Nephrotic syndrome (Glomerulonephritis)

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GLOMERULONEPHRITISGLOMERULONEPHRITIS
A critical nephrotic syndromeA critical nephrotic syndrome
A PRESENTATION ONA PRESENTATION ON
Harikesh Maurya
Ph.D. Research Scholar
Dept. of Pharmaceutical Science,
Kumaun University, Nainital (UK)

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Histology ofHistology of
KidneyKidney

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KIDNEYKIDNEY
The kidneys are a vital part of the body. Their main function is to
remove waste products from the blood, which are passed out of the
body in urine. There are about a million tiny filters in each kidney
called Glomeruli. If these filtering units get inflamed (swollen) for
some reason this is called Glomerulonephritis (GN).
Glomerulonephritis is a non-specific disorder in which the kidneys are
damaged, causing them to leak large amounts of protein from the
blood into the urine.

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GROSS FEATURESGROSS FEATURES
• Paired retroperitoneal organ
• Upper poleUpper pole :: T12; Lower pole: L3
• Weight : Adult man: 125 -170 g
Adult woman: 115 - 155 g
• Length : 11 to 12 cm
• Width : 5.0 to 7.5 cm
• Thickness : 2.5 to 3.0 cm
• Hilus: Renal pelvis, the renal artery & vein, the lymphatics, & nerve.
• Blood supply: Single renal artery
• Anterior branch: 3 segmental or lobar arteries supply the upper,
middle, and lower thirds of the anterior surface of the kidney
• Posterior branch: >½ of the posterior surface; small apical segmental
branch

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GROSS FEATURESGROSS FEATURES
Relation to other layers:
The renal fascia relates to the other layers in the following manner
(moving from innermost to outermost):
 Renal cortex
 Renal capsule
 Renal fascia
 Perinephric fat (or "perirenal fat")
 Paranephric fat (or "pararenal fat")
 Peritoneum (anteriorly)
 Transversalis fascia (posteriorly)

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SECTION OF RIGHT KIDNEYSECTION OF RIGHT KIDNEY

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CUT SURFACE OF A BISECTED KIDNEYCUT SURFACE OF A BISECTED KIDNEY
• Pale outer region (the cortex)
• Darker inner region (the
medulla)
• 8 to 18 striated conical
masses (renal pyramids)
• Base: corticomedullary
boundary
• Apex: renal pelvis to form a
papilla: 10 - 25 small
openings that represent the
distal ends of the collecting
ducts (of Bellini) → area
cribrosa

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Renal cortex:
- 1 cm in thickness
- Renal columns of Bertin
- Medullary rays of Ferrein- formed by
the collecting ducts and the straight segments
of the proximal and distal tubules.
• Renal pelvis: expanded portion of the upper
urinary tract
• Major calyces: 2 or 3 outpouchings, extend outward from the upper dilated
end of the renal pelvis
CUT SURFACE OF A BISECTED KIDNEYCUT SURFACE OF A BISECTED KIDNEY

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THE NEPHRONTHE NEPHRON
• Functional unit of the kidney 0.4 × 10 6
to
1.2 × 10 6
• Essential components: Renal or
malpighian corpuscle (glomerulus and
Bowman's capsule)
 Proximal tubule
 The thin limbs
 Distal tubule
 Connecting segment or connecting tubule
• Two main populations of nephrons:
1) Possessing a short loop of Henle (7x
more)
2) Long loop of Henle

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THE NEPHRONTHE NEPHRON
• Length of the loop of Henle is generally related to the position of its
parent glomerulus in the cortex.
• Superficial and midcortical locations: short loops of Henle
• Juxtamedullary region: long loops of Henle
• Division of the kidney (cortical & medullary) and the further subdivision
of the medulla (inner & outer zones): relating renal structure to the
ability of an animal to form a maximally concentrated urine
• Countercurrent hypothesis for urine: the maximal urine concentration
that can be achieved is directly related to the length of the multiplier
system.

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BLOOD SUPPLY OF KIDNEYBLOOD SUPPLY OF KIDNEY
 Renal artery—branch of
Abdominal aorta divides at the
hilum into segmental branches
 Lobar arteries
 Interlobar arteries ascend to
corticomedullary junction
 Arcuate arteries
 Interlobular arteries (cortical
radial) arise from arcuate
arteries

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BLOOD SUPPLY OF KIDNEYBLOOD SUPPLY OF KIDNEY
• Diameter (lumen) of afferent
arteriole is larger than efferent
arteriole
• An arrangement which maintains
pressure within glomerular
capillaries necessary for the blood
plasma to be filtered into
Bowman’s space

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AFFERENT & EFFERENT ARTERIOLESAFFERENT & EFFERENT ARTERIOLES
• Afferent arterioles of the glomerulus are
branches of interlobular arteries—give rise
to Capillaries of glomeruli
• Efferent arterioles-- form peritubular
capillary bed
-- vasa recta microcirculation of medulla &
cortex
-- Arcuate & interlobular veins
-- Renal vein-inferior vena cava—right
atrium of heart

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MICROCIRCULATION OF THE KIDNEYSMICROCIRCULATION OF THE KIDNEYS

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RENAL CORPUSCLE (GLOMERULUS)RENAL CORPUSCLE (GLOMERULUS)
• Capillary network lined by a thin
layer of endothelial cells
• Central region of mesangial cells
with surrounding mesangial matrix
material
• The visceral epithelial cells
(Podocytes) and the associated
basement membrane
• Average diameter: 200 µm
• The diameters of glomeruli from
juxtamedullary nephrons: are 20%
greater than superficial glomeruli

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RENAL CORPUSCLE (GLOMERULUS)RENAL CORPUSCLE (GLOMERULUS)
• Responsible for the production of
an ultra-filtrate of plasma
• Filtration barrier
1.fenestrated endothelium
2.peripheral GBM
3.slit pores between the foot
processes of the visceral
epithelial cells
• Mean area of filtration surface per
glomerulus: 0.136 mm2 in the human
kidney

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Mesangial cells Endothelial cell
Visceral Epithelial cell
Parietal Epithelial cell

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ENDOTHELIAL CELLENDOTHELIAL CELL
• Glomerular capillaries are lined by a
thin fenestrated endothelium
• Human kidney range fr 70 - 100 nm
• Thin diaphragms: extend across
the fenestrae w/c when present,
are not believed to represent a
significant barrier to the passage
of macromolecules.
• Surface is negatively charged
because of the presence of a
polyanionic surface glycoprotein,
podocalyxin (principal sialoprotein of
glomerular epithelial cells)

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• Synthesize both nitric oxide (EDRF) and endothelin-1 (vasoconstrictor)
• Express vascular endothelial growth factor (VEGF) receptors
• VEGF: regulator of microvascular permeability that is produced by the
glomerular VEC (Podocytes)
- In vitro studies demonstrated that VEGF increases endothelial cell
permeability and induces the formation of endothelial fenestrations.
- endothelial cell survival and repair in glomerular diseases and an
important regulator of endothelial cell function and permeability.
• Form the initial barrier to the passage of blood constituents from the
capillary lumen to Bowman's space.
• Contribute to the charge-selective properties of the glomerular capillary
wall through their negative surface charge.
ENDOTHELIAL CELLENDOTHELIAL CELL

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VISCERAL EPITHELIAL CELLS (PODOCYTES)VISCERAL EPITHELIAL CELLS (PODOCYTES)
• Largest cells in the glomerulus
• Long cytoplasmic processes
(trabeculae) that extend from the
main cell body and divide into
individual foot processes (pedicels),
that come into direct contact with
the GBM.
• Distance between adjacent foot
processes near the BM: 25 to 60 nm.
• Filtration slit membrane (slit
diaphragm) - 60 nm. fr the BM.
- role in establishing the permselec
tive properties of the filtration
barrier is still a matter of dispute.

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VISCERAL EPITHELIAL CELLS (PODOCYTES)VISCERAL EPITHELIAL CELLS (PODOCYTES)
Nephrin protein - a key component of
filtration barrier
• membrane components on the
surface of the visceral epithelial
cells (slit diaphragm)
CD2-associated protein (CD2AP) –
slit diaphragm; connect nephrin to cytoskeleton Functions:
Endocytosis (lysosomes ) uptake of proteins and other components from the
ultrafiltrate
Synthesis and maintenance of the GBM, type IV collagen, and
glycosaminoglycan, PgE2 and thromboxanes.

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MESANGIAL CELLSMESANGIAL CELLS
• Mesangium : cells + matrix
• Irregular in shape, with a dense nucleus
and elongated cytoplasmic processes that
can extend around the capillary lumen and
insinuate themselves between the BM and
the overlying endothelium.
• Provides structural support for the
glomerular capillary loops
• Contractile properties
• Regulation of glomerular filtration
• Exhibit phagocytic properties (clearance or disposal of macromolecules
from the mesangium)
• Generation and metabolism of the extracellular mesangial matrix and
participate in various forms of glomerular injury

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GLOMERULAR BASEMENT MEMBRANEGLOMERULAR BASEMENT MEMBRANE
• Central dense layer (lamina densa)
two thinner, more electron-lucent
layers, the lamina rara externa and
the lamina rara interna
• Layered configuration results from
the fusion of endothelial and epithelial
BM during development.
• Mean width: 315 nm - 329 nm
• Biochemical composition:
glycoproteins (type IV collagen,
laminin, fibronectin, entactin/
nidogen, various heparan sulfate
proteoglycan (perlecan and agrin)

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GLOMERULAR BASEMENT MEMBRANEGLOMERULAR BASEMENT MEMBRANE
• Possesses fixed, negatively charged sites that influence the filtration of
macromolecules
• aAnionic sites : glycosaminoglycans rich in heparan sulfate
• Glomerular capillary wall: sieve or filter that allows the passage of small
molecules but almost completely restricts the passage of molecules the
size of albumin or larger.
• Size-selective and charge-selective properties
• Fenestrated endothelium GBM epithelial slit diaphragm
• Fenestrated endothelium (negative surface charge) excludes formed
elements of the blood and probably plays a role in determining the
access of proteins to the GBM - - - plays a role in establishing the
ultrafiltration characteristics of the glomerular capillary wall.
• Principal structure responsible for the charge-selective permeability
properties of the glomerulus

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PARIETAL EPITHELIAL CELLSPARIETAL EPITHELIAL CELLS
• parietal epithelium: forms the outer wall
of Bowman's capsule
- continuous with the visceral epithelium
at the vascular pole.
- squamous in character, but at the
urinary pole there is an abrupt transition
to the taller cuboid cells of the proximal
tubule
• thickness of the BM of Bowman's
capsule :1200 to 1500 nm.
• In RPGN the parietal epithelial cells
proliferate to contribute to the formation
of crescents.

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PERIPOLAR CELLSPERIPOLAR CELLS
• Component of the JG apparatus
• Located at the origin of the glomerular tuft in Bowman's space and
is interposed between the visceral and parietal epithelial cells
• In most animals studied so far, they have been localized
predominantly in glomeruli in the outer cortex
• Are ideally situated to release factors into Bowman's space that
might affect subsequent tubule transport events.

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JUXTAGLOMERULAR APPARATUSJUXTAGLOMERULAR APPARATUS

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JUXTAGLOMERULAR APPARATUSJUXTAGLOMERULAR APPARATUS
• Located at the vascular pole of the
glomerulus
• Vascular component: composed of
the terminal portion of the afferent
arteriole, the initial portion of the
efferent arteriole, and the extraglo-
merular mesangial region.
• Tubule component : macula densa,
(that portion of the thick ascending limb
that is in contact with the vascular component)
• Represents a major structural component of the renin-angiotensin system.
• Role: regulate glomerular arteriolar resistance and GF and to control the
synthesis and secretion of renin.

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JUXTAGLOMERULAR GRANULAR CELLSJUXTAGLOMERULAR GRANULAR CELLS
Within the vascular component:
1. Juxtaglomerular granular cells (epithelioid / myoepithelial cells)
2. Agranular extraglomerular mesangial cells (lacis cells or
pseudomeissnerian cells of Goormaghtigh)
• Located primarily in the walls of the afferent and efferent arterioles, but
they are also present in the extraglomerular mesangial region.
• Are characterized by the presence of
numerous membrane-bound granules that
represent renin or its precursor.
• Immunohistochemical studies: presence
of both renin and angiotensin II in the
JG granular cells, with activities being
highest in the afferent arteriole.

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EXTRAGLOMERULAR MESANGIUMEXTRAGLOMERULAR MESANGIUM
(LACIS / CELLS OF GOORMAGHTIGH)(LACIS / CELLS OF GOORMAGHTIGH)
• Located between the afferent and efferent arterioles in close contact with the
macula densa
• In contact with the arterioles and the macula densa, and gap junctions are
commonly observed between the various cells of the vascular portion of the
JG apparatus
• Serve as a functional link between the macula densa and the glomerular
arterioles and mesangium.

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MACULA DENSAMACULA DENSA
• A specialized region of the thick
ascending limb adjacent to the
hilus of the glomerulus.
• Lacks the lateral cell processes and
interdigitations that are charac
teristic of the thick ascending limb.
• Sense changes in the luminal
concentrations of Na and Cl
via absorption of Na and Cl across
the luminal membrane by the Na+ -K+ -2Cl- cotransporter.

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PROXIMAL TUBULEPROXIMAL TUBULE
• begins abruptly at the urinary pole of the glomerulus
• Length:14 mm (human); Outside diameter: 40 µm
• Reabsorbs the bulk of filtered water and solutes
• Prominent brush border (↑ luminal cell
surface area) and extensive interdigitation by
basolateral cell processes that extends to the
leaky jxn providing a greatly increased
passage for the passive ion transport
• Generally divided into
3 segments: S1, S2, S3

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PROXIMAL TUBULEPROXIMAL TUBULE
It consists of:
Pars convoluta (initial convoluted
portion)
- direct continuation of the parietal
epithelium of Bowman's capsule
Pars recta (straight portion)
- located in the medullary ray; contains
a well-developed endocytic-lysosomal
apparatus that is involved in the
reabsorption and degradation of
macromolecules from the ultrafiltrate.

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LOOP OF HENLELOOP OF HENLE
Consists of:
1. Straight portion of the proximal tubule
2. Thin ascending limb
- impermeable to water
3. Thin descending limb
- highly permeable to water (aquaporin-1)
4. Thick ascending limb (diluting segment)
- water impermeable (carried away into the
cortex to the systemic circ.) but reabsorbs
considerable amounts of salt that is trap-
ped in the medulla(Na-K-2Cl cotransporter)
- Tam-Horsefall pretein
Before transition to the DCT. Thick AL contains
the macula densa.

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DISTAL COVOLUTED TUBULEDISTAL COVOLUTED TUBULE
• Exhibits the most extensive basolateral
interdigitation of cells and greatest
density of mitochondria.
• Na+
-Cl-
cotransporter – speific
Na+
transporter (Thiazide diuretics)

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COLLECTING DUCT SYSTEMCOLLECTING DUCT SYSTEM
Includes:
1. Connecting tubule
2. Cortical collecting ducts
3. Medullary CD
Outer MCD
Inner MCD
Connecting tubule (CNT) :
- Joining of 2 nephrons
- 2 types of cell:
1. CNT cell
2. Intercalated cell
Both share sensitivity to ADH; CNT cell lacks
sensitivity to mineralocorticoids

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COLLECTING DUCTSCOLLECTING DUCTS
Lined by 2 types of cells:
1. Principal cells (CD)
Contain luminal shuttle system for
aquaporin -2 under the control of
vasopressin (permeability from zero
to permeable)
• Luminal Amloride-sensitive Na channel – involved in the responsiveness
of the cortical collecting ducts to aldosterone.
• Inner medulary collecting ducts – expresses urea transporter UTB1 w/c in
an ADH – dependent fashion accounts for the recycling of urea (urine
concentrating mechanism)

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COLLECTING DUCTSCOLLECTING DUCTS
2. Intercalated cells (IC)
2 - types:
a. Type A cells – express H-ATPase at
their luminal memb.; secretes proton
b. Type B – basolateral membrane;
secrete HCO3 ions and reabsorb
protons.
• Final regulators of fluid and electrolye balance
• Impt roles in handling NA,Cl, K and acid-base.
• Urine concentrating capability

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INTERSTITIUMINTERSTITIUM
• Comparatively sparse: 5-7%: cortex (↑ w/ age); 3-4%: outer stripe;
10%: inner stripe 30%: inner medulla
• Fibroblast: central cells; forms the scaffold frame renal cortex: ecto
5 nucleotidas enzyme (5’-NT) – synthesizes epoetin renal medulla:
Lipid-laden IC; produce large amount of glycosaminoglycans and
Vasoactive lipids (Pg E2)
• Dendritic cells- MHC class II antigen
• Extracellular matrix, fibrils and interstitial fluid

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GLOMERULONEPHRIGLOMERULONEPHRI
TISTIS

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 Glomerulonephritis is a non-specific disorder in which
the kidneys are damaged, causing them to leak large
amounts of protein from the blood into the urine.
 Glomerulonephritis is a group of diseases of
inflammatory or non-inflammatory nature involving
primarily the renal glomeruli.

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ETIOLOGY OF GLOMERULONEPHRITISETIOLOGY OF GLOMERULONEPHRITIS
a. Primary or idiopathic
b. Secondary:
1. Infection (bacteria, parasite, virus).
2. Colagen disease (SLE, PAN, Rhoid).
3. Drug (Penicillamin, gold, Asprin, Paradion, heroin).
4. Metabolic diseases (DM, Amyloidosis).
5. Malignancy (Hodgkins lymphoma).
6. Heredofamilial (Alports Syndrome).

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HISTOPATHOLOGY OF GLOMERULONEPHRITISHISTOPATHOLOGY OF GLOMERULONEPHRITIS
1. Minimal change (nil-change) disease.
2. Focal and segmental glomerulosclerosis
3. Membranous glomerulonephritis
4. Proliferative glomerulonephritis.
 Mesangial proliferative GN.
 Mesangiocapillary (membranoproliferative)
GN.
 Crescentic GN.
 IgA nephropathy.

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CLINICAL MANIFESTATIONS OFCLINICAL MANIFESTATIONS OF
1. Nephrotic Syndrome.
2. Acute Nephritic Syndrome.
3. Rapidly Progressive GN.
4. Chronic Nephritic Syndrome.
5. Asymptomatic Urinary Abnormalities.

NEPHROTIC SYNDROMENEPHROTIC SYNDROME
1.1. Insidious onset of massive oedema.Insidious onset of massive oedema.
2.2. Heavy proteinuria.Heavy proteinuria.
3.3. Hypoalbuminaemia.Hypoalbuminaemia.
4.4. Hyperlipidemia.Hyperlipidemia.

ACUTE NEPHRITICACUTE NEPHRITIC
(ACUTE NEPHRITIS)(ACUTE NEPHRITIS)
1.1. Rapid onset of oedema, smooky urine,Rapid onset of oedema, smooky urine,
oliguria and hypertension.oliguria and hypertension.
2.2. Urine shows red cell casts, proteinuria.Urine shows red cell casts, proteinuria.
3.3. Serum creatinine may be high, but albuminSerum creatinine may be high, but albumin
and lipids usually normal.and lipids usually normal.
4.4. Prognosis is usually good and recoveryPrognosis is usually good and recovery
occurs.occurs.

Rapidly progressive GlomerulonephritisRapidly progressive Glomerulonephritis
(RPGN)(RPGN)
1.1. Rapid onset of nephritis with development ofRapid onset of nephritis with development of
uraemia.uraemia.
2.2. Urine shows nephritic sediment.Urine shows nephritic sediment.
3.3. Serum creatinine is high.Serum creatinine is high.
4.4. If untreated aggressively, the prognosis isIf untreated aggressively, the prognosis is
poor.poor.

CHRONIC NEPHRITIC SYNDROMECHRONIC NEPHRITIC SYNDROME
1.1. Slowly progressive (mon., years) uraemia.Slowly progressive (mon., years) uraemia.
2.2. Urine shows proteinuria, hematuria, broadUrine shows proteinuria, hematuria, broad
casts, no urine concentration.casts, no urine concentration.
3.3. Serum creatinine is high as well as otherSerum creatinine is high as well as other
stegmata of uraemia.stegmata of uraemia.

ASYMPTOMATIC URINEASYMPTOMATIC URINE
ABNORMALITIESABNORMALITIES
1.1. Microscopic hematuria or proteinuria or both.Microscopic hematuria or proteinuria or both.
2.2. Serum creatinine is normal.Serum creatinine is normal.
3.3. Prognosis is usually excellent.Prognosis is usually excellent.

A syndrome characterized by:A syndrome characterized by:
1.1. Heavy proteinuria (> 3.5 gm/1.73 mHeavy proteinuria (> 3.5 gm/1.73 m22
/d.)/d.)
2.2. Massive oedema.Massive oedema.
3.3. Hypoalbminaemia.Hypoalbminaemia.
4.4. Hyperlipidaemia.Hyperlipidaemia.

ETIOLOGY OF NEPHROTIC SYNDROMEETIOLOGY OF NEPHROTIC SYNDROME
1.1. Primary (idiopathic) N. S.Primary (idiopathic) N. S.
2.2. Secondary N. S.Secondary N. S.
 Post infection.Post infection.
 Drug inducedDrug induced
 MetabolicMetabolic
 Collagen and autoimmune.Collagen and autoimmune.
 Malignancy.Malignancy.
 Renal vein thrombosis.Renal vein thrombosis.
 Congenital.Congenital.

PATHOLOGY OF NEPHROTICPATHOLOGY OF NEPHROTIC
SYNDROMESYNDROME
 Minimal change nephritis.Minimal change nephritis.
 Focal and segmental glomerulosclerosis.Focal and segmental glomerulosclerosis.
 Membranous glomerulonephritis.Membranous glomerulonephritis.
 Proliferative glomerulonephritis.Proliferative glomerulonephritis.
 Mesangial proliferative.Mesangial proliferative.
 Mesngiocapillary.Mesngiocapillary.
 Crescentic GN.Crescentic GN.
 IgA nephropathy.IgA nephropathy.

Pathogenesis of Hypoalbuminaemia in N. S.Pathogenesis of Hypoalbuminaemia in N. S.
1.1. ProtenuriaProtenuria
2.2. Decrease influx from GITDecrease influx from GIT (poor intake and(poor intake and
poor absorption)poor absorption)
3.3. Increased tubular catabolism of filteredIncreased tubular catabolism of filtered
albumin.albumin.
4.4. Sometimes decreased rate of hepaticSometimes decreased rate of hepatic
biosynthesis.biosynthesis.

GLOMERULAR DAMAGEGLOMERULAR DAMAGE
ProteinuriaProteinuria
HypoalbuminaemiaHypoalbuminaemia
Decreased plasma oncotic pressureDecreased plasma oncotic pressure
WaterWater
retentionretention Oedema
WaterWater
retentionretention
• increased
angiotensin,
aldosteron
• Decreased ANP
Decreased effective
circulating blood volume
Pathogenesis of Oedema
in N. S.
• increased
ADH

HYPERLIPIDEMIA IN N. S.HYPERLIPIDEMIA IN N. S.
 ↑ Cholesterol, VLDL, LDL
 Triglycerids, ↓ HDL.
 ↑ Hepatic synthesis
 ↓ Peripheral utilization.
 Urinary loss of HDL.

HYPERCOAGULABILITY IN N. S.HYPERCOAGULABILITY IN N. S.
 Venous stasis.Venous stasis.
 Abnormal platelets and vascular endothelium.Abnormal platelets and vascular endothelium.
 Urinary loss of anti-thrombin III, protein C,Urinary loss of anti-thrombin III, protein C,
and protein S.and protein S.
 More in membranous G. N. & MPGN.More in membranous G. N. & MPGN.

OTHER URINARY LOSSES IN N. S.OTHER URINARY LOSSES IN N. S.
 TransferrinTransferrin
 TBGTBG
 25-OHD325-OHD3
 IgG, C1qIgG, C1q

CLINICAL FEATURES OF N. S.CLINICAL FEATURES OF N. S.
1.1. OedemaOedema
2.2. HypertensionHypertension
3.3. Lassitude, anorexia, loss of appitite, pallor.Lassitude, anorexia, loss of appitite, pallor.
4.4. Manifestations of the etiologic cause.Manifestations of the etiologic cause.
5.5. Manifestations of complications.Manifestations of complications.

COMPLICATIONS OF N. S.COMPLICATIONS OF N. S.
1.1. Subnutritional state.Subnutritional state.
2.2. Infection.Infection.
3.3. Clotting episodes (DVT) and pulmonary embolism.Clotting episodes (DVT) and pulmonary embolism.
4.4. Premature atherosclerosis.Premature atherosclerosis.
5.5. Hypovolaemia.Hypovolaemia.
6.6. Drug related complications.Drug related complications.
7.7. Acute renal failure.Acute renal failure.
8.8. Bone disease.Bone disease.
9.9. Anaemia.Anaemia.

INVESTIGATIONS OF NEPHROTICINVESTIGATIONS OF NEPHROTIC
SYNDROMESYNDROME
1.1. Urine analysis for proteinuria, microscopicUrine analysis for proteinuria, microscopic
hematuria, pyuria, and casts.hematuria, pyuria, and casts.
2.2. Blood analysis for creatinine, albumine and lipidBlood analysis for creatinine, albumine and lipid
profile.profile.
3.3. Investigations for diagnosis of the etiology inInvestigations for diagnosis of the etiology in
secondary N.S. such as DM, SLE, malignancy.secondary N.S. such as DM, SLE, malignancy.
4.4. Kidney biopsy.Kidney biopsy.

TREATMENT OF N. S.TREATMENT OF N. S.
1.1. Treatment of the cause in 2ry cases.Treatment of the cause in 2ry cases.
2.2. Treatment of complications.Treatment of complications.
3.3. Rest in bed during exacerbations and early ambulationRest in bed during exacerbations and early ambulation
with remissions.with remissions.
4.4. Diet:Diet:
 Salt restrictedSalt restricted
 Protein content equal 1 g/kg/d plus urinary lossesProtein content equal 1 g/kg/d plus urinary losses
5.5. Diuretics, mainly loop diuretics.Diuretics, mainly loop diuretics.
6.6. Human salt free albumin in certain situations.Human salt free albumin in certain situations.
7.7. Steroid, CsA, and other immunosuppressive drugs.Steroid, CsA, and other immunosuppressive drugs.

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TYPES OF GLOMERULONEPHRITISTYPES OF GLOMERULONEPHRITIS
There are some common types of glomerulonephritis:
• Acute glomerulonephritis
• Chronic glomerulonephritis
• Primary Glomerulonephritis - an autoimmune disease
• Post streptococcal glomerulonephritis,
• Focal and segmental glomerulosclerosis (FSGS)
• IgA glomerulonephritis
• IgM glomerulonephritis
• Membranoproliferative glomerulonephritis (also called mesangiocapillary)
• Membranous glomerulonephritis
• Minimal change nephropathy
• Vasculitis (including Wegener’s granulomatosis)

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DRUG-INDUCED TOXIC RENAL SYNDROMESDRUG-INDUCED TOXIC RENAL SYNDROMES
S. N. Syndrome Medication Examples
1. Acute Renal Failure:
• Prerenal (decreased perfusion)
• Intrinsic Renal (direct tubule cell
toxicity)
Diuretics, NSAIDs, ACE Inhibitor
Aminoglycosides, Radiocontrast media,
cisplatin
2. Acute tubular necrosis:
• Hemolysise
• Rhabdomyolysis
Quinine, sulfonamides, hydralazine
Lovastatin, ethanol, barbiturate
3. Acute Interstitial Nephritis
(immune-mediated) Penicillin, rifampicin, sulfonamides
4. Vascular endothelial injury:
Obstructive
Intratubular
Ureteral
Acyclovir, methotrexate, sulfonamides,
methysergide, methyldopa, gold, pencillamine,
captopril, NSAIDs, mercury
5. Chronic Renal Failure (interstitial
fibrosis)
NSAIDs, acetaminophen, cyclosporine

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RISK FACTORS FOR NEPHROTOXICITYRISK FACTORS FOR NEPHROTOXICITY
Patient-related factors:
• Age, sex, race
• Pre-existent renal disease
• Specific disease (diabetes mellitus, multiple myelome, proteinuric
patients, lupus)
• Sodium-retaining states (cirrhosis, heart failure, nephrosis)
• Dehydration and volume depletion
• Acidosis, potassium and magnesium depletion
• Hyperuricemia, hyperuricosuria
• Sepsis, shock
• Renal transplantation

70
Drug-related factors:
• Inherent nephrotoxic potential
• Dose
• Duration, frequency and form of administration
• Repeated exposure
Drug interactions:
• Combined or closely associated use of diagnostic or therapeutic with
added or synergistic nephrotoxic potential (eg. Radiocontrast agents,
aminoglycosides, NSAIDs, cisplatin, ACE-I)

71
Concurrent medications that interfere with GFR autoregulation or
renal blood supply
1.Angiotensin-converting enzyme inhibitors (ACE Inhibitors)
2.Angiotensin Receptor Blockers (ARBs)
3.Cycosporine
4.Non-Steroidal Antiinflammatory drugs (NSAIDs)
5.Tacrolimus

72
EVALUATION CRITERIA FOREVALUATION CRITERIA FOR
NEPHROTOXICITYNEPHROTOXICITY
Evaluation: Criteria to consider stopping agent due to
nephrotoxicity
A.Relative Serum Creatinine increase 50% over baseline
B.Absolute Serum Creatinine increase
1.Serum Creatinine baseline <2 mg/dl: Creatinine increase 0.5 mg/dl
over baseline
2.Serum Creatinine baseline >2 mg/dl: Creatinine increase 1.0 mg/dl
over baseline

73
CAUSES FOR NEPHROTOXICITYCAUSES FOR NEPHROTOXICITY
A. Antibiotics:
1. Aminoglycosides (10-15% Incidence of Acute Tubular Necrosis)
a) Occurs in 10-20% patients on 7 day course
b) Results in non-oliguric increased Creatinine
c) A single dose early in septic course is usually safe
2. Sulfonamides
3. Amphotericin B
4. Foscarnet
5. Quinolones (e.g. Ciprofloxacin, Levofloxacin)
6. Rifampin
7. Tetracycline
8. Acyclovir (only nephrotoxic in intravenous form)
9. Pentamidine
10. Vancomycin

74
B. Chemotherapy and Immunosuppressants: Cisplatin,
Methotrexate, Mitomycin, Cyclosporine, Ifosphamide (Causes
Fanconi's Syndrome)
C. Heavy Metals: Mercury Poisoning , Lead Poisoning , Arsenic
Poisoning , Bismuth
Lithium related kidney disorders:
1. Polydipsia and Nephrogenic Diabetes Insipidus
2. Acute Renal Failure - Dialysis indications: Creatinine >2.5 or
Seizures, ALOC, Rhabdomyolysis
3. Chronic Kidney Disease with fibrosis
D. AntiHyperlipidemics: Statin Drugs (Rhabdomyolysis),
Gemfibrozil-Associated with Acute Renal Failure due to
Rhabdomyolysis

75
E. Miscellaneous Drugs: Chronic Stimulant Laxative use (Resulting
chronic volume depletion and Hypokalemia causes nephropathy),
Radiographic contrast, ACE Inhibitors (Expect an increase of
Serum Creatinine in Chronic Kidney Disease), NSAIDs, Aspirin
(Low dose Aspirin reduces Renal Function in elderly, Decreased
Creatinine Clearance after 2 weeks of use & Changes persisted for
at least 3 weeks off Aspirin), Mesalamine (Mesalamine is an NSAID
analog and has systemic absorption from the bowel), Chinese
herbals containing aristocholic acid.
F. Drugs of abuse: Cocaine, Heroin, Methamphetamine, Methadone.
G. Reversible Serum Creatinine increase without significant effect
on GFR: Cimetidine, Fenofibrate, Trimethoprim.

76
The syndrome is characterized by:
 Heavy proteinuria
 Hypoalbuminemia
 Edema
 Hypercholesterolemia
Age:
In Children- 15 times more common in children than in adults. Most
common form is minimal-change disease.
In adults- The most common form is membranous glomerulonephritis,
followed by FSGS.

77
COMMON FEATURES OF NEPHROTICCOMMON FEATURES OF NEPHROTIC
SYNDROMESYNDROME
 Increasing edema more on face and lower extremities over
a few days or weeks.
 An increase in weight, the development of an ascetic or
pleural effusion, and a decline in urine output.
 Hematuria and hypertension are unusual but manifest in a
minority of patients.

78
DIAGNOSIS OF NEPHROTIC SYNDROMEDIAGNOSIS OF NEPHROTIC SYNDROME
 Nephrotic range proteinuria > 1 gm/24 hrs. in urine
 Urine Albumin/Creatinine ration = > 3.5
 Serum Albumin < 2.5 gm/dl
 Serum Cholesterol > 200 mg/ dl
 Serum C3 and C4 levels
 Serum IgM, IgG and IgA levels
 Kidney biopsy-Indicated in case of non-responders

79
COURSE OF DISEASECOURSE OF DISEASE
1. Urinary remission: Urine is free from albumin for consecutive 3 days
2. Complete remission: Serum albumin increases equal or > 2.5 gm/dl
3. Relapse: Albumin +++ in urine for consecutive 3 days, with or without
oedema
4. Frequent Relapse: 2 or more relapses with in 6 months of initial response
5. Steroid dependant: 2 consecutive relapses whilst tapering Prednisolone or
with in 14 days of stopping Prednisolone
6. Resistant or non responder: No remission during 8 weeks of Prednisolone
treatment initially or subsequently during the course of nephritic
syndrome

80
TREATMENT OF NEPHROTIC SYNDROMETREATMENT OF NEPHROTIC SYNDROME
 Steroids- Key drug for treatment
 Levamisole
 Cyclophosphamide
 Cyclosporine A
 Emalapril

81
 Usually good in children but 20-30% cases do not respond
to treatment.
 Patients with membranes glomerulonephritis, focal
segmental glomerulosclerosis frequently lead to end stage
renal disease.
 Factors associated with poorer prognosis are uncontrolled -
Proteinuria, blood pressure control and kidney function
(GFR).
PROGNOSIS OF NEPHROTIC SYNDROMEPROGNOSIS OF NEPHROTIC SYNDROME

82
TREATMENTS FOR NEPHROTICTREATMENTS FOR NEPHROTIC
SYNDROMESYNDROME
GOOD SUCCESS RATE OF
TREATMENT IN ADULTS WITH
 GLOMERULONEPHRITIS
 NEPHROTIC SYNDROME

83
AYURVEDA THERAPYAYURVEDA THERAPY
FOR NEPHROTIC SYNDROMEFOR NEPHROTIC SYNDROME
This is a useful therapy in cases of nephrotic syndrome and also in
cases where other treatment fails in kidney disease. This therapy is a
combination of allopathic drugs and herbal drugs/nutritional
supplement. The recommendation of the treatment combination
depends on the condition of patient. With this therapy usually the
albumin in urine stops coming with in 30-45 days and other symptoms
e.g. edema disappears gradually. The serum cholesterol comes to
normal in 120-180 days. This therapy is free from any side effects.

84
AYURVEDIC MEDICATIONAYURVEDIC MEDICATION
Plant Name
Biological Source
and Family
Parts Used Dose Uses
Punarnava
Mandoor
Boerrhavia diffusa
(Nyctaginaceae)
Roots
125 mg to 250 mg
twice daily
Diuretic, Micturition
Sarvato bhadra
Vati
Azidiracta indica
(Meliaceae)
leaves
62.5 mg to 125 mg
twice daily
Treating Nephritis
Varunadi Vati
Crataeva nurvala
(Saxifragaceae)
Bark & root 2 tablets twice daily
Very effective for
obstruction in urinary tract
and helps in removing the
renal stones
Gokhru
Tribulus terrestris
(Zygophyllaceae)
Fruits 10 – 20 grains daily
Diuretic and herbal tonic
for genitor-urinary system
Rakt Chandan
P. santalinus- Red
Sandalwood
(Santalaceae)
Heart-wood
1 teaspoon dose
mixed into a cup of
cold milk
Urinary alkalizer and acts
as a natural diuretic
Palaash
Butea monosperma
(Fabaceae)
Seeds & Fruits
Powder filled
capsules form in a
dose of 2.5 gm per
day
Urinary alkaliser and also
relieves painful micturition
Kaasni
Cichorium intybus
(Asteraceae)
Seeds
1-2 gm leaf powder
with honey or cow's
milk
In acute and chronic kidney
failure

85
Ayurvedic Formulation for Nephritis
Suvarna
vasanta
Malati Rasa
Michelia
Murantiacae
(Magnoliaceae)
Suvarna bhasma,
mouktika bhasma,
purified hingul
(cinnabar), piper nigrum,
shuddha kharpar, butter
and citrus limon.
250 mg and 500
mg (Two spoonfuls
with milk on an
empty stomach)
Treating Nephritis
Mutra-Krich-
Antak Churna
Drug
preparation
Salacia oblonga, crataeva
nurvala, butea
monosperma, boerrhavia
diffusa, tribulus
terrestris, P. Santalinus,
moringa oleifera,
achyranthes aspera,
albezzia lebbock
3 to 6 gm herbs
powder (1 tea-
spoonful twice
daily)
Kidney Failure,
Painful Urination,
Urethral Strictures,
Kidney Stones
Cystone - 120
Tabs
Drug
preparation
Ginger, Shilapuspha,
Pasanabheda, Indian
madder, Umbrella's edge,
Prickly chaff flower
1 Tablet (120 mg)
Twice Daily don’t
give to children
under 14 year old
Treats stones in the
urinary tract, and
recurrent urinary
tract infections.

86
Home Remedies for Nephritis
• 8 - 9 bananas in daily diet for 3 - 4 days can serve as remedies for
nephritis.
• Carrot juice acts effective in nephritis when it is taken with honey and
fresh lime juice early in the morning.
• Triphala powder or aqueous extract can be used in nephritic conditions.
• Avocados are effective remedies as they contain minerals and protein
for nephritis.
• Tender coconut is very effective in the treatment of nephritis as it acts
as a safe diuretic.
• 1 tumbler of radish juice for 2 - 3 times a day can serve as promising
diuretic in nephritic conditions.
• Grapes are useful for treating nephritis as it acts as a good diuretic.
• Consuming vegetable juices for 7 - 10 days in nephritic condition
causes removal of toxic substance from body.

87
REFERENCESREFERENCES
•Timoshanko JR, Tipping PG. Resident kidney cells and their involvement in glomerulonephritis. Curr Drug Targets
Inflamm Allergy, 2005. 4:353–62.
•Hayakawa K, Ohashi H, Yokoyama H, et al. Adiponectin is increased and correlated with the degree of proteinuria, but
plasma leptin is not changed in patients with chronic glomerulonephritis. Nephrology (Carlton). Apr 2009; 14(3):327-31.
•Wolf G. Antiproteinuric response to dual blockade of the renin-angiotensin system in primary glomerulonephritis. Nat Clin
Pract Nephrol. Sep 2008;4(9):474-5.
•Boulware LE, Troll MU, Jaar BG, Myers DI, Powe NR. Identification and referral of patients with progressive CKD: a
national study. Am J Kidney Dis. 2006; 48: 192.
•Coresh J, Walser M, Hill S. Survival on dialysis among chronic renal failure patients treated with a supplemented low-
protein diet before dialysis. J Am Soc Nephrol. Nov 1995;6(5):1379-85.
•Peterson JC, Adler S, Burkart JM, Greene T, Hebert LA, Hunsicker LG, et al. Blood pressure control, proteinuria, and the
progression of renal disease. The Modification of Diet in Renal Disease Study. Ann Intern Med. Nov 15 1995;123(10):754-
62.
•Wolf G, Ritz E. Combination therapy with ACE inhibitors and angiotensin II receptor blockers to halt progression of
chronic renal disease: pathophysiology and indications. Kidney Int. 2005;67:799-812.
•NKF Controlled Document No. 283, Glomerulonephritis, written 16 August 2000. Last reviewed 28 May 2009.
•Nachman PH, Jennette JC, Falk RJ. Primary glomerular disease. In: Brenner BM, ed. Brenner and Rector's The Kidney. 8th
ed. Philadelphia, Pa:Saunders Elsevier;2007:chap 30.
•Ferri FF. Glomerulonephritis, acute. In: Ferri's Clinical Advisor 2007: Instant Diagnosis and Treatment. 9th
ed. Philadelphia, PA: Mosby, An Imprint of Elsevier; 2007.
•Madaio MP, Harrington JT. The diagnosis of glomerular diseases: acute glomerulonephritis and the nephrotic
syndrome. Arch Intern Med. Jan 8 2001;161(1):25-34.
•Rovang RD, Zawada ET Jr, Santella RN, Jaqua RA, Boice JL, Welter RL. Cerebral vasculitis associated with acute post-
streptococcal glomerulonephritis. Am J Nephrol. 1997;17(1):89-92.
USP DI. Drugs (Corticosteroids, Diuretics, Penicillin). In: Drug Information for the Health Care Professional. Vol
1. Micromedex; 1997:958, 1243, 2263.

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