The risk of nephrolithiasis is causally related to inactive matrix Gla protein, a marker of vitamin K status: a Mendelian randomization study in a Flemish population (Wei et al.)
Nephrolithiasis (kidney stones) is the clinical condition characterized by the formation of crystal aggregates in the urinary tract, associated with substantial morbidity and high recurrence rates. In the US, the prevalence of nephrolithiasis is 8.8%, with men being almost twice as likely as women to have stones.
The main hypothesis of this paper was that the risk of nephrolithiasis increases with vitamin K shortage, as exemplified by higher plasma levels of desphospho-uncarboxylated MGP (dp-ucMGP). This study was the first population survey assessing the risk of nephrolithiasis in relation to dp-ucMGP, a biomarker of vitamin K status.
In 1,748 randomly recruited Flemish individuals (51.1% women; mean age 46.8 years), dpucMGP and the prevalence of nephrolithiasis was determined at baseline (April 1996–February 2015) and its incidence during followup until March 2016.
The key finding of the study is that higher levels of inactive dp-ucMGP may be causally associated with the risk of nephrolithiasis.
The authors summarized the results as follows:
- For a doubling of dp-ucMGP, the odds of nephrolithiasis increased by 31% in the cross-sectional analysis;
- The Mendelian randomization analysis suggested that this association was causal
- In the longitudinal analysis spanning 12 years of follow-up (median), the risk of having recurrent or new nephrolithiasis increased 2.5-fold for a doubling of the baseline dpucMGP level.
Additionally, the results show that one-third of the study participants had a dp-ucMGP level higher than optimal for the prevention of macrovascular complications (4.6 lg/L). These findings, therefore, suggest that increasing the dietary intake of VK, either by supplementation or by increasing the intake of nutrients rich in VK might prevent the formation of kidney stones.
To translate these present findings into clinical application, a randomized clinical trial of VK substitution to prevent stone recurrence is a research priority.
In conclusion, higher levels of inactive dp-ucMGP are associated with the risk of nephrolithiasis.
Wei et al. The risk of nephrolithiasis is causally related to inactive matrix Gla protein, a marker of vitamin K status: a Mendelian randomization study in a Flemish population. Nephrol Dial Transplant (2017) 1–9.