Renal Function in Glycogen Storage Disease Type I, Natural Course, and Renopreservative Effects of ACE Inhibition

Abstract

Background and objectives: Renal failure is a major complication in glycogen storage disease type I (GSD I). We studied the natural course of renal function in GSD I patients. We studied differences between patients in optimal and nonoptimal metabolic control and possible renoprotective effects of angiotensin converting enzyme inhibition.Design, setting, participants, & measurements: Thirty-nine GSD I patients that visited our clinic were studied. GFR and effective renal plasma flow (ERPF) were measured by means of I 125 iothalamate and I 131 hippuran clearance and corrected for body surface area. Microalbuminuria was defined as >2.5 mg albumin/mmol creatinine and proteinuria as >0.2 g protein per liter. Optimal metabolic control was present when blood glucoses were >3.5 mmol/L, urine lactate/creatinine ratios <0.06 mmol/mmol, triglycerides <6.0 mmol/L, and uric acid concentrations <450 mol/L.Results: Quadratic regression analysis showed a biphasic pattern in the course of GFR and ERPF related to age. Microalbuminuria was observed significantly less frequently in the patients with optimal metabolic control compared with the patients with nonoptimal metabolic control. A significant decrease in GFR was observed after starting ACE inhibition.Conclusions: This study describes a biphasic pattern of the natural course of GFR and ERPF in GSD I patients, followed by the development of microalbuminuria and proteinuria. Optimal metabolic control has a renoprotective effect on the development of microalbuminuria and proteinuria in GSD I patients. Treatment with ACE inhibitors significantly decreases the GFR, especially in GSD I patients with glomerular hyperfiltration.

Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics

“…The exact mechanisms by which these changes occur are not well understood, but activation of the renin-angiotensin system, prolonged oxidative stress, and profibrotic cytokines such as transforming growth factor-β have all been implicated, as well as alterations in renal tubular epithelial cell energy stores related to G6Pase defects. [133][134][135][136] These renal changes occur early, and many children with GSD I will have evidence of glomerular hyperfiltration or elevation in the glomerular filtration rate (GFR) to more than 140 ml/min/1.73 m 2 within a few years of life. 137 These changes in GFR may not be readily detected because they result in serum creatinine levels that are often reported as normal.…”

“…In one study, a significantly smaller proportion of patients with optimal metabolic control of their serum glucose, triglyceride, and uric acid concentrations and urine lactate/creatinine ratios had microalbuminuria or proteinuria than patients with poor control. 135 Once proteinuria has occurred and there is established renal injury in GSD I, it becomes less clear if metabolic control alone alters the loss of GFR over time, underscoring the importance of using other forms of treatment that may delay the process.…”

“…142 Angiotensin blockade also seems to slow the tempo of GFR loss once it has started to occur. 135 Use of either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) medication by itself can be efficacious. In cases in which there is a need for further angiotensin blockade, use of both an ACE and an ARB can prove synergistic to reduce proteinuria, with no increased rate of hyperkalemia or drug-related renal insufficiency.…”

Screening Mentally Retarded Children for Inborn Errors of Metabolism

“…Glycogen storage diseases and mucopolysaccharidoses are known to present with nephrotic syndrome. 15,16 The positive cases of proteinuria in this study were also positive either for fructose or glucose, indicating kidney dysfunction that might be secondary to metabolic disease.…”

Selected Lipid Profile in the Serum &amp; Tissues of Weaned Male Albino Rats Fed on Processed Atlantic Horse Mackerel (&lt;i&gt;Trachurus trachurus&lt;/i&gt;)

“…The glucose then remains stored as body fat or glycogen, and/or is urinated out of the body [60]. Within the brain cells, glycogen is primarily stored in astrocytes, although ependymal and choroid plexus cells, as well as certain large neurons in the brainstem contain the polysaccharide [61]. Glycogen levels in brain are low compared to liver and muscle; however, the glycogen turnover rate is very rapid; its synthesis and breakdown are regulated by the two key enzymes glycogen phosphorylase and synthase [61].…”