Development and External Validation of a Nomogram and a Risk Table for Prediction of Type 2 Diabetic Kidney Disease Progression Based on a Retrospective Cohort Study in China

Figures & data

Table 1 Baseline Clinical Characteristics of the Derivation Cohort

Characteristics	Overall (n = 307)	Patients without Outcome (n = 109)	Patients with Outcome (n = 198)	P-value
Demographics
Age (years)	66.00 (55.00, 75.00)	68.00 (56.00, 77.00)	65.00 (55.00, 74.75)	0.306
Female sex (%)	59.93	60.55	59.60	0.967
BMI (kg/m^2)	25.97 (23.63, 28.89)	25.39 (23.29, 28.34)	26.30 (23.73, 28.95)	0.074
SBP (mmHg)	147.00 (133.00, 160.00)	140.00 (130.00, 150.00)	150.00 (138.00, 160.00)	0.007
DBP (mmHg)	80.00 (72.00, 88.50)	80.00 (74.00, 80.00)	80.00 (71.25, 90.00)	0.032
Duration of DM (months)	120 (78, 240)	120 (60, 240)	120 (96, 225)	0.082
Smoking history (%)	24.43	24.77	24.24	1.000
Family history of DM (%)	11.07	12.84	10.10	0.587
Complications or Comorbidities
Diabetic retinopathy (%)	46.58	41.28	49.49	0.207
Hypertension (%)	89.25	86.24	90.91	0.284
CHD (%)	23.13	21.10	24.24	0.629
Stroke (%)	33.55	30.28	35.35	0.438
Treatment at baseline
Insulin (%)	66.45	51.38	74.75	< 0.001
RAASi (%)	44.63	55.96	38.38	0.004
Laboratory parameters at baseline
Scr (µmol/L)	126.00 (95.00, 184.00)	102.00 (83.00, 142.00)	143.50 (109.00, 204.75)	< 0.001
eGFR (mL/min/1.73m^2)	46.72 (28.83, 64.90)	56.33 (41.34, 76.47)	37.88 (25.42, 57.23)	< 0.001
Hemoglobin (g/L)	118.18 ± 23.55	126.94 ± 22.43	113.35 ± 22.80	< 0.001
Plasma ALB (g/L)	34.20 (29.00, 39.00)	38.00 (34.00, 41.00)	32.85 (27.00, 37.00)	< 0.001
FPG (mmol/L)	6.92 (5.53, 8.71)	6.89 (5.67, 8.78)	6.94 (5.42, 8.62)	0.630
Total cholesterol (mmol/L)	4.81 (4.07, 5.80)	4.50 (3.98, 5.23)	5.01 (4.20, 6.24)	0.001
LDL-C (mmol/L)	2.94 (2.36, 3.66)	2.70 (2.32, 3.16)	3.09 (2.40, 3.84)	0.001
HDL-C (mmol/L)	1.19 (1.02, 1.40)	1.14 (0.99, 1.37)	1.21 (1.06, 1.42)	0.101
Triglyceride (mmol/L)	1.78 (1.27, 2.50)	1.67 (1.26, 2.47)	1.82 (1.28, 2.50)	0.417
HbA1c (%)	7.40 (6.50, 8.80)	7.30 (6.60, 8.70)	7.45 (6.30, 8.80)	0.822
BUN (mmol/L)	8.40 (6.20, 11.40)	7.20 (5.40, 9.30)	9.30 (6.73, 12.80)	< 0.001
Serum uric acid (µmol/L)	376.00 (310.50, 454.00)	360.00 (299.00, 406.00)	391.00 (317.75, 480.25)	0.017
Serum cystatin C (mg/L)	1.77 (1.33, 2.42)	1.37 (1.18, 1.78)	2.02 (1.57, 2.65)	< 0.001
24-h urine protein (g)	1.92 (0.70, 4.44)	0.72 (0.36, 1.89)	3.19 (1.44, 5.81)	< 0.001
UACR (mg/g)	628.90 (215.24, 1133.38)	228.07 (50.20, 740.40)	785.54 (402.29, 1237.60)	< 0.001

Note: Variables are expressed as frequency (%), mean ± standard deviation, or median (IQR).

Abbreviations: IQR, interquartile range; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; DM, diabetes mellitus; CHD, coronary heart disease; RAASi, renin-angiotensin-aldosterone system inhibitor; Scr, serum creatinine; eGFR, estimated glomerular filtration rate; ALB, albumin; FPG, fasting plasma glucose; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; HbA1c, glycated hemoglobin; BUN, blood urea nitrogen; UACR, urinary albumin/creatinine ratio.

Table 2 Predictors Identified by Univariate Cox Regression Analysis

Variables	Univariate Cox Regression
	HR (95% CI)	P-value
SBP (incremented by 1 mmHg)	1.012 (1.005–1.019)	0.001
DBP (incremented by 1 mmHg)	1.016 (1.003–1.030)	0.016
Insulin treatment	1.490 (1.080–2.055)	0.015
RAASi treatment	0.576 (0.432–0.768)	< 0.001
Hemoglobin (incremented by 1 g/L)	0.976 (0.970–0.983)	< 0.001
Plasma ALB (incremented by 1 g/L)	0.890 (0.869–0.911)	< 0.001
Total cholesterol (incremented by 1 mmol/L)	1.170 (1.078–1.269)	< 0.001
LDL-C (incremented by 1 mmol/L)	1.110 (1.048–1.174)	< 0.001
Serum uric acid (incremented by 1µmol/L)	1.002 (1.001–1.003)	0.001
BUN (incremented by 1 mmol/L)	1.010 (1.005–1.016)	< 0.001
Scr (incremented by 1µmol/L)	1.010 (1.008–1.013)	< 0.001
Serum cystatin C (incremented by 1 mmol/L)	2.607 (2.205–3.083)	< 0.001
eGFR (incremented by 1 mL/min/1.73m^2)	0.975 (0.968–0.982)	< 0.001
24-h urine protein (incremented by 1 g)	1.235 (1.189–1.284)	< 0.001
UACR (incremented by 100 mg/g)	1.029 (1.020–1.037)	< 0.001

Abbreviations: HR, hazard ratio; CI, confidence interval; SBP, systolic blood pressure; DBP, diastolic blood pressure; RAASi, renin-angiotensin-aldosterone system inhibitor; ALB, albumin; LDL-C, low-density lipoprotein cholesterol; BUN, blood urea nitrogen; Scr, serum creatinine; eGFR, estimated glomerular filtration rate; UACR, urinary albumin/creatinine ratio.

Figure 1 Forest plots of the predictors selected by multivariate Cox analysis in the derivation cohort. (A) Results of the multivariate Cox regression analysis of the derivation cohort; (B) the multivariate regression results after continuous variables transformed into categorical variables in the derivation cohort. ^aRepresented the level of ALB was between 25 and 35 g/L; ^brepresented the level ALB level was less than 25 g/L. Red squares and horizontal bars represent the overall estimates and 95% CIs.

Abbreviations: HR, hazard ratio; CI, confidence interval; Scr, serum creatinine; ALB, albumin; UACR, urinary albumin/creatinine ratio.

Figure 2 A nomogram of the final prediction model.

Abbreviations: Scr, serum creatinine; ALB, albumin; UACR, urinary albumin/creatinine ratio.

Table 3 A Simple Risk Table of the Final Prediction Model

Risk Factors	Category	Points
Scr (µmol/L)	< 180	0
	≥ 180	4
Plasma ALB (g/L)	≥ 35	0
	[25,35)	2
	<25	4
UACR (mg/g)	<300	0
	≥ 300	2
Insulin treatment	No	0
	Yes	1.5

Abbreviations: Scr, serum creatinine; ALB, albumin; UACR, urinary albumin/creatinine ratio.

Figure 3 Restricted cubic spline (RCS) curves of the continuous variables involved in the final model.

Abbreviations: Scr, serum creatinine; ALB, albumin; UACR, urinary albumin/creatinine ratio.

Figure 4 Receiver operating characteristic (ROC) curve for the nomogram and the risk table. The solid blue line represented the derivation cohort, and the solid red line represented the validation cohort. (A) ROC curve for the nomogram. The AUC and its 95% CI were 0.791 (0.762–0.820) in the derivation cohort and 0.793 (0.746–0.840) in the validation cohort; (B) ROC curve for the risk table. The AUC and its 95% CI were 0.764 (0.731–0.797) in the derivation cohort and 0.763 (0.714–0.812) in the validation cohort.

Abbreviations: ROC, receiver operating characteristic; AUC, area under the ROC curve; CI, confidence interval.

Figure 5 The calibration curves for the nomogram and the risk table in the derivation and validation cohort. (A) The calibration curves for the nomogram in the derivation cohort; (B) the calibration curves for the nomogram in the validation cohort; (C) the calibration curves for the risk table in the derivation cohort; (D) the calibration curves for the risk table in the validation cohort. The calibration plot showed the agreement between the predicted probability (x-axis) and the actual probability (y-axis) of the 24-month risk of the study outcomes. A perfect prediction would correspond to the 45° grey dotted line. Spike histograms on the top of each picture reflected the number of T2DKD patients with a predicted probability corresponding to the x-axis value.

Figure 6 Risk stratification and Kaplan–Meier curve of each risk group in the derivation and validation cohort. (A) Kaplan–Meier curve in the derivation cohort; (B) Kaplan–Meier curve in the validation cohort; (C) risk stratification based on the risk table in the derivation and the validation cohort.