Glomerular and Cystic Kidney Disease Flashcards
Functional Role of the Kidney
control the balance of water in the body
control red blood cell production (erythropoietin)
control acidity of the blood
filter blood and pass waste products for excretion
control blood pressure (RAAS)
What is the average urine PHYSIOLOGIC protein excretion in adults
~80mg/day
What level of protein excretion qualifies as PATHOLOGIC proteinuria
150mg or greater over 14 hours
Albumin
smallest plasma protein
20-40% of physiologic proteinuria
filtered more readily than other globulins/plasma proteins
Microalbuminuria
excretion of 30-300 mg/day of albumin
too small to be detected by routine dipstick screening
Macroalbuminuria
excretion of albumin >300mg/day
Nephrotic range proteinuria
daily excretion of 3.5+g of protein
Glomerular Disease
MCC of pathologic proteinuria
alteration of glomerular permeability –> injury to podocytes, BM, capillary endothelium, mesangium –> pathologic proteinuria
initially: excess albumin
eventual progression to larger proteins
Overflow Proteinuria
overproduction of smaller proteins overwhelms reabsorptive ability of proximal tubule –> pathologic proteinuria
Tubular Proteinuria
tubulointestinal disease –> diminished reabsorptive capacity of the proximal tubule –> pathologic proteinuria
Classifications of Glomerular Disease
nephritic or nephrotic
primary or secondary
Glomerular Disease
cause some degree of glomerular damage
urinary loss of proteins –> hypoalbuminemia
DEFINITIVE DIAGNOSIS/GOLD STANDARD: biopsy
Nephritic Syndrome: definition
inflammatory process w/ associated immunologic response –> renal glomeruli damage –> blood cell passage
Nephritic Syndrome: clinical presentation
edema (IS THIS EXTREMITY OR FACE) hematuria (coca cola urine) (dysmorphic RBC and casts) occasional WBC subnephrotic proteinuria HTN azotemia rising creatinine oliguria
Rapidly Progressive Glomerulonephritis
severe injury to glomerular capillary wall, GBM, Bowman’s capsule
most severe of the nephritic spectrum
progresses to renal failure in wks/mos
Nephritic Syndrome: Primary
post infectious glomerulonephritis
IgA nephropathy
Henoch Schonlein purpura
Pauci immune glomerulonephritis (ANCA assn)
anti glomerular BM glomerulonephritis (good pastures)
Post Infectious Glomerulonephritis
group A beta hemolytic streptococci
immune mediated glomerular injury - deposition of immune complexes
1-3wk after strep infxn (pharyngitis, impetigo)
Post Infectious Glomerulonephritis: clinical presentation
oliguria
edema
variable hypertension
coca cola urine
UA: RBCs, red cell casts, proteinuria
ASO titer high (unless blunted by abx)
Post Infectious Glomerulonephritis: prognosis
children: good
adults: less favorable (severe disease RPGN, develop CKD)
Post Infectious Glomerulonephritis: Treatment
treat underlying infxn
supportive
- anti hypertensives (ACE-I, ARB)
- salt restriction
- diuretics (loop)
**steroids are of no benefit
IgA Nephropathy
aka Berger’s disease
IgA deposition in glomerular mesangium –> inflammatory response
MC primary glomerular disease world wide
children, young adults
M>F
IgA Nephropathy: clinical presentation
variable
follows URI or GI infxn
hematuria (coca cola urine 1-3d from illness onset)
proteinuria
INC IgA levels
NORMAL complement levels
IgA Nephropathy: prognosis
1/3: spontaneous remission
20-40%: CKD
remainder: chronic microscopic hematuria + stable creatinine
most unfavorable prognostic indicator:
proteinuria > 1g/d
IgA Nephropathy: Treatment
corticosteroids (if proteinuria 1-3.5g/d)
ACE-I or ARB (if severe proteinuria)
target BP: <130/80
Henoch Schonlein Purpura
systemic small vessel associated w/ IgA deposition in vessel walls
children
assn w/ inciting infxn (group A strep)
Henoch Schonlein Purpura: clinical presentation
palpable purpura in LE and buttock
arthralgias
abdominal sx (nausea, colic, melena)
dec GFR (w/ nephritic presentation – some may have enough damage that leads to nephrotic)
Henoch Schonlein Purpura: treatment
no definitive treatment
**some successful indications w/ plasma exchange (plasmapheresis) and DMARDs
DMARDs: disease modifying antirheumatic drugs
Pauci-Immune Glomerulonephritis
ANCA associated
seen w/ small vessel vasculitis
- granulomatosis w/ polyangiitis
- eosinophilic granulomatosis w/ polyangiitis
- microscopic polyangiitis
Pauci-Immune Glomerulonephritis: clinical presentation
fever
malaise
weight loss
purpura
granulomatosis w/ polyangiitis:
- respiratory tract sx
- nodular lesions that can bleed
Pauci-Immune Glomerulonephritis: diagnostics
Labs:
- ANCA positive (antineutrophil cytoplasmic antibodies)
- hematuria
- proteinuria
Pauci-Immune Glomerulonephritis: treatment
high dose corticosteroids
DMARDs
Anti-Glomerular Basement Membrane Glomerulonephritis
aka goodpasture syndrome
glomerulonephritis + pulmonary hemorrhage
BM injury from anti GBM antibodies
1/3: no lung injury
2/3: lung injury
Anti-Glomerular Basement Membrane Glomerulonephritis: epidemiology
bimodal peak incidence
2nd-3rd decade
6th-7th decade
Anti-Glomerular Basement Membrane Glomerulonephritis: clinical presentation
preceded by URI
hemoptysis
dyspnea
RPGN
Anti-Glomerular Basement Membrane Glomerulonephritis: diagnostics
Labs:
- hemosiderin laden macrophages in sputum
- anti-GBM antibodies
CXR:
-pulmonary infiltrates
Anti-Glomerular Basement Membrane Glomerulonephritis: treatment
plasma exchange therapy (plasmapheresis)
-removes circulating antibodies
immunosuppresive drugs (corticosteroids, DMARDs)
- prevents formation of new antibodies
- controls inflammatory response
Nephrotic Syndrome
significantly inc BM permeability
Nephrotic Syndrome: essentials of diagnosis
urine excretion 3.5+g/24hr
hypoalbuminemia (serum albumin <3g/dL)
bland urinary sediment (oval fat bodies)
peripheral edema
hyperlipidemia
Nephrotic Syndrome: clinical presentation
PERIPHERAL EDEMA:
- serum albumin <2 g/dL
- Na retention
- initially presents in dependent areas of the body (LE)
DYSPNEA:
- pulmonary edema
- pleural effusion
- diaphragmatic compromise from ascites
Nephrotic Syndrome: urinalysis findings
proteinuria
oval fat bodies (associated w/ marked HLD)
Nephrotic Syndrome: blood chemistry findings
dec serum albumin (<3 g/dL)
dec total serum protein (<6g/dL)
HLD
(inc proteinuria –> fall in oncotic pressure –> inc lipid production –>
dec VLDL clearance –> hypertriglyceridemia
dec vitamin D, zinc, copper
Nephrotic Syndrome: protein loss considerations
daily total dietary protein intake should replace the daily urinary protein losses to avoid negative nitrogen balance
protein malnutrition can occur w/ urinary protein loss >10g/d
Nephrotic Syndrome: edema considerations
dietary salt restriction
utilize thiazide and loop diuretics (combination, high dose)
Nephrotic Syndrome: HLD considerations
encourage dietary modifications and exercise
aggressive pharmacologic thearpy
Nephrotic Syndrome: hypercoaguable state considerations
serum albumin < 2 –> hypercoaguable
low antithrombin III, protein C, protein S –> inc platelet activation
prone to renal vein thrombosis
Nephrotic Syndromes
minimal change disease
membranous nephropathy
focal segmental glomerulosclerosis
Minimal Change Disease: pathogenesis
inc levels of glomerular permeability
foot process effacement
Minimal Change Disease: epidemiology
MC in children
boy>girl
adults: M=F
Membranous Nephropathy
MCC of primary nephrotic syndrome in adults
idiopathic immune mediate glomerulopathy
immune complex deposition in glomerular capillary walls –> inc permeability
Membranous Nephropathy: clinical presentation
variable
asymptomatic
EDEMA W/ FROTHY URINE
high incidence of venous thromboembolism
Membranous Nephropathy: diagnostics
Labs:
subnephrotic (<3.5 proteinuria) to classic nephrotic (>3.5 proteinuria) syndrome
Membranous Nephropathy: treatment
ACE-I or ARB
(if BP >125/75)
(reduces urine protein levels)
Corticosteroid therapy
(nephrotic syndrome only)
(if failure to improve w/ 6 mo of conservative treatment)
Focal Segmental Glomerulosclerosis
inc permeability due to podocyte injury
primary or secondary renal disease
Focal Segmental Glomerulosclerosis: primary renal disease
idiopathic
some genetic
altered podocyte formation
african descent
children
Focal Segmental Glomerulosclerosis: secondary renal disease
obesity HTN chronic urinary reflex HIV infection analgesic exposure biphosphonate exposure
Focal Segmental Glomerulosclerosis: clinical presentation
proteinuria
most w/ overt nephrotic syndrome
Focal Segmental Glomerulosclerosis: treatment
diuretic (edema)
ACE-I or ARB (proteinuria, HTN)
statin (HLD)
high dose corticosteroid (primary, overt nephrotic)
Renal Cyst Development
genetic (autosomal dominant polycystic kidney disease) and non-genetic process
childhood and adulthood diseases (acquired renal cysts secondary to chronic renal failure)
Renal Cyst Categorization
size location septations calcifications contents enhancement
Simple Renal Cyst
65-70% of all renal masses
observed in normal kidneys
MC incidental finding
little clinical significance
incidence inc w/ age
M>F
no clinical manifestations
Simple Renal Cyst: characteristics
develop in cortex and medulla
solitary/multiple
unilateral/bilateral
<1cm->10cm
round/oval
lined by single epithelial layer
fluid filled
clear to straw colored fluid
Simple Renal Cyst: potential complications
obstruction of calyxes or renal pelvis
rupture
(flank pain, hematuria)
infection –> renal abscess
(insidious fever, vague lumbo-abdominal pain, +/-hematuria or pyuria)
hypertension
(compression of renal parenchyma –> angiotensin dependent HTN)
Simple Renal Cyst: US criteria for simple cyst
sharply demarcated w/ smooth thin walls
no echoes (anechoic) w/in mass
enhanced back wall indicating good transmission through the cyst
Simple Renal Cyst: US criteria for complex cyst
thick walls and/or septations
calcifications
solid components
mixed echogenicity
vascularity
Simple Renal Cyst: diagnostics
first line: US
CT w/ and w/out contrast if US is equivocal or c/w complex cyst
Bosniak Classification of Renal Cysts: Category I
sharply demarcated w/ smooth thin walls
homogenous fluid
no contrast enhancement
simple cyst
benign
image in 6-12 months
Bosniak Classification of Renal Cysts: Category II
closely resemble simple cyst few thin septa few calcifications <3cm diameter, well marginated no contrast enhancement
complex cyst
benign
imagine in 6-12months
Bosniak Classification of Renal Cysts: Category IIF
more complicated than II
multiple thin septa
thickened walls, calcifications
>3cm diameter
complex cyst
likely benign (5% malignant)
repeat imaging in 3-6months
Bosniak Classification of Renal Cysts: Category III
indeterminate cystic masses
thickened irregular walls or septa
measurable enhancement
complex cyst
40-60% malignant
monitor in older patients
excise in younger patients
Bosniak Classification of Renal Cysts: Category IV
category III + soft tissue enhancing components adjacent to cyst wall
complex cyst
85-100% malignant
Acquired Renal Cysts
MC reason: chronic renal failure
inc risk of development w/ dialysis
inc incidence w/ duration of dialysis
may inc RCC risk
Acquired Renal Cysts: diagnostic criteria
bilateral involvement
> 4 cysts
<0.5-2/3cm diameter
Acquired Renal Cysts: clinical presentation
small to normal sized kidneys
asymptomatic
Acquired Renal Cysts: screening consideration
yearly screening after 3-5yrs of dialysis
US vs. CT w/ and w/out contrast
Simple or Complex Renal Cyst: treatment
excision (Bosniak classification)
acute/intermittent pain:
- acetaminophen
- NSAID
persistent pain:
- percutaneous aspiration w/ injection of sclerosing agent
- laparoscopic unroofing
Autosomal Dominant Polycystic Kidney Disease: etiology
autosomal dominant
- PKD1 mutation: aggressive, MC
- PKD2 mutation: slow growing
5% spontaneous
mutation –> obstructed tubules –> cyst formation –> fluid accumulation –> enlargement –> separate from nephron –> compression of neighboring renal parenchyma –> progressive compromise of renal function
Autosomal Dominant Polycystic Kidney Disease: clinical presentation
clinically silent
irreversible decline in renal function (begins in 4th decade)
HTN
pain
hematuria (microscopic)
proteinuria
Autosomal Dominant Polycystic Kidney Disease: initial presentation
30’s-40’s
pain
(abdominal, flank, back, chest, combination)
large palpable kidneys
frequent UTIs or recurrent nephrolithiasis
Autosomal Dominant Polycystic Kidney Disease: diagnostics
US
(for screening and monitoring)
Labs: CBC CMP UA genetic screening
Autosomal Dominant Polycystic Kidney Disease: associated manifestations
hepatic cysts (estrogen sensitive)
pancreatic/splenic cysts
cerebral aneurysms
mitral valve prolapse
colonic diverticula
Autosomal Dominant Polycystic Kidney Disease: treatment
no definitive treatment
treat HTN
- ACE-I or ARB
- low Na diet
- limit caffeine consumption
pain management
avoid nephrotoxic agents
avoid contact sports
manage complications
ESRD - dialysis or kidney tranplant
UTI - quinolones
Medullary Sponge Kidney
congenital disorder
MC: sporadic w/ no FH
rare: familial autosomal dominant
not diagnosed until 4th or 5th decade
Medullary Sponge Kidney: clinical presentation and characteristics
asymptomatic
characterized by:
- dilation of collecting tubules
- medullary cysts
Medullary Sponge Kidney: complications
nephrolithiasis UTI hematuria dec urinary concentrating ability renal insufficiency
Medullary Sponge Kidney: diagnostics
intravenous pyelography (brush/linear striations, radiating outward from calyces)
multidetector row CT
Medullary Sponge Kidney: treatment
no known therapy
good hydration
thiazide diuretiv (if hypercalciuria)
abx (for UTI)
Medullary Cystic Disease
aka nephronophthisis
autosomal recessive
infantile, juvenile and adolescent forms
progression to ESRD, generally before 20 years of age
Medullary Cystic Disease: characteristic findings
reduced urinary concentrating ability
(bland urinary sediment, polyuria, polydipsia)
chronic tubulointerstitial nephritis w/ renal cysts after age 9
Medullary Cystic Disease: diagnosis
clinical
extrarenal manifestations (retinitis pigmentosa)
genetic testing
US
(normal-slight dec in kidney size)
(inc echogenicity w/ loss of corticomedullary differentiation)
Medullary Cystic Disease: treatment
no specific treatment
supportive care
