KIDNEY PROTECTION

The impacts of COVID-19 on the human kidneys still uncertain. However, experts provide some explanations:

 

Revise please the abbreviation list on:

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KIDNEY PROTECTION

 

Q. How can COVID-19 harm your kidneys?

The impacts of COVID-19 on the human kidneys still uncertain. However, experts provide some explanations:

[1] Coronavirus itself may target renal tissues:

COVID-19 virus itself may infect the cellular components of renal tissues. Renal cell may express multiple receptors that permit coronavirus attaching to these receptors, invading them, and making many copies of itself, therapy damaging renal tissues. Similarly, many receptors elsewhere within the lungs and heart tissues are ubiquitous, where the new coronavirus has been proved to induce injury (AKI).

[2] Hypoxia (deficient oxygen supply) can induce renal dysfunction:

In addition, renal disease in patients with coronavirus can be attributed to an abnormally lowered oxygen concentrations in the blood (hypoxia) that can be attributed to the pneumonia commonly observed in advanced stages of this disease.

[3] Cytokine storm can damage renal tissue:

Our body response to infectious agents may be also contributing. A robust immune response to the new coronavirus can be vigorously triggered in certain individuals that results in a sever cytokine storm when the immune system sends a continuous rush of cytokines into body systems. These cytokines can be observed as minute proteins that assist the cells communicating each other whilst the immune system fighting an infectious episode. However, a sudden rush and a widespread influx of cytokines may induce robust inflammatory response. Whilst fighting to kill the invasive agent, this inflammatory response can damage the healthy tissues, including renal tissues.

[4] COVID-19 can induce blood clotting that block the kidney interior:

Human kidney promotes its function via filtration of toxins, water excess and waste products outside. COVID-19 may induce a very tiny clots formation through the bloodstream that can block the smallest blood vessels in the kidney and impeding its normal function.

 

Q.51. What are the indications for RENAL BIOPSYin asymptomatic hematuria/ proteinuria?

A. Mostly, Not necessary, but should be performed é:

1)   GFR. decline.

2)   Clinical suspicion of undiagnosed systemic dis. aproteinuria, e.g. S.L.E. & M.M.

3)   Definitive ttt. depends on biopsy results.

4)   Reassurance of the ptn. é benign course.

- A.Sm.tc hematuria NOT an absolute indication for biopsy, but some recommend biopsy é persistent hematuria, esp. é GFR decline or concomitant Prot.

Q.52.What laboratory tests help in diagnosis of glomerulonephritis(G.N.)?

A. Lab. tests help in diagnosis of G.N.:

1)  ANA [ SLE, esp. é +ve anti-ds DNA A.B or anti-Smith A.B. 

2)  ANCA [ c-ANCA [ Wegener’s G.N.

3)  P-ANCA  [ M.P.A.       

4)  Complement [ see Hypocomplementemia Q. No. 10

5)  Blood culture [ To rule out infectious dis. (e.g. Endocarditis).

6)  HBV & HCV [ M.N.- M.P. – Cryoglobulinemia.

7)  Cryoglobulinemia [ usually é HCV.

Q.53. Which antihypertensive drugs are SAFE to use in pregnancy? Which drugs are contraindicated?

1)   Methyldopa: the drug most often used in pregnancy.

2)   Hydralazine & Labetalol: also effective & safe.

3)   Atenolol & diuretics: may be effective, but some studies ⮞ affect fetal growth.

 - On the other hand, ACEI. 🠊 C.I., as they 🠊

1.    Neonatal R.F.

2.    Congenital malformation.

3.    Fetal growth retardation.

Q.54. What is the effect of pregnancy on renal function?

A. By the 2^nd trimester🠊🠉 R. Pl. flow by 70 % & remain elevated throughout pregnancy. GFR begins to incr. by the 4^th w. of gestation, é peak of 150% at 13 w. & remain elevated until term. So, a S.cr. > 0.9 in pregnancy= R.I. Kidney size enlarge 1-1.5 cm.. Hormonal changes⮞ Ureteric dilatation

⮞ Hydronephrotic picture in U/S. Tub. dysf. also occurs ⮞Hyperuricosuria, hypouricemia & glucosuria without hyperglycemia.

Q.55.What is the effect of pregnancy on underlying renal disease?

A. Ability to conceive in a women é R.I. is proportional é degree of R. dysfun-ction. Ptn. us. exhibits higher rates of urinary protein excretion owing to incr. filtration rate (🠉GFR) in pregnancy. The most important determinant whether R. function deteriorates in pregnancy is 🠊 the level of R.I. At the time of conception. Women é S.cr. > 1.4 mg/dl. at time of conception🠊 is more liable for decline of R. function. Moreover, underlying R. disease 🠊🠉 Risk of preeclampsia.

Q.56.What are the renal manifestations of preeclampsia?

A. Preeclampsia: 👉

1)       Dcr. GFR.

2)       Proteinuria.

3)       Glomeruler“Endotheliosis”: Swelling of the G. endothelial cells.

4)       Renal sodium retention  🠊 edema, ch.ch. this disorder. 

Q.57.What is the difference between eclampsia & hypertensive encephalopathy?

A. Fundal hallmark of H.T.E.: {Retinal hges, exudates, papillary edema}🠊 rare in eclampsia, wch. ch.ch. by Seizures occ. due to 🠊 cerebral V.C. & platelet micro-thrombi.    

Q.58. Describe how does endothelial function deranged in CKD?

A. Endothelial function derangement is one of the initial steps for atherosclerosis. In Non-renal ptn., endothelial function us. deranged due to:

1.               H.T.

2.               D.M.

3.               Obesity.

4.               Smoking.

5.               Dyslipidemia.

- In CKD ptn, the following factors are added:  

1)   Oxidative stress.

2)   Insulin resistence.

3)   RAAS activation.

4)   Reduced activation of vit. D.

5)   Reduced intrarenal production of N.O.

6)   Low level “persistent inflammation”.

7)   Homocysteine & ADMA (Asymmetric dimethyl-arginine) retention.

8)   Reduced production of: EPO, renalase & bone morphogenic protein.

Q.59. Discuss the impact of the aforementioned factors in CVS dis. development ?

1)   Oxidative stress: Imbalance between ROS (Reactive Oxygen Species) & body ability to inactivate them or repair their dge effect. Despite HOPE (Heart Out-comes Prevention Evaluation trial) showed: No benefit of vit. E in 🠊🠉 CVS risk, some authors still argue: Antioxidants e.g. [vit. E. & acet-ylcysteine] may be beneficial in CKD.

2)   Insulin resistence & hyperinsulinemia: 🠊🠉 athero. development, as they present early in CKD. HOMA technique (homeostatic model assess-ment) from fasting glc. & insulin: used to dgx. insulin resistance. HOMA index hs bn used to predict survival in DX. ptn. Insulin resistance & endothelial dysf.c vsc. dge. ttt.: [Diet, exercise, ACEI, glitazones].

3)   Hyperhomocysteinemia:🠉 homocysteine in CKD 🠊🠉 CVS risk. Causes 🠊 multifactorial. But can be partially corrected by:👉 [vit.B. complex].

4)   N.O. & ADMA: L-arginine – (N.O. synthase) -🠊 N.O. production é vasc. endothelium. CKD🠊🠉 GFR 🠊 ADMA retention, wch’s competitive inhibitor é N.O. synthetase. Incresed ADMA🠊🠉 CKD progression & increased mortality.

5)   Low grade inflammation: Ch. inflammation 🠊 athero. in CKD & non-CKD ptn. In CKD chronic inflammation🠊🠉 fetuin-A =[Potent inhibitor of vascular calcification].

6)   Abn. bone mineral metabolism:

(a) Hyperphosphatemia: 🠉 PO4 🠊🠉risk of death in both early CKD & DX ptn. To dcrease PO4: both {dietary restriction+ PO4  binders} :

[Ca. Carbonate - Ca.  acetate- Sevelamer HCL- Lanthanum carbonate] are needed .

Sevelamer🠊🠉 s. cholesterol & 🠉 risk of progression of established coronary a. calcification in DX. ptn.

Current recommendation é target s. PO4 (UK.):🠊

      Stage 3 & 4 CKD : 0.9-1.5 mmol/L. 

      D.X. :  1.1-1.8  mmol/L. 

(b) Hyperpara.: PTH 🠊 Defective cpll. supply to cardiac myocytes (animal/ vitro). In ptn.: correction of sev. hyperpara.🠊 beneficial in calcific uremic arteriopathy.(CUA).

- Effect of correction of hyperpara. by Cinacalcet is studied in EVOLVE study.

- CUA(Calciphylaxis) carries a v. poor prognosis, é high mortality fr. CVS. dis.

 

 

* Risk Factors for Cardiovascular Disease in Kidney Disease.

Traditional Risk F.s				Nontraditional Risk F.s
• Age • Male sex • Diabetes • Hypertension • Smoking • Dyslipidemia • Family history • Obesity				• Kidney function decline • Albuminuria. • Anemia. • Inflammation & oxidative stress • Diso. of mineral metabolism:       - Hyperphosphatemia       - Changes in vit. D metabolism       - Secondary hyperparathyroidism       - Elevated FGF-23 levels • Activation of the sympathetic nervous system

FGF-23 = fibroblast growth f. 23.     (Kendrick J, et al.).

Q.60.What are the insulin & CHO metabolic abnormalities in CKD?

1.    Insulin resistence (I.R.).

2.    Circulating inhibitors for insulin action.

3.    Dcreased islet cell insulin secretion.

- Insulin resistance hs bn described in CKD with KRU.

Q.61.What is the mechanism of insulin resistance in CKD?

A. It is thought to be due to postreceptor abnormalities induced by:

1)   Metabolic acidosis.

2)   Lack of Vit. D.

3)   Uremic toxins accumulation.

4)   Proinflammatory cytokines.

5)   Others: Uric a., pseudouredine & advanced glycation end-products.

 Q.62.What is the impact of insulin resistance in CKD? How to treat?

A.   Insulin Resistence:

1)   Endothelial dysfunction, the early step for athero. development.

2)   It correlate well é CVS mortalities in non-diabetic DX. ptn.

3)   It contributes to msc. catabolism DX. ptn.

4)   Contribute to CKD progression via deleterious R. hemodynamic effects.

***  ttt.: Drugs that improve I.R.: 

1)   ACEI.  

2)   ARBs.   

3)   25-(OH.)vit. D.

4)   Thiazolidinediones:  e.g.

“Generic Name”	“Brand Name”
“Pioglitazone”	“Actos”
“Rosiglitazone”	“Avandia”

Q.63.What is the impact of dialysis technique on insulin resistance in CKD? How to assess?

A. HDX & PD. 🠊 partially correct I.R., P.D. hs higher insulinemia thn HD. & more severe I.R. due to glucose load absorbed fr. glucose-based Dzt fluids.

- Use of “icodextrin” & a.a. as glucose-free P.D.🠊🠉I.R. incidence.

- HOMA technique (homeostatic model assessment) for assessment of I.R.:

HOMA  I.R. calculation:{[Insulin conc. (U U/ml) x fasting glucose(mmol/L)] / 22.5 }.

Q.64. What is Adipokines?

A. A group of hormones & cytokines secreted by adipocytes.The most important identified adipokines⮞Leptin  & Adiponectin.

- Biological actions of Leptin :

1)   Anorexia.  👆

2)   Incr. energy expenditure.

3)   Proinflammatory effects.

4)   Proatherogenic effects.

- Biological actions of Adiponectin :

1)   Anti-atherogenic effect.  

2)   Anti-inflammatory effect.   

3)   Potent insulin-sensitizing effect.  

Q.65.What is the impact of CRF on Adipokines? Then, what are expected effects?

A. CRF & ESRDØHyperleptinemia (5-7 times normal & P.D.> H.D.). & moderate Hyperadiponectinemia (2 folds rise in ESRD).

- Factors other thn R. function modulating hyperleptinemia & hyperadiponectinemia:

1)   Fat mass.

2)   Acidosis.

3)   Inflammation.

4)   Hyperinsulinemia.

-Accumulation of adipokines in CKD augment the decline in R. function thr.:

1)   Hyperleptinemia⮞ Protein-energy wasting in ESRD.

2)   Hyperleptinemia ⮞ Worsen sympathetic overactivity seen in CKD.

3)   Hyperleptinemia ⮞ Promotes H.T.

-Adiponectin : needs further investigation.

Q.66.What is the pathogenesis of B2  microglobulinemia?

A. B2M is a nonglycosylated polypeptide of 11.8 kDa. It is a component of the class I major histocompatibility Cx. & present in all surfaces of virtually all nucleated cells.

- Clearance by glomerular filtration foll. by proximal tubuler cells uptake & catabolism.

-Incr. B2M ⮞ A. B2M formation. Two main causes for incr. B2M:

  I. Dcr. clearance:                                                                                                

1)   Fall in GFR.     

2)   DX. modality.   

3)   Abs. of KRU.

  II. Incr. production:

1)   Metabolic acidosis.

2)   Interferon-a therapy.

3)   H.D. membrane bioincombatibility.

4)   Lymphoid cell activation:(clonal B-cell diso., viral infc., Rhoid arthritis, SLE, Crohn’s).

Q.67. What are antidiabetics that should be avoided in stage III/IV. CKD?

A. For type II. D.M. & according to K/DOKI guidelines:  

1)   1^st gen. Sulphonylurea:[Acetohexamide, tolbutamide, tolazamide, chlorpro-pamide (é GFR< 50 ml/min) ].

2)   2nd G.S.urea: [Glyburide].

3)   Biguanides: [Metformin, avoid: é GFR<40-50 ml/min)].

4)   a glucosidase inhibitors:[Acarbose, miglitol], Not é s. Cr >180 umol/l.

Q.68. What oral antidiabetics that are safe to be used in stage III/IV. CKD?

A. For type II. D.M. & according to K/DOKI guidelines:    

1)   2^ndG.S.urea: [Glipizide & Gliclazide: Nodosa., Glimepiride: Start é 1 mg.].

2)   Meglitinides: [Repaglinide (Novonorm): Nodosa., Nateglinide: Start é 60 mg.].

3)   Incretin mimetic: [Exenatide. (Byetta)].

4)   Dpp-4 inhibitor:[Sitagliptin:⮞50/75 % é GFR:< 50/30 ml/min. resp.] .

Q.69. What is the major criteria of HIVAN (HIV associated nephropathy) ?

A. Major criteria of HIVAN:      

1)   Higher % of “glomerular collapse”.  

2)   Severe tubulointerstitial disease .

3)   Greater visceral cell swelling. 

4)   Numerous “tubulo-reticuler” inclusions é G. & vascular endo-thelium.

Q. 70. How can you expect the diagnosis of Rhabdomyolysis?  

A. A comatose ptn. é [msc. tenderness + areas of pressure Necrosis + multiple injuries + Bioch.( incr. K+ Po4) + ARF. (Myoglobin Cast ATN.)+ elevated C.K. > 1000 + Normal cardiac “Troponin” & ECG]. = shd. raise the Dg.x. of rhabdomyolysis.

Q. 71. What is the possible therapy in this case?

A. Treatment of “Myoglobin Cast” ATN., (Crush Synd.):

1)   [Normal Saline]: one L./h. until urine flow à 20 ml/h. (½ L/d.) à isotonic bicarb., 500 ml/h… do PH..

2)   If ptn. is not oliguric/anuricà [Mannitol] monitor é CVP., k, Ca balance.

3)   H.DX.: intermittent rather CRRT🠊 3 sessions/d. to avoid fatal hyperk.+

** Cautions:   👆     ✌

1.    Do NOT use loop diuretics:🠝increase “cast tubuler Obstruction” & wors-ening of R.F., it has No role in AKI.☜

2.    Do NOT use mannitol in oligo/anuric ptn. (C.I.) .

Q.72. What do you know about HAN.?

A. Heroin-associated Np. including:

1)   FSGS.  

2)   Post-infectious G.N.

3)   H.B.V.⮞M.N.  

4)   H.C.V.⮞M.P.

5)   2ry Amyloidosis (multiple skin infection).        

6)   Interstitial Nephritis.  

Q.73. What is “glomerular permiselectivity”?   👆

A. A [property of G. cpll. membrane whereby solutes, including proteins, are restricted fr. passage across cpll. wall into⮞ urinary space]. Exclusion of a protein fr. Bowman’s space is based to some extent on its molecular size & conformation, but mostly fr. its net Negative charge. Negatively charged proteins are excluded fr. G.U.F due to their inability to pass thr. Negatively charged endothelial cells. تنافر G. cpll. B.M. are surrounding endothelial cells & epithelial structures that comprise the slit diaphragm.

Q.74. What is “functional proteinuria” (F.P.)?

A. [Transient protein excretion ass.: fever, strenuous exercise, emotional stress & CHF]. One explanation is🠝 R.B.F. 🠊🠉 albumin excretion, the other: H.F. & Renovscular H.T.  🠊🠉 Angio.II 🠊proteinuria, due to Direct effect of Angio.II. on G. Permiselectivity.

Q.75. Define “asymptomatic proteinuria”(A.Sm.tc Pr.)?

A. Urine excr. us. range fr. 40-80 mg/d., but most labs define  150 mg/d. = upper limit of normal. A.Sm.tc proteinuria= {urinery protein excretion >150 mg/d, but <3.5 g./ d., but No ass. Sm or Sn of N.S. (odema, hypoalbuminemia, hyperlipid-emia, thrombotic comp.}. Ptn us. excr.< one g./d. A.Sm.tc Pr. ass. é less serious consequence than those é N.S.

Q.76.What are the most common causes of asymptomatic proteinuria” (A.Sm.tc Pr.)?

A. A.Sm.tc Pr. either G. or tub. diso. (NRP. usually G.), G. proteinuria aexcr. of high m.w. proteins e.g. albumin & globulin, where as tub. proteinuria a smaller protein as well.

** “Glomerular”  causes: 

1)   Functional proteinuria.

2)   Orthostatic proteinuria.

3)   Early glomerular dis.

** “Tubular” causes”: 

1)   A.T.N.

2)   Pyelonephritis.

3)   Analgesic nephopathy.

4)   Ch. K+ depletion.

5)   Overflow proteinuria.

6)   Heavy metal intoxication.(Cadmium).

7)   Hereditary (Fanconi Synd., Wilson’s dis.). 

 

Q.77. What is “orthostatic”proteinuria (Postural proteinuria)?  What is overflow proteinuria (overproduction)?

A.“Orthostatic”proteinuria : [a condition é wch. ptn. excrete excess ur. protein only é upright position]. It occ. almost always é young men & us.< one g./24 h., é No ass. G. lesion & é spontaneous resolution é 5-10 y. Dgx.:Elevated daytime(morning to bedtime: 16 h.)+ Normal night (to morning=8 h.) ur. protein. If both collection are high a persistent proteinuria.

- overflow proteinuria: A clinical condition: conc. of filtered protein exceeds tubuler reabsorptive capacity, occurs usually é paraproteinemias, e.g. M. myeloma, monoclonal gammopathy., or light chain dis. Alth. mechanism is us. overflow, subsequent G. proteinuria cn occ. due to G. defect.