Farmakoterapi Gangguan Renal

Oleh:

Martanty Aditya

Universitas Ma Chung
2017
 Gagal Ginjal Kronis

Definisi
Penyakit kronis progresif yang ditandai dengan penurunan fungsi ginjal dan kinerja nefron secara terus
CURRENT CHRONIC KIDNEY DISEASE (CKD) NOMENCLATURE
menerus (terjadi selama beberapa tahun). USED
Pada awalnya
BY KDIGOnefron yang masih berfungsi dengan baik
berusaha mengambil alih tugas dengan cara meningkatkan filtrasi dan reabsorpsi larutan. Namun hal
CKD is defined as abnormalities of kidney structure or function, present for > 3 months,
ini akan merusak nefron sendiri
with implications sampai
for health. CKD isberkembang
classified basedmenjadi
on Cause,gagal ginjal (G1-G5),
GFR category akhir dan
andmemerlukan
Albuminuria category (A1-A3), abbreviated as CGA.
dialysis atau transplantasi.
 

Prognosis of CKD by GFR and albuminuria category

724
Prognosis CKD dengan melihat kategori GFR dan albuminuria
that is associated with an accumulation of waste products, including (I), and failure of the kidney (F) are outlined. The clinical outcomes
urea and creatinine. This relatively abrupt decline in renal function is of loss of function (L), and end-stage renal disease (E) complete the
SECTION 5

in contrast to CKD, which is defined by the presence of proteinuria/ RIFLE acronym. Thus far,albuminuria
Persistent validation studies have confirmed the value
categories
albuminuria for at least 3 months, in combination with a GFR of <90 of these criteria inDescription
predicting hospital
and mortality, although further
range
mL/min/1.73 m2.3 A decrease in urine output is often observed, but is assessment is still necessary.9,10
not required for ARF to be present.4 Compared to a normal urine
output of ≥1,200 mL/day, patients with ARF are often categorized as A1 A2 A3
Prognosis of CKD by GFR
being anuric (urine output <50 mL/day), oliguric (urine output <500 EPIDEMIOLOGY
Normal to
and Albuminuria Categories:
mL/day), or nonoliguric (urine output >500 mL/day).
Currently, there is no universally accepted definition of ARF in ARF is anmildly
Moderately Severely
uncommon condition in the community-dwelling, gener-
increased increased
KDIGO 2012 increased
Renal Disorders

clinical practice: in fact, more than 30 definitions for ARF are
reported in the medical literature.5 Many of these definitions incorpo-
rate selective aspects of ARF observed in different patient populations.
Comparisons between studies that describe incidences, treatment
effects, and patient outcomes can thus be difficult, if not impossible
to interpret. Although a serum creatinine (Scr) or calculated creatinine
clearance (Clcr) may not provide a reliable characterization of renal
G1 clinicians
function in all ARF situations, Normal or highuse some combi-
frequently ≥90 ment of ARF.11 The pharmacologic agents commonly associated with
GFR categories (ml/min/ 1.73 m2)
ally healthy population, with an annual incidence of approximately
0.02% (Table 45–1).11 In individuals with preexisting CKD, however,
the incidence may be as high as 13%. In nonhospitalized patients,
<30 mg/g 30-300 mg/g >300 mg/g
dehydration, exposure to selected pharmacologic agents such as
<3 mg/mmol 3-30 mg/mmol >30 mg/mmol
contrast media, and the presence of heart failure are associated with
an increased risk of ARF. Additionally, trauma, rhabdomyolysis,
vessel thrombosis, and drugs are common culprits in the develop-

nation of the absolute Scr value, change in Scr value over time, and/or ARF, including contrast media, chemotherapeutic agents, nonster-
urine output as the primary criteria for diagnosing the presence of oidal antiinflammatory drugs (NSAIDs), angiotensin-converting
ARF. The commonly G2
4,6
used andMildly decreased
highly variable 60-89 enzyme inhibitors, angiotensin receptor blockers, and antiviral med-
definitions for ARF
Description and range

are nonspecific and open to various interpretations. On a patient-by- ications are discussed in detail in Chap. 49. 11,12
patient basis, the semantics of Mildly
the ARF to definition
moderately are relatively ! The hospitalized individual is at high risk of developing ARF;
meaningless. However, to G3amove the prevention and treatment of ARF 45-59 the reported incidence is 7%.13 The incidence of ARF is markedly
decreased
forward, consistent definitions must be employed. Without them, higher in critically ill patients, ranging from 6% to 23%.6 The high
Moderately
clinicians will be unable to accurately to generated because
use any data mortality rate related to ARF, which is reported to range from 35% to
G3b
the nonspecific classification ofseverely
ARF will decreased
be an insurmountable 30-44 80%, is a significant clinical concern that has been relatively unre-
barrier to the identification of who was studied, and hence, to whom sponsive to therapeutic intervention over the last four decades.
the data apply. A means to standardize the various aspects of the Although the relative contribution of ARF to mortality rates of the
G4 Severely decreased 15-29
clinical presentation is necessary to allow integration of the literature underlying disease states is unclear given that current illness and ARF
observations to bedside management. A new consensus-derived defi- cannot be reliably quantified, it is certain that the presence of ARF will
nition and classificationG5system for ARF wasfailure
Kidney recently proposed, and<15is independently contribute significantly to overall mortality.6 For sur-
currently being validated (Fig. 45–1).7,8 This three-tiered classification vivors of ARF, subsequent morbidity or development of some degree
uses both GFR and urine output, plus two clinical outcomes that may of CKD is also a consideration. Although 90% of individuals recover
Green: low risk (if no other markers of kidney disease, no CKD); Yellow: moderately increased risk;
occur subsequent to an episode of ARF as components of the enough renal function to live normal lives, approximately half of
Orange: high risk; Red, very high risk.
paradigm. Definitions of risk of dysfunction (R), injury to the kidney these are left with subclinical deficits. Five percent will not regain

Risk

Injury

viiiFailure
 
Loss
GFR/Scr Scr ↑ 50%, or Scr ↑ 100%,or Scr ↑ 200%, or
GFR ↓ 25% GFR ↓ 50% GFR ↓ 75%, or
Criteria Scr > 4 mg/dL
ESRD

Persistant ARF ESRD

(> 4 weeks) (> 3 months)
UOP < 0.5 UOP < 0.5 UOP > 0.3
Urine Output mL/kg/hr mL/kg/hr mL/kg/hr
(UOP) Criteria x 6 hr x 12 hr x 24 hr, or
Anuria x 12 hr

FIGURE 45-1. RIFLE classification for acute renal failure (ARF). (ESRD, end-stage renal disease; GFR, glomerular filtration rate; S cr, serum creatinine).
(Reprinted and adapted from Crit Care Clin, Vol. 21, Bellomo R. Defining, quantifying, and classifying acute renal failure, pages 223-237, Copyright
© 2005, with permission from Elsevier.)
 Skrining untuk CKD
Hal ini perlu dilakukan karena risikonya besar pada seseorang yang mengalami CVD, pasien diabetes
mellitus, hipertensi, geriatric, infeksi sistemik, recurrent UTI, batu saluran kemih, massa ginjal yang
menurun dan penggunaan obat yang bersifat nefrotoksik. Selain itu pada GGK tahap 1 dan 2 sifatnya
asimtomatik.

Faktor risiko CKD

! Diabetik nefropati
! Hipertensi
! Glomerulonephritis
! Penyakit ginjal polisistik
! Rapidly progressive glomerulonephritis (vasculitis)/inflamasi pembuluh datah ginjal
! Renal vascular disease (renal arteri stenosis)
! Penggunaan obat tertentu
! Analgesic nephropathy (berkembang setelah penggunaan yang sangat panjang)
! Kehamilan: insiden tinggi dengan meningkatnya kreatinin dan hipertensi preeklamsia
! Retensi fosfat
! Protein >1,5g/hari
! Ras afrika amerika
! Diet tinggi protein
es of Chronic TABLE 46-2 Risk Factors Associated with Chronic Kidney Disease
Risk Factor Key Studies
Prevalencec Susceptibility
10,500,000 Advanced age Lindeman et al.,17 Goetz et al.75
7,100,000 Reduced kidney mass and low Lackland et al.24
7,600,000 birth weight
400,000 Racial/ethnic minority Tierney et al.,21 Rostand et al.,22 Perry et al.23
300,000 Family history Freedman et al.,25 FIND Research Group26
Low income or education Byrne et al.,19 Perneger et al.20
Systemic inflammation Kshirsagar et al.,27 Erlinger et al.28
ther markers of kidney
dney damage, or
Dyslipidemia Muntner et al.,29 Schaeffner et al.30
Initiation
Diabetes mellitus Hasslacher et al.,32 Brancati et al.34
Hypertension Coresh et al.,39 Perneger et al.,40 Klag et al.
Glomerulonephritis Massy et al.46
kidney disease,3
Progression
h hypertensive Glycemia (among diabetic patients) Reichard et al.,62 DCCT Research Group63
by the National Hypertension Klahr et al.,51 Jafar et al.,52 Bakris,57 UKPDS
us cosponsored Group,58 UKPDS Group,59 Bakris60
ve CKD and its Proteinuria Keane et al.,50 Klahr,51 Jafar et al.52
. The National Smoking Orth et al.,66 Orth et al.76
of early detec- Obesity Hsu et al.,82 Iseki et al.,83 Ejerblad et al.84
n Program7 to
ple at increased
. governmental
focus areas for from USRDS data is assumed to be generalizable to all stages of
Healthy People CKD. The validity of this approach to projecting future incidence
of these initia- data has not been tested. Further complicating these issues is the fact
physiology, and that the development and progression of the early stages of CKD is
e 4) CKD will a complex phenomenon.15 The risk factors associated with CKD are
 Uji GGK:
1. Memiliki faktor risiko
2. Serum kreatinin dan GFR
3. Proteinuria, MAU, urin kreatinin
4. Urin: analisis urin, sedimen urin untuk mengukur WBC, RBC, Kristal
796 5. Serum elektrolit: Ca, PO4, iPTH, Fe, Na
6. TesPRESENTATION
CLINICAL “imaging” dengan USG, renal angiography TABLE 49-1 Drug-Induced Renal Structural–Functional Alterations
Tubular epithelial cell damage
SECTION 5

! Because the most common manifestation of DIN is a decline in Acute tubular necrosis • Pentamidine
GFR leading to a rise in Scr andCKD BUN, the onset of toxicity in AKI
• Adefovir, cidofovir, tenofovir • Radiographic contrast media
hospitalized, acutely ill patients is most often recognized by routine • Aminoglycoside antibiotics • Zoledronate
laboratoryCa↓, PO4 ↑, of
monitoring PTH ↑ two chemistries. Decreased urine Kalsium
these normal B
• Amphotericin Osmotic nephrosis
• Cisplatin, carboplatin • Dextran
output may also be an early sign of toxicity, particularly with
USG: ukuran ginjal <
radiographic contrast media, NSAIDs, and ACEIs. In the outpa- Ukuran ginjal normal
• Cyclosporine, tacrolimus • Intravenous immunoglobulin
• Foscarnet • Mannitol
tient setting, nephrotoxicity is often recognized by symptoms
Hb ↓, namun tidak ada perdarahan Hb normal, kecuali jika
Hemodynamically ada perdarahan
mediated kidney injury
such as malaise, anorexia, vomiting, volume overload (shortness of • Angiotensin-converting enzyme • Cyclosporine, tacrolimus
Renal Disorders

breath orFoto
edema),
tulang:andadnormal
hypertension. Scr or
(resopsi BUN mineralisasi
tulang, concentrations Foto tulang
inhibitors
normal • Nonsteroidal antiinflammatory drugs
and urine collection for creatinine clearance may subsequently be • Angiotensin II receptor blockers • OKT3
measured↓,toosteomalasia
quantify the degree of loss of glomerular filtration. Obstructive nephropathy
Marked intrasubject between-day variability of Scr values has been Intratubular obstruction Nephrolithiasis
noted (±20% for values within the normal range; see Chap. 44). • Acyclovir • Indinavir
• Foscarnet • Sulfonamides
Furthermore, they may be altered as the result of dietary changes
• Indinavir • Triamterene
and initiation of drug therapy, which may interfere with the assay
• Methotrexate
procedure. Thus
Drug a changeKidney
Induced in Scr ofDisease
at least 0.5 mg/dL for subjects • Sulfonamides
with a baseline Scr <2 mg/dL and an increase of approximately 30% Glomerular disease
for those
TABLEwith49-1
Scr >2 Drug-Induced
mg/dL, whenRenal correlated temporally with
Structural–Functional the
Alterations • Gold • Nonsteroidal antiinflammatory drugs,
initiation of drug therapy, is a common threshold for the identifi- • Lithium cyclooxygenase-2 inhibitors
cationTubular epithelial cell damage
of DIN. • Pamidronate
N is a decline in Acute tubular necrosis • Pentamidine Tubulointerstitial disease
of toxicity in • Adefovir, cidofovir, tenofovir • Radiographic contrast media Acute allergic interstitial nephritis Nephrocalcinosis
ized by routine CLINICAL PRESENTATION
• Aminoglycoside antibiotics OF •DRUG-INDUCED
Zoledronate • Ciprofloxacin • Oral sodium phosphate solution
ecreased urine KIDNEY DISEASE
• Amphotericin B Osmotic nephrosis • Loop diuretics Papillary necrosis
• Cisplatin, carboplatin • Dextran • Nonsteroidal antiinflammatory drugs, • Nonsteroidal antiinflammatory drugs,
rticularly with General
• Cyclosporine, tacrolimus • Intravenous immunoglobulin cyclooxygenase-2 inhibitors combined phenacetin, aspirin, and
In the outpa- ■ The• Foscarnet
most common manifestation is • Mannitol
a decline in GFR leading
by symptoms • Penicillins caffeine analgesics
toHemodynamically
a rise in Scr andmediated
BUN. kidney injury • Proton pump inhibitors
d (shortness of • Angiotensin-converting enzyme • Cyclosporine, tacrolimus
Symptoms Chronic interstitial nephritis
concentrations inhibitors • Nonsteroidal antiinflammatory drugs • Cyclosporine
ubsequently be ■ Malaise,
• Angiotensinanorexia, vomiting,
II receptor blockers shortness• OKT3 of breath, or edema. • Lithium
rular filtration. SignsObstructive nephropathy • Aristolochic acid
values has been Intratubular obstruction Nephrolithiasis Renal vasculitis, thrombosis, and cholesterol emboli
■ Decreased
• Acyclovir urine output may be •an early sign of toxicity,
Indinavir
see Chap. 44). Vasculitis and thrombosis • Mitomycin C
particularly
• Foscarnet with radiographic contrast media, NSAIDs, and
• Sulfonamides
dietary changes • Hydralazine • Methamphetamines
ACEIs, with progression to volume •overload
• Indinavir and hypertension.
Triamterene • Propylthiouracil • Cyclosporine, tacrolimus
with the assay
• Methotrexate
■ Proximal tubular injury: metabolic acidosis with bicar- • Allopurinol Cholesterol emboli
dL for subjects • Sulfonamides
oximately 30% bonaturia; glycosuria in the absence of hyperglycemia; and • Penicillamine • Warfarin
Glomerular disease • Gemcitabine • Thrombolytic agents
orally with the reductions
• Gold
in serum phosphate, •uric acid, potassium, and
Nonsteroidal antiinflammatory drugs,
or the identifi- magnesium
• Lithium as a result of increased urinary losses. inhibitors
cyclooxygenase-2
• Pamidronate
■ Distal tubular injury: polyuria from failure to maximally Nephrotoxicity may be evidenced by alterations in renal tubular
Tubulointerstitial
concentrate urine, disease
metabolic acidosis from impaired urinary function without loss of glomerular filtration (Table 49–1). Indica-
Acute allergic interstitial
acidification, nephritis
and hyperkalemia Nephrocalcinosis
from impaired potassium tors of proximal tubular injury include metabolic acidosis with
DUCED • Ciprofloxacin • Oral sodium phosphate solution
excretion. bicarbonaturia; glycosuria in the absence of hyperglycemia; and
• Loop diuretics Papillary necrosis
Laboratory Tests reductions in serum phosphate, uric acid, potassium, and magne-
• Nonsteroidal antiinflammatory drugs, • Nonsteroidal antiinflammatory drugs,
sium as a result of increased urinary losses. Indicators of distal
■ A cyclooxygenase-2
change in Scrinhibitorsof at least 0.5 mg/dL combined
forphenacetin,
subjects aspirin,
with and
a
GFR leading • Penicillins caffeine analgesics tubular injury include polyuria from failure to maximally concen-
baseline Scr <2 mg/dL and an increase of >30% for those with
trate urine, metabolic acidosis from impaired urinary acidification,
S•cr Proton pump inhibitors
>2 mg/dL, when correlated temporally with the initiation
Chronic interstitial nephritis and hyperkalemia from impaired potassium excretion. Urinary
of drug therapy is commonly observed.3,10
• Cyclosporine enzymes and low-molecular-weight proteins are also used as early
, or edema. Other Diagnostic Tests
• Lithium markers of nephrotoxicity. For example, urinary excretion of N-
• Aristolochic
■ Urinary acid of N-acetyl-β-D-glucosaminidase, γ-glutamyl
excretion acetyl-β-D-glucosaminidase, γ-glutamyl transpeptidase, glutathione
n of toxicity, Renal vasculitis, thrombosis, and
transpeptidase, glutathione cholesterol and
S-transferase, emboli
interleukin-18 are S-transferase, and interleukin-18 are markers of proximal tubular
Vasculitis and thrombosis • Mitomycin C injury and have been used for the early detection of acute kidney
NSAIDs, and markers of proximal tubular injury and have been used for the
• Hydralazine • Methamphetamines
hypertension. early detection of AKI in critically ill• patients. 14,15 damage in critically ill patients. The transmembrane protein KIM-1
• Propylthiouracil Cyclosporine, tacrolimus
with bicar- ■ Kidney injury molecule-1 (KIM-1)Cholesterol
• Allopurinol is expressed
emboliin the proxi-
is expressed in the proximal tubule and is upregulated in patients
lycemia; and • Penicillamine
mal tubule and is upregulated in patients • Warfarin with ischemic acute with ischemic acute tubular necrosis, appearing in the urine within
tassium, and • Gemcitabine
tubular necrosis, appearing in the urine • Thrombolytic
within agents
12 hours after 12 hours after the ischemic insult. Similarly, NGAL protein is
e CLcr-to-CLinulin ratio in American Study of Kidney Disease (AASK) were evaluated for
or moderate impairment, kidney function based on an estimated CLcr compared with the
was 2.32. Thus, creatinine simultaneous CLcr and 125I-iothalamate, and 24-hour CLcr.78 The
patients with moderate to simultaneous CLcr provided the best estimate of GFR. The Cock-
croft-Gault method was the preferred method for estimation of
Metode
secretion of creatinine the perkiraan
GFR,GFR based on performance and ease of use. This method was noted
regimens to improve the to underestimate
1. pengumpulan urin 24 jam the GFR by
+ cuplikan 9%,serum
plasma perhaps because of the increased
kreatinin
nce as an indicator of GFR excretion rate of creatinine by black patients.78,79
Metode paling tepat, namun jarang digunakan karena kelemahan kadang cuplikan urin yan
ratio declined from 1.33 Administration of cimetidine has also resulted in improved
metidine was administered tidak lengkap
performance dan sulit
ofuntuk menghitung luas permukaan
the Cockcroft-Gault equationtubuhto predict GFR. Ixkes
80
nd during the clearance et al. gave patients three 800-mg doses of cimetidine in 24 hours,
ved when a single 800-mg and measured " Ucrcreatinine
×V % plasma levels from 3 to 7 hours following
rior to the simultaneous Clcrfinal
the = $ dose. During ' this 4-hour period, the CLiothalamate was
ratio of CLcr to CLiothalamate # S
determined as the measure & of GFR. The Cockcroft-Gault calcula-
Thus a single oral dose of tions were performed with the plasma creatinine measurement 3
ate blockade of creatinine Ucr =hours after theurin
kadar kreatinin last dose of cimetidine. The ratio of the Cockcroft-
(mikromol/L)
atinine clearance measure- Gault estimated CLcr-to-CLiothalamate decreased from 1.28 ± 0.21 to
V = laju aliran urin (ml/menit atau L/hari)
stages 3 to 5 CKD. 0.98 ± 0.11 in the presence of cimetidine. This cimetidine dosing
Scr =schedule
kadar kreatininalso serum
improved(mikromol/L)
the accuracy of Cockcroft-Gault estimates
nce relative to GFR in renal transplant patients with GFR values ranging
2 81,82
from 20 to 80 mL/min/1.73m .
athematical relationships 2. klirens UREA (BUN)
have been reported over 3. cistatin C
porate factors such as age, TABLE 44-5 Equations for the Estimation of Creatinine Clearance
4. Rumus
ncentration, without the in Adults with Stable Renal Function
y used of these estimators
Cockroft and Gault80 Men: CLcr = (140 — age) ABW/(Scr × 72)
identified age and body Women: CLcr × 0.85
ribute to the estimate of Jelliffe 89
Men: CLcr = (100/Scr) — 12
ervations from 249 male Women: CLcr = (80/Scr) — 7
whom the creatinine pro- Jelliffe 90
Men: CLcr = 98 — [0.8 (age — 20)]/Scr
Women: CLcr × 0.9
weighing more than 30% Mawer et al.88 Men: IBW [29.3 — (0.203 × age)] [1 — (0.03 × Scr]/(14.4 × Scr)
s recommended that IBW Women: IBW [25.3 — (0.175 × age)] [1 — (0.03 × Scr)]/
ABW)71 in the Cockcroft- (14.4 × Scr)
Hull et al.91 Men: CLcr = [(145 — age)/Scr] — 3
Women: Clcr × 0.85
ht in inches >60) Levey et al. GFR = 170 × (Scr)–0.999 × [age]–0.176 × [0.762 if patient is
(MDRD6)72 female] × [1.180 if patient is black] × [SUN]–0.170 × [Alb]0.318
ght in inches >60)
Levey et al. GFR = 186 × (Scr)–1.154 × (Age)–0.203 × (0.742 if patient is
CLcr (mL/min) in obese (MDRD4)24 female) × (1.210 if patient is black)
which has been shown to Alb, serum albumin concentration (g/dL); CLcr, creatinine clearance in mL/min; IBW, ideal body
oft-Gault equation in thisrumus cockroft-gault
Untuk weight (kg); Scr, serum or plasmabahwa
diasumsikan creatinine (mg/dL);
fungsi ginjalSU,stabil
serumdan
ureanilai
nitrogen concentration
kreatinin serum konstan "
(mg/dL).
jika tidak maka perlu tambahan pengukuran urin selama 24 jam
Rumus ini tidak dapat digunakan jika:
1. Usia pasien <15 tahun atau >90 tahun
2. Fungsi ginjal berubah cepat (serum kreatinin meningkat atau <40mikromol/L selama >24 jam)
3. Kreatinin serum >350mikromol/L
4. Kehamilan (meningkatkan kreatinin serum sampai 20%)
5. Katabolisme bermaknsa
6. Amputasi pada tungkai kaki dan lengan (massa otot berkurang)
 Mekanisme progresivitas penyakit renal
Kerusakan renal disebabkan oleh berbagai macam faktor. Sebagai contohnya diabetik nefropati
ditandai dengan meluasnya kerusakan mesangial glomerular. Pada nefrosklerosis hipertensi, arteriol
ginjal memiliki hyalinosis arteriolar dan kista renal ditandai dengan penyakit ginjal polisistik. Penyebab
yang memengaruhi ginjal sampai terjadi ESRD adalah menurunnya massa nefron, hipertensi kapilari
glomerular dan proteinuria.
Hipertrofi dapat menyebabkan berkembangnya hipertensi intraglomerular yang disebabkan oleh
angiotensin II yang berfungsi sebagai vasokonstriktor poten.
749

Initial pathogenic injury

CHAPTER 46
Glomerular injury

Diabetes mellitus Reduced filtration area Arteriosclerosis

Adaptive hemodynamic
Formation of advanced Hyperlipidemia
changes
glycation end-products

Chronic Kidney Disease: Progression-Modifying Therapies

Increased glomerular Increased glomerular
Systemic hypertension
blood flow capillary pressure

Glomerular hypertrophy Epithelial injury Endothelial injury Mesangial injury

Focal detachment of Proteinuria

epithelial foot processes

Glomerular Microthrombi occluding

hyaline deposition glomerular capillaries Mesangial expansion

Glomerulosclerosis Microaneurysm formation

Progression of
renal disease

FIGURE 46-1. Proposed mechanisms for progression of renal disease.

trophy can lead to the development of intraglomerular hypertension,
possibly mediated by angiotensin II.91,92 Angiotensin II is a potent
vasoconstrictor of both the afferent and efferent arterioles, but prefer-
entially affects the efferent arterioles, leading to increased pressure
within the glomerular capillaries and consequent increased filtration
fraction. The development of intraglomerular hypertension usually
correlates with the development of systemic arterial hypertension.
Animal studies have demonstrated that high intraglomerular capillary
pressure impairs the size-selective function of the glomerular perme-
ability barrier, resulting in increased urinary excretion of albumin and
frank proteinuria.93,94 Angiotensin II may also mediate renal disease
progression through nonhemodynamic effects.95
Proteinuria alone may promote progressive loss of nephrons as a
result of direct cellular damage.88,95 Filtered proteins such as albu-
min, transferrin, complement factors, immunoglobulins, cytokines,
and angiotensin II are toxic to kidney tubular cells. Numerous
studies have demonstrated that the presence of these proteins in the
renal tubule activates tubular cells which leads to the upregulated
production of inflammatory and vasoactive cytokines, such as
endothelin, monocyte chemoattractant protein (MCP-1), and
RANTES (regulated upon activation, normal T-cell expressed and
secreted).88,96–99 Proteinuria is also associated with the activation of
complement components on the apical membrane of proximal
tubules.100 Accumulating evidence now suggests that intratubular
complement activation may be the key mechanism of damage in the
progressive proteinuric nephropathies.101–103 These events ulti-
mately lead to scarring of the interstitium, progressive loss of
structural nephron units, and reduction in GFR.
CLINICAL PRESENTATION
considered for CKD screening. Recommended screening studies
include serum creatinine and GFR measurement, urinalysis, and/or
imaging studies of the kidneys. Abnormal elevations of serum creati-
nine, reflecting decreases in GFR, or presence of urinary or imaging
study abnormalities are indications for a full evaluation of CKD.1
! The rate of GFR loss can vary in CKD because of differences in
the underlying disease process and extent of kidney damage, treat-
ment responsiveness, and compliance with therapies. The NKF K/
DOQI developed a classification system that divides CKD into five
stages, with each increasing number indicating a more advanced
stage of the disease, as defined by GFR1 (see Table 46–1). These
stages are based on kidney function and evidence of kidney damage.
Therefore, one can have CKD with a normal GFR (>90 mL/min per
1.73 m2) if there is evidence of structural damage to the kidneys
(e.g., presence of proteinuria). The GFR rather than serum creati-
nine was used to define kidney function in this official classification
system because the serum creatinine is an inadequate measure of
kidney function (see Chap. 44).
The NKF K/DOQI defines kidney damage as the presence of
clinical proteinuria. Table 46–3 summarizes the methods available to
detect and interpret proteinuria and albuminuria. In addition, Chap.
44 provides a detailed discussion of the relative merits of the various
methods currently available for the detection of urinary protein.
CLINICAL PRESENTATION OF CKD STAGES 1 TO 4
General
■ CKD development and progression may be insidious in onset,
often without noticeable symptoms. The diagnosis of CKD
requires measurement of serum creatinine, estimation of
GFR, and assessment of the urine (urinalysis) for protein and/
or albumin excretion. CKD stages 3, 4, and 5 require further
Perubahan metabolik
Pada awalnya terjadi peningkatkan ekskresi natrium kemudian karena penurunan GFR secara
berkelanjutan terjadi edema di seluruh bagian tubuh terutama di kaki dan perut. Perubahan metabolik
lainnya yaitu penurunan ammonium (NH4+) karena terjadinya metabolik asidosis.
Perubahan metabolik lainnya CaCO3 tulang mulai melakukan proses keseimbangan sebagai buffer
untuk mengatasi asidosis dan menyebabkan terjadinya chronic bone loss dan bone lesion (renal
osteodystrophy).
Anemia, kelainan hematologi
Banyak terjadi pada GGK yang ditandai dengan nilai hematocrit yang rendah berkisar antara 20-25%,
normokritik dan normositik. Penyebab anemia antara lain karena menurunnya produksi eritropoetin di
ginjal, perdarahan saluran cerna dan defisiensi besi dan asam folat.
Penatalksanaan dengan rekombinan human eritropoetin baru diberikan bila tidak terdapat defisiensi
besi dan asam folat. Dosis yang diberikan 50-150 UI/kg tiga kali seminggu secara iv atau sc dengan
tujuan meningkatkan nilai hematocrit 30-35%. Alternative lain yang dapat digunakan adalah PRC.
 776

TABLE 47-3 Oral Iron Preparations

Number of Units Per Daya
SECTION 5

Iron Product Common Agents and Available Units Amount of Elemental Iron Per Unit
Ferrous sulfate Fer-In-Sol (75 mg/0.6 mL) 75 mg 2–3
Feosol (200 mg) 50 mg 4
Ferrous sulfate, various preparations (325 mg) 65 mg 3–4
Slow FE (160 mg) 50 mg 4
Ferrous fumarate Ferrous fumarate, various preparations (300 mg) 99 mg 2
Femiron (20 mg) 20 mg 10
Nephro-Fer (350 mg) 115 mg 2
Vitron-C (65–125 mg) 65 mg 3
Renal Disorders

Ferrous gluconate Ferrous gluconate, various (325 mg) 36 mg 6

Fergon (240 mg) 27 mg 6
Polysaccharide iron Hytinic (150 mg) 150 mg 1–2
Niferex (50 mg) 50 mg 4
Heme iron polypeptide Proferrin-ES (12 mg) 12 mg 17
a
Number of units per day depends on the amount of elemental iron per unit; 200 mg elemental iron per day is recommended.

Hyperkalemia/hypokalemia
Efficacy. Although supplementation using oral preparations may known as a functional iron deficiency is more questionable. Func-
Terjadi
seem morekarena
practicalmenurunnya akskresioral
than IV administration, renal,
iron asupan
therapy is kalium
tionalyang tinggi dan
iron deficiency penggunaan
is characterized by aACEI
low TSatatau ARB.
(<20%) in the
limited by poor absorption and is often inadequate to achieve goal presence of a normal or elevated serum ferritin. In other words, there
Penatalaksanaan
iron indices. In patientsyaitu dengan
with ESRD pemberian
GI absorption nabic
of iron iv, kalsium
is often glukonat
may appear iv, resinstorage
to be adequate penukar ioniron
iron, but danis not
dialysis
being carried
inadequate to meet the increase in iron demand from ESA therapy by transferrin to the bone marrow for red blood cell production.
21
Gangguan
and chronic bloodGITloss in the hemodialysis population. Oral iron Under these conditions a trial of IV iron therapy may be warranted
supplementation is more convenient for patients who do not have if the Hb is less than the target of 11 g/dL. A recent study conducted
Masalah
regular yangincluding
IV access, ditemukan antara
patients lain3anoreksia,
with stages and 4 CKD and mual, inmuntah, diare
ESA-treated dan hemodialysis
anemic tukak saluran cerna
patients with karena
a low TSat
those who are receiving peritoneal dialysis. Even these patients, (<25%) and an elevated serum ferritin (>500 ng/mL) showed a
hiperseksresi
however, asam
are likely to requirelambung. Penatalaksanaan
IV iron supplementation dapatsignificantly
periodically to menggunakangreater Hbdomperidon, serta who
response rate in patients pemberian
received a 1-g
meet iron needs and correct absolute iron deficiency. Success of oral course of IV iron as sodium ferric gluconate in conjunction with a
sirup antasida
therapy bilabymengalami
is also limited noncompliance dyspepsia
as a result ofatau
side H
2 bloker
effects, 25% increase in ESA dose than in those who only received an
primarily GI in nature, and the frequency of administration (up to increase in the ESA dose.38
three times per day). In 2005, over 80% of hemodialysis patients
received an average monthly dose of ≥200 mg of IV iron during the Adverse Effects. Adverse effects of oral iron, including constipa-
first 6 months after the start of dialysis.2 tion, nausea, and abdominal cramping, increase as the dose is
Gangguan kalsium dan fosfat
Intravenous iron therapy is an effective means to prevent iron escalated and may be present in more than 50% of patients receiving
deficiency and maintain adequate iron status for erythropoiesis. 200 mg of elemental iron per day. These unfavorable effects often
Gangguan metabolisme kalsium dan fosfat
Parenteral iron improves the responsiveness to ESA therapy and
dijumpai pada konsdisi hipokalsemia, hiperfosfatemia,
discourage patients from taking these medications on a chronic
reduces the dose required to achieve and maintain the target Hb in
hipersekresi hormone paratiroid, renal osteodistrofi.basis.
hemodialysis patients.21 Iron administration in patients with what is
Some of these GI side effects can be minimized if oral iron
Penyebabnya adalah menurunnya absorpsi
products are taken with food; however, food may decrease absorp-
kalsium karena penurunan D3 oleh ginjal. Penyebab lainnya menurunnya kadar kalsium plasma yang
TABLE 47-4 Intravenous Iron Preparations a
disebabkan meningkatnya fosfat karena penurunan GFR dan resistensi
48,51,52
hormone paratiroid pada tulang.b
Iron Compounds FDA-Approved Indications FDA-Approved Dosing Warnings Dose Ranges
Penatalaksanaan
Iron Dextran (INFeD, dengan
Patients withCaCO3 dan
iron deficiency vitamin
in whom oral DIV push:
0,25mcg/hari.
100 mg over 2 min (25-mg test dose Black box (risk of anaphy- 25–1,000 mg
DexFerrum)c iron is unsatisfactory required) lactic reactions)
Ferric gluconate Adult and pediatric HD patients age 6 years IV push (adult): 125 mg over 10 min General 62.5–1,000 mg
(Ferrlecit)d and older receiving ESA therapy IV infusion (adult): 125 mg in 100 mL of 0.9%
NaCl over 60 min
IV infusion (pediatric): 1.5 mg/kg in 25 mL of
0.9% of NaCl over 60 min; maximum dose
125 mg
Iron sucrose (Venofer)e HD patients with CKD receiving ESA IV push: 100 mg over 2–5 min General 25–1,000 mg
therapy IV infusion: 100 mg in maximum of 100 mL of
0.9% NaCl over 15 min
Nondialysis-CKD patients receiving or not IV push: 200 mg over 2–5 min on 5 different
receiving ESA therapy occasions within 14-day period
PD patients receiving ESA therapy IV infusion: 2 infusions, 14 days apart, of 300
mg in maximum 250 mL of 0.9% NaCl over
1.5 h, followed by 1 infusion, 14 days later, of
400 mg in maximum 250 mL of 0.9% NaCl
over 2.5 h
CKD, chronic kidney disease; ESA, erythropoietin-stimulating agent; HD, hemodialysis; PD, peritoneal dialysis.
a
All products may be administered IV push (small doses only).
b
Small dosing ranges (e.g., 25–150 mg per week) generally used for maintenance regimens. Larger doses (e.g. 1 gram) should be administered in divided doses.
c
Supplied in 2-mL single dose vials containing 50 mg of elemental iron per mL.
d
Available in colorless glass ampules containing 62.5 mg elemental iron (12.5 mg/mL).
e
Supplied in 5-mL single-dose vials containing 100 mg elemental iron (20 mg/mL).
Disorders
significant interactions have been reported. HD, hemodialysis; PTH, parathyroid hormone.
a
Peritoneal dialysis patients may be treated with oral doses of calcitriol (0.5–1.0 mcg) or
Dosing and Administration. Recommendations for vitamin D doxercalciferol (2.5–5 mcg) two or three times weekly. May also use oral calcitriol at 0.25 mcg daily.
therapy differ based on the stage of CKD.8 Because changes in vitamin b
If serum calcium <9.5 mg/dL, phosphorus <5.5 mg/dL, and Ca P <55 mg 2/dL2.
782 D metabolism can lead to deficiencies in vitamin D precursors in c
If serum calcium <10 mg/dL, phosphorus <5.5 mg/dL, and Ca × P <55 mg 2/dL2.
patients with stage 3 or 4 CKD, 25-hydroxyvitamin D levels should be From Eknoyan G et al. 8
TABLE 47-6 Phosphate-Binding Agents Used in the Treatment of Hyperphosphatemia in CKD Patients
measured in patients with PTH values above the upper recommended
Calcimimetics
SECTION 5

ranges of 70 pg/mL or 110 pg/mL Compound

for stages 3 and 4 CKD, respectively
Compound Trade Name Content (mg) Dose Titrationb Starting Doses Comments
(see Table 47–5). If the 25-hydryoxyvitamin D level is less than 30 ng/ Pharmacology and Mechanism of Action. Cinacalcet hydro-
Calcium carbonatea Tums 500, 750, 1,000, Increase or decrease by 0.5–1 g (elemental calcium)
chloride (Sensipar) First-lineis
agent; dissolution characteristics
a calcimimetic agentand approved for treatment
mL,(40% a elemental
vitamin D precursor (e.g., 1,250
ergocalciferol) is recommended
500 mg per meal (200 three times a day with phosphate binding affect may vary from
(Table
calcium)
8
47–7). To prevent Oscal-500 vitamin 1,250D insufficiency, mgdoses 600 to 800meals of sHPT in ESRD
ofcalcium)
elemental patients
product to product;and fordaily
try to limit treatment
intake of hypercalcemia in
units per day of ergocalciferol Caltrate 600 1,500
are recommended. According to the patients with parathyroid of elemental calciumcarcinoma.
to 1,500 mg/dayCinacalcet is the first agent in
Nephro-Calci
guidelines, active vitamin LiquiCal
D or1,500 an analog should be administered
1,200
this class to receive Approximately FDA 39 mg phosphorus bound
approval.
per 1 g calcium carbonate
This compound acts on the
orally (e.g., as oralCalciChew calcitriol, doxercalciferol,
1,250 or paricalcitol) when calcium-sensing receptor on the surface of the chief cell of the
Renal Disorders

PTH
Calciumremains
acetate elevated PhosLodespite adequate667 25-hydroxyvitamin
Increase or decreaseDbylevels. parathyroid
0.5–1 g (elemental calcium) gland First-linetoagent;mimic
comparable the effect
efficacy to cal- of extracellular ionized
(25% elemental
Active vitamin D therapy should be initiated,667 mg per meal (168
when warranted, inthree times a day withand increase
calcium cium carbonate with half the dose
the sensitivity of calcium-sensing receptor
of the
calcium) mg elemental calcium) meals elemental calcium; do not exceed 1.5
patients with stage 3 or 4 CKD as an oral daily dose of 0.25 mcg to calcium, subsequently reducing
gms of elemental calcium per day
PTH secretion.
calcitriol, 1 mcg doxercalciferol, or 1 mcg paricalcitol.102 For parical- Pharmacokinetics.
Approximately 45 mg phosphorus bound
The maximum plasma concentration of
citol the recommended daily dose is 2 mcg if the PTH is greater than per 1 g calcium acetate
cinacalcet is achieved By prescriptionin approximately
only 2 to 6 hours following oral
500 pg/mL. If theseRenagel
Sevelamer agents are administered
400, 800 intermittently (generally
Increase or decrease by 800–1,600 administration.
mg three times a First-line
The agent; lowers low-density
half-life lipopro-
is approximately 30 to 40 hours.
three times per week), the recommended initial dose
hydrochloride 800 mgisper
twice
meal the dailyday with meals
Cinacalcet has a tein cholesterol
large volume of distribution (approximately 1,000
dose.102 Higher starting doses may be required based on the severity More expensive than calcium products;
L), and is 93% topreferred 97% inbound patients attoriskplasma proteins, both characteris-
for extraskele-
of sHPT. Prior to starting therapy the serum calcium and phosphorus tics indicating that tal calcification
removal by dialysis is negligible. Cinacalcet is
should
Sevelamer becarbonate
well controlledRenvela (serum 800calcium <9.5 Same mg/dLas HCLand
salt phospho- Same as HCL salt
metabolized bySame the as HCL; associated with a lower risk
liver, specifically by the cytochrome P450
rus <4.6 mg/dL) to minimize the risk of hypercalcemia and an of GI adverse events than Renagel.
Lanthanum carbonate Fosrenol 250, 500, 750, Increase or decrease by 250–500 mg isoenzymes
three times a dayCYP3A4, CYP2D6, and CYP1A2.103
First line agent
elevated Ca × P. In patients with1,000 ESRD there is a250–500 clearly defined rolewith meals
mg per meal Available as chewable tablets
forAluminum
treatmenthydroxide withAlterna
active GELvitamin D or
600 mg/5 mL a vitamin – D analog because 300–600 mg Efficacy.
three times a dayIn placebo-controlled
Third-line agents; do not useclinicalconcurrentlytrials conducted in dialysis
the conversion of precursors Amphojel to300, vitamin D is impaired. Tablewith mealspatients (predominantly
600 (tablet);
active thoseproducts
with citrate-containing receiving hemodialysis) cinacalcet
320 mg/5 mL significantly decreased Reserve for short-term
PTH and use (4theweeks)
Cain × P product within the 6-
47–8 lists dosing recommendations based on PTH. Serum calcium
(suspension) patients with hyperphosphatemia not
and Ca × P should Alu-Capbe monitored400 regularly while the patient is month study period, regardless
responding to other binders of the severity of sHPT.104 The
Aluminum carbonate
receiving 8
therapy. Basaljel Dose adjustments 500 (tablet, should
cap- – made every 2 to450–500
be 4 starting
mg three timesdose
a day ofSame 30 asmg per dayhydroxide
for aluminum was titrated every 3 or 4 weeks to a
weeks based on PTH concentrations. sule); 400 mg/5
For patients who need to be maximum dose of 180 mg per day to achieve the target PTH of ≤250
with meals
mL (suspension)
converted
Magnesium from calcitriol Mag-Carb to paricalcitol,
70 capsule a dosing — conversion ratio 70 ofmg threepg/mL
times a dayandwith avoid hypocalcemia.
Third-line agent; diarrhea common;Approximately
moni- 66% and 93% of
of IV calcitriol to paricalcitol has been proposed; however, somemeals patients in the clinical
1:4 carbonate tor serumtrials were receiving concurrent vitamin D and
magnesium
Magnesium
clinicians suggest aMilk of
ratio of 1:3 to 300, 600 (tablet);
avoid oversuppression —
of PTH.8 300–400 mgphosphate
three times a day Same asrespectively.
binders, for magnesium carbonateIf a patient experienced symptoms
hydroxide magnesia 400 mg/5 mL, with meals
800 mg/5 mL of hypocalcemia or had a serum calcium <8.4 mg/dL, calcium
(suspension) supplements and/or calcium-based phosphate binders could be
Magnesium MagneBind 200 160 200 mg three times a day with
increased. Same as for calcium
If ineffective, carbonate and
the vitamin Dmagne-
dose could be increased. The
TABLE 47-7 Dosing
carbonate/calcium 200 Recommendations for Vitamin D in Patients meals (based median
on magne-
dose
sium carbonate
required to achieve the desired PTH by the end of the
carbonate with Stages 3 and 4 Chronic Kidney Disease sium content)
a
study period was 90 mg. Cinacalcet has also been studied in patients
Multiple preparations available which are not listed.
b Serum
Based on phosphorus levels, titrate every 25(OH)D
2 to 3 weeks until phosphorus goal reached. with Stage 3 and 4 CKD with sHPT and was effective in lowering
Definition (ng/mL) Dose of Ergocalciferola PTH while maintaining the Ca and P within the target ranges.105 This
Severe vitamin D binders
calcium-containing <5 necessary for 50,000 controlinternational units/wk orally
of phosphorus; ×
metoprolol, drug isorhowever
enalapril, oral iron were notobserved.
approved 84–86 for use in those with stage 2 CKD
Coadministra-
deficiency
however, their use may be limited by the frequent 12 weeks, of GI× 6 months
then monthly
occurrence because of
tion with ciprofloxacin did,the risk of result
however, hypocalcemia.
in a 50% decreaseBecauseincinacalcet was approved
side effects and the potential for magnesium accumulation. or 500,000 international units bioavailability
as a after
of the the K/DOQI
antibiotic. 84
There guidelines
is also some oninformation
bone disease to became available, the
single intramuscular dose suggest a potential interaction
challenge to between sevelamer
clinicians is in and cyclosporine
deciding how to most effectively use
Adverse Effects. Adverse effects of calcium-containing phosphate
Mild vitamin (decreased
×4 bioavailability of cyclosporine) and altered phosphorus
binders, as wellD as of sevelamer
5–15 and lanthanum, 50,000 areinternational units/wk orally
generally limited cinacalcet in conjunction with other therapies to manage hyperphos-
deficiency weeks,nausea,
then monthly binding in the presence of agents that increase gastric pH (e.g.,
× 6 months
to GI side effects, including constipation, diarrhea, vomiting,
omeprazole).87,88 phatemia and sHPT.
Consequently, it is prudent to monitor for changes
Vitamin
and D
abdominal pain. The16–30
risk of hypercalcemia 50,000 international
is also a concernunits/month
and orally
in phosphorus levels following initiation of concomitant therapy
mayinsufficiency
necessitate restriction of calcium intake 6from monthsthe combination Adverse Effects. The most frequently reported adverse events
with agents known to alter gastric pH. Drug interaction studies with
of calcium-containing binders and dietary intake. Aluminum bind-
lanthanum, with cinacalcet
although limited, havewereshownnausea and vomiting.
that coadministration with Although nausea and
25(OH)D, 25 hydroxyvitamin D.
a
Komplikasi
ers can no
25(OH)D
CKD
longer be recommended as first-line therapy because of
for patientswarfarin,
vomiting occurred more frequently with
with mild digoxin, and metoprolol did not affect the bioavailability of
cinacalcet, these events
the CNSlevels should and
toxicity be measured following theof6-month
the worsening anemiacourse of therapy with
associated
and severe vitamin D deficiency. those agents.81 were generally
In general, transient,
it is rational mild
to separate to moderate
the administration in nature, and infre-
! Hematologi
aluminum
From
accumulation. Although an effective phosphate binder,
G et al. 8 is often limited by side effects that include time of oral medications
quently led for which a reductionfrom
to withdrawal in bioavailability has 103
clinical trials.
use Eknoyan
of magnesium
a clinically significant effect (e.g., quinolones) from phosphate bind-
Eritropoetin
diarrhea, abdominal cramps, menurun, umumnya
hypermagnesemia, terjadi 6-12 bulan
and hyperkalemia.
ers by atsetelah ESRD
least 1 hour beforesehingga pasien
or 3 hours after mengalami
administration of the
Drug–Drug and Drug–Food Interactions. Calcium-containing phosphate binder. This is a key patient-counseling recommendation
anemia agents interfere with the absorption of several as patients are often switched from one phosphate binder to another
phosphate-binding
other oral medications that are commonly prescribed for CKD and it is easier for them to remember this general concept regarding
Terapi menggunakan
patients, including oral iron, zinc, and epo, namun
quinolone jika pasien
antibiotics. Data cukup sehat
phosphate bindersdapat
and othermenggunakan
medications. Many Fe, asam binders
phosphate folat
regarding drug interactions with sevelamer are limited; however, in are marketed as antacids or calcium supplements and often CKD
dan B12 no drug interactions with digoxin, warfarin, patients do not know why they have been prescribed these agents.
recent evaluations,

Clotting time normal, namun fungsi platelet terganggu dan menyebabkan bleeding time
memanjang
! Vascular dan hipertensi
Pada pasien non diabetik: hipertensi merupakan penyebab kematian pada CKD.
Retensi air dan sodium menyebabkan terjadinya hipertensi " terapi dengan membatasi sodium,
loop diuretic (jika fungsi ginjal masih bagus), dialysis
 Hipertensi yang resisten: karena kelebihan produk renin, peningkatan aktivitas saraf simpatik
serta defisiensi vasodilator (nitrit oksida)
Terapi dengan ACEI/ARB, vasodilator dan B bloker
! Jantung
Retensi cairan & hipertensi dapat menyebabkan LV hipertrofi
Pericarditis " jika terjadi peningkatan urea/fosfat/hiperparatiroid sekunder
! Dehidrasi
Pada sebagian pasien filtrasi normal, tetapi fungsi tubulus menurun
! Endokrin
Gangguan sistem reproduksi dimana terjadi penurunan libido dan ovulasi
! Kulit
Rasa gatal karena deposisi kalsium fosfat di jaringan " difenhidramin
Pigmentasi, pucat karena anemia
! Saluran pencernaan
Mual, muntah, anoreksia, nafas bau urin dan dispepsia
! Saraf dan psikiatri
Memengaruhi aktivitas Na/K ATP ase yang menyebabkan terganggunya neurotransmitter dan
uremia ensefalopati
! Uremia menurunkan sistem imun

!
!
!

!
!
!
!

!
!
 775

CHAPTER 47
Monitor Anemia Status
Consider and treat as appropriate

Iron Deficiency (see Figure 47–2) Infection or inflammatory disease

Hyperparathyroidism Aluminum toxicity
Vitamin B12 or folate deficiency Hypertension
Blood Loss Hemolysis

Chronic Kidney Disease: Management of Complications

Hb <10–11 g/dL Hb 11–12 g/dL Hb >12 g/dL
AT GOAL

No change in regimen,
Monitor Hb 1–2 times per month If receiving ESA therapy
discontinue or consider a dose
reduction of at least 25%

If naÏve to ESA therapy start either:

Epoetin alfa (IV or SC): Monitor
150–300 units/kg/week in divided doses • Hb at least once weekly until stable, then 1–2
Darbepoetin alfa (IV or SC): times per month
0.45 mcg/kg once weekly • Iron indices monthly for 3 months, then every 3
If receiving ESA therapy months (see Figure 47–2)
increase dose by 25%

Is there a poor response in Hb?

Yes No

Is there a functional iron Are there reasons for Monitor

Yes No Hb 1–2 times per month
See Figure 47–2 deficiency (TSat <20% resistance to erythropoietic
with normal ferritin)? therapy? Iron indices every
3 months

No Yes

Increase dose of ESA agent Treat underlying cause(s)

by 25%

FIGURE 47-3. Guidelines for erythropoietic stimulating agent therapy in the management of the anemia of chronic kidney disease. (ESA, erythropoietic-
stimulating agent; Hb, hemoglobin; SC, subcutaneous; TSat, transferrin saturation.)
Penatalaksanaan dasar CKD
! Mengobati penyakit penyerta
Pharmacology and Mechanism of Action. Iron supplements iron formulations also include ascorbic acid to enhance iron absorp-
provide the elemental iron required for production of hemoglobin tion. Although there is an association between ascorbic acid intake and
Kontrol tekanan darah ≤140/90 mmHg
and its subsequent incorporation in red blood cells, the net result of oxalate formation, this association is generally not observed at doses of
which is an increase in the transportation of oxygen to tissues. ascorbic acid contained in these iron formulations.
Kontrol gula darah
Supplementation of iron is necessary to replete iron stores and Intravenous iron preparations differ in the composition of the
maintain adequate iron for transport to the bone marrow. complex to which elemental iron is bound. These differences affect
Hilangkan sumbatan/obstruksi the rate of dissociation of iron from the complex to the reticuloendot-
Pharmacokinetics. Approximately 10% of orally administered helial system and subsequent storage as ferritin. The half-life of these
Obatiininfeksi
iron is absorbed saluran
the duodenum and kemih
upper jejunum. Absorption of formulations also differ: ferric gluconate (1 hour), iron sucrose (6
iron is decreased by food and achlorhydria. The heme form of oral hours), and iron dextran (40 to 60 hours). However, there is minimal
iron Kendalikan
! binds keseimbangan
to a different air dan
receptor in the GI tract garam iron, is
than nonheme to no correlation between the pharmacokinetics of these formulations
absorbed to a greater extent, and may be better tolerated.36 Some oral and their pharmacodynamic effects.37
! Kendalikan keseimbangan elektrolit
! Cegah dan obati renal osteodistrofi (misalnya dengan pentoksifilin)
! Obati uremia
Anemia: Fe, asam folat dan eritropoetin
Gatal: diet rendah protein, difenhidramin
 Mual: diet rendah protein
! Deteksi dini infeksi dan berikan terapi
! Pengaturan dosis obat
! Deteksi dini komplikasi dan obati
! Dialysis dan transplantasi

Pasien yang mendapatkan terapi CKD jika

! Pasien DM dengan urin ACR (albumin to creatinin ratio) >30mg albumin/g kreatinin
! Semua pasien nondiabetik dengan urin ACR >300mg albumin/g kretinin
! Pasien dengan eGFR <60ml/min/1.73m2

Terapi CKD adalah

! Diet rendah protein, natrium, kalium, fosfat, kalsium dan cairan
! Pantau Hb >11%, Ca 9-10mg%, PO4 3-4mg% dan iPTH 150-300 pg/ml
! Atasi faktor risiko CVD, terutama rokok dan hiperkolestrolemia