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Increased internal calcium mobilization in platelets of patients with chronic renal failure
A Tokumoto1, J Uemasu, H Kawasaki
1Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Japan.
Insights
Platelets in chronic renal failure (CRF) patients show elevated calcium responses to agonists, primarily from internal stores, not increased external influx. This impacts understanding platelet function in kidney disease.
Area of Science:
- Nephrology
- Hematology
- Cell Biology
Background:
- Platelet intracellular calcium ([Ca2+]i) dynamics are crucial for function.
- Altered calcium handling may contribute to complications in renal disease.
Purpose of the Study:
- To investigate intracellular calcium kinetics in platelets from patients with renal disease.
- To compare calcium responses to agonists between healthy controls and patients with chronic glomerulonephritis (CGN) and chronic renal failure (CRF).
Main Methods:
- Measurement of platelet free calcium concentrations ([Ca2+]i) using Fura-2.
- Stimulation of platelets with agonists like thrombin and adenosine diphosphate (ADP).
- Assessment of calcium responses in the presence of a calcium chelator to differentiate influx from intracellular mobilization.
Main Results:
- No significant differences in resting [Ca2+]i were observed among control, CGN, and CRF groups.
- Thrombin and ADP significantly increased [Ca2+]i in all groups.
- The agonist-induced rise in [Ca2+]i was significantly higher in CRF patients compared to controls and CGN patients.
- In the presence of a calcium chelator, the elevated [Ca2+]i response to thrombin remained significantly higher in CRF patients, indicating increased intracellular calcium release.
Conclusions:
- Platelets in CRF patients exhibit enhanced intracellular calcium mobilization in response to agonists.
- The heightened calcium response in CRF platelets is primarily driven by intracellular calcium pool release, not increased transmembrane calcium influx.
- These findings suggest altered platelet calcium kinetics in chronic renal failure, potentially impacting thrombotic risk.
Abstract:
Platelet free calcium concentrations ([Ca2+]i) were measured with Fura-2 to elucidate the intracellular calcium kinetics in patients with renal disease. There were no significant differences of the resting [Ca2+]i among the control subjects (C) (n = 12), patients with chronic glomerulonephritis (CGN) (n = 8), and patients with chronic renal failure (CRF) (n = 12). In all groups, platelets [Ca2+]i were significantly increased by agonists (thrombin, adenosine diphosphate) compared with their respective basal level. Thrombin-induced [Ca2+]i rise was significantly higher in CRF (840 +/- 265 nM) than in C (600 +/- 163) and CGN (562 +/- 137). Also adenosine diphosphate elicited similar responses. In the presence of calcium chelator in the incubation buffer, the elevation of [Ca2+]i after thrombin stimulation was statistically higher in CRF (469 +/- 85 nM) than in C (275 +/- 60) and CGN (301 +/- 41). These findings suggest that platelets of CRF were capable of increasing [Ca2+]i in response to agonists, through further mobilization of calcium from the intracellular pool rather than the elevation of transmembrane calcium influx.