Serum Levels of miR-148b and Let-7b at Diagnosis May Have Important Impact in the Response to Treatment and Long-Term Outcome in IgA Nephropathy
Abstract
:1. Introduction
2. Patients and Methods
2.1. Patients
2.2. Histology
2.3. Measurement of let-7b and miR-148b by Real-Time PCR
2.4. Measurement of Galactose-Deficient IgA1 (Gd-IgA1)
2.5. Calculation of Models Based on miRNAs and Gd-igA1 Serum Levels
2.6. Follow-Up
2.7. Statistical Analysis
3. Results
3.1. Patients
3.2. Serum Levels of Gd-IgA1, miR-148, and Let-7b at Onset
3.3. Correlation of Gd-IgA1 and miRNAs with Renal Function at Onset
3.4. Correlation of Gd-IgA1 and miRNAs Levels with Histology
3.5. Renal Function Outcome
3.6. The Different Effects on Steroid and RAAS Inhibitor Treatment
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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IgAN | Healthy Controls | |
---|---|---|
n | 61 | 55 |
Age (years) (Median, range) | 41.2 (20–66.8) | 43.2 (20.5–64) |
Gender (female), n(%) | 24 (39.34%) | 22 (40%) |
eGFR (CKD-EPI) (ml/min/1.73 m2) (M ± SD) | 60.9 ± 24.6 | n.d. |
Uprot (mg/24 h) (M ± SD) | 1.7 ± 0.9 | n.d. |
Microhematouria (mH) n(%) | 60 (98.36%) | n.d. |
Macrohematuria (MH) n(%) | 15 (24.59%) | n.d. |
SBP (mmHg) (M ± SD) | 145 ± 12 | 125 ± 10 |
DBP (mmHg) (M ± SD) | 98 ± 5 | 85 ± 4 |
Renal Biopsy | ||
M0/M1 | 9/52 | - |
E0/E1 | 45/16 | - |
S0/S1 | 20/41 | - |
T0/T1/T2 | 43/16/2 | - |
C0/C1/C2 | 47/12/2 | - |
End of follow-up | ||
Follow-up (years) (median, range) | 11.9 (0.7–25.1) | n.d. |
eGFR (CKD-EPI) (ml/min/1.73 m2) (M ± SD) | 41.27 ± 30.3 | n.d. |
Uprot (mg/24 h) (M ± SD) | 1.08 ± 0.9 | n.d. |
≥50% eGFR reduction + ESRD n(%) | 29 (47.54%) | n.d. |
Annual change of eGFR (M ± SD) | −2.9 ± 5.1 | n.d. |
SP/MP/FP | 15/24/22 | n.d. |
IgAN | Healthy Controls | p | |
---|---|---|---|
n | 61 | 55 | |
Gd-IgA1 * | 1.16(0.3–4.9) | 0.73(0.06–2.31) | 0.004 |
miR-148b | 0.42(0.16–2.14) | 0.4(0.12–1.5) | NS |
let-7b | 4.14(0.32–53.8) | 1.65(0.31–18.37) | 0.002 |
Model 1 | −0.5[(−3.3)–5.4] | −1.59[(−3.9)–2.3] | 0.001 |
Model 2 | −0.36[(−3.6)–5.3] | −1.6[(−3.8)–2.3] | 0.001 |
MH (–) | MH (+) | p | |
---|---|---|---|
n = 46 | n = 15 | ||
Gd-IgA1 * | 1.23(0.4–4.8) | 1.28(0.3–4.2) | NS |
miR-148b | 0.39(0.1–0.9) | 0.51(0.2–2.1) | 0.06 |
let-7b | 1.51(0.3–46.8) | 25.9(0.4–53.8) | <0.0001 |
Model 1 | −0.89[(−3.3)–5.4) | 1.7[(−2.9)–5.2] | <0.0001 |
Model 2 | −1.12[(−3.6)–5.3] | 2.08[(−3.4)–5.2] | <0.0001 |
SP | MP | FP | p | |
---|---|---|---|---|
n | 15 | 24 | 22 | |
Gd-IgA * | 1.55(0.9–4.8) | 1.28(0.4–4.2) | 1.1(0.3–4.1) | NS |
miR-148b | 0.5(0.1–2.1) | 0.43(0.1–0.48) | 0.39(0.2–0.8) | NS |
let7b | 3.24(0.4–32) | 1.7(0.4–38) | 10(0.3–53.8) | 0.01 |
Model 1 | −0.52[(−3.3)–1.9] | −1.28[(−2.9)–3.1] | 1.1[(−2.8)–5.4] | 0.003 |
Model 2 | −0.64[(−3.6)–2.4] | −1.26[(−3.4)–3.4] | 1.07[(−3.4)–5.3] | 0.005 |
Annual rate of progression (SP, MP, FP) | Combined ≥50% reduction and ESRD | ESRD | |||||||
---|---|---|---|---|---|---|---|---|---|
OR | 95% CI | p | OR | 95% CI | p | OR | 95% CI | p | |
All Patients | |||||||||
Model 1 (cutoff levels −0.19) | 1.1 | 0.94–1.3 | <0.0001 | 10.1 | 2.8–36 | <0.0001 | 4.6 | 1.4–14.5 | 0.007 |
Model 2 (cutoff levels −0.19) | 1.1 | 0.93–1.3 | <0.0001 | 4.9 | 1.6–14.8 | 0.003 | 3.5 | 1.1–11 | 0.02 |
Patients treated with steroids | |||||||||
Model 1 (cutoff levels −0.19) | 1.1 | 0.58–1.06 | <0.0001 | 22.8 | 2.4-−214 | 0.001 | 8.3 | 1.6–42 | 0.007 |
Model 2 (cutoff levels −0.19) | 0.7 | 0.2–1.2 | 0.006 | 6.6 | 1.3–32 | 0.01 | 4.9 | 1.2–12.3 | 0.03 |
Patients treated with RAASi | |||||||||
Model 1 (cutoff levels −0.19) | 0.4 | 0.2–1 | NS | 5.8 | 1–32 | 0.03 | 1.7 | 0.3–9.1 | NS |
Model 2 (cutoff levels −0.19) | 0.2 | −0.4–0.8 | NS | 4 | 0.8–20 | NS | 1.8 | 0.3–10 | NS |
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Kouri, N.M.; Stangou, M.; Lioulios, G.; Mitsoglou, Z.; Serino, G.; Chiurlia, S.; Cox, S.N.; Stropou, P.; Schena, F.P.; Papagianni, A. Serum Levels of miR-148b and Let-7b at Diagnosis May Have Important Impact in the Response to Treatment and Long-Term Outcome in IgA Nephropathy. J. Clin. Med. 2021, 10, 1987. https://doi.org/10.3390/jcm10091987
Kouri NM, Stangou M, Lioulios G, Mitsoglou Z, Serino G, Chiurlia S, Cox SN, Stropou P, Schena FP, Papagianni A. Serum Levels of miR-148b and Let-7b at Diagnosis May Have Important Impact in the Response to Treatment and Long-Term Outcome in IgA Nephropathy. Journal of Clinical Medicine. 2021; 10(9):1987. https://doi.org/10.3390/jcm10091987
Chicago/Turabian StyleKouri, Nikoleta M., Maria Stangou, George Lioulios, Zoi Mitsoglou, Grazia Serino, Samantha Chiurlia, Sharon Natasha Cox, Persia Stropou, Francesco P. Schena, and Aikaterini Papagianni. 2021. "Serum Levels of miR-148b and Let-7b at Diagnosis May Have Important Impact in the Response to Treatment and Long-Term Outcome in IgA Nephropathy" Journal of Clinical Medicine 10, no. 9: 1987. https://doi.org/10.3390/jcm10091987
APA StyleKouri, N. M., Stangou, M., Lioulios, G., Mitsoglou, Z., Serino, G., Chiurlia, S., Cox, S. N., Stropou, P., Schena, F. P., & Papagianni, A. (2021). Serum Levels of miR-148b and Let-7b at Diagnosis May Have Important Impact in the Response to Treatment and Long-Term Outcome in IgA Nephropathy. Journal of Clinical Medicine, 10(9), 1987. https://doi.org/10.3390/jcm10091987