This document contains presentations from the Sheffield Kidney Institute on various topics in nephrology practice. It discusses renal biopsy indications and scenarios where a biopsy may or may not be recommended. It also addresses immunosuppression treatment and whether it may be appropriate for certain patient cases. Finally, it examines the use of ACE inhibitors for chronic kidney disease, reviewing evidence on cardiovascular and renal outcomes from trials comparing ACE inhibitors to placebo. Key considerations around risks, benefits, costs and clinical utility are discussed for biopsy, immunosuppression and ACE inhibitor treatment decisions.

1. Sheffield Kidney Institute
Global Kidney Academy
GKA-JULPHAR
Nephrology Master Class
Athens, 2014

2. Sheffield Kidney Institute
To Biopsy
Or NOT…????

3. Sheffield Kidney Institute
To Immunosuppress
Or NOT…????

4. Sheffield Kidney Institute
To ACE
Or NOT to ACE…????

5. Sheffield Kidney Institute
5Whats…
• What is this BIOPSY FOR?
• What is the Evidence: VALIDITY ?
• What is the Relevance: UTILITY ?
• What is the RISK:BENEFIT?
• What is the COST:BENEFIT?

6. Sheffield Kidney Institute
Renal Biopsy
Diagnostic
Prognostic
Therapeutic
HOW WILL IT CHANGE MY MANAGEMENT

7. Sheffield Kidney Institute
85 YEAR OLD
T2DM for 8 years
Hypertension for 15 years
CAD
PVD
CKD3b: eGFR 40ml/min
Urine PCR: 1200mg/g
Hematuria: 1+
No Retinopathy
Would you BIOPSY?

8. Sheffield Kidney Institute
Mr AD
• 50 years
• New diagnosis of DM Jan 2012
• no retinopathy, no neuropathy
• BP: 125/75 on Metformin, BMI: 40
• GP referral
• Urine dipstick: protein: 2+
• Urine PCR 135, 130 mg/mmol
• eGFR 50 ml/min since 2010
• USS kidneys: normal sized kidneys
WOULD YOU BIOPSY????

9. Sheffield Kidney Institute
Mr AC
• 55 years
• No PMH, BP 145/85 not on any medications
• GP referral
• Urine dipstick: 1+ protein, No blood
• Urine PCR 120, 90, 110 and mg/mmol
• eGFR >60 ml/min
• USS kidneys: NAD
• Immunology: Negative
WOULD YOU BIOPSY????

10. Sheffield Kidney Institute
Mrs AB
• 35 years
• 8 years history of hypertension, BP 130/85 on Ramipril 10 mg
• Fit and well, went for a medical check for a new job
• Urine dipstick: 1+ blood and 1+ protein
• Urine PCR 60 and 50 mg/mmol on 2 different occasions
• eGFR >60 ml/min
• USS kidneys: solitary kidney
• Immunology: Negative
WOULD YOU BIOPSY??????

11. Sheffield Kidney Institute
Mrs AF
• 40 years
• New referral by GP with FH of ADPKD, BP: 120/80mmHg
• USS kidneys multiple bilateral cysts -ADPKD
• Urine dipstick no blood, protein: 3+
• Urine PCR: 450 mg/mmol
• eGFR: 60ml/min
• Immunology: Negative
WOULD YOU BIOPSY????

12. Sheffield Kidney Institute
Mrs AH
• 65 years
• IHD, HTN, Cr 80 in May 2012
• Acute MI July 2012 – primary angioplasty with 2 stents, on
aspirin and clopidogrel
• Non oliguric AKI post MI; sCr 200umol/l,
• sCr still 200 2 months post MI
• USS kidneys NAD
WOULD YOU BIOPSY????

13. Sheffield Kidney Institute
Mr AI
• 70 years
• No PMH, presented to A&E with respiratory arrest
• Went to ITU, ventilated, CT showed bilateral PE
Treatment: Thrombolysis
• Albumin: 18g/l, Normal serum creatinine, USS kidneys NAD
Urine PCR 1100 mg/mmol, discharged to renal ward on warfarin
WOULD YOU BIOPSY????

14. Sheffield Kidney Institute
Mrs AJ
• 30 years
• No PMH, 22 weeks pregnant
• She had previous normal delivery with no problems.
• BP: 145/87mmHg
• Normal kidney function , USS kidneys no obstruction
• Urine PCR 400 mg/mmol, 1+ blood on urinalysis
• Anti-dsDNA Abs: Strongly positive
WOULD YOU BIOPSY????

15. Sheffield Kidney Institute
To Biopsy
Or NOT…????

16. Sheffield Kidney Institute
To Immunosuppress
Or NOT…????

17. Sheffield Kidney Institute
5Whats…
• What is this TREATMENT FOR?
• What is the Evidence: VALIDITY ?
• What is the Relevance: UTILITY ?
• What is the RISK:BENEFIT?
• What is the COST:BENEFIT?

18. Sheffield Kidney Institute
Mrs AB
• 35 years
• 8 years history of hypertension, BP 130/85 on Ramipril 10 mg
• Fit and well, went for a medical check for a new job
• Urine dipstick: 1+ blood and 1+ protein
• Urine PCR 60 and 50 mg/mmol on 2 different occasions
• eGFR >60 ml/min
• USS kidneys: solitary kidney
• Immunology: Negative
WOULD YOU IMMUNOSUPPRESS??????

19. Sheffield Kidney Institute
Mr AI
• 70 years
• No PMH, presented to A&E with respiratory arrest
• Went to ITU, ventilated, CT showed bilateral PE
Treatment: Thrombolysis
• Albumin: 8G/24H, Normal serum creatinine, USS kidneys NAD
Discharged to renal ward on warfarin
WOULD YOU IMMUNOSUPPRESS????

20. Sheffield Kidney Institute
Mrs AD
• 40 years
• BMI: 40
• BP: 140/85mmHg
• GP referral
• Urine dipstick: protein: 2+
• Urine PCR 235, 330 mg/mmol
• eGFR 52 ml/min
• USS kidneys: normal sized kidneys
• Bx: FSGS
WOULD YOU Immunosuppress????

21. Sheffield Kidney Institute
Mrs AJ
• 30 years
• No PMH, 22 weeks pregnant
• She had previous normal delivery with no problems.
• BP: 145/87mmHg
• Normal kidney function , USS kidneys no obstruction
• Urine PCR 400 mg/mmol, 1+ blood on urinalysis
• Anti-dsDNA Abs: Strongly positive
WOULD YOU IMMUNOSUPPRESS????

22. Sheffield Kidney Institute
To Immunosuppress
Or NOT…????

23. Sheffield Kidney Institute
To ACE
Or NOT to ACE…????

24. Sheffield Kidney Institute
5Whats…
• What is this TREATMENT FOR?
• What is the Evidence: VALIDITY ?
• What is the Relevance: UTILITY ?
• What is the RISK:BENEFIT?
• What is the COST:BENEFIT?

25. Sheffield Kidney Institute
85 YEAR OLD
T2DM for 8 years
Hypertension for 15 years: BP 185/87mmHg
CAD, PVD
CKD3b: eGFR 40ml/min
Urine PCR: 1600mg/g
Hematuria: 1+
No Retinopathy
Comes back to see you in 2 weeks

26. Sheffield Kidney Institute
85 YEAR OLD
T2DM for 8 years
Hypertension for 15 years
BP 135/87mmHg
CAD, PVD
CKD5: eGFR 48ml/min
Next appointment 3 months?

27. Sheffield Kidney Institute
85 YEAR OLD
T2DM for 8 years
Hypertension for 15 years
BP 135/87mmHg
CAD, PVD
CKD5: eGFR 8ml/min
Fluid Overloaded
Oliguric

28. Sheffield Kidney Institute
cCKD in the Elderly
eGFR
Kidney Attacks
Kidney Attacks
Heart Attack

29. Sheffield Kidney Institute

30. Sheffield Kidney Institute

31. Sheffield Kidney Institute
AKI and RAS Prescriptions

32. Sheffield Kidney Institute
To ACE
Or NOT to ACE…????

33. Sheffield Kidney Institute
ACE inhibition CKD1-2
O’Hare et al, 2014

34. Sheffield Kidney Institute
ACE Inhibition: Renal Outcomes
Analysis 1.4. Comparison 1 ACEi versus placebo, Outcome 4 Doubling of creatinine by underlying renal
pathologies.
Review: Angiotensin-convertingenzyme inhibitorsand angiotensin receptor blockers for adultswith early (stage 1 to 3) non-diabeticchronic kidney disease
Comparison: 1 ACEi versusplacebo
Outcome: 4 Doublingof creatinine by underlyingrenal pathologies
Study or subgroup ACEi Placebo Risk Ratio Risk Ratio
n/N n/N
M-
H,Random,95%
CI
M-
H,Random,95%
CI
1 Glomerular disease
AIPRI Study 1996 11/94 27/98 0.42 [ 0.22, 0.81 ]
2 Diabetic kidney disease
AIPRI Study 1996 1/6 7/15 0.36 [ 0.06, 2.32 ]
3 Miscellaneousor unknown renal disorders
AIPRI Study 1996 6/61 9/43 0.47 [ 0.18, 1.22 ]
4 Polycystic kidney disease
AIPRI Study 1996 8/30 9/34 1.01 [ 0.45, 2.28 ]
5 Nephrosclerosis
AIPRI Study 1996 2/52 1/45 1.73 [ 0.16, 18.46 ]
6 Interstitial nephritis
AIPRI Study 1996 3/57 4/48 0.63 [ 0.15, 2.68 ]
0.01 0.1 1 10 100
Favours ACEi Favours placebo
Cochrane, 2011

35. Sheffield Kidney Institute
Casas et al, 2005

36. Sheffield Kidney Institute
Analysis 1.2. Comparison 1 ACEi versus placebo, Outcome 2 Cardiovascular events.
Review: Angiotensin-convertingenzyme inhibitorsand angiotensin receptor blockers for adultswith early (stage 1 to 3) non-diabetic chronic kidney disease
Comparison: 1 ACEi versusplacebo
Outcome: 2 Cardiovascular events
Study or subgroup ACEi Placebo Risk Ratio Weight Risk Ratio
n/N n/N
M-
H,Random,95%
CI
M-
H,Random,95%
CI
1 CKD Stage 3
AIPRI Study 1996 9/300 7/283 7.7 % 1.21 [ 0.46, 3.21 ]
PEACEStudy 2006 83/701 87/622 92.3 % 0.85 [ 0.64, 1.12 ]
Subtotal (95% CI) 1001 905 100.0 % 0.87 [ 0.66, 1.14 ]
Total events: 92 (ACEi), 94 (Placebo)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.48, df = 1 (P= 0.49); I2 =0.0%
Test for overall effect: Z = 1.01 (P= 0.31)
2 CKD Stage 3a
PEACEStudy 2006 67/622 68/581 100.0 % 0.92 [ 0.67, 1.26 ]
Subtotal (95% CI) 622 581 100.0 % 0.92 [ 0.67, 1.26 ]
Total events: 67 (ACEi), 68 (Placebo)
Heterogeneity: not applicable
Test for overall effect: Z = 0.51 (P= 0.61)
3 CKD Stage 3 b
PEACEStudy 2006 16/79 19/78 100.0 % 0.83 [ 0.46, 1.50 ]
Subtotal (95% CI) 79 78 100.0 % 0.83 [ 0.46, 1.50 ]
Total events: 16 (ACEi), 19 (Placebo)
Heterogeneity: not applicable
Test for overall effect: Z = 0.62 (P= 0.54)
0.2 0.5 1 2 5
Favours ACEi Favours placebo
Cochrane, 2011

37. Sheffield Kidney Institute
2104

38. Sheffield Kidney Institute
5Whats…
• What is this Treatment FOR?
• What is the Evidence: VALIDITY ?
• What is the Relevance: UTILITY ?
• What is the RISK:BENEFIT?
• What is the COST:BENEFIT?

39. Sheffield Kidney Institute
“Primum Non Nocere…”