Hypertonic saline resuscitation protects against kidney injury induced by severe burns in rats.

BACKGROUND: Proper fluid resuscitation can relieve visceral damage and improve survival in severely burned patients. This study compared the effectiveness of resuscitation with 400mEq/L hypertonic saline (HS) and sodium lactate Ringer's solution (LR) in rats with kidney injury caused by burn trauma. METHODS: Rats (Sprague-Dawley) underwent burn injury and were randomized into sham, LR, and HS groups. Samples from the kidney were assayed for water content ratio, histopathology, and oxidative stress (superoxide dismutase (SOD) and malondialdehyde (MDA)). Serum sodium, renal function (creatinine and cystatin (Cys)-C), and inflammatory response (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and high mobility group protein box (HMGB)-1) were also examined as serum markers. RESULTS: Hypertonic saline resuscitation reduced the renal water content ratio and improved renal histopathology caused by severe burns. This effect was accompanied by reductions in serum creatinine and Cys-C as well as TNF-α, IL-1ß, and HMGB1. Serum sodium concentration and SOD activity were increased, whereas MDA content was decreased in the kidney tissue of the HS group. CONCLUSIONS: The data indicate that 400mEq/L HS solution reduces hyponatremia and renal edema, inhibits the release of inflammatory mediators, and alleviates oxidative stress injury, thus protecting against kidney injury induced by severe burns.

Dexamethasone Modifies Cystatin C-Based Diagnosis of Acute Kidney Injury During Cisplatin-Based Chemotherapy.

BACKGROUND/AIMS: Plasma cystatin C (pCysC) may be superior to serum creatinine (sCr) as a surrogate of GFR. However, the performance of pCysC for diagnosing acute kidney injury (AKI) after cisplatin-based chemotherapy is potentially affected by accompanying corticosteroid anti-emetic therapy and hydration. METHODS: In a prospective observational study pCysC, sCr, urinary kidney injury molecule-1 (KIM-1), and urinary clusterin were measured over 2 weeks in 27 patients given first-cycle chemotherapy. The same variables were measured over 2 weeks in Sprague-Dawley rats given a single intraperitoneal injection of dexamethasone, cisplatin, or both, and in controls. RESULTS: In patients, pCysC increases were greater than sCr 41% vs. 16%, mean paired difference 25% (95% CI: 16-34%)], relative increases were ≥ 50% in 9 patients (35%) for pCysC compared with 2 (8%) for sCr (p = 0.04) and increases in sCr were accompanied by increased KIM-1 and clusterin excretion, but increases in pCysC alone were not. In rats, dexamethasone administration produced dose-dependent increases in pCysC (and augmented cisplatin-induced increases in pCysC), but did not augment histological injury, increases in sCr, or KIM-1 and clusterin excretion. CONCLUSIONS: In the presence of dexamethasone, elevation of pCysC does not reliably diagnose AKI after cisplatin-based chemotherapy.

[Changes in serum ß2-microglobulin, retinol-binding protein, and cystatin C and their value in identifying early renal dysfunction in patients with chronic hepatitis B undergoing tenofovir or entecavir monotherapy: a comparative analysis].

Objective: To investigate the dynamic changes in serum ß2-microglobulin, retinol-binding protein, and cystatin C in chronic hepatitis B(CHB)patients treated with tenofovir or entecavir alone as the anti-HBV therapy, as well as their value in identifying early renal dysfunction. Methods: A total of 61 previously untreated CHB patients who were diagnosed and treated in the Department of Infectious Diseases in Henan Provincial People's Hospital from June 2013 to August 2015 were enrolled and divided into tenofovir group and entecavir group. The serum levels of ß2-microglobulin, retinol-binding protein, cystatin C, and creatinine and estimated glomerular filtration rate(eGFR)were compared between the two groups at baseline and 4, 8, 39, 52, 78, and 104 weeks after antiviral therapy. The independent samples t-test was used for comparison of continuous data, and the chi-square test was used for comparison of categorical data. P < 0.05 was considered statistically significant. Results: A total of 61 CHB patients were enrolled, with 31 in the tenofovir group and 30 in the entecavir group. The two groups had comparable serum levels of ß2-microglobulin, retinol-binding protein, and cystatin C at baseline, but there were significant differences in ß2-microglobulin and retinol-binding protein over time(both P < 0.05). There was a significant difference in cystatin C at 78 weeks(t = -2.062, P = 0.044), but there was no significant difference at 104 weeks(t = -1.544, P = 0.128). There were no significant differences in serum creatinine or eGFR at any time point between the two groups(P > 0.05). At 104 weeks, there were no significant differences in HBV-DNA clearance rate or the level of virologic breakthrough between the two groups(P > 0.05). Conclusion: Serum ß2-microglobulin, retinol binding protein, and cystatin C are more sensitive than eGFR in the monitoring of early renal dysfunction during the anti-HBV therapy with tenofovir or entecavir alone.

Is there still a role for low-dose dopamine use in acute heart failure?

PURPOSE OF REVIEW: Acute heart failure (AHF) is a major health problem worldwide, with no proven therapy. Low-dose dopamine has been used in this entity to improve renal outcomes in the past decades. The aim of this article is to review the former and recent clinical trials about the use of low-dose dopamine in AHF. RECENT FINDINGS: The Dopamine in Acute Decompensated Heart Failure II study enrolled 161 patients with AHF and found no improvement in clinical outcomes with the addition of dopamine. Similarly, the Renal Optimization Strategies Evaluation in Acute Heart Failure trial, which included 360 patients with AHF and renal dysfunction, evaluated the efficacy of 72-h infusion of either low-dose nesiritide or low-dose dopamine versus placebo in addition to standardized diuretic treatment. No differences were found between both treatment groups and placebo with regard to the coprimary endpoints of cumulative urine volume and change from baseline in plasma cystatin C. SUMMARY: On the basis of the current data, there is no role for the routine use of low-dose dopamine in nonhypotensive patients with AHF. Further studies are needed to define the role of low-dose dopamine in patients with AHF and hypotension. Until the availability of more data, the use of dopamine in AHF should be individualized.

Cystatin C and baseline renal function among HIV-infected persons in the SUN Study.

In the combination antiretroviral therapy (cART) era, renal dysfunction remains common. The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN) (ClinicalTrials.gov number, NCT00146419) is a prospective observational cohort study of HIV-infected adults. At baseline, comprehensive data were collected, including cystatin C and measures of renal function. Univariate and multivariate regression analyses were performed to identify factors associated with baseline renal dysfunction [estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73 m(2) calculated using the simplified Modification of Diet in Renal Disease equation] and elevated cystatin C (>1.0 mg/liter) in a cross-sectional analysis. Among 670 subjects with complete data (mean age 41 years, mean CD4 cell count 530 cells/mm(3), 79% prescribed cART), the mean eGFR was 96.8 ml/min/1.73 m(2). Forty percent of subjects had renal dysfunction; 3.3% had chronic kidney disease (eGFR < 60 ml/min/1.73 m(2)). Elevated cystatin C was present in 18% of subjects. In multivariate analysis, renal dysfunction was associated with older age, non-Hispanic white race/ethnicity, higher body mass index (BMI), hypertension, higher cystatin C levels, and current prescription of ritonavir. Factors associated with elevated cystatin C included hepatitis C coinfection, hypertension, current smoking, older age, current tenofovir use, detectable plasma HIV RNA, and elevated microalbuminuria. The prevalence of chronic kidney disease (CKD) was low in this contemporary HIV cohort. However, mild to moderate renal dysfunction was common despite the widespread use of cART.

Antihypertensive and metabolic effects of telmisartan in hypertensive HIV-positive patients.

BACKGROUND: Hypertension is more prevalent among HIV-infected individuals than in the general population and contributes to increased cardiovascular risk. The angiotensin II receptor blocker telmisartan is also a partial peroxisome proliferator activated receptor-γ agonist with documented effects on glucose and lipid homeostasis. The aim of this study was to evaluate the antihypertensive and metabolic effects of telmisartan in hypertensive HIV-positive patients. METHODS: A total of 18 HIV-positive men treated with antiretroviral therapy and recently diagnosed with hypertension were administered 80 mg telmisartan daily. Systolic blood pressure (SBP) and diastolic blood pressure (DBP), viroimmunological and metabolic parameters, insulin resistance, C-reactive protein, microalbuminuria, cystatin C and plasma levels of interleukin-18 and endothelin-1 were measured at baseline (T0), 1 month (T1), 3 months (T3) and 6 months (T6). RESULTS: Treatment with telmisartan not only decreased SBP and DBP levels, but also improved insulin resistance and microalbuminuria by T1. Levels of triglycerides significantly decreased and high-density lipoprotein cholesterol increased at T1, whereas total and low-density lipoprotein cholesterol levels were statistically reduced at T3 and T6. Cystatin C and endothelin-1 showed a significant reduction at T1, whereas interleukin-18 decreased at both T3 and T6. CONCLUSIONS: Telmisartan was effective in reducing blood pressure and improving lipid metabolism and renal function. Reduction of endothelin-1 might be related to an endothelial protective effect. On the basis of these findings, and because of properties unrelated to blood pressure lowering, telmisartan might be the first choice antihypertensive drug for the treatment of HIV-positive patients.

Cystatin C concentration is correlated with disease activity in rheumatoid arthritis patients.

OBJECTIVES: Rheumatoid arthritis (RA) is a systemic, inflammatory disease. Renal involvement worsens the course of RA and increases mortality. It is suggested that chronic inflammatory processes may contribute to renal impairment. The aim of this study was to investigate the impact of chronic inflammation and RA activity on glomerular filtration rate (GFR). METHODS: The study population consisted of 140 RA patients. High disease activity was observed in 42 patients (30%), and long-term RA (duration ≥ 10 years) in 64 (45.7%). Measures of renal function included: serum cystatin C, serum creatinine (SCr), and creatinine-based estimated GFR (eGFR) calculated by Cockcroft and Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulas. RESULTS: The mean (SD) cystatin C concentration was 0.77 (0.2) mg/L, SCr 0.71 (0.23) mg/dL, eGFR(CG) 110.5 (37.8) mL/min/1.73 m², and eGFR(MDRD) 109.5 (34.5) mL/min/1.73 m². Cystatin C levels correlated positively with creatinine, and negatively with eGFR(CG) and eGFR(MDRD). Cystatin C concentration was significantly higher in patients with high disease activity, long-term RA, and hypertension, and in males. Patients currently being treated with biologics had non-significantly lower cystatin C levels than those treated with conventional modifying drugs. Cystatin C levels were significantly associated with markers of clinical, functional disease activity, and markers of inflammation. By contrast, there were no such correlations with other parameters of renal function. CONCLUSIONS: In patients with RA, cystatin C may be not only an indicator of GFR but also a marker of intensity of chronic inflammatory processes.

Effect of Olmesartan on serum cystatin C levels in the patients with essential hypertension.

AIM: We aimed to investigate whether Olmesartan had an effect on cystatin C levels in hypertensive patients, and evaluate its correlation with blood pressure (BP). MATERIALS AND METHODS: Seventy-two patients essential hypertension patients with a known for, at most, the last 3 years were enrolled to the study. Patients were divided in three groups (group 1; receives 20 mg/day olmesartan; group 2, receives 40 mg/day olmesartan; group 3, receives Olmesartan plus hydrochlorothiazide), according to their BP measurements. Blood samples (serum urea, creatinine, sodium, potassium and cystatin C) were collected initially and at the end of the study from all patients and the correlation of these parameters with BP and drug use was investigated. RESULTS: There were no significantly difference between the groups in terms of age, gender, serum urea, creatinine, cystatin C and diastolic BP levels (p > 0.05); while, systolic BP was significantly higher in group 3 at baseline (p = 0.001). After 3 months of olmesartan treatment, the mean serum cystatin C (p: 0.001, 0.023 and 0.018 respectively), systolic (p: 0.001, 0.001 and 0.001 respectively) and diastolic BP levels (p: 0.001, 0.001 and 0.001 respectively) decreased in all groups. However, there was no significant difference in serum creatinine levels (p > 0.05). There were not found correlation between the changes of systolic and diastolic BP and cystatin C levels. CONCLUSIONS: Cystatin C is a more sensitive marker to detect of early kidney dysfunction compared to serum creatinine level. Olmesartan treatment led to a decrease of cystatin C level. Therefore, olmesartan can be used to prevent the renal damage in patients with hypertensive and it is independent of drop in blood pressure.

Prenatal dexamethasone exposure does not alter blood pressure and nephron number in the young adult marmoset monkey.

The influence of prenatal factors on the development of arterial hypertension has gained considerable interest in recent years. Prenatal dexamethasone exposure was found to induce hypertension and to alter nephron number and size in rodents and sheep. However, it is not clear whether these findings are applicable to nonhuman primates. Thus, we examined the effects of prenatal dexamethasone treatment on blood pressure (BP) and nephron number in marmoset monkeys. Fifty-two marmosets were allotted to 3 groups according to the gestational stage during which their mothers were exposed to oral 5-mg/kg dexamethasone for 7 days (gestation period: 20 weeks): (1) the early dexamethasone group at week 7; (2) the late dexamethasone group at week 13; and (3) the control group. BP was determined by telemetric (n=12) or cuff measurements (n=30), along with cystatin C, proteinuria, and body weight. All of the animals were euthanized at the age of 24 months, and glomerular number and volume were determined. Prenatal exposure to dexamethasone did not lead to a significant difference between the groups with regard to BP, kidney morphology and function, or body weight. BP correlated significantly with body weight, relative kidney weight, and mean glomerular volume and the body weight with the glomerular volume regardless of dexamethasone treatment. In conclusion, prenatal exposure to dexamethasone in marmosets does not, in contrast to other mammals studied, result in hypertension or changes in kidney morphology. Our data support the role of body weight as a predictor of elevated glomerular volume and BP development rather than prenatal dexamethasone exposure.