NAG: potential cardiorenal biomarker indicates the progression of chronic kidney disease in implantable cardioverter defibrillator patients, contrary to KIM-1.

Aim: NAG and KIM-1 as markers of tubular damage are suggested as potential biomarkers for the cardiorenal syndrome. The aim of the study was to assess the prognostic capability of NAG and KIM-1 regarding progression of chronic kidney disease (CKD) in patients with implantable cardioverter defibrillator (ICD). Materials & methods: We included 313 patients with an ICD and collected plasma and urine samples. Follow-up was performed after 51 months (interquartile range [IQR]: 25-55). The outcome of interest was continuous CKD progression defined as persistent decline in estimated glomerular filtration rate category accompanied by a ≥25% drop of baseline estimated glomerular filtration rate. Results: An average of four (IQR: 2-6) follow-up values of serum creatinine per patient were obtained. During follow-up 29 patients (9%) developed a continuous CKD progression. NAG was shown as independent predictor for continuous CKD progression (p = 0.01), opposite to KIM-1 (p = n.s.). Conclusion: NAG was shown as predictor for a progressive and real deterioration of kidney function in patients with ICD.

Heart failure with recovered ejection fraction (HFrecEF): A new entity with improved cardiac outcome.

BACKGROUND: Aim of the study was a better characterization of heart failure (HF) with recovered ejection fraction (HFrecEF) and undulating EF (HFuEF) with regard to re-hospitalization due to congestive HF (CHF), adequate electric therapies (AETs) and mortality compared to HF with reduced EF (HFrEF), mid-range EF (HFmrEF) and preserved EF (pEF). METHODS: Retrospective study of 342 participants with an implantable cardioverter defibrillator (ICD) for primary or secondary prevention. Type of HF was classified according to left ventricular EF with 4.7 ± 3.1 investigations for each patient. RESULTS: Re-hospitalization due to CHF was similar in HFrecEF (7 (9.5%)), HFmrEF (2(9.0%)) and pEF (8(12.9%); p = n.s.) and significantly higher in HFrEF (62(38.0%)) and HFuEF (6(28.6%); p < .001 compared to HFrecEF and HFrEF). AETs were significantly lower in HFrecEF (13(17.6%)) compared to HFrEF (57(35.0%)), HFmrEF (7(31.8%)), pEF (18(29.0%)) and HFuEF (6(28.6%); each p < .01 compared to HFrecEF). Mortality was similar in HFrecEF (6(8.1%)) compared to HFuEF (0(0%)), pEF (4(6.5%)) and HFmrEF (2(9.0%), p = n.s.) and significantly lower compared to HFrEF (52(31.9%), p < .001). HFrEF was the strongest predictor for mortality besides age and chronic renal insufficiency according to Cox Regression (each p < .05) opposite to arterial hypertension, diabetes, type of cardiomyopathy and secondary prevention ICD indication (each p = n.s.). CONCLUSIONS: HFrecEF indicates as a new entity of HF with similar prognosis as pEF and HFmrEF with regard to re-hospitalization due to CHF and mortality and even better prognosis with regard to AETs. HFuEF showed similar rates of re-hospitalization due to CHF and AETs compared to HFrEF, but lower rates of mortality.

N-acetyl-b-D-glucosaminidase: A potential cardiorenal biomarker with a relevant impact on ICD shock therapies and mortality.

AIMS: Chronic heart failure may lead to chronic kidney disease. Previous studies suggest tubular markers N-acetyl-b-D-glucosaminidase (NAG) and Kidney-injury-molecule-1 (KIM-1) as potential markers for the cardiorenal syndrome (CRS). The prognostic value of NAG and KIM-1 regarding implantable cardioverter defibrillator (ICD) shock therapies is unknown. METHODS: We included 314 patients with an ICD and collected plasma and urine samples. Urine-values of NAG and KIM-1 got related to urinary creatinine. Outcomes of interest were sustained adequate shock therapies and a combined endpoint of all-cause mortality, rehospitalisation due to congestive heart failure and adequate shock therapies. Follow up time was 32 months (IQR 6-35 months). RESULTS: KIM-1 and NAG were positively correlated with NT-proBNP (KIM-1: r = .34, P < .001; NAG: r = .47, P < .001). NAG was significantly elevated in patients with primary prevention compared with secondary prevention ICD indication (P = .003). According to Kaplan Meier analysis, NAG as well as NT-proBNP were significant predictors for adequate ICD shock therapies and for the combined endpoint (each P < .001). Elevated KIM-1 showed no significant differences (each P = n.s.). In multivariate cox regression analysis, NAG as well as NT-proBNP were both independent predictors for adequate ICD shock therapies as well as the combined endpoint, beside ejection fraction <35% (each P < .05). Diabetes, primary prevention ICD indication, coronary artery disease, eGFR and age were no significant predictors for both endpoints (each P = n.s.). CONCLUSION: Similar to NT-proBNP, NAG showed promising value for overall prognostication in ICD patients. Especially, NAG seems to incorporate an additional prognostic value regarding occurrence of ICD shock therapies.

N-acteyl-ß-D-glucosaminidase and kidney injury molecule-1: New predictors for long-term progression of chronic kidney disease in patients with heart failure.

AIM: Patients with chronic heart failure (CHF) are often characterized by the cardiorenal syndrome (CRS). The aim of the present study was to assess whether novel markers of kidney injury are able to predict progression of chronic kidney disease (CKD) in patients with CHF. METHODS: New renal biomarkers, N-acteyl-ß-D-glucosaminidase (NAG), kidney injury molecule-1 (KIM-1) and Neutrophil Gelatinase-Associated Lipocalin (NGAL), were assessed from urine samples of 149 patients with chronic heart failure. During a 5-year-follow-up, renal function was assessed by creatinine and estimated glomerular filtration rate (eGFR CKD EPI) and was available for 138 patients. Further, data regarding all-cause mortality was obtained. RESULTS: Twenty-six patients (18.8%) developed a progression of CKD during the follow-up period, as defined by decline in eGFR category accompanied by a ≥25% drop in eGFR form baseline. No difference regarding age, sex, body mass index, hypertension, diabetes or EF was present between patients with and without CKD progression (each P = n.s.). At baseline, creatinine concentrations and eGFR were significantly different between both groups (sCr: 1.50 ± 0.67 vs 1.04 ± 0.37, P = < 0.001; eGFR: 47.8 ± 12.3 vs. 77.3 ± 23.5 mL/min per 1.73m(2) , each P < 0.001). In a Kaplan-Meier-analysis, KIM-1 and NAG were significant predictors for CKD progression (both P < 0.05). In Cox regression analysis, NAG > median (OR 3.25,P = 0.013), initial eGFR (OR 0.94, P < 0.001) and diuretic use (OR 3.92, P = 0.001) were independent predictors of CKD progression. Further, KIM-1 and NAG were also independent predictors of a combined endpoint of CKD progression and all-cause mortality by Cox regression analysis (each P < 0.05). The combination of both markers showed additive value regarding both endpoints. NGAL showed no association with CKD progression. CONCLUSIONS: During long-term follow-up chronic heart failure patients with CKD show a relevant disease progression. The current study emphasizes a strong association of the tubular biomarkers NAG and KIM-1 with CKD progression in chronic heart failure and suggests their usefulness as cardiorenal markers.