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Increased arterial stiffness and vascular calcification have been recognized as important predictors of cardiovascular mortality in patients with chronic kidney disease.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.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; P0.0001). 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.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.

The objective of this study were (1) to evaluate the prevalence of anti-annexin II antibodies in patients with various autoimmune diseases and antiphospholipid syndrome and (2) to correlate anti-annexin II antibodies with anti-phospholipid antibodies. Anti-annexin II antibodies and anti-phospholipid were detected, using an enzyme-linked immunosorbent assay, in the serum of patients with primary antiphospholipid syndrome (n = 16), systemic lupus erythematosus (n = 53), primary Sjogren syndrome (n = 71), systemic sclerosis (n = 17), systemic vasculitis (n = 18), and rheumatoid arthritis (n = 119). Healthy blood donors (n = 99) were used as controls. Anti-annexin II antibodies were significantly more prevalent in patients with connective tissue diseases (8.5%), especially antiphospholipid syndrome (14.8%) and rheumatoid arthritis (10%), than in controls (2%). An inverse correlation was observed between anti-annexin II antibodies and antiphospholipid antibodies. Annexin II can be recognized by antibodies in serum from patients with systemic autoimmune disorders. Further studies are required to determine the clinical significance of anti-annexin II antibodies in rheumatoid arthritis and to determine their diagnostic value in discriminating clinical subgroups of patients with antiphospholipid syndrome.

AimsTo evaluate vascular expression of annexin A2 (ANXA2) and its subunit S100A10 in lupus nephritis (LN).MethodsThe present histological study included 14 patients with LN and 11 controls (patients with non-lupus kidney diseases). Kidney biopsies from patients with lupus were scored for lupus glomerulonephritis (according to the International Society of Nephrology/Renal Pathology Society 2003 classification) and vascular lesions (such as microthrombi and antiphospholipid syndrome nephropathy (APSN)). ANXA2 and S100A10 expression in glomerular and peritubular capillaries was evaluated by immunohistochemistry on tissue sections. The staining intensity score ranged from 0 (no expression) to 4 (intense expression).ResultsIn patients with LN, the median age (range) at first kidney biopsy was 36 (18–49). Vascular lesions were observed in six patients (including two with APSN). We observed intense expression of ANXA2 in glomerular and peritubular capillaries while expression of S100A10 was weaker. However, one of the patients with APSN showed strong S100A10 expression. Patients with LN and controls differed significantly in terms of S100A10 expression in peritubular capillaries. We also observed a statistical difference between patients who had LN with renal vascular lesions and those without renal vascular lesions in terms of ANXA2 expression in peritubular capillaries.ConclusionsThe presence of vascular lesions in LN appears to be associated with significant differences in the vascular expression of ANXA2. Vascular expression of ANXA2 was somewhat higher in LN. Vascular expression of S100A10 was somewhat lower in LN (except one of the two patients with APSN). Further studies of ANXA2's putative value as a biomarker of active LN or of vascular lesions in LN are required.

We report a case of a retroperitoneal hematoma occurring in a patient under anticoagulation therapy for deep-venous thrombosis and presenting as an anuric acute renal failure. A coexisting polycythemia vera led to misdiagnosis that could have been life-threatening. A woman, known for polycythemia vera and a single functioning right kidney, was admitted with mild abdominal pain in a context of recent deep venous thrombosis under low-molecular weight heparin. Clinical examination revealed hepatomegaly associated with polycythemia vera. Biochemical evaluation disclosed an acute renal failure, and renal ultrasonography showed no dilation of the renal pelvis. Retroperitoneal hematoma resulted in shock, progressive anemia and obstructive renal failure, related to renal pelvic compression. A right renal indwelling catheter was introduced to restore urine flow after one hemodialysis session, and an inferior vena cava filter was placed because of anti-coagulation contra-indication. However, pulmonary embolism occurred, so that oral anticoagulants were introduced. The hematoma resorbed spontaneously, and a year after this episode, the patient is still alive and well. Retroperitoneal hematoma is a rare cause of obstructive acute renal failure and a life-threatening complication of anti-coagulation therapy.

Annexin A2 (ANXA2, an endothelial cell receptor for plasminogen and tissue plasminogen activator) has been identified as a new autoantigen in antiphospholipid syndrome (APS). The aim of the present study was to evaluate the presence of antibodies against the N-terminal domain of annexin A2 (ANXA2) in primary APS (PAPS). By using a synthetic peptide corresponding to the 31N-terminal amino acids of ANXA2 (ANXA2(N31)) as an antigen, we performed an enzyme-linked immunosorbent assay (ELISA) to measure anti-ANXA2(N31) IgG and IgM antibodies in the serum of PAPS patients (n=19), systemic lupus erythematosus (SLE) patients (n=50) and healthy blood donors (n=106). We did not find any statistically differences between the three groups in terms of IgG and IgM anti-ANXA2(N31) titres. Elevated IgG anti-ANXA2(N31) titres were not observed in the serum of PAPS or SLE patients who had previously tested positive for anti-ANXA2 antibodies. Thus, the ANXA2 N-terminal domain does not appear to be the target antigen for anti-ANXA2 antibodies in APS.

Renal involvement in sarcoidosis displays a wide range of manifestations, and kidney dysfunction may involve all three mechanisms of renal failure. We report a new case of systemic sarcoidosis presenting as a severe renal failure due to hypercalcemia, sarcoidosis-related bilateral nephrolithiasis and granulomatous interstitial nephritis. A prostate adenocarcinoma was also diagnosed, but has to be regarded as an unrelated disease.

In normal pregnancy, cross-sectional clinical data do not consistently show plasma ANF concentration differences between early pregnancy and the nonpregnant state. Sequential data in the baboon (but not in rat) show a significant decrease in plasma ANF concentration and in cardiac filling pressures in early pregnancy. The latter data support the view that pregnancy is an underfill state secondary to a primary vasodilatation. Cross-sectional and longitudinal studies in normal pregnancy in humans show that plasma ANF levels tend rise to values that are, in the third trimester, higher than in the nonpregnant state. However, late postpartum sequential data (1.5–3 months) in humans do now show a significant drop in plasma ANF concentrations, suggesting that plasma ANF is not actually increased in normal pregnancy. In the baboon (but not in the rat) there is a steady rise in plasma ANF levels to values that are significantly higher in third trimester than before pregnancy. These data suggest that in human pregnancy, in contrast with the baboon, the plasma volume expansion induced by normal pregnancy is not sensed as such by the atria probably because of an isopressive adaptation of plasma volume to an enlarged vascular bed. However, acute decrease or increase of venous return induced by low sodium diet, changing position or infusion of isotonic saline are sensed as such by the atria in normal pregnancy as in the nonpregnant state. In humans and rats, a steady rise in plasma ANF concentration is observed during the first few days after delivery suggesting that at this time the atria sense an effective hypervolemia; the latter occurring through a decrease in the functional size of the intravascular compartment owing to the elimination of the placenta as well as by the autotransfusion carried out by the emptied uterus. The resulting increase in central venous pressure may stimulate ANF release that, together with a decrease in renin and aldosterone secretion, may thus contribute to the diuretic crisis observed after delivery. In pregnancy-induced hypertension, plasma ANF levels are usually increased but may remain normal in mild hypertension. In preeclampsia, plasma ANF concentration is more consistently increased, specially in the severe form. Plasma ANF decreases to normal levels after delivery when hypertension has disappeared. Plasma ANF concentration is directly correlated to blood pressure. A deficiency in ANF secretion can not, therefore, be the primary cause of pregnancy-induced hypertension or preeclampsia. On the contrary, ANF may play a compensatory role preventing further increase of blood pressure. However, because of the suppressive effect of ANF on renin and aldosterone secretion and by promoting a shift of the plasma fluid into the interstitial space, ANF elevation in preeclampsia may actually contribute to worsen the hypovolemia and explain the paradoxical association of hypovolemia with the hypostimulation of the renin–aldosterone system. The mechanism underlying the increased ANF secretion in preeclampsia is not clear since cardiac filling pressures in untreated preeclampsia are decreased and hence increased ANF release through atrial stretch seems unlikely. It is possible that neuroendocrine mechanisms yet to be identified are responsible for this observation.Key words: atrial natriuretic factor, pregnancy, preeclampsia, pregnancy-induced hypertension.

Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous drug reaction with a long duration of eruption and serious organ involvement. The mortality rate has been estimated at about 10%. Aromatic anticonvulsants, sulphamides, minocycline and more rarely carbamazepine are the principal responsible drugs. We report the first case of chlorambucil-induced DRESS syndrome in a 70-year-old man recently diagnosed with chronic lymphocytic leukaemia. He developed recurrent skin rash, fever, hypereosinophilia, and acute renal failure after rechallenge with chlorambucil. The condition improved slowly after stopping medication and systemic steroids. Prompt recognition of a chlorambucil drug reaction is essential in patients receiving chemotherapy.

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.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.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.

A primary antiphospholipid syndrome is a very rare cause of adrenal haemorrhage.A 51 year-old man presented with a unilateral adrenal haemorrhage, enhanced by the prescription of Synacthène during the 4 days that preceded. There was no adrenal deficiency but the immunological control revealed the presence of anti-phospholipid antibodies. After 2 years of follow-up, adrenal controls have not shown any underlying tumour or endocrine insufficiency.Adrenal involvement is described in the anti-phospholipid syndrome and may present in the form of adrenal deficiency in the case of occasionally only microscopic bilateral haemorrhages. Furthermore, Synacthène is known to induce adrenal haemorrhages although this complication remains rare. Moreover, any unilateral adrenal haemorrhage requires subsequent follow-up for several months or even years in order to eliminate any underlying tumour and to control the absence of any adrenal deficiency if the involvement is bilateral.

Henoch-Schonlein purpura is one of the most frequent systemic vasculitis in children. In adults, muscle involvement is extremely rare and not very well characterized. We report a case of Henoch-Schonlein purpura with severe skin and renal involvement in witch multiple intramuscular haematoma leaded to severe anaemia. Histological examination confirms the muscle localization of the disease.A 68 years old man treated by oral anticoagulation for multiple venous thrombosis, was admitted with necrotic vasculitis of the skin, abdominal pain and segmental IgA glomerulopathy. The diagnosis of Henoch-Schonlein purpura was rapidly made and intensive steroid therapy started. After rapid improvement, a haemorrhagic shock due to voluminous intramuscular haematoma was diagnosed by MRI. Histological examination of the muscle, confirms the localization of the disease.Intramuscular haematomas are very uncommon in Henoch-Schonlein purpura. There are usually a consequence of muscular immune complex vasculitis. In our patient, high dose corticosteroid was not unable to control the disease.

Pulmonary diseases during the course of generalised amyloidosis are principally represented by tracheobronchial involvement and diffuse parenchymal localizations.The authors report the case of a 66-year-old woman presenting with pleural amyloidosis in the context of generalised amyloidosis. Thoracoscopy performed in the investigation of recurrent transudative pleural effusions found evidence of an inflamed parietal pleura with areas of calcification. Pleural biopsies confirmed amyloid infiltration pleural ossification. Talc pleurodesis was performed.The authors' conclusion is that, meeting an unexplained pleural effusion even transudative during the course of a generalised amyloidosis, the thoracoscopy is the diagnosis key test as it allows moreover a pleural pleurodesis to be performed.

Alpha interferon is increasingly used in the treatment of malignancies and viral hepatitis. Renal involvement after its use consist in more cases on proteinuria. We report one case of acute renal failure without nephrotic syndrome but with tubulointerstitiel infiltration by mononuclear cells in 65 old man who had before interferon therapy 151 mumol/l of serum creatinine. Interferon was administrated for digestive carcinoid neoplasia and bone and liver metastasis. Outcome was improvement of renal function after withdrawn of interferon, dialysis and steroid treatment.

5-aminosalicylic acid (5-ASA) used for the treatment of inflammatory bowel disease is known to induce chronic interstitial nephritis (CIN). However, the frequency of occurrence and the spectrum of severity of 5-ASA-induced CIN are not known. In this paper, we report a new case of CIN induced by 5-ASA in a patient treated for about 7 years for a Crohn disease. After that 5-ASA was discontinued and prednisone therapy started, renal function improved partially. About 30 observations of CIN induced by the use of 5-ASA in patients treated for inflammatory bowel disease have already been published. None were published in patients treated for other diseases such as arthritis rheumatism. The review of the literature suggests that the prognosis is poor and correlates with the duration of treatment, the cumulative dose and the level of renal impairment at diagnostic. We believe that the control of the renal function in patients treated by 5-ASA must be regular and prolonged.

The respective contribution of sex, type of nephropathy, degree of proteinuria, blood pressure, protein and sodium daily intakes, blood lipid profile, protidemia, hemoglobinemia, acidosis and CaPO4 product on the rate of renal failure progression is debated.The link between these parameters and the decrease of creatinine clearance, deltaCcr (according to Cockroft) was assessed in uni- and multivariate analysis in a population of 49 patients (26 women; age 60+/-15 years, weight 79+/-15 kg) selected out of 173 presently treated hemodialysis patients on the basis of availability of a quarterly follow-up for 2 years before starting dialysis. The patients were advised a moderate protein and salt restriction which could be retrospectively assessed (on urinary excretion of urea and sodium) at, respectively, 0.82 g/kg/day and 6.5 g/day.The 2-year deltaCcr was 14+/-14 ml/min. It was not different in men and women. This decrease in Ccr was neither significantly different in gomerular disease (17+/-8, n = 14), diabetic nephropathy (12+/-6, n = 7), nephroangiosclerosis (15+/-8, n = 5), interstitial nephritis (12+/-10, n = 14), and PKD (11 +/-12, n = 9). Patients with antihypertensive drugs (n = 42) had a faster progression than those without drugs (n = 7): deltaCcr = 15+/-14 vs 7+/-7 ml/min (p0.05) in spite of comparable blood pressure but with higher proteinuria. Linear regression of deltaCcr with the initial and 2-year averaged values of the quantitative parameters showed a significant positive link for both values with cholesterol, hemoglobine and proteinuria and a negative one with protidemia. A positive link was observed with the initial value of bicarbonate and the 2-year mean of diastolic and mean blood pressures. No link at all was observed with urea and Na excretion, CaPO4 product and triglycerides. Multiple regression disclosed a significant link only for protidemia (negative with both initial and 2-year averaged value), diastolic BP (only for the 2-year averaged value and hemoglobinemia (for the initial value). When the patients were classified according to a threshold value of their protidemia, DBP, hemoglobinemia, and cholesterolemia those with the combination of 2 risk factors of progression (protidemiaor = 66 g/l, DBPor = 90 mmHg, hemoglobinemia11 g/dl, proteinuriaor = 3 g/d, CT5 mmol/l) had a significantly greater decrease of Ccr than those with the 3 other combinations at the exception of the association of low protidemia with DBP.Diastolic hypertension and low protidemia are the 2 most important factors predicting progression of renal failure. A predictive synergy was furthermore pointed out between low protidemia or diastolic hypertension with proteinuria and cholesterol. On the contrary anemia attenuates progression linked to low protidemia, diastolic hypertension, proteinuria and high cholesterol.

Angiotensin II (AII) acts by 2 types of receptors: the ATI receptor which mediates its actions on vasoconstriction, renin (inhibition) and aldosterone (stimulation) secretions, cellular proliferation and angiogenesis and the non-AT1 (often called AT2) receptors. Mainly expressed in the embryon these latter may favor cellular differentiation and recruitment of collateral circulation. Angiotensin converting enzyme inhibitors (ACEI) decrease the synthesis of All and therefore the stimulation of both receptor types whereas AT1-receptor antagonists (AT1RA) block only the stimulation of these latter and increase the stimulation of AT2 receptor since they increase the production of All secondarily to the inhibition of the feedback of renin secretion by All. Experimentally ACEI and AT1RA decrease angiogenesis and cellular proliferation and favor cellular differentiation which could explain the protective effect of ACEI against cancer suggested recently in a Scotish study. Despite of their common suppressive effect on angiogenesis AT1RA may better than ACEI protect against ischemic events specially the cerebral ones because they favor the rapid recruitment of collateral circulation. This has been demonstrated for losartan in case of abrupt ligation of the carotid in the gerbil since its previous administration protects against fatal cerebral ischemia whereas its previous administration with enalapril abolishes this protection. These data may explain why, in the CAPP trial, captopril which has prevented more effectively diabetes occurrence could not be proved superior to diuretics and/or betablocker in the prevention of myocardial infarction and specially of strokes for which exist on the contrary a suspicion of a lower protection. Therefore a comparative trial between AT1RA and ACEI in the prevention of stroke recurrence should appear as a priority for Public Health and Pharmaceutical Industry Authorities.

The respective contribution of sex, type of nephropathy, degree of proteinuria, blood pressure, protein and sodium daily intake, lipid profile, protidemia, hemoglobinemia, acidosis and CaPO4 product on the rate of renal failure progression is debated. The link between these parameters and the decrease of creatinine clearance, delta Ccr (according to Cockroft) was assessed in uni and multivariate analysis in a population of 49 patients (26 men, 23 women; age 60 +/- 15 years, weight 73 +/- 15 kg) selected out of 173 presently treated hemodialysis patients on the basis of availability of a quarterly follow-up for two years before starting dialysis. The patients were advised a moderate protein and salt restriction which could be retrospectively assessed (on urinary excretion of urea and sodium) at respectively 0.82 g/kg/day and 6.5 g/day. The two years delta Ccr was 14 +/- 14 ml/min. It was not different in men and women (specially when expressed in % of initial value). This decrease in Ccr was neither significantly different in glomerular disease (17 +/- 8, n = 14), diabetic nephropathy (12 +/- 6, n = 7), nephroangiosclerosis (15 +/- 8, n = 5), interstitial nephritis (12 +/- 10, n = 14), and PKD (11 +/- 12, n = 9). Patients with antihypertensive drugs (n = 42) had a faster progression than those without drugs (n = 7): delta Ccr = 15 +/- 14 vs 7 +/- 7 ml/min (p0.05) in spite of comparable blood pressure but with higher proteinuria. Linear regression of delta Ccr with the initial and two year averaged values of the quantitative parameters showed a significant positive link for both values with cholesterol, hemoglobin and proteinuria and a negative one with protidemia. A positive link was observed with the initial value of bicarbonate and the two year mean of diastolic and mean blood pressures. No link at all was observed with urea and Na excretion, CaPO4 product and triglycerides. Multiple regression disclosed a significant link only for protidemia (negative with both initial and two years averaged value), diastolic BP (only for the two year averaged value and hemoglobinemia (for the initial value). When the patients were classified according to a threshold value of their protidemia, DBP, hemoglobinemia, and cholesterolemia those with the combination of two risk factors of progression (pro-tidemia66 g/l, DBPor = 90 mmHg, hemoglobinemia11 g/dl, proteinuria3g/d, CT5 mmol/l) had a significantly greater decrease of Ccr than those with the three other combinations at the exception of the association of low protidemia with DBP.1. diastolic hypertension and low protidemia are the two most important factors predicting progression of renal failure; 2. a predictive synergy was furthermore pointed out between on one hand low protidemia and diastolic hypertension and on the other hand proteinuria and cholesterol; 3. on the contrary, anemia attenuates progression linked to low protidemia, diastolic hypertension, proteinuria and high cholesterol.

The authors present of case of a 61-year-old man suffering from cholesterol emboli, in whom transoesophageal echocardiography revealed complex atheromatous lesions of the thoracic aorta. There is growing emphasis, at the present time, on the concept of triggering factors with the multiplication of endovascular radiological investigations, the more widespread availability of cardiac surgery and the use of anticoagulants and fibrinolytics. The prognosis is poor, treatment is only palliative and preventive measures are therefore essential.

We report a series of 27 patients included on the basis of either thrombotic microangiopathy (TMA) at renal histology (13 cases) or, in the absence of histology, non-immunological hemolytic anemia with schizocytes and thrombopenia (14 cas). The etiopathogenic treatment consisted in the administration of antiagregating agents (in all patients except 3 of group I because of the severity of thrombopenic), corticosteroids (1 case), intravenous immunoglobulins (2 cases) fresh frozen plasma (FFP) without plasma exchange (PE) in 7 cases and PE with FFP in 13 patients. According to the 6 months outcome, 4 groups were considered I: death due to neurological damage; II: chronic hemodialysis; III: partial renal recovery; IV: complete renal recovery.a/Patients with neurological complications have poor prognosis in spite of minor renal involvement and use of PE whose indication is validated in these cases. b/When renal involvement predominates, accelerated hypertension is linked to arteriolar or mixte type of TMA, exposes to an increased risk of hemorrhagic complications of the renal biopsy (4 out fo 5) which questions the usefulness of such biopsy (group II). c/TMA may precede cancer. It has per se a favorable outcome even when metastases are already present, warranting aggressive treatment.

Duplex-scan is widely used for arterial stenosis diagnosis. Its role in detection of renal artery stenosis remains controversial (2, 17, 19, 28). The aim of this study was to determine retrospectively if duplex-scan is accurate for diagnosis of renal artery stenosis. During 36 months, 764 patients had a renal artery examination with duplex-scan: 90 patients had also renal arteriography. Duplex-scan was feasible in 95% of cases (excess bowel gas or major obesity gave to duplex-scan incomplete results in four patients upon 90). Ninety-three per cent of patients had hypertension; 20% had renal failure; 61% had obstruction of coronary, carotid artery or lower limb arteries. Nineteen patients among 86 had also an intravenous renal arteriography. We compared duplex-scan with venous angiography and intra-arterial arteriography. Duplex-scan criteria for stenoses were: a maximal systolic velocity (MSV) above 180 cm/s for detection of 60% to 79% stenoses and a MSV superior to 300 cm/s for detection of 80% to 99% stenoses. Global results showed a good sensitivity 59/64 (92%) and specificity 112/117 (96%) for duplex-scan. Duplex-scan is accurate for diagnosis of renal artery stenosis in a selected population.

Besides defining the appropriate doses of frusemide in uraemic patients, A. Heidland's contribution to the treatment of hypertension in chronic renal failure consisted in the following demonstrations: (1) In patients on chronic haemodialysis, calcium antagonists have a beneficial effect on their glucose intolerance and decreased plasma levels of 25OH vitamin D while their effect on blood lipids is neutral. (2) In 5/6 nephrectomized rats, captopril, verapamil, and metoprolol have the same protective effect on their GFR and tubular secretion of protons, at equal blood-pressure-lowering effect. (3) In rats with streptozotocin-induced diabetes, atrial natriuretic peptide does not play a role in their hyperfiltration. (4) Severe retinopathy is observed in patients with uraemic nephropathies at a much smaller elevation of their blood pressure than in patients with essential hypertension. This article reviews the following points: (1) The role of hypertension in the loss of renal function is convincingly demonstrated only in a few experimental models, and in man only in malignant hypertension and diabetic nephropathy but not in essential hypertension nor in non-diabetic nephropathy. However, preliminary results suggests that antihypertensive treatment may retard the progression of renal disease in normotensive patients (DBP90 mmHg) with either microalbuminuric diabetes and normal renal function or non-diabetic uraemic nephropathy. (2) Only the ACE inhibitors have been proved to have a specific renal protective effect, independent of their diurnal blood-pressure-lowering effect, both in diabetic nephropathy and in non-diabetic uraemic nephropathy.

Rapidly progressive glomerulonephritis (RPGN) is rarely associated with macroscopic polyarteritis nodosa (PAN), as seen in this series of 7 out of 235 patients. The clinical symptoms of PAN were as follows: myalgias 6; fever 1; arthralgias and mononeuropathy multiplex 5; cutaneous vasculitis 3; arterial hypertension 4, 3 of which were malignant. The mean proteinuria was 2.7 g/24 h; creatininemia 458 microM/l; microscopic hematuria was present in 4 of the 7 patients; only 1 patient was anuric. Markers of hepatitis B virus were absent in all cases. Arteriography revealed microaneurysms and renal infarcts in 6 patients and distal arterial stenosis in one. Renal biopsies from all 7 patients demonstrated extracapillary glomerulonephritis, which was associated with tubulointerstitial fibrosis in one. Necrotizing vasculitis lesions were associated in 5 cases. Immunofluorescence was positive in 5 cases. The association of RPGN and PAN exists and may be underestimated due to the lack of systematic angiographic examinations during RPGN and renal biopsies in PAN patients with renal involvement.

To evaluate the examination of urine erythrocytes with a contrast phase microscope for the etiological diagnosis of haematuria (erythrocytes10/mm3 of non centrifuged urine) the charts of 84 patients with haematuria were reviewed. A nephrological origin had been established with certainty in 56 cases with a renal biopsy and an urological origin was also established with certainty in 28 cases thanks to appropriate radiological, endoscopical and pathological examinations. The morphological criteria of the erythrocytes deformation were those of Birch and Fairley but the quantitative criteria of these authors (either 80 or 100%) were found to be of no value. By successive approaches the threshold of 20% of deformed erythrocytes was selected and found to be the best criterion for diagnosing glomerular hematuria: the sensitivity of the test is then 73% and its specificity 60%. As these results were relatively modest, conditions which decrease the percentage of deformed erythrocytes were excluded to improve the sensitivity, such as macroscopic haematuria and also examinations made during the 6 hours following furosemide administration whereas conditions which increase the percentage of deformed erythrocytes and which are easily diagnosed such as urinary infections, lithiasis and renal insufficiency associated with an uropathy were excluded in order to improve the specificity. Then the examination has a sensitivity and a specificity of 90% which makes it clinically relevant, authorizing a wait and see attitude in case there is an isolated microscopic haematuria of glomerular type.

Between 1 January 1976 and 31 December 1986, primary glomerulonephritis was histologically diagnosed in 319 patients, living in a region of 675,000 inhabitants at the time of renal biopsy. The prevalence of primary glomerulopathy was 0.4/1000 inhabitants. The annual incidence was determined during two 5 year periods: period A (1976-1980) and period B (1981-1985): they were, respectively, 3.4 and 4.5 for 100,000 inhabitants. Berger's focal glomerulonephritis was the most common (30 p. 100) and its incidence was increasing. In contrast, membranoproliferative and acute glomerulonephritides were sharply decreased (almost disappeared), while membranous glomerulonephropathies and glomerulopathies with minimal glomerular lesions or proliferative forms with crescents increased. All primary glomerulonephritides were more prevalent in men and their frequencies increased with age. Our findings lead to the following conclusions: a) the low prevalence and incidence of primary glomerulopathies (3 times less than in other published studies) probably reflect the under medicalization of our region and the attractiveness of neighbouring metropolis, rather than a real decrease in the disease; b) the quasi- disappearance of acute and membranoproliferative glomerulonephropathies and the high incidence of IgA glomerulonephropathies suggest that their pathogenetic associations with infections sensitive to antibiotics are different; c) the increased frequency of membranous glomerulonephropathy and the glomerulopathy with minimal glomerular lesions in aged subjects is most likely due to their polymedication.

We have measured simultaneously plasma renin activity (PRA), aldosterone and catecholamines in the plasma of 3 groups of pregnant women after the 20th week: group 1 of 16 normotensive controls, group II of 17 women with rest responding hypertension (RRH), group III of 18 women with permanent hypertension (PIH). All the patients were ambulatory on a normal salt diet. PRA was significantly higher in the RRH than in the control and PIH groups (15,8 +/- 2,3ng/ml/l versus 6,7 +/- 0,5 and 8,9 +/- 0,9 respectively). Plasma epinephrine (PE) and norepinephrine (PNE) were significantly higher in the PIH than in the control and RRH groups (respectively 135 +/- 28 pg/ml versus 56 +/- 13 and 63 +/- 17 for PE and 387 +/- 91 versus 206 +/- 32 and 200 +/- 47 pg/ml for PNE). In the PIH group there was a negative correlation between PRA and blood uric acid. It is concluded that the adrenic system is activated in PIH whereas the renin angiotensin system is activated in RRH of pregnancy.

Plasma immunoreactive atrial natriuretic factor 99-126 (ir ANF), plasma volume, plasma renin activity, and plasma aldosterone were measured during pregnancy in 14 normotensive nonpregnant women, 15 normotensive pregnant women, 35 patients with pregnancy-induced hypertension (PIH), and in ten patients with preeclampsia (PE). Repeated measurements were carried out 2 months after delivery in a subgroup of the same patients. The plasma levels of ANF were found to be higher in pregnant normotensive women than in nonpregnant normotensive women, but the decrease of plasma ANF 2 months after delivery was not significant on the basis of seven paired data, so that it cannot presently be stated with certainty that pregnancy per se stimulates ANF secretion. Still higher levels of ANF were found in PIH and, especially, in PE. A positive correlation was found in the pooled population of normotensive and hypertensive pregnant women between plasma ANF and mean arterial pressure. A greater decrease of plasma ANF was found after delivery in the hypertensive patients than in the normotensive controls. This excludes an absolute deficiency of ANF secretion in the pathogenesis of hypertension. These findings suggest a compensatory role of ANF in the prevention of blood pressure increase. Plasma renin activity (PRA) and plasma aldosterone concentrations were higher in normotensive pregnant women than in normotensive nonpregnant women. Compared to normal pregnancy, plasma volume was decreased in PIH (-17%) and in PE (-25%), whereas PRA was less increased in both groups and plasma aldosterone concentration was less increased only in the PE group. The simultaneous high levels of plasma ANF may explain this inappropriate hypostimulation of renin secretion by hypovolemia in these hypertensive states.

1. The technique of combined intravenous renal arteriography and pyelography is described and results in 848 hypertensive patients are reported. 2. The procedure was tolerated better than Seldinger arteriography and the diagnostic accuracy for renal artery stenosis was 95%. 3. The prevalence of renovascular disease was 7%. 4. Cost-effectiveness calculations favour combined intravenous arteriography and pyelography rather than the usual approach based on assessment of the indications for Seldinger arteriography from clinical and urographic signs.

1. In four patients, whose hypertension was not controlled (supine blood pressure > 150–90 mmHg) by addition of 5 mg/day of prazosin to previous treatment (diuretics and β-blockers), clonidine (150–450 μg/day) led to control of hypertension in three cases. 2. In ten patients whose hypertension was not controlled by a treatment including clonidine (300–450 μg/day), the progressive addition of prazosin to a maximal dose of 4–22.5 mg/day led to control of hypertension in nine cases (mean supine blood pressure decreased from 174–102 to 144–88 mmHg). 3. In 13 hospitalized patients, clonidine was abruptly interrupted whereas prazosin was continued. Mean blood pressure (± sem) rose from 145 ± 1/85 ± 2 to 169 ± 7/104 ± 5 mmHg 48 h after clonidine withdrawal whereas plasma noradrenaline and adrenaline rose from 328 to 758 pg/ml and from 75 to 137 pg/ml. No subjective symptoms were noted. There was a negative correlation between blood pressure increase and the dose of prazosin. 4. It is concluded that (a) there is no antagonism between clonidine and prazosin in their antihypertensive action in man when used at usual clinical doses, (b) a protective effect of prazosin against an eventual clonidine withdrawal syndrome is suggested by the negative correlation between blood pressure increase and the dose of prazosin.

Nine uraemic patients not yet on dialysis received IV 1 microgram/kg/min of propranolol for 85 min after a priming dose of 1 mg. Fifteen days later six of them received IV 1.2 microgram/kg/min of metoprolol after a priming dose of 1.2 mg. Plasma concentrations of PTH and calcitonin decreased significantly with propranolol but not with metoprolol. No change was observed with either drug as regards plasma concentration of total and ionised Ca and PO4. Heart rate was decreased similarly with both drugs. We conclude that (i) propranolol acutely suppresses PTH and Calcitonin secretion in uraemic patients. This warrants further studies to assess its long term effects on the secretion of these hormones and on renal osteodystrophy; (ii) the contrast between the significant effect of propranolol and the lack of effect with metoprolol supports the concept that PTH and CT secretion are moderated through specific beta 2 receptors.

To evaluate the adequacy of simple calcium restriction for patients with idiopathic calcium stones the effect of 5 days of calcium restriction without oxalate restriction on renal excretion of calcium and oxalate, and the corresponding probability of stones were assessed in 50 controls and 48 patients. Renal excretion of calcium decreased and that of oxalate increased significantly in all groups but the importance of the changes was critically dependent upon the underlying pathophysiological condition. The probability of stones decreased only in patients with absorptive hypercalciuria type II owing to the usual excessive calcium intake and increased in those with absorptive hypercalciuria type I and renal hypercalciuria, which are associated with true hyperabsorption of calcium and represent the 2 forms of idiopathic hypercalciuria. We believe that simple calcium restriction is beneficial for patients with idiopathic calculi only when the hypercalciuria is caused by exaggerated intake of calcium, since it increases the probability of stones in patients with idiopathic hypercalciuria. Calcium restriction always is associated with an increase in oxalate excretion, suggesting that simultaneous oxalate restriction should be added in all cases to decrease the probability of stones.

The effect of oral cimetidine on parathyroid hormone and calcitonin plasma levels was evaluated in 12 uremic patients on chronic hemodialysis. Compliance to treatment was monitored by measuring cimetidine plasma concentrations. Plasma cimetidine was measurable in 7 patients and undetectable in 5. In compliant patients, there was no change in plasma concentration of calcium and parathyroid hormone but a significant fall of 75% in plasma calcitonin levels during treatment, followed by an increase towards initial values after cimetidine discontinuation. No significant change occurred in the other 5 patients. Cimetidine therefore appears to be of little value in the treatment of uremic hyperparathyroidism.

The decrease of blood pressure and the increase of plasma renin activity (PRA) after oral administration of captopril was evaluated in 104 consecutive hypertensive out-patients in whom the morphology of the renal arteries and parenchyma was assessed thanks to an intravenous digitalized angiography. Twenty five of these patients were excluded because of a natriuresis less than 50 mmol/24 h or non discontinuation of their treatment; 50 of these patients were classified as essential hypertension, 12 had renovascular disease (10 unilateral stenosis 2 of which significant; 2 bilateral significant stenosis); 9 had unilateral small kidneys (4 significant). The significance was ascertained on the PRA in the renal veins and/or the decrease of hypertension after surgery. The decrease of blood pressure after captopril was not different between the various groups. The increase after captopril of PRA was higher in unilateral significant lesions. However the highest post captopril PRA value was found in the essential hypertension group so that renovascular diseases could not be screened by higher post captopril PRA values. However taking into account that these latter were decreasing with age, a better discrimination of significant unilateral disease was possible in the hypertensive patients above 40 years of age. Furthermore once the diagnosis of unilateral kidney disease is established by radiological investigation, the captopril test allows to predict unilateral hypersecretion of renin with a sensitivity of 100% and a specificity of 78%.the captopril test does not allow to screen the non selected hypertensive patients for an efficient radiological investigation by intravenous digitalized angiography but may help to select the patients with unilateral renal disease for the renal venous PRA evaluation.

After a protein load, the glomerular filtration increases to a maximum called maximal filtration capacity (MFC). The difference of this value with that observed in the fasting state defines the functional renal reserve (FRR). Fifty oral protein loads have been performed in 16 controls (13 adults and 3 children) and 31 patients with kidney disease or hypertension (22 adults, 9 children, 3 tests being performed twice). The load consisted in the adults of 80 g of various proteins. In the children the load consisted in the 100% of the protein intake recommended of the whole day. The urinary samples were made hourly during the 5 hours following the beginning of the meal. The MFC was not always observed during the 2 hours following the end of the meal. However the mean of the clearances measured during these 2 hours allowed an acceptable evaluation of the FRR in 42 out of 50 cases and had the advantage to reduce the errors linked to incomplete bladder voiding. In the adult controls the mean of hourly determined MFC is 156 +/- 27 ml/min, the mean of the clearances measured on the 2 hours following the meal is 136 +/- 21 ml/min and the fasting clearance 96 +/- 22 ml/min. The FRR is null in all patients with a nephropathy with a fasting clearance below 40 ml/min. It is modest or null in patients with acquired or congenital solitary kidney. Three out of five patients with proteinuria have MFC and FRR higher than the mean of the patients with comparable fasting clearances but without proteinuria suggesting that proteinuria is associated with a hyperfiltration state.

To assess whether betablockers (BB) would better control blood pressure than central antihypertensive drugs (CAD) clonidine or alpha methyldopa in hypertensive patients during exercise, comparable triangular ergometric bicycle exercises were performed by the same patients while their hypertension had been controlled at rest either with CAD or BB. Blood pressure, heart rate and blood lactate before and during exercise were compared in II patients treated with metoprolol and CAD, and in 12 other patients treated with atenolol and CAD. Systolic and diastolic blood pressure on exercise were significantly lower with BB than with CAD. Heart rate and rate-pressure product were always lower with BB than with CAD. Blood lactate increase was greater with BB than with CAD. The work capacity was greater with atenolol than with CAD, but comparable between metoprolol and CAD.

After confirming hypercalcemia by 3 successive measurements of the total plasma calcium corrected for a plasma protein concentration of 72 g/l, which excludes spurious hypercalcemia due to dehydration, the physician orientates the aetiological diagnosis bearing in mind that primary hyperparathyroidism PHPT is the cause of 85 p. 100 of all asymptomatic forms of hypercalcaemia whilst overt or occult malignancy is the main cause (60 p. 100) of symptomatic forms of hypercalcaemia with PHPT responsible for 20 p. 100 of cases. Other causes, including drug toxicity with Vit D, calcium, Vit A, lithium, thiazide and aluminium hydroxide, sarcoidosis, hyperthyroidism, Addison's disease, pheochromocytoma and familial endocrine disorders are much rarer. Nevertheless, these rarer causes must be excluded on the clinical history and examination followed by radiological (chest X ray, plain abdomen X ray, bone X rays) and simple biological tests. The latter and/or scans tests should also help in a rapid diagnosis of metastatic carcinoma and multiple myeloma, so that the major diagnostic problem is to distinguish primary HPT from occult malignancy. This problem is greatly facilitated by reliable assays of C terminal or medium PTH rather than renal CAMP which is increased in 80 p. 100 of occult malignancies. When PTH assays is unavailable or unreliable Dent's hydrocortisone suppression test may be useful as a fall in'serum calcium is associated with occult malignancy in 70 p. 100 of cases and non-suppression is associated with PHPT in 91 p. 100 of cases. Discriminant analysis of the usual biochemical parameters may be helpful in this differential diagnosis and is accurate in about 90 p. 100 of cases. However, the association of PHPT and malignancy is also possible and not fortuitous.

In order to determine the effect of beta-blocking agents on secretions of parathyroid hormone and calcitonin, 9 patients with renal failure were given single doses of propranolol (a blocker of the beta 1 and beta 2 receptors) or an equivalent amount of metoprolol (a beta 1 selective agent). Propranolol causes a decrease of plasma parathyroid hormone (p less than 0.02) as well as of calcitonin (p less than 0.05) whereas metoprolol has no effect on the plasma levels of these hormones. These findings suggest that parathyroid tissue and thyroid C cells have receptors that are exclusively of the beta 2 type which are modulating the secretion of parathyroid hormone and calcitonin.

Plasma magnesium (PMg) and urinary calcium (UCaV) and magnesium (UMgV) were measured after four days of calcium-restricted diet in 60 controls and 82 patients classified according to their calcium excretion in three groups: normo-calciuric (NCa), dietary hypercalciuria (DH) and idiopathic hypercalciuria (IH). When compared to controls, higher UMgV (4.26 +/- 0.28 mmol/d versus 3.4 +/- 0.16, p less than 0.01), lower PMg (0.79 +/- 0.01 mmol/d versus 0.84 +/- 0.01, p less than 0.05) and lower UMg/UCa ratio (0.6 +/- 0.04 versus 1.68 +/- 0.15, p less than 0.001) were observed only in IH. A significant correlation between UMgV and UCaV was found in controls, in NCa and in DH but not in IH. In conclusion, (1) the coexistence of a higher UMgV and of a lower PMg in IH suggests that there is a magnesium depletion in this group of patients; (2) since the lower UMg/UCa ratio may favour a higher propensity for calcium crystallisation and is seen only in IH, magnesium supplements may be specially indicated in this group.

Tienilic acid (250 mg/day) was compared with chlorothiazide (500 mg/day) in 25 hypertensive patients in a randomized cross-over study (2 periods of 2 months). Mean supine arterial pressure was lower with tienilic acid than with chlorothiazide (106 +/- 3 vs 111 +/- 3 mm Hg, p less than 0.05) whereas no difference could be noted in body weight, natriuresis and plasma renin activity. Glucose tolerance tests were altered in the same fashion. Serum cholesterol (234 with tienilic acid and 239 mg/dl with chlorothiazide) and serum triglyceride levels (178 with tienilic acid and 179 mg/dl with chlorothiazide) were not different. Serum urate concentrations were lower with tienilic acid (4.8 mg/dl) than with chlorothiazide (7.8 mg/dl) whereas fractional excretion of urate was much higher with tienilic acid (17 +/- 2%) than with chlorothiazide (7 +/- 2%). Thus, the only metabolic advantage of tienilic acid over chlorothiazide is its hypouricemic effect which warrants long term studies to evaluate its vascular prognostic significance.

The authors review the various techniques of intravenous arteriography before an excretory urogram and discuss their role in the etiological diagnosis of hypertension. Detection of renovascular disease classically implied Seldinger arteriography, with its limited indications, because of side effects and cost. This classical approach should now be systematically replaced by the visualization of renal arteries during the intravenous pyelography procedure which appears to be a method more effective, as well as less expensive and hazardous. The pyelogram wash-out should still be performed when the visualization of the renal arteries is poor because of its value in the screening for renovascular hypertension. Furthermore, when a renal artery stenosis is clearly defined, the wash-out of the pyelogram should also be performed because of its prognostic value. As the classical approach for the etiological diagnosis of hypertension, this technique has limited indications. It is indicated in severe hypertension in the young, when medical treatment does not control blood pressure satisfactorily or when renal failure progresses rapidly. Furthermore, this technique allows a non traumatic follow up of operated or dilated stenoses.

A 59 year-old male developed the nephrotic syndrome in the course of squamous-cell lung carcinoma with metastases. Renal biopsy disclosed amyloid deposits. Immunofluorescence was positive with an anti-SAA antiserum. Amyloidosis complicates exceptionally lung tumors, despite extremely high serum levels of SAA in this type of malignancy. This infrequency shows that determinants other than high SAA serum levels are necessary to create tissue amyloid deposits.