Nephrology and renal failure

1. Acute renal failure
KIU - series

2. Objective
• Definition of ARF
• Epidemiology
• Etiology of ARF
• Management of ARF
– Diagnosis of ARF
– Treatment of ARF

3. Definition;
• Abrupt sustained decline in GFR resulting
in impaired renal physiological function.
• Diagnostic criteria1;
– Abrupt(48hrs)absolute rise in serum
cr.≥0.3mg/dl(from baseline<2mg/dl)
– OR a % serum cr. rise ≥50%
– OR oliguria <0.5mls/kg/hr > 6hrs
1) Acute Kidney Injury Network: report of an initiative to improve outcomes in AKI

4. AKIN
stage
Serum Creatinine
Criteria
Urinary Output
Criteria
Time
1  Cr ≥ 0.3 mg/dL or 
≥ 150-200% from
baseline
< 0.5
mL/kg/hr
> 6 hrs
2  Cr to > 200-300%
from baseline
< 0.5
mL/kg/hr
> 12 hrs
3 Cr to > 300% from
baseline or Cr ≥
4mg/dL with an acute
rise of at least 0.5
mg/dL
< 0.5
mL/kg/hr
or anuria
X 24 hrs
X 12 hrs
*Patients needing RRT are classified stage 3 despite the stage they were before starting RRT
Mehta R, Kellum J, Shah S, et al.: Acute kidney Injury Network: Report of an Initiative to improve
outcomes in
Acute Kidney Injury. Critical Care 2007; 11: R31.

5. Acute renal failure (ARF) or acute kidney
injury (AKI)
• Oliguria: <400 ml urine output in 24 hours
• Anuria: <100 ml urine output in 24 hours

6. Epidemiology
• It occurs in
– 5% of all hospitalized patients and
– 35% of those in intensive care units
• Mortality is high:
• up to 75–90% in patients with sepsis
• 35–45% in those without

7. Non-Oliguric vs. Oliguric vs. Anuric
• Oliguric renal failure.
– Functionally, urine output less than that required to
maintain solute balance (can’t excrete all solute taken in).
– Defined as urine output < 400ml/24hr.
• Anuric renal failure.
– Defined as urine output < 100ml/24hr.
– Less common – suggests complete obstruction, major
vascular catastrophy, or more commonly severe ATN.

8. Non-Oliguric vs. Oliguric vs. Anuric
• Classifying by urine output may help establish a
cause.
– Oliguria – more common with obstruction, prerenal
azotemia
– Nonoliguric – intrarenal causes – nephrotoxic ATN, acute
GN, AIN.
• More importantly, assists in prognosis.
– Significantly higher mortality with oliguric renal failure.
– 80% vs. 25% mortality in Oliguric vs. non-oliguric ARF
– Nonoliguric renal failure may also suggest greater liklihood
of recovery of function.

9. Etiology of ARF

10. Pre-renal AKI
– Volume depletion
• Renal losses (diuretics, polyuria)
• GI losses (vomiting, diarrhea)
• Cutaneous losses (burns, Stevens-Johnson syndrome)
• Hemorrhage
• Pancreatitis
– Decreased cardiac output
• Heart failure
• Pulmonary embolus
• Acute myocardial infarction
• Severe valvular heart disease
• Abdominal compartment syndrome (tense ascites)

11. Post-renal AKI
– Ureteric obstruction
• Stone disease,
• Tumor,
• Fibrosis,
• Ligation during pelvic surgery
– Bladder neck obstruction
• Benign prostatic hypertrophy [BPH]
• Cancer of the prostate
• Neurogenic bladder
• Drugs(Tricyclic antidepressants, ganglion blockers,
• Bladder tumor,
• Stone disease, hemorrhage/clot)
– Urethral obstruction (strictures, tumor)

12. Post-renal AKI

13. Renal
– Glomerular
• Anti–glomerular basement membrane (GBM) disease (Goodpasture
syndrome)
• Anti–neutrophil cytoplasmic antibody-associated
glomerulonephritis (ANCA-associated GN) (Wegener
granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis)
• Immune complex GN (lupus, postinfectious, cryoglobulinemia,
primary membranoproliferative glomerulonephritis)
– Tubular
• Ischemi
• Toxic
– Heme pigment (rhabdomyolysis, intravascular hemolysis)
– Crystals (tumor lysis syndrome, seizures, ethylene glycol
poisoning, megadose vitamin C, acyclovir, indinavir,
methotrexate)
– Drugs (aminoglycosides, lithium, amphotericin B,
pentamidine, cisplatin, ifosfamide, radiocontrast agents)

14. Renal
– Interstitial
• Drugs (penicillins, cephalosporins, NSAIDs,
proton-pump inhibitors, allopurinol, rifampin,
indinavir, mesalamine, sulfonamides)
• Infection (pyelonephritis, viral nephritides)
• Systemic disease (Sjogren syndrome, sarcoid,
lupus, lymphoma, leukemia, tubulonephritis, uveitis

15. Acute Renal Failure
Clinical Assessment (Volume Status,
Urinalysis and Ultrasound)
Pre-Renal Intra-Renal Post-Renal
Absolute Decrease
In ECF Volume
GI losses
Hemorrhage
Decreased
Renal
Blood Flow
Heart failure
Renal artery
stenosis
Altered Intra-Renal
Hemodynsmics
Drug-induced
NSAIDS/COX-2
Inhibitors
Calcineurin inhibitors
ACE inhibitors
AII Receptor Blockers
Sepsis
Hypercalcemia
Cirrhosis/Hepatorenal
syndrome
Abdominal compartment
syndrome
Tubulointerstitial
Disorders
Tubular Injury
Ischemic
Nephrotoxic
Interstitial Nephritis
Allergic-type
NSAID-type
Glomerular Disorders
Glomerulonephritis
Thrombotic
microangiopathies
Atheroembolic
disease
Anatomic Obstruction
Bladder Outlet
Prostate
Pelvic Tumor
Ureteral
Tumor
Stones
Stricture
Tubular Obstruction
Crystals
Calcium oxalate
(Ethylene glycol
poisoning)
Drugs
Indinovir
Methotrexate
Proteins
Myeloma cast
nephropathy
Clinical Approach to Acute Renal Failure

16. 5 Key Steps in Evaluating Acute Renal
Failure
1) Obtain a thorough history and physical;
review the chart in detail
2) Do everything you can to accurately
assess volume status
3) Always order a renal ultrasound
4) Look at the urine
5) Review urinary indices

17. Clinical feature-1
• Signs and symptoms resulting from loss of
kidney function:
– decreased or no urine output, flank pain, edema,
hypertension, or colour of urine
• Asymptomatic
– elevations in the plasma creatinine
– abnormalities on urinalysis

18. Evaluation of Renal Failure
• Is the renal failure acute or chronic?
– laboratory values do not discriminate between acute vs.
chronic
– oliguria supports a diagnosis of acute renal failure
• Clues to chronic disease
– Pre-existing illness – DM, HTN, age, vascular disease.
– Uremic symptoms – fatigue, nausea, anorexia, pruritis,
altered taste sensation, hiccups.
– Small, echogenic kidneys by ultrasound.

19. Acute Renal FAilure
• Symptoms:
– Fever, rash, joint pains, myalgias
• Concern for SLE, vasculitis, acute interstitial nephritis.
– Dyspnea – heart failure.
– Hemoptysis – Goodpasture’s, Wegener’s.
– Preceding bloody diarrhea – HUS.
– Preceding pharyngitis – post-Strep GN, post-
infectious GN.

20. Acute Renal Failure
• Urine output.
– Abrupt anuria.
• Acute obstruction, severe acute GN, sudden vascular
catastrophe.
– Slowly diminishing.
• Ureteral stricture.
• Prostatic enlargement.
– Presence of hematuria
• Painless – suggests GN.
• Painful – suggest ureteral obstruction.
Other symptoms - mental status changes and seizures

21. Acute Renal Failure
• Physical Exam.
– Skin – new rashes.
• Livedo reticularis – atheroemboli, SLE, cryoglobulins.
• Petechiae – HSP.
• Malar rash – SLE.
– Eye
• Papilledema – malignant HTN.
• Roth’s spots – endocarditis.
– CV
• Rub – suggestive of uremic pericarditis, lupus.
• Gallop – suggesting CHF.

22. • BUN/Creatinine ratio.
– > 20:1 – suggest prerenal or obstruction.
– Can be elevated by anything leading to increased urea
production/absorption.
• GI bleed
• TPN
• Steroids
• Drugs –.

23. Acute Renal Failure
Diagnosis
• Blood urea nitrogen and serum creatinine
• CBC, peripheral smear, and serology
• Urinalysis
• Urine electrolytes
• U/S kidneys
• Serology: ANA,ANCA, Anti DNA, HBV, HCV, Anti
GBM, cryoglobulin, CK, urinary Myoglobulin

24. Acute Renal Failure
Diagnosis
• Urinalysis
– Unremarkable in pre and post renal causes
– Differentiates ATN vs. AIN. vs. AGN
• Muddy brown casts in ATN
• WBC casts in AIN
• RBC casts in AGN
– Hansel stain for Eosinophils

25. Renal failure
Differentiation between acute and chronic renal failure
Acute Chronic
History
Short (days-
week)
Long
(month-years)
Haemoglobin
concentration
Normal Low
Renal size Normal Reduced
Renal osteodystrophy Absent Present
Peripheral neuropathy Absent Present
Serum Creatinine
concentration
Acute reversible
increase
Chronic
irreversible

26. Complications
• ECF expansion
• Hyperkalaemia
• Metabolic acidosis
• Hyperphosphataemia
• Hypocalcaemia
• Anaemia
• Bleeding diasthesis
• Infections
• Uraemic syndrome
• hypernatraemia

27. Treatment of AKI
• Optimization of hemodynamic and volume
status
• Avoidance of further renal insults
• Optimization of nutrition
• If necessary, institution of renal replacement
therapy

28. Replacement fluids
• Ringers lactate - since contains K+ do not give
to oliguric patient
• ½ NS – avoid in hyponatremic patient
• 0.9 NS resuscitation fluid of choice, but can
worsen hyponatremia if SIADH

29. Initial Management
• Correct hypovolaemia and hypotension
• Management of hyperkalaemia
• Avoid further nephrotoxins

30. Management priorities in AKI (I)
• Detect as early as possible even minimal AKI
• Exclude other renal causes of AKI,
• Search for and correct prerenal and postrenal
factors
• Review medications and stop nephrotoxins
• Optimize cardiac output and renal blood flow
• Restore and/or increase urine flow
• Monitor fluid intake and output, daily weight

31. - EMERGENCY THERAPY FOR
HYPERKALEMIA
- Ca gluconate
- Insulin + Glucose
- NaHCO3 ?
- 2 -Adrenergics ?
- Kayexalate Enema --slower

32. AKI - use of dopamine or diuretics
• Low dose dopamine – does not reduce the incidence
of AKI, the need for RRT or improve the outcome in
AKI. Is associated with increased myocardial 02
demand and increased incidence of atrial fib
• Diuretics - can sometimes convert oliguric to non
oliguric but no data that shorten duration of AKI,
reduce need for RRT, or improve overall outcomes.
But can help control volume overload.

33. Treatment cont’d
– Intrinsic renal AKI:
• Glucocorticoids/alkylating agents/plasmapharesis in
AGN/vasculitis
• Aggressive BP control in malignant HT
– Post renal AKI
• Ealry US and Relief of obstruction
– Supportive measures
• Restriction of salt and water intake in hypervolaemia and
diuretics
• Ultrafiltration/dialysis in refractory cases
• Hypernatraemia-free water,hypotonic saline/5%D
• Ca resonium 15g QDS orally
• If systolic BP<100mmHg despite optimal intravascular volume
start ionotropes
• Consider renal biopsy if features suggestive of multisystem disease
• Look for sepsis

34. Supportive measures should be aimed to correct the
following
• Hyperkalaemia – start on hyperkelemic protocal
• Metabolic acidosis - bicarbonate
• Nutritional mgt
• Anaemia - blood transfusion
• Antiacids -
• Avoid other nephrotoxins
• Dialysis – check on indications

35. Indications for RRT
• Refractory fluid overload
• Hyperkalemia – eg, K+ >6.5 meq/L, rapidly rising
levels, marked EKG changes especially if patient
oliguric or can not take kayexalate
• Marked metabolic acidosis in which are limited in
giving NAHCO3 due to volume constraints
• Signs of uremia, such as declining mental status, not
eating, uremic pericarditis (rare)

36. Timing of initiation of RRT
• Initiation of dialysis prior to the development
of symptoms and signs of renal failure due to
AKI is recommended.
• It is unproven whether initiation of earlier or
prophylactic dialysis offers any clinical or
survival benefit.
• If start RRT before symptoms is no concensus
on what level of BUN or creatinine to start

37. prognosis
• Depends on the underlying aetiology and severity of the
AKI
• Oliguria at presentation and cr>3mg/dl poor prognosis
• Overall mortality ~50%
• Older age-poor prognosis
• 50% subclinical renal impairment
• 5% never recover normal kidney function
• 5% have progressive decline in GFR following initial
recovery
N.B. primary goal is to achieve optimal blood volume, urine
flow is of secondary importance.

38. References
• Harrisons 16th Ed.
• Kellum et al. acute renal failure, aug 01/07
BMJ. Vol 76 No 3
• Uptodate 15.2
• Acute kidney injury network:report of an
initiative to improve outcomes in AKI