Clinical study of low dose febuxostat on improving renal function in elderly patients with asymptomatic hyperuricemia

doi:10.3969/j.issn.1674-8115.2022.07.006

Abstract

Abstract: Objective

·To investigate the efficacy, safety and effect on renal function of low-dose febuxostat in the treatment of elderly patients with chronic kidney disease (CKD) complicated with asymptomatic hyperuricemia (HUA).

Methods

·In this prospective cohort study, a total of 102 elderly patients who were hospitalized in the Wangjiangshan Branch, Zhejiang Province People's Hospital from February 2021 to July 2021 and met the enrollment conditions were selected. They were divided into low dose group (20 mg/d), normal dose group (40 mg/d) and control group (without urate-lowering drug, mainly lifestyle intervention). The total course of treatment was 3 months. The control rates of serum uric acid (SUA) were calculated in each group monthly. The changes of SUA, serum creatinine (Scr), creatinine clearance rate (Ccr) and estimated glomerular filtration rate (eGFR) were collected and calculated at baseline and after 1 and 3 months of treatment. Meanwhile, eGFR1 was calculated by the simplified diet in renal disease (MDRD) equation, and eGFR2 was calculated by the chronic kidney disease epidemiology collaboration (CKD-EPI) equation. At the same time, cardiovascular and cerebrovascular events, gout attack, allergy and other adverse events caused by febuxostat were recorded. χ² test was used to compare the differences in gender composition, basic disease and drug use among the three groups. One-way ANOVA was used to compare the differences in SUA, Scr, Ccr, eGFR1 and eGFR2 among the three groups.

Results

·After 1, 2 and 3 months of treatment, the control rates of SUA in the low dose group and normal dose group were 93.8%, 93.8%, 90.6% and 93.8%, 93.8%, 96.9%, respectively. The SUA levels in the above two groups were significantly decreased, compared with the control group (all P=0.000). Ccr, eGFR1, eGFR2 in the low dose group were higher than those at baseline (P=0.006, P=0.013, P=0.015) and those in the control group (P=0.019, P=0.020, P=0.021). There were no significant differences in the decrease of SUA between the normal dose group and the low dose group, but they were significantly greater than those in the control group (all P=0.000). The increase of Ccr, eGFR1 and eGFR2 in the low dose group was significantly higher than that in the control group (P=0.004, P=0.002, P=0.003), but the difference was not statistically significant compared with the normal dose group. Severe adverse events specific to febuxostat were not observed.

Conclusion

·Low dose and normal dose of febuxostat both have a similar urate-lowering efficacy in elderly patients with CKD complicated with asymptomatic HUA, getting a high control rate of SUA and improving renal function without serious adverse events. It is suggested a low dose of febuxostat at the beginning of the clinical intervention of asymptomatic HUA.

Key words: febuxostat, dosage, elderly people, chronic kidney disease (CKD), hyperuricemia (HUA)

CLC Number:

R589.7

LAI Xiuxiu, ZHU Qingyan, TAN Jiaqi, YANG Ling, ZHU Yan, ZHOU Gongmin. Clinical study of low dose febuxostat on improving renal function in elderly patients with asymptomatic hyperuricemia[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(7): 885-892.

Figures/Tables 4

TrendMD

References 32

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Item	Normal dose group （n=32）	Low dose group （n=32）	Control group （n=34）	F/χ²value	P value
Age/year	88.66±2.88	89.28±3.47	89.68±3.35	0.824	0.442
Male/n （%）	18 （56.3）	13 （40.6）	15 （44.1）	1.735	0.420
SBP/mmHg	126.34±11.23	127.13±8.95	126.38±13.92	0.046	0.955
DBP/mmHg	65.16±9.04	65.91±5.53	65.85±9.46	0.083	0.920
BMI/（kg·m^-2）	24.97±4.08	25.20±5.50	24.58±3.32	0.171	0.843
HbA1c/%	6.34±0.75	6.23±0.53	6.30±0.66	0.204	0.816
HB/（g·L^-1）	115.56±16.42	121.66±16.89	119.94±16.07	1.170	0.315
Albumin/（g·L^-1）	39.50±3.50	39.68±3.64	39.65±3.38	0.025	0.976
TAG/（mmol·L^-1）	1.23±0.53	1.37±0.65	1.36±0.73	0.486	0.616
TC/（mmol·L^-1）	3.94±0.95	3.72±0.85	4.09±0.85	1.457	0.238
HDL-C/（mmol·L^-1）	1.24±0.24	1.22±0.31	1.22±0.28	0.063	0.939
LDL-C/（mmol·L^-1）	2.12±0.95	1.89±0.62	2.25±0.68	1.859	0.161
SUA/（μmol·L^-1）	494.16±57.12	487.34±70.03	492.00±61.98	0.097	0.907
Scr/（μmol·L^-1）	119.71±24.01	115.80±23.52	117.33±22.81	0.227	0.798
Cys-C/（mg·L^-1）	1.71±0.36	1.68±0.35	1.71±0.37	0.109	0.897
Ccr/（mL·min^-1）	33.05±8.69	31.75±7.55	30.18±7.08	0.228	0.796
eGFR1/［mL·min^-1·（1.73 m²）^-1］	48.52±10.47	47.28±9.27	47.12±7.62	0.227	0.797
eGFR2/［mL·min^-1·（1.73 m²）^-1］	42.91±9.79	41.89±8.63	41.54±6.91	0.230	0.795
UACR	0.06 （0.05， 0.14）	0.06 （0.04， 0.09）	0.09 （0.06， 0.13）	3.547	0.170
Hcy/（μmol·L^-1）	17.03±5.23	17.51±5.24	16.83±5.28	0.141	0.868
Comorbidity/n （%）
Diabetes mellitus	13 （40.6）	7 （21.9）	7 （20.6）	4.083	0.147
Hypertension	26 （81.3）	26 （81.3）	28 （82.4）	0.018	0.991
Coronary atherosclerotic heart disease	20 （62.5）	23 （71.9）	17 （50.0）	3.355	0.187
Drug/n （%）
ACEI/ARB	17 （53.1）	12 （37.5）	12 （35.3）	2.521	0.283
Calcium antagonists	9 （28.1）	10 （31.3）	16 （47.1）	2.986	0.225
Diuretics	11 （34.4）	13 （40.6）	10 （29.4）	0.917	0.632
Sodium bicarbonate	2 （6.3）	‒	‒	‒	‒
SGLT2i	‒	‒	‒	‒	‒
Calcium dobesilate	‒	1 （3.1）	‒	‒	‒

Item	Normal dose group （n=32）	Low dose group （n=32）	Control group （n=34）	F/χ²value	P value
Age/year	88.66±2.88	89.28±3.47	89.68±3.35	0.824	0.442
Male/n （%）	18 （56.3）	13 （40.6）	15 （44.1）	1.735	0.420
SBP/mmHg	126.34±11.23	127.13±8.95	126.38±13.92	0.046	0.955
DBP/mmHg	65.16±9.04	65.91±5.53	65.85±9.46	0.083	0.920
BMI/（kg·m^-2）	24.97±4.08	25.20±5.50	24.58±3.32	0.171	0.843
HbA1c/%	6.34±0.75	6.23±0.53	6.30±0.66	0.204	0.816
HB/（g·L^-1）	115.56±16.42	121.66±16.89	119.94±16.07	1.170	0.315
Albumin/（g·L^-1）	39.50±3.50	39.68±3.64	39.65±3.38	0.025	0.976
TAG/（mmol·L^-1）	1.23±0.53	1.37±0.65	1.36±0.73	0.486	0.616
TC/（mmol·L^-1）	3.94±0.95	3.72±0.85	4.09±0.85	1.457	0.238
HDL-C/（mmol·L^-1）	1.24±0.24	1.22±0.31	1.22±0.28	0.063	0.939
LDL-C/（mmol·L^-1）	2.12±0.95	1.89±0.62	2.25±0.68	1.859	0.161
SUA/（μmol·L^-1）	494.16±57.12	487.34±70.03	492.00±61.98	0.097	0.907
Scr/（μmol·L^-1）	119.71±24.01	115.80±23.52	117.33±22.81	0.227	0.798
Cys-C/（mg·L^-1）	1.71±0.36	1.68±0.35	1.71±0.37	0.109	0.897
Ccr/（mL·min^-1）	33.05±8.69	31.75±7.55	30.18±7.08	0.228	0.796
eGFR1/［mL·min^-1·（1.73 m²）^-1］	48.52±10.47	47.28±9.27	47.12±7.62	0.227	0.797
eGFR2/［mL·min^-1·（1.73 m²）^-1］	42.91±9.79	41.89±8.63	41.54±6.91	0.230	0.795
UACR	0.06 （0.05， 0.14）	0.06 （0.04， 0.09）	0.09 （0.06， 0.13）	3.547	0.170
Hcy/（μmol·L^-1）	17.03±5.23	17.51±5.24	16.83±5.28	0.141	0.868
Comorbidity/n （%）
Diabetes mellitus	13 （40.6）	7 （21.9）	7 （20.6）	4.083	0.147
Hypertension	26 （81.3）	26 （81.3）	28 （82.4）	0.018	0.991
Coronary atherosclerotic heart disease	20 （62.5）	23 （71.9）	17 （50.0）	3.355	0.187
Drug/n （%）
ACEI/ARB	17 （53.1）	12 （37.5）	12 （35.3）	2.521	0.283
Calcium antagonists	9 （28.1）	10 （31.3）	16 （47.1）	2.986	0.225
Diuretics	11 （34.4）	13 （40.6）	10 （29.4）	0.917	0.632
Sodium bicarbonate	2 （6.3）	‒	‒	‒	‒
SGLT2i	‒	‒	‒	‒	‒
Calcium dobesilate	‒	1 （3.1）	‒	‒	‒

Group	Normal dose group （n=32）	Low dose group （n=32）	Control group （n=34）	P value^①	P value^②
SUA/（μmol·L^-1）
Baseline	494.16±57.12	487.34±70.03	492.00±61.98	0.884	0.775
1 month after treatment	233.00±89.20^③	267.87±52.98^③	448.79±46.74	0.000	0.000
3 months after treatment	245.28±86.41^③	269.78±58.87^③	439.15±64.21^③	0.000	0.000
Scr/（μmol·L^-1）
Baseline	119.71±24.01	115.80±23.52	117.33±22.81	0.681	0.789
1 month after treatment	120.00±25.76	109.85±18.80^④	117.95±25.20	0.745	0.146
3 months after treatment	117.41±32.71	109.13±20.11^⑤	120.42±24.30	0.671	0.045
Ccr/（mL·min^-1）
Baseline	33.05±8.69	31.75±7.55	30.18±7.08	0.120	0.329
1 month after treatment	33.17±9.47	33.64±8.95^⑥	29.96±7.27	0.126	0.070
3 months after treatment	34.46±10.44	33.97±9.01^⑥	29.21±7.07	0.019	0.019
eGFR1/［mL·min^-1·（1.73 m²）^-1］
Baseline	48.52±10.47	47.28±9.27	47.12±7.62	0.536	0.941
1 month after treatment	48.67±11.35	50.27±11.31^⑦	47.12±8.27	0.528	0.200
3 months after treatment	51.20±13.49^④	50.65±11.00^⑦	45.28±6.97	0.027	0.020
eGFR2/［mL·min^-1·（1.73 m²）^-1］
Baseline	42.91±9.79	41.89±8.63	41.54±6.91	0.511	0.855
1 month after treatment	43.04±10.57	44.62±10.35^⑧	41.55±7.56	0.511	0.170
3 months after treatment	45.54±12.65^⑨	44.98±10.15^⑩	40.07±6.44	0.029	0.021

Group	Normal dose group （n=32）	Low dose group （n=32）	Control group （n=34）	P value^①	P value^②
SUA/（μmol·L^-1）
Baseline	494.16±57.12	487.34±70.03	492.00±61.98	0.884	0.775
1 month after treatment	233.00±89.20^③	267.87±52.98^③	448.79±46.74	0.000	0.000
3 months after treatment	245.28±86.41^③	269.78±58.87^③	439.15±64.21^③	0.000	0.000
Scr/（μmol·L^-1）
Baseline	119.71±24.01	115.80±23.52	117.33±22.81	0.681	0.789
1 month after treatment	120.00±25.76	109.85±18.80^④	117.95±25.20	0.745	0.146
3 months after treatment	117.41±32.71	109.13±20.11^⑤	120.42±24.30	0.671	0.045
Ccr/（mL·min^-1）
Baseline	33.05±8.69	31.75±7.55	30.18±7.08	0.120	0.329
1 month after treatment	33.17±9.47	33.64±8.95^⑥	29.96±7.27	0.126	0.070
3 months after treatment	34.46±10.44	33.97±9.01^⑥	29.21±7.07	0.019	0.019
eGFR1/［mL·min^-1·（1.73 m²）^-1］
Baseline	48.52±10.47	47.28±9.27	47.12±7.62	0.536	0.941
1 month after treatment	48.67±11.35	50.27±11.31^⑦	47.12±8.27	0.528	0.200
3 months after treatment	51.20±13.49^④	50.65±11.00^⑦	45.28±6.97	0.027	0.020
eGFR2/［mL·min^-1·（1.73 m²）^-1］
Baseline	42.91±9.79	41.89±8.63	41.54±6.91	0.511	0.855
1 month after treatment	43.04±10.57	44.62±10.35^⑧	41.55±7.56	0.511	0.170
3 months after treatment	45.54±12.65^⑨	44.98±10.15^⑩	40.07±6.44	0.029	0.021

Adverse event	Normal dose group （n=32）	Low dose group （n=32）	Control group （n=34）
Gout/n （%）	0 （0）	0 （0）	0 （0）
Rash/n （%）	1 （3.1）	0 （0）	0 （0）
Cardiovascular and cerebrovascular event/n （%）	0 （0）	0 （0）	0 （0）
Gastrointestinal event/n （%）	1 （3.1）	1 （3.1）	0 （0）
Respiratory event/n （%）	6 （18.8）	7 （21.9）	5 （14.7）
Hepatic dysfunction/n （%）	3 （9.4）	1 （3.1）	2 （5.9）
Pollakiuria/n （%）	0 （0）	1 （3.1）	0 （0）
Allergy/n （%）	0 （0）	0 （0）	0 （0）