TUBULOINTERSTITIAL DISEASES Terminology 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 DISEASE Terminology ( 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 nephritis Causes 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 nephritis Pathogenetic 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 necrosis Etiology & 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 necrosis Etiology 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 Pyelonephritis Predisposing 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 : obstructive non-obstructive 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