This document discusses tubulointerstitial diseases, which involve inflammation and fibrosis of the renal tubules and interstitium. It describes two main types - acute and chronic tubulointerstitial nephritis. Causes include drugs, infections, autoimmune diseases, obstructive uropathy, and reflux nephropathy. Key histologic findings are interstitial inflammation, edema, and fibrosis with tubular injury and atrophy. Clinical features include renal dysfunction and tubular defects like aminoaciduria. Specific drug-induced forms like beta-lactam antibiotics and NSAIDs are outlined. Cystic diseases causing tubulointerstitial changes like PKD are also summarized.

1. TUBULOINTERSTITIAL
DISEASES
Al-Absi, M.D.

3. TUBULOINTERSTITIAL
DISEASES
• Tubulointerstitial nephritis:
– Primary - Inflammation limited to tubules & with uninvolved
or minimally involved glomeruli/vessels.
• Acute - Sudden onset & rapid decline in renal function
associated with interstitial edema
• Chronic - Protracted onset and slow decline in renal
function associated with interstitial fibrosis
– Secondary - Tubulointerstitial inflammation associated
with primary glomerular/vascular diseases
– Infectious – Tubulointerstitial inflammation associated with
presence of live microorganism
– Idiopathic – Tubulointerstitial nephritis where etiological agents or
causes are not known
– Reactive – Tubulointerstitial inflammation from the effects of
systemic inflammation. Kidney is sterile.

4. TUBULOINTERSTITIAL
DISEASES
• Urinary tract infection
– colonization of excretory system by live microorganism
– Pyelonephritis: tubulointerstitial nephritis
with pelvis and calyceal involvement
• Acute - usually suppurative inflammation involving
pelvi-calyceal system and parenchyma
• Chronic - involvement of pelvi-calyceal system
and parenchyma with prominent scarring

5. Tubulointerstitial Nephropathy
• Two distinct clinical presentations and course of
development:
(1) acute
(2) chronic
• Immunologic mechanisms often involved in
pathogenesis regardless of underlying cause
• Histologic changes evident on microscopy are
not specific for a given etiology

6. Immunologic Mechanisms in
Tubulointerstitial Nephropathy
• Drug acting as hapten binding to
tubulointerstitial parenchyma, making the latter
immunogenic
• Drug-induced damage through toxic
mechanisms, producing nephritogenic neo-
antigens
• Molecular mimicry by infectious agents inducing
cross-reactive immune response

7. Acute Tubulointerstitial
Nephropathy
• Drug-induced acute renal failure
allergic tubulointerstitial nephritis
nephrotoxic tubular injury
• Acute bacterial pyelonephritis
• Metabolic disorders
hypercalcemia
hyperuricosuria
• Environmental factors

8. Morphologic Features of Drug-
Induced ATIN
• Increased interstitial volume due to:
mononuclear cell infiltration
lymphocytes, plasma cells, macrophages,
granulomatous reaction, eosinophiles
interstitial edema
• Tubular injury characterized by:
disruption of tubular basement membranes
epithelial cell necrosis

11. Chronic Tubulointerstitial
Nephropathy
• Drug-induced
analgesics, cyclosporine, antineoplastic
agents
• Infection-related
chronic bacterial pyelonephritis
vesicoureteral reflux
obstructive uropathy
• Autoimmunity
SLE, Sjogren’s Disease

12. Morphologic Features of Chronic
TIN
• Interstitial fibrosis with less
prominence of cellular infiltrates
• Decreased vascularity due to
reduced volume of capillaries
• Tubular atrophy
• Secondary glomerulosclerosis

17. Clinical Evidence of Tubular
Dysfunction in TIN
• Renal glucosuria and amino aciduria
• Hypophosphatemia
• Hyperchloremic acidosis
Hypokalemia
Hyperkalemia
• Reduced urine concentrating ability
• Sodium wasting
• Pyuria and urine epithelial cells

18. UTI and Pyelonephritis
•Acute versus Chronic
•Ascending versus Hematogenous
•Bacterial Adhesion
• Vesicoureteral reflux

19. UTI and Pyelonephritis
• Asymptomatic & symptomatic
• Pathology: Interstitial edema, and
inflammation
• Chronic Pyelonephritis and Reflux

20. Clinical Aspects of TIN Related to
Specific Drugs or Other Causes
• Drugs
beta lactam derivative antibiotics
NSAIDS
analgesics
aminoglycosides
• Environmental agents
• Alternative medications
• Bacteria

21. Acute Tubulointerstitial Nephritis
Induced by Beta-Lactam
Derivatives
• Duration of drug administration may vary from
few days to several weeks; not dose-dependent
• Clinical manifestations: fever, rash,
eosinophilia, oliguric or non-oliguric renal failure
• Urinary findings: hematuria (microscopic or
gross), pyuria, proteinuria, eosinophiluria

22. Acute Tubulointerstitial
Nephritis Induced by Beta-
Lactam Derivatives
• Pathogenesis: possible immune-
medicated
• Pathology: Enlarged kidney, IS
inflammation
• Clinical Course

23. Tubulointerstitial Nephritis
Induced by Non-steroidal Anti-
inflammatory Drugs
Usually occurs after prolonged drug
administration and may present as:
• Acute impairment of renal function with non-
nephrotic range proteinuria, hyperkalemia and
other evidence of tubular dysfunction
• Clinical manifestations similar to those above,
but with nephrotic range proteinuria
• Nephrotic syndrome without other evidence of
renal impairment

24. Analgesic Abuse Nephropathy
• Initial occurrence reported in association
with phenacetin abuse
• Has been associated with long term use
of analgesic mixtures containing
phenacetin (?acetaminophen) and aspirin
or other non-steroidal anti-inflammatory
drugs
• Drug accumulates and is highly
concentrated in the renal medullary
interstitium

25. Analgesic Abuse Nephropathy
Clinical features:
• Slow progressive impairment of renal function
• Tubular dysfunction characterized by the
development of hyperkalemic, hyperchloremic
renal tubular acidosis and nephrogenic diabetes
insipidus
• Impairment of sodium reabsorption
•May progress to the development of papillary
necrosis
•Uro-epithelia cancer

26. Aminoglycoside Nephrotoxicity
• Recognized potential for causing acute renal
failure in hospitalized patients
• Drug enters the tubular lumen by glomerular
filtration and is reabsorbed by proximal tubules
where tubule cell injury leading to necrosis may
occur.
• Manifested clinically by progressive increase in
serum creatinine, renal K+ and Mg++ wasting,
renal glucosuria

27. Cystic Diseases
• Cyst Formation: large fluid-filled pouches
• Causes
• PKD

28. PKD
• Autosomal dominant or recessive
• Prevalence
• ADPKD1, and ADPKD2

30. PKD
• Pathology
• Other organs involvment
• Prognosis: ADPKD2 is worse

31. Acquired cystic disease
• Pathogenesis
• Organs involved
• Long term risks

33. Balkan Endemic Nephropathy:
Clinical Features
• Slowly progressive renal insufficiency
• Urine sediment usually unremarkable
• Proteinuria usually <1.0 g/day
• Renal tubular dysfunction
• Hypertension in <25% of patients
• Gross hematuria: may be a sign of uroepithelial
tumor

34. Chinese Herbs Nephropathy
• Rapidly progressive interstitial nephropathy
attributed to weight-reducing diets containing
Chinese herbs
• Renal pathology closely resembling the
characteristic lesions of Balkan Endemic
Nephropathy
• Multiple foci of cellular atypia in the renal pelvis
and ureters
•Aristolochic acid, a known carcinogen and
suspected etiologic agent