Nephrology Flashcards
1
Q
What are predictors of renal abnormalities in fetus ❓❓
A
🔅Volume of amniotic fluid – oligohydramnios or anhydramnios
🔅 Appearance of kidneys on antenatal ultrasonography – bright echogenicity, lack of corticomedullary differentiation, cyst formation and hydronephrosis are all signs of fetal renal abnormality
🔅high urinary sodium and amino acid levels (implying tubular damage and failure to reabsorb these) ⏩ through sampling of fetal urine by fine-needle aspiration from the fetal bladder.
2
Q
What is the major determinant of immediate postnatal period mortality in baby with congenital renal abnormalities❓❓
A
Severe oligohydramnios may lead to pulmonary hypoplasia
3
Q
What are the embryo logical development of renal system ❓❓
A
🔅week 5 of embryogenesis ⏩ the ureteric bud appears
🔅A small branch of the mesonephric duct evolves⏩ into a tubular structure which elongates into the primitive mesenchyme of the nephrogenic ridge
🔅 Ureteric bud forms the ureter, and from week 6 onwards repeated branching gives rise to the calyces, papillary ducts and collecting tubules by week 12
🔅The branching elements also induce the mesenchyme to develop into nephrons – proximal and distal tubules, and glomeruli
🔅Branching and new nephron induction continues until week 36
4
Q
What are the average nephrons per kidney ❓❓
A
▪️There are on average 600 000 nephrons per kidney.
▪️Premature birth and low weight for gestational age may both be associated with reduced nephron numbers
5
Q
When Is the nephrogenesis completed and what is GFR at that time ❓❓
A
🔅36 weeks’ gestational age
🔅glomerular filtration rate (GFR) is <5% of the adult value.
6
Q
What is The GFR of term infants at birth?
A
🔅approximately 25 ml/min per 1.73 m2,
🔅increasing by 50–100% during the first week, followed by a more gradual increase to adult values by the second year of life
7
Q
What is difference in FENa between term and preterm neonate ❓❓
A
🧡 Normal FENa in older children and adults is around 1% and <1% in sodium- and water-deprived states
🧡Premature neonates still have a relatively high FENa because of immature renal tubular function and require extra sodium supplementation to avoid hyponatraemia.
8
Q
What aravth urine concentrating ability and bicarbonate level❓❓
A
🧡 Urine-concentrating capacity is low in the premature newborn and leads to susceptibility to dehydration. Fully mature urine-concentrating capacity is reached later in the first year of life
🧡The plasma bicarbonate concentration at which filtered bicarbonate appears in the urine (bicarbonate threshold) is low in the newborn (19–21 mmol/l), increasing to mature values of 24– 26 mmol/l by 4 years. Hence plasma bicarbonate values are lower in infants
9
Q
What are the factors that determine the GFR ❓❓
A
• The transcapillary hydrostatic pressure gradient across the glomerular capillary bed (ΔP) favouring glomerular filtration
• The transcapillary oncotic pressure gradient (Δπ) countering glomerular filtration
• The permeability coefficient of the glomerular capillary wall, k
Hence GFR = k(ΔP – Δπ).
10
Q
How to estimate the GFR ❓❓
A
estimated using the Schwartz formula =
Hieght (cm) /serum creatinine ( micromol/l)
*42 ml /min 1.73 surface area.
11
Q
What is Normal mature GFR values ❓❓
A
80–120 ml/min per 1.73 m2, and are reached during the second year of life.
12
Q
How to measure the GFR❓❓
A
🔅measured on a single injection plasma disappearance curve, using 🔺inulin, or 🔺a radio-isotope such as chromium-labelled EDTA.
🔅After an intravenous injection of a known amount of one of these substances, a series of timed blood samples is taken over 3–5 h, and the slope of the curve generated by the falling plasma levels of the substance gives the GFR.
13
Q
What are the functions of the tubules ❓
A
🔅The proximal tubule and loop of Henle are the sites of major reabsorption of most of the glomerular filtrate.
🔅The distal tubule and collecting duct are where ‘fine tuning’ of the final composition of the urine occur
14
Q
What is the man transporter of the Proximal tubule??
A
🔅The primary active transport system is the Na+/K+ ATPase enzyme, reabsorbing 50% of filtered Na+.
🔅Secondary transport involves coupling to the Na+/H+ antiporter, which accounts for 90% of bicarbonate reabsorption with some Cl–. In addition:
• Glucose is completely reabsorbed unless the plasma level is high, in which case glycosuria will occur• Amino acids are completely reabsorbed, although preterm and term neonates commonly show a transient aminoaciduria
• Phosphate is 80–90% reabsorbed under the influence of parathyroid hormone (PTH), which reduces reabsorption and enhances excretion of phosphate
• Calcium is 95% reabsorbed: 60% in the proximal tubule, 20% in the loop of Henle, 10% in the distal tubule and 5% in the collecting duct
• A variety of organic solutes, including creatinine and urate, and some drugs, including trimethoprim and most diuretics, are secreted in the proximal tubule
15
Q
What are the transporter of loob of Henle ❓❓
A
➿the Na+/K+/2Cl– co-transporter in the thick ascending limb of the loop of Henle
➿40% of filtered Na+ is reabsorbed via it
16
Q
Where is medullary concentration gradient generated and why ❓❓
A
In the loobe of Henle because this segment is impermeable to water
17
Q
What is site of action of Loop diuretics ❓❓
A
block Cl–-binding sites on the co-transporter Na /K/2Cl
18
Q
What is an inborn defect in Cl– reabsorption at this same site in co-transporter Na /K/2Cl lead to ❓❓
A
Bartter syndrome
19
Q
Thiazide diuretics compete for these Cl–-binding sites and may have a powerful effect if combined with loop diuretics, which increase NaCl and water to the distal tubule
A
20
Q
What is the main functions and channels of Distal tubule ❓❓
A
🔺 A further 5% of filtered Na+ is reabsorbed here, via a Na+/Cl– co-transporter
🔺Aldosterone-sensitive channels (also present in the collecting duct) are involved in regulating K+ secretion.
21
Q
What are the main channels in the Collecting duct and what are their function ❓❓
A
• A final 2% of filtered Na+ is reabsorbed via aldosterone-sensitive Na+ channels, in exchange for K+
• Spironolactone binds to and blocks the aldosterone receptor, explaining its diuretic and K+-sparing actions
• H+ secreted into urine by H+ ATPase
• Antidiuretic hormone (ADH) opens water channels (aquaporins) to increase water reabsorption
22
Q
What is the main mechanism of secondary renal hypertension ❓❓
A
Abnormal renin release resulting in hypertension is associated with most forms of secondary renal hypertension, e.g. reflux nephropathy and renal artery stenosis
23
Q
There are syndromes of low-renin hypertension ❓❓
A
• Conn syndrome – primary hyperaldosteronism: high aldosterone leading to ECF volume expansion, hypertension, hypokalaemia and renin suppression ⤵️ renin
• Liddle syndrome – constitutive activation of amiloride-sensitive distal tubular epithelial sodium channel: ECF volume expansion leading to renin and aldosterone suppression, and hypokalaemia
⤵️ ⤵️ Renin and aldosterone
24
Q
What is the cause of Pseudohypoaldosteronism and what is the difference from aldosterone deficiency ❓❓
A
is constitutive inactivation of the amiloride-sensitive distal tubular epithelial Na+ channel, leading to excessive loss of salt and water with ECF volume depletion, and hyperkalaemia, thus mimicking aldosterone deficiency.
There are transient and permanent forms.
renin and aldosterone levels are, however, high secondary to the ECF volume depletion.
25
Erythropoietin (EPO) is released by
renal peritubular cells
26
What are the simulator of 1 hydroxylation ❓❓
Hypocalcaemia leads to enhanced 1-hydroxylase activity both directly and indirectly, by stimulating PTH secretion, which also stimulates the enzyme. Other stimuli for increased 1hydroxylase activity include low serum phosphate and growth hormone
27
28
What are the substances reabsored in the proximal tubules❓
🔅Reabsorption of 50% of filtered Na+.
🔅 90% of bicarbonate reabsorption with some Cl–.
In addition:
🔅 Glucose is completely reabsorbed
🔅 Amino acids are completely reabsorbed, although preterm and term neonates commonly show a transient aminoaciduria
🔅Phosphate is 80–90% reabsorbed under the influence of parathyroid hormone (PTH), which reduces reabsorption and enhances excretion of phosphate
🔅 Calcium is 60% reabsorbed.
🔅A variety of organic solutes, including creatinine and urate, and some drugs, including trimethoprim and most diuretics, are secreted in the proximal tubule
29
What are the types of urinary casts ❓❓
Red cell casts – isolated renal haematuria or glomerulonephritis
• Tubular cell casts – acute tubular necrosis
• White blood cell casts – pyelonephritis, acute tubular necrosis
30
What are thd causes of haematuria ❓❓
🔹UTI – bacterial – or other infections including tuberculosis and schistosomiasis
• Glomerulonephritis: • Often with proteinuria and urinary casts
• Isolated haematuria with no other evidence of clinical renal disease
• Trauma – usually a history
• Stones – usually painful
• Tumour
• Cystic kidney disease
• Bleeding disorders
• Vascular disorders, including renal vein thrombosis (especially neonates) and arteritis
• Sickle cell disease
• False positives
31
How much 24 h urinary protein excretion ❓❓
normal afebrile children, urine protein excretion should not exceed 60 mg/m2 per 24 h.
32
albumin:creatinine ratio:
• Normal – <3 mg/mmol
• Microalbuminuria – 3–30 mg/mmol
• Proteinuria – >30 mg/mmol
33
When is Orthostatic proteinuria detected ❓❓
is detectable when the patient has been in an upright position for several hours but not when the patient is recumbent. It is important to assess protein excretion on a first morning sample, when the patient has been recumbent all night, and on an evening sample when the patient has been up and about all day,
34
What are the drowback of Ultrasonography ❓❓
may not detect minor degrees of scarring.
It is not sensitive or specific at detecting vesicoureteric reflux (VUR). Doppler ultrasonography may reveal renal artery stenosis, but there is a significant false-negative rate.
35
What type of defects on DMSA ❓❓
**Some perfusion defects seen when DMSA is performed during acute UTI may resolve
** defects present 3 months after acute infection are permanent
36
DMSA (dimercaptosuccinic acid)
• A static scan, i.e. isotope is filtered and retained in renal parenchyma
• Assesses divided function and detects cortical scars
37
MAG-3 (mercaptoacetyltriglycine), DTPA (diethylenetriaminepenta-acetic acid)
• Dynamic scans, i.e. isotope is filtered, and then excreted from kidney down ureters to bladder • Assess divided function, and drainage and obstruction • Main use is in investigating upper tract dilatation seen on ultrasonography and for follow-up of surgery for obstructed kidneys or ureters
• Indirect radioisotope reflux study is a convenient way of assessing the presence of VUR in children old enough to cooperate with the scan and void on demand during the scan – in practice >3 years old. It avoids the need for a urethral catheter and has a lower radiation
38
Magnetic resonance urography (MRU)
• Assesses anatomy of urinary tract when the combination of ultrasonography and nuclear medicine scans, and often MCUG, have not clarified issues such as ureteric course and insertion
• Increasingly commonly used for diagnosis and surgical planning of complex urological disorders
39
IVU
Occasionally used for emergency evaluation of painful haematuria, if ultrasonography is uninformative, when IVU may reveal a ureteric stone
40
Renal arteriography
• Used to diagnose renal artery stenosis • Approach is via femoral artery; usually requires general anaesthesia in children. • Therapeutic approaches include balloon angioplasty of stenoses and embolization of intrarenal arteriovenous aneurysms
41
The following are the most common reasons for renal biopsy in children:
• Steroid-resistant nephrotic syndrome
• Haematuria and/or proteinuria
• Unexplained acute nephritis/acute renal failure
• Assessment of renal transplant dysfunction
42
Duplex kidney
• Often detected on antenatal ultrasonography or during investigation of UTI • Two ureters drain from two separate pelvicalyceal systems; ureters sometimes join before common entry into the bladder, but more commonly have separate entries, with the upper pole ureter inserting below the lower pole ureter
• Common complications associated with duplex systems are: • Obstructed hydronephrotic upper moiety and ureter, often poorly functioning, associated with bladder ureterocele • Dilatation and swelling of submucosal portion of ureter just proximal to stenotic ureteric orifice can be seen within bladder on ultrasonography and as a filling defect on MCUG
• Ectopically inserted upper pole ureter, entering urethra or vagina; clue to this from history is true continual incontinence with no dry periods at all, as ectopic ureter bypasses bladder • VUR into lower pole ureter, sometimes causing infection and scarring of this pole
43
44
K+ secretion is proportional to:
🔹 distal tubular urine flow rate
🔹distal tubular Na+ delivery: so natriuresis is associated with increased K+ secretion and hypokalaemia (e.g. Bartter syndrome, loop diuretics)
🔹aldosterone level – so conditions of elevated aldosterone are associated with hypokalaemia
🔹 [pH]–1
45
• Isolated haematuria with no other evidence of clinical renal disease may be the presenting feature of several important glomerulonephritides, including Alport syndrome and immunoglobulin A (IgA) nephropathy
46
What are the Causes of Acute scrotal pain
• Boys presenting with scrotal pain will often need to be assessed by a paediatric surgeon
• History and examination are the most important components of assessment
• Ultrasonography with colour Doppler to assess testicular blood flow may contribute
• Torsion of testicle
• Torsion of appendix of epididymitis
• Epididymitis
• Trauma
• Hernia or hydrocele
47
What is the difference between tortion of testicles and tortion of appendix of epididymitis ❓❓
Torsion of testicle:
• Acute abrupt onset of often severe pain • Early puberty • Swelling of testis and hemiscrotum, often with erythema/discoloration of scrotal skin • Diffuse tenderness of testis • Negative urinalysis • Treatment is surgical exploration
• Torsion of appendix of epididymis: • More common than torsion of testicle • Subacute onset of pain over hours • Pre-pubertal • Tenderness localized to the upper pole of testis • Negative urinalysis • If confident of diagnosis may be managed conservatively; however, may be difficult to distinguish from torsion of testicle so may require surgical exploration
48
Epididymitis:
• Gradual insidious onset of discomfort or pain • Adolescence • Epididymal tenderness • Urinalysis often positive (although may be negative) • May have low-grade fever; raised C-reactive protein (CRP) • Treatment with antibiotics (e.g. co-amoxiclav, cefalexin) if urinalysis suggestive of infection
49
Trauma
Trauma may cause a haematocele or testicular haematoma
50
Hernia or hydrocele:
Not usually acutely painful • Swelling in scrotum, extending into inguinal canal if hernia • No erythema or discoloration of overlying scrotal skin • Hydrocele will transilluminate with pen torch
51
Rare disorder; more common in boys
• Bladder mucosa is exposed (and with exposure and infection becomes friable), bladder muscle becomes fibrotic and non-compliant
• Anus anteriorly displaced
• Boys – penis has epispadias (dorsal opening urethra) and dorsal groove on glans, with dorsal chordee and upturning; scrotum is shallow and testes are often undescended
• Girls – female epispadias with bifid clitoris, widely separated labia• Pubic bones separated
• Requires surgical reconstruction; long-term urinary incontinence is common
52
What are the Causes of Metabolic acidosis ❓❓
A primary decrease in plasma bicarbonate and a decrease in plasma pH as a result of:
✔️Bicarbonate loss, e.g.
• Gastrointestinal loss in severe diarrhoea
• Renal loss in proximal (type 2) renal tubular acidosis (RTA)
✔️ Reduced hydrogen ion excretion, e.g. • Distal (type 1) RTA • Acute and chronic renal failure
✔️ Increased hydrogen ion load, e.g.
↑ endogenous load:
• inborn errors of metabolism, e.g. maple syrup urine disease, propionic acidaemia
• lactic acidosis, e.g. cardiovascular shock
• ketoacidosis, e.g. diabetic ketoacidosis (DKA)
✔️↑ exogenous load, e.g. salicylate poisoning
53
What is the Anion gap ❓❓
• A classification of metabolic acidosis involves assessing the anion gap – the ‘gap’ between anions and cations made up by unmeasured anions, e.g. ketoacids, lactic acid
54
How anion gap is calculated ❓❓
It Measured as [Na+ + K+] – [HCO3 – + Cl–]; thus normal anion gap is [140 + 4] – [24 + 100] = 20
• Acidosis may be a normal anion gap, when Cl– will be raised, i.e. hyperchloraemic
55
Metabolic alkalosis A primary increase in plasma bicarbonate and an increase in plasma pH as a result of the following:• Chloride depletion, the most common cause in childhood, leading to low urinary Cl– and Cl–responsive alkalosis, i.e. as soon as Cl– is made available (e.g. as intravenous saline) it is retained by the kidney at the expense of HCO3
–, correcting the alkalosis (see also Pseudo-Bartter syndrome,
Section 7.2): • Gastrointestinal loss, e.g. pyloric stenosis, congenital chloride diarrhoea • Furosemide therapy • Cystic fibrosis
• Stimulation of H+ secretion by the kidney, with normal urinary Cl– and Cl–-unresponsive alkalosis, e.g. • Bartter syndrome (see Section 7.2) • Cushing syndrome • Hyperaldosteronism (see Section 3.3)
• Excess intake of base, e.g. excess ingestion of antacid medicine (rare in childhood)
56
Total body water
Total body water (TBW) represents 85% of the body weight (bwt) of preterm infants, 80% in term infants and 65% in children
57
Osmotic equilibrium is maintained between the ICF and ECF compartments by the shift of H2O from lower to higher osmolality compartments
• ECF osmolality can be calculated as: [(Na+ + K+) × 2] + glucose + urea
58
rise in ECF osmolality, e.g. in DKA, will lead to a shift of H2O out of the ICF compartment, and
thus a reduction in ICF volume, i.e. cell shrinkage. Cell shrinkage stimulates the intracellular accumulation of organic osmolytes, which increases ICF osmolality and leads to a shift of H2O back into the cell, restoring cell volume
• Treatment of DKA may then lead to the rapid reduction of ECF osmolality, but the ICF organic osmolytes are degraded slowly and thus an osmotic gradient may be created during DKA treatment, favouring movement of H2O into the cells, causing cerebral oedema
59
Osmoregulation
A small (3–4%) increase in ECF osmolality stimulates hypothalamic osmoreceptors to cause posterior pituitary ADH release, leading to water retention and return of osmolality to normal. Increases in ECF osmolality also stimulate thirst and water drinking. Significant (>10%) ECF depletion, even if iso-osmolar, will cause carotid and atrial baroreceptors to stimulate ADH release
60
How anion gap calculated❓❓
• Measured as [Na+ + K+] – [HCO3 – + Cl–]; thus normal anion gap is [140 + 4] – [24 + 100] = 20
• Acidosis may be a normal anion gap, when Cl– will be raised, i.e. hyperchloraemic • May be an increased anion gap, when Cl– will be normal, i.e. normochloraemic
61
What is hyponatraemia ❓❓
Normal plasma Na+ is 135–145 mmol/l.
Hyponatraemia is usually defined as plasma Na+ <130 mmol/l
62
What are the Causes of hyponatraemia ❓❓
Gain of H2O in excess of Na+
♀️ Excess water intake – increased volume of appropriately hypotonic urine:
• Iatrogenic – excess hypotonic oral or intravenous fluid
• Psychogenic polydipsia
♀️ Acute renal failure – oedema and hypervolaemia, oliguria with urine Na+ >20 mmol/l
♀️Syndrome of inappropriate ADH secretion (SIADH) – inappropriately raised urine osmolality
63
What is the causes of hyponatraemia ❓❓
♀️Gain of H2O in excess of Na+
♀️Excess Na loss
64
What is the causes of hyponatraemia ❓❓
♂️♂️Loss of Na+ in excess of H2O
♀️ Renal losses – dehydration, but inappropriately high urine volume and urine Na+ content (>20 mmol/l); urine isotonic with plasma
• Loop diuretics
• Recovery phase of acute tubular necrosis
• Tubulopathies
• Salt-wasting congenital adrenal hyperplasia; adrenal insufficiency – hyperkalaemia
♀️Extrarenal losses – dehydration, appropriate oliguria and Na+ conservation with low urine Na+ (usually <10 mmol/l); urine hypertonic
• Gastrointestinal tract losses – gastroenteritis
• Skin losses – severe sweating, cystic fibrosis
65
Gain Excess water ➡️
Treatment is principally water restriction;
for severe hyponatraemia (<120 mmol/l) with neurological symptoms, correction of plasma Na+ to 125–130 mmol/l over 4 h is usually safe and effective in correcting symptoms
Loss excess Na ➡️
• Rehydration and calculation of Na+ deficit as (140 – plasma Na+) × 0.65 body weight (kg)
• Avoid over-rapid correction of hyponatraemia (risk of cerebellopontine myelinolysis)
66
What are the Causes of hypernatraemia ❓❓
***Loss of H2O in excess of Na+
♀️Renal losses – inappropriately high urine output, inappropriately low urine osmolality:
• Reduced renal concentrating ability – preterm neonates
• Diabetes insipidus – pituitary and nephrogenic.
• Osmotic diuresis – DKA
♀️ Extrarenal losses – appropriate oliguria and high urine osmolality: • Gastrointestinal losses
• Increased insensible H2O loss, e.g. pyrexia and hyperventilation
♀️Inadequate free water intake; • Breastfed neonate with inadequate maternal milk flow
67
What are the Causes of hypernatraemia ❓❓
Gain of Na+ in excess of H2O
♂️♂️ Increased volume of urine with high Na+ content:
▪️atrogenic – excess hypertonic intravenous fluid, e.g. NaHCO3, hypertonic saline
▪️Incorrect reconstitution of infant formula
▪️Accidental or deliberate (e.g. Munchausen syndrome by proxy) salt poisoning
68
What is the treatment of hypernatraemia due to water loss ❓❓
• Safest and best given with standard oral rehydration solution
• If intravenous treatment is essential, slow (48–72 h or 10–15 mmol/l per 24 h), correction of hypernatraemia with frequent measurement of plasma electrolytes is safest; a suggested fluid is 1 litre dextrose 5% + NaCl 25 mmol + KCl 20 mmol
69
What is the treatment of hypernatraemia due to excess Na ❓❓
• Treatment – recognition and removal of underlying cause; access to water while kidneys excrete excess salt load
70
What are the main causes of hypokalaemia ❓❓
♀️Inadequate provision of K+ with prolonged intravenous fluid administration
♀️Extrarenal losses ➡️ Gastrointestinal losses
♀️Renal losses ➡️
🔝 High plasma renin levels:
• diuretic use – loop and thiazide diuretics
• osmotic diuresis – DKA (hypokalaemia becomes evident when metabolic acidosis and insulin deficiency are corrected)
• Fanconi syndrome.
• Bartter syndrome
• Gitelman syndrome
• distal (type 1) RTA
⤵️Low plasma renin levels:
• Conn syndrome
• Liddle syndrome
• Cushing syndrome
♀️ Shift from ECF to ICF compartment;
• Correction of metabolic acidosis
• Insulin treatment
• High-dose or prolonged salbutamol treatment for asthma
71
What are the main causes of hyperkalaemia ❓❓
💙Excess administration in intravenous fluid
💙 Renal failure – acute and chronic
💙Shift from ICF to ECF; • Metabolic acidosis
💙Rhabdomyolysis – acute tumour lysis (both often associated with acute impairment in renal function which compounds the hyperkalaemia)
💙Hypoadrenal states;
• Salt-wasting congenital adrenal hyperplasia
• Adrenal insufficiency
• Pseudohypoaldosteronism
💙 Potassium-sparing diuretics – spironolactone
72
what is the normal K level ❓❓
Normal plasma K+ is 3.4–4.8 mmol/l.
73
What is the Treatment of hypokalaemia ❓❓❓
• Exclusion of K+ from diet and intravenous fluids
• Cardiac monitor – peaked T waves → prolonged P–R interval → widened QRS ventricular tachycardia → terminal ventricular fibrillation
• Calcium gluconate to stabilize myocardium
• Shift K+ from ECF to ICF:
• Correct metabolic acidosis if present – in acute renal failure
• Salbutamol: nebulized or short intravenous infusion
• Insulin and dextrose – but extreme caution in young children as there is a risk of hypoglycaemia
• Remove K+ from body: • calcium resonium • dialysis
74
What are the ECG abnormalities in hyperkalaemia ❓❓
peaked T waves → prolonged P–R interval → widened QRS ventricular tachycardia → terminal ventricular fibrillation
75
Syndrome of inappropriate ADH secretion (SIADH) features and causes ❓❓
♀️inappropriately raised urine osmolality, i.e. not maximally dilute ♀️increased body weight
♀️ decreased plasma urea and creatinine
♀️absence of overt renal, liver or cardiac disease
• Meningitis or central nervous system tumour
• Pneumonia
• Intermittent positive pressure ventilation
• Drugs, e.g. carbamazepine, barbiturates
76
77
What is Cystinuria ❓❓
• Defect in reabsorption of and hence excessive excretion of, the dibasic amino acids cystine, ornithine, arginine and lysine
78
What is the mode of inheritance of cystinuria and genetic defects ❓❓
Autosomal recessive; two separate cystinuria genes on 2p and 19q
79
Why cystinuria leads to recurrent stone formation ❓❓
Cystine is poorly soluble in normal urine pH; it has increased solubility in alkaline urine
80
what are the Clinical manifestation of cystinuria ❓❓
recurrent urinary stone formation
Stones are extremely hard and densely radio-opaque
81
What is the genetic cause of X-linked hypophosphataemic rickets❓❓
• Also known as vitamin D-resistant rickets
• Mutation in PEX gene on X chromosome
82
What are the abnormalities in X-linked hypophosphataemic rickets ❓❓
Isolated defect in PO4 3– reabsorption leading to:
• Inappropriately low tubular reabsorption of PO4 3– (TRP) – typically <85% – with a normal PTH and calcitriol level
• Hypophosphataemia
83
How cystinuria diagnosed and what is the treatment ❓❓
Diagnosis based on stone analysis, or high cystine level in timed urine collection
• Treatment based on
✔️ high fluid intake (>1.5 l/m2 per day) and alkalinization of urine with oral potassium citrate
✔️ If stones still form, oral D-penicillamine leads to formation of highly soluble mixed disulphides with cystine moieties
84
What is the earliest sign of X-linked hypophosphataemic rickets ❓❓
Earliest sign is ↑ alkaline phosphatase (by 3–4 months)
85
What are the chemical changes and clinical manifestation of X-linked hypophosphataemic rickets ❓❓
▪️Earliest sign is ↑ alkaline phosphatase (by 3–4 months)
▪️Plasma PO4 3– may be normal until 6–9 months of age
▪️By 12 months, have delayed growth, hypophosphataemia, ↑ alkaline phosphatase and radiological signs of rickets
▪️ Other features include delayed dentition and recurrent dental abscesses
86
What is the treatment of X-linked hypophosphataemic rickets ❓❓
Treatment is based on calcitriol or alfacalcidol, and phosphate supplements
• Recent evidence suggests that addition of growth hormone treatment may improve growth and biochemical disturbance
87
Failure to reabsorb filtered HCO3 – • Renal bicarbonate threshold is low, i.e. HCO3 – is present in the urine at levels of plasma HCO3 – lower than normal
• Distal tubular H + excretion is intact so acid urine can be produced
88
Symptoms include faltering growth, vomiting and short stature
89
Normal acidification of urine in response to ammonium chloride load • Normal increase in urine PCO2 in response to 3 mmol/kg oral bicarbonate load
90
Proximal (type 2) RTA• Failure to reabsorb filtered HCO3 –
91
Ability to excrete acid from distal tubule, and the fact that calcium salts are more soluble in acid urine, is the likely to explain why nephrocalcinosis is not a feature of proximal RTA
92
Treatment requires large doses of alkali (5–15 mmol/kg per day)
93
Usual clinical features include polyuria and polydipsia, chronic ECF volume depletion, faltering growth, constipation and rickets, with features in addition of any underlying condition
94
Fanconi syndrome
• Diffuse proximal tubular dysfunction, leading to excess urinary loss of the following: • Glucose – glycosuria with normal blood glucose • Phosphate – hypophosphataemia, low TRP, rickets • Amino acids – no obvious clinical consequence • HCO3
– – leading to proximal RTA
• K+ – causing hypokalaemia • Na+, Cl– and water – leading to polyuria and polydipsia, chronic ECF volume depletion, faltering growth • Tubular proteinuria – loss of low-molecular-weight proteins including retinol-binding protein and N-acetylglucosaminidase
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Main causes of Fanconi syndrome • Metabolic disorders:
• Cystinosis • Tyrosinaemia • Lowe syndrome (oculocerebrorenal syndrome) • Galactosaemia • Wilson disease
• Heavy metal toxicity • Lead, mercury, cadmium
• Idiopathic
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Predominant early clinical features are of: • Fanconi syndrome – see above • photophobia as the result of eye involvement with corneal cystine crystals • hypothyroidism
• Late features include the following: • Renal failure around 8–10 years of age, if untreated • Pancreatic involvement with diabetes mellitus • Liver involvement with hepatomegaly • Gonadal involvement with reduced fertility • Neurological deterioration and cerebral atrophy
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Cystinosis
Autosomal recessive defect in the transport of cystine out of lysosomes. The gene is localized to chromosome 17p and encodes an integral membrane protein, cystinosin.
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Diagnosis is based on the following: • Cystine crystals in cornea seen by slit-lamp • Peripheral blood white cell cystine level • Antenatal diagnosis available for families with positive history
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Renal tubular acidosis In normal individuals, urine pH falls as plasma HCO3
– decreases through the normal range 26–22
mmol/l. In proximal RTA, the curve has a similar shape but is shifted to the left, such that acid urine is not produced until plasma HCO3
– has fallen abnormally low, e.g. 16 mmol/l. In distal RTA, acid urine cannot be produced regardless of how low the plasma HCO3 – falls.
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Treatment • Supportive – PO4
3–, NaCl, K+ and NaHCO3 supplements, and high fluid intake; alfacalcidol; thyroxine
• Specific – cysteamine, which increases cystine transport out of the lysosome; starting treatment in early infancy appears to delay onset of renal failure
• Other – indometacin reduces the GFR, and hence the severe polyuria and secondary polydipsia, and electrolyte wasting
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What are the Causes of RENAL Tubulopathies - Proximal tubulopathies❓❓
▪️Cystinuria
▪️X-linked hypophosphataemic rickets
▪️Proximal (type 2) RTA
▪️Fanconi syndrome
▪️Cystinosis
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What is the Bartter syndrome ❓❓
Symptoms are polyuria, polydipsia, episodes of dehydration, faltering growth and constipation; there may be maternal polyhydramnios with an affected fetus
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What are the Clinical features of Bartter syndrome ❓❓
•Symptoms are polyuria, polydipsia, episodes of dehydration, faltering growth and constipation; there may be maternal polyhydramnios with an affected fetus
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What are the pathophysiological changes of Bartter syndrome ❓❓
♂️♂️The resultant ECF volume contraction causes secondary renin secretion and raised aldosterone levels, with avid Na + and water reabsorption in the distal tubule, and reciprocal K+ and H+ secretion into the urine.
♂️♂️♂️The blood pressure is normal; the hyperreninaemia is a compensatory response to maintain normal blood pressure in the presence of chronic ECF volume depletion.)
♂️♂️♂️There is also increased renal prostaglandin E2 production
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What are the characteristics biochemical changes in Bartter syndrome ❓❓and what is treatment ❓❓
♀️The above changes produce the characteristic biochemical disturbance of➡️➡️➡️➡️ hypochloraemic/hypokalaemic alkalosis
♀️Crucial to the diagnosis is the finding of inappropriately high levels of urinary Cl– and Na+ – usually >20 mmol/l; urine Ca2+ is normal or high (compare Gitelman syndrome – see below)
• Therapy involves K+ supplementation combined with prostaglandin synthetase inhibitors, usually indometacin
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What is the Pseudo-Bartter syndrome❓❓
The same plasma biochemistry – hypochloraemic hypokalaemic alkalosis – but appropriately low levels of urine Cl– and Na+ – <10 mmol/l
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What are the Main causes of pseudo-bartter syndrome ❓❓
• Cystic fibrosis – sweat loss of NaCl and water
• Congenital chloride diarrhoea – gastrointestinal loss
• Laxative abuse – gastrointestinal loss
• Cyclical vomiting
Note that all the changes of Bartter syndrome, including the high urine electrolyte levels, may be produced by loop diuretics, which block the same site in the thick ascending limb of the loop of Henle.
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Distal tubule Gitelman syndrome
• This condition is considered a variant of Bartter syndrome • There is an inborn autosomal recessive defect in the distal tubule Na+/Cl– co-transporter • Often asymptomatic, with transient episodes of weakness and tetany with abdominal pain and vomiting
• Patients have hypokalaemic metabolic alkalosis, raised renin and aldosterone, and hypomagnesaemia with increased urinary magnesium wasting, and hypocalciuria, a feature that helps distinguish it from classic Bartter syndrome (in which urinary Ca2+ is normal or high – see above)
• Biochemical changes resemble those produced by thiazide diuretics, which inhibit this distal tubule co-transporter
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Collecting duct Nephrogenic diabetes insipidus
• Resistance to action of high circulating levels of ADH • Associated with ADH-receptor gene mutations (X-linked nephrogenic diabetes insipidus) and aquaporin (water-channel) gene mutations (autosomal recessive nephrogenic diabetes insipidus)
• High volumes of inappropriately dilute urine with tendency to hypernatraemic dehydration
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NEPHROTIC SYNDROME
A triad of oedema, proteinuria and hypoalbuminaemia. It is almost always idiopathic in childhood. It is best classified by response to steroid treatment – steroid-sensitive nephrotic syndrome (SSNS; 85– 90% cases) or steroid-resistant nephrotic syndrome (SRNS; 10–15% cases), because this is the best predictor of outcome.
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Definitions
• Remission – negative urinalysis on first morning urine for three consecutive mornings • Relapse – 3+ proteinuria on three or more consecutive first morning urines • Frequently relapsing – two or more relapses within 6 months of diagnosis; or four or more relapses per year
• Steroid resistant – no remission after 4 weeks of prednisolone 60 mg/m2 per day
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What are risk factors of Infections in nephrotic syndrom ❓❓
• Tissue oedema and pleural and peritoneal fluid
• Loss of immunoglobulin in urine
• Immunosuppression with steroid treatment
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What are the most common infections in nephrotic syndrome ❓❓
• Typically with Streptococcus pneumoniae.
• Pneumonia • Primary pneumococcal peritonitis
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What are the Causes of increased Thrombosis in nephrotic syndrome ❓❓
• Loss of antithrombin III and proteins S and C in urine
• Increased production of procoagulant factors by liver
• Increased haematocrit secondary to reduced oncotic pressure
• Swelling of legs, ascites and relative immobility
• Steroid therapy
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What are the Causes of Hypovolaemia in nephrotic syndrome ❓❓
• Reduced plasma oncotic pressure leads to shift of plasma water from intravascular space to interstitial space
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What is the causes of Drug toxicity in nephrotic syndrome❓❓
• Most morbidity in childhood nephrotic syndrome arises from side effects of steroid treatment
• Nephrotoxicity from ciclosporin or tacrolimus.
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What are the features of hypovolaemia ❓❓
♀️Symptoms include oliguria, abdominal pain, anorexia and postural hypotension
♀️ Signs include cool peripheries, poor capillary refill and tachycardia
♀️Poor renal perfusion activates the renin–angiotensin–aldosterone system, and urine Na+ will therefore be very low – usually <10 mmol/L
♀️Occasionally acute tubular necrosis develops secondary to hypovolaemia
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What are thd treatment of initial presentation nephrotic syndrome ❓❓
♂️♂️♂️Prednisolone 60 mg/m2 per day for 4 weeks; then reduce to 40 mg/m2 on alternate days for 4 weeks; then stop
However, there is good evidence from controlled trials that longer duration of initial prednisolone treatment is associated with fewer relapses and lower total prednisolone dose over the first 2 years. An example of a 6-month initial course is:
♀️♀️♀️ 60 mg/m2 per day for 4 weeks; then 40 mg/m2 on alternate days for 4 weeks; 30 mg/m2 on alternate days for 4 weeks; 20 mg/m2 on alternate days for 4 weeks; 10 mg/m 2 on alternate days for 4 weeks; 5 mg/m2 on alternate days for 4 weeks; then stop
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What is the regimen of steroids for Relapse ❓❓
Prednisolone 60 mg/m2 per day until in remission; then 40 mg/m2 on alternate days for three doses; and reduce alternate-day dose by 10 mg/m2 every three doses until 10 mg/m2 on alternate days is reached; then 5 mg/m2 on alternate days for three doses; then stop
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Frequently relapsing or steroid-dependent nephrotic syndrome
Other drugs that have been successfully used to enable control without steroids, or with much lower doses of steroids, include:
• Cyclophosphamide: • Often used as first choice of second-line drug • 2 mg/kg for 12 weeks, or 3 mg/kg for 8 weeks • Hair thinning, bone marrow suppression
• Tacrolimus (FK506): • Taken twice daily long term, e.g. 12–18 months for initial trial • High relapse rate when weaned/stopped • Can cause nephrotoxicity – need to monitor plasma tacrolimus levels and GFR
• Ciclosporin: • Hirsutism, gum hyperplasia, nephrotoxicity
• Mycophenolate mofetil • Most recent immunosuppressive drug tried in nephrotic syndrome • Efficacy may be similar to tacrolimus, but not nephrotoxic • Gastrointestinal intolerance is the most common side effect
• Levamisole • Need to monitor full blood count for bone marrow suppression
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Steroid-resistant nephrotic syndrome
• Patient should be referred to specialist renal unit for assessment including renal biopsy • Usually resistant to other drug treatments also, so full remission not achieved • Aim is to reduce proteinuria so that patient is no longer nephrotic • The most common treatment is alternate-day prednisolone combined with ciclosporin long term • Screen for podocin (NPHS2) mutations – patients almost never respond to immunosuppression so can avoid unnecessary drug toxicity
• Angiotensin-converting enzyme (ACE) inhibitor (e.g. enalapril) and/or angiotensin II receptor blocker (e.g. losartan) often used to treat hypertension, with the added benefit of anti-proteinuric effect
• Significant chance of hypertension and progression to renal failure • If histology is FSGS, associated with 20–40% chance of recurrence after transplantation; however,
patients with identifiable podocin or other gene mutations have a much lower risk of disease recurrence
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Congenital nephrotic syndrome• Onset in first 3 months of life; large placenta – usually 40% of birthweight • Almost always resistant to drug treatment; clinically severe with high morbidity from protein malnutrition, sepsis
• Main causes are, in decreasing order of frequency: • Finnish-type congenital nephrotic syndrome – most severe; autosomal recessive; gene (NPHS1) on chromosome 19 normally codes for nephrin, a cell adhesion protein located at the glomerular slit diaphragm • Diffuse mesangial sclerosis – less severe; also autosomal recessive • Denys–Drash syndrome – includes pseudohermaphroditism and Wilms tumour • FSGS • Secondary congenital nephrotic syndrome – congenital syphilis
• Treatment is intense supportive care with 20% albumin infusion, nutritional support and early unilateral nephrectomy (to reduce urinary protein loss), combined with ACE inhibitors and indometacin (to reduce GFR, and thus protein loss, of remaining kidney)
• Eventual progression to renal failure occurs, when remaining kidney is removed, and the child undergoes dialysis and transplantation
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GLOMERULONEPHRITIS 9.1 General clinical features
• Inflammation of the glomeruli leading to various clinical features, or renal syndromes, which may include: • Haematuria and/or proteinuria • Nephrotic syndrome • Acute nephritic syndrome with reduced renal function, oliguria and hypertension • Rapidly progressive crescentic glomerulonephritis – rapid-onset severe renal failure and hypertension, usually associated with the histological lesion called a crescent
• These renal syndromes are not specific to particular conditions and the same condition may present with different renal syndromes in different patients
• Chronic glomerulonephritis may lead to scarring of the tubulointerstitial areas of the kidney, with progressive renal impairment
• The main causes of glomerulonephritis, and the associated changes in serum complement, include those shown in the table
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When is the onset of Acute post-streptococcal glomerulonephritis ❓❓
• Onset of reddish-brown (‘Coca Cola-coloured’) urine 10–14 days after streptococcal throat or skin infection
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What is mechanism of PSGN ❓❓
• Deposition of immune complexes and complement in glomeruli •
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what are the Investigations for PSGN ❓❓
• Throat swab
• Antistreptolysin O (ASO) titre; anti-DNAase B
• Typically ↓ C3, normal C4
• Biopsy if there is significant renal involvement – diffuse proliferative glomerulonephritis is seen, with crescents, in severe cases
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What are characteristics of Henoch–Schönlein purpura❓❓
• 70%of children with Henoch–Schönlein purpura will have some degree of renal involvement, usually just microscopic haematuria with/without proteinuria
• They may have any of the renal syndromes
• They may have a relapsing course
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What is the management and prognosis of HSP❓❓
• Refer to specialist renal unit if nephrotic, or nephritic, or sustained hypertension because these patients may require biopsy
• Prognosis is difficult to be certain about, but initial clinical severity and histological score on biopsy guide the prognosis
• No convincing evidence that treatment with steroids at onset of rash prevents renal involvement (though steroids may be used for systemic symptoms such as abdominal and joint pain)
• Treatment of severe cases includes steroids, ± azathioprine or mycophenolate mofetil (MMF)
♂️ for very severe crescentic nephritis with renal failure, methylprednisolone combined with intravenous cyclophosphamide and plasma exchange has been used
• Accounts for 5–8% of children in end-stage renal failure
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What is the Treatment of PSGN ❓❓
mainly supportive, with an excellent prognosis for recovery
✔️in very severe cases involving renal failure, steroids have been used
✔️ always check C3 and C4 3 months after acute illness – should normalize; if still lowered there may be another diagnosis, e.g. systemic lupus erythematosus or MCGN, which has much worse prognosis.
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What are the common presentations of IgA nephropathy❓❓
• Presents with incidental finding of persistent microscopic haematuria or with an episode of macroscopic haematuria which is typically associated with concurrent upper respiratory infection – these episodes may be recurrent
• Again, may have any of the renal syndromes
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What is the prognosis and treatment of IgA nephropathy ❓❓
• Prognosis for childhood presentation is quite good, although 10–15% will develop proteinuria, hypertension with/without renal failure during long-term follow-up
• Treatment as for Henoch–Schönlein purpura nephritis
✔️ ACE inhibitors used for long-term control of hypertension and to minimize proteinuria
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What are the treatment of Systemic lupus erythematosus nephritis❓❓
• Treatment of nephritis usually steroids + MMF
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What other manifestation of SLE that can affect the renal system❓❓
• Patients may also manifest the antiphospholipid/anticardiolipin antibody syndrome, with thrombotic complications affecting the renal vasculature
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‘Shunt’ nephritis
• Classically associated with infected ventriculoatrial shunts – these are now rarely used so the condition is rare
• Histologically similar to nephritis of subacute bacterial endocarditis
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ACUTE KIDNEY INJURY An acute disturbance in fluid and electrolyte homeostasis, typically associated with oliguria (<300 ml/m2 per day) and retention of urea, potassium, phosphate, H+ and creatinine. It is rare in childhood compared with the incidence in elderly people. The main cause of severe acute renal failure in otherwise normal children is haemolytic/uraemic syndrome
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Classification of acute kidney injury Prerenal failure with reduced renal perfusion • In the early stages, the kidney reacts appropriately producing small volumes of urine with very lowNa+ and high concentration of urea; may be reversible at this stage with fluid therapy (with/without inotropic support)
• If uncorrected, progresses to established acute tubular necrosis • Main causes are: • ECF volume deficiency – haemorrhage, diarrhoea, burns, DKA, septic shock with ‘third-space’ fluid loss • Cardiac (‘pump’) failure – congenital heart disease, e.g. severe coarctation, hypoplastic left heart, aortic cross-clamping and bypass for correction of congenital heart disease, myocarditis
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Intrinsic renal failure
Acute tubular necrosis Occurs as a result of:
• Uncorrected prerenal failure as above • Toxins – gentamicin, X-ray contrast, myoglobinuria; gentamicin toxicity most common in neonates, and may cause non-oliguric renal failure
• Acute glomerulonephritis – see Section 9 Vascular
• Small vessel occlusion – haemolytic/uraemic syndrome • Bilateral renal vein thrombosis – neonates • Acute renal cortical necrosis – neonatal birth asphyxia
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Intrinsic renal failure
Acute tubular necrosis Occurs as a result of:
• Uncorrected prerenal failure as above • Toxins – gentamicin, X-ray contrast, myoglobinuria; gentamicin toxicity most common in neonates, and may cause non-oliguric renal failure
• Acute glomerulonephritis – see Section 9 Vascular
• Small vessel occlusion – haemolytic/uraemic syndrome • Bilateral renal vein thrombosis – neonates • Acute renal cortical necrosis – neonatal birth asphyxia
Tubulointerstitial nephritis • Drugs – non-steroidal anti-inflammatory drugs, furosemide, penicillin, cephalosporins
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Postrenal (obstructive) renal failure
• Posterior urethral valves is main lesion, but not acute kidney injury • Neuropathic bladder – may be acute in: • Transverse myelitis • Spinal trauma or tumour
• Stones: • Bilateral pelviureteric junction or ureteral stone or bladder stone • Urethral prolapse of bladder ureterocele
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How Clinical assessment of circulation in oliguric child is crucial ❓❓
• Low blood pressure, poor capillary refill and cool peripheries suggest prerenal cause: may respond to fluid challenge
• Normal/raised blood pressure, raised jugular venous pressure (JVP), good peripheral perfusion, gallop rhythm suggest intravascular volume overload and thus not prerenal, and fluid challenge is contraindicated (though challenge with loop diuretic may improve urine output)
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What is the difference between Prerenal failure and Intrinsic renal failure❓❓
Osmolality = >500 <300
Urine Na+ = <10 >40
Urine:plasma urea ratio >10:1 <7:1
Fractional excretion of Na <1 >1
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History may give clues to diagnosis: • Sore throat and fever 10 days earlier suggests post-streptococcal glomerulonephritis • Bloody diarrhoea and progressive pallor suggest haemolytic/uraemic syndrome • Drug history may reveal use of non-steroidal anti-inflammatory drugs
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slightly increased echogenicity (if kidneys appear small with poor corticomedullary differentiation, renal failure is chronic) • Rules out or confirms obstruction of urinary tract; stones • Can detect clot in renal vein thrombosisRenal biopsy if diagnosis not clear from above assessment
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Haemolytic–uraemic syndrome (HUS) • Most common cause of acute kidney injury in children
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Early liaison with paediatric renal unit • Fluid therapy determined by clinical assessment and urine indices, as above: • Prerenal failure: fluid challenge with physiological 0.9% saline • Intrinsic renal failure:
• If clinically euvolaemic, give fluid as insensible loss (300 ml/m2 per day) + urine output • If clinically overloaded, challenge with loop diuretic and restrict to insensible losses
• If hypertensive because of ECF volume overload: • Challenge with loop diuretic • Nifedipine or hydralazine as simple vasodilating hypotensives • If hyperkalaemic, treat as in Section 6.4
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Intrinsic renal failure:
• If clinically euvolaemic, give fluid as insensible loss (300 ml/m2 per day) + urine output • If clinically overloaded, challenge with loop diuretic and restrict to insensible losses
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Note that if anaemic, e.g. in haemolytic/uraemic syndrome, transfusion usually delayed until dialysis access is established (i.e. until transferred to renal unit), because hyperkalaemia and fluid overload may be worsened
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Severe ECF volume overload – severe hypertension, pulmonary oedema, no response to diuretics • Severe hyperkalaemia, not responding to conservative treatment • Severe symptomatic uraemia – usually urea >40 mmol/l • Severe metabolic acidosis not controllable with intravenous bicarbonate • To remove fluid to ‘make space’ for nutrition (intravenous or enteral), intravenous drugs – a common reason in intensive care patients
• Removal of toxins – haemodialysis will be most effective for low-molecular-weight substances that are not highly protein bound, including: • Drugs – gentamicin, salicylates, lithium • Poisons – ethanol, ethylene glycol • Metabolites from inborn errors of metabolism – leucine in maple syrup urine disease, ammonia
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What is the cause of HUS ❓❓
Diarrhoea-associated HUS (D+ HUS) is the major type, usually as the result of Escherichia coli O157, which produces verocytotoxin (also called shiga toxin)
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What is the pathophysiology of HUS ❓❓
Toxin is released in gut and absorbed, causing endothelial damage especially in renal microvasculature, leading to microangiopathic haemolytic anaemia with thrombocytopenia and red blood cell fragmentation (seen on blood film)
• The microangiopathy leads to patchy focal thrombosis and infarction, and renal failure which is often severe and requires dialysis
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What other organs that can be affected by HUS ❓❓
Brain (fits, focal neurology), myocardium, pancreas and liver are sometimes affected
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What is the treatment for HUS ❓❓
Treatment is supportive; antibiotic treatment of the E. coli gastroenteritis increases the incidence and severity of HUS, and is thus contraindicated
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What are the long term complications of HUS ❓❓
Long-term follow-up shows that 10–15% will develop hypertension, proteinuria or impaired renal function
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What is the features of Atypical D– HUS ❓❓
Rare but more serious, with recurrent episodes, progressive renal impairment and higher incidence of neurological involvement: 💲💲Autosomal recessive forms associated with disturbances of complement regulation, e.g. mutations in complement factor H gene 💲💲 Rare complication of bone marrow transplantation
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What is chronic renal disease ❓❓
A persistent impairment of renal function, classified according to the GFR as mild (60–80 ml/min per 1.73 m2), moderate (40–59 ml/min per 1.73 m2) and severe (<40 ml/min per 1.73 m2). End-stage renal failure, where dialysis or transplantation is needed, is reached once GFR <10 ml/min per 1.73 m2.
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What are the main causes of CKD ❓❓
🔺 Congenital dysplasia ± obstruction
🔺Reflux nephropathy
🔺 Chronic glomerulonephritis – FSGS, MCGN
🔺Genetically inherited disease: • Hereditary nephritis – Alport syndrome, nephronophthisis
🔺Polycystic kidney disease
🔺 Systemic disease – Henoch–Schönlein purpura, systemic lupus erythematosus
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Clinical presentations of CKD ❓❓
• Antenatal diagnosis
• Faltering growth, poor growth, pubertal delay
• Malaise, anorexia
• Anaemia
• Incidental – blood test, urinalysis
• Hypertension
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What is the pathophysiology of Poor growth in CKD ❓❓
• Anorexia, vomiting (uraemia)
• Anaemia, acidosis and renal osteodystrophy
• Reduced effectiveness of growth hormone, probably as the result of raised levels of insulin-like growth factor (IGF)-binding protein, and hence less free IGF; levels of growth hormone are normal
• Recombinant human growth hormone is effective in improving growth in children with chronic renal failure, and is licensed for this use
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Dietary considerations
• Inadequate calorie intake and catabolism worsens acidosis, uraemia and hyperkalaemia in chronic renal failure; aggressive nutritional management is crucial to control these, and to achieve growth
• Children with chronic renal failure often have poor appetite, and infants in particular benefit from nasogastric or gastrostomy tube feeding
• Congenital dysplasia ± obstruction typically causes polyuria, with NaCl and HCO3 – wasting, and
these need supplementing along with generous water intake; note that salt and water restriction is inappropriate in many children with chronic renal failure, until they reach end-stage renal failure
• Protein intake should usually be the recommended daily intake for age; note that protein restriction is inappropriate for children with chronic renal failure
• Dietary restriction of PO4 3– (dairy produce) combined with use of PO4 3– binders (e.g. calcium carbonate) is essential in controlling secondary hyperparathyroidism
• Dietary restriction of K+ (fresh fruits, potatoes) is also commonly needed
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Anaemia in CKD ❓❓
• Dietary iron deficiency
• Reduced red blood cell survival in uraemia
• Erythropoietin deficiency; recombinant human erythropoietin is available for treatment
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What is the mechanism of renal osteodystrophy ❓❓
Phosphate retention leads to hypocalcaemia, and both increased PO4
3– and decreased Ca2+stimulate secondary hyperparathyroidism:
• Subperiosteal bone resorption
• Deficient renal 1-hydroxylase activity and deficient 1,25(OH)2-D3 also contributes to hypocalcaemia, and leads to rickets
• Treatment includes control of hyperphosphataemia and alfacalcidol (1-OHcholecalciferol) or calcitriol
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What is the effect of Metabolic acidosis in renal disease ❓❓
• Contributes to bone disease, because chronic acidosis is significantly buffered by the uptake of H+ into bone in exchange for Ca2+ loss from bone
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Is Hypertension is always present in CKD ❓❓
• Depends on the underlying cause of the chronic renal failure
• Congenital dysplasia ± obstruction – patients tend to be polyuric, salt wasting and normotensive
• Chronic glomerulonephritis, polycystic kidney disease, systemic disease – hypertension is common; usually secondary to increased renin, so ACE inhibitors are often effective
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Dialysis
Once the GFR falls to 10 ml/min per 1.73 m2, the child will usually need dialysis, or transplantation, to be maintained safely. The two main types of dialysis, peritoneal dialysis and haemodialysis, both depend on a semipermeable membrane to achieve solute removal (K+, urea, PO4
3–, creatinine, etc.), and fluid removal.
Infants and small children are better suited to peritoneal dialysis, which is more ‘physiological’ and avoids abrupt haemodynamic changes
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What are advantages of living related donor transplantation❓❓
• Better long-term survival of the graft kidney: approximate figures are 95% at 1 year, 80–85% at 5 years, 60% at 10 years
• Surgery is planned, so family life can be organized to work around this
• Increases the chance of achieving transplantation without dialysis
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What are the main immunosuppressive drugs after kidney transplantion ❓❓
📍prednisolone
📍 tacrolimus
📍azathioprine
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What are the prerequisites for transplantation ❓❓
📍Human leukocyte antigen (HLA) matching is based around HLA-A, -B and -DR; on average a parent and child will be matched for one allele, and mismatched for one allele, at each site
📍Children should receive all routine childhood immunisations, and also be immune to tuberculosis, chickenpox and hepatitis B before transplantation
📍Children must weigh >10 kg for transplantation to be performed
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What are the main complications of transplantation ❓❓
• Early surgical complications – bleeding, transplant artery thrombosis, wound infection
• Rejection – diagnosed on biopsy; usually treatable with extra immune suppression
• Opportunistic infection – fungal infections, cytomegalovirus, Pneumocystis jiroveci pneumonia
• Drug toxicity – hypertension, cushingoid changes, hirsutism and nephrotoxicity from ciclosporin
• Post-transplantation lymphoproliferative disorder – lymphoma-like condition, especially associated with primary Epstein–Barr virus infection when immunosuppressed
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Most common presenting urinary tract problem –
1% boys and 3% girls • Boys outnumber girls until 6 months (posterior urethral valves); thereafter girls outnumber boys
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Collection of an uncontaminated urine sample is crucial to accurate diagnosis of UTI – methods include:
• Clean catch
• Adhesive bag – problems with leakage and faecal contamination
• Absorbent pad – also prone to contamination
0• Catheter specimen, or suprapubic aspirate – suitable if urine sample is needed urgently, e.g. septic screen in ill infant
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– infancy
Age at greatest risk for renal damage, age in which symptoms of UTI are least specific, age group most often seen with fever by general practitioners and age at which proper urine samples are hardest to obtain
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Significance of UTI:
• Renal scar gives 15–20% risk hypertension • Reflux nephropathy causes 15–20% end-stage renal failure
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VUR: • Familial, behaves as autosomal dominant condition • May be graded according to severity on MCUG • Management based on long-term, low-dose antibiotic prophylaxis (although no convincing randomized prospective controlled trials have been reported, this remains the standard of care currently) • Significant spontaneous resolution rate; less likely in grades IV and V • Controlled studies show no benefit for surgery over conservative management for grades I–III • Surgery may be indicated where prophylaxis fails to control infection and where there is progressive reflux nephropathy; options are reimplantation of ureters or endoscopic injection of synthetic material at ureteric orifice • Screening of newborn siblings or offspring of index children or parents should be considered • In children who have normal bladder control and no symptoms of detrusor dysfunction, and who have been free of infection on prophylaxis, evidence suggests that there is little benefit from continuing prophylaxis beyond age 5 years
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VUR: • Familial, behaves as autosomal dominant condition • May be graded according to severity on MCUG • Management based on long-term, low-dose antibiotic prophylaxis (although no convincing randomized prospective controlled trials have been reported, this remains the standard of care currently) • Significant spontaneous resolution rate; less likely in grades IV and V • Controlled studies show no benefit for surgery over conservative management for grades I–III • Surgery may be indicated where prophylaxis fails to control infection and where there is progressive reflux nephropathy; options are reimplantation of ureters or endoscopic injection of synthetic material at ureteric orifice • Screening of newborn siblings or offspring of index children or parents should be considered • In children who have normal bladder control and no symptoms of detrusor dysfunction, and who have been free of infection on prophylaxis, evidence suggests that there is little benefit from continuing prophylaxis beyond age 5 years
• Incomplete bladder emptying: • Posterior urethral valves • Neuropathic bladder
• Catheterization or instrumentation of urinary tract • Stones
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Atypical UTI
Recurrent UTI Seriously ill Poor urine flow
Two or more episodes of UTI with acute pyelonephritis/upper urinary tract infectionAbdominal or bladder mass Raised creatinine
Septicaemia Failure to respond to treatment with suitable antibiotics within 48 hours Infection with non-E. coli organisms
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Recurrent UTI
Two or more episodes of UTI with acute pyelonephritis/upper urinary tract infectionOne episode of UTI with acute pyelonephritis/upper urinary tract infection plus one or more episode of UTI with cystitis/lower urinary tract infection
Three or more episodes of UTI with cystitis/lower urinary tract infection
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What are NICE guidelines for UTI diagnosis ❓❓
🔺recommend use of urgent microscopy and culture for diagnosis of UTI in infants <3 years old
🔺dipstick testing as initial test for children ≥3 years old
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What is the treatment for UTI ❓❓
📍📍If the infant or child is younger than 3 months; treat with parenteral antibiotics
📍📍♂️If the infant or child is 3 months or older with pyelonephritis/upper urinary tract infection:
• Treat with oral antibiotics for 7–10 days
• If oral antibiotics cannot be used, use intravenous antibiotics for 2–4 days followed by oral antibiotics for a total duration of 10 days
📍📍♂️ If the infant or child is 3 months or older with cystitis/lower UTI:
• Treat with oral antibiotics for 3 days
• If the child is still unwell after 24–48 hours they should be reassessed; if no alternative diagnosis, send urine for culture
• Obstructed kidneys may need drainage
• Bladder catheter if bladder outlet obstruction
• Nephrostomy insertion if PUJ or VUJ level obstruction
• Stones may need removing
• Augmented bladders may improve with mucolytic and bacteriostatic washouts: • Parvolex washouts; chlorhexidine washouts
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Prevention of UTI
• Non-pharmacological methods:
• Avoidance of constipation; correct bottom wiping
• Frequent voiding and high fluid intake; double voiding
• Lactobacilli in live yoghurt; cranberry juice
• Clean intermittent catheterization: requires training of carer or child by specialist nurse
• Prophylactic antibiotics
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Neuropathic bladder Important cause of renal damage:
• UTI caused by incomplete emptying
• High-pressure VUR
• Progressive renal scarring
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Causes of neuropathic bladder ❓❓
• Spina bifida, sacral agenesis (maternal diabetes)
• Tumour, trauma
• Transverse myelitis
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What are the types of neuropathic bladder ❓❓
• Hyperreflexic – high pressure, detrusor-sphincter dyssynergia
• Atonic – large, chronically distended, poorly emptying
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Principles of management
• Videourodynamic assessment of type of bladder dysfunction • Careful assessment of kidney structure, scarring, function, blood pressure • Improve emptying with clean intermittent catheterization • Anticholinergics (oxybutinin) may help reduce unstable contractions • Augmentation cystoplasty – larger capacity, lower pressure
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NOCTURNAL ENURESIS See http://guidance.nice.org.uk/CG111 for published NICE guideline
This is a common condition that is benign but which may cause distress and psychological upset to the child and family. Most children become dry at night 6–9 months after becoming dry by day, which is usually by 3 years. As a simple guide, 10% of 5 year olds and 5% of 10 year olds wet the bed at least one night per week. It is more common in boys.
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Primary nocturnal enuresis (80%) – never achieved night-time dryness • Secondary nocturnal enuresis – recurrence of bedwetting having been dry for >6 months • Initial successful response – 14 consecutive dry nights within 16 weeks of starting treatment • Relapse – more than 2 wet nights in 2 weeks • Complete success – no relapse within 2 years of initial success
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Genetic component: • More common where there is a first-degree relative with history of enuresis • Concordance in monozygotic twins twice that in dizygotic twins
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Evidence from studies that: • In younger children, bladder capacity is reduced compared with non-enuretic children • In older children and adolescents, there is reduction in the normally observed rise in nocturnal ADH levels and in the decrease in nocturnal urine volume (hence rationale for desmopressin [DDAVP] treatment
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No significant excess of major psychological or behavioural disturbance, although family stress, bullying at school, etc. may trigger secondary enuresis and such factors should be sought in the
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Examination should exclude abnormalities of abdomen, spine, lower limb neurology, hypertension • No routine investigations are indicated, other than urinalysis if the enuresis has started recently or if there are other symptoms suggesting UTI
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What is the Treatment for enuresis ❓❓
*** Sustained and frequent support and encouragement for child and parents from an enthusiastic carer (doctor, nurse) is the most essential factor in seeing improvement. Any treatment must involve the child, and depends for success on their motivation.
• Star charts
• Enuresis alarms
• Drug therapy
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What is the Star charts ❓❓
colouring-in charts – simple behavioural reward therapy that is successful in many children, and should be part of the monitoring of all interventions
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What are Enuresis alarms and what is their Advantages ❓❓
• Mat on bed attached to bed-side buzzer
• Small moisture sensor worn between two layers of underwear with vibrator alarm attached to pyjamas (has the advantage of detecting wet underwear rather than waiting to detect a wet bed)
• More effective than drug therapies in direct comparative trials
• Should be mainstay of treatment, but enthusiastic and supportive care, and involvement of child (e.g. they should get up and change bedding) are crucial to success
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Drug therapy:
• Desmopressin (oral or intranasal).
• Oxybutinin ➡️➡️detrusor instability
• Imipramine ➡️➡️rarely used
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What are the pros and cons of Desmopressin (oral or intranasal) ❓❓
♂️♂️ poor short-term complete response rate
♂️♂️high relapse rate and poor long-term cure rate;
♂️♂️ more effective in older children
♂️♂️useful for short-term control for special situations, e.g. school trip; may be combined with alarm
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What is abnormal?
• Consistently above the 95th centile for age
• Loss of normal diurnal pattern
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Short-term treatment of acute hypertension
• Most common clinical indication is acute nephritis with salt and water retention; simple and welltolerated combination would be a loop diuretic, e.g. furosemide, plus a vasodilating Ca2+-channel blocker, e.g. nifedipine
• Phaeochromocytoma – α and β blockers, e.g. phenoxybenzamine + labetolol
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Severe hypertension with headache, vomiting, hyperreflexia, seizures • Principle of treatment is: • controllable reduction with intravenous infusions – labetolol; sodium nitroprusside • gradual reduction – end-organ damage, e.g. seizures often controlled before normal blood pressure is seen • risk of treatment is too rapid reduction causing stroke; cortical blindness
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risk of treatment is too rapid reduction causing stroke; cortical blindness
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Long-term treatment of chronic hypertension• Aim to use single agent if possible, and select long-acting once-daily agent to aid compliance, e.g. • β blocker – atenolol • Ca2+-channel blocker – amlodipine • ACE inhibitor – enalapril; logical choice for hypertension secondary to chronic renal disease (e.g. reflux nephropathy; FSGS); also has an anti-proteinuric effect; relatively contraindicated in renal artery stenosis
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How effectiveness of enuresis alarm assessed ❓❓
• Reassess after 4 weeks of use: • Continue with alarm if early signs of some response; if 2 weeks of consecutive dry nights, stop alarm; consider alarm use again if enuresis recurs
• Consider adding desmopressin if no sign of improvement
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What is the genetic of Autosomal recessive polycystic kidney disease (ARPKD) ad what are the effect on the kidney ❓❓
• Gene is on chromosome 6
• Tubular dilatation of distal collecting ducts, i.e. not true cysts
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Clinical presentation of ARPKD ❓❓
• Antenatal ultrasonography – large echobright kidneys; oligohydramnios
• At birth or early infancy – large palpable renal masses; respiratory distress secondary to
pulmonary hypoplasia
• At any time – signs and symptoms of chronic renal failure; hypertension – often very severe
• Median age for onset of end-stage renal failure around 12 years, although may cause severe renal failure in infancy.
• Always associated with congenital hepatic fibrosis, which may vary from subclinical to causing liver disease – the dominant clinical feature; complications include ascending cholangitis
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What is the genetic cause Autosomal dominant polycystic kidney disease (ADPKD) and what is the effect on the kidney ❓❓
• At least two gene loci; most common on chromosome 16 (adjacent to tuberous sclerosis gene); normal gene product is polycystin
• True cysts arising from tubules – get larger and more numerous with time and hence cause progressive decline in renal function
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What are the Clinical presentation of ADPKD ❓❓
• Antenatal ultrasonography – discrete cysts in fetal kidneys (note; always scan parents’ kidneys)
• Microscopic haematuria
• Hypertension; renal failure
• Incidental finding of renal cysts during abdominal ultrasonography – first cysts may not appear until patient is in 20s; may be unilateral
• Associated with cerebral aneurysms and subarachnoid haemorrhage
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What is Alport syndrome❓❓
Hereditary nephritis with sensorineural deafness and anterior lenticonus (conical deformity of lens of eye seen with slit-lamp)
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What is the mode of inheritance of Alport syndrome ❓❓
X-linked (most common) and autosomal recessive forms
💖X-linked – males affected; female carriers all have microscopic haematuria; with lyonization some females may develop hypertension and renal disease, but with milder and later onset
💖Autosomal recessive (chromosome 2) – both sexes equally severe
• Basic defect is in production of subunits for type IV collagen (two subunits coded for on X chromosome, two on chromosome 2); type IV collagen is located in kidney, eye and inner ear – hence the main clinical features
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What are the Clinical features of Alport syndrome ❓❓
Presents with incidental finding of microscopic haematuria, or episode of macroscopic haematuria
• Deafness around 10 years
• Hypertension in mid-teens
• Eye signs in mid–late teens (not before 12 years)
• Average age for end-stage renal failure is 21 years
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What is the genetic cause of Nephronophthisis❓❓
• Autosomal recessive condition; gene (called NPHP1) on chromosome 2
• Produces polyuria (concentrating defect), growth delay and often severe anaemia
• Urinalysis typically ‘bland’ – sometimes a trace of glucose
• Progresses to end-stage renal failure towards the end of the first decade
• Sometimes associated with tapetoretinal degeneration: Senior–Løken syndrome^
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Nephrocalcinosis Diffuse speckling calcification is seen on ultrasound scans or plain radiograph.
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main causes are:
• Distal RTA • Ex-premature neonates: • Furosemide – hypercalciuria • Steroids – hypercalciuria
• Vitamin D treatment for hypophosphataemic rickets: • Enhances tubular reabsorption of Ca2+
• Oxalosis: • Autosomal recessive disorder • Primary hyperoxaluria associated with defect in alanine:glyoxylate aminotransferase (AGT) enzyme, which leads to excess oxalate production and urinary oxalate excretion• Calcium oxalate precipitates, nephrocalcinosis and obstructing stones form, renal failure ensues • Systemic oxalosis – joints, heart, blood vessels
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• Treatment – liver transplantation alone if renal function only moderately reduced; sequential liver then kidney transplantation if renal failure established, with intense dialysis therapy between the two operations to lower the systemic oxalate burden (simultaneous liver–kidney transplantation presents high risk of oxalate deposition in newly transplanted kidney)
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Nephrolithiasis – stones
• Uncommon in paediatrics • Clinical presentation: • Painful haematuria • Revealed during investigation into UTI
• Important to undertake metabolic analysis of timed urine collection, or of stone itself if possible, because several metabolic diseases cause stones which may be recurrent
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What is the calcium distribution in the body ❓❓
40% protein bound (of which 98% is bound to albumin)
48% ionized
12% complexed to anions such as phosphate or citrate
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What are the Normal values of calcium ❓❓
2.1–2.6 mmol/l for total Ca2+ and 1.14–1.30 for ionized (Io) Ca2+
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What is the factor that affect the degree of calcium and albumin binding ❓❓
Degree of protein binding of plasma Ca2+ is proportional to plasma pH.
♂️♂️ Beware of correcting acidosis in renal failure, where total and ionized Ca2+ often already low.
Acute rise in pH with NaHCO3 treatment leads to ↑ protein-bound Ca2+ which leads to ↓ ionized Ca2+ and may cause tetany
• Monitoring of ionized Ca2+ is useful in intensive care patients, where changes in acid–base and albumin levels make interpretation of total plasma Ca2+ difficult
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Hypocalcaemia
The main symptoms are tetany, paraesthesiae, muscle cramps, stridor and seizures.
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Hypocalcaemia
💖Calcitriol (1,25(OH)2-D3) deficiency;
• Dietary deficiency of vitamin D
• Malabsorption of vitamin D – fat malabsorption syndromes
• Renal failure (acute and chronic) – 1-hydroxylase deficiency
• Liver disease – 25-hydroxylase deficiency
💖 Hypoparathyroidism;
• Transient neonatal
• DiGeorge syndrome – 22q11.2 deletion
• Post-parathyroidectomy
💖 Pseudohypoparathyroidism;
• Autosomal dominant; end-organ resistance to raised levels of PTH • Abnormal phenotype with short stature, obesity, intellectual delay, round face, short neck, shortened fourth and fifth metacarpals
💖Acute alkalosis (respiratory or metabolic) or acute correction of acidosis in setting of already reduced Ca2+
💖Hyperphosphataemia;
• Renal failure (acute or chronic)
Rhabdomyolysis; tumour lysis syndrome
💖Deposition of Ca2+; • Acute pancreatitis
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What is Treatment of hypocalcaemia ❓❓:
• Intravenous 10% calcium gluconate, 0.2 ml (0.045 mmol)/kg, diluted 1:5 with dextrose 5%, over 10–15 min with ECG monitoring; followed by intravenous infusion of 10% calcium gluconate at 0.3 ml (0.07 mmol)/kg per day
• Oral Ca2+ supplements
• Vitamin D, or the analogue alfacalcidol (1-hydroxycholecalciferol), for nutritional deficiency, hypoparathyroidism and renal failure
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What are the Causes of Hypercalcaemia❓❓
The main symptoms are constipation, nausea, lethargy and confusion, headache, muscle weakness, and polyuria and dehydration
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What are the Causes of Hypercalcaemia❓❓
❓Vitamin D therapy;
• Renal failure
• Dietary vitamin D deficiency
• Primary hyperparathyroidism; • Neonatal • Part of multiple endocrine neoplasia syndromes I and II
• Williams syndrome; • Heterozygous deletions of chromosomal sub-band 7q11.23 leading to an elastin gene defect in >90% (detected by fluorescent in situ hybridization [FISH] test) • Hypercalcaemia rarely persists beyond 1 year of age
• Familial hypocalciuric hypercalcaemia; • Inactivation of Ca2+-sensing receptor gene in parathyroid cells and renal tubules leads to an inappropriately high plasma PTH level and inappropriately low urine Ca2+
• Macrophage production of 1,25(OH)2-D3; • Sarcoidosis • Subcutaneous fat necrosis – prolonged or obstructed labour
• Malignant disease; • Treatment includes: • Intravenous hydration plus a loop diuretic • Correction/removal or specific treatment of underlying cause, e.g. steroids for sarcoidosis • Rarely, bisphosphonates
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Phosphate and hypophosphataemia
Phosphate is excreted from the kidney under the influence of parathyroid hormone (increases excretion) and calcitriol (decreases excretion). In hypophosphataemia, calculation of the tubular reabsorption of phosphate (TRP) is useful.TRP = 1–Fractional excretion of PO4 3– i.e. Normally, TRP >85%. If the TRP is <85%, in the presence of low plasma PO4 3– and a normal PTH level, this implies abnormal tubular leakage of PO4 3–.
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Hypophosphataemia • With appropriately high TRP, i.e. low urinary PO4
3– • Dietary PO4 3– restriction
• Increased uptake into bone – the ‘hungry bone syndrome’ seen after parathyroidectomy for prolonged hyperparathyroidism, or after renal transplantation with preceding hyperparathyroidism of chronic renal failure (CRF); see also Hypocalcaemia
• With inappropriately low TRP, i.e. high urinary PO4 3–
• Hypophosphataemic rickets – see Section 7.1 • Fanconi syndrome –
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Hyperphosphataemia • With high urinary PO4
3– • With low urinary PO4
• Tumour lysis syndrome, rhabdomyolysis – see also Oliguria, Hyperkalaemia 3–
• Chronic renal failure – see Section 11.3 • Hypoparathyroidism; pseudohypoparathyroidism
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Magnesium and hypomagnasaemia
Most filtered Mg2+ is reabsorbed in the distal proximal tubule and the loop of Henle. As with Ca2+, Mg2+ transport and NaCl transport are associated. Factors enhancing Mg2+ reabsorption include hypocalcaemia and raised PTH levels. Hypomagnesaemia is often found in patients with hypocalcaemia and hypokalaemia, and to correct these the magnesium deficiency must also first be corrected. The following are the main causes of hypomagnesaemia:
• Poor dietary intake • Reduced gut absorption • Increased urinary losses: • Recovery from acute tubular necrosis • Post-transplantation diuresis• Drug induced – loop and thiazide diuretics; amphotericin B; cis-platinum • Gitelman syndrome –
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How calcium level corrected for albumin ❓❓
• Albumin-corrected Ca2+ equals
measured total plasma Ca2+ + [(40 – albumin) × 0.02]
for example, if total Ca2+ is 1.98 and albumin is 26
corrected Ca2+ = 1.98 + [(40 – 26) × 0.02] = 2.26
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What is the distribution of water in the body ❓❓
60% of boy is water
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What is the difference between renat tubular acidosis type 1 and type 2 ❓❓
Defect
T1= impaired excretion of H+
T2= Failure to reabsorb filtered HCO3, low bicarbonate threshw
Urine PH
T1=>5.8 ie.never 'acid'
T2=Variable;may be<5.3
Serum k
T1=Usually low
T2=Normal or low
Causes
T1=Primary isolated RTA * Nephrocalcinosis * Obstructive uropathy * Amphotericin; cyclosporin
T2=primary isolated RTA
Transient Infentile
Fanconi syndrom
Clinical features
T1=Nephrocalcinosis * faltering growth * episodes of severe hypokalaemia
T2= vomiting *faltering growth* short stature
Response to NH4CL
T1=failure to acidify the urine
T2=production of acid urine
Response to NaHCO3
T1=no increase in urine - plasma P (co2) gradient
T2=normal increase in urine - plasma P (co2) gradient
♀️Treatment
T1=1-2 mmol/kg/day of NaHCO
T2=5-15 mmol/kg/day of HCO3;large dosesed to overcome lowrenal threshold
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