acute kidney injury

ACUTE KIDNEY INURY

Acute renal failure/injury (AKI) describes a sudden and usually reversible loss of renal function,but not always. This develops over days or weeks and is usually accompanied by a reduction in urine volume. A high creatinine gives diagnosis of acute, acute on chronic, or chronic kidney disease.
Previous measurements is helpful to differentiate acute from acute on chronic.
Ultrasound demonstrating two small kidneys indicates chronicity.

Pre-renal acute renal failure (Reversible)

Hemodynamic disturbances can produce acute renal dysfunction that may be reversed rapidly by prompt recognition and treatment.
Pathogenesis
When there is hypovolemia, shock, heart failure or renal arteries stenosis, the physiology of the body tries to counteract by intra-renal vessels dilatation by action of:-
Vasodilator prostaglandins ( impaired by NSAIDs) .
Constriction of efferent arteriole action of rennin/angiotensin II, (impaired by ACEi).
More severe or prolonged underperfusion of the kidneys may lead decline in GFR with urine of :
A low volume of urine
Concentrated (osmolality > 600 mOsm/kg)
low in sodium (< 20 mmol/l).
These urinary changes may be absent in patients with pre-existing renal impairment or those who have received diuretics.
Clinical assessment
There may be marked hypotension
Postural hypotension on standing
Marked obvious bleeding
Signs of concealed blood loss
gastrointestinal tract
fractures of the pelvis or femur
Pregnant uterus.
Crush injuries or burns,
severe inflammatory skin diseases or sepsis.
Metabolic acidosis and hyperkalemia are often present.
When renal hypoperfusion is severe and/or prolonged, it will lead to established ARF with acute tubular necrosis.
The combination of sepsis with nephrotoxins such as NSAIDs is a common cause of ARF.
Management
Correct the underlying cause of the ARF.
If hypovolemia is present, restore blood volume as rapidly as possible (with blood, plasma or isotonic saline (0.9%), depending on what has been lost).
Follow iv fluid giving by central venous pressure and/or pulmonary wedge pressure.
Trials do not support a specific role for low-dose dopamine.
Correct metabolic acidosis:
Restoration of blood volume will correct acidosis by restoring kidney function.
Sodium bicarbonate (e.g. 50 mL of 8.4%) may be used if acidosis is severe to lessen hyperkalemia.
Prognosis
Efficiently and early treatment will correct renal function rapidly; and without residual renal impairment.


Established acute renal failure
When the treatment of reversible ARF is ineffective or delayed it will pass into established renal failure.
In patients without an obvious cause of pre-renal ARF, alternative 'renal' and 'post-renal' causes must be considered.

Acute tubular necrosis (ATN)

ATN results from ischemia or nephrotoxicity, caused by chemical, bacterial toxins, or both.
Drugs as aminoglycoside antibiotics (gentamicin), cytotoxic agent (cisplatin), and the antifungal ( amphotericin B).
Dead tubular cells may shed into the tubular lumen, leading to tubular obstruction.
Focal breaks in the tubular basement membrane and interstitial edema develop
There may also be profound alterations in the renal microcirculation.

Recovery from ATN

Tubular cells can regenerate and re-form the basement membrane which takes 10-14 days.
Regeneration phase (recovery) is often a diuretic phase in which urine output increases rapidly and remains excessive for several days before returning to normal.
This is due in part to temporary loss of the medullary concentration gradient
.
17.25 Differential diagnosis of acute renal failure in a hemodynamically stable, non-septic patientUrinary tract obstruction
Suggested by a history of loin pain, hematuria, renal colic or difficulty in micturition but often clinically silent
Can usually be excluded by renal ultrasound: essential in any patient with unexplained ARF
Prompt relief of the obstruction restores renal functionDrugs and toxins
Poisoning, e.g. some mushrooms, snake bite, paraquat, paracetamol
Therapeutic agents:
direct toxicity (aminoglycosides, amphotericin)
hemodynamic effects (NSAIDs, ACE inhibitors), often with other factors
Auto-toxins: rhabdomyolysis releasing myoglobin; myeloma cast nephropathyVascular event
Due to major vascular occlusion or small-vessel diseases, notably malignant HT and hemolytic uremic syndrome/thrombotic thrombocytopenic purpura.
May be precipitated by ACE inhibitors in critical renal artery stenosis
Urine usually shows minimal abnormalities but there may be hematuria in renal infarctionRapidly progressive glomerulonephritis
Typically, significant (dipsticks 3+) hematuria and minor proteinuria (often with red cell casts or 'glomerular' red cells)
Sometimes associated with systemic features (systemic vasculitis, SLE, Goodpasture's disease)
Useful blood tests include: ANCA, ANA, anti-GBM Abs, complement, immunoglobulins
Renal biopsy shows aggressive glomerular inflammation, usually with crescent formationAcute interstitial nephritis
Usually caused by an adverse drug reaction
Characterised by small amounts of blood and protein in urine, often with leucocyturia
Kidneys are normal size
Requires cessation of drug and often prednisolone treatment
Features of established ARF
These reflect the causal condition, such as trauma, septicemia or systemic disease, together with features of renal failure.


Urea and creatinine
The rate of rise in plasma urea and creatinine is determined by the rate of protein catabolism (tissue breakdown).
In ARF with severe infections, major surgery or trauma, the daily rise in plasma urea often exceeds 5 mmol/L (30 mg/dL).

Alterations in urine volume

Patients are usually oliguric (urine volume < 500 mL daily).
Anuria is rare and usually indicates acute urinary tract obstruction or vascular occlusion.
In about 20% of cases, the urine volume is normal or increased, but with a low GFR (non-oliguric ARF).

Disturbances of fluid, electrolyte and acid-base balance

Hyperkalemia is common
Dilutional hyponatremia (inappropriate oral fluid or intravenous dextrose)
Metabolic acidosis due to accumulation of acidic waste products.
Hypocalcemia occurs when recover is delayed
.

Figure 17.16 Pulmonary edema in acute renal failure. The appearances are indistinguishable from left ventricular failure but the heart size is usually normal. Blood pressure is often high.

Other features

'Uremic' features include initial anorexia, nausea and vomiting followed by drowsiness, apathy, confusion, muscle-twitching, hiccups, fits and coma.
Respiratory rate increased due to acidosis, pulmonary edema or respiratory infection.
Pulmonary edema (volume overload & increased pulmonary capillary permeability).
Anemia is common, due to excessive blood loss, hemolysis or decreased erythropoiesis.
Bleeding tendency occurs, when recovery is delayed
In ARF, humoral and cellular immune mechanisms are depressed.


Management
In the absence of dialysis, the most common causes of death are:
hyperkalemia
pulmonary edema
infection
uremia itself
Hyperkalemia (a plasma K+ concentration > 6 mmol/L) must be treated.
Immediate fluid management
Optimize blood volume to ensure adequate renal perfusion, with monitoring of central venous pressure
Pulmonary edema or anuria usually require dialysis to remove sodium and water.
Temporary respiratory support (CPAP), or (IPPV)) may be life-saving.
Severe acidosis - sodium bicarbonate if volume status allows.
Addressing the underlying cause of the ARF
Simple initial investigations as:-
ultrasound to exclude obstruction
renal biopsy, may be necessary.
There is no specific treatment for ATN, other than restoring renal perfusion.
Intrinsic renal disease -immunosuppressive for glomerulonephritis
Plasma exchange - microangiopathic diseases
pelvic or ureteric dilatation- bladder outlet obstruction, this needs percutaneous nephrostomy.


17.26 Acute renal failure in old agePhysiological change: nephrons decline in number with age and average GFR falls progressively.Creatinine: as muscle mass falls with age, less creatinine is produced each day. Serum creatinine can be misleading as a guide to renal function.Renal tubular function: declines with age, leading to loss of urinary concentrating ability.Drugs: increased drug prescription in older people (e.g. diuretics, ACE inhibitors and NSAIDs) may contribute to risk of ARF.Causes: infection, renal vascular disease, prostatic obstruction, hypovolemia and severe cardiac dysfunction are common.Mortality: rises with age, primarily because of comorbid conditions.
Fluid and electrolyte balance
After initial resuscitation, daily fluid intake should equal urine output plus an additional 500 mL.
If abnormal losses occur, as in diarrhea, additional fluid and electrolyte replacement is required.
Large changes in body weight, the development of edema or signs of fluid depletion indicate that fluid intake should be reassessed.
Since sodium and potassium are retained, intake of these should be restricted.

17.27 Suggested investigations in all patients with established acute renal failureInitial testInterpretation and further testsUrea & creatinineCompare to previous results. Chronically abnormal in CKDElectrolytesIf potassium > 6 mmol/L, treat urgentlyCalcium & phosphateLow calcium with high phosphate may indicate CKD
Abnormal in rhabdomyolysis: measure creatine kinaseAlbuminLow albumin in nephrotic syndrome (see urinalysis below)Low albumin in sepsis: take blood culturesC-reactive protein (CRP)Erythrocyte sedimentation rate (ESR) is misleading in renal failure
High CRP may indicate sepsis or inflammatory diseaseUrinalysisLess reliable in an oliguric catheterised patient.
Marked hematuria suggests severe GN or bladder/obstructive lesion
Heavy proteinuria in glomerular disease: measure PCR or ACRUrine microscopy

Casts or dysmorphic red cells suggest glomerulonephritis (GN)

Leucocytes suggest infection/interstitial nephritis
Crystals can be characteristic of drugs or uric acidRenal ultrasound
Hydronephrosis enlarged bladder: request prostate-specific antigen (PSA) and imaging of prostate and urinary tract
Small kidneys suggest CKD
Asymmetric kidneys in renovascular: consider renal artery imagingCultures
Blood, urine, wounds etc. as appropriate
Treat all infectionsChest X-rayPulmonary edema in fluid overload
Globular heart in pericardial effusion: perform echo
'Bat wing' appearance with normal heart size ( low Hb) may suggest pulmonary hemorrhage: measure CO transfer factor
Fibrotic change in systemic inflammatory disease with lung and kidney involvement: request pulmonary function and high-resolution CTSerologyHIV and hepatitis serology is urgent if dialysis is neededECGIf patient is > 40 yrs or has electrolyte abnormalities


17.28 Suggested investigations in established acute renal failure in particular circumstances
PossibilityConsiderVascular occlusionKidney size may be normal if occlusion acute(Of aorta, or renal artery to single kidney); pointers include newly missing pulses, complete anuriaUrgent arteriographyDoppler ultrasoundMalignant hypertension/sclerodermaClinical features; examine fundi, previous BP valuesIf very high blood pressure; often some rbc fragments on blood film and haemolysisAutoantibodies to extractable nuclear antigensSystemic inflammatory diseaseInfection as a differential diagnosis, especially endocarditis or tuberculosisPointers include suggestive history, multi-organ involvement, rash and evidence of glomerular diseaseOpportunity for urgent treatment; discuss with nephrologistComplement (see Box 17.41), antineutrophil cytoplasmic antibodies (ANCA), antinuclear factor (ANF), anti-GBM, cryoglobulins and tissue biopsyGlomerular diseaseAll tests for systemic inflammatory disease abovePointers include substantial haematuria or proteinuriaPlus urgent renal biopsy, unless cause is already knownInterstitial nephritisDetailed history and timing of drug exposuresConsider if urinary abnormalities minor but leucocytes present, exposure to possible causes, usually non-oliguric in early stagesEosinophilia and urinary eosinophilsRenal biopsyUric acid if tumour lysis possibleMyeloma kidneyFeatures of interstitial disease but cast formation often acute, so patients often oliguricOther evidence of myeloma: blood count, serum calcium, skeletal lesions, bone marrow. However, renal disease can occur without overt myelomaUrinary light chains (serum paraproteins are very common and usually incidental unless at very high level)Renal biopsyOther infections
E.g. leptospirosis, hantavirus, syphilis, post-streptococcal glomerulonephritisSerology, e.g. anti-streptolysin O titre



Protein and energy intake

If dialysis is likely to be avoided, dietary protein restriction (40 g/day).
Patients treated by dialysis may have more dietary protein (1 g/kg daily).
Give adequate energy and nitrogen to hypercatabolic patients (e.g. sepsis, burns). Enteral or parenteral nutrition may be required.
Infection control
ARF are at risk of intercurrent infection. Regular clinical exam & microbiological investigation, as clinically indicated, are required to diagnose and treat.

Drugs

Vasoactive drugs (NSAIDs and ACEi) may prolong ARF and they should usually be avoided.
Many drugs are excreted by the kidneys and dose adjustment may be required.

Renal replacement therapy

This may be required as supportive management in ARF.

Recovery from ARF

There is gradual return of urine output and a steady improvement in plasma biochemistry.
Some patients (as ATN or after obstruction), develop a 'diuretic phase'. For those fluid should be given to replace appropriatly.
Supplements of sodium chloride, sodium bicarbonate, potassium chloride, may be needed to compensate for increased urinary losses.


Prognosis
In uncomplicated ARF, (due to simple hemorrhage or drugs), mortality is low.
In ARF with serious infection and multiple organ failure, mortality is 50-70%.
Outcome is determined by the severity of the underlying disorder and other complications.









Nephrology Lectures is/ Medicine 2014 - 2015

By Dr. Nidham A. Jaleel C.A.B.M. F.R.C.P -Ed & London Professor College of Medicine -Al-Mustanseriya

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