Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with 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.

Relationship between serum Dickkopf-1 and albuminuria in patients with type 2 diabetes

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.

Urinary Neutrophil Gelatinase Associated Lipocalin as a Marker of Tubular Damage in Type 2 Diabetic Patients with and without Albuminuria

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.

Albuminuria as a marker of arterial stiffness in chronic kidney disease patients

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.

Absence of albuminuria in type 2 diabetics with classical diabetic nephropathy: Clinical pathological study

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.

Clinical Observation on Breviscapine in Treating Hypertension Patients Complicated with Micro-albuminuria of Renal Impairment

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.

Podocyte loss and albuminuria of KK-Ay mouse: A spontaneous animal model for human type 2 diabetic nephropathy

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.

Exercise-induced albuminuria and circadian blood pressure abnormalities in type 2 diabetes

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.

Microalbuminuria in hepatitis C-genotype 4:Effect of pegylated interferon and ribavirin

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.

Temporal variation in cardiovascular disease risk predicted by albuminuria: An opportunity for clinical intervention?

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.

Exercise-induced albuminuria vs circadian variations in blood pressure in type 1 diabetes

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.

Baseline moderate-range albuminuria is associated with protection against severe COVID-19 pneumonia

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.

Amelioration of Albuminuria in Japanese Type 2 Diabetic Patients by Maximal Dose of Candesartan

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.

Evaluation of Glomerular Hyperfiltration and Albuminuria in Sickle Cell Disease Adolescents: Cross-Sectional Retrospective Study

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 10th to 23rd 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/m2. 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;p = 0.02), height (155.1 ± 13.1 versus 160.6 ± 13.1 cm;p = 0.01), body mass index (19.4 ± 5.0 versus 21.0 ± 4.3;p = 0.04), haemoglobin level (88.7 ± 13.3 versus 98.1 ± 21.7 g/L;p = 0.001), and serum creatinine level (0.4 ± 0.1 versus 0.6 ± 0.2 mg/dl;p = 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;p = 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.

基于名中医经验的中医辨证组方治疗老年慢性肾炎(CKD1~3a期)患者随机对照研究

目的:观察基于名中医经验的中医辨证组方对老年慢性肾炎(CKD1-3a期)患者的有效性和安全性。方法:将84例老年慢性肾炎患者随机分成治疗组(42例)和对照组(42例)。治疗组采用西医基础联合中医辨证组方治疗;对照组仅接受西医基础治疗,疗程均为24周。观察两组治疗前后24 h尿蛋白定量(24 h UPQ)、肾小球滤过率(eGFR)等临床指标变化,以及疗效和安全性。结果:与本组基线比较,两组治疗后12、18、24周24 h UPQ均显著下降(P<0.01),且24周时治疗组优于对照组(P<0.01)。治疗组总有效率为67.57%,对照组总有效率41.67%,治疗组显著高于对照组(P<0.05)。将慢性肾脏病(CKD)3a期患者进行亚组分析提示,24周后治疗组eGFR较本组基线及同期对照组显著升高(P<0.01,P<0.05),而对照组治疗前后无显著变化。治疗组不良反应发生4例,对照组2例,两组无严重不良反应出现。结论:基于名中医经验的中医辨证组方治疗老年慢性肾炎(CKD1-3a期),可减少尿蛋白,提高临床疗效,对其中的CKD3a期患者可能具有改善eGFR作用,且安全性较好。

中医药治疗肾性蛋白尿的用药规律研究

目的:研究探讨中医药治疗肾性蛋白尿的用药规律,为临床诊疗提供新思路。方法:计算机检索中国知网数据库中有关中医药治疗肾性蛋白尿的文献,检索时间为建库至2023年2月。筛选文献后,将纳入的处方录入Excel中分别进行性味、功效统计,用Origin 2022进行可视化,用SPSS Modeler 18.0对中药进行关联规则分析,挖掘出高频药物,运用SPSS 21.0软件进行聚类分析。结果:共收集到116篇文献,涉及250味中药,出现的频次有1396次。处方中高频药物有黄芪、茯苓、山药、丹参,用药以利水渗湿药、补虚药、收涩药、活血化瘀药为主,药性多为辛、甘、苦,四气以寒、温、平居多。支持度最高的药对为黄芪-山药,常见的药对:黄芪-地龙,黄芪-川芎,黄芪-当归,黄芪-丹参-山药。对高频中药进行聚类分析,共形成四类组方:①芡实、金樱子、杜仲、菟丝子、地龙、蝉蜕、白术、薏苡仁、山茱萸;②熟地黄、牡丹皮、泽泻、茯苓、山药、丹参、生地黄、山茱萸;③党参、石韦;④白花蛇舌草、益母草、当归、川芎、黄芪、赤芍。结论:肾性蛋白尿的病机本质为本虚标实,以脾肾虚为本,兼有瘀血、湿毒,多采用补益脾肾配伍有祛瘀、解毒、利水功效的药物进行治疗,可为临床治疗及临床新药研发提供参考,但仍需进一步验证考究。

社区老年人群蛋白尿及肾功能异常发生率及其影响因素研究

背景老年人往往多种慢性病(如糖尿病和高血压)共存,而糖尿病和高血压会导致慢性肾损害,目前针对老年人慢性肾脏病研究较少。目的通过收集社区老年人群健康体检的临床数据,调查老年人群蛋白尿及肾功能异常情况,为社区老年慢性肾脏病的管理提供指导。方法纳入2020—2021年于上海市闵行区颛桥社区卫生服务中心进行体检的13080名老年居民为研究对象,收集研究对象一般资料、体检结果与实验室检查数据。将估算肾小球滤过率(eGFR)<60 mL·min^(-1)·(1.73 m^(2))-1的研究对象纳入肾功能异常组(n=713),将eGFR≥60 mL·min^(-1)·(1.73 m^(2))-1的研究对象纳入肾功能正常组(n=12367);将尿蛋白阳性的研究对象纳入蛋白尿组(n=1690),将尿蛋白阴性的研究对象纳入非蛋白尿组(n=11390);同时将研究对象按照年龄间隔10岁分为60~69岁组(n=6901)、70~79岁组(n=4867)、80~89岁组(n=1128)、≥90岁组(n=184)。采用多因素Logistic回归分析探究研究对象肾功能异常及蛋白尿的影响因素。结果60~69岁组、70~79岁组、80~89岁组、≥90岁组尿蛋白阳性和肾功能异常检出率比较,差异有统计学意义(P<0.05)。60~69岁组、70~79岁组男性尿蛋白阳性检出率高于女性,60~69岁组男性肾功能异常检出率高于女性,80~89岁组男性肾功能异常检出率低于女性(P<0.05)。肾功能异常组年龄、糖尿病比例、高血压比例、血尿素氮(BUN)、血清肌酐(Scr)、三酰甘油(TG)水平高于肾功能正常组,总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、血红蛋白(Hb)水平低于肾功能正常组,两组尿微量白蛋白/尿肌酐比值(ACR)比较,差异有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,年龄、高血压、糖尿病、蛋白尿、贫血、高TG血症、低HDL-C血症是肾功能异常的影响因素(P<0.05);男性、糖尿病、肥胖、高TG血症、Scr、BUN是蛋白尿的影响因素(P<0.05)。结论社区60岁以上人群的蛋白尿及肾功能异常检出率较高,且随年龄增大而增加。年龄、高血压、糖尿病、贫血、高TG血症及低HDL-C血症是社区老年人群肾功能异常的危险因素,男性、糖尿病、肥胖、高TG血症、Scr、BUN是社区老年人群蛋白尿的危险因素。

子痫前期患者ACR、PLT、D-D水平变化及其在预测不良妊娠结局中的价值

目的探讨子痫前期(PE)患者尿蛋白/肌酐比值(ACR)、血小板计数(PLT)、D-二聚体(D-D)水平变化及其在预测不良妊娠结局中的价值。方法回顾性选取2019年10月至2022年10月在本院就诊的103例PE患者为PE组,另取同期40例正常妊娠产妇为对照组。测定两组受试者ACR、PLT、D-D水平,根据病情严重程度,将PE患者分为重度组和轻度组,比较不同病情严重程度患者ACR、PLT、D-D水平,根据妊娠结局,将PE患者分为妊娠结局良好组和妊娠结局不良组,比较不同妊娠结局患者ACR、PLT、D-D水平,并分析ACR、PLT、D-D评估不良妊娠结局的价值。结果PE组ACR和D-D水平高于对照组,PLT水平低于对照组(P<0.05);重度组ACR和D-D水平高于轻度组,PLT水平低于轻度组(P<0.05);妊娠结局不良组ACR和D-D水平高于妊娠结局良好组,PLT水平低于妊娠结局良好组(P<0.05);ROC曲线结果显示,ACR评估患者不良妊娠结局的AUC和截点值分别为0.799、89.61mg/mmol,PLT评估患者不良妊娠结局的AUC和截点值分别为0.860、52.05×10^(9)/L,D-D评估患者不良妊娠结局的AUC和截点值分别为0.762、1.52μg/mL,联合评估患者不良妊娠结局的AUC为0.930,高于单项评估(P<0.05)。结论PE患者中ACR和D-D水平上升,PLT水平下降,这3个指标均与患者病情严重程度有关,且联合评估不良妊娠结局价值较高。

Alkaloids of Nitraria sibirica Pall. decrease hypertension and albuminuria in angiotensin II-salt hypertension

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.

维生素D_(2)对糖尿病肾病患者蛋白尿水平的影响

目的探索维生素D_(2)软胶囊对伴有糖尿病肾病(diabetic kidney disease,DKD)的2型糖尿病(type 2 diabetes mellitus,T2DM)患者蛋白尿水平的影响。方法回顾性分析2020年10月至2022年3月在北京市某三级医院内分泌科住院治疗的估算肾小球滤过率(estimated glomerular filtration rate,eGFR)≥60 mL·(min·1.73 m^(2))^(-1)的伴DKD的95例T2DM患者。根据患者的治疗方案分为未使用维生素D制剂的对照组(CON组,n=33)、使用维生素D_(2)软胶囊的普通维生素D组(NVD组,n=31)和使用骨化三醇软胶囊的活性维生素D组(AVD组,n=31)。通过医院病例系统收集基线和治疗12周时患者的临床资料及维生素D和DKD相关指标,包括血清25羟维生素D(25-hydroxy vitamin D,25OHD)、血清甲状旁腺激素(parathyroid hormone,PTH)、血钙、尿钙和尿白蛋白与肌酐比值(urinary albumin-to-creatinine ratio,UACR)等。结果基线时CON组、NVD组和AVD组大量蛋白尿患者分别为8例(24.24%)、9例(29.03%)和7例(22.58%),差异无统计学意义(P=0.831)。治疗12周时,NVD组和AVD组ln(UACR)水平均显著降低(P均<0.001),两治疗组间差异无统计学意义(P=0.371)。NVD组和AVD组的总有效率分别为80.65%和74.19%,显著高于CON组(33.33%)(P<0.001和P=0.002)。NVD组和AVD组的疗效差异无统计学意义(P=0.245)。CON组出现1例血钙增高、1例高尿钙、1例高尿酸血症、1例肾结石、1例肌肉痉挛;NVD组出现1例高尿钙、1例高尿酸血症;AVD组出现1例血钙增高、1例高钙血症、1例低PTH、2例高尿钙、2例高尿酸血症。两治疗组均无停药事件发生。结论维生素D_(2)软胶囊与骨化三醇软胶囊均可显著降低肾功能正常的伴DKD的T2DM患者尿蛋白水平。普通维生素D与活性维生素D相比可能安全性更好。