Introduction Basic principles Types Epidemiology Etiology Presentation Differential diagnosis Workup Treatment

1. 0
Glomerular disease
2018
MUSTAFA SALAH KADHIM
COLLEGE OF MEDICINE – UNIVERSITY OF BAGHDAD
STAGE 2
URINARY SYSTEM MODULE
STUDENT SELECTED COMPONENTS

2. 1
Contents:
1- Introduction …………….………………………… 2
2- Basic principles ……...…………………………… 4
3- Types ……………………………………………... 6
4- Epidemiology …………………….…………….… 8
5- Etiology …………………………..………………. 9
6- Presentation ………………………..……………. 15
7- Differential diagnosis ……………..…………….. 22
8- Workup …………………………….…………… 25
9- Treatment …………………………..…………… 28
10- Conclusion …………………..………………….. 31
11- References ………………………..……..………. 32

3. 2
Introduction
Overview:
Glomerular disease is a group of diseases that affect and damage the
glomeruli, the tiny filtering units within the kidney where blood is cleaned,
Glomerular disease includes many conditions with many different causes.
Damage to the glomeruli results in the escape of substances like protein,
excessive amounts of electrolytes, and even red or white blood cells into
the urinary fluid. As the damage progresses, glomerular function is lost.
This impairs the excretion of harmful toxic wastes, leading to their buildup
in the body. [1]
Furthermore, loss of blood proteins like albumin in the urine
can result in a fall in their level in the bloodstream leading to reduce the
capacity of blood to absorb extra fluid from the body and causes Edema.
There are many forms of glomerular disease with pathogenesis variably
linked to the presence of genetic mutations, infection, toxin exposure,
autoimmunity, atherosclerosis, hypertension, emboli, thrombosis, or
diabetes mellitus. Even after careful study, however, the cause often
remains unknown, and the lesion is called idiopathic. [2]
Glomerular diseases include many conditions with a variety of genetic and
environmental causes, but they fall into two major categories:
 Glomerulonephritis: describes the inflammation of the membrane
tissue in the kidney that serves as a filter, separating wastes and
extra fluid from the blood.
 Glomerulosclerosis: describes the scarring or hardening of the
tiny blood vessels within the kidney.
Although glomerulonephritis and glomerulosclerosis have different
causes, they can both lead to kidney failure. ]3[

4. 3
Background:
1-Glomerulonephritis:
Hippocrates originally described the natural history of GN, writing of back
pain and hematuria followed by oliguria or anuria. Richard Bright (1789-
1858) described GN clinically in 1827, which led to the eponymic
designation Bright disease. With the development of the microscope,
Theodor Langhans (1839-1915) was later able to describe these
pathophysiologic glomerular changes.
2-glomerulosclerosis:
Focal segmental glomerulosclerosis (FSGS), first described in 1957, is
currently recognized as one of the most common causes of primary
glomerular diseases in adults, and the incidence of FSGS has been
increasing in recent years. [4, 5]
FSGS causes asymptomatic proteinuria or
nephrotic syndrome (NS) with or without renal insufficiency. In adults
undergoing renal biopsy for evaluation of proteinuria, FSGS accounts for
35% of all cases and up to 80% of cases in African-American patients.
Generally, FSGS is a progressive form of kidney disease, accounting for
2.3% of end-stage renal disease (ESRD).
Although clinical features are suggestive, a diagnosis of FSGS is
confirmed only by histopathology findings. [6]
The disease represents
several patterns of glomerular injury, and biopsy findings provide no
insights into the pathogenesis. FSGS arises through idiopathic (primary) or
secondary causes.
Therapy for FSGS includes nonspecific measures (eg, nutrition) and
symptomatic treatment. Current evidence, mostly derived from
retrospective analyses, favors prolonged corticosteroid therapy to induce
remission in patients with idiopathic FSGS.

5. 4
Basic principles
What is glomerulus?
A glomerulus is a tuft network of capillaries located at the beginning of a
nephron in the kidney. It serves as the first stage in the filtering process of
the blood carried out by the nephron in its formation of urine.
The glomerulus is surrounded by a cup-like sac known as Bowman's
capsule. The blood plasma is filtered through the capillaries of the
glomerulus into the capsule. The Bowman's capsule empties the filtrate
into the proximal tubule that is also part of the duct system of the nephron.
A glomerulus receives its blood supply from an afferent arteriole of the
renal circulation. Unlike most other capillary beds, the glomerulus drains
into an efferent arteriole rather than a venule. The resistance of these
arterioles results in high pressure within the glomerulus, aiding the process
of ultrafiltration, where fluids and soluble materials in the blood are forced
out of the capillaries and into Bowman's capsule.
A glomerulus and its surrounding Bowman's capsule constitute a renal
corpuscle, the basic filtration unit of the kidney. [7]
The space between the cells of a glomerulus is occupied by intraglomerular
mesangial cells. They are not part of the filtration barrier but are
specialized pericytes that participate indirectly in filtration by contracting
and reducing the glomerular surface area, and therefore filtration rate, in
response mainly to stretch.
The capillaries are lined by a layer of cells (an endothelium) that has a
unique structure, allowing blood components to be filtered, and resulting
ultimately in the formation of urine.
Capillaries of the glomerulus are lined by endothelial cells. These contain
numerous pores (called fenestrae) 50–100 nm in diameter. [8]
Unlike those
of other capillaries with fenestrations, these are not spanned by
diaphragms. [8]
These pores allow for the free filtration of fluid, plasma
solutes and protein. However they are not large enough that red blood cells
can be filtered.
The glomerulus has a basement membrane consisting mainly of laminins,
type IV collagen, agrin and nidogen, which are synthesized and secreted
by both endothelial cells and podocytes. These form a membrane 250–
400 nm in thickness, which is thicker than basement membranes in other

6. 5
types of tissue. The effects of mutations in the constituents of the
glomerular basement membrane suggest that it plays a role in the
permeability and selectivity of the filtration barrier to large molecules, such
as albumin. [9]
The side of the basement membrane that faces outwards from the capillary
is lined with folds called podocytes. These are themselves lined with folds
of cytoplasm called foot processes, or pedicles. [8]
These control the
filtration of proteins from the capillary lumen into Bowman's space. The
space between adjacent podocyte foot processes is spanned by a slit
diaphragm formed by several proteins including podocin and nephrin. In
addition, foot processes have a negatively charged coat (glycocalyx) that
limits the filtration of negatively charged molecules, such as serum
albumin.
Functions of the glomerulus:
The main function of the glomerulus is to filter plasma to produce
glomerular filtrate, which passes down the length of the nephron tubule to
form urine. The rate at which the glomerulus produces filtrate from plasma
(the glomerular filtration rate) is much higher than in systemic capillaries
because of the particular anatomical characteristics of the glomerulus.
Unlike systemic capillaries, which receive blood from high-
resistance arterioles and drain to low-resistance venules, glomerular
capillaries are connected in both ends to high-resistance arterioles:
the afferent arteriole, and the efferent arteriole. This arrangement of two
arterioles in series determines the high hydrostatic pressure on glomerular
capillaries, which is one of the forces that favour filtration to the Bowman's
capsule. [10]
If a substance has passed through the glomerular capillary endothelial cells,
glomerular basement membrane, and podocytes, then it enters the lumen of
the tubule and is known as glomerular filtrate. Otherwise, it exits the
glomerulus through the efferent arteriole and continues circulation.
Also it participate in the regulation of blood pressure as The walls of the
afferent arteriole contain specialized smooth muscle cells that
synthesize renin. These juxtaglomerular cells play a major role in the renin-
angiotensin system, which helps regulate blood volume and pressure.

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Types of glomerular disease
In this research I will focus on three types:
1-Acute Glomerulonephritis:
Acute GN is defined as the sudden onset of hematuria, proteinuria, and red
blood cell (RBC) casts in the urine. This clinical picture is often
accompanied by hypertension, edema, azotemia (ie, decreased glomerular
filtration rate [GFR], and renal salt and water retention. Acute GN can be
due to a primary renal disease or to a systemic disease.
Acute glomerulonephritis (GN) comprises a specific set of renal diseases
in which an immunologic mechanism triggers inflammation and
proliferation of glomerular tissue that can result in damage to the basement
membrane, mesangium, or capillary endothelium. Acute nephritic
syndrome is the most serious and potentially devastating form of the
various renal syndromes.
Acute poststreptococcal glomerulonephritis (PSGN) is the archetype of
acute GN. In recent decades, however, the incidence of PSGN has fallen in
the United States and other developed countries, while postinfectious GN
from staphylococcal infection has risen. [11]
2-Chronic Glomerulonephritis:
Nearly all forms of acute glomerulonephritis have a tendency to progress
to chronic glomerulonephritis. The condition is characterized by
irreversible and progressive glomerular and tubulointerstitial fibrosis,
ultimately leading to a reduction in the glomerular filtration rate (GFR) and
retention of uremic toxins. If disease progression is not halted with therapy,
the net results are chronic kidney disease (CKD), end-stage renal
disease (ESRD), and cardiovascular disease. Chronic glomerulonephritis
is the third leading cause of CKD, and accounting for about 10% of all
patients on dialysis.
The exact cause of CKD in patients with chronic glomerulonephritis may
never be known in some patients. Therefore, it has generally been accepted
that the diagnosis of CKD can be made without knowledge of the specific
cause. [11]

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3-Focal Segmental glomerulosclerosis:
Focal segmental glomerulosclerosis (FSGS) is one of the most common
causes of primary glomerular diseases in adults. [11]
The condition causes
asymptomatic proteinuria or nephrotic syndrome with or without renal
insufficiency. Generally, FSGS is a progressive form of kidney disease,
accounting for 2.3% of end-stage renal disease (ESRD).
Fig (1): types of G.D

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Epidemiology of glomerular disease
(International statistics)
Acute glomerulonephritis:
Worldwide, IgA Nephropathy (Berger disease) is the most common cause
of GN.
With some exceptions, the incidence of PSGN has fallen in most developed
countries. Japanese researchers reported that incidence of postinfectious
GN in their country peaked in the 1990s, and that PSGN, which accounted
for almost all of the postinfectious GN cases in the 1970s, has decreased to
approximately 40-50% since the 1990s, while the proportion
of Staphylococcus aureus infection–related nephritis increased to 30%, and
hepatitis C virus infection–associated GN also increased. [12]
PSGN remains much more common in regions such as Africa, the
Caribbean, India, Pakistan, Malaysia, Papua New Guinea, and South
America. In Port Harcourt, Nigeria, the incidence of acute GN in children
aged 3-16 years was 15.5 cases per year, with a male-to-female ratio of
1.1:1; the current incidence is not much different. [13]
A study from a
regional dialysis center in Ethiopia found that acute GN was second only
to hypovolemia as a cause of acute kidney injury that required dialysis,
accoujting for approximately 22% of cases. [14]
Geographic and seasonal variations in the prevalence of PSGN are more
marked for pharyngeally associated GN than for cutaneously associated
disease. [13, 15, 16]
Chronic glomerulonephritis:
In the United States, chronic glomerulonephritis is the third leading cause
of ESRD and accounts for 10% of patients on dialysis.
In Japan and some Asian countries, chronic glomerulonephritis has
accounted for as many as 40% of patients on dialysis; however, subsequent
data suggest that in Japan, for instance, the rate of chronic
glomerulonephritis in patients on dialysis is 28%. [4, 5]
The cause of this
declining rate is not known. Concurrent with the decline in chronic
glomerulonephritis in these countries is an increase in diabetic nephropathy
in up to 40% of patients on dialysis.

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Focal Segmental glomerulosclerosis:
FSGS lesions are observed in about 10% of renal biopsies performed for
the evaluation of proteinuria.
Etiology of glomerular disease
Acute glomerulonephritis:
The causal factors that underlie acute GN can be broadly divided into
infectious and noninfectious groups.
Infectious
The most common infectious cause of acute GN is infection
by Streptococcusspecies (ie, group A, beta-hemolytic). Two types have
been described, involving different serotypes:
 Serotype 12 - Poststreptococcal nephritis due to an upper respiratory
infection, occurring primarily in the winter months
 Serotype 49 - Poststreptococcal nephritis due to a skin infection,
usually observed in the summer and fall and more prevalent in
southern regions of the United States
PSGN usually develops 1-3 weeks after acute infection with specific
nephritogenic strains of group A beta-hemolytic streptococcus. The
incidence of GN is approximately 5-10% in persons with pharyngitis and
25% in those with skin infections.

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Nonstreptococcal postinfectious GN may also result from infection by
other bacteria, viruses, parasites, or fungi. Bacteria besides group A
streptococci that can cause acute GN include diplococci, other
streptococci, staphylococci, and mycobacteria. Salmonella
typhosa, Brucella suis, Treponema pallidum, Corynebacterium bovis, and
actinobacilli have also been identified.
Cytomegalovirus (CMV), coxsackievirus, Epstein-Barr virus (EBV),
hepatitis B virus (HBV), [17]
rubella, rickettsiae (as in scrub typhus), and
mumps virus are accepted as viral causes only if it can be documented that
a recent group A beta-hemolytic streptococcal infection did not occur.
Acute GN has been documented as a rare complication of hepatitis A. [4]
Attributing glomerulonephritis to a parasitic or fungal etiology requires the
exclusion of a streptococcal infection. Identified organisms
include Coccidioides immitis and the following parasites: Plasmodium
malariae, Plasmodium falciparum, Schistosoma mansoni, Toxoplasma
gondii, filariasis, trichinosis, and trypanosomes.
Noninfectious
Noninfectious causes of acute GN may be divided into primary renal
diseases, systemic diseases, and miscellaneous conditions or agents.
Multisystem systemic diseases that can cause acute GN include the
following:
 Vasculitis (eg, granulomatosis with polyangiitis [Wegener
granulomatosis]) - This causes glomerulonephritis that combines
upper and lower granulomatous nephritides).
 Collagen-vascular diseases (eg, systemic lupus erythematosus
[SLE]) – This causes glomerulonephritis through renal deposition of
immune complexes).
 Hypersensitivity vasculitis – This encompasses a heterogeneous
group of disorders featuring small vessel and skin disease.
 Cryoglobulinemia – This causes abnormal quantities of cryoglobulin
in plasma that result in repeated episodes of widespread purpura and
cutaneous ulcerations upon crystallization.
 Polyarteritis nodosa - This causes nephritis from a vasculitis
involving the renal arteries.

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 Henoch-Schönlein purpura – This causes a generalized vasculitis
resulting in glomerulonephritis.
 Goodpasture syndrome – This causes circulating antibodies to type
IV collagen and often results in a rapidly progressive oliguric renal
failure (weeks to months).
Primary renal diseases that can cause acute GN include the
following:
 Membranoproliferative glomerulonephritis ( MPGN) - This is due
to the expansion and proliferation of mesangial cells as a
consequence of the deposition of complements. Type I refers to the
granular deposition of C3; type II refers to an irregular process.
 Immunoglobulin A (IgA) nephropathy (Berger disease) - This
causes GN as a result of diffuse mesangial deposition of IgA and
IgG.
 “Pure” mesangial proliferative GN [6]
 Idiopathic rapidly progressive glomerulonephritis - This form of GN
is characterized by the presence of glomerular crescents. Three types
have been distinguished: Type I is an antiglomerular basement
membrane disease, type II is mediated by immune complexes, and
type III is identified by antineutrophil cytoplasmic antibody
(ANCA).
Miscellaneous noninfectious causes of acute GN include the
following:
 Guillain-Barré syndrome
 Irradiation of Wilms tumor
 Diphtheria-pertussis-tetanus (DPT) vaccine
 Serum sickness
 Epidermal growth factor receptor activation, [5]
and possibly its
inhibition by cetuximab [18]

13. 12
Chronic glomerulonephritis:
The progression from acute glomerulonephritis to chronic
glomerulonephritis is variable, depending to a considerable extent on the
cause of the condition. Whereas complete recovery of renal function is the
rule for patients with poststreptococcal glomerulonephritis, several other
glomerulonephritides, such as immunoglobulin A (IgA) nephropathy,
often have a relatively benign course, and many do not progress to ESRD.
Progression patterns may be summarized as follows:
 Rapidly progressive glomerulonephritis or crescentic
glomerulonephritis – About 90% of patients progress to ESRD
within weeks or months.
 Focal segmental glomerulosclerosis – About 80% of patients
progress to ESRD in 10 years; patients with the collapsing variant
(malignant focal segmental glomerulosclerosis) have a more rapid
progression; this form may be idiopathic or related to HIV infection
 Membranous nephropathy – About 20-30% of patients with
membranous nephropathy progress to chronic renal failure (CRF)
and ESRD in 10 years
 Membranoproliferative glomerulonephritis – About 40% of patients
with membranoproliferative glomerulonephritis progress to CRF
and ESRD in 10 years [19]
 IgA nephropathy – About 10% of patients with IgA nephropathy
progress to CRF and ESRD in 10 years [6, 20]
 Poststreptococcal glomerulonephritis – About 1-2% of patients with
poststreptococcal glomerulonephritis progress to CRF and ESRD;
older children who present with crescentic glomerulonephritis are at
greatest risk
 Lupus nephritis – Overall, about 20% of patients with lupus nephritis
progress to CRF and ESRD in 10 years; however, patients with
certain histologic variants (eg, class IV) may have a more rapid
decline. [21]
The presence of antineutrophil cytoplasmic antibody
(ANCA) is also an independent risk factor for poor renal
outcomes. [17]

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Focal Segmental glomerulosclerosis:
Etiologic agents or mechanisms that initiate glomerular injury which lead
to glomerulosclerosis are largely unknown, except in certain animal
models of viral-induced renal disease.
FSGS can be classified as primary (idiopathic) or secondary.
Primary (idiopathic) FSGS
Primary (idiopathic) FSGS includes the following:
 FSGS with hyalinosis
 Progression from minimal-change disease
 Progression from immunoglobulin M (IgM) nephropathy
 Progression from mesangial proliferative glomerulonephritis
 Superimposed on other primary glomerulonephritis conditions (eg,
membranous glomerulonephritis, immunoglobulin A [IgA]
nephropathy)
Variants of primary FSGS include the following:
 Collapsing form
 Cellular variant (endocapillary and extracapillary hypercellularity)
 FSGS with mesangial hypercellularity
 FSGS with glomerular tip lesions
Secondary FSGS
Drugs associated with FSGS include the following [13]
:
 Intravenous heroin [14]
 Analgesics
 Pamidronate
 Lithium
 Anabolic steroids

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Viruses associated with FSGS include the following:
 Hepatitis B
 HIV [13]
 Parvovirus
Hemodynamic factors in patients with reduced renal mass include the
following:
 Solitary kidney
 Renal allograft
 Renal dysplasia
 Renal agenesis
 Oligomeganephronia
 Segmental hypoplasia
 Vesicoureteric reflux
Hemodynamic causes in patients without reduced renal mass include
the following:
 Massive obesity [26]
 Sickle cell nephropathy
 Congenital cyanotic heart disease
Lymphomas and other malignancies have been associated with FSGS.
Genetic cases may be familial or sporadic. Scarring may lead to FSGS
subsequent to postinfectious glomerulonephritis. Miscellaneous other
conditions associated with FSGS include the following:
 Hypertensive nephrosclerosis
 Alport syndrome
 Sarcoidosis
 Radiation nephritis
In other words, factors as diverse as infections, inflammations, toxins,
and intrarenal hemodynamic alterations can initiate injury to cells and
lead to glomerulosclerosis.

16. 15
Presentation
Acute glomerulonephritis:
1-History:
A thorough history should be obtained, focusing on the identification of
an underlying systemic disease (if any) or recent infection. Most often,
the patient is a boy, aged 2-14 years, who suddenly develops puffiness
of the eyelids and facial edema in the setting of a poststreptococcal
infection. The urine is dark and scanty, and the blood pressure may be
elevated. Nonspecific symptoms include weakness, fever, abdominal
pain, and malaise.
With poststaphylococcal infection, in contrast, the patient is likely to be
a middle-aged man, often with diabetes mellitus, with a recent history
of a visceral abscess or skin infection, possibly from methicillin-
resistant Staphylococcus aureus.Hematuria is almot always present. [11]
Ask the patient about the onset and duration of the illness. Symptom
onset is usually abrupt. In the setting of acute postinfectious
glomerulonephritis (GN), a latent period of up to 3 weeks occurs before
onset of symptoms. However, the latent period may vary; it is typically
1-2 weeks for postpharyngitis cases and 2-4 weeks for cases of
postdermal infection (ie, pyoderma). The onset of nephritis within 1-4
days of streptococcal infection suggests preexisting renal disease.
Identify a possible etiologic agent (eg, streptococcal throat infection
[pharyngitis], skin infection [pyoderma]). Recent fever, sore throat,
joint pains, hepatitis, travel, valve replacement, and/or intravenous drug
use may be causative factors. Rheumatic fever rarely coexists with
acute PSGN.
Assess the consequences of the disease process (eg, uremic symptoms).
Inquire about loss of appetite, generalized itching, tiredness,
listlessness, nausea, easy bruising, nosebleeds, facial swelling, leg
edema, and shortness of breath.]51[
Inquire about symptoms of acute glomerulonephritis, including the
following:
 Hematuria - This is a universal finding, even if it is microscopic.
Gross hematuria is reported in 30% of pediatric patients, often
manifesting as smoky-, coffee-, or cola-colored urine.

17. 16
 Oliguria
 Edema (peripheral or periorbital) - This is reported in approximately
85% of pediatric patients; edema may be mild (involving only the
face) to severe, bordering on a nephrotic appearance.
 Headache - This may occur secondary to hypertension; confusion
secondary to malignant hypertension may be seen in as many as 5%
of patients.
 Shortness of breath or dyspnea on exertion - This may occur
secondary to heart failure or pulmonary edema; it is usually
uncommon, particularly in children.
 Possible flank pain secondary to stretching of the renal capsule
Ask about symptoms specific to an underlying systemic disease that can
precipitate acute GN (see Etiology). Classic presentations include the
following:
 Triad of sinusitis, pulmonary infiltrates, and nephritis, suggesting
granulomatosis with polyangiitis (Wegener granulomatosis)
 Nausea and vomiting, abdominal pain, and purpura, observed with
Henoch-Schönlein purpura
 Arthralgias, associated with systemic lupus erythematosus (SLE)
 Hemoptysis, occurring with Goodpasture syndrome or idiopathic
progressive glomerulonephritis
 Skin rashes, observed with hypersensitivity vasculitis or SLE; also
possibly due to the purpura that can occur in hypersensitivity
vasculitis, cryoglobulinemia, and Henoch-Schönlein purpura]91[
2-Physical Examination:
Patients often have a normal physical examination and blood pressure;
most frequently, however, patients present with a combination of
edema, hypertension, and oliguria.
The physician should look for the following signs of fluid overload:
 Periorbital and/or pedal edema
 Edema and hypertension due to fluid overload (in 75% of patients)

18. 17
 Crackles (ie, if pulmonary edema)
 Elevated jugular venous pressure
 Ascites and pleural effusion (possible)
The physician should also look for the following:
 Rash (as with vasculitis, Henoch-Schönlein purpura, or lupus
nephritis)
 Pallor
 Renal angle (ie, costovertebral) fullness or tenderness, joint
swelling, or tenderness
 Hematuria, either macroscopic (gross) or microscopic
 Abnormal neurologic examination or altered level of consciousness
(from malignant hypertension or hypertensive encephalopathy)
 Arthritis
Other signs include the following:
 Pharyngitis
 Impetigo
 Respiratory infection
 Pulmonary hemorrhage
 Heart murmur (possibly indicative of endocarditis)
 Scarlet fever
 Weight gain
 Abdominal pain
 Anorexia
 Back pain
 Oral ulcers
Complications:
Progression to sclerosis is rare in the typical patient; however, in 0.5-
2% of patients with acute GN, the course progresses toward renal
failure, resulting in kidney death in a short period.

19. 18
Abnormal urinalysis (ie, microhematuria) may persist for years. A
marked decline in the glomerular filtration rate (GFR) is rare.
Pulmonary edema and hypertension may develop. Generalized anasarca
and hypoalbuminemia may develop secondary to severe proteinuria.
A number of complications that result in relevant end-organ damage in
the central nervous system (CNS) or the cardiopulmonary system can
develop in patients who present with severe hypertension,
encephalopathy, and pulmonary edema. Those complications include
the following:
 Hypertensive retinopathy
 Hypertensive encephalopathy
 Rapidly progressive GN
 Chronic renal failure
 Nephrotic syndrome
Chronic glomerulonephritis:
1-History:
The history should begin by focusing on cause-specific symptoms to
determine the source of the chronic kidney disease (CKD) if this is
unknown. Recognition of such symptoms facilitates the planning of further
workup and management of the disease (if systemic).
The next step is to look for symptoms related to uremia to determine if
renal replacement therapy is needed. The following symptoms suggest
uremia:
 Weakness and fatigue
 Loss of energy, appetite, and weight
 Pruritus
 Early morning nausea and vomiting
 Change in taste sensation

20. 19
 Reversal in sleep pattern (ie, sleepiness in daytime and wakefulness
at night)
 Peripheral neuropathy
 Seizures
 Tremors
The presence of edema and hypertension suggests volume retention.
Dyspnea or chest pain that varies with position suggests fluid overload and
pericarditis, respectively. Leg cramps may suggest hypocalcemia or other
electrolyte abnormalities. Weakness, lethargy, and fatigue may be due to
anemia.
2-Physical Examination:
Uremia-specific physical findings include the following:
 Hypertension
 Jugular venous distention (if severe volume overload is present)
 Pulmonary rales (if pulmonary edema is present)
 Pericardial friction rub in pericarditis
 Tenderness in the epigastric region or blood in the stool (possible
indicators of uremic gastritis or enteropathy)
 Decreased sensation and asterixis (indicators of advanced uremia)
Complications:
The presence of the following complications generally indicates a need for
urgent dialysis:
 Metabolic acidosis
 Pulmonary edema
 Pericarditis
 Uremic encephalopathy
 Uremic gastrointestinal bleeding

21. 20
 Uremic neuropathy
 Severe anemia and hypocalcemia
 Hyperkalemia
Focal Segmental glomerulosclerosis:
1-History:
The natural history of focal segmental glomerulosclerosis (FSGS) varies a
great deal. Spontaneous remissions are extremely rare, although the
literature contains isolated case reports. A typical course runs from edema
that is difficult to manage, to proteinuria that is refractory to
corticosteroids [19]
and other immunosuppressive agents, to worsening
hypertension and a progressive loss of renal function. In nonresponders,
the average time from the onset of proteinuria to end-stage renal disease
(ESRD is 6-8 years, although wide variations in the time course occur.
The prognosis is much worse in black persons than in whites. In the
collapsing form of FSGS, the disease is marked by severe hypertension,
more massive proteinuria, a very poor response to corticosteroids, and a
much faster rate of progression to ESRD.
In HIV-associated FSGS, the renal functional deterioration is rapid,
leading to ESRD within a few weeks to 1 year. Since the introduction of
highly active antiretroviral therapy (HAART), however, renal function is
well preserved when the viral load decreases. HAART therapy has been
shown to prevent the onset of proteinuria in patients with HIV and, in those
with established FSGS, to reduce proteinuria, preserve renal function, and
prevent the development of ESRD in select cases. With the introduction of
screening of pregnant women and early HAART therapy, no cases of HIV-
associated nephropathy have been reported in children for more than a
decade. [27]
FSGS is considered primary or idiopathic when no etiology can be
identified. Secondary FSGS is associated with illicit drug use, HIV and
other viral infections, [23]
and many diverse factors, such as infections,
inflammations, toxins, and intrarenal hemodynamic alterations.

22. 21
2-Physical Examination
The most common clinical presenting feature, found in more than 70% of
patients, is nephrotic syndrome, which is characterized by generalized
edema, massive proteinuria, hypoalbuminemia, and hyperlipidemia. Other
causes of nephrotic syndrome in adults include minimal change disease,
membranous glomerulonephritis, systemic lupus erythematosus, focal
sclerosis, HIV infection, [23]
IgA nephropathy, diabetes mellitus, and
amyloidosis. In patients with primary (essential) hypertension and
analgesic abuse, nephrotic syndrome is not a common manifestation
(although hypertension may be observed in patients with nephrotic
syndrome from all causes).
Occasionally, routine urinalysis may reveal proteinuria, prompting referral
to a nephrologist. Less than a third of patients with FSGS present with
nonnephrotic proteinuria along with microscopic hematuria and
hypertension. Typically, edema develops over a few weeks, but the onset
may be abrupt, with weight gain of 15-20 lb or more. Frequently, the onset
of edema follows a recent upper respiratory tract infection.
Pleural effusion and ascites may be present; pericardial effusions are rare.
Gross edema may predispose patients to ulcerations and infections in
dependent areas (eg, lower extremities). Abdominal pain, a common
finding in children, may be a sign of peritonitis. Rarely, xanthomas may be
evident in association with severe hyperlipidemia. In many patients,
physical examination findings are normal except for generalized or
dependent edema.
Severe hypertension (ie, diastolic blood pressure of 120 mm Hg or more)
is not uncommon, especially in black patients with renal
insufficiency.[20]
Rarely, patients experience severe renal failure with signs
and symptoms of advanced uremia (eg, nausea, vomiting, bleeding,
seizures) or altered mental status.
Patients with FSGS secondary to diseases such as massive obesity, reflux
nephropathy, and renal dysplasia/agenesis may present with non-nephritic
proteinuria. These patients often experience worsening renal function over
a course of months to years.

23. 22
Differential diagnosis and considerations
Acute glomerulonephritis:
Diagnostic Considerations:
The following four renal syndromes commonly mimic the early stage of
acute glomerulonephritis (GN):
 Anaphylactoid purpura with nephritis
 Chronic GN with an acute exacerbation
 Idiopathic hematuria
 Familial nephritis
Postinfectious GN must be differentiated from the following conditions:
 Immunoglobulin A (IgA) nephritis - The latent period between
infection and onset of nephritis is 1-2 days; alternatively, nephritis
may be concomitant with upper respiratory tract infection (ie,
“synpharyngitic nephritis,” in contrast to the “postpharyngitic
nephritis” seen in poststreptococcal GN [PSGN], which occurs 1-3
weeks later).
 Membranoproliferative GN (MPGN), types I and II - This is a
chronic disease, but it can manifest with an acute nephritic picture
with hypocomplementemia; failure of acute nephritis to resolve
should prompt consideration of this possibility.
 Lupus nephritis - Gross hematuria is unusual in lupus nephritis.
 GN of chronic infection - This can manifest as acute nephritis.
Unlike PSGN, in which the infection may have resolved by the time
nephritis occurs, patients with nephritis of chronic infection have an
active infection at the time nephritis becomes evident. Circulating
immune complexes play an important role in the pathogenesis of
acute GN in these diseases.
 Vasculitis - Nephritis of methicillin-resistant Staphylococcus
aureus (MRSA) may be associated with vasculitic lesions of the
lower extremities.]33[

24. 23
 Predominantly nonglomerular diseases - Thrombotic
thrombocytopenic purpura (TTP), hemolytic-uremic syndrome
(HUS), atheroembolic renal disease, and acute hypersensitivity
interstitial nephritis may present with features of acute nephritic
syndrome and should be differentiated.]6[
Other problems to be considered include the following:
1. Bacterial, viral, and fungal etiologies
2. Chronic GN
3. Idiopathic hematuria
4. IgA nephropathy
5. Irradiation of Wilms tumor
6. Trauma
Differential Diagnoses:
 Acute Kidney Injury
 Crescentic Glomerulonephritis
 Diffuse Proliferative Glomerulonephritis
 Focal Segmental Glomerulosclerosis
 Glomerulonephritis Associated with Nonstreptococcal Infection
 Goodpasture Syndrome
 Lupus Nephritis
 Membranoproliferative Glomerulonephritis
 Poststreptococcal Glomerulonephritis
 Rapidly Progressive Glomerulonephritis

25. 24
Chronic glomerulonephritis:
Differential Diagnoses:
 Acute Glomerulonephritis
 Azotemia
 Chronic Kidney Disease
 Crescentic Glomerulonephritis
 Diffuse Proliferative Glomerulonephritis
 Glomerulonephritis Associated with Nonstreptococcal Infection
 Membranoproliferative Glomerulonephritis
 Membranous Glomerulonephritis
 Poststreptococcal Glomerulonephritis
 Rapidly Progressive Glomerulonephritis
 Uremia
Focal Segmental glomerulosclerosis:
Diagnostic Considerations:
Distinguishing FSGS from minimal-change disease, mesangial
proliferative glomerulonephritis, membranoproliferative
glomerulonephritis, or membranous glomerulonephritis may be clinically
difficult. Rarely, nephrotic syndrome may be the initial manifestation in
patients with systemic lupus erythematosus. Young patients presenting
with nephrotic syndrome due to amyloidosis of the kidneys (except in rare
familial forms) is very uncommon. Although hematuria is the most
common presentation in whites with IgA nephropathy, nephrotic syndrome
and renal insufficiency may also be present.]55[

26. 25
Workup
Acute glomerulonephritis:
Urinalysis and sediment examination are crucial in the evaluation of
patients with acute nephritic syndrome. the following should checked :
 Protein
 Blood
 Red blood cells (RBCs)
 White blood cells (WBCs)
 Dysmorphic RBCs
 Acanthocytes
 Cellular (ie, RBC, WBC) casts
 Granular casts
 Oval fat bodies
In some instances, marked sterile pyuria is present. The presence of RBC
casts is almost pathognomonic of glomerulonephritis (GN). Urine
electrolyte, urine sodium, and fractional excretion of sodium (FENa)
assays are needed to assess salt avidity.]02[
Blood tests should include the following:
 Complete blood count (CBC)
 Blood urea nitrogen (BUN), serum creatinine, and serum
electrolytes (especially serum potassium)
 Erythrocyte sedimentation rate (ESR)
 Complement levels (C3, C4, CH50)
Streptozyme testing may be useful. Imaging studies are helpful in some
patients, for assessment of clinical signs suggesting extrarenal involvement
or for structural evaluation of the kidneys.

27. 26
Chronic glomerulonephritis:
Laboratory Studies
1. Urinalysis
The presence of dysmorphic red blood cells (RBCs), albumin, or RBC
casts suggests glomerulonephritis as the cause of renal failure. Waxy or
broad casts are observed in all forms of chronic kidney disease (CKD),
including chronic glomerulonephritis. Low urine specific gravity indicates
loss of tubular concentrating ability, an early finding in persons with CKD.
2. Urinary protein excretion
Urinary protein excretion can be estimated by calculating the protein-to-
creatinine ratio on a spot morning urine sample. The ratio of urinary protein
concentration (in mg/dL) to urinary creatinine (in mg/dL) reflects 24-hour
protein excretion in grams. For instance, if the spot urine protein value is
300 mg/dL and the creatinine value is 150 mg/dL, the protein-to-creatinine
ratio is 2. Thus, in this example, the 24-hour urine protein excretion is
2g. [13]
The estimated creatinine clearance rate is used to assess and monitor the
glomerular filtration rate (GFR). The 2 formulas available for calculation
of the GFR are the Cockcroft-Gault formula, which estimates creatinine
clearance, and the Modification of Diet in Renal Disease (MDRD) Study
formula, which is used to calculate the GFR directly.
The Cockcroft-Gault formula is simple to use but overestimates the GFR
by 10-15% because creatinine is both filtered and secreted.]53[
The estimated creatinine clearance rate is also used to monitor response to
therapy and to initiate an early transition to renal replacement therapy (eg,
dialysis access placement and transplantation evaluation). The degree of
proteinuria, especially albuminuria, helps predict the renal prognosis in
patients with chronic glomerulonephritis. Patients with proteinuria
exceeding 1 g/day have an increased risk of progression to end-stage renal
failure.

28. 27
3. Complete blood count
Anemia is a significant finding in patients with some decline in the GFR.
Physicians must be aware that anemia can occur even in patients with
serum creatinine levels lower than 2 mg/dL. Even severe anemia can occur
at low serum creatinine levels. Anemia is the result of marked impairment
of erythropoietin production.
Focal Segmental glomerulosclerosis:
Laboratory Studies
In patients with focal segmental glomerulosclerosis (FSGS), urinalysis
reveals large amounts of protein, along with hyaline and broad waxy casts,
whereas red blood cell (RBC) casts are generally absent. Broad casts may
be observed in persons with advanced cases. Serum creatinine (SCr)
concentration or creatinine clearance (CrCl) is usually within reference
ranges in early stages.
In patients with idiopathic FSGS, investigational findings for an underlying
etiology are generally negative. Such conditions may include the
following:
 Systemic lupus erythematosus (serum complement C4/C3 levels,
antinuclear antibody/anti-DNA titers)
 Hepatitis B or C infection
 Vasculitis (antineutrophil cytoplasmic antibody titers, serum protein
electrophoresis)
In patients thought to have secondary FSGS, obtain HIV antibody, CD4,
and viral load studies; serology for hepatitis B and C; and parvovirus
testing. Diagnosis of FSGS in massively obese patients is by excluding
other causes. FSGS can be considered in patients with proteinuria on the
basis of nephrotic syndrome; however, in young patients with an absence
of RBC casts and negative serologic study findings, definitive diagnosis
rests on a kidney biopsy.]56[

29. 28
Treatment of glomerular disease
Acute glomerulonephritis:
 Approach Considerations
Treatment of acute poststreptococcal glomerulonephritis (PSGN) is mainly
supportive, because there is no specific therapy for renal disease. When
acute glomerulonephritis (GN) is associated with chronic infections, the
underlying infections must be treated.
The expertise available in the intensive care unit may be needed for
management of patients with hypertensive encephalopathy or pulmonary
edema. Consultation with a nephrologist may be indicated. On an
outpatient basis, renal function, blood pressure, edema, serum albumin, and
urine protein excretion rate should be monitored.
 Pharmacologic Therapy
Antibiotics
Antibiotics (eg, penicillin) are used to control local symptoms and to
prevent spread of infection to close contacts. Antimicrobial therapy does
not appear to prevent the development of GN, except if given within the
first 36 hours. Antibiotic treatment of close contacts of the index case may
help prevent development of PSGN.
Other agents
Loop diuretics may be required in patients who are edematous and
hypertensive, in order to remove excess fluid and to correct hypertension.
Vasodilator drugs (eg, nitroprusside, nifedipine, hydralazine, diazoxide)
may be used if severe hypertension or encephalopathy is present.
Glucocorticoids and cytotoxic agents are of no value, except in severe
cases of PSGN.
 Diet and Activity
Sodium and fluid restriction should be advised for treatment of signs and
symptoms of fluid retention (eg, edema, pulmonary edema). Protein
restriction for patients with azotemia should be advised if there is no
evidence of malnutrition.]32[

30. 29
Bed rest is recommended until signs of glomerular inflammation and
circulatory congestion subside. Prolonged inactivity is of no benefit in the
patient recovery process.
 Long-Term Monitoring
Long-term studies on children with PSGN have revealed few chronic
sequelae. Results of such studies are controversial because homogenous
populations suitable for proper epidemiologic analysis have not been
assembled.
Long-term studies show higher mortality rates in elderly patients,
particularly those on dialysis. Patients may be predisposed to crescent
formation.
Chronic glomerulonephritis:
 Antihypertensive drugs may be prescribed to reduce high blood
pressure.
 Diuretics may be prescribed to reduce excess fluid retention and
increase urine production.
 Your doctor may advise you to eat a low-protein, low-salt diet and
to take iron or vitamin supplements. (Do not take iron supplements
without your doctor’s approval.)
 Steroid medication or immunosuppressive drugs may be prescribed
for some patients.
 In severe cases where kidney failure occurs, dialysis may be
necessary. Dialysis performs the functions of the kidney by
removing waste products and excess fluid from the blood when the
kidney cannot (Renal Failure, Chronic).
 A kidney transplant is an alternative to dialysis in cases of kidney
failure.]32[

31. 30
Focal Segmental glomerulosclerosis:
The type of treatment depends on the cause. Everyone is different and the
doctor will make a treatment plan that is right for the type of FSGS.
Usually, treatments for FSGS include:
 Corticosteroids and immunosuppressive drugs: These
medications are used to calm your immune system (your body’s
defense system) and stop it from attacking your glomeruli.
 ACE inhibitors and ARBs: These are blood pressure medications
used to reduce protein loss and control blood pressure.
 Diuretics: These medications help your body get rid of excess fluid
and swelling. These can be used to lower your blood pressure too.
 Diet changes: Some diet changes may be needed, such as reducing
salt (sodium) and protein in your food choices to lighten the load of
wastes on the kidneys.]02[
Fig (3)

32. 31
Conclusion
Our kidneys are important organs, they do a lot of functions each day, they
regulate water in our body and remove wastes, and they also produce
hormones. Everyday, the two kidneys filter about 120 to 150 quarts of
blood to produce about 1 to 2 quarts of urine, composed of wastes and extra
fluid.
So we must follow a Healthy lifestyle to keep our kidneys safe and
functioning well include:
 Watching our weight – being overweight increases the risk
of diabetes and high blood pressure, which in turn increase the risk
of kidney disease.
 Eating healthily – a diet high in fruit and vegetables and low in salt,
sugar and fats is best.
 Drinking plenty of water – avoiding sugary drinks like soft drinks.
 Exercising regularly.
 Avoiding toboacco.
 Limiting alcohol intake.
 Doing things that help relax and reduce stress.
 Being aware of our risk factors – have our kidneys regularly
checked.
Fig (4)

33. 32
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Figures’ references:
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Primary-idiopathic-FSGS-2-FSGS-FSGS-that-i_fig1_256837620
2. http://caribbean.scielo.org/scielo.php?script=sci_arttext&pid=S0043-
31442009000300014&lng=pt&nrm=i
3. http://www.kidney-international.org/article/S0085-2538(15)55134-X/fulltext
4. https://nephcure.org/livingwithkidneydisease/understanding-glomerular-
disease/understanding-fsgs/