NEPHROLOGY Flashcards
Management of Minimal Change Disease
- Corticosteroid
- Tuberculosis must be first ruled out
- Uncomplicated nephrotic syndrome between 1-8yo are likely to have steroid responsive MCNS
- Initiate steroids even without biopsy
- Do biopsy if with features less likely of MCNS
- Gross hematuria, hypertension, renal insufficiency, hypocomplementemia, < 1yo or > 12yo
- Prednisone or Prednisolone (60mg/BSA/day or 2mg/kg/day, max 60mg daily) for 4-6 weeks
Linear IgG and C3 on Immunofluorescence is seen in
Goodpasture syndrome
Children who fail to respond to prednisone therapy within 8 week
Steroid resistant
Cloudy urine
can be normal; due to crystal formation at room temp.
In APSGN, what major noxious products of complement activation are produced after C3 activation?
anaphylatoxin (increases vascular permeability) & C5a (release substances that damage cells & basement membranes)
The most common cause of gross hematuria in pediatric population is?
Urinary Tract Infection
Relapse within 28 days of stopping prednisone therapy
Steroid dependent
Nephrotic Syndrome most responsive to steroids
Minimal Change DIsease
GRANULAR IgG, C3 on Immunofluorescence is a characteristic of
APSGN
Triad of Hemolytic Uremic Syndrome
- Microangiopathic Hemolytic Anemia (mechanical damage to RBCs as they pass through damaged endothelium)
- Thrombocytopenia (d/t intrarenal platelet adhesion or damage)
- Uremia
- Onset is preceded by gastroenteritis (fever, vomiting, abdominal pain, bloody diarrhea)
- Sudden onset of pallor, irritability, weakness, lethargy & oliguria usually occurs 5-10 days after the initial gastroenteritis or respiratory illness
- PE: dehydration, petechiae, hepatosplenomegaly, marked irritability
- Peripheral smear: helmet cells, burr cells, fragmented RBCs
- Increased reticulocyte count, negative Coombs test, leukocytosis, thrombocytopenia, anemia, hematuria & proteinuria, normal PT & PTT, stool culture is often negative
- Supportive care: fluids & electrolytes, early institution of peritoneal dialysis, BP control, red cell transfusion
- Platelets NOT generally administered regardless of platelet count (almost immediately consumed by active coagulation and can worsen the clinical course)
- NO antibiotic therapy (can lead to increased toxin release)
Laboratory criteria for diagnosis of TTP
The following are both present at some time during the illness:
- Anemia (acute onset) with microangiopathic changes (schistocytes, burr cells, helmet cells) on peripheral blood smear
- Renal injury (acute onset) evidenced by hematuria, proteinuria, or elevated creatinine level: equal or > 1 mg/dL in < 13 years old or >1.5 mg/dL in > 13 years old or equal or >50% increase over baseline
- The urinalysis reveals 3+ or 4+ proteinuria
- Spot urine protein/creatinine ratio exceeds 2.0 and urinary protein excretion exceeds 3.5 g/24 hr in adults and 40 mg/m 2 /hr in children.
- The serum albumin level is generally <2.5 g/dL, and the serum cholesterol and triglyceride levels are elevated.
- C3 and C4 levels are normal.
- Renal biopsy is not required for diagnosis in most children.
• >95% respond to corticosteroid therapy
NEPHROTIC SYNDROME (MINIMAL CHANGE DISEASE)
In APSGN, When wil microscopic hematuria resolve and normalize?
1-2 years
Best single Ab titer to document skin infection s DNAse B antigen
DNAse B antigen
Nephrotic Range 24 hr urine protein
Nephrotic range > 40mg/m2 /hr
o Normal is = 4mg/m2/hr
o Abnormal 4-40mg/m2/hr
NEPHRITIC SYNDROMES
- PSGN
- RPGN
- IgA Nephropathy (berger disease)
- Alport Syndrome
- GoodpastureSyndrome
- MPGN - Nephrotic/Nephritic
- SLE - Nephrotic/Nephritic
In PSGN, C3 sould normalize within ___
8 weeks
Children who continue to have proteinuria (+2 or greater) after 8 week of steroid therapy
Steroid resistant
BOTTOM-UP approach - identify upper and lower tract abnormalities
UTZ then VCUG then DMSA
In APSGN, patient develops nephritic syndrome how many weeks after skin infection?
3 - 6 weeks
Subepithelial humps are seen in
PSGN
Diffuse mesangial deposits are seen in
IgA nephropathy
Detect posterior urethral valves
VCUG
In APSGN, patient develops nephritic syndrome how many weeks after throat infection?
1-2
Renal parenchyma is involved in what type of UTI?
Pyelonephritis
Documentation of prior strep infection on the skin
antideoxyribonuclease B
- LM: Diffuse thickening of glomerular capillary walls
- IF: Granular IgG and C3
- EM: Sub-epithelial deposits of electron dense material
- “Spike and Dome” appearance
Membranous Glomerulonephritis
Relapse on alternate-day steroid therapy
Steroid dependent
TOP-DOWN approach
UTZ then DMSA then VCUG
UTI prevalence with age
o 1 st year of life = male predominance
o Beyond 1-2yo = female predominance
Clinical Pictures of Glomerular Diseases
Grossly red urine with or without blood clots
from the lower urinary tract
In APSGN, When will the abnormalities resolve and normalize during acute phase?
6-8 weeks
What is involved in pyelitis?
Renal PELVIS
Nephrotic Range Urine protein: creatinine ratio
>2 is nephrotic range proteinuria
o <0.5 in <2yo is normal
o <0.2 in >2yo is normal
LM: normal
EM: diffuse effacement of epithelial foot process, no deposits
Minimal Change Disease
* often preceded by URTI and prophylactic immunization
- LM: Large, hypercellular glomeruli
- Increased mesangial matrix
- Double Contour or Tram-track appearance
Membranoproliferative Glomerulonephritis
How is HUS different from thrombotic thrombocytopenic purpura (TTP)?
- TTP has the same triad but can include CNS involvement and fever and has a more gradual onset
- Fewer cases of TTP can occur after diarrhea compared to HUS
Clinical picture of nephritic syndrome:
- Hematuria
- Oliguria
- Hypertension
- Azotemia
What is the pathogenesis of PSGN?
Ab is produced & combines with a circulating Ag unrelated to the kidney → IC accumulate in glomeruli & activate the complement system → immune injury (Type III hypersensitivity)
In APSGN, what hypothesis is given to explain the predilection to damage the glomeruli?
Localized in the glomeruli due to negatively charged capillary wall, mesangial trapping, hydrodynamic forces
Presumptive UTI
Bag sample, positive urinalysis, symptomatic AND single organism with culture colony count > 100,000
Fever may be the only manifestation.
PYELONEPHRITIS
Nephrotic Syndromes
- Idiopathic Nephrotic Syndrome
- Minimal change disease
- Focal segmental glomerulosclerosis
- Mesangial proliferation
- Glomerular diseases
- Membranous nephropathy
- Membranoproliferative glomerulonephritis
In APSGN, when will urinary protein excretion and hypertension resolve and normalize?
6 mos
CAUSES OF TRANSIENT PROTEINURIA
- Fever
- Exercise
- Dehydration
- Cold exposure
- Congestive heart failure
- Seizure
- Stress
Normal specific gravity of urine
1.015-1.025
If C3 levels did not go back to normal and the proteinuria persited after 8 weeks in PSGN, what would be your differential?
Membranoproliferative Glomerulonephritis (MPGN)
Microangiopathic hemolytic anemia, thrombocytopenia, and renal insufficiency
HEMOLYTIC-UREMIC SYNDROME
In APSGN, why does serum C3 decrease?
Inflammatory reaction follows immunologic injury due to activation of classic and alternative pathways which converge at C3 → lysis of cell membranes → hypocomplementemia
Indications for Renal Biopsy in APSGN
- Acute renal failure
- Nephrotic syndrome
- Absence of evidence of strep infection
- Normal complement level
- Hematuria and proteinuria
- Low C3 that persists more than 2 months
best to assess renal scarring
DMSA scan
UTI if with ff lab findings
o > 50,000 colonies of single pathogen from suprapubic tap or catheterized sample OR
o 10,000 colonies + symptoms
Small vessel vasculitis characterized by:
- purpuric rash
- arthritis
- abdominal pain
- glomerulonephritis with IgA deposits
HSP
False negative hematuria
o Formalin
o High urinary ascorbic acid
- Presence of persistent microscopic hematuria and isolated thinning of the GBM on E/M
- Often initially observed in childhood and is intermittent
- Isolated hematuria in multiple family members without renal dysfunction is termed as benign familial hematuria
- Important to monitor for hypertension, progressive proteinuria, or renal insufficiency
THIN BASEMENT MEMBRANE DISEASE
GAS Serotype following throat infection
1, 2, 4 , 12, 18 25
GAS Serotype following skin infection
49, 55, 57, 60
GLOMERULONEPHRITIS VS NEPHROTIC IN CHILDREN
Clinical picture of nephrOtic syndrome:
- Proteinuria (nephrotic range)
- Albumin low
- Lipid High
- Edema
Patients who respond well to prednisone therapy but relapse 4 or more times in a 12 month period
Frequent relapser
What are the only causes of Renal Insufficiency that cause decreased C3?
1. PSGN
2. MPGN
3. Lupus Nephritis
Documentation of prior strep infection in the throat
ASO
Crescentic GN is a characteristic of
RPGN
In APSGN, when will the C3 level resolve and normalize?
6-8 weeks
True or False. Administering antibiotics will NOT alter the natural history of PSGN.
TRUE
Antibiotics do not alter the course of PSGN. We give it to prevent the spread of nephritogenic steptococcus.
- LM: Focal segmental sclerosis and hyalinosis
- EM: Loss of foot process, epithelial denudation
Focal Segmental Glomerulosclerosis
* least responsive to steroids
Brown-colored / tea-colored urine
glomerular in origin
The major complication of nephrotic syndrome is
infection
* The most frequent type of infection is spontaneous bacterial peritonitis.
* The most common organism causing peritonitis is pneumococcus.
brown, cola, tea, burgundy colored urine. Proteinuria >100mg/dl on dipstick, RBC casts, dysmorphic RBCs (acanthocytes)
Glomerular source of hematuria
False positive
o Alkaline urine (pH>8)
o Hydrogen peroxide
Where is the site of the pathology as seen in the electron microscope in MPGN?
Subendothelial
- Bilateral sensorineural hearing loss (never congenital)
- Ocular abnormalities (30-40%) such as anterior lenticonus (its presence is pathognomonic), macular flecks, & corneal erosions
- Critical in the diagnosis: family history, screening urinalysis of 1 st -degree relatives, audiogram, ophthalmologic exam
- Highly likely: (+) hematuria and at least 2 of the ff: macular flecks, recurrent corneal erosions, GBM thickening or thinning, sensorineural deafness
ALPORT SYNDROME (HEREDITARY NEPHRITIS)
