| Background and ObjectiveThe prevalence of chronic kidney disease(CKD),a worldwide public health problem,has gradually increased in the last decade,and the current global prevalence of CKD is estimated to be 13.4%.Thyroid hormones not only play a huge role in maintaining the growth and development of the human body and the stability of the internal environment,but also promote the development of the kidneys and the stability of kidney function.Previous studies have shown that patients with chronic kidney disease(CKD)are often complicated by hypothyroidism,especially non-thyroidal disease syndromes.However,the findings and opinions of studies related to CKD and thyroid function are still inconsistent.In this study,we analyzed the basic information and relevant clinical laboratory examination data of non-dialysis patients with CKD to investigate the epidemiological characteristics and related risk factors of their concomitant hypothyroidism.Materials and MethodsIn this study,a retrospective study was conducted on 2154 non-dialysis patients with CKD,and basic information such as age,gender,underlying disease,and urine and blood-related laboratory tests were collected from the patients.The clinical data of CKD patients were statistically analyzed,and the differences were statistically significant at P < 0.05,and the quantitative indexes with statistical significance were constructed as ROC curves.The correlation analysis of renal function staging and urine protein level with thyroid hormone was performed by LSD-t method or Dunn method for two-by-two comparison.Grouping methods:(1)Grouped according to underlying disease:(1)primary nephropathy group and secondary nephropathy group;(2)primary nephropathy group was subdivided into primary nephrotic syndrome group and primary non-nephrotic syndrome group;(3)secondary nephropathy group was divided into hypertensive nephropathy group,diabetic nephropathy group and other secondary nephropathy groups.(2)Grouped according to clinical typing:(i)nephrotic syndrome group and non-nephrotic syndrome group;(ii)nephrotic syndrome group was divided into primary nephrotic syndrome group and secondary nephrotic syndrome group.(3)Grouping according to 24 h urine protein quantification: Grouping was performed at a spacing of 0.5g/d for 24 h urine protein quantification,and two-by-two comparison was performed between each group.If there was no significant difference in 24 h urine protein quantification between the two groups,they were combined,and if there was significant difference,they were not combined.After merging,each group continued to compare between two and two,and the above steps were repeated to arrive at the final grouping.(4)Grouped according to urine protein creatinine ratio(ACR): ACR <30mg/g for non-proteinuria group;30≤ACR <300mg/g for mild proteinuria group;300≤ACR<3000mg/g for moderate proteinuria group;3000mg/g≤ACR for severe proteinuria group.(5)Grouped according to renal function: eGFR≥90ml/min for CKD1 stage group;60≤eGFR<90ml/min for CKD2 stage group;30≤eGFR<60ml/min for CKD3 stage group;15≤eGFR<30ml/min for CKD4 stage group;eGFR<15ml/min for CKD5 stage group.(6)Grouping according to thyroid hormone levels:(1)grouping according to the presence or absence of thyroid hormone abnormalities: normal thyroid function and hypothyroidism group;(2)grouping according to the type of hypothyroidism: low T3 syndrome,low T4 syndrome,low T3 and T4 syndrome,subclinical hypothyroidism.Study results1 Epidemiological features of hypothyroidism in patients with CKDIn the total cohort of 2154 patients(including non-thyroidal disease syndromes and subclinical hypothyroidism),hypothyroidism occurred in 509 cases(prevalence23.6%),including 350 cases of low T3 syndrome(composition 16.2%),33 cases of low T4 syndrome(composition 1.5%),34 cases of low T3 and T4 syndrome(composition 1.6%),and subclinical hypothyroidism 92 cases(4.3%).In the primary kidney disease group,there were 847 cases with hypothyroidism235(prevalence 27.7%),low T3 syndrome 146(composition 17.2%),low T4 syndrome 25(composition 3%),low T3 and T4 syndrome 18(composition 2.1%),and subclinical hypothyroidism 46(composition 5.4%).In the secondary renal disease group of 1307 cases,there were 274 cases of hypothyroidism(prevalence 20.9%),204 cases of low T3 syndrome(composition15.6%),8 cases of low T4 syndrome(composition 0.6%),16 cases of low T3 and T4syndrome(composition 1.2%),and 46 cases of subclinical hypothyroidism(composition 3.5%).In the nephrotic syndrome group,there were 177 cases of hypothyroidism,77cases(43.5% prevalence),41 cases of low T3 syndrome(23.2% composition ratio),15 cases of low T4 syndrome(8.5% composition ratio),13 cases of low T3 and T4syndrome(7.3% composition ratio),and 8 cases of subclinical hypothyroidism(4.5%composition ratio).In the non-nephrotic syndrome group of 1977 patients,there were 432 cases of hypothyroidism(prevalence 21.9%),309 cases of low T3 syndrome(composition15.6%),18 cases of low T4 syndrome(composition 0.9%),21 cases of low T3 and T4syndrome(composition 1.1%),and 84 cases of subclinical hypothyroidism(composition 4.2%).In the primary nephrotic syndrome group,there were 122 cases of hypothyroidism,48 cases(39.3% prevalence),20 cases of low T3 syndrome(16.4%composition),13 cases of low T4 syndrome(10.6% composition),10 cases of low T3 and T4 syndrome(8.2% composition),and 5 cases of subclinical hypothyroidism(4.1% composition).There were 725 cases of primary non-nephrotic syndrome,187 cases of hypothyroidism(prevalence 25.8%),126 cases of low T3 syndrome(composition ratio 17.4%),12 cases of low T4 syndrome(composition ratio 1.7%),8 cases of low T3 and T4 syndrome(composition ratio 1.1%),and 41 cases of subclinical hypothyroidism(composition ratio 5.6%).In the secondary nephrotic syndrome group,there were 55 cases of hypothyroidism,29 cases(52.7% prevalence),21 cases of low T3 syndrome(38.3%composition),2 cases of low T4 syndrome(3.6% composition),3 cases of low T3 and T4 syndrome(5.4% composition),and 3 cases of subclinical hypothyroidism(5.4%composition).In the secondary non-nephrotic syndrome group of 1252 cases,there were 245 cases of hypothyroidism(prevalence 19.6%),183 cases of low T3 syndrome(composition 14.6%),6 cases of low T4 syndrome(composition 0.5%),13 cases of low T3 and T4 syndrome(composition 1.1%),and 43 cases of subclinical hypothyroidism(composition 3.4%).In the hypertensive nephropathy group,there were 282 cases,57 cases of hypothyroidism(20.1% prevalence),39 cases of low T3 syndrome(14% composition),4 cases of low T4 syndrome(1% composition),4 cases of low T3 and T4 syndrome(1% composition),and 10 cases of subclinical hypothyroidism(4% composition).In the diabetic nephropathy group of 938 cases,there were 192 cases of hypothyroidism(prevalence 20.5%),148 cases of low T3 syndrome(composition15.8%),2 cases of low T4 syndrome(composition 0.2%),10 cases of low T3 and T4syndrome(composition 1.1%),and 32 cases of subclinical hypothyroidism(composition 3.4%).In the group of 87 cases with other secondary renal diseases,there were 25 cases of hypothyroidism(prevalence 28.7%),17 cases of low T3 syndrome(composition ratio 19.5%),2 cases of low T4 syndrome(composition ratio 2.3%),2 cases of low T3 and T4 syndrome(composition ratio 2.3%),and 4 cases of subclinical hypothyroidism(composition ratio 4.6%).2 Analysis of risk factors for grouping hypothyroidism and type of clinical presentation in patients with CKDThe prevalence of coronary heart disease,retinopathy,age,ALT,total protein,albumin,urea,uric acid,creatinine,apolipoprotein A1,lipoprotein(a),calcium ion,phosphorus ion,eGFR,24 h urine protein quantification,white blood cells,total neutrophils,red blood cells,hemoglobin,red blood cell pressure product,platelets,PT,serum ferritin in the normal thyroid function group and hypothyroidism group The differences were statistically significant(P<0.05).The statistically significant indicators were included in the binary logistic regression analysis,and the results showed that ALT(OR 0.994,95% CI 0.988-1),albumin(OR 0.942,95% CI0.891-0.997),24 h urine protein quantification(OR 1.198,95% CI 1.062-1.353),total neutrophil count(OR 1.98,95% CI 1.026-3.824),and serum ferritin(OR 1.001,95%CI 1-1.002).The prevalence of coronary heart disease,hypertension,diabetes,retinopathy,age,total protein,albumin,urea,uric acid,creatinine,total cholesterol,triglycerides,apolipoprotein A1,LDL,lipoprotein(a),calcium(Ca),phosphorus(P),eGFR,24 h urine protein quantification,white blood cells,total neutrophil count,red blood cells,hemoglobin,and erythrocyte pressure product,platelets,PT,and serum ferritin showed statistically significant differences(P<0.05).Statistically significant indicators were included in the unordered logistic regression analysis,and the results showed low T4 syndrome: albumin(OR 0.887,95% CI 0.821-0.958),lipoprotein(a)(OR 1.001,95% CI 1-1.001),and erythrocytes(OR 0.329,95% CI 0.126-0.863).Low T4 syndrome: 24 h urine protein(OR 2.048,95% CI 1.281-3.274),hemoglobin(OR0.752,95% CI 0.597-0.948),erythrocyte pressure(OR 2.567,95% CI 1.067-6.171).Low T3 and T4 syndrome: total protein(OR 0.641,95% CI 0.422-0.973).Subclinical hypothyroidism: age(OR 1.046,95% CI 1.011-1.082),24 h urine protein(OR 1.453,95% CI 1.17-1.803).3 Analysis of urine protein level and grouping of hypothyroidism24h urine protein was finally divided into the following groups: 24 h urine protein quantification <0.5g/d for group 1;0.5≤24h urine protein quantification <2.5g/d for group 2;2.5≤24h urine protein quantification <3.5g/d mg/g for group 3;3.5≤24h urine protein quantification <6.5g/d for group 4;6.5g/d ≤ 24 h urine protein quantification for group 5.24h urine protein was negatively correlated with FT3 and FT4(r=-0.195,r=-0.345,respectively,P<0.001)and positively correlated with TSH(r=0.22,P<0.001).FT3 and FT4 started to decrease at 0.5g/d of urine protein;TSH started to increase at 3.5g/d of urine protein.ACR was negatively correlated with FT3 and FT4(r=-0.27,r=-0.188,respectively,P<0.001)and positively correlated with TSH(r=0.08,P=0.041).FT3 and FT4 started to decrease at ACR 300 mg/g;TSH started to increase at ACR 300 mg/g.4 Subgroup analysis of renal function and hypothyroidismThe eGFR was positively correlated with FT3 and FT4(r=0.403,r=0.117,P<0.001,respectively)and not significantly correlated with TSH(r=-0.011,P=0.624).FT3 and FT4 started to decrease in CKD stage 2 and CKD stage 5,respectively.there was no statistically significant correlation between TSH and renal function grouping(P>0.05).5 Correlation analysis of CKD underlying disease grouping and thyroid hormone5.1 Relationship between urine protein quantification and kidney function grouping and thyroid hormones in patients with primary and secondary kidney disease groupsFT3 and FT4 in patients with primary kidney disease started to decrease at 3.5g/d and 0.5g/d of urine protein,respectively;TSH started to increase at 3.5g/d of urine protein.In patients with secondary kidney disease,FT3 and FT4 started to decrease at0.5g/d of urine protein;TSH started to increase at 6.5g/d of urine protein.In patients with primary kidney disease,FT3 and FT4 started to decrease at CKD3 stage;TSH started to increase at CKD3 stage.In patients with secondary kidney disease,FT3 and FT4 started to decrease at CKD stage 2 and CKD stage 4,respectively,and TSH was not statistically significant with renal function grouping(P > 0.05).5.2 Relationship between urine protein quantification and thyroid hormones in the group of patients with and without nephrotic syndrome and renal functionTSH was lower in the range of 3.5-6.5 g/d and FT3 was higher in the range of≥6.5 g/d in patients with nephrotic syndrome,and the difference between FT4 and≥6.5 g/d in the range of 3.5-6.5 g/d in 24-h urine protein quantification was not statistically significant(P > 0.05).FT3 and FT4 started to decrease at 0.5g/d and TSH started to increase at 3.5g/d in non-nephrotic syndrome patients,respectively.In patients with nephrotic syndrome,FT3 and FT4 started to decrease at CKD stage 3 and CKD stage 4,respectively;TSH started to increase at CKD stage 4.In patients with non-nephrotic syndrome,FT3 and FT4 started to decrease at CKD stage2 and CKD stage 5,respectively;TSH and renal function grouping were not statistically significant(P > 0.05).5.3 Relationship between urine protein quantification and thyroid hormone in the primary nephrotic syndrome group and the primary non-nephrotic syndrome group of patients with renal function subgroupPatients in the primary nephrotic syndrome group had higher FT3 and FT4 in the24-h urine protein quantification in the range of 3.5-6.5 g/d compared with ≥6.5 g/d(P<0.05),and the difference between TSH in the 24-h urine protein quantification in the range of 3.5-6.5 g/d and ≥6.5 g/d was not statistically significant(P>0.05).FT4 decreased from 0.5 g/d in patients with primary non-nephrotic syndrome group,and there was no statistically significant difference between TSH,FT3 and 24 h urine protein quantification grouping(P > 0.05).FT3 in patients with primary nephrotic syndrome started to decrease in CKD stage 3,and there was no statistical significance between TSH,FT4 and renal function grouping(P > 0.05).Patients with primary non-nephrotic syndrome group FT3 and FT4 started to decrease at CKD3 stage,and TSH was not statistically significant with renal function subgroup(P > 0.05).5.4 eRelationship between urine protein quantification and thyroid hormone in patients in the primary and secondary nephrotic syndrome groups and renal function subgroupsPatients in the primary nephrotic syndrome group had higher FT3 and FT4 in the24-h urine protein quantification in the range of 3.5-6.5 g/d compared with ≥6.5 g/d(P<0.05),and the difference between TSH in the 24-h urine protein quantification in the range of 3.5-6.5 g/d and ≥6.5 g/d was not statistically significant(P>0.05).There was no statistically significant difference between FT3,FT4 and TSH in the range of3.5-6.5 g/d and ≥6.5 g/d in the 24 h urine protein quantification in patients with secondary nephrotic syndrome group(P > 0.05).FT3 in patients with primary nephrotic syndrome started to decrease in CKD stage 3,and there was no statistically significant difference between TSH,FT4 and renal function grouping(P > 0.05).FT3 in patients with secondary nephrotic syndrome started to decrease at CKD5 stage,and TSH and FT4 were not statistically significant with renal function subgroup(P > 0.05).ConclusionIn non-dialysis patients with CKD1.The prevalence of hypothyroidism in CKD patients is high,and most of them present with non-thyroidal disease syndromes,with low T3 syndrome being the most common;followed by subclinical hypothyroidism.2.Hypothyroidism is associated with underlying disease.The prevalence of hypothyroidism is higher in patients with primary renal disease than in patients with secondary renal disease.The prevalence of hypothyroidism was higher in patients with nephrotic syndrome than in patients with non-nephrotic syndrome.The difference between the prevalence of hypothyroidism in patients with hypertensive nephropathy and diabetic nephropathy was not significantly different.3.Increased urine protein amount,decreased blood albumin level,and decreased renal function are risk factors for the development of hypothyroidism in patients with CKD.4.It suggests that regular assessment of thyroid function should probably be started at urine protein quantification greater than 3.5 g/d or after entering CKD stage. |
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