1. Hematuria, Proteinuria and Glomerular Disease
N. Ganesh Yadlapalli, M.D
Professor of Medicine
University of Cincinnati Medical College

3. Proteinuria Total protein is up to 150mg/24h Higher rates:
Physiological proteinuria:
Quantity:
Total protein is up to 150mg/24h
80 +/- 20 mg/d for adults
140mg/m2/d in children
Higher rates:
children, adolescents, pregnancy
Fever, exercise, pressers.

5. Urinary Protein 3 sources -Glomurular
filtered at the glomerular level and
escaping PCT absorption
- Tubule
secreted at tubular level or leaking into
tubular lumen
- lower urinary tract

6. Proteinuria-Classification
Glomerular proteinuria
Tubular proteinuria:
reduced absorption of filtered proteins
proteins from injured tubular cells
Overflow proteinuria
filtered load more than tubular capacity
light chains, lysozymes (leukemia)
myoglobin, hemoglobin

7. Glomerulus is permeable to
Mol Weight under 60,000 Daltons may
be filtered
Albumin (MW 65,000) should be filtered minimally

8. Glomerular Capillary Wall
Fenestrated endothelium
GBM:
Laminin, Type 4 collagen, nidogen, heparin sulphate proteoglycans (lamina densa, lamina rara interna and externa).
Visceral epithelial cells: podocytes, foot process and filtration slit

9. Tubular proteinuria Renal tubular diseases Toxins and drugs:
Endogenous: Light chain damage to PT
Exogenous: Mercury, Lead, Cadmiu, Outdated Tetracicline,
Arginine or Lysine infusions
Tubulointerstitial disease:
Interstitial Nephritis, Bacterial Pyelonephritis, Obstructive
uropathy, Chronic Interstitial nephritis, Fanconi’s Syndrome

10. Overflow Proteinuria
Secondary to increased production greater than tubular capacity
Seen in
Multiple myeloma. Light Chain Disease
Amyloidosis
Hemoglobinuria, myoglobinuria

11. Proteinuria -Detection
Chemically impregnated paper strip
Dipstick for microalbuminuria
Commercial or turbidometric methods

12. Urine dipstick
Is relatively insensitive marker for degree of protein excretion.
Not generally become positive until protein excretion exceeds 300 to 500 mg/day.

13. Urinary dipstick · Negative · Trace — 15 and 30 mg/dL
It is colorimetric reaction between albumin and
tetrabromophenol blue producing different shades of light blue to green.
· Negative
· Trace — 15 and 30 mg/dL
· 1+ — and 100 mg/dL
· 2+ — and 300 mg/dL
· 3+ — and 1000 mg/dL
· 4+ — >1000 mg/dL
False (+):high alkaline urine and drugs, contrast
Highly influenced by urine concentration

14. Proteinuria-Detection
Commercial or turbidometric methods
detect albumin and globulins
as low as 5-10 mg/dl
false (+):drugs, contrast
Dipstick for microalbuminuria
g/min or mg/day

15. Proteinuria Quantification
Timed urine samples
Protein creatinine ratio
Electrophoresis

16. Urinary Protein/Creatinine Ratio
High degree of correlation with 24h urine protein
in variety of kidney disease
useful
As a screening tool in CKD patients
Monitoring glomerular proteinuria

18. Hematuria-Definition
More than 2cells/ HPF in spun urine
Detected by :
Microscopic examination
Paper strips
Highly sensitive
Also detects hemoglobinuria and
myoglobinuria,

19. Hematuria-Classification
Macroscopic/Microscopic
Persistent/Transient/
Intermittent/Reccurent
Symptomatic/Asymptomatic

20. Hematuria-pathophysiology
Glomerular Hematuria
disruptions in the glomerular capillary
wall
Tubular hematuria
disruptions in the peritubular vessels
Urinary tract bleeding

21. Glomerular Vs Extra-glomerular
Persistent hematuria
Glomerular Vs Extra-glomerular

22. Transient Hematuria Young adults In a study 18-33 years Older patients
Benign
Often cause is not identified
Fever, infection, trauma, and exercise are possibilities
Older patients
could be a symptom of underlying problem
1035 patients with transient hematuria (at least 1 out of 3
specimens)
Incidence of malignancy was 2.4%

23. Question 1 A 18 y/o healthy male came for sports check up.
Dipstick evaluation reveals moderate blood and no proteinuria. Microscopic examination of the urinary sediment reveals 10 RBC/hpf and no casts.
Physical examination is unremarkable

24. Your assessment and plan is
No workup needed as it is asymptomatic hematuria
Repeat UA
Repeat UA and cultures
Kidney biopsy

25. Question 2 A 48 y/o healthy male came for check up.
BP is WNL, no h/o DM, RF WNL. Dipstick evaluation reveals moderate blood and no proteinuria. Microscopic examination of the urinary sediment reveals 10 RBC/hpf and no casts.
Physical examination is unremarkable

26. Your assessment and plan is
No workup needed as it is asymptomatic hematuria
Repeat UA
Repeat UA and cultures
Cystoscopy , may need Kidney biopsy

27. Persistent asymptomatic isolated microscopic hematuria was diagnosed in 3690 of 1 203 626 eligible individuals (0.3%). During (SD, 6.74) years of follow-up, treated ESRD developed in 26 individuals (0.70%) with and 539 (0.045%) without persistent asymptomatic isolated microscopic hematuria, yielding incidence rates of 34.0 and 2.05 per 100 000 person-years, respectively, and a crude HR of 19.5 (95% confidence interval [CI], ). A multivariate model adjusted for age, sex, paternal country of origin, year of enrollment, body mass index, and blood pressure at baseline did not substantially alter the risk associated with persistent asymptomatic isolated microscopic hematuria (HR, 18.5 [95% CI, ]). A substantially increased risk for treated ESRD attributed to primary glomerular disease was found for individuals with persistent asymptomatic isolated microscopic hematuria compared with those without the condition (incidence rates, 19.6 vs 0.55 per 100 000 person-years, respectively; HR, 32.4 [95% CI, ]). The fraction of treated ESRD attributed to microscopic hematuria was 4.3% (95% CI, 2.9%-6.4%).

28. Copyright © 2012 American Medical Association. All rights reserved.
From: Persistent Asymptomatic Isolated Microscopic Hematuria in Israeli Adolescents and Young Adults and Risk for End-Stage Renal Disease
JAMA. 2011;306(7): doi: /jama
Figure Legend:
Date of download: 11/14/2012
Copyright © 2012 American Medical Association. All rights reserved.

30. Persistent Hematuria > 50 years In 1930 patients (mean age 58)
12% bladder cancer,
0.7% kidney and UT cancers

31. IgA nephropathy Role of biopsy
Isolated persistent hematuria with negative radiological and cystoscopic evaluation
> 50% had one of the following
IgA nephropathy
Alport syndrome (hereditary nephritis)
Thin basement membrane nephropathy
Biopsy is not generally indicated
Unless, signs of progressive renal disease evident

33. Glomerular Diseases Asymptomatic proteinuria Acute nephritis
Focal segmental glomerulosclerosis
Mesangioproliferative GN
Acute nephritis
Acute diffuse proliferative GN
Poststreptococcal GN
Poststaphylococcal GN
Focal or diffuse proliferative GN
IgA nephropathy
Lupus nephritis
Type I membranoproliferative GN
Type II membranoproliferative GN
Fibrillary GN

34. Glomerular Diseases Rapidly progressive nephritis
Crescentic GN
Anti-GBM GN
Immune complex GN
Pulmonary-renal vasculitic syndrome
Goodpasture's (Anti GBM) syndrome
Immune complex vasculitis
Lupus
ANCA vasculitis
Microscopic polyangiitis
Wegener's granulomatosis
Churg-Strauss syndrome

35. Presentation of Glomerular Disease
Nephrotic syndrome / Proteinuria
Proteinuria (> 3.5g protein / day)
Hypoproteinaemia
Oedema
Hyperlipidaemia
Nephritic syndrome / Haematuria
Haematuria
Proteinuria-- nephrotic range is very rare
Hypertension
Progressive renal failure

36. Glomerular Disease Primary glomerular disease:
MCD, FSGS,MG, MPGN, Mesangiocapillary GN
Fibrillary GN, Crescentic GN
Secondary Glomerular disease: Medications, Allergens, Infections, Neoplastic, Multisystem ds, Heredofamilial ds, transplant rejection, reflux nephropathy, toxemia of pregnancy

37. Glomerular Disease Primary glomerular disease:
MCD, FSGS,MG, MPGN, Mesangiocapillary GN
Fibrillary GN, Crescentic GN
Secondary Glomerular disease: Medications, Allergens, Infections, Neoplastic, Multisystem ds, Heredofamilial, transplant rejection, reflux nephropathy, toxemia of pregnancy

38. Thank you

39. Glomerular proteinuria
Primary glomerular disease:
MCD, FSGS,MG, MPGN, Mesangiocapillary GN
Fibrillary GN, Crescentic GN
Secondary Glomerular disease: Medications, Allergens, Infections, Neoplastic, Multisystem ds, Heredofamilial ds, transplant rejection, reflux nephropathy, toxemia of pregnancy
Other glomerular proteinuria:
Ppost exercise proteinuria, febrile and orthostatic proteinuria

40. Tubular proteinuria Toxins and drugs:
Endogenous: Light chain damage to PT
Exogenous: Mercury, Lead, Cadmiu, Outdated
Tetracicline, Arginine or Lysine infusions
Tubulointerstitial disease:
LE, Interstitial Nephritis, Bacterial Pyelonephritis, Obstructive uropathy, Chronic Interstitial nephritis
Fanconi’s Syndrome

42. Proteinuria-Mechanisms
Glomerular capillary wall permeable to water and solutes and almost impermeable to plasma proteins
Fe albumin= %
Glomerular vasculature fenestrated endothelium
GBM
epithelial cells
mesangium

44. Mechanism of glomerular disease
Visceral Epithelial Cell Injury
Immune Complex Formation
in LRE
in LRI
Antibodies against GBM
Crescent Formation and Cell-Mediated Immunity
Vascular injury: Thrombotic mycroangiopathies, Systemic vasculitis and ANCA