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Articles by D. G Warnock
Total Records ( 3 ) for D. G Warnock
  D. G Warnock and S. G. Rostand
 

The role of vitamin D in multiple organ systems is coming into sharp focus with recent advances in the understanding of its mechanisms of actions and interplay with multiple organ systems. Important distinctions between the role of 25-hydroxy metabolites that serve as substrates for subsequent hydroxylase reactions and the class of vitamin D receptor stimulating agents are important in understanding the clinical use of vitamin D in various clinical conditions.

  D. G Warnock , E Daina , G Remuzzi and M. West
 

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 m2/yr, which is that seen in the normal adult population. A systematic approach is presented for reaching this goal in the individual patient.

  R Schiffmann , D. G Warnock , M Banikazemi , J Bultas , G. E Linthorst , S Packman , S. A Sorensen , W. R Wilcox and R. J. Desnick
 

Background. In Fabry disease, progressive glycolipid accumulation leads to organ damage and early demise, but the incidence of renal, cardiac and cerebrovascular events has not been well characterized.

Methods. We conducted a retrospective chart review of 279 affected males and 168 females from 27 sites (USA, Canada, Europe). The pre-defined study endpoints included progression of renal, cardiac and cerebrovascular involvement and/or death before the initiation of enzyme replacement therapy.

Results. The mean rate of estimated glomerular filtration rate (eGFR) decline for patients was –2.93 for males, and –1.02 ml/min/1.73 m2/year for females. Prevalence and severity of proteinuria, baseline eGFR <60 ml/min/1.73 m2 and hypertension were associated with more rapid loss of eGFR. Advanced Fabry nephropathy was more prevalent and occurred earlier among males than females. Cardiac events (mainly arrhythmias), strokes and transient ischaemic attacks occurred in 49, 11, 6% of males, and in 35, 8, 4% of females, respectively. The mean age at death for 20 male patients was 49.9 years.

Conclusions. Baseline proteinuria, reduced baseline eGFR, hypertension and male gender were associated with more rapid progression of Fabry nephropathy. The eGFR progression rate may increase with advancing nephropathy, and may differ between subgroups of patients with Fabry disease.

 
 
 
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