Renal Flashcards
Name the causes of End-Stage Renal Failure
Pyelonephritis
Diabetic nephropathy
Glomerulonephritis
Polycystic Kidney Disease
Define Acute Kidney Injury
Rapid reduction in kidney function over hours to days, as measured by serum urea and creatinine
Common, occurs in up to 18% of hospital patients
What is the NICE criteria for an AKI?
Rise in creatinine >25 umol/L in 48 hours
Rise in creatinine of >50% in 7 days
Urine output of <0.5ml/kg/hour for >6 hours
What are the risk factors for AKI?
Age >75 Chronic kidney disease Heart failure Diabetes Liver disease Drugs (nephrotoxic - NSAIDs, ACE-inhibitors etc...) Sepsis Cognitive impairment Contrast medium - CT scans Poor fluid intake Previous AKI
What are the Pre-Renal causes of an AKI?
Hypotension (hypovolaemia, sepsis) Renal artery stenosis Heart failure/MI Dehydration Drugs e.g. ACE-inhibitors, NSAIDs GI bleeding Vomiting and diarrhoea
What are the Intrinsic causes of an AKI?
Acute tubular necrosis (most common)
Glomerulonephritis (SLE, HSP, infections, drugs, anti-GBM disease, ANCA vasculitis)
Interstitial nephritis (drugs, lymphoma)
Vascular disease (thrombosis, HUS/TTP, scleroderma)
Rhabdomyolysis
Radiocontrast
What are the Post-Renal causes of an AKI?
Kidney stones
Malignancy (ureteric, bladder, prostate)
Ureter or urethral strictures
Enlarged prostate or prostate cancer (BPH) (high PSA)
What are the nephrotoxic drugs?
CANT DAMAG
Contrast ACE-inhibitors NSAIDs Therapeutic index (narrow) Diuretics Antibiotics (Penicillin, cephalosporin) Metformin ARB Gentamicin/gold
Why are changes in creatinine assessed and not total amount when calculating AKI staging?
Because the total amount is affected by muscle mass, gender, age and ethnicity. Will be higher in those with a larger muscle mass etc.
What is stage 1 on the KDIGO staging system?
Creatinine increase 1.5-1.9 x baseline
Urine output <0.5 mL/kg/hour for >6 hours
What is stage 2 on the KDIGO staging system?
Creatinine increase 2.0-2.9 x baseline
Urine output <0.5 mL/kg/hour for >12 hours
What is stage 3 on the KDIGO staging system?
Creatinine increase >3 x baseline OR >354umol/L
Urine output <0.3 mL/kg/hour for >24 hours OR anuria for 12 hours
What the symptoms of AKI
Decreased urine Vomiting Dizziness (orthostatic suggests pre-renal) Orthopnoea (fluid overload) Altered mental state Signs of uraemia Peripheral oedema Hyper/hypotension Muscle tenderness (rhabdomyolysis) Ascites
Investigations in an AKI
U&E’s - elevated creatinine, high serum potassium (most important) -> hyperkalaemia >5.5, metabolic acidosis
Urinalysis - leucocytes & nitrites = infection, proteinuria and haematuria = glomerular disease (Acute nephritis), glucose = diabetes
FBC - Anaemia (CKD, blood loss), thrombocytopenia (HUS, TTP)
Imaging - Renal/urinary tract USS (KUB) -> obstruction, cysts, mass
ECG -> hyperkalaemic signs = tall tented T waves, absent P waves, broad QRS complex, sinusoidal
Management for an AKI
Stop nephrotoxic drugs - NSAIDs. ACE-inhibitors
Fluid rehydration with IV fluids in pre-renal
CTKUB for obstruction
Uraemic/acidaemia => dialysis
Treat hyperkalaemia -> Insulin + glucose, calcium gluconate
Odema = Oxygen, CPAP, Diamorphine, furosemide
Complications of an AKI
Hyperkalaemia
Pulmonary oedema
Metabolic acidosis
Uraemia (high urea) -> can lead to encephalopathy/pericarditis
Define Chronic Kidney Disease
Impaired renal function for >3 months based on abnormal structure or function (proteinuria or haematuria), or GFR <60 ml/min/1.73m/m for >3 months with or without evidence of kidney damage
Causes of CKD
Diabetes - 40% Hypertension Glomerulonephritis (IgA nephropathy, FSG, lupus, amyloidosis) Polycystic kidney disease Mediciations - lithium, PPI's, NSAID's Pyelonephritis
What is the clinical exam picture of a patient with CKD?
Hypertensive diabetic over the age of 50
Risk factors for CKD
Old age Hypertension Smoking Obesity Diabetes Medications
Symptoms for CKD
Usually asymptomatic Nausea and vomiting Fatigue (anaemia - lack of EPO) Muscle cramps Anorexia Pruritus (itching) Oedema (salt and water retention) Bone pain Pallor
Stages of CKD
Stage 1 = GFR >90 with evidence of kidney damage
Stage 2 = GFR 60-89 with evidence of kidney damage
Stage 3a = GFR 45-59 with or without kidney damage
Stage 3b = GFR 30-44 with or without kidney damage
Stage 4 = GFR 15-29 with or without kidney damage
Stage 5 = GFR <15 - End-Stage Renal Failure
Investigations for CKD
Urinalysis - haematuria, proteinuria, leucocytes or nitrites = infection
U&E’s - eGFR - two tests 3 months apart, serum creatinine is elevated
FBC - normochromic, normocytic anaemia
Glucose
Renal USS -> small kidney <9cm = obstruction, large kidney = amyloidosis, myeloma
Renal biopsy - if unexplained CKD
Name the complications of CKD
Anaemia Renal bone disease (CKD-mineral and bone disorder) CV disease Peripheral neuropathy Hyperkalaemia Dialysis related problems Pulomonary oedema Metabolic acidosis Protein malnutrition
Explain the pathophysiology behind anaemia in CKD
Anaemia is as a result of EPO deficiency (also blood loss, ACE-inhibitors, chronic disease). EPO stimulates RBC production
Treatment: Erythropoeitin
Explain the pathophysiology behind CKD mineral and bone disorder
Vitamin D deficiency causes low Calcium (hypocalcaemia) which causes PTH elevation (hyperparathyroidism)
Results in osteoporosis, osteomalacia, osteosclerosis
Treatment: Vitamin D (alfacalcidol and calcitriol), Calcium supplements, Bisphosphonates
Treatment for CKD
Stop nephrotoxic drugs
Relieve obstruction
Reduce risk of CV disease: stop smoking, lose weight
Glycaemic control
Treat BP -> ACE-inhibitors, ARB, CCB
Manage complications: Anaemia, renal bone disease
Oedema: loop diuretics (furosemide) + fluid restriction
Dialysis and renal transplant in end stage renal failure
Define nephritic syndrome including symptoms
Refers to a group of symptoms, not a diagnosis
Haematuria
Oliguria (reduced urine output)
Fluid retention
Proliferative
What are the causes of nephritic syndrome?
IgA nephropathy
Post-streptococcal
Rapidly progressive GN
SLE
Define IgA nephropathy
Most common cause of primary glomerulonephritis
Peak is 20 years old
Visible haematuria
Renal biopsy - IgA deposits and mesangial proliferation
Treatment: ACE-inhibitors or immunosuppression (steroids)
Define post-streptococcal nephritic syndrome
Occurs 1-12 weeks after a sore throat (tonsilitis)
Causative organism = Strep pyogenes
Supportive treatment -> resolves over 2-4 weeks
Define rapidly progressive GN
Histology shows crescentic glomerulonephritis
Fever, myalgia, weight loss
Goodpasture’s syndrome: Kidney failure + haemoptysis. Anti-GBM antibodies. Treatment = High dose IV steroids, cyclophosphamide, plasma exchange.
Wegener’s granulomatosis - c-ANCA
Microscopic polyangiitis - p-ANCA
Define SLE related to glomerulonephritis
More common in African’s
Vascular, glomerular and tubulointerstitial damage
Class I-IV (increasing severity), class V (membranous)
Anti DS DNA/ANA antibodies
Treatment: IV methylprednisolone + cyclophosphamide
What is the triad of nephrotic syndrome?
Oedema
Proteinuria (>3.5g/24 hours)
Hypoalbuminaemia
(Hyperlipidaemia as a fourth)
Causes of nephrotic syndrome?
Minimal change disease
Focal segmental glomerulosclerosis
Membranous nephropathy
Mesangiocapillary GN
Diabetic nephropathy Hepatitis B/C SLE Amyloidosis Drugs (NSAIDs, gold, penicillamine, anti-TNF)
Complications of nephrotic syndrome
Susceptibility to infections DVT/PE Hyperlipidaemia (Cholesterol >10mmol/L) AKI Hypertension
Define minimal change disease
Commonest cause of nephrotic syndrome in children
Caused by: NSAIDs, Hodgkin’s lymphoma
Abnormal podocytes - under electron microscope
Treatment: Prednisolone
Define focal segmental glomerulosclerosis
Most common in adults
Focal scars on glomeruli
Idiopathic causes or secondary to HIV
Responds to corticosteroids in 30%
Define membranous nephropathy
Autoimmune
Can be associated with malignancy, NSAID’s, RA
Thickened glomerular basement membrane
Spike and dome appearance
Investigations for glomerulonephritis
Renal biopsy FBC's U&E's ESR Urinalysis ANCA Hep B/C/HIV Anti-DSDNA
Treatment for glomerulonephritis
Reduce oedema -> loop diuretics (furosemide)
Diet - fluid and salt restriction
Reduce proteinuria -> ACE-inhibitors/ARB to control BP
Treat complications: Statins for hyperlipidaemia, anticoagulation for thrombosis (DVT/PE)
Stop causative drugs
Define polycystic kidney disease
Genetic condition where the kidneys develop multiple fluid filled cysts
Commonest inherited disease causing ESRF
Two types: Autosomal dominant (ADPKD) - more common Autosomal recessive (ARPKD)
What genes are affected in autosomal dominant PKD
PKD-1 chromosome 16 (85%) - reach ESRF in 50s
PKD-2 chromosome 4 (15%) - slower reach ESRF in 70s
Signs of ADPKD
Renal enlargement with cysts Abdominal pain + haematuria (haemorrhage into a cyst) Cyst infection Renal calculi Hypertension Progressive renal failure CV disease (hypertension) Palpable, enlarged kidneys
Extra-renal manifestations of ADPKD
Cerebral aneurysms -> SAH: headaches
Hepatic, splenic, pancreatic, ovarian and prostate cysts
Cardiac valve disease (mitral regurgitation)
Colonic diverticula
Aortic root dilatation
What gene is affected in autosomal recessive PKD
Gene on chromosome 6
How does ARPKD present?
Enlarged kidneys, renal cysts and congenital hepatic fibrosis
Usually ESRF before adulthood
Investigations for PKD
Genetic testing - PKD1 or PKD2 Renal USS - Age 18-39 = >3 unilateral or bilateral cysts Age 40-59 >2 cysts in each kidney Age >60 >4 cysts in each kidney U&E's - creatinine Screen for SAH - MR angiography Urinalysis - protein, bacteria ECG - LVH Echo - aortic root dilatation
Management for PKD
Hypertension = ACE-i/ARB/CCB
ESRD = Dialysis/renal transplant
Renal stones = analgesia
Infection = Antibiotics e.g. ciprofloxacin
Tolvaptan (vasopressin receptor antagonist) -> slows development of cysts
Define Alport syndrome
2nd most common inherited cause of kidney failure
Most commonly X-linked dominant
Affects young males
Mutations in COL4A5 gene - mutation in basement membrane collagen (type IV collagen)
Signs of Alport syndrome
Haematuria
Proteinuria
Renal failure
Deafness
Treatment for Alport syndrome
Possibly ACE-inhibitors
Define the stages of diabetic nephropathy
GFR increases
Glomerular hyperfiltration
Microalbuminuria
Nephropathy -> proteinuria increase
What lesions do you see in diabetic nephropathy?
Kimmelstiel-Wilson lesions -> nodular glomerulosclerosis
Treatment for diabetic nephropathy
ACE-inhibitors/ARB - to reduce intra-glomerular pressure and proteinuria/treat blood pressure
Define renal tubular acidosis
Is metabolic acidosis due to impaired acid secretion by the kidney
There is hyperchloraemic, metabolic acidosis + normal anion gap
Define type 1 renal tubular acidosis
Distal tubule pathology
Distal tubule unable to excrete hydrogen ions
Causes of type 1 renal tubular acidosis
Genetic SLE Sjogren's syndrome Marfan's syndrome Sickle cell Hyperthyroidism
Symptoms of type 1 renal tubular acidosis
Failure to thrive in children/rickets
Osteomalacia
Renal calculi
Investigations for type 1 renal tubular acidosis
Urine pH >5.5
Metabolic acidosis
Hypokalaemia
Treatment for type 1 renal tubular acidosis
Oral sodium bicarbonate
Define type 2 renal tubular acidosis
Proximal tubule pathology
Inability of the proximal tubule to reabsorb bicarbonate from the urine. Results in excess bicarbonate in the urine -> metabolic acidosis
Causes of type 2 renal tubular acidosis
Fanconi’s syndrome
Drugs (lead, acetazolamide)
Interstitial nephritis/myeloma
Investigations for type 2 renal tubular acidosis
Hypokalaemia
High excretion of bicarbonate
Treatment for type 2 renal tubular acidosis
Oral bicarbonate
Define type 4 renal tubular acidosis
Most common cause of renal tubular acidosis
Reduced aldosterone secretion -> hyperkalaemia
Causes of type 4 renal tubular acidosis
Addison's disease Diabetic nephropathy SLE HIV Drugs: ACE-inhibitors, spironolactone, NSAIDs, ciclosporin, beta-blockers
Investigations for type 4 renal tubular acidosis
Hyperkalaemia
High chloride
Metabolic acidosis
Low urinary pH <5.5
Treatment for type 4 renal tubular acidosis
Fludrocortisone - replaces aldosterone
Hyperkalaemia treatment = Calcium resonium, furosemide
Define type 3 renal tubular acidosis
Combination of type 1 and 2
Pathology in the proximal and distal tubule
Define Fanconi syndrome
Proximal tubular dysfunction leading to loss of amino acids, glucose, phosphate and bicarbonate in urine.
Complications of Fanconi syndrome
Dehydration
Metabolic acidosis
Oesteomalacia/rickets
Electrolyte abnormalities
Causes of Fanconi syndrome
Wilson's disease Lead Mercury Gentamicin Cisplatin Myeloma Amyloidosis
Treatment for Fanconi syndrome
Sodium bicarbonate
Potassium, phosphate, vitamin D supplements
Define pyelonephritis
Infection/inflammatory disease of renal parenchyma, calyces and pelvis that may be acute, recurrent or chronic
Causes of pyelonephritis
E.coli (ascending infection from lower urinary tract or due to bloodstream spread of infection (sepsis))
In diabetes -> klebsiella/candida
In HIV/Malignancy/transplant -> candida
Risk factors for pyelonephritis
Infants and old age
Structural abnormalities - PKD, horseshoe kidney, VUR
Foreign body - stone, catheterisation
Impaired renal function
Immunocompromised - DM, transplant, malignancy, radio/chemotherapy, HIV
Pregnancy
Obstruction - BPH, stone, bladder neck obstruction, foreign body
Symptoms of pyelonephritis
Loin pain
Fever/rigors
Renal tenderness
Vomiting/nausea
Investigations for pyelonephritis
MC&S of midstream urine Urine dipstick - blood, protein, nitrites, leukocytes Urinalysis Gram stains FBC ESR/CRP raised Blood cultures - sepsis Renal USS - stones, abscess Contrast CT DMSA - renal scarring
Treatment for pyelonephritis
Mild/moderate = ciprofloxacin or cefixime Severe = Admit to hospital IV ceftriaxone or IV ciprofloxacin IV fluids IV paracetamol (pain and fever) Catheterisation
Complications of pyelonephritis
Renal failure
Abscess formation
Parenchymal renal scarring
Recurrent UTI’s
Define renal cell carcinoma
Renal malignancy arising from proximal renal tubular epithelium
It accounts for 85% of renal cancer
Types of renal cell carcinomas
Clear cell (80%) - due to cholesterol and glycogen Papillary tumour (15%)
Risk factors for renal cell carcinoma
Smoking
Middle aged man - 55 years old
Renal transplant and dialysis
Von Hippel-Lindau syndrome
Symptoms of renal cell carcinoma
Classic triad = Haematuria
Loin pain
Abdominal mass
Anorexia
Malaise
Weight loss
Left sided varicocele (due to left testicular vein compression)
Stauffer’s syndrome = cholestasis/hepatosplenomegaly
Investigations for renal cell carcinoma
FBC - polycythaemia from EPO secretion Creatinine - elevated Urinalysis - haematuria +/- proteinuria LFTs - raised ALT/AST Abdominal/pelvis USS = cysts, mass, metastases CT abdo/pelvis MRI Chest X-ray
Treatment for renal cell carcinoma
Radical nephrectomy (partial for T1, laparoscopic for T2)
Radio and chemo resistant
Sunitinib, bevacizumab, sorafenib - tyrosine kinase inhibitors
Staging for renal cell carcinoma
T1 = Confined to kidney <7cm T2 = Confined to kidney >7cm T3 = To major veins or adrenals (e.g. vena cava) T4 = Beyond gerota fascia LNs = para-aortic and hilar
Define Wilm’s tumour (nephroblastoma)
Childhood tumour of primitive renal tubules and mesenchymal cells. (commonest in children)
Symptoms of Wilm’s tumour
Abdominal mass
Haematuria
Define interstitial nephritis
Inflammation of the space between cells and tubules (the interstitium)
What does acute interstitial nephritis present with?
AKI and hypertension
Causes of acute interstitial nephritis
NSAIDs Antibiotics Infection - staphs/streps Autoimmune - SLE, sarcoidosis Diuretics Allopurinol Omeprazole
Symptoms of acute interstitial nephritis
Mild renal impairment
Rash
Fever
Eosinophilia
Treatment for acute interstitial nephritis
Stop underlying cause
Prednisolone -> reduces inflammation
What does chronic interstitial nephritis present with?
CKD
Causes of chronic interstitial nephritis
Analgesic nephropathy Autoimmune - RA, SLE, Sjogren's Myeloma Sickle cell Drugs
Treatment for chronic interstitial nephritis
Manage underlying cause
Steroids
Define acute tubular necrosis
Damage and death (necrosis) of the epithelial cells of the renal tubules -> epithelial cells have ability to regenerate, takes 7-21 days.
Most common cause of AKI
Causes of acute tubular necrosis
Shock
Sepsis
Dehydration
Radiology contrast dye
Gentamicin
NSAIDs
Lithium
Heroin
Investigations for acute tubular necrosis
Urinalysis - “muddy brown casts”
Treatment for acute tubular necrosis
IV fluids
Stops nephrotoxic medications
Treat complications
Define haemolytic uraemic syndrome (HUS)
Medical emergency
Occurs when there is thrombosis in small blood vessels
Triggered by a bacterial toxin called shiga toxin -> caused by e.coli 0157 and shigella
Symptoms of haemolytic uraemic syndrome
Anorexia Diarrhoea Abdominal pain AKI Haematuria/dark brown urine Confusion Hypertension Bruising Nausea/vomiting
Investigations for haemolytic uraemic syndrome
Blood film - decreased platelets (thrombocytopenia)
Proteinuria/haematuria
Treatment for haemolytic uraemic syndrome
Dialysis for AKI
Plasma exchange
Antihypertensives
Define rhabdomyolysis
Skeletal muscle tissue breaks down and releases contents into blood.
The muscle cells (myocytes) undergo cell death (apoptosis) and release: Myoglobin (toxic to kidney = AKI), Potassium (hyperkalaemia), Phosphate, Creatine kinase
Causes of rhabdomyolysis
Prolonged immobility (elderly, frail and falling on the floor)
Rigorous exercise (ultramarathon/triathlon)
Crush injury
Seizures
Alcohol
Statins
Neuroleptic malignant syndrome
Symptoms of rhabdomyolysis
Muscle aches and pain Oedema Fatigue Red-brown urine Confusion
Investigations for rhabdomyolysis
Creatine kinase >1,000-100,000 units/L
Myoglobinuria - myoglobin in the urine “red-brown” colour
U&E’s - increased K and PO, decreased Ca, = hyperkalaemia
ECG = hyperkalaemia - tall tented t waves, absent p waves, broad QRS complex, ventricular fibrillation
Treatment for rhabdomyolysis
IV fluids for rehydration and filtration
IV sodium bicarbonate to alkalinize urine ph >6.5
IV mannitol
Treat complications: Hyperkalaemia -> insulin and dextrose, IV calcium gluconate
What are the indications for dialysis in an AKI patient?
Acidosis Electrolyte abnormalities Intoxication Oedema Uraemia symptoms
How does haemodialysis work?
Blood is passed over a semi-permeable membrane against dialysis fluid flowing through in the opposite direction.
Blood is always meeting a less-concentrated solution and diffusion of small solutes occurs down the concentration gradient
Regime: Hospital 3x per week (4 hours)
Complications of haemodialysis
Access - infection, thrombosis, aneurysms, stenosis Hypotension Time-consuming Nausea/vomiting Headache Fatigue
How does peritoneal dialysis work?
The peritoneum is used a semi-permeable membrane. A special dialysis solution containing dextrose is added to the peritoneal cavity. Involves a Tenckhoff catheter used for inserting and removing dialysis solution
Regime: Continuous ambulatory peritoneal dialysis = 4 exchanges of 20 mins. Automated dialysis = occurs overnight.
Complication of peritoneal dialysis
Bacterial peritonitis Peritoneal stenosis Weight gain Hernia Hyperglycaemia
Absolute contraindications for renal transplantation
Active infection
Cancer
Severe comorbidity
What needs to be matched for a renal transplant?
ABO blood group
HLA tissue match (A, B, C on chromosome 6)
Antibody screening
What drug is used for immunosuppresson induction in renal transplant?
Basiliximab
What drugs are used for immunosuppression maintenance in renal transplant?
Triple therapy:
Calcineurin inhibitor (Tacrolimus or ciclosporin)
Antimetabolite (Azathioprine or mycophenolate)
Prednisolone
Complications of renal transplant
Transplant rejection (hyperacute, acute or chronic) CV disease (hypertension) Infection (HSV, CMV) Malignancy (skin, lymphoma) Drug toxicity Delayed graft function
