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 1^st 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 1^st-line 🠞 [i.v. Cph + g.corticoids.], like induction.

Resist. to (Cph + g.corticoids) as 1^st-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 2^ndcourse 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.

https://www.healthline.com/health-news/russia-claims-they-have-a-covid-19-vaccine-why-you-should-be-skeptical#Later-stage-clinical-trials-cant-be-rushed