Chronic Kidney Disease

dr. Tjatur Winarsanto SpPD

Chronic Kidney Disease

• Definition– Chronic, irreversible loss of kidney

function attributable to loss of functional nephron mass – pathophysiologic processes for more than 3 months.

• definisi• Kronis kerugian, tidak dapat

diubah fungsi ginjal disebabkan hilangnya massa nefron fungsional - proses pathophysiologic untuk lebih dari 3 bulan.

Pathophysiology of CKD

• Final Common Pathway is loss of nephron mass

Structural/ Functional Hypertrophy of remnant nephrons

Sclerosis of remnant nephrons

Loss of Nephron Mass

Mediated by vasoactive molecules, cytokines

and growth factors, renin angiotensin axis

Diabetes Hypertension

Chronic GN Cystic Disease

Tubulointerstitial disease

Estimation of GFR

• Modification of Diet in Renal Disease (MDRD) Formula– Estimated GFR = 1.86 (Serum

Creat) -1.154 X (age) -0.203

• Multiply by 0.742 for women• Multiply by 1.21 for African

Americans

• Cockroft Gault Formula– (140 – age) X Body Weight (Kg)

72 X Serum Creatinine (mg/dL)• Multiply by 0.85 for women

• Modifikasi Diet di Penyakit Ginjal (MDRD) Formula

• Perkiraan GFR = 1,86 (Serum Creat) -1,154 X (umur) -0,203

• Kalikan dengan 0,742 untuk wanita• Kalikan dengan 1,21 untuk Afrika

Amerika• Cockroft Gault Formula• (140 - umur) X Badan Berat (Kg)• 72 X serum kreatinin (mg / dL)• Kalikan dengan 0,85 untuk wanita?

Staging of Chronic Kidney DiseaseStage Description GFR (ml/min/1.73 m2)

At increased risk 90 (with CKD risk factors)

1 Kidney damage with normal or increased GFR

90

2 Mildly decreased GFR 60-89

3 Moderately decreased GFR 30-59

4 Severely decreased GFR 15-29

5 Renal Failure <15 (or dialysis)

Who is at Risk for CKD?

• Family history of heritable renal disease

• Diabetes• Hypertension• Auto-immune disease• Old age• Prior episode of ARF• Current evidence of renal

damage, even with normal or increased GFR

• Riwayat keluarga dari penyakit ginjal diwariskan

• diabetes• hipertensi• Auto-imun penyakit• tua• Sebelum episode GGA• Sekarang bukti kerusakan

ginjal, bahkan dengan GFR normal atau meningkat

Etiology and Epidemiology

• 6% of the US population has CKD (Stage 1 and 2)

• Additional 4-5% have Stage 3 and 4 CKD

• Diabetic nephropathy• Hypertension – chronic

ischemic nephropathy• Very high CV disease

burden

• 6% dari penduduk AS telah CKD (Tahap 1 dan 2)

• 4-5% tambahan memiliki Tahap 3 dan 4 CKD

• diabetes nefropati• Hipertensi - nefropati

iskemik kronis• Sangat tinggi CV beban

penyakit

Monitoring of CKD• Serial measurements of

– Creatinine– GFR

• Albumin • Albumin-creatinine ratio in

the 1st morning sample• Electrolytes including HCO3,

Ca, Phos; alkaline phosphatase, iron studies, intact PTH

• Renal sonogram• Renal biopsy

• Serial pengukuran• kreatinin• GFR• albumin• Albumin-kreatinin rasio

dalam sampel pagi 1• Elektrolit termasuk HCO3, Ca,

phos, fosfatase alkali, studi besi, PTH utuh

• sonogram ginjal• biopsi ginjal

Symptoms of CKD• Stage 1 and 2

– Asymptomatic, hypertension• Stage 3 and 4

– Anemia – loss of energy– Decreasing appetite; poor

nutrition– Abnormalities in Calcium,

Phosphorus metabolism– Sodium, water, potassium and

acid base abnormalities• Stage 5

– All of the above – accentuated; eventually overt uremia

• Tahap 1 dan 2• Tanpa gejala, hipertensi• Tahap 3 dan 4• Anemia - kehilangan energi• Penurunan nafsu makan; gizi

buruk• Kelainan pada Kalsium, Fosfor

metabolisme• Natrium, air, kalium dan asam

basa kelainan• tahap 5• Semua hal di atas - ditekankan;

uremia akhirnya terbuka

Common Causes and PresentationCause Clinical Presentation

Diabetic kidney disease

History of diabetes, proteinuria and retinopathy

Hypertension Elevated BP, normal UA, family history

Non diabetic glomerular disease

Nephritic or nephrotic presentations

Cystic kidney disease

Urinary symptoms, abnormal sediment, radiologic findings

Tubulointerstitial disease

UTI, reflux, chronic med use, drugs, imaging abnormalities, urine concentrating defects

Clinical Features of Diabetic CKD

Clinical Features of Non-Diabetic CKD

Pathophysiology of Uremia• Azotemia – refers to the retention

of nitrogenous waste products. Uremia – advanced stages of azotemia with end organ dysfunction

• Accumulation of products of protein metabolism– Urea – anorexia, malaise, vomiting

and headaches• Loss of other renal functions

– Erythropoietin deficiency – anemia– Metabolic bone disease; endocrine

abnormalities– Fluid, electrolyte and acid base

disorders

• Azotemia - mengacu pada retensi produk limbah nitrogen. Uremia - stadium lanjut azotemia dengan disfungsi organ akhir

• Akumulasi produk dari metabolisme protein

• Urea - anoreksia, malaise, muntah dan sakit kepala

• Kehilangan fungsi ginjal lainnya• Erythropoietin kekurangan - anemia• Tulang metabolik penyakit; kelainan

endokrin• Cairan, elektrolit dan asam basa

gangguan

Organ System Symptoms Signs

General Fatigue, weakness Sallow-appearing, chronically ill

Skin Pruritus, easy bruisability Pallor, ecchymoses,excoriations, edema, xerosis

ENT Metallic taste in mouth, epistaxis Urinous breath / fetor

Eye   Pale conjunctiva

Pulmonary Shortness of breath Rales, pleural effusion

Cardiovascular Dyspnea on exertion, retrosternal pain on inspiration (pericarditis)

Hypertension, cardiomegaly,friction rub

Gastrointestinal Anorexia, nausea, vomiting, hiccups  

Genitourinary Nocturia, impotence Isosthenuria

Neuromuscular Restless legs, numbness and cramps in legs  

Neurologic Generalized irritability and inability to concentrate, decreased libido

Stupor, asterixis, myoclonus, peripheral neuropathy

Symptoms of Uremia

Mineral Metabolism• Calciphylaxis

– Calcemic uremic arteriopathy– Extraosseous/metastatic calcification of soft tissues

and blood vessels – Devastating complication– Treatment: controversial

• Sodium thiosulfate• ParathyroidectomycalciphylaxisCalcemic uremik arteriopathyExtraosseous / metastatik kalsifikasi jaringan lunak dan

pembuluh darahmenghancurkan komplikasiPengobatan: kontroversialnatrium tiosulfatParathyroidectomy

Cardiovascular Abnormalities

• Leading cause of morbidity and mortality in patients with CKD at all stages

• Ischemic CAD• Hypertension and LVH• Congestive heart failure• Uremic• Penyebab utama morbiditas dan

mortalitas pada pasien dengan CKD pada semua tahap

• iskemik CAD• Hipertensi dan LVH• Gagal jantung kongestif• uremic perikarditis pericarditis

Hematological Abnormalities• Anemia

– Chronic blood loss, hemolysis, marrow suppression by uremic factors, and reduced renal production of EPO

– Normocytic, normochromic– Rx: Iron and Epo as needed

• Coagulopathy– Mainly platelet dysfunction – decreased

activity of platelet factor III, abnormal platelet aggregation and adhesiveness and impaired thrombin consumption

– Increased propensity to bleed – post surgical, GI Tract, pericardial sac, intracranial

– Increased thrombotic tendency – nephrotic syndrome

• anemia• Darah kronis kerugian, hemolisis,

penekanan sumsum oleh faktor uremik, dan produksi ginjal berkurang EPO

• Normositik, normokromik• Rx: Besi dan Epo sesuai kebutuhan• koagulopati• Terutama trombosit disfungsi - aktivitas

penurunan III faktor platelet, agregasi platelet abnormal dan kelengketan dan konsumsi trombin gangguan

• Peningkatan kecenderungan untuk berdarah - posting bedah, GI Tract, pericardial sac, intrakranial

• Peningkatan trombotik kecenderungan - sindrom nefrotik

Other Abnormalities• Neuromuscular

– Central, peripheral and autonomic neuropathy– Peripheral Sensory/Motor Neuropathy– Stage 4 for more than 6 months– Restless leg syndrome

• Gastrointestinal– Uremic fetor– Gastritis, peptic disease, mucosal ulcerations, AVMs

• Endocrine– Glucose metabolism– Estrogen levels – amenorrhea, frequent abortions– Male: oligospermia, germinal cell dysplasia, delayed sexual

maturation• Dermatologic

– Pallor, ecchymoses, hematomas, calciphylaxis, pruritus, uremic frost

• neuromuskular• Tengah neuropati, perifer dan otonom• Peripheral Sensory / Motor Neuropati• Tahap 4 selama lebih dari 6 bulan• Restless leg syndrome• gastrointestinal• uremic bau mulut• Gastritis, penyakit lambung, ulserasi mukosa, AVMs• kelenjar endokrin• glukosa metabolisme• Tingkat estrogen - amenore, aborsi sering• Pria: oligospermia, displasia sel germinal,

kematangan seksual tertunda• Dermatologic• Pucat, ekimosis, hematoma, calciphylaxis, pruritus

es, uremik

Therapeutics in CKD

• Non Pharmacologic– Risk Factor Modification

• Pharmacologic• Treatment of complications

Therapeutics in CKD

• Non Pharmacologic– Risk Factor Modification

• Pharmacologic• Treatment of complications

Therapeutics in CKD

• Non Pharmacologic– Risk Factor Modification

• Pharmacologic• Treatment of complications

Sodium and water ImbalanceKetidakseimbangan

• Glomerulotubular feedback is disrupted – sodium retention, contributes to hypertension; hyponatremia is unusual.

• Higher than usual doses for diuretics. In situations with volume depletion – can be severe, because of inadequate sodium retention.

• Treatment: Salt restriction; high doses of diuretics

Umpan balik Glomerulotubular terganggu - retensi natrium, memberikan kontribusi untuk hipertensi; hiponatremia tidak biasa.

Lebih tinggi dari dosis biasa untuk diuretik. Dalam situasi dengan penurunan volume - mungkin parah, karena retensi natrium memadai.

Pengobatan: pembatasan garam; dosis tinggi diuretik

Potassium Imbalance• Potassium

– GI excretion is augmented– Constipation, dietary intake,

protein catabolism, hemolysis, hemorrhage, transfusion of stored blood, metabolic acidosis,

– Drugs: ACE inhibitors, ARBs, B blockers, K sparing diuretics and NSAIDs

– Hyporeninemic hypoaldosteronism: Diabetes, sickle cell disease

Acid Base Imbalance• Damaged kidneys are unable to

excrete the 1 mEq/kg/d of acid generated by metabolism of dietary proteins. – NH3 production is limited because

of loss of nephron mass– Decreased filtration of titrable acids

– sulfates, phosphates– Decreased proximal tubular bicarb

reabsorption, decreased positive H ion secretion

• Arterial pH: 7.33 - 7.37; serum HCO3 rarely below 15 – buffering offered by bone calcium carbonate and phosphate

• Should be maintained over 21• Treatment: Sodium bicarbonate,

calcium carbonate, sodium citrate

Bone Disease

Treatment of Secondary Hyperparathyroidism

• Phosphorus control in diet• Phosphate binders

– Calcium acetate (Phoslo), calcium carbonate (TUMS), sevelamer (Renagel) , lanthanum (Fosrenol)

• Oral Vitamin D • Calcimemetic agent:

Cinacalcet (Sensipar)

• Fosfor kontrol dalam diet• fosfat binder• Kalsium asetat (Phoslo),

kalsium karbonat (Tums), sevelamer (Renagel), lantanum (FOSRENOL)

• Oral Vitamin D• Calcimemetic agent:

cinacalcet (Sensipar)