Chronic Kidney Disease

Eva Sian Li

KDOQI 2003

Pathophysiology
Initiating mechanisms specific to the underlying etiology (e.g., immune complexes and mediators of inflammation in certain types of glomerulonephritis, or toxin exposure in certain diseases of the renal tubules and interstitium) 2. A set of progressive mechanisms, involving hyperfiltration and hypertrophy of the remaining viable nephrons, that are a common consequence following long-term reduction of renal mass, irrespective of underlying etiology _________________________________________ Harrison 17th
1.

The responses to reduction in nephron number are mediated by vasoactive hormones, cytokines, and growth factors. Eventually, these short-term adaptations of hypertrophy and hyperfiltration become maladaptive as the increased pressure and flow predisposes to sclerosis and dropout of the remaining nephrons
Harrison 17th

________________________________________

Pathophysiology and Biochemistry of Uremia

The pathophysiology of the uremic syndrome can be divided into manifestations in three spheres of dysfunction:
those consequent to the accumulation of toxins normally undergoing renal excretion, including products of protein metabolism those consequent to the loss of other renal functions, such as fluid and electrolyte homeostasis and hormone regulation progressive systemic inflammation and its vascular and nutritional consequences. ____________________________________________ Harrison 17th

Recommended Equations for eGFR

1. Modification of Diet in Renal Disease

e GFR (mL/min per 1.73 m2) = 1.86 x (PCr)1.154 x (age)0.203 (Multiply by 0.742 for women. Multiply by 1.21 for African Americans). 2. Cockcroft-Gault equation
( 140 age ) x BW 72 x Creatinin

Multiply by 0.85 for women

Stages of CKD
Stages Description GFR Classification (mL/min/1.73m2) b/o Th/

Kidney damage w/ N 90 or GFR

Kidney damage w/ mild GFR Moderate GFR 60-89 1-5 T (transplant)

30-59

4
5

Severe GFR
Kidney failure

15-29
< 15 or dialysis 5D (dialysis)

KDOQI 2003/KDIGO 2009

Simplified Classification of CKD by Diagnosis

Diabetic Kidney Disease Nondiabetic Kidney Disease Glomerular disease

autoimmune, sytemic infections, drugs, neoplasia, idiopathic

ischemic renal disease, hypertensive nephrosclerosis, microangiopathy UTO, stones, UTI, drug toxicity

Vascular disease

Tubulointerstitial disease

Cystic disease Post-Transplant

Clinical Abnormalities in Uremia

Fluid and electrolyte disturbances (Volume expansion, Hyponatremia, Hyperkalemia, Hyperphosphatemia) Endocrine-metabolic disturbances (Secondary hyperparathyroidism, Adynamic bone, Vitamin Ddeficient ,osteomalacia, Carbohydrate resistance, Hyperuricemia, dyslipidemia, Protein-energy malnutrition , Impaired growth and development, infertility and sexual dysfunction,2Microglobulin associated amyloidosis) Neuromuscular disturbances (Fatigue, Sleep disorders, Headache, Impaired mentation, Lethargy, Asterixis , Muscular irritability, Peripheral neuropathy, Restless legs syndrome , Myoclonus,Seizures , Coma , Muscle cramps, Dialysis disequilibrium syndrome , Myopathy)

______________________________________________________________ Harrison 17 th

Cardiovascular and pulmonary disturbances (Arterial hypertension, CHF, pulmonary edema, Pericarditis, hypertrophic or dilated cardiomyopathy, Uremic lung, accelerated atherosclerosis, Hypotension and arrhythmias , vascular calcification) Dermatologic disturbances (Pallor, Hyperpigmentation, Pruritus, Ecchymoses ,Nephrogenic fibrosing dermopathy, uremic frost) Gastrointestinal disturbances (Anorexia , Nausea and vomiting, Gastroenteritis, Peptic ulcer, Gastrointestinal bleeding, Idiopathic ascites, Peritonitis) Hematologic and immunologic disturbances (Anemia , Lymphocytopenia, Bleeding diathesis, Increased susceptibility to infection, Leukopenia, Thrombocytopenia) ______________________________________________________________ Harrison 17 th

A Simple Laboratory Evaluation!

Patient meets definition of Chronic Kidney Disease?

YES NO

Determine Stage of CKD Determine underlying cause Identify risk factors for progression Identify comorbidites

Risk Factor Reduction

Primary Goals of CKD Care

To prevent cardiovascular events and death

Heart Attacks Congestive Heart Failure Sudden Cardiac Death Stroke

To prevent the progression of CKD to Kidney Failure or ESRD To prevent complications of CKD To prepare for dialysis/transplantation in a timely manner

Clinical Practice Guidelines for the Detection, Evaluation and Management of CKD
Stage Description At increased risk Kidney damage with normal or GFR Kidney damage with mild GFR Moderate GFR Severe GFR Kidney Failure
1

GFR

Evaluation Test for CKD Diagnosis Comorbid conditions CVD and CVD risk factors Rate of progression Complications

Management Risk factor management Specific therapy, based on diagnosis Management of comorbid conditions Treatment of CVD and CVD risk factors

>90

60-89

Slowing rate of loss of kidney function 1

3 4 5

30-59 15-29 <15

Prevention and treatment of complications Preparation for kidney replacement therapy Referral to Nephrologist Kidney replacement therapy

Target 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.

Management of Patients with Chronic Kidney Disease

Early Detection of CKD

Interventions that delay progression

Prevention of Uremic Complications (GFR < 60 cc/min/1.73 m2)

Modifcation of Comorbidity

Preparation for Renal Replacement Therapy (GRF < 30 cc/min/1.73m2)

ACE Inhibitors

Anemia

Cardiovascular Disease

Education An "ESRD Clinic"

ARBs

Osteodystrophy

Kidney Transplant Evaluation

Choice of Dialysis Modality

BP Control

Malnutrition

Pre-emptive Transplantation

Timely Dialysis Access Placement

Blood glucose control

Reduced Functioning and Well-being

Timely Dialysis Initiation

PROGRESSIVE RENAL DAMAGE:

The Final Common Pathway
RENAL INJURY

Reduction in nephron mass

Glomerular capillary hypertension

Increased BP

Increased glomerular permeability to macromolecules Increased filtration of plasma proteins

Proteinuria
Excessive tubular protein reabsorption
Tubulointerstitial inflammation RENAL SCARRING

Patient characteristics associated with increased rate of GFR decline

Nonmodifiable

Modifiable

African American race Male gender Older age Lower baseline level of kidney function

Higher level of proteinuria Higher BP Poor glycemic control Smoking

Slowing Progression The Earlier, the Better

Pathogenic Mechanisms of High Blood Pressure in CKD

Pre-existing essential hypertension Extracellular fluid volume expansion Renin-agniotensin aldosterone system stimulation Increased sympathetic activity Alteration in endothelium-derived factors(NO/endothelin) Increased body weight Erythropoietin administration PTH secretion/hypercalcemia calcified arterial tree renal vascular disease and renal artery stenosis

JNC-7 recommends a goal blood pressure of <130/80 mm Hg for individuals with high blood pressure and CKD.

Recommendations for Controlling HTN in NonDiabetic CKD

Population CKD + >200mg/g Prot/Cr Ratio BP Goal <130/80 Nondrug Rx Reduce salt BMI25 kg/m2 Mod EtOH Stop Smoking Exercise Same Drug RX ACEI/ARB Then diuretic Then BB or CCB

CKD + no proteinuria

<125/75

Thiazide/Loop Then ACEI/ARB Then BB or CCB

Interventions that delay progression of CKD: Strict Glycemic Control

Recommended Therapy: Good control : fasting Gluc 80-100 mg/dL, pp Gluc 80-144 mg/dL, HgbA1c < 6,5% (PERKENI) Moderate control : fasting Gluc 100-125 mg/dL, pp Gluc 145-180 mg/dL, HgbA1c 6,5-8 % (age > 60 yo)

Management of Patients with Chronic Kidney Disease

Early Detection of CKD

Interventions that delay progression

Prevention of Uremic Complications (GFR < 60 cc/min/1.73 m2)

Modifcation of Comorbidity

Preparation for Renal Replacement Therapy (GRF < 30 cc/min/1.73m2)

ACE Inhibitors

Anemia

Cardiovascular Disease

Education An "ESRD Clinic"

ARBs

Osteodystrophy

Kidney Transplant Evaluation

Choice of Dialysis Modality

BP Control

Malnutrition

Pre-emptive Transplantation

Timely Dialysis Access Placement

Blood glucose control

Reduced Functioning and Well-being

Timely Dialysis Initiation

Anemia and CKD

Anemia usually associated with

Erythropoietin deficiency Fe, folic acid deficiency Blood loss (GIT bleeding, hematuria) RBC lifespan Suppression BM by uremic toxin, inflamation Assess Hemoglobin level If anemia (HgB 12) RBC indices/CBC Reticulocyte count Iron studies Test for occult GI bleeding as indicated Medical evaluation of comorbid conditions
Buku ajar IPD 4th

For Adults with Stage 3 CKD:

Prevention of Uremic Complications: Anemia Therapy

Subcutaneous administration of erythropoietin once to thrice weekly (sometimes less). Supplemental oral or IV iron to keep ferritin > 100 and iron saturation >20%. Monthly monitoring of Hgb, iron stores. Monthly adjustments in EPO dose and frequency to meet target Hgb 11-12 g/dl (HCT 33-36%).

CKD MBD

Penurunan LFG Penurunan aksi 1,25(OH) 2D Retensi fosfat

G A N G G U A N M I N E R A L P G K KDOQI

Keadaan resisten vitamin D

Peningkatan kebutuhan vitamin D

Kadar 1,25(OH) 2D darah normal atau rendah

Gangguan produksi 1,25(OH)2D oleh ginjal

Defisiensi 1,25(OH)2D3 relatif atau absolut

Penurunan ekspresi VDR di paratiroid

Resisten si skeletal terhadap aksi PTH

Penurunan absorpsi Ca intestinal

Penurunan ekspresi Casensing receptor di paratiroid

Hipokalsemia

Rickets atau osteomalasia

Resorpsi tulang (osteitis fibrosa cystica)

Hiperparatiroidism sekunder
27

Prevention of Uremic Complications: Hyperphosphatemia

Restrict dietary phosphorus 600-800 mg/d Phosphate binders Calcitriol or paricalcitriol Cinacalcet Parathyroidectomy

Prevention of Uremic Complications: Malnutrition

Contributors to protein-energy malnutrition(PEM) in CKD:

low protein and calorie intake metabolic acidosis resistance to insulin, GH, IGF-1 proinflammatory cytokines

Prevention of Uremic Complications: Nutrition Guidelines

Energy intake

RDA depends on energy expenditure 35kcal/kg/d (<65yo), 30-35kcal/kg/d (65yo),

Protein intake
0.6-0.8 g/kg/d HD 1-1.2 g/kg/d, CAPD 1.2-1.3 g/kg/d Restriction Na (if HTN), K (if oliguric or hyperK)

Management of Patients with Chronic Kidney Disease

Early Detection of CKD

Interventions that delay progression

Prevention of Uremic Complications (GFR < 60 cc/min/1.73 m2)

Modifcation of Comorbidity

Preparation for Renal Replacement Therapy (GRF < 30 cc/min/1.73m2)

ACE Inhibitors

Anemia

Cardiovascular Disease

Education An "ESRD Clinic"

ARBs

Osteodystrophy

Kidney Transplant Evaluation

Choice of Dialysis Modality

BP Control

Malnutrition

Pre-emptive Transplantation

Timely Dialysis Access Placement

Blood glucose control

Reduced Functioning and Well-being

Timely Dialysis Initiation

Dialysis
Indication : GFR <15 Indication urgent dialysis: A Acid base disturbance I Intoxication U Uremia: pericarditis, encephalopathy, bleeding E Electrolyte disorder O Overload of volume

TERIMA KASIH