GLOMERULAR
Nephritic Syndrome
Acute Proliferative
(Postinfectious and Infection-
Associated)
Glomerulonephritis
Crescentic (Rapidly Progressive)
Glomerulonephritis
Nephrotic Syndrome - Caused by a derangement in glomerular capillary walls resulting in increased permeability to plasma proteins
Membranous Nephropathy
(Membranous
Glomerulonephritis)
Minimal Change Disease (Lipoid
Nephrosis)
Focal Segmental
Glomerulosclerosis (FSGS)
Membranoproliferative
Glomerulonephritis (MPGN)
● Often characterized by inflammation of the glomeruli
● The most common causes are immunologically mediated glomerular injury
● Lesions are characterized by proliferative changes and leukocyte infiltration
Post-streptococcal GN- usually appears 1 to 4 weeks after a • Hallmark: enlarged, hypercellular glomeruli. The hypercellularity is caused by: Important laboratory
streptococcal infection of the pharynx or skin (impetigo); Most Infiltration by leukocytes, f endothelial and mesangial cells, In severe cases by findings:
frequently in children 6 to 10 years of age crescent formation, Interstitial edema and inflammation, and tubular red cell - Elevations of
casts antistreptococcal
Only certain strains of group A β-hemolytic streptococci • Immunofluorescence microscopy: granular deposits of IgG and C3, and IgM antibody titers
are nephritogenic >90% of cases being traced to types 12, 4, and • Electron microscopy: “humps”, presumably representing the - Decline in the serum
1 antigen-antibody complexes at the subepithelial cell surface concentration of C3
• Subendothelial deposits and other
components of the
complement cascade
severe glomerular injury Most common histologic picture: presence of crescents
Relatively rapid and progressive loss of renal function • Anti-GBM antibody–: mediated disease: Goodpasture syndrome- anti-GBM
associated with severe oliguria and signs of nephritic syndrome antibodies cross-react with pulmonary alveolar BM to produce pulmonary
o If untreated, death from renal failure may occur within weeks- hemorrhage associated with renal failure
months • Immune complex deposition: a complication of any of the immune complex
nephritides
• Pauci-immune crescentic GN: cytoplasmic (c-ANCA) or perinuclear (pANCA)
staining pattern, systemic vasculitis, limited to the kidneys and hence
idiopathic
- Goodpasture syndrome cases show linear GBM fluorescence for Ig and complement
Type II cases show granular immune deposits
- Pauci-immune cases have little or no deposition of immune reactants
75% are primary, the rest are secondary related to: Drugs, Light microscopy: diffuse thickening of o Insidious onset or
tumors, SLE, Infections the glomerular capillary wall; visualized using silver stain “SPIKE” with non-nephrotic
o Form of chronic immune complex–mediated disease Immunofluorescence microscopy: granular deposits proteinuria
o Hematuria and mild
hypertension
Most frequent cause of nephrotic syndrome in children; peak • Light microscopy: glomeruli appear normal (PAS-positive), normal basement massive proteinuria,
incidence is between 2 and 6 years of age; follows a respiratory membrane renal function remains
infection or routine prophylactic immunization • Electron microscopy: uniform and diffuse effacement of foot processes good, and
Association with other atopic disorders (eczema, rhinitis) • Other: laden with lipid and protein there is commonly no
Increased incidence of minimal change disease in patients hypertension or
with Hodgkin lymphoma hematuria; dramatic
response to
corticosteroid therapy;
Associated with
Hodgkin lymphoma
most common cause of nephrotic syndrome in Light microscopy: focal and segmental lesions may involve only a minority of the
adults in the United States; primary disorder of podocytes glomeruli
Primary disease – idiopathic FSGS
Secondary: Associated with HIV, heroin addiction, sickle cell
disease and morbid obesity
TYPE 1- Discrete subendothelial electron-dense deposits; GBM is thickened: double-contour” or “tramtrack” appearance,
Mesangial and occasional subepithelial deposits may also be evident in silver or PAS stains due to duplication of BM (splitting)

Secondary
Membranoproliferative
Glomerulonephritis
Dense Deposit Disease
Fibrillary Glomerulonephritis
IgA Nephropathy (Berger
Disease)
Hereditary Nephritis
Alport Syndrome
Thin Basement Membrane
Lesion (Benign Familial
Hematuria)
Chronic Glomerulonephritis
Lupus Nephritis
Henoch-Schonlein Purpura
GN associated with Bacterial
Endocarditis
Diabetic Nephropathy
Other Systemic Disorders
present; C3 deposited in granular pattern; IgG and early
complement (C1q & C4) are present
TYPE 2 - “dense deposit disease”; Deposits along basement
membrane; Irregular granular or linear foci of C3 on the BM;
Mesangial deposits of C3; C1q and C4 are absent
Congo-red negative fibrillary glomerular deposits of unknown
etiology
Isolated Glomerular Abnormalities / Other Glomerular Diseases
recurrent hematuria; presence of C3 and absence of C1q and C4 • Immunofluorescence microscopy: mesangial deposition of IgA o Hematuria after an
• Electron microscopy: confirms the presence of electron-dense deposits infection of respiratory,
predominantly in the mesangium GIT or urinary
o 30-40% only in
microscopy hematuria
o 5-10% nephritic
syndrome
o Hematuria typically
lasts for
Type 4 Collagen; Thin basement membrane nephropathy- most
common cause of benign familial hematuria
X-linked trait in approximately 85% of cases Defective assembly of Collagen IV, crucial for GBM function Nerve deafness
o Eye disorders: lens
dislocation, posterior
cataracts, and corneal
dystrophy
Develops insidiously & progresses to renal insufficiency or Kidneys are symmetrically contracted and have granular
death from uremia; hypertensive; cerebral or cardiovascular; cortical surface, cortex is thinned, Arterial and arteriolar sclerosis
End-stage glomerular disease
Glomerular Lesions Associated With Systemic Disease
purpuric skin lesion; Most common in children 3 to 8 years of Renal manifestations
age; follows an upper respiratory infection; IgA is deposited in include gross or
the glomerular mesangium; finding of Ig and C3 deposits in microscopic hematuria,
glomeruli nephritic syndrome,
nephrotic syndrome
immune complex nephritis • Capillary basement membrane thickening
• Diffuse mesangial sclerosis and nodular glomerulosclerosis
• Kimmelsteil-Wilson (KW) lesions

Acute Tubular Injury/Necrosis
Tubulointerstitial Nephritis
Pyelonephritis and UTI
Acute Pyelonephritis
Chronic Pyelonephritis and
Reflux Nephropathy
Acute Drug-induced Interstitial
Nephritis
Analgesic Nephropathy
Nephropathy associated with
NSAIDs
Aristocholic nephropathy
Urate Nephropathy
Hypercalcemia and
Nephrocalcinosis
Acute Phosphate Nephropathy
Light-Chain Cast Nephropathy
(Myeloma Kidney)
Bile Cast Nephropathy
TUBULAR AND INTERSTITIAL
• most common cause of acute kidney injury
• Ischemic ATI- Focal tubular epithelial necrosis at multiple
points with “skip areas”
• Nephrotoxic ATI - proximal convoluted tubules
• Initiation: 36 hours; slight decline in urine output
with a rise in BUN
• Maintenance: n urine output to between 40- 400
mL/day (oliguria), hyperkalemia, uremia
• Recovery: increase in urine volume (3 L/day),
Hypokalemia, vulnerability to infection
Inflammatory injuries of the tubules and interstitium
Pyelonephritis- defined as inflammation affecting the tubules,
interstitium, and renal pelvis
• Acute pyelonephritis- generally caused by bacterial infection and
is associated with urinary tract infection
• Chronic pyelonephritis- more complex disorder; bacterial
infection plays a dominant role, but other factors (vesicoureteral
reflux, obstruction) predispose to repeat episodes of acute
pyelonephritis
Disorder in which chronic tubulointerstitial inflammation and
scarring involves the calyces and pelvis
Reflux nephropathy- more common form, occurs early in
childhood due to superimposition of infection on
congenital vesicoureteral and intrarenal reflux
o Chronic Obstructive Pyelonephritis- obstruction
contribute to parenchymal atrophy
Tubulointerstitial Nephritis Induced by Drugs and Toxins
use of sulfonamides;
Non-selective cyclooxygenase inhibitors- adverse renal
effects are related to their ability to inhibit
cyclooxygenase–dependent prostaglandin synthesis
Other Tubulointerstitial Diseases
Several factors contribute to renal damage: Bence-Jones
Proteinuria and Cast Nephropathy, o Amyloidosis (AL type), Light-
chain deposition disease and Hypercalcemia & Hyperuricemia
Ischemic type: tubular necrosis is patchy, relatively short lengths of tubules are
affected, and PST segments and ascending LoH are most vulnerable
Toxic type: extensive necrosis is present along the PCT segments
Both types, lumens of the DCT and collecting ducts (CD) contain proteinaceous casts (Tamm-
Horsfall proteins); Rupture of BM
Urinary tract obstruction and stasis of urine: Benign prostatic hypertrophy - Tumors, calculi, or
neurogenic bladder dysfunction caused by diabetes or spinal cord injury
• Vesicoureteral reflux- ascend the ureter into the renal pelvis
• Intrarenal reflux- most common in the upper and lower poles
focal abscesses; Urinalysis findings: pyuria and pus casts
• Gross: kidneys usually are irregularly scarred; if bilateral, the involvement is asymmetric
(most scars are located in the upper lobe)
• Hallmarks: coarse, discrete, corticomedullary scars overlying dilated, blunted, or
deformed calyces, and flattening of the papillae
• Microscopic: (Thyroidization) - Leucocytes (more of lymphocytes and macrophages)
Xanthogranulomatous pyelonephritis- characterized by accumulation of foamy macrophages
intermingled with plasma cells, lymphocytes, polymorphonuclear leukocytes, and giant cells
o Proteus , yellowish orange nodules. mass in sonogram
fever, eosinophilia (transient), rash and renal abnormalities • Hematuria, mild proteinuria, and
leukocyturia (eosinophils)
• Acute kidney injury- due to the decreased synthesis of vasodilatory prostaglandins and
resultant ischemia
• Acute hypersensitivity interstitial nephritis
• Acute interstitial nephritis and minimal change disease
• Membranous nephropathy with nephrotic syndrome
lytic lesions of the bone

Nephrosclerosis
Benign Nephrosclerosis
Malignant Nephrosclerosis
Renal Artery Stenosis
Hemolytic Uremic Syndrome
Thrombotic
Thrombocytopenic Purpura
Renal vein thrombosis
Atherosclerotic Ischemic
Renal Disease
Atheroembolic Renal Disease
Sickle-Cell Nephropathy
Diffuse Cortical Necrosis
Renal Infarcts
CONGENITAL- 10% of people are born with malformations of the urinary system; Renal dysplasias and hypoplasias account for 20% of chronic kidney disease in children
Renal Agenesis
Renal Hypoplasia
Ectopic Kidneys
Horseshoe Kidneys
VASCULAR
Sclerosis of renal arterioles and small fine, even granularity that resembles grain leather
arteries
Strongly associated with hypertension
Hyalinization of arteriolar walls, focal
parenchymal ischemia, reduction in
functional renal mass
Disorder associated with malignant or pinpoint petechial hemorrhages may appear on the Malignant or accelerated phase of hypertension:
accelerated HTN cortical • Diastolic pressure of >130 mmHg
surface due to rupture of capillaries giving it a flea- • Papilledema retinopathy
bitten appearance • Encephalopathy
• Cardiovascular abnormalities
• Renal failure
• Atheromatous plaque- most Gross: ischemic kidney is reduced in size and shows Patients resemble those with essential hypertension
common cause of renal artery signs of diffuse ischemic atrophy, with crowded
stenosis glomeruli
• (70%) by narrowing the origin of
the renal artery
• Fibromuscular dysplasia of renal
artery- second most frequent
cause of stenosis
Thrombotic Microangiopathies
Typical HUS- diarrhea-positive &Atypical HUS- diarrhea-negative
Most common cause of deficient ADAMTS13 activity
Other Vascular Disorders
• Obstetric emergency, such as abruptio placenta
• Cortical destruction with ischemic necrosis
• Ischemic necrosis; focal intravascular & intraglomerular thromboses
• Most are due to embolism; white anemic variety
• Infarcts are wedge-shaped o Coagulation necrosis
incompatible with life
Failure of the kidneys to develop to a normal size; True renal hypoplasia is observed in low-birthweight infants and may contribute to their increased lifetime risk for
chronic kidney disease
• These kidneys lie either just above the pelvic brim or sometimes within the pelvis.
• Usually kidneys are normal or slightly small in size
• It can cause kinking or tortuosity of the ureters leading to obstruction to urinary flow
Fusion of theupper (10%) or lower poles (90%) of the kidneys produces a horseshoe-shaped structure

Autosomal Dominant (Adult)
Polycystic Kidney Disease
Autosomal Recessive
(Childhood) Polycystic
Kidney Disease
Medullary Sponge Kidney
Nephronophthisis & Adult-
Onset Medullary cystic
disease
Multicycstic Renal Dysplasia
Acquired Cystic diseases
Simple Renal Cyst
CYSTIC DISEASES OF THE KIDNEY
Many patients remain asymptomatic until renal insufficiency
announces the presence of disease
Extrarenal Congenital Anomalies - Polycystic liver disease (40%) -
Intracranial berry aneurysm - MV prolapse & other vascular
abnormality (20-25%)
Genetically distinct from adult polycystic kidney disease • Gross: kidneys are enlarged and have
Subcategories: depending on the time of presentation and a smooth external appearance
presence of associated hepatic lesions • Cut section: numerous small cysts in
o Perinatal (most common) the cortex and medulla give the
o Neonatal (most common) kidney a spongelike appearance
o Infantile • Dilated elongated channels are
o Juvenile present at right angles to the cortical
surface, completely replacing the
Caused by mutations of the PKHD1 gene maps to chromosome 6p21-23 medulla and cortex
encoding for fibrocystin • Microscopic: portal fibrosis and
proliferation of portal bile ducts
(infantile and juvenile forms)
Cystic Diseases of the Renal Medulla
Cortical tubulointerstitial damage is the cause of the eventual Clinical Manifestations: polyuria,
renal insufficiency polydipsia, sodium wasting,
Variants: tubular acidosis
o Sporadic, nonfamilial (20%)
o Familial juvenile nephronophthisis (40-50% most common)
o Renal-retinal dysplasia (15%) § Kidney disease is
accompanied by ocular lesions
o Adult-onset medullary cystic disease (15%)
Abnormal metanephric differentiation • Gross: kidneys are enlarged,
extremely irregular and multicystic
• Microscopic: lined by flattened
epithelium; normal nephrons
present, many have immature
collecting ducts
• Characteristic feature: presence of
islands of undifferentiated
mesenchyme, often with cartilage, &
immature collecting ducts
Patients with ESRD who have undergone prolonged dialysis; increased Cysts measure 0.1 to 4 cm in diameter, contain
risk of renal cell carcinoma clear fluid, are
lined by either hyperplastic or flattened
tubular epithelium,
and often contain calcium oxalate crystals
URINARY TRACT OBSTRUCTION (OBSTRUCTIVE UROPATHY)
Obstructive lesions of the urinary tract increase susceptibility to infection and to stone formation, and unrelieved obstruction lead to permanent renal atrophy termed as hydronephrosis or
obstructive uropathy

Hydronephrosis • dilation of the renal pelvis and calyces

• Progressive atrophy
• Congenital or acquired

UROLITHIASIS (RENAL CALCULI & STONES)

There are four main types of calculi:

o Calcium stones (about 70%)- composed largely of calcium oxalate or calcium oxalate mixed with calcium phosphate
o Triple-stones or struvite stones (15%)- composed of magnesium ammonium phosphate
o Uric acid stones (5-10%)
o Cysteine (1-2%)
• Increased concentration of stone constituents, changes in urinary pH, decreased urine volume, and the presence of bacteria influence the formation of calculi

NEOPLASMS OF THE KIDNEY

• Renal Cell Carcinoma– most common malignant tumor • Wilms Tumor– found in children, round blue cells, immature tubules

BENIGN NEOPLASMS
Renal Papillary Most frequently papillary
Adenoma o <0.5cm in diameter, within the cortex, appear as pale,
yellow-gray, discrete, well-circumscribed nodules
Angiomyolipoma n 25-50% of patients with tubular sclerosis
Oncocytoma Epithelial, composed of large eosinophilic cells
having small, round, benign-appearing nuclei that
have large nucleoli
MALIGNANT NEOPLASMS
Renal Cell Carcinoma Classic feature: costovertebral pain, palpable mass and
hematuria (most reliable clue); Tumor may remain silent until it attains a large size, often >10 cm.
Urothelial Carcinoma of the Clinical Manifestations: hematuria, hydronephrosis and flank pain
Renal Pelvis