Skip to main content
Download PDF

The clinical and pathological characteristics of IgA nephropathy patients in Tibet

BMC Nephrology volume 23, Article number: 269 (2022) Cite this article

Abstract

Background

There are few studies on immunoglobulin A nephropathy (IgAN) at high altitude. This study aimed to analyze the clinical and pathological characteristics of IgAN between Tibet and Beijing, which provided a basis for improving diagnosis and treatment in Tibet.

Method

The clinical and pathological data of 80 patients from the People’s Hospital of Tibet Autonomous Region (Tibetan group) and 991 patients from Peking University First Hospital (Beijing group) with IgAN proven by renal biopsy were compared retrospectively between January 2016 and July 2020. The kidney biopsy tissue was sent to the Department of Nephrology, Peking University First Hospital for pathological evaluation.

Results

The proteinuria (2.9 [2.0, 4.9] vs. 1.1 [0.5, 2.4] g/day, P < 0.001) in the Tibetan group was significantly higher than that in the Beijing group. The serum albumin (30.4 ± 7.7 vs. 38.2 ± 5.5 g/L, P < 0.001) was significantly lower in the Tibetan group. The eGFR (77.7 ± 37.8 vs. 62.1 ± 33.6 ml/min/1.73 m2, P = 0.001) was higher in the Tibetan group. The percentage of patients with nephrotic syndrome in the Tibetan group was significantly higher than that in the Beijing group (33.8% vs. 4.7%, P < 0.001).

Conclusion

There are differences in the clinical and pathological characteristics of IgAN between plateau and plain regions.

Peer Review reports

Background

Immunoglobulin A (IgA) nephropathy (IgAN) is the most prevalent primary chronic glomerular disease worldwide [1]. There are numerous studies about IgAN; however, relevant reports in high-altitude regions are few. Due to the unique geographical features and atmospheric conditions at high altitudes, such as deficient oxygen pressure, dry climate and strong ultraviolet radiation, the clinical and pathological characteristics of IgAN patients living in these regions may differ from those living in plain areas [2, 3]. Our study mainly retrospectively compared and analyzed the clinical and pathological characteristics of patients with IgAN between Tibet and Beijing to provide a basis for improving diagnosis and treatment in Tibet.

Method

Patients

The People’s Hospital of Tibet Autonomous Region in Tibet (Tibetan group) and Peking University First Hospital in Beijing (Beijing group) were chosen as the comparative hospitals. This study included 80 patients in the People’s Hospital of Tibet Autonomous Region and 991 patients in Peking University First Hospital, who were all diagnosed with primary IgA nephropathy by renal biopsy from January 2016 to July 2020. Secondary IgAN, such as chronic liver disease, Henoch-Schönlein Purpura or concomitant connective tissue disease was excluded. We also excluded IgAN with minimal renal disease changes or focal segmental glomerulosclerosis by comparison of light, immunofluorescence and in 60% of cases, electron microscopy. Kidney tissue from the Tibetan group was sent to the Department of Nephrology, Peking University First Hospital for pathological evaluation. They were examined by light microscopy, immunofluorescence and electron microscopy by two pathologists.

Data collection

All of the above patients had complete clinical records and pathological data. The data used for analysis included sex, age, systolic and diastolic blood pressure (SBP and DBP, respectively), hemoglobin (HGB), platelets (PLT), serum albumin (ALB), 24-h urine total protein (UTP), serum creatinine (Scr), serum uric acid (UA), serum phosphate (P), albumin-corrected serum calcium (CaAlb), estimated glomerular filtration rate (eGFR), serum IgG, serum IgA, serum IgM, serum C3 and serum C4 at the time of renal biopsy. Mean arterial pressure (MAP) was calculated as DBP plus one-third of the pulse. The eGFR was calculated by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation [4].

The renal biopsies were scored according to the updated Oxford classification of IgA nephropathy (MEST-C scoring system) proposed by the IgA Nephropathy Classification Working Group; however, there were no C classifications in the early cases [5]. We also collected immune deposits IgA, IgM, IgG, C3 and C1q of renal biopsy samples by immunofluorescence technique. The intensity was determined semi-quantitatively using a scale from 0 to 4 + .

Statistical analysis

Normally distributed data are presented as the means ± SDs, and nonnormally distributed data are presented as the medians [Q25, Q75]. Categorical data are summarized as counts and percentages. Clinical parameters are compared using Student’s t-tests (for normally distributed, continuous variables), Wilcoxon signed-rank tests (for nonnormally distributed, continuous variables) or χ2 tests (for nominal variables), as appropriate. All analyses were performed using SPSS Statistics, version 26.0 (SPSS Inc., Chicago, IL, USA). A p value less than 0.05 was considered statistically significant.

Results

Demographic and clinical data

Table 1 summarizes the characteristics of the patients in the Tibetan group and Beijing group. The patients in the Tibetan group were significantly younger than those in the Beijing group (32.6 ± 12.4 vs. 39.12 ± 12.6 years, P < 0.001). However, there was no difference in sex between the two groups (P > 0.05). The mean arterial pressure (106.0 ± 19.0 vs. 97.0 ± 12.6 mmHg, P < 0.001), hemoglobin (158.6 ± 83.8 vs. 126.3 ± 20.9 g/L, P < 0.001), proteinuria (2.9 [2.0, 4.9] vs. 1.1 [0.5, 2.4] g/day, P < 0.001), eGFR (77.7 ± 37.8 vs. 62.1 ± 33.6 ml/min/1.73 m2, P = 0.001), serum phosphate (1.30 ± 0.29 vs. 1.17 ± 0.27 mmol/L, P < 0.001), serum IgM (1.14 [0.92, 1.53] vs. 0.94 [0.68, 1.33] g/L, P = 0.003), serum C3 (1.18 [1.04, 1.47] vs. 0.85 [0.74, 0.98] g/L, P < 0.001) and the C3/C4 ratio (4.44 [3.84, 5.61] vs. 3.60 [3.06, 4.15], P < 0.001) in the Tibetan group were significantly higher than those in the Beijing group. The serum albumin (30.4 ± 7.7 vs. 38.2 ± 5.5 g/L, P < 0.001), albumin-corrected serum calcium (2.28 ± 0.33 vs. 2.33 ± 0.17 mmol/L, P = 0.017), serum IgG (8.66 [5.41,12.62] vs. 10.30 [8.49,12.50] g/L, P = 0.025) and the IgA/C3 ratio (2.52 [1.89, 3.16] vs. 3.58 [2.74, 4.63], P < 0.001) were significantly lower in the Tibetan group. The percentage of patients with nephrotic syndrome in the Tibetan group was significantly higher than that in the Beijing group (33.8% vs. 4.7%, P < 0.001). However, there were no differences in platelets, uric acid, serum IgA or C4 in the two groups (P > 0.05).

Table 1 Comparison of clinical characteristics between the two groups at the time of renal biopsy
Full size table

Clinicopathological features of the renal biopsy samples

As shown in Table 2, for the renal pathological scores according to the new Oxford classification there were no differences between the two groups [5]. The IgA deposits (2.5 [2.0, 3.0] vs. 3.0 [3.0, 3.5], P < 0.001) and C3 deposits (1.0 [0.5, 2.0] vs. 2.5 [2.0, 3.0], P < 0.001) in kidney tissue were less in Tibetan group than those of Beijing group. There were no differences in IgG, IgM, C1q deposits between the two groups.

Table 2 Comparison of pathological features between the two groups of patientsa
Full size table

Discussion

In Tibet, due to limited renal biopsy technology, pathological classification data for chronic kidney disease patients are extremely limited, which obviously affects the clinical diagnosis, design of therapeutic regimens and prognostic evaluation [6]. Since the medical groups aided in Tibet in 2015, with the help of experienced nephrologists from Peking University First Hospital, the local hospital has successfully carried out more kidney biopsies, which enabled more IgAN patients to be diagnosed.

Our study examined data regarding the clinical and pathological characteristics of IgAN from the plateau regions from January 2016 to July 2020. There have been few previous studies of kidney biopsy data about IgAN from plateau regions, and this may be the first report with the largest number of cases of IgAN in these regions. We found that there were differences in renal clinical features between IgAN patients in plateau and plain regions.

One valuable finding in our study is that the amount of urine protein in the Tibetan group was significantly higher than that in the Beijing group, which was consistent with previous studies [7, 8]. The pathogenesis of the proteinuria at high altitude may relate to a variety of factors, including the effects of tissue hypoxia within the kidney parenchyma, glomerular capillary hypertension, hyperviscosity and elevated right heart pressures [7, 8].

It is well known that nephrotic syndrome in IgAN is an uncommon manifestation, except in patients with minimal-change disease [9]. The prevalence of 14.7% NS in IgAN in a Chinese cohort was reported by Han et al [10]. In a Korean cohort, 10.2% of IgAN patients were found to present NS [11]. However, the incidence of nephrotic syndrome in the Tibetan group was 33.8%, which was significantly higher. The above clinical data suggest that the clinical manifestations of IgAN patients in Tibet are significantly heavier than those in the Beijing group. In addition to the relatively late visit time, it may also be related to the high-altitude environment, ethnicity, hyperuricemia, high-altitude hypertension and high infection rate [12, 13].

Regarding the secondary clinical features between the two groups in our study, the blood pressure of IgAN patients in the Tibetan group was higher than that in the Beijing group. This may be related to high-sodium diets and the high altitude of the Tibetan Plateau [14, 15], which may be one of the reasons for the increasement in proteinuria and eGFR in Tibetan patients [16]. In addition, the higher eGFR in the Tibetan group might be related to the younger ages in the Tibetan group. However, due to the higher blood pressure and urinary protein, the eGFR might decline rapidly in the Tibetan group in the future. Regrettably, our study lacked a prognostic data. In the Tibetan group, the hemoglobin was also higher, which may be related to the secondary polycythemia caused by high altitude and hypoxia in the Tibetan Plateau [17, 18].

Another major finding in the present study was that the serum C3 levels and the C3/C4 ratio were significantly higher and the IgA/C3 ratio was lower in the Tibetan group than those in the Beijing group [19,20,21]. Meanwhile, we also found that IgA and C3 deposits in kidney tissue were less in Tibetan group than those in Beijing group. Previous studies showed that glomerular complement activation was strongly associated with IgAN and may be the dominant driver of renal injury [22,23,24]. Therefore, our findings suggested there might be less complement activation in the Tibetan group than that in the Beijing group, which may at least in part explain the relatively better chronic kidney lesions and renal function observed in patients in the Tibetan group compared with those of the Beijing group. However, the detailed differences of glomerular complement activation between two groups remain to be further explored.

There are several limitations in our study. First, this was a single-center retrospective study with a lack of detailed follow-up and prognostic data. Second, our sample size was relatively small. Third, we also lacked studies about the mechanisms of IgAN in Tibet. Nevertheless, to our knowledge, this was the first study with the largest sample size to describe IgAN in Tibet.

Conclusions

In conclusion, there are differences in the clinical and pathological characteristics of IgAN between plateau and plain regions. Despite limitations in this study, it may provide insight into IgAN patients’ clinical features in plateau regions.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

IgAN:

Immunoglobulin A nephropathy

SBP:

Systolic blood pressure

DBP:

Diastolic blood pressure

MAP:

Mean arterial pressure

HGB:

Hemoglobin

PLT:

Platelets

ALB:

Serum albumin

UTP:

24-H urine total protein

Scr:

Serum creatinine

eGFR:

Estimated glomerular filtration rate (calculated using the CKD-EPI equation)

UA:

Serum uric acid

CaAlb :

Albumin-corrected serum calcium

P:

Serum phosphate

References

  1. D’Amico G. The commonest glomerulonephritis in the world: IgA nephropathy. Q J Med. 1987;64(245):709–27.

    CAS  PubMed  Google Scholar 

  2. Zhou Y, Deng YM, Li C, Gong YB, Mao ZG, Wu J, Li SZ, Liu ZH, Tang Z. Comparison of characteristics of chronic kidney diseases between Tibet plateau and plain areas. Int J Clin Exp Pathol. 2014;7(9):6172–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Arestegui AH, Fuquay R, Sirota J, Swenson ER, Schoene RB, Jefferson JA, Chen W, Yu XQ, Kelly JP, Johnson RJ, et al. High altitude renal syndrome (HARS). J Am Soc Nephrol. 2011;22(11):1963–8.

    Article  CAS  Google Scholar 

  4. Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T, Kusek JW, Manzi J, Van Lente F, Zhang YL, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med. 2012;367(1):20–9.

    Article  CAS  Google Scholar 

  5. Trimarchi H, Barratt J, Cattran DC, Cook HT, Coppo R, Haas M, Liu ZH, Roberts IS, Yuzawa Y, Zhang H, et al. Oxford Classification of IgA nephropathy 2016: an update from the IgA Nephropathy Classification Working Group. Kidney Int. 2017;91(5):1014–21.

    Article  Google Scholar 

  6. Wang N, Zhu T, Tao Y. Clinicopathological features of pediatric renal biopsies in the plateau regions of China. J Int Med Res. 2018;46(11):4539–46.

    Article  Google Scholar 

  7. Hurtado A, Escudero E, Pando J, Sharma S, Johnson RJ. Cardiovascular and renal effects of chronic exposure to high altitude. Nephrol Dial Transplant. 2012;27(Suppl 4):iv11-16.

    Article  Google Scholar 

  8. Jefferson JA, Escudero E, Hurtado ME, Kelly JP, Swenson ER, Wener MH, Burnier M, Maillard M, Schreiner GF, Schoene RB, et al. Hyperuricemia, hypertension, and proteinuria associated with high-altitude polycythemia. Am J Kidney Dis. 2002;39(6):1135–42.

    Article  Google Scholar 

  9. Wyatt RJ, Julian BA. IgA nephropathy. N Engl J Med. 2013;368(25):2402–14.

    Article  CAS  Google Scholar 

  10. Han X, Xiao Y, Tang Y, Zheng X, Anwar M, Qin W. Clinical and pathological features of immunoglobulin A nephropathy patients with nephrotic syndrome. Clin Exp Med. 2019;19(4):479–86.

    Article  CAS  Google Scholar 

  11. Kim JK, Kim JH, Lee SC, Kang EW, Chang TI, Moon SJ, Yoon SY, Yoo TH, Kang SW, Choi KH, et al. Clinical features and outcomes of IgA nephropathy with nephrotic syndrome. Clin J Am Soc Nephrol. 2012;7(3):427–36.

    Article  CAS  Google Scholar 

  12. Luks AM, Johnson RJ, Swenson ER. Chronic Kidney Disease at High Altitude. J Am Soc Nephrol. 2008;19(12):2262–71.

    Article  CAS  Google Scholar 

  13. Palatini P, Dorigatti F, Saladini F, Benetti E, Mos L, Mazzer A, Zanata G, Garavelli G, Casiglia E. Factors associated with glomerular hyperfiltration in the early stage of hypertension. Am J Hypertens. 2012;25(9):1011–6.

    Article  CAS  Google Scholar 

  14. Brito J, Siques P, Leon-Velarde F, De La Cruz JJ, Lopez V, Herruzo R. Chronic intermittent hypoxia at high altitude exposure for over 12 years: Assessment of hematological, cardiovascular, and renal effects. High Alt Med Biol. 2007;8(3):236–44.

    Article  Google Scholar 

  15. Liu M, Li YC, Liu SW, Wang LJ, Liu YN, Yin P, Liu JM, You JL, Zhou MG. Burden of disease attributable to high- sodium diets in China, 2013. Zhonghua Yu Fang Yi Xue Za Zhi. 2016;50(9):759–63.

    CAS  PubMed  Google Scholar 

  16. Narvaez-Guerra O, Herrera-Enriquez K, Medina-Lezama J, Chirinos JA. Systemic Hypertension at High Altitude. Hypertension. 2018;72(3):567–78.

    Article  CAS  Google Scholar 

  17. Yin Q, Yang Y, He T, Lai C, Liang Y, Jiang W, Wang H, Tang X, Diao Y, Huang S, et al. A case of focal segmental glomerulosclerosis syndrome secondary to high-altitude polycythemia. Ren Fail. 2014;36(1):108–10.

    Article  Google Scholar 

  18. Shoji K, Tanaka T, Nangaku M. Role of hypoxia in progressive chronic kidney disease and implications for therapy. Curr Opin Nephrol Hypertens. 2014;23(2):161–8.

    Article  CAS  Google Scholar 

  19. Kim SJ, Koo HM, Lim BJ, Oh HJ, Yoo DE, Shin DH, Lee MJ, Doh FM, Park JT, Yoo TH, et al. Decreased circulating C3 levels and mesangial C3 deposition predict renal outcome in patients with IgA nephropathy. PLoS ONE. 2012;7(7): e40495.

    Article  CAS  Google Scholar 

  20. Pan M, Zhou Q, Zheng S, You X, Li D, Zhang J, Chen C, Xu F, Li Z, Zhou Z, et al. Serum C3/C4 ratio is a novel predictor of renal prognosis in patients with IgA nephropathy: a retrospective study. Immunol Res. 2018;66(3):381–91.

    Article  CAS  Google Scholar 

  21. Gong WY, Liu M, Luo D, Liu FN, Yin LH, Li YQ, Zhang J, Peng H. High serum IgA/C3 ratio better predicts a diagnosis of IgA nephropathy among primary glomerular nephropathy patients with proteinuria </= 1 g/d: an observational cross-sectional study. BMC Nephrol. 2019;20(1):150.

    Article  Google Scholar 

  22. Tortajada A, Gutierrez E, Pickering MC, Praga Terente M, Medjeral-Thomas N. The role of complement in IgA nephropathy. Mol Immunol. 2019;114:123–32.

    Article  CAS  Google Scholar 

  23. Daha MR, van Kooten C. Role of complement in IgA nephropathy. J Nephrol. 2016;29(1):1–4.

    Article  CAS  Google Scholar 

  24. Wang Z, Xie X, Li J, Zhang X, He J, Wang M, Lv J, Zhang H. Complement Activation Is Associated With Crescents in IgA Nephropathy. Front Immunol. 2021;12: 676919.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

This work was supported by CAMS Innovation Fund for Medical Sciences (Grant/Award Number: 2019-12M-5-046) and the General Program (Key Program, Major Research Plan) of National Natural Science Foundation of China (Grant/Award Number: 82070731). The funders had no role in the study design; collection, analysis, and interpretation of data; and the decision to submit the report for publication.

Author information

Authors and Affiliations

  1. Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China

    Fenglei Si, Chen Tang, Yuxuan Yao & Lijun Liu

  2. Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China

    Fenglei Si, Chen Tang, Yuxuan Yao & Lijun Liu

  3. Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Xishiku Street No.8, 100034, Beijing, China

    Fenglei Si, Chen Tang, Yuxuan Yao & Lijun Liu

  4. Eight-Year-Program, Grade 2017, Health Science Center, Peking University, Beijing, China

    Jiarong Mei

  5. Renal Division, People’s Hospital of Tibet Autonomous Region, Lasa, China

    Yong A

Authors
  1. Fenglei Si
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jiarong Mei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yong A
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chen Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuxuan Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lijun Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Research idea and study design: LJL; data acquisition: FLS, JRM, YA, CT and YXY; data analysis/interpretation and statistical analysis: FLS; supervision and mentorship: JRM, YA, CT, YXY and LJL. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Lijun Liu.

Ethics declarations

Ethics approval and consent to participate

This study protocol was conducted in compliance with the ethical principles of the Helsinki Declaration and approved by Peking University First Hospital Clinical Research Ethics Committee (No. [2021] 681). Written informed consent was obtained from all the participants.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Si, F., Mei, J., A, Y. et al. The clinical and pathological characteristics of IgA nephropathy patients in Tibet. BMC Nephrol 23, 269 (2022). https://doi.org/10.1186/s12882-022-02895-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12882-022-02895-4

Keywords

  • Tibet
  • IgA nephropathy
  • Clinical
  • Pathological

BMC Nephrology

ISSN: 1471-2369

Contact us