Renal Flashcards
Acid base regulation in kidneys
- HCO3 reabsorption into blood
- HCO3 in tubule lumen binds to hydrogen H+ secreted by the brush border cell in exchange for a sodium ion from the tubule to form carbonic acid (H2CO3)
- Carbonic anhydrase type 4 splits carbonic acid into CO2 and H20 which can both then diffuse across membrane into the brush border cell
- Inside the brush border cell carbonic anhydrase type 2 combines them back to form carbonic acid which dissolves into HCO3 and H+ which are shuttled into blood using a cotransporter - H+ excretion in urine Proximal tubule uses Na-H counter transporter
- Na reabsorbed in exchange for H which is excreted into tubule lumen Distal tubule uses H+ATPase to pump H+ from blood into tubule lumen
Buffer systems used to ensure urine doesn’t become too acidic (pH>= 4.5): Ammonia and phosphate
- Ammonia combines with H+ in tubule lumen to form Ammonium (NH4+) which is excreted in urine
- H+ also combines with HPO42- to form H2PO4- which is excreted in urine
Formula for plasma clearance rate of X
(Concentration of X in urine x urine flow rate ml/min) divided by (plasma concentration of X)
Importance of inulin on clearance ratio
Inulin is a polysaccharide product by plants It is the only substance that is freely filtered (100% excreted) and NOT reabsorbed at all
Gives an accurate estimation of the GFR
Clearance ratio = Cx/Cinsulin
CR of 1 = substance X is completely filtered (same as inulin)
CR >1: substance X excreted more than it is reabsorbed
CR <1: substance X is reabsorbed more than it is excreted
Pathophys behind body’s response to dehydration
- Osmolarity increases (less fluid but same solute load) - Osmoreceptors in hypothalamus sense this -> production of ADH (vasopressin)
- Baroreceptors in atrium, aortic arch and carotid sinus sense decrease in blood volume and signal to hypothalamus to produce ADH
ADH → water reabsorption in collecting duct (aquaporin insertion) and vasocontriction → incr BP
ADH - what is it produced by - what effects does it have
- Produced by hypothalamus
- Binds to receptors in collecting ducts of kidneys and in smooth muscle of vessel walls
- In collecting duct, causes insertion of aquaporins -> H20 flows down concentration gradient from duct lumen into blood
- Causes vasoconstriction to increase BP
What happens when you drink a lot of water in terms of osmoregulation?
Decr plasma osmolarity inhibits osmoreceptors firing in anterior hypothalamus -> inhibits H20 reabsorption Baroreceptors sense increase stretch -> inhibits osmoreceptors firing in anterior hypothalamus -> inhibits H20 reabsorption
- NO aquaporin insertion into CD so H20 cannot be reabsorbed in CD so H20 is excreted
- Vasodilation to decrease BP
Cellular mechanism of ADH action on insertion of aquaporins in collecting duct
ADH binds to receptor in basolateral membrane of collecting duct (vasopressin receptor 2 which is G-protein coupled, involves conversion of ATP to cAMP via signaling cascade using enzyme adenyl cyclase)
Ultimately results in phosphorylation of aquaporin2 which is inserted into luminal membrane
Water travels down its concentration gradient from tubule lumen into bloodstream -> incr blood volume
Where is K mostly found?
Inside cells (concentration is 150) Small amount found in the plasma (4.5)
K homeostasis regulation in kidneys
REABSORPTION
- 67% K is reabsorbed in PCT (passively by ‘solvent drag’, follows the water that is reabsorbed)
- 20% K is reabsorbed in ascending LOH (Na/K/Cl co-transporter, loop diuretics inhibit)
EXCRETION
- K excretion occurs in the DCT/Collecting duct
- ‘fine tuning’ regulated by aldosterone (Na reabsorption via Na-K ATPase which exchanges Na for K)
Things that decrease ECF K concentration (and increase uptake into cells)
Ingestion of K -> plasma [K] increases
- Insulin causes glucose and K uptake into cells (via increased activity of Na/K ATPase)
- Adrenaline increases activity of Na/K ATPase to increase K uptake into cells
- Alkalosis
- Bicarb
- Ventolin/sabutamol
Things that increase ECF K concentration (excretion of K out of cells into ECF)
ATP (exercise) Cell lysis - Burns - Rhabdo - Chemo (TLS) Hyperosmolality Acidosis
Alport syndrome
X linked
Mutation in gene coding for type IV collagen (COL4a) in kidney glomerulus, eye, ear
- Kidneys: Persistent microscopic haematuria -> gross haematuria -> proteinuria -> kidney failure by age 18+
- Ears: Bilateral sensorineural hearing loss (born with normal hearing, loss occurs over time)
- Eyes: Anterior lenticonus
Ix - renal bx, genetic testing
tx - ACE inhibitor, hearing airs, replacement of occular lens, RRT/transplant
Anterior lenticonus is path pneumonic for what?
Alport syndrome
Mutation in what gene causes alport syndrome?
COL4A
Pathophys of Anaemia of CKD
Tx
Primarily the result of inadequate EPO production by failing kidneys
Other contributory factors = Fe deficiency, folic acid or B12 deficiency, decreased erythrocyte survival
Recombinant EPO used as treatment if other above causes are treated
Findings of renal tubular acidosis (biochemical and clinical)
Biochemical: Normal anion gap metabolic acidosis Hyperchloraemic
Normal renal function despite this
K low in types I,2 and high in type 4
Clinical: Poor growth, Polyuria, Dehydration, Ricketts (from chronic metabolic acidosis leading to reabsorption of minerals (Ph) from bone to buffer this)
What is the primary defect that causes type II RTA?
Impaired bicarb reabsorption in prox tubule leads to aciodosis in blood
Urine pH>7
Serum bicarb usually >10
Hypokalaemia
What is the primary defect that causes type I RTA?
Impaired hydrogen ion secretion (H+ ATPase isn’t working) into tubule > leads to acidosis in blood
Present with Ca renal stones (due to high tubular Ca)
Urine pH >5.5
Serum bicarb <10
Hypokalaemia
What is the primary defect that causes type IV RTA?
Decr aldosterone secretion or resistance to aldosterone
> impaired hydrogen ion secretion into tubule (Aldosterone stimulates secretion of H+ via the H+/ATPase in the collecting tubules)
> leads to acidosis in blood
Hyperkalaemia (Aldosterone stimmulates Na/K ATPase)
Urine pH < 5.5
Serum bicarb usually >10
Nephrotic syndrome Key ft Causes and treatment
Key fts: proteinuria (>3.5g protein lost/day), hypoalbuminaemia, oedema, hypercholesterolaemia
Causes
- Primary/idiopathic due to minimal change disease (85%) or focal sclerosis glomerulonephritis (10-15%) or membraneous nephropathy
- Secondary - alport syndrome, SLE, HSP, GN Pathophys - Leaky glomerulus -> proteinuria and low serum albumin
Ix - Urine - protein, lipids, fatty casts Bloods - incr lipids
Cx - Hypercoagulable state (antihrombin III lost in urine) - Incr infx risk (Ig lost in urine)
Tx Daily urine dips Daily weight No added salt in diet Albumin + furosemide Oral pred
Cyclophosphamide - second line if relapsing or steroid dependent nephrotic syndrome Penicillin if suspected peritonitis
Mx of nephrotic syndrome with ATYPICAL features (and what are atypical features)
ATYPICAL: HTN, haematuria, age <12mo or >12yrs
Further ix (atypical nephrotic syndrome)
Complement - low C3/4 in SLE and MPGN
ANA - SLE ‘
Hep B if at risk
Biopsy if steroids resistant after 4-6 wk therapy or atypical features
Causes of normal anion gap metabolic acidosis
Pneumonic = CAGE
C = chloride excess (eg. NaCl)
A = acetazolamide (Carbonic anhydrase inhibitor, incr bicarb excretion), Addison’s
G = GIT causes – diarrhoea, vomiting, fistula (pancreatic, ureters, biliary, small bowel, ileostomy)
E = extra – RTA
Causes of widened anion gap metabolic acidosis
K = ketoacidosis
U = uraemia (renal failure)
L = lactic acidosis (ischaemia)
T = toxins [ethylene glycol, methanol, aspirin (salicyclates), metformin]
What is the most common genetic mutation in autosomal recessive polycystic kidney disease
Mutation in PKHD1 gene (polycystic kidney and hepatic disease)
Mx of hyperkalaemia
Uptake of K from serum into cells
- Bicarbonate – Causes K+ to move intracellularly
- Insulin + glucose – insulin causes K+ to move intracellularly
- Nebulised salbutamol - by stimulation of β1 - adrenergic receptors, leads to rapid intracellular movement of K+
Cardioprotection
- Calcium – stabilizes cell membrane of heart cells
Excretion of K from body
- Resonium
- Furosemide (only if not anuric)
- Dialysis in setting of severe renal failure
Autosomal recessive PCKD
→ How does it affect the kidneys?
→ Associations
AR - mutations in PKHD1 gene
Both kidneys affected
Enlarged polycystic kidneys (many small cysts)
Antenatally diagnosed, oligohydramnios
Renal failure requiring RRT from birth/infancy
Associated liver fibrosis and liver failure
HTN
Often assoc w pulmonary hypoplasia/potter phenotype +/- resp distress and spontaneous pneumothorax (30% mortality rate)
What is the potter phenotype and what is it assoc with
Group of findings associated with lack of amniotic fluid and kidney failure often in setting of autosomal recessive PCKD
→ low-set ears, micrognathia, flattened nose, limb positioning defects, IUGR, pulm hypooplasia
Diabetes Insipidis
What is it? Pathophys?
Presentation
What is the classic electrolyte disturbance?
Rare congenital or more commonly acquired disorder of water metabolism Inability to concentrate urine even in the presence of ADH
Deficiency of or resistance to ADH (acts to insert aquaporins for water reabsorption)
Presentation - massive polyuria, hyperNa/hyperCl (hyperosmolar serum), poor weight gain
Goodpasture’s Syndrome
Pathophys
What organs does it affect and what are the clinical symptoms
How is it diagnosed?
Type II hypersensitivity reaction
Autoantibodies (IgG) target type IV collagen fibres (alpha 3 chain) that make up the basement membrane in lungs and kidneys -> activates C’ system -> neutrophils release free oxygen radicals which damage the basement membrane
Affects:
- Lungs - inflammation and bleeding -> haemoptysis, cough and restrictive lung disease
- Kidneys -> Haematuria and proteinuria = nephritic syndrome
Diagnosis w renal bx
Tx
- corticosteroids
- immunosuppression
- plasmapheresis
Nephritic syndrome
Pathophys
Causes
Sx
Ix
Pathophys
- inflammation, damage to glomeruli of kidney -> incr permeability -> RBC and protein can leak into urine
Causes
- IgA nephropathy
- Post-strep GN
- MPGN/C3 nephropathy
- HUS
- Goodpastures syndrome
- Alport syndrome
- SLE
Sx
- haematuria, edema, HTN
Ix
- Haematuria, proteinuria
- Uremia (less waste excreted)
- Decr GFR
- Kidney bx (changes under light/electron microscopy, immunofluorescence)
IgA nephropathy Pathophys Presentation Diagnosis Tx
Most common form of nephropathy worldwide
Type III hypersensitivity reaction
Type of nephritic syndrome
Abnormal IgA form immune complexes with IgG and deposit in Mesangium (within Bowmans capsule) of kidneys -> activation of alternative C’ pathway -> glomerular injury -> RBC and proteinuria
Typically presents in childhood with asymptomatic hematuria +/- HTN ~2/7 following URTI and reoccurs with subsequent infx
Over time with subsequent damage can cause ESRF (25–40% of patients progress to uremia within 10–20 years after the diagnostic biops)
Ix - Renal bx with light microscopy (mesangial proliferation) and electron microscopy (immune deposits) and immunofluoresnce (IgA deposits)
Tx - control BP (low salt diet, antihypertensives)
- corticosteroids (prevent formation of immune complexes)
Lupus nephritis
- Pathophys
- Presentation
- Diagnosis/ix
- Tx
Can be cause of nephritic AND nephrotic syndrome
Caused by type III hypersensitivity reaction
DNA damage -> apoptosis -> DNA, histones, other nuclear proteins exposure -> antibodies target these nuclear antigens -> Ab-Ag complexes form and move through blood and deposit in various places, including KIDNEYS
Complexes can deposit (location of deposition depends on where complexes deposit):
- Endothelial capillary wall
- Bowmans space
- Baselement membrane
- Mesangial cells
Presentation
- Proteinuria -> edema
- Hyperlipidemia -> lipiduria
- Haematuria
Diagnosis
- Bloods: Raised ESR, dsDNA (50%), anti-sm (20%), ANA, RhF (50%); Low C3 and normal CRP
- Kidney bx
Tx = immunosuppression
- Corticosteroids
- Mycophenolate
- Cyclophosphamide
Post Strep GN
- pathophys
- ix/diagnosis
- treatment
Type III HS reaction to Group A beta haemolytic streptococci (1-2 weeks post staph skin infx or pharyngitis, 6 weeks post impetigo)
- Immune complexes (IgG, IgM) form, deposits in Glom BM between podocytes
- Initiates inflammatory reaction in glomerulus, deposition of C3’, oxidants etc damage glomerulus -> haematuria, proteinuria -> peripheral and periorbital oedema
- Self-resolves within 1 month in most cases
- Minority of cases may progress to renal failure or rapidly progressive GN (-> renal failure)
Ix
- Bloods: ASOT, Anti-DNAse B, decreased C’ levels (should return to normal by 3 mo)
- Urine: dysmorphic RBCs + casts
- Renal bx
- Light micro: enlarged, hypercellular
- Electron micro: sup epithelial deposits or ‘humps’
- Immunofluorescence: “starry sky”, granular, GBM + mesangium
Tx
- 10 days of penicillin if positive throat swab
- Supportive tx: fluid restrict, Na restrict, furosemide to correct any vol overload
Rapidly progressive GN
Pathophys
Causes
Dx
Tx
Or ‘Crescentic GN’
Type of nephritic syndrome
Inflammation in glomeruli -> crescent shaped cell proliferation -> damage to glomerular BM -> sclerosis -> acute renal failure in weeks to months
Causes - idiopathic or autoimmune
- type I: anti-GBM Ab (Goodpastures)
- type II: immune-complex mediated (post strep GN, SLE, IgA nephropathy, HUS)
- type III: pauci-immune, pANCAs, cANCAs in blood (Ab against neutrophils)
Dx
- ANCAs in blood for type III
- Renal bx: crescents
- Differentiation between different types on immunofluorescence 1: linear 2: granular 3: negative (nothing lights up)
Tx - Anticoagulation reduces fibrin deposition in crescenes
- plasmapheresis
- immunosuppression
- dialysis
- kidney transplant
Membranoproliferative GN (MPGN)
- Pthophys
- Presentation
- Ix
- Tx
= mesangiocapillary GN
Immune complex and/or C’ deposits in glomerulus -> inflammation and damage of glomerular basement membrane and mesangium -> decr kidney function, proteinuria
Presentation - nephrotic syndrome (proteinuria, edema) or nephritic syndrome most commonly (haematuria, oliguria, HTN)
Ix - Renal bx and light microscopy and immunofluorescence ; low C3, C4
Tx
- steroids (but doesn’t always work)
- can progress to Chronic RF
Nephrotic syndrome
- Pathophys
- Clinical Features
Inflammation/damage to glomeruli of kidneys -> glomeruli more permeable -> leak proteins from blood into urine
Features:
- Proteinuria (>3.5/day) -> hypoalbuminaemia -> edema
- Also get hyperlipidema and lipiduria (-> foamy urine)
Pathophys of 3 types of MPGN
3 types:
Type 1 most common: SUBENDOTHELIAL deposits of circulating immune complexes or C’ deposits -> Results in BM thickening and proliferation of mesangial cells (sometimes surround BM -> ‘tram tracking’ = double BM)
Type 2 - C3 deposits (no immune complexes) in BASEMENT MEMBRANE (get low circulating plasma C3) triggered by nephritic factor (IgG ab that binds to C3 convertase making it more stable, active longer)
Type 3 - immune complexes and C’ deposits are found in SUBENDOTHERLIAL AND SUBEPITHELIAL space of mesangium. poorly understood (idiopathic).
Type 1 MGPN PAthophys
SUBENDOTHELIAL deposits of
- circulating immune complexes or C’ deposits made of Ag and Ab form (may form because of Ag release from CHRONIC INFECTION such as Hep B or Hep C)
- can have inappropriate activation of ALTERNATIVE C’ pathway and C’ complexes deposit
- if nephritic factor present, binds to C3 convertase, making it more stable so it can work longer -> get C’ deposit (not immune complexes) -> Results in BM thickening and proliferation of mesangial cells (sometimes surround BM -> ‘tram tracking’)
Minimal change
- causes
- pathophys
- ix
- tx
Most common cause of nephrotic syndrome in kids
Causes - idiopathic but can be triggered by recent infx/vaccination or immune stimulus (insect sting)
Pathophys - T cells release cytokines that damage podocytes in glomerulus -> leaky
Note - this condition causes SELECTIVE proteinuria (don’t lose Igs)
Ix
- Light microscopy: NORMAL glomerulus
- *Electron microscopy: effacement of podocyte foot processes*
- Immunofluorescence: NEGATIVE
Tx Responds well to corticosteroids
Focal segmental glomerulosclerosis
- causes
- pathophys
- ix
- tx
Primary cause of nephrotic syndrome (2nd most common in kids)
More common in adults
Can be idiopathic or triggered by hx HIV infx, IFN treatment, congenital malformations
Pathophys unknown but ultimately results in effacement of podocyte foot processes AND hyalinosis (deposits of lipids and proteins in glomerulus) -> sclerosis and fibrosis
Ix:
- Light microscopy: sclerosis and hyalinosis among glomerulus
- Immunofluorescence: often NEG but can be positive for C1/C3 or IgM deposits
Tx - inconsistent response to corticosteroids, some ppl can progress to CKD
Membraneous nephropathy
- causes
- pathophys
- ix
- tx
Associated with HBV, malignancy (lymphomas)
Primary cause of nephrotic syndrome
Causes
- Primary OR Secondary (SLE, NSAIDs, infections hep B/C/syphyllis) or solid tumours such as lymphomas
Pathophys
- Damage caused by immune complexes depositing in supeithelial space -> damages podocytes and mesangial cells
Ix
- Light microscopy: diffuse capillary and GBM thickening caused by immune complex deposition
- When stained with silver methanamine, irregular expansions from GBM can be seen
- Immunofluorescence: immune complexes IgG and C3
- Electron microscopy: flattening of popdycte processes and sub epithelial immune complex depositions
Tx: Poor response to corticosteroids → Progression to CKD
Thin glomerular basement membrane disease Presentation Genetics Mgmt
=BENIGN FAMILIAL HAMEATURIA
- Presence of persistent microscopic haematuria AND isolated thinning of GBM on EM
- Presents with episodic gross haematuria can also be present – particularly after respiratory illness often on bg of episodic microscopic haematuria throughout childhood
- Family history of isolated haematuria WITHOUT renal dysfunction (proteinuria, renal impairment, HTN) referred to as benign familial haematuria
-> most patients will not undergo renal biopsy – presumed TBMD
- Genetics: sporadic or inherited (AD, Heterozygous mutations in COL4A3 and COL4A4). NOTE - homozygous mutations in these gene = AR alport syndrome (later onset, later progression to ESRF than the x-linked form, mut in col4A5)
- Annual BP an urine PCR screening warranted • Very rare progression to ESRF
Membranous nephropathy Presentation Causes Pathophys Ix Tx
Presentation - nephrotic syndrome Causes - Primary OR Secondary (SLE, NSAIDs, infections hep B/C/syphyllis) or solid tumours such as colorectal carcinomas Pathophys - Damage caused by immune complexes depositing in supeithelial space -> damages podocytes and mesangial cells Ix - C3 and C5 levels normal in idiopathic MN [Depressed in MN secondary to SLE or hep B] Renal bx LM - Diffuse capillary and GBM thickening caused by immune complex deposition When stained with silver methanamine, irregular expansions from GBM can be seen EM - flattening of podoycte processes and sub epithelial immune complex depositions IF: Immune complexes IgG and C3 Tx - Inconsistent response to corticosteroids 20% progression CKD 40% ongoing active disease 40% remission
Pathogenesis of CKD
Hyperfiltration i. As nephrons are lost, the remaining nephrons undergo structural and functional hypertrophy characterized by an increase in glomerular blood flow ii. Compensatory hyperfiltration temporarily preserves total renal function progressive damage to surviving glomeruli Proteinuria – toxic effect on tubular cells HTN – causes arteriolar nephrosclerosis and by increases the hyperfiltration injury Hyperphosphataemia - calcium deposition in the renal interstitium and blood vessels Hyperlipidaemia – oxidant-mediated injury
Stages (eGFR cut offs) for CKD
- Stage 1 = GFR > 90 with kidney damage 2. Stage 2 = 60-90 3. Stage 3 = 30-60 4. Stage IV = 15-30 5. Stage V = < 15 plan for RRT
Consequences of CKD
Reduced waste excretion
- uraemia (-> pericarditis)
- acidosis
- hyperK
- hyperPh, hypoCa, hyperPTH
- Fluid retention or dehydration
- HTN
- Proteinuria
- Anaemia of chronic disease
- Renal osteodystrophy from secondary Hyperparathyroidism
- Growth impairment
Slowing disease progression in CKD
• Control HTN • ACEi or ARBs in children with proteinuria, even in absence of THN • Maintain normal Serum Ph • Treat infx promptly
Mechanism and management of renal osteodystrophy in CKD
High turnover bone disease caused by secondary hyperPTH
b. ↓ Activated vitamin D = reduced calcium absorption in SI and renal tubules -> hypocalcaemia + ↑PTH secretion
c. ↓ Phosphate excretion by kidneys -> hyperphosphatemia -> hypocalcaemia (Ph binds Ca) + ↑ PTH secretion
↑ PTH = bone resorption (wants to free up Ca, Ph by resorbing bone -> blood)
Leads to bone deformities, bone pain, fractures
Mx
i. Low Ph diet
ii. Vit D supplements (calcitriol)
iii. Ph binders (Ca carbonate/acetate, Mg carbonate, sevelamer hydrochloride)
Tx of anaemia in CKD
a. Due to inadequate epo production +/- deficiencies in Fe, B12, folate b. Tx – recombinant EPO (neorecormon, darbopoeitin) +/- Fe supplements +/- folic or B12 supplementation
Tx of proteinuria in CKD
Treatment w ACEi (arteriole dilatation reduces intraglomerular pressure)
Helps decr proteinuria by 50% but can incr Cr up to 25% (acceptable)
Is actually nephroprotective
Mx of fluid retention in CKD
Later CKD – salt and water retention Mx i. Low Na diet ii. Fluid restriction iii. RRT
Mx of acidosis in CKD
Due to reduced acid excretion by failing kidneys
Sodium bicarb supplements (ural sachet or sodibic)
Mx of hyperkaelamia in CKD
(only w GFR <10% unless excessive dietary K or severe acidosis)
Restrict dietary K
Furosemide
Correct acidosis
Causes of chronic renal failure
• Under 5 most commonly due to congenital abnormalities • Over 5 most commonly acquired (GN incl SLE) or inherited (Alport syndrome) • Metabolic/inherited disorders can occur throughout childhood years Glomerular • FSGS • Congenital nephrotic syndrome • Chronic GN – SLE, MPGN, HSP, IgA, membranous • Alport • HUS • Cortical necrosis Non-glomerular • Hyperplasia/ dysplasia • Reflux nephropathy • Obstructive uropathy – PUV, prune belly, neurogenic bladder • Cystic – PKD, nephropthisis • Tubulopathies – cystinosis
Definition and Sx of ESRF Tx
Definition - The point at which homeostasis and survival can no longer be sustained with native kidney function and maximal medical management - Stage V = eGFR < 15 - plan for RRT Sx • Refractory fluid overload • Electrolyte imbalance • Acidosis • Growth failure • Uremic symptoms fatigue, nausea, impaired school performance Tx - initiation of renal replacement therapy ideally PRIOR to the above sx occur
Sx, ix and mx of peritonitis
Peritonitis is suspected if the patient has ANY of the following Signs or Symptoms: +/- Cloudy effluent fluid with WCC > 100* +/- Abdominal pain +/- Vomiting or nausea +/- Fever Ix Peritoneal fluid analysis • Cell count > 100 cells/mm3 • >50% PMN Culture of exit site Blood cultures + FBE Mx Antibiotics (vanc and ceftaz to cover GP and GN organisms) +/- catheter removal
Aetiology of peritonitis
Bacteria (skin) • 45-65% GP organisms: CONS > Streptococci > Staphylococcus • 15-35% GN organisms: E coli, Klebsiella, Pseudomonas Fungi (3-5%) • Candida most common
Indications for catheter removal in peritonitis
• If not responding to abx within 5 days • Relapsing • Fungal or mycobacterial aetiology • Assoc w intra-abdominal pathology (Abscess)
Peritoneal dialysis How does it work What access do u need How to incr ultrafiltration? Main complication?
Peritoneal membrane used as a dialyzer (access to the peritoneal cavity is achieved by a surgically inserted, tunnelled catheter) Access: Tenkhoff catheter Excess body water is removed by an osmotic gradient created by high dextrose concentration in the dialysate Wastes are removed by diffusion from the peritoneal capillaries into the dialysate Ways to incr ultrafiltration o Incr ‘fill’ volume o Incr number of cycles/time on dialysis o Incr glucose concentration on dialysate Main cx - peritonitis
Hemodialysis How does it work What access do u need Where can it be done?
• Usually in a hospital setting, occurring 3 x per week (3-4 hrs each) • Access: permanent line or AV fistula • Primarily removes solute by DIFFUSION (solutes move from high concentration in blood to lower concentration in dialysate) • Dialysate fluid is used
what is the difference between the reduced GFR seen in AKI vs CKD
Reduced GFR in AKD due to reduction in single nephron GFR; vs in CKD is due to reaction in total number of nephrons
Causes of AKI
Pre-renal - Dehydration - Haemorrhage - Sepsis - Low albumin - Renal vein/arterial thrombosis Intra-renal - Glomerular: GN, TMA/HUS - Tubular: ATN (ischaemic/drug/toxin), tubular obstruction (tumour lysis) - Interstitial: Acute interstitial nephritis, pyelonephritis Post-renal = obstruction - Posterior urethral valves - Urolithiasis - Stricture/stenosis - Ureterocele - Tumour - Haemorrhagic cystitis (clots) - Neurogenic bladder
How to differentiate between pre-renal and ATN as causes for AKI
Pre-renal: retained concentrating ability of kidney
- Concentrated urine (high specific gravity, high osmolality)
- Low urinary sodium
ATN (renal): kidneys unable to concentrate, leaky
- Dilute urine (low specific gravity, low osmolality)
- High urinary sodium
- Will have casts in it
Complications of AKI
Electrolyte imbalances
- Hyperkalaemia (cardiac arrhythmias, arrest, death)
- Metabolic acidosis
- Hypocalacaemia (tetany)
- Hyponatraemia (seizures, lethargy)
- HTN (volume overload)
- Neurological sx
- Anaemia (usually mild, dilution from volume overload)
Hyperkalaemia - changes on ECG
Peaked T waves
Widened QRS
ST depression
Ventricular arrythmias
Hypocalcaemia - management
Lower the serum phosphate level (as Ph binds Ca, exacerbating hypoCa)
- Low ph diet
- Phosphate binders
Vitamin D -> incr Ca absorption, bone resorptopn. renal reabsorption
Only give IV calcium if tetany present
ATN - Aetiology - Pathophys - Ix - Tx
Aetiology
- 60% ischaemic
- 40% drugs/toxins (NSAIDs, aminoglycosides, contrast, chemotherapy)
Pathophys
- Reduction in blood flow results in constriction of efferent artery, dilation of afferent arteriole to maintain GFR AND activation in RAAS
- Incr renin/RAAS activation leads to nonspecific afferent and afferent arteriole and widespread vasoconstriction leading to ischaemic kidney injury
- obstruction by casts*
Ix - Urine muddy brown, epithelial cells (sloughed tubular epithelium)
- UEC: hyponatraemia [salt wasting (unable to reabsorb)]
- Urine: high urinary Na level, low sg and low osmolality (Dilute)
Tx - supportive
Acute interstitial nephritis
Definition
Aetiology
Presentation
Ix
Definition = Inflammatory infiltrate in the kidney interstitium, usually caused by drugs, with inflammation of the tubules (sparing of the glomeruli and blood vessels)
Aetiology: Common drugs especially NSAIDs!!! (Can be months after starting NSAIDs), Autoimmune disorders (Goodpastures, SLE, Sjogren, kawasaki)
Classic presentation = fever, rash and arthralgia in the setting of rising creatinine
i. Constitutional symptoms = nausea, vomiting, fatigue and weight loss
ii. Flank pain (stretching of renal capsule from inflammation)
IX can present with: White cells + WBC casts with low-grade haematuria +/- proteinuria AIN should be suspected in a patient who presents with an elevated serum creatinine and a urinalysis that shows white cells, white cell casts, and, in some cases, eosinophilia
In what situations can post-renal obstruction cause an AKI?
Single kidney
Kidney impairment
Bilateral obstruction
In what causes of glomerulonephritis will complement levels be low?
C3+4 = low in SLE and MPGN
Also low in post-strep GN but only transiently; should return to normal within ~3mo
ACE inhibitors
- MOA
- Side effects
Inhibit ACE (thus decr angiotensin II and thus inhibiting vasoconstriction and Na/water reabsorption, and aldosterone)
Side-effects -
- Dry cough and angioedema (due to accumulation of bradykinin)
- Hypotension
- Hyperkalaemia
Autosomal dominant polycystic kidney disease
- Genetic mutation
- Presentation
- Associated features
- Prognosis
Most common hereditary human kidney disease (1/400-1/1000)
Mutation in PCKD (polycystin) 1 and 2
- pckd1 more severe, earlier onset
Presentation: Onset in 20s and 30s (15% before age 15)
- Haematuria, flank pain, abdo masses
- HTN
- Recurrent UTIs
- Multiple bilateral macrocysts in enlarged kidneys
Assoc w
- Cysts in liver, pancreas, spleen
- Brain - cerebral aneurysm
- Heart - valve prolapses, aortic aneurysm
- Bowel - diverticular disease, abdo wall hernia
- Kidney stones
- HTN
- UTI
Prognosis
- ESRF - 50% by 60yrs
Acquired cystic kidney disease
- When does this occur
- What size are the kidneys
Occurs following ESRD (not inherited)
No renomegaly
Simple cysts
- Are they inherited/genetic?
- Presentation
- Associated features?
- How are they classified?
- Not inherited, usually appear ~20yo, 25% incr in size w time
- Mostly asymptomatic (occasionally can cause pain/haematuria/obstruction)
- No renomegaly or associated features
- Bosniak system (CT-based) of classification to stratify malignancy risk in adults, not used as much as children
Medullary cystic kidney disease (MCKD) vs Multicystic dysplastic kidney
Medullary cystic kidney disease
- Autosomal dominant inheritance - very rare
- mutation in uromodulin -> tubular cell atrophy -> progressive renal failure
- mutation in ren1 (renin) -> can cause anaemia and hypotension
- mutation in mucin-1
- Adult onset (20-50)
- US – occasional cortical cysts +/- associated obstruction / VUR
- Bx - interstitial fibrosis
- Assoc w hyperuricaemia, gout
VS
Multicystic dysplastic kidney
- Form of CAKUT (antenatally diagnosed on USS)
- Most severe form of cystic renal dysplasia
- Multiple cysts separated by dysplastic tissue w no identifiable renal tissue (non functioning kidney)
- B/L -> potter sequence, death if not on dialysis w kidney transplant earlier
- U/L - asymptomatic
- Results in involution of affected kidney so no assoc complications
Nephronophthisis
- Inheritance /gene mutation
- Pathophys
- Onset, progression to ESRF (Age)
- Presentation
- Extra-renal manifestations
- US findings/cyst appearance
AR inherited - mutation in nephrocystins (NPHP2 and NPHP3) -> affects function of tubular cilia cells -> leads to problems with reabsorption in renal tubules -> sodium wasting, dilute urine
Onset at any stage in life
a) INFANTILE
- ESRF by 12mo-3 yrs -> severe HTN -> may have oligohydramnios
b) Juvenile (most common) - ESRF by 13yrs -> Present with longstanding polydipsia, polyuria, and progressive CKD -> normal BP -> bland urinalysis
Extra-renal manifestations:
- retinitis pigmentosa
- hepatic fibrosis
- skeletal defects
- cardiac valve/septal defects
- Recurrent bronchial infections
US findings: Microscopic cysts that CANNOT be seen by US.
- Increased echogenicity of kidneys with loss of corticomedullary differentiation with normal/slightly reduced kidney size
MAG3 vs DTPA scans
- Both are dynamic (radioisotope uptake and excretion over time)
- DTPA - taken up by glomerular filtration -> gives info about GFR
- MAG3 - excreted by PCT -> measure of tubular cell function
Indications
- Functional scan
- GFR (DTPA)
- Tubular function (MAG3)
- Obstruction – proximal
- Information on differential function (better than DMSA)
DMSA scan
- What is it good for?
- Static or dynamic scan?
o Static renal scans using the radioisotope Tc-99m succimer (DMSA) provide better visualization than Tc99m MAG3 scans of focal renal parenchymal abnormalities** and better assessment of a **difference in renal function between the two kidneys
o DMSA scans can also be used in children with a febrile urinary tract infection to detect acute pyelonephritis or as a follow-up test to detect focal renal scarring.
What is IV pyelogram used for?
Wvaluates obstruction in collecting system
MCUG/VCUG
- How does it work?
- What age group?
- What is it used for?
- Child is catheterized, radioisotopes injected into the bladder (retrograde)
- XRays performed during filling and voiding
- Only tolerated < 12 months
Used to detect
- VUR
- Urethral obstruction
- Neurogenic bladder
What is the role of aldosterone?
Aldosterone is secreted by adrenal cortex and acts on distal tubules/collecting duct to cause
- Na, Cl, H20 reabsorption/retention
- K excretion
Role of angiotensin II
Produces arteriolar constriction and increases SBP and DBP.
One of the most potent vasoconstrictors known.
Also acts on adrenal cortex to increase secretion of aldosterone.
Role of thromboxane
Promotes platelet aggregation and vasoconstriction. Activated in acute severe blood loss to contract bleeding vessels and form clot.
Role of prostaglandin I2
Unstable cyclooxcygenase metabolite found in vascular endothelial cells.
Potent vasodilator and inhibitor of platelet aggregation.
Causes dilation of afferent arteriole in JGA in response to hypovolaemia/decr renal perfusion.
Melnick Fraser Syndrome
- what is the other name?
- inheritance patterns?
- main 3 features
IE Branchio-oto-renal syndrome
AD Variable expressivity
Complete penetrance
Features:
1) Brachial fistulae or cysts
2) Ear malformations, which can include the inner, middle and outer ear (pinnae malformation, hearing loss, preauricular pits)
3) Renal malformations, which can range in severity from renal hypoplasia to agenesis.
Role of 1,25 dihydroxycholecalciferol, (also called calcitriol)
IE Vitamin D (active form, activated by liver and kidneys)
- Overall role is to increase Ca and Ph serum levels
- Bone resorption releases Ca and Ph into blood
- Incr Ca and Ph absorption in SI
- Incr Ca reabsorption in PCT and DCT
- Inhibits PTH secretion
Role of PTH
In response to a drop in serum Ca levels OR elevated Ph levels, parathyroid glands secrete PTH
PTH acts to
- incr bone resorption, releasing Ca and Ph into blood
- Incr Ca reabsorption in loop of henle, DCT and collecting ducts (inhibits Ph reabsorption)
- Incr synthesis of active vitamin D in kidney
What is arginine vasopressin
IE ADH produced by hypothalamus and secreted by posterior pituitary
released in response to decreased atrial pressure, i.e. hypovolaemia
ROLES
- Incr water reabsorption in collecting duct, producing more concentrated urine
- Arterial blood vessels vasoconstrict (only in high concentrations during hypovolaemic shock)
what is normal urine osmolality?
100-400mOsm/kg
DDX haematuria 36hrs post URTI (give x3)
IgA nephropathy
Alport syndrome (usually also get bilat sensorineural hearing loss)
Thin glomerular basement membrane disease (benign familiar Haematuria)
What ix provides the most accurate measure of glomerular filtration rate?
51Cr EDTA clearance
- Is Freely filtered, not reabsorbed or secreted by tubules.
- Is used for precise measurement of GFR, is less cumbersome than the gold standard measurement which is inulin.
- IV Cr EDTA is injected and blood radioactivity is measured at 2 and 4 hrs post
What formula is used to estimate the GFR?
Shwartz formula
eGFR = k x height / serum creatinine
k is a constant that depends on muscle mass, which itself varies with a child’s age.
In 1st year of life, k=0.33 in preterms and 0.45 in full terms
For infants and children of age 1-12 years, k=0.55
How does haemofiltration work?
Hydrostatic pressure to remove solutes by convection
Does NOT use dialysate fluid
Uses highly permeable membrane
Bartter syndrome
- How does it present?
- What is it caused by?
- What would you see on a blood gas?
- What hormonal abnormalities would you see?
Presents in NEONATAL PERIOD with FTT, thirst and dehydration from litres of urine output
Resembles the action of furosemide as it results in inhibition of the same channel in the renal tubule, the Na/K/Cl co transporter
Metabolic alkalosis
LOW serum K and Cl (high in urine), Na and Ca (have calciuria - vs in gitelmans have low urinary Ca excretion)
Incr renin and aldosterone levels
Gitelman syndrome
- How does it present?
- What is it caused by?
- What would you see on a blood gas?
- What hormonal abnormalities would you see?
AR kidney tubule disorder causing hypokalaemia metabolic alkalosis
Cause: Non-functioning Na/Cl symporter in DCT
- Same channel that thiazide diuretics act on (resembles thiazide toxicity)
Presents in late childhood/adolescents with salt wasting -> nocturia, polyuria, polydipsia and sx of hypocalcaemia/magnesaemia (TETANY, muscle weakness and cramps)
Features: Metabolic alkalosis with LOW serum K, Mg, Cl, Ca and Low urine Ca (vs barter - has and calciuria)
Increased renin and aldosterone
What is the pathophys of gitelman syndrome
What is this condition
Minimal change disease (normal glomerulus)
What is this condition
FSGS
What is this condition
Alport syndrome (abnormally split glomerular basement membrane)
Acute renal failure
- Presentation
- What is the electrolyte disturbance seen?
- Treatment
Presentation:
- Oliguria
- Oedema
- HTN
- Vomiting
- Lethargy
- Electrolyte disturbance - hyperKa, hyperPh, HypoCa
- Metabolic acidosis
Mangement
- Fluid restrict to insensible loss + ongoing losses. In polyuric recovery phase maintain input and electrolytes
- Mx of hyperkalaemia if ECG changes present
- Ca carbonate as ph binder if HyperPh
- HypoCa - Ca supps
- Dietary restriction of K,Ph, Na, protein
- Bicarb if metabolic acidosis present
- Antihypertensives if HTN
- Dialysis is severe hyperK, hypoNa, metabolic acidosis, fluid overload, symptomatic uraemia or medical mx not tolerated/workig
EM of membranous nephropathy
- featuring ‘spike and done’ sub epithelial deposits
Poststreptococcal glomerulonephritis.
(a) Light microscopy: global endocapillary hypercellularity/proliferation with prominent influx of inflammatory cells, including many neutrophils in capillary lumina and swollen endothelial cells
(b) Immunofluorescence: Coarse granular pattern of C3 deposition in peripheral capillary walls and mesangial regions of a glomerulus, showing in some areas a “starry sky” pattern.
(c) Electron microscopy: Characteristic subepithelial hump-like deposits (arrows) over the subepithelial aspect of the glomerular basement membranes
What is the gold standard ix for assessment of renal scarring often post recurrent UTIs or reflux?
DMSA
Mx of (L) PUJ obstruction
Pyeloplasty
Microangiopathic haemolytic anaemia with thrombocytopaenia and acute renal failure =?
HUS
+ bloody diarrhoea, abdo pain, colitis +/- seizures from CNS disease
What is the most common way to distinguish between prerenal and renal (ATN) causes of acute renal failure?
Fractional excretion of Na (%)
= 100 × (SCr × UNa ) / (SNa × UCr)
If <1% = prerenal
If >4% = renal
Pre-Renal UNa (mmol/L) <20 (low as kidneys concentrating ability preserved and able to reabsorb Na to help incr fluid volume)
Intrinsic UNa >40
Post renal UNa >40
Causes of hypokalaemia metabolic acidosis in Children and how to differentiate them
Recurrent episodes of haematuria in an 11yo boy → Electron microscopy shows diffuse thick and thin “basket weave” patterning of the glomerular basement membrane.
?diagnosis
Alport syndrome (x-linked recessive)
What syndrome has the highest risk developing Wilms tumour?
Denys drash (90%)! - progressive renal disease, male pseudohermaphroditism, and Wilms tumor
WAGR is next, 50% - Wilms, Aniridia, Genitourinary, abnormalities, mental Retardation
What does atrial natriuretic peptide do to blood pressure?
Responds to stretching of atrial wall (indicates high blood volume/BP) by LOWERING BP
- promoting renal sodium and water excretion
- stimulating vasodilation.
- also has an anti-hypertrophic function in the heart, which is independent of its systemic blood pressure-lowering effect.
What does aldosterone do to BP and how?
Increases BP - ‘fine-tuning’
Released from adrenal cortex, activated by RAAS
Acts on distal tubule/collecting duct to reabsorb Na (and water along with this) in exchange for excretion of K
Infectious aetiology post renal transplant
The first post-transplantation month is dominated by infections directly related to the surgery. These entities include urinary tract infections (Escherichia coli), line infections (Staphylococcus aureus, Streptococcus viridans), wound infections (S aureus, S viridans), and pneumonia (Streptococcus pneumoniae).
The initial 6 post-transplant months are associated with the highest levels of immunosuppression and therefore carry the greatest risk of viral and opportunistic infections . CMV is responsible for more than two thirds of febrile episodes during this period. Other opportunistic - PJP, listeriosis meningitis, aspergillis fumigatis
Main ft of Renal coloboma syndrome
genetics
Hypoplastic kidneys, dysplasia of optic nerve, and sometimes a hole (coloboma) in the retina.
People with renal coloboma syndrome may progress to end stage kidney disease and some people experience vision loss.
Less common symptoms include vesicoureteral reflux, multiple kidney cysts, loose joints, and mild hearing loss.[1] The syndrome has an autosomal dominant pattern of inheritance and can be caused by mutations in the PAX2 gene.
CHARGE syndrome - what does it stand for?
Coloboma of the eye
Heart defects (TOF)
Atresia of the choanae
Restriction of growth and development
Genitourinary abnormalities (undesc testes, micropenis, renal abnormalities)
Ear abnormalities and deafness (outer air abnormalities and conductive hearing loss ad balance problems)
genetic mutation to CHD7 = ?
CHARGE association
A 16-year-old girl presents with primary amenorrhoea. On examination, she appears normal. An USS reveals renal agenesis and vaginal agenesis.
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare disorder that affects women. It is characterized by the failure of the uterus and the vagina to develop properly in women who have normal ovarian function and normal external genitalia. Women with this disorder develop normal secondary sexual characteristics during puberty (e.g., breast development and pubic hair), but do not have a menstrual cycle (primary amenorrhea). Often, the failure to begin the menstrual cycle is the initial clinical sign of MRKH syndrome. Can also be associated with kidney and skeletal abnormalities.
Melnick-Fraser syndrome
what are the 3 features?
= Branchio-oto-renal (BOR) syndrome
1) brachial fistulae or cysts (neck, pharynx, larynx);
2) Ear malformations, which can include the inner, middle and outer ear (hearing loss and pits/fistulae/tags);
3) Renal malformations, which can range in severity from renal hypoplasia to agenesis.
Kallman syndrome
Cause
Genetics
Presenting features
Deficiency in GnRH → hypogonadotropic hypogonadism (HH) and an impaired sense of smell from birth
- Multiple genes involved, can be inherited AD/AR/X-l depending on gene involved
Presenting features:
- Anosmia
- Delayed or absent puberty
- Males: undesc testes, micropenis, small testes, erectile dysfunction, infertility
- Females: amenorrhoea, no breast buds
- +/- renal agenesis and hearing dysfunction
*
Aetiology of Nephrogenic DI
- Drugs - Prolongued exposure to Li
- Electrolytes - Prolongued exposure to hypoK or hyperCa
- X-linked: mutation in vasopressin V2 receptor
- AR: mutation in aquaporin 2 gene
Infantile hypotonia, delayed motor milestones, seizures
Cataracts → glaucoma
Renal fanconi syndrome
What is this condition? Prognosis?
Lowe syndrome
X-linked
Reduced life expectancy of 30-40 years
Progressive renal failure from 10yo → ESRF
Renal fanconi syndrome
- What is it
- Sx
- Ix
- Mx
Proximal tubule defect → excessive urinary loss of water, glucose, aa, phosphate, bicarb, Na, Ca, K, urate (low serum levels and high urine levels of the above)
Sx: FTT, rickets, polyuria, polydipsia, dehydration + sx of underlying disease/cause
Serum electrolytes: hyperCl, hypokalaemic hypophosphataemic metabolic acidosis w normal anion gap = Type II type II proximal RTA
Mx
- diagnose and treat underlying disease
- Rickets: vit D and Ph supps
- Acidosis: bicarb supps
- Dehydration: extra salt and water
Causes of renal fanconi syndrome
Congenital
- Primary/idiopathic
- Cystinosis
- Lowe syndrome
- Galactosaemia
- Tyrosinaemia type I
- Hereditary fructose intolerance
- Wilson disease
Acquired
- heavy metals
- drugs
- chemo (ifosfamide)
- hyperPTH
- vit D deficiency
- interstitial nephritis
- glue sniffing
*
urine microscopy
showing white blood cells, eosinophils, and cellular casts =?
AIN
Urine muddy brown with sloughed epithelial cells and casts = ?
ATN
Analgesics for use in ESRF
Morphine and codeine should be avoided in renal failure/dialysis patients; hydromorphone or oxycodone are used with caution and close monitoring; and that methadone and fentanyl/sufentanil appear to be safe to use.
What gene mutations most commonly cause congenital nephrotic syndrome (x2)?
NPHS1 (encodes nephrin) - premature infants, enlarged kidneys. Finnish population
NPHS2 (encodes podocin, podocyte protein) - steroid resistant, FSGS
Mx of cysteinuria
D-Penicillamine
Mx of Hydroxyurea stones
Pyridoxine
Mx of Uric Acid stones
Allopurinol
Mx of Hypercalcuria (stones)
Thiazide
