Subclinical Diabetic Nephropathy Research Articles

#651 Diagnostiс criteria of the functional state of the kidneys in patients with type 2 diabetes mellitus

Abstract Background and Aims The constant increase in the number of patients with type 2 diabetes is clearly explained by the incidence of microvascular complications, including diabetic nephropathy (DN). According to statistics, CKD develops initially in 15% of individuals in the general population. To assess the functional state of the kidneys in patients with type 2 diabetes mellitus. Method The study included 120 patients with T2DM and were divided into 2 groups. Gr1: 60 patients with DN C1,A1, gr2 with DN C2,A2 whose average age was 60.1 ± 7.6 years. The average DM experience was 7 ± 3.16 years, HbA1C 9 ± 1.82%, BMI 28.05 ± 3.45. Average GFR cr. was 92.6 ± 11.81 ml/min/1.73 m2, albuminuria—13.19 ± 3.1 mg/g. Results In the first group, the decrease in eGFRcr was 7.1%, although the average value was within the reference values. At the same time, the level of serum cystacin C and the calculated eGFRcys in this group were significantly different from the control. The serum concentration of cystacin C was significantly higher (0.64 ± 0.09 mg/ml versus 1.07 ± 0.08 mg, p < 0.05), and the eGFRcys indicator was significantly lower (81.32 ± 6.31 ml /min versus 96.60 ± 5.22 ml/min, p < 0.05) indicator for healthy individuals. In the second group of patients, there was a significant decrease in glomerular filtration rate for both markers compared to the control and the first group. Thus, in patients with DN C2, A2, compared with the control and the first group of patients, the eGFRcr indicator was reduced by 24.2% and 18.3%, respectively (p < 0.01 and p < 0.05), which indicates a pronounced decrease in renal function in this category of patients with type 2 diabetes. Conclusion Thus, the results obtained showed that in patients with subclinical diabetic nephropathy there is a decrease in glomerular filtration rate, determined by the level of cystacin C. Therefore, eGFRcys is a more accurate indicator of a hidden impairment of renal filtration function compared to eGFRcr.

Urinary angiotensinogen level and its risk factors in patients with " subclinical" diabetic nephropathy

Objective To evaluate the level and related factors of urinary angiotensinogen in patients with subclinical diabetic nephropathy. Methods (1)A total of 80 type 2 diabetic patients without angiotensin-converting enzyme inhibitor (ACEI) or angiotensin Ⅱ receptor blocker(ARB) treatment and hypertension were divided into 3 groups according to 24-hour urinary albuminuria and estimated glomerular filtration rate(eGFR): normoalbuminuria with normal glomerular filtration rate group[urinary microalbuminuria(UMA) <30 mg/24 h, 90≤eGFR <120 ml·min-1·(1.73 m2)-1, NC group, n=28], normoalbuminuria with glomerular hyperfiltration group[UMA<30 mg/24 h, eGFR≥120 ml·min-1·(1.73 m2)-1, SDN group, n=36], microalbuminuria group[30 h≤UMA<300 mg/24 h, 90≤eGFR<120 ml·min-1·(1.73 m2)-1, EDN group, n=16]. The levels of urinary angiotensinogen among various groups were compared.(2)The levels of urine retinol binding protein(RBP), N-acetyl-β-D-glucosaminadase, α-galactosidase, and β2-microglobubin were used to evaluate the renal tubular function. Then all the patients were divided into 4 groups according to the degree of renal tubular injury; the urinary angiotensinogen was compared and the independent related factors were analyzed. (3)20 type 2 diabetic patients with microalbuminuria and ACEI or ARB treatment were also enrolled in this study. The level of urinary angiotensinogen was compared between patients with and without ACEI or ARB treatment. Results Compared with NC group, the level of urinary angiotensinogen in the SDN group was lowered[(1.47±0.11 vs 1.59±0.11)ng/ml, P<0.05], but was raised in the EDN group[(1.62±0.15)ng/ml, P<0.05]. With the aggravation of renal tubular injury, the level of urinary angiotensinogen was increased. Multiple regression analysis showed that urinary angiotensinogen was positively correlated with RBP(P<0.05)and negatively correlated with eGFR(P<0.05). Compared with the patients without ACEI or ARB treatment, the level of urinary angiotensinogen was decreased in patients with ACEI or ARB treatment [(1.43±0.16 vs 1.62±0.15)ng/ml, P<0.05]. Conclusion The level of urinary angiotensinogen in patients with subclinical diabetic nephropathy is lowered, but is then raised in patients with microalbuminuria, which may participate in the progression of renal glomerular and tubular injury in diabetic nephropathy. The renin-angiotensin system inhibitors may delay the progression of diabetic nephropathy via decreasing urinary angiotensinogen level. (Chin J Endocrinol Metab, 2015, 31: 395-399) Key words: Subclinical; Diabetic nephropathy; Urinary angiotensinogen; Renal tubular injury

Circulating Fibroblast Growth Factor 21 Levels Predict Progressive Kidney Disease in Subjects With Type 2 Diabetes and Normoalbuminuria

Elevated fibroblast growth factor 21 (FGF21) levels have been suggested, from cross-sectional studies, as an indicator of subclinical diabetic nephropathy. We investigated whether serum FGF21 was predictive of the development of diabetic nephropathy. Baseline serum FGF21 levels were measured in 1136 Chinese type 2 diabetic subjects recruited from the Hong Kong West Diabetes Registry. The role of serum FGF21 in predicting decline in estimated glomerular filtration rate (eGFR) over a median follow-up of 4 years was analyzed using Cox regression analysis. At baseline, serum FGF21 levels increased progressively with eGFR category (P for trend <.001). Among 1071 subjects with baseline eGFR ≥ 30 mL/min/1.73 m(2), serum FGF21 levels were significantly higher in those with eGFR decline during follow-up (n = 171) than those without decline (n = 900) (P < .001). In multivariable Cox regression analysis, baseline serum FGF21 was independently associated with eGFR decline (hazard ratio, 1.21; 95% confidence interval [CI], 1.01-1.43; P = .036), even after adjustment for baseline eGFR. In a subgroup of 559 subjects with baseline eGFR ≥ 60 mL/min/1.73 m(2) and normoalbuminuria, serum FGF21 level remained an independent predictor of eGFR decline (hazard ratio, 1.36; 95% CI, 1.06-1.76; P = .016). Integrated discrimination improvement (IDI) suggested that the inclusion of baseline serum FGF21 significantly improved the prediction of eGFR decline (IDI, 1%; 95% CI, 0.1-3.0; P = .013) in this subgroup, but not in the initial cohort involving all subjects. Elevated serum FGF21 levels may be a useful biomarker for predicting kidney disease progression, especially in the early stages of diabetic nephropathy.

Clinical characteristics and predictive factors of subclinical diabetic nephropathy.

To investigate the clinical characteristics and predictive factors of subclinical diabetic nephropathy in type 2 diabetes patients. A total of 298 type 2 diabetes patients were divided into 3 groups based on 24-h urinary microalbumin and estimated glomerular filtration rate: patients with normal albuminuria and glomerular filtration rate (NC), patients with normoalbuminuria and glomerular hyperfiltration (SDN) and patients with microalbuminuria (EDN). The renal size, tubular injury markers and ambulatory blood pressure were analyzed. Renal size increased in the SDN and EDN groups compared to the NC group (P<0.05), while renal length in the SDN group was greater than the EDN group (P<0.05). Patients in the SDN and EDN groups had higher level of urine retinol binding protein and N-acetyl-β-D-glucosaminidase and most of them developed proximal tubular dysfunction. The SDN group had higher 24-h mean and nocturnal diastolic blood pressure than the NC group (P<0.05), while the EDN group had higher systolic blood pressure and pulse pressure than the SDN group (P<0.01). More patients developed abnormal blood pressure rhythm in the SDN and EDN groups. The likelihood of a decrease in nocturnal systolic blood pressure was lower as the microalbuminuria increased. Increased renal size, more abnormal tubular injury markers and higher 24-h mean and nocturnal blood pressure were all risk factors of subclinical diabetic nephropathy. Patients with subclinical diabetic nephropathy had increased renal size, abnormal tubular injury markers, high blood pressure and abnormal circadian rhythm.

Value of variation in circadian rhythm of blood pressure for early diagnosis of diabetic nephropathy

Objective To investigate the change of 24 h ambulatory blood pressure in patients with diabetic nephropathy.Methods A total of 190 type 2 diabetic patients were divided into 2 groups according to estimated glomerular filtration rate (eGFR):glomerular hyperfiltration (eGFR ≥ 120 ml · min-11.73 m-2,n =65),normal glomerular filtration rate (90 ≤ eGFR＜ 120 ml · min-1 · 1.73 m-2,n =125).The groups were further divided by means of 24-hour urinary albuminuria.The variation in the ambulatory blood pressure,the circadian rhythm of blood pressure,the smoothness index of blood pressure in each group were analyzed.Results (1) Along with the increasing microalbuminuria,24-hours,diurnal,and night systolic and diastolic blood pressure increased progressively in the diabetic patients (P＜0.05),24-hours standard deviation and coefficient variation of systolic blood pressure increased,and smoothness index of systolic and diastolic blood pressure decreased progressively (P＜0.05).(2) In the patients with glomerular hyperfiltration but normal albuminuria,the incidence of abnormal blood pressure rhythmicity began to increase; and that of lowering of systolic and diastolic blood pressure during night became less evident along with increasing microalbuminuria (P ＜ 0.05).With the progression of microalbuminuria to macroalbuminuria,85.7％ patients lost normal blood pressure rhythmicity.Conclusion Abnormal circadian rhythm of blood pressure and increased variation in blood pressure occur in patients with subclinical diabetic nephropathy. Key words: Diabetic nephropathy; Ambulatory blood pressure; Glomerular filtration rate; Microalbuminuria ; Circadian rhythm

The value of different renal size indicators in early screening of subclinical diabetic nephropathy with hyperfiltration

In subclinical diabetic nephropathy with glomerular hyperfiltration,the renal size parameters are increased significantly,and this change sets in as early as before the appearance of microalbuminuria.The average kidney length discriminator value for glomerular hyperfiltration by receiver operating characteristic (ROC) curve analysis is 10.53 cm,with the best sensitivity,higher specificity and total coincidence rate,and can be a clinical indicator for screening early diabetic nephropathy with glomerular hyperfiltration. Key words: Diabetes mellitus, type 2; Diabetic nephropathy; Early diagnosis; Glomerular filtration rate; Ultrasonography

Day/night ratio of microproteinuria and blood pressure rhythm in type II diabetes

The paper discusses the results of the studies conducted with a group of patients with type II diabetes without clinical nephropathy. The aim of the study was to attempt to determine the markers for early stages of diabetic nephropaty in NIDDM patients. The following examinations were carried out: the level of selected microproteinuric components, 24 h monitoring of arterial blood pressure, and electrocardiogram (ECG). Among the patients examined, the level of alfa-1-microglobulin, albumin and immunoglobulin G (IgG) in diabetic patients was higher than in the control group, and the increased activity of βNAG was observed. The 24 h profile of blood pressure and the ratio afternoon/night of albumin excretion flattened in the majority of diabetic patients. The results of the study suggest that the proximal tubules and the membranes of renal glomeruli are damaged as early as during the period of subclinical diabetic nephropathy.

Protein-loading test, urinary albumin excretion and renal morphology in diagnosis of subclinical diabetic nephropathy.

The acute effects of protein loading (1.5 g kg-1) on glomerular filtration rate (GFR) and urinary albumin excretion (UAE) were investigated in 23 type-I diabetic patients with no clinical nephropathy, and in 7 healthy subjects (controls). The results were compared with renal morphology data. In controls and in 14 diabetic patients (group 1) GFR increased by 27 and 37%, respectively, corresponding to normal renal reserve, but in 9 patients (group 2) GFR decreased by 20%, indicating the absence of a renal reserve. Microalbuminuria was found in none of the patients in group 1 and in 50% of patients in group 2. Two hours after the load UAE increased in all groups, but the increase was most marked in group 2, despite the fall in GFR. The two groups of patients did not differ with regard to the duration and control of diabetes, but differed markedly in terms of baseline GFR (131 vs. 195 ml min-1, P less than 0.01, in groups 1 and 2, respectively). Renal morphology showed minimal non-specific glomerular injury in group 1, and signs of glomerulosclerosis in group 2. We conclude that the impaired renal response to protein load precedes other subclinical manifestations of diabetic renal injury, and may be useful in the diagnosis of latent diabetic nephropathy.