The document provides an overview of glomerulonephritis including its anatomy, epidemiology, etiology, pathophysiology, clinical presentation, diagnosis, and treatment. The glomerulus filters blood and allows small molecules to pass through while excluding larger ones like proteins. Glomerulonephritis can be caused by immune system abnormalities and is a common cause of kidney failure. Symptoms depend on whether the nephrotic or nephritic syndrome is present. Treatment involves controlling symptoms, reducing proteinuria and blood pressure, and using immunosuppressants.

1. Glomerulonephritis
Begashaw M.

2. Outline
• Anatomy and physiology of glomerulus
• Epidemiology
• Etiology
• Pathophysiology
• Clinical presentation
• Diagnosis
• Treatment

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.

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.

8. Clinical manifestation

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

25. Evaluation of Therapeutic Outcomes

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