The effect of Pyridoxine on Oxalate Dynamics in three Cases of Primary Hyperoxaluria (with Glycollic Aciduria)

1. We have measured glomerular filtration rate (GFR), extracellular fluid volume (ECF), oxalate distribution volume (OxDV), plasma oxalate concentration (POx.), plasma total clearance of oxalate (PCOx.), oxalate metabolic pool size [(OxDV) × (POx.)], renal clearance of oxalate (RCOx.), oxalate excretion, tissue clearance of oxalate (TCOx.) and tissue oxalate accumulation rate [(TOx.A) = (TCOx.) × (POx.)] in three patients with type I primary hyperoxaluria (hyperoxaluria with hypergrycollic aciduria) when they were taking pyridoxine and after discontinuation of the vitamin. 2. Seven days after stopping pyridoxine the plasma oxalate concentration, oxalate metabolic pool size and the urinary excretion of oxalate had all increased between seven- and eight-fold in two of the patients. The third patient showed no changes on stopping pyridoxine. 3. These results support the view that pyridoxine acts by reducing oxalate biosynthesis in some patients with type I primary hyperoxaluria. 4. The possible biochemical basis for this effect is discussed.

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Oxalate Dynamics and Removal Rates during Haemodialysis and Peritoneal Dialysis in Patients with Primary Hyperoxaluria and Severe Renal Failure

Clinical Science ◽

10.1042/cs0660591 ◽

1984 ◽

Vol 66 (5) ◽

pp. 591-597 ◽

Cited By ~ 57

Author(s):

R. W. E. Watts ◽

N. Veall ◽

P. Purkiss

Keyword(s):

Renal Failure ◽

Peritoneal Dialysis ◽

Renal Transplantation ◽

Extracellular Fluid ◽

Primary Hyperoxaluria ◽

Distribution Volume ◽

Pool Size ◽

Severe Renal Failure ◽

Oxalate Excretion ◽

Metabolic Pool

1. We have measured the plasma oxalate concentration (POx), urinary oxalate excretion (UOx), oxalate equilibrium distribution volume (ODV), oxalate metabolic pool size [(ODV) × (POx)], total plasma oxalate clearance (PCOx), renal (or dialyser) oxalate clearance (RCOx), non-renal oxalate clearance (NRCOx) and the tissue oxalate accretion rate (TOA)= [(NRCOx) × (POx)] in three patients with severe renal failure due to primary hyperoxaluria who were being treated by peritoneal dialysis or haemodialysis, or by renal transplantation. The clearance (either GFR or dialyser) of [99mTc]diethylenetriaminepenta-acetate (DTPA) and the extracellular fluid volume (ECF) measured as [99mTc]DTPA distribution volume were also determined. 2. Negligible amounts of 14C were found in faeces or as 14CO2 in expired air and hence (NRCOx) = (PCOx-RCOx). 3. Haemodialysis removed oxalate more efficiently than peritoneal dialysis in the patient where a direct comparison was possible. Neither treatment could keep up with the TOA when performed for clinically acceptable times. 4. The plasma oxalate concentrations calculated from 14C clearance through the dialyser and the chemically determined concentration of the oxalate in the dialysate were in the range 111–146 μmol/l. This is higher than in normals and in hyperoxaluric patients who are not in renal failure. Hence, although the ODV and ECF are similar to those of hyperoxaluric patients without renal failure and normal control subjects, the oxalate metabolic pool (ODV × POx) is grossly enlarged. 5. In the patient treated by renal transplantation, the oxalate pool size diminished concurrently with the resumption of oxalate excretion but expanded again as renal function decreased due to oxalosis. 6. The quantitative data show that dialysis procedures can only be a temporary holding operation and the prognosis with transplantation remains bad unless excessive oxalate production can be controlled.

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Oxalate Balance Studies in Patients on Hemodialysis for Type I Primary Hyperoxaluria

American Journal of Kidney Diseases ◽

10.1016/s0272-6386(12)80833-x ◽

1992 ◽

Vol 19 (6) ◽

pp. 546-553 ◽

Cited By ~ 43

Author(s):

Martino Marangella ◽

Michele Petrarulo ◽

Domenico Cosseddu ◽

Corrado Vitale ◽

Franco Linari

Keyword(s):

Primary Hyperoxaluria ◽

Type I

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Protein carbamylation is a hallmark of aging

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1517096113 ◽

2015 ◽

Vol 113 (5) ◽

pp. 1191-1196 ◽

Cited By ~ 85

Author(s):

Laëtitia Gorisse ◽

Christine Pietrement ◽

Vincent Vuiblet ◽

Christian E. H. Schmelzer ◽

Martin Köhler ◽

...

Keyword(s):

Posttranslational Modifications ◽

Type I Collagen ◽

Accumulation Rate ◽

Mammalian Species ◽

Type I ◽

Protective Mechanisms ◽

Age Related ◽

Tissue Damages ◽

Carboxymethyl Lysine ◽

Tissue Alterations

Aging is a progressive process determined by genetic and acquired factors. Among the latter are the chemical reactions referred to as nonenzymatic posttranslational modifications (NEPTMs), such as glycoxidation, which are responsible for protein molecular aging. Carbamylation is a more recently described NEPTM that is caused by the nonenzymatic binding of isocyanate derived from urea dissociation or myeloperoxidase-mediated catabolism of thiocyanate to free amino groups of proteins. This modification is considered an adverse reaction, because it induces alterations of protein and cell properties. It has been shown that carbamylated proteins increase in plasma and tissues during chronic kidney disease and are associated with deleterious clinical outcomes, but nothing is known to date about tissue protein carbamylation during aging. To address this issue, we evaluated homocitrulline rate, the most characteristic carbamylation-derived product (CDP), over time in skin of mammalian species with different life expectancies. Our results show that carbamylation occurs throughout the whole lifespan and leads to tissue accumulation of carbamylated proteins. Because of their remarkably long half-life, matrix proteins, like type I collagen and elastin, are preferential targets. Interestingly, the accumulation rate of CDPs is inversely correlated with longevity, suggesting the occurrence of still unidentified protective mechanisms. In addition, homocitrulline accumulates more intensely than carboxymethyl-lysine, one of the major advanced glycation end products, suggesting the prominent role of carbamylation over glycoxidation reactions in age-related tissue alterations. Thus, protein carbamylation may be considered a hallmark of aging in mammalian species that may significantly contribute in the structural and functional tissue damages encountered during aging.

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