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 2/24/2014 2

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

2/24/2014

Classification - Severity Staging of Patients with AKI

RIFLE - Risk / AKIN Stage 1

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

RIFLE - Injury / AKIN Stage 2

RIFLE - Failure / AKIN Stage 3

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
5

Loss and End stage renal diseases

* 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
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Algoritme for D/ AKI

Memenuhi kriteria D/ AKI

Langkah 1

Ya

Tidak

AKI

Observasi 24-48 jam

Langkah 2

D/ Etiologi AKI

Tidak

Langkah 3

D/ klinis dan tahapan AKI Gejala: komplikasi Pemeriksaan penunjang

Bukan AKI

2/24/2014

Langkah 4

Membedakan AKI dengan PGK/aCRF

Gangguan ginjal

Gangguan ginjal normal Ukuran ginjal kecil

Gangguan ginjal

Tidak ada

Riw. Peny. Ginjal (kronis)h

ada

ada

Riw. Peny. Ginjal akut (E/AKI) Hipertensi, anemia, hiperfosfatemia

Tidak ada

Tidak ada ya

ada tidak

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reversibell

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

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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.
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Pathophysiology of Ischemic ARF MICROVASCULAR Glomerular Medullary

Inflammatory and vasoactive mediators

O2

TUBULAR
Cytoskeletal breakdown Loss of polarity Apoptosis and necrosis

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

Vasodilation in response to : Endothelial and vascular

Desquamation of viable and necrotic cells

Tubular obstruction Backleak

nitric oxide, PGE2, acetylcholine bradykinine

smooth muscle cell structural damage Leucocyte-Endothelial adhesion

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

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
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

Aging kidney

Physiologic

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

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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
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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

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Urinalysis in Acute Kidney Injury

Normal/bland Abnormal sediment

Hematuria RBC casts proteinuria

Prerenal Postrenal Oncotic AKI
Glomerulopathy Vasculitis Thrombotic MA

WBC WBC casts

Eosinophils

RTE cells Crystalluria NonPigmented albumin casts proteinuria

ATN Myoglobin Hemoglobin

Pyelonephritis Interstitial nephritis

AIN Atheroembolic AKI

Uric acid Toxins Drugs

Plasma cell dyscrasia

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

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
2/24/2014

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

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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
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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 Monitor fluid balance carefully Maintance euvolemia, tissue perfusion, electrolyte balance Crystaloid Colloid
Use in hypovolemia 500-1000 ml of normal saline over 30 minutes Use in hypovolemia due to hemorrhage Blood , albumin
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Pre-renal azotemia fluid can improve condition ATN fluid can be harmful, causing fluid overload

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

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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
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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

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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
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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

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Complication
Cardiopulmonary Metabolic Gastrointestinal Neurogenic Hematologic Infection

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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 1 2 3A 3B 4 5 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 Penurunan LFG sedang Penurunan LFG sedang Penurunan LFG berat Gagal ginjal 60 89 dengan bukti lain kerusakan GK* 45 - 59 30 44 15 29 < 15 atau dialysis

KDOQI-KDIGO Guidelines 2012

Cause Diabetes Level of proteinuria Urinary albumin (mg/day) Urinary albumin/Cr ratio (mg/g Cr) Urinary protein (mg/day) Urinary protein/Cr ratio A1 Normal A2 Microalbu minuria A3 Macroalbu minuria

Nephritis Hypertension Polycistic kidney dis Unknowm Other Level of GFR (mL/min/1 .73m2) G1

Normal

Mild Severe proteinuria proteinuria

Normal or high

90

G2
G3a

Mild
Mild to moderate

60 89
45 59

G3b
G4
11/28/2012

Moderate to sever
Severe

30 44
15 29

G5

Renal failure

< 15

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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.
3.

Administration of nephrotoxic drugs

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).