Renal failure Flashcards
Main functions of the kidney?
- Fluid balance
- electrolyte balance
- RBC production
- vitamin D production
- Blood pressure
Define acute kidney injury (AKI)
- abrupt deterioration in renal function, usually over hours or days
- usually (but not always) reversible over days or weeks
- AKI usually recognised by a falling urine output, rising urea and creatinine or both.
General causes of AKI?
General outcome?
AKI may result from:
Prerenal causes (85%) –> reduced kidney perfusion leads to a falling GFR
Renal causes(5%) –> injury to glomerulus, tubule or vessels (intrinsic renal disease, or exposure to nephrotoxins)
post renal causes (10%) –> Urinary tract obstruction, functioning kidneys cannot excrete urine with back pressure
Outcome: impaired clearance and regulation of metabolic homeostasis, altered acid/base and electrolyte regulation, impaired volume regulation
Pathophysiology of AKI?
- Prerenal –>
- impaired renal perfusion, renal response is to enhance sodium and water reabsorption.
- Baroreceptors in carotid artery/ aortic arch respond to lower BP with ↑ SNS outflow.
- vasoconstriction of the efferent arteriole and dilation of afferent arteriole maintains glomerular filtration in narrow range
- decreasing perfusion promotes activation of RAAS system –> ATii vasoconstricts, promotes aldosterone release, ↑in Na/H2O absorption, higher osmolarity of the blood stimulates ADH release from hypothalamus, increase water reabsorption in collecting duct.
- Renal –>
- acute tubular necorsis due to prolonged/severe ischaemia, most common AKI
- preceded by impaired perfusion and tissue hypoxaemia –> microvascular injury and tubular ischaemia
- hypoxemia –> acute ROS, cellular dysfunction and death
- immune activation –> complement, neutrophil activation w membrane attack complexes
- can also be caused by drugs/ endotoxins/ radiocontrast media
- Post renal –>
- obstruction leads to increased intratubular pressure
- leads to tubular ischaemia and atrophy
Causes of AKI?
Pre renal:
- low vascular volume –> haemorrhage, D&V, burns, pancreatitis
- decreased cardiac output –> cardiogenic shock/ MI
- systemic vasodilation –> sepsis, drugs
- Renal vasoconstriction –> NSAID/ACEi/ARB/hepatorenal syndrome
Renal:
- Glomerular –> glomerulonephritis, ATN (avascular tubular necrosis)
- interstitial –> drug reaction, infection, infiltration (sarcoid)
- vessels –> vasculitis, haemolytic -uremic syndrome, thrombotic thrombycytopenic purpura, disseminated intravascular coagulation
Post renal:
- within tract –> stone, renal tract malignancy, stricture, clot
- extrinsic compression –> pelvic malignancy, prostatic hypertrophy, retroperitoneal fibrosis
How do we classify AKI?
KDIGO definition:
- Increase in serum creatinine by ≥0.3 mg/dL within 48 hours
- increase in serum creatinine to ≥ 1.5 times baseline - known or presumed to have occured within prior 7 days
- Urine volume <0.5 mL/kg/hour for 6 hours.
Define chronic kidney disease
- Chronic kidney disease = abnormalities in kidney structure or function, present for ≥3 months
- With implications for health
- Means a GFR less than 60mL/min/1.73m2
- often presence of one or more markers of kidney damage:
- albuminuria/proteinuria
- urine sediment abnormalities (haematuria)
- electrolyte abnormalities
- histological/structural abnormalities detected by histology/imaging
Common causes of chronic kidney disease?
- Most common cause = Diabetes (diabetic nephropathy)
- Hypertension second most common cause, hypertension is both a cause and consequence of CKD (hypertensive renal disease).
- Less common:
- polycystic kidney disease
- obstructive uropathy
-
glomerular nephrotic and nephritic syndromes:
- focal segmental glomerulosclerosis
- membranous nephropathy
- lupus nephritis
- amyloidosis
- rapidly progressive glomerulonephritis
What is the general pathophysiology of CKD?
- regardless of method of renal injury (diabetes/HTN/glomerular disorders):
- in response to renal injury there is an increase in intraglomerular pressure with glomerular hypertrophy (kidney attempts to adapt to nephron loss to maintain GFR)
- mesangial cell expansion/inflammation and glomerular scarring
- angiotensin II production - contributes to scarring
- progressive renal scarring and loss of function
- tubular disease due to reduction in blood supply and infiltration of inflammatory cells
Key features in history of CKD?
- Signs and symptoms often vague:
- Fatigue (may be related to uraemia or anaemia (decreased EPO) )
- nausea & V (related to urea rise, more advanced kidney disease)
- ankle swelling/oedema (GFR decrease, Na+ & H2O retained
- Symptoms of uraemia = raised level of blood urea and nitrogenous waste products normally eliminated by the kidneys
- N & V
- Pruritus
- restless legs
- very advanced uraemia –> seizure/coma
- Can present with lack of urine output
- fluid overload –> dysponea and orthopnea (Pulmonary oedema)
- Urine appearance –> “foamy” = proteinuria, “tea/cola coloured” = haematuria
Examination features for CKD?
- Hypertension and peripheral oedema (due to sodium retention, ECF volume expansion, RAAS activation)
- pallor –> anaemia
- Signs of end organ damage:
-
Fundoscopic eye exam:
- Diabetes –> microaneurysms, dot haemorrhages, cotton wool spots, proliferative diabetic retinopathy (advanced) –> neovascularisation, macular oedema, hard exudates, retinal detachments
- Hypertensive retinopathy –> arteriolar narrowing, AV nipping (compression of venules at sites of Arteriovenous crossing), retinal haemorrhages, hard exudates, cotton wool spots, optic disc swelling
-
Fundoscopic eye exam:
- PR exam –> prostate enlargement
- Rashes and arthritis on MSK –> autoimmune cause
- Glomerular nephrotic/nephritic syndrome –> more acute presentation, v hypertensive, periorbital and peripheral oedema
Classification of CKD?
Classification of CKD is based on GFR and/or albuminuria
GFR classification (ml/min/1.73m2) - kidney damage with:
G1: >90 normal/increased GFR
G2: 60-89 mildy decreased GFR
G3a: 45-59 moderately decreased GFR
G3b: 30-44 moderately decreased GFR
G4: 15-29 severely decreased GFR
G5: < 15 end stage kidney disease
OR Albuminuria (mg/24 hours) classification:
A1: < 30 optimal/high normal = ACR of 3
A2: 30-300 High = ACR of 3-30
A3: >300 very high/nephrotic = ACR of > 30
How can we assess risk of adverse outcomes in CKD?
KDIGO guidelines where GFR and albuminuria can be assessed together to determine risk of adverse outcomes.
Revise stages and symptoms of CKD
What is needed to classify patients in stages 1 & 2 of CKD?
To classify patients in stages 1&2 of CKD (early disease):
1) persistent microalbuminuria
2) persistent proteinuria
3) persistent haematuria
4) structural abnormality
5) biposy proven chronic glomerulonephritis
Key features in history for AKI?
AKI often asymptomatic - general sx include nausea and vomiting
Prerenal:
- hypovoleamia sx –> thirst/dizziness/tachycardia/ oliguria (urine output less than 500ml in 24 hrs) or anuria
- Advanced cardiac failure –> paroxysmal nocturnal dysponea and orthopnea
- Hx of excessive fluid loss e.g. haemorrhage/D&V
Renal:
- Patients present with acute tubular necrosis - due to infection, nephrotoxic drug exposure or major surgery
- nephritic syndrome - rash, haematuria, oedema with HTN
- Drug hx - acyclovir, methotrexate, triamterene, NSAIDS, antibiotics (sulfonamides or betalactam)
- Rhabdomyolysis –> myoglobin release from damaged muscles - suspect in patients w muscle tenderness, excessive exercise, limb ischaemia, drug or alcohol abuse.
Post renal:
- Prostatic –> urgency/ frequency/ hesitancy
- previous surgery or malignancy, kidney stones (Nephrolithiasis) –> flank pain (Dermatomes T10-S4) , haematuria
LO: Identify common and important causes of acute kidney injury:
Already known causes:
Key cause or RENAL AKI = glomerulopnephritis / glomerulonephritides
What is glomerulonephritis?
What is it broken down into and what is the main process in these two groups?
Cardinal features of each?
- Are a group of diseases, characterised by damage to the glomerular apparatus, dividided into Nephrotic and nephritic glomerulonephritides depending on where the condition lies on a clinical spectrum. Note often called glomerulonephritis but not always inflammatory process!
-
1) Proteinuric diseases –> Damage to glomerular podocytes / non inflammatory alteration in glomerular structure to podocytes –> causes proteinuria –> causes NEPHROTIC syndrome
-
Nephrotic syndrome cardinal features:
- Hypoalbuminaemia
- >3.5g proteinuria/day
- dyslipidaemia and lipiduria
- Oedema
-
Nephrotic syndrome cardinal features:
-
2) Inflammatory disease –> inflammation and cell proliferation, damage to glomerular cells and the basement membrane, breaks in GBM leads to haematuria and proteinuria –> NEPHRITIC syndromes:
-
acute glomerulonephritis –> cardinal features:
- abrupt onset haematuria –> red blood cell casts
- non nephrotic range proteinuria
- oedema
- HTN
- transient renal impairment
- Rapidly progressive glomerulonephritis –> features of acute plus focal necrosis/ crescents, progressive renal failure over weeks.
-
acute glomerulonephritis –> cardinal features:
AKI management?
- Prerenal –> decreased perfusion therefore fluids/blood/ vaspressors
- Renal –> refer for biopsy and specialist treatment
- Post renal –> catheter, nephrostomy, urological intervention
Pathophysiology of nephrotic glomerulonephritis?
- Key triad of 1) hypoalbuminaemia, 2) proteinuria 3) oedema
- Damage to podocytes leads to physically larger filtration pores in the glomerular filtration barrier which allows the passage of larger molecules:
- Abnormal function in minimal change disease (25% all cases)
- immune mediated in membranous nephropathy
- injury/death in focal segmental glomerulosclerosis
- damage leads to loss of proteins leading to proteinuria and hypoalbuminaemia
- protein loss leads to decrease in oncotic pressure in vascular compartment –> tissue oedema
- hypoalbuminaemia - increased catabolism of reabsorbed protein (largely albumin) in proximal tubules
- hyperlipidaemia occurs via unknown mechanism, thought to be liver induced increase in synthesis of lipoproteins (apolipoB/C) as direct response to low albumin. LDL increase due to internalisation of LDL receptors in liver, no change in HDL. Reduced clearance of triglycerides too.
What are the main nephrotic syndromes?
- Minimal change disease
- focal segmental glomerulosclerosis
- membranous nephropathy
- membranoproliferative GN
Minimal change disease:
Define
Pathophysiology
Who is commonly affected?
Definition: Minimal change nephropathy :
- Light MS –> appearance normal glomeruli
- EM –> fusion of foot processes but no immune compleses or anti GBM antibody on immunofluroescence
Pathophysiology:
Immature CD34 T cell mediated, and interleukins –> causes effacement/flattening of podocytes.
Drugs been implicated –> NSAID/lithium/antibiotics
Atopy and allergies –> present in 30% cases
infections –> hep C/HIV/TB rarer
Who is affected? --> more common in children (particularly boys 2:1 M:F ratio) 2-8 years old, uncommon below 1 yrs, M:F equal in adults.
Key signs on history and exam for minimal change disease?
- Generalised and/or facial oedema
- age between 1-8 yrs
- hx of recent viral illness
- absence of haematuria
- Hx of lymphoma or leukaemia
Investigations for minimal change disease?
- Urinalysis –> proteinuria, hyaline casts
- urine protein/creatinine ratio
- serum albumin –> low
- serum lipid –> high triglyceride and cholesterol
- serum creatinine and urea –> normal or slightly elevated urea, decreased sodium level
- GFR –> should be normal
- LFT –> rule out hepatitis
- renal ultrasound –> confirm kidney size and structure, in nephrotic syndrome kidneys should appear normal
- renal biopsy –> normal light microscopy but podocyte effacement on electron microscopy
Management for minimal change disease?
- Corticosteroids therapy (85% response)
- prolonged prednisilone
- Note may be at increased risk of infection and side effects –> growth failure/obesity
- can use cytotoxic agents to induce remission (ciclosporin or cyclophosphamide)
- if frequent relapse occurs with corticosteroid use consider renal biopsy to confirm diagnosis
- For oedema:
- low Na+ diet and fluid restriction
- If severe:
- albumin IV
- furosemide IV
- does not progress to CKD
Focal segmental nephrosclerosis: Key features in hx?
- Oedema –> facial and peripheral
- Foamy urine –> high levels protein in urine
- hypertension –> increased salt retention and volume overload
- Risk factors:
- male
- black race
- family hx of FSGS
- Drug hx –> heroin, lithium
- PMHx:
- chronic viral infection –> HIV
- solitary kidney
- obesity
Causes of AKI: Nephrotic syndromes:
What is Membranous nephropathy?
How many cases of nephrotic syndrome does it account for?
- Membranous nephropathy –> accounts for 25% all cases of nephrotic syndrome
- immune complex mediated glomerular basement membrane damage, thickening AND podocyte damage leading to thickened basement membrane in a spike and dome pattern, podocyte effacement
Membranous nephropathy: pathophysiology?
- Primary membranous glomerulopathy = idiopathic (majority patients)
- Secondary membranous glomerulonephropathy —>
- drugs (penicillinamine, gold, NSAIDS)
- infection (hep B/C, plasmodium malariae)
- cancer (lung/colon/stomach/breast and lymphoma)
- kidney transplantation and sickle cell
- Pathophysiology –>
- immune complexes (antibodies whether autoimmune or infection) are deposited in sub epithelial space in glomerulus. (Between basement membrane and podocytes).
- Leads to complement activation (C5b-C9), membrane attack complex activation on podocytes and mesangial cells.
- Leads to podocyte effacement and mesangial cell death.
- Mesangial cells normally remove immune complexes, therefore build up.
- Complement leads to immune cell recruitement and activation, leads to basement membrane damage.
- Basement mebrane deposited inbetween areas of immune complexes, leads to characteristic “Spiked” thickening of BM.
Nephritic syndromes:
Henoch-schonlein purpura (IgA vasculitis)
Henoch-Schonlein purpura (IgA vasculitis) = small vessel vasculitis due to immune complex deposition, inflammation of the vessel itself and bleeding –> leads to rash, abdominal pain/bleeding, arthritis/arthralgia, glomerulonephritis
Pathophysiology –> multiple triggersm (strep throat infection) lead to IgG - antigen immune complex formation, in kidney same process as IgA nephropathy. Complex deposition in joints –> arthritis, in skin vessels = purpura, in GI tract vessels –> pain / bleeding
