Diseases of the kidney:

tubules and interstitium

Prof. Wadie Elmadhoun

April 2021
UMST
 Intended learning outcomes
• By the end of this lecture, the student should be
able to:
1. Define tubulo-interstitial diseases of the
kidney.
2. Identify the causes of interstial nephritis.
3. Describe the pathogenesis of tubulo-
interstitial diseases
4. Define and describe acute and chronic
pyelonephrtitis and enumerate the causes,
clinical features and complications of each.
5. Identify acute tubular necrosis, enumerate
 Lecture outlines

1. Tubulo-interstital nephritis
2. Acute pyelonephritis
3. Chronic pyelonephritis
4. Acute tubular necrosis
 Definition of Tubulo-interstital nephritis

•Are inflammatory Kidney

diseases that primarily affect
Tubules and/ or the interstitium.
• i.e. structures in the kidney outside the glomeruli.
 Functions of the tubules
•Tubules are responsible for
concentrating the
urine(osmolality, sodium and
water reabsorption)
•Reduction of tubular or
interstitial function both result
in: impaired resorptive
capacity
 Characteristics of tubulointerstitial and glomerural diseases
Tubular Glomerular
Urine osmolality Low <350mos/kg High/norm
Urine sodium >40mM/L <40
U. sediment Muddy brown Red cell casts
casts(ATN)
Eosinophils(AAIN)
hematuria rare common
proteinuria rare common
Causes Ischemia, infections, Autoimmune or
toxins, Drugs, congen.
autoimmune
Therapy Supportive/dialysis Steroids,immunmo
dulators
Causes of Tubulo/Interstitial Nephritis

INFECTIONS: i.e., pyelonephritis

TOXINS: heavy metals, chemo, NSAIDS
METABOLIC: urates, Ca++, Oxalates
PHYSICAL: obstruction,
radiation
IMMUNOLOGIC: humoral, T- cells
and transplant rejection
 Pathophysiology
• Lethal, sublethal injury to renal cells lead to
expression of new local antigens, inflammatory
cell infiltration and activation of proinflammatory
cells and cytokines
• Acute nephritis- renal tubular dysfunction with or
without renal failure ( If the tubular basement
mebrane is preserved the damage may be
reversibile)
• Chronic nephritis- interstitial scarring fibrosis,
tubule atrophy- resulting progressive renal failure
 Clinical presentation
Acute
• Abruptly, within days of exposure to the
offending agent
• Uremic symptoms: oliguria
 Acute tubulointerstitial diseases
• Acute tubular necrosis(ATN)
• Contrast nephropathy
• Acute allergic tubulointerstitial nephritis(AAIN)
• Atheroembolic renal insuff.
• Pigment mediated renal insuff.
• Crystal mediated renal insuff.
• Myeloma related renal insuff.
• Toxin mediated renal insuff.
• Papillary necrosis.
 TUBULAR DISEASES
• Acute Tubular Necrosis
• Tubulointerstitial Nephritis
– Pyelonephritis
• ACUTE
• CHRONIC
– DRUGS
– TOXINS
• Urate Nephropathy
• Hypercalcemia/Nephrocalcinosis
• Multiple Myeloma
 Acute Tubular Necrosis (ATN)
• Destruction of renal TUBULAR epithelium
• Loss of renal function
• Is the cause of 50% of ACUTE renal failure
• Two types:

ISCHEMIC
NEPHROTOXIC
-AMINOGLYCOSIDES
-AMPHOTERICIN B
-CONTRAST AGENTS
NORMAL
ATN
 ATN Pathogenesis
• Blood flow disturbances
(ischemic)
• Tubular injury (nephrotoxic)
 Clinical course ( 3 stages)
1. INITIATION (36 hours)
1. Mild OLIGURIA
2. Mild AZOTEMIA
2. MAINTENANCE
1. More OLIGURIA
2. More AZOTEMIA
3. DIALYSIS NEEDED
3. RECOVERY
– HYPOKALEMIA main problem
– BUN, CREATININE return to normal
 Lab. Findings distinguishing ATN
from prerenal azotemia
prenrenal ATN

Urinary Na mM/L <20 >40

FE Na <1% >1%

U osm mM/kg >500 <350

BUN/Creat >20:1 10-15:1

Urinary sediment Hyalin casts Brown casts
Muddy brown casts
pigmented granular casts
 TUBULO/INTERSTITIAL NEPHRITIS
• INFECTIONS, i.e., pyelonephritis
• TOXINS, heavy metals, chemo,
NSAIDS
• METABOLIC, urates, Ca++,
Oxalates
• PHYSICAL, obstruction, radiation
• IMMUNOLOGIC, esp. transplant
rejection
 PYELONEPHRITIS
• Bacteria: Gram NEGATIVES: E. COLI, Proteus,
Klebsiella, Enterobacter, Strep. faecalis, usually
“NORMAL” flora in GIT.
• Route of infection: ASCENDING, by far, the
most common, i.e., reflux, obstruction
• HEMATOGENOUS too
• Acute Pyelonephritis, neutrophils
• Chronic Pyelonephritis: lymphocytes, scars
ACUTE or CHRONIC PYELONEPHRITIS?
ACUTE or CHRONIC PYELONEPHRITIS?
ACUTE or CHRONIC PYELONEPHRITIS?
 FACTORS
• Obstruction: congenital or acquired
• Instrumentation
• Vesicoureteral reflux
• Pregnancy
• Age,
• sex, why sex? f>>>m
• Previous lesions
• Immunosuppresion or immunodeficiency
 Drugs/Toxins causing Interstitial
Nephritis
• Synthetic Penicillins
• Rifampin
• Thiazides
• 2 weeks later: Fever, eosinophilia, rash,
and an acute renal failure type of picture
 ANALGESIC NEPHROPATHY
• ASPIRIN, NSAIDS
– TUBULOINTERSTITIAL NEPHRITIS
– PAPILLARY NECROSIS (also DM & HbS)
 Urate nephropathy
• Precipitation of Uric Acid Crystals in
the TUBULES, especially in a LOWER
than usual PH situation (mini-TOPHUS)

H & E alcohol fixed POLARIZED LIGHT MICROSCOPY

 Hypercalcemia Nephrocalcinosis

PRINCIPLE: In extreme or
uncontrolled or chronic
HYPERCALCEMIA, calcium stones form
in the tubulo-interstitium of the kidney,
which can eventually lead to tubular
obstruction and loss of function
MULTIPLE MYELOMA
• Bence Jones proteinuria
(immunoglobulin light chains)
• AMYLOIDOSIS
 Study questions
• Write a short note about each of the following points:
1. Define tubulo-interstitial diseases.
2. Identify the causes of tubulo-interstitial
diseases.
3. Enumerate the clinical features and
complications of tubulo-interstitial diseases.
 Case # 1
• A 62-year-old man has had back pain for the past 8
months. He has had a productive cough for the past
2 days.
• On physical examination his temperature is 39°C
and there is dullness to percussion at the right lung
base.
• Laboratory studies show 4+ gram-positive
diplococci in the sputum.
• A chest radiograph shows right lower lobe
consolidation.
• An abdominal CT scan shows multiple lytic lesions
of the vertebrae.
 Case # 2
• A 36-year-old woman has urinary frequency with
dysuria for the past 4 days.
• On physical examination she has no flank pain or
tenderness.
• A urinalysis reveals sp. gr. 1.014, pH 7.5, no
glucose, no protein, no blood, nitrite positive, and
many WBC's.
• She has a serum creatinine of 0.9 mg/dL.
• Which of the following is the most likely
diagnosis?
a) Lupus nephritis
 Case # 3
• A 69-year-old man incurs blunt force trauma from
a fall.
• On physical examination he has a contusion on his
lower back.
• An abdominal CT scan shows 3 peripheral 1 to 2
cm cysts in his kidneys. The kidneys are normal in
size.
• Laboratory studies show a serum urea nitrogen of
16 mg/dL and creatinine of 1.1 mg/dL.
• A urinalysis reveals no blood, ketones, protein, or
glucose. Microscopic urinalysis reveals a few
oxalate crystals.
 Case # 4
• A 51-year-old man is hospitalized for acute
myocardial infarction.
• He has decreased cardiac output with hypotension
requiring multiple pressor agents.
• His urine output drops over the next 3 days.
• His serum urea nitrogen increases to 59 mg/dL,
with creatinine of 2.9 mg/dL.
• Urinalysis reveals no protein or glucose, a trace
blood, and numerous hyaline casts.
• Five days later, he develops polyuria and his serum
urea nitrogen declines.
• Which of the following pathologic findings in his
 Case # 5
• A 60-year-old woman is admitted with sudden onset
of chest pain and is diagnosed with an acute
myocardial infarction.
• There is difficulty maintaining adequate blood
pressure and tissue perfusion for 3 days. Her serum
lactate becomes elevated.
• Her serum urea nitrogen increases to 44 mg/dL and
creatinine to 2.2 mg/dL.
• Granular and hyaline casts are present on
microscopic urinalysis.
• Which of the following renal lesions is most likely
to be present in this situation?
Chronic pyelonephritis
 Case # 6
• A 70-year-old woman has had a fever for the past 3
days. She has burning dysuria.
• On physical examination her temperature is 37.8°C
and there is dull pain on palpation of her left lower
back.
• Laboratory studies show Hgb 13.3 g/dL, Hct
40.2%, and WBC count 12,300/microliter with
differential count 72 segs, 9 bands, 13 lymphs, 5
monos, and 1 eosinophil.
• A urine dipstick analysis shows sp gr. 1.017, pH 6,
leukocyte esterase positive, nitrite positive, protein
negative, glucose negative, and blood negative.
• Which of the following microscopic urinalysis
 Case # 7
• A 53-year-old woman has had chronic arthritis pain
for the past 3 years.
• She has taken 2 gm of phenacetin and
acetaminophen a day for her pain over that time.
• She now has increasing fatigue.
• There are no abnormal findings on physical
examination.
• Laboratory studies show her serum urea nitrogen is
52 mg/dL and creatinine 5.4 mg/dL.
• Which of the following pathologic findings is most
likely to occur in her kidneys?
A Papillary necrosis
 Case # 8
• A 25-year-old woman has been hospitalized for
treatment of a Staphylococcus aureus abscess of her
left thigh complicating a puncture wound.
• The wound is incised and drained and she receives
antibiotic therapy.
• She is improving and discharged home a week later,
but the next day she develops a fever.
• On physical examination her temperature is 38.1°C
and there is a diffuse erythematous skin rash of her
trunk and extremities.
• A urinalysis shows sp gr 1.020, pH 6.5, 1+ blood,
1+ protein, no glucose, and no ketones. There are
10-20 WBCs/hpf and 1-5 RBCs/hpf, and a few
 Case # 9
• A 57-year-old man has had dysuria for the past
week.
• Over the past 2 days he has experienced shaking
chills.
• On physical examination his temperature is
39.3°C. A urinalysis shows sp gr 1.016, pH 6, 1+
glucose, 1+ blood, no ketones, and no protein.
Urine microscopic examination shows numerous
WBCs and WBC casts.
• His serum creatinine is 1.5 mg/dL and glucose 155
mg/dL with hemoglobin A1C 8.7%.
• A renal ultrasound scan shows a 0.3 cm free
 Case # 10
• A 49-year-old woman has been hospitalized for the
past 10 days for treatment of bronchopneumonia.
• She has developed chills and fever over the past 2
days.
• On physical examination her temperature is 38.8°C
and she has a diffuse erythematous skin rash.
• Laboratory studies show serum creatinine 2.2
mg/dL and glucose 73 mg/dL. A peripheral blood
smear reveals eosinophilia.
• On urinalysis she has 2+ proteinuria but no blood,
glucose, or ketones.
• Which of the following is the most likely diagnosis?
Post-streptococcal glomerulonephritis
Kidney – Pathology – Lecture one – Prof. Wadie 45
Further readings