1. ACUTE KIDNEY INJURY

2. CLASSIFICATION OF AKI RIFLE classification
Proposed by acute dialysis quality initiative.(ADQI)
Represents 3 severity of injury classes– risk , injury & failure.
2 outcomes– loss of function & end stage renal disease.
Severity of injury defined by magnitude rise in serum creatinine from baseline value( within 7 day period or less) or reduction in volume of urine for defined period of time.
Outcome is defined by duration of kidney injury
Criticism– need of baseline creatinine value to define AKI & lack of clarity concering effect of RRT requirement on stage of AKI.

3. AKIN modification
Includes rise in serum creatinine( by 0.3mg/dl ≥26.4µmol/L.
Time window of 48 hrs.
Requirement of RRT is taken into consideration for staging.
Risk of death & RRT rises with increased stage of AKI.
If staging with creatinine or urine output differ, assign highest stage.

4. KDIGO The kidney disease: improving global outcome (KDIGO)defines AKI
as increase in sr cr > 0.3mg/dl(≥26.5µmol/L within 48 hrs or
increse in sr cr >1.5 times baseline which is known or presumed to occur within 7 days
or urine volume of ≤0.5 ml/kg /hr for 6 hrs or longer

5. AKI INCIDENCE : 2-5% -- general medical surgical admissions.
3 etiology:
prerenal : %(most common in ICU) -- caused by renal hypoperfusion with intact renal parenchyma
intrarenal: 35-40% -- caused by parenchymal renal disease
postrenal : 5%-- caused by urinary tract obstruction.
The mortality of AKI requiring RRT in critically ill pt remains 50 – 80%.

6. ICU AKI
Most AKI in ICU is caused by prerenal azotemia & rest predominantly by renal parenchyaml injury with acute tubular injury(ATN )
Former may convert into latter.
The mortality of AKI requiring RRT in critically ill pt remains 50 – 80%.
Outcome is particularly poor in septic ARF.
Mortality of ICU AKI increase with every additional nonrenal organ failure present at the time of initiation of RRT.
AKI with non recovery can cause ESRD directly or superimposed on significant CKD or rarely b/l renal cortical necrosis.

7. PRERENAL ACUTE RENAL FAILURE
Occurs with decreased renal perfusion (often in setting of systemic perfusion), presence of intact renal parenchymal tissue & rapid correction of GFR with restoration of renal perfusion .
Uncorrected or severe prerenal azotemia predisposes to development of ischaemic ATN.

8. RENAL BLOOD FLOW AUTOREGULATION
Renal perfusion is largely maintained within a range of MAP between 80 – 180 mmHg.
With fall in MAP< 80 mmHg, there is prepitious fall in renal blood flow & GFR.
2 mechanisms: myogenic reflex & tubuloglomerular (TG) feedback
Myogenic reflex: stretch receptors detect decrease in perfusion pressure & autoregulatory relaxation of afferent arteioles & vasodilatation .
TG Feedback: macula densa senses chloride concentration of tubular lumen which if decreased( due to decreased renal blood flow /GFR / intravascular volume/) , a vasodilatory signal is transduced to the corresponding afferent arteriole.

9. POST RENAL ACUTE RENAL FAILURE
Obstructive uropathy comprises 5% of all ICU AKI.
Common in elderly.
Unilateral obstruction is not sufficient to cause AKI.
Renal insuffiency occurs when obstruction occurs at site involving both kidneys or single functioning kidney.
Bladder neck obstruction (prostatic hypertrophy/ prostrate cancer/ neurogenic bladder) is most common cause.
Also caused by b/l ureteral obstruction/unilateral(single kidney)– stone/clots /sloughed renal papillae/ retroperitoneal masses or fibrosis.
Bladder catheterisation & renal USG are two most diagnostic tests.

10. INTRINSIC ACUTE RENAL FAILURE
Categorised according to site of lesion--- vascular/ glomerular/ tuboluinterstitial

11. ACUTE TUBULAR NECROSIS
Accounts for 85-90% of intrinsic AKI.
Ischaemic ATN is commonly seen in pts with sepsis, severe cardiac failure or post operative pts particularly after cardiac & aortic surgery.
Diagnosis of ATN is diagnosis of exclusion.
Usually reversible by tubular regeneration in surviving pts with previously normal renal function & in some cases recovery may be less complete than clinically apparent.
Failure to recover prompts consideration of D/D like b/l cortical necrosis/ renal atheroembolism/ renal atery throbosis/dissection/stenosis/RPGN.
Calcium, ROS, phospholipases/adhesion molecules & NO are cellular mediators that play role in ATN.

12. AMINOGLYCOSIDE TOXICITY
accounts for nephrotoxicity in 10-20% pts.
Excrereted by glomerular fiteration& reabsorbed by proximal tubular cells.
Are tubular toxins & earliest morphologic change consists of vacuolisation of proximal tubules, loss of brush borders , presence of nyeloid bodies within proximal tubular cells.
AKI develops days after therapy is started.
Causes non oliguric AKI due to concentrating defect & also potassium & magnesium wasting.
Once daily dosing decreases nephrotoxicity with no apparent loss of effectiness.

13. CONTRAST INDUCED AKI Occurs within 24 – 48 hrs.
mechanism: vasoconstriction & direct tubular toxicity due to generation of oxygen free radicals.
AKI mild & recovery generally begins 3- 5 days postcontrast.
nonionic low osmolal agents & nonionic isoosmolal agents are less nephrotoxic.
Isotonic 1ml/kg /hr 12 hrs pre & post contrast had less AKI than hypotonic saline in a study.
Sodabicarb was superior in alkalisation of urine thannormal saline.
N-acetylcystine did not lower the risk of CIAKI .
Renal guard system is novel method of preventing CI-AKI– fluid management device which precisely measures urine output& replaces the same amount of fluid IV.

14. NSAIDS & acute renal failure
NSAIDS inhibit PG & reduce GFR.
Hyperkalemia is also prominent as NSAIDS impair renin secretion.
Vasodilatory prostaglandins (prostacyclin & PGE2 are essential for maintainace of renal blood flow & GFR ineffective volume depletion state like CHF, cirrhosis, nephrotic syndrome
Conterbalance vasoconstriction effect of catecholamines & angiotensin ‖.
Chronic NSAIDS use is also associated with papillary necrosis

15. ACUTE TUBULOINTERSTITIAL NEPHRITIS
Caused by allergic reaction to drugs(penicillin,cephalosporin,ciprofloxacin, rifampicin) & infection (lefgionnare’s disease, CMV & hanta virus), autoimmune(renal transplant rejection), infiterative(sarcoidosis, lymphoma, leukaemia)
Triad of fever , rash & eosinophilia.
Urinalysis show leukocyturia, eosinophiluria,leukocyte casts & low grade proteinuria.
In absence of UTI,> 5 % urinary eosinophilssuggest diagnosis of drug induced TIN.
No therapy is recommended.corticosteroid therapy is unproven& is only recommende in pts with biopsy proven acute AIN.

16. RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS
Postinfectious glomerulonephritis. Lupus nephritis & good pasteur syndrome can cause acute or subacute renal failure.
RPGN causing AKI is an emergency.
The combination of AKI with active urine sediment(heavy proteinuria/hematuria/leukocyturia & erythrocyte /leukocyte mixed cellular cast) should prompt urgent evaluation with renal biopsy & serology.

17. VASCULAR CAUSES OF ACUTE RENAL FAILURE

18. MONITORING RENAL FUNCTION IN ICU.
Clinical indices such as plasma concentration of plasma concetration of urea nitrogen, creatinine, urine output & urine chemistry & urinanalysis may be assessed in combination to monitor renal perfusion & function.
Alternation in these markers is insensitive & often delayed manifestations of renal hypoperfusion & injury.
Direct measurement of GFR is probably most revelant marker of renal function to monitor in icu.
Abbreviated creatinine clearance measurement(2-4hrs) provide a more accurate estimate of GFR than sr creatinine alone.

19. CYSTATIN C
Serum cystatinC level may provide a more accurate estimate of GFR than sr cr alone.
Cystatin c is non glycosylated 13 kDa basic protein that is member of cystatin superfamily of cystein protein inhibitors.
produced by all nucleated cells
production is unaltered by inflamatory condition or muscle mass, only thyroid dysfuction can alter its serum levels in studies till date.
Emerging data suggest rise in cystatin level 1-2 days before sr cr in AKI (including CI/ malarial/cirrhotic/renal transplant & ICU)

20. DIAGNOSTIC APPROACH TO ACUTE RENAL FAILURE
HISTORY & PHYSICAL EXAMINATION :
Prerenal AKI:
Third space fluid loss—burn, pancreatitis, peritonitis, recent abdominal surgery.
Impaired renal blood flow – RAS/ vasculitis / depressed cardiac function.
Cardinal symptoms —orthostatic increase in pulse by 15 beats per minute/ decrese in DBP by 10mmHg– 5% ECF loss.

21. Postural increse in pulse (supine to standing) by at least 30 beats /min is 96% specific for clinically significant volume depletion wheras SBP can fall upto 20 mmHg in 10% normal & 30 % of ptsof age< 65yrs
Light headedness is specific sign of hypovolemia
Skin– cool mottled extremities, dry mucous membrane & axilla/ skin tenting.

22. Obstruction of urinary tract: flank pain/ hematuria/ changes in urinary flow.
Mistaken for UTI
examination – palpable kidneys/ pelvic or abdominal mass/bladder enlargement/BPH/ aneurysmal dilatation of aorta/ signs of IBD.
Detail drug history—cocaine induced rhabdomyolysis.
Skin rash—systemic vasculitis with renal involvement or acute tubulointerstitial nephritis.
Palpable purpura due to leucocytoclastic vasculitis is characteristic of HS purpura.
If prominent thoracic symptoms—pulmonary renal syndr0me like Goodpasteur’s syndrome, wegener’s/ microscopic polyarteritis,SLE/churg strauss syndrome.

23. DIAGNOSTIC TESTS IN ARF
Daily urine volume must be measured.
Bladder catheterisation is diagnostic & therapeutic with obstruction at level of bladder neck or urethra.
Min daily urine volume to excrete daily obligate solute load is 400 ml, assuming maximal urine concentrating ability1400mosm/kg, below which positive solute balance & azotemia develop(oliguria<400ml/24hrs)
If solute appearance increases(pt’s size/ hypercatabolism/hyperalimentation) or maximal urinary concentrating is diminished, higher urine volume is required to maintain adequate solute excretion urine volume < .5-1ml/kg /hr in ICU, solute retention is expected.

24. Anuric(<100ml/d), oliguric(<400ml/hr) or nonoliguric(>400ml/d)
Prerenal AKI with polyuria isseen rarely if excessive urine loss is the cause of prerenal state.(adrenal or mineralocorticoid defiency / excessive diuresis)
polyuric pts with urinary indices , majority have polyuric ATN than prerenal AKI.
Continued use of indwelling bladder catheter, afetr cause of AKI has been determined, is unnecessary(oliguric /anuric) & merely increases the risk of nosocomial infection.
Intermittent bladder catheterisation once / twice daily is frequently can provide useful information with lower risk of urosepsis.
Condom catheter cant replace foley catheter & associated with urinary infection & hence not recommended.

25. urinalysis In prerenal failure ,sp gravity>1.020.
Intrinsic & postrenal are isosthenuric with sp gravity 1.010
Sustancial proteinuria >3g/d strongly suggest possiblity of glomerular disease with nephrotic range proteinuria>3.5 g/24hrs pathognomic of glomerular rather than tubular disease.
Confirmed by spot urea/ creatinine ratio (>3) suggestive of nephrotic range ,which can be confirmed by 24 hr urine collection.
Glycosuria in absence of hyperglycemia strongly suggest proximal tubular injury with fanconi syndrome.

26. A positive reaction for blood in urine is consistent to acute glomerular or tubular, UTI, nephrolithiasis.
disproportionate dipstick & microscopic tests, pigment nephropathy(hemoglobinuria/ myoglobulinuria should be considered.
Intrinsic AKI has characteristic/diagnostic urine sediment.

27. Erythrocytecast with proteinuria & numerous erythrocytes & leukocytes is pathognomic of GN.
Large number of leucocyte. Leukocyte casts & eosinophils in uninfected urine , strongly suggest the diagnosis of drug induced AIN.
ATN is suggested by muddy brown granular casts, free renal tubular cells & tubular cell casts.

28. URINARY ELECTROLYTE Helps in differentiating prerenal & intrinsic AKI.
Fractional excretion of sodium
Fesodium =Usodium × P cr × 100/Psodium×Ucr
FENa < 1% in oliguric patient suggest prerenal azotemia with functioning renal tubules whereas value>3% suggest tubular injury.
Urinary sodium<10meq/l in an isolated measurement is often used as evidence of prerenal state.
Urinary fractional excretion of urea is superior to Fena to distinguish prerenal azotemia .