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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aggressive immunosuppressive therapy should be considered for patients with proliferative lupus nephritis as the risk for progression to end stage renal disease is high. Intermittent intravenous cyclophosphamide therapy improves renal survival; longer duration of therapy is associated with fewer relapse of nephritis and decreased risk of diminished renal function. While azathioprine therapy does not differ statistically from steroids alone in prolonging renal survival, this therapy may be considered in patients with few risk factors for progression to renal insufficiency. Methylprednisolone as a single therapy does not prolong renal survival compared with regimens including cyclophosphamide. Plasmapheresis remains under study but has not shown additional benefit in treatment of severe lupus nephritis. The potential roles for cyclosporin A and mycophenylate mofetil in the therapy of proliferative lupus nephritis remain to be defined. Supportive care including rigorous control of hypertension, consideration of angiotensin receptor inhibition or blockade to reduce proteinuria and prolong renal function, control of hyperlipidemia, prevention of osteoporosis, and prevention of pregnancy remain important clinical goals. Current research efforts focus on genetic and socioeconomic factors involved in racial differences in expression of lupus nephritis, hormonal manipulation to preserve gonadal function during cyclophosphamide therapy, and the potential impact on lupus activity of estrogen-containing oral contraceptives or postmenopausal hormone replacement therapy.
Lupus 1998
PMID:Immunosuppressive therapy of lupus nephritis. 988 1

The therapeutic approach to patients with membranous lupus nephropathy (MLN) remains controversial. We have attempted combination therapy for MLN. Five patients with MLN (WHO class Va and Vb) and nephrotic syndrome were treated with 1 g methylprednisolone intravenously for 3 consecutive days followed by daily prednisolone at the dose of 30-40 mg plus cyclosporine at the dose of 100-200 mg and angiotensin receptor blocker(40 mg of valsartan). Initial dosage prednisolone was given for 1 month, and then tapered gradually in terms of dosage and interval. These patients were followed up for a minimum of 12 months. Complete remission was obtained in 4 patients after a mean of 7.3 +/- 2.1 months, and partial remission was obtained in the remaining patient. Daily prednisolone dosage significantly decreased from a baseline mean of 0.69 +/- 0.11 mg/kg to a mean of 0.10 +/- 0.02 mg/kg at the last follow-up. Lupus activity, as measured by SLE disease activity index, significantly decreased in all patients. Serum creatinine level and blood pressure remained stable. It was concluded that quadritherapy, including intravenous methylprednisolone, prednisolone, cyclosporine, and angiotensin receptor blocker, was beneficial in inducing remission of nephrotic syndrome, reducing lupus activity, and sparing prednisolone dosage with an acceptably low risk for side effects.
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PMID:[Quadritherapy with cyclosporine for membranous lupus nephropathy]. 1463 64

Lupus nephritis is a common complication of systemic lupus erythematosus (SLE). Early recognition of lupus nephritis requires routine serum creatinine determination, urinalysis and urinary microscopy. Since mild urinary abnormalities such as leucocyturia or proteinuria can be associated with severe lupus nephritis, a renal biopsy is usually indicated in patients with SLE and urinary abnormalities. A renal biopsy is required to determine the class of lupus nephritis which is based on histopathological criteria which have recently been revised. Aggressive immunosuppressive therapy is indicated in diffuse proliferative lupus nephritis. In class III or class V the treatment indication depends on additional prognostic criteria. Intravenous cyclophosphamide is still used but doses and intervals have been modified based on large clinical trials. Mycopheno-late may establish as an alternative for cyclophosphamide in the induction phase, but the data of the transcontinental multicenter Aspreva Lupus Management Study (ALMS) trial have not yet been published in detail. Controlled clinical trials support the use of azathioprine and mycophenolate for maintaining remission of lupus nephritis, and cyclophosphamide is no longer used in that phase. Additional control of cardiovascular risk factors and combined angiotensin and angiotensin receptor blockade are mandatory for all proteinuric SLE patients. Novel treatment options are ahead of us based on the molecular mechanisms of SLE and lupus nephritis, but as evidence from controlled clincial trials is still lacking they are not yet approved for broad clinical use. However, the treatment options for severe lupus nephritis have been improved and are likely to further improve in the near future.
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PMID:Lupus nephritis. 1829 86

Studies in humans and animal models indicate a key contribution of angiotensin II to the pathogenesis of glomerular diseases. To examine the role of type 1 angiotensin (AT1) receptors in glomerular inflammation associated with autoimmune disease, we generated MRL-Faslpr/lpr (lpr) mice lacking the major murine type 1 angiotensin receptor (AT1A); lpr mice develop a generalized autoimmune disease with glomerulonephritis that resembles SLE. Surprisingly, AT1A deficiency was not protective against disease but instead substantially accelerated mortality, proteinuria, and kidney pathology. Increased disease severity was not a direct effect of immune cells, since transplantation of AT1A-deficient bone marrow did not affect survival. Moreover, autoimmune injury in extrarenal tissues, including skin, heart, and joints, was unaffected by AT1A deficiency. In murine systems, there is a second type 1 angiotensin receptor isoform, AT1B, and its expression is especially prominent in the renal glomerulus within podocytes. Further, expression of renin was enhanced in kidneys of AT1A-deficient lpr mice, and they showed evidence of exaggerated AT1B receptor activation, including substantially increased podocyte injury and expression of inflammatory mediators. Administration of losartan, which blocks all type 1 angiotensin receptors, reduced markers of kidney disease, including proteinuria, glomerular pathology, and cytokine mRNA expression. Since AT1A-deficient lpr mice had low blood pressure, these findings suggest that activation of type 1 angiotensin receptors in the glomerulus is sufficient to accelerate renal injury and inflammation in the absence of hypertension.
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PMID:Glomerular type 1 angiotensin receptors augment kidney injury and inflammation in murine autoimmune nephritis. 1928 96

This review focuses on events subsequent to planning a pregnancy and addresses three components of concern for women with systemic lupus erythematosus: maternal, placental, and fetal. Flare rates are generally low for patients who are clinically stable at conception. For patients who have never had renal disease, there is no frm evidence that they will develop active renal disease simply due to being pregnant. For patients who begin pregnancy with an abnormal creatinine (> 2 mg/dl is ill advised), risks include hypertension, preeclampsia, high rate of fetal loss, and possible further deterioration of renal function. Discontinuation of angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and mycophenalate is mandatory. Elevated levels of sVEGF-1 may be a harbinger of preeclampsia. For patients with anti-phospholipid antibodies detected in the frst trimester of pregnancy, the lupus anticoagulant per se may be the strongest predictor of pregnancy complications. For women with anti-SSA/Ro antibodies the risk of having a child with congenital heart block is 2% which rises to a recurrence rate of 18%. Information on current approaches to prevention and treatment of heart complications of neonatal lupus is provided.
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PMID:Updates on lupus and pregnancy. 1985 49

Since most lupus nephritis patients have an incomplete response to mycophenolate mofetil, combination regimens may improve outcomes. Tacrolimus (FK506) has shown some benefit in lupus nephritis in small trials, and combined with mycophenolate mofetil is standard immunosuppression in transplant patients. We investigate the addition of FK506 to mycophenolate mofetil, in patients who were mycophenolate mofetil failures. All patients were part of a prospective cohort, but evaluated retrospectively. Seven lupus nephritis patients (mean age 27.1, 100% female, 42% Caucasian and 42% African American) were evaluated. Three patients had combined ISN class III and V, two ISN class IV, one ISN class V and II and one ISN class IV and V. Six were taking an ACE-inhibitor or angiotensin receptor blocker, 6 hydroxychloroquine and 5 prednisone (mean dose 11.5 mg; range 0-30 mg). Mean mycophenolate mofetil dose at time of tacrolimus addition was 2.8 g (range 2-3 g). Mean tacrolimus dose was 3.4 mg (range 2-8 mg) titrated to a mean level of 4.67 ng/dl (range 2.2-11.8 ng/dl) for a mean of duration of 16 months (range 2-54 months). Two patients continued both therapies, while five discontinued therapy. One patient achieved a complete renal remission, while three achieved partial remission with 82.9%, 77.1%, 55.3% reductions in proteinuria. Toxicity limited the use of combination therapy: diabetic ketoacidosis (one patient), pneumonia (two) and muscle pain (two). These data suggest that adding tacrolimus in patients refractory to mycophenolate mofetil might have some benefit, although complete responses were rare. Unfortunately, tacrolimus toxicity appeared to be prevalent in these systemic lupus erythematosus patients, limiting its long term use.
Lupus 2010 Jul
PMID:Combination therapy of mycophenolate mofetil and tacrolimus in lupus nephritis. 2038 22

We report on an 11-year-old girl who developed steroid-resistant nephrotic syndrome (NS) at the onset of systemic lupus erythematosus (SLE), and clinical and renal histological findings suggested that her NS would be associated with SLE-related podocytopathy. Although initial treatment with intravenous pulse methylprednisolone was ineffective, following treatment with cyclosporine and an angiotensin receptor blocker was effective for her nephrotic proteinuria. She had developed posterior reversible encephalopathy syndrome (PRES), and mycophenolate mofetil (MMF) was started instead of cyclosporine. At present, 45 months after the onset, she is in remission of both NS and SLE. This case indicates that NS associated with SLE-related podocytopathy should be included in the spectrum of glomerulopathy accompanying SLE, also in the pediatric population.
Lupus 2014 Jun
PMID:A case of steroid-resistant nephrotic syndrome associated with systemic lupus erythematosus. 2218 62

The members of the organic anion transporting polypeptide superfamily (OATPs) are classified within the SLCO solute carrier family. All functionally well characterized members are predicted to have 12 transmembrane domains and are sodium-independent transport systems that mediate the transport of a broad range of endo- as well as xenobiotics. Substrates are mainly amphipathic organic anions with a molecular weight of more than 300Da, but some of the known transported substrates are also neutral or even positively charged. Among the well characterized substrates are numerous drugs including statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antibiotics, antihistaminics, antihypertensives and anticancer drugs. Based on their amino acid sequence identities, the different OATPs cluster into families (in general with more than 40% amino acid sequence identity) and subfamilies (more than 60% amino acid identity). With the sequencing of genomes from different species and the computerized prediction of encoded proteins more than 300 OATPs can be found in the databases, however only a fraction of them have been identified in humans, rodents, and some additional species important for pharmaceutical research like the rhesus monkey (Macaca mulatta), the dog (Canis lupus familiaris) and the pig (Sus scrofa). These OATPs form 6 families (OATP1-OATP6) and 13 subfamilies. In this review we try to summarize what is currently known about OATPs with respect to endogenous substrates, tissue distribution, transport mechanisms, regulation of expression, structure-function relationship and mutations and polymorphisms.
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PMID:The SLCO (former SLC21) superfamily of transporters. 2350 80

The present review examines the types of hypertension that women may suffer throughout life, their physiopathological characteristics and management. In early life, the currently used low-dose oral contraceptives seldom cause hypertension. Pregnancy provokes preeclampsia, its main medical complication, secondary to inadequate transformation of the spiral arteries and the subsequent multisystem endothelial damage caused by deportation of placental factors and microparticles. Hypertension in preeclampsia is an epiphenomenon which needs to be controlled at levels that reduce maternal risk without impairing placental perfusion. The hemodynamic changes of pregnancy may unmask a hypertensive phenotype, may exacerbate a chronic hypertension, or may complicate hypertension secondary to lupus, renovascular lesions, and pheochromocytoma. On the other hand a primary aldosteronism may benefit from the effect of progesterone and present as a postpartum hypertension. A hypertensive pregnancy, especially preeclampsia, represents a risk for cardiac, vascular and renal disease in later life. Menopause may mimic a pheochromocytoma, and is associated to endothelial dysfunction and salt-sensitivity. Among women, non-pharmacological treatment should be forcefully advocated, except for sodium restriction during pregnancy. The blockade of the renin-angiotensin system should be avoided in women at risk of pregnancy; betablockers could be used with precautions during pregnancy; diuretics, ACE inhibitors and angiotensin receptor antagonists should not be used during breast feeding. Collateral effects of antihypertensives, such as hyponatremia, cough and edema are more common in women. Thus, hypertension in women should be managed according to the different life stages.
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PMID:[Hypertension in women]. 2373 98

Lupus nephritis (LN) is an inflammatory condition of the kidneys that encompasses various patterns of renal disease including glomerular and tubulointerstitial pathology. It is a major predictor of poor prognosis in patients with systemic lupus erythematosus (SLE). Genetic factors, including several predisposing loci, and environmental factors, such as EBV and ultraviolet light, have been implicated in the pathogenesis. It carries a high morbidity and mortality if left untreated. Renal biopsy findings are utilized to guide treatment. Optimizing risk factors such as proteinuria and hypertension with renin-angiotensin receptor blockade is crucial. Immunosuppressive therapy is recommended for patients with focal or diffuse proliferative lupus nephritis (Class III or IV) disease, and certain patients with membranous LN (Class V) disease. Over the past decade, immunosuppressive therapies have significantly improved long-term outcomes, but the optimal therapy for LN remains to be elucidated. Cyclophosphamide-based regimens, given concomitantly with corticosteroids, have improved survival significantly. Even though many patients achieve remission, the risk of relapse remains considerably high. Other treatments include hydroxychloroquine, mycofenolate mofetil, and biologic therapies such as Belimumab, Rituximab, and Abatacept. In this paper, we provide a review of LN, including pathogenesis, classification, and clinical manifestations. We will focus, though, on discussion of the established as well as emerging therapies for patients with proliferative and membranous lupus nephritis.
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PMID:Lupus nephritis: an update. 2647 Oct 17


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