arba minch university lectural of c1 students for internal medicine course of nephrology

1. Glomerular Diseases
Kussia Ayano[MD]

2. Glomerular diseases
• The kidneys lie in the retroperitoneal space slightly
above the level of the umbilicus.
• Each kidney contains approximately 1 million
nephrons (glomeruli and associated tubules)
• Formation is complete at birth, but functional
maturation during the first decade of life
• New nephrons cannot be formed after birth so
progressive loss of nephrons leads to renal
insufficiency
• Glomeruli: network of specialized capillaries serving
as the filtering mechanism of the kidney

3. • The glomerular capillaries are lined by endothelial cells
and have very thin cytoplasm that contains many holes
(fenestrations).
• The glomerular basement membrane (GBM) forms a
continuous layer between the endothelial and
mesangial cells on one side and the epithelial cells on
the other.
• The epithelial cells cover the capillary and project
cytoplasmic foot processes, which attach to the lamina
rara externa( outer layer of GBM). Between the foot
processes are spaces or filtration slits

4. Glomerular filtration
• As the blood passes through the glomerular capillaries,
the plasma is filtered through the glomerular capillary
walls
• The ultrafiltrate, which is cell free, contains all of the
substances in plasma (electrolytes, glucose, phosphate,
urea, creatinine, peptides, low molecular weight
proteins) except proteins having a higher molecular
weight such as albumin and globulins
• Glomerular filtration is the net result of opposing
forces applied across the capillary wall( glomerular
hydrostatic vs oncotic pressure)

5. • The GFR may be estimated by measurement of the
serum creatinine level
• How ever serum creatinine may be an insensitive
measure of decreased renal function shortly after
the onset of acute renal failure because its level does
not rise above normal until the GFR falls by 30-40%
• Major factors restricting the filtration of albumin and
other macromolecules include their size and their
ionic charge

6. • The endothelial cell, basement membrane, and epithelial cell of the
glomerular capillary wall possess strong negative ionic charges
• Proteins in the blood carry a net negative charge, and they are
repelled by the negatively charged sites in the glomerular capillary
wall, thus restricting filtration
• The size-selective filtration barrier resides within the GBM.

7. Glomerular disease
• May be a result of genetic, immunologic, or coagulation
disorders
• Immunologic injury is the most common cause and
results in glomerulonephritis
• two major mechanisms of immunologic injury:
1. localization of circulating antigen-antibody immune
complexes
2. Interaction of antibody with local antigen in situ like
anti-GBM nephritis or an antigen that has been
deposited in the glomerulus.

8. • Childhood glomerular diseases can be classified into two
clinical patterns
• A nephritic pattern is associated with inflammation on
histologic examination and produces an active urine sediment
with red cells, white cells, and often red cell and other cellular
casts, and a variable degree of proteinuria.
• A nephrotic pattern, which is not associated with
inflammation on histologic examination, presents
predominantly with nephrotic range proteinuria, with few
cells or casts
• Elements of both may be also seen in some patients
simultaneously or sequentially

9. Nephrotic syndrome

12. Classification
Primary (idiopathic) -90%
oAquired
• Minimal change disease (MCD) - 85 %
• Focal segmental glomerulo sclerosis (FSGS)
• Membranoproliferative glomerulonephritis
• Mesangial proliferative glomerulonephritis
oGenetic – congenital
Secondary
• Drugs
• Tumors
• Infections (malaria, schistosomiasis, hepatitis B virus,
hepatitis C virus, and HIV)

15. Idiopathic nephrotic syndrome
• Causes 90% of pediatric nephrotic syndrome
• Idiopathic nephrotic syndrome is associated with
primary glomerular disease without evidence of a
specific systemic cause
• Minimal change disease(MCD) is the most common
histologic sub type.
• Common age: 2 -6 yr
• M:F 2:1
• ? T cell mediated immune disorder

16. Pathophysiology
o MCD
• Normal or minimal increase in mesangial cells and matrix on light
microscopy
• Immunoflourescent –negative
• Electron microscopy - effacement of the epithelial cell foot
processes
o Focal sclerosis
o Mesangial proliferation

20. Diagnosis
Classic MCD
• Age :2-6yr
• Normotensive (90%)
• Urine dipstick albumin +3/4
• Normal serum C3
• Microscopic hematuria ( 10-20%)

27. Indicationforrenalbiopsy
• Age < 1 or > 8 yr
• Gross hematuria
• Azotemia
• Significant hypertension
• Low C3

28. complications
Infections:
peritonitis ,
pneumonia ,
cellulites
Hypercoagulability
Steroid toxicity

29. Management
• Outpatient – patients with mild to moderate edema
• Children between 1 and 8yrs of age are likely to respond to
steroid treatment
Treatment includes
1.salt restriction
2.loop diuretics if severe symptomatic edema, including large
pleural effusions, ascites, or severe genital edema in
hospitalized patients.
3.Steroid
 Prednisolone 60mg/kg/m2 daily for 4-6 weeks
 Prednisolone 40 mg/kg/m2 alternate day for 4 weeks
 Tapper steroid over 1-2 months

37. Prognosis
• About 80-90% of children respond to steroid therapy
• Many children with nephrotic syndrome experience at least
1 relapse
• The relapse rate in children treated with longer initial steroid
courses may be as low as 30-40%
• steroid dependent- relapse while on alternate-day steroid
therapy or within 28 days of completing treatment
• frequent relapsers- relapse ≥4 times in a 12-mo
• steroid resistant- proteinuria (2+ or greater) after
8 wk of steroid therapy

44. Pathogenesis and pathology
• Deposition of circulating immune complexes
• In situ immune complex formation
• The resulting glomerular immune complex disease triggers
complement activation and inflammation
• Glomeruli appear enlarged and show diffuse mesangial cell
proliferation, with an increase in mesangial matrix
• Crescents and interstitial inflammation may be seen in
severe cases
• Immunofluorescence microscopy reveals deposits of
immunoglobulin and complement on the glomerular
basement membrane (GBM) and in the mesangium

64. Management
• Hypertension – frusemide
• ARF – depends on severity
• Penicillin for 10 days
• Prognosis is good except in RPGN
• Chronic glomerulonephrits and chronic renal failure in 2 % of
patients

72. Thanks