TUBULOINTERSTITIAL DISEASESTerminology

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.

TUBULOINTERSTITIAL DISEASETerminology ( cont.)

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

Tubulointerstitial nephritisCauses

Infections: (1) Reactive (2) Infectious Drug reaction Obstruction:

(1) with infection: pyelonephritis / pyonephrosis (2) without infection : hydronephrosis

Non-obstructive : vesicoureteral reflux Immune mediated :

(1) with anti TBM antibodies, can be 10 or 20 (2) with IC deposition which can be 10 or 20

Tubulointerstitial nephritisPathogenetic mechanisms

Antibody mediated• Anti-TBM-antibody disease• Immune-complex disease

T-cell mediated Associated with infections

• Reactive• Infectious

Tubuluinterstitial nephritis

Primary anti-TBM-antibody nephritis• IgG antibodies directed against tubular basement

membrane

• Linear staining on immunofluorescence microscopy

• Edema and mononuclear cells in interstitium

• Glomeruli and blood vessels are unremarkable

Secondary anti-TBM-antibody disease• 20 to 10 glomerulonephritidies, allograft nephropathy

Tubulointerstitial nephritis with immune complexes

Primary immune complex disease • granular staining on IF microscopy on tubular

basement membrane• Primary – Rare• Secondary – Usually associated with primary

glomerulonephritidies involving TBM and interstitium– e.g SLE, MPGN, Membranous GN etc.

Cell-mediated mechanism

Delayed-type hypersensitivity reaction• Activated CD4+ T and monocyte / macrophage

cells releases cytokines which modulates inflammatory reactions and fibrogenesis

• Cytotoxic T-cell injury in which CD4+ T and CD8+ T play important role

Pathology of primary IN

bilaterally symmetrical enlargement of kidney

edema inflammatory cells in interstitium tubular change including tubulitis, breaks in

TBM, necrosis of tubular epithelial cells etc.

Pathology of renal failure

acute

chronic

Acute renal failure (ARF)

Rapid deterioration of renal function in a relatively short period of time

Sudden inability to maintain normal fluid and electrolyte homeostasis

Marked decrease in renal output May be of glomerular, tubular, interstitial or

vascular origin

Causes of ARF

acute tubular necrosis infarction & cortical necrosis organic diseases of renal vessels severe forms of glomerulonephritis severe infection acute tubulointerstitial nephritis outflow obstruction (post-renal) impairment of blood flow (pre-renal)

Acute tubular necrosis (ATN)

commonest cause of acute renal failure develops due to :

• direct poisoning of tubules (nephrotoxic lesions)

• renal ischemia (tubulorrhexic lesions)

Acute tubular necrosisEtiology & Pathogenesis

Ischemic in origin (Tubulorrhexic lesion)

Prolonged ischemia due to:

Shock: postoperative, intra-operative, post-traumatic, septic, hypotensive

Hemorrhage: postpartum hemorrhage, abruptio placentae

Other: severe burns, transfusion accidents, dehydration, heat stroke, crushing injuries, non-traumatic

rhabdomyolysis, paroxysmal hemoglobinuria etc.

Acute tubular necrosisEtiology and Pathogenesis

Direct effects of toxins (Nephrotoxic lesion)

Therapeutic agents :• Antibiotics : Aminoglycosides, NSAIDs,

chemotherapeutic agents, etc.• Heavy metals: mercury, lead, gold etc.• Radiocontrast agents• Multiple bee stings, scorpion bites etc.

Gross pathology

bilaterally enlarged & swollen kidney due to edema

Cut surface bulges and has a flabby consistency

widened & pale cortex dark & congested medulla

Light microscopy

dilated lumen with flattened epithelial cells Greatest change in proximal tubules, varies in two

forms loss of brush borders- proximal tubules evidence of regeneration of epithelial cells hyaline, granular and pigmented casts interstitial edema & inflammation Intra-vascular collection of nucleated red blood

cells

ATN- Prognosis

depends upon underlying cause, over all mortality rate 50%

post-traumatic (62%), post-operative (56%), medical (46 %), obstetric (17 %)

Higher in older debilitated pts. & in pts.with multiple organ disease

good for uncomplicated and younger patients

Chronic renal failure Occurs in all cases of end-stage renal disease of

whatever etiology GFR falls below 20% of normal End result of all chronic renal disease which can

be glomerular, tubulointerstitial or vascular in origin

Characterized by prolonged signs and symptoms of uremia

Is a major cause of death in renal disease

Chronic renal failure

Systemic (visceral) manifestations• Enlarged heart & pericarditis• Uremic pneumonitis & pleuritis• Uremic colitis• Uremic encephalopathy• Hypoplastic anemia

TUBULO-INTERSTITIAL DISEASE

Urinary tract infection • colonization of excretory system by live microorganism• Most caused by gram negative enteric organism• Most common form of renal involvement is:

– Pyelonephritis: bacterial infection of the kidney that affects parenchyma, calyces and pelvis

• Acute - usually suppurative inflammation involving – pelvi-calyceal system and parenchyma

• Chronic - involvement pelvi-calyceal system and parenchyma with prominent

scarring

Pyelonephritis

• Acute: usually suppurative, often associated

(1) with / without obstruction

(2) ascending infection through vesicoureteral reflux (3) from hematogenous dissemination.

• Chronic: inflammation with prominent scarring; may be

(1) obstructive with recurrent infection

(2) non-obstructive with vesicoureteral reflux → reflux nephropathy

Acute PyelonephritisPredisposing factors

Urinary obstruction: congenital or acquired Instrumentation of urinary tract Vesicoureteral reflux Pregnancy: 4-6% develops bacteriuria Gender and age Preexisting renal lesions Diabetes mellitus, immunosuppression &

immunodeficiency

Acute pyelonephritis route of invasion :

• via blood stream• ascending route

obstructive non-obstructive

role of vesicoureteral reflux and infected urine

Chronic pyelonephritis

It is a chronic tubulointerstitial inflammation involving renal parenchyma, pelvis and calyces associated with scarring

non-obstructive• reflux nephropathy

obstructive