Effect of febuxostat on renal function in patients from South China with CKD3 diabetic nephropathy

Wen, Huang; Yongling, Zhu; Shuying, Zheng; Jiali, Wang; Yanling, Zhao

doi:10.1590/2175-8239-JBN-2019-0091

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Brazilian Journal of Nephrology

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Original Article • J. Bras. Nefrol. 42 (4) • Oct-Dec 2020 • https://doi.org/10.1590/2175-8239-JBN-2019-0091 copy

Effect of febuxostat on renal function in patients from South China with CKD3 diabetic nephropathy

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective:

To investigate the efficacy and safety of febuxostat on renal function in CKD stage 3 diabetic nephropathy patients.

Methods:

Patients in our hospital with chronic kidney disease (CKD) stage 3 diabetic nephropathy (DN) complicated by high serum uric acid (360 µmol/L) were recruited. Patients were then divided into treatment group and control group according to the random number table method. All the patients received low purine diet, renin-angiotensin-aldosterone system (RAAS) inhibitors, and adequate routine hypoglycemic treatment. Febuxostat was employed only in the treatment group. The levels of blood uric acid (sUA), serum creatinine (Scr), cystatin C (cys-c), eGFR, 24-hour urine protein quantification, albuminuria, and creatinine ratio (ACR) were evaluated in all patients before and after treatment at 4, 8, 12, and 24 week.

Results:

No difference was found before treatment between the two groups. After treatment at 4, 8, 12, and 24 week, the levels of sUA, SCr, cys-c, and eGFR between the two groups were significant different (P<0.05). There was no difference in 24-hour urine protein quantification, albuminuria, and creatinine ratio between two groups before treatment, and significant differences were observed after treatment. Fifty percent of patients from the treatment group achieved the treatment goal with 20 mg febuxostat at 4 weeks. Tubular markers were also decreased with the treatment.

Conclusions:

Febuxostat can reduce uric acid and improve renal function effectively in patients with CKD stage 3 diabetic nephropathy, while being well tolerated. However, the conclusion is still uncertain due to the short term of the study.

Keywords:
Febuxostat; Renal Insufficiency, Chronic; Diabetic Nephropathies; Hyperuricemia

	Treatment Group (n=18)	Non-treatment group (n=20)
Sex (M/F)	16/2	17/3
Age (years)	58.73±11.50	57.46±10.96
Body mass index (kg/m2)	24.34±2.59	24.05±3.15
Systolic pressure (mmHg)	129.88±6.48	130.04±6.43
Diastolic pressure (mmHg)	76.42±4.70	75.03±4.75
Diabetes course (years)	11.78±5.71	12.10±5.69
Diabetic nephropathy course of disease (years)	3.64±1.53	3.71±0.65
Diabetic retinopathy (with/without)	10/8	11/9
Diabetic peripheral neuropathy (with/without)	9/9	9/11

Group	n	sUA (µmol/L)	SCr (µmol/L)	cys-c (mg/L)	eGFR (mL/min)
Treatment group	18
before treatment		447.5±83.6	172.9±20.1	1.98 ±0.21	45.3±10.6
treatment for four weeks		370.5±72.1^* * Significant difference between the treatment group and the non-treatment group (P<0.05); ^▲ ▲ significant differences before and after treatment in the treatment group (P<0.05).	141.1±24.9^* * Significant difference between the treatment group and the non-treatment group (P<0.05); ^▲ ▲ significant differences before and after treatment in the treatment group (P<0.05).	1.35 ±0.16^* * Significant difference between the treatment group and the non-treatment group (P<0.05); ^▲ ▲ significant differences before and after treatment in the treatment group (P<0.05).	52.8±11.5^* * Significant difference between the treatment group and the non-treatment group (P<0.05); ^▲ ▲ significant differences before and after treatment in the treatment group (P<0.05).
eight weeks		334.1±49.8^* * Significant difference between the treatment group and the non-treatment group (P<0.05); ^▲ ▲ significant differences before and after treatment in the treatment group (P<0.05).	139.8±35.1^* * Significant difference between the treatment group and the non-treatment group (P<0.05); ^▲ ▲ significant differences before and after treatment in the treatment group (P<0.05).	1.28 ±0.13^* * Significant difference between the treatment group and the non-treatment group (P<0.05); ^▲ ▲ significant differences before and after treatment in the treatment group (P<0.05).	50.9±13.7^* * Significant difference between the treatment group and the non-treatment group (P<0.05); ^▲ ▲ significant differences before and after treatment in the treatment group (P<0.05).
twelve weeks		297.4±51.1^* * Significant difference between the treatment group and the non-treatment group (P<0.05); ^▲ ▲ significant differences before and after treatment in the treatment group (P<0.05).	132.9±27.8^* * Significant difference between the treatment group and the non-treatment group (P<0.05); ^▲ ▲ significant differences before and after treatment in the treatment group (P<0.05).	1.30 ±0.22^* * Significant difference between the treatment group and the non-treatment group (P<0.05); ^▲ ▲ significant differences before and after treatment in the treatment group (P<0.05).	53.1±10.2^* * Significant difference between the treatment group and the non-treatment group (P<0.05); ^▲ ▲ significant differences before and after treatment in the treatment group (P<0.05).
twenty-four weeks		301.2±46.9^* * Significant difference between the treatment group and the non-treatment group (P<0.05); ^▲ ▲ significant differences before and after treatment in the treatment group (P<0.05).	148.1±30.2^* * Significant difference between the treatment group and the non-treatment group (P<0.05); ^▲ ▲ significant differences before and after treatment in the treatment group (P<0.05).	1.33±0.33^* * Significant difference between the treatment group and the non-treatment group (P<0.05); ^▲ ▲ significant differences before and after treatment in the treatment group (P<0.05).	53.8±9.6^* * Significant difference between the treatment group and the non-treatment group (P<0.05); ^▲ ▲ significant differences before and after treatment in the treatment group (P<0.05).
non-treatment group	20
before treatment		423.4±51.2	157.7±38.3	1.55±0.291	46.8±9.0
treatment for four weeks		419.1±60.1	163.2±35.9	1.48±0.40	48.2±10.4
eight weeks		427.8±46.8	153.3±29.8	1.53±0.33	45.6±11.7
twelve weeks		397.4±74.2	169.9±40.3	1.61±0.29	47.2±9.8
twenty-four weeks		421.1±55.7	170.6±51.9	1.70±0.52	42.7±13.4

Time	Group	24h urine protein (g/L)	ACR (mg/mmol)	urine NAG/Cr (U/mmol)	Urine β2-MG/Cr (mg/mmol)	Urine α1-MG/Cr (mg/mmol)
Before treatment	Treatment	4.15±2.58	439.62±79.10	3.75±0.92	159.32±61.25	4.26±0.54
Before treatment	Non-treatment	4.02±2.67	441.06±78.52	3.54±0.83	161.19±62.01	4.31±0.52
Treatment at four weeks	Treatment	3.17±2.65^* * Significant difference between treatment and non-treatment groups (P<0.05); ^△ △ significant differences before and after treatment in the treatment group (P<0.05).	331.56±76.45^* * Significant difference between treatment and non-treatment groups (P<0.05); ^△ △ significant differences before and after treatment in the treatment group (P<0.05).	2.71±0.89^* * Significant difference between treatment and non-treatment groups (P<0.05); ^△ △ significant differences before and after treatment in the treatment group (P<0.05).	131.12±60.93^* * Significant difference between treatment and non-treatment groups (P<0.05); ^△ △ significant differences before and after treatment in the treatment group (P<0.05).	3.18±0.49^* * Significant difference between treatment and non-treatment groups (P<0.05); ^△ △ significant differences before and after treatment in the treatment group (P<0.05).
Treatment at four weeks	Non-treatment	4.10±2.58	441.45±78.68	3.59±0.82	161.42±62.19	4.37±0.50
Eight weeks	Treatment group	2.85±0.89^* * Significant difference between treatment and non-treatment groups (P<0.05); ^△ △ significant differences before and after treatment in the treatment group (P<0.05).	201.06±78.82^* * Significant difference between treatment and non-treatment groups (P<0.05); ^△ △ significant differences before and after treatment in the treatment group (P<0.05).	1.65±0.90^* * Significant difference between treatment and non-treatment groups (P<0.05); ^△ △ significant differences before and after treatment in the treatment group (P<0.05).	98.22±60.41^* * Significant difference between treatment and non-treatment groups (P<0.05); ^△ △ significant differences before and after treatment in the treatment group (P<0.05).	1.97±0.51^* * Significant difference between treatment and non-treatment groups (P<0.05); ^△ △ significant differences before and after treatment in the treatment group (P<0.05).
Eight weeks	Non-treatment	4.21±2.66	442.96±79.04	3.63±1.01	162.05±61.97	4.45±0.53
Twelve weeks	Treatment	2.80±1.59^* * Significant difference between treatment and non-treatment groups (P<0.05); ^△ △ significant differences before and after treatment in the treatment group (P<0.05).	191.06±92.12^* * Significant difference between treatment and non-treatment groups (P<0.05); ^△ △ significant differences before and after treatment in the treatment group (P<0.05).	1.71±0.46^* * Significant difference between treatment and non-treatment groups (P<0.05); ^△ △ significant differences before and after treatment in the treatment group (P<0.05).	106.01±80.01^* * Significant difference between treatment and non-treatment groups (P<0.05); ^△ △ significant differences before and after treatment in the treatment group (P<0.05).	1.83±0.61^* * Significant difference between treatment and non-treatment groups (P<0.05); ^△ △ significant differences before and after treatment in the treatment group (P<0.05).
Twelve weeks	Non-treatment	4.81±2.09	501.32±79.65	3.90±1.81	222.05±49.31	5.12±1.09
Twenty four weeks	Treatment	3.07±1.21^* * Significant difference between treatment and non-treatment groups (P<0.05); ^△ △ significant differences before and after treatment in the treatment group (P<0.05).	191.06±92.12^* * Significant difference between treatment and non-treatment groups (P<0.05); ^△ △ significant differences before and after treatment in the treatment group (P<0.05).	2.32±1.06^* * Significant difference between treatment and non-treatment groups (P<0.05); ^△ △ significant differences before and after treatment in the treatment group (P<0.05).	126.01±60.98^* * Significant difference between treatment and non-treatment groups (P<0.05); ^△ △ significant differences before and after treatment in the treatment group (P<0.05).	2.08±0.30^* * Significant difference between treatment and non-treatment groups (P<0.05); ^△ △ significant differences before and after treatment in the treatment group (P<0.05).
Twenty four weeks	Non-treatment	4.26±2.45	491.65±70.99	4.58±1.11	282.71±99.43	4.92±2.41

Group	N	Leucopenia	Lesão hepática	Náusea	Infecção	Eritema	Coceira	Ataque agudo de gota
Treatment group	18	1(5)	2(10)	2(10)	2(10)	1(5)	3(15)	0
Non-treatment group	20	2(10)	3(15)	1(5)	2 (10)	1(5)	1(5)	0

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[1] Correspondence to: Zhao Yanling. E-mail: zyl131@163.com