An Observational Study on the Effects of Nadroparin-Based and Citrate-Based Continuous Venovenous Hemofiltration on Calcium Metabolism

Abstract

Backgrounds: To study calcium homeostasis during citrate-based compared to nadroparin-based CVVH in critically-ill patients with acute renal failure. Methods: 11 patients were observed during citrate anticoagulation, 9 with nadroparin and 10 controls. Citrate was chosen for patients with active or at risk for bleeding. Results: The controls had, at 24 h, a median serum iCa of 1.1 mmol/l, the citrate group 0.87 mmol/l and the nadroparin group 1.1 mmol/l (citrate vs. control p = 0.001, citrate vs. nadroparin p = 0.002). At 48 h, iCa was not significantly different anymore. Ca balance was negative for the citrate group in contrast to the nadroparin group (p = 0.012). Median serum PTH was higher (30.0 pmol/l vs. 6.5 pmol/l, p = 0.003) in the citrate group. Conclusion: With a relative low target-serum-iCa (0.8–0.9 mmol/l) citrate CVVH-treated patients had a negative daily calcium balance and a temporarily lower iCa level resulting in an enhanced PTH response in comparison to nadroparin.

Maintaining Normal Levels of Ionized Calcium during Citrate-Based Renal Replacement Therapy Is Associated with Stable Parathyroid Hormone Levels

“…Like Van der Voort et al [14], we found that the median PTH values were already above the normal range at baseline and rose further in the first 12-24 h before falling again. The average PTH levels were always above the normal range.…”

“…Serum calcium levels are restored by calcium supplementation and calcium release upon citrate metabolism. Some protocols allow mild systemic hypocalcaemia to occur provided clinical signs of hypocalcaemia are absent [14,15,20]. Low serum [Ca i ] is the main physiologic trigger for PTH release.…”

“…Although the role of PTH in ICU patients is still unclear, high PTH levels and disturbed calcium homeostasis are associated with bone reabsorption and poor outcomes in acutely ill patients [12,13,16,17,21,22,23]. Two small studies in critically ill patients receiving citrate-based CRRT reported a negative daily calcium balance and raised PTH levels, when aiming for relatively low systemic [Ca i ] [14,15]. Van der Voort et al [14] used a citrate protocol with target systemic [Ca i ] 0.8-1.0 mmol/l and showed a median [PTH] 28 pmol/l (254 pg/ml) at baseline which rose to 42.3 pmol/l (384.5 pg/ml) and 30 pmol/l (272.7 pg/ml) after 24 and 48 h, respectively.…”

“…Two small studies in critically ill patients receiving citrate-based CRRT reported a negative daily calcium balance and raised PTH levels, when aiming for relatively low systemic [Ca i ] [14,15]. Van der Voort et al [14] used a citrate protocol with target systemic [Ca i ] 0.8-1.0 mmol/l and showed a median [PTH] 28 pmol/l (254 pg/ml) at baseline which rose to 42.3 pmol/l (384.5 pg/ml) and 30 pmol/l (272.7 pg/ml) after 24 and 48 h, respectively. Patients who received anticoagulation with nadroparin had a median serum [PTH] 32 pmol/l (290.9 pg/ml) at baseline which declined to 9.4 pmol/l (85.5 pg/ml) and 6.5 pmol/l (59.1 pg/ml) after 24 and 48 h of CRRT, respectively.…”

“…In patients with normal kidney function, PTH also increases tubular calcium reabsorption and stimulates the conversion of 25- hydroxyvitamin D 3 to 1,25-dihydroxyvitamin D 3 . Studies in critically ill patients with acute kidney injury treated with citrate-based CRRT reported a negative calcium balance and a rise in intact PTH (PTHi) levels when accepting systemic [Ca i ] between 0.8 and 1.1 mmol/l [13,14,15]. The clinical consequences of hypocalcaemia and hyperparathyroidism have never been systematically studied in critically ill.…”