ACUTE KIDNEY INJURY AND CHRONIC KIDNEY

DISEASE

Dr. Hamed Shakhatrehconsultant nephrologist,Head of nephrology department, Al-basher hospital, M.O.H.

AKI Definition AKI is defined as any of the following : - increase in SCr by >0.3 mg/dl

(>26.5lmol/l) within 48 hours; or -Increase in SCr to>1.5 times baseline,

which is known or presumed to have occurred within the prior 7 days; or

-Urine volume <0.5 ml/kg/h for 6 hours.

Stage of AKI:

Stage 1— 1.5-1.9 times baseline OR ≥0.3 mg/dl (≥26.5 micromol/l) increase in the serum creatinine, OR urine output <0.5 ml/kg per hour for 6 to 12 hours.

Stage 2 — 2.0-2.9 times baseline increase in the serum creatinine OR urine output <0.5 ml/kg per hour for ≥12 hours.

Stage 3 — 3.0 times baseline increase in the serum creatinine OR increase in serum creatinine to ≥4.0mg/dl (≥353.6 micromol/l) OR urine output of <0.3 ml/kg per hour for ≥24 hours, OR anuria for ≥12 hours OR the initiation of renal replacement therapy OR, in patients <18 years, decrease in estimated GFR to <35 ml/min per 1.73m2

types of acute kidney injury

In pre-renal failure, the renal tissue is intact and kidney biopsy shows normal renal histology. Oliguria and high serum creatinine are due to functional impairment; since there is no sufficient blood reaching the kidney to be cleared of these toxins. Combination of hypotension, hypovolaemia resulting in diminished renal perfusion is the most common cause of acute renal failure in hospitalized patients.

I. Pre-renal injury

When renal hypoperfusion (due to hypotension and/orhypovolaemia) is not severe enough to cause renal tubular damage, it will manifest as pre-renal failure in the form of oliguria and a rise in serum creatinine and blood urea. Since there is no structural renal damage, early diagnosis and correction of renal hypoperfusion results in immediate diuresis and rapid drop in serum creatinine and blood urea levels.

If hypoperfusion is severe or neglected, renal compensatory mechanisms will fail and acute tubular necrosis occurs. In this new situation, correction of hypoperfusion will not be followed by diuresis or drop in serum creatinine. Few days or weeks (mean 2-3 weeks) are needed for tubular regeneration and recovery of kidney function to occur.

II.Acute Intrinsic Renal injury

This includes acute tubular necrosis (ATN), acute interstitial nephritis and acute glomerulonephritis.

At this presentation we well discuss ATN

as the other entity will be discussed separately in other lectures.

Acute Tubular Necrosis

Acute tubular necrosis can be induced by :

renal hypoperfusion (ischemia). exposure to nephrotoxins

(exogenous or endogenous toxins). and frequently by a combination of

both.

Causes of Ischaemic ATN:

A- Blood Loss • Haemorrhage (post partum, surgical or gastrointestinal). • Major trauma

B- Fluid Loss • Gastrointestinal (vomiting or diarrhoea) • Renal (aggressive diuresis or polyuria)

C- Third Space • Haematoma • Illius • Peritonitis

D- Severe vasodilatation as in septicaemia, rapid oedema formation, liver cell failure.

E- Renovascular disease • Renal artery occlusion by stenosis, embolism orcompression. • Renal vein thrombosis or compression.

Causes of Toxic ATN

(A) Exogenous nephrotoxins include: Antibiotics:

Aminoglycosides ,Amphotericin ,Cephalosporin, Acyclovir, Sulfonamide, Tetracyclines Bacitracin.

Anaesthetic agents: Methoxy fluoraneContrast Media:Analgesics:Metals: as Mercury, lead, arsenic, bismuth,

cadmium,antimony,organic solvents: GlycolsPoisons: snake bite, stings, bacterial toxins.

Causes of Toxic ATN

(B) Endogenous nephrotoxins include

Pigments: Crystals:Myoglobin Uric acidHemoglobin CalciumMethemoglobin Oxalate

Post –renal injury

In post-renal failure, the obstruction of the urinary tract results in increasing the pressure above the level of the obstruction up to the nephron including the urinary space of the renal glomeruli. When this back pressure exceeds that of the filtration pressure in the renal glomeruli, the process of urine formation will stop with progressive accumulation of wastes and increase of serum creatinine and blood urea.

Clinical features of AKI:1- Usually, the patient gives history of the

etiologic cause such as trauma, shock, haemolysis, drug intake, infection, or stone disease.

2- Patient may notice a change in urine volume and character, oliguria is common, but in 10-50% of cases urine volume will be normal or even higher (as in toxic ATN) this is called polyuric ATN. Absolute anuria is highly suggestive of obstructive ARF (post-renal) or very severe form of ATN (cortical necrosis).

3- Manifestation of salt and water retention (oedema, puffiness, hypertension and even heart failure).

4- By time, manifestations of uraemia appear as acidotic breathing, dyspnea, nausea, vomiting, headache, muscle twitches and even frank encephalopathy and coma.

5- Patient may present as well with any of the following complications:

Complications Of AKI:

Cardiovascular• pulmonary odema • arrhythmias• hypertension • pericardial effusion• myocardial infarction • pulmonary

embolismMetabolic• hyponatremia • hyperkalemia• acidosis • hypocalcemia• hyperphosphatemia

Neurologic:• coma • seizuresGastrointestinal:• gastritis • gastroduodenal ulcersHaematologic:• anaemia • hemorrhagic diathesisInfections• pneumonia • septicemia• UTI

Investigations of AKI:

A-Urinary indices:-May be helpful in the differentiation

between pre-renal failure and acute tubular necrosis. Diuretics should not be given at least during the preceeding 48 hours for these parameters to be valid.

B- Urinary sediment:Centrifugation of fresh urine sample and examination of the urinarysediment may be helpful in diagnosing different causes of ARF

C- Renal Imaging D-Renal bx.

TREATMENT OF AKI:

A- Treatment of the cause e.g. any condition causing renal hypoperfusion, exposure to toxic drug or chemical or systemic disease.

B- Prevention of AKI:The timing of intervention to prevent ATN is

important. Protective agents must be administered at the time of, or immediately following potential renal insult. This intervention may prevent or at least blunt the severity of ATN.

The intervention could be through the following approaches. In different combinations according to the clinical situation:• Volume expansion by saline loading.• Diuretic as mannitol and furosemide.• Calcium channel blockers as verapamil and nifedipine.• Vasodilating agents as dopamine in renal dose 1-2 ug/kg/min• ATP-magnesium chloride.

In case of contrast media, the following additional points should be adopted, these are:-

• Avoid unnecessary contrast procedures.• Avoid multiple contrast exposure within a few days.• Avoid contrast exposure in high risk patient.• Use the smallest dose possible.• Use of non-ionic contrast is to somewhat safer.• In high risk patient with renal impairment we can manage to wash the contrast out immediately after the technique (e.g. coronary angiography) by haemodialysis.

CHRONIC KIDNEY DISEASE

What is CKD? Presence of markers of kidney damage for

three months, as defined by structural or functional abnormalities of the kidney with or without decreased GFR, manifest by either pathological abnormalities or other markers of kidney damage, including abnormalities in the composition of blood or urine, or abnormalities in imaging tests.

The presence of GFR <60 mL/min/1.73 m2 for three months, with or without other signs of kidney damage as described above.

Epidemiology

19 million Americans have CKD Approx 435,000 have ESRD/HD

Annual mortality rate for ESRD: 24%

CAUSE OF CKD: The most common causes of CKD are DM,HTN

and glomerulonephritis. Together, these cause approximately 75% of all adult cases

Diabetes. It causes about 35% of all chronic kidney disease. High blood sugar levels caused by DM damage blood vessels in the kidneys. If the blood sugar level remains high, this damage gradually reduces the function of the kidneys.

hypertension. It causes another 30% of all kidney disease. Because HTN often rises with chronic kidney disease, high blood pressure may further damage kidney function even when another medical condition initially caused the disease.

Other etiologies

Renovascular diseaseNephrotic syndromeHypercalcemiaMultiple myelomaChronic UTI

Signs & Symptoms General

Fatigue & malaise Edema

Ophthalmologic AV nicking

Cardiac HTN Heart failure Pericarditis CAD

GI Anorexia Nausea/vomiting

Skin Pruritis Pallor

Neurological MS changes Seizures

GFR Calculations Cockcroft-Gault

Men: CrCl (mL/min) = (140 - age) x wt (kg) SCr x 0.81

Women: multiply by 0.85

MDRD: USUALLY WE USE COMPUTARISED FORMULA TO CALCULAT IT :

GFR (mL/min per 1.73 m2) = 186 x (SCr x 0.0113)-1.154 x (age)-0.203 x (0.742 if female) x (1.12 if African-American)

Stages of CKD Stage 1*: GFR >= 90 mL/min/1.73 m2

Normal or elevated GFR Stage 2*: GFR 60-89 (mild)

Stage 3: GFR 30-59 (moderate)

Stage 4: GFR 15-29 (severe; pre-HD)

Stage 5: GFR < 15 (kidney failure)

Management

Identify and treat factors associated with progression of CKD HTN Proteinuria Glucose control

Hypertension Target BP

<130/80 mm Hg <125/75 mm Hg

pts with proteinuria (> 1 g/d)

Consider several anti-HTN medications with different mechanisms of activity ACEs/ARBs Diuretics CCBs HCTZ (less effective when GFR < 20)

Proteinuria Single best predictor of disease

progression

Normal albumin excretion <30 mg/24 hours

Microalbuminuria 20-200 g/min or 30-300 mg/24 hours

Macroalbuminuria >300 mg/24 hours

Nephrotic range proteinuria >3 g/24 hours

Metabolic changes with CKD

Hemoglobin/hematocrit Bicarbonate Calcium Phosphate PTH Triglycerides

Metabolic changes…

Monitor and treat biochemical abnormalities Anemia Metabolic acidosis Mineral metabolism Dyslipidemia Nutrition

Anemia Common in CKD HD pts have increased rates of:

Hospital admission CAD/LVH Reduced quality of life

Managing anemia Can improve energy levels, sleep, cognitive function, and quality of life in HD pts

Metabolic acidosis Muscle catabolism

Metabolic bone disease

Sodium bicarbonate Maintain serum bicarbonate > 22 meq/L 0.5-1.0 meq/kg per day Watch for sodium loading

Volume expansion HTN

Mineral metabolism Calcium and phosphate metabolism

abnormalities associated with: Renal osteodystrophy Calciphylaxis and vascular calcification

14 of 16 ESRD/HD pts (20-30 yrs) had calcification on CT scan

3 of 60 in the control group

Dyslipidemia

Abnormalities in the lipid profile Triglycerides Total cholesterol

NCEP recommends reducing lipid levels in high-risk populations

Targets for lipid-lowering therapy considered the same as those for the secondary prevention of CV disease

Nutrition

Think about uremia Catabolic state Anorexia Decreased protein intake

CV disease

70% of HD patients have concomitant CV disease

Heart disease leading cause of death in HD patients

LVH can be a risk factor

Evaluation for CKD Blood

CBC with diff SMA-7 with Ca2+

and phosphorous PTH HBA1c LFTs and FLP Uric acid and

Fe2+ studies

Urine Urinalysis with

microscopy Spot urine for

microalbumin 24-urine collection

for protein and creatinine

Ultrasound

Key points The serum creatinine level is not

enough! Target BP for CKD

<130/80 mm Hg <125/75 mm Hg in proteinuria

HTN and proteinuria are the two most important modifiable risk factors for progressive CKD