1. Kidney Lecture 3 Obstructive, Congenital and Cystic Diseases, Acute Tubular Necrosis, Renal Transplant

2. Learning Objectives Describe the clinical and pathologic features of: –Hydronephrosis –Urolithiasis –Congenital and Cystic Renal Diseases –Acute Tubular Necrosis –Rejection of Renal Allograft

3. Obstruction Congenital abnormalities Urinary calculi Prostatic hyperplasia TumorsInflammation Sloughed papillae Pregnancy Uterine prolapse and cystocele Neurogenic bladder

4. Hydronephrosis

5. Severe Hydronephrosis and Hydroureter from Urethral Valves

6. UrolithiasisTypes –Calcium oxalate +/- phosphate – 70% Hypercalcemia, hypercalcuria, hyperoxaluria –Magnesium Ammonium Phosphate Urea-splitting bacteria –Urate Gout, leukemia, acid urine –Cystine Metabolic abnormality Clinical –Intense, colicky flank pain Small stones passing through ureter, obstruction –Hematuria Ulceration by large or small stones

7. Renal Calculus

9. Congenital and Cystic Renal Diseases Renal Agenesis Cystic renal dysplasia “multicystic kidney” Autosomal recessive polycystic disease Autosomal dominant polycystic disease Nephronophthsis medullary cystic disease Simple renal cysts (acquired)

10. Renal Agenesis -Potter Phenotype Complete absence of kidneys Oligohydramnios Flattened face Rocker-bottom feet Pulmonary hypoplasia Amnion nodosum –Nodules of fetal squamous cells on placental surface –Low fluid volume allows contact of fetal skin with amnion

11. Figure 10-4 Infant with oligohydramnios sequence. Note the flattened facial features and deformed right foot (talipes equinovarus). Downloaded from: Robbins & Cotran Pathologic Basis of Disease © 2005 Elsevier Renal Agenesis -Potter Phenotype

12. Pulmonary Hypoplasia

13. Amnion Nodosum

14. Cystic Diseases Cystic renal dysplasia –Often obstruction during renal development –Cartilage, undifferentiated mesenchyme Autosomal Dominant (Adult-type) Polycystic Kidney Disease –PDK1, PDK2 mutations –Cerebral berry aneurysms –Adult-onset hematuria followed by chronic kidney failure

16. Cystic dysplasia-irregular shape

17. Cysts, Disordered Structure

18. Primitive Mesenchyme, Tubules

19. Cartilage

20. Autosomal Dominant Polycystic Kidneys

21. Cystic Diseases (Continued) Autosomal Recessive (Infantile-type) Polycystic Kidney Disease –PKHD1 gene – fibrocystin –Severe renal dysfunction or renal failure at birth Nephronophthsis medullary cystic disease –Hematuria, renal failure in child or young adult –NPH1, NPH2, NPH3 genes Medullary Sponge Kidney –Often asymptomatic, discovered incidentally Simple cysts –Very common, obstruction of a few tubules

22. Autosomal Recessive Polycystic Kidneys

24. Dilated Collecting Ducts

27. Liver, ARPCKD

28. Ductal Plate Malformation

29. Congenital Hepatic Fibrosis

31. Simple Cysts

32. Question 1 Which of the following is characterized by oligohydramnios and absence of kidneys by prenatal ultrasound? –Chronic glomerulonephritis –Hypertensive nephrosclerosis –Reflux nephropathy –Autosomal dominant polycystic kidney disease –Renal agenesis

33. Question 1 Which of the following is characterized by oligohydramnios and absence of kidneys by prenatal ultrasound? –Chronic glomerulonephritis –Hypertensive nephrosclerosis –Reflux nephropathy –Autosomal dominant polycystic kidney disease –Renal agenesis

34. Acute Tubular Necrosis (ATN) Most common cause of renal failure Rapid reduction of renal function and urine flow Often reversible Common causes –Pre-renal: Ischemia –Toxic (drugs, contrast agents, myoglobin, hemoglobin) –Interstitial nephritis (drugs, rejection, infection) –Disseminated intravascular coagulation –Post renal: Urinary obstruction (tumors, prostatic hyperplasia, calculi, thrombi)

36. Acute Tubular Necrosis

39. ATN – Clinical Course Initiation –Initial ischemic event –Slight decrease in urine output, increased BUN Maintenance –Oliguria (40-400 ml urine per day) –Rising blood urea nitrogen (BUN) and creatinine –Electrolyte imbalance Recovery –Increasing urine output, sometimes diuresis –Hypokalemia –Normalization of BUN and creatinine levels –Often complete recovery

40. ATN –Recovery Phase

42. Question 2 Acute tubular necrosis is associated with which of the following clinical findings? –Elevated serum creatinine –Lower extremity edema –White blood cell casts –Hematuria –Proteinuria

43. Question 2 Acute tubular necrosis is associated with which of the following clinical findings? –Elevated serum creatinine –Lower extremity edema –White blood cell casts –Hematuria –Proteinuria

44. Osmotic Nephropathy- Intravenous Contrast Agents

45. Rejection of Renal Allograft Hyperacute rejection - rare Acute rejection –Banff Classification –Cellular rejection MHC, T cell mediated Interstitial lymphocytic infiltrate, tubulitis –Vascular rejection Antibody mediated Lymphocytic infiltrate of arteries, C4d deposition Chronic Graft Changes –Atherosclerosis, fibrosis, tubular atrophy, transplant glomerulopathy

46. Glomerulitis

47. Acute Cellular Rejection

48. Acute Antibody-Mediated Rejection

49. C4d C4d: presence indicates antibody mediated (humoral) rejection. Found in peritubular capillaries. C4d is a complement split product, inactivated c4b, and reflects complement activation by the classical pathway.

50. Anti C4d IF – Peritubular Capillaries

52. Chronic Changes in Allograft Chronic rejection Recurrence of renal disease Drug toxicity De novo renal disease Interstitial fibrosis and tubular atrophy

53. Chronic Allograft Nephropathy – Chronic Rejection

54. Other Causes of Graft Dysfunction Calcineurin inhibitor toxicity –Anti-rejection drugs also nephrotoxic Acute tubular necrosis –Most common from deceased donor with long ischemia time prior to transplant Polyoma and other viral infections Recurrence of initial cause of renal failure –Proteinuria from FSGS can occur in immediate post transplant period