Renal Impairment Hampers Bisphosphonate Treatment in a Quarter of Lung Cancer Patients with Bone Metastasis

Basic Clin Pharmacol Toxicol. 2018 Jan;122(1):126-132. doi: 10.1111/bcpt.12854. Epub 2017 Aug 24.

Abstract

Renal function impairment in lung cancer patients with bone metastases was investigated, as this can limit the application of bisphosphonates representing the gold standard in the management of such cases. Clinicopathological data of 570 lung cancer patients were retrospectively analysed for changes in renal function parameters. Comorbidities included hypertension (50%), COPD (33%) and diabetes mellitus (15%). Statistical analysis was performed with Fisher's exact tests and a Cox proportional hazards model. In patients suffering from hypertension, both median serum creatinine and blood urea nitrogen (BUN) were higher (81.9 versus 75.8 μmol/L, p < 0.001 and 6.0 versus 5.7 mmol/L, p = 0.005, respectively). Such a difference could not be observed in patients with diabetes. In patients with COPD, only serum creatinine was higher (81.1 versus 77.3 μmol/L, p = 0.004). In the whole cohort, we found that while at the time of lung cancer diagnosis the ratio of patients in the pathological range (PRR) was 8.67% for serum creatinine (median: 75 μmol/L) and 14.16% for BUN (median: 5.4 mmol/L), at the time of bone metastasis the PRR for serum creatinine increased to 16.11% (median: 77.0 μmol/L) and for BUN to 24.07% (median: 6.0 mmol/L), which is a significant increase for both parameters (p < 0.001). For the whole cohort, the last laboratory results showed a 26.37% PRR for serum creatinine and 45.66% PRR for BUN (significant increase for both, p < 0.001). Multivariate analysis revealed that patients with hypertension had a higher chance for switching to the pathological range sooner (p = 0.033, HR: 1.372, CI: 1.025-1.835). Also, the appearance of the bone metastasis correlated with an acceleration of the onset of such a switch (p < 0.001, HR: 2.655, CI: 1.581-4.456). Our results suggest that renal function is impaired in a significant proportion of patients with lung cancer and highlight the importance of non-nephrotoxic drug in the management of bone metastases.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Density Conservation Agents / pharmacology*
  • Bone Density Conservation Agents / therapeutic use
  • Bone Neoplasms / blood
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / epidemiology
  • Bone Neoplasms / secondary
  • Comorbidity
  • Creatinine / blood
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / epidemiology
  • Diabetes Mellitus / physiopathology
  • Diphosphonates / pharmacology*
  • Diphosphonates / therapeutic use
  • Female
  • Humans
  • Hypertension / blood
  • Hypertension / epidemiology
  • Hypertension / physiopathology
  • Kidney / drug effects
  • Kidney / physiopathology
  • Kidney Function Tests
  • Lung Neoplasms / blood
  • Lung Neoplasms / epidemiology
  • Lung Neoplasms / pathology
  • Lung Neoplasms / physiopathology*
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / blood
  • Pulmonary Disease, Chronic Obstructive / epidemiology
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Renal Insufficiency / blood
  • Renal Insufficiency / epidemiology
  • Renal Insufficiency / physiopathology*
  • Retrospective Studies
  • Urea / blood

Substances

  • Bone Density Conservation Agents
  • Diphosphonates
  • Urea
  • Creatinine