Abstract: SA-PO821
IgA Nephropathy with Complement-Associated Thrombotic Microangiopathy: A Case Series
Session Information
- C3G, TMA, MGRS, Amyloidosis, and More
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Fekrat, Ryan Evan, University of California Irvine Nephrology Hypertension & Kidney Transplantation, Orange, California, United States
- Dileep, Gayathri, University of California Irvine Nephrology Hypertension & Kidney Transplantation, Orange, California, United States
- Nguyen, Matthew Duy Thanh Luyen, University of California Irvine Nephrology Hypertension & Kidney Transplantation, Orange, California, United States
- Vadpey, Omid, University of California Irvine Department of Medicine, Orange, California, United States
- Zuckerman, Jonathan E., University of California Los Angeles – David Geffen School of Medicine - Department of Pathology and Lab Medicine, Los Angeles, California, United States
- Hanna, Ramy Magdy, University of California Irvine Nephrology Hypertension & Kidney Transplantation, Orange, California, United States
Background
Presentation of immunoglobulin A nephropathy (IgAN) with TMA has been commonly documented, however the relationship betwen IgAN and complement activation requires further exploration. Here we present a series of 7 patients with histological findings consistent with IgA nephropathy and TMA with supplementary serological data, suggesting a linkage between complement pathology and IgA nephropathy.
Methods
Coded datasets here are identified by our team using Epic software under consent of participating patients. Patients’ biopsy data with histological specimen is complemented by data from patient records. Histological specimen was read by UCLA Health Renal Pathology.
Results
The collected data shown in Table 1 shows 7 patients evaluated at UCI with the average age being 41.6 ± 8.1 years, 5/7 being male and 4/7 being Hispanic. 1/7 of the patients showed evidence of acute systemic TMA while 6 patients had renal limited TMA supported by histological slides. Average initial serum creatinine for all patients was 5.17 ± 4.74 mg/dL, average initial urine protein was 6.75 ± 5.11 g/day, and 5/7 patients had evidence of hematuria in their urine. Serological evaluation of complement levels show 2/7 (28.6%) of patients had low C3 complement levels. 1/7 (14.3%) of patients showed elevated C4 levels.
Conclusion
The patterns of histology show typical IgA nephropathy deposition and TMA. It is suggested that mesangial IgA activates mesangial cells, activating complement through the lectin and alternative pathways. This would not be the first time complement disorder is implicated as the conception of IgA TMA as reflected in some of our patients having lower C3 levels while having normal C4, however this finding may present a precedent for future research and clinical identification.
Patient Lab Values and Outcomes
| Patient # | Age | Gender | Reported Ethnicity | Outcome | Comorbidities | Initial sCR (mg/dL) | Initial Proteinuria (g/dL) | Hematuria? | Post Treatment sCR (mg/dL) | Post Treatment Urine Protein (g/day) | LDH (umol/minL) | Initial Hemoglobin (g/dL) | Haptoglobin (mg/dL) | Vitamin B12 (pg/mL) | Folic Acid (ng/mL) | Shiga Toxin | HIV Status | Hep B/Hep C Status | INR | PTT (s) | C3 (mg/dL) | C4 (mg/dL) | CH 50 (U/mL) | M | E | S | T | C | Histological Findings |
| 1 | 37 | Male | Hispanic | Currently being evalulated for Renal Transplant | HTN, HLD | 5.8 | 13.1 | Present | 12.2 | 176 | 12 | 246 | Negative | Negative | Negative/Negative | 0.97 | 33.7 | 126 | 41 | 83.9 | 0 | 0 | 1 | 2 | 0 | Mesangial hypercellularity and segmental glomerulosclerosis (periodic acid schiff stain; 400x) Acute thrombosis of an arteriole (Trichrome stain; 200x) Granular mesangial IgA immunofluorescence staining (400x) | |||
| 2 | 37 | Female | Asian | Renal Transplant | ESRD due to IgA nephropathy | 14.7 | 3.48 | Present | 1.0 | 0.2 | 8.1 | Negative | Negative | Negative/Negative | 1.1 | 26.4 | 72 | 29 | 1 | 1 | 1 | 2 | 1 | Mesangial hypercellularity and segmental fibrous crescent (periodic acid schiff stain; 400x) Acute thrombosis of an arteriole (Jones Silver stain; 400x) Granular mesangial IgA immunofluorescence staining (400x) Granular electron dense mesangial deposits (12300x) | |||||
| 3 | 29 | Male | Hispanic | BP/Renal Function controlled on pharmacotherapy | HTN | 2.0 | 10.35 | Present | 1.8 | 14.4 | Negative | Negative | Negative/Negative | 0.99 | 32.1 | 122 | 27 | 77.8 | 1 | 1 | 2 | 1 | 1 | Mesangial hypercellularity and segmental cellular crescent (periodic acid schiff stain; 400x) Acute thrombosis of an arteriole (Hematoxylin & Eosin stain; 400x) Granular mesangial IgA immunofluorescence staining (400x) Granular electron dense mesangial deposits (1100x) | |||||
| 4 | 47 | Female | Asian | On Dialysis | HTN, ESRD | 6.3 | 5.3 | Present | 2.7 | 288 | 6.1 | < 30 | 810 | 14.2 | Negative | Negative | Negative/Negative | 1.01 | 31.9 | 78 | 22 | 1 | 0 | 1 | 2 | 1 | Mesangial hypercellularity and segmental cellular crescent (periodic acid schiff stain; 400x) Acute thrombosis of an arteriole (Hematoxylin & Eosin stain; 400x) Granular mesangial IgA immunofluorescence staining (400x) | ||
| 5 | 42 | Male | Hispanic | BP/Renal Function controlled on pharmacotherapy | HTN | 5.1 | 1.0 | Absent | 4.0 | 12.5 | Negative | Negative | Negative/Negative | 1.08 | 27.8 | 125 | 33 | 1 | 0 | 1 | 2 | 0 | Mesangial hypercellularity and segmental cellular crescent (periodic acid schiff stain; 400x) Acute thrombosis of an arteriole (Hematoxylin & Eosin stain; 400x) Granular mesangial IgA immunofluorescence staining (400x) Granular electron dense mesangial deposits (560x) | ||||||
| 6 | 54 | Male | Hispanic | Recovered and Maintained on Pharmalogical (Bumex) and Supportive Therapy | HTN, DM | 1.3 | 12.37 | Absent | 1.1 | 10.1 | 787 | 18.9 | Negative | Negative | Negative/Negative | 0.93 | 41.1 | 91 | 28 | 0 | 0 | 1 | 2 | 0 | Mesangial hypercellularity and segmental glomerulosclerosis (periodic acid schiff stain; 400x) Luminal fibrinogen immunofluorescence staining of an arterial thrombus (400x) Granular mesangial IgA immunofluorescence staining (400x)" | ||||
| 7 | 45 | Male | Asian | Multiple trials of ace inhibitor (on and off due to dry cough), one episode of IgA nephropathy flare suppressed with ACEi and Plaquenil | Vitamin D Deficiency; Dyslipidemia | 1.0 | 1.66 | Present | 1.0 | 1.043 | 15.7 | Negative | Negative | Negative/Negative | 0.83 | 29.2 | 81.6 | 19 | 1 | 1 | 1 | 0 | 1 | Mesangial hypercellularity and segmental cellular crescent (periodic acid schiff stain; 400x) Platelet thrombus in glomerular capillary lumen; Electron micrograph (1100x) Granular mesangial IgA immunofluorescence staining (400x) Granular electron dense mesangial deposits (1100x) |
HTN = Hypertension; ESRD = End Stage Renal Disease, HLD = Hyperlipidemia, DM = Diabetes Mellitus, sCR = serum creatinine