Proteinuria Kidney disease Approach to proteinuria

1. Prepared by : Yahya Farwan.
Supervised by : Dr. Muneer Bashoaib.
University of Science and Technology Hospital, Sana’a, Yemen, 2023.

2. Objectives
2
1. To know the meaning of proteinuria and albuminuria
2. To identify the types of proteinuria
3. To identify the complications of proteinuria
4. To identify the clinical assessment of proteinuria
5. To identify the lines of treatment of proteinuria
I

3. Table of Contents
3
1.1 Definitions of Proteinuria ……………………………….. 1
1.2 Classifications of Proteinuria …………………………… 2
1.3 Complications of Proteinuria …………………………… 10
2.1 History Taking ………………………………………….. 12
2.2 Physical Examination .……………………..…………… 21
2.3 Investigations …………………………………….…..…. 25
3.1 Approach Considerations ……………………………….. 32
3.2 Non-Specific Treatment ……………………….……...… 33
3.3 Specific Treatment ………………………………...……. 34
1. Overview
.
2 Clinical Assessment of Proteinuria
4. Summary ……………….....………........................…. 34
.
3 Treatment of Proteinuria
II
.
5 Resources……………….....………....................……... 35

4. 4
List of abbreviations
• AER Mean albumin excretion rate
• CKD Chronic kidney disease
• PCT Proximal convoluted tubules
• LL Lower limb
• MD Diabetes mellitus
• HTN Hypertension
• GN Glomerulonephritis
• Cr Creatinine
• ANA Anti-nuclear antibody
• RBS Random blood sugar
• KUB Kidney-ureter-bladder X-ray
• ASO Anti-streptolysin O
• ACEIs Angiotensin-converting-enzyme inhibitors
• ARBs Angiotensin receptor blockers
• CCBs Calcium channel blockers
• CHF Congestive heart failure
III
• SBP Spontaneous bacterial peritonitis
• PO By mouth
• RAS Renal artery stenosis
• ATN Acute tubular necrosis
• CT Computed tomography
• MRA Magnetic resonance angiography
• ELIS Enzyme-linked immunoabsorbent assay
• MMF Mycophenolate mofetil

5. 5
Definitions of Proteinuria
1.1

6. 1.1 Definitions of Proteinuria
 Normal urinary protein excretion is < 150 mg/24 hours and consists mostly of secreted proteins
such as Tamm-Horsfall proteins.
 Proteinuria is the the urinary excretion of >150 mg /24 hours.
 The normal mean albumin excretion rate (AER) is 5-10 mg/day.
 Nephrotic-range proteinuria is defined as proteinuria greater than 3.5 g / 24 hours.
 Persistent proteinuria proteinuria for more than 3 months.
 Proteinuria can be accompanied by other clinical abnormalities :
Elevated BUN and S.creatinine, ABNL urine sediment.
1
• AER between 30 to 300 mg/day is called microalbuminuria.
• Levels greater than 300 mg/day are called macroalbuminuria.

7. 7
Classifications of Proteinuria
1.2

8. 8
1.2 Classifications of Proteinuria
1. According to quantity:
A. Microalbuminuria
B. Macroalbuminria
2. According to origin:
A. Prerenal
B. Renal:
• Glomerular proteinuria
• Tubular proteinuria
• Mixed
C. Post-renal proteinuria
3. Isolated (benign proteinuria)
A. Orthostatic proteinuria
B. Transient proteinuria
2

9. A. Microalbuminemia:
• Urine albumin excretion of 30–300 mg/day.
• Early sign of diabetic and hypertensive nephropathy.
B. Macroalbuminemia:
• Urine albumin excretion > 300 mg/day.
• Standard urine dipstick tests can be used for detection.
According to quantity:
1.
3
1.2 Classifications of Proteinuria

10. • Increased production of low-molecular-weight proteins → Overwhelming the
reabsorption capacity of the PCT → Proteinuria
 Causes:
• Multiple myeloma→ Bence Jones proteins
• Hemolysis → Hemoglobin.
• Rhabdomyolysis → Myoglobin .
A. Pre-renal proteinuria
4
1.2 Classifications of Proteinuria
According to origin:
2.

11. • Damage to the glomeruli → increased permeability of the glomerular
filtration barrier → urinary protein excretion
• Characteristic finding: appearance of large proteins in the urine, primarily albumin.
• Causes of glomerular proteinuria:
Primary glomerular disease:
1. Minimal change glomerular disease
2. Membranous nephropathy
3. Focal segmental glomerulosclerosis
4. Congenital nephrotic syndrome
Secondary glomerular disease:
1. Nephritic syndromes
2. DM and HTN
3. Systemic lupus erythematosus
4. Cryoglobulinaemic disease
5. Henoch–Schonlein syndrome
6. Drugs :NSAIDs, gold, penicillamine
.
1 Glomerular proteinuria
5
1.2 Classifications of Proteinuria
B. Renal proteinuria

12. • Damage to the PCT → failure to reabsorb small proteins in the tubules
→ urinary protein excretion, typically beta-2 microglobulin without large proteins.
• The amount of proteinuria is usually < 2 g/day.
• Causes:
▪ Tubulointerstitial nephritis
▪ Nephrolithiasis
▪ Analgesics
▪ Immunosuppressive agents
▪ Acute renal failure.
Found in diseases that affect both the glomeruli and the tubules (e.g., CKD)
.
2 Tubular proteinuria
.
3 Mixed proteinuria
6
1.2 Classifications of Proteinuria

13. • Physiological proteinuria
Proteins that are being produced in the tubules (Tamm-Horsfall protein)
• Pathological proteinuria
Abnormalities affecting urinary tract from the renal pelvis to the urethra:
▪ Stones
▪ Inflammatory: Ureteritis, Prostatitis, Cystitis, Urethritis.
▪ Neoplastic
▪ Traumatic
C. Post-renal proteinuria
7
1.2 Classifications of Proteinuria

14. 14
1.2 Classifications of Proteinuria
8

15. ▪ Defined as isolated proteinuria < 1 g/day
▪ Very common; mostly affects younger individuals
▪ No treatment necessary; excellent prognosis
Benign proteinuria :
3.
1. Orthostatic proteinuria (postural proteinuria) :
• Increased protein excretion only in the upright position for long time.
• More common in tall, thin adolescents or adults less than 30 years old.
• Dx: The patient has no proteinuria in early morning samples but has low-grade proteinuria
at the end of the day.
2. Transient proteinuria :
• Most common cause of isolated proteinuria in children
• Causes: heavy exertion, Acute illness, Fever, Seizures.
9
1.2 Classifications of Proteinuria

16. 16
Complications of Proteinuria
1.3

17. 1. Pulmonary edema due to fluid overload
2. Acute kidney injury due to intravascular depletion and progressive kidney disease
3. Increased risk of bacterial infection, including SBP
4. Increased risk of arterial and venous thrombosis, including renal vein thrombosis
5. Increased risk of cardiovascular disease
1.3 Complications of Proteinuria
10

18. 18
CLINICAL ASSESSMENT OF
PROTEINURIA
2

19. Clinical Assessment
• Mild to moderate proteinuria may be asymptomatic.
• The majority of patients with proteinuria are asymptomatic, and proteinuria will be
detected in the course of routine laboratory testing conducted to evaluate
systemic disease.
• Considering the more common and benign causes of proteinuria first is important.
11

20. 20
HISTORY TAKING
2.1

21. 2.1 History Taking
How old are
you and what
is your job ?
I’m 28 years old
and I’m
bodyguard,i came
for regular
screening.
Maybe orthostatic proteinuria
Proteinuria (less than 1g/day)
observed in tall, thin adolescent
or adults younger than 30 years
12

22. Hello dair,
What’s your
complaint ?
I have fever
rof hguoc dna
2 days
Transtent proteinuria can be
caused by Acute illness, fever,
seizures and physical exertion
13
2.1 History Taking

23. Do you have
fever, chills,
flank pain,
nausea,
vomiting
Yes Doctor,
Urinary tract infections
14
2.1 History Taking

24. Did you suffer from
URTI?
Yes Doctor, it
occurred
before one
week.
Post-infectious
glomerulonephritis
15
2.1 History Taking

25. Do you
complaining of
fever, night
sweats, weight
loss, or bone
pain?
mmm..
Yes, all of
them
Malignancies :
Multiple myeloma
Tumors of the kidney, lung,
colon, stomach or breast
16
2.1 History Taking

26. Did you have Hx of
hepatitis, tuberculosis,
malaria, syphilis,
HIV,or endocarditis?
Yes Doctor.
TB
17
Infections remote to the kidney
2.1 History Taking

27. Do you have HTN,
DM,Heart failure,chronic
inflammatory disease or
hypercholesterolemia?
Yes Doctor, I
have T1DM
for 17 years
and HTN for 5
years .
Nephropathy secondary to
systemic diseases .
18
2.1 History Taking

28. Do you taking any
medication, including
over-the-counter or
herbal remedies ?
Yes Doctor,
NSAIDs
kidney injury due to
medications:
Analgesics
Immunosuppressants
Gold and mercury
Penicillamine
19
2.1 History Taking

29. Do you have
family history
of kidney
disease or
malignancy?
Yes, Polycystic
kidney disease
Congenital nephrotic syndrome
Malignancy
PKD
20
2.1 History Taking

30. PHYSICAL EXAMINATION
2.2

31. 2.2 Physical Examination
I will examine the
JVP
Pulse rate
Blood pressure
Heart sounds
Assess intravascular volume status
Ammm
😪
21

32. I’ll look for Edema
and then i will listen to your
Breath sounds (which may be
decreased due to pleural
effusions)
Assess extravascular volume status
Okay
22
2.2 Physical Examination

33. I well examine you for retinopathy
,rash, joint swelling or deformity
,stigmata of CLD
,lymphadenopathy, cardiac
murmurs.
Examine the patient for signs of systemic disease
Okay
23
2.2 Physical Examination

34. Lastly, I well examine you for
Venous thrombosis and
Peritonitis
Examine the patient for complications
Okay
24
2.2 Physical Examination

35. INVESTIGATIONS
2.3

36. Specific Laboratory
Imaging
2.3 Investigations

37. 25
Standard urine dipstick test:
• Primarily detects albumin > 300 mg/day.
• Protein detected by urine dipstick should always be quantified with either a 24-hour urine
collection or protein-creatinine or albumin-creatinine ratio on random urine samples.
• Results interpretation:
• Trace = 50 to 150 mg/day; 1+ = 150 to 500 mg/day; 2+ = 0.5 to 1.5 g/day;
3+ = 2 to 5 g/day; 4+ = >5 g/day
2.3 Investigations

38. ○ Initial test once proteinuria is detected by dipstick test → examination of urine sediment:
• RBC casts → GN
• WBC casts → pyelonephritis or interstitial nephritis
• Fatty casts → nephrotic syndrome (lipiduria)
• Granular stsac → acute tubular necrosis
○ If urine casts are positive → treat the cause and repeat urinalysis for proteinuria
○ If urinalysis confirms the presence of protein, a 24-hour urine collection (for albumin and Cr)
is appropriate to quantify the proteinuria.
26
2.3 Investigations
Urinalysis :

39. 24-hour urine albumin:
Normal range <30mg/day
Microalbuminuria 30-300mg/ 24 hours
Macroalbuminuria >300mg/24 hours
Nephrotic syndrome ≥ 3.5 g/24hours
27
2.3 Investigations
24-hour urine collection (for albumin and Cr)
Spot urine protein or albumin/creatinine ratio :
Normal <50mg/g or <0.2mg/mg
Proteinuria ≥ 150mg/g or ≥0.2 mg/mg

40. ▪ Corresponds to albumin excretion of 30 to 300 mg/day.
▪ This is below the range of sensitivity of standard dipsticks.
▪ Special tests can detect microgrm amount of albumin, including:
.
1 Radioimmunoassay the most sensitive and specific test for microalbuminuria.
.
2 Specific urine dipstick tests
3. Sulfosalicylic acid test
.
4 ELISA
28
2.3 Investigations
Test for microalbuminuria

41. ■ BUN and Cr— for renal function
■ Serum albuminaimenimublaopyh detaicossa rof
■ ABG and electrolytes for associated metabolic acidosis
■ CBC—to detect anemia due to renal failure
■ Urine and plasma electrophoresis— to rule out tubulointerstitial diseases and multiple myeloma
■ Lipid profile —for associated dyslipidemia
■ Autoantibodies - If indicated, including ASO titers, ANA, anti-DNA, complement levels (C3 and C4).
■ Hepatitis B, hepatitis C, and HIV serologies - If indicated
29
2.3 Investigations
Other tests

42. ○ Renal ultrasound:
• Hydronephrosis suggests obstructive nephropathy.
• Small, smooth kidneys suggests chronic parenchymal renal disease.
• Renal asymmetry suggests RAS
• Renal enlargement can occur in ATN, renal vein thrombosis, and renal infiltration.
○ Plain abdominal film (KUB) if renal stones or nephrocalcinosis suspected.
○ Contrast CT angiography or Gadolinium- enhanced MRA for Atherosclerotic RAS
○ CXR –Infiltrates, CHF, pleural effusion .
○ Renal biopsy
30
Imaging Studies
2.3 Investigations

43. Kidney Biopsy Treat
underlying
disease, if
unknown ;
kidney
biopsy
31

44. Treatment of Proteinuria
3

45. 3.1 approach considerations
● Nonspecific treatment –
Treatment that is applicable irrespective of
the underlying cause, assuming the patient has no contraindications to the therapy
● Specific treatment –
Treatment that depends on the underlying renal or
nonrenal cause and, in particular, whether or not the injury is immune mediated
● Referral to a nephrologist is indicated for any patient who develops proteinuria,
especially those with any adverse prognostic markers (eg, rise in albumin
excretion of > 1 g/day), or any worsening in kidney function.
32

46. ▪ Restriction of dietary salts and proteins .
▪ Cessation of smoking
▪ Vitamin D and calcium supplements.
▪ Pneumococcal vaccine
▪ Treatment of infection
3.2 Non-Specific Treatment
33
▪ Drugs:
▪ Diuretics :loop diuretic or a combination of diuretics such as a thiazide and loop diuretics .
▪ ACE inhibitors and ARBs
▪ CCB: if ACEIs or ARBs are contraindicated.
▪ Anticoagulants
▪ Treatment of dyslipidemiasnitats htiw

47. ● Minimal change disease : most respond to prednisone (adequate dose and duration),
but may relapse ,cyclophosphamide or cyclosporine may be used for frequent relapses
● Focal segmental glomerulosclerosis : high dose long-term steroids will lead to remission in about
1/3 of patients +_ MMF ,calcineurin inhibitors
● Membranoproliferative GN :steroid +-azathioprine, MMF
● Diabetic Nephropathy : strict control of blood sugar _+ARBS,ACE-I
● SLE Nephropathy:
Therapy : depend on class ,for all class use HCQ + prednisolone
for class 3, 4 , add cyclophosphamide or MMF (mycophenolate mofetil).
3.3 Specific Treatment
34

48. SUMMARY
4

49. Summary
35
• Normal urinary protein excretion is < 150 mg/24 hours
• Proteinuria is the the urinary excretion of >150 mg /24 hours.
• Nephrotic-range proteinuria is defined as greater than 3.5 g / 24 hour
• Glomerular proteinuria mainly albumin while tubular proteinuria LMW proteins
• Prerenal and postrenal proteinuria occurs due to systemic diseases and urinary tract
abnormalities, respectively.
• Orthostatic and transient proteinuria are benign and have excellent prognosis
• Cardiovascular and pulmonary abnormalities, infections, VTE and AKI are main
complications of proteinuria
• The majority of patients with proteinuria are asymptomatic
• Considering the more common and benign causes of proteinuria first is important.
• Renal US is the most useful imaging study of kidney abnormalities
• Nonspecific treatment can be applied in all types of proteinuria
• ACEIs and ARBs can be used in patients with proteinuria regardless of the cause
• CCB can be used if there is contraindication of ACEIs or ARBs.
• Specific treatment of proteinuria according to the underlying cause.

50. Resources
4

51. Resources
☆ https://emedicine.medscape.com/article/238158-clinical?src=mbl_msp_android&ref=share
☆ https://www.amboss.com/us/knowledge/Proteinuria
☆ STEP-UP to MEDICINE, FOURTH EDITION
☆ HARRISON’S MANUAL OF MEDICINE, 19th Edition.
☆ Current medical diagnosis and treatment 2022
.
☆ Nephrology Lectures Book of Dr. Elham Al-tholaimi,UST,Sanaa,Yemen , 2021
.
☆
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52. “
52
Thanks