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Nephrology Flashcards

1
Q

Renal artery stenosis is associated with which genetic disorder?

A

Neurofibromatosis

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2
Q

What renal issues are associated with tuberous sclerosis?

A

Angiomyolipomas
Benign renal cysts (TSC2 > TSC1)
Renal cell carcinoma

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3
Q

How do you calculate serum osmolality?

A

Serum osmolality = (2 x Na) + glucose + urea

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4
Q

Renal biopsy/microscopy in IgA nephropathy vs Alports?

A
  • Alport syndrome - variable thickness of basement membrane with splitting, thick and thin, woven basket
  • IgA nephropathy - mesangial deposits and expansion (same seen in HSP as also IgA-mediated)
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5
Q

Which properties affect filtration of substances at the GBM?

A

Molecular size and electrical charge (interna and externa = charge, densa = size)

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6
Q

Describe cystinosis

A
  • Lysosomal storage disease, leading to cystine accumulation
  • Fanconi syndrome (prox tubular dysfunction), photophobia (corneal cystine crystals), hypothyroidism
  • Later develop renal failure, diabetes (panc involvement), hepatomegaly, reduced fertility, cerebral atrophy, rickets
  • Ix: slit lamp (cystine crystals), high WBC cystine levels
  • Tx: electrolyte replacement, high fluid intake, thyroxine, Vit D, cysteamine (inc transport cystine), indomethacin (decr GFR)
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7
Q

What is the renal complication of Wilson’s disease?

A

Distal renal tubular acidosis which results in kidney stones.

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8
Q

What are the complications of APCKD?

A
  • Hepatic cysts
  • Colonic diverticula (in 80%)
  • Polyuria (early manifestation)
  • Renal failure (age 40-60)
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9
Q

What are the genes associated with congenital nephrotic syndrome, and infantile nephronophthisis?

A
  • NPHS1 and NPHS2 - congenital nephrotic syndrome

- NPHP2 and NPHP3 - infantile nephronophthisis

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10
Q

What mutations are seen in Alport syndrome?

A
  • COL4A3 - AR, early onset
  • COL4A4 - AD, late onset
  • COL4A5 - X-linked, early onset, most common
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11
Q

What are the issues seen in Alport syndrome?

A
  • Recurrent micro and macroscopic haematuria, esp with URTI
  • Sensorineural hearing loss (~age 10)
  • Corneal clouding, anterior lenticonus, white or yellow spots around macula (~age 12)
  • May have family history
  • Can progress to proteinuria 2nd decade life and renal insufficiency in early 20’s.
  • Biopsy: variable thickness of basement membrane with splitting, thick and thin portions, basket weave
  • Tx: ACE- to delay progression, start when microalbuminuria
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12
Q

What is the issue causing IgA nephropathy?

A
  • Abnormal glycosylation of the IgA1 molecule, meaning it is galactose deficient and therefore excess IgA is not identified by the body and degraded as usual.
  • This leads to accumulation of IgA
  • Body doesn’t recognise these abnormal IgA as “self” and therefore creates IgG. This binds to the IgA and causes immune complexes = type 3 hypersensitivity disorder
  • These are deposited in the mesangium of the kidney.
  • Activates alternative complement pathway - pro-inflammatory cytokines and macrophages released in kidney = glomerular injury
  • Light microscopy: mesangial proliferation
  • Immunofluorescence + electron microscopy: immune complexes in mesangium
  • Same biopsy appearance in HSP (IgA nephritis)
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13
Q

When does IgA nephropathy present?

A
  • During childhood with acute illness that involve mucosal lining (resp, GI) due to increased IgA production (<20% have elevated serum IgA)
  • Microscopic haematuria with intermittent macroscopic haematuria
  • Can develop renal failure (over decades) due to repeat injury and immune complex deposition
  • Normal complement levels
  • Active phase can be treated with steroids, ACE- if proteinuria
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14
Q

Discuss thin basement membrane disease?

A
  • Mild mutation in COL4A3 or COL4A4 (less severe than Alport’s)
  • Microscopic haematuria +/- macroscopic with URTI
  • Family history, AD
  • Benign familial haematuria, don’t develop proteinuria
  • Annual BP and P:Cr screening, genetics for diagnosis
  • Thin basement membrane on biopsy
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15
Q

Anterior lenticonus is pathognomonic of which syndrome?

A
  • Alport syndrome
  • Thinning of the lens capsule leads to a regular conical protrusion on the anterior aspect of the lens which is called anterior lenticonus
  • Occurs in up to 30% of Alports
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16
Q

The macula densa is located in the?

A

Distal tubule

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17
Q

What are the classic blood test findings in acute adrenal insufficiency?

A

Hyponatremia, hypoglycemia, hyperkalaemia

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18
Q

Discuss RTA type 1 vs type 2

A
  • RTA type II = prox renal tubular acidosis = wasting HCO3-, inability to reabsorb
    • Low K+, normal Na+
    • Normal urine calcium
  • RTA type I = distal renal tubular acidosis = defective H+ secretion from distal tubule
    • Low K+, sometimes low Na+
    • Hypercalciuria
    • +ve urinary anion gap (Na + K - Cl)
    • AR and AD forms
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19
Q

Which enzymes are involved in Vitamin D metabolism in the kidney?

A
  • 1-alpha hydroxylase converts Vitamin D to its active form and 24-alpha hydroxylase converts Vitamin D to an inactive form
  • 25 hydroxylation occurs in the liver
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20
Q

Discuss the value of the fractional excretion of sodium

A
  • The fractional excretion of sodium (FENa) is the most commonly used laboratory test to distinguish between pre renal AKI and ATN
  • FENa <1% suggests pre renal AKI
  • FENa >2% suggests ATN
  • FENa between 1-2% is non-diagnostic
  • FeNa = UNa x PCreat / PNa x UCreat
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21
Q

What is the difference between the afferent and efferent arterioles?

A
  • Afferent arteriole Approaches the glomerulus

- Efferent arteriole Exits the glomerulus

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22
Q

What makes up to renal corpuscle?

A
  • Where filtration begins

- Made up of the glomerulus and Bowman’s capsule

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23
Q

What is the role and anatomy of the juxtaglomerular complex?

A
  • Involved in regulating GFR and blood pressure
  • Located between the distal convoluted tubule and the afferent arteriole
  • Made up of:
    • macula densa cells (in DCT, sense when Na and Cl are low)
    • juxtaglomerular cells (located in wall of afferent arteriole, receive messages from MD cells but also can sense low pressure in arteriole, activate RAAS)
    • extraglomerular mesangial cells (help with signalling between MD and JG cells)
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24
Q

What are the effects of renin?

A
  • Secreted from juxtaglomerular cells
  • Increases Na reabsorption, which increases blood volume
  • Causes vasoconstriction, which increases blood pressure
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25
Q

How do you calculate renal clearance?

A
  • Clearance = concentration in urine x flow rate (ml/min)/ concentration in plasma
  • Clearance is the sum of all the reabsorption and secretion of a substance
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26
Q

What are baroreceptors and where are they located?

A

Pressure sensors (detect stretch) located in carotid sinus, posterior wall of R atrium, aortic arch. If decr BP then baroreceptors signal to hypothalamus to secrete more ADH from posterior pituitary, to increase water retention and therefore increase BP.

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27
Q

What parts of the body does ADH act on?

A
  • Distal tubule and collecting ducts of the kidney
  • Once ADH binds to AVPR2 receptors, get increase of ATP-cAMP, and aquaporin-2 channels are inserted into collecting duct. Water then flows by osmosis from tubule into the interstitium and peritubular capillaries to enter systemic circulation
  • Smooth muscle of arterial walls - causes contraction, to increase BP by increasing peripheral vascular resistance
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28
Q

Discuss the function of the ascending loop of henle

A
  • Impermeable to water
  • Losses solutes via the Na/K/Cl cotransporter and the Na/K ATP pump
    = net dilution of tubular fluid with decreased osmolarity
    = increased osmolarity of the interstitial fluid
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29
Q

Discuss the function of the descending loop of henle

A
  • Is permeable to water and therefore can equilibrate with the interstitium
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30
Q

What is the corticopapillary gradient?

A
  • Gradient created by the ascending and descending loops of Henle, with lower numbers of solutes in the cortical part of the interstitium, and higher numbers in the papillary part.
  • This gradient allows fluid and solute movement in the loop of henle
  • Water is secreted and then reabsorbed, solutes are reabsorbed and then secreted
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31
Q

What is Melnick-Fraser syndrome?

A
  • Branchio-oto-renal syndrome (BOR)
  • AD, incomplete penetrance, 1;40,000
  • EYA1 + SIX1 genes
  • Preauricular pits or skin tags, neck pits or fistulae, associated with renal abnormalities such as renal agenesis + chronic kidney disease
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32
Q

Discuss Dent disease

A
  • X-linked recessive nephrolithiasis, mutation in the CLCN5 gene that inactivates a voltage-gated chloride transporter named CLC-5
  • Polyuria, microscopic haematuria, proteinuria or kidney stones (75%)
  • Some cases associated with mutations in OCRL1 gene (same as Lowe oculocerebrorenal syndrome)
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33
Q

Discuss the renal complications of Wilsons disease

A

Distal renal tubular acidosis leading to kidney stones

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34
Q

Discuss Goodpasture’s syndrome (anti-glomerular basement membrane disease)

A
  • Pulmonary haemorrhage and crescentic GN
  • Usually RPGN leading to renal failure
  • Antibodies against type IV collagen within alveolar basement membrane and GBM - anti-GBM antibodies - activates complement system -> damage
  • Light microscopy – crescentic GN
  • Immunofluorescence – continuous linear deposition of IgG along GBM (against collagen)
  • Serum anti-GBM Abs +ve, normal C3
  • Not recurrent
  • Tx: steroids, cyclophosphamide, plasmapharesis
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35
Q

What is IgA vasculitis?

A

HSP

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36
Q

What does the ureteric bud form?

A
  • Ureter

- From 6 weeks this branches into calyces, renal pelvis, papillary ducts, collecting tubules

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37
Q

What does the mesonephric duct form?

A
  • Evolves into a tubular structure, forms primitive mesenchyme of nephrogenic ridge, develops into metanephric blastema
  • Forms renal corpuscle (glomerulus, Bowman’s capsule) and renal tubule (prox and distal tubules, loop of Henle)
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38
Q

Discuss the kidney function in newborn, premature and LBW babies

A
  • Reduced nephron numbers (usually 600,000 per kidney)
  • Glomerular hyperfiltration
  • Risk of sclerosis, HTN, CV mortality
  • Premature infants have a very high FeNa and therefore need sodium supplements
  • Newborns at risk of dehydration as urine concentrating ability is low, reaches full capacity in 1st year of life
  • Also have lower bicarbonate threshold, therefore plasma bicarb levels lower
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39
Q

Discuss GFR in the baby -> adult

A
  • Nephrogenesis completed by 36/40
  • GFR <5% of adult value
  • Term GFR 25ml/min, increases by 50-100% in first week, 300% by 3m, adult range by 2y age
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40
Q

What renal abnormalities may be found on antenatal USS?

A
  • Oligo or anhydramnios
  • Echogenic kidneys
  • Lack of corticomedullary differentiation, cysts, hydronephrosis
  • Severe oligo can lead to pulmonary hypoplasia and Potter’s syndrome - major determinant of outcome, poor prognosis
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41
Q

How do you calculate the GFR?

A
  • GFR = permeability of glomerular capillary wall x (hydrostatic pressure gradient - oncotic pressure gradient)
  • absolute = ml/min x 1.73/surface area
  • estimate = height (cm) / creatinine x 42ml/min per 1.73m2
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42
Q

What are the sites of major resorption in the kidney?

A

Proximal tubule and loop of henle. Distal tubule and collecting ducts are sites of fine-tuning

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43
Q

What is the role of ACE?

A
  • Converts angiotensin I into angiotensin II. Located in endothelial cells, especially in lining of lung
  • Angiotensin II stimulated hypothalamus to make more ADH
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44
Q

What are the main regulators of renal blood flow?

A
  • Adrenaline in response to fight/flight -> acts on a-1 adrenergic receptors on afferent and efferent arterioles, causing vasoconstriction, leading to reduced renal blood flow
  • Angiotensin II in response to low BP -> binds to angiotensin receptors along afferent and efferent arterioles, causing vasoconstriction, leading to reduced renal blood flow
  • Low levels of AgII -> efferent arteriole constricts more, leading to preserved GFR
  • High levels of AgII -> both afferent and efferent arteriole constrict - leading to reduced GFR
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45
Q

Where are ANP and BNP secreted and what is their mechanism of action?

A 
ANP = atrial natriuretic peptide, secreted by atria
BNP = brain natriuretic peptide, secreted by ventricles

Secreted in response to increase cardiac stretch, cause dilation of afferent arteriole and constriction of efferent arteriole, leading to increased GFR.

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46
Q

What molecules act on the kidney to increase renal blood flow?

A
  • ANP and BNP (from heart) - cause afferent dilation and efferent constriction - inc GFR
  • Prostaglandin I2 and E2 (from kidney) - cause afferent and efferent dilation - inc GFR
  • Dopamine (from brain and kidneys) - cause afferent and efferent dilation - inc GFR
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47
Q

What are the autoregulation mechanisms of the kidney?

A
  • Mechanisms to keep kidney blood flow constant over a range of systolic blood pressures
  • Myogenic mechanism: increased stretch of arterioles due to high BP causes vasoconstriction of afferent and efferent arterioles so as to maintain constant GFR
  • Juxtaglomerular apparatus - senses high Na in distal convoluted tubule, macula densa secretes adenosine, this causes afferent arteriole constriction
  • Low renal perfusion leads to constriction of efferent arteriole in order to maintain GFR
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48
Q

Discuss the RAAS

A
  • Angiotensinogen converted to angiotensin I by renin
  • Angiotensin I converted to angiotensin II by ACE
  • Angiotensin II causes vasoconstriction and increased aldosterone release from adrenal glands
  • > this leads to increased Na and H20 absorption in distal tubule, and arteriolar vasoconstriction leading to inc GFR
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49
Q

What are causes of low-renin hypertension?

A
  • Conn syndrome: primary hyperaldosteronism - hypertension, low K+, increased ECF volume, renin suppression. Tx: spironolactone as inhibits aldosterone
  • Liddle syndrome: pseudohyperaldosteronism - causes overactivation of ENaC channels in DCT -> Na and water retention, K+ wasting, low renin and aldosterone due to suppression. Tx: amiloride as binds + inhibits ENaC channels
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50
Q

Discuss the renal changes in pseudohypoaldosteronism

A
  • Elevated aldosterone, but body failure to respond
  • Leads to hyperkalaemia and metabolic acidosis
  • Hyponatraemia and dehydration
  • Can be transient secondary to UTI in infants
  • c.f. CAH with salt wasting - would have low aldosterone
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51
Q

Discuss pseudohyperaldosteronism

A
  • Liddle syndrome
  • Mimics hyperaldosterone but renin and aldosterone levels are normal-low
  • Severe hypertension, hypokalaemia and a metabolic alkalosis are seen
  • AD
  • Treated with a combination of low sodium diet and potassium-sparing diuretics (e.g. amiloride)
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52
Q

Discuss the pathway of Vitamin D synthesis/activation

A
  • Vit D (cholecalciferol) from UV light - hydroxylated in liver to 25 (OH) vitamin D3 (by 25-hydroxylase)
  • Production of 1-25 (OH) Vit D3 (calcitriol) via renal 1-hydroxylase in kidney = most biologically active Vit D metabolite
  • 24-alpha hydroxylase in kidney converts Vitamin D to an inactive form
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53
Q

What stimulates calcitriol (active vitamin D) production?

A
  • Hypocalcaemia, hypophosphatemia, low growth hormone
  • All cause increased renal 1 hydroxylase activity to increase calcitriol production
  • Rickets associated with renal failure is due to decreased calcitriol production
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54
Q

What are the different types of urinary casts and their significance?

A
  • Red cell casts - renal haematuria, glomerulonephritis
  • Tubular casts - ATN
  • White cell casts - pyelonephritis, ATN
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55
Q

What are the causes of haematuria?

A
  • UTI
  • GN - PSGN - blood, protein casts
  • Lupus nephritis
  • IgA nephropathy and Alport’s (isolated haematuria)
  • Trauma
  • Stones
  • Tumours
  • Cystic kidney disease
  • Coagulopathy, sickle cell anaemia
  • Renal vein thrombosis (neonate)
  • False +ves: beetroot, rifampicin, myoglobinuria
  • Fever, exercise
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56
Q

Discussthe albumin:creatinine ratio

A
  • Normal <3mg/mmol
  • Microalbumin 3-30
  • Proteinuria >30
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57
Q

What is the definition of proteinuria

A

> 1+ protein on dipstick
Nephrotic range proteinuria is >40mg/hr/m²or a first morning urine protein/creatinine ratio >200mg/mmol (normal <20), or >3.5g/day

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58
Q

What are the three main causes of proteinuria?

A
  • Due to glomerular damage (e.g.GN)
  • Due to tubular damage (unable to reabsorb small proteins)
  • Due to increased production of plasma proteins e.g. multiple myeloma, rhabdo, haemolysis
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59
Q

What can cause a false negative or false positive proteinuria on dipstick?

A
  • False -ve with highly dilute urine

- False +ve with blood contamination, or urinary pH >7

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60
Q

What are causes of transient proteinuria?

A
  • Fever, exercise, dehydration, stress, seizures, cold exposure, heart failure
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61
Q

When would you use renal arteriography?

A
  • To diagnose renal artery stenosis
  • Can do balloon angioplasty and embolisation
  • Access via femoral artery
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62
Q

What are the causes of hydronephrosis?

A

VUR, PUJ obstruction, VUR obstruction

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63
Q

Discuss the severity of PUJ obstruction and management

A
  • Usually seen on AN USS
  • 5-10mm mild, 11-15mm mod, >15mm severe
  • Bilateral in 10%
  • Do a MAG3 scan (meat and tubes) - significant obstruction if poor drainage despite frusemide, and if <40% function on side of hydronephrosis
  • 10% will have ipsilateral VUR
  • Tx: pyeloplasty if worsening obstruction or hydronephrosis, or if >30mm, or complicated by UTI (noteL stent is only temporary, not a fix)
  • With VUJ obstruction manage similarly but can do surgical reimplantation of ureters
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64
Q

Discuss duplex kidneys

A
  • 2 ureters from 2 separate pelvicalyceal systems, usually upper pole inserts inferiorly into bladder
  • Lower pole refluxes (infection and scarring)
  • Upper pole obstructs (hydronephrosis, can be ectopic into urethra or vagina, bladder ureterocele with cystic dilation)
  • Tx: surgical, depends on upper pole functioning and levels of VUR on MCUG
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65
Q

Discuss multi cystic dyplastic kidney

A
  • Variable sized non-communicating cysts, no renal parenchyma, dysplastic atretic ureter
  • May present as renal agenesis, involute over time, usually by 7yrs
  • No function on MAG3/DMSA scan
  • Usually unilateral, bilateral incompatible with life
  • Most common cause of abdominal mass in a newborn
  • Contralateral hydronephrosis in 10% (VUR, PUJ obst)
  • Risks: hypertension, Wilm’s tumour
  • Monitor BP, creatinine, proteinuria until age 5
  • No routine removal unless large mass, increasing size of non-functioning parenchyma
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66
Q

Discuss horshoe kidneys

A
  • 95% lower poles, 5% upper poles
  • Isthmus at L4 below origin of IMA
  • Associated with Turner’s
  • Increased risk PUJ obstruction and VUR, may develop UTI, renal stones
  • Increased risk Wilm’s tumour
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67
Q

Metabolic acidosis

A
  • Low pH, low HCO3. Caused by:
    • Bicarb loss - GI (loss in diarrhoea), renal (proximal RTA type 2, unable to absorb bicarb)
    • Low H+ ion excretion - distal RTA type 1, acute + chronic renal failure - inability to excrete H+ into urine
    • Inc H+ ion load - exogenous e.g. salicylate poisoning, methanol, ethylene glycol, and endogenous e.g. inborn errors metabolism, lactic acidosis (shock), DKA
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68
Q

Discuss metabolic alkalosis

A
  • High pH, high HCO3. Caused by:
    - Loss of H+ ions - vomiting (also causes inc HCO3 in blood), Cushing’s, hyperaldosteronism, Bartter’s, hypokalemia due to diarrhoea or diuretics. Hypokalaemia can be a cause and result of metabolic alkalosis (as K+ exchanged for H+ to improve alkalosis). Normal urinary chloride, not responsive to Cl- administration
    - Gain of HCO3 ions - excessive ECF volume loss causes RAAS activation with H2O and HCO3 retention (e.g. frusemide + thiazides, severe dehydration), exogenous ingestion e.g. antacids.
    - Chloride depletion - GI loss (pyloric stenosis, congenital chloride diarrhoea), frusemide, CF patients. Low urinary chloride, responsive to Cl- administration
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69
Q

What are the causes of a raised/normal/and low anion gap?

A
  • Raised anion gap >20 - normochloremic. Due to accumulation of organic acids e.g. lactate, ketones, urea, alcohol abuse, toxins
  • Normal anion gap - due to loss of bicarb. Hyperchloraemia compensates for low bicarb leading to normal anion gap. e.g. severe diarrhoea or Type 2 RTA, Type 1 RTA
  • Low anion gap - hypoalbuminaemia, multiple myeloma
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70
Q

Discuss the body’s fluid composition

A
  • 60% body is fluid
  • 40% intracellular
  • 20% extracellular = intravascular 5% + interstitial fluid 15%
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71
Q

Discuss the fluid shifts in DKA

A
  • High glucose leads to inc intravascular osmolality
  • Water shifts from intracellular to extracellular (intravascular), leads to cell shrinkage
  • Cells now accumulate organic osmolytes to increase osmolality to baseline, and water shifts back to cell to restore volume
  • As DKA treated, intravascular osmolality decreases, and fluid shifts back into cells
  • Rapid fluid shifts with fluid replacement can lead to cerebral oedema
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72
Q

Discuss the body’s osmoregulation

A
  • Small increase in extracellular osmolality sensed by hypothalamus
  • Leads to increased ADH secretion into the posterior pituitary leading to water retention by insertion of aquaporin channels into DCT
  • Increased water retention causes normalisation of ECF osmolality
  • Large volume decrease (even if iso-osmolar) sensed by baroreceptors in aorta+carotid sinus which stimulate further ADH release
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73
Q

What is the normal anion gap?

A
  • 3-11

- Made up of unmeasured anions such as organic acids and negatively charged plasma proteins such as albumin

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74
Q

How does the body compensate for a metabolic acidosis?

A
  • H+ ions leave the blood and enter cells, in exchange for a K+ ion. Helps with acidosis, but results in hyperkalaemia
  • However, in cases where there are excess organic acids, the H+ can enter the cells without being exchanged for K+
  • Chemoreceptors in carotid arch and aorta fire when pH falls, leading to increased RR and minute ventilation, which decreases CO2
  • Kidneys excrete H+ ions and reabsorb HCO3- (happens days later, and only if kidneys not initial cause of issue)
  • > opposite happens in metabolic alkalosis
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75
Q

For each 10mmHg increase in CO2, how much can bicarb rise by?

A
  • Acute: blood response to resp acidosis: 1mEq/L - i.e. a rise of 20mmHg CO2 leads to an increase of 2mEq/L of HCO3 = minimal changes in pH
  • Chronic: kidney response to resp acidosis: 4mEq/L i.e. rise of 20mmHg CO2 leads to an increase of 8mEq/L of HCO3 = substantial changes in pH
  • > opposite in respiratory alkalosis
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76
Q

What are causes of respiratory alkalosis?

A
  • Overdose with salicylic (eventually leads to metabolic acidosis)
  • Anxiety/panic attack
  • Urea cycle disorder
  • Sepsis
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77
Q

What are the causes of a raised anion gap metabolic acidosis?

A 
"MUDPILES"   
 Methanol (or formic acid) 
 Uremia 
 Diabetic ketoacidosis 
 Propylene glycol 
 Iron tablets or INH 
 Lactic acidosis 
 Ethylene glycol 
 Salicylates.
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78
Q

How do you correct sodium in DKA?

A

[Na+] + (glucose -10)/3

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79
Q

Discuss the function of the proximal convoluted tubule

A
  • Main site of reabsorption of Na (65%), HCO3 (85%) K (65%), Ca, Cl, Mg, lactate, amino acids, phosphate, citrate
  • Na/glucose transporter - Na passive, glucose active transport against concentration gradient. Glucose then transported into capillaries passively via GLUT1 and GLUT2 (high to low conc.)
  • Na/K ATPase pumps Na out of cells into interstitium (3 Na for every 2 K) - active process, requires ATP
  • This leaves a low conc. of Na in cells, so Na can passively flow from tubule into cells
  • Na and H20 can slip through leaky tight junctions between cells and into interstitium
  • Na/H+ exchanger, allows 1 Na into cell for 1 H out of cell into tubule. This helps with HCO3 absorption as combines with H and diffuses across membrane as H2O + CO2 (via carbonic anhydrase). This then leaves cell into blood via Na/HCO3 transporter
  • 50% of urea reabsorbed (passive)
  • Excretion e.g. ammonia, organic acids, medications
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80
Q

Discuss the function of the loop of henle

A
  • Corticopapillary gradient from low (300) to high (1200) osmolality - due to large quantities of Na and urea
  • Aquaporin channels in descending limb: passive H20 transfusion out of tubule. Impermeable to solutes, therefore tubule osmol goes from 300->1200.
  • Ascending limb is impermeable to water due to lack of aquaporins. Thin = squamous cells, thick = cuboidal cells
  • Na and Cl channels in thin ascending limb allow passive transfusion out of tubule
  • 40% of sodium reabsorption via Na/K/2Cl- cotransporter in thick ascending limb (passive) and then via NaK-ATPase (active) into interstitium and blood
  • Process of countercurrent multiplication. By end of LoH, osm ~325mmol
  • Loop diuretics work in ascending loop by blocking Cl- binding sites
  • Inborn defect in Cl- reabsorption = Bartter syndrome
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81
Q

Discuss the function of the distal convoluted tubule

A
  • Early DCT insoluble to water, passive reabsorption of Na down gradient (5% of Na, load-dependant)
  • NaCl- cotransporter - moves 1 Cl (active) for every Na, Cl then passive diffusion out of cell into interstitium
  • NaCa+ channels on interstitial border transporting 1 Ca+ (active) for every 1 Na (passive into cell)
  • PTH causes inc NaCa+ channels, increasing reabsorption of Ca+
  • Na doesn’t build up in cell as is pumped out into interstitium by NaKATPase, meaning Na can flow down gradient into cell through NaCl- and NaCa+ cotransporters
  • Late DCT/collecting duct has: principal cells (has eNac - epithelial Na channel to absorb Na and K channel to excrete K, and NaK-ATPase on basolateral surface) and a-intercalated cells (has H+ATPase and H/K-ATPase which secrete H+ into tubule)
  • > net movement Na and Cl- into blood, and H+ into tubule
  • Aldosterone increases eNaC, ATP-dependant K+ pump, NaK-ATPase transporters, and H/K-ATPase -> net Na reabsorption and K secretion
  • ADH causes aquaporin insertion into both membranes to increase H2O reabsorption
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82
Q

Simple action of distal convoluted tubule

A
  • Early DCT: reabsorption of Na, Ca, Cl
  • Late DCT/collecting duct: principal cells absorb Na and excrete K, a-intercalated cells secrete H+
  • ADH: increases H2O reabsorption via aquaporins in principal cells
  • Aldosterone: increases Na reabsorption and K+ excretion
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83
Q

Simple action of loop of henle

A
  • Descending limb: absorption of water via aquaporins
  • Thin ascending limb: absorption of Na and Cl- via channel proteins
  • Thick ascending limb: Na, K, Cl absorption via cotransporter and channel proteins
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84
Q

Simple action of the proximal convoluted tubule

A
  • Main site of reabsorption of Na (65%) (passive + NaK-ATPase), HCO3 (85%) (via NaH+ exchanger and action of carbonic anhydrase), K, Ca, Cl, Mg, glucose, lactate, amino acids, phosphate, citrate
  • Excretion e.g. ammonia, organic acids, medications
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85
Q

What is the role of aldosterone?

A

Increases number of Na, K, and Na/K/ATPase channels in the DCT and collecting ducts, leading to absorption of sodium and water, and excretion of potassium

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86
Q

What happens to potassium levels in metabolic acidosis and metabolic alkalosis?

A
  • Metabolic acidosis leads to hyperkalaemia due to hydrogen shift into cells, in exchange for potassium which shifts into the plasma
  • Metabolic alkalosis leads to hypokalaemia, due to hydrogen shift out of cells, in exchange for potassium shifting out of the plasma into cells
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87
Q

What factors cause potassium shift into cells (hypokalaemia) and out of cells (hyperkalaemia)?

A
  • Into cells: insulin, adrenaline, metabolic alkalosis

- Out of cells: exercise, burns, rhabdomyolysis, cell lysis, hyperosmolarity, metabolic acidosis

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88
Q

Describe the mechanism of action and side effects of loop diuretics

A
  • e.g. frusemide
  • Used to treat hypertension + oedema, correct hypercalcaemia or hyperkalaemia
  • Acts on the thick ascending loop of henle by blocking the Cl- receptor on the Na/K/2Cl- cotransporter
  • This inhibits the channel, leading to a net loss of Na, K, Cl-, Ca and Mg and water
  • Causes a diuresis, or increased urine volume
  • Side effects: dehydration, hypokalaemia, hyperuricaemia (gout), metabolic alkalosis (inc Na in collecting duct causes H and K loss), hypomagnesaemia, hypocalcaemia, ototoxicity and hearing loss
89
Q

Describe the mechanism of action and side effects of carbonic anhydrase inhibitors

A
  • Weak diuretic e.g. acetazolamide
  • Used to treat oedema when there is a metabolic alkalosis, and also causes urinary alkalinisation (stops uric acid and cysteine precipitation in urine), glaucoma, decr CSF production, altitude sickness
  • Act in the proximal convoluted tubule
  • Act as carbonic anhydrase inhibitors, which stops H2CO3 (H + HCO3) being cleaved into H2O and CO2 which would normally then diffuse across the cell and be reabsorbed
  • This leads to increased bicarb and sodium excretion, and therefore water excretion
  • Side effects: metabolic acidosis (HCO3 lost in urine), hyperchloraemia, renal stones (due to Phos and Ca excretion), potassium wasting, drowsiness/parasthesia
90
Q

Describe the mechanism of action and side effects of osmotic diuretics

A
  • E.g. mannitol
  • Used to lower intraocular or intracranial pressure, treatment of rhabdo and haemolysis (flush away harmful substances in kidney)
  • Osmotic, therefore sucks water out of cells, resulting in increased renal blood flow
  • Increased flow rate through nephron means less time for Na to be reabsorbed
  • Leads to small Na loss and large water loss
  • Side effects: dehydration with hypernatraemia and hyperkalaemia
91
Q

Describe the mechanism of action and side effects of thiazide diuretics

A
  • E.g. Chlorothiazide, hydrochlorothiazide
  • Used for hypertension and oedema, prevent calcium stones, prevent osteoporosis, nephrogenic DI (hypovolaemia leads to inc Na and H2O resorption in PCT)
  • Longer lasting but less potent than loop diuretics
  • Secreted by PCT, competing with secretion of uric acid
  • Act in DCT by blocking Na-Cl- cotransporter, inhibiting resorption of Na and Cl-, but increased resorption of Ca
  • Side effects: hyperuricaemia, hypercalcaemia, hyperglycaemia, inc cholesterol and LDL, hyponatraemia, hypokalemic metabolic alkalosis (inc Na in collecting duct causes H and K loss)
92
Q

Describe the mechanism of action and side effects of potassium-sparing diuretics

A
  • e.g. spironolactone and amiloride. Weak. Often used in combo with thiazide/loop to avoid hypokalaemia
  • Spironolactone acts in the DCT/collecting duct by binding to and inhibiting aldosterone receptors
  • Amiloride inhibits effects of aldosterone by blocking eNac channels
  • Used for hypertension and oedema, hyperaldosteronism, inhibit testosterone effects (e.g. in PCOS, by binding to androgen receptor)
  • This leads to an increase in Na and H2O excretion, and a decrease in K+ and H+ excretion
  • Side effects: hyperkalaemia, metabolic acidosis, rarely anti-androgenic side effects e.g gynaecomastia, impotence
93
Q

What are the genes associated with Wilms tumour?

A

WT1 - WAGR, Denys Drash
WT2 - Beckwith Wiedemann
However, most cases not associated with either gene, or any other developmental abnormalities

94
Q

What are the two main mechanisms of hyponatraemia?

A
  • Gain of water > sodium

- Loss of sodium > water

95
Q

What are the main causes of excess water gain in hyponatraemia, and how is it treated?

A
  • Excess water intake - iatrogenic or psychogenic polydipsia. Leads to large amounts hypotonic urine
  • Acute renal failure - oedema, oliguria, hypovolaemia, urine Na > 20mmol/L
  • SIADH - inappropriately raised urine osmolality (should be dilute). Inc in: resp infxn, meningitis, IPPV, drugs
  • Tx: water restriction. If Na<120 or symptomatic then slowly correct Na to 125-130 over 4 hours
96
Q

What are the main causes of excess sodium loss in hyponotraemia, and how is it treated?

A
  • Renal losses: loop diuretics, salt wasting CAH, ATN recovery, adrenal insufficiency. Dehydration, inappropriately high UO, urine Na > 20, urine isotonic with plasma
  • Extrarenal losses: gastroenteritis, sweating, CF. Dehydration, appropriate oliguria and low urine Na <10.
  • Tx: rehydration + slowly correct deficit (risk cerebellopontine myelinolysis)
97
Q

What are the two main mechanisms of hypernatraemia?

A
  • Loss of water > sodium

- Gain of sodium > water

98
Q

What are the main causes of excess sodium gain in hypernatraemia, and how is it treated?

A
  • Iatrogenic, incorrect formula mixing, salt poisoning e.g. Munchausen. Increased volume of urine with high Na content
  • Tx: remove cause, access to H2O while kidneys excrete excess salt load
99
Q

What are the main causes of excess water loss in hypernatraemia, and how is it treated?

A
  • Renal losses: preterms, diabetes insipidus, osmotic diuresis e.g. DKA. Inappropriately high UO with low osmolarity.
  • Extrarenal losses: Gastroenteritis, pyrexia, hyperventilation. Appropriately low UO and high urine osmolarity
  • Tx: oral rehydration solution safest. IV slow over 48-72hrs correction 0.5mmol/hr
100
Q

What are causes of hypokalaemia and how is it treated?

A
  • Iatrogenic (incorrect IVF, insulin, salbutamol, amphotericin B)
  • GI losses (vomiting)
  • Renal losses with high plasma renin: diuretics, Fanconi, Bartter, Gittleman, distal T1 RTA
  • Renal losses with low plasma renin: Conn’s, Liddle’s, Cushings
  • Treatment of metabolic acidosis leading to shift of K from plasma to cells
  • Tx: oral or IV replacement
101
Q

What are causes of hyperkalaemia and how is it treated?

A
  • Metabolic acidosis
  • Haemolysis, sepsis, burns, tumour lysis, rhabdomyolysis
  • CAH, adrenal insufficiency, pseudohypoaldosteronism
  • Iatrogenic: spironolactone
  • Acute and chronic renal failure
  • Tx: calcium gluconate, insulin/glucose, salbutamol, calcium resonium, ECG monitoring, dialysis
102
Q

What ECG changes are seen in hyperkalaemia?

A
  • Peaked T waves, ST depression, wide QRS, prolonged PR, VT/VF
103
Q

What are the symptoms and treatment of hypocalcaemia?

A
  • Rickets, seizures, tetany, stridor, cramps, paresthesia

- Treatment: IV 10% calcium gluconate with ECG monitoring, PO calcium supps, Vit D/alfacalcidol

104
Q

What are the causes of hypocalcaemia?

A
  • Low calcitriol: Vitamin D def, renal failure or liver failure
  • Iatrogenic: frusemide
  • Hypoparathyroidism - transient neonatal, DiGeorge, PT removal
  • Acute pancreatitis
  • Acute alkalosis or correction of acidosis in context of normal-low calcium
  • Hyperphosphatemia (complexes free calcium): RF, rhabdo, tumour lysis
  • Pseudohypoparathyroidism e.g. Albright’s hereditary osteodystrophy
105
Q

What are the symptoms and treatment of hypercalcaemia?

A
  • Constipation, renal stones, nausea, lethargy, confusion, headaches, muscle weakness, polyuria, dehydration
  • IV hydration, loop diuretics, rarely bisphosphonates (stop bone resorption)
106
Q

What are the causes of hypercalcaemia?

A
  • Familial hypocalciuric hypercalcaemia, Williams (rarely persists >1y age)
  • Hyperparathyroidism - neonate or MEN1+2
  • Iatrogenic: Vit D excess
  • Macrophage production of calcitriol (sarcoidosis, subcut fat necrosis)
  • Malignancy
107
Q

Discuss familial hypocalciuric hypercaleamia

A
  • Cause of hypercalcaemia
  • Inactivation of calcium-sensing receptor gene, leads to inappropriate increased PTH, raised calcium, and low calcium in urine
  • …..
108
Q

Describe calcium composition in body

A
  • 40% bound to albumin
  • 48% ionized “free” -> biologically active form, more accurate measure in states with abnormal pH. Is the form that binds to calcium-receptors and is regulated by PTH and Vit D
  • 12% bound to anions
109
Q

Discuss the influence of pH on calcium

A
  • As pH decreases (acidosis), H+ displaces Ca2+ from binding sites and the amount of iCa2+ increases
  • Conversely, as the blood pH increases (alkalosis), albumin and the globulins become more negatively charged and bind more calcium, causing the amount of iCa2+ circulating to decrease. Therefore always correct acidosis prior to giving albumin, otherwise will cause hypocalcaemia as albumin will bind to the increased free calcium
110
Q

Discuss pseudohypoparathyroidism

A
  • AD, due to dysfunctional G protein
  • Albright’s hereditary osteodystrophy = type1a
  • End-organ resistance to PTH
  • Short stature, obese, mild ID, round face, hypogonadism
  • Knuckle, knuckle, dimple, dimple sign due to bone resorption (4th + 5th metacarpals)
  • High PTH, low Ca, high phosphate
  • Tx: Ca + Vit D supps, phosphate binders
111
Q

Discuss the causes and treatment of hypophosphatemia

A
  • Hyperparathyroidism (increased urinary excretion of phosphate)
  • Dietary deficiency. Appropriately high TRP (low urine phosphate)
  • Hypophosphatemic rickets, Fanconi syndrome. Inappropriately low TRP (high urine phosphate)
  • Tx: PO phosphate, Vit D replacement
112
Q

Discuss the causes and treatment of hyperphosphatemia

A
  • High urine phosphate, low TRP (appropriate) - rhabdomyolysis, tumour lysis
  • Low urine phosphate, high TRP (inappropriate) - CRF, hypoparathyroidism, pseudohypoparathyroidism
  • Tx: phosphate binders (ec calcium carbonate), dialysis
113
Q

Discuss the causes of hypomagnesaemia

A
  • Most often found in hypocalcaemia/hypokalaemia, so need to correct Mg2+ first to correct others
  • Dietary deficiency
  • Reduced gut absorption
  • Increased urinary losses (recovering from ATN, post-transplant diuresis, frusemide, amphotericin B, cisplatin, Gitelman syndrome)
114
Q

What are the proximal tubulopathies?

A
  • Fanconi syndrome
  • Proximal type 2 RTA
  • Cystinuria
  • Cystinosis
  • X-linked hypophosphatemic rickets
115
Q

Discuss nephrogenic diabetes insipidus

A
  • Resistance to action of high circulating levels of ADH
  • Usually presents in infancy
  • Polyuria, weight loss, FTT
  • Associated with ADH-receptor gene mutations AVPR2 (90%, X-linked nephrogenic DI) and aquaporin gene mutations ( 10%, AR nephrogenic DI)
  • Leads to hypernatremic dehydration with raised serum osmolality, with large volume diuresis of inappropriately dilute urine
  • Secondary causes: obstructive uropathy, Bartter, Fanconi
  • Tx: low solute diet to reduce osmotic load, high, water intake, thiazides (inc proximal tubule salt and water uptake) , NSAIDs (reduce GFR)
116
Q

Discuss cystinuria

A
  • AR
  • Defect in resorption of 4 dibasic AA: cystine, ornithine, arginine, lysine in proximal tubule, leading to increased urinary excretion
  • Recurrent urinary stones - pain/haematuria/pyelo/vomiting
  • Stones are hard and densely opaque, acidic urine
  • Dx: stone analysis, increased cystine urine levels
  • Tx: inc fluid intake >1.5L/m2/day, alkalinisation of urine to increase solubility of cystine (e.g. with potassium citrate, acetazolamide), reduce protein and Na intake, penicillamine (chelation)
117
Q

Discuss X-linked hypophosphatemic rickets

A
  • Vitamin D resistant rickets
  • Mutation in PHEX gene on X-chromosome
  • Defect in phosphate resorption, low TRP (<85%), normal PTH and calcitriol level, hypophosphatemia
  • Age 3-4m - inc ALP
  • Age 6-9m - decr phosphate
  • Age 12m - delayed growth, low phos, inc ALP, x-ray signs of rickets, delayed dentition, recurrent dental abscesses
  • Tx: phos + calcitriol supps, watch for hypercalcaemia and nephrocalcinosis, may need growth hormone
118
Q

Discuss the pathophysiology of Fanconi syndrome

A
  • Diffuse proximal tubular dysfunction leading to excess urinary loss of:
    • Glucose - glycosuria, normal BSL
    • Phosphate - low phos, low TRP, rickets
    • Amino acids - no obvious consequence
    • Bicarb - proximal RTA
    • K+ - hypokalaemia
    • Na, Cl, H2O - polyuria, polydipsia, chronic decr ECF volume, faltering growth
    • Tubular proteins - LMW e.g. retinol-binding + N-acetylglucosamine
119
Q

Discuss the features and causes of Fanconi syndrome

A
  • Diffuse proximal tubular dysfunction
  • Polyuria, polydipsia, faltering growth, constipation, rickets
  • Causes:
    • Metabolic - cystinosis, tyrosinemia, Lowe syndrome (oculocerebrorenal syndrome)
    • Galactosemia
    • Wilson disease
    • heavy metal toxicity (lead, mercury, cadmium)
    • idiopathic, ifosfamide, cisplatin, azathioprine
    • ATN, tubulointerstitial nephritis
  • Tx: replacement of fluid, bicarb
120
Q

Discuss Lowe syndrome (oculocerebrorenal syndrome of Lowe)

A
  • X-linked
  • Congenital cataracts, mental retardation, and Fanconi syndrome
  • Mutations in the OCRL1 gene, abnormal transport of vesicles within the Golgi apparatus
  • Present in infancy with cataracts, progressive growth failure, hypotonia, and Fanconi syndrome
  • Significant proteinuria is common
  • Blindness and renal insufficiency often develop
  • Characteristic behavioral abnormalities: tantrums, stubbornness, stereotypy (repetitive behaviors), and obsessions
  • There is no specific therapy for the renal disease or neurologic deficits
121
Q

Discuss proximal type 2 renal tubular acidosis

A
  • Failure of proximal tubular cells to reabsorb bicarb
  • Can be primary isolated RTA, transient infantile, Fanconi syndrome
  • Non anion gap metabolic acidosis, normal-low K+, urine pH<5.5
  • Faltering growth, vomiting, short stature, polyuria, constipation
  • Urine acidic <5.5 as distal acidification still intact
  • No nephrocalcinosis (Ca salts soluble in acidic urine)
  • Ammonium chloride load - normal urine acidification
  • Oral bicarb load - normal inc urine PCO2
  • Tx: sodium bicarb replacement (5-15mmol) - large doses bicarb needed to overcome low renal bicarb threshold
122
Q

Discuss proximal type 2 renal tubular acidosis

A
  • Failure of proximal tubular cells to reabsorb bicarb
  • Can be primary isolated RTA, transient infantile, Fanconi syndrome
  • Non anion gap metabolic acidosis, normal-low K+, urine pH<5.5
  • Faltering growth, vomiting, short stature, polyuria, constipation
  • Urine acidic <5.5 as distal acidification still intact
  • Ammonium chloride load - normal urine acidification, normal ammonia excretion
  • Oral bicarb load - normal inc urine PCO2
  • Tx: sodium bicarb replacement (5-15mmol) - large doses bicarb needed to overcome low renal bicarb threshold, K+ replacement, thiazide (inc water loss, inc reabsorb HCO3)
123
Q

Discuss distal type 1 renal tubular acidosis

A
  • Sporadic or inherited, or acquired (tubule damage e.g. amph B)
  • Impaired hydrogen ion excretion (a-intercalated cells in DCT), urine pH >6 (unable to be acidified)
  • Loss of sodium bicarb distally leads to hyperchloraemia
  • Hypokalaemia (no H+ exchange with K+ so inc secretion)
  • Hypercalciuria leads to nephrocalcinosis or nephrolithiasis
  • Low ammonia excretion
  • Chronic metabolic acidosis impairs urinary citrate excretion + hypocitraturia increases risk of calcium deposition in the tubules
  • Bone disease due to mobilisation of organic components from bone to serve as buffers to chronic acidosis
  • Growth failure, metabolic acidosis, renal stones, decr appetite, vomiting, abdo pain
  • Tx: PO bicarb + K replacement, thiazides if develop hypercalciuria (thiazides cause inc Ca resorption)
124
Q

Discuss type 4 renal tubular acidosis

A
  • Due to hypoaldosteronism (Addisons), pseudohypoaldosteronism (eNaC mutation), or transient (pyelo, urinary obstruction), severe hypovolaemia (low Na reabsorption), SLE
  • Non anion gap metabolic acidosis (cannot excrete H+), hyperkalaemia (no Na+ swap for H+), acidic or alkaline urine
  • Affects both distal and a-intercalated cells
  • Elevated urine sodium, low urine potassium
  • Polyuria, dehydration, growth failure (salt wasting)
  • Tx: bicarb replacement, sodium-potassium exchange, resin for chronic hyperkalaemia, fludrocortisone to replace aldosterone
125
Q

Discuss renal tubular acidosis type 3

A
  • Defects in distal and proximal tubule
  • Uncommon
  • ? due to congenital carbonic anhydrase deficiency
126
Q

Discuss Bartter syndrome

A
  • AR, defect in Na/K/Cl cotransporter in thick ascending loop of henle - hypokalemic metabolic alkalosis with hypercalciuria (same as chronic frusemide)
  • Antenatal 1,2,4 - maternal polyhydramnios, neonatal salt wasting, and severe episodes of recurrent dehydration, can have low BP, nephrocalcinosis. Type 4 = deafness
  • Classic = type 3 - childhood, FTT, history of recurrent episodes of dehydration
  • Polyuria, polydipsia, episodic dehydration, FTT, constipation, maternal polyhydramnios
  • Low ECF volume activated RAAS - inc Na and H2O reabsorb in distal tubule, with K and H excretion
  • Usually normal BP
  • High serum renin, aldosterone + prostaglandin E levels
  • Inappropriately high urine Cl and Na >20, high Ca
  • Tx: K supplement, spironolactone, high Na diet, prostaglandin inhibitors (indomethacin - decr renal blood flow)
127
Q

What is pseudobartter syndrome?

A
  • Hypochloremic hypokalemic alkalosis
  • Appropriately low urine Cl (helps distinguish it from normal Barters) and Na <40
  • Causes: cystic fibrosis (sweat loss), congenital chloride diarrhoea (GI loss), laxative abuse, cyclical vomiting, diuretic abuse (this will have high Cl- though)
128
Q

Discuss Gitelman syndrome

A
  • AR, defect in Na/Cl- cotransporter in the distal convoluted tubule
  • Leads to hypokalaemic metabolic alkalosis, raised renin and aldosterone, hypomagnesaemia, hypocalciuria (c.f. Bartters has hypercalciuria)
  • Often asymptomatic, transient episodes muscle cramps and spasms (low Mg), polyuria
  • Same effect as chronic thiazide diuretics
  • Usually older children, no perinatal polyhydramnios
  • Tx: KCl and Mg supplements, high Na diet, occ spironolactone
129
Q

Difference between Barter and Gitelmans

A
  • Barter - NaKCl- channel in LoH, like frusemide, hypercalciuria, presents earlier with polyhydramnios or recurrent dehydration, high renin/aldosterone/prost E2, younger
  • Gitelman - NaCl- channel in DCT, like thiazide, hypocalciuria + hypomagnesemia, no episodes recurrent dehydration , normal renin/aldosterone/prost E, usually older
  • Both have hypokalaemic metabolic alkalosis
130
Q

What is the criteria for remission in nephrotic syndrome?

A

-ve urinalysis x 3 early morning urines

131
Q

What is the criteria for relapse in nephrotic syndrome?

A

3+ proteinuria x 3 early morning urines

132
Q

What is the criteria for frequently relapsing in nephrotic syndrome?

A

2 x within 6/12, >4 in 1 year

133
Q

What is the definition of steroid-dependent nephrotic syndrome?

A

2 consecutive relapses during steroid treatment, or within 14 days of cessation

134
Q

What is the definition of steroid-resistant nephrotic syndrome?

A

No remission after 4 weeks of 60mg/m2/day steroid + 3 pulses IV methylpred (10mg/kg/dose alt days)

135
Q

What are the usual features of steroid sensitive nephrotic syndrome patients?

A
  • Toddler/preschool
  • No sustained hypertension
  • Mild/intermittent microscopic haematuria
  • Normal renal function
  • Excellent prognosis
  • Usually not biopsied
  • Usually have minimal change disease
136
Q

What are the usual features of steroid resistant nephrotic syndrome patients?

A
  • <1 year old or >8 year old
  • Hypertension
  • Persistent microscopic haematuria
  • Reduced renal function
  • Poor long term prognosis
  • Histology usually FSGS
  • Recurrent disease in transplant
137
Q

What are the complications of nephrotic syndrome?

A
  • Infection - encapsulated bacteria, loss of immunoglobulins, immunosuppressive medications
  • Thrombosis - raised haematocrit, loss of antithrombin III, protein C and S in urine
  • Hypovolaemia - fluid shifts, sepsis, diuretics, causes oliguria, hypotension, tachycardia, anorexia, abdo pain
  • Acute and chronic renal failure - hypovolaemia, medications, renal vein thrombosis
  • Drug toxicity - steroids, ciclosporin, tacrolimus
138
Q

Which infections are patients with nephrotic syndrome sensitive to, and why?

A
  • Encapsulated bacteria: strep pneumoniae (pneumonia, primary pneumococcal peritonitis), haemophilus
  • Gram -ves and VZV if on steroids
  • Due to tissue oedema, inc peritoneal fluid, loss of immunoglobulins in urine, steroid immunosuppression
139
Q

Why are patients with nephrotic syndrome at increased risk of thrombosis?

A
  • DVT, PE, renal vein thrombosis
  • Increased risk with relapse and hypovolaemic episodes
  • Loss of antithrombin III, protein C and S in urine, inc pro-coagulation factors in liver, high Hct due to low oncotic pressure, oedema and immobility, steroids
140
Q

What is the mainstay of treatment in nephrotic syndrome?

A
  • Normal protein diet, Na restrict in relapse
  • ABs: penicillin prophylaxis initially + relapses
  • Diuretics: fluid + Na restriction, frusemide
  • Antihypertensives: ACE - or ARB to decr proteinuria
  • IV albumin: hypovolaemia or severe oedema
  • Vaccinations: pneumococcal, flu, VZIg if exposure (within 96hrs, but up to 10 days)
  • Steroids 3/12 (28d 2mg/kg/day, 28d 1.5mg/kg/day then 28d taper) - some studies show 8 week course sufficient + for relapses until in remission. If steroid dependant or frequent relapsing then trial steroid alt day for 4-6/12
  • Cyclophosphamide, tacrolimus, ciclosporin, mycophenolate
  • Steroid resistant: cyclosporin +/- alt day pred -> tacrolimus
141
Q

What are the side effects of cyclophosphamide?

A 
Alopecia
Bone marrow suppression, neutropenia
Hemorrhagic cystitis
Risk future malignancy (AML)
Infertility
142
Q

What are the side effects of tacrolimus (calcineurin inhibitor)?

A 
Nephrotoxicity
Tremors + paresthesia
Alopecia
Diabetogenic, hypercholesterolaemia (unlikely)
Hypomagnesemia
Hypertension
Neurotoxicity - seizures
Gingival hyperplasia
Hyperkalaemia
143
Q

What are the side effects of cyclosporine (calcineurin inhibitor)?

A 
Hirsutism + hypertrichosis 
Nephrotoxicity
Gingival hyperplasia
Hypertension
Hypercholesterolaemia
144
Q

What are the side effects of mycophenolate (antimetabolite)?

A

Not nephrotoxic, lower incidence acute rejection
Diarrhoea, nausea, vomiting, abdo pain
Bone marrow suppression
Hepatotoxicity
Leucopenia
Significant interactions with tacrolimus + cyclosporine

145
Q

What are the causes of nephrotic syndrome?

A
  • Primary/idiopathic (INS)
  • Minimal change disease (MCD)
  • Focal segmental glomerulosclerosis (FSGS)
  • Membranoproliferative glomerulonephritis (MPGN)
  • Membranous glomerulonephropathy
  • Secondary to infections, medications or systemic disease (eg lupus or malignancy)
146
Q

What are the indications for biopsy in nephrotic syndrome?

A
  • Steroid resistance
  • Impaired renal function with normal volume status
  • Initial macroscopic haematuria
  • Persistent microscopic haematuria if associated with hypertension
  • Onset less than 6 months of age or >12 years
  • Low C3
147
Q

Discuss congenital nephrotic syndrome

A
  • Onset first 3/12 life, often large placenta (>40% of BW)
  • High resistance to treatment, high morbidity due to sepsis + protein malnutrition
  • Causes of congenital NS:
    • Finnish-type, AR, most severe, NPHS1 gene on Chr 19. Also mutations NPHS2
    • Diffuse mesangial sclerosis - AR, less severe
    • FSGS, congenital syphilis, Denys-Drash (mesangial sclerosis)
  • Tx: as per other NS + early unilateral nephrectomy to reduce protein loss, ACE -, indomethacin, dialysis, transplant
148
Q

Discuss the findings in nephrotic syndrome

A

Oedema, hypoalbuminaemia, proteinuria, hyperlipidaemia, high lipid in urine (maltese cross appearance)

149
Q

Discuss the findings in nephritic syndrome

A

Haematuria, hypertension, proteinuria, oliguria, ARF

150
Q

Discuss crescentic glomerulonephritis

A
  • Rapidly progressing, severe renal failure, hypertension
  • Crescent on biopsy is defining feature
  • Often requires dialysis, immunosuppression
  • Can be secondary to: HSP, ANCA disease, Goodpasture’s, PSGN
151
Q

What are causes of GN with normal complement?

A

FSGS, IgA nephropathy, HSP nephritis

152
Q

What are causes of GN with low complement?

A 
Acute PSGN (low C3, recovers by 6 weeks)
Mesangiocapillary GN (low C3 and C4)
Lupus nephritis (low C3 and C4)
Shunt nephritis (low C3 and C4)
153
Q

What is shunt nephritis?

A
  • Occurs in those with a cerebral shunt for hydrocephalus
  • Infected shunt with long-standing bacteraemia, usually Staph epi
  • Leads to immune complexes in the kidney
  • Proteinuria, haematuria, anaemia, hypertension, low C3
  • Tx: antibiotics, shunt removal, 50% recover but rest have persistent renal disease
154
Q

What factors can predispose to urinary stones?

A

Low urinary magnesium or citrate, high urinary sodium (inc urinary excretion causes inc calcium excretion), high urinary oxalic acid or uric acid, high urine cystine (cystinosis), distal renal tubular acidosis, Wilson’s disease

155
Q

DIscuss minimal change disease

A
  • Most common cause of nephrotic syndrome in children
  • Often idiopathic. Can be triggered by recent infection, vaccination, immune stimulus (e.g. bee sting)
  • T cells in blood release GPF cytokines (glomerular permeability factor) which damage foot processes of podocytes (effacement)
  • Selective proteinuria (only albumin escapes, not immunoglobulin as isn’t negatively charged)
  • Light microscopy: normal
  • Immunofluorescence: negative
  • Electron microscopy: effacement of podocyte foot processes
  • Only NS that can be consistently treated with steroids
156
Q

Discuss focal segemental glomerulosclerosis

A
  • More common in adults, can be idiopathic
  • History heroin abuse, HIV, congenital malformations, interferon treatment
  • Effacement of podocyte foot processes
  • Hyalinosis - deposition of lipids and proteins in glomerulus, then sclerosis or scar tissue
  • Light microscopy: sclerosis and hyalinosis (focal and segmental)
  • Immunofluorescence: usually negative, can occ. have C3, C1, IgM
  • Inconsistent response to steroids, may progress to CRF
157
Q

Discuss membranous nephropathy

A
  • Rare in children
  • Can be primary or secondary (SLE, meds (penicillamine, NSAIDs), infection (Hep B, C, syphilis), malignancy - NB)
  • Damage caused by immune complexes - subepithelial deposits between podocytes. These activate the complement system and damage podocytes and mesangial cells
  • Pts may have IgG antibodies to PLA2 receptor
  • Light microscopy: diffuse capillary + GBM thickening due to immune complex deposition. Irregular GMB seen on silver methenamine stain
  • Immunofluorescence: IgG and C3 granular immune complexes
  • Electron microscopy - flattening of podocyte foot processes, subepithelial deposits of immune complexes
  • Poor steroid response, may progress to CRF
158
Q

Discuss acute PSGN

A
  • 1-2w post GAS throat or 3-4w post GAS skin infection
  • Due to M protein virulence factor -> type 3 hypersensitivity reaction, IgG and IgM complexes with bacterial antigen -> GBM deposition -> inflammation with C3, cytokines, damages podocytes
  • Coca cola haematuria, hypertension, anaemia, red cell casts
  • Age 2-12y, recurrence rare, good prognosis
  • Low C3, should improve by 6w, often anaemia, raised ASOT/anti DNAse B, may have AKI
  • Light microscopy: enlarged and hypercellular glomeruli
  • Immunofluorescence: IgG, IgM, C3 deposits along GBM and mesangium - starry sky appearance
  • Electron microscopy: subepithelial humps/deposits
  • Tx: penicillin, fluid restriction, antihypertensives
159
Q

Discuss HSP

A
  • Palpable purpura, abdo pain, arthritis, bloody stools, oedema, renal involvement 70% (can start up to 2m later)
  • Microscopic haematuria +/- proteinuria (can use ACE-)
  • Up to 30% relapse first few months
  • If nephrotic or nephritic with sustained HTN then biopsy
  • Steroids can help abdo and joint pain, no evidence prevent renal involvement
  • Small vessel vasculitis, systemic illness
  • Histology = IgA nephritis
  • Tx: steroids +/- azathioprine, mycophenolate, if RPGN then immunosuppression
  • Accounts for 5-8% children with ESRF
  • Biopsy: mesangial deposits and expansion (same as IgA nephropathy)
160
Q

Discuss SLE nephritis

A
  • Varies from haematuria/proteinuria to nephritic/nephrotic syndrome -> diffuse proliferative GN or membranous nephropathy
  • Immune complex deposition in subendothelial space - type 3 hypersensitivity reaction
  • Light microscopy: thickening of glomerular wall “wire loop”
  • Immunofluorescence: granular immune complexes (Ig, C3) - Electron microscopy: subendothelial immune complexes
  • Increased ANCA, anti-dsDNA, low C3 and C4
  • Can also have antiphospholipid/anticardiolipin syndrome with thrombosis to kidneys
  • 90% of SLE have renal involvement. Inc risk Indian, Maori, PI. 5 classes, 3-5 need treatment (steroids, mycophenolate)
161
Q

Discuss MPGN (membranoproliferative glomerulonephritis)

A
  • Proliferation of mesangial and endothelial cells in glomerulus
  • T1 most common, idiopathic, or due to HepB/C
    • Can be due to T3 hypersensitivity reaction (immune complex) and complement subendothelial deposition due to classical complement pathway
    • Or inappropriate activation alt complement pathway by IgG autoantibody (nephritic factor) = extra C3 convertase activity -> low serum C3 levels. No immune complex deposits
    • Light microscopy: tram-track appearance, thick basement membrane, splitting
    • Immunofluorescence: granular
  • T2: involves nephritic factor but not immune complexes, inc C3 convertase, low serum C3, deposition in basement membrane. Tram-track pattern
162
Q

Discuss RPGN (rapidly progressive glomerulonephritis)

A
  • Can be initiated by T2 or 3 hypersensitivity reaction, or can be no immune complexes
  • Severe inflammation breaks GBM, leading to rapid deterioration renal function, ++ cells and inflammation -> crescent moon shape on biopsy
  • Can be idiopathic or due to:
    • T1: Goodpasture’s (T2 hypersense), anti-GBM antibodies, linear immune complexes on immunofluorescence
    • T2: PSGN or diffuse proliferative GN (SLE nephritis) (T3 hypersense), granular immune complexes in subendothelial space on immunofluorescence
    • T3: pauci-immune vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis), negative immunofluorescence
  • Light microscopy: crescent-moon shape, made up of fibrin
163
Q

What are types of type 3 hypersensitivity reactions causing glomerulonephritis?

A
  • Acute PSGN - subepithelial deposits
  • IgA nephropathy - mesangial deposits
  • Diffuse proliferative GN e.g. SLE - subendothelial deposits
164
Q

Discuss the causes of pre-renal failure

A
  • Low urine volume, FeNa <1, inc urea
  • Reversible with fluids and inotropes
  • Uncorrected leads to ATN
  • Can be due to:
    • Hypovolaemia: bleeding, diarrhoea, burns, DKA, shock
    • Cardiac failure: CHD, bypass, myocarditis
165
Q

Discuss the causes of intrisnic renal failure

A
  • ATN due to: uncorrected pre-renal failure, toxins (gent, contrast, myoglobin), acute GN - muddy-brown urine casts, FeNa >2%
  • Vascular - small vessel occlusion (HUS), bilateral renal vein thrombosis, acute renal cortical necrosis (birth asphyxia)
  • Tubulointerstitial nephritis - NSAIDS, frusemide, penicillin, cephalosporins
166
Q

Discuss the causes of post-renal failure

A
  • Obstructive: posterior urethral valves, neuropathic bladder (transverse myelitis, tumour, spinal trauma), stones (PUJ/urethral/bladder, inc risk with TPN), urethral prolapse of bladder ureterocele
167
Q

Appearance of kidneys on RUSS in acute and chronic RF?

A
  • Acute: large, hyperechoic

- Chronic: small kidneys

168
Q

Treatment of acute kidney injury

A
  • Determine underlying cause
  • Fluids: insensible losses (300ml/m2/day) + UO
  • Correct dehydration
  • HTN: frusemide, nifedipine
  • Treatment of hyperkalaemia
  • May require dialysis
169
Q

Indications for dialysis in acute renal failure?

A
  • Severe overload (HTN, oedema, no response to diuretics)
  • Severe inc K and urea (usually >40)
  • Metabolic acidosis (not responding to bicarb)
  • Toxin removal (drugs, poisons, IEoM eg ammonia)
170
Q

Discuss haemolytic uraemic syndrome

A
  • Microangiopathic haemolytic anaemia, thrombocytopenia, and renal insufficiency
  • Usually due to: E.Coli 0157 (meat or milk) which produces shiga toxin, shigella, or (rare) neuraminidase-producing strep pneumoniae (is coombs +ve)
  • Classic presentation: bloody diarrhoea then 1/52 later pale, irritable, bruises, oedema, HTN, vomiting
  • Toxin release in gut causes endothelial damage. Can affect brain, myocardium - seizures, enceph, arrhythmia
  • Patchy focal thrombosis and infarction. Platelet-fibrin thrombi leading to renal cortical necrosis, can eventually develop glomerular sclerosis
  • Raised LDH, bilirubin, low haptoglobin, RBC fragments
  • 5 mortality, 5-10% ESRF, 30% require dialysis
  • Tx: supportive, IVF, RBC, no platelets, dialysis, antibiotics contraindicated (releases more toxin), plasmapharesis
171
Q

Discuss atypical haemolytic uraemic syndrome

A
  • More rare but more serious, often recurrent episodes, progressive chronic renal failure, neurological involvement
  • Can be complement-mediated: familial AR or AD, or alternative pathway over-activation
  • Recurrent episodes haemolysis and renal failure, high risk ESRD
  • Absence of preceding diarrhoeal prodrome
  • Can be triggered by BMT, cyclosporin, tacrolimus
  • Tx: plasma exchange, immunosuppression
172
Q

What GFR indicates mild, mod, severe, and ESRF?

A
  • Mild 60-80
  • Mod 40-59
  • Severe <40
  • ESRF <15 or on dialysis
173
Q

What are the main causes of chronic kidney disease in children?

A
  • Congenital dysplasia and obstruction
  • Reflux nephropathy
  • Congenital nephrotic syndrome
  • Prune Belly syndrome
  • Chronic GN (FSGS, MPGN)
  • HUS
  • Renal vein thrombosis
  • Alport’s, nephronophthisis, PCKD
  • HSP, SLE nephritis
174
Q

What are the main issues seen in chronic kidney disease?

A
  • Poor growth/FTT
  • Anorexia
  • Anaemia
  • Renal osteodystrophy
  • Metabolic acidosis - impaired bicarb resorp, decreased H+ excretion
  • Hyperphosphatemia leads to calcium-phosphate deposition
  • Hypertension due to volume overload or hyperreninism
  • Hyperfiltration injury leading to further glomerular destruction
175
Q

What are the causes of poor growth in CKD?

A
  • Anorexia and vomiting due to uraemia
  • Raised IGF binding protein - less free IGF-1, decreased GH effectiveness (normal level GH) - can give recombinant GH to improve growth
176
Q

What are the dietary considerations in CKD?

A
  • Aggressive nutrition, many need NGT/PEG
  • Generous H20 intake, Na+ supps (wasting in polyuria) or restriction (if oedema + water retention)
  • No protein restriction
  • Phosphate restriction, use of phosphate binders (calcium carbonate) to control secondary hyperparathyroidism
  • Restriction of potassium (fresh fruit, potatoes)
  • Sodium bicarb supps for acidosis
177
Q

What are the causes of anemia in CKD?

A
  • Dietary Fe deficiency
  • Decr RBC survival in uraemia
  • EPO deficiency
  • Treat with recombinant EPO + iron supps
178
Q

Discuss bone disease in CKD

A

= Renal osteodystrophy - weak and brittle bones

  • Muscle weakness, bone pain, fractures
  • Due to lack of Vitamin D activation in the liver leading to hypocalcaemia
  • This activates parathyroid hormone release, which increases Ca+ resorption from bones, leading to renal osteodystrophy
  • Hypocalcaemia also leads to Ricket’s changes in bone
  • Phosphate retention by the kidneys leads to low calcium and further parathyroid hormone release
  • Low Ca, inc phos, inc ALP, inc PTH
  • Tx: calcitriol, low phosphate in the diet, phosphate binders
179
Q

What is the maincause of renal osteodystrophy seen in CKD?

A

Secondary hyperparathyroidism

180
Q

What is the management of hypertension in CKD?

A
  • If overloaded - fluid restriction
  • Stage 1-3 CKD use thiazide
  • > stage 3 use frusemide as thiazide ineffective
  • If proteinuria then use ACE inhibitor or ARB
181
Q

What are the complications of renal transplant?

A
  • Transplant artery thrombosis
  • Rejection
  • Opportunistic infections
  • Drug toxicity (HTN, Cushing, hirsutism)
  • Post-transplant lymphoproliferative disease (lymphoma-like), often associated with primary EBV
182
Q

Predisposing factors for UTI

A
  • VUR
  • Incomplete bladder emptying - PUV, neuropathic bladder
  • Catheterisation
  • Stones
183
Q

What are the causes and complications of neurogenic bladder?

A
  • Spina bifida, sacral agenesis (maternal diabetes), tumour, trauma, transverse myelitis
  • Can lead to renal damage, incontinence, UTI (incomplete emptying), high pressure VUR, progressive renal scarring, detrusor-sphincter dyssynergia (leading to bladder hypertrophy and trabeculation, hydronephrosis), atonia (large, chronically distended, poor emptying)
  • Ix: video urodynamic assessment, kidney function/scarring
  • Tx: bladder relaxation with oxybutynin if unstable contractions, and clean intermittent catheterisation, augmentation cystoplasty (larger capacity, low pressure)
184
Q

Causes of nocturnal enuresis

A
  • Younger: decreased bladder capacity
  • Older: decreased ADH rise overnight, increased nocturnal urine volume
  • UTI, stress/social, diabetes insipidus or mellitus
  • Genetic, often 1st degree relative
185
Q

Discuss the cut-offs for hypertension

A

<13 years:
Normal BP: < 90th centile
Elevated BP: > 90th - 95th centile
Stage 1 HTN: > 95th centile, < 95th centile + 12mmHg or 130/89 - 139/89, whichever is lower
Stage 2 HTN: > 95th centile + 12mmHg, whichever is lower

>13 years:
Normal BP: < 120/80
Elevated BP: 120/80 - 129/80
Stage 1 HTN:  130/80 - 139/89
Stage 2 HTN:  > 140/90

Stage 1 - repeat BP over 3 visits, if still high then treat
Stage 2 - start treatment (or if on ward, then repeat)

186
Q

Causes of sustained hypertension in children?

A
  • Coarctation of aorta.
  • Renin-dependent hypertension:
    • Renovascular: renal artery stenosis
    • Renal parenchyma: scarring (reflux nephropathy, obstructive uropathy, neuropathic bladder), GN, PCKD, HUS
    • Renal tumour
    • Catecholamine-excess (pheochromocytoma, neuroblastoma)
  • Corticosteroid excess (CAH, Cushing’s, Conn’s syndrome)
  • Essential hypertension
  • Medications
  • Lung: BPD, OSA
187
Q

What is hypertensive urgency?

A
  • BP >99th centile x 3 over 30 min apart
  • No evidence of end organ injury, stable, may have headache or nausea
  • B-blocker (labetalol), vasodilator (isradipine), ACE-, frusemide (if fluid overload)
188
Q

What is a hypertensive emergency?

A
  • Severe elevation of BP associated with rapid and progressive CNS, visual, myocardial, haematological or renal deterioration
  • LVH and CHF, hypertensive encephalopathy, renal failure, retinopathy
  • Tx: ICU, IV labetalol, isradipine nitroprusside, or hydralazine, slow reduction in BP 1/3rd over 24 hrs, then rest over 48 hrs
  • At risk of stroke, cortical blindness
189
Q

What is the work-up for hypertension?

A
  • Frequent BP checks - may need ambulatory monitoring
  • Urinalysis, U+Es, creat, pH
  • Fundoscopy, neuro exam
  • ECHO, renal USS
  • DMSA
  • Urinary catecholamines, renin and aldosterone
  • May need CT angio or renal biopsy
  • Tx: underlying cause,
  • ABCD = ace inhibitors, beta blockers, CB, diuretics
  • Lifestyle - low sodium, exercise, sleep hygiene
190
Q

Discuss autosomal recessive PCKD

A
  • PKHD1 gene
  • Dilation of distal collecting ducts (not true cysts), bilateral
  • AN USS - oligohydramnios, large hyperechoic kidneys
  • Bilateral flank masses, pulm hypoplasia, Potter syndrome
  • Can develop interstitial fibrosis, tubular atrophy
  • HTN within weeks, and ESRF by age 10yrs (if severe then renal failure in infancy)
  • Associated with congenital hepatic fibrosis, bile duct proliferation and ectasia - can be subclinical or cause liver disease, ascending cholangitis, portal HTN
  • Absent renal cysts in parents
  • Tx: ACE-, resp support, dual renal-liver transplant
191
Q

Discuss autosomal dominant PCKD

A
  • 85% PKD1 gene (encodes polycystinin), 15% PKD2 gene
  • Both kidneys enlarged, cortical and medullary cysts originating from all regions of the nephron
  • Variable clinical severity, can occur in child or 4-5th decade life. Don’t screen children except annual BP and urine (proteinuria)
  • Abdo mass, HTN, UTI, renal failure as cysts grow, haematuria
  • Cysts in liver, pancreas, spleen, brain, saccular cerebral aneurysms (SAH), intestinal diverticula, MVP, coronary aneurysms
  • Tx: ACE -, screening for SAH, lifestyle modifications
192
Q

Discuss nephronophthisis

A
  • AR, NPHP1 most common - affects primary cilia and centrioles
  • Polyuria and polydipsia, growth delay, anaemia, uraemia
  • Renal fibrosis, tubular atrophy, medullary cyst formation. Tubulointerstitial nephritis, loss of urinary concentrating ability, salt wasting
  • Concentrating defecting, urinalysis often normal or trace glucose
  • 20% have retinitis pigmentosa (poor night and peripheral vision), liver fibrosis, situs inversus
  • ESRF by end of 1st decade
  • Infantile type leads to severe hypertension
  • Similar to medullary cystic kidney disease (adults)
193
Q

Discuss nephrocalcinosis

A
  • USS: diffuse speckled calcification
  • Calcification of renal tissue
  • Causes of nephrocalcinosis: distal RTA, ex-prems (frusemide, steroids), Vit D treatment for phosphatemic rickets, oxalosis
194
Q

Discuss nephrolithiasis (kidney stones)

A
  • Present with pain, vomiting, haematuria
  • Require metabolic analysis of stones or timed urinary collection to rule out metabolic causes
  • Types:
    • Calcium-phosphate: RTA, hypercalciuria, radioopaque
    • Calcium-oxalate 60%: oxalosis, CF, malabsorption, radioopaque
    • Magnesium-ammonium-phosphate/ struvite: proteus UTI, urinary stasis, radioopaque
    • Cystine: cystinosis, cystinuria, radioopaque
    • Uric acid: Lesch-Nyhan, tumour lysis, IBD
    • Xanthine: xanthinuria
  • Tx: alpha blocker, lithotripsy, stent, low sodium diet, high fluid intake, thiazide (reduce calcium excretion), allopurinol (reduce uric acid)
195
Q

Discuss oxalosis

A
  • AR, primary hyperoxaluria due to AGT enzyme defect
  • Increased urinary oxalate excretion
  • Leads to formation of stones, obstruction, renal failure
  • Can get systemic oxalosis in joints, heart, blood vessels
  • Tx: liver +/- renal transplant
196
Q

Bilateral renal dilation in a male newborn…?

A

Need to rule out posterior urethral valves

197
Q

Retrograde vs. antegrade urogram

A
  • Retrograde - via cystoscope

- Antegrade - via nephrostomy tube

198
Q

What is the 10-4 rule with albumin?

A

A 10g/L drop in albumin leads to a 4mmol/L drop in the anion gap

199
Q

What is the RIFLE criteria?

A
  • For acute kidney injury
  • Risk - decr GFR by 25%, <0.5ml/kg/hr for 8 hrs
  • Injury - decr GFR by 50%, <0.5ml/kg/hr for 12 hrs
  • Failure - decr GFR by 75%, anuric 12hrs
  • Loss - persistent failure > 4 weeks
  • End stage - persistent failure > 3 months
200
Q

Prerenal vs. ATN

A
  • Prerenal: urine osm >500, urine Na <20, urinalysis bland, urea:creat ratio >100, FeNa <1%
  • ATN: urine osm <350, urine Na >40, urinalysis casts, urea:creat ratio <40, FeNa >1%
201
Q

Discuss acute interstital nephritis

A
  • Immune-mediated infiltration of kidney interstitium by inflammatory cells
  • Causes: hypersensitivity to drugs (NSAIDs, penicillin, sulfonamide, cephalosporin), autoimmune with uveitis, infection (HIV, Hep B, CMV)
  • Tiredness, rash/fever, polyuria
  • Sterile pyuria +/- eosinophiluria, microhematuria
  • Tubular dysfunction: glycosuria, loss of electrolytes, tubular proteinuria
  • DDx nephronophthisis (but they will have poor growth)
  • Tubular damage is reversible
202
Q

What is the most common cause of AKI in neonate?

A
  • Prerenal, usually due to perinatal asphyxia
  • Serum creatinine >133 (or inc by 17-27 per day) - remember until 1st week of life creatinine reflect mother’s
  • Suspect AKI if no UO noted by 48 hours of age
203
Q

What are the daily insensible losses of neonates >2500g, 1500-2500g, <1500g?

A

> 2500g - 15-25ml/kg
1500-2500g - 15-35ml/kg
<1500g - 30-60ml/kg

204
Q

What are mutations in the HNF1B gene associated with?

A
  • MODY (5)
  • Bilateral cystic kidney
  • Uterine abnormalities
  • High uric acid
205
Q

What are the renal manifestations of tuberous sclerosis?

A
  • Renal angiomyolipomas 80% (if >4cm tx sirolimus)
  • Cystic disease 20%
  • Renal cell carcinoma <1%
206
Q

Why do patients with tuberous sclerosis develop cystic kidney disease?

A

TSC2 gene located adjacent to PKD1 gene - some patients found to have contiguous deletions of both genes

207
Q

What is the updated Schwartz equation and when may it be incorrect?

A

eGFR = 36.5 x height (cm) + serum creat (umol/L)
- Can overestimate GFR (underestimate severity of CKD) in tubular secretion of creat, nephrotic syndrome, low muscle mass

208
Q

Discuss the process of fluid removal in dialysis

A
  • Ultrafiltration
  • Via osmosis
  • Osmotic gradient created by glucose/dextrose in dialysate - draws water in
209
Q

Discuss the process of solute removal in dialysis

A
  • Clearance
  • Via diffusion down concentration gradient
  • Convection/solute drag via ultrafiltrate
210
Q

Treatment of bacterial peritonitis in dialysis patients?

A
  • Intraperitoneal cefazolin and ceftazidime
  • Covers gram +ve and gram -ve organisms
  • Usually 2-3 week treatment
  • Need antifungal prophylaxis (fungal peritonitis has 50% mortality)
  • Usually CONS, staph epi > staph aureus > gram -ves
211
Q

What is the most common cause of spontaneous bacterial peritonitis (e.g. nephrotic syndrome)?

A
  • Strep pneumoniae, followed by E.Coli
212
Q

Discuss acute rejection in renal transplant

A
  • 10-20% within first year
  • Decr rates due to better immunosuppressive agents
  • Can only be diagnosed histologically on biopsy
  • Hyperacute: within 48hrs, fever, malaise, must remove
  • Acute: up to 2yrs: oliguria, inc BP, flank tender, inc creat, fluid retention
  • Chronic: over 2 years, proteinuria, fatigue
213
Q

Medication for hypertension post kidney transplant?

A
  • 1st line vasodilators = CCB
  • Diuretics if hypervolaemic
  • ACE inhibitors long term, only once graft function stable >2-3/12 post-op
214
Q

Triple regime for immunosuppression post renal transplant

A

Tacrolimus (CNI), mycophenolate, corticosteroids

215
Q

Presentation of CMV infection in immunosuppressed patients

A
  • Mononucleosis syndrome

- Fever, colitis, cytopenias, deranged LFTs, pneumonitis, retinitis

216
Q

Discuss post-transplant lymphoproliferative disease

A
  • EBV-drive in many cases
  • B-cell proliferation (due to lack of T-cell surveillance)
  • Risk inc esp >10yrs of immunosuppression
  • Uncommon in children
  • Most common = skin cancers, then lymphoma (PTLD)
  • Related to intensity/duration of immunosuppression
217
Q

What is the time frame until resolution of PSGN?

A
  • Macroscopic haematuria 2 weeks
  • Hypertension 4 weeks
  • Low C3 6-8 weeks
  • Persistent proteinuria 6 months
  • Intermittent proteinuria 1 year
  • Microhematuria 2 years
218
Q

What is the significance of moderately increased albuminuria (without proteinuria)?

A
  • Strong correlation with risk of diabetic nephropathy
  • CVD
  • Obesity, metabolic syndrome
  • Markers of glomerular injury
  • Progressive renal injury
219
Q

What are causes of transient proteinuria?

A

Fever (resolves 10-14 days), exercise (resolves 48hrs), heart failure

Paeds (25 decks)

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