Precision nephrotoxicity testing using 3D in vitro models.

Nephrotoxicity is a significant concern during the development of new drugs or when assessing the safety of chemicals in consumer products. Traditional methods for testing nephrotoxicity involve animal models or 2D in vitro cell cultures, the latter of which lack the complexity and functionality of the human kidney. 3D in vitro models are created by culturing human primary kidney cells derived from urine in a 3D microenvironment that mimics the fluid shear stresses of the kidney. Thus, 3D in vitro models provide more accurate and reliable predictions of human nephrotoxicity compared to existing 2D models. In this review, we focus on precision nephrotoxicity testing using 3D in vitro models with human autologous urine-derived kidney cells as a promising approach for evaluating drug safety.

PTH-Related Protein Assays in Advanced Kidney Disease: Implications for Evaluation of Hypercalcemia.

Hypercalcemia is a common and potentially serious electrolyte abnormality that is often observed in patients with chronic kidney disease (CKD). When malignancy is considered, parathyroid hormone-related protein (PTHrP) levels are often measured. PTHrP is produced by cancer cells and mimics the effects of parathyroid hormone (PTH) to elevate serum calcium concentrations. The amino and carboxy termini of PTHrP are of functional relevance. C-terminal PTHrP levels accumulate with CKD and can be elevated in normocalcemic CKD patients who lack malignancy. The existence of amino (N)-terminal and carboxy (C)-terminal PTHrP assays and how their concentrations are impacted by CKD are reviewed herein. The case of a patient on maintenance hemodialysis who developed prolonged hypercalcemia with elevated PTHrP concentrations is presented. The workup revealed suppressed intact PTH, low 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D levels. The initial PTHrP assay returned elevated. However, it was unappreciated that it was the C-terminal assay and the patient underwent an unnecessary search for malignancy. A subsequent N-terminal PTHrP assay returned within the normal range. Many commercial labs run the C-terminal PTHrP assay as their first-line test. This can lead to inaccurate differential diagnoses in hypercalcemic patients with CKD. We emphasize the need to specifically request N-terminal PTHrP assays in patients with advanced kidney disease when humoral hypercalcemia of malignancy is suspected.