Urinary Excretion and Deficiency of Prothrombin in Nephrotic Syndrome

Vaziri, Nosratola D.; Toohey, Julianne; Paule, Petra; Hung, Eleanor; Darwish, Riad; Barton, Cyril H.; Alikhani, S.

doi:10.1016/s0022-5347(17)48970-1

Cited by 6 publications

(8 citation statements)

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“…In spite of the fact that deficiency of factor IX is the most frequently published alteration, it has been found in studies performed with a high number of patients that the factor IX concentration is high |46] or normal [531. Prothrom bin has been found to be low [56], high [56,57], or normal [47,56,57]. In figure 6.…”

Section: Intrinsic Pathwaymentioning

confidence: 97%

Abnormalities of Coagulation in Experimental Nephrotic Syndrome

Cruz

Juárez-Nicolás

Tapia

et al. 1994

Nephron

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The human nephrotic syndrome is accompanied by important alterations of the coagulation system related proteins. The purpose of the present study was to examine the activity of coagulation- and fibrinolysis-related proteins in plasma and urine of control and puromycin aminonucleoside injected rats on days 2 (prenephrotic stage) and 10 (nephrotic stage). We measured the prothrombin time (PT), the activated partial thromboplastin time (aPTT), and the activities of (1) the coagulation factors (CFs) I, II, V, and VII-XII; (2) the inhibitor of coagulation antithrombin III (ATIII), and (3) the component of the fibrinolytic system α₂-antiplasmin (α₂-APL). PT and aPTT and the activities of CF, ATIII, and α₂-APL were not measurable in the urine of control and puromycin aminonucleoside injected rats on day 2. On this same day, plasma ATIII and CF VIII decreased. On day 10 (1) PT and aPTT decreased in plasma and were not measurable in urine; (2), plasma CFs I, II, V, VII, VIII, X, and XI increased; (3), plasma ATIII decreased; (4), plasma CFs IX and XII and α₂-APL did not change, and (5) ATIII and CFs II, VII, VIII, IX, X, XI, and XII, but not CFs I and V and α₂-APL, appeared in urine on day 10. ATIII deficiency was secondary probably to the urinary losses; however, the plasma activity of CFs II, VII, VIII, X, and XI increased and that of CFs IX and XII remained unchanged in spite of their urinary losses which suggests that other mechanisms such as deranged catabolism and altered hepatic synthesis may be involved. This model may be useful to study the pathophysiology of the abnormalities of coagulation in humans with nephrotic syndrome.

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Section: Intrinsic Pathwaymentioning

confidence: 97%

Abnormalities of Coagulation in Experimental Nephrotic Syndrome

Cruz

Juárez-Nicolás

Tapia

et al. 1994

Nephron

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“…After this initial scission, the released thrombin cleaves F1j2 to fragment 2 (F2) and fragment 1 (F1) [18]. It is widely believed that prothrombin is absent from human urine, except in patients with nephrotic syndrome or during so-called hypercoagulable states [19]. None-theless, we have routinely detected prothrombin and F1j2 in the urine of healthy men and women who do not have haematuria, as well as in CaOx crystals generated from them [20].…”

Section: Introductionmentioning

confidence: 80%

“…One protein which may fulfil such a role is UPTF1, whose presence in urine could result directly from the renal synthesis of prothrombin [17] and\or the glomerular filtration of F1, resulting from turnover of the protein circulating in plasma. Although it is a widely held view that prothrombin itself is present in human urine only in certain disease states [19], we have frequently detected it in the urine of healthy male and female subjects who do not have haematuria and in CaOx crystals precipitated from it, although in far lower quantities than UPTF1 [20]. The fact that prothrombin contains the entire primary sequence of UPTF1 is sufficient to suggest that it too would be an efficient inhibitor of CaOx crystallization, a supposition that we have confirmed using a seeded inorganic crystallization system [26].…”

Section: Discussionmentioning

confidence: 99%

Effect of prothrombin and its activation fragments on calcium oxalate crystal growth and aggregation in undiluted human urine in vitro: relationship between protein structure and inhibitory activity

Grover

Ryall

2002

Clinical Science

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In recent years there has been great interest in the putative role of prothrombin and its activation peptides, especially the urinary form of prothrombin fragment 1, in the pathogenesis of calcium oxalate (CaOx) urolithiasis. Previously, we showed that prothrombin and its activation peptides inhibit CaOx crystallization in inorganic conditions in vitro. The aim of the present study was to determine if this inhibitory activity is retained in undiluted human urine and, therefore, whether it is likely to have any influence under physiological conditions. A secondary objective was to assess the relationship between the structures of the proteins and their inhibitory activities. Prothrombin was purified from Prothrombinex-HT, cleaved with thrombin and the resulting fragment 1 (F1) and fragment 2 (F2) were purified. The purity of each protein was confirmed by SDS/PAGE, and their effects on CaOx crystallization in undiluted ultrafiltered human urine were determined at a final concentration 80.65 nmol/l using Coulter Counter and [(14)C]oxalate analysis. The precipitated crystals were visualized using scanning electron microscopy. The Coulter Counter data revealed that, whereas prothrombin and its activation peptides did not affect the urinary metastable limit and the size of the precipitated particles, F1 did significantly reduce the latter. These findings were corroborated with scanning electron microscopy which also revealed that the reduction in particle size caused by F1 resulted from a decrease in the degree of crystal aggregation, rather than in the size of the individual crystals. The [(14)C]oxalate data showed that none of the proteins added significantly inhibited the mineral deposition. It was concluded that with the exception of F1, which does inhibit CaOx crystal aggregation, prothrombin and its activation peptides do not alter the deposition and aggregation of CaOx crystals in ultrafiltered human urine in vitro. Also, the gamma-carboxyglutamic acid domain of prothrombin and F1, which is absent from thrombin and F2, is the region of the molecules that determines their potent inhibitory effects. The superior potency of F1, compared with prothrombin, probably results from the molecule's greater charge-to-mass ratio.

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“…Therefore, this protein is sup posed to be considerably excreted in urine of NS patients. It has been reported that deficiency of certain proteins can be induced by urinary loss [15][16][17], Erythropoietin may be listed among such proteins. However, the urinary loss of erythropoietin is difficult to be evaluated, because more than 95% of urinary erythropoietin is degraded [ 18] and the results of urinary erythropoietin measurements in NS patients seem inconsistent in earlier studies [5,19].…”

Section: Discussionmentioning

confidence: 99%

Successful Erythropoietin Treatment for Severe Anemia in Nephrotic Syndrome without Renal Dysfunction

Ishimitsu

Ono²,

Sugiyama³

et al. 1996

Nephron

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A 62-year-old woman presented with nephrotic syndrome and severe anemia although the renal function was not impaired. Renal biopsy revealed the histology of membranoproliferative glomerulonephritis, and the proteinuria was resistant to steroid therapy. Iron deficiency, bleeding and other causes of anemia were ruled out, however, her serum erythropoietin level was inappropriately low. The anemia was rapidly corrected by administration of recombinant human erythropoietin. It is suggested that inappropriately low erythropoietin level, in part at least, accounts for the anemia in nephrotic syndrome. It is proposed that erythropoietin therapy should be taken into consideration for severe anemia in nephrotic syndrome even when the renal function is not impaired.

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Urinary Excretion and Deficiency of Prothrombin in Nephrotic Syndrome

Cited by 6 publications

References 0 publications

Abnormalities of Coagulation in Experimental Nephrotic Syndrome

Abnormalities of Coagulation in Experimental Nephrotic Syndrome

Effect of prothrombin and its activation fragments on calcium oxalate crystal growth and aggregation in undiluted human urine in vitro: relationship between protein structure and inhibitory activity

Successful Erythropoietin Treatment for Severe Anemia in Nephrotic Syndrome without Renal Dysfunction

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