Angiotensin Receptor-Neprilysin Inhibitor Suppresses Renin-Angiotensin-Aldosterone System Activation After Cardiac Surgery Using Cardiopulmonary Bypass.

BACKGROUND: Sacubitril/valsartan, being both a neprilysin inhibitor and angiotensin receptor blocker, exhibits a renin-angiotensin-aldosterone system (RAAS) inhibitory effect. However, no study has investigated the administration of sacubitril/valsartan in patients early after surgery using cardiopulmonary bypass.Methods and Results: This was a prospective observational study of 63 patients who underwent open heart surgery and were treated with sacubitril/valsartan. No serious adverse events occurred. Among the 63 patients, sacubitril/valsartan was discontinued in 13 due to hypotension (n=10), renal dysfunction (n=2), and dizziness (n=1). Atrial natriuretic peptide concentrations increased significantly from Day 3 of treatment (P=0.0142 vs. Postoperative Day 1) and remained high thereafter. In contrast, plasma renin activity was significantly suppressed from Day 3 onwards (P=0.00206 vs. Postoperative Day 1). A decrease in creatinine concentrations and an increase in the estimated glomerular filtration rate were observed on Day 3; this improvement in renal function was not observed in the historical control group, in which patients did not receive sacubitril/valsartan. New postoperative atrial fibrillation was less frequent in the study group compared with the historical control (12.7% vs. 38.0%; P=0.0034). CONCLUSIONS: Sacubitril/valsartan administration was safe immediately after open heart surgery in patients without postoperative hypotension. It enhanced serum atrial natriuretic peptide concentrations and suppressed RAAS activation.

Mincle is an ITAM-coupled activating receptor that senses damaged cells.

Macrophage-inducible C-type lectin (Mincle) is expressed mainly in macrophages and is induced after exposure to various stimuli and stresses. Here we show that Mincle selectively associated with the Fc receptor common gamma-chain and activated macrophages to produce inflammatory cytokines and chemokines. Mincle-expressing cells were activated in the presence of dead cells, and we identified SAP130, a component of small nuclear ribonucloprotein, as a Mincle ligand that is released from dead cells. To investigate whether Mincle is required for normal responses to cell death in vivo, we induced thymocyte death by irradiating mice and found that transient infiltration of neutrophils into the thymus could be blocked by injection of Mincle-specific antibody. Our results suggest that Mincle is a receptor that senses nonhomeostatic cell death and thereby induces the production of inflammatory cytokines to drive the infiltration of neutrophils into damaged tissue.

Sarcopenia assessed by the quantity and quality of skeletal muscle is a prognostic factor for patients undergoing cardiac surgery.

PURPOSE: Sarcopenia was assessed as a prognostic factor for patients undergoing cardiac surgery by evaluating the quantity and quality of skeletal muscle. METHODS: Sarcopenia was assessed by perioperative abdominal computed tomography using the total psoas muscle index (TPI) and intra-muscular adipose tissue content (IMAC). Patients were classified into high- (HT, n = 143) and low- (LT, n = 63) TPI groups and low- (LI, n = 122) and high- (HI, n = 84) IMAC groups. RESULTS: There were significantly more complications in the LT and HI groups than in the HT and LI groups. (HT 15.4% vs. LT 30.2%, P = 0.014) (LI 11.5% vs. HI 31.1%, P < 0.001). There were more respiratory complications in the LT group (HT 0% vs. LT 6.3%, P = 0.002) and more surgical site infections in the HI group than in the LI group (LI 0.8% vs. HI 7.1%, P = 0.014). A multivariable analysis showed that low TPI and high IMAC significantly predicted more major complications than other combinations (odds ratio [OR] 2.375; 95% confidence interval [CI] 1.152-5.783; P = 0.036, OR 3.973; 95% CI 1.737-9.088; P = 0.001). CONCLUSIONS: Sarcopenia is a risk factor for complications. The quantity and quality of muscle must be assessed to predict operative outcomes. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000027077.

Lung-diffusing capacity for carbon monoxide predicts early complications after cardiac surgery.

PURPOSE: Preoperative pulmonary dysfunction has been associated with increased operative mortality and morbidity after cardiac surgery. This study aimed to determine whether values for the diffusing capacity of the lung for carbon monoxide (DLCO) could predict postoperative complications after cardiac surgery. METHODS: This study included 408 consecutive patients who underwent cardiac surgery between June 2008 and December 2015. DLCO was routinely determined in all patients. A reduced DLCO was clinically defined as %DLCO < 70%. %DLCO was calculated as DLCO divided by the predicted DLCO. The association between %DLCO and in-hospital mortality was assessed, and independent predictors of complications were identified by a logistic regression analysis. RESULTS: Among the 408 patients, 338 and 70 had %DLCO values of ≥ 70% and < 70%, respectively. Complications were associated with in-hospital mortality (P < 0.001), but not %DLCO (P = 0.275). A multivariate logistic regression analysis with propensity score matching identified reduced DLCO as an independent predictor of complications (OR, 3.270; 95%CI, 1.356-7.882; P = 0.008). CONCLUSIONS: %DLCO is a powerful predictor of postoperative complications. The preoperative DLCO values might provide information that can be used to accurately predict the prognosis after cardiac surgery. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000029985.

Effect of Atomic Charges on Octanol-Water Partition Coefficient Using Alchemical Free Energy Calculation.

The octanol-water partition coefficient (logPow) is an important index for measuring solubility, membrane permeability, and bioavailability in the drug discovery field. In this paper, the logPow values of 58 compounds were predicted by alchemical free energy calculation using molecular dynamics simulation. In free energy calculations, the atomic charges of the compounds are always fixed. However, they must be recalculated for each solvent. Therefore, three different sets of atomic charges were tested using quantum chemical calculations, taking into account vacuum, octanol, and water environments. The calculated atomic charges in the different environments do not necessarily influence the correlation between calculated and experimentally measured ∆Gwater values. The largest correlation coefficient values of the solvation free energy in water and octanol were 0.93 and 0.90, respectively. On the other hand, the correlation coefficient of logPow values calculated from free energies, the largest of which was 0.92, was sensitive to the combination of the solvation free energies calculated from the calculated atomic charges. These results reveal that the solvent assumed in the atomic charge calculation is an important factor determining the accuracy of predicted logPow values.

A study on an unusual SN2 mechanism in the methylation of benzyne through nickel-complexation.

In this study, three reaction mechanisms of a benzyne-nickel (Ni) complex ([Ni(C6H4)(dcpe)]) with iodomethane during the methylation process were investigated, namely (a) SN2 reaction of the benzyne-Ni complex with iodomethane, (b) concerted σ-bond metathesis during the bond breaking/forming processes, and (c) oxidative addition of iodomethane to the Ni-center and the subsequent reductive elimination process. DFT calculations revealed that the reaction barrier of the SN2 reaction is slightly lower than those of the other mechanisms. The results of orbital analyses suggest that [Ni(C6H4)(dcpe)] forms a metallacycle structure between benzyne and the NiII (3d8) center instead of the η2-structure with the Ni0 (3d10) center. The metallacycle structures became inappropriate as the intermediates of oxidative addition in the formation of the NiII-Me bond, avoiding further oxidation to the high-valent NiIV. The high free energy along σ-bond metathesis was generated from the steric hindrance, thus invoking methylation and Ni-I bond formation concertedly.

Incidence of acute kidney injury among patients with chronic kidney disease: a single-center retrospective database analysis.

BACKGROUND: Acute kidney injury (AKI) is a serious complication among hospitalized individuals and is closely associated with chronic kidney disease (CKD). METHODS: This retrospective cohort study evaluated the incidences of AKI according to CKD stage at Kochi Medical School hospital during 1981-2011. AKI was defined and staged according to the kidney disease improving global outcomes criteria, using serum creatinine levels. RESULTS: We analyzed data from 122,653 Japanese patients (57,105 men, 46.6 %). The incidence of AKI was 7.8 % (95 % confidence interval 7.7-8.0 %). Compared to non-AKI patients, patients with stage 1-2 AKI were more likely to be men. Patients with stage 1-2 AKI were significantly older than non-AKI or stage 3 AKI patients. The incidences of AKI were 6.7, 5.9, 10.4, 18.4, 30.0, and 48.8 % among individuals with estimated glomerular filtration rates of ≥90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73 m2, respectively; these were significantly different from the incidence for the baseline eGFR. The proportions of inpatients with AKI exhibited step-wise increases with more severe pre-existing reduced kidney function, and the proportions among outpatients exhibited step-wise increases with milder pre-existing reduced kidney function. CONCLUSIONS: CKD was a risk factor for AKI, and the incidence of AKI was positively associated with pre-existing reduced kidney function (CKD stage). We also found that the prevalence of AKI at early-stage CKD among outpatients was higher than expected. We suggest that outpatients should be monitored for AKI, given its unexpected incidence in that population.

Structural changes in the S3 state of the oxygen evolving complex in photosystem II.

The S3 state of the Mn4 CaO5 -cluster in photosystem II was investigated by DFT calculations and compared with EXAFS data. Considering previously proposed mechanism; a water molecule is inserted into an open coordination site of Mn upon S2 to S3 transition that becomes a substrate water, we examined if the water insertion is essential for the S3 formation, or if one cannot eliminate other possible routes that do not require a water insertion at the S3 stage. The novel S3 state structure consisting of only short 2.7-2.8 Å Mn-Mn distances was discussed.

Serum uric acid level as a risk factor for acute kidney injury in hospitalized patients: a retrospective database analysis using the integrated medical information system at Kochi Medical School hospital.

BACKGROUND AND OBJECTIVES: Recent studies have shown that both low and high levels of serum uric acid (SUA) before cardiovascular surgery are independent risk factors for postoperative acute kidney injury (AKI). However, these studies were limited by their small sample sizes. Here, we investigated the association between SUA levels and AKI by performing a retrospective database analysis of almost 30 years of data from 81,770 hospitalized patients. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENT: Hospitalized patients aged ≥18 years were retrospectively enrolled. AKI was diagnosed according to the Kidney Disease: Improving Global Outcomes 2012 Clinical Practice Guideline (KDIGO) criteria. Multivariate logistic regression analyses were performed to investigate the independent association between SUA levels and the incidence of AKI. SUA levels were treated as categorical variables because the relationship between SUA and the incidence of AKI has been suggested to be J-shaped or U-shaped. In addition to stratified SUA levels, we considered kidney function and related comorbidities, medications, and procedures performed prior to AKI onset as possible confounding risk factors. RESULTS: The final study cohort included 59,219 adult patients. Adjusted odds ratios of AKI incidence were higher in both the high- and low-SUA strata. Odds ratios tended to become larger in the higher range of SUA levels in women than in men. Additionally, this study showed that AKI risk was elevated in patients with SUA levels ≤7 mg/dL. An SUA level >7 mg/dL is considered the point of initiation of uric acid crystallization. CONCLUSIONS: SUA level could be an independent risk factor for AKI development in hospitalized patients. Additionally, our results might suggest that intervention to lower SUA levels is necessary, even in cases of moderate elevation that does not warrant hyperuricemia treatment. Results also showed that SUA levels that require attention are lower for women than for men.

Activation of CO2 by ionic liquid EMIM-BF4 in the electrochemical system: a theoretical study.

The electrochemical reduction of CO2 to CO by an ionic liquid EMIM-BF4 is one of the most promising CO2 reduction processes proposed so far with its high Faradaic efficiency and low overpotential. However, the details of the reaction mechanism are still unknown due to the absence of fundamental understandings. In this study, the most probable and stable geometries of EMIM-BF4 and CO2 were calculated by quantum chemistry in combination with exhaustive search. A possible reaction pathway from CO2 to CO catalyzed by EMIM-BF4, including the most plausible intermediates and the corresponding transition states, was proposed. The role of EMIM-BF4 is explained as forming a complex of [EMIM-COOH](-) with CO2 followed by decomposing to CO.

Theoretical study on carbon-carbon short contact of ∼2.3 Å: intermediate state between nonbonding and σ-covalent bonding.

An unusual intermolecular carbon-carbon short contact, observed previously in the crystal structure of the copper complex of pyridoxal-5-phosphate- pyridoxamine-5-phospate Schiff base, was investigated from a standpoint of quantum chemistry by DFT calculations with plane wave basis sets. The DFT-optimized structure qualitatively reproduced the short contact (2.6-2.8 Å) of the intermolecular carbon-carbon pairs for the dimer of the copper complexes in the unit cell, compared to that (∼2.3 Å) of the X-ray diffraction data. By the occupied and unoccupied orbitals, the dimer showed the in-phase and out-of-phase interactions along the direction of the intermolecular distance. The dimer of the copper complexes was confirmed as the stable intermediate between nonbonding and σ-covalent bonding by the electronic energy curve along the distance of the monomers.

Possible roles of tumor necrosis factor-α and angiotensin II type 1 receptor on high glucose-induced damage in renal proximal tubular cells.

Recent studies have identified that high glucose-induced renal tubular cell damage. We previously demonstrated that high glucose treatment induced oxidative stress in human renal proximal tubular epithelial cells (RPTECs), and angiotensin II type 1 (AT1) receptor blockers reduce high glucose-induced oxidative stress in RPTEC possibly via blockade of intracellular as well as extracellular AT1 receptor. However, exact roles of tumor necrosis factor (TNF)-α and AT1 receptor on high glucose-induced renal tubular function remain unclear. N-acetyl-beta-glucosaminidase (NAG), concentrations of TNF-α/angiotensin II and p22(phox) protein levels after high glucose treatment with or without AT1 receptor blocker or thalidomide, an inhibitor of TNF-α protein synthesis, were measured in immortalized human renal proximal tubular epithelial cells (HK2 cells). AT1 receptor knockdown was performed with AT1 receptor small interfering RNA (siRNA). High glucose treatment (30 mM) significantly increased NAG release, TNF-α/angiotensin II concentrations in cell media and p22(phox) protein levels compared with those in regular glucose medium (5.6 mM). Candesartan, an AT1R blocker, showed a significant reduction on high glucose-induced NAG release, TNF-α concentrations and p22(phox) protein levels in HK2 cells. In addition, significant decreases of NAG release, TNF-α concentrations and p22(phox) protein levels in HK2 cells were observed in high glucose-treated group with thalidomide. AT1R knockdown with siRNA markedly reversed high glucose, angiotensin II or TNF-α-induced p22(phox) protein levels in HK2 cells. TNF-α may be involved in high glucose-induced renal tubular damage in HK2 cells possibly via AT1 receptor signaling.

Binding free-energy calculation is a powerful tool for drug optimization: calculation and measurement of binding free energy for 7-azaindole derivatives to glycogen synthase kinase-3ß.

Present computational lead (drug)-optimization is lacking in thermodynamic tactics. To examine whether calculation of binding free-energy change (ΔG) is effective for the lead-optimization process, binding ΔGs of 7-azaindole derivatives to the ATP binding site of glycogen synthase kinase-3ß (GSK-3ß) were calculated. The result was a significant correlation coefficient of r = 0.895 between calculated and observed ΔGs. This indicates that calculated ΔG reflects the inhibitory activities of 7-azaindole derivatives. In addition to quantitative estimation of activity, ΔG calculation characterizes the thermodynamic behavior of 7-azaindole derivatives, providing also useful information for inhibitor optimization on affinity to water molecules.

New insights into highly efficient reduction of CO2 to formic acid by using zinc under mild hydrothermal conditions: a joint experimental and theoretical study.

We report here a theoretical study with quantum chemical calculations based on experimental results to understand highly efficient reduction of CO2 to formic acid by using zinc under hydrothermal conditions. Results showed that zinc hydride (Zn-H) is a key intermediate species in the reduction of CO2 to formic acid, which demonstrates that the formation of formic acid is through an SN2-like mechanism.

Utility of growth differentiation factor-15 as a predictor of cardiovascular surgery outcomes: Current research and future directions.

In a world increasingly confronted by cardiovascular diseases (CVDs) and an aging population, accurate risk assessment prior to cardiac surgery is critical. Although effective, traditional risk calculators such as the Japan SCORE, Society of Thoracic Surgeons score, and EuroSCORE II may not completely capture contemporary risks, particularly due to emerging factors such as frailty and sarcopenia. These calculators often focus on regional and ethnic specificity and rely heavily on evaluations based on age and underlying diseases. Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine that has been identified as a potential biomarker for sarcopenia and a tool for future cardiac risk assessment. Preoperative plasma GDF-15 levels have been associated with preoperative, intraoperative, and postoperative factors and short- and long-term mortality rates in patients undergoing cardiac surgery. Increased plasma GDF-15 levels have prognostic significance, having been correlated with the use of cardiopulmonary bypass during surgery, amount of bleeding, postoperative acute kidney injury, and intensive care unit stay duration. Notably, the inclusion of preoperative levels of GDF-15 in risk stratification models enhances their predictive value, especially when compared with those of the N-terminal prohormone of brain natriuretic peptide, which does not lead to reclassification. Thus, this review examines traditional risk assessments for cardiac surgery and the role of the novel biomarker GDF-15. This study acknowledges that the relationship between patient outcomes and elevated GDF-15 levels is not limited to CVDs or cardiac surgery but can be associated with variable diseases, including diabetes and cancer. Moreover, the normal range of GDF-15 is not well defined. Given its promise for improving patient care and outcomes in cardiovascular surgery, future research should explore the potential of GDF-15 as a biomarker for postoperative outcomes and target therapeutic intervention.

Impella - Current issues and future expectations for the percutaneous, microaxial flow left ventricular assist device.

The importance of temporary mechanical circulatory support for treating acute heart failure with cardiogenic shock is increasingly recognized, and Impella (Abiomed, Danvers, MA, USA) has received particular attention in this regard. Impella is an axial flow left ventricular assist device (LVAD) built into the tip of a catheter. It is inserted via a peripheral artery and implanted into the left ventricle. Although the morphology of Impella is different from a typical LVAD, it has similar actions and effects as an LVAD in terms of left ventricular drainage and aortic blood delivery. Impella increases mean arterial pressure (MAP) and systemic blood flow, thereby improving peripheral organ perfusion and promoting recovery from multiple organ failure. In addition, left ventricular unloading with increased MAP increases coronary perfusion and decreases myocardial oxygen demand, thereby promoting myocardial recovery. Impella is also useful as a mechanical vent of the left ventricle in patients supported with veno-arterial extracorporeal membrane oxygenation. Indications for Impella include emergency use for cardiogenic shock and non-emergent use during high-risk percutaneous coronary intervention and ventricular tachycardia ablation. Its intended uses for cardiogenic shock include bridge to recovery, durable device, heart transplantation, and heart surgery. Prophylactic use of Impella in high-risk patients undergoing open heart surgery to prevent postcardiotomy cardiogenic shock is also gaining attention. While there have been many case reports and retrospective studies on the benefits of Impella, there is little evidence based on sufficiently large randomized controlled trials (RCTs). Currently, several RCTs are now ongoing, which are critical to determine when, for whom, and how these devices should be used. In this review, we summarize the principles, physiology, indications, and complications of the Impella support and discuss current issues and future expectations for the device.

All-atom molecular dynamics simulation of photosystem II embedded in thylakoid membrane.

The molecular dynamics simulation is reported. The latest data on photosystem II structure, a thylakoid membrane model with the same lipid class distribution and fatty acid composition as the native thylakoid membrane, are used. The results indicate that the transfer of water, oxygen and protons has different pathways. The root mean square (rms)-fluctuation analysis of trajectory revealed that the residues surrounding the oxygen-evolving center (OEC) show small fluctuations and that most of the water molecules there show large fluctuation and are on proposed pathways for water and oxygen transfer. The water molecules near the OEC having small fluctuation could be involved in proton transfer. We assume that each kind of pathway characterized in this study plays a role in photosynthesis.

Sestrin-2 and BNIP3 regulate autophagy and mitophagy in renal tubular cells in acute kidney injury.

Autophagy is a cellular recycling process induced in response to many types of stress. However, little is known of the signaling pathways that regulate autophagy during acute kidney injury (AKI). Bcl-2/adenovirus E1B 19 kDa-interacting protein (BNIP)3 and sestrin-2 are the target proteins of hypoxia-inducible factor (HIF)-1α and p53, respectively. The aim of this study was to investigate the roles of BNIP3 and sestrin-2 in oxidative stress-induced autophagy during AKI. We used rat ischemia-reperfusion injury and cultured renal tubular (NRK-52E) cells as in vivo and in vitro models of AKI, respectively. Renal ischemia-reperfusion injury upregulated the expression of BNIP3 and sestrin-2 in the proximal tubules, as measured by immunohistochemical staining and Western blot analysis. In vitro, NRK-52E cells exposed to hypoxia showed increased expression of BNIP3 mRNA and protein in a HIF-1α-dependent manner. In contrast, sestrin-2 mRNA and protein expression were upregulated in a p53-dependent manner after exposure to oxidative stress (exogenous H2O2). NRK-52E cells stably transfected with a fusion protein between green fluorescent protein and light chain 3 were used to investigate autophagy. Overexpression of BNIP3 or sestrin-2 in these cells induced light chain 3 expression and formation of autophagosomes. Interestingly, BNIP3-induced autophagosomes were mainly localized to the mitochondria, suggesting that this protein selectively induces mitophagy. These observations demonstrate that autophagy is induced in renal tubules by at least two independent pathways involving p53-sestrin-2 and HIF-1α-BNIP3, which may be activated by different types of stress to protect the renal tubules during AKI.

Direct binding targets of the stringent response alarmone (p)ppGpp.

The Escherichia coli stringent response, mediated by the alarmone ppGpp, is responsible for the reorganization of cellular transcription upon nutritional starvation and other stresses. These transcriptional changes occur mainly as a result of the direct effects of ppGpp and its partner transcription factor DksA on RNA polymerase. An often overlooked feature of the stringent response is the direct targeting of other proteins by ppGpp. Here we review the literature on proteins that are known to bind ppGpp and, based on sequence homology, X-ray crystal structures and in silico docking, we propose new potential protein binding targets for ppGpp. These proteins were found to fall into five main categories: (i) cellular GTPases, (ii) proteins involved in nucleotide metabolism, (iii) proteins involved in lipid metabolism, (iv) general metabolic proteins and (v) PLP-dependent basic aliphatic amino acid decarboxylases. Bioinformatic rationale is provided for expanding the role of ppGpp in regulating the activities of the cellular GTPases. Proteins involved in nucleotide and lipid metabolism and general metabolic proteins provide an interesting set of structurally varied stringent response targets. While the inhibition of some PLP-dependent decarboxylases by ppGpp suggests the existence of cross-talk between the acid stress and stringent response systems.

Serum level of soluble (pro)renin receptor is modulated in chronic kidney disease.

BACKGROUND: Prorenin, the precursor of renin, binds to the (pro)renin receptor [(P)RR] and triggers intracellular signaling. The ligand binding sites of (P)RR are disconnected and are present in the soluble form of the receptor in serum. Given that the clinical significance of serum prorenin and soluble (P)RR in chronic kidney disease (CKD) is unclear, we investigated the relationship between serum prorenin, soluble (P)RR, and various clinical parameters in patients with CKD. METHODS: A total of 374 patients with CKD were enrolled. Serum samples were collected, and the levels of soluble (P)RR and prorenin were measured using ELISA kits. Serum creatinine (Cr), blood urea nitrogen (BUN), uric acid (UA), hemoglobin (Hb), soluble secreted α-Klotho, and the urine protein/Cr ratio were also measured. Similarly, clinical parameters were also evaluated using serum and urine sample collected after 1 year (n = 204). RESULTS: Soluble (P)RR levels were positively associated with serum Cr (P < 0.0001, r = 0.263), BUN (P < 0.0001, r = 0.267), UA (P < 0.005, r = 0.168) levels, CKD stage (P < 0.0001, r = 0.311) and urine protein/Cr ratio (P < 0.01, r = 0.157), and inversely with estimated glomerular infiltration rate (eGFR) (P < 0.0001, r = -0.275) and Hb (P < 0.005, r = -0.156). Soluble (P)RR levels were inversely associated with α-Klotho levels (P < 0.001, r = -0.174) but did not correlate with prorenin levels. With respect to antihypertensive drugs, soluble (P)RR levels were significantly lower in patients treated with an angiotensin II receptor blocker (ARB) than in those without ARB therapy (P < 0.005). Soluble (P)RR levels were significantly lower in CKD patients with diabetes mellitus or primary hypertension than in those without these conditions (P < 0.05). In contrast, serum levels of prorenin did not correlate with parameters related to renal function. Serum prorenin levels were significantly higher in CKD patients with diabetes mellitus than in nondiabetic patients (P < 0.05), but not in CKD patients with hypertension (P = 0.09). Finally, with respect to the relationship between basal soluble (P)RR levels and the progression rates of renal function, soluble (P)RR levels were positively associated with ΔCr (P < 0.05, r = 0.159) and inversely associated with ΔeGFR (P < 0.05, r = -0.148). CONCLUSION: Serum levels of soluble (P)RR correlated with the stage of CKD. Our findings suggest that soluble (P)RR may be involved in renal injury and influence the progression of CKD.