Dr. Bassam A Alhelal Head of Nephrology and Dialysis

Division Al Adan Hospital

CKDPrevention and Treatment of

CKD, Early Diagnosis and aggressive Treatment

Definition of CKD Epidemiology of CKD Screening & Diagnosis Prognosis and Progression Complications of CKD Prevention of CKD progression

Objective

Structure abnormality with or without low GFR

Imaging Urinary abnormalities ( protein, blood) Histological abnormalities

GFR less or equal 60 ml/min 1.73m2 Persistent for > 3 months

Definition

Measured GFR Estimated GFR

GFR Measurement

Inulin GFR is the Gold standard modality Not used often in practice

Cost $$$$ Time consuming

Useful in limited clinical scenarios

Kidney donors with borderline GFR GFR > 60 Older patients (more accurate) Nephrotoxic drug dosing Post Transplant CKD

Concerns of measured GFR

Cockroft-Gault Formula

Modification of Diet in Renal Disease (MDRD)

CKD Epidemiology Collaboration Equation (CKD-EPI)

Estimated GRF

Cockroft-Gault equation

Age WeightCr

MDRD equation

AgeSexRaceCr

CKD-EPI equation

AgeSex RaceCr

CommentsCockroft-Gault

Estimate CrCL not GFR (overestimate GFR)Not Accurate for GFR > 60Issues with obese and elderly patients

MDRD More accuracy and precision over CG equation Validated for Af American, DM CKD and Tx RecipientNot validated in Elderly, Pregnant women and Children Underestimate GFR in patients with normal GFR (Type 1 DM and Kidney Donors)

CKD-EPI More accurate than MDRD esp for GFR >60Replaces MDRD as per KDIGO 2012 recommendation

Common world wide disease Incidence and prevalence increasing Progressive ESRD leads to

Increased cost on the health care system 52 Billion $ by 2030 2% of UK health service budget

Higher patient morbidity / mortality lower quality of life despite the cost

Epidemiology

Earlier report showed Over all prevalence of CKD 11%

9% males 12% females

Factors affect the true prevalence Most of the studies are based on single GFR result Micro-albuminuria can be associated with other disorders & can be

transient Elderly patients (Age related low GFR rather than CKD) Error in the measurement of GFR with formulas like CG and

MDRD

Epidemiology of CKD

Study Country Design

Number Micro Alb

CKD

NHANES III

USA CS/L 15K 12% 11%

PREVEND Netherland

CS/L 40K 7%

NEOERICA

UK CS 130K 17%

HUNT II Norway

CS 65K 6% 10%

EPIC-NORFOLK

UK CS 24K 12%

MONICA Germany CS 2K 8%AusDiab Australia CS 11K 6% 10%TAIWAN Taiwan CS/L 462K 12%Beijing China CS 14K 13%Takahat Japan CS 2K 14%

Prevalence of CKD

About 1% of the prevalence of CKD

Improve patient survival on dialysis

Improve dialysis Therapy Better management of CVS diseases Improve management of ESRD

Anemia CKD

Epidemiology of ESRD

Incidence Prevalence USA 360 1626 Caucasians

279 1194

African Am

1010 5004

Natives Am

489 2691

Hispanic 481 1991Australia 115

aboriginal 441

789 2070

Japan 275 1956UK 113 725France 140 957Germany 213 1114Italy 133 1010Spain 132 991

Epidemiology of ESRD

Year New Patients

Transplantes

PD Death Total

2011 94 13 6 182102 90 17 7 302013 96 15 4 28 260

Data from Kuwait

Population ESRDMubarak 152500 203Al-Adan 180500 274

Farwania 164083 117Jahra 95000 193MK 136127 ---

Total = 728211

Total = 787

Kuwait 4 centers ESRD prevalance

Rate of ESRD based on 2005 censes is 1 per 1000 or 1000 per million population

Diagnosis and Prognosis

Screening for the general population is not cost-effective

NKF Recommend screening for all High risk population

Measure BP Measuring serum CR Measuring Urine for ACR Urine for RBC and WBC

ACP 2013 clinical practice guideline recommend not to scren for albuminuria for patients already on ACEI or ARB

Screening for CKD

Target Group KDOQI UK NICE

CARI CSN

Elderly ✔HTN ✔ ✔ ✔ ✔DM ✔ ✔ ✔ ✔Atherosclerosis ✔ ✔ ✔CVS and Heart Failure ✔ ✔Urological disease, Stone or UTI

✔ ✔Systemic Autoimmune disease

✔ ✔ ✔

Nephrotoxic drugs ✔ ✔ ✔High risk ethnic groups ✔ ✔ ✔Family history if CKD ✔ ✔

International Recommendations for Target population Screening for CKD

New staging system is based on triad

GFR category

Albuminuria and ACR

Cause Systemic or not

Staging & Prognosis of CKD

GFR Albuminuria Cause

Systemic Not

Stage 3 further divided to 1a & b

Staging and Classification

A1 A2 A3

Albuminuria

< 30mg 30-300mg >300mg

ACR < 3mg/mmol 3-30 mg/mmol

> 30mg/mmol

Measurment of Albuminuria

Variable course of Progression Disease related Age Ethnicity

Not all progress to ESRD Many die from other causes esp CVS before

reaching ESRD

Natural History of CKD

Progression in descending order

DM (10 ml/min per year) Chronic GN HTN Interstitial nephritis

Non-modifiable Modifiable Age HypertensionGender Proteinuria Race Albuminuria, CKD &

CVSGenetics RAASLoss of renal mass Glycemic control

Obesity LipidSmokingUric Acid

Progression Factors

Risk Stratification & Prognosis

Progression of CKD Drop of GFR > 25%

from baseline with drop in GFR category

Sustained decline in GFR of > 5 ml/min/1.73 m2/yr that is Rapid progression

Detecting CKD Progression and GFR monitoring

Slowing GFR progression

Relaxed Target blood Pressure as compared with previous recommendations.Current recommendation

- Less than 140/90-Less than 130/80 for those with proteinuria

ACEI or ARB should be the first line therapy Lower BP (SBP < 120 and/or DBP < 70) should be avoided

- No proven benefit - Increased CVS complication

1. BP Target

All CKD pts are a increased risk of AKI Heavy proteinuria, DM & HTN increase likelihood AKI impacts progression conversely Extra care is taken during:

Major surgery, intercurrent illness, exposure to nephrotoxins

2. CKD and AKI

Diabetes is the leading cause of CKD worldwide 25-40% of T1 & T2 DM develop DKD within 20-25ys of

onset Mortality of DM with high AER is twice that of normal

AER Aim for HbA1c of 7% to prevent or delay DKD

Avoid HbA1c < 7% in pts at risk of hypoglycemia

3. Glycemic Control

High protein intake causes accumulation of uremic toxins This may suppress appetite & cause muscle protein wasting

Poor protein intake may cause loss of LBM & malnutrition

Value of protein restriction in slowing GFR loss is unclear Effect of good BP & BS control & proteinuria reduction?

Avoid high protein intake (>1.3g/kg/d) in progressive CKD High intake of non-dairy animal protein must be avoided

Aim for protein intake of 0.8g/kg/d when GFR < 30 ml/min Very low protein intake may not protect against GFR decline

4. Protein Intake

Lower salt intake to < 5 g/d That is < 2 g/d or < 90 mmol/d of sodium

CKD pts have impaired sodium excretion High sodium intake

Raises BP & proteinuria & induces glomerular hyperfiltration

Blunts the response to RAAS blockade Salt restriction reduces albuminuria

Independent of effect of salt restriction on BP reduction

5. Salt Intake

Hyperuricemia (uric acid > 400) is common in CKD pts

Growing body of evidence implicate hyperuricemia in:

CKD progression adverse CV outcome in CKD

Treatment of asymptomatic hyperuricemia may: Delay progression of CKD Improve LV mass & endothelial function

However, evidence are inadequate to support the recommendation of treating asymptomatic hyperuricimia

6. Uric Acid and CKD

Prevalence of acidosis in CKD: GFR < 90 – 8.5% GFR < 60 – 9.5% GFR < 45 – 18% GFR < 30 – 30%

Chronic metabolic acidosis is associated with: Increased protein catabolism & muscle wasting Uremic bone disease Impaired glucose homeostasis Impaired cardiac function CKD progression & increased mortality

7. Metabolic Acidosis

CKD pts with HCO3 < 22 should be given oral HCO3 Reverses harmful effects of acidosis Did not affect BP control or hospitalization for

heart failure These effects are seen with NaCl & not NaHCO3

Cont, metabolic acidosis

Exercise 30 min 5 days a week Keep BMI 20-25 Stop smoking

9. Life style modification

Refer to nephrology in the following circumstances: AKI or abrupt sustained fall in GFR GFR < 30 ml/min/1.73 m2

Albuminuria > 300 mg/d or proteinuria > 500 mg/d

Progression of CKD Drop of GFR > 25% from baseline with drop in GFR

category Sustained decline in GFR of > 5 ml/min/1.73 m2/yr

Timing of Referral to Nephrologist

RBC casts or unexplained hematuria CKD & HTN resistant to ≥ 4

antihypertensive agents Hereditary kidney disease Persistent K abnormalities Recurrent or extensive nephrolithiasis

Cont, referral to nephrologist