What are the renal toxic manifestations of antiviral therapy? How to manage?
CLINICAL NEPHROLOGY
Revise please the abbreviation list on:
https://draft.blogger.com/u/0/blog/post/edit/8610857019469578230/4564412989605988372
Q. How can acute kidney injury (AKI) complicate COVID-19 infection?
Early reports (Wuhan) denotes that almost 3-9% of hospitalized COVID-19 infected patients may develop AKI. This percentage, however, have been jumped to 15% of hospitalized subjects and almost 20% or more in ICU-admitted patients where dialysis therapy may be commenced. Furthermore, AKI can be considered a clinical marker of COVID-19 intensity that can be associated with a high mortality. Many COVID-19-related factors have been implicated in AKI development:
1) Enhanced blood clotting,
2) Microinflammatory processes,
3) Directly infected renal tissues.
4) Renal tubular injury (ATN) with associated sepsis,
The post-COVID-19-related AKI period is characterized by a lowered kidney function after discharge.
Q127. What
are the renal toxic manifestations of antiviral therapy? How to manage?
A. Renal toxicity of antiviral therapy:
I.
“Protease”
inhibitors:
1. Indinavir:🠊 {Crystalluria-Nephrolithiasis-Dysuria- AKI-
I.N.}. ttt.🠊 Daily fluid intake>2 L/d. N.B. Ritonavir & Lopinavir:🠝 indinavir toxicity.
2. Ritonavir:🠊 {Reversible AKI, us. in combination é nephrotoxic drugs}.
3. Saquinavir & Nelfinavir:🠊{Renal calculi,
rare}. ttt.🠊 🠝 fluid intake.
II.
Reverse
Transcriptase inhibitors:
1. Tenofovir, abacavir: 🠊 {Renal tub. dge: proximal tub. dysf.,
Fanconi synd., Nephrogenic D.I., ATN, AKI}. ttt. 🠊 Pt.
on tenovir: monitor Sn of tub. dysf.:[🠝 S. Cr., HypoPo4,🠋 S.
uric a., glucosuria, Prot. & acidosis.].
2. Didanosine, Lamivudine, Stavudine:🠊{Tub. dysfunction.}.
III.
Others: Cidofovir, adefovir:🠊 {R. tub. dge, proximal tub. dysf. (cidovir)}.
Q.128. What recommendations should
be applied with Methotrexate
prescription in CKD patients?
A. “Methotrexate”:
⮚ Not é GFR < 50 ml/min./1.73 m2.
⮚ Not é TMP/SMX 🠞 severe pancytopenia.
⮚Folic a. 5 mg. B.D. should be added.
-
Dose: 0.3 mg/kg/w., max, 15 mg/w.
Q.129. What are the general
indications of infliximab?
A. “Infliximab”:
(Remicade 100 mg.) is a monoclonal chimeric Anti-TNFa blocker, used é the foll. indications:
(1) Wegener’s granulomatosus.
(2) Sarcoid kidney. , .. Other medical indications:
(3) Chronic
inflamm. bowl dis.( U.C. & Crohn’s dis.).
(4) Rhomatoid arthritis.
(5) Psoriatic arthritis & Plaque.
-
Other TNFa : Etanercept (Enprel) 50 mg/w.
Q.130. When can you expect the Dgx. of Lead Nephropathy?
A. [R.F.
+ H.T. + Gout = ⮞Lead Np.]. Although hyperurecemia is common in R.F., Gout is unusual, but if present, shd raise the possibility of ⮞ Lead
Np.
Q.131. Enumerate the different types of renal disease in S.L.E.? 👍
(1) Abnormal urinalysis (hematuria and/or proteinuria) with or without 🠉 Pl.
cr. observed in up to 75 % of ptn. The most frequent abnormality is proteinuria.
(2) Classification system (2004) ⮞ 6 diff.
G. dis. classes (biopsy guided):
Class I: (minimal
mesangial): msng. immune deps. identified either by I.F. alone, or
by I.F. & E/M., but without L.M. abn. Class I. hs
N. urinalysis & s. cr..
Class II(mesangial
prolif.):L.M.: Msng. hypercellularity & matrix expan-sion.I.F.
& E/M:few isolated
subepith. or subendoth. deposits, but no subendoth.
depos. seen on L.M. Ptns present é microscopic hematuria and/or
proteinuria; H.T. is uncommon & N.S. & R.I.
virtually never sn.
C. III: (focal Prolif.)L.M.: endo-
or extracpll. G.N. é < 50 % of G.. Focal
sub-endothial depos.
on E/M. It’s further subdivided acc. to chronicity. Hematuria & proteinuria
sn in almost all
ptns, some hv N.S., H.T., and/or 🠉Pl.
cr.. Progr. R.I.: uncommon if< 25% of G.
affected &G.: segmental
prolif. without necrosis.
Class IV (diffuse Prolif.):>50 % of G. hv endocpll. é or without extracpll. G.N.. Class IV. subdided
into segmental (IV-S) & global (IV-G) dep. on G. hv segm-ental
or global les., resp..Subclasses depend on chronicity. Hematuria
& proteinuria occ. in all ptns é active
dis., & N.S., H.T., R.I. are frequently observed.
Class V (membranous L.N.): L.M: diffuse thickening of
G. Cpll. wall. I.F
or E/M: subepith.
immune depos.. Alth. subendothelial depos. cn be sn by I.F or E/M alone, such depos.
detected by L.M need combined Dgx. of C.III/IV.&V .. N.S. us. sn., alth. hematuria
& H.T. may be sn., Pl. cr. us. N. or mildly raised.
C.VI (adv. sclerosing):global sclerosis é >90 % of G. It represents healing of prior inflmm. inj.,
& advanced stage
of ch. C.III, IV, or V. L.N.. Ptns display slowly progr. R. dysf. + proteinuria &
relatively bland urine sediment.
(3) Tub. interstitial dis. occ. é G. dis. & may be the only
manifestaion of L.N.. Ptn.s present é
rising pl. cr.+ bland urinalysis. Sn of tub. dysf.
may be present.
(4) Vascular dis.: common and cn affect the prognosis of R.
dis.. Ptns may present é G.
& vasc. thrombi,
often + aPL A.B.(e.g.
LA & anticardiolipin A.B.).
(5)Silent L.N.: Msng., focal, or diffuse
prolif. G.N. No clinical dis.(us. benign).
(6)Drugs: ⮞ lupus-like
synd., esp. those acetylated in liver, [e.g. hydralazine, procainamide & INH.]. R.
dis.: uncommon but prolif. G.N. or N.S. cn occur.
Q.132. How
to treat diffuse or
focal proliferative lupus nephritis?
A. Clinical risk f. for
progression:[🠉 S. cr. at
time of R. biopsy, H.T., NRP, anemia, blacks or Hispanics &
on R. biopsy: crescents & sev. tub. interstitial
dis.].
Prompt Dgx. & therapy🠞 clinical
remission of active disease🠞 improved
long-term prognosis. Non-im/m.
therapy: given to almost all ptns é prolif. L.N.,
even those requiring im/m.. Persistent Prot: ACEI/ARBs, initiate
monothp. & target minimum dcr. in Prot. 🠞 60 % from baseline é goal of < 500-1000 mg/d.
Goal B.P.< 130/80 mmHg. Thpy
directed also to dyslipidemia & hypercoagulability é N.S.
Im/m. thp. for proliferative
L.N consists of induction & maintenance:
Induction:
involves im/m. drugs to achieve clinical remission; delayed initiation
of such thp & failure to attain clinical remission 🠞 worse
outcomes.
v Focal prolif.:(=<25 % of G. affected on L.M.
+ no necrotiz les. or crescent form., N. B.P. & s. cr., & Non-NRP):
trial of Steroids alone:60 mg. /d./one w.,
taper. to 30 mg/E.O.D./total3m. Goals
of thp 🠞 loss of hematuria &🠋 Prot. Ptns not resp. or
progress: ttted as if they hv diffuse proliferative LN.
v Moderate/Sev. focal prolif.
or diffuse prolif.
LN.🠞 im/m. thpy: [Steroids + either i.v. Cph or oral MMF].
Choice depends upon clinical features
(e.g, “MMF” prefered in blacks & Hispanics) and
ptn preference (e.g., young woman want to avoid
ovarian toxicity of Cph). We recomm.:i.v. Cph in more
sev. dis. (e.g., elev. s. cr. and/or crescents
on R. biopsy) .
-If i.v. Cph is chosen 🠞 short course regimen is recommended .
- If MMF is chosen 🠞 ALMS trial:[MMF comp. é Aza. ws
ass. é statistically & clinicl signif. dcr.
in relapse rate in ALMS maintenance
Trial & nonsignificant trend toward benefit in MAINTAIN
nephritis trial. ] «ألَمَظ» Sev. active dis.
(eg, ARF, florid
crescentic G.N., sev. extrarenal
dis.) 🠞 Sterods
initiated é i.v. Mprd (500-1000 mg/30 min./d./3d.)🠞 rapid im/m. effect since resp.
to i.v. Cph is not seen for 10-14 d. . (هام جداً)
Q.133. What about maintenance therapy of diffuse or focal proliferative L.N.?
A. {Ptns completed induction therapy& attained remission maintenance im/m. for at least 18-24 m. or longer . { سنَتِين}.
Aza. or MMF are
recommended over Cph for maintenance, it depends upon
➳ initial induction therapy:
Ptns received i.v. Cph 🠊 Aza; 2 mg/kg/d.
max. 150-200 mg/d..
Don’t start Aza until WBCs => 4000 cells/microL& absolute neutrophil =>1500 cells/microL,
then start Aza within¸2-4 w. after last
monthly dose of i.v. Cph (time of leukocyte nadir).
Ptns received MMF as induction🠊 MMF 1-2 g/d. contin. as
maintainance.
Low-dose oral prednisone (or
its equiv.): 0.05-0.20 mg/kg/d.
for
all ptn. on maintenance therapy. Goal is to attain minimum dose needed for control of extrarenal
Sms & avoid relapses,.. therefore vary among ptns.
Q.134. How does
ESRD due to L.N. differ from other causes?
A. 10-30 % of proliferative L.N.
progress to ESRD acc. to: [severity of dis., ancestral
& socioeconomic variables & efficacy of initial
thp.This’s us. ass. é gradual complete/partial resolution of extrarenal
& serologic mnf. of Lupus. Survival é either
H.DX/CAPD is similar
to general population of ESRD, there’s incr. risk
of 💀 death é 1st 3 m. of DX.,
due to ➳ sepsis
& other complc. of high-dose steroid. P.D. : incr. risk of peritonitis &
non-cath. related infection.
Graft survival at 5-10 y. foll. R.Tx. (deceased or living)Ø similar
to
other dis.. lupus ptn. shd be on DX. for
at least 3-6 m. before R.Tx., esp. é rapid
progress to R.F.. wch. 🠞 further 🠋 in lupus activity & giving relative
ARF time to recover sufficiently for D.X. to be stopped. Rate of recurrence
is variable é reported incidence
ranges fr. 2-30%. Incidence of graft loss due to
recurrent dis. is low.
Serology: C.
& titers
of anti-d.s. DNA, doesn’t help predict dis. recurrece in allograft. lupus recip.
+ APA is at incr. risk for thrombotic
events. Ptn.é T/E
events shd be ttted é warfarin
as long as APA persist, é regimen
similar to tht for Sm.tic APA synd..
Optimal thpy é no P.H. of thrombotic
event is unclear.
Accelerated athero. is obs. in all R.Tx. recip.,
independent of Iry R. dis. Paucity of data exists about incidence of vasc.
dis. in R.Tx. in lupus, aggressive ttt of dyslipidemias is needed, given
the potential risk for vascular diseas.
Q.135. What are the indications for renal biopsy in L.N.?
I.
“Six” hist.
subtypes of L.N.: Optimal thrpy
& prognosis varies
é subtype.
II.
Determine
optimal im/m.
since subtype cannot be us. predicted fr. C.P.
III.
Repeat biopsy é active ur.
sediment & rapidly rising s.cr. (crescentic dis.).
IV.
Repeat
biopsy é new or worsening
N.S. in ttted prolif. L.N since such ptns may
hv. concurrent membranous
lesion, requring different therapy.
v R.
biopsy in é protein excretion>500 mg/d.
and/or active ur.
sed. + hem-aturia (typically
dysmorphic),
often pyuria, & cellular casts. Such ptns mostly hv focal/diffuse
prolif. G.N. or membranous
lupus. (Dangerous area.)
v Slowly rising s.cr. in esp. blacks, é ur.
sediment🠞Possible
low grade dis. activity, or R.
dis. unrelated to lupus.(eg, drug-induced Ac. interstitial N.).
Q.136. How
to treat resistant/relapsing diffuse or focal
proliferative L.N.?
A.“Resistant” to induction:=[failure to achieve complete or partial
remission]. Others:ØRemission,
thn. relapse as maintenance im/m. tapered or discontinued.
Resist.
to (MMF + Steroids) as 1st-line 🠞 [i.v.
Cph + g.corticoids.],
like induction.
Resist. to (Cph + g.corticoids) as 1st-line🠞[ MMF + g.corticoids.],
like induction.
Failed or unable to tolerate both (Cph
& MMF) 🠞[Rituximab]: 0.5-1 g. d.: 1 , 15,…. or 375 mg/w./4 w.s.
“Relapsing L.N.”:
💢 Mild= activ.
sediment é <50 % éin Prot.+
stable s. cr. ØPrdn. thp
.
💢 Moderate/sev.:
Choice of im/m. varies é drug
used for initial induction,
whether or not ptn still on maintenance im/m.: All
reg. incl.: G.corticoids & same as those é initial induction or maint.
im/m.
If Cph used
for induction & ptn is taking Aza. as maintenance➤ a
trial of MMF & stop Aza.
Most experts us avoid 2ndcourse
of Cph. ☝
If MMF used for induc. & mainten. & MMF hs bn stopped ➤ Restart MMF.
If MMF used for induc. & mainten. & relapse occ. while still on MMF➤ Cph.
Ptns continue to relapse despite above
intervene ➤ a trial of Rituximab.
(Concurrent prolif.
+ membr. LN ) & resistant to Cph➤ [MMF + tac-rolimus]. Prefered
regimen is tht used in trials.
Q.137. Can you
please summarize the clinical trials of immunosuppressive therapy in proliferative
lupus nephritis (summary)?
A. Induction therapy = Initial thp. reg. given in attempt to produce remission of active dis.. This’s foll. in almost all ptns by maintenance thpy, us. é less toxic drugs. National Institutes of Health (NIH) trials showed higher remission & lower relapse rates but also a higher incid. of adverse events associated é Cph. Comp. to Mprd without Cph.. A trial by “Dutch Working Party” demonstrates lower rates of relapse, doubling of s. cr. & deaths or ESRD ass. é Cph. compared to Aza.. The “Lupus Nephritis Collabration Study”& the “Euro-Lupus Nephritis trial” evaluates shorter courses Cph. regimen. The “Euro-Lupus Nephritis Trial” suggest: a low dose Cph. induction reg. ws as effective as a high dose reg. Several trials hv shown tht MMF provides similar or perhaps “greater” efficacy & “fewer” adverse effects thn Cph., at least in ptns é relative N. kid. func. & modest proteinuria, esp. among ptns who refuse or cannot tolerate Cph. MMF may provide greater benefit thn Cph. among black & Latino ptn. There’re limited data regarding efficacy of different maintenance regimens.
CORONAVACCINE NEWS
v Russian health authorities
claimed the approval of experimental coronavirus vaccine for
international utilization prior to the clinical documentation of its
safety/efficacy via advanced stages of clinical trials
v One expert said this
approval is “breaking ALL the guiding roles” to assure the necessary safety and
efficacy of a newly administrated vaccine.
v President “Putin” said
that their coronavirus vaccine that has been manufactured in Moscow-based
Gamaleya Research Institute has been approved for international spread,
despite it doesn’t have been examined in the vital stage of phase 3 clinical testing.
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