Cancer before and after the start of hemodialysis and association with mortality – an Eastern-European multicenter study

Figures & data

Figure 1. Flow diagram of the study inclusion and exclusion process.

Table 1. Comparison between ESKD patients without cancer versus patients with cancer before HD initiation versus patients with de novo cancer after HD initiation.

Variables	Overall ESKD patients (n = 1377)	NoC group (n = 1232)	CPI group (n = 50)	DNC group (n = 95)	P* (NoC vs. CPI)	P** (NoC vs. DNC)	P*** (CPI vs. DNC)	P (NoC vs. CPI vs. DNC)
Age (years)^a	61 [18]	61 [17]	63 [12]	67 [14]	0.134	<0.001	0.789	<0.001
Gender (male), n (%)^c	799 (58.02)	711 (57.71)	26 (52)	62 (65.26)	0.466	0.161	0.152	0.242
Primary renal disease
Glomerulonephritis, n (%)^c	361 (26.21)	331 (26.86)	7 (14)	23 (24.21)	0.048	0.613	0.196	0.115
Diabetes mellitus, n (%)^c	276 (20.04)	262 (21.26)	2 (4)	12 (12.63)	0.001	0.048	0.139	0.002
Arterial hypertension, n (%)^c	191 (13.87)	179 (14.53)	4 (8)	8 (8.42)	0.299	0.124	0.930	0.194
Tubulointerstitial diseases, n (%)^c	269 (19.53)	211 (17.12)	27 (54)	31 (32.63)	<0.001	0.0005	0.02	<0.001
Cystic kidney disease, n (%)^c	124 (9)	118 (9.57)	2 (4)	4 (4.21)	0.280	0.095	0.952	0.096
Unknown, n (%)^c	65 (4.72)	59 (4.79)	1 (2)	5 (5.26)	0.566	0.802	0.664	0.638
Others, n (%)^c	91 (6.61)	72 (5.84)	7 (14)	12 (12.63)	0.03	0.015	0.801	0.003
Comorbidities
Coronary artery disease, n (%)^c	698 (50.69)	593 (48.13)	33 (66)	72 (75.79)	0.014	<0.001	0.242	<0.001
Stroke, n (%)^c	258 (18.74)	224 (18.18)	10 (20)	24 (25.26)	0.710	0.100	0.54	0.227
Peripheral vascular disease, n (%)^c	318 (23.1)	296 (24)	7 (14)	15 (15.78)	0.125	0.078	0.966	0.055
Hepatitis B virus infection, n (%)^c	58 (4.21)	55 (4.46)	0 (0)	3 (3.15)	0.27	0.79	0.55	0.265
Hepatitis C virus infection, n (%)^c	194 (14.08)	176 (14.28)	4 (8)	14 (14.74)	0.297	0.879	0.297	0.448
Age at cancer diagnosis (years)^b	–	–	58.63 ± 10.23	68.32 ± 10.73	–	–	<0.001	–
Time from cancer identification to dialysis start (years)^b	–	–	3.97 ± 4.96	–	–	–	–	–
Time from dialysis start to cancer identification (years)^a	–	–	–	1 [2.75]	–	–	–	–
Hemoglobin (g/dl)^b	10.84 ± 1.34	10.93 ± 1.28	10.01 ± 1.83	9.9 ± 1.70	<0.001	<0.001	0.743	<0.001
Ferritin (ng/ml)^a	1153 [846.62]	1090.5 [889]	851.9 [964.4]	1048 [993.5]	0.638	0.542	0.991	0.672
Albumin (g/dl)^a	4.3 [0.3]	4.7 [0.2]	3.55 [1.09]	3.64 [0.78]	<0.001	<0.001	0.697	0.057
hsCRP (mg/L)^a	0.63 [1.34]	0.71 [1.68]	3.29 [20.1]	4.45 [11.43]	<0.001	<0.001	0.894	0.984
Calcium (mg/dl)^b	8.86 ± 1.18	8.83 ± 0.73	8.71 ± 1.28	8.77 ± 0.92	0.573	0.436	0.586	0.868
Phosphate (mg/dl)^b	5. 03 ± 1.6	5.08 ± 1.49	4.47 ± 1.51	4.31 ± 1.49	0.008	0.006	0.555	<0.001
iPTH (pg/ml)^a	329.1 [508.9]	338 [516.6]	167.3 [241.4]	207.05 [345.6]	0.009	0.08	0.143	0.001
25-OH vitamin D (ng/ml)^a	23.07 [19.17]	22.92 [19.48]	16.13 [19.78]	14.8 [15.15]	0.005	0.02	0.495	0.001
eKt/V^b	1.38 ± 0.21	1.39 ± 0.21	1.34 ± 0.27	1.26 ± 0.23	0.004	0.022	0.361	<0.001
ESA dose (U/week)^a	80 [80]	80 [80]	90 [134.95]	100 [70]	0.949	0.014	0.423	0.013
Mortality rate, n (%)^c	371 (26.94)	264 (21.42)	38 (76)	69 (72.63)	<0.001	<0.001	0.696	<0.001
Time from cancer to death (years)^b		–	3.88 ± 3.81	0.73 ± 1.06	–	–	<0.001

*Differences are significant.

^aDistributions are not Gaussian. Data are presented as medians and [interquartile ranges].

^bData is presented as mean ± SD.

^cData is presented as numbers and (percentages of the total). The p-value was calculated using the chi-square test.

CPI: cancer prior to HD initiation; DNC: de novo cancer after HD initiation; eKt/V: effective Kt/V; ESA: erythropoiesis-stimulating agents; hsCRP: high-sensitivity C-reactive protein; iPTH: intact parathyroid hormone.

Table 2. Primary site of cancer in the CPI and DNC groups.

Cancer site	CPI group (N = 50)	DNC group (N = 95)
Hematologic	11 (22%)	15 (15.78%)
Digestive	10 (20%)	28 (29.47%)
Kidney and urinary tract	8 (16%)	18 (18.95%)
Female genital tract	9 (18%)	8 (8.42%)
Prostate	5 (10%)	0 (0%)
Breast	2 (4%)	3 (3.15%)
Respiratory	1 (2%)	11 (11.58%)
Endocrine	0 (0%)	3 (3.16%)
Unknown origin	4 (8%)	9 (9.47%)

CPI: cancer before HD initiation; DNC: de novo cancer after HD initiation.

Figure 2. Survival curves of HD patients with cancer after HD initiation, with cancer before HD initiation and without cancer.

Table 3. Cox proportional hazards regression analysis for risk factors of all-cause mortality.

Predictor	Unadjusted HR [95% CI]	P	Adjusted HR [95% CI]	P
Age (years)	1.045 [1.034–1.056]	<0.001	1.03 [1.001–1.064]	0.043
Diabetes mellitus	1.598 [1.145–2.231]	0.006	–	–
Coronary artery disease	2.948 [2.041–4.258]	<0.001	3.60 [1.429–9.108]	0.007
Stroke	2.042 [1.450–2.875]	<0.001	–	–
Cancer	3.686 [2.901–4.683]	<0.001	6.89 [4.47–10.62]	<0.001
Hemoglobin (g/dl)	0.584 [0.534–0.638]	<0.001	0.71 [0.57–0.88]	0.002
Phospate (mg/dl)	1.091 [1.021–1.066]	0.005	–	–
Calcium (mg/dl)	0.697 [0.597–0.814]	<0.001	–	–
25-OH Vitamin D (ng/ml)	0.925 [0.911–0.939]	<0.001	0.95 [0.92–0.98]	0.001
iPTH (pg/ml)	1.00 [0.99–1.00]	0.009	–	–
hsCRP (mg/L)	1.270 [1.217–1.325]	<0.001	1.006 [1.003–1.009]	<0.001
eKt/V	0.155 [0.060–0.397]	<0.001	0.14 [0.04–0.47]	0.001

eKt/V: effective Kt/V; hsCRP: high-sensitivity C-reactive protein; iPTH: intact parathyroid hormone.

Data availability statement

The original contributions of this study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.