Correlation between serum asymmetric dimethylarginine and blood pressure variability in chronic kidney disease patients

Objective To determine the correlation between serum asymmetric dimethylarginine (ADMA) and non-spoon-shaped blood pressure of non-dialysis chronic kidney disease (CKD) patients, also to observe the impact of the serum ADMA level on the structure and function of left ventricle. Methods One hundred and twenty cases of non-dialysis CKD patients underwent 24-hour ambulatory blood pressure monitoring were divided into three groups: CKD1-2, CKD3, CKD 4-5. Serum ADMA concentration was measured using liquid chromatograph and other clnical data such as uric acid (UA), left ventricular mass index (LVMI), 24 h urine protein, and high-sensitivity C-reactive protein (hs-CRP) were collected for further statistical analysis. Results (1) With the decline of renal function, ADMA concentration was increased, from CKD 1-2 (1.70±0.48) μmol/L rose to CKD 4-5 (4.46±1.56) μmol/L (P＜0.05). (2)There were 42 cases of CKD patients with hypertension and 78 cases of CKD patients with normal blood pressure. The serum ADMA levels in hypertension group was significantly higher than those in non-hypertensive group [(3.53±1.70) μmol/L vs (2.01±0.65) μmol/L, P＜0.05]. (3)There were 50 cases of non-spoon-shaped normotensive CKD patients and 28 cases of spoon-shaped normotensive CKD patients. Serum ADMA level and LVMI in non-spoon-shaped group were significantly higher than that in spoon-shaped group when kidney functions appeared to be equal (P＜0.05). (4)Serum ADMA level was positively correlated with UA(r=0.352, P＜0.01), LVMI (r=0.345, P＜0.05), 24 h urine protein(r=0.200, P＜0.05), and high-sensitivity C-reactive protein (r=0.309, P＜0.01), but negatively correlated with the left ventricular ejection fraction (LVEF)(r=-0.329, P＜0.01) and estimated glomerular filtration rate (eGFR)(r=-0.011, P＜0.01). Multiple regression results showed that eGFR, UA, LVMI, hs-CRP, 24 h urine protein were associated with ADMA level. The regression equation was Y=1.991-0.011×[eGFR]+0.002×[UA]+0.008×[LVMI]+0.036× [hs-CRP]-0.084×[24 h urinary protein]. Conclusions Serum ADMA level begins to increase in early stage CKD and it progressively increases with the decline of renal function, also the non-spoon-shaped blood pressure ratio and the left ventricular damage increase. Kidney function, urine protein and microinflammatory state may impact on the serum ADMA level.     

Impact of vitamin E on plasma asymmetric dimethylarginine (ADMA) in chronic kidney disease (CKD): a pilot study.

BACKGROUND: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase and a proposed cardiovascular risk factor, is elevated in chronic kidney disease (CKD). Pharmacological strategies that lower plasma concentration of ADMA may be expected to increase nitric oxide (NO.) bioavailability and potentially limit atherosclerosis. We hypothesized that the antioxidant alpha-tocopherol (vitamin E) reduces ADMA levels in CKD. METHODS: An open-label pilot interventional study using 800 IU of vitamin E was undertaken in eight stable out-patients with non-diabetic CKD (creatinine clearance <30 ml/min/1.73 m(2)) and six healthy controls, with the objective of measuring plasma ADMA levels at baseline and after 8 weeks of treatment. Plasma ADMA, symmetric dimethylarginine (SDMA) and alpha-tocopherol concentrations were determined at study entry and exit using high-performance liquid chromatography, while plasma total F2-isoprostanes, an index of oxidative stress, were measured using a commercially available enzyme-linked immunosorbent assay kit. RESULTS: ADMA and SDMA concentrations were significantly higher in the plasma of patients compared with that of controls (P 相似文献   

血浆不对称二甲基精氨酸对慢性肾脏病患者心脏结构及功能的预测价值

目的 探讨血浆不对称二甲基精氨酸(ADMA)水平对慢性肾脏病(CKD)患者心脏结构及功能的预测价值.方法 选取100例非透析CKD患者为研究对象.依照K-DOQI指南的分期标准,将患者分为5组.选取年龄匹配的健康体检者20例为健康对照组.用高效液相色谱法检测血浆ADMA水平和超声心动图检测心脏结构及功能.结果 CKD患者血浆ADMA水平(μmol/L)随着肾功能的减退而增高.CKD3、4、5期患者血浆ADMA水平(1.3318±0.4684、1.5712±0.4210、2.1093±0.7714)显著高于健康对照组(0.4611±0.1615)及CKD1、2期患者( 0.4387±0.2575、0.4809±0.2846)(均P＜0.01);而CKD5期患者血浆ADMA又高于CKD3、4期患者.CKD4、5期患者左心室心肌质量指数(LMVI)( 140.24±40.52、150.21±46.23)显著高于健康对照组及CKD1 ～3期患者(均P＜0.01).ADMA与LMVI呈正相关(r=0.476,P=0.028),与心脏射血分数(EF)呈负相关(r=-0.327,P=0.041).多因素逐步回归分析结果显示血浆ADMA是EF降低的独立危险因素(OR=0.984,P＜0.01).结论 CKD患者血浆ADMA水平在CKD3期开始升高,并随着肾功能的减退而增加.血浆ADMA与左心室肥厚呈正相关,且是EF降低的独立危险因素,对心血管并发症有预测价值.     

血浆不对称二甲基精氨酸与慢性肾脏疾病非透析患者心血管并发症的关系

目的 探讨不对称二甲基精氨酸（ADMA）与慢性肾脏疾病（CKD）非透析患者心血管并发症（CVD）的关系。 方法 高效液相色谱-质谱联用仪检测76例患者的血浆ADMA水平，分析其与颈动脉超声、心脏超声等相关指标及既往CVD病史的关系。 结果 CKD非透析患者的血浆ADMA水平较健康对照组显著升高[(41.56±12.76) 比 (17.12±7.09) mg/L, P < 0.01]。逐步多元回归分析显示ADMA是颈总动脉内-中膜厚度（β = 0.544, P < 0.01）和左室心肌重量指数（β = 2.521, P < 0.01）的独立危险因素。既往有CVD史者其血浆ADMA水平较既往无CVD史者显著升高[(47.60±15.14)比 (36.93±8.10) mg/L，P < 0.01]。Logistic回归分析显示血浆ADMA（β = 1.117，95%CI：1.013~1.232, P < 0.05）是CKD非透析患者CVD的独立危险因素。 结论 CKD患者普遍存在CVD，ADMA可能参与了CKD非透析患者CVD的发生发展。     

Day-by-day variability of home blood pressure in patients with chronic kidney disease

PURPOSE: We examined the characteristics of the day-by-day variability of home blood pressure (HBP) in patients with chronic kidney disease (CKD). METHODS: We obtained HBP recordings from 368 CKD patients (63+/-13 years, eGFR 34+/-23 mL/min/1.73 m2, males 253). The day-by-day variability of HBP was defined as the coefficient of variation (CV) values of BP measurements every morning after waking and every evening before sleeping on 7 consecutive days. In a portion of the patients, the CV values of HBP were collected every 6 months during a 2-year period and the association with a decline in GFR was examined. RESULTS: CV values of morning/evening systolic BP (SBP) were 5.4+/-2.4%, 6.1+/-2.9 % (p<0.01). The CV values of morning SBP in females or patients with diabetic nephropathy (DN) were significantly greater than those in males or patients without DN, respectively (females 5.9+/-2.3%, males 5.2+/-2.4%, p< 0.01, DN 6.1+/-2.8 %, non DN 5.2+/-2.2 %, p<0.05). Multivariate linear regression analysis showed that female gender, DN, the number of antihypertensive drugs, higher heart rate and higher CV values of heart rate were associated with higher CV values of the morning SBP. CV values of the morning SBP showed no significant change during the 2-year period (0; 5.4+/-2.6%, 1 year; 5.3+/-2.9%, 2 years 5.6+/-3.1%, n=200). There was no significant difference in the change in eGFR between a group with high CV values (greater than 5 %) and a group with low CV values (lower than 5 %) during the 2-year period. CONCLUSIONS: In CKD patients, the day-by-day variability of HBP tended to be greater in the evening, in female and DN patients. There was no significant association between the day-by-day variability of HBP and decline rate in eGFR. Further studies are needed to clarify the clinical significance of the day-by-day variability of HBP in CKD patients.     

Olmesartan medoxomil and azelnidipine therapy in patients with hypertension and chronic kidney disease in Japan

Background: In the present investigation we extracted data on hypertensive patients with chronic kidney disease (CKD) who were enrolled in 3 studies - 2 studies of the angiotensin receptor blocker (ARB) olmesartan medoxomil (OLM), lasting 12 weeks and 2 years, respectively, and one of the calcium channel blocker (CCB) azelnidipine (AZ) lasting 12 weeks - to assess the effects of OLM and AZ on blood pressure (BP), estimated glomerular filtration rate (eGFR) and proteinuria in hypertensive patients with CKD in the setting of daily clinical practice. Methods: The 3 studies followed open prospective cohort designs that represented daily clinical practice in Japan. Patients with CKD at baseline were selected. Change of BP, eGFR and proteinuria on OLM therapy or AZ therapy were analyzed. Results: At 12 weeks, OLM (n=1,317) and AZ (n=952) therapies exhibited similar BP-lowering effects. AZ led to a significantly (p=0.0069) greater increase of eGFR compared with OLM, while OLM tended to improve proteinuria to a greater extent than AZ. Treatment with OLM for 2 years (n=109) significantly improved proteinuria but did not alter eGFR. Conclusion: This study shows that OLM and AZ reduced BP and proteinuria without decreasing eGFR in Japanese hypertensive patients with CKD in the setting of daily clinical practice.     

Effect of simvastatin on plasma asymmetric dimethylarginine concentration in patients with chronic kidney disease

BACKGROUND: The endogenous inhibitor of nitric oxide (NO) synthase, asymmetric dimethylarginine (ADMA), is a strong cardiovascular (CV) risk marker in patients with chronic renal insufficiency. Statins have pleiotropic effects and are currently considered as potential ADMA-lowering agents. METHODS: We investigated the effect of simvastatin on plasma ADMA levels in 35 patients with chronic kidney disease (CKD) by performing a secondary analysis of a randomized double-blind placebo-controlled trial where patients were randomized to receive simvastatin or placebo for 6 months. RESULTS: Plasma ADMA was higher in CKD patients (0.84 +/- 0.14 micromol/L) than in healthy subjects (0.69 +/- 0.10 micromol/L) (p<0.001). In CKD patients, ADMA at baseline was related directly with triglycerides (r=0.42, p=0.01) and inversely with HDL cholesterol (r=-0.37, p=0.03) and creatinine clearance (p=0.03). As expected, simvastatin caused significant reductions in total cholesterol, LDL cholesterol and triglycerides, as well as in C-reactive protein (CRP; -28%, p=0.001) and IL-6 (-20%, p=0.05) but failed to decrease plasma ADMA both in crude and adjusted analyses. CONCLUSIONS: Simvastatin does not modify plasma ADMA. Because raised ADMA is known to prevent the favorable effect of statins on myocardial blood flow, cointerventions aimed at lowering or antagonizing ADMA may either prompt or potentiate the cardiovascular protective effect of simvastatin.     

Asymmetric dimethylarginine may be a missing link between cardiovascular disease and chronic kidney disease

Decreased nitric oxide (NO) production and/or impaired NO bioavailability may occur in patients with chronic kidney disease (CKD), and could contribute to the elevation of blood pressure, cardiovascular disease (CVD) and the progression of renal injury in these patients. However, the underlying molecular mechanisms for reduced NO action in patients with CKD remains to be elucidated. Asymmetric dimethylarginine (ADMA) is a naturally occurring L-arginine analogue found in plasma and various types of tissues, acting as an endogenous NO synthase inhibitor in vivo. Further, plasma level of ADMA is elevated in patients with CKD and found to be a strong biomarker or predictor for future cardiovascular events. In addition, plasma level of ADMA could predict the progression of renal injury in these patients as well. These findings suggest that elevation of ADMA may be a missing link between CVD and CKD. In this review, we discuss the molecular mechanisms for the elevation of ADMA and its pathophysiological role for CVD in high-risk patients, especially focusing on patients with CKD.     

Prevalence of chronic kidney disease risk factors among low birth weight adolescents

Background

By adulthood, low birth weight infants have an increased risk for chronic kidney disease (CKD). The extent to which objective CKD risk factors are present at earlier ages is unclear.

Methods

We analyzed 5352 participants aged 12–15 years in the National Health and Nutrition Examination Survey, 1999–2012. Participants were classified as low birth weight (LBW; < 2500 g), very low birth weight (VLBW; < 1500 g), or normal (2500–4000 g) by parental/proxy recall. Albuminuria (albumin/creatinine 30 – <300 mg/g), decreased estimated glomerular filtration rate (eGFR; < 90 ml/min/1.73 m²; Counahan–Barratt), and elevated systolic blood pressure (BP; ≥ 95th percentile for age, height, and sex) were considered CKD risk factors.

Results

While albuminuria did not vary by birth weight, elevated blood pressure (BP) and decreased eGFR occurred more frequently in LBW/VLBW adolescents (elevated BP: LBW 6.0 %, VLBW 11.2 %, normal 2.4 %; decreased eGFR: LBW 23.2 %, VLBW 32.5 %, normal 16.1 %). After multivariable adjustment, LBW/VLBW adolescents had greater odds for both elevated BP (LBW: OR 2.90, 95 % CI 1.48–5.71; VLBW: 5.23; 1.11–24.74) and decreased eGFR (LBW: 1.49, 95 % CI 1.06–2.10; VLBW 2.49, 95 % CI 1.20–5.18).

Conclusions

In the U.S. population, both decreased eGFR and elevated systolic BP occur frequently among adolescents with history of LBW/VLBW.

     

The natural history of renal functional decline in patients undergoing surveillance in the DISSRM registry

ObjectiveTo describe the natural history of renal function in patients on active surveillance (AS) for small renal masses (SRM) in the Delayed Intervention and Surveillance for Small Renal Masses Registry.MethodsDelayed Intervention and Surveillance for Small Renal Masses is a prospective, multi-institutional registry of patients with SRM (≤4 cm) who choose intervention or AS. Of these, 64 patients on AS had longitudinal serum creatinine (sCr) values and underwent analysis of estimated glomerular filtration rate (eGFR). eGFR was calculated using the Modification of Diet in Renal Disease formula. The Kidney Disease Outcomes Quality Initiative chronic kidney disease (CKD) classification was used to categorize patients’ eGFR values.ResultsMedian age was 74 (range: 34–88) years at onset of AS. Overall, 9% (6/64) of patients had CKD at baseline. Median initial tumor size was 2.1 cm (range: 0.8–4.0). Median Charlson comorbidity index score was 4 (range: 0–8). Median baseline sCr was 1.0 mg/dl (range: 0.4–2.1) and median baseline eGFR was 70.25 (range: 24.07–165.52). After a median follow-up of 17 (range: 2–46) months, 64% of patients experienced a decrease in eGFR, with average yearly decrease in eGFR of 1.82 ml/min/1.73 m² (P = 0.092) and average yearly increase in sCr of 0.046 (P = 0.012). A total of 15 (24%) patients experienced an upstaging in classification of CKD.DiscussionNearly two-thirds of patients on AS experienced a decrease in eGFR and nearly one-fourth had upstaging of CKD classification. The annual eGFR decline experienced by patients on AS minimally exceeded the annual decline of 1.49±0.3 ml/min/1.73 m² that an individual who was 70 to 79 years of age can expect from aging alone. Further follow-up is necessary to assess this in a more definitive manner, but this trend should be considered when evaluating AS as an alternative to interventional therapies for SRM.     

Impact of visit-to-visit variability in blood pressure on renal function of stage 3-4 chronic kidney diseases patients with hypertension

Objective To clarify the clinical significance of visit-to-visit variability in blood pressure (BP) of stage 3-4 chronic kidney disease (CKD) patients with hypertension. Methods One hundred and fifty-two cases of stage 3-4 CKD patients with hypertension were enrolled in the study. Variability in BP was defined as the standard deviation (SD) in BP. For each patient, SD and mean BP from BP measurements were calculated at all the visits. Correlations between the decline in estimated glomerular filtration rate (eGFR) and SD in BP were analyzed by multivariable regression. Results Visit-to-visit variability in BP was significantly associated with renal function decline (P＜0.05), in addition, baseline eGFR, baseline albuminuria and mean SBP during follow-up were significantly associated with renal function decline as well (all P＜0.05). The percentage of CCBs used in low SD of the SBP group was higher than that in high SD of the SBP (76.1% vs 58.2%, P＜0.05). Conclusion Visit-to-visit variability in BP is significantly associated with renal function decline. Drugs which can decrease the variability of blood pressure should be the first choice in the treatment of hypertension.     

Handling of asymmetrical dimethylarginine and symmetrical dimethylarginine by the rat kidney under basal conditions and during endotoxaemia.

BACKGROUND: Asymmetrical dimethylarginine (ADMA) is capable of inhibiting nitric oxide synthase enzymes, whereas symmetrical dimethylarginine (SDMA) competes with arginine transport. The potential role of inflammation in the metabolism of ADMA has been elucidated in an in vitro model using tumour necrosis factor-alpha, resulting in a decreased activity of the ADMA-degrading enzyme dimethylarginine dimethylaminohydrolase (DDAH). The kidney probably plays a crucial role in the metabolism of ADMA by both urinary excretion and degradation by DDAH. We aimed to further elucidate the role of the kidney in a rat model under basal conditions and during endotoxaemia. METHODS: Twenty-five male Wistar rats weighing 275-300 g were used for this study. The combination of arteriovenous concentration differences and kidney blood flow allowed calculation of net organ fluxes. Blood flow was measured using radiolabelled microspheres according to the reference sample method. Concentrations of ADMA, SDMA and arginine were measured by high-performance liquid chromatography. RESULTS: The kidney showed net uptake of both ADMA and SDMA and fractional extraction rates were 35% and 31%, respectively. Endotoxaemia resulted in a lower systemic ADMA concentration (P = 0.01), which was not explained by an increased net renal uptake. Systemic SDMA concentrations increased during endotoxaemia (P = 0.007), which was accompanied by increased creatinine concentrations. CONCLUSIONS: The rat kidney plays a crucial role in the regulation of concentrations of dimethylarginines, as both ADMA and SDMA were eliminated from the systemic circulation in substantial amounts. Furthermore, evidence for the role of endotoxaemia in the metabolism of dimethylarginines was obtained as plasma levels of ADMA were significantly lower in endotoxaemic rats.     

Asymmetric dimethyl-arginine (ADMA) response to inflammation in acute infections.

BACKGROUND AND METHODS: The endogenous inhibitor of nitric oxide synthase (NOs) asymmetrical dimethyl-arginine (ADMA) has been implicated as a possible modulator of inducible NOs during acute inflammation. We examined the evolution in the plasma concentration of ADMA measured at the clinical outset of acute inflammation and after its resolution in a series of 17 patients with acute bacterial infections. RESULTS: During the acute phase of inflammation/infection, patients displayed very high levels of C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin and nitrotyrosine. Simultaneous plasma ADMA concentration was similar to that in healthy subjects while symmetric dimethyl-arginine (SDMA) levels were substantially increased and directly related with creatinine. When infection resolved, ADMA rose from 0.62 +/- 0.23 to 0.80 +/- 0.18 micromol/l (+29%, P = 0.01) while SDMA remained unmodified. ADMA changes were independent on concomitant risk factor changes and inversely related with baseline systolic and diastolic pressure. Changes in the ADMA/SDMA ratio were compatible with the hypothesis that inflammatory cytokines activate ADMA degradation. CONCLUSIONS: Resolution of acute inflammation is characterized by an increase in the plasma concentration of ADMA. The results imply that ADMA suppression may actually serve to stimulate NO synthesis or that in this situation plasma ADMA levels may not reflect the inhibitory potential of this methylarginine at the cellular level.     

Levels of bisphenols in patients with chronic kidney disease and their correlation with renal function

Objective To observe the levels of four bisphenols (bisphenol A, B, S and F) and their correlation with renal function in chronic kidney disease (CKD) patients. Methods Patients with CKD were identified according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Sixty-three CKD patients and eleven healthy controls were enrolled. CKD patients were further classified as mild renal injury group (CKD stage 1 and 2, n=30), moderate renal injury group (CKD stage 3, n=19) and severe renal injury group (CKD stage 4 and 5, n=14). The levels of four bisphenols in serum were determined by high performance liquid chromatography (HPLC). The correlation between concentrations of four bisphenols and estimated glomerular filtration rate (eGFR) was assessed by Spearman's rank correlation analysis. The associations of four bisphenols with coronary heart disease, diabetes and hypertension in CKD patients were estimated by binary multivariate logistic regression. Results (1) Four bisphenols were not detected in serum of healthy control. In the mild renal injury group the bisphenol A and bisphenol S were not detected, and patients had 5.24 (5.24, 9.38) μg/L bisphenol B and 0.74 (0.74, 0.74) μg/L bisphenol F. In the moderate renal injury group bisphenol S was not detected, and patients had 2.79 (1.01, 4.53) μg/L bisphenol A, 5.24 (5.24, 5.24) μg/L bisphenol B and 0.74 (0.74, 0.74) μg/L bisphenol F. In severe renal injury group patients had 14.30 (7.97, 18.17) μg/L bisphenol A, 0 μg/L bisphenol B, 23.73 (23.73, 136.59) μg/L bisphenol S and 0.74 (0.74, 1.42) μg/L bisphenol F. The levels of bisphenol A and bisphenol S in severe renal injury group were higher than those in the healthy control group, mild renal injury group and moderate renal injury group (all P＜0.05). Bisphenol B and bisphenol F were not statistically different among four groups. (2) Bisphenol A and bisphenol S were negatively correlated with eGFR (r=-0.779, P＜0.001; r=-0.546, P＜0.001). (3) Among CKD patients, bisphenol A was correlated with diabetes (OR=4.951, 95%CI 1.603-15.294, P=0.005), and bisphenol S was correlated with hypertension (OR=4.466, 95%CI 1.575-12.666, P=0.005). Conclusions CKD patients have a variety of bisphenol compounds, especially bisphenol A and bisphenol S. Bisphenol A and bisphenol S have high levels, and their exposures are correlated with renal function.     

Improvement in eGFR in patients with chronic kidney disease attending a nephrology clinic

BACKGROUND: The adverse effects arising from late referral to a nephrologist of patients with chronic kidney disease (CKD) are well known. Retrospectively we examined the initial characteristics of patients referred in various stages of CKD to our nephrology division and tried to identify potential baseline factors associated with subsequent changes in estimated glomerular filtration rate (eGFR). PATIENTS AND METHODS: Between September 1997 and June 2006 1,443 patients (909 male, 534 female) with CKD, with eGFRs ranging from 15 to 89 ml/min, were referred to our nephrology division and categorized using the National Kidney Foundation classification for CKD based on eGFR. The slope of eGFR change (ml/min-1/1.73/m2-1/year-1) was determined by linear regression analysis and the patients were divided into five groups: (1) significantly progressive slope (deterioration) (more negative than -5 ml/min/year); (2) mildly progressive slope (>-5 to -1 to +1 to or=+5). RESULTS: At the first nephrology referral, 5.8% of the patients were on CKD stage 2 (eGFR: 90-60 ml/m), 46.7% on CKD stage 3 (eGFR: 59-30 ml/m), and 47.5% on CKD stage 4 (eGFR: 29-15 ml/m) CKD. Significantly improved slope was detected in 48.2% of CKD stage 2 patients, 29.3% of CKD stage 3 patients, and only 14.7% of CKD stage 4 patients (P<0.05). Being in stage 4 or stage 3 versus being in stage 2 significantly reduced the likelihood of an improved slope in logistic regression analysis whereas age, gender, presence of hypertension, and diabetes mellitus did not reach the level of significance. CONCLUSION: Referral to a nephrology clinic can lead not only to arrest of progression of CKD but also to regression/improvement. Early referral is a positive predictive factor for improvement in eGFR, which emphasizes the importance of such referral. The previously held idea that, once established, CKD progresses invariably is not valid anymore.     

Chronic kidney disease prevalence in a UK residential care home population.

BACKGROUND: Chronic kidney disease (CKD) is common ( approximately 30%) in non-institutionalized older people but little is known about the prevalence of CKD amongst older people living in residential care. METHODS: An observational study of older subjects [n = 250, median age 86 (range 67-100) years, 79% female, 100% Caucasian, 16% diabetic, 48% hypertensive, 5% known renal disease, mean number of medications 7] who were recruited over a 9-month period from 155 residential care homes in east Kent (total population 3811) using a randomization process. The estimated glomerular filtration rate (eGFR, ml/min/1.73 m(2)) was calculated using the Cockcroft and Gault equation corrected for the body surface area and the simplified Modification of Diet in Renal Disease (MDRD) Study equation. Serum cystatin C concentration was also measured. RESULTS: Using the MDRD equation 18% had eGFR >/=60, 39% stage 3A CKD (eGFR 45-59), 34% stage 3B CKD (eGFR 30-44) and 10% stage 4 CKD (eGFR 15-29). By the Cockcroft-Gault equation the equivalent figures were 3%, 18%, 48% and 31%, respectively. Agreement between the equations for staging of CKD was poor (kappa = 0.07). However, >80% of residents were categorized as having stage 3 CKD (>40% stage 3B) or worse whichever equation was used. Serum cystatin C concentration was increased in 92% of the population. Increasing age and higher body mass index were predictive of decreased renal function. CONCLUSION: Significant CKD is prevalent and unrecognized in this population. This may have important management implications particularly for treatment with renally excreted drugs, fracture prevention or managing cardiovascular risk.     

Competitive Interaction Between Fibroblast Growth Factor 23 And Asymmetric Dimethylarginine in Patients With CKD

Both fibroblast growth factor 23 (FGF-23) and asymmetric dimethylarginine (ADMA) are associated with progression of CKD. We tested the hypothesis that ADMA and FGF23 are interactive factors for CKD progression in a cohort of 758 patients with CKD in Southern Europe (mean eGFR±SD, 36±13 ml/min per 1.73 m²) and in a central European cohort of 173 patients with CKD (MMKD study, mean eGFR, 64±39 ml/min per 1.73 m²). In the first cohort, 214 patients had renal events (decrease in eGFR of >30%, dialysis, or kidney transplantation) during a 3-year follow-up. Both intact FGF-23 and ADMA predicted the incidence rate of renal events in unadjusted and adjusted analyses (P<0.001). There was a strong competitive interaction between FGF-23 and ADMA in the risk of renal events (P<0.01 in adjusted analyses); the risk associated with raised ADMA levels was highest in patients with low FGF-23 levels. These results were confirmed in the MMKD cohort, in which FGF-23 level was again an effect modifier of the relationship between plasma ADMA level and renal events (doubling of baseline serum creatinine, dialysis, or kidney transplantation) in the adjusted analyses (P<0.01). Furthermore, in the MMKD cohort there was a parallel, independent competitive interaction between symmetric dimethylarginine level and c-terminal FGF-23 level for the risk for renal events (P=0.001). These findings indicate that the association of ADMA level with the risk of CKD progression is modified by FGF-23 level and provide further evidence that dysregulation of the nitric oxide system is involved in CKD progression.     

Effect of urate-lowering therapy on renal function in chronic kidney disease stages 2-5

Objective To investigate the effect of urate-lowering therapy on renal function in chronic kidney disease (CKD) stages 2-5 patients with hyperuricemia (HUA). Methods A total of 132 patients of CKD stages 2-5 with HUA between July 2016 and December 2017 in Department of Nephrology of the Second Affiliated Hospital of Anhui Medical University were prospectively and self-controlled analyzed. Serum uric acid (SUA), estimated glomerular filtration rate (eGFR) and other clinical parameters were measured at baseline and after 1-6 months treatment. The patients were divided into group A (CKD stages 2-3a) and group B (CKD stages 3b-5) on the baseline value of eGFR. The changes of SUA and eGFR before and after treatment were compared. According to the level of SUA after 6 months treatment, patients were divided into attainment group (SUA＜360 μmol/L) and nonattainment group (SUA≥360 μmol/L). The difference of renal function in pre-treatment and post-treatment was compared. Multiple stepwise linear regression was used to analyze the relationship among the change of eGFR after receiving 6 months' treatment (deGFR) and SUA level, baseline eGFR and other indexes. Results After 1, 3, 6 months treatment, the average levels of SUA, Scr and urea nitrogen of all patients were decreased significantly while eGFR value was increased significantly (all P＜0.050) than those in pre-treatment period. After six-month-therapy, proteinuria and hematuria were improved significantly in all patients (P＜0.001, P=0.001). Compared with pre-treatment period, both the SUA levels of group A and group B were declined significantly while eGFR had a significant rise after treatment (P＜0.001). The change of eGFR post-treatment in group A was significantly higher than that of group B [(13.64±15.35) vs (8.97±9.79) ml?min-1?(1.73 m2)-1, P=0.044]. At 6 months after treatment, the eGFR value increased markedly in both attainment group and nonattainment group compared with pre-treatment period (P＜0.001). After six-month-therapy, the eGFR value in attainment group was increased more obviously than that of nonattainment group [(13.96±14.64) vs (8.03±9.69) ml?min-1?(1.73 m2)-1, P=0.021]. Multiple stepwise linear regression analysis showed that the baseline eGFR value was an influencing factor of deGFR (b=0.161, P=0.020). Conclusions The renal function of CKD stages 2-5 patients with HUA can be significantly improved by urate-lowering therapy, which can effectively reduce proteinuria and hematuria.     

The unrecognized prevalence of chronic kidney disease in diabetes.

BACKGROUND: Diabetes mellitus and chronic kidney disease (CKD) are common and exhibit synergistic associations with premature mortality. Current diabetes guidelines in the UK recommend annual urinary albumin and serum creatinine determinations to screen for diabetic kidney disease. The aim of this study was to estimate the burden of CKD in patients with diabetes and examine the ability of serum creatinine and albuminuria to detect clinically meaningful CKD compared with estimated glomerular filtration rate (eGFR). METHODS: All adults known to have diabetes in primary and secondary care in Salford, UK, alive with independent renal function on 1 January 2004 were included in this observational study (n=7596). Demographic and laboratory parameters were obtained from the Electronic Patient Record. eGFR was determined using the 4-variable modification of diet in renal disease (MDRD) formula. Clinically meaningful CKD was defined as an eGFR <60 ml/min/1.73 m(2). RESULTS: Creatinine and albuminuria were measured in the preceding 2 years in 82.3 and 55.2% of subjects, respectively. In patients with CKD, normoalbuminuria was present in 48.8%, and serum creatinine was normal (or=120 micromol/l) had a sensitivity and specificity of 45.3 and 100%, respectively, to identify CKD. The combination of abnormal creatinine and albuminuria had an improved performance but still failed to detect a large number with CKD (sensitivity 82.4%, specificity 75.4%). Serum creatinine failed to identify CKD more often in females (OR 8.22, CI 6.56-10.29). CONCLUSIONS: Undiagnosed CKD is common in diabetes. Current screening strategies, based on creatinine or albuminuria, fail to identify a considerable number of subjects with CKD. Incorporating eGFR into screening for CKD would identify individuals earlier in the natural history of the disease and enable early effective treatment to delay progression of CKD.     

CKD stage-to-stage progression in native and transplant kidney disease.

BACKGROUND: Kidney half-life and inter-stage progression rates in native chronic kidney disease (CKD) and CKD-transplant (CKD-T) remain unknown. METHODS: We examined stage-to-stage progression/regression rates in patients with CKD (n = 601) and CKD-T (n = 431) between 1991 and 2001. Kidney function was estimated by Cockcroft-Gault and MDRD eGFR formulae. Kaplan-Meier analyses determined progression and regression half-lives, defined as the time required for 50% of kidneys to advance towards a higher or lower stage of CKD, respectively. RESULTS: Most (67%) of the patients were in stage 3. Patients with native CKD were more likely to progress compared to CKD-T (inter-stage progression rates 12 vs 4 cases per 100 patient-years, P < 0.0001). Accordingly, estimated glomerular filtration rate (eGFR)-based progression half-lives were significantly shorter in CKD compared to CKD-T [6 vs 9.6 years, P < 0.0001, hazard ratio (HR) 3.1, 95% confidence interval (CI) = 2.5-3.7]. Creatinine clearance (CCR)-based stage half-lives were 7.2 months shorter in each group (5.4 and 9 years in CKD and CKD-T, respectively). Despite slower progression rates in patients with transplant kidney disease, adjusted patient survival rates were significantly decreased in CKD-T compared to CKD. Only Scr and CCR-based formulae were significantly associated with patient and allograft outcomes in the CKD-T group. Moreover, death rates were not different in stage 3 compared to stage 2 CKD-T, suggesting that eGFR and the current staging classification have a limited value to predict patient death in this cohort. CONCLUSION: Kidney half-lives per stage of CKD may be a novel tool to examine disease progression.