Several experimental studies have demonstrated that fibroblast growth factor 23 (FGF23) may induce myocardial hypertrophy via pathways independent of α-Klotho, its co-factor in the induction of phosphaturia. On the other hand, few studies have clearly demonstrated the relationship between FGF23 level and left ventricular hypertrophy among subjects without chronic kidney disease .To investigate the data from 903 patients admitted to the cardiology department with various degrees of renal function, including 234 patients with CKD stage G1/G2.Serum levels of full-length FGF23 and α-Klotho were determined by enzyme immunoassay. After adjustment for sex, age, and estimated glomerular filtration rate (eGFR), the highest FGF23 tertile was significantly associated with left ventricular hypertrophy among patients with CKD stage G1/G2 and those with CKD stage G3a/G3b/G4 as compared with the lowest FGF23 tertile, and the association retained significance after further adjustment for serum levels of corrected calcium, inorganic phosphate, and C-reactive protein, as well as diuretic use, history of hypertension, and systolic blood pressure. FGF23 was also associated with low left ventricular ejection fraction among patients with CKD stage G1/G2 and those with CKD stage G3a/G3b/G4 after adjusting for age, sex, eGFR, corrected calcium, and inorganic phosphate. On the other hand, compared with the highest α-Klotho tertile, the lowest α-Klotho tertile was associated with left ventricular hypertrophy and systolic dysfunction only among patients with CKD stage G3b and stage G3a, respectively.An association between FGF23 and cardiac hypertrophy and systolic dysfunction was observed among patients without CKD as well as those with CKD after multivariate adjustment. However, the association between α-Klotho and cardiac hypertrophy and systolic dysfunction was significant only among patients with CKD G3b and G3a, respectively. Fibroblast growth factor 23 (FGF23) is a bone-secreted circulating endocrine hormone that causes phosphaturic effects  via the In addition to these effects on maintaining phosphate homeostasis, several studies have shown an association between FGF23 and cardiac hypertrophy and/or left ventricular dysfunction in various populations such as patients with chronic kidney disease (CKD) ,8, elderklotho gene  + 0.6  + 0.6 . Body su present .Baseline characteristics were assessed with standard descriptive statistics. Data were expressed either as mean ± standard deviation  or median and interquartile range (IQR) . Spearman rank correlation test was used to assess the correlation between two variables that were not normally distributed. Data analysis was performed by SPSS statistics version 21.0 . Multivariate receiver operating characteristic (ROC) curve analysis was performed by STATA 12 .Of the 903 patients enrolled, 19 (2.1%), 215 (23.8%), 311, (34.4%), 253 (28.0%), and 93 (10.3%), and 12 (1.3%) had CKD stage G1, G2, G3a, G3b, G4, and G5, respectively. Thus, about a quarter of the study population  were considered to have no-CKD. Ischemic heart disease and arrhythmic disease were, respectively, the first and the second most common disorders among the study subjects. A history of hypertension was more prevalent among patients with CKD  than among patients without CKD (stage G1/G2), although systolic blood pressure did not differ significantly across the groups . Among tThe proportion of patients in the highest FGF23 tertile increased with declining renal function . SimilarThe correlation coefficient for the association between FGF23 and α-Klotho was 0.81 (P = 0.743), 0.12 (P = 0.837), -0.12 (P = 0.080), -0.03, (P = 0.670), 0.11 (P = 0.304), and -0.24 (P = 0.443) among patients who had CKD stage G1, G2, G3a, G3b, G4, and G5, respectively.Among the various CKD stage subgroups , the correlation between FGF23 and LVMI was significant among those with CKD stage G1/G2, G3a, and G4  and thatWhen the data were assessed as tertiles of FGF23 by CKD stage, the mean LVMI seem to increase with FGF23 value in all CKD stage subgroups . In factUnlike FGF23, α-Klotho did not seem to be associated with either LVMI or LVEF . α-Klothχ2 test). Among these, a significant association with LVH was found for hemoglobin (P = 0.001), albumin (P < 0.001), uric acid (P = 0.002), CRP (P = 0.009), eGFR (P = 0.001), iPTH (P = 0.032), FGF23 (P < 0.001), α-Klotho (P = 0.016), use of diuretic (P < 0.001), ACE/ARB (P = 0.009) β blocker (P < 0.001), aldosterone antagonist (P < 0.001); and a significant association with low LVEF was found for systolic blood pressure (P < 0.001), hemoglobin (P = 0.001), platelet count (P = 0.002), albumin (P < 0.001), uric acid (P < 0.001), CRP (P < 0.001), eGFR (P < 0.001), iPTH (P = 0.036), FGF23 (P < 0.001), α-Klotho (P = 0.007), use of diuretic (P < 0.001), β blocker (P < 0.001), and aldosterone antagonist (P < 0.001)We first examined the univariate association of various parameters with LVH or low LVEF; including age, BMI, systolic blood pressure, pulse rate, white blood cell count, hemoglobin, platelet count, total protein, albumin, uric acid, CRP, eGFR, cCa, iP, FGF23, α-Klotho (by Mann-Whitney test), sex, smoking status, use of either diuretics (loop or thiazide), statin, angiotensin converting enzyme (ACE)/angiotensin receptor blocker (ARB), β blocker, calcium channel blocker, and aldosterone antagonist ; and corrected calcium, and inorganic phosphate (model 2); however, it lost statistical significance after further adjustment for diuretic use and CRP .As compared with the highest α-Klotho tertile, the lowest α-Klotho tertile was not associated with LVH or low LVEF among patients with CKD stage G1/G2 irrespective of the model used . On the Among patients with CKD stage G3a and those with CKD stage G3b, the correlation coefficient (by Spearman’s test) for the association between FGF23 and α-Klotho was 0.01 (P = 0.837) and -0.03 (P = 0.370), respectively. When FGF23  was included as an additional covariate in model 5, the association between the lowest α-Klotho tertile and LVH among patents with CKD stage G3a  and that between the lowest α-Klotho tertile and low LVEF among patents with CKD stage G3b  retained statistical significance.When the analysis was performed using model 5 in We next investigated the association between FGF23 and LVH or low LVEF among the subgroup of patients with CKD who were not undergoing chronic hemodialysis .When the model was adjusted for the variables used in model 4 in Tables In ROC curve analysis for the prediction of LVH, addition of FGF23 , G1/G2 , and G3-In ROC curve analysis for the prediction of low LVEF, addition of FGF23 to the combination of age, sex, and eGFR significantly improved the prediction of LVH for patients with CKD stages G1-G4 , but wasWe found that serum FGF23 was significantly associated with LVH independent of sex, age, eGFR, and serum calcium and inorganic phosphate levels among patients with no CKD . In addition, this association remained significant after further adjustment for intact PTH or diuretic use. In addition, it was found that serum FGF23 was significantly associated with LVEF among patients with CKD stages G1/G2 and G3a ; unexpecSimilar to the current study, we previously assessed the possible relationship between FGF23 (or α-Klotho) and cardiac hypertrophy and systolic dysfunction among patients admitted to the cardiology department, although the study population was much smaller . In that2, but not among elderly patients with eGFR ≥ 60 mL/min/1.73m2 [Previously, the relationship between FGF23 and cardiac morbidity and mortality has been best demonstrated among patients with CKD. For example, Faul et al. demonstrated that, among subjects with CKD, those with higher serum FGF23 levels had a higher risk of LVH and low LVEF . In addin/1.73m2 . Furthern/1.73m2 .2) [2 [2 and those with eGFR < 60 mL/min/1.73m2 with similar hazard ratios [In a few studies, on the other hand, the relationship between FGF23 and cardiac abnormalities or cardiovascular outcome has been studied in patients without renal dysfunction or with relatively preserved renal function. For instance, Seiler et al. analyzed the data from subjects undergoing elective coronary angiography, and showed that the association between FGF23 and LVEF and that between FGF23 and LVH was significant among patients with preserved renal function (eGFR ≥ 60 mL/min/1.73m2) . Imazu e2) [2 . In addid ratios . Furtherd ratios .In the current study, by analyzing a relatively large study sample, we have been able to demonstrate an association, or non-association, between FGF23 and LVH and cardiac dysfunction according to CKD stage. To this end, we verified the association between FGF23 and these parameters among CKD stage G1/G2 patients in a multivariate model in which various possible confounding variables were used as covariates . This obWe found that FGF23 was not associated with LVH among patients with CKD stage G3b and that FGF23 was not associated with low LVEF among patients with CKD stage G3b and G4 in some models ; notablySeveral previous studies have suggested that FGF23 may promote cardiac hypertrophy via FGF receptor 4 (FGFR4)-mediated activation of the calcineurin-NFAT signaling pathway ,29, althIn the current study, we found that lower α-Klotho levels were not associated with cardiac hypertrophy or systolic dysfunction among patients with CKD G1/G2 ; on the klotho gene delivery [What might be the possible mechanism, if present at all, by which circulating α-Klotho exerts a direct effect on cardiac cells? Xie et al. demonstrated that cardiac hypertrophy and dysfunction were aggravated in response to the induction of renal failure in heterozygous klotho deficient mice; this aggravation was independent of hypertension or FGF23, and was ameliorated by delivery . Mechanidelivery , which idelivery . It has delivery . Whether2D3, which may have a relationship with cardiac parameters [There are several limitations to the current study. First, owing to the cross-sectional nature of the study, we cannot conclude whether the relationship between FGF23 and cardiac hypertrophy or systolic dysfunction was causal or resultant. Second, we did not take into account 25(OH)D3 or 1,25(OH)rameters . On the rameters .It should be noted that two-types of ELISA are available for the determination of human FGF23: an assay for intact FGF23 that detects only full-length FGF23, and one for C-terminal FGF23. In the current study, we used the ELISA for full-length FGF23. Some previous studies have used the full-length assay, and thus measured serum levels of intact FGF23 ,10, wherIn summary, by analyzing data from 903 cardiology patients who had various degrees of renal dysfunction, we found that FGF23 levels were associated positively and negatively with, respectively, LVH and low LVEF independent of age, sex, eGFR, corrected calcium, CRP, diuretic use, systolic blood pressure, and history of hypertension not only among patients with CKD (CKD stage G3a/G3b/G4) but also those without (CKD stage G1/G2). The association between serum α-Klotho and LVH and low LVEF was significant among patients with CKD stage G3b and G3a, respectively, after adjustment for age, sex, and eGFR. Whether modulating FGF23 levels might have an impact on cardiac remodeling and functional impairment irrespective of the CKD status awaits further investigation.


A 67-year-old woman with drug-refractory essential hypertension was admitted for renalsympathetic denervation (RDN). The secondary causes of hypertension were fullyinvestigated in this patient. A 24-h ambulatory blood pressure (BP) monitor documented amean daytime BP of 172/101 mmHg, a mean nighttime BP of 151/84 mmHg, and an overall meanBP of 167/97 mmHg despite compliance with metoprolol (50 mg twice daily), amlodipine (10mg once daily), lisinopril (20 mg once daily), prazosin (2 mg thrice daily), andhydrochlorothiazide (50 mg once daily).μg of fentanyl, a 7-F Renal Double Curve guide catheter  was inserted into the right renal artery (no accessoryvessel). A 0.014-in Runthrough floppy guide wire  was advanced into place. A 6-mm ONESHOTTM  irrigated RDN balloon was advanced into place .She was given intravenous dopamine that was titrated to response. At 102. In such instances, abnormal renalexcretory function, which is largely influenced by renal sympathetic nerve activity, mayhave a central role3. Catheter-basedRDN, which is a modern incarnation of a historically effective treatment, has recentlyemerged as a novel therapeutic strategy. Proof of concept and subsequent randomized(unblinded) data that were collected while using the Symplicity® catheter have demonstrated reductions in office BP of20/10, 24/11, 25/11, and 23/11 mmHg at 1, 3, 6, and 12 months, respectively, in a groupof patients taking an average of five antihypertensive drugs5. Such earlyexciting reports have stimulated the development of numerous other similar devices,including the ONESHOTTM catheter that was used in this case6.Around 12% of patients with essential hypertension who are considered resistant toconventional therapy have persistently elevated BP despite the use of three or morepharmacological agents7. Explanations for thisbroad variability in outcome are uncertain, except that raw BP measurements may lack thesensitivity required for them to be considered a true measure of successfulRDN8. This may in part explainthe lackluster performance of RDN in the Symplicity-3 trial, in which RDN failed todemonstrate superiority over conventional treatments when compared to a sham-controlprocedure9. However, despitethis, the use of RDN does seem to significantly reduce renal norepinephrinespillover10. Therefore, it ispossible that those patients who exhibit more sympathetic over-activity may experience agreater degree of BP reduction with RDN. Because sympathetic over-activity is notroutinely measured in clinical practice, this remains speculative.In some cases, early BP reductions have been reported following RDN. However, in othercases, the response is not always immediate, or it can take several months to appear.Additionally, RDN is associated with a failure rate of 10%-30%, and the only predictorof response in early studies is the magnitude of the systolic BP elevation atbaselineNonetheless, the role of RDN in the treatment of resistant hypertension remainsuncertain, but the sustained and impressive BP reductions that were observed in this andother cases should encourage further research to improve the understanding of themechanisms through which hypertension is mediated and to identify those patients who arelikely to achieve the most dramatic responses with RDN.


We examined the relationship between an early spontaneous type V blood pressure fluctuation and the post-thrombolysis prognosis of patients with acute cerebral infarction. Patients were admitted consecutively. All patients were categorized into the type V blood pressure fluctuation group or non-type V blood pressure group. Their blood pressure was monitored before thrombolysis and until 6 h after thrombolysis. Baseline data and clinical outcomes were compared. Of 170 patients, 43 (25.2%) had an early type V blood pressure fluctuation. The National Institute of Health Stroke Scale (NIHSS) score before thrombolysis and 24 h after thrombolysis, and the modified Rankin scale score at 90 days differed significantly between the two groups (P < 0.05). Multiple logistic regression analysis showed that an unfavorable prognosis at 3 months was associated with the NIHSS score before thrombolysis (P = 0.000) but probably not with this blood pressure fluctuation (P = 0.058). An early spontaneous type V blood pressure fluctuation is common in patients with acute cerebral infarction who received venous thrombolysis, especially if they have a higher NIHSS score before thrombolysis. The type V blood pressure fluctuation may not influence patients’ prognosis; however, this needs to be confirmed in future trials. Acute cerebral infarction is a neurological emergency usually with an elevated blood pressure (BP) during the early period. There are several possible causes such as the inadequate treatment of hypertension, undiagnosed hypertension, stress reaction caused by an activated neuroendocrine system, an impaired cerebral autonomic regulatory center, and elevated intracranial pressure456et alCurrently, early intravenous thrombolysis is an effective therapy for acute cerebral infarction8During clinical routine workups, we note that spontaneous BP fluctuation, which is the recovery after an abrupt decrease of BP, is exhibited early after intravenous thrombolysis in some patients with acute cerebral infarction. This is an interesting phenomenon which has been reported previously12From February 2013 to March 2015, patients with acute cerebral infarction who received intravenous rtPA were admitted consecutively in the Department of Neurology at East Hospital. Inclusion criteria were as follows: (1) patients with acute cerebral infarction during the observation period confirmed with cranial computed tomography or magnetic resonance imagingWe defined the BP fluctuation as a type V fluctuation as follows: (1) the patients’ systolic BP decreases abruptly from peak pressure following partial recovery; (2) peak BP is the highest systolic BP during the first 15 min since the beginning of thrombolysis; (3) amplitude of systolic BP decreases over 20% of its peak pressure; and (4) recovery amplitude of systolic BP is over 10% of its peak pressure. The patients’ BPs were monitored before thrombolysis and until 6 h after thrombolysis, with the main observational index of supine brachial systolic BP. The BP was recorded every 15 min during the first 2 h since thrombolysis was started, and then it was recorded every half hour during the next 2–6 h. According to whether type V BP fluctuation appeared within 6 h after thrombolysis, all patients were categorized into the type V BP fluctuation group (type V BP group) or non-type V BP group (non-type V BP group). The patients’ sex; age; prior history of hypertension, diabetes mellitus, atrial fibrillation, ischemic stroke, and smoking; onset to thrombolysis time; and the National Institute of Health Stroke Scale (NIHSS) score  were evaluated before thrombolysis, and they were followed up for 3 months. The thrombolysis dosage was 0.9 mg/kg per body weight.The study was carried out in accordance with the guidelines, which was approved by the local institutional review board at East Hospital, Tongji University, and the informed consent was obtained from the patients.The NIHSS scores 24 h after thrombolysis and 2 wk after thrombolysis were assessed. The patients’ outcomes were assessed 90 days after stroke using the modified Rankin scale . The other endpoints included recurrent stroke, death, and lost to follow-up. All clinical assessments were made by experienced neurologists.Data were expressed as One hundred ninety-three patients underwent venous thrombolysis during the study; of those, 15 took antihypertensive agents because their BP was over 185/110 mmHg before thrombolysis or during the first 6 h of thrombolysis, 2 received vasopressors, 3 received percutaneous intervention therapy after thrombolysis, and 3 misdiagnosed as cerebral infarction were all excluded.Thus, 170 patients were enrolled; 101 (59.4%) were men and 69 (40.6%) were women. They were 25–92 years old with an average age of 65.5 ± 10.8 years. All enrolled patients were categorized into the type V BP group (43 patients [25.3%]) or non-type V BP group (127 patients [74.7%]). One hundred sixteen (68.2%) patients had an NIHSS score ≤8 before thrombolysis, whereas 54 (31.8%) had an NIHSS score >8. The onset-treatment time ranged from 40–320 min with an average time of 182 ± 53 min. Finally, 164 patients completed the follow-up . Five patients were lost to follow-up, 1 from the type V BP group (2.3%) and 4 from non-type V BP group (3.1%), one patient got recurrent stroke .ExamplesThere was no significant difference in sex, age, hypertension, diabetes mellitus, atrial fibrillation, ischemic stroke, smoking, and onset-treatment time between the two groups. There was a statistical difference in the NIHSS score before thrombolysis between the two groups (P < 0.001) .In the first 2 wk, 4 of 170 patients died, 2 of whom died of cerebral edema, 1 of pulmonary embolism, and 1 of pulmonary infection. During the 3 months, 1 patient had a recurrent cerebral infarction, 5 were lost to follow-up, and there were no new deaths. There was a statistical significance in the difference of the NIHSS score 24 h after thrombolysis (P < 0.05) but no statistical significance in the difference of the NIHSS score 2 wk after thrombolysis. Additionally, there was statistical significance in the difference of the mRS score during the following 3 month after thrombolysis (P < 0.05)  and 3.The prognosis of patients was defined as favorable or unfavorable according to the mRS scores. Distributions of the modified Rankin scale scores of patients in two groups are shown in Intravenous rtPA was approved for treating acute cerebral infarction by the United States Food and Drug Administration in 1996, and it is the only drug for thrombolysis confirmed by clinical trials performed in the United States and Europe that is recommended for ischemic stroke. This drug is a type of fibrin dissolved suppository that can selectively combine fibrin in the surface of a thrombus and develop a fibrin complex to activate plasminogen to transform into plasmin, which can dissolve fibrin and restore blood flow to rescue neurons in ischemic penumbra and accordingly restore neurological functionAs mentioned earlier, the increased systolic blood pressure or systolic blood pressure variation in acute cerebral infarction patients within 24 hours after the intravenous thrombolytic therapy was associated with a poor prognosis, so close monitoring and strict management of blood pressure after thrombolysis has been widely deemed necessary. It was confirmed in our study that spontaneous type V BP fluctuation had occurred early after venous thrombolysis in 25% of patients with acute cerebral infarction. Further analysis indicated that the NIHSS score was higher in the type V BP group than in the non-type V BP group before thrombolysis, and it was significantly different (P < 0.001). Thus, it is speculated that a spontaneous type V blood pressure fluctuation occurs more commonly in patients with a higher NIHSS score before thrombolysis, which usually indicates a more severe neurologic defect. The “V type” blood pressure fluctuation phenomenon in this study was different from previously reported post-thrombolytic blood pressure variability in terms of calculation methods and definitions12The type V BP fluctuation for acute cerebral infarction after venous thrombolysis has been reported in the past, but its clinical significance or whether clinical intervention was needed were not clear. Our current study confirmed the existence of such phenomenon, furthermore, our result suggested that this BP fluctuation did not influence patients’ prognosis, and it probably does not require clinical intervention.et al found that a decrease of systolic blood pressure ≥20 mmHg 24 h post-thrombolysis than that of pre-thrombolysis accompanied by neurological improvement may indicate revascularization21The possible mechanism of a type V BP fluctuation for acute cerebral infarction after venous thrombolysis may be that there is an autonomic regulation of cerebral blood flow in patients with ischemic stroke. Temporary systolic BP elevation occurs in 80% of patients with acute cerebral infarction to raise the cerebral perfusion pressureDuring follow-up, there was a difference in the 24 h NIHSS score but no obvious difference at 2 wk between the two groups, which indicated that the spontaneous type V BP fluctuation had no obvious influence on patients’ short-term prognosis. However, after the 3-month follow-up, we found that 40.5% of patients in the type V BP group had a favorable prognosis (mRS score 0–1), and 63.9% of patients in the non-type V BP group had a favorable prognosis, which indicated that patients with the early spontaneous type V BP fluctuation  may have had an even worse long-term prognosis. Thus, the prognosis at 3 months was further evaluated using multivariate logistic analysis in which the mRS scores were regressed on the baseline covariates, and we found that only NIHSS scores >8 before thrombolysis were associated with an unfavorable prognosis (P = 0.000) but not the type V BP fluctuation (P = 0.058).Currently there is no definitive conclusion on the reasonable range of blood pressure management in acute cerebral infarction after thrombolysis, retrospective data analysis suggested that the prognosis was better in patients with a mean systolic blood pressure of 140–150 mmHg within 24 hours after thrombolysisThere are some limitations to our study. It was a single center study with a small sample and relatively simple observational index (only the systolic BP). Besides, the observation time was only within 6 h after thrombolysis. During the study, some patients with severely impaired neurological function had a BP > 180/110 mmHg. These patients were given antihypertensive agents for intravenous thrombolysis, and they were finally excluded (15 cases) from this study. Thus, the enrolled patients did not represent all patients with cerebral infarction at our hospital during the study, which may have caused some bias . Lastly, the loss of follow-up caused by removal and contact information changes for some of the patients may have influenced the results.In conclusion, we confirmed that a spontaneous type V BP fluctuation occurs early after intravenous thrombolysis in some patients with acute cerebral infarction, especially in those with a higher NIHSS score. This type V BP fluctuation may not influence patients’ prognosis, and it probably does not require clinical intervention; however, larger multicenter clinical observation trials with larger sample size are needed to clarify whether this type V BP fluctuation influences the prognosis of patients and whether it requires intervention. The practical implications of this study may lead to further investigations of this topic, assisting in the development of novel guidelines in the treatment of acute cerebral infarction.How to cite this article: Zuo, L. et al Relationship of Early Spontaneous Type V Blood Pressure Fluctuation After Thrombolysis in Acute Cerebral Infarction Patients and the Prognosis. Sci. Rep.6, 27656; doi: 10.1038/srep27656 (2016).


The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function. The kidney is susceptible to insult from a variety of exogenous  and endogenous  substances because of its complex anatomical, physiological, and biochemical features. Factors contributing to the sensitivity of the kidney include its large blood flow (20–25% of resting cardiac output corresponding to approximately 1.2-1.3 L/min), concentration of filtered solutes during urine production (kidneys reabsorb more than 99% of the glomerular filtrate), and the presence of a variety of xenobiotic transporters and metabolizing enzymes. The list of the potential nephrotoxic substances includes drugs, environmental agents, heavy metals, radiocontrast agents, and immunoglobulin free light chains (FLCs). Each of them may adversely affect one or more sites along the nephron, leading to a progressive organ damage and impairment named toxic nephropathy [Monoclonal gammopathies refer to a spectrum of disorders characterized by the monoclonal proliferation of lymphoplasmacytic cells in the bone marrow and, sometimes, tissue deposition of monoclonal immunoglobulins (Igs) or their components . The mosκB), and AP-1 (c-fos and c-jun) complexes. These transcription factors induce in turn the synthesis of the proinflammatory cytokines interleukin-6 (IL-6), macrophage chemoattractant protein-1 (MCP-1), and tumor necrosis factor α (TNFα) and activate signaling pathways, such as mitogen-activated protein kinases (MAPK), extracellular signal regulated kinase (ERK1/2), Jun kinase (JNK), and p38 MAPK [In MM, the high monoclonal serum FLCs concentration results in a burden of FLCs on the proximal tubule that overwhelms the capacity of both the megalin and cubilin receptors to reabsorb the FLCs. As a consequence, large amounts of FLCs reach the distal tubule lumen where they interact specifically with Tamm-Horsfall proteins , generating myeloma casts. Cast formation in the distal tubule can block glomerular flow and cause proximal tubular atrophy , also cop38 MAPK . As a rep38 MAPK .κ light chains comprise 40 Vκ and 5 Jκ sections, whereas λ light chains have 30 Vλ and 8 Jλ. Although designed to bind antigens, the presence of tyrosine and tryptophan allows additional binding possibilities to lipid-rich cell membranes by binding to sphingomyelin [κ and λ FLCs interacts with THP; the binding affinities of FLCs for THP are related to the amino acid composition of the CDR3 domain [κ1 subfamily and are derived from only two germ line genes, IGKV1-39 and IGKV1-33 [κ domain to proteolysis, resulting in light chain crystallization [λ6 and Vκ4 subgroups, respectively, N-glycosylation of the V region, and substitutions of key amino acids induced by somatic mutations that might account for the propensity of certain FLCs to aggregate and influence tropism of deposition [ in vitro and in vivo [The risk of AKI in patients with MM increases with the concentration of FLCs in urine; however, not all monoclonal FLCs are nephrotoxic. Nephrotoxicity appears to be an intrinsic property of some FLCs, as indicated by the recurrence of similar renal lesions after kidney transplantation , 25. Frogomyelin , 28. The3 domain . On the IGKV1-33 . The replization . In AL a in vivo . Unfortuκ or λ that may deposit in the kidney, as described above. The use of loop diuretics may also contribute to cast formation, leading in turn to serum creatinine levels increase. Loop diuretics are an established risk factor for myeloma kidney. In 1990, it was demonstrated that increasing the concentration of sodium chloride facilitated coprecipitation of Bence Jones proteins with human Tamm-Horsfall glycoprotein in vitro [ in vivo with cast-forming Bence Jones protein [Patients with MM are at an increased risk of kidney disease not only from the kidney injuries and damages due to the primary disease, but also from a number of additional concomitant factors that can substantially contribute to worsen kidney function, leading to AKI, ESRD, and ultimately to renal replacement therapy. A list of these risk factors is reported in in vitro . Furosem protein . Vasocon protein . Hyperca protein . ElevateP < 0.001) [P = 0.002; sensitivity 87%, specificity 70%; AUC 0.85; OR 13.29). In a study using cystatin C as an early marker for AKI, a cutoff cystatin C increase concentration of ≥10% at 24 hours after contrast media exposure was detected in 21.2% of patients and was the best cutoff value for the early identification of patients at risk for CI-AKI with a negative predictive value of 100% and a positive predictive value of 39% [In most cases, the onset of contrast induced-acute kidney injury (CI-AKI) consists of a transient nonoliguric form of AKI with serum creatinine levels peaking at 48–72 h after administration of the medium and returning to baseline values within the subsequent ten days . While t< 0.001) . A 5% ine of 39% . As in oe of 39% . Past efe of 39% .μmol/L), medium risk 1.5–2.0 mg/dL (132.6–176.8 μmol/L), and high risk more than 2.0 mg/dL (>176.8 μmol/L). Data from a survey performed in 2006 showed that 36% of USA radiologists never administer intravascular contrast agent to patients with MM and 47% do it sometimes [For a long time, MM was considered a significant risk factor for developing contrast nephropathy . This asometimes ; in addiometimes . Dehydraometimes . Therefoometimes –58. Mainometimes , namely,ometimes . Howeverometimes , 61. Sinometimes , 63, it ometimes .The standard assessment of renal function in patients with MM includes serum creatinine and creatinine clearance, although both measurements probably underestimate the prevalence of renal dysfunction, because of the additional tubular secretion of creatinine and its dependence on extrarenal factors. In particular, serum creatinine is a retrospective, insensitive, and even deceptive measure of kidney injury. Retrospective because its concentration may result in a very delayed signal even after considerable kidney injury . Insensi lcn2, is one of the most upregulated transcripts in the early postischemic mouse kidney and this finding has been confirmed in several other transcriptome profiling studies. Downstream proteomic studies have also revealed NGAL to be one of the earliest and most robustly induced proteins in the kidney after ischemic or nephrotoxic AKI in animal models, and NGAL protein is easily detected in the blood and urine soon after AKI [1H NMR) of rodent urine and serum demonstrated that liver and kidney toxicity can be predicted with sensitivities of 41 and 67% and specificities of 100% and 77%, respectively [Identification of novel toxic nephropathy and AKI biomarkers has been designated as a top priority by the American Society of Nephrology. The concept of developing a new toolbox for earlier diagnosis of disease states is also prominently featured in the National Institute of Health (NIH) road map for biomedical research. In 2007, the Acute Kidney Injury Network (AKIN), a collaborative group of investigators from all major critical care and nephrology societies, proposed a staging system based on serum creatinine and urine output and consisting of 3 categories  in a way similar to those  used by the RIFLE staging system. AKIN criteria have been included and recommended in the recent AKI guideline published by the Kidney Disease: Improving Global Outcomes (KDIGO) . Despitefter AKI . These ffter AKI . KIM-1 rfter AKI , 75. An fter AKI . Additiofter AKI , Krüppelfter AKI , thrombofter AKI , and IL-fter AKI . New encfter AKI . Metabolfter AKI . Predictectively .Although plasma cell dyscrasia would not be “per se” risk factors for the occurrence of CI-AKI, when comorbidities are present, patients require to be carefully monitored after contrast media injection. Kidney impairment, a major risk factor for developing CI-AKI, is one of the more frequent clinical features of symptomatic multiple myeloma. Other coexisting morbidities include anemia, hypercalcemia, and potentially nephrotoxic drugs like NSAIDs, chemotherapeutic agents, and antibiotics. Often, multiple factors may coexist, like kidney impairment with anemia, infections with nephrotoxic drugs, diabetes with aging, and increasing the risk of CI-AKI . The manμmol/L) [μmol/L) in men and ≥1.0 mg/dL (≥88.4 μmol/L) in women [2 [β2-microglobulin increases with both higher tumor burden and diminished renal function, it was suggested that evaluation of β2-microglobulin levels may be useful before intravenous injection of iodinate contrast agents to patients with multiple myeloma [β2-microglobulin likely serves as a marker of patients who are at a higher risk of developing CI-AKI. According to previous results published elsewhere, a value of β2-microglobulin below 2.8 mg/L may be the most clinically useful marker for patients at low risk of developing CI-AKI, showing a 100% negative predictive value [According to the 2012 KDIGO AKI guideline , before μmol/L) . Howeverin women . The guiwomen [2 . When a women [2  or a dip myeloma . Serum βve value . N-acetylcysteine (NAC) together with intravenous isotonic crystalloids (strength of recommendation 2D). A meta-analysis on 41 studies showed that NAC is the most effective agent for preventing CI-AKI in patients with CKD [According to the 2012 KDIGO AKI guideline, pharmacological and nonpharmacological preventive measures for reducing risk factors for CI-AKI in patients with multiple myeloma include (a) the use of either iso-osmolar or low-osmolar rather than high-osmolar iodinated contrast media (strength of recommendation 1B); (b) extracellular volume expansion at the time of radiocontrast media administration with either isotonic sodium chloride or sodium bicarbonate solutions (strength of recommendation 1A). It is desirable not to use oral fluids alone (strength of recommendation 1C), while it is recommended to use oralwith CKD . Followiwith CKD , 89, alkwith CKD . Urine awith CKD , 61. Whewith CKD . This emwith CKD . AlthougMultiple myeloma inpatients monitoring consists of measurement of serum creatinine together with the calculation of eGFR at 12 and 48 hours after contrast media injection. If there is evidence of CI-AKI, it is recommended to repeat these tests on days 3–5 after contrast media administration, monitoring also urine output, and it is reasonable to prolong the discontinuation of the therapeutic treatment with NSAIDs, aminoglycosides, high dose diuretics, antineoplastic drugs, and metformin .Finally, diagnosis of CI-AKI can be improved by adding the measurement of serum cystatin C, which allows for an earlier assessment of changes in renal filtration . Urine NData from recent meta-analyses have led to the conclusion that the overall incidence of CI-AKI is low, not exceeding 6.4%; moreover, an association between the presence of malignancy with contrast-induced nephropathy was found , 93. NevSo far, there is limited evidence that myeloma per se may be a risk factor for developing CI-AKI. A careful medical history examination together with serum creatinine and the estimation of GFR by using the equation CKD-EPI-sCr-Cys may be considered the best cost/effective strategy to prevent CI-AKI in patients with multiple myeloma. The use of NGAL and KIM-1 as tandem markers for early detection and later confirmation, respectively, of kidney injury in patients at high risk should be considered. When serum FLCs level exceeds 500 mg/L in patients with multiple myeloma and other lymphoproliferative disorders, it is reasonable to achieve a rapid reduction in serum FLCs levels before administrating the contrast medium. Additional preventive measures include the use of the lowest volumes required and the removal of concomitantly administered nephrotoxic substances/drugs, especially NSAIDs. We should avoid redundant laboratory tests, like Bence Jones proteinuria, since this test cannot be considered as a surrogate biomarker of kidney function.


Retinal artery lesions have been reported to be a risk marker of morbidity and mortality for cardiovascular and cerebrovascular diseases in various study populations. Nonalcoholic fatty liver disease (NAFLD) is also a risk factor for cardiovascular disease. However, the relationship between retinal artery lesions and NAFLD is less certain.Data were obtained from 2,454 patients who attended their annual health examination . NAFLD was diagnosed by hepatic ultrasonography. Retinal artery lesions were diagnosed according to the criteria. Total plasma cholesterol, plasma triglyceride and fasting glucose levels were determined by using a multichannel analyzer; the body mass index, systolic blood pressure, diastolic blood pressure, incidence of hypertension and coronary artery disease were measured or analyzed by statistical analysis.p < 0.01). Retinal artery lesions were taken as a dependent variable, and age, gender, BMI, systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol and triglyceride levels, and NAFLD were taken as covariates. We found that age ≥65 years , being male , BMI ≥ 25 , SBP ≥ 140 mmHg  and NAFLD  were significantly associated with a risk of retinal artery lesions by binary logistic regression analysis.Patients with NAFLD had older age and higher values of BMI, systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol and triglycerides and had a higher incidence of hypertension, coronary artery disease and retinal artery lesions (Patients with NAFLD were older and had higher values for BMI, systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol and triglycerides, and higher incidence of hypertension, coronary artery disease and retinal artery lesions. NAFLD is a risk factor for retinal artery lesions. Nonalcoholic fatty liver disease (NAFLD) has been recognized as the most common liver disease, with an estimated prevalence of 20–30 % , 2. NAFLRetinal artery lesions are associated with both prevalent and incident metabolic syndrome , 10. It Other studies have documented a significant association between NAFLD and carotid artery intima media thickness, an early indicator of subclinical atherosclerosis , 14. RetStudy population and data collection: All of the subjects were residents in the community whose health care was provided by our hospital and initially attending their annual health examination in 2012. Inclusion criteria were complete available medical records; normal blood pressure [diastolic blood pressure (DBP) of <90 mmHg and systolic blood pressure (SBP) of <140 mmHg] or well-controlled hypertension (DBP of <90 mmHg and SBP of <150 mmHg); and no smoking or history of alcohol consumption. The hypertensive patients were taking antihypertensive medication, and all the observed subjects were taking acetylsalicylic acid (100 mg/day). Exclusion criteria were the presence of hematological system diseases; past history of cancer; major gastrointestinal surgery, including partial or total gastrectomy or colorectomy; pulmonary disease; nephrotic syndrome or serum creatinine levels higher than 115umol/l; total parenteral nutrition; viral hepatitis, autoimmune hepatitis and liver degeneration, etc.; and taking statin drugs or other drugs that damage the liver. Diabetes mellitus was diagnosed according to the 2009 American Diabetes Association diagnostic criteria [All patients were required to refrain from exercise for 1 day prior to the examination. Blood pressure was measured in the right arm using a mercury sphygmomanometer after 20 min of rest with the patient in a sitting position. Standing height, body weight and waist circumference were recorded for all subjects. Waist circumference was measured with the measuring tape positioned midway between the lowest rib and the superior border of the iliac crest as the patient exhaled normally. Body mass index (BMI) was calculated as weight divided by height squared.The blood samples were drawn from the participating patients after an overnight fast of more than 12 h. The serum levels of plasma creatinine concentration, blood urea nitrogen, total plasma cholesterol, plasma triglyceride and fasting glucose were measured using a multichannel analyzer .The diagnosis of NAFLD was based on the criteria suggested by the Chinese Liver Disease Association . UltrasoHypertension was defined as a SBP ≧140 mmHg or DBP ≧90 mmHg according to the Seventh Report of the Joint National Committee , or whenThe diagnostic criteria for coronary heart disease included patients with previous onset of myocardial infarction, with angina symptoms or ECG changes at the same time of more than 75 % narrowing of the coronary artery confirmed by coronary angiography. The symptoms of angina pectoris include chest pain, dyspnea, diaphoresis and palpitation, and the changes in electrocardiograms include significant ST-T wave change or Q wave presentation.The eye fundus examination was carried out for all the patients before ultrasonic examination by direct ophthalmoscopy performed after pupil dilation. The ophthalmologists who conducted the ophthalmoscopy did not know the patients' ultrasonic examination results. For all patients, the upper temporal quadrants and the first three arterial branches were analyzed. The extent and severity of atherosclerotic vascular lesions in the retinal arteries were classified according to Scheie. Stage 1 is defined as a broadening of the light reflex from the artery with minimal or no arteriovenous compression. Stage 2 is defined as changes similar to those in stage 1, but more prominent. In stage 3, the arteries have a “copper wire” appearance, the arteriovenous compression is much greater, and serious atherosclerotic changes of the retinal arteries are present. Stage 4 is the most severe form of atherosclerosis of the retinal arteries.p < 0.05. The independent-samples t test was used for the comparisons of continuous data, while the chi-square test was used for the comparisons of categorical variables. Binary logistic regression analysis was used to determine the factors that were associated with retinal artery lesions.Data were expressed as mean ± SD or counts. Statistical analysis was performed using SPSS version 16.0 , and the level of statistical significance was defined as p < 0.01).Among the 2,454 enrolled patients , 872  met the diagnostic criteria for NAFLD; the prevalence of NAFLD was 35.53 % . The characteristics of the patients, classified by the presence or absence of NAFLD, are presented in Table p < 0.01, OR 1.968), being male , BMI ≥ 25 , SBP ≥ 140 mmHg  and NAFLD  were significantly associated with the risk of retinal artery lesions (Table Binary logistic regression analysis was used to evaluate the risk factors for retinal artery lesions. Retinal artery lesions were taken as the dependent variable and age, gender, BMI, SBP, DBP, fasting glucose, total cholesterol, triglyceride, NAFLD and coronary artery disease were taken as covariates. We found that age ≥65 years (The retinal artery is part of the cerebral circulation system and offers an opportunity to explore atherosclerosis in the small peripheral arteries noninvasively. An assessment of the retinal artery may offer the opportunity to determine the extent of atherosclerosis in human body.NAFLD is a hepatic manifestation of the metabolic syndrome and is closely related to other clinical features of the metabolic syndrome; thus, cardiovascular disease is increased in NAFLD, and NAFLD represents the main cause of death in these patients. Patients with NAFLD have significantly higher rates of prevalent coronary, cerebrovascular and peripheral vascular disease than their counterparts without NAFLD –21.This research is a study on the community residents whose health care was provided by our hospital. In our study, the retinal artery lesions were significantly increased in NAFLD patients; retinal artery lesions were associated with age, being male, BMI, DBP, total cholesterol, triglycerides and NAFLD, showing that NAFLD is associated with cerebral atherosclerosis. Other research , 23 has The mechanisms underlying the association between retinal artery lesions and NAFLD are currently unclear. The pathogenetic mechanism might include endothelial dysfunction, oxidative stress, inflammation, inflammatory cytokines, dyslipidemia and glucose metabolism disorder .Several studies have demonstrated that metabolic syndrome has important implications for the clinical results of NAFLD patients –27 and tOxidative stress and inflammation are associated with retinal artery lesions . IncreasRetinal artery lesions have been associated with blood pressure . In our Another possible mechanism linking NAFLD and retinal artery lesions could be decreased plasma levels of adiponectin, an adipose-secreted cytokine with antiatherogenic properties. It has been shown that hypoadiponectinemia closely correlates to NAFLD in obese individuals, unrelated to insulin resistance and other metabolic syndrome components , 31. HowA few limitations warrant consideration. First, the diagnosis of NAFLD was based on ultrasound imaging. The patients did not undergo liver biopsy and histological examination, which is the gold standard technique for identifying steatosis. The sensitivity of ultrasonography in detecting steatosis varies between 60 and 94 % and is dependent on the degree of steatosis. Second, our research was a single-center study; thus, our relatively small sample size may have posed a limitation to the study. Therefore, our findings need to be confirmed in multicenter and prospectively designed studies. Finally, retinal artery lesions were not observed dynamically; thus, it remains unclear whether retinal artery occlusion increases incrementally whether the patient’s condition progressively deteriorates or not.In conclusion, NAFLD is extremely common in the middle-aged and elderly Chinese population. Patients with NAFLD had older age and higher levels of BMI, SBP, DBP, fasting glucose, and total cholesterol and triglycerides, and they had higher incidences of hypertension, coronary artery disease and retinal artery lesions. NAFLD is a risk factor for retinal artery lesions. NAFLD may be involved in the formation of cerebrovascular atherosclerosis, and the prevention of NAFLD has an effect on the prevention of cerebral vascular disease. Patients with NAFLD should always be assessed for retinal artery lesions to ensure early diagnosis and entry into proper and thorough medical care.


Loss of physical strength and hypertension are among the most pronounced detrimental factors accompanying aging. The aim of this study was to evaluate the influence of a supervised 8-week Nordic-walking training program on systolic blood pressure in systolic-hypertensive postmenopausal women. This study was a randomized control trial on a sample of 24 subjects who did not take any hypertension medications. There was a statistically significant decrease in systolic blood pressure and an increase in lower and upper-body strength in the group following Nordic-walking training. There was a decrease in serum levels of total cholesterol, triglycerides, and low-density cholesterol. The obtained results indicate that an 8-week Nordic-walking program may be efficiently employed for counteracting systolic hypertension through a direct abatement of systolic blood pressure and an increase of maximal aerobic capacity. Among many detrimental factors accompanying aging, loss of strength  and deteThis observation spurred the studies on prevention of age-related loss of strength  as well An extended span of a human life is also accompanied by an age-dependent deterioration of health-related quality of life (HRQoL), driven, among others, by an increase in blood pressure , which mThe aforementioned phenomena, i.e., increased blood pressure and a decreased level of physical fitness, incited a search for means, other than pharmaceutical, allowing to counteract age-dependent deterioration of HRQoL.During the last decade, a derivative of walking (W) called Nordic-walking (NW) has become a very popular mode of physical activity in Central and Northern Europe. Its clinical viability, among young and elderly women, has already been confirmed in several studies .Because of growing popularity of NW among Europeans, we made an attempt to test its efficacy in preventing hypertension in postmenopausal systolic-hypertensive women. For the purpose of our research we designed a moderate 8-week NW training program that comprised of three mesocycles, and carried out a randomized control trial under the null hypothesis that NW may be utilized as means of reducing systolic blood pressure in postmenopausal women.The following inclusion criteria were employed: last period >12 months ago, systolic blood pressure (SBP) ≥ 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg.Exclusion criteria were: (a) SBP ≥ 180 mmHg and/or DBP ≥ 90 (b) taking anti-hypertensive drugs, (c) oophorectomy, (d) chemotherapy within six months before screening, (e) coronary artery disease, (f) renal failure, (g) rheumatoid arthritis, (h) pulmonary disease, (i) diabetes mellitus or type II diabetes treated with insulin, (j) myocardial infarction or surgery within six months before screening, (k) smoking of more than two cigarettes per day or consuming more than the equivalent of one glass of wine per day, and (l) inability to obtain approval for participation in the study form a primary-care physician.Of 1200 women who agreed for the primary screening only 25 met all the criteria to participate in the study .Body mass and height were measured using a standard scale and a stadiometer with accuracy of 0.1 kg and 0.5 cm, respectively.Resting SBP and DBP were registered using an Omron HEM-907XL apparatus .A fasting blood draw was completed to measure blood glucose, total cholesterol, triglycerides, and high- and low-density lipoprotein cholesterol. Serum lipid levels were measured on the first and the last days of the training program on an empty stomach using ARCHITECT ci8200 Integrated System, Abbott Diagnostic.Subjects were advised to be well hydrated and to limit their physical activity one day before the laboratory test, as well as to remain physically inactive the evening before and the morning of the test.2max peak was assessed by open-circuit spirometry using the following protocol: (a) the test was preceded by a 2 min warm up: walking at the speed of 2–3 km/h, (b) the subject started walking, without holding onto the handrails during the test, at 4 km/h and 0% grade. The elevation was increased by 2% each 2 min stage until volitional fatigue. The test was continued until the subject could no longer continue due to an excessive elevation, achieved a respiratory-exchange ratio > 1.0, a maximal heart rate greater than HRmax = 206 − 0.88*age, or other clinical criteria for test termination were observed.VO2max was measured using a breath-by-breath gas-exchange system . In this study VO2max data are expressed as VO2peak.VOFunctional fitness was assessed by means of a tailored Fullerton battery test including: a) chair stand (CST), b) arm curl (CURL). All tests were performed one hour after breakfast to avoid results skewing by daily activities.Changes induced by the training/sedentary period in an analyzed parameter were examined using the Wilcoxon signed-rank test. Differences between the groups were evaluated by means of the Wilcoxon rank sum test using the p-value of 0.05 as the statistical threshold.Relative changes induced by the experiment were measured using a “natural” relative difference, employing a natural logarithm, denoted as log percent (L%) .max = 206 − 0.88•(age) (max − HRrest)•(0.4 to 0.6)] + HRrest; II: 3 weeks walking the distance of 3.1 km with an average heart rate between 45–68%, and III: 3 weeks of walking the distance of 3.8 km with an average heart rate between 38–69%. The heart rate was monitored using a GARMIN Forerunner 405 apparatus.All exercise sessions were performed outdoors on a flat area, and consisted of a 10 to 12 min warm-up followed by 45 min of NW and a 10 min stretching. The NW program was divided into three mesocycles: I: 2 weeks of walking the distance of 3 km, an average heart rate between 40–60% of an age-dependent maximal heart rate; HR88•(age) , [ 130 g/day of carbohydrates, (c) 0.8 g of protein per kilogram of body mass assessed at baseline, (d) 20–30% of total calories should be covered by fat, (e) no eating after 7 P.M. or three hours before sleep, and (f) four meals a day. Allsubjects were preconditioned using the above outlined guidelines two weeks before the start of the experiment.The following dietary guidelines were followed during the experiment: (a) consume Basic statistics of the baseline and experimental period are presented in 2max, TC, TG and LDL-C levels was observed.The supervised NW program significantly decreased SBP, and increased upper and lower-body strength in the experimental group. Furthermore, a positive trend in body mass, WC, HC, DBP, VOThe control group was defined by an unfavorable augmentation in body mass, TG, and LDL-C, and a decrease in lower-body strength.Although SBP and DBP diminished in both groups, changes in SBP and DBP in the control group were relatively 1.6 and 3.4 smaller than those in the experimental group, respectively.st and 2nd stage of hypertension (2004), and assessed changes in anthropometric, cardiorespiratory, and functional fitness variables as a function of an 8-week supervised NW program.We studied postmenopausal women who did not take any anti-hypertensive drugs during the 1A dearth of information on modulation of isolated hypertension (ISH) through physical exercises, leads to inconsistent conclusions; for example, 2max equal to 2.63 L% in this study versus a significant increase of 4 L% in the latter, i.e., 12-week aerobic NW training which comprised of three 90 min sessions, (b) a non significant decrease of 1.77 L% vs. a significant decrease of 6.90 L% in WC, (c) a non-significant decrease of 4.58 L% vs. a significant decrease of 6.12 L% in TC, (d) a non-significant decrease of 9.69 L% vs. a significant decrease of 3.17 L% in TG, (e) lack of changes in HDL-C vs. a non-significant increase of 6.57 L% in HDL-C, (f) a non-significant decrease of 5.44 L% vs. a significant decrease of 7.38 L% in LDL-C, and (g) a non-significant increase in the BMI of 0.31 L% vs. a significant decrease of 4.77 L% in the BMI.However, a comparison of current results with previous findings regarding the influence of NW on HRQoL  in healtAlthough, we were not able to confirm a significant decrease in the BMI of postmenopausal women who had undergone a supervised NW program, as shown in previous studies , we obseAdditionally, we also showed that the use of walking poles during NW exercises lead not only to an enhancement in oxygen uptake , but als2max SBP can be modulated. We conjectured that NW was superior than W and jogging (A conjunction of delineated relations between changes in physiological variables and the NW program with the results of the study on physical fitness and coronary risk factors  makes it jogging  for rehaHypertension has become one of the most profound health problems among the elderly in many societies. This spurred a search for a means, other than pharmaceutical, allowing to maintain proper blood pressure in elderly subjects.In this study we showed that a supervised 8-week NW program could be effectively employed for averting detrimental changes in SBP in systolic-hypertensive postmenopausal women.


Atrial fibrillation (AF) is the most frequent arrhythmia in elderly patients. Aims of this study were to evaluate the predictors of arterial stiffness after external cardioversion (ECV) of AF and to establish whether a link exists between vascular properties and left atrial diameter (LAD).We studied 33 patients (age 73 ± 12 years). After 5 h from ECV of persistent AF, an echocardiogram was recorded and arterial stiffness was evaluated with cardio-ankle vascular stiffness index (CAVI).R = 0.538, p = 0.006), CAVI (mean 9.60 ± 1.63) increased with age (p = 0.018) and with an AF length ≤3 months (p = 0.022). LAD was significantly related to CAVI (p = 0.007) even after adjustment for interventricular septum thickness (p = 0.018) .In multivariate analysis (In patients with AF, immediately after ECV, arterial stiffness is associated with age and AF length, and could represent an important factor for left atrium remodeling and, therefore, for AF maintenance. Atrial fibrillation (AF) is the most common sustained arrhythmia in the elderly ; its preWe enrolled all patients admitted to a day-hospital for ECV of persistent AF between January and June 2013; the only exclusion criterion was non-restoration of SR. The protocol was approved by an institutional committee and conforms to the 1975 Declaration of Helsinki ethical guidelines; patients gave their consent to participate. ECV was performed using a biphasic defibrillator, after a 4-week period of effective oral anticoagulation [Ps/Pd are systolic/diastolic pressures, ΔP is “Ps–Pd”, ρ is blood density, and a/b are constants [The cardio-ankle vascular index (CAVI) , a measuonstants . CAVI waonstants .t test and analysis of variance were used to compare continuous variables. The association between categorical variables was evaluated with χ2 test. Linear regression analysis models were used to define univariate and multivariate predictors of CAVI and LAD. A p value <0.05 was considered statistically significant.IBM SPSS for Windows (ver. 20) was used for statistical analysis. Continuous variables were expressed as mean ± SD, categorical variables as numbers with percentages. Student’s 2 score) was moderate in 72.7 % and high in 18.3 % of cases. Beta-blockers, ACE-inhibitors or angiotensin receptor blocking agents were the most frequently used cardiovascular drugs (Table p = 0.78). Therefore, only the results related to right CAVI will be presented.Thirty-three patients underwent ECV Table . Median R = 0.390, p = 0.025), BMI , the presence of mitral regurgitation  and an AF length ≤3 months . CAVI was not affected by gender or current smoking status, nor did we find any link with arterial hypertension, CHF, chronic renal failure, coronary artery and cerebrovascular disease, diabetes, dyslipidemia or other causes of AF. Heart rate, systolic, diastolic and pulse pressure, hemoglobin concentration and drug therapy did not correlate with CAVI. Interventricular septum thickness, left ventricular (LV) diameters, and LVEF were not associated with CAVI, but LAD was . A multivariate regression analysis model  showed that age  and an AF length ≤3 months  were significantly related to CAVI, while BMI lost its statistical significance (p = 0.11).In univariate analysis, CAVI was significantly associated with age . A multivariate model  demonstrated that both interventricular septum thickness  and CAVI  were predictors of LAD (Fig. LAD was not associated with age, gender, BMI, comorbid conditions, mitral regurgitation, AF length, drugs, arterial pressure, LV diameters, LVEF or hemoglobin concentration. Apart from CAVI, only interventricular septum thickness showed a direct association with atrial dimensions (The results of this preliminary study confirm the existence of a direct relationship between CAVI and age, also in patients treated with ECV for persistent AF. Interestingly, a shorter length of AF seems to be associated with higher CAVI values. We also showed that AS, together with interventricular septum thickness, is a significant determinant of LAD.The inverse correlation between CAVI and duration of AF, observed in the first few months after arrhythmia development, might be attributed to the increase in afterload due to the early effects on cardiac performance associated with the loss of atrial systole .Few data exist aimed at clarifying the interaction among AF, LAD and AS, and results are sometimes conflicting. In a previous study, Reiffel  found thThe study is preliminary and the sample is small, with only 5 women. The echocardiogram was recorded 5 h after effective ECV; yet, current evidence seems to suggest that such a short period of SR is unable to revert the electrical and structural changes which characterize atrial remodeling . FinallyIn conclusion, the results of our preliminary study support the hypothesis that age-related AS is independently associated with atrial size in patients with persistent AF. Therefore, the concept that “atrial fibrillation begets atrial fibrillation”  might re


While hypertension still is a major health problem worldwide, some studies have indicated that the blood pressure level has decreased in some populations. This population based cohort study aims at analysing blood pressure changes in a large Norwegian population over a 22 year period.Data is acquired from three comprehensive health surveys of the HUNT Study conducted from 1984–86 to 2006–08. All citizens of Nord-Trøndelag County, Norway, >20 years were invited: 74,549 individuals participated in 1984–86; 64,523 in 1995–97; and 43,905 in 2006–08.Both systolic and diastolic blood pressure levels decreased substantially from mid 1980s to mid 2000s, with the most pronounced decrease from 1995–97 to 2006–08 (from 136.0/78.9 to 128.3/70.9 mmHg in women and from 140.1/82.1 to 133.7/76.5 mmHg in men). Although the use of blood pressure lowering medication increased, there was a considerable decrease even in those who reported never use of medication (mean decrease 6.8/7.2 mmHg in women and 6.3/5.3 mmHg in men), and the decrease was most pronounced in the elderly (mean decrease 16.1/12.4 mmHg in women and 14.7/10.4 mmHg in men aged 80+). Mean heart rate, total cholesterol and daily smoking decreased, self-reported hard physical activity increased, while body weight and the prevalence of diabetes increased during the same period.The BP decrease might seem paradoxically, as body weight and prevalence of diabetes increased during the same period. Salt consumption might have decreased, but no salt data is available. The parallel decrease in mean heart rate might indicate reduction in the white-coat phenomenon, or increased use of beta blockers or calcium channel blockers for other diagnosis than hypertension. Additionally, the data could support the “healthy obese” hypothesis, i.e., that subgroups in the population can sustain obesity without serious health consequences.The online version of this article (doi:10.1186/s12872-016-0257-8) contains supplementary material, which is available to authorized users. A large number of studies have shown the health benefits of lowering of blood pressure (BP) and the efficacy of specific lifestyle and pharmacological interventions, but hypertension is still a major health problem world-wide. In a study covering 5.4 million participants, mean systolic blood pressure (SBP) decreased by only 1 mmHg per decade for men and women between 1980 and 2008, and in some countries SBP had increased .The aim of the present study was therefore to improve the understanding of the population BP changes. We systematically assessed both SBP and DBP changes in a large population over a 22 year period. Having collected a number of health- and other background data, we have analyzed the nature of the BP changes in all age groups 20 years and over, special emphasizing on people who have never taken BP medication.N = 74,549, 88 % of invited), 1995–97  and 2006–08   is stable and homogenous, and is representative of the Norwegian population regarding demography, socioeconomic factors, morbidity and mortality [We included individuals from the Nord-Trøndelag Health Study (HUNT), a population-based health study with medical histories on approximately 120,000 individuals from Nord-Trøndelag County, Norway, collected in three surveys  –6. All rAre you taking medication for high blood pressure? . Have you had or do you have: Myocardial infarction (heart attack)? (Yes/No), Diabetes? (Yes/No). Do you smoke?(Yes/No). Daily cigarette smoker? (Yes/No). How much of your leisure time have you been physically active during the last year? (Hours per week: None/Less than 1/1-2/3 or more). Vigorous physical activity (sweating/out of breath)? (Yes/No). What is your highest level of education? .Each participant completed two extensive questionnaires. First, they received a questionnaire by mail prior to attending the clinical exam regarding health and life style factors, including blood pressure treatment, information of cardiovascular related diseases and diabetes, physical exercise and smoking. At attendance, they were handed a second questionnaire to be completed at home and returned by mail mainly regarding self-reported diseases . For thin = 6,188), and they were excluded from the analyses [In HUNT1 , SBP andFor HUNT2 and HUNT3, non-fasting blood samples were drawn whenever the participants attended the screening site. In HUNT2 total serum cholesterol was measured using an enzymatic colorimetric cholinesterase method, HDL by enzymatic colorimetric cholesterol esterase method after precipitation with phosphor tungsten and magnesium ions, non-fasting triglycerides by enzymatic hexokinase method, non-fasting serum glucose by an enzymatic hexokinase method and serum creatinin by Jaffè method .2) [2) in HUNT2 minus BMI (kg/m2) at HUNT3, delta Se-cholesterol: total cholesterol (mmol/L) at HUNT2 minus total cholesterol (mmol/L) at HUNT3, delta heart rate (HR): HR (beats/min) at HUNT2 minus HR (beats/min) at HUNT3. We performed linear regression analyses in women and men separately with delta DBP as the dependant variables. P < 0.05 was considered significant. Nonparametric kernel-density plots were constructed in Stata (version 13) with the kdensity command and the default Epanechnikov kernel function was utilized. A kernel-density plot is a smoothed representation of a histogram where the area under the curve shows the proportion of values compared to all values and sums to 1. The other statistical analyses were performed using the Statistical Package for the Social Science, version 21.0 .All HUNT data are linked to the unique 11-digit personal identification number given to each Norwegian citizen at birth, enabling linkage of data for each individual. We used the second BP reading in HUNT1, and the mean of the second and third reading in HUNT2 and HUNT3. Body Mass Index (BMI) was calculated according to WHO (kg/m2) . QuartilValid BP measurements were available on 74,519 individuals from the mid 1980s (HUNT1), 64,523 individuals from the mid 1990s (HUNT2) and 43,905 individuals from mid 2000s (HUNT3). Clinical characteristics of the study participants are summarized in Table We did not observe change in mean SBP from HUNT1 to HUNT2, while for mean DBP we observed a decrease of 3.7 mmHg for women and 3.4 mmHg for men . From HUNT2 to HUNT3 mean SBP decreased by 7.7 mmHg in women and 6.4 mmHg in men  and mean DBP decreased by 8.0 mmHg in women and 5.6 mmHg in men . Figure The distribution of BP according to the ESH/ESC definitions  shows a The prevalence of self-reported BP lowering drug treatment increased from 12.9 % in HUNT1 via 13.7 % in HUNT2 to 20.6 % in HUNT3, and we observed a decrease in BP for participants who were currently or had previously been under treatment between the three measurements. In accordance with the great increase in self-reported drug treatment from HUNT2 to HUNT3, the decrease was more pronounced in this period (16.2 mmHg for SBP and 11.9 mmHg for DBP) compared to the change observed from HUNT1 to HUNT2 (1.5 mmHg for SBP and 4.8 mmHg for DBP) . As expected, in both genders mean SBP increased from HUNT1 to HUNT2 (8.9 mmHg in women and 5.8 mmHg in men). The increase from HUNT2 to HUNT3 was less pronounced, and in one age group (60–79 years) the observed BP was lower than 11 years previously. Mean DBP was roughly identical in HUNT1 and HUNT2. However, from HUNT2 to HUNT3 the observed diastolic pressures showed a general 2; Additional file To follow up on this observation, we further examined the BP of participants not under current or past treatment. We found several changes in cardiovascular related risk factors from HUNT2 to HUNT3. Among these individuals both BMI and non-fasting glucose increased, while total cholesterol, heart rate and self-reported daily smoking decreased. Also, we observed that self-reported hard physical activity increased in the same period. These changes occurred in both sexes  to mid 2000s (HUNT3), but most pronounced from mid 1990s (HUNT2) to mid 2000s (HUNT3). The decrease was observed both in SBP and DBP, in both genders and the decrease increased by age. The volume of antihypertensive drug treatment increased in the same period and explains some of the BP decrease. However, the BP decrease was significant even in those who reported they had never taken BP medication. An unexpected finding was the consistent association between blood pressure decrease with ageing and with decreasing heart rate.Strengths of our study are the large unselected and stable population, the large number of health variables and the consistent methods for clinical measurements and data collection. In HUNT1 BP was measured manually, while in HUNT2 and HUNT3 it was used automatic devices. The devices were checked and calibrated by specialists several times during the examination periods, finding no major errors. The automatic method was calibrated against manually procedures, showing slightly lower values, but this could not explain the large discrepancies in BP levels between the HUNT2 and HUNT3 surveys . AdditioThe increased drug treatment since HUNT2 was an important aspect when studying blood pressure changes in this population. We therefore estimated in a model the potential effect on population BP level from the increased drug treatment between HUNT2 and HUNT3: Provided those with BP above the 90 percentile in HUNT2 had their SBP decreased with 20 mmHg and DBP decreased with 10 mmHg, this effect on a population level could only explain about 2 mmHg decrease in SBP and 1 mmHg in DBP (data not shown).The main challenge is to understand the large BP decrease from HUNT2 to HUNT3 in individuals reporting they had never taken BP medication, and especially since the decrease occurred in a period with large increase in body weight and diabetes. Recall bias or misinterpretation of the purpose of drugs prescribed might occur, however, validation of this question gave no indication of major misclassification . The carBP decrease is reported in other industrialized populations since 1990s, along with increasing body weight . In the The larger BP decrease with increasing age in the present study has, to our knowledge, not been described previously. The parallel decrease in BP and heart rate and the association between BP decrease and heart rate decrease (linear regression) might indicate some kind of increased parasympathetic activity with strongest effect in elderly obese individuals. One explanation could be reduction in the white-coat phenomenon, but we have no data indicating why this effect should be so strong in the period from HUNT2 to HUNT3. Increased use of calcium channel blockers and beta blockers for other diagnosis than hypertension might explain some of the heart rate and blood pressure decrease, however, no data was available. In the period between HUNT2 and HUNT3 the Norwegian population increased consumption of fruit and vegetables, increasing the potassium (K) intake . If the This large population based health study has demonstrated that in the period from mid 1980s to mid 2000s BP in the population decreased considerably, especially in the period from mid 1990s to mid 2000s, and even in those who reported they had never taken BP medication. The BP decrease was larger in elderly and might seem paradoxically given the fact that body weight and the prevalence of diabetes increased during the same period. The BP decrease was, however, consistent with the general improvement in the cardiovascular risk profile and decreasing cardiovascular morbidity and mortality. We have no reason to assume that the methods of blood pressure measurement or selection bias can explain the findings. The parallel decrease in heart rate might indicate increased parasympathetic activity, like reduction in the white-coat phenomenon, and a possible increased use of beta blockers or calcium channel blockers for other diagnosis than hypertension could have had some effect. Additionally, salt consumption might have decreased. Finally, the data could support the “healthy obese” hypothesis, i.e., that subgroups in the population can sustain obesity without serious health consequences.The participation was voluntary and participants gave their written consent to participate and the use of data in research. All three surveys were approved by the Norwegian Data Inspectorate. In addition, HUNT2 and HUNT3 were approved by the Regional Committee for Medical and Health Research Ethics (REC). At the time of HUNT1 REC was not yet established. The current study protocol was approved separately by REC.HUNT Research Centre, University of Science and Technology (NTNU), has consented to publish the present manuscript.http://www.ntnu.edu/hunt.All HUNT-data are stored at HUNT Research Centre, and are available upon request according to general rules, see


The risk of acute kidney injury (AKI) with the use of albumin-containing fluids compared to starches in the surgical intensive care setting remains uncertain. We evaluated the adjusted risk of AKI associated with colloids following cardiac surgery.We performed a retrospective cohort study of patients undergoing on-pump cardiac surgery in a tertiary care center from 2008 to 2010. We assessed crystalloid and colloid administration until 36 hours after surgery. AKI was defined by the RIFLE  risk and Acute Kidney Injury Network (AKIN) stage 1 serum creatinine criterion within 96 hours after surgery.2. Twenty-three percent had a reduced left ventricular ejection fraction (LVEF), thirty-one percent were diabetics and twenty-three percent underwent heart valve surgery. The incidence of AKI was 5.3% based on RIFLE risk and 12.0% based on the AKIN criterion. AKI was associated with a reduced LVEF, diuretic use, anemia, heart valve surgery, duration of extracorporeal circulation, hemodynamic instability and the use of albumin, pentastarch 10% and transfusions. There was an important dose-dependent AKI risk associated with the administration of albumin, which also paralleled a higher prevalence of concomitant risk factors for AKI. To address any indication bias, we derived a propensity score predicting the likelihood to receive albumin and matched 141 cases to 141 controls with a similar risk profile. In this analysis, albumin was associated with an increased AKI risk . We repeated this methodology in patients without postoperative hemodynamic instability and still identified an association between the use of albumin and AKI.Our cohort included 984 patients with a baseline glomerular filtration rate of 72 ± 19 ml/min/1.73 mAlbumin administration was associated with a dose-dependent risk of AKI and remained significant using a propensity score methodology. Future studies should address the safety of albumin-containing fluids on kidney function in patients undergoing cardiac surgery. Acute kidney injury (AKI) following cardiac surgery is prevalent and associated with considerable morbidity and mortality ,2. PerioStudy results regarding administration of albumin-containing fluids have been conflicting. Hyperoncotic albumin has demonstrated a clear benefit in patients with cirrhosis ,9. HowevIn 2009, we reported a dose-dependent risk of AKI using pentastarch 10% (250 kDa/0.45) following cardiac surgery . Since tWe conducted a retrospective cohort study of patients who underwent on-pump cardiac surgery between 1 January 2008 and 31 December 2010 at the Hôpital du Sacré-Coeur de Montréal, a tertiary care teaching hospital. The intensive care unit is a 24-bed mixed medical-surgical and trauma unit. The research ethics board of the Hôpital du Sacré-Coeur de Montréal approved the study protocol and waived the need for consent from the study participants.2 or treatment with dialysis [We included all adult patients who required either coronary artery bypass graft (CABG) and/or valve replacement and who were hospitalized at least 96 hours after surgery. Patients known to have end-stage renal disease (ESRD) or AKI  serum creatinine criterion), kidney transplant, autoimmune kidney disease or kidney cancer were excluded as being those who had undergone urgent aortic surgeries. ESRD was defined as a baseline creatinine clearance inferior to 15 ml/min/1.73 mdialysis . Data weWe recorded baseline risk factors for AKI, including patient demographics, history of hypertension, diabetes, peripheral vascular disease, stroke, recent myocardial infarction (within 7 days before surgery), left ventricular ejection fraction (LVEF) and preoperative hemoglobin level. We assessed any use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, nonsteroidal anti-inflammatory drugs, contrast agents and diuretics within 5 days before surgery. Preoperative kidney function was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation .We collected type of surgery , as well as perioperative variables, including the Sequential Organ Failure Assessment (SOFA) score for cardiovascular system immediately after surgery , use of Glomerular filtration rate (GFR) was estimated by using the CKD-EPI formula . Postopet-test. Nonparametric continuous variables were expressed as median (interquartile range (IQR)) and compared using the Mann–Whitney U test, and categorical variables were expressed in percentages and compared using the Pearson’s χ2 test. Spearman’s correlation was used to perform a trend test between tertiles of colloids and AKI.Normally distributed variables were expressed as mean ± standard deviation and compared using Student’s Because colloids are indicated for restoration of the circulating volume, they are given in situations associated with AKI in which it may be difficult to distinguish the effect of the colloid from the underlying condition. Adjustment for an indication bias was further assessed using a propensity score. This methodology permits the comparison of patients who received a colloid to controls with a similar AKI risk profile. We followed the Strengthening the Reporting of Observational Studies in Epidemiology guidelines . The proP-values were two-tailed, and values <0.05 were considered statistically significant. Analyses were carried out using SPSS software .In the statistical analyses, we excluded cases with missing covariates. All The characteristics of the 984 individuals included in the study are detailed in Table Fourteen percent of surgeries were defined as urgent, and twenty-three percent included valve replacement or repair. The median duration of ECC was 1.1 hour . The median volume of crystalloids received from the beginning of surgery until 36 hours postoperatively was 63 ml/kg . Eighty-two percent, forty-three percent and sixteen percent of individuals received HES 6%, pentastarch 10% or albumin, respectively, with median volumes of 13 ml/kg  and 9 ml/kg  and a median dose of 1.4 g/kg , respectively , marginal with the use of pentastarch 10%  and absent with the use of HES 6%. There was a dose-dependent risk for AKI with the use of albumin and pentastarch 10% .P = 0.28). The only exception was the volume of pentastarch 10%, which was lower in the albumin group .The adjustment for selection bias was further addressed using a propensity score. Because albumin administration was identified as a novel risk factor of AKI following cardiac surgery, we further studied this finding by pairing those who received albumin with similar individuals who did not. Albumin administration was associated with multiple clinical variables, including age, LVEF, heart valve surgery, GFR, cardiovascular SOFA score, fluids , transfusions , preoperative hemoglobin, duration of ECC and use of diuretics. We derived the probability of receiving albumin (propensity score) with logistic regression using variables associated with its use, and then we matched individuals with a similar risk profile (propensity score ±0.05) who either received albumin or did not. Our ratio of variable/event was 8.3. Using a caliper size of 0.2 times, the standard deviation of the propensity score would have been similar at 0.042. Within the group of 153 individuals given albumin, we could match 141 of them to 141 similar controls. Risk factors for AKI between these groups were balanced, including the amount of fluid administered . Within this subgroup, we derived a new propensity score predictive of the use of albumin with the same defining variables that we used for the entire cohort. We were able to match 50 cases to 50 controls with a similar risk profile, all of whom had a perioperative cardiovascular SOFA score of zero (Table P = 0.005).We also addressed the subgroup of individuals without hemodynamic instability as defined by a perioperative cardiovascular SOFA score of zero n = 90. WithiIn our present study, we found that albumin administration was associated with a dose-dependent increased risk of AKI in patients undergoing cardiac surgery. To further assess the risk associated with albumin and adjust for potential indication biases, we paired individuals who received albumin to controls who received no albumin. On the basis of this propensity score, albumin administration was still associated with a twofold increased risk for AKI. We repeated this methodology in individuals without significant postoperative hemodynamic instability and found similar results.To our knowledge, this is the first study to show a dose–response relationship between albumin administration and increased risk for AKI. Our study offers new insights into the association between albumin administration and kidney function. Current evidence regarding the beneficial or deleterious effect of albumin in this context is inconclusive, especially in surgical patients and those without hypoalbuminemia ,12,21-23post hoc study [post hoc analysis and did not find a difference between the two groups [In contrast to these findings, other studies have shown a protective or neutral effect on kidney function due to albumin administration ,9,12,27.oc study  and no ioc study . In compo groups -32. In oAs highlighted in previous studies, the effect of albumin administration seems to differ between subgroups -29. In oOur study was not designed to investigate underlying biological mechanisms to explain the effect of albumin on kidney function. Postmortem examinations of a limited number of patients who received large doses of 25% albumin showed no evidence of abnormal albumin storage . The resAlthough our present study was focused on kidney function as a primary endpoint, perioperative kidney function is a very relevant parameter in predicting long-term outcomes -43. AKI Our study has several strengths. It is the largest study to date on the effect of albumin administration on kidney function in patients undergoing cardiac surgery, a clinical setting with very limited data and a different pathophysiological model of AKI than severe sepsis or shock. We were able to demonstrate a twofold increase risk in AKI after adjustment with a propensity score that included baseline characteristics, surgical aspects, severity of illness scores and amounts of blood products, colloids and crystalloids administered. As recently shown, propensity scores may underestimate the true effect size compared to RCTs in critically ill patients . The useOur study also has limitations inherent to its retrospective and single-center design. First, there is a concern regarding hemodynamic instability (and risk of AKI) and the need to optimize left ventricular end-diastolic filling pressure using colloids. However, 86% of surgeries were elective, and any unstable condition was likely to surface after ECC at the end of the surgery. Our propensity score included the postoperative cardiovascular SOFA score. In addition, we obtained similar results in patients who had cardiovascular SOFA scores of zero. Second, we assessed whether the use of albumin by clinicians wishing to avoid giving patients synthetic colloids in the setting of impending AKI could have been a consequence of early AKI rather than its cause. However, the timing of AKI was similar in both groups. Third, it is possible that the period between the onset of oliguria and the rise of creatinine was a window within which albumin may have been preferred over synthetic colloids, again in the setting of impending AKI. However, we would have expected at least a trend toward greater use of crystalloids in the albumin group; however, the doses of crystalloids were not statistically different between groups , even when addressing diagnosis of AKI <36 hours, 36 to 48 hours and >48 hours after surgery separately. We also had limited data on albumin levels. Recent studies have suggested a relationship between hypoalbuminemia and risk for AKI ,51. In oWe found that albumin administration was associated with a twofold increased risk for AKI after adjustment with a propensity score in cardiac surgery patients, a population with a different pathophysiological model of AKI than severe sepsis or shock and with limited data on the effect of albumin administration. The detrimental effect was proportional to the dose administered. The results of this study are in accordance with recent guidelines suggesting the use of crystalloid solutions for most patients with or at risk for AKI ,11. FutuIn a retrospective cohort study including 984 patients undergoing cardiac surgery, we found that albumin administration was a risk factor for AKI.This finding remained significant when we used a propensity score methodology, even in patients without postoperative hemodynamic instability.We also identified a dose–response relationship between albumin administration and the risk for AKI.Future RCTs should address the safety of albumin in terms of dose and concentration compared to crystalloids in cardiac surgery.