This document discusses acute renal failure (ARF). It defines ARF and describes its pathophysiology, which can be prerenal, intrinsic, postrenal, or functional. Clinical presentation depends on setting but can include edema, colored urine, and hypotension. Treatment involves preventing ARF through avoiding nephrotoxins, maximizing renal perfusion, and controlling risk factors. For established ARF, management supports the patient through the recovery period with renal replacement therapy, fluid management with diuretics, and electrolyte and nutrition management. Drug dosing is also challenging in ARF patients.

1. therapeutics
• By saidi wazir (pharmacist)
• Soroti pharmaceutical trainning college
• Uganda

2. Physiological principles of the renal
system
The kidney is both structurally and functionally
complex, and plays a central role in homeostasis.
Thus, many possible forms of renal malfunction can
cause a wide range of clinical conditions.
Manifestations of renal disorder include fluid,
electrolyte and pH imbalances, haemodynamic
imbalance, the accumulation of drugs, toxins and
waste metabolic products, loss of essential
metabolites, and endocrine abnormalities such as
anaemia and bone disease.

3. Pathological processes such as infection,
inflammation, auto-immunity, neoplasia and
toxins can cause structural damage to the
glomeruli, the tubules or the urinary tract.
Systemic or local circulatory insufficiency can also
seriously compromise renal function. The most
common pathologies are glomerular
inflammation, urinary-tract infection and drug
induced nephrotoxicity.
In this section we review the physiological
principles of normal renal function, so that
abnormalities of the renal system may be better
understood.

5. FUNCTIONS OF THE KIDNEY
Elimination
of waste/surplus
Carbohydrate-
derived,
Nitrogenous and
others.
Water, carbondioxide .
Urea creatinine, uric
acid, guanidine,
amines, etc. Sulphate,
phosphate, exogenous
toxins
Regulation
of fluid and
electrolyte
balance
Total body water
Plasma osmotic
pressure, pH,
Na, K, Ca, Mg, etc.
Chloride, bicarbonate,
phosphate, etc.
Endocrine
homeostasis
Blood pressure
Calcium and bone
metabolism
RBC production

6. In certain less common renal diseases, e.g.
polycystic kidney and renal tumour, there is
erythropoietin over-production,with
consequent polycythaemia.

7. Acute Renal Failure
• Acute renal failure (ARF) is broadly defined as
a decrease in glomerular filtration rate (GFR)
occurring over hours to weeks that is
associated with an accumulation of waste
products, including urea and creatinine.

8. PATHOPHYSIOLOGY
• ARF can be categorized as prerenal (resulting
from decreased renal perfusion), intrinsic
(resulting from structural damage to the
kidney), postrenal (resulting from obstruction
of urine flow from the renal tubule to the
urethra), and functional (resulting from
hemodynamic changes at the glomerulus
independent of decreased perfusion or
structural damage

9. CLINICAL PRESENTATION
• The presentation can be subtle and depends on
the setting. Outpatients often are not in acute
distress; hospitalized patients may develop ARF
after a catastrophic event.
• Symptoms in the outpatient setting include
change in urinary habits, weight gain, or flank
pain. Clinicians typically notice symptoms of ARF
before they are detected by inpatients.
• Signs include edema, colored or foamy urine, and,
in volume-depleted patients, orthostatic
hypotension.

10. RIFLE classification for acute renal failure (ARF).
(ESRD, end-stage renal disease; GFR, glomerular
filtration rate; Scr
, serum creatinine.)

11. DESIRED OUTCOME
• The primary goal of therapy is to prevent ARF.
If ARF develops, the goal are to avoid or
minimize further renal insults that would
delay recovery and to provide supportive
measures until kidney function returns.

12. TREATMENT
PREVENTION OF ACUTE RENAL FAILURE
• Risk factors for ARF include advanced age,
acute infection, preexisting chronic respiratory
or cardiovascular disease, dehydration, and
chronic kidney disease (CKD). Decreased renal
perfusion secondary to abdominal or coronary
bypass surgery, acute blood loss in trauma,
and uric acid nephropathy also increase risk.

13. • Nephrotoxin administration (e.g., radiocontrast
dye) should be avoided whenever possible.
When patients require contrast dye and are at
risk of contrast dye–induced nephropathy, renal
perfusion should be maximized through
strategies such as assuring adequate hydration
with normal saline or sodium bicarbonate
solutions and administration of oral
acetylcysteine 600 mg every 12 hours for four
doses. Strict glycemic control with insulin in
diabetics has also reduced the development of
ARF.

14. • Nephrotoxin administration (e.g., radiocontrast
dye) should be avoided whenever possible.
When patients require contrast dye and are at
risk of contrast dye–induced nephropathy, renal
perfusion should be maximizedm through
strategies such as assuring adequate hydration
with normal saline or sodium bicarbonate
solutions and administration of oral
acetylcysteine 600 mg every 12 hours for four
doses. Strict glycemic control with insulin in
diabetics has also reduced the development of
ARF.

15. MANAGEMENT OF ESTABLISHED
ACUTE RENAL FAILURE
• No drugs have been found to accelerate ARF
recovery. Therefore, patients with established
ARF should be supported with
nonpharmacologic and pharmacologic
approaches through the period of ARF.

16. Nonpharmacologic Approaches
• Supportive care goals include maintenance of adequate cardiac
output and blood pressure to optimize tissue perfusion while
restoring renal function to pre-ARF baseline.
• Medications associated with diminished renal blood flow should be
stopped. Appropriate fluid replacement should be initiated.
Avoidance of nephrotoxins is essential in the management of
patients with ARF.
• Renal replacement therapy (RRT), such as hemodialysis and
peritoneal dialysis, maintains fluid and electrolyte balance while
removing waste products. See Table 75-4 for indications for RRT in
ARF. Intermittent and continuous options have different advantages
(and disadvantages) but, after correcting for severity of illness, have
similar outcomes. Consequently, hybrid approaches (e.g., sustained
low-efficiency dialysis and extended daily dialysis) are being
developed to provide the advantages of both.

17. • Intermittent RRT (e.g., hemodialysis) has the
advantage of widespread availability and the
convenience of lasting only 3 to 4 hours.
Disadvantages include difficult venous dialysis
access in hypotensive patients and hypotension
due to rapid removal of large amounts of fluid.
• Several continuous renal replacement therapy
(CRRT) variants have been developed. CRRT,
performed as continuous hemodialysis, continuous
hemofiltration, or both, is becoming increasingly
popular. CRRT gradually removes solute resulting in
better tolerability by critically ill patients.
Disadvantages include limited availability, need for
24-hour nursing care, high expense, and incomplete
guidelines for drug dosing (see Chap. 77).

18. Pharmacologic Approaches
• Loop diuretics have not been shown to accelerate
ARF recovery or improve patient outcome;
however, diuretics can facilitate managementof
fluid overload. The most effective diuretics are
mannitol and loop diuretics.
• Mannitol 20% is typically started at a dose of 12.5
to 25 g IV over 3 to 5 minutes. Disadvantages
include IV administration, hyperosmolality risk,
and need for monitoring because mannitol can
contribute to ARF.

19. • Equipotent doses of loop diuretics (furosemide,
bumetanide, torsemide, ethacrynic acid) have
similar efficacy. Ethacrynic acid is reserved for
sulfa-allergic patients. Continuous infusions of
loop diuretics appear to be more effective and
to have fewer adverse effects than intermittent
boluses. An initial IV loading dose (equivalent to
furosemide 40 to 80 mg) should be
administered before starting a continuous
infusion (equivalent to furosemide 10 to 20
mg/hour).

20. ELECTROLYTE MANAGEMENT AND
NUTRITION THERAPY
• Hyperkalemia is the most common and serious
electrolyte abnormality in ARF. Potassium must be
restricted to less than 3 g/day and monitored daily.
• Hypernatremia and fluid retention commonly occur,
necessitating restricting daily sodium intake to no more
than 3 g. All sources of sodium, including antibiotics,
need to be considered when calculating daily sodium
intake.
• Phosphorus and magnesium should be monitored;
neither is efficiently removed by dialysis.
• No parenteral nutrition has been shown to improve
patient outcomes.

21. DRUG-DOSING CONSIDERATIONS
• Drug therapy optimization in ARF is a challenge.
Confounding variables include residual drug clearance,
fluid accumulation, and use of RRTs.
• Volume of distribution for water-soluble drugs is
significantly increased due to edema. Use of dosing
guidelines for CKD does not reflect the clearance and
volume of distribution in critically ill ARF patients.
• ARF patients may have a higher residual nonrenal
clearance than CKD patients with similar creatinine
clearances; this complicates drug therapy
individualization, especially with RRTs.

22. • The mode of CRRT determines the rate of drug
removal, further complicating
individualization of drug therapy. The rates of
ultrafiltration, blood flow, and dialysate flow
influence drug clearance during CRRT.

25. Other renal disease
• Pyelo nephritis
• Nephrotic syndrome
• Poly cystic disease