Acute Renal Failure Syed Rizwan MD 1 Acute

Acute Renal Failure Syed Rizwan, MD 1

Acute Renal Failure n n Comprises a family of syndromes Abrupt decrease in GFR(over hours to days) 2

MANIFFESTATIONS of ARF n n n Increase in BUN Increase in creatinine Oligouria(< 400 – 500 cc) 3

DEFINITION n n n No consensus Multiple Relative rise in Serum Creatinine > 0. 5 mg/dl if baseline creatinine is normal > 1 mg/dl if baseline serum creatinine is high 4

Creatinine and GFR « Creatinine produced in muscles « Creatinine excretion depends on, • Glomerular filtration • Proximal tubular excretion « Change in Serum Creatinine with no change in GFR • Muscle wasting or amputation lowers creatinine • Medications(Trimethoprim, Cimetidine) increase creatinine by deceasing tubular excretion 5

Blood Urea and GFR n Increase BUN with no change in GFR u u u n GI Bleed Hyper catabolic states Protein loading Glucocorticoids Tetracycline Decrease BUN with no change in GFR u u Protein Malnutrition Severe Liver disease 6

ARF and Biomarker n n Lack of sensitivity of BUN and creatinine Need for Biomarkers Kidney Injury Molecules-1(KIM-1) increased in Patients with Acute Tubular Necrosis None available for cliniical utility yet 7

Epidemiology of ARF n n Incidence, etiology and outcome varied depending on Population studied and Definition used Mostly in-Patient than out –Patient 5 -7% of hospital admissions Mortality varies between 20%-85% depending on cause 8

ARF Classification n Prerenal Renal Postrenal 9

Prerenal ARF n n n Hemodynamically mediated reduction in GFR in absence on Renal Parenchymal injury. ARF resolves if hemodynamic insult is reversed If hemodynamic insult is sustained, can result in overt renal injury 10

Renal ARF n Renal Parenchymal injury 11

Postrenal ARF n Acute obstruction to the Urinary Tract 12

Prerenal Azotemia n Decreased Glomerular perfusion(no renal injury) True Volume Depletion e. g. Diarrhea u Effective Volume Depletion, cirrhosis u Altered Intrarenal Hemodynamics e. g. ACEI u « Affenet dilatation « Efferent vasoconstriction 13

Prerenal Azotemia n True or Effective Volume depletion, Neurohumoral vasoconstrictor u Increased catecholamine u Renin-angiotensin system activation u Increased vasopressin release u 14

Renal Autoregulation n n Maintains Glomerular Blood Flow and thus GFR Afferent Vasodialtaion, Prostaglandins u Kallikrein-kinin u Myogenic influence u Nitiric oxide u n Efferent vasoconstriction u Angiotension 11 15

Prerenal Azotemia n Prerenal ARF presents with Oligouria u Low Urine Na from Na retention u Increased BUN : creatinine ratio >20: 1 u FENa < 1% u n Existing Renal Insufficiency or Diuretic can alter this picture 16

ARF and ACEI &ARB n ACEI & ARB have greatest benefits in Patients with high risk of ARF Old age u Diabetics u Cardiomyopathy u CHF with higher dose oh Diuretic u Renal Vascular disease u Chronic Kidney disease u 17

Prerenal ARF with ACEI &ARB n n n n Efferent Vasodilatation deceases GFRmedications Lower GFR raises serum creatinie but usually less than 30% Must monitor serum creatinine and electrolytes before and after starting or changing dose of these medications Stop if ARF Correct volume status W/u for renal Artery Stenosios Can reintroduce cautiously if reversible factors corrected 18

Prerenal ARF & NSAIDs n n n Both COX 1/Cox!! Inhibitors cause lower Prostaglandins synthesis Impairs Afferent vasodilatation decrease Glomerular perfusion Effect greatest in high risk population u u u CHF Cirrhosis CKD Vascular disease elderly 19

Abdominal Compartment Syndrome n n n Unusual cause of ARF Associated with increased intraabdominal pressure Manifestations, u u u n n Respiratory compromise Decreased cardiac output Intestinal ischemia Hepatic Dysfunction Oliguric ARF Increased renal venous pressure Recovery with decreased intraabdominal pressure 20

Post-Renal ARF n n Obstruction – complete or Partial Anuria or variable urine output Recovery depends on duration of obstruction Conditions Sonogram may not show obstruction, u u u n Retroperitoneal fibrosis Tumors Adenopathy Encasing ureter prevent dilatation 21

ARF- Renal n n Useful to categorize according to Anatomical injury. Primary sites, u u n n Glomerulus- Acute Glomerulonephritis Tubules- Acute Tubular Necrosis Interstitium- Acute Interstial Nephritis Vascular- Atheroembolism ATN- most common U/A-Protein, RBC, Casts, pigments 22

Acute Tubular Necrosis n n n Ischemic vs Nephrotoxic Most frequently multi-factorial Medical vs Surgical Ischemic- Hypotension, shock Nephrotoxic- Dye induced, Rhabdomyolysis 23

Acute Tubular Necrosis n n Initiation, maintenance, recovery Phases Mortality from very low to very high Potentially Preventable Long –term outcome in survivors very good 24

ATN- Specific Syndromes n n Radiocontrast Nephropathy Rhabdomyolysis Aminoglycoside Related Amphotericin B associated 25

Radiocontrast Nephropathy n n n 10% of Hospital acquired ATN Mild and Transient in Majority Risk factors, u u u u Amount of Dye(> 100 cc) Volume Depletion Renal Insufficiency DM Old Age CHF ACEI or NSAIDs 26

Radiocontrast Nephropathy n Risks higher with higher creatinine Normal- negligible risks u Mild- Moderate RI(Creatinine< 2)– 5 -10% risks u Mild- Moderate RI with DM- 1040% risks u Advanced Renal Disease- >50% u 27

Radiocontrast Nephropathy n n Pathogenesis incompletely understood Severe Renal vasoconstriction within seconds of contrast administration Direct Renal Tubular injury FENa < 1% 28

Radiocontrast Nephropathy n n n n n Independent risk factor of death Prevention in high risk Patients Consider Alternate imaging. g. MRI Volume repletion with Saline Minimize amount of Dye Low Osmolality contrast media? N-Acetylcysteine(Mucomyst)? Fenoldopam-Selective Dopamine agonist? Lasix, Mannitol, Dopamine –not helpful, may be risky Prophylactic Hemodialysis- not helpful 29

Radiocontrast Nephropathy n n N-Acetylcysteine – reducing agent, scavenge reactive oxygen species(ROS) No good large randomized trial to prove its efficacy Impact on morbidity and mortality unknown Used commonly in practice b/o potential benefits and lack of Toxicity 30

Aminoglycoside Nephrotoxicity n n n Usually after 7 -10 days Depends on dose and frequency Direct Proximal Tubular injury Once a day dosing may be less Nephrotoxic K. Ca. MG wasting Risk factors- age, Renal insufficiency, Dose, Volume depletion 31

ARF from Rhabdomyolysis n n n Muscle injury leading to ARF Most cases subclinical Myoglobinuria cause, u u u n n n Renal vasoconstriction Proximal tubular damage Intratubular cast (Obstruction) Hypovolemia(Third Spacing) Metabolic Acidosis, Electrolyte Imbalance(K, Ca, P) 32

ARF from Rhabdomyolysis n Subclinical causes more common Drugs u PVD u Seizure u n n FENa < 1% U/A- Heme/+vie but no RBC Aggressive Volume replacement Urinary Alkalization? , Mannitol? 33

Amphotericin B Nephrotoxiciy n n n n Very high incidence of ARF Binds to sterol in cell membrane Multiple sites in Nephrons Distal Tubular Acidosis Mg and K wasting Dose dependent Liposomal Amphotercin formulation less toxic Saline loading helpful 34

Postoperative ARF n n n ARF after vascular, cardiac and major abdominal surgery. Very high mortality Multifactorial 1 -5% after CABG. Risk factors, u Renal disease, cardiogenic shock, emergent surgery, Left main disease etc, 35

Acute Interstitial Nephritis n n n n Classical triad(fever rash & eosinophilia) not usually seen Mostly Drug related e. g. Cipro Infection : Strept. , Staph, CMV, EB virus, Hantaan virus etc Systemic Diseases : SLE, Sarcoidosis. Eosinophiluria may be absent Dx by renal Biopsy. Rx supportive, Hold Drug, Steroids ? 36

Atheroembolic ARF n n n n Require high degree of suspicion Cholesterol emboli Renal failure – acute or subacute Multisystem disorder Lived reticularis Digital Ischemia(Blue Toe Syndrome) GI bleed, TIA, Rahbdomyolysis 37

Atheroembolic ARF n n n ARF after vascular procedure ARF can be abrupt needing dialysis within few days. Can be subacute occurring in staggered steps separated by stable renal function. Patients on Anticoagulants are at high risk Eosinphilia, eosinphiluria, low complement. High mortality 38

Hepatorenal Syndrome n n n Profound renal vasoconstriction Resemble Pre-renal Azotemia Volume Expansion fail to improve renal function. Pathogenesis incompletely understood Oligiuric ARF, FENa low Diagnosis of exclusion 39

Hepatorenal Syndrome n n n Two Types Type 1 HRS: rapid ARF, hospitalized Pt. , >90% mortality Type 11 HRS : insidious onset, slow progression of RI, refractory ascites, better prognosis. ATN vs HRS Low FENa I n ATN casts in Bilirubinemia with HRS 40

Hepatorenal Syndrome n n n Rx difficult Volume expansion with Albumin Terlipressin(vasopressin analogue) Midodrine (selective alpha 1 adrenergic agonist)+ octreotide(a somstoastatin analogue) TIPS, Liver Transplantation Dialysis in selective Patients 41

ARF in HIV/AIDS n n n n Prerenal Azotemia Renal salt wasting from Adrenal Insufficiency. HIV Nephropathy High risk for ATN Drug side effects e. g. Pentamidine. Crystal nephropathy(indinavir) TTP(prognosis worse ) Rhabomyolysis 42

ARF from RPGN n n n n Less common Rapidly Progressive Glomerulonephritis include vasculitis, SLE, Wagner's Active Urinary sediments(RBC cast diagnostic) Higher degree of Proteinuria Serology helpful(ANCA, ANA, Ig. Mantibodyetc 0 Renal Biopsy usually required. Early diagnosis essential to prevent ESRD Rx with Steroids and Cytoxan 43

Rx of ARF n n n No proven Drugs Many cause preventable Volume expansion Withdrawal of Drugs Diuretics help in management but not curative Dopamine potentially harmful 44

RRT in ARF n n Renal Replacement Therapy usually the only option in severe ARF. Indication of RRT u u u n HYPERKALEMIA METABOLIC Acidosis Uremic Symptoms Fluid Load “Prophylactic” RRT u u Intermittent Hemodialysis CVVHD Extended Daily Dialysis(6 -12 h) Peritoneal Dialysis- not favored 45

CVVHD vs Hemodialysis n HD – u n CVVHD u n more stable Pt, SBP >90, no heparin, allows larger amount of fluid removal in 34 hours Unstable Pt. , low BP with high dose Pressers, allows gradual removal of fluids 24 h EDD u Allows no heparin dialysis, gradual removal of fluids, but expensive b/o Nursing Support 46

RRT- how to improve outcome? n n Lot of Questions to answer Frequency of Dialysis Quantification of Dialysis Type of Membrane of Dialysis u n n Synthetic vs. Cellulose Does Erythropoietin improves outcome? Faster fluid removal vs. slow fluid removal? 47