AKI Dr Chuka Oti, a slide on acute kidney injury

Internal Medicine

1. ACUTE KIDNEY INJURY(AKI) Dr. Chukwuka Oti House Officer, Nephrology Unit, Dept of Internal Medicine, Federal Medical Centre, Yenagoa. 31/05/24.

2. OUTLINE Introduction/Definition Aetiology/Classification Epidemiology Pathophysiology Clinical features Investigations Treatment Complications Prognosis Differentials Conclusion References

3. INTRODUCTION/DEFINITION Acute Kidney Injury(AKI) is defined as sudden reduction in renal function over hours to days evidenced by deranged urea and creatinine or reduction in urine output, leading to failure to maintain fluid and electrolyte balance Kidney Diseases Improving Global Outcome(KDIGO) in 2012 defined AKI as increase in serum creatinine concentration>=0.3mg/dl or 26.5umol/l within 48hrs or >=1.5 times baseline within 7 days, or urine output <0.5ml/kg/hr for 6hrs

4. RIFLE CRITERIA FOR AKI Was developed by Acute Dialysis Quality Initiative(ADQI) in 2004 Makes use of any of three parameters namely; Serum Creatinine level, Estimated glomerular filtration Rate(eGFR) and Urine Output. It characterizes three levels of dysfunction(Risk, Injury and Failure) together with two outcome measures(Loss, End Stage).

5. RIFLE CRITERIA

6. RIFLE CRITERIA CONTD R=RISK=Serum Creatinine(SCr)>=0.3mg/dl or >=1.5x baseline OR Urine Output <0.5mls/kg/hr for 6-12hrs I=INJURY=SCr 2-2.9x baseline OR Urine Output<0.5ml/kg/hr for>=12hrs F=FAILURE=SCr>3x baseline OR>=4mg/dl OR Urine Output<0.3ml/kg/hr>=24hrs OR Anuria>=12hrs L=LOSS=Persistent loss of Function for >4 weeks E=END STAGE= Loss of Function >3 Months

7. AETIOLOGY/CLASSIFICATION Broadly classified into 3 based on Aetiology 1) PRE RENAL/HEMODYNAMIC AKI(55%) 2) RENAL/INTRINSIC/PARENCHYMAL AKI(40%) 3) POST RENAL/OBSTRUCTIVE AKI(5%)

8. PRE RENAL AKI Occurs due to inadequate perfusion to the kidneys Causes include Shock Sepsis Hemorrhage Fulminant hepatic failure Nephrotic Syndrome Congestive cardiac failure Hepatorenal syndrome

9. INTRINSIC/RENAL AKI Cellular damage to the renal parenchyma Causes A) Renal Vessel Obstruction eg renal vein thrombosis, renal arterial obstruction, hemolytic uremic syndrome, polyarteritis nodosa, other vasculitis B) Glomerular Damage eg Acute glomerulonephritis, Rapidly progressive glomerulonephritis, Lupus nephritis C) Acute Interstitial Nephritis D) Acute Tubular Necrosis eg in Prolonged pre renal insult, snake bite and other euvenomation, intravascular hemolysis, sepsis, nephrotoxic agents eg iodinated contrast agents, aminoglycosides, cisplatin, NSAIDS, cyclosporin.

10. INTRINSIC/RENAL AKI CONTD E) Developmental eg Polycystic kidney disease, dysplastic kidneys, etc.

11. POST RENAL AKI Occurs due to obstruction to normal flow of urine(obstructive uropathy) Causes include Luminal causes eg stones, clots Mural causes eg strictures, Benign Prostatic Hyperplasia, PUV, Malignancy Extrinsic Compression eg retroperitoneal fibrosis

12. EPIDEMIOLOGY AKI complicates 5-7% of hospital admissions worldwide and >30% of admissions in the Intensive Care Unit(ICU) Epidemiology of AKI differs between developed and developing countries owing to differences in demographics, economies, geography and comorbid disease burden In Nigeria, overall hospital prevalenceis 3.07% with community acquired AKI at 2.23% and Hospital Acquired AKI at 0.84%(Olowu et al, 2012)

13. EPIDEMIOLOGY CONTD Anochie et al in 2017 reported a hospital prevalence of 11.7 cases/yr, an incidence of 4.7% in Port Harcourt, 6.6% in Zaria and 7.1% in Enugu.

14. AKI PATIENT DEMOGRAPHICS AND INCIDENT RATES(SOURCE: RESEARCHGATE)

15. PATHOPHYSIOLOGY Dependent on aetiology In pre renal AKI, there is inbalance between vasoconstrictive and vasodilating factors 1) Decrease in effective circulatory volume 2) Activation of central baroreceptors(Angiotensin11, Norepinephrin, ADH, Endothelin 1, Thromboxane A2, Prostaglandin H2, Leukotriene C4 and D4) 3) Vasoconstriction of renal vascular bed which maintains renal blood flow and GFR 4) If hypotension can overwhelm the renal autoregulatory defense, leading to preferential constriction of efferent arterioles. This leads to ischemic injury to renal parenchyma.

16. PATHOPHYSIOLOGY CONTD Renal AKI occurs due to damage of one or more of the kidney structures, including the glomeruli, kidney tubules or interstitium Intrinsic renal AKI presents mostly as Acute Tubular Necrosis Sepsis Associated AKI; Sepsis causes generalized arterial vasodilation especially of the efferent arteriole, mediated by mainly cytokines, and leads to reduction in GFR it also causes microvascular thrombosis by causing endothelial damage Activation of reactive O2 species cause injury to renal tubules

17. PATHOPHYSIOLOGY CONTD Ischemia associated AKI; Ischemia causes infiltration and cytokine production by neutrophils, macrophages, B and T lymphocytes, complement activation and upregulation of adhesion molecules like integrins, selectins, TNFa, etc. Nephrotoxin associated AKI: Kidneys are highly susceptible to nephrotoxicity due to extremely high blood perfusion resulting to high concentration of exposure of tubular, endothelial and interstitial cells to toxins. Post Renal AKI: Involves hemodynamic alterations triggered by an abrupt increase in intratubular pressures

18. PATHOPHYSIOLOGY CONTD An initial period of hyperemia from afferent arteriolar dilation is followed by intrarenal vasoconstriction The vasoconstriction is from the generation of Angiotensin11, Thromboxane A2 and Vasopressin, with a reduction in Nitric Oxide production Reduced GFR is due to underperfusion of glomeruli and possibly changes in the glomerular ultrafiltration coefficient.

19. CLINICAL FEATURES 1) HISTORY: Serves to identify the aetiology PRE RENAL AKI: Hx of excessive fluid loss(vomiting, diarrhoea), excessive blood loss, compromised cardiac function(CHF, MI), liver cirrhosis/hepatorenal syndrome, drug history(NSAIDS, ACEIs, Cyclosporine etc) On Examination, symptoms in keeping with hypovolemia eg increased thirst, reduced urinary output, postural hypotension, dizziness, fatigue, muscle cramps Signs of hemodynamic compromise eg reduced capillary refill time, reduced skin tugor, dryness of mouth and mucous membrane, recent reduction in body weight etc

20. CLINICAL FEATURES INTRINSIC/RENAL AKI History: Use of nephrotoxic agents, exposure to contrast agents, past and current medications, history of hematuria, hypertension, previous throat infection or skin infection. On examination: Peripheral edema, raised JVP, signs of possible uremia eg asterixes, pericardial rub, nausea/vomitting, myoclonus etc

21. CLINICAL FEATURES POST RENAL HISTORY; Urinary frequency, urgency, urge incontinence, nocturia, dysuria, weak streaming, straining, hesitsncy, overflow incontinence, history of trauma to urogenital system or invasive procedures to the urinary tract EXAMINATION; Renal angle tenderness, pelvic masses, rectal masses, distended bladder, prostatic hypertrophy on digital rectal exam

22. INVESTIGATIONS HEMATOLOGICAL: Full Blood Count+differentials, blood culture, serology(HBV, HCV, ANA, ANTI GBM ANTIBODY) BLOOD CHEMISTRY: Serum Electrolyte, Urea and Creatinine(SEUCR), Blood Urea Nitrogen(BUN) IMAGING: Renal ultrasound, Non contrast CT Urography, Abdominopelvic Xray MICROBIOLOGY: Urinalysis, Urine MCS, Stool MCS Kidney biopsy if indicated

23. TREATMENT Treatment of AKI is multidisciplinary in nature and usually tailored according to aetiology Treatment Goals are: 1) Early recognition and correction of underlying cause 2) Restoration of renal perfusion 3) Prevention of ongoing kidney injury 4) Management of complications 5)Relieve obstruction if present 6) Aggresive supportive care

24. TREATMENT CLASSICAL CLINICAL STAGES OF AKI 1) Initiation stage 2) Oligo-anuric phase 3) Polyuric phase 4)Recovery phase

25. TREATMENT Pre Renal AKI: 1) Correction of volume depletion: Therapy is directed to restoring the fluid similar to that lost In severe acute hemorrhage, packed red blood cell is indicated In less severe ones like burns and pancreatitis, isotonic normal saline is used(0.9% Normal saline) In GIT fluid losses, variation in electrolyte content determine the type of replacement fluid Give 500-1000mls bolus in 1hr for young patients, but in the elderly in whom cardiac status is unknown, bolus of 250mls in 1hr

26. TREATMENT Monitor patient closely Total fluid replacement=Total output in previous 24hrs plus additional 500-1000mls to cover for insensible loss In case of cardiac failure, diuretic agents and digoxin therapy may increase cardiac output and improve renal perfusion In case of cirrhosis and hepatorenal syndrome, give Albumin 1gm/kg max 100g/24hrs Terlipressin(a vasopressin analogue, reduces portal hypertension) Milrodrine Norepinephrine

27. TREATMENT Monitor vitals regularly. In ideal situation a central venous catheter is to be used Normal CVP 8-12cmH2O For Intrinsic AKI: 1) Access volume status and correct if euvolemic 2)Avoid nephrotoxic drugs 3) Adjust drug dosages 4) Treat underlying cause 5) Supportive therapy: Restrict salt intake to 1-1.5g/day. Diuretic therapy if there is fluid retention.

28. TREATMENT Corret Electrolyte Imbalance HYPERKALEMIA: 1) Restrict dietary potassium 2) 10mls of IV 10% Calcium Gluconate given over 10 minutes 3) 50mls of IV 50% Dextrose Water 1:1 dilution+ 10IU IV Soluble Insulin 4) Nebulized Salbutamol 10-20mg in 4mls 0.9% N/Saline over 10 mins 5) Potassium binding resins 6) IV Sodium Bicarbonate 150meq in 1L dextrose water to correct metabolic acidosis 7) Dialysis

29. TREATMENT Hyponatriemia; Restrict oral and IV water intake POST RENAL Site of obstruction defines treatment approach Transurethral or suprapubic bladder catheterization for urgent decompression in acute obstruction. Ureteric obstruction may be treated by percutaneous nephrostomy tube placement or urethral stent placement

30. TREATMENT Relief of obstruction is usually followed by post decompression diuresis for several days

31. TREATMENT INDICATIONS FOR DIALYSIS IN THE MANAGEMENT OF AKI: CLINICAL INDICATIONS: Anuria (<100mls/24hrs for >3 days), uremic encephalopathy, uremic pericarditis, refractory pulmonary edema, uremic gastritis, bleeding diasthesis, uncontrolled hypertension, urine output <200mls for 12hrs or Anuria(<100mls/24hrs) BIOCHEMICAL INDICATIONS: cREATININE >600umol/l, Bicarbonate <12mmol/l, Urea>25mmol/l or daily rise >10mmol/l, BUN>100mg/dl, hyperkalemia>6.0mmol/L or daily rise >1mmol/l

32. TREATMENT MODES OF DIALYSIS; PERITONEAL DIALYSIS, HEMODIALYSYS HEMOFILTRATION

33. PATIENT ON HEMODIALYSIS

34. PROGNOSIS OF AKI(SOURCE:NATIONAL LIBRARY OF MEDICINE)

35. COMPLICATIONS OF AKI Chronic Renal Failure Uremic encephalopathy Cardiac Arrythmias Pulmonary Edema Infections Congestive cardiac failure Seizures

36. DIFFERENTIAL DIAGNOSES OF AKI Alcohol toxicity Gastrointestinal bleeding Sickle Cell Anemia Urinary Tract Infection Heart failure Chronic Renal Failure

37. CONCLUSION AKI is increasimgly common It involves high cost of management and carries hih morbidity and mortality risks The most common cause of in-hospital aki is Acute Tubular Necrosis that results from muitiple acute insults(sepsis, ischemia, nephrotoxins) No drug treatment has been shown to limit the progression of, or speed up recovery from AKI Review medications and adjust dose Recognize risk factors and interval promptly Best treatment is prevention.

38. REFERENCES Kidney disease: improving global outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012 Mar;2(1):1-138.Full text Palevsky PM, Liu KD, Brophy PD, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. Am J Kidney Dis. 2013 May;61(5):649-72.Full text Abstract National Institute for Health and Care Excellence. Acute kidney injury: prevention, detection and management. Dec 2019 [internet publication].Full text

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