What are the major categories of ATN?

 

Tubulointerstitial Diseases  

Revise please the abbreviation list on:

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

Q.242. What are the major categories of ATN?

  A.  Two major categories:   ✌

                                                     I.        Ischemic ATN.  

                                                   II.        Nephrotoxic ATN.

- Both ischemic & nephrotoxic cn co-exist in the same critically ill ptn. & 50 % of cases are multifactorial.

Q.243. What is ischemic ATN?

A. When kid. hypoperfusion is severe & persistent in a case of pre-renal azot-emia, Ischemic ATN, wch’s us. more severe than nephrotoxic ATN, cn be self -limited. Ischemia is foll. by Reperfusion Injury, wch’s ch.ch. by [generation of O2 free-radicles, disruption of cell membrane, leak of ca+ & other cations into cells, depletion of high energy phosphate compounds, mitochondrial dysfunction & Cell death.]. **

Q.244. Enumerate the causes of nephrotoxic ATN?    ✋

A. I. Endogenous toxins: 

(1) Hemolysis (H.B.).

(2) Rhabdomyolysis (Myoglobin).

(3) Tumor lysis syndrome.

(4) Hypercalcemia.

(5) Multiple Myeloma.

  II. Exogenous toxins:  

1)   Lithium.

2)   Heavy metals (Lead, mercury).

3)   Radiocontrast agents.

4)   Organic Solvents (e.g. ethylene glycol).

5)   Nephrotoxic antibiotics (e.g. aminoglycosides).

6)   Nephrotoxic anticancer agents (e.g. Cisplatin).

7)   Fluorinated anesthetics (methoxyflurane, halothane).

Q.245. Describe the pathologic lesions of ATN?

A. Parenchymal changes Patchy & irregular, whether ischemic or nephrotoxic:

(1) Tub. cell necrosis of varying degrees of regeneration.

(2) Reflecting finding in urine analysis, there’s:

                                                     i.        Loss of tub. brush border membranes.

                                                    ii.        Renal tub. cell casts are frequent.

 

(3) Interstitial edema & interstitial inflammation.

- Finding are relatively non-specific & may persist even é recovery phase.

Q.246. What is the pathophysiology of ATN?   

A. GFR decline ch.ch. ATN, occurs through four different mechanisms:

v  Intratub. obstruction: [tub. cells+ cellular debris (brush border mem-brane) + crystals (e.g. uric a.) + Casts (H.B., Myoglobin, proteins) 🠞 slough into tub. lumen🠞 🠝 intratub. pressure🠞 Occlude filtration flow .

v  Tub. back leak: tub. B.M. disrupt.🠞 Abn. reabsorption of filtrate & dcr. ur. flow.

v  V.C.: Tub. damage V.C. thr. [RAAS - Endothelin-  V.D.🠋 e.g. N.O. & P.G.I2].

v  G. permeability disruption: Ischemic/nephrotoxic insult directly alter the intrinsic glomerular cpll. B.M. permeability.

N.B.: The underlying process of ischemic ATN occurs in multiple steps, incl.: pre-renal, initiation, extension, maintenance & repair. This leads to a variety of major hist. changes, incl.: {the effacement & loss of proximal tubule brush border, patchy loss of tubule cells, focal areas of proximal tub. dilatation, distal tub. casts & areas of cellular regeneration that appear duration the phase of recovery of renal function}. A No. of processes contribute to pathogenesis of tub. necrosis, incl.: [endothelial & epithelial cell injury, intra-tubular obstruction & immunologic or inflammation processes].

v  ATN is a common complication of severe ischemia (often due to prolonged Hpt.), major surgery, or sepsis. ATN frequently occurs in combination with underlying co-morbidities.

v  For unclear reasons, ATN appears to be an unusual complication of H.F. even at degrees of systemic Hpt., tht’re ass. é ATN in other circumstances.

Q.247. How can laboratory parameters help in D.D. of prerenal azotemia from ATN?

A. ATN{High ur. Na >20 mEq/L- High FENa (>2 %)- R. tub. cells & muddy-brown granular casts- Low, fixed Sp. G. 1010 - Low osmolality: 280 mOsmol/ L }.

v  Pre-R. azotemia {Low ur. Na< 10 mEq/L-Low FENa. (<1%)- Normal sediment or clear hyaline casts- High Sp. G.>1018- High Osmolality > 500 mosmol)}.

** Summery:

ATN [HighNa- HighFENa- Active muddy granular sed.- LowSp. G.- Low Osmolality].

Pre-R.azot. [Low Na- Low FNa- Normal sediment- High Sp.G.-High Osmolality].

Q.248. What risk factors increase the risk of developing of ATN é radio-contrast agents?

A. Risk factors that increase the risk of developing of ATN:  ⮞ 👌

(1) D.M.

(2) Ch. R.I.

(3) Dehydration.

Q.249. How to prevent contrast nephropathy (C.Np.)?

A. Optimal ttt. is uncertain, the foll. preventive measures é increase risk of C. Np., defined as: s. cr. ≥1.5 mg/dL (132 micromol/L) or GFR <60 ml/1.73 m2, esp. Dc.s. :

(1)         Use, if possible, U/S., MRI or CT, without radiocontrast.

(2) Don’t use high osmolal ag.s (1400-1800 mosmol/kg) .

(3) Use:iodixanol or nonionic low osmolal ag.s (iopamidol or ioversol) rather iohexol.

(4) Use low dose contrast & avoid repetitive, closely spaced studies (<48 h. apart).

(5) Avoid: volume depletion & NSAID.

(6) If no C.I. to vol. expansion:⮞ isotonic i.v. fluids prior to & continued sev. h.s after contrast. Optimal type of fluid & timing are not well established. We sugg.: isotonic bicarbonate rather thn isotonic saline.

(7) Isotonic bicarbonate:bolus of 3 mL/kg of for one h. prior to procedure, continued é 1 mL/kg/h./6 h.s after procedure. Isotonic bicarb.= {150 mEq of sod. bicarb. (three 50 mL ampules of 1 mEq/mL sod. bicarb.) + 850 mL of sterile water}.

(8) If isotonic saline chosen: 1 mL/kg/h., begun at least 2 & preferably 6-12 h. prior to the procedure & continuing for 6-12 h.s after contrast. Dur. of fluid thpy shd be directly proportional to degree of R.I. (longer for sev. R.I.).

(9) Acetylcysteine be given day before & the day of procedure, based upon its potential for benefit & low toxicity & cost: 1200 mg orally twice/d. rather thn 600 mg twice/d. the day before & the day of the procedure .

(10)      Do NOT use: i.v. acetylcysteine for prevention of C. Np. (lack of evidence of benefit & potential risk of anaphylactoid reactions.).

(11)      Do NOT use: mannitol or other Prox. diuretics.

(12)      CKD3/4: Do NOT perform Prox H.F. or HDX after contrast exposure.

Stage 5 CKD:Prox. HDX. after contrast exposure if there’s already a functioning HDX access . We wd not place a temporary access for Prox HDX. in these ptns. Some clinicians would not perform Prox HDX. in any of these ptn..

Q250. How can you get an approach to the etiology and diagnosis of ATN & pre-renal disease?

A. 

Approach to the etiology & dgx of ATN & prerenal disease

 

1)      Two majorAcauses of AKI in hospitals: {prerenal dis. & ATN}. They account for 70-75 % of all AKI causes. Dcr. R. function due to prerenal dis. occ. when R. ischemia is a part of generalized dcr. in tissue perfusion & é selective R. ischemia. ATN cn occ. é prolonged and/or sev. ischemia  🠞 hist-ologic changes, incl.: necrosis. 

2)   Both prerenal & ATN can occur in may settings. Prerenal dis. cn occ. é true vol. depletion, Hpt., edematous states & selective R. ischemia, while ATN is mainly due to all causes of sev. prerenal dis., esp. Hpt. & nephrotoxins. 

3)   Careful history & physical examination can identify events and/or dis. processes that underlie pre-renal dis. or ATN, suggest the underlying diagnosis .

4)   Initial evaluation to distinguish ATN fr. pre-renal dis. incl.: 3 measures: [Urinalysis, resp. to fluid repletion(if not C.I.) & FENa. are used in combination é clinical setting to help diagnose the underlying disorder.   

5)   Urinalysis: normal or near normal in prerenal dis.; hyaline casts may be sn, but these’re not an abn. finding. In comparison, classic urinalysis in ATN 🠞  {muddy brown granular & epithelial cell casts & free epithelial cells}. However, the abs. of these urinary findings doesn’t exclude ATN. 

6)   C.P. consistent é fluid loss & hypovolemia (Hpt. & tachycardia) and/or oliguria:  🠞 i.v. fluid, unless C.I.. Fluid challenge attempts to identify prerenal failure tht cn progress to ATN if not ttted promptly. 

7)   FENa typically < 1 % in prerenal dis.(= sodium retention) & > 2 % in ATN .

8)   S. CR.: widely used in dgx. AKI. However, as it’s a suboptimal biomarker, different urinary & s. proteins hv been intensively investigated. Although there’re promising candidate biomarkers, none are currently used clinically.

Q251. What is the possible prevention & therapy of postischemic (ischemic) ATN?

 

A. Prevention & therapy of postischemic (ischemic) ATN:

1)   Try to preserve R. function via the foll. : {preserving cell viability; atten-uateing inflmm., preserving RBF & preventing or reversing intratub. obstruction}. 

2)   Several barriers exist for successful completion of clinical trials in post-ischemic ATN., incl.: heterogeneous & complex. ptn. f.s, lack of a standardized definition of  AKI, diagnostic criteria & lack of clear & sp. endpoints for the trials. 

3)   Definitions of AKI varied widely. The Acute Dialysis Quality Initiative (ADQI) hs used a set of criteria called “RIFLE” (Risk, Injury, Failure, Loss & End stage) criteria. High-risk ptn. incl.: those é risk f.s for AKI but a normal baseline GFR. This incl.: D.M. & H.T. ptn. or are taking medications e.g. NSAID. 

4)   1^st step: identify ptn. at increase risk. or early in ischemic phase: Optimize volume status é i.v. fluids (if necessary) é goal of optimizing:[cardiac preload, C.O. & RBF]. Exact approach may vary based upon ptn. ch.ch. & sp. settings in wch postisch. ATN is most likely to occr. Additional measures shd include: avoid nephrontoxins & Hpt., a surrogate for reduced RBF. Inotropes may be considered in clinically signif. Hpt. refractory to vol. optimization.

5)   Many pharmacologic ag. hv bn evaluated for prevention of postisch. ATN. None hs bn proven effective & some were harmful. So, do NOT give any. 

6)   Established ATN: assess etiology & vol. status, % institution of therapeutic measures to prevent or dcr. worsening R. function., which incl.: keep adequate hemodynamic status to ensure R. perfusion & avoid further R. injury.

7)   If necessary (volume control): use diuretics for a short time é established post-ischemic ATN. DON’T use diuretics  as prolonged therapy in established ATN .

8)   Do NOT give low dose dopamine to ptn. é established postischemic ATN.

Q252. What are the possible renal and patient outcomes after A.T.N.?

A. Renal & patient outcomes after A.T.N.:

1)   ATN ptn. hv a kidney failure phase tht typically lasts between 7-21 d., Duration is variable. Duration is dependent upon length & severity of initial ischemic episode, whether or not recurrent isch. occ. or nephrotoxic therapy is continued, and perhaps whether ptn. is oliguric or nonoliguric. Whereas some ptn.s recover within days, others require DX for weeks to months. 

2)   Ptn. who recover fr. ATN may not return to their baseline kidney function. An irreversible decline in kidney function after recovery is more likely in ptn. over age 65, those who hv atheroembolic dis., and those é underlying CKD. Ptn. é CKD who dev. AKI are more likely to progress to ESRD compared é patients é CKD who do not experience an episode of AKI. 

3)   ATN dur. hospitalization is ass. é high in-hospital & long-term M.R.. A variety of f.s hv been associated é increase M.R., incl. male gender, race, elderly, oliguria, sepsis, respiratory or liver failure & cerebrovascular events, and esp., overall severity of illness.