PHARMACEUTICAL CARE CONCEPT

ACUTE RENAL FAILURE

DEFINITION:

Acute kidney injury (AKI) is characterized clinically by an abrupt decrease in renal function over a period of hours to days, resulting in the accumulation of nitrogenous waste products (azotemia) and the inability to maintain and regulate fluid, electrolyte, and acid–base balance. Traditionally, AKI has been defined as an increase in serum creatinine (SCr) of more than 0.5 mg/dL when the baseline SCr is less than 2.5 mg/dL, and an increase in SCr of more than 1.0 mg/dL when the baseline SCr is more than 2.5 mg/dL. These criteria are often inaccurate because SCr and glomerular filtration rate (GFR) do not follow a linear relationship.

EPIDEMIOLOGY:

The epidemiology of AKI varies widely depending on the patient population, geographical location, and the criteria used to evaluate the patient. AKI is generally considered to be an uncommon condition in the community-dwelling population, with an annual incidence of 520 per 100,000 person-years for nondialysis requiring AKI and 30 per 100,000 person-years for dialysis-requiring injury. AKI is more common in hospitalized individuals, with a reported incidence ranging from 2% to 20%. Intensive care unit (ICU) patients have the highest risk of developing AKI, with 20% to 60% of critically ill patients being affected.

CLASSIFICATION AND ETIOLOGY:

ARF is classified according to its cause.

1.      Prerenal ARF

2.      Intrinsic ARF (intrarenal or parenchymal ARF)

3.      Postrenal ARF

1. Prerenal ARF: Stems from impaired renal perfusion, which may result from

·         Reduced arterial blood volume (e.g., dehydration, haemorrhage, vomiting, diarrhoea, other

·         Gastrointestinal [GI] fluid loss).

·         Urinary losses from excessive diuresis.

·         Decreased cardiac output (e.g., from congestive heart failure [CHF] or pericardial tamponade).

·         Renal vascular obstruction (e.g., stenosis).

·         Severe hypotension.

2. Intrinsic ARF (intrarenal or parenchymal ARF) reflects structural kidney damage resulting from any of the following conditions.

·         Acute tubular necrosis (ATN), the leading cause of ARF, may be associated with

o   Exposure to nephrotoxic aminoglycosides, anesthetics, pesticides, organic metals, and

·         Radiopaque contrast materials.

o   Ischemic injury (e.g., surgery, circulatory collapse, severe hypotension).

o   Pigment (e.g., haemolysis, myoglobinuria).

·         Acute glomerulonephritis

·         Tubular obstruction, as from haemolytic reactions or uric acid crystals

·         Acute inflammation (e.g., acute tubulointerstitial nephritis, papillary necrosis)

·         Renal vasculitis

·         Malignant hypertension

·         Radiation nephritis

3. Postrenal ARF results from obstruction of urine flow anywhere along the urinary tract including:

·         Ureteral obstruction, as from calculi, uric acid crystals, or thrombi

·         Bladder obstruction, as from calculi, thrombi, tumors, or infection

·         Urethral obstruction, as from strictures, tumors, or prostatic hypertrophy

·         Extrinsic obstruction, as from hematoma, inflammatory bowel disease, or accidental surgical ligation.

PATHOPHYSIOLOGY:

CLINICAL PRESENTATIONS

Patients with Prerenal failure usually have

·         Volume contraction,

·         Hypotension or

·         Impaired cardiac function.

Diagnosis is confirmed when renal perfusion improves with volume repletion, improvement in cardiac function or repair of renal artery stenosis.

Postrenal failure may be evident from a

·         Distended bladder,

·         Large prostate,

·         Pelvic mass or hydronephrosis.

The pattern of urinary flow may indicate total obstruction (anuria) or partial obstruction (polyuria).

Crystals or infection may be evident in urinary sediment.

ARF due to intrinsic renal disease may require a renal biopsy for diagnosis.

RBC casts and heavy proteinuria suggest Glomerulonephritis or vascular inflammatory disease.

Interstitial nephritis may cause

·         Fever,

·         Skin eruption and

·         Pyuria with eosinophils in the urinary sediment.

The ischaemic ARF consists of three phases.

1. Initiation phase: It takes hours to days. It is the initial period of renal hypo-perfusion during which Ischaemic injury is evolving.

2. Maintenance phase: It takes one to two weeks. It is the phase in which renal injury is established with low urine output resulting in uraemic complications.

3. Recovery phase: This phase is characterised by repair and regeneration and gradual return of GFR to Normal. It results in marked diuresis.

 COMPLICATIONS:

·         Sodium and water overload

·         Hypertension

·         CCF

·         Hyperkalaemia (due to decreased excretion)

·         Metabolic acidosis with an anion gap (due to retention of acids)

·         Hypophosphatemia (due to decreased excretion)

·         Hypocalcaemia

·         Hypomagnesaemia

·         Hyperuricaemia

·         Anaemia

·         Infection

·         GI bleeding

·         Paralytic ileus

·         Pericarditis.

DIAGNOSIS: An algorithmic approach

v  Urinalysis includes an examination of sediment; identification of proteins, glucose, ketones, blood, and nitrites; and measurement of urinary pH and urine specific gravity (concentration) or osmolality (dilution). Prior administration of fluids, diuretics, and changes in urinary pH may confound accurate diagnosis, using urinalysis.

v  Urinary sediment examination

·         Few casts and formed elements are found in Prerenal ARF.

·         Pigmented cellular casts and renal tubular epithelial cells appear with ATN.

·         Red blood cell and white blood cell casts generally reflect inflammatory disease.

·         Large numbers of broad white cell casts suggest chronic renal failure.

·         The presence of blood in the urine (haematuria) or proteins (proteinuria) indicates renal dysfunction.

v  Urine-specific gravity ranges from 1.010 to 1.016 in ARF.

v  Urine osmolality typically rises in Prerenal ARF due to increased secretion of antidiuretic hormone.

v  Measurement of urine sodium and creatinine levels can help classify ARF.

·         In Prerenal ARF, the urine creatinine concentration increases and urine sodium level decreases.

·         In intrinsic ARF resulting from ATN, the urine creatinine concentration decreases and the urine sodium level increases.

v  Creatinine clearance, an index of the glomerular filtration rate (GFR), allows estimation of the number of functioning nephrons; decreased creatinine clearance indicates renal dysfunction.

·         A timed urine collection should be used to calculate GFR in acute renal failure.

v  Blood chemistry provides an index of renal excretory function and body chemistry status.

·         Findings typical of ARF include:

·         Increased blood urea nitrogen (BUN).

·         Increased serum creatinine concentration.

·         Possible increase in haemoglobin and haematocrit values due to dehydration.

·         Abnormal serum electrolyte values.

·         Serum potassium level above 5 mEq/L

·         Serum phosphate level above 2.6 mEq/L (4.8 mg/dL)

·         Serum calcium level below 4 mEq/L (8.5 mg/dL), reflecting hypocalcaemia. (The serum Calcium level must be correlated with the serum albumin level. Each rise or fall of 1 g/dL of serum albumin beyond its normal range is responsible for a corresponding Increase or decrease in serum calcium of approximately 0.8 mg/dL. A below-normal Serum albumin level may result in a deceptively low serum calcium level.)

·         Serum sodium level below 135 mEq/L, reflecting hyponatremia

·         Abnormal arterial blood gas values (pH below 7.35, bicarbonate concentration [HCO_3] below 22), reflecting metabolic acidosis

v  Renal failure index (RFI) is the ratio of urine sodium concentration to the urine-to-serum creatinine ratio. The RFI helps determine the etiology of ARF. Typically, the RFI is less than 1 in prerenal ARF or acute glomerulonephritis (a cause of intrinsic ARF). The RFI is greater than 2 in postrenal ARF and in other intrarenal causes of ARF.

v  Electrocardiography (ECG) may show evidence of hyperkalemia that is, tall, peaked T waves; widening QRS complexes; prolonged PR interval, progressing to decreased amplitude and disappearing P waves; and, ultimately, ventricular fibrillation and cardiac arrest.

v  Radiographic findings

v  Ultrasound may detect upper urinary tract obstruction.

v  Kidney, ureter, or bladder radiography may reveal:

·         Urinary tract calculi.

·         Enlarged kidneys, suggesting ATN.

·         Asymmetrical kidneys, suggesting unilateral renal artery disease, ureteral obstruction, or chronic pyelonephritis.

v  Radionuclide scan may reveal:

·         Bilateral differences in renal perfusion, suggesting serious renal disease.

·         bilateral differences in dye excretion, suggesting parenchymal disease or obstruction

·         As the cause of ARF.

·         Diffuse, slow, dense radionuclide uptake, suggesting ATN.

·         Patchy or absent radionuclide uptake, possibly indicating severe, acute glomerulonephritis.

v  Computed tomography (CT) scan may provide better visualization of an obstruction.

v  Renal biopsy may be performed in selected patients when other test results are inconclusive.

MANAGEMENT OF ACUTE RENAL FAILURE:

General Issues

v  Optimization of systemic and renal hemodynamics through volume resuscitation and judicious use of vasopressors

v  Elimination of nephrotoxic agents (e.g., ACE inhibitors, ARBs, NSAIDs, aminoglycosides) if possible

v  Initiation of renal replacement therapy when indicated

Specific Issues

v  Nephrotoxin-specific

o   Rhabdomyolysis: aggressive intravenous fluids; consider forced alkaline diuresis

o   Tumor lysis syndrome: aggressive intravenous fluids and allopurinol or rasburicase

v  Volume overload

o   Salt and water restriction

o   Diuretics

o   Ultrafiltration

v  Hyponatremia

o   Restriction of enteral free water intake, minimization of hypotonic intravenous solutions including those containing dextrose

o   Hypertonic saline is rarely necessary in AKI. Vasopressin antagonists are generally not needed.

v  Hyperkalemia

o   Restriction of dietary potassium intake

o   Discontinuation of potassium-sparing diuretics, ACE inhibitors, ARBs,

v  NSAIDs

o   Loop diuretics to promote urinary potassium loss

o   Potassium binding ion-exchange resin (sodium polystyrene sulfonate)

o   Insulin (10 units regular) and glucose (50 mL of 50% dextrose) to promote entry of potassium intracellularly

o   Inhaled beta-agonist therapy to promote entry of potassium intracellularly

o   Calcium gluconate or calcium chloride (1 g) to stabilize the myocardium

v  Metabolic acidosis

o   Sodium bicarbonate (if pH <7.2 to keep serum bicarbonate >15 mmol/L)

o   Administration of other bases, e.g., THAM

o   Renal replacement therapy

v  Hyperphosphatemia

o   Restriction of dietary phosphate intake

o   Phosphate binding agents (calcium acetate, sevelamer hydrochloride, aluminium hydroxide—taken with meals)

v  Hypocalcemia

o   Calcium carbonate or calcium gluconate if symptomatic

v  Hypermagnesemia

o   Discontinue Mg2+ containing antacids

v  Hyperuricemia

o   Acute treatment is usually not required except in the setting of tumor lysis syndrome

v  Nutrition

o   Sufficient protein and calorie intake (20–30 kcal/kg per day) to avoid negative nitrogen balance. Nutrition should be provided via the enteral route if possible.

v  Drug dosing

o   Careful attention to dosages and frequency of administration of drugs, adjustment for degree of renal failure

o   Note that serum creatinine concentration may overestimate renal function in the non–steady state characteristic of patients with AKI

REFERENCES:

(1)   Brian k. Alldredge, pharmd, et all koda-kimble and young’s applied therapeutics: the clinical use of drugs. 10th edition.

(2)   Joseph t. Dipiro, pharmd, fccp, et all pharmacotherapy a pathophysiologic approach, 9^th edition.

(3)   Harrison’s principles of internal medicine, 19^th edition.

(4)   Yasmeen agosti, et all medmaps for pathophysiology.

(5)   Leon shargel, [et al.]. Comprehensive pharmacy review for naplex, 8th edition.

(6)   R. Alagappan, manual of practical medicine, 4^th edition.

(7)   Stuart b. Mushlin, md, facp, facr, et all, decision making in medicine: an algorithmic approach, third edition