How to treat High risk idiopathic M.N.?
RENOPROTECTION
Revise please the abbreviation list on:
https://draft.blogger.com/u/0/blog/post/edit/8610857019469578230/4564412989605988372
Q. Can COVID-19 induce renal failure in otherwise healthy subjects?
Recent data about non-elderly adults who developed COVID-19 infection and were complicated by AKI-related sudden loss of kidney function. Those subjects were adults with no associated comorbidities. However, with prompt therapy, including dialysis, if indicated, AKI can be completely reversed.
Q.110. How to treat High risk idiopathic M.N.?
Ptns remaining at high risk over 3 m. observed
period & have N. or near normal R.
func. (Cr. Cl.> 80 mL/min):🠞im/m.
therapy rather
than observation
Im/m.: cytotoxic or CNI. Choice depends upon: clinician & ptn. pref-erence, e.g., CNI may be prefered
to avoid cytotoxic toxicity
.
Ptn.s consid. at high
risk because of reduced R. function that's considered due to MN🠞: initiation of im/m. without delay é either Cph or CNI rather thn others. Choice depend upon clinician & ptn preference,
after discussion of benefits & risks. CNI usually prefered. Dose adj. may
be needed é R.I.
An
exception to this is tht we would
not use im/m. é
1. substantial ch. interstitial fibrosis and/or
2. vascular dis., unless these finding can be explained by concurrent dis. (e.g. H.T.& D.M.), which’s unlikely due to MN if present on initial biopsy.
Q.111. How to treat relapsing patients?
Relapse of Prot.
occurs in 25-30 %
of ptns ttt.ed é Cph. &
higher % of those ttt é CNI.
Choice of thpy varies é initial
reg. used & concerns é toxicity
Ptns initially ttted é CNI🠞repeat course of
therapy é same
dose used é initial reg.. An
alternative, esp. ptns not
tolerating initial regimen🠞use
a Cph reg..
Ptns initially ttted é Cph: repeat
the original regimen. (weighed
against S.E.), or switching to CNI. if gonadal
toxicity is an issue, CNI is recommended .
Resistant ptn.s=
Moder./high risk,who fail to respond to both Cph & CNI:
trial of rituximab: é careful evaluation of potential risks & benefits of fur-ther im/m. A clinically relevant resp. is less likely é Cr.Cl.< 75 mL/min/1.73 m2.
“Alternative agents” in ttt of Iry MN:
v Iry reg. used to ttt idiopathic MN incl. cytotoxic drugs e.g. Cph or chlorambucil, or CNI(Csp. or tacrolimus) both + Steroids.
v [MMF+ G. corticoids]: may be as effective as Cph & chlorambucil in remitting proteinuria but ass. é 🠞high rate of relapse. MMF may be therapeutic option for some ptn.s é either relapse after cytotoxic therapy, or Csp, or are unable to tolerate these regimen, despite no data é long term effect of MMF on R. survival.
v Synth. ACTH🠞complete or partial remission in a large % of ptn.(Study).
Q.112. Give short account about classification & causes of M.P. G.N.?
v M.P. is an uncomm. G. lesion 3 hist. forms have been identified. Type I is the most common form & may be idiopathic or 2ndry to a wide variety of diso. Type II, also called dense deposit dis., is now consid. a distinct entity caused by [dysregulation of the alternative complement pathway].
urv HypoC. is common in all MPGN types. C. activ. in I & III occur é classic pathway. HypoC., due to activ. of alternate pathway, occur in type II.
v Type I is most commonly caused by [HCV., é or without mixed cryoglobulinemia, mixed cryog. not due to HCV or B.V. infection, monoclonal gammopthy, autoimm. disorers, such as SLE. & infc. other than hepatitis C or B].
v Thrombotic microangiopathy🠞MPGN pattern on R. biopsy. This ‘s obs. in [ch. T.x. G.pathy., APA syndrome, healing TTP/HUS syndrome & scleroderma].
Q.113. How to treat M.P. G.N. type I & III?
Optimal ttt of Idiop. MPGN still uncertain. Most studies, were comprised é type I. Alth. there’s much less data in types II & III, clinical course & resp. to thp is similar. However, there’s evid. that types II & III. less responsive to steroids.🔒 Sp. therapy. is not indic. é nonnephrotic Prot., since long-term out-come is rel-atively benign. In view of successful use of prol. low-dose steroids in 3 diff. studies in children , a similar reg. may be tried in nephrotic adults if HCV infection has been excluded. 120 mg prednisone E/O/D.:12-16 w.s é urinalysis, protein excretion & pl. Cr. being monitored. Ptns who resp. é decline in Prot., activity of urine sediment, and/or pl. cr. shd be gradually tapered⮟over a period of m. to 20-30 mg E.O.D.; maintenance dose is continued for several years. More prolong. therap. is indicated if the dis. relapses as the steroids are tapered or discontinued.
Role of [aspirin + dipyridamole] is unclear. Benefit requires “prolonged therapy”. Trial of may be offered to ptns refusing or not respondingto steroids & in whom HCV hs bn excluded. A paucity of data exists é [Csp. + prednisone].
Q.114. What is the clinical picture of MPGN type II (DDD)(dense deposit dis.)?
A. DDD= rare G. dis. ch.ch. by ➵ electron dense depos. é B.M. é no evidence of immune c.x. formation. It’s caused by uncontrolled activity of alternative C. pathway through abnormal in regulatory molecules, including absence or dysfction f. H or presence of C3 Ne F. C.P.:[Variable degrees of Prot./hematuria, isolation or + Ac. nephritic or N.S.]
Prognosis is poor. Limited studies: ESRD occur in mj. of affected individuals. DX is made by R. biopsy utilizing E/M. D.D. including: [almost all causes of Ac. G.N. & N.S., esp. P.S.G.N.]. Once Dgx. is made, measure of specific C. proteins may guide therapy, e.g.: [C3, C4, CH50, AH50, C3Ne F. level, f. H level & activity].
If f. H level or activity are low, ptn & family members should be tested for genetic mutations in f. H & f. H-related genes. R. biopsy should be done in family members who test +ve for such genetic mutations & have clinical evidence of G. disease. A.Smtic family members should be closely foll. for developed of G. dis.. In adult-onset DDD, a monoclonal gammopathy should be excluded.
Q.115. How to manage DDD?
v ttt of all ptns é DDD incl. general measures to preserve R. function., e.g. aggressive B.P. control &
🠋proteinuria with angiotensin inhibition.
v All ptn. é DDD shd be evaluated & ttt for dyslipidemia.
v Ptn. who
have f. H def. and/or elev.
C3NeF 🠞Pl. infusion
or exchange.
Preferred reg.: Ptn é identified mutations in f. H or ass. é monoclonal gam-mopathy🠞Pl. infusion or exchange é FFP (10-15 mL/kg b.w.) infused/14 d./6-12 w. é monitoring for Sn of R. recovery as measured by decline in Prot & s. cr..Pl. infusion or Pph shd be contin. indefinitely as long as ptn. continue to respond. Monoclonal gammopathy🠞Sp. ttt of underling Pl. cell dyscrasia.
Ptn.s é 🠝C3NeF & normal f. H 🠞Pph é albumin twice/w.. Pph shd be continued until C3NeF activity dcr. by at least 50%, provided concurrent stabiliz-ation of R. function. Frequency of Pph: dcr. to weekly or twice monthly once R. func. stabilized. Pph may be contin. indefinitely, according to C3NeF level & C.P.
Im/m. therapy: steroids, Cph. & CNI, hv not bn shown to be effective in ttt DDD. They may be used, however, in RBGN. Ptn. NOT resp. to pl. infusion or Pph, or don’t have abn. in C3Nef. or f. H 🠞experimental ttt e.g.: [rituximab, sulodexide & eculizumab] (only é controlled trials).
Q116. What is new in the treatment of dense deposit disease (DDD) & C3 G.N.?
A. Eculizumab(Ecz.)=a humanized monoclonal A.B. tht binds é high affinity to C5. It prevents cleavage of C5, So, prevents C5a & terminal C. cx (C5b-9) formation, wch hv bn implicated in pathogenesis of both (DDD) & C3 G.N.. Three case rep. & one phase I open-label trial hv experienced Ecz. (total 9 ptn.). S. membrane attack cx were normal-ized in 7 ptn.. S. cr. improved in 4 ptn., worsened in 3 ptn. & remained unchanged in 2. Prot. dcr. in 6 ptns, many of whom hd NRP prior to beginning ttt. but worsened in one ptn. & remained unchanged in 2 ptn.. Based upon these data, Ecz. cn be used in DDD or C3 G.N. ptns. who hv deteriorating R. function or sev. N.S. despite ttt. é Pph.
Q.117. What is the C.P. & diagnosis of poststreptococcal G.N.(PSGN)?
A. PSGN is the most common cause of Ac. nephritis worldwide. It occ. mainly é developing world. Risk is greatest in children (5-12 y.) & elderly>60 y.. PSGN is caused by G. immune cx. dis. induced by sp. nephritogenic strains of G. A beta-hemolytic strept. (GAS).Two leading candidate nephritogenic Ag.:
v Nephritis-ass. plasmin receptor &
v streptococcus pyrogenic exotoxin B.
Ch.Ch. pth. features: E/M: (dome-shaped🛎subepith. deposits) & I.F.: (depos. of IgG & C3 in a diffuse granular pattern é msng. & G. cpll. walls. L.M.: cellular infil-tration & G. proliferation are nonsp..
The Most comm. “C.P.”.:[edema, gross hematuria & H.T.], presentation varies fr. a.Sm.tic microscopic hematuria to full-blown Ac. N.S.(gross hem-aturia, Prot., edema, H.T. & AKI.). Lab.: [abn. urinalysis (dysmorphic RBCs, Prot., RBCs casts & pyuria), +ve serology for A.B. to strept. Ag. & hypoC.].
PSGN typically Dgx.🠞[ Acute nephritis + recent GAS infection.]. Alth. sev. G.N. (eg, M.P. & IgA Np.) have similar present. to PSGN, sp. clinical differences can D.D. them. If Dgx is uncertain🠞R. biopsy may be needed to identify specific renal disease.
Q.118. How to treat PSGN.?
There is no sp. therapy to treat PSGN. Management is supportive & focused upon ttt volume overload tht causes clinical complic. of PSGN. General measures incl.: sodium & water restriction &diuretic thpy.
Ptn. é ARF.:DX. may be required. H.T. ptn.🠞lasix for prompt diuresis &🠟B.P.. H.T. encephalopathy due to severe H.T., will require emergent thpy to 🠟B.P.
Most ptns, espcially children🠞complete clinical recovery & resol.utionof dis. process begins é 1st 2 w.. Small No. have late complication (i.e, H.T.,🠝proteinuria & R.I.).
Q. 119. What biological agents associated with post-infectious G.N.?
A. Bacterial infections:
- Skin or throat (Strept. G. A).
- Endocarditis (Staph. aureus, Strept. viridans).
- Visceral abcess (Staph. aureus, E. coli, Pseud., Proteus mirabilis).
- Shunt nephritis.(Staph. aureus, Staph. albus, Strept. viridans).
- Pneummonia. (Diplococcus pn., Mycoplasma).
- Thyphoid fever. (Salmonella typhi).
B. Viral infection:
1) Mumps.
2) Hepatitis B.
3) Epstein Barr virus.
4) Parvovirus B19 .
5) Varicella .
6) CMV infection.
7) Coxsackie.
8) Rubella.
C. Parasitic infections.
1) Shistosoma mansoni.
2) Plasmodium falciparum.
3) Toxoplasma gondii.
4) Filaria.
Q.120. How to distinguish different forms of FSGS?
A. DD. I.ry & II.ry FSGS hs important theraputic implications. I.ry FSGS may resp. to im/m. ag. e.g. steroids, while II.ry usually fails to do & may be best ttt é modalities that🠟intraG. pressure, e.g ACEI. Distinction can usually be made from P.H. (e.g. disorders associated é I.ry disease), ch.ch. of onset, find. on E/M & degree of Prot.
In contrast to II.ry FSGS who present é slowly incr. Prot. & R.I. over time, Iry FSGS typically present é Ac. onset of N.S. & usually ass. é peripheral edema, hypo-alb. & NRP. By comparison, Prot in IIry FSGS is often nonnephrotic & both low s. albumin & edema are unusual even when protein excr. >3-4 g/d. 👍 E/M. find. also different in Iry & IIry FSGS. Iry is associated é diffuse foot process fusion; in comp., it’s focal in IIry dis. & largely limited to sclerotic areas .
To D.D.: (healed vasculitis) fr. (Idiopathic FSGS) or that due to (nephron loss). É healed vasculitis, the obsolescent segment of cpll. tuft is us. incorporated into scar tissue that is us. composed of collagens type I & III & that may fragment the tuft. On PAS st., this scar tissue stains less intensely thn the strongly PAS-+ve segm. of collapsed capillery B.M. material in Iry FSGS.
Familial & idiop. FSGS: DD.: extremely difficult since familialdis. hs high % of steroid-resistant🔒ptn. (at least in children). Familial disorder🠞wide range of clinical dis., ranging fr. M.C. to adult onset FSGS . Finding suggestive (but not diagnostic) familial dis.:[F.H. of disease & onset in infancy or childhood.]. Steroid-resist. is a consistent finding in Iry FSGS. Steroid-resistant FSGS is due to familial dis. in many children; its predictive value in adults is uncertain. Genetic screening may identify famil. dis..
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