Urinary Pyrophosphate Excretion Research Articles

Renal handling of calcium and phosphorus in primary Sjogren syndrome

The excretion of inorganic pyrophosphate was studied in daily, fasting and postprandial urine specimens of normocalciuric and hypercalciuric patients with recurrent renal calcium stone disease (40 men and 40 women), and healthy controls (20 men and 20 women). Both populations were subdivided into younger (20 to 40 years old) and older (more than 40 years old) individuals.In general, there was a tendency towards higher urinary pyrophosphate excretion with increasing age (both sexes and all groups studied), and lower excretion in women than in men. The urinary pyrophosphate excretion rate was unchanged in daily and fasting urine specimens of the younger male normocalciuric and idiopathic hypercalciuric stone patients, whereas in the daily and postprandial urine of younger women the median excretion rate was reduced (controls versus normocalciuric plus idiopathic hypercalciuric subjects, 3 versus 1 μmol., p less than 0.05). In contrast, in older men urinary pyrophosphate was reduced in daily specimens (controls versus normocalciuric plus idiopathic hypercalciuric subjects, 55 versus 33 μmol., p less than 0.05) but it was unchanged in fasting urine specimens. In older women no change was detectable in any of the 3 urine portions. Factorization of urinary pyrophosphate for the associated urinary creatinine did not alter these results substantially, and the presence of renal stones did not modify pyrophosphate excretion significantly. Urinary pyrophosphate was correlated significantly with urinary volume, citrate and phosphorus.We conclude that only subclassification of stone patients with respect to sex, age and type of calciuria, and consideration of additional urine portions besides the daily urine may help to uncover states of urinary pyrophosphate deficit. On the basis of the data, we recommend that clinically relevant studies on inhibitory effects of urinary pyrophosphate on the nucleation and growth of crystals and stones should be done preferentially in urine portions with a proved pyrophosphate deficit.

Urinary Pyrophosphate in Patients with Recurrent Calcium Urolithiasis and in Healthy Controls: A Re-Evaluation

The excretion of inorganic pyrophosphate was studied in daily, fasting and postprandial urine specimens of normocalciuric and hypercalciuric patients with recurrent renal calcium stone disease (40 men and 40 women), and healthy controls (20 men and 20 women). Both populations were subdivided into younger (20 to 40 years old) and older (more than 40 years old) individuals.In general, there was a tendency towards higher urinary pyrophosphate excretion with increasing age (both sexes and all groups studied), and lower excretion in women than in men. The urinary pyrophosphate excretion rate was unchanged in daily and fasting urine specimens of the younger male normocalciuric and idiopathic hypercalciuric stone patients, whereas in the daily and postprandial urine of younger women the median excretion rate was reduced (controls versus normocalciuric plus idiopathic hypercalciuric subjects, 3 versus 1μmol., p less than 0.05). In contrast, in older men urinary pyrophosphate was reduced in daily specimens (controls versus normocalciuric plus idiopathic hypercalciuric subjects, 55 versus 33μmol., p less than 0.05) but it was unchanged in fasting urine specimens. In older women no change was detectable in any of the 3 urine portions. Factorization of urinary pyrophosphate for the associated urinary creatinine did not alter these results substantially, and the presence of renal stones did not modify pyrophosphate excretion significantly. Urinary pyrophosphate was correlated significantly with urinary volume, citrate and phosphorus.We conclude that only subclassification of stone patients with respect to sex, age and type of calciuria, and consideration of additional urine portions besides the daily urine may help to uncover states of urinary pyrophosphate deficit. On the basis of the data, we recommend that clinically relevant studies on inhibitory effects of urinary pyrophosphate on the nucleation and growth of crystals and stones should be done preferentially in urine portions with a proved pyrophosphate deficit.

Urinary pyrophosphate excretion in renal stone formers with normal and impaired renal acidification

A recently described method for analysis of inorganic pyrophosphate (PPi) was used to investigate urinary excretion of PPi in renal calcium stone formers with normal (n=44) or impaired renal acidification capacity (RTA; n=13) as well as in controls (n=22) of corresponding sex and age. The mean values of the 24 h urinary PPi excretion were lower in stone-forming groups than in the control group. There was no statistical difference in the mean 24-h PPi excretion between stone-forming groups with normal and with defective urinary acidification, but there was an overrepresentation of low values for PPi excretion in the latter subject group. Positive relationships existed in all subject groups between the urinary excretion of phosphate and PPi when pooled data from various conditions of phosphate intake (fasting, non-fasting, oral phosphate loading) were examined. In the fasting state the PPi excretion was similar in stone formers and controls. Oral orthophosphate loading after phosphate deprivation with aluminium hydroxide invariably caused a rise in urinary PPi excretion in all subjects, with no difference between stone formers with normal acidification, RTA stone patients and controls. The increment in urinary PPi was positively correlated to the increment in urinary phosphate but not to changes in serum phosphate. In conclusion, these results suggest that renal stone formers may have a lower daily PPi excretion compared with controls. This was most pronounced in patients with impaired renal acidification capacity and may be due to a generalized disturbed tubular function.

Enzymic measurement of urinary pyrophosphate with a centrifugal analyzer.

We describe a simple, rapid, and fully automated technique for measuring urinary pyrophosphates with a centrifugal analyzer (the ENI GEMSAEC). This technique depends on the enzymic magnesium-dependent reaction with UDPG pyrophosphorylase (UTP: alpha-D-glucose-1-phosphate uridylyl transferase, EC 2.7.7.9) and spectrophotometry of the NADPH formed in a combined system of phosphorylation and reduction. Many samples of urine can be analyzed quickly without pretreatment, with high sensitivity (1.3 mA/mumol of substrate) and good reproducibility. The mean within-run coefficient of variation for a 50 mumol/L pyrophosphate solution was 1.4%. We determined the optimum enzyme and magnesium concentrations necessary for use in a 4-min reaction. Because there is no inhibitory effect of chloride and phosphate ions, pyrophosphate can be measured directly in urine, without prior extraction. With this technique, the mean value (and SD) for urinary pyrophosphate excretion by 30 healthy subjects was 39.3 (SD 17.2) mumol/24 h.

Renal Stones and Intravenous Fielding

Adelman et al1 report nephrolithiasis as another complication that may be seen associated with total parenteral nutrition (TPN). The authors implicate parenteral calcium infusion as the cause of calcium phosphate calculi in their patient. Another possible etiologic factor in renal stone formation is that of hypophosphatemia. Urinary excretion of pyrophosphate, a potent inhibitor of calcium crystal formation, is decreased in the presence of hypophosphatemia, thus favoring calculi formation. It has also been shown that a decrease in cellular phosphate in the renal cortex2 may stimulate increased formation of 1,25(OH)2D3, which in turn will cause an increase in urinary calcium excretion.3

Increased Inorganic Serum Pyrophosphate in Serum and Urine of Patients with Osteogenesis Imperfecta

Abstract Inorganic pyrophosphate can be accurately determined in 2 to 4 ml of serum or urine by an ion-exchange method. Pyrophosphate degradation by serum alkaline phosphatase and pyrophosphatase is stopped by adding to the serum 0.1 mmol of dithiothreitol (Cleland's reagent) per liter. This method is suitable for screening large numbers of patients. All of the patients studied who had classical symptoms of active osteogenesis imperfecta also had abnormally high concentrations of pyrophosphate in their serum. Of this group, 62% excreted increased amounts of pyrophosphates in their urine. Seven adults with inactive osteogenesis imperfecta had normal concentrations of inorganic pyrophosphate in their serum, but their urinary excretion of pyrophosphate was abnormally great. Patients undergoing therapy with magnesium oxide or calcitonin had normal values for serum and urine pyrophosphate. Determination of inorganic pyrophosphate concentrations in serum may be helpful in studying the progress of this disease and in monitoring therapy.

High urinary pyrophosphate excretion in the acute phase of pseudogout

High urinary pyrophosphate excretion in the acute phase of pseudogout

Basal urinary pyrophosphate excretion in pseudogout.

AbstractUrinary pyrophosphate excretion was measured in 4 patients with calcium pyrophosphate crystal deposition disease, and was found to be in the low normal range reported by others. A more strictly controlled diet may account for the relatively low values obtained.

73 The In Vitro Control of Calcification in Osteogenesis Imperfecta

Previous work has implicated bone collagen obtained from patients with osteogenesis imperfecta as a potent inhibitor of the in vitro formation of bone mineral. The present investigation further examines the mechanism of inhibition and suggests a possibility for therapy. It was observed that the citrate-soluble fraction of bone collagen from two patients with the disease had a pyrophosphate content of 1.4 μm/mg collagen which is four times the normal value. Urinary excretion of pyrophosphate was also elevated. As pyrophosphates are thought to be inhibitors of calcification both in vitro and in vivo (FLEISCH, H. et al. Nature 212: 903-3 [1966].), the abnormal collagen was treated with the enzyme pyrophosphatase in the presence of Mg as cofactor during the in vitro mineralization procedure. It was found that Mg alone significantly increased the catalytic properties of osteogenesis imperfecta collagen and this effect was doubled when pyrophosphatase was present. These results suggest that collagen-bound pyrophosphate is partly responsible for the failure of bone matrix to calcify. The possibility that these patients need a high level of Mg as cofactor for their pyrophosphatase activity is being investigated. (Supported by U.S.P.H.S. AM 08757–03) (SPR).

Excretion of Pyrophosphate in Disorders of Bone Metabolism

Measurements of urinary inorganic pyrophosphate in clinical disorders characterized by increased turnover of bone have demonstrated significant pyrophosphaturia. Pyrophosphate excretion paralleled the hydroxyprolinuria noted in each instance and was unrelated to total urinary inorganic orthophosphate. These observations suggest that urinary pyrophosphate excretion may reflect the abnormal patterns of bone resorption and remodeling in clinical disorders of bone metabolism.