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

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Nov 26, 2023 193 likes •409 views

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

SLIDE 1

Pathophysiology of CKD Progression

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

SLIDE 2

CKD Progression

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

SLIDE 3

Glomerulosclerosis

Normal FSGS

SLIDE 4

Tubulointerstitial fibrosis

SLIDE 5

5/6 Nephrectomy Model

SLIDE 6

Glomerular Haemodynamics

Afferent arteriole Efferent arteriole Glomerular capillaries

QA Pgc

SNGFR

SLIDE 7

Changes after 5/6 Nephrectomy

Afferent arteriole Resistance ↓↓ Efferent arteriole Resistance ↓ Glomerular capillaries

Pgc ↑

SNGFR ↑↑

QA ↑↑↑

SLIDE 8

Mechanical Stress after 5/6 Nephrectomy

Podocyte Endothelial cell

Hostetter et al. AJP10:F85-93; 1981

Normal 1 week after 5/6 nephrectomy Normal 1 week after 5/6 nephrectomy

SLIDE 9

Progression after 5/6 Nephrectomy

Taal et al. KI 58: 1664-76; 2000 Hostetter et al. AJP10:F85-93; 1981

1 Week 10 20 30 40 50 60 70 4 8 12 SHM VEH ENA CSN Glomerulosclerosis (%)

Weeks

SLIDE 10

The Haemodynamic Theory

 Pgc  SNGFR Nephron Loss 2°Glomerulosclerosis Glomerular Cell Injury Systemic Hypertension 1°Renal Disease

Brenner et al. NEJM 307:652-659;1982

SLIDE 11

Angiotensin II

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

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Proteinuria

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

SLIDE 13

Loss of peritubular capillaries

Hohenstein B et al. Kidney Int 2017; 91: 9-11

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Acute Kidney Injury

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

SLIDE 15

CKD Progression 2019

 Pgc  SNGFR Nephron Loss Inflammation Fibrosis 2° FSGS and TIF

Ang II

Mechanical Stress 1°Renal Disease Proteinuria Systemic Hypertension Aldosterone ROS Acidosis

AKI

↓Peritubular Capillaries

SLIDE 16

CKD Treatment Approach

 Pgc  SNGFR Nephron Loss Inflammation Fibrosis 2° FSGS and TIF

Ang II

Mechanical Stress 1°Renal Disease Proteinuria Systemic Hypertension Aldosterone ROS Acidosis

AKI

Weight loss SGLT2i  Proteinuria

Anti-oxidants

Prevention

Alkali Diet

Inhibit RAAS Antihypertensives Antiinflammatory Antifibrotic ↓Peritubular Capillaries

SLIDE 17

MRI measures and pathology

Buchanan C et al. NDT June 2019 ePub

SLIDE 18

MRI measures and CKD Progression

 Pgc  SNGFR Nephron Loss Inflammation Fibrosis 2° FSGS and TIF

Ang II

Mechanical Stress 1°Renal Disease Proteinuria Systemic Hypertension Aldosterone ROS Acidosis

AKI

Nephron number

Perfusion (ASL)

MRI changes after recovery

T1 ADC ↓Peritubular Capillaries

Nephron number BOLD?

SLIDE 19

Multiparametric assessment

20 40 60 80

T1 ADC Perfusion Volume T2*

20 40 60 80

T1 ADC Perfusion Volume T2* End-stage kidney disease Inflammation but may respond to therapy?

SLIDE 20