Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lupus nephritis remains a major cause of morbidity and mortality in patients with systemic lupus erythematosus. Although the renal prognosis has improved, the optimal therapeutic regime has not been definitively established, and significant challenges remain in the management of disease progression and recurrent renal relapse. We performed a prospective study to evaluate the outcome of 38 patients with severe lupus nephritis treated with standard cyclophosphamide and methylprednisolone pulse therapy, and to determine the variables associated with poor outcome. Five patients developed end-stage renal disease (ESRD) (13%), 10 (26%) developed persistent proteinuria (> 1 g/24h) and 15 (39%) suffered at least one relapse after 8 years of follow-up. A high chronicity index, interstitial fibrosis (P = 0.04), persistent hypertension (P < 0.0001) and hypocomplementaemia (P = 0.002) after treatment were the major variables associated with ESRD. Tubular atrophy (P = 0.01), persistent hypertension (P = 0.0001) and hypocomplementaemia after treatment (P = 0.0281) were associated with persistent proteinuria. Persistence of anti-dsDNA antibodies and hypocomplementaemia after treatment (P = 0.0118) were associated with renal relapse. Our data suggest that the group of patients with persistence of hypocomplementaemia and raised anti-dsDNA antibodies titres are at high risk of renal relapse and may be candidates for continuation of immunosuppressive treatment. Patients with persistent proteinuria alone or a high chronicity index are less likely to respond to immunosuppression, and strict control of the hypertension may be the best approach.
Lupus 2003
PMID:Predictors of poor renal outcome in patients with lupus nephritis treated with combined pulses of cyclophosphamide and methylprednisolone. 1272 52

We have explored the therapeutic potential of statins in patients with different inflammatory rheumatic diseases refractory to conventional therapy. We found that simvastatin (80mg o.d. for eight days) induced a rapid and significant reduction in proteinuria levels in three systemic lupus erythematosus (SLE) patients. A similar kind of therapy had a marked beneficial effect in a patient with Wegener's granulomatosis and a patient with erythema nodosum. On the other hand, five patients with rheumatoid arthritis (RA) who received atorvastatin for eight days (20mg/day) showed reduction in C-reactive protein levels and a clinical improvement that was classified as an ACR20 response. Prior to the administration of statins, all these patients had received aggressive conventional therapy with no satisfactory response. A significant reduction in spontaneous apoptosis of peripheral blood lymphocytes and expression of CD69 and HLA-DR was observed in SLE patients after simvastatin therapy. These results prompted us to perform a pilot short-time comparative (simvastatin versus chloroquine) open clinical trial in 15 patients with RA who were receiving methotrexate as a single disease modifying antirheumatic drug with no satisfactory response. Most patients (9/10) who received simvastatin (40mg/day) showed an ACR50 or better response after eight weeks, whereas such a response was not observed in any patient (0/5) treated with chloroquine. Our preliminary results indicate that statins may be an important therapeutic tool for the treatment of inflammatory rheumatic diseases.
Lupus 2003
PMID:Therapy with statins in patients with refractory rheumatic diseases: a preliminary study. 1294 19

The majority of patients seen at the renal clinic of the University Hospital of the West Indies (UHWI) are of African descent. The case notes of patients with systemic lupus erythematosus (SLE) with class 4 nephritis and who were given standard pulse intravenous cyclophosphamide therapy during the period 1990-2000 were retrospectively reviewed. Primary outcomes were doubling of serum creatinine and development of end stage renal disease (ESRD). Secondary outcomes were return of proteinuria to normal and renal remission. A total of 117 patients had a renal biopsy for SLE nephritis at the UHWI between 1990 and 2000. Of the patients, 34 (29%) had diffuse proliferative glomerulonephritis (WHO class 4), of which 29 were reviewed. Twenty-two patients of 24 in whom it was measured (92%) had significant proteinuria at presentation. The 24-hour proteinuria was measured at final review in 16 patients and in 10 patients it went into complete remission. At the beginning of therapy, 24 patients (83%) had renal impairment. Of the 18 who had final creatinine values, the renal function returned to normal in eight patients (44%) and an additional six patients showed a significant improvement in renal function at final review. Six patients developed end stage renal disease (ESRD). The risk (95% confidence interval) of developing ESRD at one year was 16.2% (CI, 6.4-37.6) and at two years was 23.2% (CI, 10.0-48.5). There were three deaths, two from sepsis and one from heart failure. The one-year mortality (95% CI) was 8% (CI, 2.0-28.5), the two-year mortality was 15.6% (CI, 4.9-43.5) and the five-year mortality was also 15.6% (CI, 4.9-43.5). Intravenous pulse cyclophosphamide for Jamaican patients with SLE and diffuse proliferative glomerulonephritis is an ineffective form of treatment.
Lupus 2003
PMID:Severity of systemic lupus erythematosus with diffuse proliferative glomerulonephritis and the ineffectiveness of standard pulse intravenous cyclophosphamide therapy in Jamaican patients. 1294 26

T cell costimulatory pathways are believed to play important roles in the pathogenesis of various autoimmune diseases including systemic lupus erythematosus (SLE). Animal models of SLE support the role of T cell costimulation in B cell activation and the production of autoantibodies. CTLA4Ig is a novel fusion protein that interferes with T cell costimulation by inhibiting the CD28-B7 interaction. A pivotal study demonstrated the ability of CTLA4Ig to suppress the production of anti-dsDNA antibodies and decrease nephritis in lupus prone mice. In an additional study, the combination of CTLA4Ig and cyclophosphamide significantly reduced proteinuria and prolonged survival in mice with advanced nephritis. In small human studies of psoriasis and rheumatoid arthritis, CTLA4Ig improved clinical outcomes and was well tolerated. These promising experiences with CTLA4Ig have paved the way for future studies in human SLE.
Lupus 2004
PMID:CTLA4Ig: a novel inhibitor of costimulation. 1523 Feb 95

Twelve systemic lupus erythematosus (SLE) patients with mild to moderate disease activity (SLEDAI of > or = 6 and on prednisolone < 0.5 mg/kg/day) were included in a prospective, randomized, double-blind, placebo-controlled pilot study for 24 weeks. Six were randomized to receive oral leflunomide and six received placebo. Primary outcome of this study included the mean change of SLEDAI at 24 weeks. Secondary outcomes included the changes in proteinuria, complement levels, anti ds-DNA binding, and prednisolone dosage. The mean age of the 12 patients was 41+/-9 years, and the mean disease duration was 8.5+/-5.8 years. All were female except one patient. The disease activity of both groups of patients decreased significantly after six months of treatment (14.7+/-6.0 to 3.7+/-2.3 in leflunomide group, P = 0.028, and 9.7+/-3.4 to 5.2+/-4.1 in placebo group, P = 0.027). Reduction in the SLEDAI from baseline to 24 weeks was significantly greater in the leflunomide group than the placebo group (11.0+/-6.1 in the leflunomide group and 4.5+/-2.4 in the placebo group respectively, P = 0.026). Minor adverse events included transient elevation in ALT, hypertension and transient leucopenia. In summary, leflunomide was more effective than placebo in treating SLE patients with mild to moderate disease activity and was safe and well-tolerated.
Lupus 2004
PMID:Double-blind, randomized, placebo-controlled pilot study of leflunomide in systemic lupus erythematosus. 1546 90

A 18-year-old female had low grade fever, butterfly rush, proteinuria, leukocytopenia and hypocomplimentemia in 1988, and she was diagnosed as systemic lupus erythematosus (SLE) with lupus nephritis (WHOIIb). Treatments with prednisolone and mizoribine resulted in the remission for three years. In May 2001, she presented neurosis and polakisuria despite of the increase of prednisolone to 20 mg/day. Finally, she admitted in our hospital because of manic and repressive state and disorientaion. A brain MRI revealed high intensity lesions in bilateral basal ganglia in T2 weighted images, and cerebrospinal fluid showed elevated protein and IFN-alpha (421 IU/ml). In addition, she manifested neurogenic bladder, muscle weakness and hyperactive deep tendon reflex of bilateral lower limbs due to both supranuclear disorder and hypesthesia under the Th 10 level. Spinal MRI revealed marked atrophy and high intensity signals at the middle to lower thoracic spinal cord in T2 weighted images, indicating complication of lupus myelitis as well as cerebral involvement. Although the symptoms of CNS lupus did not respond to prednisolone, twelve monthly cyclophosphamide pulse therapy (IV-CY) has resolved urinary disturbance, muscle weakness and sensory loss, along with the improvement of both cerebral and spinal MRI images. Lupus myelitis and neurogenic bladder are the rare, but very refractory manifestation among CNS involvement of SLE. We here propose IV-CY as an invaluable choice for the treatment of not only active lupus myelitis but also neurogenic bladder resisted for steroid.
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PMID:[Successful treatment of intravenous cyclophosphamide pulse therapy for lupus myelitis with urinary disturbance and acute confusional state]. 1555 23

The American College of Rheumatology renal criteria require re-evaluation to incorporate recent advances in the classification of glomerulonephritidies. Renal biopsy is now common and safely performed by experienced nephrologists in community as well as academic settings. The optimal criterion is renal histopathology findings of an immune complex mediated glomerulonephritis as interpreted by an experienced pathologist employing accepted criteria. Renal biopsies should be analysed by routine histopathology, immunofluorescent and electron microscopy. Rating of activity and chronicity should be noted. Secondary criteria for patients unable to undergo renal biopsy includes a combination of findings. These include proteinuria, hypocomplementemia, elevated anti-dsDNA antibodies and an active urine sediment. Proteinuria is a nonspecific finding and, most importantly, can be associated with a number of comorbidities including diabetes, hypertension and atherosclerotic disease. Persistent proteinuria > 0.5 g per day or a spot protein to creatine ratio of > 0.5 should be accompanied by an additional feature supporting active lupus such as positive serologies (hypocomplementemia and/or elevated anti-dsDNA antibodies) and/or active urinary sediment. Similarly, active urinary sediment should be accompanied by the additional criterion of proteinuria to meet renal criteria. Decline in renal function is not a reliable criterion given the numerous medications, comorbidities and other clinical circumstances which may result in this feature.
Lupus 2004
PMID:Review of ACR renal criteria in systemic lupus erythematosus. 1558 Sep 82

The diversity of clinical presentations of lupus nephritis parallel the diversity of pathologic lesions seen in the kidneys of patients with SLE. Renal manifestations range from asymptomatic hematuria or proteinuria to overt nephritic and nephrotic syndromes, rapidly progressive glomerulonephritis, and chronic renal failure. Subclinical nephropathy both during presentation and during monitoring of disease activity is frequently missed because of the notorious unreliability of routine screening urinalyses performed in high-throughput clinical pathology laboratories. Requisitions for urine microscopy should be flagged for special attention in patients at risk for lupus nephritis. Depression of classic complement pathway components and high titers of anti-DNA, anti-nucleosome, or anti-Clq antibodies identify patients are increased risk of renal involvement or flares of nephritis. Several disease activity and damage indexes are available, but they are mostly used in clinical research setting and none has achieved wide use for standard clinical practice.
Lupus 2005
PMID:Clinical presentation and monitoring of lupus nephritis. 1573 84

Membranous lupus nephritis (MLN) represents about 20% of clinically significant renal disease in lupus. Few studies have addressed directly the pathogenesis of MLN. Our assumptions about the underlying mechanisms are based on the combination of extrapolations from idiopathic membranous nephritis (mainly from animal models) and proliferative lupus nephritis. Natural history studies of MLN suggest a relatively low rate of progression to end-stage renal disease but a high rate of significant comorbidities. Historical changes in the criteria for pathologic diagnosis and classification of membranous lupus nephropathy have precluded definitive descriptions of the natural history, prognosis and treatment of this disorder. Patients with membranous lupus nephropathy should be treated early with angiotensin antagonists to minimize proteinuria, as well as lifestyle changes and appropriate drugs to reduce attendant cardiovascular risk factors. In patients with protracted nephrotic syndrome, consideration should be given to immunosuppressive therapies, including corticosteroids, cyclosporine, mycophenolate and cyclophosphamide. Prospective controlled trials are clearly needed in order to establish solid clinical practice guidelines for use of these drugs and other experimental therapies currently under study in membranous lupus nephropathy.
Lupus 2005
PMID:Membranous lupus nephritis. 1573 91

Optimal care of lupus nephritis patients should include the treatment of proteinuria and hypertension, other measures to delay the progression of chronic kidney disease, the vigorous management of cardiovascular risk factors and finally, the treatment of advanced chronic kidney disease and its consequences. These topics are briefly reviewed in the present paper, with particular emphasis on the recent progresses in antiproteinuric treatment.
Lupus 2005
PMID:Optimal care of lupus nephritis patients. 1573 92


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