The relationship between thyroid dysfunction and nephrotic syndrome: a clinicopathological study

www.nature.com/scientificreports OPEN Received: 14 October 2018 Accepted: 11 April 2019 Published: xx xx xxxx The relationship between thyroid dysfunction and nephrotic syndrome: a clinicopathological study Ling-Zhi Li1, Yao Hu1,2, Shuang-Lan Ai1, Lu Cheng1, Jing Liu1, Emily Morris3, Yi Li3, Shen-Ju Gou1 & Ping Fu1 Abnormalities of thyroid function are common in patients with nephrotic syndrome (NS). However, a limited number of studies have reported on the association between clinicopathologic features and thyroid dysfunction in patients with NS. We retrospectively studied 317 patients who had been definitively diagnosed with NS. The NS patients with thyroid dysfunction showed higher urine protein, creatinine and lipid levels and lower albumin and hemoglobin than those with normal thyroid function, with no significant differences of pathological types. After dividing thyroid dysfunction groups into five subgroups, interestingly, membranous nephropathy was the most common pathologic type, both in normal thyroid group and in subclinical hypothyroidism group (40.4% and 46.7%, respectively), followed by minimal change disease (28.1% and 21.7%, respectively); while in the hypothyroid, low T3, and low T3T4 groups minimal change disease is now the leading type (48.8%, 33.3% and 38.6%, respectively). High levels of urinary protein, creatinine, cholesterol, and platelets were independent risk factors predicting thyroid dysfunction, while higher albumin and hemoglobin were protective factors. We demonstrated that the type of renal pathology was different among NS patients in different thyroid dysfunction subgroups. Interpretation of the interactions between thyroid and renal function is a challenge for clinicians involved in the treatment of patients with NS. Nephrotic syndrome (NS) is one of the most common glomerular diseases and is defined by edema, substantial proteinuria (>3.5 g/24 hours), hypoalbuminemia (<30 g/L) and hyperlipidemia. It is often associated with thromboembolism and an increased risk of infection1. Endocrine abnormalities are common in NS patients. As a primary endocrine organ, the thyroid plays an important role in kidney growth and function2,3. Kidneys in return play a crucial role in metabolism and elimination of thyroid hormone (TH)4. A variety of altered thyroid hormone levels and metabolisms such as hypothyroidism and subclinical hypothyroidism (SCH) have been reported in NS and CKD patients5–7. Recently, much interest has been focused on euthyroid sick syndrome (ESS), which is characterized by decreased serum FT3 and/or FT4 levels and no significant increase in TSH8. However, the data related to different types of thyroid dysfunction in NS, especially the relationship between thyroid function and pathological characteristics of NS patients, are scarce. This study was to evaluate the thyroid hormone profile in patients with NS, to identify clinical predictors of thyroid dysfunction in patients with NS, and to analyze the associations of pathological characteristics with the thyroid function among patients with NS. Results Baseline demographics and clinical characteristics of the enrolled patients. Initially, 348 NS patients were enrolled from January 2013 to December 2016. After excluding patients with primary thyroid disease (including two patients with hyperthyroidism) and patients without a renal biopsy or data on thyroid function, 317 patients remained in the study. Among these patients, we found that 140 (44.16%) underwent the testing after steroid therapy. The baseline demographics and clinical characteristics of the enrolled patients were summarized in Table 1. We first divided NS patients into the normal thyroid function group (n = 57) and the thyroid dysfunction group (n = 260). The mean age, sex, and duration of NS did not differ between the two groups. 1 Renal Division, Department of Medicine, West China Hospital of Sichuan University, Kidney Research Institute, Chengdu, 610041, China. 2Renal Division, Department of Medicine, Affiliated Hospital of Chengdu University, Chengdu, 610081, China. 3Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, United States of America. Ling-Zhi Li and Yao Hu contributed equally. Correspondence and requests for materials should be addressed to S.-J.G. (email: ) Scientific Reports | (2019) 9:6421 | https://doi.org/10.1038/s41598-019-42905-4 1 www.nature.com/scientificreports www.nature.com/scientificreports/ Normal thyroid (n = 57) Thyroid dysfunction (n = 260) P Clinical characteristics Age (Year) 41.3 ± 14.33 40.65 ± 16.16 0.779 Male (%) 31(54.40%) 139(53.60%) 0.517 Duration of NS (Month) 3.00 [1.00, 8.00] 6.00 [1.00, 10.00] 0.098 HB (g/L) 143.14 ± 23.55 132.24 ± 25.17 0.003 WBC (109/L) 7.36 ± 2.53 8.02 ± 3.41 0.099 PLT (109/L) 202.23 ± 72.02 232.79 ± 86.77 0.014 UA (umol/L) 354.36 ± 87.87 361.52 ± 102.29 PRO (g/24 h) 4.03 ± 2.45 8.27 ± 6.56 0.637 <0.001 PCR (g/mmol Cr) 0.47 ± 0.4 0.9 ± 0.6 <0.001 ALB (g/L) 28.68 ± 6.19 22.08 ± 5.88 <0.001 SCR (umol/L) 55.00 [61.00, 75.5] 70.00 [55.00, 104.95] 0.027 TG (mmol/L) 2.03 ± 1.06 2.46 ± 1.6 0.055 <0.001 TC (mmol/L) 7.15 ± 2.24 8.48 ± 3.23 LDL (mmol/L) 4.54 ± 1.93 5.54 ± 2.78 0.002 FT3 (pmol/L) 4.49 ± 0.64 3.17 ± 1.39 <0.001 TT3 (nmol/L) 1.64 ± 0.26 1.2 ± 0.43 <0.001 FT4 (pmol/L) 15.8 ± 2.18 12.81 ± 3.42 <0.001 TT4 (nmol/L) 87.32 ± 12.8 66.07 ± 25.38 <0.001 TSH (mU/L) 4.57 [2.60, 6.81] 3.00 [2.02, 3.60] <0.001 RT3 (nmol/L) 0.36 ± 0.14 0.3 ± 0.15 0.215 Hypertension 17.50% 20.20% 0.653 Diabetes 1.80% 5.70% 0.365 Pulmonary infection 7.00% 15.20% 0.157 AKI 1.80% 4.20% 0.624 CKD 1.80% 8.00% 0.163 MN 40.4% 30.7% 0.339 MCD 28.1% 36.2% IgAN 10.5% 7.8% MPGN 3.5% 1.9% MsPGN 0.00% 3.50% FSGS 3.5% 3.5% Secondary NS 14.0% 16.3% Coexisting diseases (%) Renal biopsy (%) Table 1. Comparisons of clinical features and laboratory findings between the normal thyroid group and the thyroid dysfunction group. Data are expressed as mean ± standard deviation, median and interquartile range, or percent frequency, as appropriate. MN membranous nephropathy, MCD minimal-change disease, FSGS focal segmental glomerulosclerosis, MPGN membrane proliferative glomerulonephritis, MsPGN mesangial proliferative glomerulonephritis, secondary NS secondary reasons of nephrotic syndrome. However, PRO was significantly higher, and serum ALB was significantly lower in NS patients with thyroid dysfunction compared to those with normal thyroid function (8.27 ± 6.56 g/24 h vs. 4.03 ± 2.45 g/24 h, P < 0.001; 22.08 ± 5.88 g/L vs. 28.68 ± 6.19 g/L, P < 0.001; respectively). Blood lipid parameters at presentation showed that the levels of TC and LDL were significantly higher in the thyroid dysfunction group than those in the normal thyroid function group (8.48 ± 3.23 g/L vs. 7.15 ± 2.24 g/L, P < 0.001; 5.54 ± 2.78 g/L vs. 4.54 ± 1.93 g/L, (...truncated)