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
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