Acute Kidney Injury and Laboratory Investigations Part II PDF

Acute Kidney Injury and Laboratory Investigations Part II Dr Taryn Pillay Department of Chemical Pathology University of Witwatersrand Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) NHLS ...

Acute Kidney Injury and Laboratory Investigations Part II Dr Taryn Pillay Department of Chemical Pathology University of Witwatersrand Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) NHLS  RECAP Acute Kidney Injury(AKI) is characterized by a rapid loss of renal function Characterized by: Retention of Urea, Creatinine, Hydrogen ions and other Metabolic products +/- Oliguria Potentially Reversible Can be associated with a high mortality  Conventionally divided into 3 categories depending on functional impairment: Pre-Renal → related to a decrease in renal blood flow Renal/Intrinsic → intrinsic damage to kidneys Post-Renal → related to urinary obstruction  Outline Diagnostic Evaluation ❖History and Physical Examination ❖Biochemical Tests of Renal Function ❖Criteria from Guidelines (KDIGO Guidelines) ❖Novel Biomarkers Summary  Diagnostic Evaluation History and Physical Examination The clinical context, history, and physical examination can narrow the differential diagnosis for the cause of AKI Prerenal azotemia: - Clinical setting: Blood Loss, Vomiting, Diarrhoea, Glycosuria causing polyuria, Drugs eg) Diuretics, NSAIDs, ACE inhibitors, and ARBs - Physical signs: Orthostatic hypotension, Tachycardia, Reduced jugular venous pressure, Decreased skin turgor, and Dry mucous membranes  Intrinsic Renal: - History: Suggestive of progression from Pre-Renal AKI (Ischaemic Spectrum) Exposure to specific Nephrotoxins  A careful review of all medications is imperative in the evaluation of AKI. - Drugs are commonly a cause of AKI - Drug doses must be adjusted for estimated GFR - Idiosyncratic reactions to a wide variety of drugs may occur AKI accompanied by prominent physical signs may also be strongly suggestive of the cause: - palpable purpura, pulmonary hemorrhage → systemic vasculitis with Glomerulonephritis - Livedo reticularis and other signs of emboli to the legs → Athero-Embolic disease - Signs of limb ischemia may be clues to the diagnosis of rhabdomyolysis  Post-Renal AKI: - History of prostatic disease, nephrolithiasis, or pelvic or para-aortic malignancy - Presence of symptoms depends on the location of obstruction: *Ureteric Obstruction → Colicky flank pain radiating to the groin *Prostatic Disease → Nocturia, Urinary Frequency or Hesitancy *Bladder enlargement → Abdominal fullness and suprapubic pain - Definitive diagnosis of obstruction requires radiologic investigations Biochemical Tests of Renal Function Assessment of Renal function should start with examination of the Urine Simple observation still contributes to the investigation of patients with suspected renal disease NB: Observations must be made on a freshly voided sample  Diseases affecting the kidneys can selectively damage glomerular or tubular function Isolated disorders of tubular function are relatively uncommon In Acute Kidney Injury, there is a loss of function of whole nephrons Tests of Glomerular function are invariably required in the investigation and management of renal disease  RECAP Principal Function of the Glomeruli: ✓ Filter water ✓Filter Low Molecular Components ✓Retain High Molecular Components ✓Retain Cells Principal Function of the Tubules: ✓Reabsorption of Glucose, K, Na, Bicarbonate, Amino Acids ✓Reabsorption of Water → Urine concentration ability ✓Acid Base Regulation  Assessment of Glomerular Integrity The most frequently used tests are those that assess either the : - Glomerular Filtration Rate (GFR), or Urea, Creatinine, Cystatin C - Integrity of the Glomerular Filtration Barrier Proteinuria Haematuria (Red Blood Cells) Red Cell Casts  Assessment of Tubular Integrity Performed less frequently than tests of glomerular function Glycosuria Amino Aciduria Proximal Tubular Reabsorption Ability Acid-Base Regulation Renal Concentrating Ability → Osmolality  Urinalysis The urinalysis and urine sediment examination are invaluable tools → needs clinical correlation due to limited sensitivity and specificity 1. Volume: A reduction in urine output usually denotes more severe AKI (i.e., lower GFR) and is associated with a poorer prognosis Oliguria: 2% → This is due to tubular injury and resultant inability to reabsorb sodium NB: Several causes of ischemia-associated and nephrotoxin-associated AKI can present with FeNa < 1%, including sepsis, rhabdomyolysis, and contrast nephropathy  Osmolality The urine concentrating ability of the kidney is dependent upon many factors Adequate tubular function in multiple regions of the kidney is vital Pre-Renal : Urine Osmolality > 500 mOsm/kg → This is consistent with: - an intact medullary gradient and - elevated serum vasopressin levels causing water reabsorption resulting in concentrated urine Renal AKI : Urine Osmolality < 350 mOsm/kg → due to loss of concentrating ability NB: This finding is not specific Urine Osmolality: Serum Osmolality Pre-Renal AKI Urine Osmo : Serum Osmo > 1.3 Reflects concentration of the urine due to stimulation of ADH secretion ATN Urine Osmo : Serum Osmo < 1.3 Impaired ability of tubular cells to concentrate or dilute the urine This is one of the most useful indices Summary Pre-renal AKI ATN Urine Normal or Muddy brown Coarse granular microscopy + Hyaline casts casts, free renal tubular cells Spot Urine Na < 20 mmol/L > 20 mmol/L Usually < 10mmol/L FENa 2 % (usually > 3 %) Serum Urea : > 70 Usually “normal” i.e. 40 -60 Creatinine ratio NB. Normal has limited diagnostic utility Calculated Urinary Indices Urine : Serum > 1.3 < 1.3 Osmolality (usually 2 – 3) U: S Urea or Cr > 14 < 14  Novel Biomarkers – Emerging Surrogate Biomarkers Neutrophil gelatinase-associated lipocalin (NGAL) Protein expressed by neutrophils and epithelial cells including those of the PCT The encoding gene is upregulated in the presence of renal ischemia, tubule injury, and Nephrotoxicity Measured in plasma and urine Within 2-6 hrs of AKI → useful early predictor with prognostic value Non-Specific: Systemic Stress in the absence of AKI Kidney Injury Molecule 1 (KIM-1) Transmembrane protein Abundantly expressed in proximal tubular cells injured by ischemia or nephrotoxins such as cisplatin Not expressed in appreciable quantities in the absence of tubular injury or in extrarenal tissues Functional role may be to confer phagocytic properties to tubular cells, enabling them to clear debris from the tubular lumen after kidney injury Detected shortly after ischemic or nephrotoxic injury in the urine  IL-18 (Interleukin) Liver fatty acid–binding protein (L-FABP), Tissue inhibitor metalloproteinase inhibitor 2 (TIMP-2) Insulin growth factor– binding protein 7 (IGFBP7) Guidelines  Acute Kidney Injury - Diagnosis The presence of AKI is usually inferred by an elevation in the Serum Creatinine concentration Definition(KDIGO) AKI is defined as any of the following(Not Graded): ❖Increase in Serum Creatinine by >26.5 mol/l within 48 hours; or ❖Increase in Serum Creatinine to >1.5 X baseline, which is known or presumed to have occurred within the prior 7 days; or ❖Urine volume ↓ excretion of acids Impaired H secretion & Regeneration of HCO3 Reduced ammoniagenesis (due to impaired tubular cell function) (Acid-Base Status in Pre-Renal AKI on the other hand will depend on the type of fluid lost that caused the hypovolaemia e.g. vomiting vs diarrhoea; the underlying disease process e.g. DM and the electrolyte balance)  HIGH ANION GAP ATN - ↓ GFR Decreased filtration of anions: phosphates, sulphates, lactate & other organic anions -------> High Anion Gap  HYPERKALAEMIA ATN Due to ↓ tubular excretion of K HYPERPHOSPHATAEMIA ATN Due to ↓ glomerular filtration of phosphate NORMO/HYPOCALCAEMIA ↓ Serum Total Calcium ATN Hyperphosphataemia ---> when the Ca Pi solubility product is exceeded → precipitation of CaPO4 complexes in tissues → free Ca is consumed Hyperphosphataemia stimulates FGF23 which inhibits 1α hydroxylase → no activation of 25(OH)VitD Decreased functioning tubular cell function → decreased synthesis of 1,25(OH)2D, Klotho etc. (Mineral disorders in Kidney disease will be covered in detail later on in the Block) SUMMARY DIAGNOSIS OF HYPOVOLAEMIC PRE-RENAL AKI vs ISCHAEMIC CAUSES of RENAL AKI Combination of : History Preexisting disease & Risk factors Clinical findings Imaging e.g. ultrasound (Size discrepancies, hydronephrosis, cysts, stones etc.) Laboratory Tests and Indices – showing evidence of tubular damage and impairment of renal function