Kidney Week

Abstract: SA-OR65

Serial Measures of Urine Soluble CD163 Predict Kidney Failure in ANCA-Associated Glomerulonephritis

Session Information

• Glomerular Diseases: Clinical Advances
  October 26, 2024 | Location: Room 6D, Convention Center
  Abstract Time: 04:40 PM - 04:50 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Stoneman, Sinead, Cork University Hospital, Cork, Cork, Ireland

Sinead Stoneman, MBChB

• Cowhig, Cliona, Cork University Hospital, Cork, Cork, Ireland

Cliona Cowhig, MBChB

• Coughlan, Conor, Cork University Hospital, Cork, Cork, Ireland

Conor Coughlan, DrMed, PhD

• Conlon, Niall P., St James's Hospital, Dublin, Ireland

Niall P. Conlon, MBChB, DrPH

• Dunne, Jean, St James's Hospital, Dublin, Ireland

Jean Dunne, PhD

• Scott, Jennifer, Trinity Health Kidney Centre, Trinity College Dublin, Dublin, Ireland

Jennifer Scott, MBChB

• Power, Julie, Trinity Health Kidney Centre, Trinity College Dublin, Dublin, Ireland

Julie Power

• Little, Mark Alan, Trinity Health Kidney Centre, Trinity College Dublin, Dublin, Ireland

Mark Alan Little, MBChB, PhD

• Clarkson, Michael, Cork University Hospital, Cork, Cork, Ireland

Michael Clarkson, MD

• Moran, Sarah Margaret, Cork University Hospital, Cork, Cork, Ireland

Sarah Margaret Moran, MBBS, MBChB, PhD

Group or Team Name

• On behalf of RITA-Ireland.

Background

ANCA vasculitis-glomerulonephritis [AAV-GN] affects 70 – 85% of ANCA vasculitis [AAV] patients. 26% of patients progress to end-stage kidney disease [ESKD] and 43% progress without a recognised disease flare. Identifying those at highest risk of progression to kidney failure is an unmet need. Urine soluble CD163 [usCD163] has excellent biomarker characteristics and has been validated as a clinical biomarker in detecting active AAV-GN at diagnosis and flare. The use of usCD163 to predict ESKD in those considered to be in clinical remission is undefined.

Methods

We utilised longitudinal clinical data and biobank urine samples from a national multicentre rare kidney disease registry to evaluate the utility of serial usCD163 measurements to predict of kidney failure in AAV-GN. Inclusion criteria were 4 or more urine sCD163 measurements and diagnosis of AAV. The primary endpoint was kidney failure defined as death, ESKD or GFR <15mls/min/1.73m². Statistical analysis was performed using GraphPad Prism and R.

Results

We identified 113 participants with 4 or more usCD163 measurements over at least a 12-month period. 26 (23%) participants developed kidney failure (death (13), ESKD (17), GFR <15 (16)). Excluding the initial urine sample (generally from a period of disease activity) the median usCD163 level normalized to urine creatinine was higher in those meeting the endpoint (median 385ng/mmol vs 89ng/mmol, p<0.0001). In those with kidney failure 62.6% (128) of values were above the diagnostic threshold for active renal vasculitis. Analysis of this cohort identified the optimal diagnostic threshold for usCD163 for the future development of kidney failure as 160ng/mmol, with a sensitivity of 77.7%, a specificity of 69%, negative predictive value [NPV] of 92.3, and positive predictive value [PPV] 39.4.

Conclusion

A urine sCD163 result less than 160 ng/mmol has a strong NPV for predicting future kidney failure. This suggests that in addition to detecting active GN, urine sCD163 may provide reassurance that subclinical glomerular injury is not missed in AAV. The suppression of usCD163 associates with a significantly lower risk of progression to kidney failure, supporting a key role for undetected disease activity as the major driver of progression to kidney failure.

Funding

• Private Foundation Support