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Steroid-resistant nephrotic syndrome (SRNS) is characterized by nephrotic-range proteinuria, hypoalbuminemia and edema that does not respond to steroid treatment. Its etiologies are diverse, including primary and secondary glomerulopathies, as well as genetic causes. It is noteworthy to highlight SRNS caused by variants related to coenzyme Q10 (CoQ10) biosynthesis, as this may be potentially treatable, in contrast to other SRNS causes that tend to progress to advanced chronic kidney disease (CKD) without therapeutic options.
A 15-year-old patient from Chiloé with a history of a mother with IgA nephropathy and CKD stage II-III. Nephrocalcinosis was detected at 8-9 years through renal ultrasound when studying enuresis. Since 2020, the patient has had non-nephrotic range proteinuria and enalapril was prescribed with a partial response. In 2022 she developed nephrotic syndrome, with nephrotic-range proteinuria (5 g/24 hrs), hypercholesterolemia, hypertriglyceridemia, hypoalbuminemia (2.8 mg/dl), mild hypertension, and an increase in creatinine up to 1.5 mg/dl. Prednisone (60 mg/m2) was prescribed with a partial response after a month, maintaining nephrotic-range proteinuria (2 g/24 hrs), hypoalbuminemia (2.8 mg/dl) and an increase in creatinine to 2.1 mg/dl. Renal ultrasound showed microcysts. Due to the suspicion of a genetic origin, a panel of 401 genes associated with nephropathies was requested, identifying 10 variants of uncertain significance (VUS), including a homozygous deletion of exon 13 in the COQ8B (ADCK4) gene, predicting loss of a segment of the kinase domain. Subsequent direct sequencing confirmed that COQ8B was inherited from both parents. Prednisone treatment continued for another month with a partial response. A renal biopsy revealed 10 globally sclerosed glomeruli and 7 with segmental sclerosis, with 70% tubular atrophy. The estimated glomerular filtration rate (eGFR) reached 43.9 ml/min/1.73 m², with proteinuria of 3 g/24 h. Treatment with CoQ10 (20 mg/kg/day), along with atorvastatin, vitamin D, and transient suspension of ACE inhibitors (ACEi), was initiated. During the first 12 months of treatment, their renal function remained stable, and their proteinuria decreased to 1 g/24 hrs. Subsequently, there was a loss of function and an increase in proteinuria to 3 g/24 hrs. In the last months, they transitioned from pediatric nephrology to adult nephrology.
SRNS poses a high risk of progression to End-Stage Renal Disease (ESRD) and exhibits high genetic heterogeneity. Conducting a comprehensive genetic panel can quickly identify a genetic cause. The patient described represents the first known case in Chile with a variant in COQ8B, a gene associated with the mitochondrial biosynthesis of CoQ10. It manifests with proteinuria in adolescence and a biopsy compatible with global and segmental glomerulosclerosis. The timely initiation of CoQ10 treatment can slow down the progression of ESRD, and in the case of transplantation, recurrence is not expected.