Progression Maarten Taal Centre for Kidney Research and Innovation - PowerPoint PPT Presentation

Pathophysiology of CKD Progression Maarten Taal Centre for Kidney Research and Innovation University of Nottingham and Royal Derby Hospital

CKD Progression Weldegiorgis M et al. AJKD 2017; 71(1):91-101.

Glomerulosclerosis Normal FSGS

Tubulointerstitial fibrosis

5/6 Nephrectomy Model

Glomerular Haemodynamics Glomerular capillaries Efferent arteriole Afferent arteriole Q A P gc SNGFR

Changes after 5/6 Nephrectomy Glomerular capillaries Efferent arteriole Afferent arteriole Resistance ↓ Resistance ↓↓ P gc ↑ Q A ↑↑↑ SNGFR ↑↑

Mechanical Stress after 5/6 Nephrectomy Normal Normal 1 week after 1 week after 5/6 nephrectomy 5/6 nephrectomy Endothelial cell Podocyte Hostetter et al. AJP10:F85-93; 1981

Progression after 5/6 Nephrectomy 70 1 Week Glomerulosclerosis (%) 60 SHM VEH 50 ENA CSN 40 30 20 10 0 4 8 12 Weeks Hostetter et al. AJP10:F85-93; 1981 Taal et al. KI 58: 1664-76; 2000

The Haemodynamic Theory 1°Renal Systemic Hypertension Disease  Pgc  SNGFR Glomerular Nephron Cell Loss Injury 2°Glomerulosclerosis Brenner et al. NEJM 307:652-659;1982

Angiotensin II Taal M, Brenner BM. KI 57:1803; 2000

Proteinuria Abbate, M. et al. J Am Soc Nephrol 2006;17:2974-2984

Loss of peritubular capillaries Hohenstein B et al. Kidney Int 2017; 91: 9-11

Acute Kidney Injury Venkatachalam MA et al. AJP 298: F1078-94; 2010

CKD Progression 2019 Systemic Hypertension  Pgc 1°Renal  SNGFR Disease Mechanical Stress Nephron Ang II Loss Proteinuria Acidosis ROS Aldosterone Inflammation ↓Peritubular 2° FSGS Capillaries and TIF AKI Fibrosis

CKD Treatment Approach Systemic Hypertension Antihypertensives Weight loss  Pgc 1°Renal SGLT2i  SNGFR Disease Mechanical Stress Inhibit Nephron Ang II RAAS Loss Proteinuria Anti-oxidants Alkali Acidosis Diet  Proteinuria ROS Aldosterone Prevention Inflammation ↓Peritubular 2° FSGS Antiinflammatory Capillaries and TIF Antifibrotic AKI Fibrosis

MRI measures and pathology Buchanan C et al. NDT June 2019 ePub

MRI measures and CKD Progression Systemic Hypertension  Pgc 1°Renal Nephron number  SNGFR Disease Mechanical Stress Nephron Nephron Ang II number Loss Proteinuria Acidosis ROS Aldosterone BOLD? MRI changes after recovery Inflammation ↓Peritubular 2° FSGS T1 Capillaries and TIF ADC AKI Fibrosis Perfusion (ASL)

Multiparametric assessment T1 T1 80 80 60 60 40 40 T2* ADC T2* ADC 20 20 0 0 Volume Perfusion Volume Perfusion End-stage kidney disease Inflammation but may respond to therapy?