[Hemoglobin targets in anemic patients with chronic kidney disease treated with erythropoietin]. / Erythropoïétine et insuffisance rénale: jusqu'où ne pas aller?

PURPOSE: Erythropoietin is the treatment of the anaemia in chronic kidney disease. A target rate of haemoglobin higher than 11 g/dl was usually proposed, but recent recommendations stated that higher limit of haemoglobin was to be reached, with the aim to improve the quality of life of the patients and to reduce their risks of cardiovascular diseases. These objectives are to be revised, according to the results of recently published clinical trials. CURRENT KNOWLEDGE AND KEY POINTS: Patients treated to reach a high rate of haemoglobin (between 13 and 14,5 g/dl) have an improved quality of life, but a 30% higher mortality rate, compared to patients treated with a lower objective of haemoglobin rate (10-12 g/dl). Hypertension and vascular access thromboses were also more frequent in the patients with the highest haemoglobin rate. Two to three times more erythropoietin was necessary to reach the higher rate of haemoglobin. These results favour a target rate of haemoglobin not higher than 12 g/dl. A polemic followed the results of these clinical trials, mostly in the United States, questioning the way in which the higher limit had been fixed whereas precise data were unavailable. The role of pharmaceutical industry and of for profit dialysis centres was underlined. FUTURE PROSPECTS AND PROJECTS: The next step is now to explain if the excess in cardiovascular morbimortality is related to the haemoglobin rate or to a direct effect of the erythropoietin. Such an understanding is important, the more so as new erythropoiesis-stimulating agents are being developed.

[Is there an evidence-based management of idiopathic retroperitoneal fibrosis?]. / Peut-on proposer une prise en charge de la fibrose rétropéritonéale idiopathique validée par les données de la littérature?

BACKGROUND: Nowadays it is quite easy to diagnose idiopathic retroperitoneal fibrosis (IRF), particularly with the help of medical imaging. However there is no guideline about the treatment. PURPOSE: Looking for data about an evidence-based management. METHODS: Screening of the database Medline. Titles and abstracts of articles published between 01/01/1985 and 31/12/2004 have been read to identify clinical trials and series about more than ten patients. RESULTS: No record of any therapeutic trials has been found. Eight series in total, which included 177 patients, were identified. Two of the patients have been treated by an ureteral desobstruction only (endoscopy or nephrostomy), 45 by surgery (ureterolysis), 65 by corticotherapy and 64 both by surgery and steroids. For 38 patients, immunosuppressive drugs were combined with corticotherapy (azathioprine, cyclophosphamide or D-penicillamine). According to the authors, doses and duration of corticotherapy varied. Median follow-up lasted 56 months. The outcome is satisfactory in 73% for surgery alone, 86% for medical treatment alone and 73% for both. The association between steroids therapy and immunosuppressive drugs is efficient in 97% of the cases. No clear data about side effects was mentioned. DISCUSSION: Treatment of the IRF is still empirical, based on surgery and corticotherapy. There is no guideline about the treatment strategy. Although tamoxifen has been proposed, efficacy evidence is lacking. Prospective multicenter studies will help us to progress in the management of the IRF.

[Use of nitrates in hospitalised elderly patients aged 65 and over]. / Utilisation des dérivés nitrés chez les patients âgés de 65 ans et plus hospitalisés en médecine interne.

BACKGROUND: Nitrates are frequently prescribed drugs, although their indications are limited. We studied nitrates' prescription in elderly patients hospitalised in the internal medicine ward of a French teaching hospital. METHODS: Hospitalised patients aged 65 years and more and receiving nitrates in their usual treatment were identified prospectively. A standardised questionnaire was used during a structured medical interview conducted by the same physician for all patients. Informations regarding nitrates' prescription were studied according to the actual recommendations for their use: angina in patients with contraindication to betablockers, acute myocardial infarction and acute pulmonary oedema. RESULTS: Among 256 hospitalised elderly patients, 49 (19% [IC95%: 15-25]) were under nitrates therapy, because of either angina pectoris, heart failure or unknown reason. Cardiologists prescribed nitrates in accordance with guidelines significantly more frequently than non-cardiologists. Transdermal treatment was used in 69% of patients. DISCUSSION: In hospitalised patients aged 65 years and more who are prescribed nitrates in their usual treatment, at least one quarter have no recommended indication for its use. As almost one fifth of patients are receiving nitrates in their usual treatment, the medicoeconomic impact of these useless prescriptions could be significant. Nitrates prescribing can be optimized by following guidelines for their use, and restraining from prescribing the transdermal treatment which is more costly and without evidence-based clinical benefit compared to the oral route.

In vitro prostaglandin synthesis by various rat renal preparations.

Prostaglandin synthesis by eight different structures from the rat kidney (while cortex, cortical tubules, glomeruli, outer medulla, papilla, glomerular cultured epithelial and mesangial cells, cultured interstitial medullary cells) was measured in vitro after incubation with [14C] arachidonic acid using high-performance liquid chromatography followed by RIA with four specific anti-prostaglandin antibodies (prostaglandin E2, prostaglandin F2 alpha, 6 keto-prostaglandin F1 alpha, thromboxane B2). Prostaglandin production by the whole cortex and cortical tubules was very low. The order of abundance for isolated glomeruli was thromboxane B2 great than prostaglandin E2 greater than prostaglandin F2 alpha greater than 6 keto-prostaglandin F1 alpha. Mesangial cells synthesized prostaglandin E2 at a markedly high rate, in decreasing order: prostaglandin F2 alpha, thromboxane B2 and 6 keto-prostaglandin F1 alpha. The same order of abundance was observed for epithelial cells. The papilla synthesized essentially prostaglandin E2 and prostaglandin F2 alpha, whereas the main product for the outer medullar was 6 keto-prostaglandin F1 alpha. Cultured interstitial cells synthesized mainly prostaglandin E2 and to a lesser extent prostaglandin F2 alpha. Unidentified peaks eluting between 6 keto-prostaglandin F1 alpha and thromboxane B2 were also observed chiefly with glomeruli but they were absent with the medullary preparations. They disappeared after incubation with indomethacin or aspirin and represented for glomeruli the greatest percentage of conversion of [14C] arachidonic acid. These results show that the prostanoid profile varies markedly with the different regions and cells of the rat kidney.

Heparin cofactor II deficiency in renal allograft recipients: no correlation with the development of thrombosis.

Heparin cofactor II (HC II) is a thrombin inhibitor in human plasma which displays great similarities with antithrombin III (AT III). Hereditary HC II deficiency was recently reported to be associated with thrombophilia. Since thromboembolism constitutes an important post-operative complication after renal transplantation, we measured HC II and AT III in the plasma of 118 healthy renal allograft recipients (RAR) and found stable low HC II and high AT III levels. Administration of azathioprine (AZA), cyclosporine A (CSA) or both as immunosuppressive therapy did not affect HC II levels, but CSA seems to have raised plasma AT III. The proportion of patients with HC II deficiency was significantly higher in RAR than the proportion we previously found (11) in healthy individuals (16.9% vs 1.5%). However, the proportions with low plasma HC II were not different in healthy RAR and in ten RAR with thrombotic events, suggesting that in transplanted patients, HC II deficiency is not in itself a risk factor for the development of thrombosis.

Renal failure in myeloma: relationship with isoelectric point of immunoglobulin light chains.

Renal failure is a frequent but inconstant complication of myeloma related to light chain excretion. Since it has been suggested that cationic light chains (lc) are most likely to induce renal damage, we have studied the isoelectric point (pI) of light chains produced by 17 patients with myeloma and related the results to the type and severity of renal damage assessed clinically and pathologically. In order to do so, we have applied immunoenzymatic techniques which allow identification of light chain types as well as measurement of pI without prior purification. Ten of fifteen patients with renal failure produced lambda light chains. There was no simple relationship between the isoelectric point and nephrotoxicity. However, light chains with the lowest pI observed in this series were associated with normal renal function in two cases and with acute reversible but severe renal failure requiring dialysis in five cases. By contrast, pI values above 6.0 observed in the remaining patients were associated with moderate renal failure in six patients with recently diagnosed myeloma and with irreversible renal failure, and in two patients in whom myeloma had been evolutive for several years. We thus suggest that further pI measurements may help to identify light chains with different nephrotoxic potentials.

Distinct phenotypic composition of diffuse interstitial and perivascular focal infiltrates in renal allografts: a morphometric analysis of cellular infiltration under conventional immunosuppressive therapy and under cyclosporine A.

Phenotypic analysis of interstitial mononuclear cell infiltrates was undertaken in 40 transplant renal specimens obtained from 38 patients in order to assess the influence of immunosuppressive therapy. Thirteen patients were given conventional immunosuppressive treatment (azathioprine and prednisone) and the other 25 received cyclosporine. The immunostaining was performed using seven antileucocyte antibodies by alkaline phosphatase-anti-alkaline phosphatase method. Interstitial infiltrates were distributed in two patterns: diffuse infiltrates and periglomerular/perivascular aggregates. The phenotypic composition was distinct in these two patterns: in diffuse infiltrates, monocytes/macrophages (EBM 11) represented the predominant inflammatory cell and were associated with a minor component of T cells (T 11). In contrast, aggregates had a major T lymphocyte phenotype in addition with few foci of B cells. T4 subset of T lymphocytes always predominated over T8 subset. The repartition and the proportion of each cell type were not significantly different in rejecting and not rejecting grafts and were not affected by the immunosuppressive regimen.

Computerized patient management in a nephrology department.

An integrated approach is described for the computerized management of a nephrology department. On a medical point of view, the system comprises a minimum medical record for every patient, different specialized records and knowledge bases presently covering hypertension, diabetes and chronic renal failure. From a technical point of view, the methodology used integrates data and knowledge management techniques. Various individual reports facilitate patient management. For hypertensive patients, an expert system is combined with the record system. The results of a preliminary evaluation are reported and future developments considered.

[Acute pancreatitis in rheumatoid purpura. Apropos of 2 cases]. / Pancréatite aiguë au cours d'un purpura rhumatoïde. A propos de deux cas.

Abdominal pain observed in Henoch-Schönlein purpura (HSP) is usually attributed to digestive tract involvement. Pancreatic involvement is a rare and benign complication. The authors report two cases of acute pancreatitis as a complication of HSP. Pancreatitis was confirmed in both cases by clinical presentation and increase of serum amylase levels. Abdominal echography has demonstrated ascites or alithiasic cholecystitis without pancreatic abnormality. The prognosis was favourable in each case. Pathophysiologic mechanism is presumably a vasculitis of the small vessels specially within the pancreas leading to inflammation. Abdominal pain can be explained by a digestive tract involvement but also by an acute pancreatitis. This later occurrence is not as exceptional as reported in the literature. Thus, serum amylase levels should be evaluated in patients with HSP who have intense epigastric or abdominal pain, in order to recognize a pancreatic involvement.

[Treatment of an aneurysm of the abdominal aorta above a transplanted kidney. Renal protection by inert subclavian-femoral bypass]. / Cure d'un anévrysme de l'aorte abdominale en amont d'un rein transplanté. Protection rénale par un shunt inerte sous-clavio-fémoral.

Opening and grafting of an aneurysm of the abdominal aorta located between and below the renal arteries were carried out in a 44-year old patient with a transplanted kidney in right hypogastric position. Renal ischaemia during clamping of the aorta was prevented by means of an inert bypass between the right subclavian and femoral arteries. The patient's renal function remained normal. The different techniques available to protect renal transplants are compared.

[Tubular renal acidosis]. / Les acidoses tubulaires rénales.

Renal tubular acidosis (RTAs) are a group of metabolic disorders characterized by metabolic acidosis with normal plasma anion gap. There are three main forms of RTA: a proximal RTA called type II and a distal RTA (type I and IV). The RTA type II is a consequence of the inability of the proximal tubule to reabsorb bicarbonate. The distal RTA is associated with the inability to excrete the daily acid load and may be associated with hyperkalaemia (type IV) or hypokalemia (type I). The most common etiology of RTA type IV is the hypoaldosteronism. The RTAs can be complicated by nephrocalcinosis and obstructive nephrolithiasis. Alkalinization is the cornerstone of treatment.

[Oncogenic osteomalacia: increased production of fibroblast growth factor 23 is not the unique actor]. / Ostéomalacie oncogénique : le FGF 23 ne fait pas tout.

The importance of fibroblast growth factor 23 (FGF 23) has been highlighted in the mechanism of urinary leakage of phosphate in the oncogenic osteomalacia (OO). It is now a component of diagnosis of this disease. We report a 58-year-old man who presented with osteomalacia and hypophosphatemia secondary to urinary leakage of phosphorus. Although serum FGF 23 was normal, the diagnosis of OO was obtained after another cause of acquired prolonged hypophosphatemia has been excluded (hyperparathyroidism and Fanconi syndrome in particular). The search for a deep tumor was performed, allowing the detection of a 12 mm hemangiopericytoma in the upper thigh. Its removal allowed the rapid resolution of clinical symptoms and laboratory abnormalities. The importance of functional sequelae in OO depends on prompt diagnosis. Tumorectomy remains the optimal treatment. Thus, the search for a secreting tumor is essential even in the absence of elevated serum FGF 23.

Renal excretion of antidiuretic hormone in healthy subjects and patients with renal failure.

Urinary clearance of antidiuretic hormone (ADH) has been measured under basal conditions and during intravenous administration of arginine vasopressin in ten healthy subjects, and only under basal conditions in 18 patients with chronic renal failure and seven patients with acute renal failure at the polyuric phase of the disease. In healthy subjects studied under conditions of mild water diuresis plasma concentration, urinary excretion rate, urinary clearance and fractional clearance of ADH were 3.3 +/- 0.36 pg/ml, 25.2 +/- 5.5 pg/min, 7.5 +/- 1.2 ml/min and 6.4 +/- 1.0% (means +/- SEM) respectively. When plasma ADH was raised to levels between 7 and 26 pg/ml during intravenous administration of the hormone, urinary excretion rate and urinary clearance of ADH increased. Tubular reabsorption of ADH did not reach a plateau but progressively increased in the range of plasma ADH studied. In patients with chronic renal failure, plasma concentration, urinary excretion rate, urinary clearance and fractional clearance of ADH were 2.8 +/- 0.19 pg/ml, 9.4 +/- 2.0 pg/min, 3.4 +/- 0.6 ml/min and 10.0 +/- 2.9% (means +/- SEM) respectively. Urinary excretion rate and urinary clearance were significantly lower than in healthy subjects. In patients with acute renal failure, plasma concentration, urinary excretion rate, urinary clearance and fractional clearance of ADH were 4.6 +/- 0.47 pg/ml, 52.8 +/- 15.8 pg/min, 9.5 +/- 2.7 ml/min and 24.9 +/- 4.4% (means +/- SEM) respectively. Urinary excretion rate and fractional clearance were higher than in healthy subjects and patients with chronic renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Prostaglandin synthesis by glomeruli isolated from rats with glycerol-induced acute renal failure.

In vitro PG synthesis by glomeruli isolated from rats with glycerol-induced acute renal failure (ARF) was measured by radiometric high performance liquid chromatography after incubation with [14C]arachidonic acid and radioimmunoassay (RIA). The four PGs, 6-keto-PGF1 alpha, TXB2, PGF2 alpha, and PGE2 were each synthesized by glomeruli from both control and treated rats but the synthesis rates were greater after glycerol. This increase was not apparent 1 hour after injection but, at 24 hours, all PGs were produced in greater amounts by glomeruli of treated rats. Thus, we studied PGE2, PGE2 alpha, and TXB2 synthesis by glomeruli at various time intervals after induction of ARF using direct RIA, PGF 2 alpha and TXB2 synthesis were greater only at 24 hours and only in the presence of arachidonic acid, whereas PGE2 synthesis was greater at 24 hours, irrespective of arachidonic acid, but at 48 hours only with arachidonic acid. The stimulatory effect of arachidonic acid was always greater in glycerol-treated than in control rats for these three PGs in the later period, whereas a significant decrease for PGE2 was observed at 1 hour. The late increase in PG synthesis may be due to stimulation of the renin-angiotensin system since it was abolished in rats pretreated for 48 hours with captopril. A late increase in PG synthesis by the papilla of the treated rats also was observed. We concluded that any increase in the glomerular production of vasoconstrictor PGs could contribute to the maintenance of acute renal failure, whereas the early fall in the stimulatory effect of arachidonic acid on PGE2 synthesis could play a role in its initiation.

Severe valvular heart disease in patients on chronic dialysis. A five-year multicenter French survey.

A retrospective multicenter survey of the 230 chronic dialysis centers in metropolitan France, conducted between January 1 1998 and December 31 1992, to assess the incidence, causes and features of severe valvular heart disease among chronic dialysis patients, identified 98 patients. The annual incidence was estimated to be 15 to 19 cases per 10,000 dialysed patients. The most common etiologies were calcific valvular disease (69%) and endocarditis (19%). Calcific valvular disease led mostly to aortic stenosis, whereas endocarditis primarily caused mitral insufficiency. Two valves were damaged in 32% of the endocarditis patients versus 9% of those with calcific valvular disease. Sixty-one patients underwent surgery. Median overall survival after surgery was 25 +/- 3.0 months. Patients who underwent surgery for calcific valvulopathy, aortic stenosis or only aortic valve replacement had a median survival of 36 months. Patients who underwent surgery for endocarditis or replacement of 2 valves had a median survival of < 12 months. Actuarial survival of surgical patients differed significantly between: i) the patients for whom presurgical evaluation showed a single valvular lesion and those with multiple valvular lesions (p = 0.002), ii) the patients who had surgery to replace a single heart valve and those who had another type of surgery (p = 0.001), and iii) the patients who had surgery to insert a single aortic prosthetic heart valve and those who had another type of surgery (p = 0.004). Multivariate analysis (including etiologies, number of valvular lesions and type of surgery) showed that survival was significantly dependent only on the number of severe valvular lesions (p = 0.002). Five patients with severe calcific aortic stenosis died before scheduled surgery could be performed. These data suggest that, for patients on chronic dialysis, calcific aortic stenosis is the most frequent form of severe valvular disease. Because aortic stenosis progresses rapidly in these patients and thus quickly leads to irreversible cardiac failure, the operative risk, although high in this population, seems acceptable when only one valve is affected.

[Experience of decentralized informatics at a nephrology unit of a general hospital]. / Expérience d'informatique décentralisée dans un service de néphrologie en hôpital général.

The computerized medical specialized records covering the follow-up of hypertension (ARTEMIS), diabetes (MELLITEE), chronic renal failure and the minimum medical record of Nephrology (THESEE) using the temporal database management system LIED, have been developed in several units of University Hospitals. The authors show that these computerized records are usable in a Nephrology Unit in a General Hospital.

[Glomerulonephritis by glomerular anti-basement membrane antibodies after renal transplantation]. / Glomérulonéphrites à anticorps anti-membrane basale glomérulaire (MBG) après transplantation rénale.

Glomerulonephritis (GN) due to antiglomerular basement membrane (GBM) antibodies after kidney transplantation may be classified into two groups: 1. Recurrent GN are very rare provided circulating anti-GBM antibodies are absent at grafting. If present, linear fixation along the GBM occurs but does not lead to GN in some cases. 2. De novo anti-GBM diseases have been rarely reported. They developed in 8 patients with Alport's syndrome and in at least 3 additional patients in whom hereditary nephritis was not the original disease. A prospective and retrospective study was performed in 54 transplanted patients with hereditary nephritis: circulating anti-GBM antibodies were detected in only one case; linear fixation along the GBM was found but no evidence of GN. The risk of anti-GBM disease after kidney transplantation is low in patients with hereditary nephritis but this complication must be rapidly identified. Its occurrence is probably related to the defect in GBM antigenicity involving the Goodpasture antigen, found in some patients with Alport's syndrome or related hereditary nephritis.