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)

Chlorambucil, in combination with prednisone, was compared with prednisone alone in a randomized controlled trial in 21 children with either steroid-dependent or frequently relapsing nephrotic syndrome to assess its effect on the duration of remission and the rate of relapse. All control patients treated with prednisone alone continued to relapse at the same rate, with all patients experiencing a return of proteinuria by seven months. Conversely, those who received the same prednisone therapy along with chlorambucil for six to 12 weeks remained in complete remission, without further medication, during 12 to 34 months of follow-up observation. Complications were minimal. Immediate side effects commonly reported with cyclophosphamide were not seen with chlorambucil. Comparison with published reports also suggests that remission induced by chlorambucil is more stable than that after cyclophosphamide. Chlorambucil appears to be of value in the frequently relapsing nephrotic patient, adding an effect that is unattainable with prednisone alone.
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PMID:Chlorambucil treatment of frequently relapsing nephrotic syndrome. 95 61

Nephrotic syndrome is defined as proteinuria sufficiently severe to result in hypoalbuminaemia, oedema and hyperlipidaemia. The early modern history of this illness was characterised by the serendipitous development of renal biopsy technique at approximately the same time as the use of corticosteroids for nephrotic syndrome. The coincidence of these events set the stage for evaluating therapeutic response to corticosteroids and cytotoxic agents in relation to renal histology and ultimate clinical outcome. The International Study of Kidney Disease in Children (ISKDC) was initiated in the 1960s as a multicentre study examining these relationships in children. Over the next decade this study, as well as contributions from other investigators, helped define optimum therapy for these children. It was determined that a child with nephrotic syndrome under the age of 6 years, who did not present with hypertension, azotaemia, hypocomplementaemia or signs of systemic illness, had an approximately 85% chance of responding to corticosteroid therapy. If only those children who had minimal change histology on biopsy were considered, 94% responded. The original regimen which is still used today, was 60 mg/m2 bsa/day prednisone administered on a 3 times per day dosage schedule for 4 weeks, followed by an additional 4 weeks of therapy at a dose of 40 mg/m2 bsa given as a single oral dose every other day. Of those who respond roughly one-third will have no relapses, while almost half will have frequent relapses (greater than or equal to 2 in 6 months) and the rest will have infrequent relapses. Patients in relapse are treated as at presentation but are usually converted to the 40 mg/m2 bsa dose when the urine has been free of protein for 3 days, and are then tapered off or maintained on this dose for several weeks, depending on the individual's history of relapses and incidence of side effects from corticosteroids. For those children who are suffering frequent relapses and severe corticosteroid side effects (e.g. growth failure, morbid obesity, aseptic necrosis of bone), cytotoxic agents were identified as providing long term remission. After inducing remission with conventional corticosteroid dosages, cyclophosphamide is administered at a dose of 2 mg/kg/day given as a single dose for 8 weeks. This regimen was shown to lead to approximately 70% of patients being in remission 2 years after completion of this course of therapy. Chlorambucil given at a dose of 0.2 mg/kg/day as a single oral dose has been equally efficacious.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Management of nephrotic syndrome in childhood. 171 84

Primary chronic glomerulonephritis may emerge clinically as acute nephritis, the nephrotic syndrome as well as asymptomatic hematuria and proteinuria. Therapeutic consequences still depend on the morphological diagnosis. In cases of minor proteinuria [< 3,5 g/24 h] immunosuppressive therapy is not superior to symptomatic therapy. In patients with nephrotic syndrome immunosuppressive therapy depends on the morphological diagnosis. Glucocorticoids are the therapy of choice in minimal changes glomerulopathy and should be tried in focal segmental sclerosing glomerulonephritis. Steroids may be tried in pure mesangial as well as in IgA and IgM nephropathy. Especially Ponticelli claims significant therapeutic success in patients with membranous glomerulonephritis treated with Prednisolone and Chlorambucil. Failures and relapses may be treated with Cyclophosphamide, Chlorambucil or Cyclosporin A. Anticoagulants may be advantageous in the therapy of membranoproliferative glomerulonephritis.
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PMID:[Therapy of primary chronic glomerulonephritis]. 778 93

Because of the high rate of spontaneous remission, treatment of membranous nephropathy with prednisolone and chlorambucil is still controversial. The aim of this study was to give this therapy only to those patients at risk of developing renal insufficiency and to test the efficacy of a low-dose therapeutic regimen. Seventeen patients with more than 10 g protein excretion per day (mean 16.9) and/or a deterioration in renal function (mean serum creatinine, 162 mumol/l) were included. Serum total protein, serum lipids, proteinuria, serum creatinine, and blood pressure were measured, along with the diuretic and antihypertensive medication. The observation time before the start of treatment was 27 +/- 27 months. Steroids were given during months 1, 3, and 5 (methylprednisolone 3 x 500 mg intravenously) prednisolone 0.5 mg/kgBW daily per os for 1 week, then tapered by 0.1 mg/kg BW/week for 1 month). Chlorambucil was given during months 2, 4, and 6 at a dose of 0.12 mg/kgBW daily. At the end of treatment proteinuria had significantly decreased (mean of all patients, 7.8 +/- 1.4 g/d) in all patients. Six months after the end of treatment proteinuria was significantly lower than at baseline in 14 of 17 patients. Hypoproteinemia and hyperlipidemia had improved; diuretic and antihypertensive medication were reduced. Elevated serum creatinine decreased in 7 of 9 patients (pretreatment, 227 +/- 39 mumol/l; 6 months, 176 +/- 28 mumol/l). Nonresponders with respect to serum creatinine responded with respect to proteinuria. Regarding adverse effects, two patients complained of dyspepsia while taking steroids; during chlorambucil treatment two patients experienced nausea and lack of appetite, and one developed leukopenia (1600/microliters).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low-dose prednisolone/chlorambucil therapy in patients with severe membranous glomerulonephritis. 804 74

Glucocorticoids, cytostatic agents and cyclosporin are frequently employed in the treatment of glomerular diseases of immunologic origin. In order to assess the efficacy of these drugs, we retrieved--with the help of a Medline-based search--and analysed all controlled studies published since 1966 dealing with immunosuppressive therapy of glomerulonephritis. Of the 34 identified controlled studies, only 27 had a prospective and randomized design. In patients with minimal-change glomerulonephritis, proteinuria decreases and disappears during therapy with prednisone. A comparable effect can be obtained with cyclosporin. Occasionally, there is a relapse of proteinuria after cessation of the immunosuppressive therapy in some patients. These relapses can be controlled with a chlorambucil-based regimen. Chlorambucil may be successfully utilized in the treatment of focal-segmental glomerulosclerosis, a form of glomerulonephritis which is more refractory to glucocorticoid therapy and is probably pathogenetically related to minimal-change glomerulonephritis. Patients with membranous glomerulonephritis and a nephrotic syndrome seem to benefit from an alternate month prednisone and chlorambucil regimen. However, an indiscriminate treatment of all patients with this regimen is not legitimate, because some patients would be overtreated as the disease may undergo spontaneous remission. There are no well-documented valuable therapies for the IgA-associated glomerulonephritis and the membranoproliferative glomerulonephritis. The combination of prednisone with cytotoxic substances, particularly cyclophosphamide and azathioprine, seem to remarkably improve the renal prognosis of the diffuse proliferative lupus glomerulonephritis. The efficacy of cyclophosphamide and prednisone with or without plasma exchange in the treatment of the rapidly progressive glomerulonephritis due to other systemic diseases (M. Wegener, panarteritis nodosa, Goodpasture syndrome) is a widely accepted therapeutic modality, although controlled studies are lacking. Immunosuppressive therapy of glomerulonephritis bears notable risks and sometimes questionable efficacy. Thus, before prescribing any immunosuppressive therapy, it is mandatory to evaluate in every single patient the prognostic factors of the underlying disease, the probability of the onset of severe side effects and the possible acceptance of a renal replacement therapy, including renal transplantation.
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PMID:[Immunosuppressive therapy of glomerulonephritis--controlled studies]. 845 16

Chronic lymphocytic leukemia is a common disease in the elderly but is rarely associated with a nephrotic syndrome. The rarity of this association suggests that leukemic cells may have certain properties or features that may lead to the development of glomerulonephritis. Effective medical treatment of the leukemia may not necessarily allow regression of the nephrotic syndrome; however, the effects of splenectomy on nephrotic proteinuria when associated to chronic lymphocytic leukemia have never been evaluated. We report the case of a 50-year-old male with stage C CD5+ chronic lymphocytic leukemia associated with a nephrotic syndrome due to Type I membranoproliferative glomerulonephritis. Chlorambucil and prednisone were unable to control the leukemia and the nephrotic range proteinuria, and were discontinued because of poor hematologic tolerance. A splenectomy immediately resulted in a spectacular remission of both chronic lymphocytic leukemia and the nephrotic syndrome. Spleen lymphocytes were collected and tested in quantitative flow cytometry for the expression of the main B cell associated markers. They did not exhibit any particular immunophenotypic pattern. This report of a remission of a glomerulonephritis associated with chronic leukemia following splenectomy is evidence of a possible relationship between the two diseases.
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PMID:Nephrotic syndrome associated with chronic lymphocytic leukemia resistant to immunosuppressive drugs: remission obtained by splenectomy. 904 65

The best treatment of idiopathic membranous nephropathy remains an area of clinical controversy. At the moment only patients with nephrotic syndrome and/or declining renal function should be treated. Despite the negative trials, prolonged oral administration of corticosteroids alone may be a safe and an effective first-line treatment in nephrotic patients. If corticosteroids are ineffective, prolonged use of cyclosporine in low-doses can be recommended as an alternative treatment, that diminishes rapidly proteinuria in the majority of patients. Both treatments (intravenous high doses of corticosteroids and cyclosporine) may also be effective in patients with declining renal function. Because of their toxicity, the routine use of alkylating agents for patients with nephrotic syndrome is not justified. They may be retained for patients, in whom other treatment modalities have failed. Chlorambucil may be preferred over cyclophosphamide since it carries less toxicity. A lower dose of chlorambucil, than that usually suggested, for a short period of time seems to be prudent in an effort to avoid serious side-effects.
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PMID:Treatment of idiopathic membranous nephropathy (IMN). 1110 59