Gangguan ginjal akut (GgGA)

atau Acute kidney injury (AKI)

Linda Armelia

Definisi
AKI : penurunan mendadak fungsi ginjal (dalam 48 jam)
yang ditandai dengan:
peningkatan kadar kreatinin serum sebesar 0,3
mg/dl (26,4 umol/l) atau
kenaikan kadar kreatinin serum lebih dari 1,5 kali
(>50%) bila dibandingkan dengan kadar sebelumnya
atau
penurunan urine output menjadi kurang dari 0,5
cc/jam selam lebih dari 6 jam
Roesli R, 2008
4/30/2013

Classification and diagnosis

1
2
3

*setting a 48- hour window

*failure if treated with RRT

Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Crit Care 2007; 11:R31.
Cruz D, Ricci Z, Ronco C.Critical Care 2009, 13:211

4/30/2013

Classification - Severity Staging of Patients

with AKI
RIFLE - Risk / AKIN
Stage 1

RIFLE - Injury /
AKIN Stage 2

RIFLE - Failure /
AKIN Stage 3

Loss and End stage

renal diseases

the most important group, due to the

potential of reversibility of this stage*
the likelihood that the are purely functional (i.e. prerenal)
becomes smaller
one third (36.8%) of the patients proceeded to stage 3**
urine osmolality and FE Na discriminate between prerenal
physiology and renal injury

RRT becomes an important consideration

expanded to providing supporting therapy**
13.8% of AKI patients remained dialysis dependent***
full recovery was achieved in less than 50% of survivors of
AKI requiring RRT

* Srisawat N, Hoste EAE, Kellum JA. Blood Purif 2010;29:300307.

** Hoste EA, Clermont G, Kersten A, Venkataraman R, Angus DC, De Bacquer D, et al. Crit Care 2006; 10:R73.
*** Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C. JAMA
294: 813818, 2005

Acute Kidney Failure Symptoms

Some people have no symptoms, at

least in the early stages.
The symptoms may be very subtle.
Decreased urine production
Body swelling
Problems concentrating
Confusion
Fatique
Lethargy
Nausea, vomiting
Diarrhea
Abdominal pain
Metallic taste in the mouth
4/30/2013

Algoritme for D/ AKI

Memenuhi kriteria D/ AKI

Langkah 1

Ya

AKI

Langkah 2

Langkah 3

Langkah 4

4/30/2013

D/ Etiologi AKI

D/ klinis dan tahapan AKI

Gejala: komplikasi
Pemeriksaan penunjang

Tidak

Observasi 24-48 jam

Tidak

Bukan AKI

Membedakan AKI dengan PGK/aCRF

Gangguan ginjal

Gangguan ginjal
normal

Ukuran ginjal

Tidak ada

Riw. Peny. Ginjal (kronis)h

ada

Tidak ada

4/30/2013

Gangguan ginjal

ya

Riw. Peny. Ginjal akut (E/AKI)

Hipertensi, anemia,
hiperfosfatemia

reversibell

kecil

ada

Tidak ada

ada
tidak

Acute Kidney Failure Causes

Causes of AKI fall following categories:
Prerenal: the flow of blood before it reaches the kidneys
Postrenal: the movement of urine out of the kidneys
Renal: Problems with the kidney itself that prevent proper
filtration of blood or production of urine

4/30/2013

Acute tubular necrosis (ATN)

The kidney tubules are damaged and do not function normally.
Usually the end result from the other causes of ARF.
When there is necrosis cells form the tubules become
dysfunctional and "die".
90% of cases of primary ARF
Causes : shock, drugs (esp. antibiotics) and chemotherapy
agents, toxins and poisons and dyes used in certain kinds of xrays
Symptomstiredness, swelling, lethargy, nausea, vomiting,
abdominal pain, loss of appetite, and rash.
Sometimes there are no symptoms.
4/30/2013

12

Pathophysiology of Ischemic ARF

MICROVASCULAR
Glomerular

Medullary

Vasoconstriction in response to :
endothelin, adenosine,
angiotensin II, thromboxane A2,
leukotrienes, sympathetic nerve
activity

Vasodilation in response to :

nitric oxide, PGE2, acetylcholine

bradykinine

Endothelial and vascular

smooth muscle cell structural

damage
Leucocyte-Endothelial adhesion
vascular obstruction, leucocyte
activation and inflammation
J am Soc Nephrol 14: 2199-2210, 2003

O2

TUBULAR
Cytoskeletal breakdown

Inflammatory
and
vasoactive
mediators

Loss of polarity
Apoptosis and necrosis

Desquamation of viable
and necrotic cells
Tubular obstruction
Backleak

Aki in specific setting - Sepsis

Ronco C. Clin J Am Soc Nephrol 3: 531-544, 2008

Aki in specific settings contrast induced

Efforts come with little success 12% prevalence of CIN today remains
unchanged.
Low osmotic vs. iso osmotic agents conflicting data, tends to favor iso osmotic
agents.*
Volume expansion seems to be beneficial.
NaCl i.v. (0.9%), 1 mL/kg per hour, 12 hours before and after CM
administration.*
Sodium bicarbonate infusion proved beneficial.**
154 mEq/L sodium bicarbonate in dextrose and H2O.
IV 3 mL/kg/h for 1 hour immediately before contrast injection. Then, the same
fluid at a rate of 1 mL/kg/h during contrast exposure and for 6 hours after the
procedure.
NAC contrasting evidence, others no benefit.*

*Reddan D. JNEPHROL 2009; 22: 333-351

**Briguori C. Circulation 2007;115;1211-1217

Aki in specific settings cardiorenal syndrome

Cardio-Renal Axis blunted in ADHF
In ADHF
Release of vasoconstricting and sodium-retaining neurohormones (Ang II, NE,
endothelin, adenosine, and arginine vasopressin )
Release of vasodilatory and natriuretic hormones (natriuretic peptides,
prostaglandins, bradykinin, and nitric oxide)

Renal failure in ADHF hemodynamic and neurohormonal dysregulation

Important management issues
Use of continuous loop diuretic is recommended
Use of anti-aldosterone if there is diuretic resistance, caution for hyperkalemia
Nesiritide associated with worsening of renal function, especially in
combination with diuretics

Sarraf M. Clin J Am Soc Nephrol 4: 20132026, 2009

Aki in specific settings hepatorenal syndrome

Three main causes of AKI in chronic liver disease:
Volume responsive pre-renal failure (68%),
Volume unresponsive pre-renal failure with tubular dysfunction and
ATN (33%), and
Hepatorenal syndrome type 1 (25%)

Hepatorenal syndrome
Liver transplantation the best therapeutic option.
Survival improved with vasoconstrictors (ie.terlipressin) with
albumin, or
Transjugular intrahepatic portosystemic shunt (TIPS).

RRT is usually only started if liver transplantation is

considered a viable option
Slack et al. Critical Care 2010, 14:214
Fry AC. Postgrad Med J 2006;82:106116

Aki in specific settings aki in lung dysfunction

Renal failure increasing pulmonary vascular permeability
and promoting pulmonary hemorrhage.
Loss of the normal balance of immune, inflammatory, and soluble
mediator metabolism.
AKI downregulate pulmonary epithelial Na, K ATPase, EnaC, and
aquaporin 5.
AKI increase ADMA decrease eNOs increase free radicals
lung injury
AKI increase IL-1, TNF-a, ICAM-1 cardiac dysfunction lung
injury

Stresses the importance of low tidal volume ventilation in

AKI
Microvasc Res. 2009 January ; 77(1): 812.

Aki in specific settings - elderly

Anatomic

Aging
kidney

Physiologic

Loss of renal mass

Glomerular drop out and glomerulosclerosis
Diminished glomerular filtering surface area
Decreased tubular size and number
Increased tubulointerstitial fibrosis
Thickened glomerular and tubular basement
membranes
Decreased afferent arteriolar luminal area
Increased arteriosclerosis

Decreased renal blood flow

Decreased glomerular filtration rate
Diminished urinary concentrating and diluting
capacity
Diminished capacity for sodium conservation
Decreased plasma renin and aldosterone levels
Decreased prostaglandin production
Increased vasoconstrictive response to stimuli
(e.g., volume depletion)

Abdel Kader K. Clin Geriatr Med. 2009 August ; 25(3): 331358.

Aki in specific settings hiv nephropathy

Incidence of AKI were higher than HIV negative (6% vs. 2.7%)
Risk factors for AKI in HIV:
Older age
Diabetes mellitus
Chronic kidney disease
Liver disease/ Hepatitis C
Low CD4 count
High HIV RNA
History of AIDS-defining illness
History of antiretroviral exposure
Etiology of AKI in HIV
Intrinsic AKI (ATN and nephrotoxic drugs) 46%
Nephrotoxic drugs pentamidine, amphotericin B, acyclovir, streptomycin, ARV
(indinavir, atazanavir, didanosine).
Prerenal (38%)
Overall, 52% associated with infection
HIV-associated nephropathy (HIVAN), rare but relevant

Kalim S. Semin Nephrol. 2008 November ; 28(6): 556562

AKI: urgent need for early diagnosis

Early forms of AKI are often reversible
Early diagnosis may enable timely therapy
Animal and human studies have revealed a
narrow window of opportunity
The paucity of early biomarkers has impared
our ability to institute timely therapy in
human

4/30/2013

22

Diagnosis Biomarker in diagnosis of AKI

SCr imperfect tubular secretion, steady-state
determination and confounding (muscle mass and
volume distribution).
Cystatin C (LMW protein produced by all nucleated cells)
Freely filtered then reabsorbed and metabolized by
the proximal tubule
Cystatin C may be superior to SCr for the earlier
detection of reduced GFR
Srisawat N, Hoste EAE, Kellum JA. Blood Purif 2010;29:300307.

Diagnosis biomarkers of AKI

Biologic response to ischemic or nephrotoxic injury early
indicators of AKI.
Urine >>> serum or plasma to identify the earliest markers of
kidney injury.
Urinary injury markers may be present in the urine because of:
Impaired tubular reabsorption and catabolism of filtered
molecules,
Release of enzymes or exosomes from tubular cells, and
As a response of tubular cells to ischemic or nephrotoxic
injury.
Srisawat N, Hoste EAE, Kellum JA. Blood Purif 2010;29:300307.

Biomarkers: from bench to bedside

Discovery phase
Identification of candidate biomarkers using basic
science technologies

Translational phase
Development of robust assays for the candidate
biomarker and testing in limited clinical studies

Validation phase
Testing the assays in large clinical trials
4/30/2013

25

Soni SS. Blood Purif 2009;28:165174

Urinalysis
Unremarkable in pre and post renal causes
Casts: differentiates ATN vs AIN vs AGN
Muddy brown casts ATN
WBC casts AIN

Specific gravity: </> 1.020

Occult blood

4/30/2013

27

Urinalysis in Acute Kidney Injury

Normal/bland

Abnormal sediment

Hematuria
RBC casts
proteinuria
Prerenal
Postrenal
Oncotic
AKI

Glomerulopathy
Vasculitis
Thrombotic MA

WBC
WBC casts

Pyelonephritis
Interstitial
nephritis

Hilton R. Acute renal failure. BMJ 2006;333:78690

Eosinophils

AIN
Atheroembolic
AKI

RTE cells Crystalluria

NonPigmented
albumin
casts
proteinuria
ATN
Myoglobin
Hemoglobin

Uric acid
Toxins
Drugs

Plasma cell
dyscrasia

Urine diagnostic indices in pre-renal vs intrinsic renal ARF

Fry AC. Postgrad Med J 2006;82:106116

Other test
24 hour urine for protein and
creatinine
urine eosinophil Hansen stein
Cholesterol, albumin, glucose
ANA panel, C-ANCA, Hep B/C,
ASTO, HIV
Post void residual or
catheterization
Plain film, USG, CT or MRI
distinguish between acute and
CRF and to exclude acute
obstructive uropathy
4/30/2013

Radionuclide scans ass RBF,

GF, tubule function and
infiltration
MRA detecting RAS,
evaluation of acute
renovascular crises
Dopler USG
Spiral CT
PSA
Renal biopsy

32

Management
Prevention
Etiology treatment correct prerenal and post
renal factor, treat underlying diseases, stop
nephrotoxic drugs
Prevention additional injury
Establish diuresis
Treatment of complication
Conservative measurement
RRT
4/30/2013

33

Treatment - principles

Identify and correct pre-renal and post-renal factors

Optimise cardiac output and renal blood flow
Review drugs
Accurately monitor fluid balance and daily body weight
Identify and treat acute complications
Optimise nutritional support
Identify and aggressively treat infection
Identify and treat bleeding tendency
Initiate dialysis before uraemic complications emerge

Hilton R. Acute renal failure. BMJ 2006;333:78690

Treatment Renal replacement therapy in AKI

Conventional indications for RRT initiation in AKI

Refractory hyperkalemia,
Severe metabolic acidosis,
Hypervolemia, and
Uremic end-organ complications.
Early vs. Late initiation of RRT
Data inconclusive on specific benefit.
One retrospective trial Early (BUN<60mg/dL) vs. Late (BUN >60mg/dL)
survival better on early RRT group (39% vs. 20%).*
One RCT trial early dialysis (7 hours of UO <30 mL/h) vs. Late (42 hours
of UO <30mL/h) did not affect mortality or dialysis dependence in
survivors.**
One prospective trial RRT with blood urea nitrogen levels of 76 mg/dL (27
mmol/L) or less (adjusted hazard ratio, 0.54; 95% CI, 0.34-0.86).***

*Gettings LG. Intensive Care Med. 1999 Aug;25(8):805-13

**Boumann CS. Crit Care Med. 2002 Oct;30(10):2205-11.
***Liu KD. Clin J Am Soc Nephrol. 2006 Sep;1(5):915-9. Epub 2006 Jul 6.

Volume control
Must know patients status fluid
Pre-renal azotemia fluid can improve condition
ATN fluid can be harmful, causing fluid overload

Monitor fluid balance carefully

Maintance euvolemia, tissue perfusion, electrolyte
balance
Crystaloid
Use in hypovolemia
500-1000 ml of normal saline over 30 minutes

Colloid

Use in hypovolemia due to hemorrhage

Blood , albumin
4/30/2013

36

Treatment renal replacement therapy in aki

Intermittent hemodialysis

Alternate days
4 or more hours
Blood flows of 250 mL/min or greater
Sufficient with or without concomitant critical illness.

CRRT
Target dose should be 35 mL/kg per hour (3 L/h in a 70kg person)

Pannu N. JAMA. 2008;299(7):793-805

Guide for volume expansion

CVP 8-14 cmH2O

PCWP 12-16 mmHg
Urine output 0,5-1 mL/kg/hour
IWL 500 mL/day

4/30/2013

38

Diuretics
For use in pts with adequate IV volume
Help kidneys to start working again increase
tubular flow, preventing obstruction
Loop diuretic increase RBF
Mannitol reduces cells swelling
Main goal is to maintain UOP
Loop diuretics
Furosemide most commonly used
Initial dose 40-80 mg iv bolus, max dose 2000 mg/day
Continous infusion start 40-80 mg iv bolus, then starr 1020 mg/hour and titrate up
4/30/2013

39

Dopamine
Low dose 0,5-2 ug/kg/min can selectively
dilated renal blood vessel increases RBF,
GFR and UOP
Side effect : vasoconstriction at higher doses,
tachycardia, angina
MP UOP, BP, COP

4/30/2013

40

Conservative measurement Prevent futher

ischemic toxic injury

Fluid balance Monitoring I/O and body weight

Fluid restriction
Usually < 1 L/dayin oliguric ARF
Total intake < urine output + extrarenal losses

Electrolit and aci-base balance

Hyperkalemia, hyponatremia, hyperphosphatemia
Keep serum bicarbonate > 15
Treat hypocalcemia only if symptomatic

Uremia nutrition restriction protein and but maintain

calori intake
Drug
Review all medication
Stop magnesium containing medication
4/30/2013

41

Nutrition implication of ARF

ARF causes :
anorexia, nausea, vomiting,bleading
rapid nitrogen loss and LBM loss (hypercatabolism)
Gluconeogenesis with insulin resistance

Dialisys loss AA and protein

Uremic toxic impaired glucose utilization and protein
syntesis

4/30/2013

42

Complication

Cardiopulmonary
Metabolic
Gastrointestinal
Neurogenic
Hematologic
Infection

4/30/2013

44

Prognosis
Incidence rate of mortality 8.9 vs. 4.3 per 100 personyears in survivors of AKI vs. without AKI (RR 2.59, 95% CI
1.97-3.42).
AKI was
Associated independently with mortality risk adjusted RR 1.6-3.9
Associated with myocardial infarction RR 2.05, 95% CI 1.61-2.61

The incidence rate of CKD after AKI 7.8 per 100 patient
years.
Rate of ESRD was 4.9 per 100 patient-years.

Coca SG. Am J Kidney Dis. 2009 June ; 53(6): 961973.

Gagal ginjal kronik (GGK) atau

Chronic kidney diseases (CKD)

Penyakit Ginjal Kronik

Klasifikasi PGK berdasarkan perkiraan LFG
Stage

Gambaran

LFG (ml/min/1.73m2 )

Kerusakan ginjal dengan normal atau peningkatan 90 dengan bukti lain

LFG
kerusakan GK*

Kerusakan ginjal dengan penurunan LFG minimal

60 89 dengan bukti lain

kerusakan GK*

3A
3B

Penurunan LFG sedang

Penurunan LFG sedang

45 - 59
30 44

Penurunan LFG berat

15 29

Gagal ginjal

< 15 atau dialysis

KDOQI-KDIGO Guidelines 2012

Cause

Level of proteinuria

A1

A2

A3

Diabetes

Urinary albumin (mg/day)

Urinary albumin/Cr ratio
(mg/g Cr)

Normal

Microalbu
minuria

Macroalbu
minuria

Nephritis
Hypertension
Polycistic kidney dis
Unknowm
Other

Urinary protein (mg/day)

Urinary protein/Cr ratio

Normal

Mild
Severe
proteinuria proteinuria

Level of
GFR
(mL/min/1
.73m2)

G1

Normal or
high

90

G2

Mild

60 89

G3a

Mild to
moderate

45 59

G3b

Moderate to
sever

30 44

G4

Severe

15 29

G5

Renal failure

< 15

11/28/2012

11/28/2012

Etiologi
Chronic Kidney Disease (CKD)
Hilangnya fungsi nefron karena:
Penyakit ginjal primer, Penyakit sistemik
Kerusakan ginjal sekunder
Penyebab ESRD/PGT:
diabetes (43%)
hipertension (26%)
GN kronik (8%)
Pdrt dg pykt KV 5x mempunyai resiko KV
Prediksi kematian: albumin rendah, komorbiditas, malnutrisi dan
anemia

Estimated GFR (eGFR) Equations

Serum Creatinin (mg/dl) eGFR (ml/min/1.73m2):
a) CKD-EPI = 141 min(sCr/, 1) max(sCr/, ,1)-1.209
0.993Age 1.018 [if female]
= 0.7 for females and 0.9 for males
=-0.329 for females and -0.411 for males
min indicates the minimum of sCr/ or 1
max indicates the maximum of sCr/ or 1
b) S-MDRD = 175 sCr -1.154 Age -0.203 0.742 [if female]
c) C-MDRD = 175 sCr -1.154 Age -0.203 1.233 0.742 [if female]
d) J-EPI = 0.813 CKD-EPI
e) T-GFR = 375.5 sCr 0.848 Age-0.364 0.712 [ if female]
11/28/2012

MANAGEMENT OF CKD

Treatment of reversible causes of renal dysfunction

Preventing or slowing the progression of renal disease
Treatment of the complications of renal dysfunction
Identification and adequate preparation of the
patient in whom renal replacement therapy will be
required

Reversible causes of renal dysfunction

Identified and corrected underlying reversible process :

1.

Decreased renal perfusion

2.

Administration of nephrotoxic drugs

3.

Urinary tract obstruction

Decreased renal perfusion

Common causes of potentially reversible declines in renal function :
Hypovolemia (such as vomiting, diarrhea, diuretic use, bleeding)
Hypotension (due to myocardial dysfunction or pericardial
disease)
Infection (such as sepsis)
Administration of drugs which lower the glomerular
filtration rate (such as nonsteroidal antiinflammatory
drugs and ACE inhibitors)

Hypovolemia should be diagnosed by the history and

physical examination:
The presence of relative hypotension
A low jugular venous pressure

Poor skin turgor.

A judicious trial of fluid repletion may result in

the return of renal function to the previous
baseline.

Administration of nephrotoxic drugs

The administration of drugs or diagnostic agents
which adversely affect renal function are a frequent
cause of worsening renal failure.
Aminoglycoside antibiotics (particularly with
unadjusted doses),
nonsteroidal antiinflammatory drugs, and radiographic
contrast material, particularly in diabetics.

The administration of such drugs should therefore be

avoided or used with caution in patients with
underlying chronic renal disease

Urinary tract obstruction

Should always be considered in the patient with
unexplained worsening renal function.
Patients with slowly developing obstruction typically
have no changes in the urinalysis, no symptoms
referable to the kidney, and initially maintain their
urine output.
Given this lack of clinical clues, renal ultrasonography
is often performed to exclude urinary tract
obstruction in patients with an unexplained elevation
in the serum creatinine.

Slowing the rate of progression

The progression in chronic renal disease may be due
to secondary factors that are unrelated to the activity
of the initial disease.
The major factors are thought to be intraglomerular
hypertension and glomerular hypertrophy leading to
glomerular scarring (glomerulosclerosis).

Additional causes may include hyperlipidemia,

metabolic acidosis, and tubulointerstitial disease.

 In diabetic nephropathy and nondiabetic chronic

renal diseases that the administration of angiotensin
converting enzyme (ACE) inhibitors or angiotensin II
receptor blockers (ARBs) slows the progression of
chronic renal failure, with the greatest benefit in
patients with higher degrees of proteinuria.

JNC 7 and the K/DOQI

Clinical Practice Guidelines on hypertension
Antihypertensive agents in chronic kidney disease
recommended:
Aggressive goals are recommended for both proteinuria
and blood pressure.
Antihypertensive therapy is given for both renal
protection and cardiovascular protection, since chronic
kidney disease is associated with a marked increased in
cardiovascular risk.

 A reduction in protein excretion to < 500 to 1000

mg/day
A reduction in blood pressure to < 130/80 mmHg.

Lower systolic pressure may be more effective in

slowing progressive renal disease in patients with a
spot urine total protein-to-creatinine ratio 1000
mg/g (which represents protein excretion of greater
than 1000 mg/day)
Caution is advised about lowering the systolic blood
pressure below 110 mmHg.

 These aggressive goals will require therapy with

multiple drugs.
Starting with an ACE inhibitor or an ARB
If the blood pressure goal is not reached, a diuretic
should be added followed, if necessary by diltiazem,
verapamil, or a beta blocker.
If the proteinuria goal is not reached after use of the
above drugs to reach goal blood pressure, add an ACE
inhibitor or ARB, whichever has not been used.

 ACE inhibitors and ARBs can cause a decline in renal

function and a rise in plasma potassium that typically
occur soon after the onset of therapy. As a result, a
repeat plasma creatinine and potassium should be
measured within three to five days.
In patients with nonproteinuric renal disease, most
often a tubulointerstitial disease, none of the above
drugs has been shown to slow progression of the renal
disease and therapy is limited to blood pressure
control.

Other therapeutic modalities also may

offer some renal protection:
Protein intake restrict to 0.8 to 1.0 g/kg of high biologic
value protein, accompanied by phosphate restriction

Hyperlipidemia and metabolic acidosis should be

treated, they may enhance the rate of progression of
the renal disease.
Smoking cessation, with smoking stoppage being
associated with a reduced rate of progression of renal
failure . Heavy smoking also correlated with increased
risk of kidney disease.

Treatment of complication of renal

dysfunction

Volume overload
Hyperkalemia
Metabolic acidosis
Hyperphosphatemia
Hypertension
Anemia
Malnutrition
Hyperlipidemia
Bone disease
Pericarditis

Volume overload
Sodium and intravascular volume balance are usually
maintained via homeostatic mechanisms until the GFR falls
below 10 to 15 mL/min.
Patient with mild to moderate chronic renal failure is less able to
respond to rapid infusions of sodium and is therefore prone to
fluid overload.
Patient generally respond to the combination of dietary sodium
restriction and diuretic therapy, a loop diuretic given daily.
Limiting sodium intake may also help decrease progression of
chronic kidney disease by lowering intraglomerular pressure

Hyperkalemia
Develops in the patient who is: oliguric , high potassium diet,
increased tissue breakdown, or hypoaldosteronism and impaired
cell uptake of potassium.

Due to ACE inhibitor or ARB therapy is occur in patients in whom

the serum potassium concentration is elevated or in the high
normal range prior to therapy.
Institution of a low-potassium diet or concurrent use of a loop
diuretic often ameliorates the degree of hyperkalemia.

Low dose Kayexalate (5 grams with each meal) can be used to

lower the serum potassium concentration.

Hyperkalemia
Prevention
A low potassium diet (eg, less than 40 to 70 meq/day
[1500 to 2700 mg/day]
Avoiding the use of drugs that raise the serum
potassium concentration such as nonsteroidal
antiinflammatory drugs.
Nonselective beta blockers make the postprandial rise
in the serum potassium concentration but does not
produce persistent hyperkalemia

Metabolic acidosis
Tendency to retain hydrogen ions.
Progressive metabolic acidosis with the serum
bicarbonate concentration tending to stabilize between
12 and 20 meq/L, and rarely falling below 10 meq/L.
Exogenous alkali was not usually given to treat the
generally mild metabolic acidosis (arterial pH generally
above 7.25) in asymptomatic adults with renal failure.

This was primarily due to concerns related to the

exacerbation of volume expansion and hypertension.

Two major reasons why treatment of the

acidemia may be desirable:
Bone buffering of some of the excess hydrogen
ions is associated with the release of calcium and
phosphate from bone, which can worsen the
bone disease.
Uremic acidosis can increase skeletal muscle
breakdown and diminish albumin synthesis,
leading to loss of lean body mass and muscle
weakness.

 Alkali therapy to maintain the serum

bicarbonate concentration above 22 meq/L.
Sodium bicarbonate (in a daily dose of 0.5 to 1
meq/kg per day) is the agent of choice.
Sodium citrate (citrate is rapidly metabolized to
bicarbonate) should be avoided in patients who
also taking aluminum-containing antacids, it
markedly enhances intestinal aluminum
absorption.

Hyperphosphatemia
Phosphate retention begins early in renal disease.
Due to the reduction in the filtered phosphate load.
Phosphate retention is intimately related to the common
development of secondary hyperparathyroidism.
Hypersecretion of parathyroid hormone (PTH) is initially
appropriate.
PTH can correct both hyperphosphatemia and hypocalcemia.
Phosphate balance and a normal serum phosphate
concentration are generally maintained in patients with a GFR
of greater than 30 mL/min.

Hyperphosphatemia (cont)
Dietary phosphate restriction limit the development of
secondary hyperparathyroidism.
An intake of about 800 mg/day. (recommended by the
K/DOQI guidelines)
Once the GFR falls below 25 to 30 mL/min, the
addition of oral phosphate binders are usually
required to prevent hyperphosphatemia.
The K/DOQI guidelines recommend that serum
phosphorus levels should be between 2.7 and 4.6
mg/dL (stage 3 and 4 chronic kidney disease)
Between 3.5 and 5.5 mg/dL (stage 5 disease)

Hyperphosphatemia (cont)
Phosphate binders: calcium carbonate, and calcium
acetate, are most effective if taken with meals to bind
dietary phosphate.
In patients with stage 3 to 5 CKD, the K/DOQI
guidelines suggest that total elemental calcium intake
should not exceed 2,000 mg/day.
Hypercalcemia is a common complication of this
regimen, particularly in patients also treated with
calcitriol to protect against the development of renal
osteodystrophy. Thus, careful monitoring of the serum
calcium concentration is essential.

Hyperphosphatemia (cont)
Sevelamer contains neither calcium nor aluminum, is a
cationic polymer that binds phosphate through ion
exchange.
Sevelamer controls the serum phosphate concentration
without inducing hypercalcemia.
It may be best used in patients who cannot tolerate
calcium-based phosphate binders (eg, due to
hypercalcemia or constipation) or have persistent
hyperphosphatemia.
It may also be used in combination therapy with
calcium-containing antacids among those with serum
phosphate levels consistently above target levels despite
single-agent binder therapy.

Hyperphosphatemia (cont)
Most other phosphate binders should be avoided:

Aluminum hydroxide, the previous standard, because of the

gradual induction of aluminum toxicity

Magnesium-containing antacids (such as magnesium

hydroxide), because of the risk of hypermagnesemia and the
frequent development of diarrhea

Calcium citrate, since it markedly increases intestinal

aluminum absorption

The increased intake of calcium may enhance coronary

arterial calcification, to be associated with the development
of coronary atherosclerosis.

Anemia (cont)
The 2000 K/DOQI guidelines: initial erythropoietin
dose 80 to 120 U/kg per week.
Erythropoietin given in two to three doses per week
It is currently commonly given only once per week (or
even less frequently).
In practice begin most patients on 10,000 U
subcutaneously once weekly.
If necessary, subsequent adjustments are made in
interval and/or dose. Initially, to help detect changes
in levels, weekly testing of the hemoglobin level is
recommended.

Anemia (cont)
Darbepoetin alfa
Another erythropoietic agent, is also indicated for the
treatment of anemia associated with chronic kidney
disease.

Three-fold longer half-life and greater biological activity

of darbepoetin alfa enables this agent to effectively
maintain target hemoglobin levels with less frequent
dosing.
The infrequent darbepoetin alfa dosing schedule of
once weekly or once every two weeks, with the
possibility of monthly dosing in some patients.

Anemia (cont)
The recommended starting dose of darbepoetin alfa in
recombinant erythropoietin-naive patients with
chronic kidney failure is 0.45 g/kg administered once
weekly.
Data in patients with chronic renal failure who are not
dialysis dependent also demonstrate that darbepoetin
alfa administered once every other week at a dose of
60 g is an effective dosing strategy.
Darbepoetin alfa can be given by either intravenous or
subcutaneous injection.

Anemia (cont)
An adequate response to erythropoietin or darbepoetin alfa
requires the maintenance of sufficient iron stores.
The 2006 K/DOQI guidelines suggest administering iron to
maintain the percent transferrin saturation 20 percent, and
the serum ferritin level >100 ng/m.

If oral iron is given, adults should receive a daily dose of

approximately 200 mg of elemental iron, usually as ferrous
sulfate 325 mg three times daily (65 mg elemental iron per
tablet).

Dyslipidemia
Abnormal lipid metabolism is common in patients with
renal disease.
The primary finding in chronic renal failure is
hypertriglyceridemia with the total cholesterol
concentration usually being normal (perhaps due in
part to malnutrition in some patients).

Patients with chronic renal failure should be assessed

for dyslipidemia, including a total cholesterol, LDL,
HDL, and triglycerides.

Dyslipidemia (Cont)
Dietary modification may be helpful for the
hypertriglyceridemia.

Drug therapy in patients without renal failure may be

beneficial in selected patients with isolated marked
hypertriglyceridemia (serum triglycerides 500 mg/dL)
who have proven coronary disease, a strong family
history of CHD, or multiple coexisting cardiac risk
factors.

Dyslipidemia (Cont)
A statin can safely lower the plasma cholesterol concentration to
or near acceptable levels.
The goal LDL-cholesterol is similar to that in patients with CHD,
which has been less than 100 mg/dL (2.6 mmol/L).

A similar more aggressive lipid-lowering goal, beginning with

statin therapy, should be administered to patients with chronic
renal failure.
Lipid lowering may have an additional benefit in patients with
chronic renal failure, which is slowing the rate of progression of
the underlying renal disease.

Treatment of complications of ESRD

Once the patient has reached the stage of
near end-stage renal disease (GFR less than 15
mL/min), signs and symptoms related to
uremia begin to occur, such as:
Malnutrition, anorexia, nausea, vomiting,
fatigue, sexual dysfunction, platelet
dysfunction, pericarditis, and neuropathy.

Malnutrition
Malnutrition is common in patients with advanced
CKD because of: a lower food intake (principally due
to anorexia), decreased intestinal absorption and
digestion, and metabolic acidosis.
Among participants 60 years of age in the United
States Third National Health and Nutrition
Examination Survey (NHANES), a GFR <30 mL/min was
independently associated with malnutrition (odds
ratio of 3.6)
Many additional studies have shown a strong
correlation between malnutrition and death in
maintenance dialysis patients.

Malnutrition (Cont)
A low plasma concentration of albumin and/or
creatinine (which varies with muscle mass as well as
glomerular filtration rate) may be indicative of
malnutrition.

Serum albumin concentration and body weight should

be measured serially every one to three months for
those with GFRs <20 mL/min, and more frequently if
necessary for those with GFRs 15 mL/min

Malnutrition (Cont)
Protein restriction remain controversial, it is probably
reasonable to restrict intake to 0.8 to 1.0 g/kg of high
biologic value protein since this level of restriction
avoids protein malnutrition and may slow
progressive disease.
It is reasonable to prescribe this diet to all patients
with a GFR below 20 mL/min per 1.73 m2.

The diet of most patients with chronic renal failure

should provide approximately 30 to 35 kcal/kg per
day.

Uremic bleeding
An increased tendency to bleeding is present in both acute and
chronic renal failure.
This appears to correlate most closely with prolongation of the
bleeding time, due primarily to impaired platelet function
No specific therapy is required in asymptomatic patients.
However, correction of the platelet dysfunction is desirable in
patients who are actively bleeding or who are about to undergo
a surgical or invasive procedure (such as a renal biopsy).
A number of different modalities can be used in this setting,
including the correction of anemia, the administration of
desmopressin (dDAVP), cryoprecipitate, estrogen, and the
initiation of dialysis.

Pericarditis
Fever, pleuritic chest pain, and a pericardial friction rub are the
major presentations of uremic pericarditis.
The electrocardiogram does not usually show the typical
diffuse ST and T wave elevation, presumably because this is a
metabolic pericarditis and epicardial injury is uncommon.
The development of unexplained pericarditis in a patient with
advanced renal failure is an indication to institute dialysis
(providing there is no circulatory compromise or evidence of
impending tamponade).
Most patients with uremic pericarditis respond rapidly to
dialysis with resolution of chest pain as well as a decrease in
the size of the pericardial effusion.

Choice of renal replacement therapy

Hemodialysis (in-center or at home), peritoneal dialysis
(continuous or intermittent modalities), and renal
transplantation (living or deceased donor).
Patients with a GFR < 30 mL/min per 1.73 m2 should be
educated
Kidney transplantation is the treatment of choice for end-stage
renal disease
Not all patients are appropriate candidates for a renal allograft
because of absolute and/or relative contraindications to this
procedure.
Referral to a transplant program should occur once renal
replacement therapy is thought to be required within the next
year

Choice of renal replacement therapy

Living donor transplants have the additional
advantage of being performed with minimal
delay, thereby permitting preemptive
transplantation (transplantation prior to
dialysis).
There is some evidence that such patients
have improved graft survival compared to
those who undergo a period of dialysis before
transplantation

Preparation for hemodialysis

Hemodialysis requires a stable access to the
bloodstream to permit dialysis to be performed.
The access should generally be placed in the
nondominant upper extremity
There are three major types of vascular access for
maintenance hemodialysis: primary arteriovenous
(AV) fistulas; synthetic arteriovenous fistulas (AV
grafts); and double-lumen, cuffed tunneled catheters

Preparation for peritoneal dialysis

Peritoneal dialysis catheters, which are placed into
the abdominal cavity, can be used immediately after
placement.
To minimize the risk of fluid leak, it is preferable to
wait at least 10 to 14 days before beginning dialysis.
If dialysis is required less than 10 days following
catheter placement, small volume exchanges
performed in the recumbent position can be
performed with little risk of leak.

Preparation for renal transplantation

Preparation for renal transplantation, which
principally involves evaluation of the potential renal
transplant recipient and/or the living donor.
Referral of patients with CKD to a transplant center
should occur at least when the GFR decreases to less
than 30 mL/min or, among diabetics, when the GFR
is between 30 to 40 mL/min

Established indications for renal

replacement therapy
Absolute clinical indications to initiate maintenance dialysis, include:

Pericarditis
Fluid overload or pulmonary edema refractory to diuretics
Accelerated hypertension poorly responsive to antihypertensive
medications
Progressive uremic encephalopathy or neuropathy, with signs
such as confusion, asterixis, myoclonus, wrist or foot drop, or, in
severe, cases, seizures
A clinically significant bleeding diathesis attributable to uremia
Persistent nausea and vomiting
Plasma creatinine concentration above 12 mg/dL (1060 mol/L)
or blood urea nitrogen (BUN) greater than 100 mg/dL (36
mmol/L).