Nephrology Flashcards
Acute Kidney Injury
Diagnostic Criteria
Risk Factors
Investigations
Management
1.) Diagnostic Criteria - serum creatinine or urine output
- ↑50% (x1.5) over 2-7 days (normal is 60-120)
- stage 1: x1.5-2, stage 2: x2-3, stage 3: >x3/>354mM
- 1: <0.5mL/kg/hour for >6hrs, 2: >12 hrs, 3: <0.3 >24hrs
2.) Risk Factors
- elderly (>65s), HTN or vascular disease, diabetes mellitus
- history of AKI, CKD, sepsis, heart failure, liver disease
- nephrotoxic medications: ACEi/ARBs, NSAIDs, furosemide, metformin, antibiotics (e.g. aminoglycosides)
- post-op hypotension, had contrast agent administered within last 7 days
3.) Routine Investigations
- examinations: hydration status, fluid balance, CVS, resp, abdo
- urinalysis (including MC+S and A:CR): normal suggests pre-renal causes, protein++ suggests renal, blood++ suggests post-renal
- bloods: FBC, CRP, U+Es, LFTs, bone profile, glucose
- additional tests: ABG (resp/CVS compromise), USS-KUB (?obstructive), CK (?rhabodyolysis), renal immunology (?glomerulonephritis)
4.) Additional Investigations - non-routine, only completed if suspected
- USS-KUB: suspected obstructive cause of AKI
- ABG: signs of cardiovascular or respiratory compromise or low venous bicarbonate
- Creatine Kinase: rhabdomyolysis:
- Renal Immunology (ANCA, ANA, ds-DNA, RhF, C3/C4, anti-GBM): ?glomerulonephritis
- serum electrophoresis: ?myeloma
- Antistreptolysin O: ?recent streptococcal infection
- Blood film and LDH: suspected haemolysis and microangiopathy
5.) Management
- treat underlying cause, review medications and dosing
- maintain euvolaemia: IV fluids or diuretics if needed
- monitoring: 4hrly NEWS, 1hrly urine output, strict fluid balance chart, daily weight, daily bloods, ensure adequate nutrition
- referral to nephrology: stage 3 AKI, stage 4/5 CKD, unexplained cause, ?specialist renal cause, inadequate response to treatment, previous renal transplant, AKI complications
- consider temporary dialysis: acidosis, hyperkalaemia, pulmonary oedema, uraemia
Causes of AKI
Pre-Renal
Renal
Acute Tubular Necrosis
Post-Renal
1.) Pre-Renal - can be reversed if recognised quickly
- decreased circulating blood flow: dehydration, shock (esp SEPSIS), congestive HF, liver failure, anti-hypertensives
- impaired renal autoregulation: NSAIDs, ACEi, ARBs
2.) Renal
- acute tubular necrosis: most common cause of intrinsic AKI
- exogenous nephrotoxins: NSAIDs, PPI, cisplatin, radiocontrast dye, Abx (aminoglycosides, amphotericin B)
- endogenous nephrotoxins: rhabdomyolysis (myoglobin is toxic), haemolysis, myeloma
- other renal causes include: SEPSIS, acute glomerulonephritis, vasculitis, malignant hypertension, TTP-HUS
3.) Acute Tubular Necrosis - pre-renal –> renal (intrinsic) cause
- often due to prolonged pre-renal AKI where ischaemia damages tubular cells (proximal tubules most at risk due to highest metabolic demand w/ poorer perfusion)
- haemorrhage is one of the most common causes
- can also be due to toxins damaging the tubular cells e.g. rhabdo
- Ix: high urinary Na (>40mm) with low urinary osmolality (<350)
- will have a poor response to a fluid challenge
4.) Post-Renal - bladder outlet obstruction
- a blockage in the ureters leads to hydronephrosis
- commonly caused by stones or malignancies
- oliguria is hallmark of post-renal AKI
Complications/Indications for Dialysis in AKI (AEIOU)
Acidosis
Electrolyte Distrubance
Intoxication
Oedema
Uraemia
1.) Acidosis
- persisting or worsening metabolic acidosis (often raised anion gap)
- raised anion gap (build up of organic acids): lactic acid (sepsis, tissue ischaemia), urate (renal failure), ketones (DKA), drugs/toxins (salicylates, methanol, ethylene glycol)
- normal anion gap (↑H+/↓ HCO3-): diarrhoea, renal tubular acidosis, Addison’s disease, pancreatic fistula
2.) Electrolyte Disturbance
- hyperkalaemia (K+ released from damaged cells) unresponsive to medical treatment
- hyponatraemia (↓GFR causing fluid overload)
- hypocalcaemia (↓conversion to active vitD)
3.) Intoxication
- lithium, salicylates (aspirin), methanol
4.) Oedema
- pulmonary oedema due to fluid overload
5.) Uraemia - ↓excretion due to ↓kidney function
- uraemic encephalopathy - N/V, confusion, reduced consciousness, drowsiness
- uraemic pericarditis
Nephrotic Syndrome
Aetiology
Clinical Triad
Investigations
Management
1.) Aetiology - podocyte damage leading to glomerular charge-barrier disruption causing protein leakage
- most common cause is minimal change disease
2.) Clinical Triad
- proteinuria: >3g/24h in urine OR urine PCR >300, urine dipstick +++, frothy urine
- hypoalbuminaemia: <30 serum albumin
- oedema: periorbital and bilateral pitting leg swelling
- other features: hypertension, hypercoagulability, deranged lipid profile (↑cholesterol, TGs, LDLs) , low total thyroxine levels (loss in the urine)
3.) Investigations
- bloods: FBC, U+Es, albumin, HbA1c
- urinalysis, 24hr urine collection or urinary PCR
- USS guided renal biopsy to confirm the type: only performed
4.) Management
- steroids: high dose PO prednisolone for 4wks then gradually weaned over the next 8wks, 80% are steroid-sensitive
- renal biopsy: only performed if no response to steroids
- steroid-resistant: ACEi and DMARDs (1°cyclophosphamide)
- proteinuria: ACEi or ARBs, also control BP
- fluid overload: diuretics, salt and water restriction
- hypoalbuminaemia: albumin infusions if severe
- treat potential complications
Causes of Nephrotic Syndrome
Minimal Change Disease
Focal Segmental Glomerulosclerosis (FSGS)
Membranous Nephropathy
Secondary to Systemic Illness
1.) Minimal Change Disease - commonly ages 2-5yrs
- reversible so usually no progression to renal failure
- without any clear underlying condition or pathology
- diagnosis: urinalysis (small molecular weight proteins and hyaline casts), renal biopsy is not useful
- Mx: can be fully treated w/ high dose prednisolone
- if no improvement w/ steroids, consider FSGS
- can advance to FSGS
2.) Focal Segmental Glomerulosclerosis - can affect children and adults
- scarring of small sections of each glomeruli
- circulating factor damaging podocytes
- HIV infections can be a cause of FSGS
- can progress to renal failure
3.) Membranous Nephropathy - affects mainly adults
- can be primary (autoimmune) or secondary (caused by other diseases e.g. lymphoma)
4.) Secondary to Systemic Illness
- Henoch schonlein purpura (HSP), diabetes
- infection: HIV, hepatitis and malaria
Complications of Nephrotic Syndrome
Hypovolaemia
Infection
Thromboembolism
Hyperlipidaemia
Hypocalcaemia
AKI/Worsening CKD
1.) Hypovolaemia - fluid leaks from intravascular space into interstitial space causing oedema and low BP
- must assess their hydration status
- albumin infusions can be given if severe
2.) Infection - due to leakage of immunoglobulins
- antibiotic prophylaxis may be given in severe cases
3.) Thromboembolism - loss of ATIII (ATIII deficiency), plasminogen
- stroke, DVT
- renal vein thrombosis: can present as flank pain + haematuria
- prophylactic dalteparin if albumin <20
4.) Hyperlipidaemia - altered lipoprotein metabolism
- can start patients on a statin
5.) Hypocalcemia - loss of vitamin D
6.) AKI/Worsening CKD
- may require renal replacement therapy if severe
Nephritic Syndrome
Aetiology
Clinical Features
Investigations
Management
1.) Aetiology - disruption of endothelium results in an inflammatory response causing damage to the GBM
2.) Clinical Features
- haematuria +/- proteinuria +/- mild-moderate oedema
- proteinuria <3g/24hrs or urine PCR <300
- AKI (↓GFR): rapidly progressive GN
- hypertension
3.) Investigations
- bloods: FBC, U+Es, clotting, PSA
- urinalysis, 24hr urine collection or urine PCR
- exclude infection and malignancy for haematuria
- renal biopsy to confirm diagnosis/type
4.) Management
- fluid overload: diuretics, salt and water restriction
- proteinuria: ACEi or ARBs, also control BP
- immunosuppressive therapy depending on specific cause of GN, decided by renal +/- resp + rheum
- plasma exchange for anti-GM or ANCA vasculitis
- dialysis in severe AKI due to RPGN
Causes of Nephritic Syndrome
Anti-GBM Disease (Goodpasture’s)
ANCA-associated Vasculitis
SLE Nephritis
IgA Nephropathy/Henoch-Schonlein Purpura
Post Streptococcal/Infectious
1.) Anti-GBM Disease- antibodies to type 4 collagen in GBM and alveolar basement membrane (rarer)
- pulmonary haemorrhage (haemoptysis) more likely w/ smokers (pre-existing damage to alveolar endothelium)
- often presents as haemoptysis + AKI/haematuria/proteinuria
- can lead to RPGN
- anti-GBM antibodies, pulmonary infiltration on CXR
- renal biopsy: linear IgG deposits along the basement membrane
2.) ANCA-associated Vasculitis - small vessel vasculitis
- granulomatosis w/ polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic GPA (Churg-Strauss)
- pulmonary and nasopharyngeal involvement –> haemoptysis, nasal ulcers/polyps
- nasal crusting and saddle-shaped nasal deformity are classic features of GPA
- eosinophilic has atopic features + purpura and peripheral neuropathy as well as eosinophilia
- all have positive ANCA antibodies (c-ANCA in GPA and p-ANCA in eosinophilic)
3.) SLE Nephritis - can be nephritic or nephrotic
- +ve ANA and anti-dsDNA antibodies
4.) IgA Nephropathy (Berger’s Disease) - usually presents in teenagers and young adults
- related to Henoch-Schonlein Purpura (IgA vasculitis)
- IgA deposits in the nephrons causes inflammation
- sx: visible haematuria associated with a recent URTI or GI infection (1-2 days), purpuric rashes (bleeding underneath skin), can also have joint pain and abdominal pain
- Mx: supportive treatment of renal failure and immunosuppressants to slow progression
5.) Post-Streptococcal GN (Post-Infectious)
- occurs 1-3wks after a group A ß-haemolytic strep (pyogenes), tonsillitis/pharyngitis, impetigo/cellulitis
- acute deterioration in renal function –> AKI
- low serum C3, + anti-streptococcal antibodies
- biopsy: immune complex deposition (IgG, IgM, C3)
- Mx: self-limiting, ACEi/ARB, low sodium diet
Chronic Kidney Disease
Definition
Staging
Clinical Features
Investigations
1.) Definition - irreversible and progressive kidney damage causing ↓GFR or albuminuria for > 3months
- diagnosis requires an eGFR of <60 on 2 occasions, performed > 3 months apart
- loss of excretory and hormonal kidney functions
2.) Staging - uses eGFR and albuminuria
- 1 = >90, 2 = >60, 3a = >45, 3b = >30, 4 = >15
- Stage 5 is end stage kidney disease (ESRD) and is characterised by a eGFR of <15
3.) Clinical Features
- anaemia: fatigue, SOB, light-headedness etc..
- ↓GFR: oliguria (max output 1-2L), over-drinking leads to oedema (bilateral pitting leg swelling)
- ADH insensitivity at night: nocturia
- accumulation of waste products: N+V, ↓appetite, pruritus, insomnia, seizures, difficulty concentrating
- ↑infection, ↓libido and ↓fertility
4.) Investigations
- bloods: FBC, CRP, U+Es, LFTs, HbA1c
- albumin, bone profile, lipid profile, iron studies
- investigate causes of AKI and glomerulonephritis
- USS abdo (ADPKD), angiogram (stenosis)
Causes of Chronic Kidney Disease
Diabetic Nephropathy
Hypertensive Nephropathy
Autosomal Dominant Polycystic Kidney Disease
Others
1.) Diabetic Nephropathy - most common cause in UK
- poorly controlled diabetes, T1 or long-duration T2
- raised urine ACR/PCR, bilateral enlargement of the kidneys found on ultrasound (chronic DM nephropathy)
- treatment: ACEi/ARBs, control diabetes, control HTN, CVD risk modification, screen for other complications
2.) Hypertensive Nephropathy - chronic raised BP
- difficult to tell which came first, the CKD or the HTN
- causes bilaterally shrunken kidneys
- investigate potential secondary causes of HTN:
- hyperthyroidism, Cushing’s syndrome, renal artery stenosis, primary aldosteronism, pheochromocytoma
3.) ADPKD - mutation in PKD1/2 gene
- strong FH, presents in adulthood (cysts grow w/ age)
- sx: infection (flank pain, haematuria, fever), bleeding into cysts, can also be asymptomatic
- diagnosed w/ USS and FH, control BP
- tolvaptan (vasopressin receptor 2 antagonist) can be used to slow progression of CKD: reduces the rate of cyst development and renal insufficiency in patients with CKD stage 2 or 3 at the start of treatment, with evidence of rapidly progressing disease
- offer genetic counselling/testing
4.) Others
- glomerulonephritis, renovascular disease (stenosis)
- chronic/recurrent pyelonephritis, hydronephrosis
- HIV nephropathy (bilateral enlarged kidneys)
- prolonged AKI
Complications of Chronic Kidney Disease (+management)
Anaemia of Chronic Kidney Disease
Mineral Bone Disease
Cardiovascular Disease
Hypertension
Malnutrition
End-Stage Renal Disease
1.) Anaemia of Chronic Kidney Disease
2.) Mineral Bone Disease
3.) Cardiovascular Disease - No. 1 cause of mortality
- CKD –> HTN, hyperlipidaemia
- ↓CVD risk: weight loss, exercise, stop smoking, control BP and diabetes, start all patients diagnosed with CKD on a statin
4.) Hypertension - kidney can’t regulate blood volume
- ↑RAAS –> vasoconstriction and Na+ retention
- SNS overactivity –> vasoconstriction +Na+ retention
- Na+ retention –> arterial stiffness –> ↑BP
5.) Malnutrition - multifactorial
- ↓intake, acidosis, dialysis, ↓absorption (gut oedema)
6.) End-Stage RD - similar to AKI complications
- fluid overload: Na+ retention
- electrolyte disturbance: esp ↑K+ (↓excretion), patients should have a low potassium diet
- metabolic acidosis: ↓secretion of HCO3-
- uraemia: encephalopathy and pericarditis
Anaemia and Mineral Bone Disease in CKD
Anaemia of Chronic Kidney Disease
Management of Anaemia of CKD
Mineral Bone Disease
Management of MBD
1.) Anaemia of CKD - many causes
- ↓EPO production –> normocytic anaemia
- iron deficiency due to ↓clearance of hepcidin
- vitB12/folate deficiency
- bone marrow suppression from uraemia
2.) Management of Anaemia of CKD - Hb (100-120)
- EPO injections (SC): must have adequate iron stores before giving
- haematinics: IV iron/vitB12/folate replacement
- ferrous sulphate
3.) Mineral Bone Disease
- ↓phosphate excretion –> ↑PTH –> ↑bone resorption
- ↓calcitriol –> ↓serum Ca2+ –> ↑PTH
- ↑PO4- –> vascular and or soft tissue calcification
- bone profile: ↓Ca2+, ↑PO4-, ↑PTH, ↑ALP, ↓vitD
- secondary hyperparathyroidism: parathyroid gland nodular hyperplasia a consequence of advanced CKD
4.) Management of MBD
- hyperphosphatemia: low phosphate diet, phosphate binders (Sevelamer)
- secondary hyperparathyroidism: calcimimetics, calcitriol, synthetic vitD analogues
- vitamin D supplements (cholecalciferol)
Renal Replacement Therapy (Dialysis)
Haemodialysis (HD)
Pros and Cons of HD
Peritoneal Dialysis (PD)
Pros and Cons of PD
1.) Haemodialysis
- pumps blood through dialyser (artificial kidney) which removes waste solutes, salt and excess fluid
- requires AV fistula or central line (permcath)
- 4-hour dialysis sessions x3 a week
- can be used temporarily for AKI (vascath)
2.) Pros and Cons of HD
- pros: most efficient, help and support, longer-term
- cons: fluid and diet restrictions, cannot travel, ↑CVD strain, expensive
- complications: sepsis, fluid overload, DIC, hematomas, muscle cramps, dialysis equilibrium syndrome
3.) Peritoneal Dialysis - home-based therapy
- uses the patient’s own peritoneal membrane to filter
- solutes move down the conc gradient across the peritoneal membrane into the dialysate fluid
- water is removed due to osmotic gradient created by high conc of glucose in the dialysate fluid
4.) Pros and Cons of PD
- pros: ↑QoL, fewer diet restrictions, empowers patients, often a good first choice for new patients
- cons: need to be competent, short-term (eventually need HD), more complications
- complications: peritonitis (S epidermis), leaks, herniae, drainage problems, hydrothorax, peritoneal sclerosis
Kidney Transplantation
General Details
Pros and Cons
Contraindications
Treatment
1.) General Details
- treatment of choice for most patients w/ ESRF
- can be live/dead related/un-related
- best outcomes in terms of survival and QoL
- can be simultaneous w/ pancreas (type 1 DM) or liver (cirrhosis) transplants
2.) Pros and Cons
- pros: best survival and QoL, near-normal renal function, cheap
- cons: criteria, lifelong immunosuppression, rejection, can be long waiting times, don’t last forever
3.) Contraindications
- active infection or malignancy
- severe heart or lung disease, short life expectancy
- substance abuse, psychiatric illness, non-adherence
4.) Treatment - w/ immunosuppressants
- used at induction and for maintenance
- corticosteroids, DMARDs
Acute Interstitial Nephritis
Pathophysiology
Causes
Clinical Features
Management
1.) Pathophysiology
histology: marked interstitial oedema and interstitial infiltrate in the connective tissue between renal tubules
2.) Causes - most commonly caused by drugs
drugs: antibiotics (penicillin, rifampicin), NSAIDs, allopurinol, furosemide
systemic disease: SLE, sarcoidosis, and Sjögren’s syndrome
infection: Hanta virus, staphylococci
3.) Clinical Features
- fever, rash, joint pain
- impaired renal function, hypertension
- ‘allergic-type picture’: raised urinary WCC, IgE, and eosinophils
- urinalysis: sterile pyuria, white cell casts
4.) Management
- definitive diagnosis is with a renal biopsy
- identifying and removing the underlying cause
- supporting the patient with fluids and medications to help manage the symptoms and prevent further kidney damage
- severe cases may require steroids and potentially dialysis
