BACKGROUND: In glomerulonephritis the final common pathway to end-stage renal disease (ESRD) is tubulo-interstitial damage (TID) whose main determinants are proteinuria and hypoxia consequent to haemodynamic and vascular alterations that reduce interstitial blood flow. Since oxygen tension is difficult to measure in human disease, arteriolar hyalinosis and arterial hypertension have been considered as possible surrogate markers of interstitial hypoxia. METHODS: The relationship between TID and arteriolar hyalinosis and arterial hypertension was evaluated in 132 IgA nephropathy (IgAN) and 79 idiopathic membranous nephropathy (IMN) patients. At biopsy tubulo-interstitial damage and arteriolar hyalinosis score were semi-quantitatively evaluated; urinary protein/creatinine ratio (P/C), fractional excretion (FE) of α1-microglobulin, urinary β-NAG/creatinine ratio (NAG/C/eGFR) and urinary SDS-PAGE pattern were measured. RESULTS: In IgAN arteriolar hyalinosis (AH) score correlates with TID score (P < 0.0001), FE α1m (P = 0.004) and NAG/C/eGFR (P = 0.001), but not with P/C (P = 0.10). Patients with or without AH were different in terms of global glomerulosclerosis (GGS: P < 0.001), TID score (P < 0.001), FE α1m (P = 0.015), NAG/C/eGFR (P = 0.002), but not of P/C (P = 0.19). In IMN AH score correlates with TID score (P < 0.0001), FEα1m (P = 0.04), NAG/C/eGFR (P = 0.001), SDS-PAGE pattern (P = 0.018), but not with P/C (P = 0.10). Patients with or without AH were different in term of GGS% (P = 0.05), TID score (P = 0.001), FE α1m (P = 0.039), NAG/C/eGFR (P = 0.001), SDS-PAGE pattern (P = 0.02), but not of P/C (P = 0.065). Similar results for normal versus high blood pressure. CONCLUSIONS: Arteriolar hyalinosis and arterial hypertension, associated with TID and GGS, factors that reduce interstitial capillary bed and blood flow, may be considered as reliable surrogate markers of hypoxia and co-determinants of TID.
BACKGROUND: In glomerulonephritis the final common pathway to end-stage renal disease (ESRD) is tubulo-interstitial damage (TID) whose main determinants are proteinuria and hypoxia consequent to haemodynamic and vascular alterations that reduce interstitial blood flow. Since oxygen tension is difficult to measure in human disease, arteriolar hyalinosis and arterial hypertension have been considered as possible surrogate markers of interstitial hypoxia. METHODS: The relationship between TID and arteriolar hyalinosis and arterial hypertension was evaluated in 132 IgA nephropathy (IgAN) and 79 idiopathic membranous nephropathy (IMN) patients. At biopsy tubulo-interstitial damage and arteriolar hyalinosis score were semi-quantitatively evaluated; urinary protein/creatinine ratio (P/C), fractional excretion (FE) of α1-microglobulin, urinary β-NAG/creatinine ratio (NAG/C/eGFR) and urinary SDS-PAGE pattern were measured. RESULTS: In IgANarteriolar hyalinosis (AH) score correlates with TID score (P < 0.0001), FE α1m (P = 0.004) and NAG/C/eGFR (P = 0.001), but not with P/C (P = 0.10). Patients with or without AH were different in terms of global glomerulosclerosis (GGS: P < 0.001), TID score (P < 0.001), FE α1m (P = 0.015), NAG/C/eGFR (P = 0.002), but not of P/C (P = 0.19). In IMN AH score correlates with TID score (P < 0.0001), FEα1m (P = 0.04), NAG/C/eGFR (P = 0.001), SDS-PAGE pattern (P = 0.018), but not with P/C (P = 0.10). Patients with or without AH were different in term of GGS% (P = 0.05), TID score (P = 0.001), FE α1m (P = 0.039), NAG/C/eGFR (P = 0.001), SDS-PAGE pattern (P = 0.02), but not of P/C (P = 0.065). Similar results for normal versus high blood pressure. CONCLUSIONS:Arteriolar hyalinosis and arterial hypertension, associated with TID and GGS, factors that reduce interstitial capillary bed and blood flow, may be considered as reliable surrogate markers of hypoxia and co-determinants of TID.
Authors: Catherine P Jayapandian; Yijiang Chen; Andrew R Janowczyk; Matthew B Palmer; Clarissa A Cassol; Miroslav Sekulic; Jeffrey B Hodgin; Jarcy Zee; Stephen M Hewitt; John O'Toole; Paula Toro; John R Sedor; Laura Barisoni; Anant Madabhushi Journal: Kidney Int Date: 2020-08-22 Impact factor: 10.612