Clinical predictors of progression of renal disease.
Revise please the abbreviation list on:
https://draft.blogger.com/u/0/blog/post/edit/8610857019469578230/4564412989605988372
GLOMERULAR DISEASE
Q.96.What
are the clinical predictors of progression? (see also Q.5)
A. Clinical predictors of progression : Ptn. develop progressive disease
typically have one or more of the foll. at time dgx, each of which is a marker
for more severe dis. :
1)
Elevated S. creatinine
.
2)
Hypertension.
3)
Persistent protein excretion > 1000 mg/d.
Q.97. Describe how is Henoch-Schönlein purpura (HSP) related to IgA Np?
A. HSP 🠞 a small vessel systemic vasculitis ch.ch. by small B.V. deposition
of IgA esp. é skin, joint, gut & kidney. Nephritis of HSP
ch.ch. by mesangial IgA deposition, it may
be indistinguishable fr. IgA Np. The following
indirect evidence has been
observed: 👌
v Monozygotic twins: one
has IgA & the other HSP é same
time.
v HSP has been
described é adults &
children é background of proven IgA
Np.
v IgA immune system abn.
incl. abn. IgA glycosylation, described
in both dis.
Q.98. What is Oxford classification of IgA nephropathy? Enumerate 2ry causes of IgA
Np.?
A. Pathologic
classification of IgA Np has been developed by the International IgA Np Network
Group working in collaboration with the R. Pathology Society:
1)
Mesangial
hypercellularity.
2)
Segmental glomerulosclerosis.
3)
Endocapillary hypercellularity.
4)
Tubular
atrophy/interstitial fibrosis.
A. 2.ry
causes of IgA Np.:
H.I.V.
Henöch-Schönlin purpura.
Crohn’s dis.
Celiac dis.
Glutin sensitive entropthy.
Liver disease.
Alcoholic cirrhosis.
Lung cancer.
Pulm. hemosidrosis.
Sicca syndrome.
Alkylosing spondylitis.
Rieter’s syndrome.
Leprosy.
Toxoplasmosis.
Q.99.What is the pathogenesis of IgA Np.?
A.{Aberrant synthesis &
metabolism of IgA🠞 mesangial
depos. of Ig A} = is the main
event. Initiating event 🠞 msng.
deposition of IgA,
which’s polymeric IgA1. Inciting factorss are
poorly understood, but may include aberrant synthesis & metb.
of IgA🠞 IgA immune complex é
ch.ch. favoring msng. deposition.
v
Etiology is unknown, but genetic ch.ch.s may predispose to developed of kid. dis. & mucosal infection may drive generation
of IgA immune complex.. Infection causes incl.:[CMV, H. parainfluenzae, S. Aureus
& Toxoplasmosis] 🠞 mucosal immune injury.
v
Ig. A Np is
complex polygenic
dis. involving both MHC & non-MHC alleles.
Q.100. What is new in the pathogenesis of IgA nephropathy?
A. MicroRNAs: [Are endogenous small (18-24 nucleotides long) noncoding single-stranded RNAs tht regulate gene
expression at posttranscriptional level]. They bind to messenger
RNAs of many genes, leading to† their degradation.
Ptn. hv high % of poorly O-galactosylated IgA1.
One of the enzymatic response for galactosylation of IgA1,👉 core1 b1,3-galactosyltransferase 1, is inhibited by sp.
microRNA called 👉 miR-148
b. This micro-RNA is
upregulated in ptn. leukocytes é IgA Np as comp. é healthy.
N.B. Upregulation:=
incr. in No. of receptors on surface of target cells, making them more sensitive to
a hormone or another agent. e.g., there’s an increase in uterine oxytocin receptors in 3rd trimester of pregnancy,
promoting the contraction of the smooth muscle of the uterus.
Q.101. What is the clinical picture? How to
diagnose?
v A. Ig A Np is
the most common cause of Iry G.N . It’s
more common Pathologically: [prominent, globular
deposits of IgA in msngial on I.F] L.M.: [diffuse msng. prolif.
& matrix expan. with proliferation G.N. & crescents in more adv. dis.]
. E/M sh. [dense
deposits primarily in msngial].
v Manif.
us. restricted to kidney. However, Ig A Np depos., us. clinically
silent, but may be sn é cirrhosis, celiac disease& HIV
infection, clinically apparent dis. may
occur Ig.A Np may rarely be sn é other
G. dis.: e.g. MCD &W.G.
v Presentation: Gross hematuria (single
or recurrent), foll. upper resp. infection , or microscopic hematuria
é or without mild Prot incidentally é routine exam., rarely, ARF with or
without oliguria, due either to crescentic Ig.A Np, or to gross
hematuria🠞tub. occlusion and/or damage by
RBCs, may occur.
v D.gx.: Susp.
on basis of C.P.,
but can be confirmed only by
R. biopsy,
which’s usually performed for susp. Ig A Np only if there’re Sn. suggestive of more
severe or progressive dis. such as protein excretion > 0.5 - 1 g/d.,🠝 s. cr. , or H.T. among Asians & Caucasians
, é 2:1 male to female predominance.
Q.102. What is the prognosis of Ig.A. Np.?
A. Ptns
without signif. proteinuria or R. dysf. us.
undergo complete
remission. However, most
ptn will hv stable or slowly progr.
dis..On
the other hand, ptns é 💢 persistent proteinuria and/or H.T. and/or🠉 s.
cr. are at incr. risk for progression, é incid
of ESRD: 20-30 % at 20 y., é another 20 % have 🠋 R.
function.
Hist. finding ass.. é worse prognosis incl.:crescent form., which’s uncommon
& more importantly, Sns of irreversible 💣 damage[G. scarring, tub. Atrophy & interstitial fibrosis ]. ARF é gross hematuria is us. reversible & s.Cr.
returns to
baseline but this us. leave residual hist. damage that could🠞 worse
long-term prongosis. If episode is more severe or prolonged, R. biopsy us. required
to rule out new onset crescent formation. Ptn é concurrent msngial IgA deposits & N.S. é minimal ch. dis. pattern on R. biopsy
appear to have a course similar to MCD.
Q.103. How to treat?
v “No ttt” for:👉 isol. hematuria, no or minimal Prot. & normal
GFR . instead: periodical
monitored 6-12
m. intervals to assess for progression.
v Persist. prot. (>500-1000 mg/d.)🠞ACEI or ARB :
monothp. &
target reduction in protein excretion 👉 50-60 % from basel. é goal of <500 or <1000 mg/d.
v Ptns
meetig criteria for ACE inhibition also receive fish oil . ptns é persistent
N.S. and/or CKD & dyslipidemia
ttt é ➤statin. Ptns é Ac. onset of N.S. & minimal
change dis. as well as msngial IgA deposits on R. biopsy ➤ Gl.coid thpy as in other ptns with MCD.
v Progr.
active dis. (hematuria é incr. Prot. and/or
incr.
s. cr. despite ACEI/ARB ➤Start Glcoid alone.
Two reg. us. recomm : I.V. Mprd.:(½ g./ dose & in
child. 7-15
mg/kg/dose, max. one
g.)/3d. é begin. of 1st, 3rd & 5th m.& altern. d. oral
pred.:0.5
mg/kg./6 m.,
thn taper ⮟ to discounted.
v Alternative regimen:
avoids pulse thp:2 mg/kg
pred. (max.100-120 mg)
E.O.D./2 m.,
é rapid taper⮟ to: 0.5 mg/kg (30-40 mg) E.O.D./add. 4 m.. thn taper ⮟ to discounted.. Severe
dis. é
baseline (initial >1.5 mg/dL /133 µmol/L.) or progr. dis. é Glcoid alone (🠉s.Cr. and/or
protein
excr.) & have
no signif. ch. damage é R.
biopsy ➤ oral
prednisone &
Cph..
v One reg.:Pred. (1
mg/kg,
max.60-80
mg/d.)/2-3
m., slow taper ⮟to 10
mg/d. for 1-2
y.s.Cph (1.5
mg/kg/ d.)
orally/3m.,
following, if cr. stab. &
protein excretion fallen, by either aza. (1.5
mg/kg /d.)
or MMF (one g.
twice/d.,taper. to ½g twice/d.)/1-2 y.s (maint.)
Crescentic
GN & rapidly
progr. clinical course ➤ i.v.
pulse Gl.coid &
aza..
v Another regimen: I.V. Mprd. for 3 consecutive d.½-1g./dose or, in children, 7-15 mg/kg
in
child./dose max. of 1g.) foll. by oral
pred. (1mg/kg
/d., max.
60-80 mg) for
2-3 m., thn a slow taper to a maintenance of 10 mg/d. for 1-2 y.s. Cph.:
(0.5 g/m2.
i.v.)
m./3 m. foll., if s. cr. stabilized & protein excrtion falls, by either aza.
(1.5
mg/kg/d.) or
MMF(1mg
twice/d.&tapering to ½g twice /d.) for/1-2 y.s as maintenance
therapy, provided tht cr. stabilized & Prot.
was reduced. If s. cr. or degree of proteinuria have not improved after
initial Cph:👉repeat biopsy to estimate
activity of the dis. &
amount
of t. interstitial damage (the irreversible
component) before deciding to continue
im/m..
Q.104.What is the D.D. of glomerular hematuria (persistent isolated G. Hematuria)?
A. 3
disorders 👌 account for most cases:{IgA Np, Alport synd. &
thin B.M. Np.}. These condition can be distinguished by history & examination urine of aSmtic family
members. Isolated G. hematuria, in abs.
of F.H. of R.F., typically has a 👉 benign outcome. So, R. biopsy us. not indicated, since finding
a treatable dis. is v. low.
Some ptns present é isolated Hematuria will
developed (H.T. and/or proteinuria) over time, and will be at increase
risk for developed R.I.. So they should undergo regular control of B.P. & screening for Prot,
to identify candidates for early intervention. Initial step in evaluation of red/brown urine is
urine centrifugration to see if the red/brown color is in urine sediment
or supernatant. Red/brown sedim. & clear supernatant estivesugg.: 🠞 hematuria. Red/brown supernatant
wch’s +ve for heme sugg. 🠞 Myogl.uria or H.B.uria. A red to
brown supernatant tht is -ve for heme cn be sn é setting
of use of bladder analgesic phenazopyridine or other drugs,
certain food dyes,
ingestion of beets
in susceptible subj., porphyria
& hydroxocobalamin for
ttt of cyanide intoxication.
Q.105.What are the causes & diagnosis of membranous nephropathy (MN)?
A. MN is among the most common causes of N.S. in non-Dc.
adults, (one-3rdof biopsies). Charecterized
by:[diffuse
thickening
of GBM]
on L.M, ["spikes"
on silver
st., diffuse granular IgG &
C. deposition] on I.F. & [subepith. dense
deposits] on E/M. Msng. and/or subendoth. depos. occ.
é 2ndry MN, sugg.:immune
c.x dis..
Pathg.:Immune
depos. ch.ch. of
this diso. may dev. in situ é
movement across GBM of circul. IgG AB directed agnst endogenous Ag expressed on or
near podocyte foot processes or agst circulating cationic or low
m.w. Ag tht hv crossed anionic charge barrier in GBM. The M type phospholipase A2 receptor. (PLA2R ) is a mj Ag in human idiop. MN. Neutral
endopeptidase(NEP) is an Ag in an antenatal
form of MN.
MN is most often idiop., although it has
been associated é special varieties, include hepatitis B, auto-immune
dis. (e.g, lupus), malignancy,
drugs e.g. [gold,
penicillamine & NSAIDs] & in é other G. disease such as Dc Np. Most ptns
present é N.S., but some hv only
aSm.tic proteinuria. S. cr. is generally N. or near normal at
presentation.
D.gx of MN cn only
be made by R. biopsy.
2ndry MN: ANA. A.B., C. & hepatitis B & C serology. Screening
for malignancy
is reasonable if age is suspicious, or
there’s finding e.g. [guaiac +ve stools or unexplained anemia or wt loss].
Q.106. What
are the causes of MN?
1)
Idiopathic: may represent autoA.B. agnst podocyte
Ag.
2)
S.L.E. (WHO Class V).
3)
Drugs:
1. Penicillamine
2. Bucillamine
3. Gold salts
4. Anti-TNF
thpy
5. Tiopronin
6.
NSAIDs
4)
Hepatitis B virus .
5)
Hepatitis C virus
(rare) .
6)
Malignancy (may not be causative).
7)
Hematopoietic cell transplant / GVHD
8) Status post
renal transplantation
9)
Sarcoidosis
(uncommon)
Q.107.What is the prognosis of idiopathic M.N?