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)

Data from a prospective study of the clinical course in 223 patients with systemic lupus erythematosus followed for 655 patient-years were analyzed by computer to determine the influence on frequency of infection of 1) corticosteroid dose; 2) azathioprine; 3) active disease, measured by new disease exacerbations, elevated ESR, hypocomplementemia, active urinary sediment, and proteinuria; 4) uremia; and 5) leukopenia. The frequency of all infections, and of bacterial and opportunistic infections specifically, increased progressively with increasing steroid dose. Azathioprine use, independent of steroid dose, did not account for an increased risk of bacterial, opportunistic, or nonspecific viral infections. Leukopenia did not predispose to infection, except possibly when associated with azathioprine-induced bone marrow suppression. Active renal disease, especially when manifested by abnormal urine sediment, was associated with an increase in infection frequency.
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PMID:Computer analysis of factors influencing frequency of infection in systemic lupus erythematosus. 41 59

In tests conducted with 165 mongrel sexually mature and immature rats it is shown that azathioprine used in nephrotoxic nephritic improves the general condition, reduces the edema of subcutaneous cellular tissues, as well as the intensity of proteinuria and helps retaining its selective type, lessens the degree of hypo- and dpsproteinemia and, especially, of hyper-beta-lipoproteinemia; in the kidneys the pathomorphological changes characteristic of nephritis become less marked. Azathioprine does not influence the process of acido-and ammoniogeness in the tubuloar system of the nephron, nor does it modify diuresis. The effect of azathioprine is most spectacular in the acive phase of developing nephritis. In rattlings with nephritis theaction af azathioprine in regard to a number of factors (proteins, beta-lipoproteids, gamma-globulins of the blood) is somewhat stronger than in the sexually mature rats.
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PMID:[Experimental study of azathioprine in nephrotoxic nephritis in rats]. 65 69

In this paper, the effect of the administration of prednisone and azathioprine on an experimental immune complex glomerulonephritis is studied. During the observation period of 3 months, it appeared that prednisone had no effect either on the morphology of glomerulonephritis or on the proteinuria caused by it. Azathioprine, especially when given 4 days before or simultaneously with the induction of the experimental immune complex glomerulonephritis, showed a clear effect on the morphology of the glomerulonephritis as well as on the proteinuria. The damage to the glomerular basement membrane as a result of deposition of immune complexes was less and the proteinuria was significantly lower. The effect of azathioprine was not present when given 10 days after the induction of glomerulonephritis, at a time when the autologous phase had already developed.
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PMID:Experimental glomerulonephritis in the rat induced by antibodies directed against tubular antigens. II. Influence of medication with prednisone and azathioprine: a histologic and immunohistologic study at the light microscopic and the ultrastructural level. 108 43

The course of eight pregnancies in seven renal transplant patients was analyzed. Immunosuppression consisted of Azathioprine and Prednisone. Pregnancy lasted from 32 to 39 weeks and the fetal development corresponded to the gestational age in every case. There were three cases which had complications during the pregnancy. One case had severe arterial hypertension, proteinuria and pedal edema, which was thought to be due to pre-eclampsia. Another patient had cholestatic jaundice and premature fissure of membranes and the third patient also had this last complication. Four patients had vaginal deliveries and in four cesarean section was performed. Renal function did not deteriorate during any of the pregnancies nor during the follow-up period, but the expected increase in creatinine clearance was not found. Clinical evaluation of the children, 4 months to 8 years of age, did not disclose any abnormalities.
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PMID:[Pregnancy in renal transplant recipients. Long-term evaluation of their children]. 145 32

Focal segmental glomerulosclerosis (FSGS) is the most common glomerulopathy leading to end-stage renal disease in children and transplantation is complicated by recurrent disease in a significant percentage of children. Treatment of recurrent FSGS has included high-dose steroids, high-dose cyclosporine (CSA), plasmapheresis, and ACE inhibitors with mixed results. We have had a consistent approach using oral cyclophosphamide (CTX) to treat recurrent FSGS since 1982. Three patients with ESRD secondary to nephrotic syndrome had recurrent disease. Biopsies in all 3 were consistent with recurrent FSGS. Patients were begun on a 8-12 week course of 1-2 mg/kg/day of CTX and dosage was adjusted for WBC count. Azathioprine was with held during CTX. Patients' dosage at the end of 12 weeks ranged from 0.89-1.75 mg/kg/day. All patients tolerated CTX well. After 8-12 weeks of treatment, 2 patients with nephrotic syndrome normalized their serum albumin and had negative to trace protein on urinary dipstick. One patient with proteinuria decreased his protein excretion from 770 to 340 mg/m2/day. At follow-up at 8, 38, and 125 months post-transplant, these 3 patients have stable graft function and negative to trace protein on urinalysis. The patient followed for 125 months has had 2 additional relapses at 51 and 82 months post-transplant that were treated successfully with pulse intravenous steroids. Three pediatric patients with recurrent focal segmental glomerulosclerosis post-renal transplant were treated with oral CTX and had significant improvement in proteinuria and preservation of graft function. This suggests that oral CTX is a potentially effective and well-tolerated treatment for recurrent FSGS in children.
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PMID:Recurrent focal segmental glomerulosclerosis in pediatric renal transplant recipients: successful treatment with oral cyclophosphamide. 786 17

Lupus nephritis in childhood usually presents after the age of 10 years, and presentation under 5 years is very rare. More males (F:M ratio 4.5:1) are affected than in adult-onset cases, but the ratio is the same in prepubertal and pubertal children. The incidence of clinically evident renal disease is greater at onset than in adults (82%), the usual presentation being with proteinuria, 50% having a nephrotic syndrome. Half the children show World Health Organisation class IV nephritis in renal biopsies. Neuropsychiatric lupus is present at onset in 30%, may complicate 50% at some point and remains a major problem. Prognosis has improved greatly over the past 30 years, at least in part the result of immunosuppressive treatment. Treatment of the initial phase may be guided by the severity of the renal biopsy appearances, more aggressive treatment including cytotoxic agents, i.v. methylprednisolone and perhaps plasma exchange, although the value of exchange is not established. Controversy persists as to the most effective cytotoxic treatment in the acute phase, both oral and i.v. cyclophosphamide and azathioprine being used in different units. In the chronic maintenance phase it seems established both clinically and histologically that addition of a cytotoxic agent improves outcome, but again the drug and route of administration are contentious. Azathioprine has the advantage of being safe for pregnancy and not gonadotoxic, whilst i.v. cyclophosphamide has been demonstrated to improve results over prednisolone alone in controlled trials and has advantages in non-compliant patients. No trial comparing the two regimes has been carried out, and one is needed. Today children much less commonly go into renal failure, and the main causes of actual death (15% of patients over 10 years) are now infections and extra-renal manifestations of lupus, principally neurological. Morbidity of the disease and the treatment remain a major problem, especially when treatment exacerbates complications of the disease itself, such as infections, osteonecrosis, thrombosis, vascular disease and possibly neoplasia.
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PMID:Lupus nephritis in childhood and adolescence. 801 6

The highly atherogenic lipoprotein(a) [Lp(a)] is significantly elevated in patients with renal disease. It is discussed controversially whether Lp(a) concentrations decrease after renal transplantation and whether the mode of immunosuppressive therapy influences the Lp(a) concentrations. In a prospective study the Lp(a) concentrations before and on average 48 months after renal transplantation were measured in 145 patients. The determinants of the relative changes of Lp(a) concentrations were investigated in a multivariate analysis. Patients treated by CAPD showed a larger decrease of Lp(a) than hemodialysis patients, reflecting their markedly higher Lp(a) levels before transplantation. The relative decrease of Lp(a) was higher with increasing Lp(a) concentrations before transplantation in combination with an increasing molecular weight of apolipoprotein(a) [apo(a)]. That means that the relative decrease of Lp(a) is related to the Lp(a) concentration and the apo(a) size polymorphism. With increasing proteinuria and decreasing glomerular filtration rate, the relative decrease of Lp(a) became less pronounced. Neither prednisolone nor cyclosporine (CsA) had a significant impact on the Lp(a) concentration changes. Azathioprine (Aza) was the only immunosuppressive drug which had a dose-dependent influence on the relative decrease of Lp(a) levels. These data clearly demonstrate a decrease of Lp(a) following renal transplantation which is caused by the restoration of kidney function. The relative decrease is influenced by Aza but not by CsA or prednisolone.
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PMID:Lipoprotein(a) plasma concentrations after renal transplantation: a prospective evaluation after 4 years of follow-up. 1040 99

This series of articles on the management of glomerulonephritis (GN) has been prepared by a team of experts in the evidence-based format consistent with peer review of published data. Each author was asked to review the literature for his assigned histological type, with emphasis on therapy and limited to adult studies. The age limit was not considered for minimal change disease and focal segmental glomerulosclerosis, because of the high prevalence of these glomerulopathies in children. The particular treatment recommendations for each type of glomerular disease were graded by each author according to the amount of evidence provided in these reviewed studies. The first two articles concentrate on indications and techniques for kidney biopsy. Each subsequent article focuses on and describes the highest level of evidence supporting the recommendation for therapy in IgA nephropathy (Ig-GN), minimal change nephropathy (MCN) and focal segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MGN), lupus nephritis, ANCA-associated vasculitis, HCV-associated cryoglobulinaemia and renal involvement in paraproteinemic disorders. The article on IgA nephropathy emphasises the importance of carefully evaluating both clinical and histologic findings before settling on the treatment. The recent, renewed interest in steroids and many immunosuppressive agents is discussed in detail. Recommendations related to the patient's age are also provided. MCN and FSGS are treated together because these forms share similar evidence-based recommendations. For both of these diseases, in fact, the initial treatment approach in children should be prednisone or prednisolone for four to six weeks. The therapeutic response in adults is slower than in children, but adults experience fewer relapses and a more prolonged remission. There is also a discussion on treatment of relapse, frequent relapsing disease and true steroid-resistant disease as well as the role of new immunosuppressive agents. Membranous nephropathy is a frequent cause of nephrotic syndrome in adults and, in one third of these patients, leads to end-stage renal disease. However, the treatment of this form is as yet a matter of discussion. Based on extensive critical review of the literature, the following recommendations are put forward: (a) no treatment in the absence of nephrotic syndrome; (b) patients with heavy proteinuria should receive a 6-month treatment with i.v. methylprednisolone (MP) pulse therapy for three consecutive days followed by oral MP (0.4 mg/kg/day) (months 1, 3, 5) and chlorambucil or cyclophosphamide (months 2, 4, 6); (c) the dosage of chlorambucil or cyclophosphamide should be lowered in older patients; (d) cyclosporine is a second-choice treatment. The treatment of lupus nephritis depends on the histologic class. No specific treatment is usually necessary for class I and IIA. Oral steroids are indicated in patients with class IIb, proteinuria and active systemic disease. Steroids and azathioprine are the treatment of choice for patients with class III and IV, but cyclosporine can be an effective alternative therapy. Cyclophosphamide is more effective than azathioprine when severe acute renal involvement is present. The treatment of ANCA-associated vasculitis depends mainly on clinical presentation, oral prednisone + oral or i.v. cyclophosphamide are generally effective. In the most severe cases, the association of MP pulse therapy with cyclophosphamide is probably more effective. Plasma exchange is probably justified in unresponsive patients. Azathioprine should replace cyclophosphamide during the maintenance therapy. In HCV-associated mixed cryoglobulinemia the treatment also depends on the severity of renal involvement. The treatment for chronic HCV infection involves alpha interferon alone or preferably in combination with ribavirin. Aggressive therapy, including i.v. MP, plasmapheresis and cyclophosphamide is primarily reserved for patients with acute severe disease, as manifested by progressive renal failure, distal necroses requiring amputation, or advanced neuropathy. Uncontrolled studies suggest that this regimen can improve renal function. Renal involvement is a common problem in paraproteinemic disorders that include multiple myeloma, Waldentrom's macroglobulinaemia and monoclonal gammopathy. The most common renal diseases in this setting are cast nephropathy, primary amyloidosis cast nephropathy, primary amyloidosis, and light chain deposition disease that are related to the overproduction of monoclonal immunoglobulin light chains. The approach to therapy varies with the cause of the renal dysfunction. Patients with amyloidosis or light-chain deposition disease are generally treated with chemotherapy, but the most effective therapy for myeloma kidney is prevention by minimising the risk factors that promote light chain filtration and subsequent obstruction by cast formation within the tubules. Chemotherapy or stem cell or bone marrow transplantation to decrease filtered light chain load, prevent volume depletion and maintain high fluid intake to reduce light chain concentration within the tubular lumen are indicated in almost all the patients.
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PMID:[Instructions and implementations for percutaneous renal biopsy. Guidelines for the therapy of glomerular nephropaties]. 1466 2

Until recently, intravenous cyclophosphamide pulses with oral corticosteroids were regarded standard therapy for proliferative lupus nephritis (LN). Azathioprine, a less toxic alternative, was never proven to be inferior. In the first Dutch lupus nephritis study (enrollment between 1995 and 2001), we randomized 87 proliferative LN patients to either cyclophosphamide pulses (750 mg/m(2), 13 pulses in 2 years) combined with oral prednisone (CY) or to azathioprine (2 mg/kg/day in 2 years) combined with intravenous pulses of methylprednisolone (3 x 3 pulses of 1000 mg) and oral prednisone (AZA). After a median follow-up of 5.7 years (interquartile range 4.1-7.2 years), doubling of serum creatinine was more frequent in the AZA group, although not statistically significant (relative risk (RR): 4.1, with 95% confidence interval (95% CI): 0.8-20.4). Relapses occurred more often in the AZA group (RR: 8.8, 95% CI: 1.5-31.8). Creatinine and proteinuria at last visit did not differ between the two treatment arms. Moreover, 88.4% of the patients in the AZA arm were still free of cyclophosphamide treatment. During the first 2 years, the frequency of remission was not different, but infections, especially herpes zoster virus infections (HZV) were more frequent in the AZA group. Parameters for ovarian function did not differ between the two groups. In conclusion, in this open-label randomized controlled trial, cyclophosphamide was superior to azathioprine with regard to renal relapses and HZV. At last follow-up, there were no differences in serum creatinine or proteinuria between the two groups. However, since our study lacked sufficient power, longer follow-up is needed to reveal putative differences.
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PMID:Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial. 1690 Feb 18

Systemic Lupus Erythrematosus (SLE) is an inflammatory autoimmune disorder that may affect multiple organ systems. The clinical course is marked by spontaneous remission and relapses. Severity may vary from mild episodic disorder to a rapidly fulminant life threatening illness. Clinical manifestations of Lupus Nephritis (LN) are varied according to the renal pathologic lesions. Treatment of LN remains controversial. As a chronic disease with periods of remission and relapses, it is unclear whether relapses should be treated as the initial presentation of the disease. This prospective study was designed to compare between three different modalities of therapy for treating LN patients. The study includes all systemic lupus patients seen in Alexandria University Hospital since January 2004 for 6 months. Forty-three patients with SLE were presented to us by SLE, only 31 had LN and 22 were included in the study. The patients were classified randomly into 3 arms. All patients received steroid therapy plus from the beginning either Cyclophosphamide (CYP) [Group I, n=7], or Cyclosporine (CsA) [Group II, n=7], or Azathioprine (AZA) [Group III, n=8], Full history and examination were done. Laboratory investigations included routine and immunological studies of ANA, Anti-DNA, C3 and C4. Renal biopsy was done in all patients. After 6 months of follow up; Serum creatinine was stationary in CYP group from 2.2 +/- 1.1 to 2.1 +/- 1.7; while significantly decreased in CsA from 2.8+1.7 to 1.0 +/- 0.5 mg/dl. Moreover; while proteinuria decreased in CYP from 2.7 +/- 0.7 to 1.8 +/- 2.2; there was more pronounced decreased from 6.9 +/- 10.0 to 2.4 +/- 1.2 g/24 hr in CsA group despite very huge increase in glomerular filtration rate (GFR). 2 out 7 cases of CsA group; while 2 of 6 of CYP group did not show improvement. Moreover; 3 of 6 of CYP group and 1 of 6 of AZA group needed to be shifted to CsA group because of side effects and/or no response to CYP and showed good response. These patients were either class V or IV. However; only one case in this study with signs of acute CsA toxicity was reversed by monitoring the dose. In conclusion, CsA in this study proved to be superior over CYP in LN at least in the short term follow up; provided to be given with appropriate doses even if it is used in class IV, which was thought to be very responsive to CYP.
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PMID:Comparative clinical prospective therapeutic study between cyclophosphamide, cyclosporine and azathioprine in the treatment of lupus nephritis. 1797 49


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