TUBULOINTERSTITIAL DISEASES

Q. 253. Can you compare nonoliguric versus oliguric A.T.N.?

TUBULOINTERSTITIAL DISEASES

Revise please the abbreviation list on:

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Q253. Can you compare nonoliguric versus oliguric A.T.N.?

A. Dcr. in GFR occ. in ATN is not always ass. é dcr. in urine output. While anuria (= urine output <50 mL/d.) is relatively rare, urine output cn vary fr. olig-uric levels (< 500 mL/d.) to relatively normal values. Anuria is rare, however. Difference in urine output betw. oliguric & nonoliguric ATN may be due to variations GFR or in rate of tub. reabsorption. Animal & human studies sugg.: less sev. injury is present in nonoliguric  compared é oliguric subjects.  

Use of diuretics to incr. urine output in ptns é established oliguric ATN does not shorten the duration of R.F., dcr. requirement for DX, or improve survival. Among ptn. é oliguria & established ATN, diuretics shd not be used as a possible therapy of ATN. Diuretics may be given for a short length of time for vol. control, but such use shd not postpone initiation of DX. (if required).

Q.254. How could H.B. & Myoglobin (M.G.) harm the tubules? 

A. (1) Iron released fr. H.B. & M.G. generate ➤free radicles that.:

      Attack & oxidize cell membrane ➤ Cell death.

      Consume endogenous V.D. substances, e.g. N.O. ➤ more R. ischemia.

     (2) Markedly oxidized lipids, e.g. F2-isoprostanes ➤ V.C.

Q.255. What is medullary sponge kidney?

A. Disorder of R. collecting duct ➤ Spatulous & dilated ➤ Slow movement of ur. flow fr. tub. to R. pelvis ➤ Supersaturation & crystal formation ➤ Crystal adherence to urothelium ➤ Nucleation, aggregation & stone formation. However, the dis. is asymptomatc.

Q.256. What is the “novel therapy” for APKD?   Is there any harm of a simple renal cyst?   

A. “Novel therapy” for APKD:

1)   Tolvaptan: (vasopressin–receptor antagonist|) ..

         as : (Vasopressinà incr. c. Amp➤ increase Cytogenesis).

2)   Somatostatin (Octreotide )à Dcrease “intracystic fliud” accmmulation.

3)   “m. Tours”: Rapamycin à stabilizes cystic volume.

- N.B.:Tolvaptan in ADPKD: Course is us. ass. é pain, H.T., & R.F. Preclinical studies indicated tht vasopressin V₂-receptor antagonists inhibit cyst growth & slow the kid. function decline. Conclusions: Tolvaptan, as comp. é placebo, slowed the incr. in total kidney vol. & kidney func. decline over a 3-y. period in ADPKD but ws ass. é higher discontinuation rate, owing to adverse events. FDA: Drug safety: Samsca (tolvaptan),Warning: Potential Risk of liver Injury: Healthcare providers shd perform liver tests promptly é Sm. indicating liver inj-ury, incl.:[fatigue, anorexia, Rt. upper abd. discomfort, dark urine or jaundice ]. If hepatic injury is suspected, Samsca shd be discontin-ued, appropriate ttt shd be started & investigations shd be performed to deter-mine the cause. Samsca shd not be re-initiated unless the cause for liver injury is established to be un-related to Samsca. (N Engl J Med 2012; 367:2407-2418. Dec. 20, 2012).

- N.B.: “Simple renal cyst”, recently:

Simple renal cysts are obs. frequently in normal kidney and most nephrologists consider them of little clinical significance. In a large study of healthy potential kidney donors, after adjusting for age and sex, cysts ≥5 mm were ass. é ➤ higher albumin excretion, H.T. & hyperfiltration.

Q.257. Describe the outpatient workup of a patient with nephrolithiasis?

A. Outpatient workup of a patient with nephrolithiasis:

(1) Urine analysis:

               Sp. Gr.>1.020, too concentrated urine ➤Oral fluid intake.

               Ur. P.H. > 6.0 & s. HCO3 ➤ RTA !

               Pyuria ➤ C & S ➤  proper A.B.

               Cystine crystals ➤ 24 h. urinary cysteine.

(2) S. Ca+:

               > 10.5 mg/dl.   Consider Iry hyperpara.➤ P.T.H.

               <10.5 mg/dl.   Normal.

(3) S. Po4:< 2.8 mg/dl é Ca+ stone former add: KPo4  q.i.d. to“thiazide” reg..

(4) S. uric a.:  > 8 mg/dl  if + Hyperuricosuria or uric a. stone present ➤🠟dietary intake of purines & consider Allopurinol thpy.

(5) S. Hco3: < 22 mEq/L. RTA or incomplete “distal RTA” (document é acid loading test) ➤ ttt.: K+ Ctrate. (one mEq./kg/d.).

(6) 24 h. Ur.Cr.:

               Vol. <1500 ml/24 h. Oral fluid intake.

               > 1-1.5 g./d. Adequate 24 h. urine collection.

               < 1.0 g./d.  inaccurate collection (affecting other values).

(7) Urinary Calcium:

    > 300 mg/d. (♂) & > 250 mg/d. (♀) or > 4 mg/kg/d.  if stone analysis is consistent➤ Hydro-chlorothiazide: 25-50 mg q.d.+ K+ Citrate 20-40 mEq/d.

               > 150 mg/d. & Ca+ stones present ➤ thiazide + K Citrate.

(8) Ur. Uric a.:

                                   I.        >700 mg/d. Ur. alkz. (K Citrate 50 mEq./d), Allopurinol 300 mg/d.

                                 II.        < 700 mg/d As above, if uric a. stone still present.

(9) Ur. Po4: calculate (tub. Po4 reabsorption): TRP= {[U/P Po4]/[U/P Cr.]}-1

➤If < 0.8 = R.Po4 wasting 2^ndry to R. tub defect or Hyperpara, is considered.

(10)Ur. Citrate: N. =140-940 mg/d. , Low Ur. Citrate ➤ RTA.

(11)Ur. Oxalate:

               25-50 mg/d.: Reduce dietary Oxalate intake.

               50-150 mg/d. Hyperoxaluria 2^ndry to G.I.T. disease ➤Correct the cause & Cholestyramine 8-10 g/d. PO., to bind bile acids.

               >150 mg/d. Iry Hyperoxaluria ttt.: Pyridoxine (150-400 mg/d.).

Q.258. What is the relationship between bacteria & Struvite stone formation?

A. G.-ve bacteria (Pseudomonas, Klebsiella, Proteus) & G+ve bacteria (Strepto-coccus fecalis)  ➤ Bacterial urease (splitting enz.)➤ ammonium➤Ur. Alkaln-ization. Ch. ch. lamellated structure of struvite stone= Layers of bacterial products + minerals. ttt: stone =foreign body, is difficult to penetrate, So Complete removal+ proper A.B.

Q.259. What tubular transport defect leads to metabolic alkalosis & hypokalemia?

A.Two genetic syndromes, Bartter’s syndrome (B.S.) & Gitelman’s syndrome (G.S.) : ass é mutation in transport proteins é Distal nephron:

B.S. [Metabolic alkalosis + Hypokalemia + N. B.P. + 2^ndry Hyperrenninemic hyperaldosteronism.].

G.S.[Metabolic alkalosis + Hypokalemia, if severe tetany, HypoMg+ Hypocalciuria]. It’s caused by loss of function mutations in thiazide-sensitive NaCl co-transporter in “coll-ecting ducts”. While B.S. is caused by: defects in one of the molecules involved in NaCl transport across TAL. Recently, a new gene (BSND) responsible for antenatal variant of B.S., é sensorineural deafnss, hs bn identified & encode a new protein, barttinبارطين , wch’s essential subunit for basolateral Cl channels.

Q.260. What is Fanconi syndrome(F.S.)?

A. A generalized diso. of R. tub. transport [Po4.uria, a.a.uria, glucosuria+ Loss of K+, uric a., HCO3].Transport abn. are mainly proximal but cn also occ. é distal tub.. Partial F.S. cn occ., but if multiple transport defects occ. this means multiple processes e.g.: Krebs cycle, Na, K+-ATPase, are defective. Ult-rastructural abn. involve mitochondria & endoplasmic reticulum. C.P.: {Rick-ets, osteomalacia, metabolic acidosis, stunted growth (children) & hypo-kalemia]. In “Pediatric”: Cystinosis is ass. é F.S.. In adults, hypoPo4 is Sm.-tc. and acquired F.S., may be ass. é M.M., Wilson’s dis. & tub. toxins. F.S. may be an 👉 early feature of M.M.  

Q.261. What is difference between renal tubular disorder & tubulointerstitial diseases?

A. Interstitial dis. are ch.ch.by: [inflammation or fibrosis “between“ tubules tht – transport abnormalities, wch’r 2^ndry to the inflmm. or fibrotic process].   While...

- R. tub. defects: ch.ch. by [transport abn.+”preserved R.➤architecture”]. Filtered substances [Gluc., a.a., Po4, Ca, Mg.,Na, K+, uric a.] us. reabsorbed in proximal tub., then their excretion is regulated in distal tub.. A reduction in transport of any of them inadequate reabsorption & appearance in urine. Defects may be genetic or acquired.

Q.262. What causes Nephrogenic diabetes insipidus (D.I.)?

A. Inability of the collecting ducts “to respond to Vasopressin”➤ D.I., due to:

(1) Toxic: [Amphotericin B., Li-thpy, HyperCa+, sev. hypok+, distal nephron injury].

(2) Genetic loss of function of proteins incl.: V2 vasopressin receptor & water channel, aquaporin-2.

(3) Obstructive injury.

Q.263. What is “Heymann” Nephritis?

A. Injection of crude preparation of (tub. brush border extract) called (Fx1A) into allogeneic rats ➤ [A.B. mediated response, mimic M.N. in humans + tubulointerstitial injury]. The responsible Ag. MEGALIN.

Q.264. What are the causes of Ac. tubulointerstitial nephritis (TIN)?

A. Aetiology of Ac.TIN :

1)   A.B.: [Cephalosporins- Ciprofluxacin- Sulfonamide].

2)   NSAID – Allopurinol- Aza- Acyclovir.

3)   Infection: {CMV-EBV-HIV- Mumps- Leptospira- Legionella.}

4)   Idiopathic:(Im/m):Anti-tub. B.M dis.

5)    TINU: Tubulointerstitial Nephritis & Uviitis syndrome.                                               

- All NSAID esp. [Fenoprofen & Refocoxib (vioox)]:➤ Risk of TIN dis.

Q.265. What is the hallmark of Ac. tubulointerstitial nephritis?

A. The hallmark of TIN.: { Eosinophilic & Lymphocytic inflamm. cell infiltration é interstitium, “Sparing👉 B.V. & Glomeruli”}.