ACUTE KIDNEY INJURY

Acute kidney injury (AKI), previously termed as acute renal failure (ARF), denotes quot;rapid deterioration of renal functions, resulting in retention of nitrogenous wastes and complex fluid and biochemical derangementsquot;.

• Documented oliguria with urine output lt;0.5 ml/kg/ hr for gt;6 hours, or

• Rise in serum creatinine by gt;0.3 mg/dl over 8 hours or gt;50% above the baseline in last 7 days

Severity of the AKI may be further graded into three stages by KDIGO criteria (Table 21.12).

Etiology: Depending on the site of lesion, AKI may be divided into: (a) pre-renal, (b) intrinsic or renal, and (c) post-renal kidney injury (Table 21.13). Diarrhea-induced dehydration and APSGN are the two most common causes of ARF in children.

a. Pre-renal AKI (40-55%), is a protective and reversible response to poor renal perfusion, where functional integrity of kidney is well preserved. However, untrea­ted cases may rapidly progress to intrinsic disease.

b. Intrinsic AKI (40-50%) involves primary or secondary impairment of glomerular filtration, tubular functions or interstitial damage, leading to complex biochemical abnormalities, which may/may not be reversible.

TABLE 21.13: Causes of acute kidney injury

Pre-renal causes (impaired perfusion)

• Fluid loss: Diarrhea, vomiting

• Massive blood loss: Trauma, surgery

• Hypoproteinemia: Nephrotic syndrome, burns

• Hypoperfusion: Shock, CCF, septicemia

Renal causes (impaired filtration/reabsorption)

• Glomerulonephritis: AcPSGN, RPGN, secondary GN

• Hemolytic uremic syndrome

• Acute tubular necrosis: Shock, hypoxia, acidosis

• Infections: Leptospirosis, septicemia, dengue

• Drugs: Aminoglycosides, Amphotericin, NSAIDs

• Toxins: Snake bite, hemoglobinuria, heavy metals

• Congenital dysplastic kidney

• Others: Hereditary nephropathies, TLS

Post-renal causes (obstructive)

• Congenital anomalies: PU valves, PUJ obstruction

• Functional: VUR, neurogenic bladder

• Acquired: Stones, tumors, blood clot

PU valves: Posterior urethral valves; PUJ: Pelvi-ureteric junction; VUR: Vesico-ureteric reflux; TLS: Tumor Lysis syndrome

c.

Pathogenesis: Irrespective of the etiology, all cases of AKI are characterized by—(a) volume overload due to oliguria with Solute and fluid retention, (b) uremia due to retention of nitrogenous wastes, (c) electrolyte abnormalities, e.g. hyponatremia, hyperkalemia, hyper­phosphatemia and acidosis, due to altered tubular functions, and (d) impairment of non-excretory renal functions, leading to hypertension (renin-mediated), anemia (erythropoietin-mediated), etc.

Clinical presentation of AKI is generally preceded by features of etiological disease. Important manifestations of established AKI include:

• Oliguria/anuria in gt;80% cases. Non-oliguric renal failure is common in infants and newborns.

• Edema of variable severity, including pulmonary edema in severe cases.

• Hypertension of variable severity, occasionally leading to encephalopathy, pulmonary edema and retinal hemorrhage.

• Signs of uremia, e.g. vomiting, stress ulcers, bleeding diathesis, encephalopathy, etc.

• Signs of electrolyte disturbances and acidosis

• Signs of primary disease, e.g. hematuria (APSGN), dehydration, pallor, dysentery (HUS), jaundice (Leptospirosis), etc.

• Signs of pre-existing renal disease, e.g. failure to thrive, anemia, rickets, etc.

Diagnostic evaluation: Presence of oliguria/anuria for gt;6 hours indicates possibility of impending or established AKI, which is confirmed and graded by elevated serum creatinine levels. However, detailed evaluation is essential to identify etiology and exact biochemical status for rational therapy, based on following:

History specially related to preceding events, e.g.

• Frothy or dark urine

• Vomiting/bleeding (pre-renal, HUS)

• Recent Skin/throat infection (APSGN)

• Drug/toxin exposure (interstitial nephritis)

• Fever/jaundice (leptospirosis, malaria)

• Family history (congenital/hereditary renal disease, stones, etc.

Examination specially to detect:

• Dehydration (pre-renal)

• Hypertension (APSGN)

• Palpable kidneys (obstructive uropathy)

• Full bladder (obstructive uropathy)

• Fundus examination (hypertensive changes)

Laboratory investigations

• Blood examination:

± Severe anemia (HUS, chronic renal disease)

± Hemolytic picture on smear (HUS, renal vein thrombosis)

± Thrombocytopenia - HUS, vasculitides

• Urine exam:

± Hematuria (nephritis), proteinuria (nephrotic)

± Casts: RBC (Glomerulonephritis), granular or tubular (tubular necrosis)

± Pus cells (pyelonephritis), eosinophils (interstitial nephritis)

• Renal functions tests:

± BUN, S. creatinine, S. uric acid

± S. electrolytes and blood gas analysis

• Immunological studies:

± C₃ levels (APSGN, collagen disorders)

± Antibody titers: ASO (APSGN), ANA (SLE)

• Microbiological investigations:

± Urine culture (UTI)

± Throat culture (APSGN)

• Others (for complications):

± Chest X-ray for pulmonary edema

± Ultrasonography for obstructive uropathy

± ECG for hyperkalemia

Renal biopsy is indicated only in cases with—(a) rapidly progressive glomerulonephritis, (b) unremitting AKI for gt;2-3 weeks, (c) unexplained etiology with suspected interstitial nephritis or underling systemic disease, e.g. SLE, IgA vasculitis, etc. However, it should be deferred during anuric phase and in presence of uremia and hypertension.

Presence of underlying chronic kidney disease with superimposed AKI should be considered in cases with—(a) growth failure, (b) severe anemia, (c) rickets/ mineral bone disease with high PTH, (d) hypertensive retinopathy, (e) contracted kidneys on USG.

Management of AKI aims to: (a) restore renal functions with hemodynamic and biochemical normality, (c) prevent and treat complications, and (d) provide alternative avenues for removal of toxic metabolic products, till recovery of renal functions. A step-wise approach is preferable in most cases, as follows:

Step I.

• Fluid challenge: In clinically dehydrated cases, IV normal saline (10-15 ml/kg) is given as bolus infusion over 45-60 minutes and urine output is collected preferably by catheterization. Additional boluses may be required in cases with severe dehydration. Urine output of gt;2 ml/kg in next 2-3 hours indicate probable pre-renal failure and further fluid therapy is continued. However, if oliguria persists, then:

• Diuretic challenge: In well-hydrated cases or after no response to fluid challenge as above, IV Furosemide (1-1.5 mg/kg) may be administered as a single dose. Urine output of lt;3 ml/kg in next 3-4 hours suggests intrinsic AKI with stage II/III disease. Furosemide should not be repeated if there is no improvement in urine output, due to potential risk for further AKI and drug-toxicity.

Step II. Management of established/intrinsic AKI: Fluid or diuretic challenge has no role in management of established AKI, who should be managed conservatively, unless indications for dialysis are present, as follows:

• Constant monitoring for intake, output, weight gain, blood pressure, renal functions (BUN, S.creatinine), and serum electrolytes (Na⁺, K⁺, Bicarbonates).

TABLE 21.14: D/D pre-renal vs intrinsic renal AKI

*(U.

• Fluid restriction: Total daily fluid requirement must be restricted to 300-400 ml/m²/d plus urine output and extra-renal loss in last 24 hours, and given orally or intravenously, as required. Fluid restriction is considered adequate, if patient looses 0.5-1.0% weight per day.

• Nutrition: As fluid restriction limits the caloric intake, high carbohydrate diet with additional fats is necessary to provide minimum 60-80 cal/kg/day and 1-1.2 gm/kg/day of proteins, along with micronutrient supplements. If oral intake is inadequate, additional calories may be given as concentrated IV infusions.

• Correction of dyselectrolytemia, which is invariably present in AKI, should be monitored frequently and managed as follows:

- Hyperkalemia is the commonest electrolyte abnor­mality in AKI. While restricted potassium intake in IV fluids/diet is enough for mild hyperkalemia, severe cases must be treated with IV calcium gluconate, sodium bicarbonate and Dextrose- insulin combination (Ch 7.3). Severe and refractory hyperkalemia is an indication for dialysis.

- Hyponatremia is often dilutional and rarely needs correction unless serum Na⁺ levels drop lt;120 mEq/L or seizures develop, which can be corrected slowly with 3% NaCl solution 6-12 ml/kg over 30-90 minutes. Hypernatremia usually indicates inadequate fluid replacement.

- Hypocalcemia and hyperphosphatemia are not as common in AKI as in chronic kidney disease and need to be treated accordingly (Chapter 21.10).

• Correction of acidosis: Metabolic acidosis is common in AKI due to reduced H⁺ and ammonia excretion and needs to corrected with IV NaHCO₃ only if serum bicarbonate levels drop lt;18 mEq/L. Refractory acidosis is an absolute indication for dialysis.

• Hypertension is usually treated with oral Nifedipine (0.3-3 mg/kg/day q8hr), though severe hypertension or hypertensive crisis may require IV sodium nitro­prusside infusion (0.5-8.0 mg/kg/min).

• Treatment of other complications includes:

- Seizures may develop due to primary cause, hyper­tension, hyponatremia or uremia, usually treated with IV diazepam (0.2-0.5 mg/kg).

- GIT bleeding may be prevented by antacids and H1 antagonists, e.g. ranitidine. Aluminium-containing antacids should be avoided due to higher risk of aluminium toxicity in uremia.

- Anemia is rarely severe and usually indicates dilution of ECF due to fluid retention. However, severe anemia (Hb gt;7 gm/dl) needs low-dose packed cell transfusions (3-5 ml/kg) cautiously due to risk of overload or exchange transfusion.

- Pulmonary edema is treated with oxygen supple­mentation, diuretics and dopamine infusion.

TABLE 21.15: Indications for dialysis

• Severe uremia with fluid overload (Pulm. edema)

• Severe/refractory hyperkalemia (gt; 6.5 or ECG signs)

• Severe/refractory metabolic acidosis (pH lt; 7.2)

• Severe/refractory hypertension, encephalopathy

• Dialyzable poisonings, e.g. barbiturates, salicylates

• Severe catabolic states, e.g. sepsis, burns, HUS, etc.

• Inborn errors of metabolism, e.g. urea cycle defects

- Control of infections: While prophylactic antibiotics are not recommended, nosocomial infections are common and should be treated with antibiotics in modified doses as per creatinine values.

Step III. Dialysis is indicated in refractory cases to conservative therapy, to remove excess of toxic meta­bolites (Table 21.15). There are three modalities for dialysis: (a) peritoneal dialysis, (b) intermittent hemodialysis, or (c) continuous kidney replacement therapies (CKRT).

While the choice of procedure depends on the age, hemodynamic status, integrity of peritoneal membrane and available facility/expertise, most cases in children can be successfully managed with simple, economical and effective peritoneal dialysis.

Peritoneal dialysis (PD) involves removal of toxic metabolites in the capillary blood by allowing them to equilibrate with dialysis fluid in peritoneal cavity, across the semi-permeable peritoneal membrane. The net trans-membrane movement of solutes is determined by osmotic gradient, electric gradient, molecular weight and pore size.

Indications: PD is preferred mode of dialysis in children with: (a) acute kidney injury, (b) dialyzable poisonings and (c) to tide over the crisis in chronic renal failure, till other modes of renal replacement therapy, discussed later are possible.

Procedure: PD is a simple procedure that involves:

• Insertion of appropriate size PD catheter, usually in midline between umbilicus and pubic symphysis, directed towards right iliac fossa;

• PD cycles, i.e. infusion of 30-50 ml/kg of commercial PD fluid through PD catheter (inflow), allowing it to remain in peritoneal cavity for some time (30-60 minutes) for diffusion of solutes (dwell-time) and finally, the removal of fluid using siphon-effect through same catheter. Same steps are repeated till biochemical parameters return to safe limits, with each cycle lasting for ~ 60-70 minutes, including 5-10 minutes of inflow time, 30-60 minutes of dwell time and 5-10 minutes of outflow time.

Usually 30-40 cycles are performed initially, using commercial lactate-based dialysates with 1.36% dextrose, though higher concentrations of 2.5-3% may be used for faster ultrafiltration. Potassium should be added only after first 5-10 cycles as 3 mEq/L.

• Serial monitoring of renal parameters, e.g. BUN, creatinine and electrolytes, to modify the speed of infusions, dwell time, composition of PD fluid and to decide about stoppage of PD.

Contraindications for PD include: (a) severe ascites/ peritonitis, (b) severe bleeding tendencies, (c) abdominal wall defects or prior abdominal surgery/adhesions. In these cases, hemodialysis is necessary.

Complications of PD include: (a) local trauma, e.g. gut perforation, (b) infections, e.g. peritonitis, (c) metabolic problems, e.g. dyselectrolytemia, hyperglycemia (due to high dextrose PD fluid), (d) abdominal distension with respiratory embarrassment, and (e) procedure-related, e.g. leak/blockage of catheter. Risk of infection is directly related to duration of catheter in situ, and PD should not be continued from the same site for gt;72 hours.

Hemodialysis is the more efficient but more expensive option, which requires adequate infrastructure, exper­tise and good vascular access. It is also unsuitable for hemodynamically unstable patients or those with bleeding disorders.

HD requires HD machine, pediatric size dialyzers with tubings and Dialysate fluid. A double-lumen long venous catheter is used for vascular access, usually through femoral, internal jugular or subclavian veins, with each cycle lasting for 3-4 hours. Complications include hemodynamic instability, vascular access injuries and dialyzer reactions.

Continuous kidney replacement therapy (CKRT) is an extracorporeal purification technique, used round-the- clock in sick and hemodynamically unstable patients in ICUs, though it is expensive, needs expertise and carries risk of bleeding. Modalities include continuous venovenous hemofiltration or hemodialysis (CVVH/ CVVHD), continuous venovenous hemodiafiltration (CVVHDF) or slow continuous ultrafiltration (SCUF).

Some specific situations with AKI are as follows:

AKI in newborns is defined as Oliguria lt;1ml/kg/hr for 6-12 hours or Serum creatinine rise of gt; 0.3 mg/dl in 48 hours or gt;50% rise in 7 days. S. Creatinine gt;2.5 mg/dl indicates stage III AKI in newborns.

Etiologically, AKI in newborn is secondary to birth asphyxia. Sepsis, hypovolemia, congenital anomalies, nephrotoxic drugs or renal vein thrombosis.

Management is similar to that in older children, though fluids should be limited to 30 ml/kg/day (50-100 ml/ kg/day in preterms) and peritoneal dialysis is preferred. However, abdominal distension with respiratory embarrassment should be watch for and dialysis fluids should be carefully warmed to avoid hypothermia.

Acute cortical necrosis is a common cause of AKI in newborns following asphyxia, shock, DIC etc, while in older children it is mostly seen with HUS, burns or snake-bite.

Histopathologically characterized by presence of cortical infarcts in involved portions, most cases present with acute hematuria or renal failure.

Diagnosis is supported by USG (enlarged unobstructed kidneys) in a suspected case, with poor or no renal blood flow or function on renal scan.

Treatment is supportive and prognosis depends on amount of surviving cortex.

TABLE 21.17: Causes of chronic kidney disease

• Chronic glomerulonephritis:

- Idiopathic: MPGN, MGN

- Secondary: HSP, SLE, polyarteritis nodosa

• Hemolytic: Uremic syndrome

• Congenital anomalies: Polycystic or dysplastic kidney

• Hereditary: Alport syndrome, nephronophthisis

• Obst. uropathy: PUJ obstruction, PU valves, VUR

• Others: Amyloidosis, Wilms' tumor, cortical necrosis

21.10