Interna Uro Sistem

Urogenitalia SystemUrogenitalia System( Nephrology Division )( Nephrology Division )

Prof Dr dr Syakib Bakri,SpPD,K-GH

dr Hasyim Kasim,SpPD,K-GH

dr Haerani Rasyid,Mkes,SpPD,KGH

dr MeldaTessy,SpPD

dr Dina Nilasari,SpPD

Syndromes in NephrologySyndromes in Nephrology

Acute nephritisUrinary tract infection

GlomerulopathiesGlomerulopathiesAcute renal failure

Chronic kidney diseasePolycystic kidney symptomatic

Urinary tract obstructionNephrolithiasisHypertension

Renal tubular defects

Kompetensi DokterKompetensi Dokter

Nyeri saat buang air kecilSering buang air kecil pada malam hariKencing mengedanKencing tidak puasRetensi urinInkontinensia urin

Akhir kencing menetes Pancaran kencing menurunKencing bercabangWaktu kencing preputium

melembung/ballooningFrekuensi urinDisuriaNokturia

UrgensiKencing merah (hematuria)Kencing campur udara (pnematuria)Darah pada muara uretraHemospermiaAnuria,Poliuria,OliguriaPerubahan warna

Tingkat kemampuan yang diharapkan dicapai pada akhir pendidikan dokter

Tingkat Kemampuan 1 Dapat mengenali dan menempatkan gambaran-

gambaran klinik sesuai penyakit ini ketika

membaca literatur. Dalam korespondensi, ia dapat mengenal gambaran klinik ini, dan tahu

bagaimana mendapatkan informasi lebih lanjut. Level ini mengindikasikan overview level.

Bila menghadapi pasien dengan gambaran klinik ini dan menduga penyakitnya, Dokter segera merujuk.

Tingkat Kemampuan 2Mampu membuat diagnosis klinik berdasarkan

pemeriksaan fisik dan pemeriksaan-pemeriksaan tambahan yang diminta oleh dokter (misalnya : pemeriksaan laboratorium sederhana atau X-ray). Dokter mampu merujuk pasien secepatnya ke spesialis yang relevan dan mampu menindaklanjuti sesudahnya

Tingkat Kemampuan 3A

Mampu membuat diagnosis klinik berdasarkan pemeriksaan fisik dan pemeriksaanpemeriksaan tambahan yang diminta oleh dokter (misalnya : pemeriksaan laboratorium sederhana atau X-ray). Dokter dapat memutuskan dan memberi terapi pendahuluan, serta merujuk ke spesialis yang relevan (bukan kasus gawat darurat).

Tingkat Kemampuan 3B

Mampu membuat diagnosis klinik berdasarkan pemeriksaan fisik dan pemeriksaan-pemeriksaantambahan yang diminta oleh dokter (misalnya : pemeriksaan laboratorium sederhana atau X-ray). Dokter dapat memutuskan dan memberi terapi pendahuluan, serta merujuk ke spesialis yang relevan (kasus gawat darurat).

Tingkat Kemampuan 4Mampu membuat diagnosis klinik

berdasarkan pemeriksaan fisik dan pemeriksaanpemeriksaan tambahan yang diminta oleh dokter (misalnya : pemeriksaan laboratorium sederhana atau X-ray). Dokter dapat memutuskan dan mampu menangani problem itu secara mandiri hingga tuntas.

AKI (2) intertitial nefritis, acut tubular necrosis ( 2-3 )

Nehprotic syndrom (2)CKD (2)Glomerulonefritis (3A)ISK (4)Renal cell carsinoma (1) Polycystic disease (1)Renal colic

Cross-Section of the KidneyCross-Section of the Kidney

R E N A L A N A E M I AR E N A L A N A E M I A

Renal VeinRenal VeinRenal ArteryRenal ArteryRenal PelvisRenal Pelvis

UreterUreter

Renal MedullaRenal MedullaPapillaPapilla

Renal CortexRenal Cortex

Branch of theBranch of theRenal VeinRenal Vein

Branch of theBranch of theRenal ArteryRenal Artery

NephronNephron

Manifold Tasks of the KidneyManifold Tasks of the Kidney

Bone StructureBone StructureBone StructureBone Structure

Vitamin DVitamin DActivationActivation

CalciumCalciumBalanceBalance

Blood FormationBlood FormationBlood FormationBlood Formation

ErythropoietinErythropoietinSynthesisSynthesis

Cardiac ActivityCardiac ActivityCardiac ActivityCardiac Activity

PotassiumPotassiumBalanceBalance

Regulation of Blood pHRegulation of Blood pHRegulation of Blood pHRegulation of Blood pH

Recovery ofRecovery ofBicarbonateBicarbonate

Blood PressureBlood PressureBlood PressureBlood Pressure

Water BalanceWater Balance

SodiumSodiumRemovalRemoval

MetabolicMetabolicEnd ProductsEnd Products

MetabolicMetabolicEnd ProductsEnd Products

Removal ofRemoval of Urea, Creatinine etc. Urea, Creatinine etc.

FunctionsFunctions

Filtration, ReabsorptionFiltration, Reabsorption and Secretionand Secretion

Normal GFR 120 ml/min/1.73m2

Only 20% nephrons work at a time

In a day 210 L of water is filtered

2 L /day of urine is excreted

Factors Influencing Renal FunctionFactors Influencing Renal Function

NPs

Aldosteron

ADH

PTH

Water retention

Na excretion

Na reabsorbtionCa reabsorption,

PO4 excretionVit D synthesis

Angiotensin IIRenin

AldosteronSodium Reabsorbti

on

Calcium and Phosphate Reabsorbtio

n

Vitamin D

EPO

Bone marrow

Red blood cells PO4 release

Ca release

Phosphate absorbtion

Calcium absorbtion

Vasoconstriction

Infectious Urinary DisordersInfectious Urinary Disorders

Urinary Tract Infections (UTI)Urinary Tract Infections (UTI)

Frequent clinical problemFrequent clinical problem

Any site in the urinary tract may be involved : the urethra, prostate, Any site in the urinary tract may be involved : the urethra, prostate,

bladder, ureter, kidney and perinephric space.bladder, ureter, kidney and perinephric space.

Bacterial infection is most common, but fungi, chlamydia, viruses Bacterial infection is most common, but fungi, chlamydia, viruses

and parasites may be responsible in some patientsand parasites may be responsible in some patients

Women >>> MenWomen >>> Men

Terminology of Urinary Tract Infections (1)

Bacteriuria : Presence of bacteria in the urine.

Asymptomatic bacteriuria : 105 CFU/ml urine with or without pyuria, in a patient without symptoms of UTI.

Cystitis : inflammation of the bladder • Bacterial cystitis• Abacterial cystitis (urethral syndrome)

Acute pyelonephritis: acute bacterial infection of the kidney characterized by chills and fever (often high) and flank pain (usually unilateral), as well as tenderness.

Ribeiro RM, et al. Int Urogynecol 2002;13:198-199.

Chronic pyelonephritis : Radiological diagnosis where there is evidence of focal scarring of the kidneys with associated calyceal abnormality indicating renal damage due to a combination of reccurent infection with obstruction of the pelviocalyceal system (chronic obstructive nephropathy) or vesicoureteral reflux (reflux nephropathy).

Reinfection : An infection with a different strain of microorganism or a different serological type after (end of therapy) eradication of previous infection.Most likely represent infections of the bladder, occur weeks to months after Most likely represent infections of the bladder, occur weeks to months after treatment of the previous infection, response well to therapy, treatment of the previous infection, response well to therapy, usually associated with a normal urinary tractusually associated with a normal urinary tract

Relapse : A consecutive urinary infection caused by the same strain or serotype of bacteria, usually represent infection of the kidney or prostat, often recur usually represent infection of the kidney or prostat, often recur within 1 – 6 weeks after antimicrobials have been discontinued, some cases within 1 – 6 weeks after antimicrobials have been discontinued, some cases represent persistent infection, anatomic abnormalities or renal insuficiency represent persistent infection, anatomic abnormalities or renal insuficiency are more common with relapsing or persistent infection, a long course of are more common with relapsing or persistent infection, a long course of antimicrobials or surgery may be required if the urine is to be permanently antimicrobials or surgery may be required if the urine is to be permanently sterilized sterilized

Ribeiro RM, et al. Int Urogynecol J 2002;13:198-199.


Recurrent UTI: patients with at least two infections within 6 months or three or more during a single year, in which the initial episode is resolved and is followed by another infection.

Ribeiro RM, et al. Int Urogynecol J 2002;13:198-199.


Persistence : the continued presence of the microorganisms isolated at the beginning of the treatment, owing to resistance to antimicrobial therapy, inadequate drug dosage, or a urological abnormality. These unresolved infections may be also in consequence of the patient’s non-compliance in taking medication, mixed infections with two different bacterial strains with mutually exclusive susceptibilities, or renal insufficiency (leading to an inadequate drug concentration in the urine).

Diagnosis Urinary Tract InfectionDiagnosis Urinary Tract Infection

1.1. SymptomsSymptoms : :

Lower UTI :Lower UTI :• Frequency, dysuria, suprapubic pain

Upper UTI :Upper UTI :• Fever, flank pain, and chills as well as symptoms similar to bladder infection

2.2. UrinalysisUrinalysis

3.3. CultureCulture

• The presence of 10 WBC / mm3 fresh un-spun midstream urine • The presence of 10 WBC / high-power field sediment midstream urine

4.4. Radiological evaluationRadiological evaluation

• Ultrosound• Plain abdominal radiography• Intravenous urography• CT scanning

Criteria for diagnosis of significant bacteriuriaCriteria for diagnosis of significant bacteriuria

Symptomatic women :Symptomatic women :• 101022 coliform organisms/ml urine plus pyuria, or coliform organisms/ml urine plus pyuria, or

• 101055 of any pathogenic organism/ml urine, or of any pathogenic organism/ml urine, or

• Any growth of a pathogenic organism from urine obtained by Any growth of a pathogenic organism from urine obtained by

suprapubic aspirationsuprapubic aspiration

Symptomatic men :Symptomatic men :

• 101033 pathogenic organism/ml urine pathogenic organism/ml urine

Asymptomatic patients :Asymptomatic patients :

• 101055 pathogenic organism/ml urine in two pathogenic organism/ml urine in two

consecutive samplesconsecutive samples

Classification of Urinary Tract Infection (1)Classification of Urinary Tract Infection (1)

II. Upper urinary tract infection ( Pyelonephritis )II. Upper urinary tract infection ( Pyelonephritis )

I. Lower urinary tract infection ( Cystitis )I. Lower urinary tract infection ( Cystitis )

Fever, flank pain, and chills as well as symptoms similar to bladder infection

Frequency, dysuria, suprapubic pain

I. Uncomplicated urinary tract infection I. Uncomplicated urinary tract infection

• Occurs in individuals with structurally and functionally normal genitourinary tracts• Most common bacterial infection that occurs in women, but is uncommon in men• May involve the bladder or the kidneys and may be symptomatic or asymptomatic

II. Complicated urinary tract infectionII. Complicated urinary tract infection

• As acute or chronic parenchymal infection associated with a functional or structural urinary tract abnormality e.g. : Neurogenic bladder, urinary tract obstruction, immunocompromized

patients, diabetes mellitus, polycystic kidney disease, renal transplant recipient.

Classification of Urinary Tract Infection (2)Classification of Urinary Tract Infection (2)

Bacterial etiology of urinary tract infectionBacterial etiology of urinary tract infection

• E. coliE. coli : 70-95% (uncomplicated UTI), 21-54% (complicated) : 70-95% (uncomplicated UTI), 21-54% (complicated)

• S. Saprophyticus : 5-20% (uncomplicated), 1-4% (complicated)S. Saprophyticus : 5-20% (uncomplicated), 1-4% (complicated)

• Enterococci : 1-2% (uncomplicated), 1-23% (complicated)Enterococci : 1-2% (uncomplicated), 1-23% (complicated)

• Proteus mirabilis : 1-2% (uncomplicated ), 1-10% (complicated)Proteus mirabilis : 1-2% (uncomplicated ), 1-10% (complicated)

• Klebsiella spp : 1-2% (uncomplicated), 2-17% (complicated)Klebsiella spp : 1-2% (uncomplicated), 2-17% (complicated)

• Pseudomonas aeruginosa : <1% (uncomplicated), 2-19%Pseudomonas aeruginosa : <1% (uncomplicated), 2-19%

(complicated)(complicated)

Clinical Classification of Urinary Tract Infection

1.Acute uncomplicated cystitis in women

2. Acute uncomplicated pyelonephritis in women

3. Complicated UTI in both sexes

4. Recurrent infections in women

5. Asymptomatic bacteriuria

McBryde C, Redington. Primary Care Case Rev 2001 ; 4 : 2

Single dose or 3-day course of treatment(trimethoprim sulfamethoxasole, quinolone, amoxycillin)

Acute uncomplicated cystitis in women

Follow-up urine culture 7-14 days later

Cured(sterile urine)

Failure or relapse(identical pathogens)

Reinfection(new pathogen)

No investigationUltrasonography urinary tract

KUB radiograph

Catel WR. Clin Drug Invest 1995 ; 9 (suppl 1) : 8-13.

Treatment for 2 weeks


1. Acute uncomplicated cystitis in women






Moderate severitySevere illness

Outpatients and oral therapy possible

(trimethoprim sulfamethoxasole,

quinolone, amoxycillin)

Treatment 14 days

Hospitalization with initial parenteral therapy

(trimethoprim-sulfametaxazol,

ceftriaxone, quinolone, gentamicin

with/without ampicilin

Oral treatment 14 days or longer as required

Acute uncomplicated pyelonephritis in women

No resolution in 5 days

No resolution in 5 days

Urologic evaluation

Radiologic evaluation

Resolution in 5 days




3.Complicated UTI in both sexes




Hospitalize, urine culture, blood cultureHospitalize, urine culture, blood culture

Empiric therapy with parenteral regimen

Significant clinical improvement Significant clinical improvement

Yes No

Switch to or continue oral regimen

For total 2 weeks

Review antimicrobial susceptibility patternReview antimicrobial susceptibility patternRadiologic & urologic evaluationRadiologic & urologic evaluation

Correct reversible risk factorsCorrect reversible risk factors

Review treatment plan as appropriate, Review treatment plan as appropriate, treat for total 2 weeks or longers if necessarytreat for total 2 weeks or longers if necessary

Follow-up urine culture after treatment Follow-up urine culture after treatment

Complicated UTI in both sexes

5 Days





4.Recurrent infections in women



Recurrent infections in women

Reccurent UTI in women

DiagnosisRelapse Reinfection

Conventional antibiotic therapy 2-6 weeks

≥ 3 year ≤ 2 year

Sexually active PostmenopausalConventional antibiotic

therapy 3-7 days

Estrogen substitution (oral & topical)

Antibiotic therapy : On demand or

Longterm prophylaxis

Antibiotic therapy :On demand orPostcoital or

Longterm prophylaxis

Madersbacher S, et al. Curr Opin Urol 2000 ; 10 : 32.

Drug regimens for long-term, low-dose prophylaxis of Drug regimens for long-term, low-dose prophylaxis of

recurrent urinary tract infectionrecurrent urinary tract infection

DrugDrug Dose*Dose*

NitrofurantoinNitrofurantoin 50 mg50 mg

TrimethoprimTrimethoprim 100 mg100 mg

Co-trimoxazoleCo-trimoxazole 0.24 g0.24 g

NorfloxacinNorfloxacin 200 mg200 mg

CiprofloxacinCiprofloxacin 125 mg125 mg

CephalexinCephalexin 125 mg 125 mg

( useful if renal insufficiency)( useful if renal insufficiency)

Hexamine hippurateHexamine hippurate 1 g1 g

* Treatment is effective if taken each night, alternate nights, three times a week, * Treatment is effective if taken each night, alternate nights, three times a week, or just after intercourseor just after intercourse





4. Recurrent infections in women5. Asymptomatic bacteriuria


Indication for the treatment of patients with

asymptomatic bacteriuria

Definitive Possible Not indicated

Pregnancy Diabetes mellitus Elderly

Before an invasive genitourinary

procedure

Short-term indwelling

catheterization

Intermittent catheterization

School girls and premanopausal women

Children with reflux

Renal transplant Long-term indwelling catheter

Patients with abnormal urinary tract

Raz R. Nephrol Dial Transplant 2001 ; 16 (suppl 6) : 135.

Indication for imaging studies in Indication for imaging studies in patients with Urinary Tract Infectionspatients with Urinary Tract Infections

Infections in a newborn

Reccurent infection occuring in childhood

Two or more infections in adult females

One infection in adult males

Elevated creatinine level

History of urinary calculi

Neurologic bladder dysfunction

Persistent hematuria

Previous genitourinary surgery

Prolonged fever after initiation of antibiotic therapy

Relapsing infection

Urea-splitting organisms

Unusual causative organism

GLOMERULOGLOMERULOPPHHATIESATIES

dr Haerani Rasyid, MS, SpPD, K-GHdr Hasyim Kasim , SpPD, K-GH

Prof Dr dr Syakib Bakri, SpPD, K-GH

Division of Nephrology Department of Internal Medicine

Faculty of Medicine, Hasanuddin University

GlomerulopathiesGlomerulopathies

Glomerulopathy : a group of diverse conditions – including, but not limited Glomerulopathy : a group of diverse conditions – including, but not limited

to, glomerulonephritis – having in common the fact that the disease to, glomerulonephritis – having in common the fact that the disease

process begins in the glomerulus or that the glomerulus is the most process begins in the glomerulus or that the glomerulus is the most

importantly diseased part of the nephron.importantly diseased part of the nephron.

Glomerulopathies are the most common causes of end-stage renal diseaseGlomerulopathies are the most common causes of end-stage renal disease

ClassificationClassification

Clinical Presentation (5 Clinical manifestation).

Histopathological Classification: (percutaneus biopsy and open biopsy).

Etiology and Pathogenesis Classification. Immunological Classification.

AsymptomaticProteinuria 150mg to 3g/dayHematuria > 2 red blood cells

Perhigh-power field (> 10x106 cells/LIn spun urine (red blood cells

Usually dysmorphic

Chronic glomerulonephritisHypertension

Renal insufficiensyProteinuria > 3 g/day

Shrunken smooth kidneys

Nephritic syndromeOliguria

Hematuria : red cells castsProteinuria; usually < 3g/day

HypertensionOedema

Abrupt onset

Nephrotic syndromeProteinuria; adult > 3,5 g/day

Child > 40 mg/h per m2 Edema

Hypercholesterolemia Lipidemia

Rapidly progressive glomerulonephritisRenal failure over days/weeksProteinuria usually < 3 g/day

Hematuria; red cell castsBlood pressure often normal

May have other features of vasculitis

Clinical Presentations of Glomerular Disease

Clinical syndrome Manifestation Major etiologies

Asymptomatic proteinuria Urinary protein excretion < 2 g/d Low-grade glomerular disease ( IgA nephropathy, MN or MPGN)Heriditary glomerular disease (Alport’s syndrome)Tubulointerstitial disease

Asymptomatic hematuria Urinary RBCs > 2/ HPF (spun sediment)

Low-grade glomerular disease ( IgA nephropathy, Thin basement membran disease)

Nephrotic syndrome Heavy proteinuria (>3,5 g/d), edema, high serum cholesterol, urine lipids

MCNS, FSGS, MN, MPGNDiabetic nephropathyAmyloid (myeloma, LCDD)Fibrillary GN

RPGN Presents as GN with ARF (oliguria, rising serum creatinin)

Anti GBM nephritis (Goodpasture’s)Vasculitis Syndromes (Wegener’s polyangiitis, HSP, mixed cryoglobulinemia)Immune-complex associated (IgAN, poststrep GN)

Nephritic syndrome RBCs, RBC cast, proteinuria, hypertension, renal disfunction.

Poststreptococcal AGNOther post infectious GN (abcess, endocarditis)IgA nephropathyLN (WHO class III/ IV)

GLOMERULONEPHRITISGLOMERULONEPHRITISGlomerulonephritis (GN)o Initially coined by Klebs (1889).

o A group of diseases occuring either as primary renal disorders or a secondary manifestation of a sistemic disease state.

o Inflammation within the glomerulus.

o Renal manifestation of hematuria, proteinuria and impaired glomerular filtration

o Unpredicteble disease course make clinical management problematic

DEFINITIONDEFINITION

Glomerulonephritis: (GN) injury with evidence of inflammation :

leukocyte infiltration

antibody deposition

complement activation.

GN primary: pathology is confined to the kidney. GN secondary: when part of a multisystem

disorder.

Dwi-Lestari

NOMENCLATURENOMENCLATURE

Acute: glomerular injury occurring over days or weeks.

Sub acute or rapidly progressive (RPGN): over weeks or a few months.

Chronic: over many months or years.

Injury LocalizationInjury Localization

1. Overview of slides : assesses injury and localizes to the specific anatomic compartment (glomerular/ vascular/ tubulointerstitial).

2. Assessment of type of injury, extent of injury in each glomerulus. Terminology : diffuse, focal, global and segmental.

Diffuse : at least 60% glomeruli involved.

Focal : some glomeruli < 60%.

Global : involved 1 glomerulus as a whole.

Segmental : part of 1 glomerulus.

Proliferative : glomerular cell number (intracapillary and extracapillary)

A crescent: is a half-moon shaped. Cells in Bowman`s space.

Membranous : expansion of the GBM by immune deposits.

Sclerosis : non-fibrilar extracellular material Fibrosis : Collagens type I and III

Immuno pathogenesis

InflammationGeneticInfluence Genetic

Influence

Resolution Scarring

Variable rateof progression

Renal Failure

Mechanism of Injury in Glomerulonephritis

Immunologic Mechanism of Glomerular Injury

• In situ antigen-antibody interaction (1) Exogenous planted antigens (1)

• Circulating immune complexes (2) Intrinsic glomerular antigen (3)

• Cell-mediated mechanism (?)

Activation of

mediators of

glomerular injury

Activation of

mediators of

glomerular injury

NEPHROTIC SYNDROMENEPHROTIC SYNDROME

Nephrotic syndromeNephrotic syndrome

• Clinical entity having miltiple causes and characterizedClinical entity having miltiple causes and characterized

by increased glomerular permeability manifested by increased glomerular permeability manifested

by massive proteinuria and lipiduria.by massive proteinuria and lipiduria.

• Massive proteinuria > 3.5 g/day/1.73mMassive proteinuria > 3.5 g/day/1.73m22 body surface area body surface area

in the absence of a depressed GFR.in the absence of a depressed GFR.

Clinical Features of The Nephrotic SyndromeClinical Features of The Nephrotic Syndrome

Manifestations of the nephrotic syndrome itselfManifestations of the nephrotic syndrome itself

Signs and symptoms determined by the underlying disease Signs and symptoms determined by the underlying disease involving the kidneyinvolving the kidney

Classification of the disease states associated with the development of Classification of the disease states associated with the development of nephrotic syndromenephrotic syndrome

I. Idiopathic nephrotic syndrome due to Primary Glomerular DiseaseI. Idiopathic nephrotic syndrome due to Primary Glomerular Disease

II.Nephrotic syndrome associated with spesific etiologic events or in which II.Nephrotic syndrome associated with spesific etiologic events or in which glomerular disease arises as a complication of other diseaseglomerular disease arises as a complication of other disease

1.1. MedicationsMedications

2.2. AllergensAllergens

3.3. Infection ( bacterial, viral, protozoal, helminthic )Infection ( bacterial, viral, protozoal, helminthic )

4.4. Neoplasmic ( solid tumors, leukemia and lymphoma )Neoplasmic ( solid tumors, leukemia and lymphoma )

5.5. Multisystem diseaseMultisystem disease

6.6. Heredofamilial and metabolic diseaseHeredofamilial and metabolic disease

7.7. MiscellaneousMiscellaneous

Clinical manifestation of nephrotic syndrome :Clinical manifestation of nephrotic syndrome :

OedemaOedema

HypertensionHypertension

DyslipidemiaDyslipidemia

Hypercoagulable stateHypercoagulable state

Hypoproteinemia / proteinuriaHypoproteinemia / proteinuria

Progressive renal failureProgressive renal failure

Trace metal deficienciesTrace metal deficiencies

Endocrine disturbancesEndocrine disturbances

Infectious / Infectious / immimmunodeficiency statesunodeficiency states

Clinical features of nephrotic syndrome

•Proteinuria (>3.5g/24h)

Nephrotic Syndrome Pathophysiology

Diagnostic triad•Proteinuria > 3.5g/dL•Serum Albumin < 30g/L•Oedema

Disease of glomerular capillary wallUrinary protein lossLow plasma oncotic pressureSalt and water retention by kidneys

ComplicationsHypercholesterolemia Increased hepatic synthesis and reduced

metabolism of lipoproteins

Thrombosis Venous obstruction caused by oedemaIncreased hepatic synthesis of clotting factorsurinary loss of anti thrombotic protein (prot C,prot S, ATIII)

Infections Urinary loss of immunoglobulins and other defence protein

Renal Failure Intravascular volume depletion (acute)Intrarenal oedema (acute)Primary renal disease causing glomerular damageProteinuria causing interstitial inflamation

Malnutrition Severe protein loss

UnderfillProteinuria

Hypoalbuminemia

Plasma colloidOncotic pressure

Reducedplasma volume

Vasopresin Atrial natriureticPeptide (ANP)Normal/low

Renin angiotensinSystem activated

Aldosteron

Vasopressinnormal

ANP Aldosteron

OverfillTubular

Defect causingSodium retention

Normal/raisedPlasma volume

Waterretention

Edema

Sodiumretention

Formation of nephrotic edema

Pathophysiology of the Nephrotic SyndromePathophysiology of the Nephrotic Syndrome

Lipid abnormalities in nephrotic Lipid abnormalities in nephrotic syndromesyndrome

Lipoprotein (a)↑Lipoprotein (a)↑

HDL

HDL3 ↓

HDL2 ↓

HDL

HDL3 ↓

HDL2 ↓

VLDL ↑

IDL ↑

LDL ↑

VLDL ↑

IDL ↑

LDL ↑

Hepatic synthesis

↑

Catabolism ↓Endhotelial

lipoprotein lipase ↓

VLDL deposition in vascular tissues ↑VLDL deposition in vascular tissues ↑

Oxidized

LDL ↑

Atherogenicity↑

Atherogenicity↑

Urine clearance of

smaller HDL3

Cholesterol removal from tissue to liver impaired

Atherogenicity↑Atherogenicity↑

Hepatic secretion

HDL↑

Lecithin cholesterol

acyltransferase (LCAT) activity ↓

Coagulation abnormalities in Coagulation abnormalities in NNephrotic ephrotic SSyndromeyndrome

Unchanged/reduced:Prothrombin factors

IX, X, XI, XII, antithrombin III

Unchanged/reduced:Prothrombin factors

IX, X, XI, XII, antithrombin III

Hepatic

synthesis ↑Hepatic

synthesis ↑

Coagulation proteins

Raised: fibrinogen, factors V, VII, von Willebrand factor, protein C α1 -macroglobulin

Coagulation proteins

Raised: fibrinogen, factors V, VII, von Willebrand factor, protein C α1 -macroglobulin

Urine clearance

↑

Urine clearance

↑

Platelets aggregability ↑ Platelets aggregability ↑

Volume concentrationHemoconcentration

Volume concentrationHemoconcentration

ImmobilityImmobility

HyperlipidemiaHyperlipidemia

Accelerated atherogenesisAccelerated

atherogenesis

Arterial thrombosisArterial thrombosisVenous

thromboembolism

Venous thromboembolis

m

Diagnostic approach in nephrotic syndromeDiagnostic approach in nephrotic syndrome

I.I. ClinicalClinical

II.II. Laboratory studiesLaboratory studies

III.III. Renal biopsyRenal biopsy

I. ClinicalI. Clinical

HistoryHistoryPreexisting diseasePreexisting diseasePrevious infectionPrevious infectionDrug ingestionDrug ingestionArthritis, rashArthritis, rashCurrent pregnancyCurrent pregnancyFamily history of renal diseaseFamily history of renal disease

Physical examinationPhysical examinationSevere obesitySevere obesityRash, arthritisRash, arthritisDiabetic retinopathyDiabetic retinopathyHypertensionHypertensionEvidence of malignancyEvidence of malignancyLipodystrophyLipodystrophyLymphoadenopathy/hepatosplenomegalyLymphoadenopathy/hepatosplenomegaly

II. Laboratory StudiesII. Laboratory Studies

Urinalysis

In all cases ( nondiagnstic )Creatinine clearanceSerum protein electrophoresisSerum tota;cholesterol, lipoproteinSerum ionized calciumParathyroid hormone

In selected cases ( to establis the diagnosis )Complement levelAntinuclear antibody assay CryoglobulinsHepatitis and HIV serologySerum and urine immunoelectrophoresis

III. Renal biopsyIII. Renal biopsy

• Minimal change diseaseMinimal change disease• Focal segmental glomerulosclerosisFocal segmental glomerulosclerosis• Membranous nephropathyMembranous nephropathy• Membranoproliferative glomerulonephritisMembranoproliferative glomerulonephritis• Other glomerulonephritisOther glomerulonephritis

Suggested approach for initial treatmentSuggested approach for initial treatment( Minimal change disease )( Minimal change disease )

ChildrenChildrenPrednisone 60 mg/mPrednisone 60 mg/m22/day until remission, then 40 mg/m/day until remission, then 40 mg/m22/48 h for /48 h for 12 weeks, then reduce by 5-10 mg/m12 weeks, then reduce by 5-10 mg/m22/48 h every month./48 h every month.

AdultsAdultsPrednisone 1mg/kg/day until remission or for 6 weeks, then 1.6 mg/kg/48 hPrednisone 1mg/kg/day until remission or for 6 weeks, then 1.6 mg/kg/48 hfor 1 month, then reduce by 0.2-0.4 mg/kg/48 h.for 1 month, then reduce by 0.2-0.4 mg/kg/48 h.

ElderlyElderlyPrednisone 1 mg/kg/day until remission or for 4 weeks, then 0.8 mg/kg/day Prednisone 1 mg/kg/day until remission or for 4 weeks, then 0.8 mg/kg/day for 2 weeks, then 1.6 mg/kg/48 h for 2 weeks. Then reduce by 0.4 mg/kg/48 hfor 2 weeks, then 1.6 mg/kg/48 h for 2 weeks. Then reduce by 0.4 mg/kg/48 hevery 2 weeks. If no remission continue with 1.2 mg/kg/48 h for another every 2 weeks. If no remission continue with 1.2 mg/kg/48 h for another 4 weeks then reduce.4 weeks then reduce.

Contraindications to prednisoneContraindications to prednisoneCyclophosphamide 2 mg/kg/day or chlorambucil 0.15mg/kg/day for 8-12 Cyclophosphamide 2 mg/kg/day or chlorambucil 0.15mg/kg/day for 8-12 weeksweeks

ACUTE KIDNEY INJURY (AKI)

Acute Kidney Injury (AKI) digunakan oleh

Acute Dialysis Quantitative Initiative (ADQI), (2002), menggantikan definisi

Acute Renal Failure (Gagal Ginjal Akut).

Di Indonesia, definisi AKI telah digunakan secara resmi oleh PERNEFRI.

:

Gangguan Ginjal Akut (GGA = GgGA)

Acute Kidney InjuryAcute Kidney Injury

An abrupt and sustained decrease (days to weeks/within 48 hours) in renal function resulting in retention of nitrogenous (urea and creatinine) and non-nitrogenous waste products.

Depending on severity and duration of the renal dysfunction, this accumulation is accompanied by metabolic dysturbance, such as metabolic acidosis and hyperkalaemia, changes in body fluid balance, and effects on many other organ systems.

Acute Acute KKidney idney IInjurynjury

An acute and sustained increase in serum creatinine

concentration of 0.5 mg% if the baseline is < 2.5 mg%,

or an increase in serum creatinine concentration of >

20% if the baseline is > 2.5 mg%/. An Increase %

more than or equal 50%/1.5 fold from base line

Reduction in urine out put(documented oliguria of less

then 0.5 ml/kg perhour for more than six hours)

UO < 0.5 ml/kg/h x 12 hrIncreased creatininex2 or GFR decrease > 50%

Injury

High

Sensitivity

UO < 0.5 ml/kg/h x 6 hrIncreased creatininx1.5 or GFR decrease > 25%

Risk

End Stage Kidney Disease (> 3 months)ESKD

Persistent ARF = complete loss of kidney function > 4 weeks

Loss

High

Specivity

UO < 0.3 ml/kg/h x 24 hr or Anuria x 12 hrs

Increase creatininex3 or GFR decrease > 75%

Failure

UO CriteriaGFR CriteriaCategory

RIFLE Criteria for Acute Renal Dysfunction

GFR=Glomerular Filtration Rate ARF; Acute Renal FailureUO = Urine Output ESKD; End Stage Kidney DiseaseReferences :Bellomo R, Kellum JA, Mehta R, Palevsky PM, Ronco C. Curr Opin Crit Care. 2002 Dec; 8(6):505-8.

TABEL 2 : RIFLE criteria ADQI Bellomo et al, Curr Opin Crit Care 2002;6:505-8

EPIDEMIOLOGYEPIDEMIOLOGY

1% of hospitalized patients

20% of patients treated in ICU

4-15% of patients after cardiovascular surgery

Cause of mortality

1. (75%) : Sepsis/multy organ dysfuntion

syndrome 2. Cardiopulomonal( 50%)

Acute Kidney InjuryAcute Kidney Injury

Zöllner,Innere Medizin, modified

Dialysis Treatments

CreatinineM/l

Time / days

Urinel/day

3. PolyuriaUncontrolled Urine Quantities(1 - 2 weeks)

1. DamageDamage toRenal Tissue(minutes to days)

2. Oliguria / AnuriaComplete Loss of Renal Function(up to 6 weeks)

4. Recoveryslow Recovery of Renal Function (several months)

CLASSIFICATION

OF

ACUTE KIDNEY INJURY

PrerenalPrerenal

RenalRenal

PostrenalPostrenal

35 %

50 %

10 %

ACUTE KIDNEY INJURYACUTE KIDNEY INJURY

PRERENALPRERENAL

Absolute decrease in effective blood volumeHaemorrhageVolume depletion

Relative decrease in blood volume (ineffective arterial volume)Congestive heart failureDecompensated liver cirrhosis

Arterial occlusion or stenosis of renal artery

Haemodynamic formNSAIDsACE-inhibitors or angiotensin-II receptor antagonists in renal-artery stenosis or congestive heart failure

HypovolemiaHypovolemia Baroreceptor activation Reduced affective Reduced affective

circulation volume circulation volume

↑ Respons neurohormonal

↑ Axis renin-angiotensin aldosterone

↑ Vasopressin ↑ Sympathetic nervous system

↑ Vasoconstriction↑ contraction of mesangial cells↑ Reabsorpsi natrium and water

Reduced renal blood flow and glomerular filtration rate

Acute renal failure pre-renal

VascularVasculitis,Malignant HT

Acute interstitial nephritisDrugsAllergy

Acute tubular necrosis

Ischaemic (50%) Nephrotoxic (35%)

ExogenousAntibiotics (gentamicin)Radiocontrast agentsCisplatin

EndogenousIntratubular pigments (haemoglobinuria, myoglobinuria)Intratubular proteins (myeloma)Intratubular crystals (uric acid, oxalate)


INTRINSIC RENALINTRINSIC RENAL

Glomerulonephritis

Obstruction of collecting system or extrarenal drainage

Bladder-outlet obstructionBilateral ureteral obstruction or unilateral in one functioning kidney


POSTRENALPOSTRENAL

Acute Tubuler Necrosis(ATN) is an abrupt Decrease of GFR caused By tubular damage from:- renal hypo perfusion- nephrotoxic injury- Tubulo-interstitial nephritis Hypotension, exposure to nephrotoxic drugs Recent radiographic procedure with contrast

Rapidly reversible decreaseIn GFR caused by renal Hypo perfusion. Volume depletion Congestive heart failure Severe liver disease or other edematous state

Causes 50% of ARF

Rapidly reversible decrease In GFR caused by obstructionIn renal or Uretero -Uretheral - vesico urinary (OBSTRUCTIVEUROPATHY). Palpable bladder or hydronephrotic kidneys Enlarge prostat

Abnormal pelvic examination Large residual bladder urine volume History of renal calculi (perform USG to screen obstruction

Dwi Lestari

Assessment of a Patient with Acute Kidney Injury(1)

Procedure Information Sought

Clinical history and examination

Urinalysis and urine microscopy

Plasma biochemistry

Urine biochemistry

Full blood count

Clues to the cause of acute renal failureIndicators of severity of metabolis disturbanceEstimate of volume status (hydration)

Markers of glomerular or tubulointerstitial inflammation, urinary tract infection or crystal uropathy

To assess extent of GFR reduction and metabolic consequences

To differentiate prerenal from established renal failure

To determine presence of anemia, leucocytosis, and platelet consumption

Finding in the urine sediment

If no abnormalities: suspect prerenal or postrenal azotemia

If eosinophils: suspect acute interstitial nephritis

If red blood cell casts: suspect glomerulonephritis or vasculitis

If renal tubular ephitelial cells and muddy brown casts: suspect acute tubular necrosis

Assessment of a Patient with Acute Kidney Injury(2)

Procedure Information Sought

Renal ultrasound

Plus, where appropriate :

Abdominal CT-Scan

Radionuclide scan

Cystoscopy +/- retragrade pyelograms

Renal biopsy

To determine kidney size, presence of obstruction, abnormal renal parenchymal texture

To define structural abnormalities of the kidneys or urinary tract

To assess abnormal renal perfusion

To evaluate / relieve urinary tract obstruction

To define pathology of renal parenchymal disease

Dwi Lestari

Management priorities in patients Management priorities in patients with acute kidney injurywith acute kidney injury

Search for and correct prerenal and postrenal factors.

Review medications and stop administration of nephrotoxins.

Optimise cardiac output and renal blood flow.

Monitor fluid intake and output; measure bodyweight daily.

Search for and treat acute complications (hyperkalaemia, hyponatraemia, acidosis, hyperphospataemia, pulmonary oedema).

Provide early nutritional support.

Search for and aggressively treat infections.

Expert nursing care (management catheter care and skin in general; physicological support).

Initiate dialysis before uraemic complication emerge.

Give drugs in doses appropriate for their clearance.

MEMENUHI KRITERIA DIAGNOSISGANGGUAN GINJAL AKUT (GgGA)

YA TIDAK

Observasi24-48 jam

GgGA

DIAGNOSISETIOLOGI GgGA

DIAGNOSIS KLINIK & TAHAPAN GgGA

Gejala & Komplikasi

PEMERIKSAANPENUNJANG

TIDAK

BUKAN GgGA

LANGKAH 1

LANGKAH 2

LANGKAH 3

LANGKAH 4

ALGORITMA UNTUK MENEGAKKAN DIAGNOSIS GgGA

KKomplikasi yang menyertaiomplikasi yang menyertai GgGA GgGA

1. Gangguan keseimbangan cairan tubuh dan elektrolit (retensi Natrium, edema)

2. Gangguan keseimbangan elektrolit (terutama hiperkalemia)

3. Asidosis metabolik

4. Gagal Jantung

5. Gagal Nafas

6. Azotemia

Dwi Lestari

Tujuan terapi konservatif adalah :•Mencegah memburuknya faal ginjal secara progresif•Meringankan keluhan-keluhan akibat akumulasi toksin azotemia•Mempertahankan dan memperbaiki metabolisme secara optimal•Memelihara keseimbangan cairan dan elektrolit

Beberapa prinsip terapi konservatif :•Hati-hati pemberian obat yang bersifat nefrotoksik•Hindari keadaan yang menyababkan deplesi volume cairan ekstraseluler dan hipotensi•Hindari gangguan keseimbangan elektrolit dan asidosis metabolik•Hindari instrumentasi (kateterisasi dan sistoskopi) tanpa indikasi medis yang kuat •Hindari pemeriksaan radiologi dengan media kontras tanpa indikasi medis yang kuat•Kendalikan hipertensi sistemik dan tekanan intraglomerular•Kendalikan keadaan hiperglikemia dan infeksi saluran kemih (ISK)•Diet protein yang proporsional

Dwi Lestari

Best cure is to preventBest cure is to prevent

Have a high index of suspicion for reversible factors - volume depletion, decreasing cardiac function, sepsis, urinary tract obstruction

Be sure patient is well-hydrated when exposing patient to nephrotoxic drugs

Dwi Lestari

Indications for dialysis in acute kidney injuryIndications for dialysis in acute kidney injury

Indications Characteristics

Uremia

Hyperkalemia

Fluid overload

Metabolic acidosis

Asterixis, seizures, nausea & vomiting, pericarditis

K+ >6.5 mmol/L; K+ 5.5-6.5 mmol/L if ECG changes

Fluid overload resistant to diuretics, especially pulmonary edema

pH < 7.2 despite sodium bicarbonate therapy; sodium bicarbonate not tolerated because of fluid overload

Proposed criteria for the initiation of renal replacement therapy in adult critically ill Proposed criteria for the initiation of renal replacement therapy in adult critically ill patientspatients

1. Oliguria (urine output < 200 ml/12 hr)2. Anuria/extreme oliguria (urine output < 50 ml/12 hr)3. Hyperkalemia ([K+] > 6.5 mmol/liter)4. Severe acidemia (pH < 7.1)5. Azotemia ([urea] > 30 mmol/liter)6. Clinically significant organ (especially lung) edema7. Uremic enchepalopathy8. Uremic pericarditis9. Uremic neuropathy/myopathy10. Severe dysnatremia ([Na] > 160 or < 15 mmol/liter)11. Hyperthermia/Hypothermia12. Drug overdose with dialysable toxin

The presence of : - one of the above criteria is sufficient to initiate renal replacement therapy in a critically ill patients - two of these criteria makes renal replacement urgent and mandatory. - combined derangements suggest initiation of renal replacement therapy even before the above mentioned limits have been reached.

WHEN ?WHEN ?

Renal Renal ReplacementReplacement

HDHD

CAVH

HYBRIDHYBRIDDIALYSISDIALYSIS

PD

CAPDCAPD

George Haas 1914-1915Haas 1914-1915Dialysis in Animal

Willem KOLF 1943-1944KOLF 1943-1944Dialysis in 15 pts(1 survived)l

KRAMERKRAMER19771977

SELLIGMENT & FINESELLIGMENT & FINE19451945

Belding SCRIBNER 1960SCRIBNER 1960, begin chronic dialysis

Fred Fred BOENBOEN19611961

APDAPD

SLEDSLED

EDDEDD

IHDIHD

CAVHDCAVHDCVVHDCVVHD

CAVHFCAVHFCVVHFCVVHFCAVHDFCAVHDFCVVHDFCVVHDF

Dialysis modalities for acute kidney injuryDialysis modalities for acute kidney injury

Intermittent therapiesIntermittent therapies

(up to 12 hours)(up to 12 hours)Continuous therapiesContinuous therapies

(24 hours)(24 hours)

HemodialysisHemodialysis

intermittentintermittent

dailydaily

HemodiafiltrationHemodiafiltration

Slow Continous Ultra-FiltrationSlow Continous Ultra-Filtration

Extended Daily DialysisExtended Daily Dialysis

Sustained Low Efficient DialysisSustained Low Efficient Dialysis

Peritoneal dialysisPeritoneal dialysis

Ultrafiltration (SCUF)Ultrafiltration (SCUF)

Hemofiltration (CAVH, CVVH)Hemofiltration (CAVH, CVVH)

Hemodialysis (CAVHD, CVVHD)Hemodialysis (CAVHD, CVVHD)

Hemodiafiltration (CAVHDF, CVVHDF)Hemodiafiltration (CAVHDF, CVVHDF)

Adapted from Mehta RL. Supportive therapies; intermittent hemodialysis, continuous renal replacement therapies and peritoneal dialysis. In : Schrier RW, editor. Adapted from Mehta RL. Supportive therapies; intermittent hemodialysis, continuous renal replacement therapies and peritoneal dialysis. In : Schrier RW, editor. Atlas of diseases of the kidney, Current Medicine, Philadelphia: Blackwell Science; 1998: with permission.Atlas of diseases of the kidney, Current Medicine, Philadelphia: Blackwell Science; 1998: with permission.

WHICH ?WHICH ?

# Proses difusiProses difusi ( Perpindahan molekul melalui membran semi permeable Dengan cara difusi)

# Dipengaruhi oleh : - berat molekul - perbedaan konsentrasi - Resistensi/ jenis membran

# Proses FiltrasiProses Filtrasi (Perpindahan cairan dengan cara “convective”)# Dipengaruhi oleh : - Perbedaan tekanan (transmembrane) - Koefisien ultrafiltrasi

Proses difusi dan ultrafiltrasi

Darah kotormasuk

Darah bersihkeluar

dialisatmasuk

ultrafiltratkeluar

Ultra- DarahFiltrat

Prosesdifusi

ProsesFiltrasi

dialisatDarahbersih

Dengan dialisis darah dibersihkan dengan proses difusi dan filtrasiMelalui membran semi-permeable dalam Ginjal Buatan

GINJAL BUATAN

Membran semi-permeableDidalam ginjal buatan

Proses yang terjadi

a. Modifikasi proses dialysis, dengan - Qb = 150 cc/menit - Qd = 300 cc/menit- tD = 6 – 12 jam / hari

b. Dimulai Juli, 1998 di University of Arkansas, Amerika

c. Indikasi untuk ARF dengen hemodinamik tidak stabil

d. Merupakan alternatif terapi dari CAVHD atau CVVHD

e. Biasanya menggunakan Mesin Fresenius 4008, dengan ginjal BUKAN Cellulosa Acetate

Chronic Kidney DiseasesChronic Kidney Diseases ( (CKCKD)D)==

Penyakit Ginjal Kronik (PGK)Penyakit Ginjal Kronik (PGK)

Haerani Rasyid

Nephrology and Hypertension Division,

Department of Internal Medicine

Medical Faculty Hasanuddin University

CKD – A Silent KillerCKD – A Silent KillerCKD – Increased Death CKD at a glance

CKD – A Global Pandemic CKD 1-2 are asymptomatic 10 million people of CKD Term ‘CRF’ no longer used Dialysis ↑ death rate 100 x Small ↑ in Creatinin - ↑ ↑ in

CV

Estimated Prevalence of CKD Estimated Prevalence of CKD (Stages 3-5) in the World(Stages 3-5) in the World

World Population is 6.65 BillionCKD (Stages 3-5): ≈ 200 - 333 million

Prevalence of CKDPrevalence of CKD

Do we care about CKD ?Do we care about CKD ?

1. Doctors do not realize that CKD is hidden in their

patients of DM, HT and in elderly people

2. Most doctors screen less than 10% of their clinic

patients for CKD in its early stages

3. Patients are refered very late to nephrologists especially

after the CKD is irreversible

4. Only < 1/4 of people with identified CKD get an ACE

Inhibitor

All are true - all over the globe

Now we know Now we know why the titanic sank !!why the titanic sank !!

< 0.5 %

5- 10%

LET US LEARN ABOUT CKD

Some useful DefinitionsSome useful Definitions1. Azotemia - Elevated blood urea nitrogen - Biochemical

(BUN >28 mg/dl) and creatinine (Cr >1.5mg/dl)-

2. Uremia is Azotemia + symptoms or signs of renal failure

3. End Stage Renal Disease (ESRD) - Uremia requiring transplantation or dialysis (Renal replacement therapy)

4. Chronic Renal Failure (CRF) - Irreversible kidney dysfunction with azotemia >3 months – now not used

5. Creatinine Clearance (CCr) - The rate of filtration of creatinine by the kidney (a marker of GFR)

6. Glomerular Filtration Rate (GFR) - The total rate of filtration of fluid from blood by the kidney

Definition of Chronic Kidney Disease

Criteria

1. Kidney damage for ≥ 3 months, as defined by structural or functional

abnormalities of the kidney, with or without decreased GFR,

manifest by either :

• Pathological abnormalities, or

• 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 for ≥ 3 months, with or without

kidney damage

Am J Kidney Dis 2002 ; 39 (suppl 1) : S18.

Etiologi CKD

Etiologi 1989 * 1996 2000

Glomerulonephritis 40,12% 46,19% 39,64%Obstruction 36,7% 12,85% 13,44%Diabetic nephropaty 6,13% 18,65% 17,54%Lupus nephritis 4,17% 0,16% 0,23%Polycystic KD 2,12% 1,41% 2,51%Hypertension 2,09% 8,46% 15,72%Unknown 9,32% 15,2% 10,93%

Nephrology Centre in IndonesiaSidabutar RP ( 1989 ) *

Methods of Glomerular Filtration Rate (GFR) Measurement

Inulin Clearance

Alternative Filtration Markers125I-Iothalamate, 51Cr-EDTA, 99mTc-DTPA and

non-radioactive iohexol

Plasma Creatinine

Creatinine Clearance

Predictive Creatinine Clearance (the Cockroft-Gault Formula)

Creatinine ClearanceCreatinine Clearance

Ccr = Ucr x V

Pcr

Pcr = Plasma concentration of creatinineUcr = Urine concentration of creatinineV = Urine flow rate

Note (V) : 24 hr collectionOver night collectionTime collection

1. Cockcroft – Gault Formula1. Cockcroft – Gault Formula

Age – yearsWeight – KgPcr – plasma creatinineThe formula estimates Ccr in obese patients and those on a low protein diet

Men

Ccr =

(140-age)(weight)

72 × Pcr (mg/dl)

Ccr =

(140-age)(weight)

85 × Pcr (mg/dl)

or

or

Ccr =

1.23 (140-age)(weight)

Pcr (mol/L)

Ccr =

1.04 (140-age)(weight)

Pcr (mol/L)

Estimated creatinine clearence (Ccr) with Estimated creatinine clearence (Ccr) with

respect age, gender and body weightrespect age, gender and body weight

Women

2. MDRD2. MDRD

STAGES OF CKDSTAGES OF CKD

NORMAL INCREASED RISK DAMAGE LOW GFR

RENAL FAILURECKD

DEATHCOMPLICATIONS

CKD Stage

eGFR (mL/1.73 cm2)

Other Features Suggested Management

1 90+ Normal renal function but urine dipstick abnormalities or known structural abnormality if renal tract or diagnosis of genetic kidney disease

Observation, control of BP. Consider investigation for cause of urine dipstick abnormalities

2 60-89 Mildly reduced renal function plus urine/structural abnormalities or diagnosis of genetic kidney disease

Observation, control of BP. Management of cardiovascular risk factors. Consider investigation for cause of renal impairment

3 30-59 Moderately reduced renal function

Observation, control of BP. Management of cardiovascular risk factors. Measure Ca2+, PO4, PTH, Hb and cholesterol. The patient may need treatment for anaemia or secondary/tertiary hyperparathyroidism.

4 15-29 Severely reduced renal function

Regular observation, control of BP and CVS risk factors. Measure Ca2+, PO4, PTH, Hb and cholesterol. Management as for stage 3. Preparation for ESRF with an early decision on the preferred mode of RRT.

5 <15 End-stage renal failure Can be managed conservatively but RRT should be considered for most patients (i.e. provision of dialysis or transplantation

BP: blood pressure; CVS: cardiovascular system; Hb: hemoglobin;PTH: parathyroid hormone; RRT: renal replacement therapy

Individuals at increased risk for CKD should be

tested at the time of a health evaluations to

determine if they have CKD.

• Diabetes• Hypertension• Autoimmune diseases• Systemic infections• Exposure to drugs or procedures associated with acute

decline in kidney function• Recovery from acute kidney failure• Age > 60 years• Family history of kidney disease• Reduced kidney mass (includes kidney donors and

transplant recipients)

Chronic kidney diseases ( CKD )Chronic kidney diseases ( CKD )

* Renal injury destruksi nefron yang bersifat chronic progressive , irreversible

* Penurunan jumlah massa nefron menyebabkan perubahan struktur dan hiper fungsi dari sisa nefron

* Respon mekanisme predisposisi sklerosis nefron CKD

* uremia sindrom klinik yang mengenai seluruh organ / sistim

Chronic kidney diseaseChronic kidney disease

PathophysiologyNitrogen and Lipid Metabolism

Pts are often hypercatabolic and have a decrease capacity to eliminate nitrogenous end products of protein catabolism.

Hypertriglyceridemia and, decreased HDL are common in pts with CRF.

–High incidence of premature atherosclerosis

Clinical Manifestation of Chronic Kidney Disease

Bone AbnormalitiesOsteomalacia

Osteitis fibrosa

Osteosclerosis

Aluminum associated

osteomalacia

ElectrolytesHyperkalemia

Hyponatremia

Hyperphosphatemia

Hypocalcaemia

Hyperuricaemia

Metabolic Acidosis

Neurologic AbnormalitiesCentral

Cognitive change

Lethargy

Stupor

Coma

Peripheral

Motor neuropathy

Sensory neuropathy

Myoclonus

Fasciculations

Cardiovascular AbnormalitiesHypertension

Pericarditis

Accelerated atherosclerosis

Vascular calcifications


Hematologic AbnormalitiesAnemia

Leukocyte & lymphocyte dysfunction

Platelet defect

Gastrointestinal AbnormalitiesAnorexia, nausea, vomiting

Gastroparesis

Hypomotility of bowel

Mucosal bleeding


Dermatologic AbnormalitiesPruritisCalcium-phosphate deposition

Rheumatologic AbnormalitiesMyopathyCalcific bursitisAvascular necrosisCarpal tunnel syndromeArticular amyloid deposition

Metabolic AbnormalitiesGlucose intoleranceHyperparatiroidismVitamin D deficiencyHyperlipidemiaSexual dysfunctionMalnutrition

Pleural-Pulmonary AbnormalitiesPleuritis and effusionParenchymal calcificationEdema


Investigating CKDInvestigating CKD

THE MECHANISM OF PROGRESSION OF THE MECHANISM OF PROGRESSION OF CHRONIC KIDNEY DISEASECHRONIC KIDNEY DISEASE

1.1. HYPERTENSIONHYPERTENSION

2.2. PROTEINURIAPROTEINURIA

3.3. ANGIOTENSIN-IIANGIOTENSIN-II

4.4. HYPERGLYCEMIA.HYPERGLYCEMIA.

5.5. PROTEIN INTAKE PROTEIN INTAKE

6.6. SODIUM INTAKESODIUM INTAKE

7.7. WATER INTAKEWATER INTAKE

8.8. HYPERLIPIDEMIAHYPERLIPIDEMIA

9.9. SMOKINGSMOKING

10.10. NSAIDNSAID

11.11. ANEMIAANEMIA

12. HYPERINSULINEMIA 12. HYPERINSULINEMIA

13. HOMOCYSTEINEMIA13. HOMOCYSTEINEMIA

14.HYPERPHOSPHATEMIA14.HYPERPHOSPHATEMIA

15. POTASSIUM 15. POTASSIUM

DEPLETIONDEPLETION

16. HYPERCOAGULATION16. HYPERCOAGULATION

17. GENDER17. GENDER

= LEVEL 1 = LEVEL 2 = LEVEL 3Hebert LA, et al : Kidney Int 2001; 59 :

804

Treatment of chronic kidney disease should include :

• Spesific therapy, based on diagnosis

• Evaluation and management of co-morbid conditions

• Slowing the loss of kidney function

• Prevention and treatment of cardiovascular disease

• Prevention and treatment of complications of decreased kidney function

• Preparation for kidney failure and kidney replacement therapy

• Replacement of kidney function by dialysis and transplantation, if sign and

symptoms of uremia are present


Evaluation and Treatment

Interventions to slow the progression of chronic kidney disease should be considered

in all patients with CKD

• Interventions that have been proven to be effective

include :

(1) Stric blood pressure control

(2) Strict glucose control in diabetes

(3) Angiotensin-converting enzyme inhibitor or angiotensin-2 receptor

blockade

• Interventions that have been studied, but the

results of which are inconclusive, include :

(1) Dietary protein restriction

(2) Lipid-lowering therapy

(3) Partial correction of anemia Am J Kidney Dis 2002 ; 39 (suppl 1) : S30.

1. Control blood pressure2. ACE inhibitor therapy Angiotensin receptor blocker (ARB) if ACE

inhibitor intolerant3. Control blood glucose in diabetes4. Dietary interventions Protein intake, NaCl intake Fluid intake5. Control blood lipids6. No cigarette smoking7. Avoid regular use of NSAIDs8. Correct anemia9. Control hyperphosphatemia

Renoprotective Strategies Recommendation

Hebert LA, et al : Kidney Int 2001; 59 : 1215

Aims of Dietary protein restriction :

• To slow the progression of kidney disease

• Minimize accumulation of uremic toxins

• Preserve protein nutritional status

• CKD stages 1-3 (GFR > 30 mL/min) :

- Protein 0.75 g/kg/d

• CKD stages 4-5 (GFR < 30 mL/min) :

- Protein 0.6 g/kg/d

Uremia : diit protein 0,8 – 0,6 gr / kg bb / hariHiperkalemia : diit rendah kalium ; 60 – 80 meq/hariAsidosis metabolik : diit rendah protein / fosfat; HCO3

Stop rokokKontrol lipid ( preparat statin )HbA1C < 7 %

HipertensiAnemiaOsteodistrofi renalKomplikasi kardiovaskuler

Hypertension and Antihypertensive Agents in Diabetic Kidney Disease(K/DOQI)

Clinical Assessment

Target BP Preffered Agents for CKD

Other Agents to Reduce CVD Risk and Reach

Target BP

BP >130/80 mmHg <130/80 mmHg ACE inhibitor or ARB

A Diuretic preffered, then beta blocker or calcium chanel blocker dh la

A

BP <130/80 mmHg ACE inhibitor or ARB

A

K/DOQI, 2004 / ADA, 2003 / JNC 7, 2003 : Target BP 130/80 mmHg

Lifestyle modification : DASH diet, exercise, etc

Agent is ARB, ACE-inh (initial) : Hypertension Diabetic Kidney Disease and Nondiabetic Kidney Disease

Hypertension

BP < 125 / 75 mmHg ( ekskresi protein > 1 gr / hari )

Target hematocrit pre-dialysis , hemodialysis

Relieve symptom, low risk side effect :

Hb 11g% / Ht 33% ( Pernefri/NKF-DOQI) - erithropoetin - preparat - iron ( bila kadar serum iron kurang )

improvements in the quality of life, cardiacfunction, physical work capacity, cognitive function, and sexual function have been reported at a hematocrit of 36% to39%.

Anemia

Defisiensi Eritropoetin pada GGK

Potential Risk Factors for Susceptibility to

and Initiation of Chronic Kidney Disease

Clinical Factors

DiabetesHypertension

Autoimmune diseasesSystemic infections

Urinary tract infectionsUrinary stones

Lower urinary tract obstructionNeoplasma

Family history of CKDRecovery from acute renal failure

Reduction in kidney massExposure to certain drugs

Low birth weight

Sociodemographic Factors

Older age

US ethnic minority status: African American, American Indian,

Hispanic, Asian or Pasific Islander

Exposure to certain chemical andEnvironmental conditions

Low income / education


Risk factors forRisk factors for acute decline in GFR on acute decline in GFR on

chronic kidney disease. :chronic kidney disease. :

• Volume depletion

• Intravenous radiographic contrast

• Selected antimicrobial agents (i.e.: aminoglycosides

and ampotericin B)

• NSAIDs, including cyclo-oxygenase type 2 (COX 2)

inhibitors

• ACE-inhibitors and ARB

• Cyclosporine and tacrolimus

• Obstruction of the urinary tract

Definitions of Progression, Remission, and Definitions of Progression, Remission, and

Regression of Proteinuric Chronic NephropathyRegression of Proteinuric Chronic Nephropathy

VariableVariable ProgressionProgression RemissionRemission RegressioRegressio

nn

Proteinuria

Glomerular filtration rate

Renal structural changes

≥ 1g/24 h

Declining

Worsering

< 1g/ 24 h

Stable

Stable

< 0.3g / 24 h

Increasing

Improving

Ruggenenti P, et al. Lancet 2001 ; 357 : 1602.

Polycystic Kidney Disease Polycystic Kidney Disease (Congenital Disorder)(Congenital Disorder)

Key Features:Abdominal or flank painHypertensionNocturiaIncreased abdominal girthConstipationBloody or cloudy urineKidney stones

Physical Assessment/Clinical Physical Assessment/Clinical ManifestationsManifestations

Inspect abdomen (protruding and distended) Gently palpate (polycystic kidneys easily palpated) Dull and aching pain or sharp, intermittent discomfort Change in urine color if cyst ruptures Nocturia is an early sign Declining renal function results in increased hypertension,

edema, vomiting, pruritis, and fatigue Severe headache with or without neurologic or visual

alteration is cause for concern because of the potential for rupture of berry aneurysms

Diagnostic Assessment Diagnostic Assessment

Urinalysis Urine Culture & SensitivitySerum Creatinine and BUNRenal SonographyCT ScanMRI

InterventionsInterventions

Pain managementBowel managementMedication managementEnergy managementFluid monitoringUrinary retention careInfection protection Blood pressure monitoring

Renal Cell CarcinomaRenal Cell CarcinomaHealthy kidney tissue damaged and replaced

by cancer cellsParaneoplastic syndrome:

– Anemia– Erythrocytosis– Hypercalcemia– Liver dysfuntion– Hormonal effects– Increased sedimentation rate– Hypertension

Renal Cell Carcinoma Renal Cell Carcinoma Management Management

Nonsurgical– Radiofrequency

ablation– Chemotherapy– Biological response

modifiers and tumor necrosis factor lengthen survival time

Surgical– Pre-op care– Nephrectomy– Post-op care:

Monitoring for hemorrhage and adrenal insufficiency

Pain management Prevention of

complications

Renal colicRenal colicRenal colicRenal colic

Health History– Changes in Voiding– GI Symptoms

Physical Examination– Abdominal assessment– Palpation of kidneys– Bladder percussion– Prostate palpation– Inspection of urinary

meatus

Pemeriksaan FisikPemeriksaan Fisik

Kaitan Lokasi Batu dengan Keluhan NyeriKaitan Lokasi Batu dengan Keluhan NyeriLokasi Batu Lokasi Batu Gejala Gejala

GinjalGinjal Nyeri Nyeri pinggang pinggang ringan, ringan, hematuriahematuria

Ureter Ureter proksimalproksimal

Kolik ginjal, Kolik ginjal, nyeri nyeri pinggang, pinggang, nyeri nyeri abdominal abdominal atasatas

Ureter tengahUreter tengah Kolik ginjal, Kolik ginjal, nyeri nyeri pinggang, pinggang, nyeri nyeri abdominal abdominal depan depan

Ureter distalUreter distal Kolik, nyeri Kolik, nyeri pinggang, pinggang, nyeri nyeri abdominal abdominal depan, depan, disuria, disuria, sering sering kencingkencing

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Systemic HypertensionPrimary Renal Disease

Renal Ablation

AgingDiabetes Mellitus

Dietary Factor

ENDOTHELIAL INJURYRelease of vasoactive factorsVascular lipid depositionIntracapillary throbosis

MESANGIAL INJURYAccumulation of macromoleculesMatrix productionCell proliteration

EPITHELIAL INJURYProteinuriaPermeability to water

GLOMERULAR SCLEROSIS

GLOMERULAR HYPERTENSION

Pivotal role of glomerular hypertension in the initiation and

progression of structural injury

Brenner B M

Glomerular HemodynamicsACE I / ARBs 1. Arteriolar vasodilation Efferent arteriole > Afferent arteriole Intraglomerular capillary pressure (PGC) ↓ Glomerular hypertension ↓ 2. Partially block renal autoregulatory function

Renal Protection

CCBs( traditional) –Dihydropyridipine CCBs1. Arteriolar vasodilation Afferent arteriole > Efferent arteriole Intraglomerular capillary pressure (PGC) Glomerular hypertension 2. Completely block renal autoregulatory function

Glomerular Injury

Interna Uro Sistem

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