1. Acute Renal Failure (Acute Kidney Injury)

2. Objectives Acute Renal Failure ,Acute tubular Necrosis (Definition)
Causes.
Clinical presentations.
Complications and Treatment.
Preventions.

3. Acute Renal Failure (ARF)
ARF; also referred to as acute kidney injury (AKI) describes a sudden and usually reversible loss of renal function, which develops over days or weeks and is usually accompanied by a reduction in urine volume.
Azotaemia: retention of urea and other nitrogen compounds in blood
Uraemia : synonymous with azotaemia, also means uraemic syndrome, i.e., the clinical manifestation of renal failure

4. Classifications of Renal Failure
Acute versus chronic
Pre-renal, renal, post-renal
Anuric, oliguric, polyuric

5. Acute Versus Chronic Acute Chronic
Sudden onset
Rapid reduction in urine output
Usually reversible
Tubular cell death and regeneration
Chronic
Progressive
Not reversible
Nephron loss
75% of function can be lost before its noticeable

6. Acute Renal Failure Pre-renal = 55% Renal parenchymal (Intrinsic)= 40%
Post-renal = 5-15%

7. Causes of ARF
Renal 40%
Pos-renal 5%
Pre-renal 55%

9. Clinical assessment
There may be marked hypotension and signs of poor peripheral perfusion, such as delayed capillary return. It may occur without hypotension like in NSAIDs, ACEI.
Not always the cause of reduced blood flow is clear like in concealed blood loss can occur into the gastrointestinal tract, following trauma or in to into the pregnant uterus.

10. Clinical assessment
In sepsis there is systemic circulatory vasodilation hence relative underfilling of the arterial tree even after fluid resuscitated.
The combination of sepsis with nephrotoxins such as NSAIDs is a common cause of ARF.

11. Clinical Manifestations
Patients with AKI may report symptoms such as anorexia, fatigue, nausea and vomiting, and pruritus, as well as a decline in urine output or dark-colored urine.
Furthermore, if the patient has become volume overloaded, shortness of breath and dyspnea on exertion may be noted.

12. Clinical Manifestations
On physical examination, findings such as asterixis, myoclonus, or a pericardial rub may be evident.
If volume overload is present, peripheral edema, pulmonary crackles, and jugular venous distention may be found.
It is also not unusual for a patient to be entirely asymptomatic, with advanced AKI discovered only by laboratory testing.

13. Management Establish and correct the underlying cause of the ARF.
If hypovolaemia is present, restore blood volume as rapidly as possible (with blood, plasma or isotonic saline (0.9%), depending on what has been lost).

14. Management
Optimise systemic critically ill patients may require inotropic drugs to restore an effective blood pressure. Recent trials do not support the use of low-dose dopamine in severely ill patients at risk of ARF.
Correct metabolic acidosis:
-Restoration of blood volume will correct acidosis by restoring kidney function.
-Sodium bicarbonate (e.g. 50 mL of 8.4%) may be used if acidosis is severe to lessen hyperkalaemia. 

15. Prognosis
 If treatment is given sufficiently early, renal function will usually improve rapidly; in such circumstances residual renal impairment is unlikely. In some cases, however, treatment is ineffective and renal failure becomes established.

16. Established acute renal failure
Established ARF may develop following severe or prolonged underperfusion of the kidney (pre-renal ARF), when the histological pattern of Acute tubular necrosis is usually seen.
Differential diagnosis of acute renal failure in a haemodynamically stable, non-septic patient
Urinary tract obstruction should always be excluded by history, Ultrasound.
Due to major vascular occlusion or small-vessel diseases .
Rapidly progressive glomerulonephritis (RPGN)
Acute interstitial nephritis.
Drugs and toxins  (NSAIDs, ACE inhibitors, aminoglycosides), (mushrooms, snake bite, paraquat, paracetamol).

17. Acute tubular necrosis (ATN)
ATN may result from
Ischaemia or
Nephrotoxicity, caused by chemical or bacterial toxins, or a combination of these factors.
Drugs which are toxic to renal tubular cells include the aminoglycoside antibiotics, such as gentamicin, the cytotoxic agent cisplatin, and the antifungal drug amphotericin B.
Dead tubular cells may shed into the tubular lumen, leading to tubular obstruction

18. During recovery, depending on the severity of the renal damage and the rate of recovery, there is often a diuretic phase in which urine output increases rapidly and remains excessive for several days before returning to normal. This is due in part to temporary loss of the medullary concentration gradient, and which depends on continued delivery of filtrate to the ascending limb of the loop of Henle and active tubular transport.

19. Urine findings in Prenal azotemia vs. Acute Renal Failure
Laboratory Tests            
Prenal azotemia  or   Glomerulonephritis
Acute renal failure or  Postrenal azotemia
Specific gravity  
>1.018
<1.012
Urine osmolality
>
<
Urine Na (meq)  
< 20 meq/l
> 40 meq/l
Urine/plasma creatinine  
> 40
< 20
Renal failure index (U Na/ U/P creat)  
< 1
>2
Fractional excretion Na (U/P Na/ U/P creat)x100
<1
Response to fluid challenge ++ ?
Urine sediment
normal
hyaline cast brown granular casts, cellular debris

20. Complications Expansion of extracellular fluid volume.
Hyperkalemia is a frequent complication of ARF; Coexistent metabolic acidosis may exacerbate hyperkalemia by promoting potassium efflux from cells. Hyperkalemia may be particularly severe, even at the time of diagnosis, in patients with rhabdomyolysis, hemolysis, and tumor lysis syndrome.
Metabolic acidosis, often with an increased anion gap. Acidosis can be particularly severe when endogenous production of hydrogen ions is increased by other mechanisms (e.g., diabetic or fasting ketoacidosis; lactic acidosis complicating generalized tissue hypoperfusion, liver disease, or sepsis; metabolism of ethylene glycol or methanol).

21. 4. Hyperphosphatemia is an almost invariable complication of ARF
4. Hyperphosphatemia is an almost invariable complication of ARF. Severe hyperphosphatemia may develop in highly catabolic patients or following rhabdomyolysis, hemolysis, or tissue ischemia. Metastatic deposition of calcium phosphate can lead to hypocalcemia, 5. Anemia develops rapidly in ARF and is usually multifactorial in origin. Contributing factors include impaired erythropoiesis, hemolysis, bleeding, hemodilution, and reduced red cell survival time. 6. Prolongation of the bleeding time is also common. Common contributors to the bleeding diathesis include mild thrombocytopenia, platelet dysfunction, and/or clotting factor abnormalities (e.g., factor VIII dysfunction).

22. 7. Infection is a common and serious complication of ARF. 8
7.Infection is a common and serious complication of ARF. 8.Cardiopulmonary complications of ARF include arrhythmias, pericarditis and pericardial effusion, and pulmonary edema. 9.Vigorous diuresis can occur during the recovery phase of ARF.

23. Investigations Urea and creatinine. Electrolytes.
Full blood count Clotting screen.
Urinalysis.
Renal ultrasound
Others; Albumin, Chest X-ray, Serology and ECG.

24. Management
In the absence of dialysis, the most common causes of death are
Hyperkalaemia and
Pulmonary oedema, followed by
Infection and uraemia itself.

25. Management of Ischemic and Nephrotoxic Acute Renal Failure
Therapy
Management Issue
Reversal of Renal Insult
Restore systemic hemodynamics and renal perfusion through volume resuscitation and use of vasopressors
Ischemic ATN
Eliminate nephrotoxic agents
Nephrotoxic ATN
Consider toxin-specific measures: e.g., forced alkaline diuresis for rhabdomyolysis, allopurinol/rasburicase for tumor lysis syndrome

26. Management of Ischemic and Nephrotoxic Acute Renal Failure
Therapy
Management Issue
Prevention and Treatment of Complications
Salt and water restriction
Intravascular volume overload
Diuretics
Ultrafiltration
Restriction of enteral free water intake
Hyponatremia
Avoidance of hypotonic intravenous solutions, including dextrose-containing solutions
Sodium bicarbonate (maintain serum bicarbonate >15 mmol/L or arterial pH >7.2)
Metabolic acidosis
Administration of other bases, e.g., THAM
Dialysis

28. Hyperkalemia & EKG K > 5.5 -6 Tall, peaked T’s Wide QRS Prolong PR
Diminished P
Prolonged QT
QRS-T merge – sine wave

30. Therapy
Management Issue
Restriction of dietary K+ intake
Hyperkalemia
Eliminate K+ supplements and K+-sparing diuretics
Loop diuretics to promote K+ excretion
Potassium binding ion-exchange resins (e.g., sodium polystyrene sulfonate or Kayexelate)
Insulin (10 units regular) and glucose (50 mL of 50% dextrose) to promote intracellular mobilization
Inhaled β-agonist therapy to promote intracellular mobilization
Calcium gluconate or calcium chloride (1 g) to stabilize the myocardium
Dialysis

31. Therapy
Management Issue
Calcium carbonate or gluconate (if symptomatic)
Hypocalcemia
Discontinue Mg++ containing antacids  
Hypermagnesemia
Treatment usually not necessary if <890 µmol/L or <15mg/Dl
Hyperuricemia
Allopurinol, forced alkaline diuresis, rasburicase
Protein and calorie intake to avoid net negative nitrogen balance
Nutrition
To prevent complications of acute renal failure
Dialysis
Avoid other nephrotoxins: ACE inhibitors/ARBs, aminoglycosides, NSAIDs, radiocontrast unless absolutely necessary and no alternative
Choice of agents
Adjust doses and frequency of administration for degree of renal impairment
Drug dosing

32. Absolute indications for dialysis include:
Marked volume overload.
Severe metabolic acidosis.
Hyperkalemia refractory to medical therapy.
Pericarditis.
Asterixis, Encephalopathy +Peripheral neuropathy.
PEM.
Anorexia, vomiting + nausea after exclusion of other causes.
blood urea levels of >100 mg/dL

33. Prognosis
In uncomplicated ARF mortality is low even when renal replacement therapy is required. In ARF associated with serious infection and multiple organ failure, mortality is 50-70%.
Outcome is usually determined by the severity of the underlying disorder and other complications, rather than by renal failure itself.