A Brain–Kidney Connection: The Delicate Interplay of Brain and Kidney Physiology

The central nervous system (CNS) and kidneys are strongly interconnected. Afferent impulses from the CNS regulate renal blood flow, glomerular filtration rate (GFR), and affect renal sodium handling [1]. Vasopressin hormone is secreted from the posterior pituitary gland and acts on the collecting ducts of the distal nephron to regulate water balance and serum osmolality. However, the kidney is not a target organ that solely responds to impulses from the CNS. Impulses originating from the kidney are carried via unmyelinated and thinly myelinated fibers to the CNS and the contralateral kidney to regulate CNS activity and coordinate renal sodium handling with the contralateral kidney. In animal models with acute kidney injury (AKI), the levels of inflammatory cytokines increase in the brain with evidence of anatomic and functional brain injuries [2]. Both organs also share a common feature—a tight autoregulatory mechanism that maintains constant blood flow over a wide range of blood pressures. It is unclear, however, whether both the renal and brain autoregulatory mechanisms are interconnected in such a way that changes that occur in one organ affect the blood flow in the other. In this issue of Neurocritical Care, two articles by two separate NeuroICU teams report some important observations on the connection between the brain and kidney vascular beds and autoregulatory mechanisms. The first article by Dias et al. [3] reports a retrospective small series of 18 TBI patients in which various laboratory values were analyzed, including serum creatinine. The authors estimated both creatinine clearance (CrCL) and GFR using two creatinine-based equations: the Cockroft–Gault and the four-point Modification of Diet in Renal Diseases (MDRD) equations, respectively. ICP recording with mean arterial pressure (MAP) via a multimodal monitoring (MMM) computer was obtained, and the authors utilized the MMM data to acquire pressure-reactivity index (PRX) as a surrogate for cerebrovascular auto regulation (CVAR) and correlated PRX with CrCL and GFR, as well as other physiological and laboratory parameters. The authors’ data suggest that patients with brain injuries with better CVAR as measured by PRX were statistically associated with renal hyperfiltration, augmented renal clearance (ARC), and potentially better outcomes. While these findings are intriguing, the results should be interpreted with great caution. First, this study was not intended to monitor GFR, and therefore no ‘‘gold standard’’ method for GFR measurement, such as continuous infusion of iothalamate, was utilized. Second, intravenous fluid infusion in critically ill patients and mannitol use in TBI patients will affect serum creatinine concentration without any meaningful change in kidney function [4]. Third, although using creatinine-based equations to calculate CrCl (in the case of CG) and GFR (in the case of MDRD) seems appealing, in reality, serum creatinine is the only variable in these equations that demonstrates day-to-day changes, while the remaining variables in the equation such as age, gender, and race will remain constant. In addition, it is unclear whether ideal body weight, admission weight, or daily weight was utilized in calculating CrCl by CG. MDRD is intended for chronic kidney disease (CKD) patients and is biased in patients without CKD. Because of the way ‘‘hyperfiltration’’ was actually measured and reported, the whole idea of ARC should be taken with a grain of salt. A fourth W. D. Freeman (&) Departments of Neurosurgery, Neurology and Critical Care, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224, USA e-mail: freeman.william1@mayo.edu