Chronic Kidney Disease“The 6 Pillars”

Dr. Tiina PodymowAssociate Professor

Division of Nephrology McGill University Health Centre

Disclosures

• None

Objectives1. Describe evidence-based measures to slow the

progression of chronic renal disease

2. Recognize and treat the complications of renal failure in an evidence-based manner including anemia, bone metabolism disorders, and electrolyte abnormalities

3. Recognize the importance of ongoing medication reviews in patients with decreasing eGFR

4. Recognize when and how to plan for long-term renal replacement therapy and/or renal transplantation

Poll Everywhere

• I am a:

• Community Internist• Trainee (Stu/Res/Fel)• Family Physician• Academic Internist

Case• 73M divorce lawyer, referred to nephrology clinic Cr 180 µmol/L

• PMHx• COPD• CABG age 64• AAA rupture/repair age 65• Afib on warfarin

• Medications• Bisoprolol• Atorvastatin• Warfarin• Perindopril

• ROS: no hematuria, some ankle edema, occasional ibuprofen

• Omeprazole• Synthroid• Isosorbide mononitrate• Vitamin D

Questions/Objectives• What is the cause of his chronic kidney disease?

• What is the likely course of his CKD?

• Likelihood of needing dialysis?

• What is the best stabilization/preservation strategy

• What are the “six pillars”?

• When should patients be referred to nephrology?

Labs

What is the likely cause of CKD?

• Burned out glomerulonephritis e.g. IgA• Diabetic nephropathy• Glomerulosclerosis• The cause is not especially relevant to

management and prognosis

Urine Protein Interpretation

• Microalbumin: answers the question: is the endothelium healthy?< 1.9 yes it is>1.9 no it might not be

• Urine protein/Cr is a surrogate for 24 hour urine collection and protein quantification

Urine Protein

Dipstick: .3 (which is 1+)

U protein/Cr ratio is equivalent to 0.5 g/24 hour urine

Urine microalbumin is positive- upper normal is 1.9 mg/mmol

Urine Protein Quantification<1 gram tubular or hemodynamic

(glomerulosclerosis- ischemic nephropathy-hypertensive nephropathy)

1-3 g nondiagnostic- could be tubular or glomerular

>3 g/24 h is always glomerular

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Patient’s diagnosis

• Glomerulosclerosis• U protein ~ 1 g/day• Relatively stable Cr

Hypertensive Glomerulosclerosis

• Bright: “hard pulse means granular kidneys on autopsy”

• Meaning: hypertension clinically predicts glomerulosclerosis on autopsy

Glomerulosclerosis• Hypertension alters the endothelial

lining of glomerular capillaries• Leads to atherosclerosis and scarring of

the glomerulus

Normal glomerulus Glomerulosclerosis

Natural History of Hypertension

• MR FIT trial

• 322,000 men, 16 year follow up correlating blood pressure to end-stage renal disease of any cause

MR FIT trial

NEJM1996 Jan 4;334(1):13-8.

1-4% needing dialysis does not seem so bad

• But it is.. The number of hypertensive patients is so large that even the small percentage at risk means a large number of people with renal failure

Question

• If I told you that this patient also had a history of type 2 diabetes x 15 years, could his CKD be attributable to diabetic renal disease?

• Yes• No

Diabetes

Clinically: 1. Microalbuminuria2. Albuminuria3. nephrotic proteinuria4. ↑ Cr5. renal failure

Kimmelstiel Wilson lesions

Diabetic Renal Disease

• Type 1: 4-17% on dialysis at 20 years

• Type 2: 1-10%

Kimmelstiel Wilson lesions

U ptn vs. Cr in 41F with Diabetic Nephropathy

Is there any difference in prognosis between:

1. 73M glomerulosclerosis eGFR of 30 ml/min

2. 41F with diabetic nephropathy eGFR 30 ml/min?

73M glomerulosclerosis: what is the likelihood of needing dialysis?• http://mdrd.com/ to calculate GFR• http://kidneyfailurerisk.com/

73M eGFR 31

41F DM nephropathy eGFR 31 high U alb/Cr

Course of CKD due to glomerulosclerosis

• Prognosis is actually quite good

• Patients tend to be very volume sensitive-Cr fluctuates

• No NSAIDS

• Dose meds to GFR 30 ml/min (mdrd.com and Uptodate)

Course of CKD due to Diabetic Nephropathy

• Poor prognosis

• Type 1: 4-17% on dialysis at 20 years from onset

• Type 2: 1-10%

Kimmelstiel Wilson lesions

Chronic Glomerulonephritis

• IgA: 20% at 10 years on dialysis

• FSGS 25%

• Membranous 15%

AD Polycystic Kidney Disease

• progression to end-stage renal failure most commonly occurs in middle age and later

• Dialysis:2% @ age 40, 20-25% @ 50,35-45% @ 60, and 50-75% @ age 75

Slowing the Progression of Chronic Kidney Disease

www.kidney.orgThe National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI)

Hypertension in CKD• Hypertension is found in 85% with stage 3 CKD

• High systemic BP transmitted to the glomerulus

• Hypertension almost always accelerates the loss of renal function

• BP is the most important thing to control to limit progression of CKD to dialysis

Hypertension and CKD• Most patients with renal failure have

hypertension and need more than 3 meds to control it

• Hydrochlorothiazide no longer works after~ CrCl <30 ml/min

• ACEI/ARB- expect a rise in Cr of 15%- this is OK (represents lowered intraglomerular pressure (good), not failing kidney)

Doubling Cr

Jafar, T. H. et. al. Ann Intern Med 2003;139:244-252

• Hypertension and proteinuria conspire to accelerate chronic kidney disease

Proteinuria from Diabetes• Diabetes – type 1 and type 2 are the commonest

causes of chronic renal failure leading to dialysis

• In patients with microalbuminuria treatment of blood pressure to <120/75 mm Hg and use of ACEI or ARBs can reverse proteinuria

• Before these drugs, all patients with proteinuria and CKD ended up on dialysis

• Takes ~ 10 years from onset of DM for microalbuminuria to occur

Type 1 diabetes Lewis NEJM 1993Captopril, the first ACEI, alters the naturalhistory of diabetes as we knew it (PCr >1.5)

25% on dialysis with placebo

vs. 12% on ACEI

Blood Pressure Goals• BP goal for uncomplicated hypertension is

<140/90 mm Hg,

• Proteinuria > 1 g/day with CKD, the BP goal is <130/80 mm Hg.

• HOWEVER: No benefit in patients with <1 g/day proteinuria- target 140/90

BP recommendations in CKD

Am J Kidney Dis. 2013;62(2):201-213

The 6 Pillars

Chronic Renal Insufficiency1. Anemia2. Bone disease3. Volume overload4. Hypertension5. Increased K6. Acidosis

At what eGFR would you firstexpect anemia, acid base

disturbances, etc.• 50 ml/min• 40 ml/min• 30 ml/min• 20 ml/min• 10 ml/min

1. Anemia in CKD• CrCl below 30 ml/min- usually 15-20 ml/min

• Approach to Hb <100

• Target Hb?

1. Check Fe, IBC, % sat and fix iron stores. 2. Then use ESA (erythrocyte stimulating

agents) erythropoetin or darbopoetin

100-120 and not more or less (increased mortality)

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2. Secondary Hyperparathyroidism/ Bone disease

• Comes down to Ca/PO4/ and PTH• PO4 rises in renal failure

• Parathyroid is stimulated to PTH ↑ this is secondary hyperparathyroidism

• PO4 uses free Ca and bone for buffer (so Ca can become low)

• Vitamin D is not converted to 1,25 vit D

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Management• Want normal Ca and PO4• Target PTH 5 x normal (~50 max)

• Low PO4 diet – renal diet

• Binders: CaCO3, Sevelamer, Lanthanum bind PO4 in gut

• Vitamin D = Calcitriol is 1,25 vitamin D and it suppresses PTH BUT it increases PO4 by increasing its gut absorption (so control PO4 first before Rxing)

• Cinacalcet (Sensipar)- a calcimimetic for the calcium sensing receptor in the parathyroid gland- “medical parathyroidectomy” for patients with 3o hyperPTH

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Ca (2.1-2.6)

PO4(N 0.8–1.6)

PTH pmol/L (target is 35-50)

Rx

Normal 3 35

Normal Normal 70

2.8 2 50

Normal 3 on CaCO3

35

Normal Normal 300 (tertiary hyperPTH)

Start 1,25 vit D (calcitriol)

Low PO4 diet +Start CaCO3

Start sevalemer or lanthanum

Start cinacalcet

Start sevalemer or lanthanum

3. Volume overload• Really becomes a management issue if

LVEF is low

• Fluid restriction

• Furosemide in renal failure doses

• BEWARE of pre renal failure

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4. Acidosis

• The kidney can’t generate bicarbonate

• Want to give bicarb?

• 500 BID or TID

• Target bicarb >21 mmol/L

• Bicarbonate Supplementation Slows Progression of CKD JASN September 1, 2009 vol. 20 no. 9

5. Increased K• Renal diet

• Avoid K increasing meds- NSAIDS (not to mention that they kill the kidney)

• Kayexelate is a poor long term solution- it is poorly tolerated

6. Dialysis• Planned start, with a functioning fistula or CAPD

catheter

• GFR 10 ml/min followed monthly in nephrology clinic

• Guided by, but not based on GFR

• Based on how the patient feels

• If the patient starts to have decreased appetite, nausea, feels unwell, trouble concentrating with GFR 15 ml/min or less- start that day or the next

6. Dialysis planning• Need at least 8 weeks for a surgically

created fistula to mature• Save an arm

Peritoneal Dialysis6 weeks for a Tenchoff catheter site to heal

CKD eGFR ≤30 ml/min• Treat or consider

1. Hb and Fe/ESA treatment2. Ca PO4 PTH3. HCO34. K5. Volume status6. Prepare for dialysis- save an arm

• BP to target

• Dose medications to current GFR (Uptodate), and hold the ones that are overtly nephrotoxic like NSAIDS

When to refer to a Nephrologist?

U protein 3 g/day

AKI on CKD• CKD patients are especially volume sensitive

• NSAIDs, aminoglycoside antibiotics, and radiocontrast media commonly aggravate renal disease

• NSAIDS with ACEI/ARB = AKI

• educate patient to NEVER take Ibuprofen (Advil, Motrin), Aleve, Celebrex etc. (often Rx by surgery)

– Aspirin or Tylenol are fine

Summary• Use U albumin and U protein/Cr ratio to diagnose and risk

stratify

• Use MDRD.com and kidneyfailurerisk.com

• BP is the most important thing for secondary prevention, to limit progression of CRF to dialysis

• use ACEI/ARB for proteinuric patients

• Remember the 6 pillars

• Dose meds to to eGFR

• Nephrologist should co-follow eGFR ≤30 ml/min