保肾活血排毒法治疗早中期慢性肾脏病临床疗效评价

目的评价保肾活血排毒法治疗早中期慢性肾脏病（chronic kidney disease,CKD）的临床疗效。方法对40例CKD2～3期患者采用自身前、后对照的方法,在优质低蛋白饮食、控制血压、纠酸等基础治疗的同时,给予江苏省名中医龚丽娟主任保肾活血排毒经验方水煎服,每日1剂,连续治疗12个月以上。观察治疗前后患者临床症状,中医证候积分,肾功能（BUN、SCr）,肾小球内生肌酐清除率（creatinine clearance rate,CCr）的变化,并通过血肌酐倒数（1／SCr）随时间（月）直线回归斜率b值观察对CKD病程进展的影响。结果40例患者中显效7例（占17．5％）,有效13例（占32．5％）,稳定13例（占32．5％）,无效7例（占17．5％）,治疗总有效率82．5％。临床症候积分、血肌酐、CCr较治疗前有所改善,治疗12个月后,全组b值为（0．0001±0．00029）,其中5例b值为负值,87．5％患者的b值为正值。结论保肾活血排毒法能显著改善CKD患者的临床症状,延缓肾功能进程,无明显不良反应,适合于CKD早中期患者的长期治疗。     

Evaluation of the usefulness of novel biomarkers for drug-induced acute kidney injury in beagle dogs

As kidney is a major target organ affected by drug toxicity, early detection of renal injury is critical in preclinical drug development. In past decades, a series of novel biomarkers of drug-induced nephrotoxicity were discovered and verified in rats. However, limited data regarding the performance of novel biomarkers in non-rodent species are publicly available. To increase the applicability of these biomarkers, we evaluated the performance of 4 urinary biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), clusterin, total protein, and N-acetyl-β-D-glucosaminidase (NAG), relative to histopathology and traditional clinical chemistry in beagle dogs with acute kidney injury (AKI) induced by gentamicin. The results showed that urinary NGAL and clusterin levels were significantly elevated in dogs on days 1 and 3 after administration of gentamicin, respectively. Gene expression analysis further provided mechanistic evidence to support that NGAL and clusterin are potential biomarkers for the early assessment of drug-induced renal damage. Furthermore, the high area (both AUCs = 1.000) under receiver operator characteristics (ROC) curve also indicated that NGAL and clusterin were the most sensitive biomarkers for detection of gentamicin-induced renal proximal tubular toxicity. Our results also suggested that NAG may be used in routine toxicity testing due to its sensitivity and robustness for detection of tissue injury. The present data will provide insights into the preclinical use of these biomarkers for detection of drug-induced AKI in non-rodent species.     

Shrunken pore syndrome,preeclampsia, and markers of NO metabolism in pregnant women during the first trimester

Shrunken pore syndrome (SPS) is a condition that manifests itself as the decreased renal clearance of low-molecular-weight proteins but normal clearance of creatinine. Pregnant women with evidence of SPS during the first trimester have an increased risk of developing preeclampsia (PE). The nitric oxide (NO) metabolism markers arginine and ADMA, especially their ratio (Arg/ADMA), are recognized markers of endothelial dysfunction. The aim of this nested case–control study was to establish first-trimester reference intervals (RI) for markers of NO metabolism and to study these markers in women with evidence of SPS at the end of the first trimester. Seventy-four women were stratified in the first trimester according to evidence of SPS (SPS?+?or SPS–) and the occurrence of PE during subsequent pregnancy (PE?+?or PE–), as follows: SPS–/PE–, SPS+/PE–, SPS–/PE+, and SPS+/PE+. RIs were determined according to the CLSI EP28-A3c guidelines. Serum Arg and ADMA levels were analyzed. The Arg and ADMA concentrations did not differ among the four groups. However, women in the SPS+/PE?+?group had a significantly lower Arg/ADMA ratio than those in the other 3 groups (p?=?.02). In conclusion, we defined the first-trimester RI of Arg, ADMA and the Arg/ADMA ratio as markers of NO metabolism. Our results suggest that SPS in the first trimester predicts a pathophysiological hallmark of subsequent PE, i.e. lower NO production leading to increased vessel tone. Early identification of women at risk for later PE could lead to adaptive prophylactic interventions, such as supplementation with Arg or an NO-donor drug in order to mitigate the risk of developing PE.     

长期有效控制血压改善高危高血压患者的肾功能

目的对《1999WHO/ISH高血压治疗指南》(《指南》)危险分层为高危和极高危组的患者单用或联合使用《指南》推荐的一线降压药,以血压<140/90mmHg作为目标血压,观察长期有效控制血压对高危高血压患者肾功能的影响。方法患者763例确定危险分层入选后,随机进入目标治疗组(n=382)和对照组(n=381)。目标治疗组在高血压专科门诊定期随访,按5步法治疗方案,直到达到或接近目标血压为止。对照组在普通门诊治疗。测定基线和治疗后的血清肌酐浓度并计算肾小球滤过率。结果两组患者的基线特征无明显差异。在平均4.4年随访期间,目标治疗组平均收缩压/舒张压为(133.8±6.6)/(79.7±5.5)mmHg,明显低于对照组[(151.7±12.7)/(87.7±8.0)mmHg,P<0.01]。尽管两组治疗强度不同,但两组间使用各类抗高血压药物的比例相似。共有526例患者复查血清肌酐1次以上。目标治疗组(n=304)血清肌酐由(90.9±29.1)降至(87.0±26.1)μmol/L,下降4.5%(P=0.006);对照组(n=222)则由(91.6±30.1)增至(96.4±46.4)μmol/L,增加5.2%(P=0.074),两组间治疗后比较,差异有非常显著意义(P<0.01)。目标治疗组血清肌酐清除率由(67.5±21.9)升至(70.0±22.3)mL/(min.1.73m2),升高4.5%(P=0.019);对照组则无明显变化[(66.9±24.2)vs(67.3±27.6)mL/(min.1.73m2),P=0.737]。结论与一般治疗相比,长期严格控制血压能降低高危高血压患者的血清肌酐,并提高血清肌酐清除率。     

Differences in composition of sweat induced by thermal exposure and by running exercise

To determine the differences in sweat composition between sweat induced by thermal stress alone and that induced by physical exercise, seven young healthy men first sat in a hot room and then performed running exercise. A 20-minute stay in a climate chamber at 40 degrees C resulted in a 5% reduction in body weight. The same body weight loss was induced by running exercise. Both sodium and chloride concentrations were much lower in the sweat induced by thermal exposure than that induced by the running exercise (p less than 0.01), while urea nitrogen and creatinine concentrations were significantly higher after thermal exposure than after the running exercise (p less than 0.01). Potassium concentrations did not differ significantly with either procedure. These findings suggest that sweat composition varies with the kind of induction and that more salt seems to be lost through exercise-induced sweating than by just sitting in a hot environment.     

Phenazopyridine associated acute interstitial nephritis and review of literature

Phenazopyridine is a urinary analgesic; commonly seen side-effects of this drug include, orange discoloration of urine, methemoglobinemia, yellowish skin discoloration, hepatitis and acute renal failure. Various case reports with phenazopyridine associated acute renal failure secondary to acute tubular necrosis have been reported in the literature. Acute kidney injury in these patients is caused by either direct injury to renal tubular epithelial cells or secondary to pigment induced nephropathy from hemolytic anemia. Hypoxic injury from phenazopyridine-induced methemoglobinemia has been well documented. We report a case of biopsy proven acute interstitial nephritis, associated with therapeutic doses of phenazopyridine without any evidence of methemoglobinemia or other mechanism of renal injury. Clinicians should be aware of the toxicity of this commonly used drug and should look closely for signs of renal insufficiency. Identifying and stopping the offending medication stays as the first step, but recent studies indicate that early steroid administration improves renal recovery, as well as decreasing the risk of progression to chronic kidney disease with fibrosis and consequent permanent renal damage.     

A Meta-analysis on diagnostic value of serum cystatin C and creatinine for the evaluation of glomerular filtration function in renal transplant patients

Objectives

This meta-analysis aimed to perform a systematic review on comparing the diagnostic value of serum cystatin C and creatinine for glomerular filtration rate in renal transplant patients.

Methods

The data was extracted into 2×2 table after the articles were assessed by the tool of QUADAS and heterogeneity analysis. The SROC curve and meta-analysis were performed by MetaDisc1.4.

Results

Meta-analysis showed that the serum cystatin C had no heterogeneity (P=0.418, I2=2.2%, DOR=25.03), while creatinine heterogeneity was high (P=0.109, I2=37.5%, DOR=9.11). The values of SEN, SPE and SAUC were calculated as 0.86, 0.70 and 0.9015 for cystatin C, and 0.78, 0.73 and 0.8285 for creatinine individually. This study utilized GFR detection and subgroups analysis by cutoff. The PLR was 6.13 and the NLR was 0.12 for cystatin C, compared to SCr (3.72, 0.32). There was homogeneity among these studies using PENIA testing for cystatin C (χ2=2.61, P=0.4560, I2=0.0%.

Conclusions

There were significant correlations among cystatin C , creatinine and glomerular filtration rate (GFR). Cystatin C had more sensitivity but less specificity than creatinine for evaluation of GFR. Cystatin C had strong ability in diagnosing renal function after renal transplant and ruling out diagnostic efficacy.     

Utility of a Score for Predicting Glomerular Filtration Rate Overestimation in Patients with Cardiovascular and Renal Diseases and Their Risk Factors

Objective We recently reported a novel score for the detection of glomerular filtration rate (GFR) overestimation using a creatinine-based equation. We examined the utility of this score in patients with cardiovascular/renal diseases and diabetes mellitus. Methods We enrolled 1,425 patients (65±15 years old; 37% women) who were admitted to our hospital for the management of cardiovascular and renal diseases and their risk factors. Overestimation of the GFR (OE) was defined as a creatinine-based GFR (eGFRcre) ≥120% of the cystatin C-based estimated GFR. The OE score was calculated as the sum of the scores for the body weight, hemoglobin concentration, and blood urea nitrogen (BUN)/serum creatinine (Scr), totaling 1 point if the body weight was <63.0 kg in men or <42.0 kg in women, 1 point if the hemoglobin concentration was <12.4 g/dL in men or <11.0 g/dL in women, and 1 point if the BUN/Scr was >26.5. Results The proportion of patients with OE was 14.2%. The score predicted OE with a sensitivity of 70.8% and a specificity of 99.6%, and the sensitivity was increased in patients ≥75 years old (88.3%) and decreased in diabetics (58.6%). When patients were divided into subgroups by the total score, the frequencies of OE were 8% (59/754), 14% (72/502), 38% (58/151), and 72% (13/18) in patients with scores of 0, 1, 2, and 3, respectively. Conclusion The OE score is useful for detecting elderly cases of cardiovascular and renal diseases in which eGFRcre overestimates the GFR, although its utility is limited in diabetics.     

Mild impairment of renal function (shrunken pore syndrome) is associated with increased risk for future surgery for aortic stenosis

Abstract

Recently, a new approach was proposed to detect mild impairment in renal function: a reduced ratio between estimated glomerular filtration rate (eGFR) calculated by cystatin C and eGFR calculated by creatinine. We aimed to evaluate if this ratio is associated with aortic stenosis (AS) requiring surgery. We identified 336 patients that first participated in population surveys and later underwent surgery for AS (median age [interquartile range] 59.8 [10.3] years at survey and 68.3 [12.7] at surgery, 48% females). For each patient, two matched referents were allocated. Cystatin C and creatinine were determined in stored plasma. eGFR_{cystatin C} and eGFR_creatinine and their ratio were estimated. Conditional logistic regression analyses were used to estimate the risk (odds ratio (OR) with [95% confidence interval (CI)]) related to one (ln) standard deviation increase in the ratio between eGFR_{cystatin C} and eGFR_creatinine. A high ratio was associated with lower risk for AS requiring surgery (OR [95% CI]) (OR 0.84 [0.73–0.97]), especially in women (0.74 [0.60–0.92] vs. 0.93 [0.76–1.13] in men). After further stratification for coronary artery disease (CAD), the association remained in women with CAD but not in women without CAD (0.60 [0.44–0.83] and 0.89 [0.65–1.23], respectively). In conclusion, a high ratio between eGFR_{cystatin C} and eGFR_creatinine was associated with lower risk for surgery for AS, especially in women. Mild impairment of renal function is thus associated with future risk for AS requiring surgery.