Diabetic kidney disease (DKD) is one of the primary causes of end-stage renal disease (ESRD). Early diagnosis is very important in preventing the development of DKD. Urinary albumin excretion rate (UAER) and glomerular filtration rate (GFR) are widely accepted as criteria for the diagnosis and clinical grading of DKD, and microalbuminuria has been recommended as the first clinical sign of DKD. The natural history of DKD has been divided into three stages: normoalbuminuria, microalbuminuria, and macroalbuminuria. However, this clinical paradigm has been questioned recently, as studies have shown that a portion of diabetes mellitus (DM) patients with normoalbuminuria have progressive renal insufficiency, referred to as normoalbuminuric diabetic kidney disease (NADKD) or nonalbuminuric diabetic nephropathy. Epidemiologic research has demonstrated that normoalbuminuric diabetic kidney disease is common, and the large number of NADKD patients suggests that the traditional paradigm needs to be shifted. Currently, the pathogenesis of NADKD remains unclear, but many clinical studies have identified some clinical and pathological features of NADKD. In addition, the long-term outcomes of NADKD patients remain controversial. In this article, we reviewed the latest studies addressing the pathogenesis, pathology, treatment and prevention of NADKD.
Percentage of patients with GFR<60 ml/(min·1.73 m2)
Low GFR participants with
Normo (%)
Micro (%)
Macro (%)
Retnakara et al. [17]
7462
2
CKD-EPI otherwise
16%
28%
NA
NA
Kramer et al. [21]
9737
2
CKD-EPI otherwise
12.3%
36%
45%
19%
New et al. [23]
162 113
2
CKD-EPI otherwise
3%
63%
NA
NA
Boronat et al. [24]
78
2
CKD-EPI otherwise
100%
22%
20%
58%
Dwyer et al. [13]
11 573
2
CKD-EPI otherwise
22.3%
20.5%
30.7%
35%
Mottl et al. [9]
21 366
2
CKD-EPI equation
13.1%
52%
48%
NA
Giuseppers et al. [20]
15 773
2
CKD-EPI otherwise
37.5%
56.5%
30.8%
12.6%
Maclsaac et al. [7]
625
2
CKD-EPI otherwise
36%
39%
35%
26%
Tab.1
Fig.1
MacIsaac et al. [7]
Kramer et al. [14]
Rigalleau et al. [16]
Thomas et al. [19]
Ekinci et al. [39]
Shimizu et al. [65]
Age (year)
73±1
62.9±10.3
68±9
73±1
67±2.0
62.5±6.2
Female (%)
56%
51%
66%
64%
62%
53%
Duration of diabetes (year)
14±1
10.1±7.0
14±5
9±1
12±2.4
7.4±6.4
BMI (kg/m2)
30.8±1
29±5.4
27.0±4.5
30.11
34±1.6
22.2±2.2
Smoking (%)
38%
11.4%
?
29%
0
?
HbA1c (%)
7.3±0.3
6.74±2.35
9.0±1.3
7.0±0.1
6.8±0.2
8.3±2.2
SBP (mmHg)
138±3
146±23.7
143±16
135±1
?
129±14.3
DBP (mmHg)
75±2
87.0±16.9
79±8
75±1
?
75.6±10
TC (mmol/L)
4.4±0.2
5.76±1.3
2.37±0. 7
?
4.4±0.2
?
LDL-C (mmol/L)
2.6±0.1
3.69±1.1
1.26±0.5
2.4±0.1
?
?
HDL-C (mmol/L)
1.15±0.05
1.16±0.3
0.64±0.3
1.2±0.1
?
?
TG (mmol/L)
21.9±1.1
4.55±1.1
1.91±1.9
1.9±0.1
2.6±0.4
?
Tab.2
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