SOME RENAL CAUSES OF AKI

1. Contrast induced nephropathy: Defintion: Impairment of renal function and is measured as either a 25% increase in serum creatinine from baseline or 0.5 mg/dL (44 mol/L) increase in absolute value, within 48-72 hours of intravenous contrast administration. For renal insufficiency to be attributable to contrast administration, it should be acute, usually within 2-3 days, although it has been suggested that RI up to 7 days postcontrast administration be considered CIN; it should also not be attributable to any other identifiable cause of renal failure. Following contrast exposure, SCr levels peak between 2 and 5 days and usually return to normal in 14 days. Risk Factors: (CKD) eGFR < 60 mls/min/1.73m2, older age (> 75 years old), cardiac failure, HTN, DM, nephrotoxic medications: aminoglycosides, NSAIDs, Amphotericin B, hypovolaemia, sepsis, dose of contrast and its characteristics (viscosity & osmolality), intra-arterial administrationMetabolic syndrome, anemia, multiple myeloma, hypoalbuminemia, renal transplant Mechanism: Contrast media cause a direct cytotoxic effect on the renal proximal tubular cells, enhance cellular damage by reactive oxygen species, and increase resistance to renal blood flow. They also exacerbate renal vasoconstriction, particularly in the deeper portions of the outer medulla. Prevention: Intravenous volume expansion with 0.9% sodium chloride or isotonic sodium bicarbonate, use minimal amounts of isoosmloar, less viscous contrast agent, methylxanthines (theophylline 200 mg iv 30 min before contrast administration, N-acetylcysteine600 mgorally twice a day, on the day before and of the procedure if creatinine clearance is estimated to be less than 60 mL/min, ascorbic acid and prophylactic hemodialysis. 2. Vancomycin Induced Nephrotoxicity: Mechanism: Vancomycinstimulates oxidative phosphorylation and formation of free radicals which appears to be the main mechanism causing damage to PCT. Vancomycin can affect the kidney by causing acute interstitial nephritis, glomerulonephritis, tubular cell toxicity and altered intra-glomerular hemodynamics Risk Factors: Dosage (>4 gm per day), prolonged therapy (> than 7 days), high trough levels (>20 mg/L), concomitant use of other nephrotoxic agents, obesity, prolonged stay in ICU with long term use of vasopressors. Prevention and Treatment: Monitoring of serum Vancomycin levels, Hydration, Antioxidants, High-flux hemodyalisis in case of pediatric patients/overdose.

3. Post infectious Glomerulonephritis:IT IS A TYPE OF NEPHRITIC SYNDROME. It is the most common cause of a glomerular disorder in children between 5 and 15 yrs; it is rare in children40 yr. Etiology: Mostly caused by Group A b hemolytic streptococci. It can also be caused after bacterial endocarditis and ventriculoatrial shunt infections. Other less common organisms include: Mycoplasma, N. Meningitidis, S. Typhi, Staphylococcal infections, Streptococcus Pneumoniae, Visceral abscesses (due to Escherichia coli, Pseudomonas,Proteus, Klebsiella, Clostridium sp) Mechanism: Microbial antigens are thought to bind to the glomerular basement membrane and activate primarily the alternate complement pathway both directly and via interaction with circulating antibodies, causing glomerular damage, which may be focal or diffuse. Alternatively, circulating immune complexes could precipitate on the glomerular basement membrane. Signs & Symptoms: asymptomatic hematuria (in about 50%) and mild proteinuria to full-blown nephritis with microscopic or gross hematuria (cola-colored, brown, smoky, or frankly bloody urine), proteinuria, oliguria, edema, hypertension, and renal insufficiency. Renal failure with fluid overload with heart failure and severe hypertension requiring dialysis affects 1 to 2% of patients and may manifest as a pulmonary-renal syndrome with hematuria and hemoptysis . Clinical manifestations of nonstreptococcal PIGN may mimic other disorders (eg, polyarteritis nodosa, renal emboli, antimicrobial druginduced acute interstitial nephritis). Diagnosis: Clinical evidence of recent infection, urinalysis typically showing dysmorphic RBCs, proteinuria (0.5 to 2 g/m2/day), random (spot) urinary protein/creatinine ratio is usually between 0.2 and 2 but may occasionally be in the nephrotic range ( 3).WBCs, and renal tubular cells, often hypocomplementemia , biopsy (hypercellular glomeruli, initially with neutrophilic infiltration and later with mononuclear infiltration, microthrombosis, epithelial crescents formed within Bowman space, multiplication of endothelial and mesangial cells Treatment: Treatment is supportive and may include restriction of dietary protein, Na, and fluid and, in more severe cases, treatment of edema and hypertension. Dialysis is occasionally necessary. Antimicrobial therapy is preventive only when given within 36 h of infection and before GN becomes established.

4. Multiple Myeloma: Mechanism:Protein: Myeloma cells produce monoclonal proteins of varying types, most commonly immunoglobulins (antibodies) and free light chains, resulting in abnormally high levels of these proteins in the blood. Depending on the size of these proteins, they may be excreted through the kidneys. Kidneys can be damaged by the tubulopathic effects of proteins or light chains.Calcium:Increased bone resorption leads to hypercalcemia and causes nephrocalcinosis thereby contributing to the kidney failure.Amyloidosis: Patients with Amyloidosis have high levels ofAmyloidprotein that can be excreted through the kidneys and cause damage to the kidneys and other organs. Tubulointerstitial and Glomerular damage are the most common types of renal damage. Signs & Symptoms: Predominantly those of the myeloma (eg, skeletal pain, pathologic fractures, diffuse osteoporosis) and a normochromic-normocytic anemia. Diagnosis: Urine sulfosalicylic acid test or urine protein electrophoresis (myeloma kidney), Biopsy (glomerulopathy), renal insufficiency, bland urine sediment, negative or trace-positive dipstick for protein, elevated total urinary protein Treatment: Management of multiple myeloma, prevention of volume depletion and maintenance of a high urine flow rate5. Tumour Lysis Syndrome: Definition: Group ofmetaboliccomplications that can occur after treatment ofcancer, usuallylymphomasandleukemias, and sometimes even without treatment. These include: hyperkalemia,hyperphosphatemia,hyperuricemiaandhyperuricosuria,hypocalcemia, and consequentacute uric acid nephropathyandacute renal failure. Pretreatment spontaneous tumor lysis syndrome. This entity is associated with acute renal failure due to uric acid nephropathy prior to the institution of chemotherapy and is largely associated with lymphomas and leukemias. It is not associated with hyperphosphatemia. Prevention: Allopurinol, Rasburicase, adequate hydration Treatment: Acute renal failure prior to chemotherapy: Rasburicase, loop diuretics, hemodialysis.Acute renal failure after chemotherapy: Hemodialysis

6. Sepsis induced kidney injury: Incidence: Acute kidney injury (AKI) occurs in about 19% patients with moderate sepsis, 23% with severe sepsis and 51% with septic shock, when blood cultures are positive. Mechanism: ischemia-reperfusion injury, direct inflammatory injury, coagulation and endothelial cell dysfunction, and apoptosis. Diagnosis: RIFLE (risk, injury, failure, loss, end-stage) criteria and acute kidney injury network (AKIN) criteria Protective measures: Volume resuscitation, vasopressor support, maintenance of intra-abdominal pressure, low tidal volume ventilation & tight glucose control Pharmacological interventions: Fenaldopam, Activated protein C Hemodialysis