Diseases of the kidney

1. DISEASES OF THE KIDNEY

2. Learning Objectives
The normal functioning of the kidney.
The Classification of Glomerular Diseases.
The Glomerular Syndromes
Pyelonephritis
Diabetic Glomerulosclerosis
Benign and Malignant Nephrosclerosis
Hydronephrosis
Tumors of the Kidney

3. The Kidneys
• A pair of bean-shaped
organs located at the
posterior wall of the
abdomen
• Dimensions
– 11 cm long, 6 cm wide
and 3 cm thick
– weighs about 160g

5. Kidney Functions
• Regulates extracellular
fluid & osmolarity,
electrolyte
concentrations, & acid-
base balance
• Excretes wastes
• Secretes renin
• Produces erythropoietin
• Converts vitamin D to
active form

6. Clinicopathologic Classification of
Glomerular Diseases.
I. PRIMARY GLOMERULONEPHRITIS
1. Acute GN
i) Post-streptococcal
ii) Non-streptococcal
2. Rapidly progressive GN
3. Minimal change disease
4. Membranous GN
5. Membrano-proliferative GN
6. Focal and diff use proliferative GN
7. Focal segmental glomerulosclerosis
(FSGS)
8. IgA nephropathy
9. Chronic glomerulonephritis
II. SECONDARY SYSTEMIC GLOMERULAR
DISEASES
1. Lupus nephritis (SLE)
2. Diabetic nephropathy
3. Amyloidosis
4. Polyarteritis nodosa
5. Wegener’s granulomatosis
6. Goodpasture’s syndrome
7. Henoch-Schönlein purpura
8. Systemic infectious diseases (bacterial
e.g. bacterial endocarditis,
syphilis, leprosy; viral e.g. HBV, HCV, HIV;
parasitic e.g. falciparum
malaria, fi lariasis)
9. Idiopathic mixed cryoglobulinaemia
III. HEREDITARY NEPHRITIS
1. Alport’s syndrome
2. Fabry’s disease
3. Nail-patella syndrome

7. CLINICAL MANIFESTATIONS

8. POSTSTREPTOCOCCAL GLOMERULONEPHRITIS
• 1 to 4 weeks after group A β-hemolytic streptococcal
infection of pharynx or skin – types 12, 4 and 1
• 6 to 10 years
• Immune complexes produced against streptococcal
antigen – endostreptosin and cationic antigen

9. POSTSTREPTOCOCCAL GLOMERULONEPHRITIS
Microscopy
• Enlarged, hypercellular
glomeruli,
hypercellularity- due to
infiltration of
inflammatory cells,
proliferation of
endothelial cells and
mesangial cells and in
severe cases by crescent
formation

10. POSTSTREPTOCOCCAL GLOMERULONEPHRITIS
• Immune fluorescence:
granular deposits of
IgG, IgM and C3 in the
mesangium and along
the basement
membrane

11. POSTSTREPTOCOCCAL GLOMERULONEPHRITIS
• Clinical course
• Acute nephritic syndrome – 1 to 2 weeks after recovery
from streptococcal infection
• Elevated ASO titers
• Decreased serum C3
• 95% recover; 1% progress to RPGN and others progress to
CGN

12. RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS
• Type 1 RPGN
• Goodpasture syndrome
• Idiopathic
• Type II RPGN (immune complex)
• Idiopathic
• Post infectious
• Systemic lupus erythematosus
• Henoch-schonlein purpura
• Others

13. RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS
• Type III RPGN (pauci-immune)
• ANCA associated
• Idiopathic
• Wegener granulomatosis
• Microscopic polyarteritis nodosa/microscopic polyangitis

14. RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS
Microscopy :
• proliferation of parietal cells
and by migration of
monocytes and macrophages
into urinary space,
neutrophils and lymphocytes
may be present
• Obliterate bowman space
and compress the glomerular
tuft
• Fibrin strands between
cellular layers
Crescents

15. NEPHROTIC SYNDROME
• Massive proteinuria, with the daily loss of
3.5 gm per 24hours of urine or more of
protein (less in children)
• Hypoalbuminemia, with plasma albumin
levels less than 3 gm/dl
• Generalized oedema
• Hyperlipidemia
• Lipiduria

16. CAUSES OF NEPHROTIC SYNDROME

18. MINIMAL CHANGE DISEASE
• Common cause of nephrotic syndrome in children
• Peak age – 2 to 6years
• Selective proteinuria (albuminuria)
• Etiology
– No immune complexes
– Immune dysfunction resulting in visceral epithelial damage by
cytokines
– In some cases, mutation in glomerular protein (Nephrin)

19. MINIMAL CHANGE DISEASE
• Characterized by
diffuse effacement of
foot processes of
epithelial cells in
glomeruli that appear
virtually normal by
light microscopy
• Most characteristic
feature is its usually
dramatic response to
corticosteroid therapy A, Ultrastructural characteristics of minimal change
disease: effacement of foot processes (double arrows),
absence of deposits, vacuoles (V), and microvilli in visceral
epithelial cells (single arrow). B, Schematic representation
of minimal change disease, showing diffuse effacement of
foot processes.

20. CHRONIC GLOMERULONEPHRITIS
• Gross – symmetrical
contracted kidneys having
diffuse granular cortical
surface
• Thinned out cortex and
increase in peripelvic fat
• Micro – hyaline obliteration
of glomeruli leads to
eosinophilic acellular masses
• Hyaline arterial and
arteriolar sclerosis and
marked tubular atrophy
• Masson trichrome stain –
complete replacement of all
glomeruli by collagen (blue
in color)
Masson trichrome preparation shows
complete replacement of virtually all
glomeruli by blue-staining collagen

21. CHRONIC GLOMERULONEPHRITIS
• Slowly progress to CRF or death due to uremia
• Loss of appetite, anemia, vomiting or weakness
• Edema, proteinuria, hypertension or azotemia
• Treatment – dialysis or renal transplant

22. PYELONEPHRITIS
• Infection of renal pelvis, interstitium and tubules
• Acute – associated with bacterial UTI
• Chronic – bacterial infection and vesico ureteral reflux
• Gram –ve bacilli – E.coli, proteus and klebsiella
• Immunocompromised patients – polyoma virus and CMV

23. PYELONEPHRITIS
• Hematogenous – septicemia and infective endocarditis
• Ascending – most common
• Colonization of distal urethra and introitus
• Urethra to bladder during instrumentation,
• Multiplication in the bladder
• Vesicoureteral reflex
• Intrarenal reflex

24. ACUTE PYELONEPHRITIS
• Patchy interstitial suppurative inflammation, intra
tubular aggregates of neutrophils and tubular necrosis
• Papillary necrosis – usually bilateral
• Pyonephrosis
• Perinephric abscess

25. ACUTE PYELONEPHRITIS
Cortical surface exhibits grayish white areas of
inflammation and abscess formation
Acute pyelonephritis marked by an acute
neutrophilic exudate within tubules and
the renal substance.

26. CHRONIC PYELONEPHRITIS
• Gross – coarse, discrete corticomedullary deep V and Y
shaped scar leading to asymmetrically contracted
kidney
• Tubular atrophy in some areas and dilatation in some
areas
• Dilated tubules with flattened epithelium filled with
colloid casts (thyroidization)
• Varying degree of interstitial mononuclear inflammation
and tubular atrophy
• Periglomerular fibrosis
• Obliterative intimal sclerosis of arterioles in scarred
areas

27. CHRONIC PYELONEPHRITIS
GROSS
• The kidneys are usually small and
contracted, weighing less than
100 gm each, showing unequal
reduction.
• The outer surface of the kidneys
is irregularly scarred.
• These deep V and Y shaped scars
are of variable size and show
irregular depressions on the
cortical surface.
• The pelvis of the kidney is dilated
and calyces are blunted and may
contain renal stone taking the
shape of pelvicalyceal system
called staghorn stone

28. CHRONIC PYELONEPHRITIS
MICROSCOPY
• The interstitium shows chronic
inflammatory infiltrate with
pronounced interstitial fibrosis.
• Dilated atrophic tubules may
contain colloid casts producing
thyroidisation of tubules.
• The wall of dilated pelvicalyceal
system shows marked chronic
inflammation and scarring.
• Periglomerular fibrosis and
hyalinisation of some glomeruli

29. DIABETIC GOMERULOSCLEROSIS
MICROSCOPIC FEATURES
• Diffuse involvement of the glomeruli
showing thickening of the glomerular
basement membrane.
• Diffuse increase in the mesangial matrix
with mild proliferation of mesangial cells
and exudative lesions (fibrin caps and
capsular drops)
Diffuse glomerulosclerosis

30. DIABETIC GOMERULOSCLEROSIS
MICROSCOPIC FEATURES
• There are one or more hyaline nodules
within the lobules of glomeruli,
surrounded peripherally by glomerular
capillaries with thickened walls.
• These nodular lesions of diabetic
glomerulosclerosis are also called as
Kimmelstiel-Wilson (KW) lesions or
intercapillary glomerulosclerosis.
• Th e nodules are PAS-positive and
contain lipid and fibrin.
Nodular glomerulosclerosis

31. HYPERTENSIVE CHANGES
BENIGN NEPHROSCLEROSIS
GROSS FEATURES
 Both the kidneys are affected
equally and are reduced in size
and weight, often weighing about
100 gm or less.
 The capsule is often adherent to
the cortical surface.
 The external surface of the kidney
is finely granular and shows V-
shaped areas of scarring.
 The cut surface shows firm kidney
and narrowed cortex.

32. HYPERTENSIVE CHANGES
BENIGN NEPHROSCLEROSIS
Microscopy :
a) Hyaline arteriolosclerosis
that results in
homogeneous and
eosinophilic thickening
of the wall of small
blood vessels.
b) Intimal thickening due to
proliferation of smooth
muscle cells in the
intima.
c) variable degree of atrophy
of parenchyma

33. Causes of ‘small contracted kidney’
• Chronic GN (granular appearance)
• Chronic pyelonephritis (U-shaped scars)
• Benign nephrosclerosis (V-shaped scars).
• Amyloidosis of the kidney,

34. HYPERTENSIVE CHANGES
MALIGNANT NEPHROSCLEROSIS
• The kidneys are variable
in size -
– small in size, shrunken
reduced in weight and
have finely granular
surface.
– enlarged, oedematous and
have petechial
haemorrhages on the
surface producing so called
‘flea-bitten kidney’.*
• Cut surface shows red
and yellow mottled
appearance

35. HYPERTENSIVE CHANGES
MALIGNANT NEPHROSCLEROSIS
MICROSCOPY
• Necrotising arteriolitis
develops on hyaline
arteriolosclerosis.
• The vessel wall shows
fibrinoid necrosis, a few
acute inflammatory cells
and small haemorrhages.
• Ischaemic changes include
tubular loss, fine interstitial
fibrosis and foci of
infarction necrosis.

36. Causes of flea-bitten kidney
• Malignant nephrosclerosis,
• Acute post-streptococcal GN,
• Rapidly progressive GN,
• Haemolytic-Uraemic Syndrome
• Thrombotic thrombocytopenic purpura
• Henoch-Schonlein purpura.

38. HYDRONEPHROSIS
• Aseptic dilatation of
the renal pelvis or
calyces.
• May be associated
with obstruction but
may be present in the
absence of
obstruction.
• Accompanied
destruction of kidney
parenchyma.

39. Etiology
• Can be Unilateral or bilateral.
• Unilateral maybe extramural, intramural or
intraluminal
• Bilateral causes are either congenital or
acquired

40. Causes of Unilateral hydronephrosis
A. Extramural
1. Compression by growth ( CA cervix, carcinoma
rectum)
2. Retroperitoneal fibrosis

41. B. Intramural
1. Congenital PUJ obstruction
2. Ureterocele
3. Neoplasm of ureter
4. Narrow ureteric orifice
5. Stricture ureter following removal of stone, pelvic
surgeries or tuberculosis of ureter.

42. C. Intraluminal
1. Stone in the renal pelvis
2. Sloughed papilla in papillary necrosis

43. Bilateral Hydronephrosis
• Result of urethral obstruction ; but may also
be caused by one of the lesions described
above occurring on both sides

44. Causes of Bilateral hydronephrosis
A. Congenital
• Congenital stricture of external urethral meatus,
pin-hole meatus.
• Congenital posterior urethral valve.
B. Acquired
• BPH
• Carcinoma prostate
• Postoperative bladder neck scarring
• Inflammatory / traumatic urethral stricture
• Phimosis
• Carcinoma cervix
• Bladder carcinoma

45. GROSS
• Kidney may have slight to
massive enlargement
• Earlier features are those of
simple dilation of the pelvis
and calyces
• In far-advanced cases, kidney
may become transformed into
a thin-walled cystic structure
having a diameter of up to 15
to 20 cm with striking
parenchymal atrophy, total
obliteration of the pyramids,
and thinning of the cortex.
Hydronephrosis of kidney, with marked
dilation of the pelvis and calyces and
thinning of the renal parenchyma

46. MICROSCOPY
• The wall of hydronephrotic
sac is thickened due to fi
brous scarring and chronic
inflammatory cell infiltrate.
• Progressive atrophy of
tubules and glomeruli along
with interstitial fi brosis.
• Stasis of urine in
hydronephrosis causes
infection (pyelitis) resulting
in filling of the sac with pus,
a condition called
pyonephrosis

47. TUMORS OF THE KIDNEY
• Benign- rare
• Renal papillary adenoma-from tubular epithelium
• Renal fibroma
• Angiomyolipoma - associated with tuberous sclerosis
• Oncocytoma - from intercalated cells of collecting duct
• Malignant
• Renal cell carcinoma
• Clear cell carcinoma
• Papillary carcinoma
• Chromophobe carcinoma
• Collecting Duct carcinoma
• Urothelial carcinoma of renal pelvis

48. RENAL CELL CARCINOMA
• 6th -7th decade
• Risk Factors:
– Cigarette smoking
– Obesity
– Hypertension
– Family history of the disease
– Patients with inherited diseases like von Hippel
Lindau disease
– Hysterectomy is associated with doubled risk
– Dialysis patients with acquired cystic disease of
kidney show greater risk

49. EPIDEMIOLOGY
• The incidence of renal cell carcinoma is rising steadily.
• More common in men than women, male to female ratio
is 1.6:1.
• Blacks at an higher risk than whites.

50. CLASSIFICATION OF RCC
• Clear cell carcinoma - 70% to 80%
• 95% sporadic,5% familial associated with VHL disease
• 98% of clear cell carcinoma have (3p-) which harbor
VHL gene
• Papillary carcinoma - 10% to 15%
• Trisomy 7 in familial, trisomy 7, 16 and 17 and loss of
y in male in sporadic
• In familial form - MET proto oncogene
• Chromophobe carcinoma - 5%
• Arises from intercalated cells of collecting dusts and
have excellent prognosis
• Collecting duct (Bellini duct) carcinoma - 1%

51. RENAL CELL CARCINOMA
Gross-
 usually arise from
upper pole
 spherical bright yellow
masses with
hemorrhage and
necrosis
Typical cross-section of yellowish, spherical
neoplasm in one pole of the kidney.

52. CLEAR CELL CARCINOMA
• Growth pattern varies
from solid to
trabecular or tubular.
• The tumour cells have
rounded or polygonal
shape and abundant
clear or granular
cytoplasm.
• The tumours have
delicate vasculature.

53. MORPHOLOGY
Papillary carcinoma –
• cuboidal or low columnar
cells arranged in papillary
fronds
• Interstitial foam cells are
present in papillary core
• Psammoma bodies may be
present
Chromophobe
carcinoma-
– pale eosinophilic cells with
perinuclear halo in solid
pattern
Collecting duct
carcinoma- irregular
channels lined by atypical

54. SIGNS AND SYMPTOMS
• Classic triad of:
– Hematuria
– Flank pain
– Abdominal mass
Signs:
• Malaise, weight loss and
anorexia
• Anemia
• Varicocele. enlargement of
testicle on left side
• Pallor
• Constipation
• Hypertension
• Hypocalcaemia
• Leg and ankle swelling

55. DIAGNOSIS
• Physical examination:
• Fever
• High blood pressure
• Lab tests:
• Complete blood count
• Urine analysis
• Serum calcium
• Imaging tests:
• Ultrasound abdomen
• Abdominal CT scan
• MRI scan
• PET scan
• Renal angiography
• Intravenous pyelogram
• Chest x ray
• Bone scan
• Biopsy
Fine needle aspiration
Core needle biopsy