PMC8514980_01
Timeline of the case after admission. (A-C) Time course of CK, myoglobin, plasma creatinine, and levels of uPCR and uACR. (D) Time of treatment regimens and kidney biopsy. CK, creatinine kinase; CYC, cyclophosphamide; uACR, urinary albumin-to-creatinine ratio; uPCR, urinary protein-to-creatinine ratio.
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U/L (reference range: 29-168), myoglobinemia of >12,000 microg/L (reference range: <=106,  Figure 1A ), and acute kidney injury (AKI) with serum creatinine levels of 1.38 mg/dl (reference range: 0.7-1.2,  Figure 1B ) and an estimated glomerular filtration rate (eGFR) of 33.5 ml/min/1.73 m2. Urinary analysis revealed leukocyturia, hematuria (no dysmorphic erythrocytes), few renal tubular epithelial cells, and nephrotic range proteinuria of >18,000 mg/g creatinine and albuminuria of <5,000 mg/g creatinine (reference range: <30 mg/g,  Figure 1C ). The patient received intravenous crystalloids with decreasing CK levels and myoglobinemia ( Figure 1A ). However, progressive deterioration of kidney function with worsening of serum creatinine levels up to 6.57 mg/dl (reference range: 0.7-1.2 mg/dl,  Figure 1B ) and an eGFR of <15 ml/min/1.73 m2 occurred. AAV, the patient received a steroid pulse with intravenous methylprednisolone for 3 days (250 mg per day) and oral prednisone 1 mg/kg daily thereafter (60 mg per day,  Figure 1D ). Based on the diagnosis of AAV presenting with massive rhabdomyolysis and pauci-immune crescentic GN, intravenous cyclophosphamide (CYC) was initiated at 10 mg/kg (per CYCLOPS trial dosing,  Figure 1D ). Thereafter, kidney function normalized without requirement of dialysis and proteinuria decreased to 1,603 mg/g creatinine and albuminuria to 351 mg/g creatinine (reference range: <30 mg/g,  Figures 1B, C ).
Histopathological findings in a kidney biopsy confirming pauci-immune crescentic GN. Representative photomicrographs of the kidney biopsy including staining for IgA (scale bar: 50 mum), IgG (scale bar: 50 mum), IgM (scale bar: 50 mum), C1q (scale bar: 50 mum), and C3c (scale bar: 50 mum); periodic acid-Schiff staining showing a glomerulus with crescent formation (scale bar: 50 mum); and hematoxylin/eosin staining with myoglobin casts (asterisks, scale bar: 100 mum) and tubulointerstitial inflammation with prominent eosinophilic infiltration (scale bar: 100 mum). C1q, complement component 1q; C3c, complement factor 3 conversion product; IgA, immunoglobulin A; IgG, immunoglobulin G; IgM, immunoglobulin M; GN, glomerulonephritis.
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A kidney biopsy confirmed severe acute tubular injury with pauci-immune crescentic GN and interstital nephritis: cellular crescents in 1/15 (6.7%) glomeruli, global glomerular sclerosis in 2/15 (13.3%), mild (5%) interstitial fibrosis and tubular atrophy (IF/TA), interstitial inflammation (25%) with prominent eosinophilic infiltration, and severe acute tubular injury with myoglobin casts ( Figure 2  and  Table 2 ). According to histopathological scoring, focal class ANCA GN and intermediate risk ANCA renal risk score (ARRS) were present ( Table 2 ).