Focal segmental glomerulosclerosis (FSGS) is defined by segmental expansion of the glomerular matrix and obliteration of capillary lumina in at least one glomerulus on kidney biopsy [1]. The etiology of FSGS is heterogeneous and includes primary (idiopathic) forms, genetic causes, and secondary factors such as medications, infections, obesity, and hypertension [2]. Regardless of origin, podocyte injury disrupts the glomerular filtration barrier and leads to proteinuria [3]. Emerging evidence suggests that obstructive sleep apnea (OSA), characterized by intermittent hypoxia and sleep fragmentation that affect multiple organ systems, may contribute to renal disease pathophysiology, including proteinuria and accelerated progression of kidney dysfunction [4-6]. However, data directly linking OSA treatment with continuous positive airway pressure (CPAP) to improved renal outcomes, particularly in patients with FSGS, remain limited.

We report a clinical case of biopsy-proven FSGS in which exclusive adherence to CPAP therapy for severe OSA was followed by a rapid reduction in proteinuria and preservation of renal function.

A 51-year-old female patient initially presented to the nephrology clinic with diffuse joint aches, rash, and new-onset proteinuria following treatment with cephalexin and nonsteroidal anti-inflammatory drugs. Her 24-hour urine protein level was elevated to 1,294 mg. Biopsy of the rash revealed granulomatous inflammation with eosinophils, and urinalysis showed no red blood cells or casts. Antinuclear antibody (ANA), anti-cyclic citrullinated peptide (CCP), rheumatoid factor, and anti-neutrophil cytoplasmic antibody (ANCA) serologies were negative. Due to persistent nephrotic-range proteinuria, a kidney biopsy was performed, which demonstrated FSGS with mild glomerulomegaly and focal segmental sclerosis. Because her renal function remained stable, with creatinine levels ranging from 0.77 to 0.94 mg/dL, her FSGS was managed conservatively through blood pressure control using losartan 100 mg daily and diltiazem 240 mg daily, resulting in blood pressure of 118–136/77–84 mm Hg across 3 clinic visits over a 3-month period.

Despite conservative management, proteinuria fluctuated over the following years, peaking at 2,013 mg/24 hours. Due to complaints of wheezing and whistling sounds during sleep, she was referred to a sleep medicine clinic. Diagnostic polysomnography revealed severe OSA, with an apnea-hypopnea index (AHI) of 87.3 events/hour (obstructive apnea index of 3.0, hypopnea index 84.3, with 0 central apneas) and significant oxygen desaturation (SpO₂ nadir 80%, with 36.9 minutes spent at SpO₂ ≤88%). CPAP titration was performed in the sleep laboratory, starting at 5 cm H₂O and increasing to a maximum of 11 cm H₂O. Because of positional variation observed during manual titration, the patient was subsequently prescribed auto-titrating CPAP with pressure settings ranging from 5 to 15 cm H₂O. At the time of OSA diagnosis and CPAP initiation, her weight was stable at approximately 97 kg and remained unchanged over the following 2 months. Prior to a trial of CPAP titration, the 6-hour average ambulatory blood pressure was approximately 129/78 mm Hg. With no change in medications, her systemic blood pressure declined to the 110s/60s mm Hg range after CPAP initiation (Fig. 1). At her 2-year follow-up, her adherence was 100% (≥4 hours/night) over 30 days, with a 95th percentile pressure of 11.1 cm H₂O and residual AHI of 0.8 events/hour.

Within 2 months of initiating CPAP therapy, her proteinuria decreased by 49%, from 2,013 mg/24 hours to 1,022 mg/24 hours. Concurrently, her albumin-to-creatinine ratio improved from 1,194 mg/g to 266 mg/g over 6 months of consistent CPAP use. At the subsequent follow-up visit, her weight had decreased to 86 kg, and her AHI improved to 0.8 events/hour. Renal function remained stable throughout the study period.

This case emphasizes the potential impact of OSA treatment on renal outcomes in patients with FSGS. Although the precise mechanisms linking OSA to proteinuric kidney disease remain under investigation, proposed pathways include intermittent nocturnal hypoxia causing ischemic damage, sympathetic activation, elevated blood pressure, particularly at night, systemic inflammation, and increased intraglomerular pressure, all of which may exacerbate proteinuria and renal dysfunction [7]. Although growing evidence supports the renal benefits of CPAP, including reduced hypoxemia and oxidative stress, improved renal hemodynamics, lower blood pressure, and suppression of renin-angiotensin-aldosterone systems (RAAS) activity, no studies to date have specifically demonstrated a direct benefit of CPAP therapy in reducing macroproteinuria [6,8,9].

This case also highlights the importance of actively assess-ing comorbidities, including OSA, in patients with proteinuric kidney diseases such as FSGS, particularly when clinical features raise suspicion. Timely diagnosis and treatment may contribute significantly to effective disease management.