Oxford Classification and Clinical Remission After Initial Treatments in Patients With IgA Nephropathy

Oxford Classification and Clinical Remission After Initial Treatments in Patients With IgA Nephropathy：a Cohort Study

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis and one of the leading causes of end-stage renal disease in China. The clinical manifestations of IgAN varies widely among individuals, and renal pathology is crucial for determining the severity of renal damage and predicting the renal progression. However, the association between renal pathology and patient response to medication has not been reported, and the majority of earlier RCT studies have not taken renal pathology into consideration when enrolling patients. The Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group, one of the most prestigious kidney disease organizations in the world, claims that there is not enough evidence to support the use of Oxford Classification to decide whether to administer immunosuppressive therapy to patients with IgAN.Therefore, the goal of this study was to investigate the relationship between Oxford Classification and clinical remission rates following initial teatments in patients with IgAN, with the aim of providing a basis for individualized clinical treatment plans. This study was a single-center prospective cohort study, and patients who were hospitalized in Shenzhen Second People's Hospital from January 2011 to January 2021 and diagnosed as IgAN by renal biopsy were collected continuously and followed up until December 2022. Cox regression models were used to analyze the effect of different Oxford Classifications on the clinical remission rates of patients at 6, 12, 18, and 24 months of treatments, and the relationship between Oxford Classification and secondary outcome indicators such as long-term renal function and urinary protein changes were analyzed using generalized additive mixed models.

Study Overview

• Status: Recruiting
• Conditions: IgA Nephropathy

• Study Type: Observational
• Enrollment (Anticipated): 474

Contacts and Locations

• Study Contact: Name: Ricong Xu; Phone Number: 0755-83366388-8058; Email: xrc224@126.com

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Second People's Hospital
      • Contact: Ricong Xu; Phone Number: 0755-83366388-8058; Email: xrc224@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Consecutive patients admitted to Shenzhen Second People's Hospital from January 2011 to January 2021 with IgAN confirmed by renal biopsy were included.

Description

Inclusion Criteria:

• Age≥18 years；
• Initial renal biopsy；
• Glomeruli>8；
• eGFR>15ml/min；
• Proteinuria/creatinine ratio（PCR）>0.5g/g

Exclusion Criteria:

• Secondary IgAN
• Combined with other kidney diseases
• Combined with acute kidney injury
• Combined with tumor
• Followed-up time <6 months

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
mesangial hypercellularity, M; the histopathology was graded based on the revised Oxford Classification system as follows: M absent (M0) or M present (M1)
endocapillary hypercellularity, E; E absent (E0) or E present (E1)
segmental glomerulosclerosis, S; S absent (S0) or S present (S1)
tubular atrophy/interstitial fibrosis, T; T ≤ 25% (T0) or T 26%-50% (T1), or T > 50% (T2)
crescents, C; C absent (C0) or C present ≥ 1 glomerulus (C1) or C > 25% glomeruli (C2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical remission rates (including complete and partial clinical remission rates) at 6, 12, 18, and 24 months for IgAN patients with different Oxford pathology scores (M, E, S, T, C) after being treated with the initial treatments.	Complete clinical remission: 24h urine protein <0.2g/d (or total urine protein/urine creatinine <0.2g/g) . Partial clinical remission: ≥50% decrease in urine protein from baseline and urine protein <1g/d (or total urine protein/urine creatinine <1g/g).	6, 12, 18, and 24 months after being treated with the initial treatments.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The longitudinal changes in renal function and urinary protein in IgAN patients with different Oxford Classification scores (M, E, S, T, C) after the initial treatments.	The rate of change in renal function: the estimated rate of change in glomerular filtration rate (eGFR). The rate of change of urine protein: the rate of change of total urine protein/urine creatinine.	During the follow-up period, the study will be terminated if the patient is transferred to renal transplantation, hemodialysis, peritoneal dialysis, or other centers, and the remaining patients will be followed until December 31, 2022

Collaborators and Investigators

• Sponsor: Shenzhen Second People's Hospital
• Investigators: Study Director: Qijun Wan, Shenzhen Second People's Hospital

Publications and helpful links

General Publications

• Trimarchi H, Barratt J, Cattran DC, Cook HT, Coppo R, Haas M, Liu ZH, Roberts IS, Yuzawa Y, Zhang H, Feehally J; IgAN Classification Working Group of the International IgA Nephropathy Network and the Renal Pathology Society; Conference Participants. Oxford Classification of IgA nephropathy 2016: an update from the IgA Nephropathy Classification Working Group. Kidney Int. 2017 May;91(5):1014-1021. doi: 10.1016/j.kint.2017.02.003. Epub 2017 Mar 22.
• Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021 Oct;100(4S):S1-S276. doi: 10.1016/j.kint.2021.05.021.
• Coppo R. Towards a personalized treatment for IgA nephropathy considering pathology and pathogenesis. Nephrol Dial Transplant. 2019 Nov 1;34(11):1832-1838. doi: 10.1093/ndt/gfy338. Review.
• Lv J, Zhang H, Wong MG, Jardine MJ, Hladunewich M, Jha V, Monaghan H, Zhao M, Barbour S, Reich H, Cattran D, Glassock R, Levin A, Wheeler D, Woodward M, Billot L, Chan TM, Liu ZH, Johnson DW, Cass A, Feehally J, Floege J, Remuzzi G, Wu Y, Agarwal R, Wang HY, Perkovic V; TESTING Study Group. Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial. JAMA. 2017 Aug 1;318(5):432-442. doi: 10.1001/jama.2017.9362.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): June 30, 2025

Study Registration Dates

• First Submitted: September 1, 2022
• First Submitted That Met QC Criteria: September 1, 2022
• First Posted (Actual): September 6, 2022

Study Record Updates

• Last Update Posted (Actual): September 6, 2022
• Last Update Submitted That Met QC Criteria: September 1, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: IgA nephropathy; Oxford Classification; clinical remission rate
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Kidney Diseases; Glomerulonephritis, IGA
• Other Study ID Numbers: 20223357009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: all IPD that underlie results in a publication
• IPD Sharing Time Frame: starting 1 year after publication
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No