RENAL DISORDER

ACUTE RENAL FAILURE

DEFINITION:

“Acute renal failure (ARF) is manifested as an abrupt decline in glomerular filtration rate occurring over a period of days or weeks. This results in accumulation of water, nitrogenous wastes products and other toxins.”

The patient may be anuric (<50mL urine/24hrs), oliguric (<400 mL urine/24hrs), pass normal volumes of urine or may even be polyuric.

CLASSIFICATION:

RIFLE classification

Stage	Serum Creatinine		Urine output
Risk renal failure	Cr. x 1.5 normal	or	UO < 0.5ml / kg / hour for 6 hours
Injury to kidney	Cr. x 2 normal	or	UO < 0.5ml / kg / hour for 12 hours
Failure of kidney function	Cr. x 3 normal	or	Anuric for 12 hours
Loss kidney function	Need renal replacement therapy x 4 weeks
End stage renal disease	Need renal replacement therapy for > 13 weeks

TYPES OF RENAL FAILURE:

1. Pre renal (functional)

2. Intra renal (renal or intrinsic)

3. Post renal

1. 1-Pre-RENAL (FUNCTIONAL):

If renal tubular and glomerular function is intact but clearance is limited by factors compromising renal perfusion, the failure is termed pre renal failure. It results from hypo perfusion of the renal parenchyma, with or without systemic arterial hypotension. Pre renal ARF is rapidly reversible if the underlying cause is corrected. In prerenal acute kidney injury, there is nothing wrong with the kidney itself.

CAUSES:

Ø Hypovolemia

o Diarrhea, vomiting, dehydration

o Inappropriate diuretic therapy

Ø Decreased cardiac output

o Cardiac failure

o Hypotension

Ø Sepsis

Ø Drugs;

o NSAIDs, ciclosporin

o ACE inhibitors

o Angiotensin receptor blockers (ARBs)

Ø preexisting medical conditions, such as atherosclerosis

Ø excessive use of diuretics (water pills) is a major cause of prerenal ARF

2. INTRARENAL ARF:

“Any form of damage to the renal infrastructure (renal parenchyma) usually involving some form of ischemic or nephrotoxic insult may result in intra renal ARF”

CAUSES:

The most common causes of intrinsic acute kidney injury are acute tubular necrosis (ATN), acute glomerulonephritis (AGN), and acute interstitial nephritis (AIN).

i. Acute Tubular Necrosis:

The most common cause that result from ischemia or direct exposure to toxins, severe burns etc.

ii. Tubulointerstitial Nephritis:

Acute interstitial nephritis (AIN) is inflammation of the kidneys. It is usually caused by a medicine, such as an antibiotic or a nonsteroidal anti-inflammatory drug like naproxen or ibuprofen. Be safe with medicines. Read and follow all instructions on the label.AIN may also be caused by a streptococcal, viral infection.

Symptoms of AIN include a skin rash, fever, and an abnormal sediment in the urine.

iii. Glomerulonephritis:

Glomerulonephritis is a condition in which the tiny blood vessels in the kidneys become inflamed and damaged. Damaged glomeruli do not filter blood properly. Acute glomerulonephritis may be caused by an abnormal immune system response. Such as in

Lupus (systemic lupus erythematosus).
Bacterial or viral infections.

3. POST RENAL ARF:

Post renal ARF may develop as the result of obstruction at any level within the urinary collection system from the renal tubule to urethra. Postrenal ARF is caused by an acute obstruction that affects the normal flow of urine out of both kidneys. The blockage causes pressure to build in all of the renal nephrons (tubular filtering units that produce urine). The excessive fluid pressure ultimately causes the nephrons to shut down. The degree of renal failure corresponds directly with the degree of obstruction. Postrenal ARF is seen most often in elderly men with enlarged prostate that obstructs the normal flow of urine.

i. Bladder Outlet Obstruction:

due to an enlarged prostate gland or bladder stones

ii. Ureteral:

It includes the obstruction from calculi, clot, carcinoma, surgery.

iii. Renal Pelvis or Tubules:

End channels of the renal nephrons. It is induced by Uric acid, Sulfonamides, Acyclovir & Oxalates.

Stages of Acute Renal Failure:

Course of ARF may be divided into the three phases;

1. Initiating phase or oligouric phase.

2. Maintenance or diuretic phase.

3. Recovery phase

1. Initiating phase or oligouric phase:

It is usually of 7-14 days but may last for 6 weeks. It starts from renal insult and ends at the point at which external factors no longer reverse the damage caused by the obstruction or other causes of ARF.

Urine Output; It may drop to 400mL/day or even less (oligouric).

Nitrogen Waste Products; Serum creatinine, urea, sulphate, phosphate and organic acid level rise rapidly.

Hyponatremia

Hypocalcemia

Hyperkalemia; may lead to neuromuscular depression, impaired cardiac conduction, arrhythmia, respiratory depression, cardiac arrest and ultimately death.

2. MAINTENANCE OR DIURETIC PHASE:

If patient survives in the 1^st phase then it enters the 2^nd phase i.e. diuretic phase. It involves the marked increase in urine output (> 500mL/day) to several liters. It lasts for 7days and corresponds to recommencement of tubular function. This phase carries risk of GI bleeding and fluid and electrolyte imbalance.

3. Recovery Phase:

Patient who survives in diuretic phase has a good prognosis and pass to recovery phase. It involves the recovery of renal function where the regeneration of tubule cells take place slowly over the period of months to years.

SIGNS AND SYMPTOMS OF ARF:

decreased urine output (although occasionally, urine output remains normal)
chest pain or pressure
jugular vein distention
fluid retention, causing edematous legs, ankles, or feet
shortness of breath
confusion
nausea
seizures or coma in severe cases

9. ARF with Volume Depletion:

It includes dry mucosa, postural hypotension, tachycardia, and cold extremities. Other signs & symptoms associated with uremia as a result of accumulation of wastes include nausea, vomiting, headache, muscle cramps, fatigue and decline level of consciousness.

10. ARF with Volume Overload:

It includes odema, weight gain, orthopnea and pulmonary crackles.

Acute Kidney Failure Diagnosis

Kidney failure is often detected from blood or urine tests.

Ø Levels of urea (blood urea nitrogen [BUN]) and creatinine are high in kidney failure. This is called azotemia.

Ø Electrolyte levels in the blood may be abnormally high or low because of improper filtering.

Ø When the duration and severity of kidney failure is severe, the red blood cell count may be low. This is called anemia.

Ø The amount of urine produced over a period of hours may also be measured for quantity and quality or the amount of wastes being excreted. When kidney tissue is injured, protein and desirable substances may be inappropriately excreted in the urine. In some cases, the amount of urine remaining in the bladder after urination will be measured by an ultrasound device called a bladder scanner.

Ø In some cases, tissue samples of the kidneys are taken (biopsy) to find the cause of the renal failure.

MANAGEMENT OF ACUTE RENAL FAILURE:

EARLY PREVENTIVE AND SUPPORTIVE THERAPY:

Ø Improving the renal blood flow

Ø Reducing renal vasoconstriction

Ø And removing Nephrotoxins from kidney

1. Identification of Patient at Risk:

Patient with pre-existing chronic renal failure, diabetes, jaundice and elderly are at a high risk. Their condition will deteriorate more quickly than the other.

2. Withdrawal and Avoidance of Nephrotoxic Drugs

3. Optimization of Renal Perfusion:

It includes rapid correction of body fluid and electrolyte balance in order to maximize renal perfusion. Sodium chloride 0.9% is an appropriate choice for it. Where needed inotropes should be used to provide cardiac output.

4. Establishing and Monitoring an Adequate Diuresis:

If kidney does not show response to renal perfusion with fluid replacement therapy then measures include;

ü Loop diuretics

ü Mannitol

LOOP DIURETICS (Furosemide, Bumetanide ):

Loop diuretics reduce the renal tubular cell metabolic demand and improve renal blood flow by stimulating release of prostaglandins. It should be initiated after circulatory volume is restored otherwise its use produce a negative fluid balance and precipitate pre renal ARF.

Drug	Dosage Regimen
Furosemide	1-2g in 24hr in I.V infusion at a rate not more than 4mg/min
Bumetanide	0.5-1mg/day or maximum upto 20mg/day I.V or I.M

Mannitol:

It can wash intrarenal obstruction caused by tubular debris. A dose of 0.5-1g/kg as a 10-20% infusion was previously recommended. But it is associated with renal medullary hypoxia & potential damage in heart failure patients.

ACE inhibitors and angiotensin receptor blocker in ARF:

ACE inhibitor is completely contraindicated in a patient with aortic or bilateral artery stenosis. Renin angiotensin system is stimulated by low perfusion resulting from stenosis. Then angiotensin II is produced which causes renal vasoconstriction which increases efferent arteriolar tone which creates back pressure which maintain glomerular pressure in poorly perfuse kidney. If angiotensin II production is inhibited then efferent arteriolar dilatation results. Since increased efferent vascular constriction maintains filtration in such patients then overall result of such therapy will reduce the filtration at glomerulus leading to ARF.

NON DIALYSIS TREATMENT OF ESTABLISHED ACUTE RENAL FAILURE:

1. Treatment of Uremia:

Symptoms of uremia may be reduced by restricting protein intake. Fat and carbohydrate should be taken to maintain a high energy intake to prevent protein catabolism and promote anabolism. In severely ill patients use of parenteral or enteral nutrition should be considered at an early stage.

2. Treatment of Hyperkalemia:

Extracellular potassium level rises as a result of tissue damage in sepsis, burns and acidosis. Dietary potassium should be restricted. Avoid potassium supplements and potassium sparing diuretics removed from treatment. Emergency treatment is necessary when there are progressive changes in electrocardiogram associated with hyperkalemia.

Emergency Treatment of Hyperkalemia:

ü 10-30 ml of calcium gluconate 10% intravenously over 5-10 minutes. This effect is short lived and dose can be repeated.

3. Treatment of acidosis:

ü Sodium bicarbonate 1-6g/day in divided doses intravenously may be used.

4. Treatment of Hypocalcaemia:

ü Oral calcium supplementation with calcium gluconate or lactate and vitamin D may be used to treat the hypocalcaemia of ARF if needed.

ü Calcium gluconate is given IV in a dose of 1-2g over a period of 10min followed by slow infusion (6-8hours) of an additional 1g.

5. Treatment of Hyperphosphatemia:

ü Phosphate binding agent may be used such as calcium carbonate or aluminium hydroxide in the mixture or capsules.

6. Treatment of Hyponatremia:

ü 3-5% sodium chloride may be administered by slow IV infusion.

7. Treatment of Underlying Infection:

ü Treat with appropriate antibiotic.

Renal Replacement Therapy:

Renal replacement therapy is indicated in a patient with ARF when kidney function is poor and life is at risk. It is used;

ü To remove toxins with severe symptoms (impaired consciousness, pericarditis, and seizures).

ü To remove fluid resistant to diuretics (pulmonary edema) to facilitate parenteral nutrition.

ü Hyperkalemia with marked ECG changes.

ü Increased acidosis (pH<7.1)

Forms of Renal Replacement Therapy:

ü Hemodialysis

ü Haemofilteration

CHRONIC RENAL FAILURE

DEFINITION:

Chronic renal failure (CRF) is the progressive loss of kidney function leading to irreversible structural damage to existing nephron.

PATHOPHYSIOLOGY

There are approximately 1 million nephrons per kidney, each maintaining its own single nephron eGFR (estimated glomerular filtration rate). Progressive loss of nephron function results in adaptive changes in remaining nephrons to increase single nephron eGFR which in turn causes hypertrophy and irreversible nephron loss leading to continuous cycle of nephron destruction.

Factors involved in pathophysiology:

Susceptibility factors

These factors increase the risk for kidney disease but do not directly cause kidney damage.

· Advanced age

· Reduced kidney mass and low birth weight

· Family history

· Systemic inflammation

· Dyslipidemia (abnormal amount of lipids)

Initiation factors

These factors initiate kidney damage and can be modified by drug therapy.

· Diabetes mellitus

· Hypertension

· Autoimmune disease

· Polycystic kidney disease

· Drug toxicity

Progression factors

These factors cause decline in kidney function after initiation of kidney damage.

· Glycemia in diabetics

· Hypertension

· Proteinuria

· Smoking

CLASSIFICATION OF CRF:

1: Pre-renal

2: Renal

3: Post-renal

PRE-RENAL:

Causes of pre-renal CRF are

· Chronic liver failure

· Poor cardiac function

· Atherosclerosis (hardening of renal arteries)

RENAL:

Causes of renal CFR are as under:

· Diabetic nephropathy: Kidney disease associated with diabetes: the most common cause of kidney disease.

· Hypertension nephron-sclerosis: the second leading cause of CRF

POST-RENAL:

Interference with normal flow of urine produce back pressure with kidney, damage nephron and lead to obstructive neuropathy, a disease of urinary tract.

· Bladder outlet obstruction: It is due to enlarged prostate gland or bladder stone.

· Neurogenic bladder: An over distended bladder caused by impaired communicator nerve fibers from bladder to the spinal cord.

· Kidney stone: In both ureters, the tubes that pass urine flow from each kidney to bladder.

Stages of CRF:

STAGE	GFR	Symptoms and Effects
Stage 1	Normal >/=90ml/min	No such symptoms
Stage 2	Mild reduction (GFR 60 – 89 ml/min) GFR of 60 may represent 50% loss in function.	• Higher than normal levels of creatinine or urea in the blood • Blood or protein in the urine • Evidence of kidney damage in an MRI, CT scan, ultrasound or contrast X-ray
Stage 3	Moderate reduction (GFR 30 – 59 ml/min)	· Calcium absorption decreases · Malnutrition onset · Anemia
Stage 4	Severe reduction (GFR 15 – 29 ml/min)	· Serum triglycerides increase · Hyperphosphatemia · Metabolic acidosis · Hyperkalemia
Stage 5	(GFR less than 15 ml/min)	· Marked decrease in: Hemoglobin, Hematocrit, Calcium · Fluid overload · Uremic syndrome develops affecting all body systems can be diminished with early diagnosis & treatment. · Fatal if no treatment

Diagnosis:

· Blood test

Blood test (BUN) may be ordered to determine whether waste substances are being adequately filtered out. If levels of urea and creatinine are persistently high, the doctor will most likely diagnose end-stage kidney disease.

· Urine test

Urine test helps find out whether there is either blood or protein in the urine.

· Kidney scans

Kidney scans may include MRI, CT scan or an ultrasound scan. The aim is to determine whether there are any blockages in the urine flow. These scans can also reveal the size and shape of the kidneys. In advanced stages of kidney disease the kidneys are smaller and have an uneven shape.

· Kidney biopsy

· Small sample of kidney tissue is extracted and examined for cell damage. An analysis of kidney tissue makes it easier to make a precise diagnosis of kidney disease.

· Glomerular filtration rate (GFR)

GFR is a test that measures the glomerular filtration rate - it compares the levels of waste products in the patient's blood and urine. GFR measures how many milliliters of waste the kidneys can filter per minute. The kidneys of healthy individuals can typically filter over 90 ml per minute.

Causes and associated conditions:

In the majority of cases, progressive kidney damage is the result of a chronic disease (a long-term disease), such as:

Diabetes

Chronic kidney disease is linked to diabetes types 1 and 2. If the patient's diabetes is not well controlled, excess sugar (glucose) can accumulate in the blood. Kidney disease is not common during the first 10 years of diabetes; it more commonly occurs 15-25 years after diagnosis of diabetes.

Hypertension (high blood pressure)

High blood pressure can damage the glomeruli - parts of the kidney involved in filtering waste products.

Obstructed urine flow

If urine flow is blocked it can back up into the kidney from the bladder (vesicoureteral reflux). Blocked urine flow increases pressure on the kidneys and undermines their function. Possible causes include an enlarged prostate, kidney stones, or a tumor.

Kidney diseases

Including:

· Polycystic kidney disease (inherited kidney disorder, fluid filled cysts are formed in kidneys)

· Pyelonephritis (life threatening infection leading to renal scarring)

· Glomerulonephritis (group of diseases that injure the part of kidney that filters blood, glomeruli)

Kidney artery stenosis

The renal artery narrows or is blocked before it enters the kidney.

Certain toxins

Including fuels, solvents (such as carbon tetrachloride), and lead (and lead-based paint, pipes, and soldering materials).

Fetal developmental problem

If the kidneys do not develop properly in the unborn baby while it is developing in the womb.

Systemic lupus erythematosis

It is an autoimmune disease. The body's own immune system attacks the kidneys as though they were foreign tissue.

Malaria and yellow fever

It is known to cause impaired kidney function.

Some medications

Overuse of, for example, NSAIDs (non-steroidal anti-inflammatory drugs) such as aspirin or ibuprofen.

Illegal substance abuse

Such as heroin or cocaine.

Injury

A sharp blow or physical injury to the kidney(s) can result in kidney disease.

Chronic kidney disease treatment

There is no current cure for chronic kidney disease. However, some therapies can help control the signs and symptoms, reduce the risk of complications, and slow the progression of the disease. Patients with chronic kidney disease typically need to take a large number of medications. Treatments include:

Anemia treatment

Hemoglobin is the substance in red blood cells that carries vital oxygen around the body. If hemoglobin levels are low, the patient has anemia. Some kidney disease patients with anemia will require blood transfusions. A patient with kidney disease will usually have to take iron supplements, either in the form of daily ferrous sulphate tablets, or occasionally in the form of injections.

Phosphate balance

People with kidney disease may not be able to eliminate phosphate from their body properly. Patients will be advised to reduce their nutritional phosphate intake - this usually means reducing consumption of dairy products, red meat, eggs, and fish.

Vitamin D

Patients with kidney disease typically have low levels of vitamin D. Vitamin D is essential for healthy bones. The vitamin D we obtain from the sun or from food has to be activated by the kidneys before the body can use it. Patients may be given alfacalcidol, or calcitriol.

High blood pressure

High blood pressure is a common problem for patients with chronic kidney disease. It is important to bring the blood pressure down to protect the kidneys, and subsequently slow down the progression of the disease.

Fluid retention

People with chronic kidney disease need to be careful with their fluid intake. Most patients will be asked to restrict their fluid intake. If the kidneys do not work properly, the patient is much more susceptible to fluid build-up.

Skin itching

Antihistamines, such as chlorphenamine, may help alleviate symptoms of itching.

Diet

Following a proper diet is vital for effective kidney failure treatment. As mentioned above, restricting the amount of protein in the diet may help slow down the progression of the disease. Salt intake needs to be carefully regulated to control hypertension. Potassium and phosphorus consumption, over time, may also need to be restricted.

NSAIDs (non-steroidal anti-inflammatory drugs)

NSAIDs, such as aspirin or ibuprofen should be avoided and only taken if a doctor recommends them.

End-stage kidney disease treatment

This is when the kidneys are functioning at less than 10-15 percent of normal capacity. Measures used so far - diet, medications, and treatments controlling underlying causes are no longer enough. The kidneys of patients with end-stage kidney disease cannot keep up with the waste and fluid elimination process on their own. The patient will need dialysis or a kidney transplant in order to survive. Most doctors will try to delay the need for dialysis or a kidney transplant for as long as possible because they carry the risk of potentially serious complications.

Kidney dialysis

Peritoneal dialysis is a treatment option for chronic kidney disease. This is the removal of waste products and excessive fluids from blood when the kidneys cannot do the job properly any more. Dialysis has some serious risks, including infection.

There are two main types of kidney dialysis.

Hemodialysis

Blood is pumped out of the patient's body and goes through a dialyzer (an artificial kidney). The patient undergoes hemodialysis about three times per week. Each session lasts for at least 3 hours.

Peritoneal dialysis

The blood is filtered in the patient's own abdomen; in the peritoneal cavity which contains a vast network of tiny blood vessels. A catheter is implanted into the abdomen, into which a dialysis solution is infused and drained out for as long as is necessary to remove waste and excess fluid.

Kidney transplant

A kidney transplant is a better option than dialysis for patients who have no other conditions apart from kidney failure. Even so, candidates for kidney transplant will have to undergo dialysis until they receive a new kidney.

The kidney donor and recipient should have the same blood type, cell-surface proteins and antibodies, in order to minimize the risk of rejection of the new kidney. Siblings or very close relatives are usually the best types of donors. If a living donor is not possible, the search will begin for a cadaver donor (dead person).

References

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• 2. Pharmacotherapy Handbook Seventh Edition by Barbara G. Wells, PharmD, FASHP, FCCP, BCPP & Joseph T. DiPiro, PharmD, FCCP

• 3.clinical Pharmacy & therapeutics by Roger walker

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