TUBULOINTERSTITIAL

DISEASE
SANDRA DEL MUNDO, M.D.
FPCP,DPSN

Tubulointerstial disease of the

Kidney
Characterized by histologic and functional
abnormalities that involve the tubules and
interstitium to a greater degree than the
glomeruli and renal vasculature

Acute Interstitial Nephritis

DRUGS
ANTIBIOTICS
ANALGESICS
DIURETICS

Presents with FEVER, EOSINOPHILIA

(IMMUNE MECHANISM)
INFECTION
Bacteria ( streptococcal, staphylococcal, legionella, salmonella)
Viral( EBV, CMV, HIV)
Leptospiral

Chronic tubulointerstitial diseases

Hereditary
Polycystic kidney disease
Medullary sponge kidney
Medullary cystic disease
Exogenous toxins
Analgesic nephropathy
Lead nephropathy
Misc( lithium, cyclosporine, heavy
metals, slimming regimens)

Chronic tubulointerstitial diseases

Metabolic toxins
Hyperuricemia
Hypercalcemia
misc. ( hypokalemia, hyperoxaluria, cystinosis)
Neoplastic disorders
Leukemia
Lymphoma
Multiple myeloma
Miscellaneous disorders
Chronic pyelonephritis
Chronic urinary tract obstruction
Radiation nephritis
VUR

Functional consequences of
tubulointerstitial disease

Defect

Reduced GRF

Causes

Obliteration of microvasculature
and obstruction of tubules
Damage to PT reabsorption of
Fanconi syndrome
glucose, amino acids,
phosphate, and HCO3
1. Reduced ammonia production
Hyperchloremic acidosis
2. Inability to acidify the collecting
duct fluid
3. Proximal HCO3 wasting

Functional consequences of
tubulointerstitial disease

Defect

Causes

Tubular or small molecular Failure of PT protein reabsorption

wt. proteinuria
Polyuria, isothenuria
Hyperkalemia
Salt wasting

Damage to medullary tubules and

vasculature
K+ secretory defects including
aldosterone resistance
Distal tubular damage with
impaired Na reabsorption

Analgesic nephropathy
Chronic analgesic intake 1 gm of phenacetin OD for 1-3
years
Presents as:
Chronic interstitial disease with obstruction
Chronic Renal Failure
Papillary necrosis
Overwhelming UTI
Ureteral Obstruction
Sterile pyuria
Acidosis / concentration defects

Papillary necrosis
FOUND IN:
1. DM
2. OBSTRUCTION
3. ANALGESIC ABUSE
4. PYELONEPHRITIS
5. TB OF THE KIDNEYS
Impaired medullary perfusion

deformity and
sclerosis of papilla

Papillary necrosis

Urinary tract infection

Normally
Bladder urine is sterile ---becomes
contaminated by:
1. Bacterial flora that colonize the
urethral mucosa
2. Vagina
3. Surrounding skin

Urinary tract infection

Significant Bacteriuria
100,000 organisms / ml
May still be significant even if < 100,000
1. Acutely symptomatic women
2. Symptomatic men
3. Catheterized patients

Urinary tract infection

CLINICAL ENTITIES:
1. CYSTITIS - bladder and urethra (lower tract)
- dysuria, frequency, urgency,
suprapubic tenderness
2. PYELONEPHRITIS (upper tract)
- flank pain, fever,

Urinary tract infection

MAY OCCUR AS:
1. Single event
2. Recurrent infection
2.1 RELAPSE -occurs 1-2 weeks after
stopping antibiotics; common in kidney
infection, structural abnormalities,
chronic bacterial prostatitis
2.2 REINFECTION diff. organisms;
new infection

Urinary tract infection

PATHOGENESIS:
3 Pathways:
1. Blood stream
2. Lymphatic channels
3. Ascending infection through the
ureters

Urinary tract infection

PATHOGENESIS:
- Gender and Sexual activity
- Pregnancy
- Obstruction
- Neurogenic bladder dysfunction
- Vesicoureteral reflux
- Bacterial virulence factors
- Genetic factors

Urinary tract infection

PRINCIPLES OF TREATMENT:
1.Diagnostic tests
2. Predisposing factors
3. Relief of symptoms does not always
indicate bacteriologic cure
4. Classify treatment
Cure / Failure / Recurrent

Urinary tract infection

PRINCIPLES OF TREATMENT:
5. Choice of Drugs / duration of
treatment
6. Repeated infections

Lead nephropathy
LEAD INTOXICATION
* Children ingesting lead-based paints
* Occupational exposure where lead containing
metals or paints are heated to high temperature such as
battery factories, smelters, salvage yards,
firing
ranges
* Environmental lead exposures

Lead nephropathy
Kidneys become atrophic as a result of ischemia to glomeruli,
fibrosis of the tubules
Hyperuricemic due to enhanced reabsorption of filtered
urates
Acute gouty arthritis may occur
Hypertension
Elevated serum level of lead

Lead nephropathy
Diagnosis:
elevated serum levels of lead
quantitation of lead excretion ffg
infusion of Ca disodium edetate
Treatment:
remove source
chelation

Acute Uric Acid nephropathy

Acute over production of uric acid and
extreme hyperuricemia seen in tumor lysis
syndrome in px given cytotoxic drugs in
lympho or myeloproliferative disorders
Prevention:
allupurinol 200-800 mg/d
Increase urine vol with diuretic
alkalinization

Gouty Nephropathy
Prolong form of hyperuricemia
Presence of crystalline deposits of uric acid
and monosodium urate salts in kidney
parenchyma.

Multiple myeloma
OVERPRODUCTION OF ONE IMMUNOGLOBULIN
MONOCLONAL GAMMOPATHY
BENCE JONES PROTEINS
BONE INVOLVEMENT
ANEMIA
NEPHROTIC SYNDROME/ PYELONEPHRITIS/
RENAL FAILURE

MEDULLARY SPONGE KIDNEY

DILATED COLLECTING DUCTS AND
MEDULLARY CYSTS
CALCULUS COLIC, HEMATURIA,
INFECTION

POLYCYSTIC KIDNEY DISEASE

CYSTS ARE FORMED FROM MONOCLONAL PROLIFERATION OF THE
TUBULAR EPITHELIUM
REMAINING RENAL PARENCHYMA REVEALS VARYING DEGREES OF
TUBULAR ATROPHY, INTERSTITIAL FIBROSIS, NEPHROSCLEROSIS

KIDNEYS ARE LARGE AND GRAPELIKE, CONTAINING CYSTS OF VARYING

SIZES, REDUCING BY COMPRESSION THE FUNCTIONING TISSUE

AUTOSOMAL DOMINANT INHERITANCE

DISCOMFORT, PAIN, GROSS HEMATURIA, INFECTION, COLIC,

RENAL FAILURE
PALPABLE, BILATERAL, IRREGULAR, RENAL MASSES

POLYCYSTIC KIDNEY DISEASE

NEPHROLITHIASIS OCCURS IN 15-20% USUALLY CA OXALATE AND
URIC ACID STONES

HYPERTENSION

HIGH HEMATOCRITS FOR THEIR LEVEL OF RENAL FUNCTION

FLUID OVERLOAD IS UNCOMMON BEC OF RENAL SALT WASTING

HEPATIC CYSTS, SPLEEN, PANCREAS, OVARY

INTRACRANIAL ANEURYSMS
COLONIC DIVERTICULAR DISEASE

POLYCYSTIC KIDNEY DISEASE

DIAGNOSIS:

AT LEAST 3-5 CYST IN EACH KIDNEY

TREATMENT:

TREAT HYPERTENSION AND INFECTION AGGRESSIVELY

ACE INHIBITOR

Proximal Tubule
Reabsorbs isosmotically about 55-60%

the filtrate
Almost all of the filtered glucose and
amino acids are reabsorbed but only
about 90% of the HCO3, 65% of the Na,
and 55% of the Cl

of

Phosphate
Amino
acids

Comparison of Normal anion gap acidosis

Finding

RTA type 1

RTA type 2 RTA type 4

Basic defect

distal
acidification

proximal

HCO3
reabsorption

Aldosterone
defc. or
resistance

Urine pH

>5.5

<5.5

<5.5

Plasma HCO3

<10 meq/L

14-20

>15

% filtered HCO3
excreted

<10

>15

<10

Serum K

low

low

High

Fanconi
syndrome

No

Yes

No

Comparison of Normal anion gap acidosis

Finding

RTA type 1 RTA type 2

Stones/
nephrocalcinosis

Yes

Rickets or
osteomalacia

Daily acid
excretion

low

normal

Daily HCO3
replacement
needs

<4 mmol/kg >4mmol/kg

1-2
10-15
meq/kg/day
adult
4-14 in
child

RTA type 4

Low
<4 mmol/kg
1-3; may not
need alkali if
hyperkalemia
corrected

BARTTERS SYNDROME:
- reabsorption of K
- S/S - dilute urine, polyuria,
hyperkaluria,
- defective growth
Tx - K supplement, Spironolactone

Ca
Ca BP

IDIOPATHIC FANCONI SYNDROME

- reabsorption of glucose, amino
acids, phosphates, bicarbonates, uric
acid, water, sodium, potassium
- S/S - growth failure, rickets,
hypokalemia, polyuria
- Tx Vitamin D

VITAMIN D RESISTANT RICKETS

- REABSORPTION OF PHOSPHATE
- S / S - PHOSPHATURIA
- LOW SERUM PHOSPHATE
- RICKETS
- TX VITAMIN D

Thank you