Publications

CONTEXT

Serum creatinine has been reported to increase in patients receiving Vemurafenib, yet neither the prevalence nor the mechanism of this adverse event are known.

OBJECTIVE

We aimed to evaluate the frequency and the mechanisms of increases in plasma creatinine level in patients receiving Vemurafenib for advanced melanoma.

METHODS

We performed a retrospective monocentric study including consecutive patients treated with Vemurafenib for an advanced melanoma. We collected clinical and biological data concerning renal function before introduction of Vemurafenib and in the course of monthly follow-up visits from March 2013 to December 2014. Cystatin C-derived glomerular filtration rate was evaluated before and after Vemurafenib initiation, as increase in serum cystatin C is specific to a decrease in the glomerular filtration rate. We also performed thorough renal explorations in 3 patients, with measurement of tubular secretion of creatinine before and after Vemurafenib initiation and a renal biopsy in 2 patients.

RESULTS

70 patients were included: 97% of them displayed an immediate, and thereafter stable, increase in creatinine (+22.8%) after Vemurafenib initiation. In 44/52 patients in whom Vemurafenib was discontinued, creatinine levels returned to baseline. Serum cystatin C increased, although proportionally less than serum creatinine, showing that creatinine increase under vemurafenib was indeed partly due to a renal function impairment. In addition, renal explorations demonstrated that Vemurafenib induced an inhibition of creatinine tubular secretion.

CONCLUSION

Thus, Vemurafenib induces a dual mechanism of increase in plasma creatinine with both an inhibition of creatinine tubular secretion and slight renal function impairment. However, this side effect is mostly reversible when Vemurafenib is discontinued, and should not lead physicians to discontinue the treatment if it is effective.

BACKGROUND

Since 2007, immigration applicants 2-14 years old with a tuberculin skin test (TST) ≥10 mm and an otherwise negative evaluation for tuberculosis (TB) are assigned a classification for TB infection and instructed to seek domestic evaluation upon arrival in the US in accordance with Centers for Disease Control and Prevention instructions. We examined the characteristics and outcome of domestic evaluation of immigrant children who arrived in California with a positive TST on preimmigration examination to inform the preimmigration TB screening process.

METHODS

Retrospective analysis of the characteristics and results of domestic evaluation of immigrants 2-14 years old who arrived in California with a classification for TB infection during October 1, 2008-September 30, 2013 was performed. TB disease was determined by matching preimmigration records with the California TB registry.

RESULTS

Among a total of 12,544 immigrant children included, 7786 (62%) were evaluated for TB postentry. Of these, 5243 (67%) were tested with TST or interferon gamma release assay (IGRA), and 2371 (45%) had a positive test. Of those tested with IGRA (n = 4035), 914 (23%) were positive. The proportion with positive IGRA increased significantly with age (years): 2-4 (11%), 5-9 (19%), 10-14 (28%), P < 0.0001; was lowest among arrivers from China (6%) and highest among arrivers from Mexico (48%). Nine children (0.07%) had TB disease within 5 years after arrival.

CONCLUSIONS

The majority of immigrant children with a positive preimmigration TST tested negative for TB infection on domestic evaluation using TST or IGRA. Inclusion of IGRA in preimmigration TB screening is likely to reduce subsequent testing, treatment and cost of evaluations among immigrant children to the US.