function (creatinine clearance 4-112 ml min-1 1.73 m-2). 2. The pharmacokinetics of trandolapril were unaffected by differences in renal function. 3. In contrast, there was a close correlation between the renal clearance (0-96 h) of trandolaprilat and creatinine clearance (r = 0.95, P = 0.0001). The maximum plasma concentration of trandolaprilat, and the area under the concentration curve (0-96 h) correlated inversely with creatinine clearance (r = -0.59, P < 0.001; and r = -0.61, P < 0.001 respectively). 4. Significant changes in plasma trandolaprilat concentrations were seen only in patients with creatinine clearances of 30 ml min-1 1.73 m-2 or less, suggesting that a dose reduction in trandolapril might be advisable in severe renal impairment. 5. However, the majority of parameters of ACE inhibition were unrelated to creatinine clearance, although area under the curve for ACE inhibition (0-336 h) showed a weak negative correlation (r = -0.49, P < 0.01). Similarly, weighted mean changes in blood pressure were not influenced by renal function. 6. Therefore, while the pharmacokinetic parameters of trandolaprilat correlated with creatinine clearance, pharmacodynamic measurements (ACE inhibition and blood pressure changes) in general showed no such relationship, indicating that dose adjustment of ACE inhibitors in renal impairment should be based on pharmacokinetic results only in conjunction with pharmacodynamic data.

Chronical administration of anti-DNA antibodies by subcutaneous injection of hybridoma clones in BALB/c and NZBxNZW/F1 mice. Experimental model of the pathogenic role of DNA in acute lupus disease.

Several sets of data suggest that specific classes of anti-DNA antibodies could be implicated in the genesis of glomerular lesions in SLE. The goal of this work is to investigate if this pathogenic role could be related to the antibodies' genetic origin--from BALB/c or NZBxNZW/F1 mice--or to their physiological origin--induced either by DNA or by polyclonal B cell activation in normal mice. For this purpose, anti-DNA antibody hybridoma clones produced from different origins were subcutaneously injected in BALB/c or NZBxNZW/F1 female mice, followed by studies of immunological parameters and kidney lesions. Results concur that the induced anti-DNA antibodies can play a role in fatal disease development, related to clonal specificity but not to the way of stimulation which was either polyclonal B cell activation or DNA immunization. Also, they emphasize the possible very lethal role of serum circulating DNA.

[Renal microscopic hematuria in rheumatoid polyarthritis]. / Hématurie microscopique d'origine rénale au cours de la polyarthrite rhumatoïde.

In a retrospective study of 162 cases of rheumatoid arthritis we found that 24 patients (14.8%) had presented with microscopic haematuria with or without proteinuria. Renal biopsy had been performed in 15 of these 24 patients. Apart from the classical lesions of extramembranous glomerulonephritis, amyloidosis and interstitial nephritis, 60% of histological results showed lesions of mesangial glomerulonephritis. These lesions seemed to be independent of maintenance treatments, but they might have been facilitated by the chronic inflammation kept going by the rheumatoid disease itself.

[Renal involvement in rheumatoid polyarthritis]. / L'atteinte rénale au cours de la polyarthrite rhumatoïde.

Urinary disorders were investigated in 162 patients with specific or standard rheumatoid disease, over a period of 5 years. 43 patients presented disturbances of the urinary laboratory tests, or 26.5 p. cent and 17 of them underwent a renal needle-biopsy. The findings were as follows: 11 isolated proteinurias, iatrogenic and reversible when the treatment in question was discontinued (gold salts, D-penicillamine), 13 microscopic hematurias, 3 isolated leucocyturias, 3 combinations hematuria-leucocyturia, 3 combinations hematuria-leucocyturia-proteinuria, 6 nephrotic syndromes including 5 of iatrogenic origin, 4 isolated renal failures. The most interesting discussion concerns microscopic hematurias. Besides the standard lesions of extra-membranous glomerulonephritis, amyloidosis and interstitial nephritis, 50 p. cent of the renal histologic examinations corresponded to lesions of mesangial glomerulonephritis. This lesion seems unrelated to long-term treatments and could be encouraged by the chronic inflammatory condition of the rheumatoid disease.

[Measurement of arterial pressure using 3 measurement methods in medial arterial calcification]. / Mesure de la pression artérielle par trois méthodes de mesure en présence d'une médiacalcose.

Medial calcification of the arteries, because of non-distensibility of the blood vessel walls, may overestimate the real intra-arterial pressure when blood pressure (BP) is measured by indirect sphygmomanometry cuff. In order to assess the best method for measuring BP, we compared direct intra-arterial measurements with indirect cuff sphygmomanometry as well as automatic oscillometric measurements in 15 hypertensive patients. Mean age +/- standard deviation (SD) was 62 +/- 9 years; all patients had medial calcifications of forearm and/or brachial arteries, and Osler's maneuver was negative in all. Ten sets of direct and indirect BP measurements were obtained for each patient. Results are expressed as mean +/- SD: (table; see text) There was no significant difference between cuff pressure and systolic intra-arterial pressure. The automatic oscillometric method underestimated systolic intra-arterial BP. Great individual variability was observed and could not be predicted clinically. Indirect diastolic BP values were greater than intra-arterial BP in all patients with the sphygmomanometer cuff and in 10 patients with the oscillometric recorder. There existed a direct relation between intra-arterial BP and differences between indirect BP measurements and intra-arterial BP as follows: intra-arterial BP was overestimated by indirect methods for values under 150 mmHg, and underestimated above 150 mmHg. In conclusion, invasive intra-arterial BP measurement seem to be necessary to distinguish between hypertensive and pseudo-hypertensive patients, in case of radiologic evidence of arterial calcification.

[Non-occlusive mesenteric ischemia in patients undergoing maintenance hemodialysis]. / Ischémie mésentérique non occlusive chez l'hémodialysé périodique.

Non occlusive mesenteric ischaemia is a serious complication of maintenance haemodialysis. Its physiopathological mechanisms are controversial and its frequency is underestimated. Eight cases (in 5 patients) are reported: the clinical syndrome consisted of acute abdominal pain without evidence of shock or abdominal wall rigidity at palpation, associated with hyperleucocytosis and hyperkaliemic acidosis. The normality of the mesenteric vessels was confirmed at autopsy in one patient and during surgery in all others. Two patients were found to have caecal necrosis, 2 had diffuse necrotizing enterocolitis and 1 had necrosis of the left colon. The prognosis of this complication is sombre: 4 of our 5 patients died, including 3 who had relapsed 1, 4 and 18 months respectively after surgery (diffuse ileocolic necrosis). The usually accepted physiopathological mechanism is volaemic contraction consecutive to haemodialysis in often atheromatous subjects; however, the fact that the mesenteric infarction is not occlusive, that it occurs sometime after the end of the haemodialysis session and above all, the lack of haemodynamic changes during or immediately after the session suggest that other factors (bioincompatibility) are involved.

[Serum lipase and amylase levels in chronic renal failure: interpretation of results--effects of extrarenal purification]. / La lipasémie et l'amylasémie au cours de l'insuffisance rénale chronique: interprétation des résultats--effets de l'épuration extra-rénale.

Serum amylase and lipase activities were studied in two groups of patients without clinical evidence of pancreatitis: 47 with stable chronic renal failure, 61 treated by haemodialysis. Amylase activity was significantly increased in 73 of 108 patients (68%) and lipase activity in 67 of 108 (62%). After dialysis, both enzymatic activities were decreased, despite of the lack of extraction by the artificial kidney. Laboratory confirmation of the diagnosis of pancreatitis is difficult in patients with chronic renal failure, and cannot be supported only by serum amylase and lipase activity measurements.

Pharmacokinetics of bendazac-lysine and 5-hydroxybendazac in patients with renal insufficiency.

The pharmacokinetics of bendazac and its major metabolite, 5-hydroxybendazac, have been investigated in 15 patients with moderate to severe renal insufficiency and renal failure following a single oral dose of 500 mg bendazac-lysine. The pharmacokinetic parameters were compared to those obtained in 10 healthy adult volunteers. The rate and the extent of absorption of bendazac was not modified in the patients with moderate and severe renal insufficiency, nor was there any change in plasma tmax, Cmax, apparent elimination t1/2 and AUC. There was a significant increase in the unbound fraction of bendazac in renal failure patients undergoing haemodialysis, with a consequent increase in the apparent volume of distribution (V/F) and apparent plasma clearance (CL/F), and a decrease in plasma Cmax and AUC. Simultaneous changes of V/F and CL/F lead to an unchanged plasma t1/2 in these patients. Renal clearance (CLR) was decreased, but CL/F was not affected, since renal excretion is a minor route of elimination of bendazac. Bendazac is mostly eliminated by metabolism to 5-hydroxybendazac, in healthy subjects greater than 60% of a dose being excreted in urine as 5-hydroxybendazac and its glucuronide. In patients with renal insufficiency urinary excretion of 5-hydroxybendazac was decreased and the systemic availability of the metabolite (AUC), was increased about three-fold, irrespective of the degree of renal failure. Plasma 5-hydroxybendazac glucuronide accumulated according to the degree of renal insufficiency. Overall it can be assumed that the pharmacological effect of the drug will not be enhanced in renal failure and that the dosage regimen of bendazac-lysine in such patients need not be modified.

Rapidly progressive glomerulonephritis associated with amyloidosis: efficacy of plasma exchange.

This report describes one case of rapidly progressive glomerulonephritis associated with amyloidosis in a 53-year-old woman with rheumatoid arthritis, successfully treated with intensive plasma exchange and immunosuppression. Amyloid deposits were present in all of 20 glomeruli in the kidney biopsy specimen and eight out of nine nonfibrosed glomeruli contained crescents. With intensive plasma exchange and immunosuppressive drugs, renal function improved, and hemodialysis was discontinued. After 2 years, renal function was stable at a moderate level of impairment, but heavy proteinuria persisted.