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

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

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

Hydronephrosis

Severe Hydronephrosis and Hydroureter from Urethral Valves

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

Renal Calculus

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)

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

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

Pulmonary Hypoplasia

Amnion Nodosum

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

Cystic dysplasia-irregular shape

Cysts, Disordered Structure

Primitive Mesenchyme, Tubules

Cartilage

Autosomal Dominant Polycystic Kidneys

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

Autosomal Recessive Polycystic Kidneys

Dilated Collecting Ducts

Liver, ARPCKD

Ductal Plate Malformation

Congenital Hepatic Fibrosis

Simple Cysts

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

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

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)

Acute Tubular Necrosis

ATN – Clinical Course Initiation –Initial ischemic event –Slight decrease in urine output, increased BUN Maintenance –Oliguria ( 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

ATN –Recovery Phase

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

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

Osmotic Nephropathy- Intravenous Contrast Agents

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

Glomerulitis

Acute Cellular Rejection

Acute Antibody-Mediated Rejection

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.

Anti C4d IF – Peritubular Capillaries

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

Chronic Allograft Nephropathy – Chronic Rejection

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