CLINICAL NEPHROLOGY GUIDE
CLINICAL NEPHROLOGY
Q.11. What non-immune complex-mediated disease can cause low complement level?
A. Non-im/m. complex-mediated R. disease 🠞 C.P. that mimic a primary G.N. include: 👌
1) Atheroembolic R. dis.: H.C. is seen only during active phase of disease.
2) HUS/TTP: 50% ⮞ compl. activated by endothelial damage or bacterial toxin.
3) Severe sepsis, Ac. pancreatitis & advanced liver disease⮞H.C.
Q.12. So, what are other diseases associated with normal complement?
A. H.C. is us. due to C. activation by im/m. depostion é rate > that new complement proteins synthetize. In comp., slower rate of C. activation occur with :
- Focal G.N. (such as IgA Np.).
- Fibrillary G.N.
- M.N., complement us. Normal excep. in M.N. due to lupus or HBV .
- Anti-glomerular BM. AB. dis.
- Wegener's granulomatosis.
- Polyarteritis nodosa.
- Henoch-Schönlein purpura. etc..
Q.13 How to gain an access to isolated proteinuria?
A. Start é Quantitate Prot. excretion & GFR: either Normal or Reduced:
[I] Normal GFR + Non-nephrotic range prot:
1. Recumbent overnight: -ve dipstick= Orthostatic Prot & No further action.
2. Persistenat fixed Prot: Reassess at 6-12 m. (GFR & ur. Prot & B.P.):
a) Normal all à assess annually.
b) BP abnormality +🠉Prot Serology & U/S. Consider R. biopsy.
[II.] Reduced
GFR: Serology & U/S.
Consider: R. biopsy.
Q.14.What kidney disease associated with arthritis?
A. Renal disease associated with arthritis:
1) Lupus Nephritis.
2) Amyloidosis.
3) Sarcoidosis.
4) Cryoglobulinemia.
5) Henöch Schönlein pupura.
Q. 15. Enumerate the causes of “Finger Prints” (tubulo-reticuler inclusions) in renal histopathology?
1) H.I.V.
2) S.L.E.
3) Mixed Cryoglobulinemia.
4) Interferon a. therapy (interferon foot processes).
Q.16.Which renal diseases associated with hemoptysis? (See Q. 25)
A. Renal disease associated with hemoptysis:
1) A.P.O. 2ndry to ARF or CRF.
2) Goodpasture’s syndrome.
3) P.E. or infarct 2ndry to G.N. or RVT.
4) Bacteria Endocarditis.
Q.17. What renal disease associated with skin rashes?
A. Renal disease associated with “skin rashes”:
1) Discoid Lupus⮞ S.L.E.
2) Impetigo ⮞ Post-streptococcal G.N.
3) Angiokeratoma ⮞ Fabry’s disease.
4) Hives ⮞
Ac.
interstitial Nephritis.
Henöch Schönlein pupura.
5) Petechiae ⮞
I. H.U.S.
II. Ac. Interstitial Nephritis.
III. Focal G.N. 2ndry to S.B.E.
6) Purpura ⮞
Idiopathic
TTP.
Henöch Schönlein pupura.
Other
forms of vasculitis.
Q. 18. Enumerate the causes of “N.S.” with glomerulopathy?
A. Causes of “N.S.” with glomerulopathy:
1) M.N.
2) FSGS.
3) Minimal change Nephropathy.
4) C1Q Np.
5) Fibrillary G.N.
Q. 19. Which drugs can cause “N.S.”?
A. [Gold-Silver-Mercury-Lithium-Contrast media-Captopril] can cause N.S.
Q.20. What are the “primary” causes of acute proliferative G.N.?
A. Primary” causes of acute proliferative G.N.:
I. Membranoproliferative G.N. (MPN).
II. Mesangioproliferative G.N.:
i. Ig. A Np.
ii. Ig. M Np.
iii. Idiopathic.
Q.21. What are the “secondary”causes proliferative G.N.?
A. The “secondary”causes proliferative G.N.:
1) Lupus Nephritis.
2) Post infectious G.N.
3) G.N. 2ndry to HBV & HCV. Infection
4) Vasculitis: [Wegener’s, polyarteritisNodosa, Henöch-Schönlein purpura].
Q22. Enumerate various causes of lung hemorrhage and RBGN?
A. “lung hge + RBGN”:
I. Dis. é A.B. to GBM (20-40 %): Goodpasture’s disease (spontaneous anti-GBM dis.).
II. Dis. ass. é systemic vasculitis:
1. W.G. (common).
2. MPA.
3. SLE.
4. HSP.
5. Churg-Strauss synd.
6. Behcet’s synd.
7. Rhoid. arthritis.
8. Essential mixed cryo.
9. Drugs: [Hydralazine, Penicillamine, Propylthiouracil].
Q23. Enumerate various causes of pulmonary renal syndrome?
A. Pulmonary renal syndrome: {Renal + respiratory failure}, due to:
(A) Lung hge + RBGN & RF: see last Q.
(B) Non- immune causes:
I. With pulmonary edema:
1. Acute kid. inj. é hypervolemia.
2. Severe cardiac failure.
II. Infective:
1) Hantavirus infection.
2) Opportunestic infections in im/m. ptn.
3) Sev. bacterial pneumonia (e.g. Legionella) with R.F..
III. Others:
1) Paraquat poisoning.
2) ARDS é R.F. in MODS
3) R.V. /I.V.C. thrombosis é pulmonary emboli.
Q.24. How can the variable causes of renal injury affect the clinical manifestations?
A. Etiology of renal injury & clinical manifestations:
I. Prerenal:
1. Vol. depletion:
Sepsis:⮞ Fever.
G.I. losses: n. & v.:⮞Hypotension.
Hypercalcemia: ⮞ Polyuria & polydipsia.
2. Hemodynamic:
NSAID: ⮞ Oliguria & Hyperkalemia.
3. Others:
Hyperuricemia: ⮞ Tumor lysis.
Hyperviscosity (IgA, IgG3):⮞ Mental state alterations.
II. Renal:
(1) Proximal tub. injury from light chain, urate & distal tub. injury from casts:
Fanconi syndrome.
Tubular proteinuria.
Crystalluria.
(2) Glomerular dis.: (LCDD, amyloid.):
N.R.P.
Hematuria, active sediment.
III. Post renal: Calculi Colic.
Q25. Enumerate various causes of pulmonary/renal syndrome?
A. “Pulmonary/renal” syndrome(another clacification.):
I. Systemic vscaculitis:
(1) Anti-GBM dis. (Goodpastures).
(2) ANCA associated:
1. W.G.
2. MPA.
3. Churg-Strauss synd..
4. Drugs: (Penicillamine, hydralazine, Propylthiouracil).
(3) Immune complex dis.:
1. SLE.
2. HSP.
3. Mixed cryoglobulinemia.
4. Rheumatoid arthritis.
II. Infection: Sev. bacterial pneumonia- post-infectious G.N.; Legionella, hantavirus, opportunistic infections in im/m. ptn., infective endocarditis.
III. Pulmonary edema & AKI: Volume overload, severe LVH.
IV. Multiorgan failure: “ARDS” & “AKI”.
V. Others: Paraquat poisoning, R.V. or IVC thrombosis é pulmonary emoli.
{Paraquat = trade name for N,N′-dimethyl-4,4′-bipyridinium dichloride, one of the most widely used herbicides in the world. It’s, a viologen, quickly-acting & non-selective, killing green plant tissue on contact. It’s toxic to human beings & animals}.
Q26. What are the disorders involved in gastro-renal syndromes?
A. Gastro-renal syndromes:
I. Diabetes:⮞ [Prot., CKD.] & [Gastroparesis, Dc. Entropathy, Constipation].
II. Systemic vasculitis:⮞[Proliferative G.N., CKD.] & [Intestinal ischemia- G.I. hge, bowel perforation, Hepatobilliary dis., Ac. Pancreatitis.].
III. Systemic Amyloidosis:⮞[N.S., CKD.] & [Drr., malabsorption, Splenic rupture].
IV. APKD (Auto. dom.): ⮞ [CKD, cyst hge, infection] & [Abd. pain (R. or hepatic cyst), diverticular dis., hernia.].
V. Inflammatory bowel disease:⮞[AA amyloidosis, drug-induced interstitial nephritis, Ig A Np., Oxalate renal calcili (é terminal ileal Crohn’s dis.)] & [Abd. pain, Drr., G.I. hge., malabsorption.].
VI. Scleroderma:⮞ [Ac. Renal crisis, CKD.] & [Dysphagia, constipation, mal-absorption, bacterial overgrowth.].
VII. Fabry’s disease:⮞ [Hematuria, Prot., CKD] & [Abd. pain, Drr./ Constipation.]
VIII.
Coeliac
dis.:⮞
[IgA Np.] &
[Malabsorption, iron def. anemia].
Q27. What
are the criteria for definition of CKD?
A. Criteria for CKD definition (National Kid. Foundation):
Kidney damage for > 3 m., defined by structural or functional abn. of the kidney, with or without dcr. GFR, that cn lead to dcr. GFR, manifest by either:⮞Pathologic abnormalities.
GFR < 60 ml/min./1.73 m2 for>3 m., with or without kidney dge.
Markers of kid. dge, incl. blood or urine composition abn., or imaging tests.
Q.28. Which drugs can elevate S. Cr. without reduction of GFR?
A. Two main categories of drugs, incr. S.cr. without affecting the GFR:
I. Drugs that impede proximal tubular secretion of Cr.:
Cimetidine (H2 blocker).
Trimethoprim.
- Cimetidine is used to estimate GFR accurately, by🠝Cr. secretion. Normally, Cr.Cl, overestimate GFR by 15 %.
II. Drugs, falsely raise S.Cr.(Cr. Chromogens)⮞ Interfere é pl. assay:
Cefoxitin. (Mefoxin, cephalosporin).
Fluoxytosine.
- All the above drugs ⮞ S.Cr. + Normal BUN level.
Q.29. What are the RBCs Casts?
A. Ac. G.N.: RBCs ⮞ extravasated thr. the glomerulus ⮞ into the tubular lumen. Ac. G.N.⮞ urinary stasis ⮞Prolonged time for “Tamm-Horsfall” glycoprotein in tub. lumen, quite often in acidic urine⮞ Cast formation with cellular trapping.
Q.30. Give
the D.D. of “Red Urine” ?
A. Centrifugation of urine:
* Red “Sediment”➪ “hematuria”.
* Red “Supernatant” ⮞ Heme Dipstix ⮞ -ve ⮞{beeturia, porphyria, Ibuprofen, rifambicin}.
“Heme Dipstix” ⮞+ve ⮞ either: H.B.uria (Red plasma).
Or ⮞ Myoglobinuria (Clear plasma).
Q. 31. How can glomerular disease induce tubulointerstitial involvement?
A. Five explanations :
1) Immunomodulation 🠞 tub. injury.
2) Diminished glom. blood flow 🠞 tub. ischemia.
3) Inflmm. mediators 🠞 Seep fr. G. to urinary space.
4) Nephron loss 🠞metabolic changes🠞 T.I. nephritis.
5) Impaired glom. “permiselectivity”:🠞 Escape of toxins to urinary space.
Q.32. What is the GFR? What is its normal value?
A. GFR = [The amount of plasma filtered through glomeruli per unit time]. It refers to the sum filtration rate of all functioning glomeruli].
** Normal GFR in men: 115-125 ml/min.
Women: 90-100 ml/min.
Q. 33. What is the main physiological regulators of the GFR?
A. Four factors :
1) Glomerular plasma flow.
2) Systemic (oncotic pressure) (pl. proteins).
3) G. transcapillary hydrostatic pressure difference (not in human).
4) G. U.F. coefficient K.F.= [product of hydrolic conduction of G. Cpll. & its S.A.].
Q.34. What is the clinical significance of GFR?
A. GFR: is the 👆 single best index of functioning renal mass. Serial meas-urement of GFR allows early detection, management, monitoring severity & course of R. disease.
Q.35. In routine clinical practice, how can GFR be interpreted?
A. It is important to consider whether GFR is increasing, declining (R. dis.), or stable, it is Not necessary to determine its 👉exact value. The most widely used, s. Cr. (as clinical index of GFR) is a by-product of the nonenzymatic conversion of Cr. & phospho-creatine in skeletal msc.. Cr. production is pro-portion to msc. mass. Convenience (as endogenous constant marker), reproducibility & low cost of s.cr., account for its popularity. S.cr. varies inversely é GFR.
“Stages of CKD”
|
Stage |
“Description” |
eGFR (mL/min/1.73 m2) |
|
1 |
Normal or incr. eGFR with evid. of kidney dge* |
≥ 90 |
|
2 |
Mild dcr. in eGFR with evid. kidney dge* |
60-89 |
|
3A† |
Moderate reduction in eGFR |
45-59 |
|
3B† |
Moderate reduction in eGFR |
30-44 |
|
4 |
Sev. reduction in eGFR |
15-29 |
|
5 |
Kidney failure (ESRD) |
< 15 |
eGFR = estimated GFR; ESRD = end-stage renal dis. * e.g., path. abn., markers of kid. dysfu-nction, abn. bld or urine tests, or imaging tests.† The incr. risk for death & CVS events if eGFR: < 45 mL/min/1.73 m2 led to subdivision of stage 3 to 3A & 3B. Adapted(Bain S, et al) (Medscape ) .
Q.36.What are the major limitations of S.cr. as a clinical index of renal disease?
1) Low s. Cr. 👉 misleading é low msc. mass (false low).
2) S.Cr. rise é certain drugs(🠋 tub. secr.)👉[trimethoprim, Cimetidine].
3) S.Cr. rise é certain drugs (detected as cr.)⮞ [Cefoxiten, flucytosine, Cephalosp.].
4) Acetoaciticacid (K.A.) ⮞ false rise (detected as cr.).
5) Cooked meat & Rhabdomyolysis ⮞ increasedcr. production ⮞ spurious rise.
6) S.Cr. ⮞ insensitive é early & advanced R. dis.: S.cr. doesn’t incr. until major decline in GFR occ., due to:
1. Tub. scr. incr. é R. dis. progress ⮞ Normal cr.
2.
Compensatory hypertrophy &
hyperfiltration by
injured nephrons, So, S.cr. & GFR ⮞ Normal, despite dcreased in functin-ning glomeruli.
Q.37. How can creatinine clearance (Cr.cl.) be measured?
A. Cr.cl. = [U cr. x V.] / [S.cr.].
U.Cr.= urine conc. of Cr., V= Urine vol. in 24 h.
- N. value=120+/- 25 ml/min. in men & 95 +/- 20 ml/min in women.
- Carefully timed urine collection is necessary is mandatory for accurate measurement.
Q.38. Can GFR & creatinine clearance be estimated from S.cr. measurement?
A.To improve S.cr. accuracy acc. to variables, Cockcroft-Gault & Levey hv bn dev.:
Cockcroft-Gault: Cr. Cl.= [(140-Age) x Wt.(kg)]/ [72 x Pl. Cr.].
- Age in years, B.W. in kg., S.cr. mg/dl.
- In women: multiply by 0.85.
- Children>2 y.: Cr.Cl. : [0.55 x height.(cm)]/ [S.cr.(mg/dl)].
-Levey formula, based on general data fr. MDRD study (difficult & complicated).
N.B. Comparison of Equations for Dosing of Medications Requiring Renal Adjustment:
Bethany A. Lessard, PharmD, Kathy Zaiken, PharmD, J Am Pharm Assoc. 2013;53(1):54-57:
Abstract: To compare Cockcroft-Gault (CG) & Modification of Diet in Renal Disease (MDRD) equations for renal dosing of medications in primary care ptns..The rate at wch CG ideal B.W. & MDRD equations recommended the same dose ws 59.6% (P = 0.001). The rate at wch the CG actual B.W. & MDRD equations recommended the same dose ws 71.1% (P = 0.001). Conclusion A significant difference exists in the doses derived fr. CG & MDRD equations in the primary care setting. CG shd continue to be used for renal dosing until further recommendations are available.
*****************************************************************
Q.39. Can BUN serve as an index of GFR?
A. No, BUN is unreliable index of GFR., due to two limitations:
Renal
tubules reabsorb urea according to the state of
hydration.
BUN
conc. strongly affected by:
Changes in catabolism. &
protein intake.
Q.40.What factors can cause false high urea & false low urea?
A. False high urea [Sulfa- tetracycline- Uric a. - Bilirubin - Lipase -hydration].
- False low urea. [Vit. C- Streptomycin- Levodopa- Lipemia].
Q.41. Define oliguria? ].
A. It is decline of urine volume < 400 ml/d or 20 ml/h.
Q.42. What is acute renal failure?
A. A.R.F. = [Sudden dcr. in R. function, us. manifested by azotemia (🠉 S.cr. & BUN) sometimes ass. é oliguria.].
N.B. Fluoroquinolones (F.Q.) May Double Acute Kidney Injury (AKI) Risk.
Current F.Q. use may incr. the risk for AKI, acc. to the findings of a population-based retrospective study. "Case rep. of AKI é use of F.Q. hv bn published, and the product label incl. R.F. in a list of potential, but uncommon, adverse reactions," the authors write. "In clinical practice, when oral F.Q. are prescribed, the potential for AKI is generally not a clinical consideration." In the study, the authors assessed the risk for AKI ass. é F.Q. among men (40-85) y. who were enrolled in the US LifeLink Health Plan Claims Database between 2001 & 2011. Current F.Q. use ws linked é 2.18-fold higher risk for AKI comp. é no use, whereas recent and past F.Q. use were not linked to AKI risk. The authors excluded men é history of CKD or DX. They used logistic regression to calculate rate ratios, adjusting for F.Q. indication, dis. ass. é AKI, potentially nephrotoxic drugs é high use, and markers of healthcare use. When they looked at individual drugs, they saw tht ciprofloxacin ws ass. é higher risk for AKI , as were moxifloxacin & levofloxacin . In contrast, neither amoxicillin nor azithromycin showed an AKI. In a case-time-control analysis, F.Q., but not or azithromycin , were ass. é higher risk for AKI. Although RAAS blockers alone were not ass. é incr. risk for AKI, the combined use of F.Q. & RAAS blockers ws ass. é greater risk for AKI. Limitations of the study incl.: lack of information on AKI severity, an inability to assess the risk ass. é dosage or duration of ttt, and residual confounding inherent to observational research. "We found a twofold incr. risk of AKI requiring hospital admission é F.Q. among adult men, the authors write. "Although it’s clear that the risk of death due to serious infections outweighs the risks ass. é use of F.Q., the potential for AKI raises the importance of vigilant prescribing."
Medscape Medical News, Joe B. Jr, PhD, Jun 03, 2013. Steven T. B., PharmD, fromUS FDA in Silver Spring, Maryland, and Univ. of Florida in Gainesville & colleagues. June 3 in Canadian Med. Ass. Jl.
Q.43. How accurate and specific are the clinical tests for proteinuria?
A. Dipstix & sulfosalicylic acid (S.S.C.) us. yield similar results that roughly correlate with the exact measurement of urine proteins using sophisticated techniques, but dipsticks indicators are more sensitive to albumin where as S.S.C. recognizes all proteins. I.G. light chains are detected by S.S.C. but not by dipsticks. So, M.M. ptn., proteinuria can be missed unless S.S.C. is used.
44. What is the pathophysiology of proteinuria? Can proteinuria be estimated without performing a 24 h. urine collection?
A. Glomerular proteinuria results from⮞ [structural dge to any of the charge- or size-selective properties of the G. cpll.], while tub. proteinuria results from ⮞ [disruption tub. absorption of the few normally filtered proteins].
- When accurate collections are inconvenient or impossible (e.g. incontinent ptns or small children), proteinuria cn be estimated fr. a single, randomly collected urine sample, by ⮞ calculating the ratio of total urine protein to urine cr. (mg/mg) in a single urine sample {Albumin/Cr. ratio} , which approximate 24-h. protein excretion in g./d./ 1.73 m2 B.S.A.
Q.45. What is pre-renal azotemia?
A. Definition: [Elevation of s.Cr. & BUN, due to “effective” volume depletion🠊🠉R. perfusion 🠊🠉R. bld flow 🠊🠉GFR 🠊urea nitrogen & Cr. retention].The intrinsic ability of kidney function is intact. Pre-renal azotemia is the commonest cause of ARF & is potentially reversible, if ttt.ed promptly & early. It can also superimpose CRF.
Q.46. What medications can induce pre-renal azotemia? Explain the mechanism?
A. Medications-induced pre-renal azotemia:
1) NSAID🠊🠟 PGE2 & I2 production (responsible of R. affererent arteriolar adaptive resp. to hypovolemia, namely affer. V.D.)🠊🠟pre-R. azotemia esp. é vol. depletion.
2) ACEI/ARBs🠊🠉Angio.II. (wch. maintain G.F. pressure in R. hypoperfusion, by “efferent”. arteriolar V.C.) 🠊 dissociation of R.B.F & GFR autoregulation🠊🠉GFR, esp. é bil. RAS & sometimes seen é hypovolemic ptn.
3) Csp. 🠊Endothelin release (a potent V.C. peptide released fr. arteriolar wall endothelial cells) 🠊 intrarenal V.C.
4) Anti-H.T.🠊 extreme B.P.🠊 pre-renal azotemia.
5) Amphotericin B :
Intrarenal V.C.🠊 R. ischemia & pre-R. azotemia é high doses.
Direct proximal epithelial cell toxicity.
Q.47. What is the clinically significant hematuria? Define asymptomatic hematuria?
A. Microscopic finding of > 3 RBCs (H.P.F.), in a centrfugatedur. Clinically significant.
- A.Sm.tc hematuria= painless hematuria, wch’s us., but not always, microscopic. Prevalence: 2.5-13 %.
- Painful hematuria, us. occ. due to: {Infections, stone or neoplasm.}.
Q.48.What is the D.D. of asymptomatic hematuria?
A. I. “Systemic” causes:
1) Fever.
2) Coagulopathies.
3) Hemolytic disorder.
4) Strenuous exercise.
5) Factitious. (e.g. menstruation).
II. “Lower tract” diso.:
1) Stone.
2) Trauma.
3) Tumor.
4) Infections.
5) Endometriosis.
6) Vascular malformations.
III. “Upper tract” diso. (Kidney):
1) Vascular: [infarction, embolism, venous thrombosis, A/V malformations, vasculitis].
2) Glomerular: [IgA Np., thin B.M. dis., Alport synd., Henoch-Schonlein pupura, Goodpasture’s synd., Fabry’s dis., proliferative G.N., Post infectious, Lupus nephritis.].
3) Tubulointerstitial: [Ac. tubulointerstitial nephritis, P.N., Cystic dis., Sickle cell Np.].
Q.49.What is the significance of presence of blood clots within the U.T.?
A. Lower U.T. origin. Rarely glomeruler. It indicates pres. of a large amount of blood, it is not dangerous, unless they obstruct urine flow.
Q.50. What do you suggest for workup for asymptomatic hematuria?
A. Hematuria shd be confirmed first by at least two separate urinalysis:
1) Exclude infection first by ur. C & S to rule out infectious etiology.
2) –ve C. & S.aur.:[RBCs Casts +Dysmorphic RBCs + proteinuria]= G. dis. a R. Biopsy.
3) If the above data are absentaU/S (tumor, cyst) & urologic consult. For Cystoscopy.
4) Additional radiologic imaging & workup if +ve finding in (3).
5) Negative results:a open the argument about R. biopsy, as a final resort.
COMMENTS