Elevated neutrophil-lymphocyte ratio combined with hyponatremia indicate poor prognosis in renal cell carcinoma

Figures & data

Table 1. Clinical and pathological characteristics of RCC patients stratified according to NLR level.

	NLR ≤3		NLR >3		Total
	n	%	n	%	n	%
Total	411	42.4	559	57.6	970	100.0
Age (years)
≤60	143	34.8	151	27.0	294	30.3
>60	268	65.2	408	73.0	676	69.7
Sex
Female	162	39.4	197	35.2	359	37.0
Male	249	60.6	362	64.8	611	63.0
Stage
I	142	34.5	109	19.5	251	25.9
II	39	9.5	60	10.7	99	10.2
III	70	17.0	70	12.5	140	14.4
IV	54	13.1	179	32.0	233	24.0
Unknown	106	25.8	141	25.2	247	25.5
Localized vs. metastatic RCC
Localized	251	61.1	239	42.8	490	50.5
Metastatic	54	13.1	179	32.0	233	24.0
Unknown	106	25.8	141	25.2	247	25.5
Histologic subtype
Clear cell RCC	220	53.5	174	31.1	394	40.6
Non-clear cell RCC	47	11.4	56	10.0	103	10.6
Non-class. RCC	144	35.0	329	58.9	473	48.8
Tumor size
<4 cm	49	11.9	17	3.0	66	6.8
4–7 cm	56	13.6	30	5.4	86	8.9
>7 cm	65	15.8	70	12.5	135	13.9
Unknown	241	58.6	442	79.1	683	70.4
Fuhrman’s grade
Grade 1	24	5.8	18	3.2	42	4.3
Grade 2	115	28.0	76	13.6	191	19.7
Grade 3	75	18.2	76	13.6	151	15.6
Grade 4	17	4.1	35	6.3	52	5.4
Unknown	180	43.8	354	63.3	534	55.1
Presence of tumor necrosis
Yes	44	10.7	61	10.9	105	10.8
No/Unknown	367	89.3	498	89.1	865	89.2
Sarcomatoid differentiation
Yes	7	1.7	15	2.7	22	2.3
No/unknown	404	98.3	544	97.3	948	97.7
Leibovich score
0–2	33	8.0	11	2.0	44	4.5
3–5	43	10.5	13	2.3	56	5.8
>6	27	6.6	35	6.3	62	6.4
Unknown	308	74.9	500	89.4	808	83.3
Type of nephrectomy
Partial	89	21.7	46	8.2	135	13.9
Radical	267	65.0	296	53.0	563	58.0
None nephrectomy	55	13.4	217	38.8	272	28.0
Method of surgery
Laparoscopic	231	56.2	182	32.6	413	42.6
Open	125	30.4	160	28.6	285	29.4
No surgery	55	13.4	217	38.8	272	28.0
Low hemoglobin level
No	236	57.4	191	34.2	427	44.0
Yes	175	42.6	367	65.7	542	55.9
Unknown	0	0.0	1	0.2	1	0.1
Low sodium level
No	352	85.6	378	67.6	730	75.3
Yes	59	14.4	181	32.4	240	24.7
Unknown	0	0.0	0	0.0	0	0.0
Low albumin level
No	285	69.3	268	47.9	553	57.0
Yes	99	24.1	253	45.3	352	36.3
Unknown	27	6.6	38	6.8	65	6.7
High calcium level
No	279	67.9	306	54.7	585	60.3
Yes	60	14.6	138	24.7	198	20.4
Unknown	72	17.5	115	20.6	187	19.3
High LDH level
No	257	62.5	252	45.1	509	52.5
Yes	60	14.6	123	22.0	183	18.9
Unknown	94	22.9	184	32.9	278	28.7
High CRP level
No	159	38.7	96	17.2	255	26.3
Yes	169	41.1	404	72.3	573	59.1
Unknown	83	20.2	59	10.6	142	14.6
High platelets level
No	225	54.7	288	51.5	513	52.9
Yes	64	15.6	187	33.5	251	25.9
Unknown	122	29.7	84	15.0	206	21.2
Charlson Comorbidity Index
Score 0	247	60.1	324	58.0	571	58.9
Score 1–2	131	31.9	176	31.5	307	31.6
Score 3+	33	8.0	59	10.6	92	9.5

Figure 1. Kaplan-Meier curves for overall survival according to (A) NLR and (B) NLR and serum sodium groups at time of initial RCC diagnosis.

NLR: neutrophil-lymphocyte ratio; RCC: renal cell carcinoma; LLN: lower limit of normal.

Table 2. The association between NLR at time of initial RCC diagnosis and mortality.

	NLR ≤3 5-year survival % (95% CI)	NLR >3 5-year survival % (95% CI)	Unadjusted HR (95% CI)	Adjusted HR^a (95% CI)	Adjusted HR^b (95% CI)	Adjusted HR^c (95% CI)
I) Total (n = 970)	69.2 (63.4–74.2)	35.2 (30.7–39.7)	3.1 (2.5–3.9)	2.4 (1.9–3.0)	2.0 (1.6–2.6)	1.8 (1.4–2.2)
II) Restricted to clear cell RCC (n = 394)	74.9 (64.2–82.8)	44.8 (34.0–55.1)	3.4 (2.3–5.0)	2.7 (1.8–4.0)	2.3 (1.5–3.5)	2.1 (1.3–3.1)
III) Restricted to localized disease at time of initial RCC diagnosis (n = 490)	80.0 (72.6–85.4)	58.1 (50.6–64.8)	2.6 (1.8–3.8)	2.2 (1.5–3.3)	1.9 (1.3–2.9)	1.9 (1.3–2.9)

NLR: neutrophil-lymphocyte ratio; RCC: renal cell carcinoma; HR: hazard ratio; CI: confidence interval.

^aModel 1 = Adjusted for age, sex, stage and Charlson Comorbidity Index.

^bModel 2 = Adjusted for age, sex, stage, Charlson Comorbidity Index, calcium, albumin, serum sodium and LDH.

^cModel 3 = Adjusted for age, sex, stage, Charlson Comorbidity Index, calcium, albumin, serum sodium, LDH, hemoglobin, CRP and platelets.

Table 3. The association between NLR at time of initial RCC diagnosis and mortality. Results from stratified analysis.

	NLR ≤3	NLR >3	Unadjusted HR (95% CI)	Adjusted HR^a (95% CI)	Adjusted HR^b (95% CI)	Adjusted HR^c (95% CI)
	5-year survival % (95% CI)	5-year survival % (95% CI)
Low hemoglobin
Yes	51.5 (42.4–59.8)	28.0 (23.1–33.01)	2.2 (1.7–2.9)	1.9 (1.4–2.4)	1.7 (1.3–2.2)	1.5 (1.2–2.0)
No	83.3 (76.5–88.2)	47.8 (38.6–56.4)	3.8 (2.5–5.7)	2.9 (1.9–4.4)	2.6 (1.7–4.0)	2.4 (1.5–3.7)
High CRP
Yes	57.3 (48.7–65.0)	26.3 (21.7–31.1)	2.5 (1.9–3.2)	2.1 (1.6–2.7)	1.9 (1.4–2.5)	1.8 (1.4–2.4)
No	76.2 (63.8–84.8)	63.8 (47.9–76.0)	2.1 (1.2–3.7)	2.1 (1.1–3.8)	2.2 (1.1–4.1)	2.1 (1.1–4.1)
Low platelets
Yes	44.0 (30.2–57.0)	21.1 (15.0–27.9)	2.1 (1.4–3.1)	2.0 (1.4–3.0)	2.0 (1.4–3.1)	2.0 (1.3–3.1)
No	71.2 (63.6–77.5)	39.3 (33.0–45.6)	3.0 (2.2–4.1)	2.4 (1.7–3.3)	2.0 (1.4–2.7)	1.7 (1.2–2.3)

NLR: neutrophil-lymphocyte ratio; RCC: renal cell carcinoma; HR: hazard ratio; CI: confidence interval.

^aModel 1 = Adjusted for age, sex, stage and Charlson Comorbidity Index.

^bModel 2 = Adjusted for age, sex, stage, Charlson Comorbidity Index, calcium, albumin, serum sodium and LDH.

^cModel 3 = Adjusted for age, sex, stage, Charlson Comorbidity Index, calcium, albumin, serum sodium, LDH and hemoglobin, CRP and platelets (excluding the variable being stratified by).

Table 4. The combined prognostic effect of NLR and serum sodium at time of initial RCC diagnosis.

NLR & sodium levels	n	5-year survival % (95% CI)	Unadjusted HR (95% CI)	Adjusted HR^a (95% CI)	Adjusted HR^b (95% CI)	Adjusted HR^c (95% CI)
NLR ≤ 3 & Na ≥ LLN	352	73.2 (67.1–78.4)	ref.	ref.	ref.	ref.
NLR ≤ 3 & Na < LLN	59	45.3 (29.7–59.7)	2.7 (1.7–4.1)	2.2 (1.4–3.4)	2.0 (1.3–3.1)	1.8 (1.2–2.8)
NLR > 3 & Na ≥ LLN	378	41.9 (36.2–47.5)	3.1 (2.4–4.0)	2.3 (1.8–3.0)	2.1 (1.6–2.8)	1.9 (1.4–2.4)
NLR > 3 & Na < LLN	181	21.7 (15.4–28.7)	5.6 (4.2–7.4)	4.1 (3.1–5.5)	3.5 (2.6–4.7)	2.8 (2.1–3.8)

NLR: neutrophil-lymphocyte ratio; RCC: renal cell carcinoma; HR: hazard ratio; CI: confidence interval; Na: serum sodium; LLN: lower limit of normal.

^aModel 1 = Adjusted for age, sex, stage and Charlson Comorbidity Index.

^bModel 2 = Adjusted for age, sex, stage, Charlson Comorbidity Index, calcium, albumin and LDH.

^cModel 3 = Adjusted for age, sex, stage, Charlson Comorbidity Index, calcium, albumin, LDH, hemoglobin, CRP and platelets.