1. Done by dr ali abdul-razak
Acute Renal Failure
Done by dr ali abdul-razak

2. Acute renal failure
Is a clinical syndrome in which a sudden deterioration in renal function results in inability of the kidney to maintain fluid and electrolyte homeostasis.

3. Pathophysiology
The driving force for glomerular filtration is the pressure gradient from the glomerulus to the Bowman space.
Glomerular pressure is primarily dependent on renal blood flow (RBF) and is controlled by combined resistances of renal afferent and efferent arterioles.
Regardless of the cause of ARF, reductions in RBF represent a common pathologic pathway for decreasing GFR.

4. CRITERIA ESTIMATED CCl URINE OUTPUT
 PEDIATRIC-MODIFIED RIFLE (RIFLE) CRITERIA
CRITERIA
ESTIMATED CCl
URINE OUTPUT
Risk
eCCl decrease by 25%
<0.5 mL/kg/hr for 8 hr
Injury
eCCl decrease by 50%
<0.5 mL/kg/hr for 16 hr
Failure
eCCl decrease by 75% or eCCl <35 ml/min/1.73 m2
<0.3 mL/kg/hr for 24 hr or anuric for 12 hr
Loss
Persistent failure >4 wk
End-stage
End-stage renal disease (persistent failure >3 mo)
eCCl = estimated creatinine clearance

5. Pathophysiology
The etiology of ARF comprises 3 main mechanisms.
Prerenal failure
Is caused by decrease in the circulating arterial volume, which leads to inadequate renal perfusion & decreased glomerular filtration rate, evidence of kidney damage is absent.

6. 2. Intrinsic renal failure includes diseases of the kidney itself, predominantly affecting the glomerulus or tubule, which are associated with release of renal afferent vasoconstrictors. Ischemic renal injury is the most common cause of intrinsic renal failure.
3. Postobstructive
renal failure initially causes an increase in tubular pressure, decreasing the filtration driving force.

7. Depressed RBF eventually leads to ischemia and cell death.
The initial ischemic insult triggers a cascade of events that includes production of oxygen free radicals, cytokines and enzymes, endothelial activation and leukocyte adhesion, activation of coagulation.

8. Recovery from ARF is first dependent upon restoration of RBF.
In prerenal failure, restoration of circulating blood volume is usually sufficient.
Rapid relief of urinary obstruction in postrenal failure results in a prompt decrease of vasoconstriction.
With intrinsic renal failure, removal of tubular toxins and initiation of therapy for glomerular diseases decreases renal afferent vasoconstriction.

9. Common causes of acute renal failure:
Prerenal
Renal
Postrenal
Dehydration
Hemorrhage
Sepsis
Hypoalbuminemia
Cardiac failure
GN(PSGN, SLE, ,HSP, membranoproliferative)
HUS,
Acute tubular necrosis
Renal vein thrombosis
Rhabdomyolysis
Acute interstitial nephritis
Tumor infiltration
Tumor lysis syndrome
Posterior urethral valve.
Ureteropelvic junction obstruction
Ureterovesicular junction obstruction
Ureterocele
Tumor
Urolithiasis
Hemorrhagic cystitis
Neurogenic bladder

10. Clinical features ( approach)
History
Infants with history of acute GE & dehydration most likely has prerenal RF.
6yr old child with a recent pharyngitis who presented with periorbital edema, hypertension & gross hematuria most likely has intrinsic ARF

11. Neonate with history of hydronephrosis on prenatal ultrasound & a palpable bladder most likely has congenital urinary tract obstruction like posterior urethral valve.
The presence of rash & arthritis may suggest SLE or HSP nephritis.
Palpable flank masses may suggest renal vein thrombosis, tumors, cystic disease, or urinary tract obstruction.

12. Common manifestations of established ARF:
Pallor, anorexia, nausea, vomiting.
GI bleeding( hematemesis and melena).
Fluid overload and pulmonary edema, hence cough, orthopnea and pulmonary rales.
Congestive HF, hypertension and pericarditis.
Neurologic complications include: headache, fatigue, muscle twitching, confusion, hallucinations.
Decreased immunity and liability to infections.

13. Diagnosis
Urinalysis
-- Normal urinary sediment without hemoglobin, protein, cells, or casts generally consistent with prerenal and postrenal failure
Granular casts == glomerulonephritis, interstitial nephritis
RBC casts =Glomerulonephritis
WBC casts = Pyelonephritis

14. Diagnosis
Blood urea nitrogen (BUN): is usually elevated but it correlates poorly with the GFR
Serum creatinine is increased.

15. Diagnosis
Cystatin C is emerging as a superior biomarker for early kidney injury. 
It is generated at a constant rate by all nucleated cells and is not secreted by the tubules or eliminated by other routes than renal excretion.
One of its principal advantages is that it identifies kidney injury while creatinine levels remain in the normal range. 

16. Diagnosis Complete blood cell count:
Anemia (dilutional or hemolytic as in SLE, renal vein thrombosis, & HUS, or blood loss, or decreased erythropoiesis).
Or leucopenia (SLE), thrombocytopenia( SLE, renal vein thrombosis, HUS).
Platelets dysfunction.

17. Blood biochemistry:
Hypocalcemia (moderate) is common in ARF, due to increase phosphate level
Hyperkalemia is a common and important complication of ARF.
Hyponatremia.
Metabolic acidosis
Serum C3 level may be depressed (post strep. GN) , & antinuclear Ab(SLE).

18. Imaging studies:
Chest x-ray may show cardiomegaly & pulmonary congestion (fluid overload).
Renal ultrasonography :
for detecting hydronephrosis due to obstruction
kidneys smaller than 9 cm suggest chronic renal failure. 
Renal parenchyma , hyperechogenicity indicates diffuse parenchymal disease
Color Doppler allows assessment of renal perfusion and can allow diagnosis of large-vessel etiologies of ARF.

19. Diagnosis
Electrocardiography: Obtain routine ECGs to look for manifestations of hyperkalemia and arrhythmias
Renal biopsy:
is often helpful in finding specific cause of intrinsic renal failure, is especially important when glomerular causes of ARF are suspected.

20. Urinary indices in distinguishing prerenal from intrinsic ARF:
index
Prerenal
Intrinsic renal
Specific gravity
Urine osmolality (mosm)
Urine sodium (meq/L)
Fractional Excretion of Na
Blood urea nitrogen/creatinin
>1.020
>500
<20
<1%
>20
<1.010
<350
>40
>2%

21. Treatment
Bladder catheter should be placed especially in cases of obstruction & in nonambulatory patient to ensure adequate urine drainage.
Determination of volume status is important in the initial evaluation of patients with ARF.

22. In case of hypovolemia, intravascular volume should be expanded by IV administration of isotonic saline 20ml/kg over 30 min
After volume resuscitation, hypovolemic patients generally void within 2hr: failure to do so points toward presence of intrinsic or postrenal ARF.

23. If after volume replacement the child didn't void, furosemide may be given as a single IV dose of 2-4mg/kg. Bumetanide is an alternative 0.1mg/kg.
If there is no response to diuretic challenge, diuretics should be discontinued & fluid restriction is essential & limited to 400ml/m²/24hr (insensible loss) plus the amount of urine output.

24. In general glucose containing solutions 10-30% without electrolytes are used as a maintenance fluids & the fluid is modified according to electrolyte balance.
Fluid intake, urine & stool output, body weight, & serum chemistries should be monitored on daily basis.

25. Exogenous sources of potassium should be eliminated.
Hyperkalemia (serum potassium>6meq/L):
Earliest ECG changes are peaked T wave followed by widening of QRS intervals, ST segment depression, ventricular arrhythmias, &cardiac arrest.
Exogenous sources of potassium should be eliminated.
Sodium polystyrene sulfonate resin (kayexalate), this will exchange sodium for potassium, 1g/kg its effect may take several hours.

27. 1-Calcium gluconate 10% solution, 1ml/kg IV, over 5-10 min.
If serum k >7meq/L with ECG changes, the following measures can be given:
1-Calcium gluconate 10% solution, 1ml/kg IV, over 5-10 min.
2-Sodium bicarbonate, 1-2 meq/kg IV over 5-10 min.
3-Regular insulin, 0.1 U/kg, with glucose 50% solution, 1ml/kg over 1hr .

28. Metabolic acidosis:
Mild acidosis is common as a result of retention of hydrogen ions; phosphate & sulfate, but rarely requires treatment.
If acidosis is severe (PH <7.15; serum bicarbonate<8meq/L) should be corrected by IV sodium bicarbonate to raise arterial PH 7.2.

29. Hypocalcemia:
Patient should follow low phosphorus diet & phosphate binders should be given by mouth
to bind any ingested phosphate & increase gastrointestinal phosphate excretion, e.g calcium carbonate, the starting dose 1-3 tablets with meal.
GI symptoms Oral or IV H2 blockers such as ranitidine can be given.

30. Hyponatremia:
It is commonly dilutional disturbance which must be corrected by fluid restriction rather than sodium chloride administration, which should be limited to those patients with symptomatic hyponatremia (seizure, lethargy) or those with serum sodium less than 120 mEq/L.
Acute correction of the serum sodium to 125 mEq/L (mmol/L) should be accomplished using the following formula:
Meq NaCl required=
0.6 x body weight(kg) x [125- S.Na meq/l]

31. Hypertension may result from the primary disease process like GN or HUS or from expansion of extracellular fluid volume.
Salt & water restriction is critical, & diuretic administration may be useful,
Isradipine (  mg/kg/dose, maximum dose 5 mg qid) may be administered for relatively rapid reduction in blood pressure
Or amlodipine mg/kg/day qd or bid),
B- blockers(propranalol) mg/kg/day divided bid-tid

32. Neurologic symptoms in ARF may include headache, seizure, lethargy & confusion.
Diazepam is the most effective agent in controlling seizure.

33. Correction of anemia and if Hb falls below 7g/dl, give packed RBC
Nutrition is of critical importance, sodium, potassium, & phosphorus should be restricted.
Protein intake should be restricted moderately while maximizing caloric intake to minimize accumulation of nitrogenous wastes.

34. Dialysis: indicated in the following:
1-Volume overload with evidence of hypertension &/or pulmonary edema refractory to diuretic therapy.
2-Persistent hyperkalemia.
3-Severe metabolic acidosis unresponsive to medical management.
4-Neurologic symptoms (altered mental status, seizures)

35. 6-Calcium/phosphorus imbalance, with hypocalcaemic tetany.
5-Blood urea nitrogen greater than mg/dl or lower if rapidly rising.
6-Calcium/phosphorus imbalance, with hypocalcaemic tetany.

36. Three types of dialysis available:
1-Intermittent hemodialysis: useful in patients with relatively stable homodynamic status, it can be done 3-7 times a week.
2-peritoneal dialysis:
Hyperosmolar dialysate is infused into the peritoneal cavity via a percutaneously placed catheter, the fluid is allowed to dwell for min & is then drained from the patient by gravity, cycles are repeated for 8-24 hr/day based on patients fluid & electrolyte balance.
It is contraindicated in abdominal disorders.

37. 3--Continuous renal replacement therapy:
This is useful in patients with unstable hemodynamic status, concomitant sepsis, or multiorgan failure in the intensive care unit;
it is an extracorporeal therapy in which fluid, electrolytes, & small & medium sized solutes are continuously removed from the blood (24hr/day).

38. prognosis
The mortality rate in children with ARF depends on the nature of the underlying disease process rather than on the renal failure itself.
In general, children with ARF caused by renal limited conditions (postinfectious GN) have a very low mortality rate < 1%
Those with ARF related to multiorgan failure have a very high mortality rate >90%.