The Effect of Postoperative Fluid Balance on the Occurrence and Progression of Acute Kidney Injury After Cardiac Surgery.

OBJECTIVES: In addition to the association between positive fluid balance (FB) and acute kidney injury (AKI) after cardiac surgery reported by former studies, this study examined the relationship between FB and progressive AKI. DESIGN: A retrospective, observational study. SETTING: University teaching, grade A tertiary hospital in Shanghai, China. PARTICIPANTS: Adult patients after cardiac surgery from July-December 2016. INTERVENTIONS: Perioperative data relating to postoperative fluid intake and output were collected. AKI progression was defined as a worsening of AKI stage. FB was calculated as (fluid intake [L] - fluid output [L]/body weight [kg] × 100%). MEASUREMENTS AND MAIN RESULTS: The study comprised 1,522 patients. The incidences of AKI and progressive AKI were 33.1% (n = 504) and 18.1% (n = 91), respectively. There was an exponential increase between 24-hour FB and AKI occurrence, and an approximate "U"-shape association between 48-hour FB and AKI progression. Multivariate logistic regression showed that 24-hour FB ≥5% was an independent risk factor for AKI incidence (odds ratio [OR] 3.976; p < 0.001) and 48-hour FB <-5% or ≥3% was associated with an increase of AKI progression (FB <-5%, OR 7.078 [p = 0.031]; FB 3%-5%, OR 6.598 [p = 0.020]; FB ≥5%, OR 16.453 [p < 0.001]). CONCLUSIONS: An exponential increase was found between 24-hour FB and AKI occurrence and a "U"-shape association between 48-hour FB and AKI progression. Both excessively negative and positive accumulative 48-hour FB increased the risk of AKI progression, suggesting cautious monitoring and application of fluid load in clinical practice.

Incidence, Risk, and Prognosis of Cancer in Patients on Chronic Hemodialysis.

BACKGROUND: Information concerning the cancer issue in Chinese patients on hemodialysis (HD) was lacking. Thus, we examined data from our dialysis registry to investigate the incidence of cancer, identify the possible factors, and explore outcomes after cancer diagnosis in patients on chronic HD. METHODS: A retrospective cohort study of 639 new-onset end-stage renal disease patients who started HD therapy during the period from July 1999 to December 2017 was retrieved from the database in our dialysis center. All eligible patients were followed up until renal transplantation, death, or end of study (March 31, 2019). The definition of a newly diagnosed cancer was that diagnosed 6 months after HD therapy initiation. RESULTS: Within a median follow-up period of 5.61 years, 58 patients (9.08%) have been diagnosed with cancer with the incidence of 1,494 per 105 person-years. The mean duration from HD initiation to cancer diagnosis was 5.22 ± 3.55 years. Digestive cancer (32.76%) was the most common followed by urologic cancer (18.97%) and lung cancer (15.52%). Advanced age at starting HD therapy (hazard ratio [HR] 1.04) and erythropoietin dosage ≥20,000 U/week (HR 1.95) were independent predictors for cancer occurrence. Of the 256 deaths during the follow-up period, 29 cases (11.33%) were attributed to cancer, with the mortality rate of 717 per 105 person-years. The 1-, 5-, and 10-year cumulative survival rates after cancer diagnosis were 58.73, 34.64, and 20.41%, respectively. A total of 32 patients (55.17%) did not receive any anti-cancer therapy, and the mortality in those patients was significantly increased as compared to patients who received anti-cancer therapy. CONCLUSION: Cancer is common in HD patients due to the improved survival, and it has a negative effect on patient prognosis. Many patients have failed to receive optimal anti-cancer therapy, which calls for effective communication and cooperation among patients, dialysis unit, and oncology teams.

Efficacy of Early Goal-Directed Renal Replacement Therapy for the Treatment of Acute Kidney Injury After Heart Transplantation: A Single-Center 10-Year Experience.

OBJECTIVE: Acute kidney injury (AKI) after heart transplantation is a common and serious complication. The present study aimed to evaluate the efficacy of early goal-directed renal replacement therapy (GDRRT) for the treatment of AKI after heart transplantation. DESIGN: Retrospective, observational study. SETTING: Grade A tertiary hospital that performs more than 4,000 cardiac surgery procedures per year. PARTICIPANTS: Patients who underwent heart transplantation with postoperative AKI and received renal replacement therapy from January 2008 to June 2018. INTERVENTIONS: Patients were divided into a late GDRRT group (LGDRRT) (January 2008-September 2012) or an early GDRRT group (EGDRRT) (October 2012-June 2018). RESULTS: The LGDRRT group comprised 30 patients, and the EGDRRT group comprised 46 patients. Duration between surgery to renal replacement therapy (RRT) initiation in the EGDRRT group was significantly shorter than in the LGDRRT group (1 [1-3] d v 2 [2-3] d; p = 0.020). The in-hospital mortality in the EGDRRT group was significantly lower than that of the LGDRRT group (39.1% v 63.3%; p = 0.039). After multivariate adjustment for confounding factors, the hazard ratio for death in the LGDRRT group relative to the EGDRRT group was 2.028 (95% confidence interval 1.072-3.655; p = 0.048). Length of intensive care unit and hospital stays in the EGDRRT group was significantly shorter than that of the LGDRRT group (26 ± 18 d v 38 ± 20 d; p = 0.008 and 38 ± 33 d v 64 ± 45 d; p = 0.005, respectively). The complete renal recovery rate was much greater in the EGDRRT group than that of the LGDRRT group (50.0% v 20.0%; p < 0.001). Serum creatinine at discharge was significantly less in the EGDRRT group than that of the LGDRRT group (134.8 ± 97.3 µmol/L v 220.7 ± 113.6 µmol/L; p < 0.001). Cost of RRT in the EGDRRT group was significantly less than that of the LGDRRT group (0.54 ± 0.10 v. 0.63 ± 0.11 ten thousand USD; p < 0.001). CONCLUSIONS: For heart transplantation recipients with AKI, EGDRRT can reduce the in-hospital mortality and the length of intensive care unit and hospital stays, improve the complete renal recovery rate, and reduce the cost of RRT.

The significance of serum levels of soluble interleukin-2 receptor in patients undergoing maintenance hemodialysis.

Background: Elevated serum levels of sIL-2R are commonly observed in patients undergoing maintenance hemodialysis (MHD). However, the clinical implications in these subjects are unclear. This study is aimed to assess the significance of elevated sIL-2R levels in MHD patients.Methods: A total of 382 MHD patients were followed-up from September 2016 to December 2019. Patients were divided into two groups: high sIL-2R, with sIL-2R levels ≥2-fold of the upper limit of normal (710 U/ml); and low sIL-2R, with sIL-2R levels < 2-fold the upper limit of normal. The relationships between sIL-2R levels and other clinical parameters, as well as patient prognosis were both assessed.Results: The median concentration of sIL-2R was 1268 U/mL. A total of 372 (97.38%) patients exhibited sIL-2R levels higher than the upper limit of the normal range. Multiple linear regression analysis revealed that monocyte count (ß = 0.1571, p = 0.01), and ß2-MG (ß = 0.2635, p < 0.0001), hemoglobin (ß = -0.1610, p = 0.001), SCr (ß = -0.3471, p < 0.0001), and HDL-C (ß = -0.1091, p = 0.029) levels were independent factors influencing serum concentrations of sIL-2R. High sIL-2R was significantly correlated with non-cardiovascular-related mortality (OR 2.97 [95% CI 1.59-5.56; p = 0.001), of which 39 (82.98%) were attributed to infection and/or cancer.Conclusions: Elevated sIL-2R is prevalent in MHD patients and related with several unfavorable parameters. sIL-2R appears to have no ability to predict cardiovascular mortality, which accounts for approximately one-half of all deaths. However, sIL-2R may be beneficial in predicting noncardiovascular mortality.

Association of trimethylamine N-Oxide with cardiovascular and all-cause mortality in hemodialysis patients.

BACKGROUND: Trimethylamine-N-Oxide (TMAO) is a proatherogenic and prothrombotic metabolite. Our study examined the association of plasma TMAO level with cardiovascular and all-cause mortality in hemodialysis (HD) patients. METHODS: Patients who were at least 18 years-old and received HD for at least 6 months were enrolled within 6 months. Patients with coronary heart disease, congestive heart failure, arrhythmia, or stroke within 3 months before study onset were excluded. The primary endpoints were cardiovascular and all-cause death, and the secondary endpoint was cerebrovascular death. RESULTS: We recruited 252 patients and divided them into a high-TMAO group (>4.73 µg/mL) and a low-TMAO group (≤4.73 µg/mL). The median follow-up time was 73.4 months (interquartile range: 42.9, 108). A total of 123 patients died, 39 from cardiovascular disease, 19 from cerebrovascular disease, and 65 from other causes. Kaplan-Meier analysis indicated that the high-TMAO group had a greater incidence of cardiovascular death (Log-Rank: p = 0.006) and all-cause death (Log-Rank: p < 0.001). Cox regression analysis showed that high TMAO level was significantly associated with cardiovascular and all-cause mortality. After adjustment for confounding, this association remained significant for cardiovascular mortality (TMAO as a continuous variable: HR: 1.18, 95%CI: 1.07, 1.294, p < 0.001; TMAO as a dichotomous variable: HR: 3.44, 95%CI: 1.68, 7.08, p < 0.001) and all-cause mortality (TMAO as a continuous variable: HR: 1.14, 95%CI: 1.08, 1.21, p < 0.001; TMAO as a dichotomous variable: HR: 2.54, 95%CI: 1.71, 3.76, p < 0.001). CONCLUSIONS: High plasma TMAO level is significantly and independently associated with cardiovascular and all-cause mortality in HD patients.

The Prognostic Value of Red Blood Cell Distribution Width in Patients on Maintenance Hemodialysis.

AIMS: To examine the association between red blood cell distribution width (RDW) and mortality in hemodialysis (HD) patients. METHODS: Three hundred fifty six patients on HD for >3 months were enrolled and followed for 2 years. Patients were divided into 2 groups according to the median RDW value. Patient survival and risk factors for mortality were investigated. RESULTS: The 2-year survival rate was significantly lower in the high-RDW group (>14.9%; log-rank = 10.00, p = 0.0016). RDW (hazard ratio (HR) 1.34, 95% CI 1.04-1.71, p = 0.021), hemoglobin (HR 0.98, 95% CI 0.96-1.00, p = 0.023) and albumin (HR 0.90, 95% CI 0.82-0.99, p = 0.026) were independent predictors of mortality. Receiver operating characteristic curves of RDW to predict 2-year mortality had an area under the curve of 0.6487 (95% CI 0.5714-0.7260). CONCLUSIONS: Abnormal RDW was common in HD patients and significantly related with poor outcomes in these patients.

Clinical status of Sagliker syndrome: a case report and literature review.

In a 53-year-old woman, Sagliker syndrome developed during 22 years of treatment with intermittent hemodialysis as a result of severe secondary hyperparathyroidism (SHPT) complicating end-stage renal disease. She failed medical managements and lost her renal graft just after the kidney transplantation due to acute rejection. Although surgical parathyroidectomy was effective, the parathyroid hormone level became extremely high again due to recurrent hyperparathyroidism. It is possible that such patient could survive long-term with dialysis, but prevention of severe SHPT is the most important.

Immunological features of ESRD patients undergoing hemodialysis of various ages.

AIMS: To investigate the immunological characteristics of hemodialysis (HD) patients with end-stage renal disease (ESRD) of various ages, and the impact of age-related immune alterations on these patients, with a focus on peripheral T cells. METHODS: From September 2016 to September 2019, HD patients were enrolled and followed prospectively for 3 years. Patients were divided into three groups based on their ages: < 45, 45 to 64, and ≥ 65. The distribution of T cell subsets in different age groups was investigated and compared. The effects of altered T cell subsets on overall survival were also investigated. RESULTS: A total of 371 HD patients were enrolled. The reduced number of naive CD8+ T cells (P < 0.001) and increased number of EMRA CD8+ T cells (P = 0.024) were independently associated with the advanced age among all T cell subsets studied. Patient survival may be affected by numerical changes in naive CD8+ T cells. However, when HD patients were < 45 or ≥ 65 years, the reduction had no significant impact on survival. Only in HD patients aged 45 to 64 years, the number of naïve CD8+ T cells found to be insufficient but not deficient, identified as an independent predictor of poor survival. CONCLUSIONS: The most significant age-related immune change in HD patients was a decrease in peripheral naive CD8+ T cells, which was an independent predictor of 3-year overall survival in HD patients aged 45 ~ 64 years.

ELISA examining urinary angiotensinogen as a potential indicator of intrarenal renin-angiotensin system (RAS) activity: a clinical study of 128 chronic kidney disease patients.

In the current study, we measured urinary angiotensinogen (AGT) through enzyme-linked immunoadsordent assay (ELISA) and analyzed its correlation with intrarenal renin-angiotensin system (RAS) activity in 128 chronic kidney disease (CKD) patients. Urinary and plasma renin activity, AGT, angiotensin II (Ang II) and aldosterone levels were also measured by radioimmunoassay (RIA) or ELISA in these participants. Further, the expression level of intrarenal renin, AGT, Ang II and Ang II receptors were examined by immunohistochemistry staining (IHCS) in 72 CKD patients. Their correlations with urinary AGT were also analyzed. We found that the urinary AGT level was positively correlated with hypertension (ρ = 0.28, P < 0.01), urinary protein (r = 0.38, P < 0.01), urinary Ang II (r = 0.29, P < 0.05), urinary type IV collagen (Col IV) (r = 0.56, P < 0.01), and was negatively correlated with estimated glomerular filtration rate (eGFR) (r = -0.28, P < 0.01), urinary sodium (r = -0.22, P < 0.05) and serum AGT (r = -0.27, P < 0.01). Multiple regression analysis indicated low serum AGT (P < 0.01), high urinary protein (P < 0.01), high urinary Ang II (P < 0.05) and high urinary Col IV (P < 0.01) were correlated significantly with high urinary AGT. Urinary AGT level was positively correlated with intrarenal expression level of AGT (ρ = 0.46, P < 0.01), Ang II (ρ = 0.56, P < 0.01) and Ang II type 1 receptor (ρ = 0.32, P < 0.01), as detected by IHCS. Together, these data suggest that urinary AGT might be a potential biomarker of intrarenal RAS and Ang II activities in CKD patients.

Metagenome-wide analysis uncovers gut microbial signatures and implicates taxon-specific functions in end-stage renal disease.

BACKGROUND: The gut microbiota plays a crucial role in regulating host metabolism and producing uremic toxins in patients with end-stage renal disease (ESRD). Our objective is to advance toward a holistic understanding of the gut ecosystem and its functional capacity in such patients, which is still lacking. RESULTS: Herein, we explore the gut microbiome of 378 hemodialytic ESRD patients and 290 healthy volunteers from two independent cohorts via deep metagenomic sequencing and metagenome-assembled-genome-based characterization of their feces. Our findings reveal fundamental alterations in the ESRD microbiome, characterized by a panel of 348 differentially abundant species, including ESRD-elevated representatives of Blautia spp., Dorea spp., and Eggerthellaceae, and ESRD-depleted Prevotella and Roseburia species. Through functional annotation of the ESRD-associated species, we uncover various taxon-specific functions linked to the disease, such as antimicrobial resistance, aromatic compound degradation, and biosynthesis of small bioactive molecules. Additionally, we show that the gut microbial composition can be utilized to predict serum uremic toxin concentrations, and based on this, we identify the key toxin-contributing species. Furthermore, our investigation extended to 47 additional non-dialyzed chronic kidney disease (CKD) patients, revealing a significant correlation between the abundance of ESRD-associated microbial signatures and CKD progression. CONCLUSION: This study delineates the taxonomic and functional landscapes and biomarkers of the ESRD microbiome. Understanding the role of gut microbiota in ESRD could open new avenues for therapeutic interventions and personalized treatment approaches in patients with this condition.

The serum free triiodothyronine to free thyroxine ratio as a potential prognostic biomarker of chronic kidney disease in patients with glomerular crescents: A retrospective study.

Background: Crescent formation indicates severe glomerular pathology, and hypothyroidism usually predicts poor prognosis for severe diseases. However, the relationship between thyroid function and the progression of chronic kidney disease (CKD) is unclear. This study analysed the prognostic predictive value of the serum free triiodothyronine (FT3) to free thyroxine (FT4) ratio and its correlation with renal function in patients with CKD with crescent formation. Methods: This single-centre study included 162 CKD patients with glomerular crescents confirmed by renal pathology between March 2012 and December 2014. According to the first tertile (0.284) of FT3/FT4 ratio, the patients were divided into high and low FT3/FT4 ratio groups. Kaplan-Meier and Cox regression analyses were performed to evaluate the prognostic value of the FT3/FT4 ratio. Results: The age, haemoglobin, eGFR, urinary albumin-to-creatinine ratio, cardiac troponin T, N-terminal brain natriuretic peptide precursor, FT3, FT4, percentage of total crescents in non-globally sclerotic glomeruli, prevalences of hypertension, moderate to severe renal tubulopathy and crescentic nephritis, and proportion of patients receiving glucocorticoids and immunosuppressants were significantly different between high and low FT3/FT4 ratio groups (P < 0.05). Multivariate Cox regression analysis showed that when compared with patients with a high FT3/FT4 ratio (>0.284), those with intermediate and low FT3/FT4 ratios (≤0.284) had an increased risk of the long-term composite endpoint (P < 0.05 for various adjustment models). Conclusions: A low FT3/FT4 ratio is associated with increased mortality and worse outcome risk in CKD patients with crescent pathology.

Prostaglandin E2 induced cardiac hypertrophy through EP2 receptor-dependent activation of ß-catenin in 5/6 nephrectomy rats.

AIMS: Prostaglandin E2 (PGE2) is involved in the development of cardiac hypertrophy. However, whether PGE2 regulates the chronic kidney disease-associated cardiac hypertrophy and the tentative mechanism remains to be elucidated. METHODS AND RESULTS: We explored the effect of PGE2 receptor inhibitors on cardiac hypertrophy in vitro and in a 5/6 nephrectomy (5/6NT) rat model using quantitative reverse transcription polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay, immunohistochemical staining, and immunofluorescence staining assays. The result showed that EP2 and EP4 receptors were both up-regulated in the PGE2-treated cardiomyocyte cells. PGE2 treatment enhanced active ß-catenin (non-phosphorylated) signalling through mediating EP2 and EP4 receptors. Interestingly, inhibition of EP2 receptor suppressed PGE2-induced cardiomyocyte hypertrophy and cardiac fibrosis-related proteins in vitro. In the 5/6NT rat model, the increased secretion PGE2 was identified in the 5/6NT rat model for 2 weeks (P = 0.0251). EP2 receptor inhibitor administration significantly improved the cardiac function and fibrosis in 5/6NT rats. CONCLUSIONS: Our study demonstrated that inhibition of EP2 receptor could improve PGE2-induced cardiac hypertrophy in 5/6NT rats. The exploration of these mechanisms may contribute to the optimization of therapy in chronic kidney disease accompanied cardiac hypertrophy in clinic.

Survival analysis in the incident dialysis patients by different modalities.

BACKGROUND: To analysis survival in onset uremic patients who initiating HD or PD dialysis in our dialysis center. METHODS: Between Jan. 2015 and June. 2018, patients with onset uremia and initiating planned-start dialysis were retrospectively enrolled in this study and followed up to January, 2019. The relationships between the types of dialysis modality and patient prognosis were assessed. RESULTS: A total of 460 patients were included in the final analysis. Of which, 213 patient (46.30%) undergoing PD and 247 patients (53.70%) undergoing HD with arteriovenous fistula. The average follow-up time was 27.9 months. Eighty-seven (18.91%) patients died during the study period. The all-cause mortality was 127 per 1000 person-year. It was 102 per 1000 person-year in the HD group and 171 per 1000 person-year in the PD group (p < 0.01). However, dialysis modality was not an independent predictor for survival. During the first year after dialysis initiation, patient survival was comparable between the PD and HD groups (log-rank p = 0.14). As the dialysis age increased over 1 year, HD patients seemed to have a better survival as compared to that of PD patient (log-rank p < 0.05), especially those older than 65 years and without DN. CONCLUSIONS: Though dialysis modality was not an independent factor for overall survival, HD therapy seemed to be more suitable for patients without DN.

Preoperative hidden renal dysfunction add an age dependent risk of progressive chronic kidney disease after cardiac surgery.

BACKGROUND: To study different value of estimated glomerular filtration rate with normal serum creatinine whether is a risk factor for hidden renal function of cardiac surgery outcomes. METHODS: A total of 1744 cardiac surgery patients with serum creatinine ≤1.2 mg/dL (female)/1.5 mg/dL (male) were divided into 3 groups: estimated glomerular filtration rate ≥ 90 mL/min/1.73 m2 (no renal dysfunction, n = 829), 60 ≤ estimated glomerular filtration rate < 90 mL/min/1.73 m2 (hidden renal dysfunction, n = 857), estimated glomerular filtration rate < 60 mL/min/1.73 m2 (known renal dysfunction, n = 58) and followed up for 3 years. Multivariate regression analyses for risk factors of postoperative acute kidney injury. RESULTS: The proportion of preoperative hidden renal dysfunction was 67.1% among patients ≥  65 years old and 44.1% among patients < 65 years old. Multivariate Cox regression analyses showed that for patients < 65 years, known renal dysfunction was a risk factor for postoperative acute kidney injury (P <  0.01) and progressive chronic kidney disease (P = 0.018), while hidden renal dysfunction was a risk factor for progressive chronic kidney disease (P = 0.024). For patients ≥  65 years, only known renal dysfunction was a risk factors for 3-year mortality (P = 0.022) and progressive chronic kidney disease (P <  0.01). CONCLUSION: Hidden renal dysfunction was common in patients with normal serum creatinine for cardiac surgery, with a prevalence of 49.1%. For patients < 65 years old, hidden renal dysfunction was an independent risk factor for progressive chronic kidney disease.

Indoxyl sulfate, a valuable biomarker in chronic kidney disease and dialysis.

Chronic kidney disease (CKD) is an increasingly recognized disease with high global incidence and mortality. Yet, the existing diagnostic tools are not sufficient enough to predict prognosis of CKD and CKD comorbidities. Indoxyl sulfate, a typical uremic toxin, is of great importance in the development of CKD with its nephrotoxicity, cardiovascular toxicity, and bone toxicity. Some reports suggest that indoxyl sulfate directly associate with renal function loss and mortality in CKD patients. This review discusses the diagnostic value of indoxyl sulfate from its biological characteristics, pathophysiological effects, related therapies, and its diagnostic value in clinical studies.

Decreased percentage of peripheral naïve T cells is independently associated with ischemic stroke in patients on hemodialysis.

PURPOSE: Cerebrovascular complications, including ischemic stroke, account for poor outcomes in patients on hemodialysis. T cell responses may be involved in the pathogenesis of ischemic stroke. We aimed to evaluate the role of naïve T cells in development of ischemic stroke in patients on hemodialysis. METHODS: In this cross-sectional study, 156 patients on hemodialysis in our blood purification center were included. These patients were divided into the ischemic stroke (IS) group (61 cases) and non-ischemic stroke (non-IS) group (95 cases) according to a new diagnosis after initiation of hemodialysis. After being lysed with red blood cell lysis solution, peripheral blood was tested by flow cytometry to detect the expression of CD45RO and CCR7 in CD4 T and CD8 T cells. Correlation analysis and logistic regression analysis were conducted to identify potential independent risk factors for ischemic stroke. RESULTS: The percentage of peripheral naïve T cells was lower in the IS group [median (interquartile range (IQR)) 13.9% (8.6-22.9%)] compared with the non-IS group [median (IQR) 22.7% (15.9-32.2%), P < 0.001]. Spearman correlation analysis showed that naïve T cells were negatively associated with ischemic stroke (r = -0.308, P < 0.001). Multivariate logistic regression analysis showed that CD4 naïve T cells had an independent negative association with ischemic stroke in patients on hemodialysis (odds ratio 0.933, 95% CI 0.883, 0.986; P = 0.013). CONCLUSION: A decrease in percentage of peripheral CD4 naïve T cells is a risk factor for ischemic stroke in patients on hemodialysis.

Inappropriately elevated endothelin-1 plays a role in the pathogenesis of intradialytic hypertension.

The aim of this study is to investigate the effects of endogenous vasoactive substances on the occurrence of intradialytic hypertension (IDH) in patients during maintenance hemodialysis. Thirty-four maintenance hemodialysis patients were enrolled in this trial, and 17 of them were diagnosed with IDH (defined as an increase in blood pressure of at least 10 mmHg during or immediately after a hemodialysis session), while 17 age-matched and sex-matched controls without IDH were selected for a retrospective comparison. We collected patients' blood samples before and after a dialysis session and measured the plasma levels of N-terminal fragment brain natriuretic peptide, renin, angiotensin-II, aldosterone (ALD), angiotensin-converting enzyme (ACE), endothelin-1 (ET-1), nitric oxide (NO), norepinephrine (NOR), and adrenomedullin. The post-dialysis serum ET-1 concentrations were significantly higher (4.09 ± 2.06 vs. 2.75 ± 1.34 pg/mL, P < 0.05), while the post-dialysis ratio of NO to ET-1 was lower (17.79 ± 5.65 vs. 24.78 ± 12.04, P < 0.05) in IDH patients compared with the control group. Post-dialysis ALD and NOR values were significantly lower (P < 0.01) and ACE levels were significantly higher (P < 0.01) than the pre-dialysis concentrations only in the control and not in the IDH group. All other measured factors did not differ significantly between the groups and between pre-dialysis and post-dialysis determinations. Compared with blood angiotensin-II, ALD, ACE, NOR, adrenomedullin, N-terminal fragment brain natriuretic peptide, and NO status, inappropriately elevated ET-1 plasma concentrations may play a predominant role in the pathogenesis of IDH.

Association of indoxyl sulfate with heart failure among patients on hemodialysis.

BACKGROUND AND OBJECTIVES: Indoxyl sulfate, a protein-bound uremic toxin, may be associated with cardiovascular events and mortality in patients with CKD. This study aimed to investigate the relationship between indoxyl sulfate and heart failure in patients on hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients on hemodialysis for >6 months were enrolled within 6 months. Patients with congestive heart failure, angina pectoris, acute myocardial infarction, cerebral infarction, or cerebral hemorrhage within 3 months before the study or those <18 years old were excluded. The primary end point was first heart failure event during follow-up. RESULTS: In total, 258 patients (145 men) with a mean age of 57.0 ± 14.6 years old were enrolled. Median plasma indoxyl sulfate level was used to categorize patients into two groups: the low-indoxyl sulfate group (indoxyl sulfate ≤ 2.35 µg/ml) and the high-indoxyl sulfate group (indoxyl sulfate >32.35 µg/ml). Then, patients were prospectively followed up for a median of 48.0 (interquartile range: 33.5-48.0) months. During follow-up, 68 patients experienced episodes of first heart failure. Kaplan-Meier analysis revealed the incidence of first heart failure event in the high-indoxyl sulfate group was significantly higher than in the low-indoxyl sulfate group (log rank P<0.001). Cox regression analysis showed indoxyl sulfate was significantly associated with first heart failure event (indoxyl sulfate as the continuous variable: hazard ratio, 1.02; 95% confidence interval [95% CI], 1.01 to 1.03; P=0.001; indoxyl sulfate as the dichotomous variable: hazard ratio, 3.49; 95% CI, 1.97 to 6.20; P<0.001). After adjustment for other confounding factors, the results remained significant (indoxyl sulfate as the continuous variable: hazard ratio, 1.04; 95% CI, 1.02 to 1.06; P<0.001; indoxyl sulfate as the dichotomous variable: hazard ratio, 5.31; 95% CI, 2.43 to 11.58; P<0.001). CONCLUSIONS: Plasma indoxyl sulfate was associated with first heart failure event in patients on hemodialysis. Whether indoxyl sulfate is only a biomarker or involved in the pathogenesis of heart failure in hemodialysis warrants additional study.

24-h residual urine volume at hemodialysis initiation: a possible predictor for acute ischemic stroke incurrence in hemodialysis patients.

BACKGROUND: Residual renal function (RRF) recently has been confirmed to be a significant predictor of morbidity and mortality in hemodialysis (HD) patients. As RRF is not exactly the same with 24-h residual urine volume, the aim of our study is to evaluate the association of residual urine volume with acute ischemic stroke (AIS) among HD patients. METHODS: 282 patients starting chronic HD in our center during January 2005 and December 2008 were enrolled. The clinical data at HD initiation and the occurrence of AIS since starting HD were recorded and obtained from our database. According to the prevalence of AIS, we divided 282 patients into the AIS group (n=69) and non-AIS (n=213) group. RESULTS: A total of 69 (24.5%) patients suffered from AIS since HD initiation. Patients with AIS were much older, with more diabetes, had higher levels of hemoglobin, while lower levels of residual urine volume and serum uric acid. In multivariate logistic regression analysis, old age (OR, 1.036; 95% CI, 1.009-1.063; P=0.008), diabetes (OR, 2.385; 95% CI, 1.074-5.294; P=0.033) and 24-h residual urine volume<1290 ml at HD initiation (OR, 2.446; 95% CI, 1.219-4.907; P=0.012) was significant predictors for future AIS occurrence during HD. CONCLUSION: This study indicates that residual urine volume levels at HD initiation are inversely associated with AIS risk in future in chronic HD patients. Besides, aging and diabetes should also be noticed for prevention of AIS.