SM 217 Pediatric Nephrology Flashcards
What is the Pronephros in development?
Simple tubes
When is the Pronephros present in development?
The Pronephros is present 3 weeks EGA
What is the Mesonephros in development?
Filtering units and glomeruli with tubules that eventually degenerate into the Wolffian duct; formed caudal to the Pronephros at 4 weeks EGA
What forms the Ureteric bud?
Mesonephros
When is the Mesonephros present in development?
The Mesonephros is present 4 weeks EGA
What does the Ureteric bud do and when?
At 5 weeks EGA, the Ureteric bud invades the surrounding mesenchyme and begins signaling at the tips of it’s expansion to convert Metanephric Mesenchyme into renal epithelia
What is reciprocal signaling in the developing signaling?
Bidirectional signaling between the Ureteric Bud and the Metanephric Mesenchyme that allows for renal branching and the development of collecting ducts, renal pelvis, etc.
What embryonic structure forms the renal collecting ducts, pelvis, and ureters?
The Ureteric bud
What embryonic structure forms the glomeruli, proximal tubule, loop of Henle, and distal tubules?
The Metanephric Mesenchyme
When do the first glomeruli form and when have they all formed?
The first glomeruli forms at 9-10 weeks, and they form exponentially until development is complete at 32-36 weeks
What are CAKUT?
Congenital Anomalies of the Kidney and Urinary Tract - the main cause of ESRD in pediatric populations
What is renal agenesis?
Failure of the Ureteric bud to form or induce the Metanephric Mesenchyme, leading to Apoptosis
What is the most common CAKUT?
Hydronephrosis
What causes Hydronephrosis?
Vesicoureteral reflux
What are other, less common CAKUTs?
Renal cysts and renal dysplasia
What are the major causes of CKD/ESRD in adults?
Diabetic Nephropathy, HTN, ADPKD
Are the major causes of CKD/ESRD the same in adults and kids?
Nope
What are the major causes of CKD/ESRD in kids?
Wide differential, including: Renal aplasia/dysplasia, FSGS, Obstructive Uropathy
What are the complications of CKD in kids?
Impaired growth Anemia HTN Bone Disorders CV Risk Cognitive Development/Transition to Adult Care
How does CKD impair growth in kids?
Since 1/3rd of growth occurs in the first 2 years of life, infants with CKD have stunted growth due to malnutrition, metabolic acidosis, and mineral/bone disorders
How is impaired growth in kids with CKD treated?
Treatment of acidosis
Nutritional support via G-tube feeds
Growth Hormone therapy
How does anemia progress in kids with CKD?
Higher stages of CKD have a higher prevalence of anemia in CKD
What causes anemia in CKD in kids?
Decreased production of Erythropoietin and iron dysregulation in the kidney
How is anemia in CKD in kids treated?
Iron supplementation + recombinant human erythropoietin
How does HTN manifest in kids with CKD?
HTN effects more than half of kids with CKD and resists anti-hypertensive medications, is often masked, and is a major risk factor for CV mortality and LV Hypertrophy
How should HTN be managed in kids with CKD?
Intensified BP control to < 50th percentile for age/height is better, and ambulatory blood pressure monitoring is required
How do mineral bone disorders manifest in CKD in kids?
Dysregulation of the Ca/Phos/PTH/FGF23 axis leads to bone growth issues and vascular calcifications
How are bone disorders in kids with CKD managed?
Try and lower serum Phosphorus and PTH levels with:
Dietary restrictions Phosphorus binders (taste awful) Vit D Supplements
What causes CV risk and mortality in kids with CKD?
Compounded effects of other CKD manifestations such as HTN/LV Hypertrophy, bone disorders, and anemia
What is the leading cause of death in the pediatric CKD population?
Cardiovascular mortality
What forms the comma-shaped body and s-shaped body during kidney development?
The Metaneprhic Mesenchyme
What is Renal Dysplasia?
Irregular signaling between the Metaneprhic Mesenchyme and the Ureteric Bud
What could cause Renal Hypoplasia?
Premature birth
What can cause hydronephrosis?
UVJ obstruction
What could cause bilateral hydronephrosis?
A posterior uretrhal valve in the bladder
How do genetic factors contribute to the development of CAKUT?
Large combination of genetic factors of varying modes of inheritance
What determines the severity of CKD in kids?
Age of onset, primary renal disease (systemic disease is worse), metabolic acidosis, and malnutrition + anemia/bone disorder/growth distrubances
Why is sodium tricky in kids with CKD?
Traditional CKD management in adults focuses on low sodium, but in kids, some sodium is needed for development
How do CV causes of death differ between adults and kids with CKD?
Adults with CKD have CHF and atherosclerosis
Kids with CKD have arrythmyias, cardiomyopathy, medial calcifications
Kids with CKD have CV risk with less warning signs
How does CKD effect cognitive development in kids?
CKD leads to low cognitive ability and quality of life, as well as low social development due to short stature
Why is there a high risk period of transition to adult care in kids with CKD?
Adolescents have poor judgment as is, and this can lead to treatment non-adherence with most kidney transplants failing between 17 - 24 years of age
What are renal ultrasound and VCUG used for?
Searching for hydronephrosis and renal enlargement
Why might UTI’s be concerning in kids with CKD?
UTI may indicate urinary tract obstruction or posterior urethral valves, which can have long term consequences such as repeated infections
What is VUR?
Vesicoureteral Reflux, the retrograde flow of urine from the bladder into the ureters which predisposes UTI and hydronephrosis
What are consequence of recurrent UTI in kids with CKD?
Renal scars, hypertension, and CKD (due to whatever is causing the recurrent UTI’s, not the UTI’s themselves)
What factors should be considered in interpreting gross hematuria?
Timing: part of stream = urinary tract, full stream = kidney
Color: Red/Pink = urinary tract, brown = kidney
Pain: Painful = urinary tract, painless = kidney
How should microscopic hematuria be interpreted in kids with CKD?
More concerning in the presence of proteinuria and a family history of kidney failure/kidney stones
What defines remission of nephrotic syndrome?
Proteinuria < 3.5mg/day for 3 consecutive days with resolution of edema
What defines relapse of nephrotic syndrome?
Proteinuria > 3.5mg/day for 3 consecutive days with resolution of edema
What is the most common cause of nephrotic syndrome in kids?
Minimal Change Disease
What are the types of Steroid Sensitive Nephrotic Syndrome?
Steroid Dependent NS
Frequently Relapsing NS
What is Steroid Resistant Nephrotic Syndrome?
Failure to achieve remission after 4 weeks of prednisone, suggesting steroid resistant MCD or something else like Membranous Nephropathy
What is the DDx for kids with Nephrotic Syndrome?
MCD FSGS Membranous Nephropathy Congenital Nephrotic Syndromes Familial Nephrotic Syndromes
What are complications of Nephrotic Syndrome in kids?
Hypogammglobulinemia
Loss of anticoagution factors
AKI
What infections are kids with Nephrotic Syndrome predisposed to and why?
Loss of immunoglobulins = risk for Pneumococcal infections
How do complement levels change in PSGN?
Low C3, normal C4
How do complement levels change in Lupus and MPGN?
Low C3, Low C4
How could PSGN and IgA Nephropathy be differentiated by timing?
IgA Nephropathy occurs during or shortly after a mucosal infection, while PSGN occurs 2 weeks after a pneuomococcal infection
What is an abscess?
Chronic bacterial infection
Which GN have low complement levels?
PSGN
MPGN
Lupus
Which GN have normal complement levels?
IgA Nephropathy
ANCA-associated GN
What is Henoch Schonlein Purpura?
A vascular infection that presents with normal complement levels and hematuria and nephrotic range proteinuria
How do MPA and GPA differ with respect to granulomas?
GPA has necrotizing granulomas in the airways + kidneys while MPA is non-granulomatous in the vasculature
What can suggest Hemolytic Uremic Syndrome in kids?
Bloody diarrhea
Is Eculizumab indicated for D-HUS or aHUS
Eculizumab is a C5 convertase inhibitor, so it is indicated for aHUS (driven by defects in the CRP) and not D-HUS
What diseases can cause a HUS-like syndrome in kids (ie DDx)?
Pneumococcal-associated HUS (due to Neuraminidase) Atypical HUS (recurrent episodes)
Which type of HUS uses the MAC to cause damage?
aHUS, since it is driven by complement and can form the MAC to damage cells
How does medullary sponge kidney present?
Neprholithiasis, collecing duct dilation
Is Multycystic Dyplastic Kidney Disease symptomatic and bilateral?
Nope, unilateral and asymptomatic
What gene mutation and gene product cause ARPKD?
ARPKD is driven by mutations in PKHD1 and result in altered production of Fibrocystin, with the different mutations setting severity of disease
Are ADPKD and ARPKD unilateral or bilateral?
ADPKD and ARPKD are bilateral
Which causes hepatic fibrosis and portal hypertension, ADPKD or ARPKD?
ARPKD effects the liver and causes fibrosis as well as hepatic hypertension
Which causes compressed lungs, ADPKD or ARPKD?
ARPKD has much larger kidneys and causes compressed lungs
Which causes ESKD earlier, ADPDK or ARPKD?
ARPKD causes ESKD much earlier, in utero or early childhood, while ADPKD causes kidney failure in adulthood
How is ADKPD diagnosed?
Ultrasound
What is Nephronophtisis?
An Autosomal Recessive ciliopathy caused by mutation in NPHP genes, associated with eye disease and leads to ESKD
What is Primary Hyperoxaluria?
Mutation in AGXT gene that leads to systemic overproduction of oxalate and kidney failure
What is Nephropathic Cystinosis?
Autosomal Recessive lysosomal storage disorder caused by mutation in CTNS gene that leads to proximal RTA, treated with Cysteamine
What characterizes Multicystic Dysplastic Kidney?
No functional kidney tissue
How many RBC’s need to be seen on a microscopic urinalysis to define microscopic hematuria?
5+
What defines a nephrotic range protein-creatinine ratio?
2-3 or more
How can IgA Nephropathy and PSGN be differentiated?
IgA Nephropathy does not effect Complement levels while PSGN has low C3
