Assessment of GFR in Patients with Cancer: A Statement from the American Society of Onco-Nephrology.

Accurate assessment of GFR is crucial to guiding drug eligibility, dosing of systemic therapy, and minimizing the risks of both undertreatment and toxicity in patients with cancer. Up to 32% of patients with cancer have baseline CKD, and both malignancy and treatment may cause kidney injury and subsequent CKD. To date, there has been lack of guidance to standardize approaches to GFR estimation in the cancer population. In this two-part statement from the American Society of Onco-Nephrology, we present key messages for estimation of GFR in patients with cancer, including the choice of GFR estimating equation, use of race and body surface area adjustment, and anticancer drug dose-adjustment in the setting of CKD. These key messages are based on a systematic review of studies assessing GFR estimating equations using serum creatinine and cystatin C in patients with cancer, against a measured GFR comparator. The preponderance of current data involving validated GFR estimating equations involves the CKD Epidemiology Collaboration (CKD-EPI) equations, with 2508 patients in whom CKD-EPI using serum creatinine and cystatin C was assessed (eight studies) and 15,349 in whom CKD-EPI with serum creatinine was assessed (22 studies). The former may have improved performance metrics and be less susceptible to shortfalls of eGFR using serum creatinine alone. Since included studies were moderate quality or lower, the American Society of Onco-Nephrology Position Committee rated the certainty of evidence as low. Additional studies are needed to assess the accuracy of other validated eGFR equations in patients with cancer. Given the importance of accurate and timely eGFR assessment, we advocate for the use of validated GFR estimating equations incorporating both serum creatinine and cystatin C in patients with cancer. Measurement of GFR via exogenous filtration markers should be considered in patients with cancer for whom eGFR results in borderline eligibility for therapies or clinical trials.

Physiopathology of Phosphate Disorders.

Intracellular phosphate is critical for cellular processes such as signaling, nucleic acid synthesis, and membrane function. Extracellular phosphate (Pi) is an important component of the skeleton. Normal levels of serum phosphate are maintained by the coordinated actions of 1,25-dihydroxyvitamin D3, parathyroid hormone and fibroblast growth factor-23, which intersect in the proximal tubule to control the reabsorption of phosphate via the sodium-phosphate cotransporters Npt2a and Npt2c. Furthermore, 1,25-dihydroxyvitamin D3 participates in the regulation of dietary phosphate absorption in the small intestine. Clinical manifestations associated with abnormal serum phosphate levels are common and occur as a result of genetic or acquired conditions affecting phosphate homeostasis. For example, chronic hypophosphatemia leads to osteomalacia in adults and rickets in children. Acute severe hypophosphatemia can affect multiple organs leading to rhabdomyolysis, respiratory dysfunction, and hemolysis. Patients with impaired kidney function, such as those with advanced CKD, have high prevalence of hyperphosphatemia, with approximately two-thirds of patients on chronic hemodialysis in the United States having serum phosphate levels above the recommended goal of 5.5 mg/dL, a cutoff associated with excess risk of cardiovascular complications. Furthermore, patients with advanced kidney disease and hyperphosphatemia (>6.5 mg/dL) have almost one-third excess risk of death than those with phosphate levels between 2.4 and 6.5 mg/dL. Given the complex mechanisms that regulate phosphate levels, the interventions to treat the various diseases associated with hypophosphatemia or hyperphosphatemia rely on the understanding of the underlying pathobiological mechanisms governing each patient condition.