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Les Articles version anglaise - Renal Involvement in Systemic Lupus Erythematosus

Introduction

The kidneys filter the blood and remove the waste product in the urine. Small kidney filters, called "glomeruli", let through water, salt and waste, but don't let the albumin and blood cells. In the systemic lupus erythematosus, glomeruli can be damaged by the deposit of antibodies and by an inflammatory of up destruction. It let go then albumin in the urine (sometimes in large quantities, with drop of blood albumin, it's called "nephrotic syndrome" and tend to retain water and salt (which can caused elevation of blood pressure and edema). We refer to "lupus nephritis" or "lupus glomerulonephritis".

The Renal Involvement of Lupus is it frequent?

The renal involvement of lupus concerned 20 to 30% of patients with systemic lupus erythematosus in France. Subjects with black skin have an increased risk of developing a renal lupus. This involvement may be present early in the disease, or secondarily appear in a patient followed for joint or hematologic lupus skin lesions.

What are the signs of Renal Involvement with Lupus?

Renal disease lupus can occur when skin or joint flare of the disease, but can also occur in the isolated way. It can manifest itself by appearance edema (swelling of the feet) headaches (associated an outbreak of blood pressure) or severe fatigue, or be discovered after venous thrombosis....But it can manifest without the patient doesn't feel any particular symptom : the renal involvement isn't painful, the amount and colour of urine can be normal. Lupus nephritis is most often detected by doctor in charge of the follow-up in front of abnormalities in the urinary strip (presence of proteins, blood, or leukocytes in urine, see box), or on laboratory examinations of blood test (increased blood creatinine) and urinary (proteinuria, presence of red bloods cells or white blood cells in the ECBU).

Is it serious to have a Renal  Involvement with Lupus?

The renal involvement is a severe manifestations of lupus, but we must distinguish several forms, which all don't have the same severity and don't require the same treatment. In the severe cases; there is a risk of kidney failure (impaired kidney function) which can required a dialysis, temporary or prolonged need for a kidney transplant. Nevertheless, most of patients, even with those severe renal impairment, respond well to treatment and don't develop renal failure. Renal involvement of lupus can also have a negative effect on the life expectancy of patients, in particularly important in patients with lupus nephritis. In addition to clinical examination and laboratory tests, exam to distinguish severe forms of the less severe forms of lupus nephritis is the kidney biopsy.

What is Nephritis Kidney biopsy?

The renal biopsy is used to study the microscopic renal impairment of a patient with lupus, confirmed that this attack is linked to lupus, and to determine the severity to guide treatment. Only a kidney biopsy (disease affecting the symmetrically way the two kidneys) and two fragments (each one about the size of a rice grain) are removed for anatomopathologic analysis. This exam is done Under local anaesthesia and is usually not painful. The patient is lying on his stomach, the nephrologist mark by ultrasound and aesthetic skin, subcutaneous tissue, muscle, the casing that surrounds the kidney. Two fragments (the size of a rice grain) are removed with a biopsy gun for single use, which is painless because there is no sensory nerve in the kidney. Then the patient is at rest until the next day, his blood pressure and the colour of his urine is monitored.

(http://www.soc-nephrologie.org/PDF/enephro/recommandations/SN/PBR.pdf).

The results obtained after a few days will guide treatment . Thus, there are severe forms called "proliferative" and "non proliferative" with a less severe forms. This exam can also distinguish the "chronic" injuries (sequelae of old flares of disease and does not require modification of the immunological treatment) lesions "active".

What are the treatments for Lupus Nephritis?

The proposed treatments depend on the severity of the renal involvement, as assessed by clinical, laboratory tests (existence of renal failure, nephrotic syndrome) and a renal biopsy.

A. Lupus Nephropathy Severe or "proliferative" requires treatment to calm the immune system attack (treatment "immunosuppression). This treatment is done in 2 phases :

  1.  An attack phase, which lasts between 3 and 6 months, with the aim to obtain remission. The drugs currently used for this phase are the corticosteroids, associated with cyclophosphamide (which is usually made in infusion every 15 days  during 3 months) or Cellcept (which it takes into tablets morning and evening).
  2. A maintenance phase, which lasts at least 2 years, to prevent relapse. The medicine currently used in this phase are Cellcept (in tablet morning and evening) or Imurel (in tablets evening), often associated with low-dose by corticosteroids, and still continuing the Plaquenil. We don't know now if it's necessary to continue the maintenance immunosuppressive treatment over 2 years and the study "WIN-Lupus" is being conducted at the National Level to answer to this issue (http://www.socnephrologie.org/enephro/protocoles/WIN-lupus.htm).

B. Lupus Nephropathy Proliferative don't need immunosuppressive therapy (except in some clinically severe forms), but the continuation of Plaquenil associated to "nephro-protective" treatment.

The nephroprotective treatment is prescribed in all Lupus Nephropathy, in a severe renal involvement or not. It's based on the family of drugs "ACE" (Angiotensin Converting Enzyme), which decrease the amount of protein in the urine. This is drug of hypertension, but it can be prescribed even in patient with normal blood pressure, to decrease the pressure in the glomeruli and protect renal function in the long term.

What is the surveillance when there is a Renal Involvement of Lupus?

In case of Renal Infringement, after the first weeks of attack treatment where the surveillance is close, the follow-up in the first years is usually done every 3 months for consultation, with control of blood pressure, blood test and urine analysis.

This monitoring is to check the proper answer to the immunosuppressive therapy, no relapse of the disease and to monitor the potential side effects of the treatment. We are particularly vigilant to the risk of infections, because a patient treated with immunosuppressive, for example a cough or a fever, can be a potentially serious infection. That's why vaccination against flu and pneumococcus is recommended in patient with Renal Lupus. Bactrim treatment is often prescribed for prevention of severe pulmonary infection (PCP) during immunosuppressive therapy attack. Moreover, to reduce the risk of osteoporosis related to corticosteroids treatment, a treatment by calcium and vitamin D is often prescribed. Finally, it's important to prevent pregnancy as a remission of Renal disease is not obtained and Lupus well stabilize. 

What are the risks in relation to pregnancy?

Renal Lupus Flare may occur during pregnancy and can be difficult to distinguish from a non lupic disease of a pregnancy, preeclampsia (which is also manifest by high blood pressure and albumin in urine). To avoid those flares during the pregnancy, it's now recommended to continue Plaquenil in patients with lupus during the pregnancy. For women having a kidney flare and wishing to carry a pregnancy , the pregnancy should be planned with the medical specialist (nephrologist or internist) in accordance with the team of obstetricians trained. Some drugs must be replaced (such as Cellcept which must be replaced by Imurel before pregnancy) or be stopped (in particularly IEC) before the pregnancy. To consider a pregnancy, Lupus, and in particular Renal disease must be in remission since 12 to 24 months. Pregnancy can indeed worsen a preexistent Renal Impairment and a Renal Impairment can have an effect on the evolution of pregnancy . When the pregnancy is well planned and followed, it generally proceeds normally.

Where is Research in Lupus Nephritis?

We don't yet know cured Lupus (we talk about "remission"), but current treatments allow to obtain a good answer at the majority of the patients having a Lupus Nephritis. Now the objective is to reduce side effects of these treatments, while avoiding the relapses. Clinical trials have shown that we could use to Endoxan lower doses than in the past, or use Cellcept to avoid infusions. Other studies are underway to study if doses of corticosteroids can be reduced in severe disease such as Renal Impairment.

The study WIN-Lupus is also part in this process of reduces treatments. It compares 2 strategies in stable patients, treated by Plaquenil, who are in remission : the stop of the immunosuppressive maintenance therapy (Cellcept or Imurel) during 2 years, against the continuation of this treatments until 4 years. Currently these 2 strategies are used by the specialists of the Lupus, and WIN-Lupus make possible to know if one is better than the other (less relapses, or, less side-effects).

Lupus is a heterogeneous disease, which can evolve in a different way among patients. The research also focuses on blood biomarkers or urinary which can make possible to evaluate at a given patient, the disease activity, to personalize the care by anticipating flares or otherwise authorizing the reduction in the treatment. Concerning Renal Lupus, it doesn't exist yet biomarker to replace renal biopsy to evaluate the severity of Lupus Nephritis, but many groups such as GCLR (Cooperative Group on Lupus Renal), seek to identify these biomarker.

The research also focuses on the cardiovascular prevention among lupus patients, in particular for patients in dialysis or renal transplant.

 

Dr Noemie JOURDE- CHICHE Aix-Marseille University

The Nephrology Department of Pr BERLAND. Conception Hospital

 

 


Date de création : 08/10/2014 . 14:43
Dernière modification : 30/11/2015 . 12:37
Catégorie : Les Articles version anglaise
Page lue 2078 fois


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