Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002986 (Fabry)
 5,646 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was performed to determine whether adult male patients with Fabry disease who demonstrate a continuing decline in renal function despite 2 to 4 yr of conventionally dosed agalsidase alfa therapy (0.2 mg/kg every other week [EOW]) show an improved slope of decline with weekly administration using the same dosage. Eleven (27%) of 41 adult male patients with Fabry disease who participated in long-term agalsidase alfa clinical trials and who had demonstrated a slope of decline in estimated GFR (eGFR) of > or =5 ml/min per 1.73 m(2)/yr while receiving long-term treatment with agalsidase alfa at the currently recommended dosage of 0.2 mg/kg, infused EOW, were enrolled in this open-label, prospective study. Patients were switched from EOW to weekly infusions and followed for an additional 24 mo. Before switching to weekly dosing, eGFR was 53.7 +/- 6.3 ml/min per 1.73 m(2) (mean +/- SEM), and mean rate of change in eGFR was -8.0 +/- 0.8 ml/min per 1.73 m(2)/yr. During the 24-mo follow-up period after switching to weekly dosing, the mean rate of change in eGFR was observed to slow to -3.3 +/- 1.4 ml/min/1.73 m(2)/yr (P = 0.01 versus EOW). After switching to weekly dosing, three patients demonstrated an improvement in eGFR and six patients demonstrated a slowing in the rate of eGFR decline; only two patients failed to improve their eGFR slope. A multiple regression model confirmed that the weekly infusion regimen was the strongest explanatory variable for the change in eGFR (P = 0.0008), with a weaker contribution from the concomitant use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (P = 0.02). These results suggest that weekly infusions of agalsidase alfa at a dosage of 0.2 mg/kg may be beneficial in the subgroup of patients who have Fabry disease and whose kidney function continues to decline after 2 to 4 yr or more of standard EOW dosing.
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PMID:Weekly enzyme replacement therapy may slow decline of renal function in patients with Fabry disease who are on long-term biweekly dosing. 1742 46

This report describes an open-label, nonrandomized, prospective evaluation of the effects of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy on patients who have Fabry disease and also received enzyme replacement therapy with agalsidase-beta, given at 1 mg/kg body wt every 2 wk. Previous placebo-controlled phase III and phase IV trials with agalsidase-beta demonstrated clearing of globotriaosylceramide from vascular endothelia but little effect on proteinuria or progressive loss of kidney function in patients with Fabry disease and severe chronic kidney disease marked by overt proteinuria and/or estimated GFR <60 ml/min per 1.73 m2. Angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker therapy is the standard of care for patients with proteinuric kidney diseases, but their use is challenging in patients with Fabry disease and low or low-normal baseline systemic BP. A group of patients with Fabry disease were treated with antiproteinuric therapy, in conjunction with agalsidase-beta; sustained reductions in proteinuria with stabilization of kidney function were achieved in a group of six patients who had severe Fabry nephropathy; the progression rate was -0.23 +/- 1.12 ml/min per 1.73 m2 per yr with 30 mo of follow-up.
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PMID:Antiproteinuric therapy and fabry nephropathy: sustained reduction of proteinuria in patients receiving enzyme replacement therapy with agalsidase-beta. 1769 7

The aim of this study was to determine the effects of enzyme replacement therapy with agalsidase alpha on renal function in patients with Fabry nephropathy. Serum creatinine data were collected from 165 adult patients during 3 years of treatment. Serum creatinine increased in all men whereas it was stable in women, except in stage II renal disease (Kidney Disease Outcomes Quality Initiative). The estimated glomerular filtration rate (eGFR) declined in males with stage I and II (from 115.0 +/- 22.2 to 98.3 +/- 27.3 and from 76.5 +/- 8.1 to 66.3 +/-21.6 ml/min/1.73 m(2), respectively; both p < 0.01), whereas eGFR was stable in stage III. In females, eGFR was stable in stages I and III, and decreased in stage II (from 72.5 +/- 8.3 to 67.3 +/- 13.6 ml/min/1.73 m(2); p = 0.01). The 24-hour proteinuria was <1 g in all patients, and most patients (96%) were treated with angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors. Agalsidase alpha in combination with ACE inhibitors/ARB may be effective in slowing the deterioration in renal function in Fabry nephropathy.
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PMID:Agalsidase alfa slows the decline in renal function in patients with Fabry disease. 1897 35

Involvement of the kidneys in Fabry disease ("nephropathy") occurs in male and female individuals. The majority of patients with progressive nephropathy will have significant proteinuria and develop progressive loss of kidney function, leading to ESRD. All too often, treating physicians may ignore "normal" serum creatinine levels or "minimal" proteinuria and fail to assess properly the severity of kidney involvement and institute appropriate management. Fabry nephropathy is treatable, even in patients with fairly advanced disease. Although the cornerstone of therapy remains enzyme replacement therapy with agalsidase, this treatment alone does not reduce urine protein excretion. Treatment with angiotensin receptor blockers or angiotensin-converting enzyme inhibitors must be added to enzyme replacement therapy to reduce urine protein excretion with the hope that this will stabilize kidney function. Kidney function, with at least estimated GFR based on serum creatinine and measurements of urinary protein, should be measured at every clinic visit, and the rate of change of the estimated GFR should be followed over time. Antiproteinuric therapy can be dosed to a prespecified urine protein target rather than a specific BP goal, with the proviso that successful therapy will usually lower the BP below the goal of 130/80 mmHg that is used for other forms of kidney disease. The overall goal for treating Fabry nephropathy is to reduce the rate of loss of GFR to -1 ml/min per 1.73 m(2)/yr, which is that seen in the normal adult population. A systematic approach is presented for reaching this goal in the individual patient.
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PMID:Enzyme replacement therapy and Fabry nephropathy. 2000 80

Introduction: Chronic kidney disease (CKD) is characterized by increased risks of progression to end-stage kidney disease requiring dialysis and cardiovascular mortality, predicted to be among the five top causes of death by 2040. Only the design and optimization of novel strategies to develop new drugs to treat CKD will contain this trend. Current therapy for CKD includes nonspecific therapy targeting proteinuria and/or hypertension and cause-specific therapies for diabetic kidney disease, autosomal dominant polycystic kidney disease, glomerulonephritides, Fabry nephropathy, hemolytic uremic syndrome and others.Areas covered: Herein, the authors review the literature on new drugs under development for CKD as well as novel design and development strategies.Expert opinion: New therapies for CKD have become a healthcare priority. Emerging therapies undergoing clinical trials are testing expanded renin-angiotensin system blockade with double angiotensin receptor/endothelin receptor blockers, SGLT2 inhibition, and targeting inflammation, the immune response, fibrosis and the Nrf2 transcription factor. Emerging therapeutic targets include cell senescence, complement activation, Klotho expression preservation and microbiota. Novel approaches include novel model systems that can be personalized (e.g. organoids), unbiased systems biology-based identification of new therapeutic targets, drug databases that speed up drug identification and repurposing, nanomedicines that improve drug delivery and RNA targeting to expand the number of targetable proteins.
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PMID:Design and optimization strategies for the development of new drugs that treat chronic kidney disease. 3173 79