Isotope-specific breath analysis to track the end-stage renal disease during hemodialysis

The underlying mechanisms towards the progression of end-stage renal disease (ESRD) in chronic kidney disease (CKD) are poorly understood and it still remains a major clinical stumbling block for early detection of CKD. Most patients with CKD pass through ESRD with the necessity of frequent hemodialysis (HD) treatment. At present, plasma urea and creatinine levels are examined in most CKD patients to monitor their health status after dialysis. But it is impossible to get immediate feedback on the patients' health as the conventional tests involve the collection of blood samples, laboratory processing for a prolonged period of time and, finally, analysis of those samples. However, the test results are very important in deciding the treatment plan for those ESRD patients. Here, we show that the enzymatic activity of carbonic anhydrase in erythrocytes is distinctly altered in ESRD subjects under HD. This, in turn, leads to the isotopic enrichments of oxygen-18 (¹⁸O) and carbon-13 (¹³C) of CO₂ during respiration in HD treatment. High-resolution cavity-enhanced absorption spectroscopic measurements show that ¹⁸O and ¹³C-isotopic fractionations of breath CO₂ are correlated with Kt/V values, suggesting a novel unifying strategy for ESRD patients that can be used as an isotope-specific methodology for non-invasive assessment of dialysis adequacy and hence ¹²C¹⁸O¹⁶O and ¹³C¹⁶O¹⁶O could be used as novel markers for tracking the physiological parameters of ESRD individuals. Our findings suggest that the monitoring of ¹⁸O and ¹³C isotopes of breath CO₂ may facilitate the proper management of advanced CKD patients. The primary advantage of this isotopic breath test is that it may reduce the valuable time lag between the completion of dialysis and obtaining the clinical report on the status of patients' health.