Tubulointerstitial Disorders PDF - Ponce Health Sciences University

Pathology Tubulointerstitial Disorders Tubulointerstitial Disorders Axel Báez-Torres, M.D.,FCAP Associate Professor Pathology Department Ponce Health Sciences University TUBULOINTERSTITIAL DISORDERS Acute tubular injury: Ischemic acute tubular injury Nephrotoxic acu...

Pathology Tubulointerstitial Disorders Tubulointerstitial Disorders Axel Báez-Torres, M.D.,FCAP Associate Professor Pathology Department Ponce Health Sciences University TUBULOINTERSTITIAL DISORDERS Acute tubular injury: Ischemic acute tubular injury Nephrotoxic acute tubular injury Tubulointerstitial nephritis: Infectious TIN Non-infectious TIN ACUTE TUBULAR INJURY Formerly called acute tubular necrosis. Severe, but potentially reversible, renal failure due to impairment of tubular epithelium caused by ischemia or toxic injury  Tabla 16-11 Causes of Acute Tubular Injury Ischemia Nephrotoxins Massive hemorrhage Antibiotics (e.g.: aminoglycosides, amphrotericin B) Septic shock Radiographic contrast agents Severe burns Heavy metals (e.g.: mercury, lead, cisplatin) Dehydration Organic solvents (e.g.: ethylene glycol, carbon tetrachloride) Prolonged diarrhea Poisons (e.g.: paraquat) Congestive heart failure Heme proteins Volume redistribution Myoglobin (from rhabdomyolysis, e.g.: with crush injury) (e.g.:pancreatitis, peritonitis) Hemoglobin (from hemolysis, e.g.: with transfusion reaction ISCHEMIC ATI Seen in a variety of conditions that result in decreased renal perfusion Most common type of ATI and one of the most common causes of acute renal failure Onset is most commonly signaled by oliguria (less than 400 ml of urine per day) ISCHEMIC ATI The pathogenesis of ischemic ATI is mediated by both disturbance in blood flow and tubule cell injury. TOXIC ATI Now an uncommon type of ATI The majority of cases currently seen are associated with drugs such as antibiotics The most likely pathogenetic mechanism is direct toxicity against the tubular epithelium ACUTE TUBULAR INJURY Pathology: Ischemic ATI causes patchy focal tubular epithelial necrosis with preferential involvement of straight segments of proximal tubules and thick ascending limb of Henle ACUTE TUBULAR INJURY Pathology: Toxic ATI causes extensive tubular epithelial necrosis along the proximal tubule segments ACUTE TUBULAR INJURY Clinical course: No specific treatment is known for ATI once it is established If the cause of ATI is removed immediately, renal function often recovers within 1 to 2 weeks Dialysis may be required for those who develop uremia Increased urine output and a fall in serum creatinine herald the recovery phase TUBULOINTERSTITIAL NEPHRITIS Disorders which affects primarily the tubules and interstitium, causing functional alterations manifested clinically by defects in tubular function such as impaired ability to concentrate urine, salt wasting and diminished ability to excrete acids  Table 20-9. Causes of Tubulointerstitial Nephritis Infections Acute bacterial pyelonephritis Physical Factors Chronic pyelonephritis (including reflux nephropathy) Chronic urinary tract obstruction Other infections (e.g., viruses, parasites) Radiation nephropathy Toxins Neoplasms Drugs Multiple myeloma (cast nephropathy) Acute hypersensitivity interstitial nephritis Immunologic Reactions Analgesic nephropathy Transplant rejection Heavy metals Sjögren syndrome Lead, cadmium Sarcoidosis Metabolic Diseases Vascular Diseases Urate nephropathy Miscellaneous Nephrocalcinosis (hypercalcemic nephropathy) Balkan nephropathy Hypokalemic nephropathy Nephronophthisis-medullary cystic disease complex Oxalate nephropathy "Idiopathic" interstitial nephritis  TUBULOINTERSTITIAL NEPHRITIS May be broadly divided in two categories: Infectious TIN (pyelonephritis) Non-infectious TIN PYELONEPHRITIS Infection of the renal parenchyma with involvement of the pelvis and calyces Clinically divided in acute and chronic variants  ACUTE PYELONEPHRITIS Renal lesion associated with urinary tract infection In 95% of cases bacteria gain access to the kidney via the ureters (ascending infection) In the remaining cases, bacteria gain access to the kidney through the blood (hematogenous infection)  RENAL INFECTIONS The most common bacteria associated to urinary tract infection is Escherichia coli, followed by Proteus, Klebsiella and Enterobacter Hematogenous infections are usually due to bacteremia with virulent organisms such as Staph aureus ACUTE PYELONEPHRITIS Clinical features: The classic symptoms are fever, back pain and dysuria The white blood cell count is usually elevated The urinalysis shows bacteriuria, pyuria, and frequently hematuria Urine culture demonstrates more than 105 colony- forming units per milliliter in more than 80% of patients ACUTE PYELONEPHRITIS Clinical course: Antibiotic therapy results in complete recovery in the majority of cases Complications are occasionally seen, most frequently associated to urinary tract obstruction, diabetes, immunosuppression or severe systemic infection ACUTE PYELONEPHRITIS Clinical course: The most feared complications of acute pyelonephritis are: Papillary necrosis: Seen mainly in diabetics and in those with urinary tract obstruction Pyonephrosis: Associated to total or almost complete obstruction Perinephric abscess: Associated to poor response to antibiotic therapy.  CHRONIC PYELONEPHRITIS Implies chronic infection of the renal parenchyma or the sequela of past episodes of repeated infections Important cause of end-stage kidney disease  CHRONIC PYELONEPHRITIS Variants: Reflux neprhopathy Chronic obstructive pyelonophritis  REFLUX NEPHROPATHY More common form of chronic pyelonephritis Associated with permanent renal scarring Results from superimposition of a urinary tract infection on congenital vesicoureteral reflux and intrarenal reflux  REFLUX NEPHROPATHY Clinical features: Many patients have impaired renal function Many patients do not have prior history of renal diseases or urinary tract infection  REFLUX NEPHROPATHY Morphology: External surface shows single or multiple large, broad- based, U-shaped depressions Beneath the surface scars are deformed papillae, with flattening of calyces and dilation of pelvis  CHRONIC OBSTRUCTIVE PYELONEPHRITIS Morphology: Generalized atrophy of the parenchyma and dilatation of all portions of the pelvis Calculi may be present CHRONIC PYELONEPHRITIS Microscopy: Atrophic dilated tubules (thyroidization) Chronic interstitial inflammation Interstitial fibrosis  XANTHOGRANULOMATOUS PYELONEPHRITIS Rare form of chronic pyelonephritis often associated with calculi and Proteus infection Results in a yellow nodular appearance of the kidney owing to the presence of lipid-laden foamy macrophages  CHRONIC PYELONEPHRITIS Clinical course: Chronic obstructive form may be insidious in onset or may present with acute recurrent pyelonephritis Reflux type may have a silent onset, with patients coming to medical attention late in the course of the disease  CHRONIC PYELONEPHRITIS Clinical course: Patients with reflux nephropathy who develop proteinuria are prone to have focal segmental glomerulosclerosis. Those patients shows an increase likelihood of progression to chronic renal failure NON-INFECTIOUS TUBULOINTERSTITIAL NEPRHITIS Primarily induced by drugs and toxins Three predominant pathogenetic mechanisms: Induction of interstitial immunologic reaction Immediate direct injury to tubules Subtle but cumulative injury to tubules  ACUTE DRUG-INDUCED INTERSTITIAL NEPRHITIS Commonly associated with use of antibiotics, NSAID’S and diuretics Currently the most common cause of interstitial nephritis Believed to result from allergic or immune reaction to the medications  ACUTE DRUG-INDUCED INTERSTITIAL NEPRHITIS Pathogenesis: The combination of the medication bound to the tubular basement membrane elicits an immune reaction with production of antibodies directed against the antibiotic- TBM complex  ACUTE DRUG-INDUCED INTERSTITIAL NEPRHITIS Clinical features: Non-specific symptoms including nausea, vomiting, malaise and fever The most common clinical finding is renal insufficiency Functional defects of tubules Low-grade proteinuria  ACUTE DRUG-INDUCED INTERSTITIAL NEPRHITIS Clinical features: The disease usually develops after the patient has been taking the medication between 1 and 30 days, with a mean of approximately one week ACUTE DRUG-INDUCED INTERSTITIAL NEPRHITIS Laboratory values: Blood eosinophilia (greater than 400 cells per microliter) seen in 50% of cases Eosinophils in the urine, present in less than half of cases Proteinuria Hematuria  ACUTE DRUG-INDUCED INTERSTITIAL NEPRHITIS Morphology: Interstitial edema Interstitial inflammation with prominent eosinophils Fibrosis (if present suggest a chronic disease)  ACUTE DRUG-INDUCED INTERSTITIAL NEPRHITIS Clinical course: Favorable prognosis providing that the precipitating cause is promptly recognized and removed The presence of interstitial fibrosis indicated probable long-term decrease in renal function  ANALGESIC NEPRHOPATHY Tubulointerstitial disorder caused by excessive intake of analgesic mixtures and characterized morphologically by chronic tubulointerstitial inflammation and papillary necrosis  ANALGESIC NEPRHOPATHY The majority of cases have been associated with intake of products containing phenacetin or acetaminophen, acetylsalicylic acid, and caffeine, codeine, or barbiturates  ANALGESIC NEPRHOPATHY Pathogenesis: Related to direct toxic effect of analgesics of their metabolites on renal tubules and blood vessels combined with the ischemic damage induced by aspirin intake by decreasing the vasodilatory effects of prostaglandin ANALGESIC NEPRHOPATHY Clinical features: Insidious onset of renal failure Complications include hypertension, pyelo- nephritis, hydronephrosis, pyonephrosis and urolithiasis Urothelial carcinoma of the renal pelvis is the most serious potential complication ANALGESIC NEPRHOPATHY Morphology: Bilateral small kidneys with yellow and friable papillae and cortical scarring Microscopically there is papillary necrosis, tubular atrophy, chronic interstitial inflammation and interstitial fibrosis  ANALGESIC NEPRHOPATHY Clinical course: The disease frequently runs a progressive course The prognosis is better if the patient discontinues taking analgesics before the development of severe renal insufficiency PATHOLOGY OF RENAL TRANSPLANTATION  RENAL TRANSPLANTANTION Cadaveric and living related donors used Living related organs fair slightly better  RENAL TRANSPLANTATION REJECTION Major barrier to transplantation The recipient immune system recognizes the graft as being foreign and attacks it RENAL TRANSPLANTATION Graft failure In the absence of rejection, it should be ascertained whether the graft failure results from acute tubular injury, acute infectious pyelonephritis, obstruction, recurrent or de novo glomerulonephritis, or toxicity associated with the therapeutic agents used to modulate the immune response RENAL TRANSPLANTATION T-cell mediated rejection: Also called cellular rejection Destruction of graft cells by CD8+ CTLs, or Hypersensitivity reactions triggered by cytokines- secreting activated CD4+ helper cells RENAL TRANSPLANTATION B-cell mediated rejection: Also called humoral or antibody-mediated rejection Preformed or formed antibodies attack alloantigens in the graft, activating complement via the classical pathway RENAL TRANSPLANTATION PATHOLOGY Banff Diagnostic Categories for Renal Alograft Biopsies Normal Antibody-mediated rejection -Acute rejection -Chronic active rejection Borderline/Suspicious for acute T cell rejection T-cell mediated rejection -Acute rejection -Chronic active rejection Non-specific interstitial fibrosis and tubular atrophy Other  HYPERACUTE ANTIBODY-MEDIATED REJECTION Occurs within minutes to hours after transplantation Mediated be presence of preformed circulating antibodies against donor endothelial antigens Manifested clinically by a sudden cessation of urine output, pain in the area of graft site and fever  HYPERACUTE ANTIBODY-MEDIATED REJECTION Quite rare rejection pattern due to pre-transplant crossmatching (testing the recipient for anti-donor antibodies) The only treatment is immediate removal of the graft  ACUTE ANTIBODY-MEDIATED REJECTION Seen within the first few weeks or months after transplantation Characterized by abrupt onset of azotemia and oliguria due to development of anti-donor antibodies  ACUTE ANTIBODY-MEDIATED REJECTION Characterized morphologically by vascular damage manifested as arteritis, fibrinoid necrosis and thrombosis. A key diagnostic feature is positive immunofluorescence for anti-C4d in peritubular capillaries Patients responds poorly to immunosuppressive therapy  ACUTE T-CELL MEDIATED REJECTION Occurs within days or weeks after transplantation Characterized morphologically by interstitial infiltrates of lymphocytes and macrophages, edema, lymphocytic tubulitis and tubular necrosis In its pure form is the most benign or treatable form of rejection, responding well to immunosuppressive therapy  CHRONIC REJECTION Appears month to years after transplantation Clinically characterized by progressive azotemia, oliguria, hypertension and weight gain Microscopically is characterized by arterial / arteriolosclerosis, tubular atrophy and interstitial fibrosis  CHRONIC REJECTION Most frequent cause of graft loss today The pathogenesis is apparently related to low-grade rejection or due to repeated clinically inapparent acute rejection episodes Patients does not respond to immunosuppressive therapy  OTHER PATHOLOGIC PROCESSES THAT MAY BE SEEN IN TRANSPLANTED KIDNEYS Recurrent disease Acute tubular necrosis Cyclosporine or FK506 toxicity BK virus or cytomegalovirus infection Post-transplant lymphoproliferative disorder Figures and tables in this presentations are from Robbins Pathology 10th edition.