Aims: Chronic heart failure is often accompanied by chronic kidney disease and may lead to its aggravation. NAG and KIM-1 as tubular markers are suggested as potential biomarkers for the cardiorenal syndrome. The prognostic capability of tubular markers regarding progression of CKD in patients with chronic heart failure is unclear.

Methods: We included 313 patients with an ICD and collected plasma and urine samples. Follow-up was performed after 51 months (IQR 25-55) and the progress of renal function was evaluated by semiannual glomerular filtration rate (eGFR CKD-EPI) values. We excluded one patient, as there was no follow-up value of eGFR available. Further, data regarding ICD shock therapies and all cause mortality were obtained. Outcomes of interest were continuous progression of CKD, progression to CKD and a combined endpoint of continuous progression of CKD, ICD shock therapies and all-cause mortality. Continuous progression of CKD was defined by consistent decline in eGFR category accompanied by a ≥ 25% drop of baseline eGFR and progression to CKD as patients without CKD at baseline, but decline in eGFR category ≥ 3a accompanied by a ≥ 25% drop of baseline eGFR.

Results: Average four (IQR 2-6) follow-up values of serum creatinine per patient were obtained . CKD was initially evident in 127 patients (40.6%). During follow-up 29 patients (9.3%) developed a continuous progression of CKD. Marker levels of NAG were significantly elevated in patients with continuous progression of CKD (p < 0.001), opposite to KIM-1 (p = n.s.). According to Kaplan-Meier analysis, NAG ≥ median was a significant predictor for continuous CKD progression and the combined endpoint (each p < 0.01). In Cox regression analysis NAG was a significant predictor for continuous CKD progression beside serum creatinine, age and diabetes (each p < 0.05).

Further, 23 patients (7.3%) developed a progression to CKD. NAG was significantly elevated in patients with progression to CKD (p < 0.05), opposite to KIM-1 (p = n.s.). According to Kaplan-Meier analysis, NAG ≥ median was a significant predictor for progression to CKD (p < 0.01), opposite to KIM-1 (p = n.s.). In Cox regression analysis, NAG was an independent predictor for progression to CKD, beside age.

Conclusion: NAG showed promising value for long-term prognosis of CKD in patients with chronic heart failure, opposite to KIM-1. The current study shows a strong association between the tubular biomarker NAG and continuous progression of CKD as well as progression to CKD.