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Given its rarity and the lack of strong evidence of therapeutic options, a therapeutic plan for C3 glomerulonephritis (C3GN) can be challenging to balance the conservative management to avoid side effects of immunosuppressive medications while avoiding progressive disease from under-therapy. We report a case of a young adult woman with C3GN who responded well to the anti-proteinuric effect of renin-angiotensin-aldosterone system (RAAS) blockage.
Case report: A 28-year-old woman with chronic migraines and postural orthostatic tachycardia syndrome (POTS) presented with eye pain when she moved her eyes to the left. She also had bilateral upper and lower extremity edema and palpitation. She often noticed foamy urine but denied gross hematuria. She takes rizatriptan for migraine and propranolol 10 mg twice a day for POST. Vital signs were normal except for a heart rate of 101 beats/minute. Cardiovascular, respiratory, and neurological examinations were unremarkable. There was no lower extremity edema. Urinalysis showed pH 7, Sp.Gr. 1.019, 1+ protein, 0-2 RBC/hpf, 0-5 WBC/hpf, 0-10 squamous epithelial cells/lpf, and negative crystal, nitrite, leukocyte esterase, or bacteria. The urine microscopy was bland (Figure 1-3). Workup revealed a persistent low level of C3 and occasionally low C4. CH50 and AH50 were low. ANA was positive, but ds-DNA and anti-chromatin antibodies were negative. A spot urinary protein/creatinine ratio (UPCR) was 1,000 mg/g of creatinine. Due to persistent proteinuria, she underwent a kidney biopsy 6 months later. Pathology revealed C3 glomerulopathy and mild arteriosclerosis, minimal tubulointerstitial scarring. No active crescentic glomerular injury. Electron microscopy showed 70% podocyte foot process effacement without tubuloreticular inclusion. A next-generation sequencing genetic test by whole-exome sequencing was negative but revealed a carrier variant of MEFV gene associated with familial Mediterranean fever and other variants of uncertain significance including heterozygous of APOA1, STX16, COL11A1, PRODH, OPLAH, GRIP1, and FANCM. Serum creatinine was at 0.61–0.78 mg/dL and UPCR and urinary microalbumin/creatinine ratio have been gradually decreased to 288 and 93 mg/g of creatinine, respectively over 4.5 years with lisinopril 10 mg daily.
Discussion: With a wide spectrum of kidney prognosis in G3GN from low-grade proteinuria to rapidly progressive glomerulonephritis, close monitoring for kidney function and proteinuria after initiating therapy with RAAS is a reasonable approach to avoid early exposure to immunosuppressive medications. Since potential kidney function decline is expected, preparation for future kidney transplantation by her potential living kidney donor through a paired living donor kidney exchange separated in time (PEST) or a National Kidney Registry Family Voucher Program by starting a chain as an altruistic donor will not only allow the donor to overcome chronological incompatibility but also facilitate our patient to have preemptive kidney transplantation when she ever needs transplantation.
In addition to its uncertainty in the current therapeutic options, C3GN involves the complexity of medical, genetic, and therapeutic plans that require further strong evidence to optimize care. PEST can be another option to provide the best currently available kidney replacement therapy through preemptive living donor kidney transplantation.
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