Renal Flashcards
Features ARPKD
AR- mutation in PKHD1 gene- fibrocystin/polducin (affects cilia of liver/kidney), 1/6,000-10,000
Present in first year of life/perinatally
Can lead to FDIU/Potter
Large kidney, hyperechoic, NO microcysts- mostly distal nephron/CD- dilation
- Progressive interstitial fibrosis, tubular atrophy
- HTN first week of life
Assoc renomegaly & ESRF
- Congenital hepatic fibrosis 45% liver involvement, fibrosis >portal HTN > Carolis disease
Rx: supportive, workup for transplant
70-80% 15yr survival, 30% die in neonatal, liver disease = poor prognisis
Features ADPKD
1/400-1000, polycystin 1&2 gene PKD1/2 (2 hit hypothesis = phenotypic variation)- most common heritable kidney disease
Present in 20s/30, <2% before 15
Cysts of variable sizes in cortex and medulla
HTN, poor concentrating ability
Assoc renomegaly & ESRF
Cysts in liver, pancreas, spleen
Intracranial aneurysms- 15%
12% mitral valve prolapse
Rx: supportive, avoid trauma/NSAIDS, ACEi for HTN
Good prognosis if diagnosed in late childhood
CKD by 60s- correlated to degree of HTN
Features simple renal cysts, other solitary masses as DDx?
Present in adulthood mostly, 50% >4yrs
Thin walled, no septation/calcification & often solitary/unilateral
25% increase with time and can cause rupture, infection, hemorrhage
Bosniak classification defines risk of malignancy
Rx vasopressin (dec cyst development), rapamycin, somatostatin, ACEi
Features nephronopthisis?
AR- 1/80,000, nephrocystins/NPHP1-9 gene (ciliopathy)
- Destruction of tubular BM, glomerular/tubular cysts
Present in childhood/adolescence
Polyuria& polydipsia- NORMAL BP
Juvenile most common (ESRF 13yrs), infantile worst prognosis (ESRF 3yrs), hepatic/cardiac/resp Cx
Assoc: retinitis pigmentosa, situs inversus, skeletal abn
NPHP8 = Joubert- cerebella hypoplasia, polydactyly/ Meckel Gruber- cleft, CNS malf, polydactyly
NPHP2 = infantile form encodes inversin 🡪 has glomerular AND tubular cysts, situs invertus
Features medullary sponge kidney?
1/5000-20,000, present usually in 30s
Cysts in CD/medulla
Not assoc renomegaly/ESRF
Features MCDK?
Kidney parenchyma replaced by cysts- does not function
Due to non-union of ureteric bud with mesenchyme
L>R, often unilateral (bilat incompatible with life)
Most common cause of abdominal mass
Sx: unilateral flank mass, UTI, haematuria/proteinuria- 1/3 have contralateral PUJ obstruction
Often involute over time
0.3% Wilms tumor transformation
Causes of Potter sequence (and definition)
Potter sequence: lack of amniotic fluid (oligohydramnios) + kidney failure
Causes
- Cystic renal dysplasia
- Obstructive uropathy
- Infantile ARPCKD
- Renal agenesis/aplasia (20% of cases)
- Medullary hypoplasia
- Prune belly syndrome (Xlinked abdominal muscle defect, pulm hypoplasia)
Causes of Potter sequence (and definition)
Potter sequence: lack of amniotic fluid (oligohydramnios) + kidney failure
Causes
- Cystic renal dysplasoa
- Obstructive uropathy
- Infantile ARPCKD
- Renal agenesis/aplasia (20% of cases)
- Medullary hypoplasia
Associations with horseshoe kidney?
Most fused in midline/isthmus
- Turner (7% cases will have)
- Trisomies 21,13,18
- VACTERL
- 4x risk of Wilms tumor
Most common cause of antenatally detected hydronephrosis?
PUJ obstruction
- 1/400 births, M>F, 60% L) sided
- Assoc: CHARGE, horseshoe kidney
- Sx: intermittent flank/abdo pain, worse with diuresis
- DTPA scan to investigate
Needs pyeloplasty if split func <40%, increasing HN, symptomatic or patient preference
Renal scans & function
DMSA- scarring
DTPA - compare split kidney function, GFR measurement, upper pole obstruction (PUJ)
MCUG- inject dye into bladder via cath, lower pole obstruction (gold standard for VUR)
Medullary Cystic Kidney Disease (ADTKD)
AD condition- cysts affecting tubulointerstitium
Slow decline 20-70yrs to ESRF
UMOD gene- most common- gout in teenage years
REN gene mutation- rare, hypotension & CKD
Mucin1- 30% of cases
Outline causes/Ix of hyponatremia?
- Hypovolemic & appropriate ADH response
- Decrease in salt > decrease in water
- GI losses (Na+ pumped into GIT)
- Diuretic use
- Renal salt wasting (Bartter/Gittelman, 21-OH, hypoaldosteronism)
- Cerebral salt wasting (like SIADH with hypovolemia- due to CNA tumor/surg/infec)
- Exercise, CF with insensible salt losses - Normovolemic & inappropriate ADH
- Increase in water
- Resp/CNS disease
- Hypothyroid, cortisol deficiency
- AVPR2 mutation
- Cyclophosphamide, vincristine, valproate, CBZ (^ ADH sensitivity in kidneys)
- Urine osmol >100 = SIADH
- Urine osmol <100 = adrenal insuff/polydipsia - Hypervolemic
- Fluid higher than solute (in ECF)
- ADH/Aldo activated as low plasma volume
- Organ failure- oedema, water retention
Pseudo
- Normal body water/sodium
- Excess lipids/proteins
- ie hypertrig/MM
Sx: N&V, cramps, confusion/coma (cerebral oedema)
Rx:
- Hypovolemia= Saline bolus
- SIADH = fluid restrict
- Severe = Hypotonic saline 0.45% (carefully to avoid cerebral pontine myelosis)
Outline causes/Ix hypernatremia?
- Water loss > Na
- Diarrhoea (hyperosmolar rehydration), severe burns
- Decreased intake
- Impaired thirst
- DI= decreased ADH: central (hypothalamus), vs nephrogenic
- Osmotic diuresis
- Insensible losses, ^ temperature - Gain of sodium
- Excess ingestion, iatrogenic
Rx:
Central DI = desmopressin
Nephrogenic = thiazide diuretic
Slow correction of fluids (2/3rds maintainence) to avoid cerebral oedema
Nephrogenic vs Central DI test?
Differentiate with water deprivation test
- Central: Urine osmolality lower than serum, >50% increase after DDAVP
- Nephrogenic: urine <2x plasma osmolality, minimal increase after DDAVP <9%
Cause of short stature in CKD?
- Elevated GH/resistance
- Decreased insulin-like growth factor 1 levels and major abnormalities of insulin-like growth factor–binding proteins.
Leads to short stature
If <2SD can trial GH
Difference between Bartter & Gitelman Sx?
Bartter’s and Gitelman are salt-losing nephropathies resulting in hypokalaemia and metabolic alkalosis
(both AR)
Gitelman (MAg)
- Presents later in life, muscle spasms, nocturia/polyuria
- Blood:, Low Mg2+,
- Urine: High Mg2+, low Ca2+
- Similar to thiazide diuretic- NaCl cotransporter
Bartter
- Present childhood: polyuria & dehydration, FTT
- Blood: High renin/aldosterone & PGE
- Urine: High Ca+
- Similar to loop diuretic NK2Cl
- Nephrocalcinosis
Dent’s disease genetics, Sx & Rx?
Inherited tubulopathy
X-linked
CLC5/OCRL1 (Lowe)
- Prox tubulopathy (RTA2): LMW proteinuria, Fanconi syndrome – glycosuria, aminoaciduria, phosphaturia
- Stones & hypercalciuria
- Hypophosphatemic Ricketts
- ESRF
Rx: Low NaCl, vit D/PO4, replace Na/K/H20
Gordon Syndrome
Excessive NCCT-mediated salt reabsorption with the clinical picture of pseudohypoaldodosteronism type 2
- Low Na
- High K+
Types of RTA
ALL have hyperchloremic acidosis
Type 1 = Distal (decreased H+ secretion)
1. Primary: HCO3-Cl cotransporter, H+ pump, carbonic anhydrase deficiency, some may have SNHL
2. Secondary: AIN, amphoB/lithium, Marfan/EDS, SLE/Sjogren
Sx: STONES, high urine pH, , low/N K+, low serum HCO3
Rx: alkali therapy
Type 2 = Proximal (decreased HCO3 reabsorption)
1. Primary: AD- Na/HCO3 cotransporter, AR- carbonic anhydrase 2
2. Secondary: Cystoniosis, PNH, Wilsons, Tyrosinemia, topiramate
Sx: FTT, polyuria, constipation, ricketts
Low urine pH, plasma HCO3 high, low K- worsens with Rx
Rx: alkali therapy
Type 4 = Decreased Aldosterone
1. Primary: eNAC/hypoaldosteronism
2. Secondary: spiro/amiloride
Sx: Polyuria, dehydration, CKD, low urine pH, high K+, high serum HCO3
R’ship between WAGR/Denys-Drash
Both WT1/PAX6 gene on 11p13 gene
Deletion in:
- WT1 = Wilms (50% chance of tumor)
- PAX6 = Aniridia
WAGR = Wilms, Aniridia, Gu abnormalities, Retardation/dev delay
Denys-Drash = renal nephropathy, Wilm’s, gonadal dysgenesis
Prevalence of nocturia at 5,7,15yrs
5 yrs = 15%
7yrs = 10%
5% 15yrs
1% adults
Most common cause of atypical HUS?
50-70% complement gene mutations
- C3, CD46, complement factors- H,B,I
