Abstract
Over 20 years after the introduction of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, CKD remains a major public health burden with limited therapeutic options to halt or slow kidney disease progression at all ages. The consensus is that oxidative stress contributes to CKD development and progression. Yet, to date, there is no clear evidence that broad use of antioxidant therapy provides a beneficial effect in CKD. Understanding the specific pathophysiologic mechanisms in those who are genetically most susceptible to oxidative stress is a crucial step to inform therapy in an individualized medicine approach, considering differing exposures and risks across the life span. Glutathione-S-transferase μ 1 (GSTM1) is a phase 2 enzyme involved in inactivation of reactive oxygen species and metabolism of xenobiotics. In particular, those with the highly prevalent GSTM1 null genotype (GSTM1[0/0]) may be more susceptible to kidney disease progression, due to impaired capacity to handle the increased oxidative stress burden in disease states, and might specifically benefit from therapy that targets the redox imbalance mediated by loss of the GSTM1 enzyme. In this review, we will discuss the studies implicating the role of GSTM1 deficiency in kidney and related diseases from experimental rodent models to humans, from the prenatal period through senescence, and the potential underlying mechanism.