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)

We each have nephrotic patients who become steroid dependent and in whom multiple immunosuppressive agents are employed. There is a need to balance possible therapeutic benefits with drug toxicity. This case report describes such a patient, who has suffered from nephrotic syndrome for over 11 years and had become resistant to the usual therapies. He was therefore given a single dose of the anti-CD20 drug rituximab, to which he showed a prompt response, leaving him free of proteinuria for the past 10 months.
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PMID:Is there a role for rituximab in the treatment of idiopathic childhood nephrotic syndrome? 1731 Mar 62

Idiopathic membranous glomerulonephritis (MGN) is a rare cause of end-stage renal failure, which can lead to chronic hemodialysis. This glomerulopathy can recur after renal transplantation despite immunosuppressive therapy. To date, there is no confirmed therapy for treatment of renal grafts after recurrence of MGN. Herein, we report on a 27-year-old man who underwent cadaveric renal transplantation for MGN in September 2001. At 2 months posttransplant, a renal biopsy showed membranous deposition on immunofluorescence staining evocative of recurrence of MGN. Proteinuria developed progressively and, at one year, was estimated at 7.65 g/24 h, with hypoalbuminemia of 24 g/l. This persisted despite symptomatic treatment with anti-proteinuric agents (enalapril 20 mg/day and irbesartan 75 mg/day) and atorvastatin (10 mg/day). By March 2004, his proteinuria was 11 g/day; therefore, therapy with rituximab (monoclonal anti-CD20) at 375 mg/m(2) weekly was initiated for four consecutive weeks, followed by the same dosage every four months for one year. Biological controls performed two weeks after the fourth infusion of rituximab showed a fall in proteinuria, assessed at 1 g/24 h, with albuminemia of 29 g/l and normalized lipidic results. A renal biopsy performed 6 months after the first infusion was unchanged. Follow-up at 30 months showed consistent remission of membranous nephropathy, demonstrated by a serum creatinine level of 150 mumol/L, microalbuminuria of 107 mg/24 h and normal albuminemia of 43.7 g/l. There were no side effects; in particular, no infectious complications occurred, despite CD19 lymphocytes being still negative after 30 months. Monoclonal CD-20 antibodies have shown efficacy against MGN compared to conventional therapies in native kidneys. It has recently been shown that CD20 mRNA is overexpressed in the renal interstitium in patients suffering from MGN and that the interstitial infiltrates is mainly composed of B-cell lymphocytes in these patients. These data may explain the efficiency of rituximab in these circumstances.
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PMID:[Efficiency of rituximab treatment for recurrence of membranous glomerulopathy after renal transplantation]. 1745 3

We describe a child presenting with oligoclonal plasma IgM (1.2 g%) and nephrotic syndrome with focal segmental glomerulosclerosis. Oligoclonality was demonstrated by the analysis of the complementary determining region 3 (CDR 3) on immunoglobulin heavy chains and by two dimensional electrophoresis and Western blot analysis that showed the bulk of isoforms having a cationic muU chain compared with the normal homologue (pI 7.5 vs 6.5). Urinary light chains were absent, and bone marrow aspirate was normal. Usual therapies for nephrotic syndrome with steroids and cyclosporin were useless. At the age of 9 years the patient was treated with plasmapheresis plus cyclophosphamide (2 mg/kg per day for 60 days), which temporarily reduced plasma IgM, and proteinuria was normal for 3 years. After this period, due to new recurrence of nephrotic syndrome, the patient received a cycle with anti-CD20 antibodies (500 mg/m(2) every week for a month) associated with a cycle of plasmapheresis that normalized proteinuria again, and, after 3 years, the proteinuria is still in remission. This is the first case of nephrotic syndrome associated with oligoclonal plasma IgM and mesangial IgM deposits. Both cyclophosphamide and anti-CD20 antibodies associated with plasmapheresis induced, at different stages, stable and protracted remission of proteinuria without evident side effects. Long term efficacy and safety of the association are still to be determined.
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PMID:Protracted remission of proteinuria after combined therapy with plasmapheresis and anti-CD20 antibodies/cyclophosphamide in a child with oligoclonal IgM and glomerulosclerosis. 1766 Oct 91

Rituximab effectively reduces proteinuria in patients with idiopathic membranous nephropathy (IMN), but response to treatment may vary from patient to patient. The association between baseline clinical, laboratory, and histology covariates and proteinuria reduction was evaluated retrospectively by multiple linear regression analysis at 3 mo after rituximab therapy in 14 patients with IMN with proteinuria > 3.5 g/24 h while on angiotensin-converting enzyme inhibition for at least 6 mo and no previous remissions. The association strength was expressed by standardized beta coefficients (SbetaC). Glomerular (SbetaC = 0.48, P = 0.049) and tubulointerstitial (TI) scores (SbetaC = 0.61, P = 0.003) predicted the outcome. Among glomerular and TI score components, tubular atrophy (SbetaC = 0.59, P = 0.003) and interstitial fibrosis (SbetaC = 0.60, P = 0.001) were significantly associated with 3-mo proteinuria. Urinary protein excretion decreased from 9.1 +/- 4.0 to 4.6 +/- 3.5 g/24 h (P < 0.001) in eight patients with TI score 1.7 but did not change in six with a score > or = 1.7. Nine additional patients with IMN then were allocated prospectively to rituximab treatment on the basis of a TI score < 1.7. Three-month proteinuria decreased in all patients from 8.9 +/- 5.3 to 4.9 +/- 3.9 g/24 h (P < 0.001) and serum albumin increased from 2.2 +/- 0.6 to 2.8 +/- 0.5 mg/dl (P < 0.01). Changes in serum albumin and cholesterol were inversely correlated (P < 0.02, r = -0.44). Rituximab achieved CD20 and CD19 depletion in all patients. In patients with IMN and nephrotic proteinuria despite angiotensin-converting enzyme inhibition therapy, renal biopsy findings may help in predicting response to rituximab and defining selection criteria for randomized trials that aim to assess the risk/benefit profile of B cell target therapy as compared with aspecific immunosuppressants and/or conservative therapy alone.
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PMID:Rituximab for idiopathic membranous nephropathy: who can benefit? 1769 81

Idiopathic membranous nephropathy is a common cause of nephrotic syndrome whose pathogenesis may involve B-cell functions. Rituximab is a monoclonal antibody that binds to the CD20 antigen on B cells thereby deleting them. We conducted an open-label pilot trial of rituximab treatment in 15 severely nephrotic patients with proteinuria refractory to angiotensin-converting enzyme inhibition and/or receptor blockade but with adequately controlled blood pressure. Rituximab was given 2 weeks apart and, at 6 months, patients who remained proteinuric but had recovered B-cell counts were given a second course of treatment. Proteinuria was significantly decreased by about half at 12 months. Of the 14 patients who completed follow-up, full remission was achieved in two and partial remission in six patients based upon the degree of proteinuria. Side effects were minor; however, we found no relationship between the response and number of B cells in the blood, CD20 cells in the kidney biopsy, degree of tubulointerstitial fibrosis, starting proteinuria or creatinine values. Rituximab appears effective in reducing proteinuria in some patients with idiopathic membranous nephropathy but prospective identification of responsive patients was not possible.
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PMID:Rituximab treatment of idiopathic membranous nephropathy. 1862 1

We present the cases of two children with steroid-resistant nephrotic syndrome (SRNS) who were treated with rituximab (anti-CD20 monoclonal antibody). Both were resistant to conventional therapy, and renal biopsy showed focal segmental glomerulosclerosis (FSGS). Combination therapy with methylprednisolone pulse therapy and plasmapheresis was the only way to decrease proteinuria. However, the patients suffered severe reactions to steroid treatment. We therefore treated them with rituximab in a single dose of 375 mg/m(2), which resulted in the rapid clearing of circulating CD19-positive B cells. One month after rituximab treatment, both achieved partial remission; one patient has maintained complete remission for 8 months, and the other relapsed 8 months after the first rituximab treatment with the recovery of peripheral B-cell counts and received a second rituximab treatment. She achieved complete remission 5 months after the second course and has maintained the remission for 2 months. We conclude that rituximab may be an effective treatment for refractory SRNS with FSGS.
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PMID:Rituximab for refractory focal segmental glomerulosclerosis. 1797 21

Rituximab (RTX), an anti-CD20 monoclonal antibody, has been proposed for use in the therapy of systemic lupus erythematosus (SLE). We present the initial long-term experience of the safety and efficacy of rituximab for treatment of SLE in children. Eighteen patients (mean age 14 +/- 3 years) with severe SLE were treated with rituximab after demonstrating resistance or toxicity to conventional regimens. There was a predominance of female (16/18) and ethnic African (13/18) patients. All had lupus nephritis [World Health Organization (WHO) classes 3-5] and systemic manifestations of vasculitis. Clinical disease activity of the SLE was scored with the SLE-disease activity index 2K (SLEDAI-2K). Patients were followed-up for an average of 3.0 +/- 1.3 years (range 0.5 to 4.8 years). B-cell depletion occurred within 2 weeks in all patients and persisted for up to 1 year in some. Clinical activity scores, double-stranded DNA (dsDNA) antibodies, renal function and proteinuria [urine protein to creatinine ratio (Upr/cr)] improved in 93% of the patients. Five patients required multiple courses of RTX for relapse, with B-cell repopulation. One died of infectious endocarditis related to severe immunosuppression. In conclusion, our data support the efficacy of rituximab as adjunctive treatment for SLE in children. Although rituximab was well tolerated by the majority of patients, randomized controlled trials are required to establish its long-term safety and efficacy.
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PMID:Rituximab therapy for juvenile-onset systemic lupus erythematosus. 1809 88

Fibrillary glomerulonephritis belongs to a group of disorders characterized by pathogenic deposition of fibrils in glomeruli. This glomerulopathy tends to progress to end-stage kidney disease, and there currently are no treatments of proven benefit, including corticosteroids and cytotoxic agents. Because the glomerular deposits contain an immunoglobulin component, it was postulated that anti-B-cell therapy with rituximab, an anti-CD20 monoclonal antibody, may be effective in the treatment of patients with fibrillary glomerulonephritis. We describe 3 patients with fibrillary glomerulonephritis who were treated with rituximab for nephrotic-range proteinuria. Each patient also received standard antiproteinuria therapy, including blockade of the renin-angiotensin system and strict blood pressure control. All patients showed a decrease in proteinuria to less than 1.5 g/d of protein by 27 months, and kidney function was preserved throughout the duration of therapy and follow-up. No adverse effects were seen with rituximab. These outcomes suggest that treatment with rituximab may be a promising approach to the management of fibrillary glomerulonephritis, an entity previously considered refractory to therapy.
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PMID:Rituximab treatment of fibrillary glomerulonephritis. 1882 85

Resistance to steroids and immunosuppression in pediatric nephrotic syndrome may be related to focal segmental glomeruloslerosis (FSGS). Rituximab, monoclonal anti-B-CD20-cell antibody is currently regarded as novel effective drug in selected cases. We describe the case of 8-years-old male pediatric patient, resistant to combined immunosuppression and presenting renal insufficiency (GFR 32.8 ml/min/1.73 m2). Patient was given overall 5 doses of rituximab [375 mg/m2/dose]. Nevertheless significant decrease of proteinuria, the further progress of renal disease was unaffected and patient developed end-stage renal failure. The efficacy of rituximab in nephrotic syndrome must be verified in controlled trials. Late onset of therapy in course of renal insufficiency might be the one of the reasons of treatment failure in our case.
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PMID:[No effect of rituximab in pediatric case of severe nephrotic syndrome and focal segmental glomeruloslerosis accompanied by renal insufficiency]. 1920 86

Transplant glomerulopathy (TG) is a lesion with specific morphology and strong evidence of an immune mechanism. The incidence of TG is approximately 20% by 5 years after transplantation. TG is characterized by proteinuria, hypertension and declining graft function. Appearances on light microscopy include thickened capillary walls and double contours, with reduplication or lamination of the glomerular basement membrane on electron microscopy. TG is associated with acute rejection, the antibody status before transplantation and de novo HLA antibodies. HLA class II and/or donor-specific antibodies incur additional risks. Desensitization protocols do not always prevent the development of TG in highly sensitized individuals. Associations between TG, past or current C4d and the presence of alloantibodies are recognised, however, C4d in the peri-tubular capillaries or glomeruli is not a prerequisite at the time of diagnosis. Clinical observation and animal models suggest that TG arises as a consequence of chronic endothelial cell (EC) injury by the humoral arm of the immune system. In some cases, this follows a period of EC accommodation after an episode of acute injury. Proposed treatments include augmentation of background immunosuppression, and trials of monoclonal therapies targeted at CD20-positive B cells are underway.
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PMID:Transplant glomerulopathy: morphology, associations and mechanism. 1959 Feb 29


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