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KIDNEY PROTECTION

How to make a diagnosis of TTP-HUS in adults?

 

 KIDNEY PROTECTION

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Q.211. How to make a diagnosis of TTP-HUS in adults?

A. Dgx. of TTP/HUS usually made on clinical grounds é ch.ch. clinical + lab. finding:

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      Microangiopathic hemolytic anemia (MAHA).

      Thrombocytopenia

      ARF. (varying degrees of severity).

      Neurologic abnormal, (fluctuating).

      Fever.

Confirming Dgx: Only👆presence of { MAHA + thrombocytopenia } without other causes is sufficient to make initial Dgx. & start Pph.

Idiopathic TTP-HUS:🠞markedly ADAMTS 13(<5%) + AutoA.B. agnst ADAMTS 13. However, results of these tests are not us. available quickly enough for ttt decisions.

D.D.: Distinction fr. other causes is important as they do not resp. to Pph.:

             1)   Vasculitis & other connective tissue diso.

2)   Catastrophic APA syndrome.

3)   Scleroderma renal crisis.

4)   Disseminated malignancy.

5)   Malignant H.T.

6)   D.I.C.

Q.212. What are the secondary causes of TTP-HUS?

A. Most cases of in adults are idiopathic, However, some have associated conditions:
 
Childhood HUS :

      Following severe Drr.é enterohemorrhagic E. coli

      Idiopathic (rare).

Adult TTP/HUS syndrome :

      Idiopathic.

      Drug toxicity. 

      Cancer chemotherapy.

      Mitomycin C. 

      Bleomycin & cisplatin. 

      Gemcitabine. 

      Cyclosporine & tacrolimus. 

      Immune mediated. 

      Quinine.

      Ticlopidine & less often, clopidogrel.

Less certain causes :

      Oral contraceptives. 

      Valacyclovir.

      Condition of hematopoietic cell Tx. (Sm caused by sepsis and/or Ac. GVHD).

      Pregnancy/postpartum. (difficult to DD TTP/HUS fr. Pre-eclampsia/eclampsia-HELLP).

Autoimmune dis.:

      SLE.

      APA syndrome 

      Scleroderma renal crisis (SRC).

      AIDS & early symptomatic HIV infection

      Following bloody Drr. Due to enterohemorrhagic E. coli, typically E. coli 0157:H7.

Q.213. What is the treatment of TTP-HUS in adults?

A. Suspecting Dgx: Idiop. dis. should be suspected: é MAHA & thrombocytopenia without an alternative etiology. Dgx of TTP/HUS is supported if neurologic abn., us. fluctuating (e.g., confusion, headache, seizures, coma) or R.I. also present., although one of TTP/HUS feature é era before effective ttt, is rare.The only request for making initial Dgx of idiop. TTP/HUS & initiating ttt é Pph is: {presence of thrombocytepenia & MAHA without another clinically apparent cause}.   

Initial ttt:  Idiop. TTP/HUS is: MEDICAL EMERGENCY that’s almost always fatal if not well ttted. So, all ptns diagnosed shd be admitted without delay to Pph center: All ptns ttted on urgent basis é Pph, rather thn pl. infusion or im/m. therapy alone. Pph should be initially started daily until platelet count hs normalized & hemolysis largely ceased, as evidenced by a return of the s. LDH to normal or near  normal. If Pph is not immediately available, pl. infusion may serve as TEMPORARY ttt until ptn transfered to Pph medical center.

Adjunctive ttt é “G.corticoids” in the foll.:

      If there’s no evidence for a drug-induced etiology or a bloody Drr prodrome, or

      In ptns whose platelet counts do’nt incr. within sev. days of ttt é Pph, or

      In those in whm thrombocytopenia recurs when Pph ttts are or stopped.

Refractory/recurrent TTP-HUS :  Ptns e sev. course who don’t rapidly resp. to  Pph, worsen é neurologic abn. despite Pph+steroids, or hv relapsing dis.:

*      Add. of rituximab or Csp is recommended.

*      Incr. Pph frequency to twice daily.

Q.214. How does the recurrence of TTP/HUS occur after transplantation?

TTP/HUS describes Ac. synd. é abn. in multiple systems in adults. Some evid-ence sugg.: the two entities may be distinguished, based upon presence and/or activity of  von Willebrand f. cleaving protease (ADAMTS13). Recurrennce of HUS after R.Tx.: 25-50 %, wch may be overestimating, as both Ac. Vsc. Rj. & CAI Vasc. Rj. & thrombotic microangiopathy indistinguishable fr. Iry dis.. Multiple clinical ch.ch. may be ass. é recurrent HUS in R. allograft. As examples: Ptns é P.H. of HUS due to non-Drr. causes (non-shiga associated [NStx] HUS) may be at a much higher risk of recurrence after T.x. thn those é HUS foll. an episode of Drr..

Meta-analysis: recurrence HUS ws signif. ass. é [older age at onset, short dur. betw. onset & ESRD or T.x. , use of living related donors & to lesser degree, use of CNI.].  Recurrence occ. in most familial HUS, which’s usually. due to mutations é C. inhibitor genes . Lower recurrence occ. é nephrectomy (limited evidence). Ptns typically present é: [MAHA, thrombocytopenia & ARF]. Graft loss rep. in 10-50 % of cases. Prognosis: Overall graft success may dcr. é recurrent TTP/HUS.

Q.215. How to manage TTP-HUS recurrence after transplantation?

A.: First Phases: prevention by:[low-dose aspirin + dipyridamole ]. It’s also sugg.: Csp & ALS should be used é caution.

Second: ttt of recurrence: Csp>50 % é 1st Sn of recurrence, Pl. infusions & Pph, as in Iry dis., have been given é some success in selected ptns. Same is applied to TTP.

DE NOVO HUS: Rare problem except for: early Csp toxicity & Ac. vsc. Rj.. Some ptns receiving OKT3 à a. & v. thrombi within allog. graft loss. This comp. is mostly occ. é high-dose OKT3 (10 mg/d. rather thn recomm. of 5 mg/d.).

De novo HUS occ.:

*       Tacro. (FK506). However, R. allog. recip. dev. TTP-HUS while taking Csp may hv high rate of graft salvage after switching to tacro. (13 of 16 in one report).
*      Siro/Csp combination. 
*      Valacyclovir .
*      HIV, parvovirus B19 (ass. é red cell aplasia) & other infc., incl. CMV .
*      A.B. agnst v.W. f.-cleaving metalloprotease ADAMTS13: responsible of idiop. TTP.
*      Mutations in complement receptors.
 

De novo dis. may be localized to allog., while others hv other systemic manf., e.g. thrombocytopenia & hemolytic anemia. De novo localized dis. app. to be ass. é better R. prognosis, é allog. loss & need for Pph and/or DX. being less likely thn obs. é systemic dis. Withdawal of suspect drug resolution of de novo dis., use of tacro. or siro. instead of Csp. Use of [pred .+ MMFthrombopathy resolve . Success also rep. é: [Pph., i.v. IgG., rituxi-mab & belatacept ].

Q.216. IgA Np is the renal limited form of which systemic disease? Describe the biopsy features?

A. Henoch-Schönlein purpura (HSP) is the systemic form of IgA Np.

- HSP nephritis is defined by: { Presence of IgA deposits  detected by I.F. & I.P. = Same features of IgA Np.}.


Q.217. What are the dyslipidemic changes that associate CKD?

A. CKD dyslipidemia:

1)   Dcr. HDL.

2)   Incr. LDL.

3)   Incr. intermediate density lipoproteins.

4)   Incr. proatherogenic lipid particles.

        - All of these changes promote atherogenesis.

Q.218. What are the target level for statin therapy for dyslipidemia in CKD?

A. Current UK guidelines suggest: adoption of guidelines for Iry & IIry prevention of CVS dis, tht apply to general population: Statin ttt. é 10 y. risk of >30 % (Based on: joint British Societies’chart or CVS risk calculator). Statin diso. shd be incr. to achieve:

*      Total cholesterol of < 5 mmol/L.

*      30 % reduction fr. baseline;   or

*      Fasting LDL-cholesterol <3 mmol/L.

- The aim to achieve the target wch. represent the greatest reduction.

 Q.219. What is thrombotic microangiopathy (T.M.A.)?

 A. T.M.A. = [Alteration in microvasculature é detachment & swelling of endothelium+ deposition of amorphous material é endothelial space + luminal platelet aggregation microthrombosis].                         

**  Lab. criteria:

                 I.        Schistocytes.  

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               II.        Thrombocytopenia.

             III.        Hemolytic anemia.

Q.220. What is T.T.P. pentad?

 A. T.T.P. pentad:    

1)   Fever.

2)   Thrombocytopenia.

3)   Renal dysfunction.

4)   Neurological manifestations.

5)   Microangiopathic hemolytic anemia.


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