Kidney disease progression in patients of upper tract urothelial carcinoma following unilateral radical nephroureterectomy

Figures & data

Figure 1. Flow chart for patient enrollment in UTUC and RCC patients. *Serum creatinine doubling and/or ESRD necessitating dialysis. Notes: ESRD, end-stage renal disease; RN, radical nephrectomy; RNU, radical nephroureterectomy; RCC, renal cell carcinoma; UTUC, upper tract urothelial carcinoma.

Table 1. Demographic and clinical characteristics of study subjects with UTUC and RCC receiving unilateral RN.

	UTUC	RCC
Characteristics	(n = 297)	(n = 319)	p-Values
Male, n (%)	171 (57.6)	237 (74.3)	<0.001
Age (SD), years	70.0 (11.3)	63.1 (14.2)	<0.001
Smoking			0.172
Current smoker, n (%)	8 (2.7)	18 (5.6)
Ex-smoker, n (%)	13 (4.4)	16 (5.0)
Nonsmoker, n (%)	276 (92.9)	285 (89.3)
Comorbidity
Hypertension, n (%)	142 (47.8)	161 (50.5)	0.510
Diabetes mellitus, n (%)	79 (26.6)	57 (17.9)	0.009
Cerebrovascular disease, n (%)	19 (6.4)	13 (4.1)	0.194
Coronary artery disease, n (%)	37 (12.5)	18 (5.6)	0.003
Peripheral artery disease, n (%)	7 (2.4)	0	0.006
eGFR, mL/min/1.73 m^2			<0.001
≥90, n (%)	9 (3.0)	57 (17.9)
60–89, n (%)	49 (16.5)	145 (45.5)
45–59, n (%)	86 (29.0)	82 (25.7)
30–44, n (%)	86 (29.0)	25 (7.8)
15–29, n (%)	44 (14.8)	9 (2.8)
<15, n (%)	23 (7.7)	1 (0.3)
Body mass index (SD), kg/m^2	23.5 (4.4)	24.6 (3.6)	0.005
Serum albumin (SD), g/dL	4.0 (0.4)	4.1 (0.4)	0.012
Tumor stage			<0.001
Stage I, n (%)	89 (30.0)	134 (42.0)
Stage II, n (%)	31 (10.4)	54 (16.9)
Stage III, n (%)	73 (24.6)	82 (25.7)
Stage IV, n (%)	104 (35.0)	49 (15.4)

Notes: All data were described as number (%), except means ± SD for age and body mass index. SD, standard deviation; eGFR, estimated glomerular filtration rate; RCC, renal cell carcinoma; UTUC, upper tact urothelial carcinoma.

Figure 2. Kaplan–Meier curves of the cumulative incidence of serum creatinine doubling and/or ESRD necessitating dialysis (A) and all-cause mortality (B) in patients of UTUC and RCC after unilateral RN during a 10-year follow-up. Notes: RCC, renal cell carcinoma; UTUC, upper tract urothelial carcinoma.

Table 2. Incidence rate and risk of renal outcome, overall mortality, tumor recurrence and metastasis among patients with UTUC compared with those with RCC receiving unilateral RN.

				Crude		Model 1^a		Model 2^b
Endpoints	No. of event	Person-years	Incidence rate*	Hazard ratio (95% CI)	p-Values	Hazard ratio (95% CI)	p-Values	Hazard ratio (95% CI)	p-Values
Renal outcome
Serum creatinine doubling
UTUC	121	922	13.12	4.76 (3.27–6.93)	<0.001	3.29 (2.11–5.12)	<0.001	3.51 (2.25–5.48)	<0.001
RCC	36	1381	2.61	1		1
Composite endpoint^c
UTUC	128	853	15.01	4.94 (3.42–7.15)	<0.001	2.90 (1.88–4.49)	<0.001	3.13 (2.01–4.87)	<0.001
RCC	37	1380	2.68	1		1
All-cause mortality
UTUC	81	1100	7.36	1.33 (0.97–1.82)	0.080	0.62 (0.41–0.94)	0.026	–
RCC	74	1488	4.97	1		1
Tumor recurrence
UTUC	127	804	15.81	15.45 (8.70–27.42)	<0.001	16.44 (8.64–31.28)	<0.001	17.04 (8.75–33.19)	<0.001
RCC	13	1462	0.89	1		1		1
Tumor metastasis^d
UTUC	43	1072	4.01	0.78 (0.53–1.16)	0.217	0.43 (0.25–0.73)	0.002	0.47 (0.26–0.84)	0.011
RCC	63	1307	4.82	1		1		1

Notes: CI, confidence interval; ESRD, end-stage renal disease; RCC, renal cell carcinoma; UTUC, upper tact urothelial carcinoma.

* per 10² person-years.

^aAdjusted for all covariate listed in Table 1.

^bAdjusted for all covariate listed in Table 1 and competing the risk of death.

^cSerum creatinine doubling and/or ESRD necessitating dialysis.

^dExcluding patients with metastatic tumor in index date.

Figure 3. Multivariate regression analysis of potential predictors for composite renal outcome among patients with UTUC and RCC after unilateral RN. *Composite renal outcome: serum creatinine doubling and/or ESRD necessitating dialysis. Notes: RCC, renal cell carcinoma; UTUC, upper tract urothelial carcinoma.

Table 3. Potential predictors for composite renal outcome in patients with UTUC and RCC receiving unilateral RN.

	Univariate analysis		Multivariate analysis^a
Variables	HR (95% CI)	p-Values	HR (95% CI)	p-Values
UTUC (RCC as reference)	4.94 (3.42–7.15)	<0.001	3.73 (2.46–5.65)	<0.001
Age, per 1 year old	1.04 (1.03–1.05)	<0.001	1.03 (1.01–1.04)	0.005
Sex, male vs. female	0.71 (0.52–0.97)	<0.001	0.90 (0.63–1.28)	0.558
Smoking
Current smoker	1.99 (1.15–3.45)	0.014	0.82 (0.33–2.08)	0.681
Ex-smoker	0.59 (0.24–1.44)	0.249	1.83 (0.99–3.38)	0.053
Nonsmoker (as reference)	1		1
Comorbidity
Hypertension	1.30 (0.96–1.77)	0.092	1.04 (0.74–1.47)	0.810
Diabetes mellitus	2.03 (1.47–2.80)	<0.001	1.52 (1.07–2.14)	0.018
Cerebrovascular disease	1.60 (0.86–2.95)	0.135	1.25 (0.66–2.36)	0.498
Coronary artery disease	2.08 (1.34–3.21)	0.001	1.21 (0.74–1.98)	0.449
Peripheral artery disease	3.63 (1.49–8.87)	0.005	1.09 (0.41–2.88)	0.869
eGFR (mL/min/1.73 m^2)
≥60 (as reference)	1		1
45–59	1.26 (0.83–1.90)	0.278	0.82 (0.52–1.28)	0.375
30–44	2.30 (1.51–3.51)	<0.001	0.84 (0.53–1.35)	0.480
15–29	3.83 (2.22–6.61)	<0.001	1.30 (0.70–2.41)	0.405
<15	12.58 (7.16–22.10)	<0.001	4.14 (2.20–7.78)	<0.001
Body mass index, per 1 kg/m^2	0.96 (0.92–1.00)	0.079	0.98 (0.94–1.03)	0.516
Serum albumin, per 1 g/dL	0.42 (0.29–0.62)	<0.001	0.69 (0.41–1.15)	0.158
Tumor stage
Stage I (as reference)	1
Stage II	1.19 (0.66–1.57)	0.472
Stage III	1.09 (0.72–1.67)	0.675
Stage IV	1.34 (0.68–1.78)	0.464

Notes: CI, confidence interval; HR, hazards ratio; eGFR, estimated glomerular filtration rate; RCC, renal cell carcinoma; UTUC, upper tact urothelial carcinoma.

^a All factors with a p < 0.1 in univariate analysis were included in the Cox multivariate analysis.