KIDNEY PROTECTION

Q.221. What is the hallmark lab. of TTP-HUS?

KIDNEY PROTECTION

Revise please the abbreviation list on:

https://draft.blogger.com/u/0/blog/post/edit/8610857019469578230/4564412989605988372

Q.221. What is the hallmark lab. of TTP-HUS?    ✋

 A.    Hallmark lab. of TTP-HUS: (Microangiopathic hemolytic anemia):

                  LDH.

                  Retics.

                  Indirect Bilirubin.

                  Low Haptoglobin.

Q.222. How to D.D. DIC. from TMA?

 A. TMA has Normal: (PT, PTT, Fibrinogen level & Coagulation profile).

Q.223. How to ttt. refractory TTP-HUS?

A. Ptns é: 

1)   Relapsing dis.,or

2)   Severe course who don’t rapidly respond to Pph, or

3)   Worsen é neurologic abnormal despite (Pph + steroids), we recommend:

                     ✌   [Rituximab or Csp + Pph twice/d.].

Q.224. What are the criteria of good & poor prognosis?

A. “Good prognosis”:   😃😃

                Young Age.

      Summer diarrhea.

      Early Dgx. & ttt.

“Poor prognosis”:    😌😌

•      Older children.

•      Winter cold months diarrhea.

•      CRP.

•      PMN.

•      IL6,10.

•      Need for DX.

•      Severe vascular lesion é R. “Biopsy”.

 

Q.225. How can you diagnose R.A. occlusion (thrombosis)?

 

A. RAT: [Hematuria + loin pain + LDH. +anuria]. (contralateral reflex spasm).

- The gold standard in Dgx. 👉”Angiography”.

N.B. Radiographic evaluation of peripheral a. or coronary a. disease often reveals that R.A. lesion are also present (ie, incidentally discovered RAS). Such ptn. do not require therapy directed at R. vasculature since there’s evidence that R.A. revascularization does not improve B.P., R. function, or other outcomes in this setting.   

Q.226. For how long can the kidney afford absence of blood? ⌚⌚

A. Our Kidney can tolerate abs. of blood (e.g. R.A.T.) for 60-90 min. (1½ h. maximum).

Q.227. What are the most common coagulation disorder in nephrotic syndrome?

A. “Two principle” mechanisms are responsible:  ✌

       I.        Activation of G. hemostatic mech.: “intraglomeruler thrombin formation”.

     II.        Urinary loss of: †† 

(1) Antithrombin III.

(2) Plasminogen.

(3) a2-antiplasmin

(4) Free protein S.

-    N.B.: Hypoalbuminemia:

1)   Platelet hyperaggrigability.

2)   Alteration in fibrinolytic system.

3)   Procoagulation proteins.

Q.228. What is the most common complication of atherosclerosis, and what is the most common organ involved ?

A. H.T. is the most common complication of atherosclerosis, and Kidney is the most common organ involved in autopsy.

Q.229. What is the most common extrarenal complication of atherosclerosis? What is its significance?

A. “Cutaneous” manifestations, it heralds ➳ ♠ Renal involvement.

Q230. What is the role of APOL1 in evolution of early renal dis. in African Americans?

A.Two separate dis. -causing polymorphisms in apolipoprotein L1 (APOL1) gene found exclusively in African Americans, inherited as autosomal recessive traits confer a higher risk of ESRD. In addition, APOL1mutations are ass. é earlier on-set of kid. dis.. Study: 407 African Americans receiving HDX, ptn. é two mutant alleles were signif. younger at time of DX initiation thn those without any dis.-causing APOL1 mutation (49 vs 62 y.). In a large population based study incl. 1776 African Americans without known kid. dis. (mean age 45 y.s), homozygotes for APOL1 mutations were more likely to hv microalbuminuria (18 vs 9 %) & estimat-ed GFR < 60 mL/ min per1.73 m2 (6 vs 3 %) comp. é other individuals.

Q.231. Explain how is the incidence of vascular calcification increased in CKD?

Mammogram:extensive vascular calcification complicating CRF:

Vascular calcification occur due to calcification of either atherosclerotic pla-que or the media & recognized as active regulated process not just passive ppt. of Ca+& Po4 crystals. So, vascular calcification is a multistep process similar to bone formation: Vascular smooth msc. cells undergo a phenoltypic switch into osteoblast-like cell & then express ALP, osteocalcin & ost-eopontin Ossification of the extracellular matrix. Po4 retention (R.F.) 🠝intracellular Po4 phenotypic changes in vsc. s.m. described above, So, Po4 retention is a major f. in vsc. calcification.

Fig.: Mechanisms by wch phosphate contribute to initiation/progression of vasc. calcif-ication. FGF-23 = fibroblast growth f. 23; VSMC = vasc. s. m. cells.  Kendrick J, et al.

“Role of Vit. D in Elevated iPTH” in Early-Stage CKD”

 

Sustained rise in s. iPTH occ. in resp. to { R. function decline,  PO4 retention & inability to activate vit. D to calcitriol (1,25-dihydroxycholecalciferol or 1,25-dihydroxyvit. D₃) the hormonally active form of vit. D}. Abnormal vit. D metb. play a significant role é cascade of events † sustained raised iPTH. To maintain Ca+ homeostasis: incr. in PTH to incr. production of calcitriol, eventually † 2ry hyperpara. (SHPT). In resp. to incr. iPTH, further rise in s. P (vicious cycle) occur. Over time, dcr. s. Ca+, incr. extracellular PO4 & dcrease s. calcitriol stimulate parathyroid gland † further incr. in iPTH. Elevated/sustained PTH eventually cause iPTH-mediated removal of Ca+ fr. bone to balance s. deficit of Ca+. Ca+ therefore moves to bloodstream, leading to🠞adynamic bone dis., or to R. osteodystrophy & bone weakening 🠞joint pain, fractures & loss of mobility. Goal of ttt. in pre-DX CKD is to dcr. PTH to normal stage-sp. levels, é eventual return to normal homeostasis – although ptn. é pre-DX. CKD typically do not hv changes in s. Ca &  PO4, and only mild incr. in iPTH. They also may hv incr. FGF-23. So, testing for 25-hydroxy vit. D [25 (OH) D] shd be performed. Active vit. D & vit. D analogues incr. uptake of Ca+ fr. G.I.T. into bloodstream & incr. R. tub. reabsorption of Ca+, thereby dcr. ur. excretion of Ca+. They also stimulate Ca+ release fr. bone by reacting é osteoblasts † RANKL (Receptor activator of nuclear f. kappa-B ligand) release, wch in turn activates osteo-clasts. Along é vit. D sterols, PTH cn work to improve s. Ca+ imbalance  by incr. ur. excretion of inorganic PO4, which🠞Ca+/PO4 cx. to dissolve out of bone, thereby increase s. Ca+. PTH also stimulates calcitriol production, wch inhibits calcitonin release, the hormone responsible for inhibiting Ca+ release fr. bone. Calcitriol is produced in proximal tubule cells and its activity is stimulated by PTH. High s. PO4 dcr. calcitriol  production and the incr. FGF-23 production by osteocytes & osteoblasts. Active vit. D sterols in pre-DX CKD who hv slightly elevated s. iPTH incr. G. absorption of Ca+ & P , thereby stimulating PTH synthesis.”ttt”:[Calcitriol, alfacalcidol (prodrug of calcitriol), doxercalciferol or paricalcitol]. Doxercalciferol & paricalcitol are equally effective as calcitriol for PTH suppression, although “paricalcitol” has been shown to decrease  PTH faster. “ttt” should also including: normalization of s. P. by dietary restriction & PO4 binders, alth. their safety hs not bn proven in this pop-ulation. Calcimimetics, (cinacalcet), are:T C.I. in CKD not on DX. (use is restricted to DX. ptn.) as, they can increase s. PO4 in pre-DX. CKD. Due to narrow therapeutic window, vit. D sterols can 🠞hypercalcemia & hyperphosphatemia. (Medscape ).

Q.232. What are the key inhibitors implicated in vascular calcification in CKD?

A. Several inducers & inhibitors hv bn described in the process of vasc calcifi-cation, the current key inhibitors implicated in vasc. calcification in CKD incl.:

      Pyrophosphate.

      Osteoprotegerin(OPG).

      Bone morphogenic proteins  (BMP)7.     👈

      Matrix-carboxyglutamic acid protein(MGP).

      Fetuin A (2-Heremans-Schmid glycoprotein(AHSG).

Q.233. Describe the role of (BMP)-7 in management of vascular calcification?

A. BMP-7 shows the most promise as a future therapeutic agent. It hs the following effects:

1)   Inhibits vasc. calcification.

2)   Prevents ostoblastic transformation.

3)   Maintains vsc. smooth msc. cell differentiation.

-BMP-7 is mainly expressed by the kidney, wch. dcr. fr. the early CKD stages  progressive loss of ability to inhibit vasc. calcification.

- “Recombinant human BMP-7” hs bn used in human trials for osseous repair after bone fracture, and was shown to be safe & well tolerated.

* Risk Factors for Vascular Calcification in Kidney Disease. (Medscape).

Traditional Risk Factors								Nontraditional Risk Factors
• Age. • Diabetes. • Hypertension. • Dyslipidemia. • Smoking.								• Kidney function decline. • Dialysis vintage. • Disorders of mineral metabolism:       - Hyperphosphatemia.       - Hyperparathyroidism.       - Changes in vit. D metb.       - Elevated FGF-23 levels • Inflammation & oxidative stress. • Osteogenesis factors (CBFA1/RUNX2)

Q.234. What are the future prospects helping in stratification & management of CVS in CKD?

A. Future prospects in this issue incl. the following trials:

v  SHARP,

v  TREAT,

v  AURORA,

v  EVOLVE studies.

- {BMP-7} shows the most promise as a future therapeutic agent.

Q.235. What is calcific uremic arteriopathy (CUA)? 

A. CUA= Calciphlaxis: Ch.Ch. by diffuse medial calcification of the small & medium-sized arterioles. Intimal proliferation & thrombosis occur Painful skin ulceration & necrosis. Parathyroidectomy (Pec.) may be beneficial if there’s marked hyperpara. Warfarin ppt. the syndrome, probably by f.VII-depend-ent anticoagulant proteins.