C - NEPH STUDY GROUP March 12 2014

C - NEPH STUDY
GROUP
March 12th 2014
Selected Renal Disorders
Areas to be Covered
• Diabetic Nephropathy
• Obstructive Diseases
• Renal Syndromes and Glomerular Diseases
• Nephrotic
• Nephritic
• Interstitial Disease
• Vascular Diseases
Diabetic Complications
• Microvascular
• Retinopathy
• Nephropathy
• Neuropathy
• peripheral & autonomic
• Macrovascular
• Cerebrovascular
• Cardiovascular
• Peripheral vascular
Natural History of Type I
• 5 stages
• 1. Hyperfiltration at diagnosis (low s. creat)
• 2. Microalbuminuria > 5-10 years (urine ACR)
• 3. Overt proteinuria with BP & retinopathy for 2-5 years,
minimal haematuria (MSU)
• 4. CKD with normal-sized kidneys (renal U/S)
• 5. ESKD 18-24 months after CKD
Stage
1
Diabetes
Duration
0 – 3-5
2
3-5 +
3
7-15 +
4
15-20 +
5
15 – 25+
Manifestations
Renal hypertrophy
 GFR
Basement M thickening
Mesangial expansion
Microalbuminuria
HPT
Proteinuria
HPT
↓ GFR
6
ESKD
Natural History of Type II Diabetic
Nephropathy
• Far commoner than Type I
• Long asymptomatic phase
• HPT, nephropathy & retinopathy often present at time of
Dx
• Degree of proteinuria correlates with general vascular risk
and 20x CKD risk
Hyperfiltration Phase
• Elevated GFR 2o
•
BSL/BP/protein/obesity
Intra-glomerular pressure
• “Too good to be true” serum creatinine
• Accelerated progression to CKD
Albuminuria then Proteinuria
• Microalbuminuria first (lower MW)
• Raised by GFR (i.e. BSL, protein diet, fever, exercise)
• Spot urine ACR or PCR
• more convenient than 24hr collection
• more accurate than urinalysis
• adjusts for fluid intake
• underestimates the muscular patient
Diabetic Nephropathy
• From haemodynamic & metabolic stresses
• Metabolic stress
• deposition of advanced glycosylation end products in
connective tissue & sml vessels.
• May take 10-20 yrs but many T2DM asymptomatic for
several yrs, hence nephropathy may already be present
at Dx
• 1st clinical sign is microalbuminuria (ACR)
• Kidney not able to catabolise albumin
• This can also occur transiently with
• Fever
• Exercise
• Short term hyperglycaemia
• High protein meal
• Hence, repeat at a later date/rule out reversible
• DM + HPT,  x 20 risk of progressive nephropathy
• DM + HPT + poor diabetic & lipid control,  x 40 risk
Nephropathy Risk Factors
• DM Type & Duration
• 20% of Type I after 20 years
• 40% of Type II any duration
• Poor diabetic control
• Hypertension
• Aboriginal > Indian > Caucasian
• Smokers
• Family history
Nephropathy Risk Factors
• Modifiable
• HbA1c, BP & total cholesterol (Odds Ratio 43)
• Obesity, smoking
• Non-modifiable
• Age, ethnicity, male sex
Delaying Complications
• Tight diabetic control
• Prevention of microvascular Cmplx
• Risk of hypos
• Tight BP control
• Prevention and management of micro & macro Cmplx
• Use ACEI, ARB’s or both combined
ACE Inhibitors can prevent
progression of renal failure
Normotensive Type 2 Diabetics
110
400
Proteinuria
350
320
% Initial GFR
105
(mg/day)
Placebo
100
Enalapril
280
95
240
200
90
160
Placebo
Enalapril
85
120
80
80
0
1
2
3
Years
Ann Intern Med 118 577-581.1993
4
5
6
0
1
2
3
Years
4
5
6
Use of ACEi/ARBs
• BUT:
• ARF risk if underperfused
• Hyperkalaemia risk with many types of pills
(spironolactone)
• SO:
• Check BP & electrolytes at 1/12 and 6/12
• Check all new pills
OBSTRUCTIVE
NEPHROPATHY
Obstructive nephropathy
• Obstructive nephropathy is obstruction of the urinary
tract at any point from the kidney top the urethral meatus.
Etiology of the obstruction
Within the lumen of
the Urinary tract:
Within the wall of the
Urinary tract:
Pressure on the urinary
tract from outside:
-Stones
-Ureter neuromuscular
dysfunction
-Tumor (retroperitoneal,
colon)
-Strictures (ureter,
uretoviscular)
-Diverticulitis
-Urethra strictures
-Surgical ligation of the
ureters
-Pin-hole meatus
-Prostate enlargement
-Blood clot
-Tumors in the bladder,
renal pelvis & ureter
In men the most common cause of obstruction is prostatic hypertrophy or cancer,
stones, urethral structures
In women the most common cause of obstruction is secondary to pregnancy &
stones
Pathophysiology
Obstruction
Long term intravesical pressure on the bladder
Hypertrophy of the
muscle wall
trabeculation and cellule
formation in the bladder wall
mucosal diverticula
detrusor muscle decompensation
Inadequate emptying of the bladder
Urine stasis
Increases the risk for
infection
Back pressure on the ureter
- compress the papillae
Decreases GFR
-Loss of nephrones
Renal parenchyma
Impaired renal function
Ureteral wall
hypertrophy
trying to
propel urine
into the
bladder
Symptoms & Signs
Symptoms & signs of Upper
Urinary tract obstruction
Symptoms & signs of lower Urinary
tract obstruction
Symptoms
Loin pain
Anuria
Hematuria
Physical findings
Enlarged Kidney
Pelvic masses that obstruct the
ureter
Urine extravasations presented
as ascites
Symptoms
Straining to void
Hesitancy
urine stream
Sense of incomplete bladder
emptying
Post-void dribbling
Urge incontinence
Supra-pubic pain
Signs
Supra-pubic mass
Rectal Exam  enlarged prostate
Meatal stenosis
Investigations
• Urinalysis to detect:
• Pyuria : WBCs in urine that suggests inflammation
• Hematouria suggesting infection, stones or tumors
• Urine cytology if tumor is suspected
• Serum electrolytes to detect:
• Renal insufficiency by  Urea & creatinine due to GFR
• Electrolyte imbalance (hyperkalemia and acidosis) due to 
renal clearance of K+ and H+
• CBC to detect
• anemia of chronic disease
Imaging studies
1.
2.
3.
Ultrasound: dilated collected system & distended
bladder secondary to obstruction
CT scan: Not very clear anatomical details of urinary
tract. Used if external compression of urinary tract
MRI: used to be able to delineate tissue planes for
surgical planning.
Imaging studies
4. Antegrade pyelography: direct percutaneous
puncture of the pelvicalyceal system with a fine
needle (22 gauge) for diagnostic opacification of the
renal collecting system or for aspiration in
pyonephrosis
A partial
obstruction
in the distal
ureter is
caused by a
small
calculus
Imaging studies
5. Retrograde pyelography: inject contrast directly
into uretral orifice to visualize the upper collecting
system.
Retrograde
pyelography
demonstrates a
narrowed
ureteropelvic
junction without an
intrinsic mass or
stone.
Other studies
• Cystoscopy: used to visualize the entire urethra and
bladder by scope.
Management
• Medical therapy (supportive therapy)
• Analgesics
• Antibiotics
Surgical therapy (definitive therapy)
• Surgical therapy for lower Urinary tract
• Urethral catheter: catheter is placed through the urethral
meatus into the bladder. It is an absolute contraindication if
bladder damage is suspected.
• Supra-pubic catheter: insert the catheter into the bladder
directly from the anterior abdominal wall.
Urethral catheter
Supra-pubic catheter
Surgical therapy (definitive therapy)
• Surgical therapy for upper Urinary tract
• Ureter stents: endoscopicaly placed tube from the renal
pelvis to the bladder
• Percutaneous nephrostomy: small tube placed in the renal
pelvis, ureter, bladder.
Ureter
stent
Percutaneous
nephrostomy
Post-operative considerations
• After the relieve of a long standing obstruction,
diuresis occur due to:
• Water overload
• Osmotic affect of retained salt
• Defect in the renal reabsorption capacity
• Diuresis is self-limiting but some patients may
develop severe hyponatremia, hypokalemia, alkalosis
& dehydration & may require IV replacement.
Complications
• Urinary tract infection
• Urinary extravasations
• Renal parenchyma loss  renal insufficiency and renal
failure
• Bladder decompensation  neurogenic bladder
Renal Syndromes
• Asymtpomatic Urinary Abnormalities
• Proteinuria
• Hematuria
• Nephrotic Syndrome
• Nephritic Syndrome
• Acute Kidney Injury
• Chronic Kidney Disease
OBJApproach to Glomerular Diseases
ECTIVES
• Syndrome Diagnosis
• Clinical Diagnosis
• Histologic Diagnosis
• Clinicopathologic Correlation
• General Principles of Management
Afferent arteriole
Parietal EC
Capillary
loop
Endothelium
Macula densa
Mesangium
JG cells
Urinary
space
Efferent
arteriole
Visceral EC
Mesangium
Normal
Glomerulus
Normal glomerulus
PADefinition of Terms
THOLOGY
• Glomerulopathy vs. Glomerulonephritis
• Primary vs. Secondary
• Diffuse vs. Focal
• Global vs. Segmental
• Fibrosis vs. Sclerosis
• Membranous vs. Proliferative
• Endocapillary vs. Extracapillary
Fibrosis – increase in
the deposition of
collagen fibers
Sclerosis – increase in the
amount of homo-genous
nonfibrillar extracellular
material
Sclerosis
Segmental – lesion
involves < 50% of
the glomerulus
Sclerosis
Global – lesion
involves > 50%
of the glomerulus
Sclerosis
Diffuse Global Glomerulosclerosis
Focal – lesion seen in less
than 50% of glomeruli
Diffuse – lesion seen in
more than 50% of glomeruli
Mesangial
cells
Normal glomerulus
Proliferation – increase
in the glomerular cell
number
Mesangial
cells
Mesangial proliferativeGN
Endocapillary
proliferation
Extracapillary
proliferation
Normal glomerulus
Membranous – expansion
and thickening of the
glomerular basement
membrane (GBM) by
immune deposits
Primary Mechanisms of Glomerular Injury
Mechanism of
Injury
Renal Insults/ Defects
Glomerular Disease
Immunologic
Immunoglobulin
Immune-complex GN
Goodpastures
Cell-mediated injury
Pauci-immune GN
Cytokine
Primary FSGS
Complement activation
MPGN Type II
Hyperglycemia
DM Nephropathy
Fabry’s disease/ sialidosis
FSGS
Systemic hypertension
HTN Nephrosclerosis
Intraglomerular hypertension
Secondary FSGS
Metabolic
Hemodynamic
Primary Mechanisms of Glomerular Injury
Mechanism Renal Insults/ Defects
of Injury
Glomerular Disease
Toxic
E. coli-derived verotoxin
Thrombotic
microangiopathy
Therapeutic drugs (NSAIDs)
Minimal change disease
Recreational Drugs (Heroin)
FSGS
Deposition
Amyloid fibrils
Amyloid nephropathy
Infectious
HIV
HIV Nephropathy
Subacute Endocarditis
Immune complex GN
Inherited
Genetic defect for α5 chain of Alport’s Syndrome
type IV collagen
Abnormally thin basement
membrane
Thin basement
membrane disease
Immunologic Glomerular Injury
Humoral Antibody-Mediated Injury
• Autoantibodies against intrinsic antigens
(example: Goodpasture’s syndrome)
• Autoantibodies against extrinsic “trapped antigens
(example: Postinfectious GN)
• Trapping of circulating immune complexes (example:
Cryoglobulinemic GN)
Cellular Mediated Injury
GN
Loss of nephrons
Glomerular hyperfiltration
Glomerular HTN
Non-selective
prtoteinuria
Glomerular
sclerosis
Tubulointerstitial
inflammation
Ischemia
Tubulointerstitial atrophy/fibrosis
Two Final Common Pathways in Glomerular Injury
Approach to Glomerular Diseases
• Syndrome Diagnosis
• Clinical Diagnosis
• Histologic Diagnosis
• Clinicopathologic Correlation
• General Principles of Management
Approach to Glomerular Diseases
• Syndrome Diagnosis
• Clinical Diagnosis
• Histologic Diagnosis
• Clinicopathologic Correlation
Syndrome Diagnosis
History
Physical Examination
Ancillary Laboratory Tests
• Chemistry
• Serology
• Urinalysis
Syndromes in
Glomerular Diseases
Syndrome
Clues to
Diagnosis
Common
Findings
Rapidly
Progressive
Renal Failure
(RPRF)
Anuria
Oliguria
Decline in GFR
over weeks
HTN, Hematuria,
Proteinuria,
Pyuria
Nephritic
Syndrome
Hematuria, RBC
casts, Azotemia,
Oliguria, Edema,
HTN
Proteinuria,
Syndromes in
Glomerular Diseases
Syndrome
Clues to Diagnosis
Common
Findings
Nephrotic
Syndrome
Proteinuria > 3.5 gms
Hypoalbuminemia
Hyperlipidemia
Lipiduria
Casts
Edema
Asymptomatic Isolated hematuria
urinary
Isolated proteinuria
abnormality
(AUA)
Approach to Glomerular Diseases
• Syndrome Diagnosis
• Clinical Diagnosis
• Histologic Diagnosis
• Clinicopathologic Correlation
Clinicopathologic Correlation
Syndrome
Diagnosis
Histologic
Diagnosis
Etiologic
Diagnosis
Nephritic
Diffuse
Immune complex GN (>70%)*
Proliferative GN Pauci-immune GN (<30%)**
Nephritic
Nephrotic
MembranoImmune complex GN*
Proliferative GN Thrombotic microangiopathy
RPRF
Crescentic GN
Isolated
hematuria
Mesangial
IgA nephropathy
Proliferative GN HSP
Immune complex GN (≅45%)*
Pauci-immune GN (≅45%)**
Anti-GBM disease (≅10%)
* SLE, Postinfectious GN, IE, Cryoglobulinemia
** Wegener’s granulomatosis, Microscopic PAN
Clinicopathologic Correlation
Syndrome Histologic
Diagnosis Diagnosis
Etiologic
Diagnosis
Nephrotic
Minimal Change
Disease (MCD)
Idiopathic, drugs, heroin,
HIV, lymphoma
Nephrotic
Focal Segmental
Glomerulosclerosis
(FSGS)
Idiopathic, HIV, heroin,
secondary forms from
reduced nephron number
Nephrotic
Membranous
Glomerulopathy
Idiopathic, infections, drugs,
autoimmune diseases,
paraneoplastic syndrome
Nephrotic
CRF
Nodular sclerosis
DM nephropathy
Chronic GN
Clinical Diagnosis
Disease
Renal
Syndrome
Clinical Features
Diabetic
nephropathy
Nephrotic
CRF
Chronic course, (+) DM
retinopathy, nl-sized kidneys,
bland urine sediment
Goodpasture’s
syndrome
Nephritic
RPRF
antiGBM-aby (+), cANCA (-),
nl C3
Nephritic
Wegener’s
granulomatosis RPRF
antiGBM-aby (-), cANCA (+),
nl C3
Clinical Diagnosis
Disease
Renal
Clinical Features
Syndrome
Lupus nephritis
Nephritis
RPRF
antiGBM-aby (-), cANCA (-),
low C3, ANA (+), (+) ACR
criteria for the diagnosis of
SLE
Poststreptococcal Nephritis
GN
antiGBM-aby (-), cANCA (-),
low C3, ASO (+), prior
Streptococcal infection
Sample Case
• 28 year old female referred for acute onset of pedal
•
•
•
•
•
•
edema X 1 week
No other associated signs and symptoms
Single; sexually active; silent past medical history;
not on any medications; no history of IVDA
ROS: denies other symptoms
Well-nourished, not obese
BP = 120/80, clear BS
Grade III pedal edema
SAMPLE CASE
• Serum creatinine = 70 umol/l EGFR 90 mls/min (nl)
• Albumin = 20 mg/mL (low); Cholesterol = 8 umol/l
(high); FBS = 6 umol/l (nl)
• CXR: normal; UTS of kidneys: normal
• Urinalysis: +4 protein, 0-1 RBC/hpf, 0-1 WBC/hpf, no
casts
• 24-hour urine study: creatinine clearance of 98 cc/min
and proteinuria of 4.5 g/day
Approach to Glomerular Diseases
• Syndrome Diagnosis
• Clinical Diagnosis
• Histologic Diagnosis
• Clinicopathologic Correlation
SAMPLE CASE
What is the renal syndrome present?
• Nephritic syndrome
• Nephrotic Syndrome
• Rapidly progressive renal failure
• Asymptomaric urinary abnormality
SAMPLE CASE
Answer: Nephrotic syndrome
• Edema
• Hypoalbuminemia
• Hyperlipidemia
• Proteinuria > 3.5 g/day
Approach to Glomerular Diseases
• Syndrome Diagnosis
• Clinical Diagnosis
• Histologic Diagnosis
• Clinicopathologic Correlation
SAMPLE CASE
Is it possible to make a clinical diagnosis?
• Yes or No ?
• If yes, what is your clinical diagnosis?
• If no, is a kidney biopsy indicated?
SAMPLE CASE
Answer: No
• No signs of systemic disease, ROS negative
for other symptoms
• PE normal except for edema
• Normal FBS
• Adult nephrotic syndrome – unlike children,
no room for empiric steroid therapy
• Kidney biopsy indicated
Approach to Glomerular Diseases
• Syndrome Diagnosis
• Clinical Diagnosis
• Histologic Diagnosis
• Clinicopathologic Correlation
Sclerosis
Foot process fusion
SAMPLE CASE
Histologic Diagnosis:
• Focal segmental glomerulosclerosis
Approach to Glomerular Diseases
• Syndrome Diagnosis
• Clinical Diagnosis
• Histologic Diagnosis
• Clinicopathologic Correlation
SAMPLE CASE
• What are the possible causes of FSGS?
• What additional test/s is/are needed?
• Is this primary vs. secondary FSGS?
Etiology of FSGS
Idiopathic (Majority)
Systemic Diseases or Drugs
• HIV
• Diabetes mellitus
• Fabry’s disease
• Sialidosis
• Charcot Marie-Tooth Disease
• Heroin
Etiology of FSGS
Congenital Oligonephropathies
Acquired nephron loss
• Surgical resection
• Reflux nephropathy
• Chronic GN/ renal disease
Other adaptive responses
• Sickle-cell nephropathy
• Obesity with sleep apnea
• Familial dysautonomia
SAMPLE CASE
• No signs of systemic diseases
• No history or sign (normal kidneys on UTS) of
•
•
•
•
•
nephron loss
Not obese
No history of IVDA/ heroin use
Sexually active – need to rule out HIV
HIV ELISA test ordered – negative
Final diagnosis: Idiopathic Primary FSGS
OBJECTIVES
Introduction
Approach to Glomerular Diseases
• Syndrome Diagnosis
• Clinical Diagnosis
• Histologic Diagnosis
• Clinicopathologic Correlation
General Principles of Management
General Principles of Management
• Disease-specific therapy for primary and
secondary GN
• Therapy to retard the progression of disease
• Therapy to address complications
Disease-specific
therapy
GN
Loss of nephrons
Glomerular hyperfiltration
Glomerular HTN
Non-selective
prtoteinuria
Glomerular
sclerosis
Tubulointerstitial
inflammation
Ischemia
Tubulointerstitial atrophy/fibrosis
Two Final Common Pathways in Glomerular Injury
Disease-Specific Therapy
for Primary (Idiopathic) GN
Syndrome
Disease
Therapy
Nephritic
MPGN
Aspirin plus dipyridamole
Nephrotic
MCD
Steroids
Nephrotic
FSGS
Steroids
Nephrotic
Membranous
Steroids plus chlorambucil
(Ponticelli protocol)
Disease-Specific Therapy
for Secondary GN
Syndrome
Disease
Therapy
Nephritic
Poststreptococcal GN
Penicillin; supportive
RPRF
Wegener’s
granulomatosis
Steroids plus PO
cyclophosphamide
RPRF
Goodpasture’s
syndrome
Plasmapharesis
Nephritic
Lupus nephritis IV
Steroids, IV
cyclophosphamide
Nephrotic
Hep B membranous GN Interferon
Nephrotic
MCD due to NSAIDs
Discontinue offending
drug
GN
Loss of nephrons
Glomerular hyperfiltration
Measures to
delay
progression
Glomerular HTN
Non-selective
prtoteinuria
Glomerular
sclerosis
Tubulointerstitial
inflammation
Ischemia
Tubulointerstitial atrophy/fibrosis
Two Final Common Pathways in Glomerular Injury
Renoprotective Strategies
(Hebert, 2000)
• Control blood pressure (< 127/75). (1)
• Use of ACE-I for BP. (1)
• Control of blood glucose for diabetics.(1)
• Limit protein intake to 0.8 g/kg IBW/day.(1)
• Limit NaCl intake (2-3 g/day).(3)
• Control lipids using statins (HMG-CoA reductase
inhibitor therapy). (2)
• Avoid cigarette smoking. (2)
• Avoid regular intake of NSAIDs.(3)
( ) Level of Recommendation
Renoprotective Strategies
(Hebert, 2000)
• Control plasma homocysteine level using folic acid
•
•
•
•
•
•
•
(2-15 mg/d). (3)
Control hyperinsulinemia (exercise and weight
reduction). (3)
Use of antioxidants (Vit C and Vit E). (3)
Correct anemia (HgB 11-12). (2)
Avoid hypokalemia. (3)
Control hyperphosphatemia. (3)
Low dose ASA. (3)
Estrogen replacement for women. (3)
( ) Level of Recommendation
Treatment of Complications
• Diuretics to control edema.
• ACE-I/AII-RBs to control BP.
• Anticoagulants (warfarin) for hypercoagulable states.
• Statins for hyperlipidemia
• Measures to prevent osteoporosis for patients on
steroids (Calcium, Vit D, biphosphonates).
• Co-trimoxazole to prevent Pneumocystic pneumonia
for patients on steroids
SUMMARY
Introduction
Approach to Glomerular Diseases
• Syndrome Diagnosis
• Clinical Diagnosis
• Histologic Diagnosis
• Clinicopathologic Correlation
General Principles of Management
DISEASES OF THE RENAL
TUBULE AND INTERSTITIUM
Two very broad groups of conditions
1. Acute tubular necrosis
(ischaemic or toxic necrosis of tubular cells)
2. Tubulointerstitial nephritis (a.k.a. interstitial nephritis)
(inflammatory reactions involving the tubules and/or
interstitium)
Acute tubular necrosis (ATN)
• important cause of acute renal failure
• characterized by acute destruction of tubular epithelial
cells
• most commonly secondary to ischaemia, but can also be
due to direct toxic cell damage
• potentially reversible, since tubular cells can regenerate
given time
ATN due to ischaemia
•
due to
1) “shock” (rapid uncompensated fall in systemic BP)
e.g. in trauma, burns, falciparum malaria,
pancreatitis, sepsis, DIC, blood transfusion
reactions etc OR
2) reduction in intrarenal blood flow (RPGN, acute
interstitial nephritis, urinary obstruction)
•
remember, tubular blood flow is from postglomerular capillary bed - and tubules are
metabolically very active, thus susceptible to
ischaemia
ATN due to toxins
• heavy metals – Pb, Au, As, Cr etc
• organic solvents – CCl4, chloroform
• drugs – antibiotics (espec gentamicin), anti-viral agents,
NSAIDs, mercurial diuretics
• iodinated contrast agents used for X rays
• pesticides
• glycols – ethylene glycol
In both types of ATN
• tubular cell degeneration and death
• tubular casts of dead cells & debris
• (may be accompanied by myoglobinuria in crush injury or
Hb/uria in haemolysis)
• interstitial oedema & secondary inflammation
• pale swollen kidneys
ATN causes acute renal failure
Clinically variable, but classically in 3 phases –
1.
2.
3.
initial (~ 36 hrs) (often missed) – slight increase in urine
output and rise in serum urea
oliguric – urine output 400 ml or less/day, so Na+, K+ &
water retention, rising urea, metabolic acidosis –
danger of pulmonary oedema & cardiac dysrhythmias
diuretic – urine output above normal, so loss of water,
Na+ & K+ – danger of dehydration
Complete recovery possible
Renal cortical necrosis
• more severe effect of shock on the kidneys than ATN
•
•
•
•
produces
also caused by rapid uncompensated fall in systemic BP
(“shock”)
but, in this situation, hypotension so severe that renal
blood flow diverted into medullary vasa recta away from
cortex
so whole cortex becomes infarcted
irreversible
(Tubulo)interstitial nephritis
• heterogeneous group of conditions
• similar morphology and clinical features, but wide
variety of causes
• other than acute infective cases, T cell reaction
probably involved in most
• some agents (e.g. certain drugs) can cause ATN
in some patients, interstitial nephritis in others
(and even GN in still others!): not clear why
• interstitial nephritis can be clinically
overshadowed by other systemic manifestations
of primary cause/condition
Causes of interstitial nephritis 1
• immunological reactions, notably
• hypersensitivity reactions
• transplant rejection
• infection
• especially pyelonephritis
• direct toxic damage
• drugs, particularly analgesics
• heavy metals
• metabolic diseases, e.g. gout
Causes of interstitial nephritis 2
• physical factors
• urinary tract obstruction
• radiation nephritis
• neoplasia, particularly myeloma kidney
• vascular diseases, including
• hypertension (also causes glomerular damage)
• papillary necrosis
• etc etc
• in many cases, precise cause never identified
Analgesic nephropathy
• excess & long-term intake (“abuse”) of analgesic
mixtures
• especially aspirin (ischaemic effect) & phenacetin (toxic
effect)
• chronic accumulative damage
• chronic interstitial nephritis, often with renal
papillary necrosis as the initial feature
• more common in women
• headache, anaemia, hypertension and GI
symptoms are common
• rarely, carcinoma of renal pelvis supervenes
Myeloma kidney
• the most common example of “cast nephropathy*”
• protein casts block tubules, causing them to rupture producing
tubulointerstitial nephritis
• due to glomerular filtration of Bence-Jones protein (light chains)
• in myeloma, kidneys may also show
• (primary) amyloidosis
• pyelonephritis secondary to UTI
• calcification (“metastatic” type) secondary to bone disease
• glomerular lesions because of trapped Igs
• *“cast nephropathies” – associated with diseases producing abnormal
plasma proteins which tend to block renal tubules
Vascular diseases and the kidney
• Nephrosclerosis – benign & accelerated
• Renal artery stenosis
• Infarcts
• Cortical necrosis
• Sickle cell disease
• Haemolytic uraemic syndrome – ATN in severe
haemolysis
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