Nephrology Flashcards
Components of eGFR
Creatinine
Age, Gender, Race (Weight)
Creatinine
What
Cr vs eGFR
Chemical waste product from muscle metabolism (Muscley people have lots)
Therefore Cr clearance is > GFR - Because secreted as well as filtered!
Therefore inhibitors of secretion will make Cr rise and function look worse e.g. trimethoprim
Volume control
Aldosterone
Angiotensin II
ANP
Aldosterone (adrenal) -> decreased excretion
Angiotensin II -> decreased excretion
ANP - released by heart in response to high pressure -> increases excretion
Renal blood pressure control
Via volume control and vasoconstriction
Decreased BP at afferent arteriole -> juxtaglomerular apparatus -> renin
Prostaglandin - Preferentially dilates afferent arteriole
Angiotensin II - Preferentially constricts efferent arteriole (maintain GFR)
Antihypertensives -> ACEI (e.g. ramipril) and ARB (e.g. losartan)
ACE inhibitors
Indications
Dose
Side effects (4)
HTN, heart failure, post MI
Ramipril - start on 1.25/2.5mg PO OD at night
May impair renal function: decrease GFR (avoid NSAIDs), hyperkalaemia (avoid K+ spare diuretics)
Postural hypotension
Bradykinin mediated dry cough
Fatigue
Angiotensin receptor blockers Mechanism Indications Dose Side effects (3)
Modulation of RAAS, similar to ACEI but no dry cough
HTN, heart failure, diabetic nephropathy
Losartan - usually 50mg PO OD, elderly =- 25mg PO OD
Renal impairment
Postural hypotension
Hyperkalaemia
Location of Sodium reabsorption
PCT (70%)
Potassium control
Potassium freely filtered at proximal tubule and loop of henle
Distal secretion determines renal excretion (Na, aldosterone driven)
Hypokalaemia meds
Hyperkalaemia meds
Loop diuretics, thiazide diuretics
Spironolactone, amiloride, ACEI, ARB
Hormones functions the kindey, function & physiology
Erythropoietin stimulates RBC production
Renal cortex acts as an O2 sensor; blood flow and oxygen requirement matched.
1-alpha hydroxylation of vitamin D
@proximal tubule calcitriol increases Ca and PO4 absorption from gut and suppresses PTH
*This process is inhibited by FGF-23 which is increased in CKD
Effects of angiotensin II (5)
Increase sympathetic activity Increase aldosterone secretion Increase ADH secretion Tubular Na Cl and H2O re absorption. K excretion (aided by aldosterone) Arteriole constriction.
Mechanism of
Spirolactone
Furosemide
Thiazides
Effect of BP/Na/K
Competitive binding of aldosterone receptor
Blocks Na/Cl/K pump in ascending limp of henle
Blocks Na/Cl pump in DCT
All cause hypotension/natremia/kalaemia (besides Spiro)
Fanconi syndrome
Generalised dysfunction of renal proximal tubule -> urinary loss of bicarb, glucose, aa, phosphate, peptides, organic acids. Leads to salt wasting and volume depletion
Types of renal tubular acidosis and findings (4)
Type 1: classic distal RTA
AD or AR mutations of proton pump. Inability to excrete H+ in distal tubules.
Min urine pH > 5.5, stones, serum potassium low-normal, plasma bicarb < 10
Type 2: inherited isolated proximal
Mutation of sodium bicarbonate cotransporter that transfers bicarb back to peritubular capillary. Inability to reabsorb bicarbonate
Min urine pH < 5.5, serum potassium low-normal, plasma bicarb < 12-20
Type 4: hyperkalaemic distal
Hyperkalaemia inhibits production of ammonia and decreases urine buffering capacity
Min urine pH < 5.5, serum potassium high, plasma bicarb > 17
Fanconi’s syndrome: Myeloma proteins and various drugs cause proximal tubule injury and proximal RTA, or AD inherited, bicarb <18
Presentation of RTA
Growth retardation/failure to thrive (children)
Muscle weakness (Fanconi)
Hypoglycaemia after fructose
Rickets (Fanconi and Type 2 proximal have persistent phosphate loss)
Distal RTA with deafness may be inherited (AR - H+-ATPase)
Kussmaul breathing if severe
Management of RTA
Classic distal (T1) Sodium alkali or potassium alkali (1mmol/kg) e.g. Shohl’s solution ± potassium supplementation
Proximal (T2 and Fanconi)
Sodium alkali or potassium alkali (1mmol/kg) ± potassium supplementation ± thiazide diuretic
Hyperkalaemia + mineralocorticoid deficiency
Fludrocortisone + dietary restriction of potassium
Complications of RTA (5)
Volume depletion - loss of sodium etc at proximal tubule dysfunction
Nephrocalcinosis - classic distal, increased loads of filtered calcium because of release of calc phos and calc carb in bone buffering of acidosis
Osteoporosis - bone buffering of acidosis leads to demineralisation
Growth retardation - acidosis associated with muscle catabolism
Renal rickets - Fanconi, can’t reabsorb phosphate
Causes of end stage renal failure (4)
Glomerulonephritis
Pyelonephritis
Diabetes
PKD
Pyelonephritis
What
Bacteria
Risk factors (4)
Infection/inflammatory disease of renal parenchyma, calyces and pelvis that may be acute, recurrent or chronic
Gram -ve: E. coli (60%), proteus (15%), klebsiella (15%)
@Diabetes = klebsiella or candida
@HIV, malignancy, transplant = candida
Age - Infants and older
Anatomical abnormality - VUR, PKD, horseshoe, double ureter
Foreign body - Stone, catheter
Impaired renal function
Immunocompromised
Obstruction - BPH, stone, foreign body, bladder neck obstruction, posterior ureteral valve, neurogenic bladder
Pregnant
Pyelonephritis presentation
Tirad
Extras
Loin pain
Fever - may not be the case if patient is on steroids or anti-inflammatory
Renal tenderness/costovertebral angle
+ nausea/vomiting, DUF (associated with cystitis or urethritis), rigors
Pyelonephritis Ix (6)
URINE MC&S
-Urine dip: blood, protein, nitrites, leukocyte esterase
-Urinalysis
-Gram stain: G -ve rods (e.coli, klebsiella, proteus)
-Urine culture
FBC: leukocytosis
ESR/CRP raised
Blood culture (systemic infection SEPSIS)
IMAGING (mandatory in recurrent pyelonephritis)
*Renal USS: gross abnormality, hydronephrosis, stones, abscess
*Contrast CT: altered perfusion, structural abnormality
DMSA (renal scarring)
Pyelonephritis Mx
Mild
Severe/complicated/pregnant
Mild/moderate + uncomplicated
Ciprofloxacin (500mg PO BD 7-14D) or cefixime (400mg PO OD 14D) - 3rd gen
Severe or complicated or pregnant Admit to hospital IV ceftriaxone (3rd gen ceph) OR IV ciprofloxacin OR IV gentamicin (not to preg) IV fluids IV paracetamol (pain and fever) Catheterisation if compromised
Renal cell carcinoma
What
Types
Presentation
Renal malignancy arising from renal parenchyma/cortex
80% clear cell/adeno renal carcinoma (renal cortical parenchyma) -> due to cholesterol and glycogen
15% papillary tumor (types 1 and 2)
*Haematuria
*Flank pain
*Abdominal mass - * = classical triad <10% cases
Systemic: weight loss, anorexia, malaise
Left sided varicocele by invasion of left renal vein
Lower limb oedema
RCC risk factors
Smoking, obesity, HTN, age, renal transplant and dialysis (15%)
+ve family history x4 risk
-Hippel Lindau (AD): 30% develop RCC -> born with germline loss of one VHL tumour suppressor gene.
RCC spread
Direct
Lymphatic
Haem
Direct - renal vein
Lymphatic - paraaortic then mediastinal
Haem - bone, liver, lung (cannonball mets + colono)
Stuaffers syndrome
Presence of a RCC causing:
Cholestasis in absence of liver metastasis (elevated bilirubin, alkaline phosphatase and gamma GT) with elevated PT (coag), thrombocytosis and hepatosplenomegaly
RCC Ix (5)
BP - increased from renin secretion
Percutaneous renal biopsy
FBC - polycythaemia (EPO)
LDH - raised is poor prognosis (x 1.5)
Corrected calcium - >2.5 mmol/l poor prognosis
LFT - raised AST/ALT = metastatic disease
Cr - elevated with reduced clearance
Urinalysis - haematuria and/or proteinuria
*Abdominal/pelvis USS - cyst, mass, mets
*CT abdo/pelvis - lymphadenopathy, mass, bone mets inc contralateral kidney
MRI - for local invasion etc
CXR - cannonball metastasis, bone scan, MRI brain/spine
Wilms tumour
Nephroblastoma
Childhood tumour of primitive renal tubules and mesenchymal cells
Abdominal mass and haematuria
AKI
What
Risk factors
Abrupt (within 48 hours)/ absolute increase in:
- serum creatinine of ≥ 26.4 μmol/l above baseline,
- a serum creatinine increase of ≥ 50%, or
- oliguria of less than 0.5 mL/kg per hour for more than six hours
Elderly, DM, dehydration, underlying kidney disease, nephrotoxins & sodium retaining states (CHF, cirrhosis, nephrotic syndrome)
Types of AKI (3)
Pre-renal (50%)
Azotaemia (high nitrogen compounds e.g. Ur, Cr) due to reduced perfusion causing hypovolaemia, haemorrhage, sepsis, third spacing of fluids (severe panc), overdiuresis, heart failure
Hepatorenal syndrome = azotaemia not responsive to fluids (liver disease)
Renovascular disease - *giving NSAIDs to patient with bilateral renal artery stenosis
Intrinsic (30%)
*Acute tubular necrosis (mainly due to sepsis = most common)
*Rapidly progressive glomerulonephritis
*Interstitial nephritis
Vascular disease: HUS, TTP, scleroderma, atheromatous embolisation, thrombosis
Post-renal (20%)
Mechanical obstruction to urinary tract
Retroperitoneal fibrosis, lymphoma, tumour, prostate hyperplasia, renal calculi, urinary retention, pyelonephritis
Acute tubular necrosis
Death of tubular epithelial cells that form the renal tubules of the kidneys.
ATN presents with acute kidney injury (AKI) and is one of the most common causes of AKI.
Common causes of ATN include low blood pressure and use of nephrotoxic drugs.
Nephrotoxic drugs
Prerenal
Intrarenal
Post renal
Drugs causing GI loss
NSAIDS -> hypoperfusion
ACEI if compromised renal perfusion (e.g. renal artery stenosis) (DO NOT PRESCRIBE WITH NSAID)
Glomerulonephritis - captopril, penicillamine, gold, penicillins, rifampicin
Interstitial nephritis - penicillins, cephalosporins, thiazide, furosemide, NSAID, rifampicin
ATN - aminoglycosides, amphotericin, ciclosporin
Anticholinergics (TCA) + alcohol -> retention
AKI presentation
Decreased urine
Vomiting (early could be causative, late could be uraemia)
Dizziness (orthostatic suggests pre-renal)
Orthopnoea (fluid overload)
Altered mental status (uraemia)
Signs of uraemia - asterixis (flapping tremor)
Peripheral oedema
Muscle tenderness (rhabdomyolysis)
AKI Ix (6)
U+E+Cr: Elevated creatinine, *high serum potassium (or on *VBG), *metabolic acidosis
Urine dip, MC + S - Infection -> leukocytes/nitrates, Glomerular disease -> blood/protein
- Anaemia (CKD/blood loss), leukocytosis (infx), thrombocytopenia (HUS, TTP)
Imaging *priority if anuric - Renal USS -> obstruction, cysts, mass
ECG - For *hyperkalaemia - increased PR, widened QRS, peaked T, sine wave
Ratio serum urea:creatinine + other tests of cause
20:1 -> pre-renal cause
AKI management
Stop nephrotoxic drugs
ABCDE
Including fluid challenge if hypotensive, diuretic if hypertensive
Catheterise for accurate urine output
Urgent VBG/ABG (for K+) + ECG
Urgent USS KUB for obstruction (? nephrostomy)
Urine dip for GN/infx
If uraemic, severe metabolic acidosis, severe hyperkalaemia -> dialysis
CKD
What
Proteinuria or haematuria (evidence of kidney damage) and/or reduction in GFR to <60ml/min/1.73m2 for more than 3 months
CKD stages
Stage 1: kidney damage with normal or increased GFR (> 90)
Stage 2: kidney damage with mild decrease GFR (60-89)
CKD below
*Stage 3a: kidney damage with mod decrease GFR (45-59)
*Stage 3b: kidney damage with mod decrease GFR (30-44)
*Stage 4: kidney damage with severe decrease GFR (15-29)
*Stage 5: kidney failure (ESRD) with GFR < 15
Causes of CKD
Diabetes (40% of ESRF): diabetic nephropathy = macroalbuminuria ± reduction in GFR to <90
HTN (33% of ESRF) + renal vascular disease (stenosis)
Glomerular nephrotic/nephritic syndromes: Focal segmental glomerulosclerosis Membranous nephropathy Lupus nephritis Amyloidosis
Polycystic kidney disease
Obstructive uropathy Myeloma (due to stones from hypercalaemia) Renal tumour BPH Stones
Uraemic syndrome
Symptoms
Complications
Management
Fatigue, metallic taste, nausea/vomiting, itch, delirium, seizures, anorexia
Uraemic tinge (grey/yellow)
- Uraemic encephalopathy
- Pericarditis
- Bleeding
Rapid RRT
CKD complications (5)
Anaemia - due to diminished EPO at S3 signs of anaemia
Renal osteodystrophy - due to elevation in PTH as a result of phosphorus retention and hypocalcaemia from
1,25 vitamin D deficiency as GFR declines phosphate itch, parasthesia, tetany and bone pain, can cause Ca to deposit in blood vessels
CV disease - (CKD is risk factor independent of DM, HTN, dyslipidaemia)
Protein malnutrition - protein loss in urine
Metabolic acidosis - unable to excrete acid at GFR < 50
Hyperkalaemia - unable to excrete potassium as GFR declines
Pulmonary oedema - fluid overload (Rx with loop diuretics)
CKD Ix (5)
Serum creatinine elevated
Urinalysis: haematuria or proteinuria
Urine microalbumin: microalbuminuria
Renal USS: small kidney, obstruction/hydronephrosis, large kidney (infiltration myeloma, amyloidosis)
eGFR < 60
Blood sugar
FBC - anaemia, normochromic normocytic
Osteodystrophy: hypocalcaemia, hyperphosphataemia and hyperparathyroidism, high alkaline phosphatase
Antibodies: autoantibodies, antibodies to streptococcal antigens of hep B/C antibodies
CKD Mx (5)
Treat BP + CV risk - ACEI/ARB2 target 140/90 ± 2nd and 3rd line etc…+ Statin, smoking cessation, weight loss, aspirin
Treat anaemia - Epoeitin alfa (EPO stimulating agent) ± ferrous sulfate (oral) if necessary
Treat renal bone disease - Dietary modification (based on Ca and PO4 - milk, cheese, eggs) and phosphate binding drug (calcium acetate/carbonate) ± calcitriol if low
Treat metabolic acidosis - Oral sodium bicarbonate
Treat oedema - Loop diuretics and restrict sodium
High potassium - Low potassium diet
Indications for RRT in AKI (6)
Uraemia (pericarditis, gastritis, encephalopathy)
Pulmonary oedema (fluid retention) unresponsive med Rx
Severe hyperkalaemia (>6.5) unresponsive to med Rx
Severe hypo/hypernatramia
Severe metabolic acidosis (<7.0) unresponsive to bicarb
Severe renal failure (urea > 30)
Renal transplant risks
Immediate operative: local infx, pain, DVT
Infections due to immunosuppression (viral HSV for 4 weeks then CMV, bact, fungal)
Urinary tract obstruction
Drug toxicity: bone marrow suppression
*Cancer (skin, lymphoma)
*CV disease (main cause of death), hypertension, dyslipidaemia
Rejection
- Hyperacute (mins), rare due to crossmatch
- Accelerated (days), T cell mediated crisis -> fever, swollen kidney, increased Cr -> IV steroids
- Acute cellular (weeks), 25% in <3 weeks -> fluid retention, rising BP, rising Cr, high dose IV steroids
- Chronic (years), gradual rise in Cr and proteinuria, resistant HTN -> graft biopsy shows vascular changes, fibrosis and atrophy
Glomerulonephritis
Glomerular injury by a group of diseases characterised by changes in the glomerular capillaries and glomerular basement membrane. Changes are most likely immune mediated
Causes of Glomerulonephritis
Commonly idiopathic
Infection - GABH streptococcus (pyogenes), resp/GI infection, hep B/C
Systemic inflammatory conditions - SLE, RA, Goodpasture’s, Wegener’s, HSP, HUS, scleroderma
Drugs - Penicillamine, gold, NSAIDs, ciclosporin, mitomycin
Metabolic - DM, HTN
Malignancy, hereditary, deposition
Nephrotic syndrome
Causes (5)
Features
Nephrotic = non-proliferative Deposition disease (amyloidosis + light chain dep) Minimal change disease Focal and segmental GN Membranous nephropathy Membranoproliferative GN
Proteinuria (>3.5g/24 hours)
Hypoalbuminaemia (<30g/L)
Peripheral oedema
Hyperlipidaemia
Nephritic syndrome
Causes (4)
Features
Nephritic = proliferative IgA nephropathy (1ary) - Macroscopic haematuria 24/48 hours post GI/URTI & IgA deposition in mesangial matrix
Membranoproliferative - Primary (immune mediated) or secondary (SLE). Thickening of glomerular basement membrane and mesangium
Postinfectious GN (1ary) - Weeks after URTI -> strep pyogenes -> resolves
Rapidly progressive GN
- Vasculitis - Wegener’s - cANCA & Microscopic polyangiitis - pANCA
- Anti-GBM GN (1ary) - Goodpasture’s syndrome - AI, antiGBM
Oliguria/AKI (renal dysfunction)
HTN
Haematuria: active urinary sediment (red cells and casts)
Nephrotic syndrome complications (5)
Susceptibility to infection - increased urinary loss of IgG (streptococcal), or secondary to steroids
Hypercoagubility and thromboembolism - renal vein thrombosis (lupus or urinary loss of antithrombin, altered protein C and S)
Hypercholesterolaemia - increased hepatic lipoprotein synthesis and loss of lipid regulating proteins
Hypervolaemia - severe decrease in GFR resulting in oedema
AKI - more likely with acute GN
HTN - impaired GFR and increased reabsorption of salt and water
Minimal change disease Who Cause Light microscopy & Immunofluorescence Electron microscopy Mx
Kids - 90% in < 10yrs
Idiopathic, NSAIDs or Hodgkin’s lymphoma
Light microscopy & Immunofluorescence - normal
Electron microscopy - effacement of podocyte foot processes
Responds to steroids
Focal segmental glomerulosclerosis
Who
Cause
Light microscopy
Younger adults
Idiopathic or secondary to HIV
Light microscopy - segmental areas of mesangial collapse and sclerosis (focal not widespread)
Membranous nephropathy Who Cause Light microscopy Immunofluorescence Electron microscopy
Most common adult/older
Usually idiopathic or secondary to Hep B, gold, penicillamine, NSAIDs
Light microscopy - basement membrane thickening and associated cellular proliferation
Immunofluorescence - granular IgG deposition
Electron microscopy - electron dense deposits in subepithelial space
Ix for glomerulonephrits
Routine (5)
Specific
FBC - anaemia -> systemic
U + E + Cr + LFT -> ?hepatitis, advanced disease, albumin
Urinalysis -> haematuria, proteinuria, RBC casts
GFR -> normal or reduced
Lipid profile + glucose
24 hour urine collection
ESR - vasculitis
Complement - low in immune complex
RF - RA
ANCA - anti GBM disease
Anti GBM antibody - anti-GBM disease or Goodpasture’s
Antistreptolysin O antibody/anti DNase - post strep
Anti DS DNA/ANA - SLE
Hep B/C/HIV serology
Electrophoresis - raised gamma globulin in lymphoma and amyloidosis
Glomerulonephritis Mx
Mod - severe (Criteria)
Rapidly progressive (3)
(haematuria, proteinuria and reduced GFR)
Oral meds:
Proteinuria reducing meds (ACEI/ARB), + ABX + furosemide + prednisolone (1 mg/kg/day) with immunosuppressant e.g. cyclophosphamide
IV meds:
Anti-GBM - plasma exchange (remove aB) + IV methylprednisolone + IV cyclophos
Immune complex - IV methylpred or oral pred ± ABX
Lupus nephritis - IV methylprednisolone + cyclophosphamide
Polycystic kidney disease
Types
Features
Complications
2 forms, ADPKD (most common) and ARPKD
Renal cysts, extrarenal cysts (liver), intracranial aneurysms, aortic root dilation and aneurysms, mitral valve prolapse, abdominal wall hernias
HTN, increased CV morbidity, CKD, ruptured intracranial aneurysm, ESRD
PCKD presentation
FHx of PKD/ESRD or stroke Flank/abdominal discomfort due to enlarging kidneys, haemorrhage or stone formation Lumbar pain (females) Haematuria (males) HTN (at 20-35) ****** -> mandatory screening with renal USS DUFS (infection, UTI) Palpable kidneys Headaches (intracranial aneurysm) Hepatomegaly (liver)
PCKD Ix (4)
Renal USS -> Ravine’s criteria (With positive fam history)
- <30yrs = 2 or more unilateral or bilateral cysts
- 30-60yrs = 2 cysts in each kidney
- 60+yrs = 4 cysts in each kidney
Genetic testing - PKD1 or PKD2 mutation
CT abdo pelvis
Relevant further testing
Urinalysis (protein, bacteria), ECG - LVH + echo - aortic root dilation, MR angiography - screen for aneurysm
PCKD Mx
HTN - ACEI or ARB lifelong aim 130/80
UTI/Infected cyst - Ciprofloxacin
