R. Makdassi

Pulse wave velocity and vascular calcification at different stages of chronic kidney disease.

Background Increased arterial stiffness and vascular calcification have been recognized as important predictors of cardiovascular mortality in patients with chronic kidney disease. Method In order to examine the precise temporal link between aortic stiffness and cardiovascular risk at the earliest stages of chronic kidney disease, we studied a cohort of 150 patients with chronic kidney disease (52 stage 2/3 patients, 51 stage 4/5 patients and 47 stage 5D patients). Each patient underwent a plain, lateral lumbar radiograph and an abdominal and thoracic multislice spiral computer tomography scan in order to identify and quantify aortic and coronary calcifications. Pulse wave velocity was used as a measure of arterial stiffness. Results Regardless of the disease stage, patients with chronic kidney disease had higher adjusted pulse wave velocity than controls with preserved renal function (14.6 ± 3.8 vs. 10.7 ± 1.7 m/s, respectively; P < 0.0001). Regarding aortic calcification, there was a gradual but significant rise in later chronic kidney disease stages. A similar trend was found for coronary calcification. In a multivariate analysis only age, mean arterial pressure, diabetes and the aortic calcification score were independent determinants of higher pulse wave velocity. Conclusion We found that both vascular stiffness and vascular calcification appear early in patients with chronic kidney disease, but only vascular calcification worsens as the disease progresses. The increase of vascular stiffness in adult patients with chronic kidney disease seems to be more related to age, systolic blood pressure, diabetes and vascular calcification than to uremic toxicity.

Ulcérations buccales après prise de mycophénolate de sodium (Myfortic

BACKGROUND: Mycophenolate sodium (Myfortic) is an enteric-coated formulation of the immunosuppressant therapy mycophenolic acid. We report a case of diffuse mouth ulceration in a patient treated with Myfortic presenting recurrence after another dose of drug. PATIENTS AND METHODS: We report the case of a 26-year-old female patient with systemic lupus erythematosus, initially treated with corticosteroids and mycophenolate mofetil, but which was stopped because of varicella-zoster dissemination and leucopoenia. She consulted for mouth ulcers occurring two weeks after the introduction of Myfortic. There were no signs of opportunist infection or lupus activity. Mucosal ulcerations disappeared when Myfortic was stopped. Several weeks later, the patient presented recurrence of mouth ulcerations after another treatment of Myfortic. DISCUSSION: Myfortic is a new enteric-coated formulation of mycophenolic acid developed to reduce gastrointestinal upset associated with Cellcept. In certain cases, Cellcept toxicity can present as a number of oral ulcerations. Direct toxicity is involved in these cases. This side effect has never been described with Myfortic. In our case, the distinctive characteristic is that the patient was never treated with Cellcept without mucosal toxicity despite equivalent systemic mycophenolic acid exposure.

Hématome surrénalien unilatéral inaugural d'un syndrome des antiphospholipides

Resume Introduction Le syndrome primaire des antiphospholipides est une cause tres rare d’hemorragie surrenalienne. Observation Un patient de 51 ans a eu une hemorragie surrenalienne unilaterale, favorisee par la prescription de Synacthene ® pendant les 4 jours precedents. Il n’avait pas d’insuffisance surrenalienne, mais le bilan immunologique a revele la presence d’anticorps anti-phospholipides. Apres un recul de 2 ans, la surveillance des surrenales n’a montre ni tumeur sous-jacente, ni insuffisance endocrinienne. Commentaires L’atteinte surrenalienne est bien decrite dans le syndrome des anti-phospholipides et peut se presenter sous la forme d’une insuffisance surrenalienne en cas d’hemorragies bilaterales parfois seulement microscopiques. De plus, Synacthene ® est connu pour pouvoir declencher des hemorragies surrenaliennes, mais cette complication reste rare. Par ailleurs, toute hemorragie surrenalienne unilaterale necessite une surveillance ulterieure de plusieurs mois a plusieurs annees pour eliminer une tumeur sous-jacente et pour controler l’absence de survenue d’une insuffisance surrenalienne si l’atteinte est bilaterale.

Hématomes surrénaliens potentialisés par le Synacthène® (HSS)

OBJECTIVE Many spontaneous adrenal hematomas have been observed in patients being treated by Synacthène. The purpose of this study is to define how to take those patients in charge on a short-, mid- and long-term. PATIENTS AND METHODS From January 2000 to December 2008, five patients (four males and one female), mean age 47, were taken in charge in our service for spontaneous adrenal hematomas. All those patients had been treated with Synacthène for a mid-sciatic pain for 72 hours. We associated a clinical, endocrine and radiologic staging to treat those patients. RESULTS Four patients underwent a watchful waiting, only one patient needed surgery. No adrenal tumor was ever found during the mean two years follow-up (one to four). Two patients suffered of the condition of the antiphospholipid syndrome. CONCLUSION Spontaneous adrenal hematomas are a most uncommon pathology. The clinical attitude has thus to be defined clearly. The patient must be under close clinical evaluation. Biological and morphological parameters have to be often repeated. An adrenal tumor has to be excluded by the evaluation, as that tumor could be secreting or could not be secreting. Antiphospholipid syndrome must also be excluded.

Steady-state captopril renography: Continuous monitoring of the captopril-induced increase in99mTc-MAG3 mean parenchymal transit time in renovascular hypertension

Steady-state captopril renography (SSCR) is an original technique for assessing the captopril-induced increase in technetium-99m mercaptoacetyltriglycine99mTc-MAG3 mean parenchymal transit time (MPTT) in kidneys affected with functional renal artery stenosis (RAS). The steady-state parenchymal activity achieved by constant infusion of99mTc-MAG3 is directly linked to the MPTT of the radiopharmaceutical. This steady-state parenchymal activity was continuously monitored from 15 min before to 60 min after a single dose of captopril in order to detect possible disruption of the steady state. SSCR was performed in 11 hypertensive patients with unilateral RAS and in two with RAS of a solitary kidney before renal revascularization (RR). In four of these patients, an additional SSCR was performed after RR. Of the ten patients whose hypertension was cured or improved by RR, one presented an uninterpretable SSCR and six presented a positive SSCR on the affected side. Control SSCR performed in four of these six patients was bilaterally negative. SSCR was also bilaterally negative in the three patients who showed no blood pressure response to RR. These preliminary results tend to indicate that, in spite of the stability of pre- and post-captopril hydration and data acquisition conditions allowed by this steady-state technique, the sensitivity is lower than expected. However, the reason for the false-negative results does not seem to be inherent to SSCR.

Recent Advances in the Treatment of Renal Osteodystrophy

Renal osteodystrophy becomes clinically significant when the following features are present: clinical symptoms (pain, muscle weakness, pruritus), radiological signs (subperiosteal erosions, osteopenia, fractures or pseudofractures, slipped epiphysis with coxa vara or genu valgum in children, metastatic calcification) and marked plasma abnormalities, particularly uncontrollable hyperphosphatemia. Clinically significant bone disease is not usually seen in adults until they have been on dialysis for several years but may be seen earlier (even before dialysis has been started) in children. Such bone disease may be due either to hyperparathyroidism or to aluminum (Al) bone disease. In favor of hyperparathyroidism are the following features (1, 2): rarity of pain and fractures, greater elevation of alkaline phosphatase, greater elevation of parathyroid hormone (PTH) plasma concentration and lower basal plasma concentration of Al (<300 µg/l) with smaller increase of plasma Al after i.v. administration of desferoxamine (increase <175 µg/l). It is only by bone biopsy, however, that it is possible to differentiate with certainty osteitis fibrosa, the bone expression of hyperparathyroidism, from osteomalacia or adynamic bone disease, both of which have been linked to Al intoxication (1, 2).

Risk reduction for stroke and coronary events.

Sir—Jan Staessen and colleagues (Oct 20, p 1305) show with appropriate techniques that the risk reduction for stroke and coronary events is correlated with differences in blood pressure between the experimental and reference groups in randomised clinical trials with bloodpressure-lowering drugs. They note little, although for some significant, differences between tested pharmacological classes of drug or regimens. They think their main finding is that results of outcome trials for antihypertensive drugs can be explained by blood pressure differences between randomised groups. This statement seems to convey the message that the effect of the antihypertensive treatment is explained by the decrease of blood pressure because of the treatment. The findings presented by Staessen and colleagues do not support such a conclusion, and even suggest that the risk reduction does not parallel the treatment effect on blood pressure. First, the significant metaregressions (for stroke and for myocardial infarction) show a correlation between risk reduction and blood pressure differences between experimental and reference groups, a difference which is assumed to represent the experimental treatment effect on blood pressure over the reference treatment effect. Correlation does mean causality, and tells us very little about the relation between differences in blood pressure and differences in risk between the groups, other than that they are linked statistically. Second, the shape of the curves on figure 5 suggests that the relation between risk reduction and antihypertensive treatment effect on blood pressure is not linear or log-linear, adding clues to a more complex relation than anticipated under the assumption that the risk reduction shown is fully explained by the reduction of blood pressure. In any case, these findings do not support Staessen and colleagues’ claim that the results show the desirability of lowering blood pressure as much as possible to achieve the greatest reduction in cardiovascular complications. Rather, they strengthen the hypothesis of a Jcurve with all its consequences on the management of individuals with raised blood pressure. Thus, by no means should the results obtained by Staessen and colleagues be interpreted in the way they are.