[Is C-reactive protein a marker of inflammation?]. / La CRP est-elle plus qu'un marqueur de l'inflammation?

C-reactive protein (CRP) is the prototype of acute-phase protein which is secreted by the liver in response to a variety of inflammatory cytokines. Levels of CRP can increase up to 1000-fold very rapidly after the onset of inflammation and decrease just as rapidly with the resolution of aggression. CRP is a member of the ancient highly conserved pentraxin family of proteins and it is arranged in a cyclic homopentameric structure. The important role of CRP in innate immunity is largely due to its opsonizing abilities, its capability to activate human complement and to bind to immunoglobulin G receptors. CRP can bind phosphocholine largely present in bacterial membranes, cell membrane and lipoproteins, in addition CRP can recognize nuclear constituent in damaged cells. CRP can activate C3 convertase through the classical pathway but not C5 convertase resulting in generation of opsonic complement fragments. Interactions of CRP with Fc receptors lead to the generation of proinflammatory cytokines and reactive oxygen species by monocyte/macrophage while inhibit neutrophiles functions. Recently, CRP was demonstrated to play an active role in atherogenesis and it has been largely proven that a microinflammatory state as defined by a moderate increase in CRP (up to 3 mg/l), is associated with an increased risk for arterial disease. Moreover it has been postulated that CRP may be a useful tool for monitoring drug therapy.

Microbiological purity of dialysate for on-line substitution fluid preparation.

Dialysate purity has become a major concern in recent years since it was shown that low levels of endotoxin in dialysate were able to induce the production of proinflammatory cytokines, which were putatively implicated in the development of dialysis-related pathology. On-line haemodiafiltration (HDF; or haemofiltration) using the dialysate as the source of substitution fluid magnifies this risk and reinforces the critical role of the dialysate quality to be used. In order to virtually abolish the risk related to dialysate contaminants, it is mandatory to ensure the highest purity of the dialysate used in order that the substitution fluid produced satisfies the quality demands of a sterile and pyrogen-free infusion solution. Ultrapure dialysate production is therefore a common need for all on-line systems where substitution fluid is prepared continuously by sterilizing filtration of the dialysate. However, since dialysate purity plays a role in the complex haemocompatibility interaction which occurs during the haemodialysis session, the use of ultrapure dialysate must be considered as a suitable option for all haemodialysis modalities. To achieve this goal, one must keep in mind that ultrapure dialysate and infusate result from a complex chain of production where ultrapurity and/or sterility of the final solution relies on the weakest or worst component of the chain. Reliable production of ultrapure dialysate and infusate relies on several prerequisites: use of ultrapure water, use of clean electrolytic concentrates, implementation of ultrafilters on specifically designed HDF machines, microbiological monitoring of the chain with adequate and sensitive methods, and hygienic handling of the chain including frequent disinfection to reduce the level of contamination and to prevent biofilm formation. When properly done, the safety and reliability of on-line systems have been confirmed in large clinical studies. It is now time to validate the on-line process in large controlled clinical trials.

Microbiologic purity of dialysate: rationale and technical aspects.

Dialysate purity has become a major concern in hemodialysis since it has been shown that microbial-derived products were stimulating the production and the release of proinflammatory cytokines in hemodialysis patients. This chronic microinflammatory state induced by hemodialysis has been putatively implicated in the development of dialysis-related pathology. In order to prevent risk related to these offenders and to reduce patient/dialysis interaction, it appears highly desirable to use ultrapure dialysis fluid aiming at sterility and apyrogenicity on a regular basis. Ultrapure dialysate results from a complex chain of production where purity grade relies on the weaker link of this chain. Technical aspects and pitfalls in the production of ultrapure dialysate are summarized in this paper. Production of ultrapure dialysate may be achieved on a routine basis, provided adequate components are used, and hygienic handling is regularly ensured. It includes the use of ultrapure water, clean and or sterile electrolytic concentrates (liquid or powder), implementation of ultrafilters on hemodialysis machines, microbiologic monitoring and hygienic handling of the chain with frequent disinfection. Safety and reliability of ultrapure dialysate production relies on a continuous quality assurance process, where results are coupled to corrective action in a feedback loop process.

On-line haemodiafiltration: state of the art.

Faced with the shortcomings of conventional dialysis on a long-term basis, as illustrated by the dialysis-related pathology, a need for a new strategy exists to improve the overall quality of treatment in end-stage renal failure (ESRF) patients. On-line haemodiafiltration (HDF) seems to be the best therapeutic option to achieve this goal at the present time. By enhancing convective clearances through highly permeable membranes, HDF offers the greatest solute fluxes both for low and higher molecular weight uraemic toxins. As for example, in our routinely performed HDF programme based on 3 weekly sessions lasting 3-4 h each, double-pool urea Kt/V achieved was 1.55+/-0.20 and beta2-microglobulin Kt/V was 0.91. By producing substitution fluid from fresh dialysate, the technique of HDF is simplified and becomes economically affordable. By improving the haemodynamic tolerance, HDF allows more elderly and high risk cardiovascular patients to be treated more safely. By using bicarbonate-buffered infusate, HDF facilitates the correction of acidosis. Both by using ultrapure bicarbonate dialysate and down-regulating the membrane reactivity via a 'protein cake', HDF introduces the first step for a full haemocompatibility concept. Finally, by giving access to virtually unlimited amounts of sterile and non-pyrogenic fluid, HDF should introduce new therapeutic options such as a totally automated and feed-back-controlled machine. Today's on-line HDF is already a step forward to enhance the overall efficacy of renal replacement therapy and to improve the global care of ESRF patients.

Amyloidosis-related cauda equina compression in long-term hemodialysis patients. Three case reports.

STUDY DESIGN: These case reports illustrate the neurologic manifestations due to beta 2 microglobulin amyloid deposition at the lumbar spine level in long-term hemodialysis patients. OBJECTIVE: Radiologic investigations suggested the amyloid origin of extradural soft tissue deposition, which was confirmed by histologic examination after surgical excision. SUMMARY OF BACKGROUND DATA: Although cervical myelopathy is a recently recognized complication of long-term dialysis-related beta 2 microglobulin amyloidosis, neurologic manifestations due to amyloid deposition at the lumbar spine level have rarely been reported. METHODS: Three case reports of cauda equina compression in long-term hemodialysis patients are presented. Follow-up radiography, computed tomography, and magnetic resonance imaging were performed and patients underwent surgical decompression of the thecal sac. RESULTS: In two patients, the compression resulted from the development of a destructive spondylarthropathy, and from the infiltration of extradural spaces and ligaments by an abnormal soft tissue. The third patient had lumbar spinal stenosis due to multiple disc protrusion and to hypertrophy of facet joints and ligamentum flavum. Multilevel laminectomies enabled excision of an abnormal fibrous tissue responsible for the thecal sac compression. Histologic examination of the excised fibrous tissues disclosed amyloid deposits in intervertebral discs, apophysial joints, and ligaments. CONCLUSIONS: In long-term hemodialysis patients, cauda equina compression may develop as the consequence of beta 2 microglobulin amyloid deposition in lumbar intervertebral discs, facet joints, and ligaments. Magnetic resonance imaging is well suited to show the extent of the compression and supports the argument for the amyloid origin of extradural soft tissue.

[Angiosarcoma arising from an arterio-venous fistula in a renal transplant recipient. An unusual complication]. / Angiosarcome sur fistule artério-veineuse chez un transplanté rénal. Une complication inhabituelle.

An angiosarcoma arising at the site of an arteriovenous fistula in a renal transplant recipient is reported. Only two similar cases have yet been described. This report is documented with an immunohistochemical study and etiopathogenesis is discussed. Immunosuppressive therapy and the arterio-venous fistula might both be involved in the occurrence of this neoplasm. We focus attention on this uncommon complication which should always be entertained when a renal transplant recipient complains about a painful arterio-venous fistula.

Extensive necrotizing livedo reticularis in a patient with chronic renal failure, hyperparathyroidism and coagulation disorder: regression after subtotal parathyroidectomy.

Necrotizing livedo reticularis is an infrequent, life-threatening complication of chronic renal failure. Since Selye's studies in 1962, calciphylaxis, i.e. acute calcium deposition in tissue, is considered the main pathomechanism, especially because hyperparathyroidism are very frequently present. However, other etiological and/or triggering factors, such as coagulation disorders, direct cellular toxicity of parathormone or calcium on endothelium, might be involved, acting perhaps in a cumulative way. We report a case with a circulating anticoagulant which supports this hypothesis.

[Necrotic angiodermatitis revealing a secondary hyperparathyroidism due to chronic renal insufficiency: healing after subtotal parathyroidectomy]. / Angiodermite nécrotique révélatrice d'une hyperparathyroïdie floride secondaire à une insuffisance rénale chronique: guérison après parathyroïdectomie subtotale.

Severe skin necrosis of poor prognosis have been rarely reported among chronic renal failure patients. Their clinical outbreak must rapidly lead to search for a secondary hyperparathyroidism. Early parathyroidectomy seems is the only treatment able to stop the progression of the skin lesions. From an original clinical observation we discuss the different mechanisms involved.

[Amanita proxima poisoning: a new cause of acute renal insufficiency]. / Intoxication par Amanita proxima: une nouvelle cause d'insuffisance rénale aiguë.

To our knowledge Amanita proxima poisoning has never been reported. Amanita proxima is a mushroom seldomy encountered, similar to a common and edible species: Amanita ovoïdae. During October 1992, we had the opportunity to care for five cases of intoxications with Amanita proxima. In all cases early digestive disorders, cytolytic hepatitis and acute renal failure were noted. Outcome was favourable for all patients within three weeks with total recovery of both renal and hepatic functions with symptomatic treatment. Temporary dialysis was required in four patients.

[Temporary vascular access: from peripheral to central, from temporary to permanent]. / Accès vasculaire temporaire: du périphérique au central, du temporaire au permanent.

Temporary vascular access (TVA) is a basic requirement in clinical nephrology. TVA permits immediate and repeated hemodialysis for all type of ESRD patient. Going from peripheral to central and from temporary to permanent angioaccess are the two main trends observed in TVA in contemporary dialysis. Our experience over the last decade illustrates this TVA changes. On the one hand peripheral arterio-venous shunt has been forsaken in favour of percutaneous implanted central venous catheters. On the other hand, two types of central venous catheters have been used covering up our preferences: catheters for short term use (< 7 days) usually via femoral vein and catheters for long term use (7 days to months) mainly via the internal jugular vein. Due to traumatic and/or long term mechanical risks (venous stenosis and/or thrombosis), the subclavian way has been abandoned in our unit. Performances (blood flow rate 250-350 ml/min, recirculation rate 9-12%) obtained in about 1500 patients warranted dialysis efficiency. Traumatic and/or mechanic lesions were the most frequent complications observed with the femoral catheter, while infection remained the most important one associated with the long term use of jugular vein catheters. Therefore, it is clear that over the last decade temporary vascular access was becoming synonymous with percutaneous central venous catheter. Such an approach has greatly simplified the task of physicians while facilitating the management of large uremia treatment program.

Endosulfine, an endogenous peptidic ligand for the sulfonylurea receptor: purification and partial characterization from ovine brain.

Antidiabetic sulfonylureas act through receptors coupled to ATP-dependent potassium channels. Using the binding of [3H]glibenclamide, a highly potent sulfonylurea, to rat brain membranes to follow the purification procedure, we extracted from ovine brain, purified, and partially characterized two peptides that are endogenous ligands for the central nervous system sulfonylurea receptors. These peptides, referred to as alpha and beta endosulfine, differ by their isoelectric points, the beta form being more basic. Each form of endosulfine is recognized equally by the sulfonylurea receptors from the central nervous system and from insulin-secreting beta cells. In the same concentration range that is active on the receptors, beta endosulfine releases insulin from a beta-cell line. Endosulfine is a good candidate for being implicated in the physiology of beta cells and their disorders (e.g., type II diabetes) and in certain pathologies related to modifications of ion fluxes.

[Parvovirus B19 infection revealed by acute renal insufficiency]. / Infection à parvovirus B19 révélée par une insuffisance rénale aiguë.

Human adult Parvovirus B19 infection is a well known disease most frequently seen in haematology and cancerology. To our knowledge, however, renal involvement in this context has never been reported. A case of severe infection caused by this virus is reported, where multiple organ involvement is associated with acute renal failure. The outcome was favourable with temporary dialysis and symptomatic treatment. Mechanisms of renal failure, presumably multifactorial, are discussed in the light of this case.

[Dilated cardiomyopathy during post-partum hemolytic and uremic syndrome (HUS)]. / Cardiomyopathie dilatée au cours d'un syndrome hémolytique et urémique (SHU) du post-partum.

A 24-year-old woman presented a severe HUS followed 3 months later by a cardiac failure diagnosed echographically as a dilated cardiomyopathy. The patient was hemodialysed and successfully transplanted. Later course of dilated cardiomyopathy was favourable. Review of literature confirms the rare and severe nature of cardiac lesions occurring in the course of HUS. We suggest a related pathophysiology concerning these two entities.