EMC - Néphrologie最新文献

Most nephropathies are characterized by a progression that may result in end-stage renal failure (ESRF). Apart from the specific treatment implemented when possible, ESRF may be delayed by nephroprotective therapy. Following the definition of the risk factors likely to induce progressive renal disease, the various therapeutic strategies that may play a nephroprotective role are reviewed. The potential results are described with regard to published data, in particular randomised trials, as recommended by the evidence-based medicine principles. Blockade of the renin-angiotensin system plays a major role in terms of nephroprotection. However, this strategy should not replace lifestyle measures and pharmacological treatment of the metabolic disorders associated to nephropathies.

Renal involvement is relatively common in certain systemic autoimmune diseases, but can be clinically silent. Active surveillance is, therefore, essential because the early recognition of renal involvement may influence the extent of renal recovery. Blood pressure control is also essential, regardless of the underlying disease. In systemic lupus erythematosus, therapy usually depends on the renal biopsy findings as not all forms of renal involvement respond in the same way. Typically, for aggressive disease, therapy is with steroids and a cytotoxic agent, usually cyclophosphamide initially and then azathioprine. In systemic vasculitis with renal involvement, a similar approach is adopted, therapy including steroids and cyclophosphamide initially and then steroids and azathioprine. With severe fulminant disease, plasma exchange or pulsed intravenous methylprednisolone is added initially. Scleroderma renal crises are managed by blood pressure control using angiotensin-converting enzyme inhibitors and other agents as required. Dialysis and transplantation can be successful in these conditions.

Diuretics are pharmacological agents that increase natriuresis through inhibition of tubular re-absorption of sodium. The mechanism and site of this inhibition differ with each drug class, accounting for their additive effects on natriuresis increase and for their hydroelectrolytic side effects. The response to a given diuretic dose depends on the diuretic concentration in the urine at its action site. This concentration may be decreased by pharmacokinetic factors such as those encountered in renal insufficiency or in the nephrotic syndrome. These resistance mechanisms of diuretics may be corrected by dose increase, previous diuretic fixation on albumin or warfarin administration. Once these mechanisms are opposed, the diuretic concentration for maximal efficacy is reached at its action site and the natriuresis obtained has the normal maximal plateau. This is not the case when an oedematous systematic disease with effective hypovolemia is present, like in heart failure or cirrhosis, or when chronic use of loop diuretics has induced a hypertrophy of the more distal parts of the tubule. In these cases, a pharmacodynamic resistance exists, resulting in a lower maximal natriuresis plateau in spite of adequate concentration of the diuretic at its action site, even in the absence of pharmacokinetic resistance factors. The main indications of diuretics are systemic oedematous disease and hypertension. In the oedematous diseases, diuretic indication is both straightforward and sufficient only if effective hypervolemia is present. The therapeutic approach is discussed according to the various clinical conditions and pathophysiological background. In uncomplicated hypertension, diuretics are the cornerstone of the therapy. The most suitable diuretic treatment for hypertension is an association of low dose thiazide (12.5-50 mg/day) with potassium sparing diuretics. Rare indications of diuretics are also reviewed.

Extra-membranous nephropathy is characterised by immune complex deposits on the external side of the basement membrane. Activation of complement and oxidation pathways lead to basement membrane lesions. The most frequent form is idiopathic. At 5 and 10 years, renal survival is respectively around 90 and 65 %. A prognostic model can be based on the level and duration of proteinuria and the rate of progression of renal insufficiency on several months. Excretion of C5b-9, β2 microglobulin and IgG are strong predictors of outcome. Symptomatic treatment is based on anticoagulation if the patient has a nephrotic syndrome, conversion enzyme inhibitor, angiotensin II antagonist, statins, antioxidant and pentoxyfilline. Immunosuppressors are discussed for patients with bad prognostic factors. Corticosteroids alone are not indicated. Treatment must include corticosteroids and an alkylant agent for a minimal duration of 6 months. This treatment lessens proteinuria but evidence is still lacking about long term renal prognosis. Some patients with renal failure at the initiation of treatment experience slowered progression of renal failure. Cyclosporine also allows an improvement of proteinuria but there is no definite evidence for an improvement in long-term renal prognosis.

Acute renal failure (ARF) in pregnancy includes all causes of acute impairment of renal function, from the beginning of pregnancy to delivery. The threshold-level of plasma creatinin that indicates ARF in the pregnant woman is lowered to 80 μmol l^–1 due to the physiological increase of the glomerular flow during normal pregnancy. In clinical practice, specific pregnancy ARFs follow a bi-modal distribution: ARFs of the 1^st trimester include those ARFs associated to septic abortions and gravidic emesia. 3^rd trimester ARFs include essentially those renal complications related to severe pre-eclampsia and, more exceptionally, to acute gravidic steatosis. The other causes of ARFs remain more rare. In countries where abortion is legal and where pregnancies are bound to strict follow-up, the incidence of this dangerous obstetrical complication has considerably regressed (from 1/ 3,000 births to less than 1/ 20,000). This incidence remains highly variable from a country to another, and differs according to the local legislation. The vital prognosis, both for the foetus and the mother, is related to the earliness of the diagnosis, and the rapidity of treatment initiation. The management of such patients at the 3^rd trimester of pregnancy should be undertaken in a sanitary environment fully equipped with follow-up and treatment means, both for the mother and the foetus, and combining competences in obstetrics, paediatrics, nephrology, and intensive care as well. Gestational ARF is to be suspected in any case of increased creatinin level (>80 μmol l^–1) and/ or oliguria since the blood creatinin level is normally lowered during pregnancy.

Polyuria is defined as a urine flow rate greater than 3 l per day. A water balance disorder (natremia disorder) appears when polyuria and fluid load are not adequately adapted. Major complications can thus occur. Diagnostic approach is essential in order to adapt treatment and consists of determining whether polydipsia is primary and responsible for polyuria or polyuria is primary (diabetes insipidus or solute diuresis) and responsible for polydipsia.