Association of the cystatin C/creatinine ratio with the renally cleared hormones parathyroid hormone (PTH) and brain natriuretic peptide (BNP) in primary care patients: a cross-sectional study

The ratio of cystatin C to creatinine (cysC/crea) is regarded as a marker of glomerular filtration quality and predicts mortality. It has been hypothesized that increased mortality may be mediated by the retention of biologically active substances due to shrinking glomerular pores. The present study investigated whether cysC/crea is independently associated with the levels of two renally cleared hormones, which have been linked to increased mortality. We conducted a multicenter, cross-sectional study with a random selection of general practitioners (GPs) from all GP offices in seven Swiss cantons. Markers of glomerular filtration quality were investigated together with estimated glomerular filtration rate (eGFR), albuminuria and urinary neutrophil gelatinase associated lipocalin (uNGAL) as well as two renally cleared low-molecular-weight protein hormones (i.e. BNP and PTH), Morbidity was assessed with the Charlson Comorbidity Index (CCI). A total of 1000 patients (433 males; mean age 57?±?17 years) were included. There was a significant univariate association of BNP (r?=?0.36, p?r?=?0.18, p?相似文献   

H型高血压早期肾损伤患者UAlb/Cr、eGFR、SCr、Cys-C的表达及意义

目的研究H型高血压早期肾损伤患者尿清蛋白/肌酐(UAlb/Cr)、肾小球滤过率估计值(eGFR)、血肌酐(SCr)、胱抑素C(Cys-C)的表达及意义。方法对2015年7月至2016年6月该院收治的130例H型高血压患者进行分析。根据肾小球率过滤(GFR)分为高血压肾功能正常组62例(GFR≥90mL/L)和高血压肾损伤组73例(GFR90mL/L)。使用胶乳免疫比浊法检测Cys-C水平,肌氨酸氧化酶法检测UAlb/Cr、SCr水平,MDRD公式计算eGFR。比较两组研究对象UAlb/Cr、eGFR、SCr、Cys-C表达情况,对UAlb/Cr、eGFR的危险因素进行Logistic回归分析。结果高血压肾功能正常组的UAlb/Cr、SCr、Cys-C水平低于高血压肾损伤组(P0.05),eGFR水平高于高血压肾损伤组(P0.05)。年龄、病程、同型半胱氨酸、舒张压(DBP)与UAlb/Cr存在密切关联性(P0.05)。年龄、病程、同型半胱氨酸与eGFR存在密切关联性(P0.05)。结论 UAlb/Cr、eGFR、SCr、Cys-C的水平和H型高血压早期肾损伤患者存在着密切关联性。     

血管紧张素Ⅱ受体阻断剂对慢性肾脏病患者肾素-血管紧张素系统表达的影响

目的：研究血管紧张素Ⅱ受体阻断剂（angiotensinⅡ receptor blocker,ARB）对慢性肾脏病（chronic kidney disease,CKD）患者循环和肾脏肾素-血管紧张素系统（renin-angiotensin system,RAS）表达的影响。方法：行肾脏活组织检查且2个月内未曾服用血管紧张素转换酶抑制剂的CKD患者,其中2周内ARB治疗的患者17例（ARB治疗组）,另选取2周内未应用ARB治疗的患者17例（空白对照组）,根据年龄、性别、血压、估算肾小球滤过率（eGFR）、24h尿蛋白、尿钠等进行配对。采用放射免疫法和酶联免疫吸附分析（ELISA）方法测定血、尿RAS组分的浓度,并采用免疫组织化学方法评价肾脏肾素、血管紧张素原（AGT）、血管紧张素Ⅱ（AngⅡ）和血管紧张素Ⅱ受体的表达。分析ARB对血、尿和肾组织RAS表达的影响。结果：ARB治疗组与空白对照组在性别、年龄、eGFR、24h尿蛋白、尿钠和血压等方面均显著差异。ARB治疗组血浆AngⅡ高于空白对照组[（63.09±15.14）pg/mL比（53.66±8.33）pg/mL,P〈0.05],肾内肾素免疫组织化学染色面积高于空白对照组[（48.65±19.58）%比（30.29±24.98）%,P〈0.05]。ARB治疗组肾内AGT、AngⅡ和血管紧张素Ⅱ1型受体免疫组织化学染色面积略低于空白对照组,但差异无统计学意义。结论：ARB治疗对循环和肾脏局部RAS表达的影响不同,可使循环AngⅡ升高,并可能抑制肾脏局部AngⅡ的表达。     

Association between urinary VEGFA and renal pathology of IgA nephropathy patients

BackgroundRenal biopsy remains the golden standard for diagnosing and monitoring IgA nephropathy (IgAN). Vascular endothelial growth factor A (VEGFA) was crucial for the survival of glomerular cells. Our aim was to screen the expression pattern of urinary, circulating and renal VEGFA in IgAN patients to reveal their relationship with renal pathology and outcomes.MethodsBaseline VEGFA levels were determined with ELISA, real‐time PCR and immunohistochemistry. Associations between VEGFA expression and clinical–pathological parameters, and renal outcomes were evaluated.ResultsCompared with healthy controls, urinary VEGFA level was obviously elevated in IgAN patients (76.19 ± 63.67 pg/mg Cr vs 146.67 ± 232.71 pg/mg Cr, p = 0.0291) and not correlated with serum VEGFA level. Baseline urinary VEGFA was significantly associated with gender and tubular atrophy/interstitial fibrosis by stepwise multivariate regression analysis. Urinary VEGFA was higher in male patients accompanied with higher serum creatinine, larger proportion of hypertension and recurrent hematuria than in female patients. In the kidney of IgAN patients, VEGFA were robustly expressed in the parietal epithelial cells, podocytes, mesangial cells and tubular epithelial cells. After a follow‐up duration of 38.53 ± 27.14 months, IgAN patients with higher urinary VEGFA level were found to have a poorer renal outcome of renal replacement therapy (HR = 1.027, p = 0.037) or composite outcome (HR = 1.023, p = 0.039) after adjusting for confounders.ConclusionsIncreased urinary VEGFA might reflect certain renal pathology and, although not fully specific, still could be served as a valuable noninvasive indicator in predicting renal progression of IgAN.     

Estimated glomerular filtration rate (eGFRCystC) from serum cystatin C shows strong agreement with iohexol clearance in patients with low GFR

Objective. Estimation of glomerular filtration rate (eGFR) is essential in the diagnosis and monitoring of patients with kidney disease and for correct dosage of drugs eliminated from the circulation by the kidneys. Cystatin C has been shown in several studies to be superior to creatinine in estimating eGFR. However, there are few studies on the performance of cystatin C estimated eGFR (eGFR_CystC) in patients with advanced kidney disease and low GFR. Material and methods. We measured serum cystatin C, together with serum creatinine, during iohexol clearance in patients with iohexol clearance below 30?mL/min/1.73?m². The cystatin C values were used to calculate eGFR_CystC using the formula eGFR (mL/min/1.73m²) = 79.901*(cystatin C value in mg/L)^?1.4389. Results. There was good correlation between eGFR_CystC and iohexol clearance (r = 0.88) in patients with iohexol clearance <30?mL/min/1.73?m² and none of the patients had a difference between eGFR_CystC and iohexol clearance exceeding 50?%. The Modification of Diet in Renal Disease (MDRD) equation and corrected MDRD eGFR showed a positive bias and weaker correlations with iohexol eGFR (MDRD = 5.32+1.22*iohexol clearance; corrected MDRD = 4.76+1.10*iohexol clearance; r = 0.59). For MDRD eGFR, 42 of 94 (44.7?%) samples showed more than 50?% difference to iohexol clearance. Conclusions. eGFR_CystC is an efficient, practical and cost‐effective alternative to iohexol clearance in patients with reduced GFR.     

The effects of cytotoxic therapy in progressive IgA nephropathy

Background: IgA nephropathy (IgAN) is not always benign, and some patients at high risk of end-stage renal disease (ESRD) experience a rapid decline in renal function. This study retrospectively examined the beneficial effects of cytotoxic therapy. Methods: We identified 102 patients with progressive IgAN despite optimal conservative management. Of these, 31 who received cytotoxic therapy and 55 who were managed conservatively were included. Results: Median eGFR and urinary protein-to-creatinine ratio (uPCR) at baseline did not differ between the groups (p?=?0.475 and 0.259, respectively). Median GFR slope was also similar (p?=?0.896). Cumulative renal survival was better in the cytotoxic therapy group than in the control group (p?=?0.009). Cytotoxic therapy was associated with lower risk of progression to ESRD, independent of eGFR, uPCR, GFR slope and kidney histologic findings (HR 0.13, 95% CI 0.03–0.66). In the cytotoxic therapy group, the median GFR slope decreased from ?7.8 (?10.5, ?5.0) mL/min/1.73 m² per year to ?3.4 (?5.1, ?1.8) mL/min/1.73 m² per year after treatment (p?Conclusions: Cytotoxic therapy attenuated the rate of GFR decline and was associated with a favorable renal outcome in patients with progressive IgAN.

• Key messages

• Cytotoxic therapy was associated with a favorable renal outcome in IgA nephropathy patients whose glomerular filtration rate progressively declined despite optimal conservative management.

• Cytotoxic therapy significantly attenuated the rate of glomerular filtration rate decline as well as the amount of proteinuria in patients with progressive IgA nephropathy.

• Adverse events following cytotoxic therapy were comparable to conservative management.

     

Assessment of urinary γ-glutamyltransferase and alkaline phosphatase for diagnosis of diabetic nephropathy

BackgroundUrinary biomarkers of tubular damage can be useful for early diagnosis of diabetic nephropathy. Thus, the aim of this study was to test the diagnostic accuracy of the urinary excretion of γ-glutamyltransferase (GGT) and alkaline phosphatase (ALP) for diagnosis of diabetic nephropathy (DN).MethodsFasting glucose, fructosamine, serum creatinine, glomerular filtration rate (GFR), serum uric acid, serum albumin, and urinary albumin, creatinine, GGT and ALP were assessed in 74 type 2 diabetic patients without nephropathy and 38 type 2 diabetic patients with nephropathy.ResultsUrinary GGT and ALP were threefold higher in type 2 diabetic patients with nephropathy. Significant correlations were observed between urinary albumin and GGT (r = 0.439, P < 0.001) and urinary albumin and ALP (r = 0.305, P < 0.01). Areas under the curve for GGT and ALP were 0.7696 (P < 0.001) and 0.7233 (P < 0.001), respectively. At a cut-off value of 72 U/g creatinine, GGT demonstrated a sensitivity of 96.0% and a specificity of 52.6%. At a cut-off value of 20 U/g creatinine, ALP demonstrated a sensitivity and specificity of 83.8% and 36.8%, respectively.ConclusionsUrinary GGT and ALP have potential value in the diagnosis of nephropathy in type 2 diabetic patients, but GGT has a slightly higher ability to discriminate nephropathy than ALP.     

尿肾损伤分子-1水平变化与狼疮肾炎合并肾功能不全患者预后的关系

目的:观察狼疮肾炎(LN)合并肾功能不全(RI)患者尿中肾损伤分子(KIM-1)变化趋势及临床意义。方法:收集本院LN患者31例,分正常肾功组(A组)、RI+肾功改善组(B组)、RI+肾功未改善组(C组),检测血肌酐(SCr)、尿KIM-1等指标。比较各组尿KIM-1变化,探讨其与肾小球滤过率估计值(eGFR)关系及判断预后价值。结果:入院时三组尿KIM-1较对照组明显增加(P<0.05),B组最高(P<0.001)。14d后B组SCr、eGFR好转时尿KIM-1下降(均P<0.05),尿KIM-1与eGFR负相关(r=-0.385,P=0.048)。ROC曲线分析示尿KIM-1、NAG、GAL、SCr预测LN患者肾功能改善曲线下面积分别为0.93、0.86、0.77、0.57。结论:LN合并RI患者入院时尿KIM-1水平升高与14d内肾功能改善密切相关;合理治疗后,尿KIM-1水平在肾功能明显改善的LN患者中有显著下降;尿KIM-1是预测肾功能改善的准确指标。     

Is nonalbuminuric renal insufficiency in type 2 diabetes related to an increase in intrarenal vascular disease?

OBJECTIVE: To investigate the role of intrarenal vascular disease in the pathogenesis of nonalbuminuric renal insufficiency in type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied 325 unselected clinic patients who had sufficient clinical and biochemical information to calculate an estimated glomerular filtration rate (eGFR) using the Modified Diet in Renal Disease six-variable formula, at least two estimations of urinary albumin excretion rates (AER), and a renal duplex scan to estimate the resistance index of the interlobar renal arteries. The resistance index, measured as part of a complications surveillance program, was compared in patients with an eGFR < or >or=60 ml/min per 1.73 m(2) who were further stratified into normo- (AER <20), micro- (20-200), or macroalbuminuria (> 200 microg/min) categories. RESULTS: Patients with an eGFR <60 ml/min per 1.73 m(2) had a higher resistance index of the renal interlobar arteries compared with patients with an eGFR >or=60 ml/min per 1.73 m(2). However, the resistance index was elevated to a similar extent in patients with an eGFR <60 ml/min per 1.73 m(2) regardless of albuminuric status (normo- 0.74 +/- 0.01, micro- 0.73 +/- 0.01, and macroalbuminuria resistance index 0.75 +/- 0.11). Multiple regression analysis revealed that increased age (P < 0.0001), elevated BMI (P = 0.0001), decreased eGFR (P < 0.01), and decreased diastolic blood pressure (P < 0.01), but not an increased AER, were independently associated with an elevated resistance index in patients with impaired renal function. CONCLUSIONS: Subjects with type 2 diabetes and reduced glomerular filtration rate had similar degrees of intrarenal vascular disease, as measured by the intrarenal arterial resistance index, regardless of their AER status. The pathological mechanisms that determine the relationship between impaired renal function and AER status in subjects with type 2 diabetes remain to be elucidated.     

Effect of polymyxin B-immobilized fiber on bone resorption in patients with sepsis

Objective To analyze the effects of polymyxin B-immobilized fiber (PMX-F) on bone resorption in septic patients.Design and setting Observational prospective study in intensive care units of a general hospital.Patients and participants 25 patients with severe sepsis and 20 healthy controls.Measurements and results Septic patients were randomly assigned to two groups: PMX-F treatment group (n=15) and conventional treatment group (n=10). Total pyridinium crosslink pyridinoline (PYD) and deoxypyridinoline (DPD) in urine were determined by modified high-performance liquid chromatography. Nitric oxide production was assessed by measuring the ratio of the nitric oxide breakdown products to urinary creatinine (NOx/Cr). Plasma endotoxin levels were determined by endospecy test. The blood albumin, ionized calcium, and parathyroid hormone were also measured. PMX-F treatment was performed twice separated by 24 h. Urinary NOx/Cr, PYD/Cr, and DPD/Cr were significantly increased in septic patients compared with those in healthy controls. Blood ionized calcium in septic patients was lower than in healthy controls, while parathyroid hormone levels in septic patients were higher than in healthy controls (P<0.01). PMX-F treatment reduced plasma endotoxin, urinary NOx/Cr, PYD/Cr, DPD/Cr, and serum parathyroid hormone levels and increased blood ionized calcium significantly; however, conventional treatment did not affect these levels.Conclusions Septic patients increased nitric oxide production and bone resorption, and PMX-F treatment is effective in reducing nitric oxide levels and bone resorption markers.     

早期糖尿病肾病患者尿高迁移率族B1蛋白、尿外泌体miR-129表达水平及临床意义研究

目的 探讨早期糖尿病肾病(DN)患者尿外泌体miR-129、尿高迁移率族B1蛋白(HMGB1)表达水平,分析其临床意义.方法 选取自2018年7月至2019年12月长江大学附属仙桃市第一人民医院收治的168例2型糖尿病患者作为研究对象,根据Mogensen分期将患者分为单纯糖尿病组(n=93)与早期DN组(n=75),...     

Renal function and the oxidative status among children with thalassemia major and healthy controls: A cross-sectional study

BackgroundRenal dysfunction is an underestimated complication of thalassemia major.ObjectivesThe aim of this study is to compare the glomerular and tubular functions in children with β- Thalassemia major (β- TM) with healthy controls and assess the oxidative stress caused by high ferritin levels.Design and settingThis prospective cross-sectional study was conducted in tertiary care hospital.MethodsComplete blood count (CBC), calcium (Ca), urea, creatinine (Cr), serum cystatin C before transfusion and urinary calcium (uCa), creatinine (uCr), protein (UPr) levels were analyzed in fresh samples. Beta-2-microglobulin (uβ2-MG), N- acetylglucosaminidase (uNAG), retinol binding protein (uRBP), malonedialdehyde (uMDA) secretion and creatinine levels were analyzed. Serum total antioxidant capacity (sTAC) and total oxidant capacity (sTOC) were measured with colorimetric micro-ELISA method. Last four serum ferritin values were recorded and the mean value was used for statistical analyzes.ResultsData from 47 patients and 32 controls were analyzed. The urinary RBP/Cr, Ca/Cr and Protein/Cr, were significantly higher in β-TM group. A statistically insignificant increase in urinary β2MG/Cr, uNAG/Cr, MDA/Cr was also found in the TM group. Proteinuria was present in 46 % (n: 22) and hypercalciuria in 34 % (n: 16) of the patients with β- TM. Serum total antioxidant capacity and total oxidant status (TOS) levels were significantly elevated in the patient group. Serum ferritin was significantly correlated with proteinuria, cystatin C levels, urinary Protein/Cr and uRBP/Cr.ConclusionAsymptomatic renal dysfunction is prevalent in β- TM patients that necessitate regular screening. Urinary RBP may be useful for early diagnosis.     

尿清蛋白与肌酐比值对2型糖尿病肾病的早期诊断价值

目的探讨测定尿清蛋白／肌酐比值对诊断早期糖尿病肾病的价值。方法选取105例2型糖尿病患者,其中包括45例早期糖尿病肾病患者,分别计算尿清蛋白／肌酐比值、24h尿蛋白定量及尿清蛋白排泄率,并比较它们之间的关系。结果早期糖尿病肾病组尿清蛋白／肌酐比值与24h尿蛋白定量及蛋白排泄率呈显著相关性（r=0．921,P〈0．01;r=0．857,P〈0．05）。结论尿清蛋白／肌酐比值是诊断早期糖尿病肾病的一项敏感且可靠的指标。     

IgA肾病患者AGTM235T基因多态性分析

目的探讨血管紧张素原（AGT）M235T基因多态性与上海地区IgA肾病（IgAN）遗传易感性及临床病理表现的相关性。方法选取上海地区经肾穿刺病理活检证实为IgAN患者105例和健康对照者120例,采用聚合链式反应一限制性片段长度多态性技术（PCR—RFLP）检测AGTM35T基因多态性,并比较不同基因型患者临床病理表现之间的相关性。结果105例IgAN肾病患者的AGTM235T基因多态性与正常对照相比,基因型分布频率差异无统计学意义;年龄、性别、血压、血清肌酐、24h尿蛋白定量、初始的估算肾小球滤过率（eGFR）值等临床指标与AGTM235T基因型无相关性;病理资料显示AGTM235T各基因型病理表现无相关性。结论AGTM235T基因多态性与IgAN患者无显著相关性。     

Time courses of urinary creatinine excretion,measured creatinine clearance and estimated glomerular filtration rate over 30 days of ICU admission

PurposeBaseline urinary creatinine excretion (UCE) is associated with ICU outcome, but its time course is not known.Materials and methodsWe determined changes in UCE, plasma creatinine, measured creatinine clearance (mCC) and estimated glomerular filtration (eGFR) in patients with an ICU-stay ≥30d without acute kidney injury stage 3. The Cockcroft-Gault, MDRD (modification of diet in renal disease) and CKD-EPI (chronic kidney disease epidemiology collaboration) equations were used.ResultsIn 248 patients with 5143 UCEs hospital mortality was 24%. Over 30d, UCE absolutely decreased in male survivors and non-survivors and female survivors and nonsurvivors by 0.19, 0.16, 0.10 and 0.05 mmol/d/d (all P < 0.001). Relative decreases in UCE were similar in all four groups: 1.3, 1.4, 1.2 and 0.9%/d respectively. Over 30d, mCC remained unchanged, but eGFR rose by 31% (CKD-EPI) and 73% (MDRD) and creatinine clearance estimated by Cockcroft-Gault by 59% (all P < 0.001).ConclusionsOver 1 month of ICU stay, UCE declined by ≥1%/d which may correspond to an equivalent decline in muscle mass. These rates of UCE decrease were similar in survivors, non-survivors, males and females underscoring the intransigent nature of this process. In contrast to measured creatinine clearance, estimates of eGFR progressively rose during ICU stay.     

Applicability of estimated glomerular filtration rate in stratifying chronic kidney disease

Objective. The aim of this audit was to evaluate the degree of glomerular filtration rate (GFR) among inpatients and outpatients in a District General Hospital, with special attention given to laboratory testing and impact on health delivery. Background. UK Chronic Kidney Disease guidelines recommend that investigation of renal function should be accompanied by an estimation of GFR (eGFR) in order to identify and manage patients with chronic kidney disease (CKD). The estimated GFR forms the basis for classification of CKD and appropriate action plans for patient management and follow‐up. Method. A retrospective audit of 8160 results from a predominantly British Caucasian population was carried out; extracting creatinine results from two isolated months in years 2001 and 2004. The estimated GFR (eGFR) was calculated using the MDRD formula. The data were classified according to demography, serum creatinine and eGFR. Patients from the 2001 database were classified according to eGFR and those with a value of <60?mL/min/1.73m² were followed up in 2004. Results. The difference in eGFR between the men and women was significantly different with medians (confidence intervals) of 80.1 (41–109) and 64.4 (30–84.6) (p<0.0001), respectively. There was an inverse association between age and eGFR in both genders (p<0.0001), with a decrease in eGFR of around 7?% for each decade increase in age. 1926 patients (24?%) of results studied had eGFR <60?mL/min, of whom 64?% were females and 36?% males. Follow‐up of patients with eGFR<60?mL/min from 2001 showed that 4?% progressed to stages 4 and 5 CKD. Conclusion. eGFR is inversely associated with increasing age and female gender. MDRD derived eGFR fails to completely compensate for age and gender variations and thus different action limits may be required. Small but significant numbers of patients progressed to stages 4 and 5 CKD. Additional clarity in describing “progressive fall in eGFR” in the guidelines would improve identification of the population most at risk.     

Urinary Cystatin C and Tubular Proteinuria Predict Progression of Diabetic Nephropathy

OBJECTIVE

The aim of this study was to evaluate the association of urinary cystatin C, a tubular damage marker, with the progression of type 2 diabetic nephropathy.

RESERCH DESIGN AND METHODS

The baseline values of serum and urinary cystatin C were measured as primary parameters and those of urinary nonalbumin protein (NAP) were measured as secondary parameters. In this prospective observational study, a total of 237 type 2 diabetic patients were followed up for 29 months (13–44 months).

RESULTS

Both the urinary cystatin C-to-creatinine ratio (CCR) and NAP-to-creatinine ratio (NAPCR) were significantly different according to the degree of albuminuria. Both markers had strongly positive correlations at baseline. After adjusting for several clinical factors, both urinary CCR and NAPCR had significant associations with the decline of the estimated glomerular filtration rate (eGFR) (r = 0.160, P = 0.021; r = 0.412, P < 0.001, respectively). Urinary CCR had positive correlations with the decline of eGFR in the subpopulation of patients with eGFR ≥60 mL/min/1.73 m². In patients with eGFR ≥60 mL/min/1.73 m² and normoalbuminuria, only urinary NAPCR showed a significant association with the decline of eGFR; urinary CCR did not. In multivariate regression analysis, the number of patients who progressed to chronic kidney disease stage 3 or greater was higher in those in the upper tertiles of both the urinary levels of cystatin C and NAP than in those in the lower tertiles.

CONCLUSIONS

The results of this study suggest that urinary cystatin C and NAP may be predictors of the progression of type 2 diabetic nephropathy.Diabetic nephropathy is a complication with high morbidity and mortality as well as a major cause of end-stage renal disease. Although glomerular dysfunction is thought to be a major factor for the development and progression of diabetic nephropathy, tubulointerstitial damage may also play an important role in the pathogenesis of diabetic nephropathy (1–3). Recently, several studies have shown that some tubular damage markers have clinical implications as biomarkers for the development and progression of diabetic nephropathy (4–10).Cystatin C is a 13-kDa cysteine proteinase inhibitor and is produced by all nucleated cells at a constant rate (11). In healthy subjects, cystatin C is almost freely filtered by the renal glomeruli and almost entirely reabsorbed in the proximal tubule like other low molecular weight proteins; there is no tubular secretion of cystatin C (12–14). Similar to the serum cystatin C, the urinary cystatin C level is not affected by age or muscle mass in healthy subjects or in proteinuric patients without renal tubular damage (15). On the other hand, increased urinary cystatin C has been recognized as a marker of renal tubular dysfunction (16,17). In addition, urinary leakage of proteins other than albumin (nonalbumin protein [NAP]) can also indicate tubular damage rather than glomerular damage (18).The aims of this study were to evaluate the impact of urinary cystatin C on the progression of type 2 diabetic nephropathy and to determine whether urinary cystatin C has an association with the decline of the glomerular filtration rate (GFR) in type 2 diabetic patients. In addition, we also evaluated whether urinary NAP has any correlation with urinary cystatin C or has any effect on the decline in GFR.     

Sympathetic nervous activity, renin-angiotensin system and renal excretion of prostaglandin E2 in cirrhosis. Relationship to functional renal failure and sodium and water excretion

Abstract. To investigate if functional renal failure in cirrhosis could be related to disturbances of vasoactive systems, plasma renin activity, plasma catecholamines and urinary prostaglandin E₂ (PGE₂) were determined in twenty-two normal subjects and sixty-five cirrhotics. Furthermore, in thirty-three of these subjects, the effect of lysine-acetylsalicylate (450 mg i.v.) on renal function was studied. Patients with ascites without renal failure showed higher renin, noradrenalin and urinary PGE² than normal subjects (5.9±0.8 v. 1.1±0.1 ng ml^-1 h^-1, P < 0.001; 512 ± 39 v. 224±17 pg/ml, P < 0.001; and 603 ± 71 v. 377±36 ng/day, P < 005, respectively). Patients with functional renal failure showed higher (P < 0001) renin (13.5±1.9) and noradrenalin (1114±134) and lower (P < 005) urinary PGE₂ (199 ± 36) than normal subjects and cirrhotics without renal failure. On the whole, patients glomerular filtration rate correlated (P < 0001) with urinary PGE₂ (r= 0.55), renin (r=-0.52) and noradrenalin (r=-0.52). Lysine-acetylsalicylate did not alter renal function in normal subjects and cirrhotics without ascites. However, it reduced water diuresis (8.8 ± 0.9–2.7 ± 0.5 ml/min) and sodium excretion (from 57.1 ± 13.9 to 3.9 ± 11 μmol/min) in all the nineteen cirrhotics with ascites studied and the glomerular filtration rate (95.4 ± 11.8–46.7 ± 9.5 ml/min) in eleven of these patients. Urinary PGE₂ decreased in all patients (3.13 ± 0.65–0.54 ± 0.11 ng/min). The study suggests that: (a) functional renal failure in cirrhosis with ascites may be a consequence of an imbalance between vasoactive systems, (b) renal prostaglandins are involved in the tubular handling of sodium and water in these patients.     

Effect of renal function on whole blood and fibrin clot formation in atrial fibrillation patients on warfarin

Objective: Atrial fibrillation (AF) brings a risk of thrombosis, requiring oral coagulation, and is associated with renal impairment. The two processes may be linked, as altered fibrin clot structure is present in end-stage renal failure. We hypothesised that progressively deteriorating renal function is linked to altered whole blood and fibrin clot properties and fibrinolysis. Methods: Thrombogenesis and fibrinolysis in 200 warfarinised AF patients was assessed by thromboelastography (TEG), a micro-plate assay (MPA) and the international normalized ratio (INR). Renal function was determined by creatinine clearance and two versions of the estimated glomerular filtration rate (eGFR). Results: Two TEG indices independently reflecting thrombogenesis were linked to creatinine clearance (p?p?p?p?p?=?0.001). The INR was unrelated to any renal function index, and the CHA₂DS₂VASc score was unrelated to any index. Conclusion: In warfarinised AF patients, renal function is linked to whole blood clot and fibrin clot formation, structure and dissolution, but has no effect on the INR.

• Key messages

• Despite oral anticoagulation, patients with atrial fibrillation (AF) still suffer from stroke and venous thromboembolism.

• The effect of renal function in warfarinised patients with AF is unknown and may account for excess thrombosis and/or haemorrhage.

• Using two different laboratory methods, our data point to an effect of renal function on clot structure and function that is independent of an effect of warfarin.

     

Urinary connective tissue growth factor excretion in patients with type 1 diabetes and nephropathy

OBJECTIVE: Excretion of growth factors in the urine has been implicated in the pathogenesis of tubulointerstitial disease that characterizes proteinuric renal disease. In this cross-sectional study, we sought to examine the urinary excretion of the profibrotic cytokine connective tissue growth factor (CTGF) in type 1 diabetic patients with incipient and overt diabetic nephropathy. RESEARCH DESIGN AND METHODS: We recruited 31 subjects with type 1 diabetes from a hospital diabetes outpatient clinic. Of these, 10 subjects were normoalbuminuric, 8 were microalbuminuric and not receiving ACE inhibitor treatment, and 13 were macroalbuminuric, 8 of whom were receiving ACE inhibitor treatment. Urinary CTGF NH(2)-terminal fragment (CTGF-N) was determined by enzyme-linked immunosorbent assay and expressed relative to urinary creatinine. RESULTS: Urinary CTGF-N was closely correlated with the degree of albuminuria (r = 0.76, P < 0.001). In comparison with normoalbuminuric subjects, urinary CTGF-N was increased 10- and 100-fold in micro- and untreated macroalbuminuric subjects, respectively (CTGF-N-to-creatinine ratio: normoalbuminuria 0.23 x// 1.3 ng/mg, microalbuminuria 2.1 x// 1.7 ng/mg, untreated macroalbuminuria 203 x// 3.8 ng/mg, and geometric mean x// tolerance factor; P < 0.05 for normoalbuminuria versus microalbuminuria, P < 0.001 for microalbuminuria versus macroalbuminuria). Urinary CTGF-N was lower (<30-fold) in macroalbuminuric subjects treated with ACE inhibitors (6.5 x// 1.7 ng/mg; P < 0.01 vs. untreated macroalbuminuria) compared with their untreated counterparts. CONCLUSIONS: In this cross-sectional study, the magnitude of urinary CTGF-N excretion was related to the severity of diabetic nephropathy. In the context of its known profibrotic actions, these findings suggest that CTGF may contribute to the chronic tubulointerstitial fibrosis that accompanies proteinuric renal disease. Prospective and interventional studies will be needed to determine whether urinary CTGF-N may provide a reliable surrogate marker of renal injury and a meaningful indicator of response to therapy.