Definitionà-a syndrome characterized by rapid decline in glomerular filtration rate (hours to days), retention of nitrogenous waste products, and perturbation of extracellular fluid volume and electrolyte and acid-base homeostasis.-usually asymptomatic and diagnosed when biochemical monitoring of hospitalized patients reveals a recent increase in blood urea (BUN) and creatinine concentrations (Serum creatinine)- Classified into 3 catogoriesà Prerenalà Postrenalà Intrinsic
Pre-renal
àmost common form of ARF due to mild to moderate renal hypoperfusion.
àrapidly reversible upon restoration of renal blood flow and glomerular ultrafiltration pressure.
àAutoregulatory dilation of afferent arterioles is maximal at means systemic arterial blood pressures of 80mmHg and hypotension below this level is associated with precipitous decline in GFR.

Post-Renal
à Urinary tract obstruction, very infrequent, < 5% of all ARF
à Requires obstruction to urine flow between the external meatus and bladder neck, bilateral ureteric obstruction or unilateral ureteric obstruction in a patient with one functioning kidney.
àDuring the early stages of obstruction (hours to days), continued glomerular filtration leads to increased intraluminal pressure above the site of obstruction. As a result there is gradual distention of the proximal ureter, renal pelvis, calyces and a fall in GFR.

Intrinsic Renal ARF
à Can be further divided to 4 causesà Disease of larger renal vessels, diseases of the renal microcirculation and glomeruli, ischemic and nephrotoxic ARF, and tubulointerstitial inflammation.
à Difference from pre-renal ARFà hypoperfusion induces ischemic injury to renal parenchymal cells, particularly in tubular epithelium undergoing necrosis and apoptosis.
à With severe tubular injurym debris accumulates within tubules causing obstruction of fluid flow; tubules then dilate and compress nearby peritubular capillaries causing greater ischaemic damage.

Angiography (Radio contrast)
àIntrarenal vasoconstriction triggered by radiocontrast agents (contrast nephropathy). It induces ARF at prerenal stage, causing an acute fall in renal blood flow and GFR, (a relatively benign urine sediment, and a low fractional excretion of sodium). Severe cases may show clinical or pathologic evidence of ATN. Contrast nephropathy classically presents as an acute (onset within 24 to 48 h) but reversible (peak 3 to 5 days, resolution within 1 week) rise in blood urea nitrogen and creatinine and is most common in individuals with preexisting chronic renal insufficiency, diabetes mellitus, congestive heart failure, hypovolemia, or multiple myeloma. The syndrome appears to be dose-related, and its incidence is only slightly reduced in high-risk individuals by use of more expensive low osmolality, nonionic contrast agents

Patients with advanced atherosclerosis can develop ARF after manipulation of the aorta or renal arteries at surgery or angiography, following trauma, or, rarely, spontaneously due to embolization of cholesterol crystals to the renal vasculature (atheroembolic ARF). Cholesterol crystals lodge in small- and medium-sized arteries and incite a giant cell and fibrotic reaction in the vessel wall with narrowing or obstruction of the vessel lumen. Atheroembolic ARF is frequently irreversible. A myriad of structurally diverse pharmacologic agents induce ARF by triggering allergic interstitial nephritis, a disease characterized by infiltration of the tubulointerstitium by granulocytes (typically but not invariably eosinophils), macrophages, and/or lymphocytes and by interstitial edema. The most common offenders are antibiotics (e.g., penicillins, cephalosporins, trimethoprim, sulfonamides, rifampicin) and NSAIDs (Table 260-1).









Renal Vascular Hypertension
à In patient with atherosclerotic disease in aorta and peripheral arteries (15-25% with symptomatic lower limb atherosclerotic vascular disease has renal stenosis.
Renal stenosis reduces blood flow into kidneys thus activates RAAS. Causes Hypertension.
Hypertension causes RENAL Failure
àChronic hypertension leads to nephrosclerosis (arteriosclerosis of the kidney arteries). This reduces blood perfusion intrinsically in the kidneys and ischaemia.

Diabetes and Renal Failure
àHyperglycemia leads to glomerular hypertension and hyperfiltration, which in turn lead to deposition of protein in the mesangium. These protein deposits ultimately lead to sclerosis of the glomerulus and renal failure. Due to microalbuminurea.
à Diabetic vasculopathy, resulting in damaged arterioles in kidneys and hypoperfusion.

Effects of drug on Renal failure
-Direct toxicity to tubule epithelial cells and/or intratubular obstruction


NSAIDS, ACE- inhibitors and Angiotension 2 Receptor blockersà Inhibit renal prostaglandin biosynthesis and angiontensin 2 enzymeà inhibit vasodilation in arterioles to increase renal perfusion.