IRC

Dr. Nabil Basil

H. Saint Joseph

Background

•1 in 10 people in the UK have chronic kidney disease (CKD)

•Treatment can prevent or delay the progression of CKD

and reduce the risk of cardiovascular disease.

•CKD is frequently unrecognised, often existing with other conditions

such as cardiovascular disease or diabetes.

•30% of patients with advanced CKD are referred late to nephrology services from primary and secondary care.

Definition of CKD

Structural or functional abnormalities of the kidneys for >3 months, as manifested by either:

1. Kidney damage, with or without decreased GFR, as defined by

• pathologic abnormalities• markers of kidney damage, including

abnormalities in the composition of the blood or urine or abnormalities in imaging tests

2. GFR <60 ml/min/1.73 m2, with or without kidney damage

Prevalence of CKD and Estimated Number of Adults with CKD in the US (NHANES 88-94)

Stage DescriptionGFR

(ml/min/1.73 m2)

Prevalence*

N (1000s) %

1Kidney Damage with

Normal or ↑ GFR≥ 90 5,900 3.3

2Kidney Damage with

Mild ↓ GFR60-89 5,300 3.0

3 Moderate ↓ GFR 30-59 7,600 4.3

4 Severe ↓ GFR 15-29 400 0.2

5 Kidney Failure < 15 or Dialysis 300 0.1

*Stages 1-4 from NHANES III (1988-1994). Population of 177 million with age ≥20. Stage 5 from USRDS (1998), includes approximately 230,000 patients treated by dialysis, and assuming 70,000 additional patients not on dialysis. GFR estimated from serum creatinine using MDRD Study equation based on age, gender, race and calibration for serum creatinine. For Stage 1 and 2, kidney damage estimated by spot albumin-to-creatinine ratio ≥17 mg/g in men or ≥25 mg/g in women in two measurements.

ClassificationStages of chronic kidney disease (updated)

1 ≥ 90 Normal or increased glomerular filtration rate (GFR), with other evidence of kidney damage

2 60–89 Slight decrease in GFR,with other evidence of kidney damage

3A 45–59 Moderate decrease in GFRwith or without other evidence of kidney damage3B 30–44

4 15–29 Severe decrease in GFR, with or without other evidence of kidney damage

5 < 15 Established renal failure

a Use suffix (p) to denote presence of proteinuria when staging CKD

Classification of CKD by Diagnosis

• Diabetic Kidney Disease• Glomerular diseases (autoimmune diseases,

systemic infections, drugs, neoplasia)

• Vascular diseases (renal artery disease, hypertension, microangiopathy)

• Tubulointerstitial diseases (urinary tract infection, stones, obstruction, drug toxicity)

• Cystic diseases (polycystic kidney disease)

• Diseases in the transplant (Allograft nephropathy, drug toxicity, recurrent diseases, transplant glomerulopathy)

Early identification– Offer testing for CKD where the following risk factors are

present: • hypertension• cardiovascular disease• diabetes• structural renal tract disease• renal calculi• prostatic hypertrophy• multisystem diseases with potential kidney involvement • opportunistic detection of haematuria or proteinuria• family history of stage 5 CKD or hereditary kidney disease

• Monitor GFR in people prescribed nephrotoxic drugs

Measurement of kidneyfunction

•Clinical laboratories should:

–report estimated GFR (eGFR) when serum creatinine is measured

–correct for ethnicity

•Interpret eGFR with caution at extremes of muscle mass•In new cases of reduced eGFR confirm by retesting within 2 weeks•Urgent despatch and testing of blood minimisesincorrect results

Testing for proteinuria

– To detect and identify proteinuria, use urine albumin:creatinine ratio (ACR) in preference,as it has greater sensitivity than protein:creatinine ratio (PCR) for low levels of proteinuria

– For quantification and monitoring of proteinuria,PCR can be used as an alternative

– ACR is the recommended method for people with diabetes

CKD progression

– Steps to identify progressive CKD– obtain a minimum of three eGFR over not less

than 90 days– in new cases of reduced eGFR, repeat within 2

weeksto exclude acute deterioration of GFR

• CKD progression is either a decline in eGFR: of > 5 ml/min/1.73 m2 within 1 year or > 10 ml/min/1.73 m2 within 5 years

Referral criteria

– Refer the following people with CKD for discussion or specialist assessment:

•stage 4 and 5 CKD (with or without diabetes)

•higher levels of proteinuria

•proteinuria together with haematuria

•rapidly declining eGFR

•poorly controlled hypertension

•people with rare or genetic causes of CKD

•suspected renal artery stenosis

Cardiovascular Mortality in the General Population and in ESRD Treated by

Dialysis

0.01

100

10

1

0.1

Annual mortality (%)

25–34 45–54 65–74 ≥8535–44 55–64 75–84

Male

Female

Black

White

Dialysis

General population

Age (years)

Prevalence of Abnormalities at each level of GFR

*>140/90 or antihypertensive medication p-trend < 0.001 for each abnormality

Clinical Practice Guidelines for the Detection, Evaluation and Management of CKD

Stage Description GFR Evaluation Management

At increased

risk Test for CKD Risk factor management

1

Kidney damage with normal or ↑

GFR

>90

Diagnosis Comorbid conditions

CVD and CVD risk factors

Specific therapy, based on diagnosis Management of comorbid conditions

Treatment of CVD and CVD risk factors

2 Kidney

damage with mild ↓ GFR

60-89 Rate of

progression Slowing rate of loss of kidney function 1

3 Moderate ↓ GFR

30-59 Complications Prevention and treatment of complications

4 Severe ↓ GFR 15-29 Preparation for kidney replacement therapy

Referral to Nephrologist

5 Kidney Failure <15 Kidney replacement therapy 1Target blood pressure less than 130/80 mm Hg. Angiotension converting enzyme inhibitors

(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot urine total protein-to-creatinine ratio of greater than 200 mg/g.

Importance of Proteinuria in CKDInterpretation Explanation

Marker of kidneydamage

Spot urine albumin-to-creatinine ratio >30 mg/g orspot urine total protein-to-creatinine ratio >200 mg/gfor >3 months defines CKD

Clue to the type(diagnosis) of CKD

Spot urine total protein-to-creatinine ratio >500-1000 mg/g suggests diabetic kidney disease,glomerular diseases, or transplant glomerulopathy.

Risk factor for adverseoutcomes

Higher proteinuria predicts faster progression ofkidney disease and increased risk of CVD.

Effect modifier forinterventions

Strict blood pressure control and ACE inhibitors aremore effective in slowing kidney diseaseprogression in patients with higher baselineproteinuria.

Hypothesizedsurrogate outcomesand target forinterventions

If validated, then lowering proteinuria would be agoal of therapy.

Albuminuria as a Risk Factor for CVD in PREVEND

Hillege HL et al. Circulation 2002: 106: 1777-1782

Clinical Practice Guidelines for Management of Hypertension in CKD

Type of Kidney Disease Blood Pressure Target

(mm Hg)

Preferred Agents for CKD, with or

without Hypertension

Other Agents to Reduce CVD Risk

and Reach Blood Pressure Target

Diabetic Kidney Disease

<130/80

ACE inhibitor or ARB

Diuretic preferred, then BB or CCB

Nondiabetic Kidney Disease with Urine Total

Protein-to-Creatinine Ratio ≥200 mg/g

Nondiabetic Kidney Disease with Spot Urine

Total Protein-to-Creatinine ratio <200 mg/g None preferred

Diuretic preferred, then ACE inhibitor,

ARB, BB or CCB

Kidney Disease in Kidney Transplant Recipient

CCB, diuretic, BB, ACE inhibitor, ARB

Other recommendations

– Offer a renal ultrasound to all people with CKD who:

•have progressive CKD

•have visible or persistent invisible haematuria

•have symptoms of urinary tract obstruction

•have a family history of polycystic kidney disease and are aged over 20

•have stage 4 or 5 CKD

•are considered by a nephrologist to require a renal biopsy

Other recommendations (cont’d)

–Provide people with CKD:

•high quality education at appropriate stages of their condition to enable informed treatment choices

•tailored information to their stage and cause of CKD

• Information and education programmes should be provided by healthcare professionals with specialist knowledge of CKD and the skills to facilitate learning