16 The Kidney J. Charles Jennette FPO FPO FPO FPO CONGENITAL ANOMALIES IgA Nephropathy (Berger Disease) Renal Agenesis Anti-Glomerular Basement Membrane Ectopic Kidney Glomerulonephritis Horseshoe Kidney ANCA Glomerulonephritis Renal Dysplasia VASCULAR DISEASES CONGENITAL POLYCYSTIC KIDNEY DISEASES Renal Vasculitis Autosomal Dominant Polycystic Kidney Disease Hypertensive Nephrosclerosis (Benign Nephrosclerosis) (ADPKD) Malignant Hypertensive Nephropathy Autosomal Recessive Polycystic Kidney Disease Renovascular Hypertension (ARPKD) Thrombotic Microangiopathy Nephronophthisis–Medullary Cystic Disease Cortical Necrosis ACQUIRED CYSTIC KIDNEY DISEASE DISEASES OF TUBULES AND INTERSTITIUM GLOMERULAR DISEASES Acute Tubular Necrosis (ATN) Nephrotic Syndrome Pyelonephritis Nephritic Syndrome Analgesic Nephropathy Glomerular Inflammation and Immune Mechanisms Drug-Induced (Hypersensitivity) Acute Tubulointerstitial Minimal-Change Glomerulopathy Nephritis Focal Segmental Glomerulosclerosis (FSGS) Light-Chain Cast Nephropathy Membranous Glomerulopathy Urate Nephropathy Diabetic Glomerulosclerosis RENAL STONES (NEPHROLITHIASIS AND Amyloidosis UROLITHIASIS) Hereditary Nephritis (Alport Syndrome) OBSTRUCTIVE UROPATHY AND HYDRONEPHROSIS Thin Glomerular Basement Membrane Nephropathy RENAL TRANSPLANTATION Acute Postinfectious Glomerulonephritis MALIGNANT TUMORS OF THE KIDNEY Type I Membranoproliferative Glomerulonephritis Wilms’ Tumor (Nephroblastoma) Type II Membranoproliferative Glomerulonephritis Renal Cell Carcinoma (RCC) (Dense Deposit Disease) Transitional Cell Carcinoma Lupus Glomerulonephritis {AU1} The kidney serves as the principal regulator of the fluid tabolism and blood pressure as well as erythropoietin, and electrolyte content of the body. The task is accom- a hormone that stimulates red cell production in the plished by the complex filtering mechanism of the bone marrow. The nephron is the architectural unit of glomerulus and the selective tubular reabsorption of the kidney and includes the glomerulus and its tubule, solutes from the filtrate. The kidney also has endocrine the latter terminating at the common collecting system function secreting renin, which regulates sodium me- (see Fig. 16-4). 437437 438 Essentials of Rubin’s Pathology The kidney consists of the glomerular, vascular tubular, PATHOLOGY: The histologic hallmark of renal and interstitial anatomic compartments. Many renal dis- dysplasia is undifferentiated tubules and ducts eases are best understood in relation to the compartments lined by cuboidal or columnar epithelium. These affected and the associated functional impairment. structures are surrounded by mantles of undifferentiated mesenchyme, which sometimes contain smooth muscle and islands of cartilage (Fig. 16-1). Rudimentary glomeruli CONGENITAL ANOMALIES may be present, and the tubules and ducts may be cystically dilated. Renal dysplasia can be unilateral or bilateral, the in- Renal Agenesis Is the Complete Absence of Renal volved kidney can be abnormally large or very small, and the Tissue kidney may contain multiple cysts. Most infants born with bilateral renal agenesis are stillborn CLINICAL FEATURES: In most patients with and have Potter sequence (see Chapter 6). Bilateral agenesis is cystic forms of renal dysplasia, a palpable flank often associated with other congenital anomalies, especially mass is discovered shortly after birth, although elsewhere in the urinary tract or lower extremities. Unilateral small multicystic kidneys may not become apparent until renal agenesis is not a serious matter if there are no associ- many years later. Unilateral dysplasia is adequately treated ated anomalies, because the contralateral kidney undergoes by removing the affected kidney. Bilateral aplastic dysplasia sufficient hypertrophy to maintain normal renal function. in the fetus can cause oligohydramnios and the resulting Potter sequence and life-threatening pulmonary hypoplasia. Ectopic Kidney Is an Abnormal Location of the Organ CONGENITAL POLYCYSTIC KIDNEY The misplaced kidney is usually in the pelvis. Most com- monly, this condition results from failure of the fetal kid- DISEASES ney to migrate from the pelvis to the flank. Renal ectopia Congenital polycystic kidney diseases are a heterogeneous group of may involve only one kidney, or it may be bilateral. genetic disorders that are characterized by distortion of the renal parenchyma by numerous cysts. The diseases vary in age of onset, Horseshoe Kidney Is a Single, Large, Midline Organ severity, mode of inheritance, and structure of cysts (Fig. 16-6). Horseshoe kidney results when an infant is born with fused kidneys, usually at the lower poles. This anomaly usually has no clinical consequences but can increase the risk for obstruction and pyelonephritis (see below) because the ureters must cross over the junction between the two kid- neys that are fused at their lower pole. Renal Dysplasia Is a Developmental Disorder Renal dysplasia is characterized by undifferentiated tubular struc- tures surrounded by primitive mesenchyme, sometimes with hetero- topic tissue such as cartilage. Cysts often form from the abnormal tubules. PATHOGENESIS: Renal dysplasia results from an abnormality in metanephric differen- tiation that reflects multiple genetic and so- matic causes. Some familial forms of dysplasia proba- bly result from abnormal differentiation signals that affect the inductive interactions between the ureteric bud and the metanephric blastema. Many forms of dys- plasia are accompanied by other urinary tract abnor- malities, especially those that cause obstruction of urine flow. This association suggests that an obstruc- Renal dysplasia. Immature glomeruli, tubules, and FIGURE 16-1. tion to urine flow in utero can cause dysplasia. cartilage are surrounded by loose, undifferentiated mesenchymal tissue. CHAPTER 16: THE KIDNEY 439 Autosomal Dominant Polycystic Kidney Disease Cysts arise in segments of renal tubules and develop (ADPKD) Features Enlarged Multicystic Kidneys from a few cells that proliferate abnormally. The wall of the tubule becomes covered by an undifferentiated epithelium Autosomal Dominant Polycystic Kidney Disease (ADPKD) is composed of cells with a high nucleus-to-cytoplasm ratio the most common of a group of congenital diseases that are charac- and only few microvilli. Eventually, most of the cysts be- terized by numerous cysts within the renal parenchyma (Fig. 16- come disconnected from the tubules. Cyst fluid initially ac- 2). It affects 1:400 to 1:1000 individuals in the United cumulates from glomerular filtrate, followed by fluid de- States. Half of all patients with this disease eventually de- rived from transepithelial secretion. Cysts originate in less velop end-stage renal failure. than 2% of nephrons; therefore, factors other than crowd- ing of normal tissue by the expanding cysts likely con- PATHOGENESIS: About 85% of ADPKD is tribute to the loss of functioning renal tissue. caused by mutations in the polycystic kidney disease 1 gene (PKD1) and 15% by mutations PATHOLOGY: The kidneys in ADPKD are in PKD2. The products of these genes, polycystin-1 and markedly enlarged bilaterally, each weighing as polycystin-2, are in the primary cilia of tubular epithe- much as 4,500 g (Fig. 16-3). The external contours lial cells. These cilia sense urine flow and regulate of the kidneys are distorted by numerous cysts as large as 5 tubule growth. cm in diameter, which are filled with a straw-colored fluid. Microscopically, the cysts are lined by a cuboidal and columnar epithelium. They arise from virtually any point along the nephron, and areas of normal renal parenchyma are found between the cysts. One third of patients with ADPKD also have hepatic cysts, with a lining that resembles bile duct epithelium. One fifth have an associated cerebral aneurysm, and in- tracranial hemorrhage is the cause of death in 15% of pa- tients with ADPKD. CLINICAL FEATURES: Most patients with ADPKD do not develop clinical manifestations until the fourth decade of life, although a small Autosomal dominant Autosomal recessive minority become symptomatic during childhood. polycystic disease polycystic disease Symptoms include a sense of heaviness in the loins, bilat- eral flank and abdominal masses, and passage of blood clots in the urine. Azotemia (elevated blood urea nitrogen) is common and in half of patients progresses to uremia (clinical renal failure) over a period of several years. Medullary Medullary cystic sponge kidney disease complex Simple cyst Adult polycystic disease. The kidneys are enlarged, Cystic diseases of the kidney. FIGURE 16-3. FIGURE 16-2. and the parenchyma is almost entirely replaced by cysts of varying size. 440 Essentials of Rubin’s Pathology Autosomal Recessive Polycystic Kidney Disease ACQUIRED CYSTIC KIDNEY DISEASE (ARPKD) Occurs in Infants Simple renal cysts are usually incidental findings at au- Autosomal Recessive Polycystic Kidney Disease (ARPKD) is char- topsy and are rarely clinically symptomatic unless they are acterized by cystic transformation of collecting ducts. It is rare very large. These fluid-filled cysts may be solitary or multiple compared with ADPKD, occurring in about 1 in 10,000 to and are usually located in the outer cortex, where they ex- 50,000 live births. Seventy-five percent of these infants die pand the capsule. Simple cysts less commonly occur in the in the perinatal period, often because of pulmonary hy- medulla. Microscopically, they are lined by a flat epithelium. poplasia caused by oligohydramnios