Kidney Injury

Kidney Injury

• Urea most commonly

measured

• Variable rate of urea

production; creatinine

more useful guide to GFR

but

• Plasma

[Creatinine]>Normal

equates to 50-60%

reduction GFR

Assessment of renal function

Serum creatinine and urea levels:

Definition:

•Failure of renal function

oReduced glomerular filtration rate

•Acute or chronic (or acute on chronic!)

Renal failure

Criteria for acute renal failure:

Grade ‘GFR’ criteria Urinary Output

criteria

Risk [Creatinine]x1.5 <0.5 ml/kg/hr x 6hr

Injury [Creatinine]x2 <0.5 ml/kg/hr x 12hr

Failure [Creatinine]x3 or

>350µmol/L with an acute

rise >40µmol/L

<0.3 ml/kg/hr x 24hr

Loss Persistent Failure >4wks

End stage

kidney disease

Persistent Failure

>3 months

Acute renal failure

Causes of acute renal failure:

•Pre-renal

•Renal (renal parenchymal disease)

•Postrenal

Pre-renal renal failure:

•Impaired renal perfusion

oHypovolaemia/systemic hypotension

oAcute cardiac failure

oObstruction of the renal vasculature

Clinical features of acute renal failure (uraemia):

•Anorexia, nausea, vomiting

•Pruritis

•Confusion, reduced consciousness, fits, coma

Acute renal failure

Features of pre-renal renal failure:

• Increased tubular Na+/H2O re-absorption (renal

compensation for hypoperfusion)

• Increased urine osmolality (>500 mOsm/kg)

• Increased urine specific gravity (>1.020)

• Decreased urine [Na+] (<20 mmol/l)

• Reduced fractional excretion Na+ (FENa) (<1%)

Acute renal failure

Fractional excretion Na+:

FENa expresses Na+ excretion as % Na+ filtration

Na+ excretion rate = UNa.V

Na+ filtration rate = GFR x Pna

= Creatinine Clearance x PNa

= (UCr.V/PCr)PNa

FENa = Na+ excretion ÷ Na+ filtration

= (UNa.V) ÷ (UCr.V/PCr)PNa

= (UNa.V/PNa) ÷ (UCr.V/PCr)

FENa = Na+ Clearance ÷ Creatinine Clearance

= UNa/PNa ÷ UCr/PCr

Acute renal failure

Treatment of pre-renal renal failure:

• Treat cause of hypoperfusion

• E.g. restore BP

• Monitor carefully for fluid overload

• Increased CVP/JVP

• Signs of pulmonary oedema

Acute renal failure

Renal failure due to renal parenchymal disease:

• Often caused by ischaemic damage (pre-renal failure may lead to

acute tubular necrosis)

• Pathogenic features include:

oTubular cell injury

oConstriction of renal microvessels

oReduced glomerular filtration

• Tubular re-growth: recovery in 7-21 days

Acute renal failure

• Features of renal failure due to acute tubular necrosis:

• Reduced tubular Na+/H2O re-absorption (tubular damage)

• Reduced urine osmolality (<350 mOsm/kg)

• Reduced urine specific gravity (<1.010)

• Increased urine [Na+] (>40 mmol/l)

• Increased fractional excretion Na+ (FENa) (>1%)

• Reduced plasma [Na+]

• Reduced tubular K+ secretion

• Increased plasma [K+]

• Reduced tubular H+ secretion

• Metabolic acidosis

• Reduced glomerular filtration: risk of fluid overload

Acute renal failure

•Management of acute tubular necrosis:

• Manage underlying condition/complications and allow

recovery

• Limit Na+/K+/fluid intake

• Control protein intake

• Limit if dialysis not option (<40g /day)

• Maintain if dialysed (>70g/day)

• Dialysis until renal function recovers

Acute renal failure

Causes of post-renal renal failure:

• Urinary tract obstruction

• Within lumen

• Within wall

• Outside wall

Management of post-renal renal failure:

• Relieve obstruction

• Treat any underlying cause

• Prevent/treat infection

Chronic kidney disease

Causes of CKD (kidney damage or GFR > 3mths):

• Congenital/inherited, eg polycystic kidney disease

• Glomerular disease

• 1˚ glomerulonephritis

• 2˚ eg diabetes

• Vascular disease, eg hypertension, renovascular disease

• Tubulointerstitial disease, eg reflux nephropathy, diabetes

• Urinary tract obstruction

• 70% cases:

• diabetes

• hypertension

• atherosclerosis

Progressive impairment in chronic kidney disease

Chronic kidney disease glomerular scarring + proteinuria deterioration

Possible mechanisms: •Compensatory increase in glomerular pressure •Glomerular hypertrophy

•Angiotensin II: oincreases glomerular pressure oincreases filtration pore size: proteinuria ostimulates collagen synthesis (TGFb): scarring

Chronic kidney disease

Stages of chronic kidney disease:

•Based on GFR (normalised to SA of a standard man: 1.73m2)

Stage Description GFR (ml/min/1.73m2)

1 Kidney damage: normal or GFR >90

2 Mild GFR 60-89

3 Moderate GFR 30-59

4 Severe GFR 15-29

5 Kidney failure <15 or on dialysis

Pathophysiology of chronic kidney disease

Reduced GFR: • fluid retention

• heart failure • oedema

• reduced metabolite excretion • uraemia • increased plasma creatinine • increased plasma urate (gout) • increased lipids (cause unclear) • (increased drug levels: prolonged half life)


Reduced tubular function: • reduced fluid reabsorption polyuria/nocturia

• reduced K+ secretion hyperkalaemia

• reduced H+ secretion metabolic acidosis

Anaemia: • reduced erythropoietin

• normocytic/normochromic • may also be nutritional deficiency: Fe2+/B12


Renal bone disease: •reduced Vit D activation

Cholecalciferol 25 hydroxy-cholecalciferol 1:25 dihyrdroxy-cholecalciferol

skin/diet liver kidney

• GIT Ca2+-absorption osteomalacia

• [PO43-] (reduced renal excretion, reduced [Ca2+])

• VitD and [Ca2+] PTH (2˚ hyperparathyroidism, AlkPhos)

• PTH stimulates bone resorption (pepperpot skull)

• Chronic stimulation 3˚ hyperparathyroidism ([Ca2+], AlkPhos)

• Other forms bone disease


Cardiovascular complications: • Renin-angiotensin activation PR BP • Fluid retention heart failure • Increased cholesterol atherosclerosis

Skin disease: • Pruritis (related to retained nitrogenous waste)

Endocrine problems: • Various (prolactin, gonadotrophins, thyroid + sex hormones)

Neurological problems: • Reduced consciousness/seizures (nitrogenous waste) •Sympathetic nervous activity

Signs symptoms of chronic kidney disease

Management of chronic kidney disease

Renoprotection: slow disease progression

Targets: normal BP, restrict proteinuria

Restrict pathogenesis: reduce AII action

• ACE inhibitor • + AII receptor antagonist • + diuretic (reduce BP and K+) • + Ca2+ channel blocker (reduce BP)

Treat other pathogenic conditions: • Diabetes/smoking


Treat complications: • Anaemia (EPO) • Hyperlipidaemia (statins) • Hyperkalaemia (restrict intake) • Acidosis (oral bicarbonate) • Hyperphosphataemia (phosphate binders) • Osteomalacia and 2˚ hyperparathyroidism (activated Vit D analogues)

Haemodialysis •Deals with waste products and fluid/electrolyte overload •Does not counteract other features of renal failure

Renal transplantation


Renal transplantation

• graft rejection • immunosuppression

Urinary Tract Infections

Typical causing bug: E. Coli (also Proteus, Klebsiella, Staph eg epidermidis)

Risk Factors:

• Gender (ascending infection- shorter urethra in females)

• Stasis of urine (eg renal calculi, reflux, tumours)

• Medical plastic (catheters)

P/C:

Lower UTI (cystitis & urtheritis)- frequency, urgency, dysuria

Upper UTI (pyelonephritis)- as above plus fever, loin pain, rigors

Ix:

• Pre-treatment MSSU for microscopy & culture. Urine dipstick

• May need structural /functional imaging to rule of reflux & renal scarring if UTIs recurrent

Urinary Tract Infections

Infection: >105 colony forming units/ml of one bacterial species from correctly obtained sample

• Contamination: < 104 CFU/ml of >1 bacterial species

Sterile pyuria: White cells in urine >103 but sterile at culture (no bugs grown)

Caused by:

• abx prior to sample

• neoplasia

• difficult to culture micro-organisms e.g M. Tuberculosis

Rx:

• LUTI - Trimethoprim

• UUTI - depends on severity & sensitivity

Kidney Injury

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