is an organ which is of most interest in the urinary system. it has a main role
in filter of circulating blood to remove the waste products from the body which
results from direct ingsstion or by catabolism of an organism. kidneys regulate
and maintain the levels of extracellular body, blood pressure, and circulating
blood volume normal by regulating the fluid and electrolyte volume which gets
excreted via urine.
The nephron is the functional unit of the kidney.
There are two types, they are cortical and Juxtaglomerular apparatus. Each
nephron consists of a renal corpuscle which is located in the cortex of the
kidney. in juxtaglomerular nephronsit
extends deep into the medulla toward the tip of the renal kidney wheras in
cortical nephrons tubular component in the cortex of the kidney.
Nephrotoxicity is an
kidney abnormal or dysfunction that mainly causes due to exposure to external
agents thay may be drugs and environmental chemicals. Toxic metals and heavy
metals shows toxic effects has been known for years on kidney by accumulating
and producing morphological and functional changes in kidney. Certain nephrotoxin
drugs includes pencillin, cephalosporin, sulphonamides, tetracyclines and
aminoglycosides. (Gaddam. Supriya Reddy et al(2015)). Exposure
to chemical reagents like ethylene glycol, sodium oxalate, carbon tetrachloride
also induces nephrotoxicity. Drugs and their metabolites are taken up by
the renal medulla particularly that has a relative vasculature compare to
cortex leading to toxic damage.
agents & chemical are well known to be nephrotoxic. The following are some
of the important nephrotoxic agents (Schrier RW et al (1993))
arsenic, lead, bismuth
B. Antineoplastic agents
Streptozotocin, Carmustine, Lomustine & Semustine
dose Methotrexate, Cytosine Arabinose, high dose 6-thioguanine, 5-flurouracil
Recombinant leukocyte and interferon
C. Antimicrobial agents:
Tetracycline, Acyclovir, Pentamidine,
Sulphadiazine, Trimethoprin, Rifampicin, Amphotericin B
D. Aminoglycosides :
Amikacin, Kanamycin, Streptomycin
anti-inflammatory agents (NSAID’s):
Indomethacin, Aspirin etc.
Gentamicin is an wide
spectrum antibiotic which shows effective against gram negative bacterial
infections (Reiter RJ et al (2002)).it shows nephrotoxicity as its side effect,
causes acute renal failure that was observed on 10 to 30% of patients(Kahlmeter
G et al (1984),Mathew TH(1992). the pathogenesis behind
this gentamicin nephrotoxicity is proximal tubular necrosis(Kosek JC et al
studies investigated that gentamycin nephrotoxicity caused by reactive oxygen
species leading to proximal tubular necrosis by lipid peroxidation of membrane
lipids, protein denaturation and DNA damage.(Banday AA et al (2008),Baliga R et
al (1998),Parlakpinar H et al (2005)). Gentamicin also acts as
an iron chelator is a potent catalyst of radical generation.
The term acute renal
failure was substituted currently as acute kidney injury.it is an reversible
kidney injury caused by sudden decrease in kidney function which is manifested
by hourly or daily or weekly increase in sr creatinine and blood urea nitrogen
(Schrier R et al ,2004) Different
definition has been given my different organizations that includes acute
dialysis quality intitiative(ADQI), Acute kidney injury network (AKIN), Kidney
disease international global outcome (KDIGO).KDIGO was an most acceptable one
to define AKI.
“Increase in serum creatinine (SCr) by ?0.3 mg/dl (
26.5 mmol/ within 48 h” Or “Increase in SCr to ?1.5 times baseline, which
is known or presumed to have occurred within the prior 7 days ” or “Urine volume <0.5 ml/kg/h for 6 h". (Cerd a J et al, 2008 and Khwaja A ,2012) Acute kidney injury shows 2147 and 4085 per million populations per year of incidence in community in developing nations (Ali T et al ,2007 and Hsu C et al, 2007). Recent survey indicates that AKI was seen in 3.2 to 9.6% of hospital admission with 20 to 50% of mortality in ICU patients.(Fang Y et al, 2010, Lafrance J et al, 2010) Acute renal failure defined as a rapid deterioration of renal functions resulting in the accumulation of nitrogenous wastes such as urea and creatinine. There are different types of renal failure, they are pre-renal, intrinsic renal, post- renal. Pre-renal failure The most common cause of pre-renal failure is hypotension and hypovolaemia in combination. In decreased GFR condition there will be a increase urea production i.e., large protein intake and increased protein catabolism. Intrinsic renal failure It includes acute tubular necrosis, acute interstitial nephritis and acute glomerulonephritis. Acute tubular necrosis induced by renal hyperperfusion or due to exposure to nephrotoxins that may be exogenous or endogenous toxins and combination of both. Causes of ischaemic acute tubular necrosis A. Intravascular volume depletion Major trauma, burn and crush injury. Haemorrhage Pancratitis, vomiting, diarrhea, peritonitis, dehydration. Hypoalbuminemia. Fluid volume depletion secondary to renal losses. B. Decreased cardiac output Congestive heart failure at severe and low cardiac output syndrome. Pulmonary hypertension and pulmonary embolism. C. Increased vascular resistances ratio: Renal vasoconstriction Systemic vasodilation Liver cell failure D. Renovascular obstruction: Renal artery: Atherosclerosis, embolism, thrombosis, vasculitis. Renal vein: Thrombosis, compression. E. Increased blood viscosity Multiple myeloma Macroglobulinaemia Polycythaemia F. Aggravation of renal hypoperfusion by interference with renal auto regulation: Prostaglandin synthesis inhibitors as NSAIDs. Angiotensin converting enzyme inhibition in patients with renal artery stenosis. Causes of acute tubular necrosis: A. Exogenous nephrotoxins include: Antibiotics: aminoglycosides, cephalosporin, sulphonamide, quinolone, tetracyclines. Amphotericin, polymyxin, pentamidine, acyclovir, bacitracin. Anaesthetic agents: methoxy florane. Contrast media: Diatrizoate, lopanoic acid Anti-ulcer: cimetidine, excess milk –alkali. Analgesics: Phenacetin. Diuretics: Mercurials. Metals: mercury, lead, arsenic, bismuth, cadmium, antimony. Organic solvents: Carbon tetrachloride, tetrachlorethane, tetrachlorethylene. Glycols: ethylene glycol, xylitol. Poisons: Paraquat, diquat, mushroom, snake bite, stings, bacterial toxins. Chemotherapeutic and immunosuppressive agents: Cisplatin, methotrexate, mitomycin, nitrosoureas, cyclosporine A and D-Pencillamine. B. Endogenous nephrotoxins include Pigments : myoglobin, haemoglobin, methemoglobin. Crystals : uric acid, Calcium, oxalate. Tumour specific syndromes: tumour lysis syndrome, Plasma cell dyscrasias. Risk factors associated with contrast media nephropathy includes renal insufficiency, Diabetes mellitus, hepatic insufficiemcy, cardiovascular disease, increasing age, dehyadration, multiple myeloma- Hypoalbuminaemia, Dose of contrast- Hyperuricaemia.