Urinary cGMP predicts major adverse renal events in patients with mild renal impairment and/or diabetes mellitus before exposure to contrast medium

Abstract

BackgroundThe use of iodine-based contrast agents entails the risk of contrast induced nephropathy (CIN). Radiocontrast agents elicit the third most common cause of nephropathy among hospitalized patients, accounting for 11–12% of cases. CIN is connected with clinically significant consequences, including increased morbidity, prolonged hospitalization, increased risk of complications, potential need for dialysis, and increased mortality rate. The number of in-hospital examinations using iodine-based contrast media has been significantly increasing over the last decade. In order to protect patients from possible complications of such examinations, new biomarkers are needed that are able to predict a risk of contrast-induced nephropathy. Urinary and plasma cyclic guanosine monophosphate (cGMP) concentrations are influenced by renal function. Urinary cGMP is primarily of renal cellular origin. Therefore, we assessed if urinary cGMP concentration may predict major adverse renal events (MARE) after contrast media exposure during coronary angiography.MethodsUrine samples were prospectively collected from non-randomized consecutive patients with either diabetes or preexisting impaired kidney function receiving intra-arterial contrast medium (CM) for emergent or elective coronary angiography at the Charité Campus Mitte, University Hospital Berlin. Urinary cGMP concentration in spot urine was analyzed 24 hours after CM exposure. Patients were followed up over 90 days for occurrence of death, initiation of dialysis, doubling of plasma creatinine concentration or MARE.ResultsIn total, 289 consecutive patients were included into the study. Urine cGMP/creatinine ratio 24 hours before CM exposure expressed as mean±SD was predictive for the need of dialysis (no dialysis: 89.77±92.85 μM/mM, n = 277; need for dialysis: 140.3±82.90 μM/mM, n = 12, p = 0.008), death (no death during follow-up: 90.60±92.50 μM/mM, n = 280; death during follow-up: 169.88±81.52 μM/mM, n = 9; p = 0.002), and the composite endpoint MARE (no MARE: 86.02±93.17 μM/mM, n = 271; MARE: 146.64±74.68 μM/mM, n = 18, p<0.001) during the follow-up of 90 days after contrast media application. cGMP/creatinine ratio stayed significantly increased at values exceeding 120 μM/mM in patients who developed MARE, required dialysis or died.ConclusionsUrinary cGMP/creatinine ratio ≥ 120 μM/mM before CM exposure is a promising biomarker for the need of dialysis and all-cause mortality 90 days after CM exposure in patients with preexisting renal impairment or diabetes.

Activation of soluble guanylyl cyclase signalling with cinaciguat improves impaired kidney function in diabetic mice

“…Therefore, treatment with cinaciguat showed also only a slight, non‐significant induction of cGMP excretion in diabetic eNOS KO animals. Natriuretic peptides are enhanced under diabetic conditions (Malek et al, 2019; Moore et al, 2007; Obineche et al, 2006) and are mainly responsible for release of extracellular cGMP (Chaykovska et al, 2018). So, urinary cGMP probably come mainly from particulate GC signalling and high cGMP concentrations in urine of eNOS KO mice arise from a counterregulation due to reduced NO/sGC signalling.…”

“…Samples were loaded as follows: (a) NG + Dmannitol; (b) HG; (c) HG + 8-Br-cGMP; (d) HG + Cin. *P < .05, significantly different as indicated; Kruskal-Wallis test with Dunn's multiple comparisons test and are mainly responsible for release of extracellular cGMP(Chaykovska et al, 2018). So, urinary cGMP probably come mainly from particulate GC signalling and high cGMP concentrations in urine of eNOS KO mice arise from a counterregulation due to reduced NO/sGC signalling.…”

Biomarkers for the early prediction of contrast-induced nephropathy after percutaneous coronary intervention in adults: A systematic review and meta-analysis

“…ROC analyses of (tissue inhibitor of metalloproteinases 2 (TIMP-2)×)(insulin-like growth factor binding protein 7 (IGFBP7)) 65 on day one after transcatheter aortic valve implantation (TAVI) revealed a sensitivity of 100% and a specificity of 90% for predicting AKI. Other emerging biomarkers, such as urinary cyclic guanosine monophosphate (cGMP) 66 and serum kynurenine, 67 may have promising prospects. It is important to predict CIN and necessary to predict adverse events in CIN patients.…”

The SGLT2 Inhibitor Empagliflozin Might Be a New Approach for the Prevention of Acute Kidney Injury

“…The higher the clinical stage of AKI, the higher the morbidity and mortality, even the minimal increases in serum creatinine within 48 h following cardiac surgery resulted significantly worse outcomes and higher costs [14, 17-19]. AKI is a big challenge both to the medical institutes and society, resulting in a tremendous medical expenditure [13, 20, 21]. Prevention the development and treatment of AKI patients should be taken seriously to improve the outcome.…”