Definition

1. Kidney damage for 3 months Structural or functional abnormalities of the kidney With or without decreased GFR Manifest by: pathological abnormalities or markers of kidney damage (abnormalities in the composition the blood or urine or abnormalities in imaging tests) 2. GFR < 60 mL/min/1.73m2 for 3months, with or without kidney damage

KDOQI 2002

AJKD vol 53 no 56 2009 Numerous suggested revisions:

Collapsing stages 1 and 2 into 1 stage Lowering GFR from 60 to 45 Adding 2 sub cateories of stage 3: 45-59 30-44 Introducing age & sex GFR specific value

Definition & stages of CKD

KDOQI 2002

Epidemiology

USRDS 2000

Epidemiology
Prevalence of CKD GFR 60 mL/min/1.73m2: Japan & USA 20% Taiwan 6.4-9.8% China 2.6-13.5 % Singapore 17.7% Thailand 1.6-9.1% Pernefri 12.5% decreased GFR

JNHC 2009

Epidemiology
Incidence & prevalence of ESRD in USA 1996 Characteristic Prevalence Incidence

Total population
Age 20-44 45-64 65-74 Diabetes Hypertension GN

1041/mill population
692 2280 3518 339 256 185

268
117 542 1144 113 70 29

USRDS 1998

Pathophysiology
Renal Injury Reduction of nephron numbers Glomerular capillary hypertension Increased glomerular permeability to macromolecules

Accumulation of protein in proximal tubular cells

Excessive tubular reabsorption

Increased filtration of plasma proteins

Nuclear signals for NF-kB dependent & independent vasoactive & inflammatory genes corresponding protein products released to interstitium

Fibroblast proliferation Tubular cells transdifferntiation

Fibrogenesis

Renal scarring

Pathophysiology

Pathology, etiology
Pathology Diabetic glomerulosclerosis Glomerular disease Etiology (examples) DM type 1 & 2 SLE, vasculitis, hep B, hep C, HIV Prevalence among ESRD 33% 19%

Vascular disease
Tubulointerstitial diseases Cystic diseases Diseases in the transplant

Renal artery stenosis Hypertension, HUS

Infection, stones, NSAID, antibioticd, MM Autosome dominant, recessive Cyclosporin, tacrolismus

21%
3% 6%

USRDS 1998

Risk factors
Definition Susceptibility factors Initation factors Increase susceptibility to kidney damage Directly initiate kidney damage Examples Older age, family history DM, Ht, autoimmune, UTI, stones, obstruction, drug toxicity High level of proteinuria, higher blood oressure level, poor glycemic control, smoking

Progression factors

Cause worsening kidney damage & faster decline in kidney fubction after initiation of kidney damage

Clinical manifestation
Undetected CKD Related to underlying diseases Uremic syndrome

Clinical manifestation

Clinical manifestation

Harrisons 16th ed

Laboratory measurements
Estimation of GFR Assesment of proteinuria Markers of CKD other than proteinuriaI, nuclear

Estimation of GFR

Estimation of GFR

A 24-haour urine sample for: a. Estimation of GFR in individual with exceptional dietary intake or muscle mass b. Assesment of diet & nutritional status c. Need to start dialysis

Assesment of proteinuria
Spot urine samples to detect & monitor proteinuria in adult Not necessary to obtain a timed ( 24 hrs) urine collection Standard urine dipsticks acceptable for screening Positive 1+ should undergo confirmation with quantitative measurements (protein to creatinine ratio or albumin to creatinin ratio) within 3 months

Assesment of proteinuria
Adults at increased risk for CKD, screening with spot urine: . Albumin specific dipstick . Albumin to creatinin ratio Monitoring spot urine samples:
. Albumin to creatinin ratio . Total protein to creatinine ratio if albumin to creatinine ratio is > 500-1000 mg/gr

Association with complications

Hypertension Anemia Nutritional status Bone disease, calcium & phosporus metabolism Neuropathy Indices of functioning & well being CV diseases Diabetic complication

Management

Management

The object therapy for CKD: to detect kidney disease at a higher level of kidney function ( open arrow) & to reduce rate of decline in kidney function thereafter (filled arrow),: reducing adverse outcomes

Management
Goals of evaluation To identify thr stage of CKD To diagnose the type of kidney disease To detect reversible causes To identify the risk factors for progression To identify the risk factors for CVD To detect complications of decreased GFR

Management
Hypertension
BP target Non diabetic Ht & CKD (JNC 7) DM (JNC 7, ADA) CKD (KDOQI, JNC 7) Protein excretion > 1gr daily (NKF) Prevent pregression of CKD <140/90 <130/80 <130/80 < 125/75 < 120/80

Management
Type BP Preferred agents for CKD ACEI or ARB ACEI or ARB None preferred Other agents to reduce CVD risk& reach BP target Diuretic preferred then BB or CCB Diuretic preferred then BB or CCB Diuretic preferred then ACEI, ARB, BB or CCB Diabetic kidney Nondiabetic spot urine P/C 200 Nondiabetic kidney disease with spot urine P/C < 200 Kidney disease in the kidney transplant patient <130/80 <130/80 <130/80

<130/80

None preferred

CCB, diuretic, BB, ACEI, ARB

Management

Anemia

Anemia
EPO Indication Hb 10, Ht 30 Other causes of anemia excluded Iron store: serum ferritin > 100 gr/L, transferrin sat > 20% No severe infection Contraindication: hypersensitivity Precaoution: uncontolled Ht, hypercoagulable state, fluid overload

Nutrition

Nutrition

Clinically stable MHD dietary protein intake/DPI 1.2 gr/kgBW/day, 50% high biological value CPD DPI 1.2 gr/kgBW/day if cannot demonstrate adequate protein status: 1.3 gr/kgBW/day should be prescribed Calory 30-35 kcal/kgBW/day CKD st 1-3 0.75 gr/kgBW/day in the absence of malnutrition CKD st 4-5 0.6 gr/kgBW/day if not tolerated 0.75 gr/kgBW/day

CKD-MBD

Monitoring Ca, PO4, CaxPO4, PTH

Stage 3 Stage 4 Stage 5

Q 12 months Q 3 months Q 1 months

Dyslipidemia
LDL-C in CKD 1-4: < 100 mg/dL but < 70 mg/dL is preferable Statin recommended for LDL-C > 100 Atorvastatin & pravastatin no adjustment

Clinical performance measures for CKD

Preparation for RRT when GFR < 30 Individuals at increased risk for CKD should be tested: DM, Ht, autoimmune, systemic infections, exposure to drugs or procedures, recovery from AKI, age > 60, Fx history, reduced kidney mass Measurements: Serum Cr for eGFR Assesment of proteinuria Urinary sediment or urine dipstick for RBC & WBC

eGFR should be the parameter used Protein (albumin)/creatinine ratio in spot urine should be monitoredin all pts w/ CKD BP according to JNC or ADA GFR< 60: anemia/Hb, nutritional status ( dietary energy+ protein intake, weight, serum albumin, total chol), bone disease (PTH, Ca, Po4), functioning & well being

eGFR yeraly & more frequently in: GFR<60, fast GFR decline in the past (4mL/min/1.73m2), risk factors for faster progression, ngoing th/ to slow peogression, exposure to risk f/ Diabetic kidney: evaluated & managed according to guidelines

Clinical Evaluation of patients at increased risk of CKD

All patients Measurement of blood pressure SCr to estimate GFR Protein to creatinine ratio or albumin to creatinin ratio in the first morning of random untimed spot urine specimen Examination of the urine sedimen or dipstick for RBC and WBC Selected patients depending on risk factors Ultrasound imaging (e.g pts with urinary tract obstruction, infection or stone or family history of polycystic kidney disease) Serum electrolytes (sodium, potassium, chloride, bicarbonate) Urinary concentration or dilution (specific gravity or osmolality) Urinary acidification (pH)

Simplified classification of CKD by diagnosis

Diseases Diabetic kidney disease Non diabetic kidney disease Major types ( example) Type 1 and type 2 diabetes Glomerular disease ( autoimmune disease, drugs, neoplasia, systemic infection) Vascular disease (large vessel, microangiopathy, hypertension) Tubulointerstitial disease ( UTI, stones, obstruction, drug toxicity) Cystic disease Chronic rejection Drug toxicity (cyclosporine or tacrolimus) Recurrent disease (glomerular disease) Transplant glomerulopathy

Disease in the transplant

All patients Serum creatinine to estimate GFR Protein to creatinine ratio or albumin to creatinine ratio in a first morning or random untimed urine specimen Examination of the urine sediment or dipstick for RBC and WBC Imaging of the kidney usually ultrasound Serum electrolyte ( Sodium, potassium, chloride, bicarbonate)