Acute Renal Failure aka Acute Kidney Injury. Dr H Bierman

Transcription

1 Acute Renal Failure aka Acute Kidney Injury Dr H Bierman

2 RIFLE criteria for diagnosis of AKI based on The Acute Dialysis Quality Initiative Increase in S Cr Urine output Risk of renal injury Injury to the kidney Failure of kidney function 0.3 mg/dl increase 2 X baseline 3 X baseline OR > 0.5 mg/dl increase if S Cr >=4 mg/dl < 0.5 ml/kg/hr for > 6 h < 0.5 ml/kg/hr for >12h Anuria for >12 h Loss of kidney function End-stage disease Am J Kidney Dis Dec;46(6): Persistent renal failure for > 4 weeks Persistent renal failure for > 3 months

3 Increase in Creatinine without AKI Inhibition of tubular creatinine secretion Trimethoprim, Cimetidine, Probenecid Interference with creatinine assays in the lab (false elevation) glucose, acetoacetate, ascorbic acid, cefoxitin flucytosine

4 Increase in BUN without AKI Increased production GI Bleeding Catabolic states (Prolonged ICU stay) Corticosteroids Protein loads (TPN-Albumin infusion)

5 Major Disease Categories Causing AKI Disease Category Incidence Prerenal azotemia caused by acute renal hypoperfusion 55-60% Intrinsic renal azotemia caused by acute diseases of renal parenchyma: -Large renal vessels dis. -Small renal vessels and glomerular dis. -ATN (ischemic and toxic) -Tubulo-interestitial dis. -Intratubular obstruccttion 35-40% *>90%* Postrenal azotemia caused by acute obstruction of the urinary tract <5%

6 Prerenal Azotemia Intravascular volume depletion bleeding, GI loss, Renal loss, Skin loss, Third space loss Decreased cardiac output CHF Renal vasoconstriction Liver Disease, Sepsis, Hypercalcemia Pharmacologic impairment of autoregulation and GFR in specific settings ACEi in bilateral RAS, NSAIDS in any renal hypoperfusion setting

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8 Acute Kidney Injury Prerenal and ATN encountered most often in the hospital setting: 70-75% in many studies Most common diagnostic consideration is therefore between these two conditions Prerenal: 1. Intravascular volume depletion 2. Hypotension 3. Edematous states 4. Localized renal ischemia ATN: 1. All causes for prerenal, leading to post-ischemic ATN 2. Toxins

9 Intrinsic Renal Azotemia Large Renal Vessel Disease Thrombo-embolic disease Renal Microvasculature and Glomerular Disease Inflammatory: glomerulonephritis, allograft rejection Vasospastic: malignant hypertension, scleroderma crisis, pre-eclampsia, contrast Hematologic: HUS-TTP, DIC Acute Tubular Necrosis (ATN) Ischemic Toxic Tubulo-interestitial Disease Acute Interstitial Nephritis (AIN), Acute cellular allograft rejection, viral (HIV, BK virus), infiltration (sarcoid) Intratubular Obstruction myoglobin, hemoglobin, myeloma light chains, uric acid, tumor lysis, drugs (indinavir, acyclovir, foscarnet, oxalate in ethylene glycol toxicity)

10 Postrenal azotemia Stones Blood clots Papillary necrotic tissue Urethral disease anatomic: posterior valve functional: anticholinergics, L-DOPA Prostate disease Bladder disease anatomic: cancer, schistosomiasis functional: neurogenic bladder

11 Initial diagnostic tools in AKI History and Physical exam Detailed review of the chart, drugs administered, procedures done, hemodynamics during the procedures. Urinalysis SG, PH, protein, blood, crystals, infection Urine microscopy casts, cells (eosinophils) Renal imaging US, Retrograde Pyelogram, CT etc Markers of CKD ipth, size<9cm, anemia, high phosphate, low bicarb Renal biopsy

12 AKI: Diagnostic studies-urine Urinalysis for sediment, casts Response to volume repletion with return to baseline SCr hr c/w prerenal event Urine Na; FENa FENa (%) = UNa x SCr x 100 FENa < 1%: Prerenal FENa 1-2%: Mixed FENa > 2%: ATN Hansel s stain SNa x UCr

13 iomarkers: AMI versus AKI Urinalysis in Acute Kidney Injury Normal/bland Abnormal sediment Hematuria RBC casts proteinuria WBC WBC casts Eosinophils RTE cells Pigmented casts Crystalluria Nonalbumin proteinuria Prerenal Postrenal Oncotic AKI Glomerulopathy Vasculitis Thrombotic MA Pyelonephritis Interstitial nephritis AIN Atheroembolic AKI ATN Myoglobin Hemoglobin Uric acid Toxins Drugs Plasma cell dyscrasia

14 Acute Kidney Injury IMAGING STUDIES Ultrasound: evaluates renal size, able to detect masses, obstruction, stones CT: detects masses, stones; caveat exists when IVCD is considered MRI/MRA: can detect RAS; use of Gadolinium carries uncertain R/B ratio in AKI 2 potential hemodynamic changes similar to IVCD, and NFD In the AKI setting, U/S provides most information with the most favorable R/B ratio

15 AKI: Acute Tubular Necrosis Non-oliguric vs. Oliguric Prognosis worse with oliguric ATN in most series Ischemic insult: medulla most susceptible to hypoxic event, cellular ATP depletion, oxidative injury AKI/ARF phase of ATN: 7-21 days on average Recovery phase of ATN: also known as diuretic phase High urine output (>3-4 L) K, Mg, PO4 wasting Associated with high FENa

16 AKI: Acute Tubular Necrosis Saline loading effective in lowering ATN risk from drugs/pigments/toxins; sometimes limited in post-ischemic ATN, particularly if CO/CI compromised Maintenance of CO, BP, avoid new insults Preventative agents have shown promise in animal models, but poorly translated to clinical situations Dopamine, fenoldopam, mannitol, statins, loop diuetics Identification of high risk AKI patients is essential to prevention: DM, CKD, CVD, poor nutrition

17 Acute Kidney Injury: AIN causes DRUGS ACEI Allopurinol Cephalosporins Cimetidine Fluoroquinolones Loop diuetics NSAIDS PCN Phenytoin Rifampin Sulfonamides Tegretol Thiazides INFECTION Bacterial Agents causing pyelonephritis Legionella Brucella Yersinia Viral Hantavirus HIV CMV,EBV,HSV

18 AKI: Glomerulonephritis (RPGN)/Systemic Immune-Complex Mediated SLE Cryoglobulinemic vasculitis Henoch-Schönlein purpura Post-strep GN Direct Ab attack Anti-GBM disease Goodpasture s syndrome Vasculitis Pauci-immune vasculitis Microscopic polyangiitis Wegener s granulomatosis Churg-Strauss syndrome Thrombotic Microangiopathy TTP HUS Scleroderma renal crisis Preeclampsia Malignant hypertension

19 Treatment of AKI Treatment is largely supportive in nature! Pharmacologic treatments under study: Dopamine: no benefit Atrial Natriuretic Peptide (ANP) or ANP-analogue (Anaritide): promising Human Insulin like growth factor 1: no benefit Renal Replacement therapy remains the cornerstone of management of minority of patients with severe AKI Nephron Clin Pract 2009;112:c222-c229

20 Is there a role for diuretics in the treatment of AKI in ICU setting? PICARD Study: Cohort study of 552 pts in 4 UC hospitals: no effect on in hospital mortality or longterm renal outcome Improved urine output and shorter duration of RRT (none has clinical relevance in ICU pts) But diuretics continue to be used for volume control in AKI in ICU setting! JAMA Nov 27;288(20): Crit Care Resusc Mar;9(1):60-8

21 When to do renal biopsy in AKI? Any evidence of glomerular disease -nephrotic range proteinuria -sub-nephrotic range proteinuria with hematuria -RBC cast AKI in renal allograft Determine the prognosis and chance of recovery of renal function in dialysis dependent AKI. Whenever potential Bx result can change the management or prognosis.

22 Acute Kidney Injury INDICATIONS FOR RENAL REPLACEMENT THERAPY Consensus generally includes: 1. Refractory volume overload 2. Severe metabolic acidosis; HCO3 may be variable, but declining level; also falling ph to Hyperkalemia, with levels > 6.5, or documented rapid rise refractory to medical therapy 4. Major uremic target organ manifestations i.e. pericarditis, progressive neuropathy, seizure, or unexplained AMS 5. Platelet dysfunction, bleeding diasthesis 6. AKI in setting of dialyzable drug/toxin

23 Acute Kidney Injury: conclusions Major advances in understanding AKI, but no clear definition that guides research on prophylaxis, prognosis AKI still carries high M/M risk, especially in ICU setting Improving volume status, hemodynamics rapidly aids in minimizing ischemic AKI risk; volume resuscitation, relief of urinary obstruction can be done concurrently Patient history, hosp chart review, routine labs, UA may establish cause in 40-60% of AKI Serologies and consideration of Bx are also adjuncts Advent of urinary biomarkers of ischemic tubular injury i.e. urine NGAL, will be next front in redefining AKI

24 Thank you!