BACKGROUND Diabetic kidney disease is a microvascular complication of diabetes with complex pathogenesis.Wingless signaling-mediated renal fibrosis is associated with diabetic kidney disease.Dickkopf-1,a negative regu...BACKGROUND Diabetic kidney disease is a microvascular complication of diabetes with complex pathogenesis.Wingless signaling-mediated renal fibrosis is associated with diabetic kidney disease.Dickkopf-1,a negative regulator of Wingless,has been proven to participate in renal fibrosis,glucose metabolism,and inflammation.However,whether serum Dickkopf-1 levels are associated with diabetic kidney disease remains unclear.AIM To assess the relationship between serum Dickkopf-1 levels and albuminuria in individuals with type 2 diabetes.METHODS Seventy-three type 2 diabetes patients and 24 healthy individuals were enrolled in this case-control study.Diabetic individuals were separated into normal albuminuria,microalbuminuria,and macroalbuminuria groups based on their urinary albumin/creatinine ratios(UACRs).Clinical characteristics and metabolic indices were recorded.Serum Dickkopf-1 levels were determined by enzymelinked immunosorbent assay.RESULTS No significant difference in serum Dickkopf-1 levels was found between healthy individuals and the normal albuminuria group.However,the levels in the microalbuminuria group were significantly lower than those in the normal albuminuria group(P=0.017),and those in the macroalbuminuria group were the lowest.Bivariate analysis revealed that serum Dickkopf-1 levels were positively correlated with hemoglobin A1c level(r=0.368,P<0.01)and estimated glomerular filtration rate(r=0.339,P<0.01),but negatively correlated with diabetes duration(r=-0.231,P=0.050),systolic blood pressure(r=-0.369,P=0.001),serum creatinine level(r=-0.325,P<0.01),and UACR(r=-0.459,P<0.01).Multiple and logistic regression showed that serum Dickkopf-1 levels were independently associated with UACR(odds ratio=0.627,P=0.021).CONCLUSION Serum Dickkopf-1 levels are negatively associated with UACR.Lower serum Dickkopf-1 levels could be a critical risk factor for albuminuria in diabetes.展开更多
In traditional Chinese medicine, Nitraria sibirica Pall.(Nitrariaceae) is used to treat hypertension. This study determined the effects of the total alkaloids of the leaves of Nitraria sibirica(NSTA) on blood pressure...In traditional Chinese medicine, Nitraria sibirica Pall.(Nitrariaceae) is used to treat hypertension. This study determined the effects of the total alkaloids of the leaves of Nitraria sibirica(NSTA) on blood pressure and albuminuria in mice treated with angiotensin II and a high-salt diet(ANG/HS). Adult mice were divided into three groups: control; infused with angiotensin II and fed a diet containing 4% NaCl(ANG/HS; and ANG/HS plus injection of NSTA(1 mg·kg-1·d-1, i.p.). After treatment of these regimens, daily water and food intake, kidney weight, blood pressure, urinary albumin excretion, renal concentrations of inflammatory markers, including soluble intercellular adhesion molecule-1(sICAM-1) and monocyte chemoattractant protein-1(MCP-1), and the expression of renal fibrosis markers were determined. Compared to the control group, the ANG/HS group had higher blood pressure and urinary albumin excretion. Treatment with NSTA in ANG/HS mice for three weeks significantly reduced blood pressure and urinary albumin excretion. ANG/HS treatment caused elevated levels of sICAM-1 and MCP-1, as well as increased fibrosis markers. Concurrent treatment with ANG/HS and NSTA attenuated the levels and expression of renal inflammatory and fibrosis markers. Treatment with NSTA effectively reduces hypertension-induced albuminuria through the reduction of renal inflammatory and fibrosis markers.展开更多
Background: Neuttrophil gelatinase associated lipocalin (NGAL) was shown to be a good marker for predicting acute kidney injury (AKI). Some recent reports demonstrated that NGAL may be an early biomarker for kidney af...Background: Neuttrophil gelatinase associated lipocalin (NGAL) was shown to be a good marker for predicting acute kidney injury (AKI). Some recent reports demonstrated that NGAL may be an early biomarker for kidney affection in diabetic patients. The aim of this work is to investigate urinary NGAL (UNGAL) in type 2 diabetic patients with and without albuminuria. Methods: This study included 46 type 2 diabetic patients and 15 healthy age and sex matched individuals as the control group. Diabetic patients were divided into three groups according to urinary albumin excretion (UAE), normoalbuminuria, microalbuminuria and macroalbuminuria. UNGAL was measured in all populations and corrected to urinary creatinine to account for day to day variation in urine volume and transformed log. Comparison between 4 groups (control, normoalbuminuria, microalbuminuria and macroalbuminuria) was done. Results: Log UNGAL/Creatinine ratio showed significant difference when comparing control group (0.70 ± 0.58) versus normoalbuminuria (1.71 ± 1.06), microalbuminuria (1.57 ± 0.72) and macroalbuminuria (1.92 ± 0.63), however, there was no significant difference among diabetic groups. Pearson’s correlation showed that log UNGAL/Creatinine ratio positively correlated with glycated hemoglobin (HbA1c) and inversely with estimated glomerular filtration rate (eGFR). Regression analysis showed that HbA1c, urinary creatinine and eGFR were the independent predictors of log UNGAL/Creatinine ratio. Conclusion: Tubular markers like UNGAL may be early elevated in type 2 diabetic patients even before the incidence of glomerular injury detected by microalbuminuria and it can be used as an early marker for detection of kidney involvement in diabetic patients.展开更多
Objective: To evaluate the efficacy of Breviscapine on essential hypertension (EH) patients complicated with micro-albuminuria of renal impairment. Methods: Seventy-six EH patients were randomly assigned to the contro...Objective: To evaluate the efficacy of Breviscapine on essential hypertension (EH) patients complicated with micro-albuminuria of renal impairment. Methods: Seventy-six EH patients were randomly assigned to the control group and the treated group, the former was given amlodipine, captopril/uropidil and the latter was given in addition Breviscapine intravenously dripped for 2 treatment courses. The indexes of serum creatinine (Cr), blood urea nitrogen (BUN), blood and urinary β 2-microglobulin (β 2-MG), and quantitative determination of 24 hrs urinary protein were evaluated before and after treatment. Results: In the control group, compared with before treatment, the quantitative determination of 24 hrs urinary protein got reduced significantly ( P <0.05), while in the treated group, both urinary β 2-MG and quantitative determination of 24 hrs urinary protein got lowered significantly ( P <0.05 and P <0.01). But after treatment, compared with the control group, urinary β 2-MG and quantitative determination of 24 hrs urinary protein in the treated group were obviously reduced ( P <0.05). Conclusion: Besides lowering blood pressure effectively, Breviscapine could improve the renal function significantly and reduce the urinary micro-albuminuria, hence showing promising effect on renal protection.展开更多
AIM： To access the association between albuminuria levels and arterial stiffness in non-diabetic patients with hypertension and chronic kidney disease （CKD） stages 1-2, treated with renin angiotensin blockade agent...AIM： To access the association between albuminuria levels and arterial stiffness in non-diabetic patients with hypertension and chronic kidney disease （CKD） stages 1-2, treated with renin angiotensin blockade agents plus other hypertensive drugs when needed.METHODS： One hundred fifteen patients [median age 52 years （68% males）] were consequently enrolled in the study. For each patient, we recorded gender, age, body mass index （BMI）, peripheral systolic blood pressure （pSBP）, peripheral diastolic blood pressure, peripheral pulse pressure, central systolic blood pressure （cSBP）, central diastolic blood pressure （cDBP）, central pulse pressure （cPP）, hematocrit, hemoglobin, hsCRP, total cholesterol triglycerides, high-density lipoprotein-C, low-density lipoprotein-C, calcium, phosphorus, parathormone, and albumin, as well as 24 h urine albumin excretion. According to 24-h urine albumin collection, patients were then classified as those with moderately increased albuminuria （formerly called macroalbuminuria） （≤ 300 mg/d） and those with severely increased albuminuria （formerly called macroaluminuria （〉 300 mg/d）. We considered aortic stiffness （AS） indices [carotid femoral pulse wave velocity （PWVc-f） and augmentation index （AIx）] as primary outcomes of the study. We explored potential correlations between severely increased albuminuria and AS indices using a multiple linear regression model. RESULTS： Fifty-eight patients were included in the moderately increased albuminuria group and 57 in the severely increased albuminuria. Blood pressure measurements of the study population were 138 ± 14/82 ± 1.3 mmHg （systolic/diastolic）. There were no significant differences in age, sex, and BP measurements between the two groups. Patients with severely increased albuminuria had higher PWV and AIx than patients with moderately increased albuminuria （P 〈 0.02, P 〈 0.004, respectively）. In addition these patients exhibited higher BMI （P 〈 0.03）, hsCRP （P 〈 0.001）, and fibrinogen levels （P 〈 0.02） compared to patients with moderately increased albuminuria. In multivariate linear regression analysis, severely increased albuminuria （β = 1.038, P 〈 0.010） pSBP （β = 0.028, P 〈 0.034） and Ht （β = 0.171, P = 0.001） remained independent determinants of the increased PWVc-f. Similarly, severely increased albuminuria （β = 4.385, P 〈 0.012）, cSBP （β = 0.242, P 〈 0.001）, cPP （β = 0.147, P 〈 0.01） and Ht levels （β = 0.591, P 〈 0.013） remained independent determinants of increased AIx.CONCLUSION： These fndings demonstrate an independent association between AS indices and severely increased albuminuria in non-diabetic, hypertensive patients with CKD stages 1-2 treated with renin angiotensin aldosterone system blockers.展开更多
Background: Diabetic nephropathy is the most common cause of chronic kidney disease and the number afflicted patients continues to rise. The presence of proteinuria has been considered as a prerequisite for the diagno...Background: Diabetic nephropathy is the most common cause of chronic kidney disease and the number afflicted patients continues to rise. The presence of proteinuria has been considered as a prerequisite for the diagnosis of diabetic nephropathy. But one third to one half of type 2 diabetics with CKD have no proteinuria and the pathology of non proteinuric CKD in this group remains unclear as renal biopsy is commonly not performed in these patients. The present study addresses the question: Can a classical diabetic nephropathy occur in the absence of proteinuria? Method: We examined renal biopsies of subjects who underwent nephrectomy from 1999 to 2009 for renal cancer, had eGFR < 60 ml/min and no microalbuminuria or proteinuria. 10 diabetics were matched with 10 non diabetics for age, hypertension and baseline creatinine. Results: The diabetic subjects had advanced diabetic lesions even in absence of proteinuria. Tubules and tubular-interstitium was relatively well preserved. Diabetic glomerulosclerosis can occur in the absence of microalbuminuria. Conclusions: It is becoming increasingly apparent that a considerable proportion of subjects with type 2 diabetes can develop renal impairment in the absence of albuminuria. Diabetic glomerulosclerosis may develop before the proteinuria can be detected and relying on albumin excretion as first sign for renal involvement may be too late in diagnosing and modifying the progression of the kidney disease.展开更多
Podocyte loss was well known in type 2 diabetic nephropathy patients. The objective of the present study was to determine the number of podocytes and the degree of albuminuria in diabetic KK-Ay/Ta (KK-Ay) mice which h...Podocyte loss was well known in type 2 diabetic nephropathy patients. The objective of the present study was to determine the number of podocytes and the degree of albuminuria in diabetic KK-Ay/Ta (KK-Ay) mice which had been reported as diabetic nephropathy model. Diabetic KK-Ay mice, diabetic KK/Ta mice and non-diabetic BALB/cA Jcl (BALB/cA) mice were studied. We analyzed glomerular lesions in all mice by morphometric analysis and immunofluorescence to determine the number of podocytes. Level of urinary albumin was also measured. Glomerular enlargement and mesangial expansion were observed in KK-Ay mice. Mean number of podocytes per glomerulus (NG pod) in diabetic KK-Ay mice was significantly lower than that in non-diabetic BALB/cA mice. Mean NG pod/glomerular area (GA) per glomerulus was also significantly decreased in diabetic KK-Ay mice. The level of urinary albumin/creatinine ratio (ACR) in diabetic KK-Ay mice was significantly higher than that in non-diabetic BALB/cA mice. These data suggest that podocyte loss might induce albuminuria in KK-Ay mice. This finding confirmed our previous report that KK-Ay mice, especially in terms of histological findings, are a suitable animal model for glomerular injury in type 2 diabetic nephropathy.展开更多
AIMTo investigate the relationship between circadian vari-ations in blood pressure （BP） and albuminuria at rest, and during exercise in non-hypertensive type 2 diabetes （T2D） patients.METHODSWe conducted a cross-s...AIMTo investigate the relationship between circadian vari-ations in blood pressure （BP） and albuminuria at rest, and during exercise in non-hypertensive type 2 diabetes （T2D） patients.METHODSWe conducted a cross-sectional study in well controlled T2D patients, non-hypertensive, without clinical pro-teinuria and normal creatinine clearance. In each parti-cipant, we recorded the BP using ambulatory bloodTankeu AT et al . Exercise-induced albuminuria and BP in T2DMpressure monitoring （ABPM） for 24-h, and albuminuria at rest and after a standardized treadmill exercise.RESULTSWe enrolled 27 type 2 patients with a median age of 52; and a mean duration of diabetes and HbA1c of 3.6 ± 0.8 years and 6.3% ± 0.5% respectively. Using a 24-h ABPM, we recorded a mean diurnal systolic blood pressure （SBP） of 128 ± 17 mmHg vs nocturnal of 123 ± 19 mmHg （ P = 0.004）, and mean diurnal diastolic blood pressure （DBP） of 83 ± 11 mmHg vs nocturnal 78 ± 14 mmHg （ P = 0.002）. There was a signifcant difference between albuminuria at rest [median = 23 mg, interquartile range （IQR） = 10-51] and after exercise （median = 35 mg, IQR = 23-80, P 〈 0.001）. Patients with exercise induced albuminuria had an increase in nocturnal BP values on all three components （128 mmHg vs 110 mmHg, P = 0.03 for SBP; 83 mmHg vs 66 mmHg, P = 0.04; 106 vs 83, P = 0.02 for mean arterial pressure）, as well as albuminuric patients at rest. Moreover, exercise induced albuminuria detect a less increase in nocturnal DBP （83 vs 86, P = 0.03） than resting albuminuria.CONCLUSIONExercise induced albuminuria is associated with anincrease in nocturnal BP values in T2D patients.展开更多
BACKGROUND Diabetic kidney disease is one of the common complications of type 2 diabetes(T2D).There are no typical symptoms in the early stage,and the disease will progress to moderate and late stage when albuminuria ...BACKGROUND Diabetic kidney disease is one of the common complications of type 2 diabetes(T2D).There are no typical symptoms in the early stage,and the disease will progress to moderate and late stage when albuminuria reaches a high level.Treatment is difficult and the prognosis is poor.At present,the pathogenesis of diabetic kidney disease is still unclear,and it is believed that it is associated with genetic and environmental factors.AIM To explore the relationship between the glucokinase regulatory protein(GCKR)gene rs780094 polymorphism and T2D with albuminuria.METHODS We selected 252 patients(126 males and 126 females)with T2D admitted to our hospital from January 2020 to October 2020,and 66 healthy people(44 females and 22 males).According to the urinary albumin/creatinine ratio,the subjects were divided into group I(control),group II(T2D with normoalbuminuria),group III(T2D with microalbuminuria),and group IV(T2D with macroalbuminuria).Additionly,the subjects were divided into group M(normal group)or group N(albuminuria group)according to whether they developed albuminuria.We detected the GCKR gene rs780094 polymorphism(C/T)of all subjects,and measured the correlation between GCKR gene rs780094 polymorphism(C/T)and T2D with albuminuria.RESULTS Gene distribution and genotype distribution among groups I-IV accorded with the Hardy-Weinberg equilibrium.Genotype frequency was significantly different among the four groups (P = 0.048, χ^(2)= 7.906). T allele frequency in groups II, III, and IV was significantly higherthan that in group I. Logistic regression analysis of the risk factors for T2D with albuminuria showed that the CT +TT genotype (odds ratio = 1.710, 95% confidence interval: 1.172-2.493) was a risk factor.CONCLUSION CT + TT genotype is a risk factor for T2D with albuminuria. In the future, we can assess the risk of individualscarrying susceptible genes to delay the onset of T2D.展开更多
AIM:To study the relation between hepatitis C virus (HCV) genotype 4 and microalbuminuria and renal impairment in relation to hepatic histology, and viremia in the absence of cryoglobulinemia, and to examine the effec...AIM:To study the relation between hepatitis C virus (HCV) genotype 4 and microalbuminuria and renal impairment in relation to hepatic histology, and viremia in the absence of cryoglobulinemia, and to examine the effect of treatment on microalbuminuria.METHODS: Three hundred subjects, including 233 HCV genotype-4 infected patients, were tested for cryoglobulinemia, microalbuminuria, albumin creatinine ratio (ACR), urea, creatinine, and estimated glomerular filtration rate (eGFR). The parameters were measured again in the HCV patients after 48 wk of treatment with pegylated interferon and ribavirin.RESULTS: Significantly higher levels of microalbumin- uria were detected in HCV-positive patients compared to HCV-negative controls (median 9.5 vs 5.9, respectively, Kruskal-Wallis P=0.017). Log microalbuminuria was significantly correlated with hepatic inflammation (r=0.13, P=0.036) and f ibrosis (r=0.12, P=0.061), but not with viral load (r=-0.03, P=0.610), or alanine transaminase (r=-0.03, P=0.617). Diabetes mellitus neither significantly moderated (χ2=0.13, P=0.720), nor mediated (Sobel test P=0.49) the HCV effect. HCV status was signifi cantly associated with log microalbu-minuria (χ2=4.97, P=0.026), adjusting for age, gender, diabetes, cryoglobulinemia, urea and creatinine. A positive HCV status was not significantly associated with low eGFR (<60 mL/min every 1.73 m2) [odds ratio (OR): 0.5, 95% confidence interval (CI):0.2-1.4], nor with high ACR (OR: 1.7, 95% CI:0.7-4.1). End-of-treatment response (ETR) was achieved in 51.9% of patients. Individuals with ETR had significantly lower microalbuminuria post-treatment (χ2=8.19, P=0.004).CONCLUSION: HCV affected the development of microalbuminuria independent of diabetes or cryoglobulinemia. Combination therapy of pegylated interferon-ribavirin had a positive effect in reducing microalbuminuria.展开更多
Albuminuria predicts cardiovascular disease (CVD) events but it is likely to vary over time in a nonlinear fashion. The aim of this study was to estimate the potentially differing predictive effect of albuminuria on t...Albuminuria predicts cardiovascular disease (CVD) events but it is likely to vary over time in a nonlinear fashion. The aim of this study was to estimate the potentially differing predictive effect of albuminuria on the risk of CVD or related death over time. Data were from a cohort study of 3505 predominately indigenous adults from remote communities in Queensland,Australia, 1999-2006. Cox Proportional Hazards model analysis of the predictive effects of urinary albumin creatinine ratio on the risk of CVD or CVD-related death was undertaken for incident and prevalent CVD. Analyses sequentially removed those who had a cardiovascular event or related death for the first year through to six years. The baseline prevalence of microalbuminuria was 21.2% and for macroalbuminuria 6.7%. The incidence of CVD was92 in13,812 person-years. Microalbuminuria predicted incident CVD with a Hazard Ratio (HR) of 3.0 (95% CI 1.83 - 4.96) and for macroalbuminuria HR 10.8 (95% CI 6.58 - 17.68) and for those with pre-existing CVD, HR 2.6 (95% CI 1.65 - 3.97) and HR 9.7 (95% CI 6.38 - 14.82) respectively. People with macroalbuminuria who survived the first three years had a crude HR of an incident cardiovascular event or death of 13.0 (95% CI 6.45 - 26.39) to a peak of 32.3 (95% CI 8.55 - 121.77) for those who survived the first five years. The hazard appeared to drop in the 6th year although this is based on small numbers.The first three years after finding macroalbuminuria provide a potential window opportunity to actively manage the risk of incident CVD before the risk elevates.展开更多
AIM To investigated the relationship between exerciseinduced ambulatory blood pressure measurement(ABPM) abnormalities in type 1 diabetes mellitus(T1DM) adolescents. METHODS We conducted a case-control at the National...AIM To investigated the relationship between exerciseinduced ambulatory blood pressure measurement(ABPM) abnormalities in type 1 diabetes mellitus(T1DM) adolescents. METHODS We conducted a case-control at the National Obesity Center of the Yaoundé Central Hospital, Cameroon. We compared 24 h ABPM and urinary albumin-to-creatinine ratio(ACR) at rest and after a standardized treadmill exercise between 20 Cameroonian T1 DM patients and 20 matched controls. T1 DM adolescents were aged 12-18 years, with diabetes for at least one year, without proteinuria, with normal office blood pressure(BP) and renal function according to the general referencepopulation. Non-diabetic controls were adolescents of general population matched for sex, age and BMI.RESULTS Mean duration of diabetes was 4.2 ± 2.8 years. The mean 24 h systolic blood pressure(SBP) and diastolic blood pressure(DBP) were respectively 116 ± 9 mm Hg in the diabetic group vs 111 ± 8 mm Hg in the nondiabetic(P = 0.06), and 69 ± 7 mm Hg vs 66 ± 5 mm Hg(P = 0.19). There was no difference in the diurnal pattern of BP in diabetes patients and non-diabetic controls(SBP: 118 ± 10 mm Hg vs 114 ± 10 mm Hg, P = 0.11; DBP: 71 ± 7 mm Hg vs 68 ± 6 mm Hg, P = 0.22). Nighttime BP was higher in the diabetic group with respect to SBP(112 ± 11 mm Hg vs 106 ± 7 mm Hg, P = 0.06) and to the mean arterial pressure(MAP)(89 ± 9 mm Hg vs 81 ± 6 mm Hg, P = 0.06). ACR at rest was similar in both groups(5.5 mg/g vs 5.5 mg/g, P = 0.74), but significantly higher in diabetes patients after exercise(10.5 mg/g vs 5.5 mg/g, P = 0.03). SBP was higher in patients having exercise-induced albuminuria(116 ± 10 mm Hg vs 108 ± 10 mm Hg, P = 0.09). CONCLUSION Exercise-induced albuminuria could be useful for early diagnosis of kidney damage in adolescents with T1 DM.展开更多
BACKGROUND Diabetes mellitus is considered a leading contributor to severe coronavirus disease 2019(COVID-19).AIM To characterize differences between hospitalized diabetic patients with vs without COVID-19,and paramet...BACKGROUND Diabetes mellitus is considered a leading contributor to severe coronavirus disease 2019(COVID-19).AIM To characterize differences between hospitalized diabetic patients with vs without COVID-19,and parameters associated with COVID-19 severity for prediction.METHODS This case-control study included 209 patients with type 2 diabetic mellitus hospitalized at the Galilee Medical Center(Nahariya,Israel)and recruited between September 2020 and May 2021,65 patients with COVID-19 infection in dedicated wards and 144 COVID-19-negative patients in internal medicine wards hospitalized due to other reasons.Clinical parameters-including age,type of antiglycemic medications,presence of retinopathy,smoking history,body mass index(BMI),glycosylated hemoglobin,maximum neutrophil:lymphocyte ratio(NLR_(max)),C-reactive protein(CRP),estimated glomerular filtration rate(eGFR),and albumin(blood and urine)-were compared between the two primary patient groups,and then between COVID-19-negative patients hospitalized due to infectious vs non-infectious disease.Finally,we explored which parameters were associated with severe COVID-19 pneumonia.RESULTS COVID-19-negative patients were older(63.9±9.9 vs 59.8±9.2,P=0.005),and had longer duration of diabetes(P=0.031),lower eGFR(P=0.033),higher albumin(P=0.026),lower CRP(P<0.001),greater smoking prevalence(P<0.001),and more baseline albuminuria(54.9%vs 30.8%,P=0.005)at admission;70%of COVID-19 patients with albuminuria had moderate-range albuminuria(albumin:creatinine 30-300 mg/g).Most of the patients with albuminuria had chronic kidney disease stage II(CKD II).Oral antiglycemic therapies were not significantly different between the two groups.Multivariable logistic regression showed that higher BMI was significantly associated with severe COVID-19(OR 1.24,95%CI:1.01-1.53,P=0.04),as was higher NLR_(max)(OR 1.2,95%CI:1.06-1.37,P=0.005).Surprisingly,pre-hospitalization albuminuria,mostly moderate-range,was associated with reduced risk(OR 0.09,95%CI:0.01-0.62,P=0.015).Moderate-range albuminuria was not associated with bacterial infections.CONCLUSION Moderate-range albuminuria in COVID-19-positive diabetic patients with CKD II is associated with less severe COVID-19.Further studies should explore this potential biomarker for risk of COVID-19-related deterioration and early interventions.展开更多
Introduction: It was recently reported that candesartan, an angiotensin II receptor blocker, had a protective effect against cardiovascular events, comparable to that of calcium channel antagonists. Moreover, a renopr...Introduction: It was recently reported that candesartan, an angiotensin II receptor blocker, had a protective effect against cardiovascular events, comparable to that of calcium channel antagonists. Moreover, a renoprotective effect and anti-diabetic action of candesartan had also been demonstrated. However, whether the renoprotective effect of candesartan, especially in diabetes, was dose-dependent or not remain to be fully elucidated. The present study attempted to clarify the dose effect of renoprotection by candesartan in Japanese type 2 diabetic patients. Subjects and Method: In this case series study, we recruited 26 type 2 diabetic patients with albuminuria whose blood pressure did not reach the target BP level (<130/80 mmHg) despite administration of 4 or 8 mg/day of candesartan. Subsequently, these lower doses of candesartan were increased to the maximal dose in Japan, 12 mg/day. Clinical parameters were examined before, at 6 and 12 months after the increase in dose. Results: An ameliorating effect of the increased dose of candesartan on albuminuria and hypertension was distinctly observed. No severe adverse effect was observed. Conclusion: It was highly possible that the maximal dose of candesartan provided more effective renoprotection in hypertensive type 2 diabetic patients initially treated with lower doses of candesartan.展开更多
Background The influence ofalbuminuria on clinical outcomes in patients with type 2 diabetes mellitus （T2DM） after elective percutaneous coronary intervention（PCI） with drug-eluting stent （DES） implantation rema...Background The influence ofalbuminuria on clinical outcomes in patients with type 2 diabetes mellitus （T2DM） after elective percutaneous coronary intervention（PCI） with drug-eluting stent （DES） implantation remains unclear. Methods We observed 386 patients with T2DM after elective PCI. The patients were stratified based on the early morning urinary albumin： negative （n = 309）, trace （urine dipstick trace, n = 39）, and positive group （urine dipstick≥1＋, n = 38）. Kaplan-Meier curve analysis was used to compare the cumulative rates of clinical outcomes （all-cause death, cardiovascular death, MACEs： cardiovascular death, non-fatal myocardial in- farction, stroke or revascularization）. Cox regression was performed to assess the risk factors for all-cause death and cardiovascular death. Results Median follow-up was 25 months （IQR： 17-37 months）. Twenty eight （7.3%, 13 in the negative group, 3 in the trace group and 12 in the positive group） patients died during the entire study period, 2 of them （0.7%,1 in the negative group and I in the trace group）died during index hospitalization. Posi- tive albuminuria group suffered more contrast-induced acute kidney injury （CI-AKI） and dialysis during hospital- ization. The cumulative all-cause death （34.5% vs. 8.9% vs. 4.9%, P Negati Trace = 0.333, PNegati Positive 〈（ 0.001, PTracevs.Positive = 0.013, log-rank P 〈 0.001） and cardiovascular death （29.5% vs. 7.4% vs. 3.4%, P Negative vs Trace = 0.458, PNegati Positive 〈 0.001, PTrace vs.Positive = 0.014, log-rank P 〈 0.001） were highest in the positive group. MACE also tends to increase in positive group. After adjusting for potential confounding risk factors, positive albuminuria was still related to all-cause death （HR = 5.13, 95% CI： 2.21-11.89, P 〈 0.001） and cardiovascular death （HR = 5.40, 95% CI： 2.07-14.09, P = 0.001）. Conclusion Preprocedural albuminuria predicts poor clinical outcomes, including all-cause death and cardiovascular death, in T2DM patients after elective PCI with DES implantation.展开更多
Background: Sickle Cell Disease (SCD) renal abnormalities commence early in childhood. The glomerular abnormalities, glomerular hyperfiltration and albuminuria are the most prevalent. However, these SCD glomerulopathi...Background: Sickle Cell Disease (SCD) renal abnormalities commence early in childhood. The glomerular abnormalities, glomerular hyperfiltration and albuminuria are the most prevalent. However, these SCD glomerulopathies have not been considered exclusively in the adolescent age group. Objective: To determine the prevalence of glomerular hyperfiltration and albuminuria as well as identify the determinants for glomerular hyperfiltration in adolescents with SCD. Patients and Methods: The electronic patient records of 153 adolescents with SCD aged 10 - <19 years, attending the Paediatrics Haematology Clinic at Evelina London Children’s Hospital, United Kingdom, were reviewed from the 10<sup>th</sup> to 23<sup>rd</sup> June 2019. Clinical information and laboratory parameters were obtained. The glomerular filtration rate was derived using the Bedside Schwartz’s method. Grouping of the adolescents was based on the presence and absence of glomerular hyperfiltration, which was defined as glomerular filtration rate > 140 ml/min/m<sup>2</sup>. The presence of albuminuria was defined as urine albumin-to-creatinine ratio > 3 mg/mmol or protein-to-creatinine ratio of >15 mg/mmol. The clinical and laboratory determinants of glomerular hyperfiltration in the total study population were investigated. Result: Prevalence of glomerular hyperfiltration was 33.3% in the adolescents studied, and that of albuminuria was 15.7% amongst the SCD adolescents studied, of which 13.7% of those with glomerular hyperfiltration also had albuminuria. On univariable analysis, the SCD adolescents with glomerular hyperfiltration had significantly lower weight (48.0 ± 18.0 versus 54.8 ± 17.0 kg;<i>p</i> = 0.02), height (155.1 ± 13.1 versus 160.6 ± 13.1 cm;<i>p</i> = 0.01), body mass index (19.4 ± 5.0 versus 21.0 ± 4.3;<i>p</i> = 0.04), haemoglobin level (88.7 ± 13.3 versus 98.1 ± 21.7 g/L;<i>p</i> = 0.001), and serum creatinine level (0.4 ± 0.1 versus 0.6 ± 0.2 mg/dl;<i>p</i> = 0.0001) as compared to those with no glomerular hyperfiltration. The SCD adolescents with glomerular hyperfiltration also had significantly higher lactate dehydrogenase levels (525.9 ± 180.3 versus 449.6 ± 170.3 IU/L;<i>p</i> = 0.01) than those with no glomerular hyperfiltration. But, multivariable analysis revealed no associations. Conclusion: This study revealed that the prevalence of glomerular hyperfiltration in SCD children in the adolescent age group is high, and the high glomerular filtration rates begin to decline toward normal values in middle adolescence.展开更多
BACKGROUND Global longitudinal strain(GLS)of the left ventricular is a highly sensitive and reliable marker of systolic function and GLS outperforms ejection fraction(EF)in detecting preclinical left ventricular systo...BACKGROUND Global longitudinal strain(GLS)of the left ventricular is a highly sensitive and reliable marker of systolic function and GLS outperforms ejection fraction(EF)in detecting preclinical left ventricular systolic dysfunction(LVSD).In patients with type 2 diabetes(DM2)albuminuria is a predictor of symptomatic heart failure,but data on the relationship between GLS and albuminuria are conflicting.AIM To explore the relationship between GLS and albuminuria in a contemporary cohort of DM2 patients.METHODS The study was performed on DM2 patients consecutively enrolled in the TESEO study.Patients with symptoms/signs of heart failure,EF<50%,coronary artery,other cardiac diseases,or non-adequate acoustic window for GLS assessment were excluded.We collected clinical data,screened for complications,and measured GLS by speckle-tracking echocardiography.Univariate and multiple linear regression analyses were performed to identify independent explanatory variables associated with GLS.Logistic regression analysis was used to assess whether albuminuria was independently associated with GLS-diagnosed(GLS>-18%)LVSD.RESULTS Patients(n=193,age:60.6±8.1,male:57%)had a short DM2 duration(3.8±4.9 years)and good metabolic control(glycated haemoglobin A1c:6.5%±1.0).Preclinical GLS-LVSD was present in 21.8%of the patients.GLS values were significantly higher in patients with albuminuria(-19.88±2.16 vs-18.29±2.99,P<0.001)and in multivariate analysis natural logarithm of albumin-creatinine ratio and uric acid were independent predictors of GLS.In logistic regression analysis,albuminuria was associated with a 6.01(95%confidence interval:1.874-19.286)increased odds ratio of GLS-LVSD,independent of age,sex,diastolic blood pressure,chronic kidney disease,EF,mitral annulus velocity lateral,uric acid,and treatments.CONCLUSION Albuminuria was independently associated with subclinical LVSD in our contemporary cohort of DM2 patients.展开更多
The underlying molecular changes that result in minimal change disease(ne-phrotic syndrome)require an in-depth analysis.Current molecular studies have shown the involvement of zinc fingers and homeobox transcriptional...The underlying molecular changes that result in minimal change disease(ne-phrotic syndrome)require an in-depth analysis.Current molecular studies have shown the involvement of zinc fingers and homeobox transcriptional factors in its pathogenesis.The application of therapeutic drugs relies on understanding the cascade of molecular events to determine their efficacy in managing the clinical condition.展开更多
Emerging evidence suggests that intestinal dysbiosis and chronic low-gradeinflammation play a critical role in the development and progression of diabetickidney disease (DKD), particularly in the elderly. Reduced micr...Emerging evidence suggests that intestinal dysbiosis and chronic low-gradeinflammation play a critical role in the development and progression of diabetickidney disease (DKD), particularly in the elderly. Reduced microbial diversity,loss of beneficial genera and over-representation of pathogenic bacteria are closelyassociated with declining kidney function. There is a possible causal relationshipbetween specific gut microbiota profiles and DKD. Experimental models alsoshow that gut-derived metabolites and altered intestinal permeability can promoterenal inflammation, fibrosis and metabolic dysfunction. This editorialdiscusses the implications of these findings for future research and clinicalpractice, emphasizing the growing potential of microbiota-targeted therapies.Understanding the gut–kidney axis could ultimately open up new avenues forprecision nephrology and metabolic care.展开更多
BACKGROUND Diabetes is a significant risk factor for chronic kidney disease,and diabetic kidney disease(DKD)is prevalent among patients with diabetes.Previous studies have indicated that the duration of diabetes and p...BACKGROUND Diabetes is a significant risk factor for chronic kidney disease,and diabetic kidney disease(DKD)is prevalent among patients with diabetes.Previous studies have indicated that the duration of diabetes and poor glycemic control are associated with an increased risk of DKD,but data on how the duration and severity of hyperglycemia specifically relate to DKD progression are limited.AIM To investigate the relationship between diabetes duration and glycemic control,and DKD progression in South Korea.METHODS We included 2303 patients with diabetes using the 2019-2021 Korea National Health and Nutrition Examination Surveys data.DKD was defined as an estimated glomerular filtration rate(eGFR)<60 mL/min per 1.73 m2,urinary albumin-to-creatinine ratio≥30 mg/g,or both.Diabetes duration and severity were classified into six categories each.RESULTS DKD prevalence was 25.5%.The DKD risk significantly increased in diabetes lasting 10-15 years or hemoglobin A1C(HbA1c)≥8%compared to patients with newly diagnosed diabetes or HbA1c<6.5%.Albuminuria developed with shorter diabetes duration and lower HbA1c than eGFR decline.The adjusted odds ratios for DKD were 3.77[95%confidence interval(95%CI):2.60-5.45]and 4.91(95%CI:2.80-8.63)in patients with diabetes lasting≥20 years and HbA1c≥10%,respectively,compared to those with new-onset diabetes and HgA1c<6.5%.CONCLUSION Patients with diabetes lasting>10 years or HbA1c>8%had a higher risk of DKD,emphasizing the importance of early monitoring and management is crucial to prevent DKD progression.展开更多
基金Supported by National Natural Science Foundation of China,No.81870593Natural Science Foundation of Shandong Province of China,No.ZR2018MH008+1 种基金Shandong Province Higher Educational Science and Technology Program for Youth Innovation,No.2020KJL004Municipal Science and Technology Development Program of Weifang,No.2018YX025.
文摘BACKGROUND Diabetic kidney disease is a microvascular complication of diabetes with complex pathogenesis.Wingless signaling-mediated renal fibrosis is associated with diabetic kidney disease.Dickkopf-1,a negative regulator of Wingless,has been proven to participate in renal fibrosis,glucose metabolism,and inflammation.However,whether serum Dickkopf-1 levels are associated with diabetic kidney disease remains unclear.AIM To assess the relationship between serum Dickkopf-1 levels and albuminuria in individuals with type 2 diabetes.METHODS Seventy-three type 2 diabetes patients and 24 healthy individuals were enrolled in this case-control study.Diabetic individuals were separated into normal albuminuria,microalbuminuria,and macroalbuminuria groups based on their urinary albumin/creatinine ratios(UACRs).Clinical characteristics and metabolic indices were recorded.Serum Dickkopf-1 levels were determined by enzymelinked immunosorbent assay.RESULTS No significant difference in serum Dickkopf-1 levels was found between healthy individuals and the normal albuminuria group.However,the levels in the microalbuminuria group were significantly lower than those in the normal albuminuria group(P=0.017),and those in the macroalbuminuria group were the lowest.Bivariate analysis revealed that serum Dickkopf-1 levels were positively correlated with hemoglobin A1c level(r=0.368,P<0.01)and estimated glomerular filtration rate(r=0.339,P<0.01),but negatively correlated with diabetes duration(r=-0.231,P=0.050),systolic blood pressure(r=-0.369,P=0.001),serum creatinine level(r=-0.325,P<0.01),and UACR(r=-0.459,P<0.01).Multiple and logistic regression showed that serum Dickkopf-1 levels were independently associated with UACR(odds ratio=0.627,P=0.021).CONCLUSION Serum Dickkopf-1 levels are negatively associated with UACR.Lower serum Dickkopf-1 levels could be a critical risk factor for albuminuria in diabetes.
基金supported by the West Light Foundation of the Chinese Academy of Science(No.XBBS201011)AHA Grant-in-Aid(AHASE 0054)DODI grant from Georgia Health Sciences University to M.H.Wang
文摘In traditional Chinese medicine, Nitraria sibirica Pall.(Nitrariaceae) is used to treat hypertension. This study determined the effects of the total alkaloids of the leaves of Nitraria sibirica(NSTA) on blood pressure and albuminuria in mice treated with angiotensin II and a high-salt diet(ANG/HS). Adult mice were divided into three groups: control; infused with angiotensin II and fed a diet containing 4% NaCl(ANG/HS; and ANG/HS plus injection of NSTA(1 mg·kg-1·d-1, i.p.). After treatment of these regimens, daily water and food intake, kidney weight, blood pressure, urinary albumin excretion, renal concentrations of inflammatory markers, including soluble intercellular adhesion molecule-1(sICAM-1) and monocyte chemoattractant protein-1(MCP-1), and the expression of renal fibrosis markers were determined. Compared to the control group, the ANG/HS group had higher blood pressure and urinary albumin excretion. Treatment with NSTA in ANG/HS mice for three weeks significantly reduced blood pressure and urinary albumin excretion. ANG/HS treatment caused elevated levels of sICAM-1 and MCP-1, as well as increased fibrosis markers. Concurrent treatment with ANG/HS and NSTA attenuated the levels and expression of renal inflammatory and fibrosis markers. Treatment with NSTA effectively reduces hypertension-induced albuminuria through the reduction of renal inflammatory and fibrosis markers.
文摘Background: Neuttrophil gelatinase associated lipocalin (NGAL) was shown to be a good marker for predicting acute kidney injury (AKI). Some recent reports demonstrated that NGAL may be an early biomarker for kidney affection in diabetic patients. The aim of this work is to investigate urinary NGAL (UNGAL) in type 2 diabetic patients with and without albuminuria. Methods: This study included 46 type 2 diabetic patients and 15 healthy age and sex matched individuals as the control group. Diabetic patients were divided into three groups according to urinary albumin excretion (UAE), normoalbuminuria, microalbuminuria and macroalbuminuria. UNGAL was measured in all populations and corrected to urinary creatinine to account for day to day variation in urine volume and transformed log. Comparison between 4 groups (control, normoalbuminuria, microalbuminuria and macroalbuminuria) was done. Results: Log UNGAL/Creatinine ratio showed significant difference when comparing control group (0.70 ± 0.58) versus normoalbuminuria (1.71 ± 1.06), microalbuminuria (1.57 ± 0.72) and macroalbuminuria (1.92 ± 0.63), however, there was no significant difference among diabetic groups. Pearson’s correlation showed that log UNGAL/Creatinine ratio positively correlated with glycated hemoglobin (HbA1c) and inversely with estimated glomerular filtration rate (eGFR). Regression analysis showed that HbA1c, urinary creatinine and eGFR were the independent predictors of log UNGAL/Creatinine ratio. Conclusion: Tubular markers like UNGAL may be early elevated in type 2 diabetic patients even before the incidence of glomerular injury detected by microalbuminuria and it can be used as an early marker for detection of kidney involvement in diabetic patients.
文摘Objective: To evaluate the efficacy of Breviscapine on essential hypertension (EH) patients complicated with micro-albuminuria of renal impairment. Methods: Seventy-six EH patients were randomly assigned to the control group and the treated group, the former was given amlodipine, captopril/uropidil and the latter was given in addition Breviscapine intravenously dripped for 2 treatment courses. The indexes of serum creatinine (Cr), blood urea nitrogen (BUN), blood and urinary β 2-microglobulin (β 2-MG), and quantitative determination of 24 hrs urinary protein were evaluated before and after treatment. Results: In the control group, compared with before treatment, the quantitative determination of 24 hrs urinary protein got reduced significantly ( P <0.05), while in the treated group, both urinary β 2-MG and quantitative determination of 24 hrs urinary protein got lowered significantly ( P <0.05 and P <0.01). But after treatment, compared with the control group, urinary β 2-MG and quantitative determination of 24 hrs urinary protein in the treated group were obviously reduced ( P <0.05). Conclusion: Besides lowering blood pressure effectively, Breviscapine could improve the renal function significantly and reduce the urinary micro-albuminuria, hence showing promising effect on renal protection.
文摘AIM： To access the association between albuminuria levels and arterial stiffness in non-diabetic patients with hypertension and chronic kidney disease （CKD） stages 1-2, treated with renin angiotensin blockade agents plus other hypertensive drugs when needed.METHODS： One hundred fifteen patients [median age 52 years （68% males）] were consequently enrolled in the study. For each patient, we recorded gender, age, body mass index （BMI）, peripheral systolic blood pressure （pSBP）, peripheral diastolic blood pressure, peripheral pulse pressure, central systolic blood pressure （cSBP）, central diastolic blood pressure （cDBP）, central pulse pressure （cPP）, hematocrit, hemoglobin, hsCRP, total cholesterol triglycerides, high-density lipoprotein-C, low-density lipoprotein-C, calcium, phosphorus, parathormone, and albumin, as well as 24 h urine albumin excretion. According to 24-h urine albumin collection, patients were then classified as those with moderately increased albuminuria （formerly called macroalbuminuria） （≤ 300 mg/d） and those with severely increased albuminuria （formerly called macroaluminuria （〉 300 mg/d）. We considered aortic stiffness （AS） indices [carotid femoral pulse wave velocity （PWVc-f） and augmentation index （AIx）] as primary outcomes of the study. We explored potential correlations between severely increased albuminuria and AS indices using a multiple linear regression model. RESULTS： Fifty-eight patients were included in the moderately increased albuminuria group and 57 in the severely increased albuminuria. Blood pressure measurements of the study population were 138 ± 14/82 ± 1.3 mmHg （systolic/diastolic）. There were no significant differences in age, sex, and BP measurements between the two groups. Patients with severely increased albuminuria had higher PWV and AIx than patients with moderately increased albuminuria （P 〈 0.02, P 〈 0.004, respectively）. In addition these patients exhibited higher BMI （P 〈 0.03）, hsCRP （P 〈 0.001）, and fibrinogen levels （P 〈 0.02） compared to patients with moderately increased albuminuria. In multivariate linear regression analysis, severely increased albuminuria （β = 1.038, P 〈 0.010） pSBP （β = 0.028, P 〈 0.034） and Ht （β = 0.171, P = 0.001） remained independent determinants of the increased PWVc-f. Similarly, severely increased albuminuria （β = 4.385, P 〈 0.012）, cSBP （β = 0.242, P 〈 0.001）, cPP （β = 0.147, P 〈 0.01） and Ht levels （β = 0.591, P 〈 0.013） remained independent determinants of increased AIx.CONCLUSION： These fndings demonstrate an independent association between AS indices and severely increased albuminuria in non-diabetic, hypertensive patients with CKD stages 1-2 treated with renin angiotensin aldosterone system blockers.
文摘Background: Diabetic nephropathy is the most common cause of chronic kidney disease and the number afflicted patients continues to rise. The presence of proteinuria has been considered as a prerequisite for the diagnosis of diabetic nephropathy. But one third to one half of type 2 diabetics with CKD have no proteinuria and the pathology of non proteinuric CKD in this group remains unclear as renal biopsy is commonly not performed in these patients. The present study addresses the question: Can a classical diabetic nephropathy occur in the absence of proteinuria? Method: We examined renal biopsies of subjects who underwent nephrectomy from 1999 to 2009 for renal cancer, had eGFR < 60 ml/min and no microalbuminuria or proteinuria. 10 diabetics were matched with 10 non diabetics for age, hypertension and baseline creatinine. Results: The diabetic subjects had advanced diabetic lesions even in absence of proteinuria. Tubules and tubular-interstitium was relatively well preserved. Diabetic glomerulosclerosis can occur in the absence of microalbuminuria. Conclusions: It is becoming increasingly apparent that a considerable proportion of subjects with type 2 diabetes can develop renal impairment in the absence of albuminuria. Diabetic glomerulosclerosis may develop before the proteinuria can be detected and relying on albumin excretion as first sign for renal involvement may be too late in diagnosing and modifying the progression of the kidney disease.
文摘Podocyte loss was well known in type 2 diabetic nephropathy patients. The objective of the present study was to determine the number of podocytes and the degree of albuminuria in diabetic KK-Ay/Ta (KK-Ay) mice which had been reported as diabetic nephropathy model. Diabetic KK-Ay mice, diabetic KK/Ta mice and non-diabetic BALB/cA Jcl (BALB/cA) mice were studied. We analyzed glomerular lesions in all mice by morphometric analysis and immunofluorescence to determine the number of podocytes. Level of urinary albumin was also measured. Glomerular enlargement and mesangial expansion were observed in KK-Ay mice. Mean number of podocytes per glomerulus (NG pod) in diabetic KK-Ay mice was significantly lower than that in non-diabetic BALB/cA mice. Mean NG pod/glomerular area (GA) per glomerulus was also significantly decreased in diabetic KK-Ay mice. The level of urinary albumin/creatinine ratio (ACR) in diabetic KK-Ay mice was significantly higher than that in non-diabetic BALB/cA mice. These data suggest that podocyte loss might induce albuminuria in KK-Ay mice. This finding confirmed our previous report that KK-Ay mice, especially in terms of histological findings, are a suitable animal model for glomerular injury in type 2 diabetic nephropathy.
文摘AIMTo investigate the relationship between circadian vari-ations in blood pressure （BP） and albuminuria at rest, and during exercise in non-hypertensive type 2 diabetes （T2D） patients.METHODSWe conducted a cross-sectional study in well controlled T2D patients, non-hypertensive, without clinical pro-teinuria and normal creatinine clearance. In each parti-cipant, we recorded the BP using ambulatory bloodTankeu AT et al . Exercise-induced albuminuria and BP in T2DMpressure monitoring （ABPM） for 24-h, and albuminuria at rest and after a standardized treadmill exercise.RESULTSWe enrolled 27 type 2 patients with a median age of 52; and a mean duration of diabetes and HbA1c of 3.6 ± 0.8 years and 6.3% ± 0.5% respectively. Using a 24-h ABPM, we recorded a mean diurnal systolic blood pressure （SBP） of 128 ± 17 mmHg vs nocturnal of 123 ± 19 mmHg （ P = 0.004）, and mean diurnal diastolic blood pressure （DBP） of 83 ± 11 mmHg vs nocturnal 78 ± 14 mmHg （ P = 0.002）. There was a signifcant difference between albuminuria at rest [median = 23 mg, interquartile range （IQR） = 10-51] and after exercise （median = 35 mg, IQR = 23-80, P 〈 0.001）. Patients with exercise induced albuminuria had an increase in nocturnal BP values on all three components （128 mmHg vs 110 mmHg, P = 0.03 for SBP; 83 mmHg vs 66 mmHg, P = 0.04; 106 vs 83, P = 0.02 for mean arterial pressure）, as well as albuminuric patients at rest. Moreover, exercise induced albuminuria detect a less increase in nocturnal DBP （83 vs 86, P = 0.03） than resting albuminuria.CONCLUSIONExercise induced albuminuria is associated with anincrease in nocturnal BP values in T2D patients.
基金the Key R&D Project of the Ministry of Science and Technology,No.2016YFC0901200 and 2016YFC0901205.
文摘BACKGROUND Diabetic kidney disease is one of the common complications of type 2 diabetes(T2D).There are no typical symptoms in the early stage,and the disease will progress to moderate and late stage when albuminuria reaches a high level.Treatment is difficult and the prognosis is poor.At present,the pathogenesis of diabetic kidney disease is still unclear,and it is believed that it is associated with genetic and environmental factors.AIM To explore the relationship between the glucokinase regulatory protein(GCKR)gene rs780094 polymorphism and T2D with albuminuria.METHODS We selected 252 patients(126 males and 126 females)with T2D admitted to our hospital from January 2020 to October 2020,and 66 healthy people(44 females and 22 males).According to the urinary albumin/creatinine ratio,the subjects were divided into group I(control),group II(T2D with normoalbuminuria),group III(T2D with microalbuminuria),and group IV(T2D with macroalbuminuria).Additionly,the subjects were divided into group M(normal group)or group N(albuminuria group)according to whether they developed albuminuria.We detected the GCKR gene rs780094 polymorphism(C/T)of all subjects,and measured the correlation between GCKR gene rs780094 polymorphism(C/T)and T2D with albuminuria.RESULTS Gene distribution and genotype distribution among groups I-IV accorded with the Hardy-Weinberg equilibrium.Genotype frequency was significantly different among the four groups (P = 0.048, χ^(2)= 7.906). T allele frequency in groups II, III, and IV was significantly higherthan that in group I. Logistic regression analysis of the risk factors for T2D with albuminuria showed that the CT +TT genotype (odds ratio = 1.710, 95% confidence interval: 1.172-2.493) was a risk factor.CONCLUSION CT + TT genotype is a risk factor for T2D with albuminuria. In the future, we can assess the risk of individualscarrying susceptible genes to delay the onset of T2D.
文摘AIM:To study the relation between hepatitis C virus (HCV) genotype 4 and microalbuminuria and renal impairment in relation to hepatic histology, and viremia in the absence of cryoglobulinemia, and to examine the effect of treatment on microalbuminuria.METHODS: Three hundred subjects, including 233 HCV genotype-4 infected patients, were tested for cryoglobulinemia, microalbuminuria, albumin creatinine ratio (ACR), urea, creatinine, and estimated glomerular filtration rate (eGFR). The parameters were measured again in the HCV patients after 48 wk of treatment with pegylated interferon and ribavirin.RESULTS: Significantly higher levels of microalbumin- uria were detected in HCV-positive patients compared to HCV-negative controls (median 9.5 vs 5.9, respectively, Kruskal-Wallis P=0.017). Log microalbuminuria was significantly correlated with hepatic inflammation (r=0.13, P=0.036) and f ibrosis (r=0.12, P=0.061), but not with viral load (r=-0.03, P=0.610), or alanine transaminase (r=-0.03, P=0.617). Diabetes mellitus neither significantly moderated (χ2=0.13, P=0.720), nor mediated (Sobel test P=0.49) the HCV effect. HCV status was signifi cantly associated with log microalbu-minuria (χ2=4.97, P=0.026), adjusting for age, gender, diabetes, cryoglobulinemia, urea and creatinine. A positive HCV status was not significantly associated with low eGFR (<60 mL/min every 1.73 m2) [odds ratio (OR): 0.5, 95% confidence interval (CI):0.2-1.4], nor with high ACR (OR: 1.7, 95% CI:0.7-4.1). End-of-treatment response (ETR) was achieved in 51.9% of patients. Individuals with ETR had significantly lower microalbuminuria post-treatment (χ2=8.19, P=0.004).CONCLUSION: HCV affected the development of microalbuminuria independent of diabetes or cryoglobulinemia. Combination therapy of pegylated interferon-ribavirin had a positive effect in reducing microalbuminuria.
文摘Albuminuria predicts cardiovascular disease (CVD) events but it is likely to vary over time in a nonlinear fashion. The aim of this study was to estimate the potentially differing predictive effect of albuminuria on the risk of CVD or related death over time. Data were from a cohort study of 3505 predominately indigenous adults from remote communities in Queensland,Australia, 1999-2006. Cox Proportional Hazards model analysis of the predictive effects of urinary albumin creatinine ratio on the risk of CVD or CVD-related death was undertaken for incident and prevalent CVD. Analyses sequentially removed those who had a cardiovascular event or related death for the first year through to six years. The baseline prevalence of microalbuminuria was 21.2% and for macroalbuminuria 6.7%. The incidence of CVD was92 in13,812 person-years. Microalbuminuria predicted incident CVD with a Hazard Ratio (HR) of 3.0 (95% CI 1.83 - 4.96) and for macroalbuminuria HR 10.8 (95% CI 6.58 - 17.68) and for those with pre-existing CVD, HR 2.6 (95% CI 1.65 - 3.97) and HR 9.7 (95% CI 6.38 - 14.82) respectively. People with macroalbuminuria who survived the first three years had a crude HR of an incident cardiovascular event or death of 13.0 (95% CI 6.45 - 26.39) to a peak of 32.3 (95% CI 8.55 - 121.77) for those who survived the first five years. The hazard appeared to drop in the 6th year although this is based on small numbers.The first three years after finding macroalbuminuria provide a potential window opportunity to actively manage the risk of incident CVD before the risk elevates.
文摘AIM To investigated the relationship between exerciseinduced ambulatory blood pressure measurement(ABPM) abnormalities in type 1 diabetes mellitus(T1DM) adolescents. METHODS We conducted a case-control at the National Obesity Center of the Yaoundé Central Hospital, Cameroon. We compared 24 h ABPM and urinary albumin-to-creatinine ratio(ACR) at rest and after a standardized treadmill exercise between 20 Cameroonian T1 DM patients and 20 matched controls. T1 DM adolescents were aged 12-18 years, with diabetes for at least one year, without proteinuria, with normal office blood pressure(BP) and renal function according to the general referencepopulation. Non-diabetic controls were adolescents of general population matched for sex, age and BMI.RESULTS Mean duration of diabetes was 4.2 ± 2.8 years. The mean 24 h systolic blood pressure(SBP) and diastolic blood pressure(DBP) were respectively 116 ± 9 mm Hg in the diabetic group vs 111 ± 8 mm Hg in the nondiabetic(P = 0.06), and 69 ± 7 mm Hg vs 66 ± 5 mm Hg(P = 0.19). There was no difference in the diurnal pattern of BP in diabetes patients and non-diabetic controls(SBP: 118 ± 10 mm Hg vs 114 ± 10 mm Hg, P = 0.11; DBP: 71 ± 7 mm Hg vs 68 ± 6 mm Hg, P = 0.22). Nighttime BP was higher in the diabetic group with respect to SBP(112 ± 11 mm Hg vs 106 ± 7 mm Hg, P = 0.06) and to the mean arterial pressure(MAP)(89 ± 9 mm Hg vs 81 ± 6 mm Hg, P = 0.06). ACR at rest was similar in both groups(5.5 mg/g vs 5.5 mg/g, P = 0.74), but significantly higher in diabetes patients after exercise(10.5 mg/g vs 5.5 mg/g, P = 0.03). SBP was higher in patients having exercise-induced albuminuria(116 ± 10 mm Hg vs 108 ± 10 mm Hg, P = 0.09). CONCLUSION Exercise-induced albuminuria could be useful for early diagnosis of kidney damage in adolescents with T1 DM.
文摘BACKGROUND Diabetes mellitus is considered a leading contributor to severe coronavirus disease 2019(COVID-19).AIM To characterize differences between hospitalized diabetic patients with vs without COVID-19,and parameters associated with COVID-19 severity for prediction.METHODS This case-control study included 209 patients with type 2 diabetic mellitus hospitalized at the Galilee Medical Center(Nahariya,Israel)and recruited between September 2020 and May 2021,65 patients with COVID-19 infection in dedicated wards and 144 COVID-19-negative patients in internal medicine wards hospitalized due to other reasons.Clinical parameters-including age,type of antiglycemic medications,presence of retinopathy,smoking history,body mass index(BMI),glycosylated hemoglobin,maximum neutrophil:lymphocyte ratio(NLR_(max)),C-reactive protein(CRP),estimated glomerular filtration rate(eGFR),and albumin(blood and urine)-were compared between the two primary patient groups,and then between COVID-19-negative patients hospitalized due to infectious vs non-infectious disease.Finally,we explored which parameters were associated with severe COVID-19 pneumonia.RESULTS COVID-19-negative patients were older(63.9±9.9 vs 59.8±9.2,P=0.005),and had longer duration of diabetes(P=0.031),lower eGFR(P=0.033),higher albumin(P=0.026),lower CRP(P<0.001),greater smoking prevalence(P<0.001),and more baseline albuminuria(54.9%vs 30.8%,P=0.005)at admission;70%of COVID-19 patients with albuminuria had moderate-range albuminuria(albumin:creatinine 30-300 mg/g).Most of the patients with albuminuria had chronic kidney disease stage II(CKD II).Oral antiglycemic therapies were not significantly different between the two groups.Multivariable logistic regression showed that higher BMI was significantly associated with severe COVID-19(OR 1.24,95%CI:1.01-1.53,P=0.04),as was higher NLR_(max)(OR 1.2,95%CI:1.06-1.37,P=0.005).Surprisingly,pre-hospitalization albuminuria,mostly moderate-range,was associated with reduced risk(OR 0.09,95%CI:0.01-0.62,P=0.015).Moderate-range albuminuria was not associated with bacterial infections.CONCLUSION Moderate-range albuminuria in COVID-19-positive diabetic patients with CKD II is associated with less severe COVID-19.Further studies should explore this potential biomarker for risk of COVID-19-related deterioration and early interventions.
文摘Introduction: It was recently reported that candesartan, an angiotensin II receptor blocker, had a protective effect against cardiovascular events, comparable to that of calcium channel antagonists. Moreover, a renoprotective effect and anti-diabetic action of candesartan had also been demonstrated. However, whether the renoprotective effect of candesartan, especially in diabetes, was dose-dependent or not remain to be fully elucidated. The present study attempted to clarify the dose effect of renoprotection by candesartan in Japanese type 2 diabetic patients. Subjects and Method: In this case series study, we recruited 26 type 2 diabetic patients with albuminuria whose blood pressure did not reach the target BP level (<130/80 mmHg) despite administration of 4 or 8 mg/day of candesartan. Subsequently, these lower doses of candesartan were increased to the maximal dose in Japan, 12 mg/day. Clinical parameters were examined before, at 6 and 12 months after the increase in dose. Results: An ameliorating effect of the increased dose of candesartan on albuminuria and hypertension was distinctly observed. No severe adverse effect was observed. Conclusion: It was highly possible that the maximal dose of candesartan provided more effective renoprotection in hypertensive type 2 diabetic patients initially treated with lower doses of candesartan.
基金supported by Industrial Foundation of Ministry of Health of China(No.200902001)
文摘Background The influence ofalbuminuria on clinical outcomes in patients with type 2 diabetes mellitus （T2DM） after elective percutaneous coronary intervention（PCI） with drug-eluting stent （DES） implantation remains unclear. Methods We observed 386 patients with T2DM after elective PCI. The patients were stratified based on the early morning urinary albumin： negative （n = 309）, trace （urine dipstick trace, n = 39）, and positive group （urine dipstick≥1＋, n = 38）. Kaplan-Meier curve analysis was used to compare the cumulative rates of clinical outcomes （all-cause death, cardiovascular death, MACEs： cardiovascular death, non-fatal myocardial in- farction, stroke or revascularization）. Cox regression was performed to assess the risk factors for all-cause death and cardiovascular death. Results Median follow-up was 25 months （IQR： 17-37 months）. Twenty eight （7.3%, 13 in the negative group, 3 in the trace group and 12 in the positive group） patients died during the entire study period, 2 of them （0.7%,1 in the negative group and I in the trace group）died during index hospitalization. Posi- tive albuminuria group suffered more contrast-induced acute kidney injury （CI-AKI） and dialysis during hospital- ization. The cumulative all-cause death （34.5% vs. 8.9% vs. 4.9%, P Negati Trace = 0.333, PNegati Positive 〈（ 0.001, PTracevs.Positive = 0.013, log-rank P 〈 0.001） and cardiovascular death （29.5% vs. 7.4% vs. 3.4%, P Negative vs Trace = 0.458, PNegati Positive 〈 0.001, PTrace vs.Positive = 0.014, log-rank P 〈 0.001） were highest in the positive group. MACE also tends to increase in positive group. After adjusting for potential confounding risk factors, positive albuminuria was still related to all-cause death （HR = 5.13, 95% CI： 2.21-11.89, P 〈 0.001） and cardiovascular death （HR = 5.40, 95% CI： 2.07-14.09, P = 0.001）. Conclusion Preprocedural albuminuria predicts poor clinical outcomes, including all-cause death and cardiovascular death, in T2DM patients after elective PCI with DES implantation.
文摘Background: Sickle Cell Disease (SCD) renal abnormalities commence early in childhood. The glomerular abnormalities, glomerular hyperfiltration and albuminuria are the most prevalent. However, these SCD glomerulopathies have not been considered exclusively in the adolescent age group. Objective: To determine the prevalence of glomerular hyperfiltration and albuminuria as well as identify the determinants for glomerular hyperfiltration in adolescents with SCD. Patients and Methods: The electronic patient records of 153 adolescents with SCD aged 10 - <19 years, attending the Paediatrics Haematology Clinic at Evelina London Children’s Hospital, United Kingdom, were reviewed from the 10<sup>th</sup> to 23<sup>rd</sup> June 2019. Clinical information and laboratory parameters were obtained. The glomerular filtration rate was derived using the Bedside Schwartz’s method. Grouping of the adolescents was based on the presence and absence of glomerular hyperfiltration, which was defined as glomerular filtration rate > 140 ml/min/m<sup>2</sup>. The presence of albuminuria was defined as urine albumin-to-creatinine ratio > 3 mg/mmol or protein-to-creatinine ratio of >15 mg/mmol. The clinical and laboratory determinants of glomerular hyperfiltration in the total study population were investigated. Result: Prevalence of glomerular hyperfiltration was 33.3% in the adolescents studied, and that of albuminuria was 15.7% amongst the SCD adolescents studied, of which 13.7% of those with glomerular hyperfiltration also had albuminuria. On univariable analysis, the SCD adolescents with glomerular hyperfiltration had significantly lower weight (48.0 ± 18.0 versus 54.8 ± 17.0 kg;<i>p</i> = 0.02), height (155.1 ± 13.1 versus 160.6 ± 13.1 cm;<i>p</i> = 0.01), body mass index (19.4 ± 5.0 versus 21.0 ± 4.3;<i>p</i> = 0.04), haemoglobin level (88.7 ± 13.3 versus 98.1 ± 21.7 g/L;<i>p</i> = 0.001), and serum creatinine level (0.4 ± 0.1 versus 0.6 ± 0.2 mg/dl;<i>p</i> = 0.0001) as compared to those with no glomerular hyperfiltration. The SCD adolescents with glomerular hyperfiltration also had significantly higher lactate dehydrogenase levels (525.9 ± 180.3 versus 449.6 ± 170.3 IU/L;<i>p</i> = 0.01) than those with no glomerular hyperfiltration. But, multivariable analysis revealed no associations. Conclusion: This study revealed that the prevalence of glomerular hyperfiltration in SCD children in the adolescent age group is high, and the high glomerular filtration rates begin to decline toward normal values in middle adolescence.
基金Supported by the Italian Ministry for Education,University and Research under the Programme“Dipartimenti di Eccellenza 2018-2022”Project,No.D15D18000410001Novo Nordisk“Gestione delle complicanze croniche del diabete:From bedside to bench?”,No.n1/2021.
文摘BACKGROUND Global longitudinal strain(GLS)of the left ventricular is a highly sensitive and reliable marker of systolic function and GLS outperforms ejection fraction(EF)in detecting preclinical left ventricular systolic dysfunction(LVSD).In patients with type 2 diabetes(DM2)albuminuria is a predictor of symptomatic heart failure,but data on the relationship between GLS and albuminuria are conflicting.AIM To explore the relationship between GLS and albuminuria in a contemporary cohort of DM2 patients.METHODS The study was performed on DM2 patients consecutively enrolled in the TESEO study.Patients with symptoms/signs of heart failure,EF<50%,coronary artery,other cardiac diseases,or non-adequate acoustic window for GLS assessment were excluded.We collected clinical data,screened for complications,and measured GLS by speckle-tracking echocardiography.Univariate and multiple linear regression analyses were performed to identify independent explanatory variables associated with GLS.Logistic regression analysis was used to assess whether albuminuria was independently associated with GLS-diagnosed(GLS>-18%)LVSD.RESULTS Patients(n=193,age:60.6±8.1,male:57%)had a short DM2 duration(3.8±4.9 years)and good metabolic control(glycated haemoglobin A1c:6.5%±1.0).Preclinical GLS-LVSD was present in 21.8%of the patients.GLS values were significantly higher in patients with albuminuria(-19.88±2.16 vs-18.29±2.99,P<0.001)and in multivariate analysis natural logarithm of albumin-creatinine ratio and uric acid were independent predictors of GLS.In logistic regression analysis,albuminuria was associated with a 6.01(95%confidence interval:1.874-19.286)increased odds ratio of GLS-LVSD,independent of age,sex,diastolic blood pressure,chronic kidney disease,EF,mitral annulus velocity lateral,uric acid,and treatments.CONCLUSION Albuminuria was independently associated with subclinical LVSD in our contemporary cohort of DM2 patients.
文摘The underlying molecular changes that result in minimal change disease(ne-phrotic syndrome)require an in-depth analysis.Current molecular studies have shown the involvement of zinc fingers and homeobox transcriptional factors in its pathogenesis.The application of therapeutic drugs relies on understanding the cascade of molecular events to determine their efficacy in managing the clinical condition.
文摘Emerging evidence suggests that intestinal dysbiosis and chronic low-gradeinflammation play a critical role in the development and progression of diabetickidney disease (DKD), particularly in the elderly. Reduced microbial diversity,loss of beneficial genera and over-representation of pathogenic bacteria are closelyassociated with declining kidney function. There is a possible causal relationshipbetween specific gut microbiota profiles and DKD. Experimental models alsoshow that gut-derived metabolites and altered intestinal permeability can promoterenal inflammation, fibrosis and metabolic dysfunction. This editorialdiscusses the implications of these findings for future research and clinicalpractice, emphasizing the growing potential of microbiota-targeted therapies.Understanding the gut–kidney axis could ultimately open up new avenues forprecision nephrology and metabolic care.
基金Supported by the National Research Foundation(NRF)of Korea,No.RS-2023-00217317。
文摘BACKGROUND Diabetes is a significant risk factor for chronic kidney disease,and diabetic kidney disease(DKD)is prevalent among patients with diabetes.Previous studies have indicated that the duration of diabetes and poor glycemic control are associated with an increased risk of DKD,but data on how the duration and severity of hyperglycemia specifically relate to DKD progression are limited.AIM To investigate the relationship between diabetes duration and glycemic control,and DKD progression in South Korea.METHODS We included 2303 patients with diabetes using the 2019-2021 Korea National Health and Nutrition Examination Surveys data.DKD was defined as an estimated glomerular filtration rate(eGFR)<60 mL/min per 1.73 m2,urinary albumin-to-creatinine ratio≥30 mg/g,or both.Diabetes duration and severity were classified into six categories each.RESULTS DKD prevalence was 25.5%.The DKD risk significantly increased in diabetes lasting 10-15 years or hemoglobin A1C(HbA1c)≥8%compared to patients with newly diagnosed diabetes or HbA1c<6.5%.Albuminuria developed with shorter diabetes duration and lower HbA1c than eGFR decline.The adjusted odds ratios for DKD were 3.77[95%confidence interval(95%CI):2.60-5.45]and 4.91(95%CI:2.80-8.63)in patients with diabetes lasting≥20 years and HbA1c≥10%,respectively,compared to those with new-onset diabetes and HgA1c<6.5%.CONCLUSION Patients with diabetes lasting>10 years or HbA1c>8%had a higher risk of DKD,emphasizing the importance of early monitoring and management is crucial to prevent DKD progression.
