Pamidronate preserves renal function, improves mortality in chronic critical illness

Issue: July 2015

NASHVILLE, Tenn. — Use of the intravenous bisphosphonate pamidronate to prevent bone resorption was associated with improved mortality, ventilator discontinuation and renal parameters in patients with chronic critical illness, according to data presented here.

Rifka C. Schulman, MD, of the Long Island Jewish Medical Center in New Hyde Park, NY, and colleagues at other institutions, reviewed a series of 148 patients with chronic critical illness admitted to the Mount Sinai Hospital respiratory care unit from 2009 to 2010. Of these patients, 31 were administered intravenous pamidronate 90 mg (titrated down to 30 mg, as necessary). The decision to use pamidronate was determined by 24-hour urine collagen cross-linked N-telopeptide (NTx) ≥ 70 nmol BCE/mmol Cr (n = 7), serum NTx ≥ 40 nMBCE/L (n = 3), 24-hour urine collagen cross-linked > 103 nmol BCE/mmol Cr (n = 8), 24-hour urine calcium ≥ 250 mg (n = 11) or ionized calcium > 1.29 mmol/L (n = 2). All levels of chronic kidney disease were represented among those who did and did not receive pamidronate. All patients had normal renal function, and those without hypercalcemia received calcium carbonate, ergocalciferol and calcitriol.

Rifka C. Schulman

Compared with the patients who did not receive pamidronate, the treatment group had significantly lower rates of readmission to the respiratory care unit (23% vs 0%; P = .0079) and 1-year mortality (55% vs 19%; P = .0015) and was more likely to be weaned from ventilator use (HR = 1.87; 95% CI, 0.84-4.15; P = .1254).

The patients in the pamidronate group had significantly lower creatinine levels 7 days after pamidronate administration (P = .0025), and there was no significant difference 14 days after treatment compared with 14 days prior to treatment. No significant change in mean glomerular filtration rate between admission and discharge was observed in either group. After adjustment for length of stay and baseline albumin levels, mean albumin levels improved more between admission and discharge for the pamidronate group (2.50 to 3.23 g/dL) than for the other patient group (2.49 to 2.72 g/dL; P <.0001).

In addition, no significant differences were found between patient groups for measures of glucose control or glycemic variability, but patients who received pamidronate experienced fewer episodes of hypoglycemia, Schulman said in the oral presentation.

After adjustment for hypoglycemic events, the pamidronate group had the same risk of dying in the respiratory care unit as the other patients (P = .0773) but were significantly less likely to die at 1 year (P = .0018).

“So tying this all together — and this is just really theoretical and requires a lot more studies — but there may be both short-term and long-term effects that bring us from pamidronate infusion to decreased mortality,” Schulman said. “Regarding the bone/beta-cell connection, possibly the pamidronate is suppressing osteocalcin, which suppresses adiponectin, which may cause a short-term insulin resistance, but it’s still all theoretical. … It may be [that] in the setting of the [respiratory care unit] where there were intense insulin protocols to monitor keeping the glucose in a tight range that insulin resistance might prevent hypoglycemia. This needs to be assessed further.” — by Jill Rollet

Reference:

Schulman RC, et al. Abstract #514. Presented at: AACE 24th Annual Scientific & Clinical Congress; May 13-17, 2014; Nashville, Tenn.

Disclosure: Grant support for this project was provided by Select Medical. Schulman and the other researchers report no relevant financial relationships. Mechanick reports receiving honoraria from Abbott Nutrition.