3. NORMAL GLOMERULAR ANATOMYAND
FUNCTION
• The glomerulus, which is enclosed within the Bowman’s
capsule, consists of two important components:
• The capillary wall: primary filtration barrier,
• The mesangium: provides support for the glomerular
capillaries and also modulates blood flow through the
capillaries (respond to AgII and PG).
• CW: allows small nonprotein plasma constituents up to the
size of inulin(5.2KDa) to pass freely while excluding
macromolecules equal to or larger than albumin (69KDa).
• Passage through the GM is impacted by both the size and
charge (-vely charged restricted) of the solute.
4.
5. EPIDEMIOLOGY AND ETIOLOGY
• In the US, glomerulonephritis was the third most common
cause of ESRD,
• accounting for approximately 16% of all the living ESRD
patients.
• About 9,100 patients (7.9% of all patients) develop stage 5
CKD because of glomerulonephritis each year.
• Humoral and cellular immunologic mechanisms participate
in the pathogenesis of most glomerulonephritis.
• Abnormalities in coagulation and metabolism, as well as
hereditary and vascular diseases, also contribute to
glomerular damage/lesion.
6. PATHOPHYSIOLOGY
• The glomerular lesion characterized/appeared as;
• diffuse (involving all glomeruli),
• focal (involving some but not all glomeruli), or
• segmental, also known as local (involving part of the individual
glomerulus).
• The pathologic manifestations may also be described as
proliferative (overgrowth of epithelium, endothelium, or
mesangium), membranous (thickening of GBM), and/or
sclerotic.
7. • The glomerular capillary wall is particularly susceptible to
immune-mediated injury.
• Antigens and antibodies tend to localize in the glomerulus,
• because of its high blood flow and capillary hydrostatic pressure.
• Parenchymal damage can be induced as a result of humoral-
and cell-mediated immune reactions.
• Antibodies and sensitized T lymphocytes are the primary mediators
• This days an increasing body of evidence show that
infections initiate most forms of GN through activation of
innate immune response.
9. Nephrotic Syndrome
• NS is characterized by proteinuria greater than 3.5
g/day/1.73 m2, hypoproteinemia, edema, and hyperlipidemia.
• A hypercoagulable state may also be present in some
patients.
• The syndrome may be the result of primary diseases of the
glomerulus, or be associated with systemic diseases
• such as diabetes mellitus, lupus, amyloidosis, and preeclampsia.
10. Nephritic Syndrome
• Glomerular bleeding resulting in hematuria is typical in
nephritic syndrome.
• Dysmorphic red cells, especially acanthocytes, are a sensitive and
specific marker of glomerular bleeding.
• The presence of pus and cellular and granular casts in the
urine is common.
• The extent of proteinuria is variable. Patients with severe
nephritic glomerular injury tend to have reduced GFR
• because of the reduced glomerular surface area available for
filtration, as a result of constriction of the capillary lumen by
proliferating mesangial or inflammatory cells.
11. DIAGNOSTIC CONSIDERATIONS
• History to identify potential systemic causes.
• Medication, environmental, and occupational histories may also help
identify exposure to potentially nephrotoxic agents.
• A comprehensive physical examination and laboratory
evaluation may reveal the presence of systemic diseases that
may contribute to the development of glomerular disease.
• Urinalysis to differentiate the nephrotic from nephritic
disease.
• The GFR may be used to determine the extent of glomerular
damage.
• In the early stages of the disease, the GFR may remain normal.
• Biopsy: for specific Dx.
12. Treatment
General approach
• In secondary glomerular diseases, such as PSGN, after the
initiating factor is removed, the prognosis of the renal
disease is often good.
• In contrast, the rates of renal function deterioration among
the primary glomerulonephritis vary markedly.
• The majority of patients with minimal-change disease, IgA
nephropathy, and membranous nephropathy have a good
prognosis.
13. Non-pharmacologic Therapy
For patients with nephrotic syndrome, dietary measures
involve;
• restriction of sodium intake to 50 to 100 mEq/day
(mmol/day),
• protein intake of < 0.8 to 1 g/day and
• a low-fat diet of less than 200 mg cholesterol per day.
• Total fat should account for less than 30% of daily total calories.
• Stop smoking
14. Pharmacologic Therapy
Immunosuppressive Agents
• Immunosuppressive agents, alone or in combination, are
commonly used to alter the immune processes.
• Corticosteroids, as a result of their immunosuppressive and
anti-inflammatory activities reduce the production and/or
release of many substances that mediate the inflammatory
process,
• such as prostaglandins, leukotrienes, platelet-activating factors,
tumor necrosis factors, and interleukin-1 (IL-1).
• Cytotoxic agents, such as cyclophosphamide, chlorambucil,
or azathioprine, are commonly used to treat glomerular
diseases.
15. • Cyclosporine can reduce lymphokine production by
activated T lymphocytes, and it may decrease proteinuria by
improving the permeability of the GBM.
• Several new agents, such as monoclonal antibodies
(rituximab), imidazole nucleoside (mizoribine), are now
being evaluated for their usefulness
16. Diuretics
• Management of nephrotic edema involves salt restriction,
bed rest, and use of support stockings and diuretics.
• Large doses of the loop diuretic, such as 160 to 480 mg
of furosemide, may be needed for patients with moderate
edema.
• availability at luminal receptor sites ↓
• In some instances, a thiazide diuretic or metolazone may be
added to enhance natriuresis.
17. • For patients with morbid edema, albumin infusion may be
used.
• To expand plasma volume and increase diuretic delivery to the renal
tubules, thus enhancing diuretic effect.
• May precipitate congestive heart failure.
• For patients with significant edema, the goal of treatment
should be a daily loss of 1 to 2 lb (0.45-0.9 kg) of fluid until
the patient’s desired weight has been obtained.
18. Antihypertensive Agents
• ACEIs/ARBs delay the loss of renal function for patients
with diabetic and nondiabetic (primarily glomerulonephritis)
renal diseases.
• ACEIs/ARBs can reduce proteinuria through different
mechanisms and combined use has been shown to be more
effective than monotherapy.
• NDHP CCB (diltiazem and verapamil) reduce proteinuria
and preserve renal function and could be used as an
additional agent.
• In contrast, the DHP CCB (nifedipine, amlodipine) are
effective in lowering blood pressure, but without the benefit
of proteinuria reduction.
19. NSAIDS
• Probably reduce proteinuria through PGE2inhibition,
resulting in a reduction of intraglomerular pressure,
• Indomethacin and meclofenamate, the two most evaluated
NSAIDs
• similar efficacy to ACEIs, and combined treatment with an ACEI.
• However, adherence to a low-sodium diet or concurrent use
of a diuretic is needed to maximize the antiproteinuric effect.
• Because of their potential for nephrotoxicity, especially for
patients with preexisting CKD, long-term use of an NSAID
for renoprotection is not commonly prescribed.
20. Adrenocorticotropin
• A synthetic ACTH analog has been used in Europe for
proteinuria reduction associated with nephrotic syndrome.
• It was reported to have effects similar to alternating months
of steroids and cyclophosphamide.
• Instead of the synthetic analog, a natural, purified ACTH gel
is available in the US and is approved by the FDA
21. Statins
• It is important to treat patients with persistent nephrotic
syndrome, especially those with high VLDL and LDL
cholesterol levels.
• Therapy is especially needed for those with concurrent
atherosclerotic cardiovascular disease, or with additional risk
factors for atherosclerosis,
• such as smoking and hypertension.
• HMG-CoA reductase inhibitors, also known as “statins”
such as simvastatin, atorvastatin are considered the
treatment of choice
22. • They reduce total plasma cholesterol concentration, LDL
cholesterol, and total plasma triglyceride concentrations
• Aside from the lipid-lowering effects, statins can reduce
cardiovascular risk independent of serum lipid
concentrations.
• Renoprotection: through the reduction of cell proliferation
and mesangial matrix accumulation and their anti-
inflammatory and immunomodulatory effects.
• Limited studies revealed the effect on renal function
preservation is not clear.
23. Anticoagulants
• Renal vein thrombosis, PE, or other thromboembolic events
are serious and common complications of nephrotic
syndrome,
• Documented thromboembolic episodes should be
anticoagulated with warfarin until remission of nephrotic
syndrome
• The use of prophylactic anticoagulation is controversial/not
recommended.
24. Selective prophylactic use recommended in the following
circumstances:
• Severe nephrotic syndrome & serum albumin concentration
less than 2-2.5 g/dL
• Those who require prolonged bed rest,
• Those receiving high-dose IV steroid therapy,
• Individuals who are dehydrated
• Postsurgical patients
