Background People with reduced glomerular filtration rate (GFR) often have elevated cardiac troponin T (cTnT) levels. It remains unclear how cTnT levels develop over time in those with chronic kidney disease (CKD). The aim of this study was to prospectively study the association between cTnT and GFR over time in older advanced‐stage CKD patients not on dialysis. Methods and Results The EQUAL (European Quality Study) study is an observational prospective cohort study in stage 4 to 5 CKD patients aged ≥65 years not on dialysis (incident estimated GFR, <20 mL/min/1.73 m²). The EQUAL cohort used for the purpose of this study includes 171 patients followed in Sweden between April 2012 and December 2018. We used linear mixed models, adjusted for important groups of confounders, to investigate the effect of both measured GFR and estimated GFR on high‐sensitivity cTnT (hs‐cTnT) trajectory over 4 years. Almost all patients had at least 1 hs‐cTnT measurement elevated above the 99th percentile of the general reference population (≤14 ng/L). On average, hs‐cTnT increased by 16%/year (95% CI, 13–19; P <0.0001). Each 15 mL/min/1.73 m 2 lower mean estimated GFR was associated with a 23% (95% CI, 14–31; P <0.0001) higher baseline hs‐cTnT and 9% (95% CI, 5–13%; P <0.0001) steeper increase in hs‐cTnT. The effect of estimated GFR on hs‐cTnT trajectory was somewhat lower than a previous myocardial infarction (15%), but higher than presence of diabetes mellitus (4%) and male sex (5%). Conclusions In CKD patients, hs‐cTnT increases over time as renal function decreases. Lower CKD stage (each 15 mL/min/1.73 m 2 lower) is independently associated with a steeper hs‐cTnT increase over time in the same range as other established cardiovascular risk factors.

Background and PurposePhosphate imbalance is often present in chronic kidney disease (CKD), and it contributes to a higher cardiovascular mortality rate. A phosphate binder is typically part of a treatment strategy for controlling phosphate imbalance. However, safety concerns and low compliance are two well-recognized disadvantages of on-market phosphate binders. This report describes the preclinical studies of VS-505, a non-absorbable, calcium- and aluminum-free, plant-derived polymer currently being evaluated in haemodialysis patients in Australia.Experimental ApproachNormal Sprague Dawley (SD) rats or uraemic SD rats induced by 5/6 nephrectomy fed a high-phosphate diet were treated with VS-505 or sevelamer (0.05-10% in food) for 5 and 28days respectively.Key ResultsUrinary and serum phosphate levels were significantly elevated in untreated rats, and were decreased by VS-505 and sevelamer. VS-505 increased faecal phosphate levels in a dose-dependent manner. High-phosphate diet also caused an increase in serum FGF-23 and parathyroid hormone in nephrectomized (NX) rats, effects prevented by VS-505 or sevelamer. Significant aortic calcification was observed in NX rats treated with 5% sevelamer, whereas VS-505 at all doses tested did not show effects. VS-505 had no effects on small intestine histomorphology and intestinal sodium-dependent phosphate cotransporter gene expression. In vitro characterizations showed that VS-505 has a relatively high density and low expansion volume when exposed to simulated gastric fluid.Conclusions and ImplicationsVS-505 is a safe and effective phosphate binder and may offer the advantage of having a reduced pill burden and minimal GI side effects for CKD patients.

Inadequate control of serum phosphate in chronic kidney disease can lead to pathologies of clinical importance. Effectiveness of on‐market phosphate binders is limited by safety concerns and low compliance due to high pill size/burden and gastrointestinal ( GI ) discomfort. VS ‐501 is a nonabsorbed, calcium‐ and aluminum‐free, chemically modified, plant‐derived polymer. In vitro studies show that VS ‐501 has a high density and a low swell volume when exposed to simulated gastric fluid (vs. sevelamer). When male Sprague–Dawley ( SD ) rats on normal diet were treated with VS ‐501 or sevelamer, serum phosphate was not significantly altered, but urinary phosphate levels decreased by >90%. VS ‐501 had no effect on serum calcium (Ca) or urinary Ca, while 3% sevelamer significantly increased serum and urine Ca. In 5/6 nephrectomized ( NX ) uremic SD rats on high‐phosphate diet, increasing dietary phosphate led to an increase in serum and urine phosphate, which was prevented in rats treated with VS ‐501 or sevelamer (0.2–5% in food). High‐phosphate diet also increased serum fibroblast growth factor‐23 and parathyroid hormone in 5/6 NX rats that was prevented by VS ‐501 or sevelamer. VS ‐501 or sevelamer increased fecal phosphate in a dose‐dependent manner. More aortic calcification was observed in 5/6 NX rats treated with 5% sevelamer, while VS ‐501 and sevelamer did not show significant effects on cardiac parameters, fibrosis, intestine histology, and intestinal sodium‐dependent phosphate cotransporter gene expression. These results suggest that VS ‐501 is effective in binding phosphate with no effects on calcium homeostasis, and may have improved pill burden and GI side effects.