The Kidneys

Figure 10.1

Normal kidney, gross

This normal adult kidney with the capsule removed has a pattern of fetal lobulations that still persists, as it sometimes does in adults. The hilum at the center contains some yellow adipose tissue. An adult kidney ranges from 11 to 15 cm in length and weighs 125–200 g, depending on the size of the person. There is ordinarily enough renal reserve function to survive with just half of one normal kidney. There is an incidental smooth-surfaced, small, clear fluid–filled simple renal cyst (◀). Such cysts are typically small, occur either singly or scattered around the renal parenchyma, have no effect upon renal function, and are common in adults.

Figure 10.2

Normal kidneys, CT image

This normal abdominal CT scan with contrast enhancement at the L2–L3 level shows the right (▶) and left (◀) kidneys, liver ( ), gallbladder (♦), gastric antrum (✚), jejunum (▪), colon (□), spleen ( ), aorta (▲), psoas muscle ( × ), and rectus abdominis muscle (▼). The kidneys are located in the retroperitoneum and are well protected by surrounding connective tissues with fat and skeletal muscle. Normal renal blood flow, which is about 25% of the cardiac output, is indicated here by the bright attenuation of the kidneys from the inflow of the injected intravenous contrast material. Branches of renal artery within each kidney have no anastomoses; branch arterial occlusion leads to focal infarction. Also, because renal tubular capillary beds derive from efferent arterioles, glomerular disease leads to parenchymal ischemia, and glomerular loss with aging eventually results in diminution of renal size.

Figure 10.3

Normal kidney, gross

In cross-section, this normal adult kidney shows the lighter outer renal cortex ( ), normally 5–10 mm in thickness, and darker inner medulla (♦) with central pelvis containing yellow adipose tissue. Note renal papillae (▲) projecting into the calyces, through which collecting ducts drain the excreted urine into the renal pelvis. The amount of renal reserve capacity is remarkable, and it explains why renal failure is not associated with aging. In addition to excretion of waste products, the kidney contributes to acid-base balance, salt and water volume with regulation of blood pressure, and maintenance of red-blood-cell mass through elaboration of erythropoietin.

Figure 10.4

Normal kidney, microscopic

The corticomedullary junction of the kidney is shown. The cortex contains a medullary ray—a renal column (♦) extending to the medulla (□). Within the cortex ( ) are glomeruli and tubules. Arcuate arteries (▲) arising from interlobar arteries course along the corticomedullary junction, giving rise to interlobular arteries from which the afferent arterioles originate to supply blood to individual glomeruli.

Figure 10.5

Normal kidney, JG apparatus, microscopic

The afferent arteriole (♦) enters the glomerulus at the vascular pole ( + ). The juxtaglomerular apparatus is a region of specialized smooth muscle cells called juxtaglomerular (JG) cells located in the afferent arteriole, which, along with a set of columnar cells called the macula densa in the adjacent segment of distal convoluted tubule (▪), sense changes in blood pressure and sodium concentration. The JG cells secrete renin, which catalyzes conversion of angiotensinogen to angiotensin I. Angiotensin I is biologically inactive and converted to angiotensin II by angiotensin-converting enzyme. Angiotensin II is a potent vasoconstrictor and regulator of aldosterone secretion, which promotes sodium reabsorption and potassium excretion by the kidneys.

Figure 10.6

Normal kidney, microscopic

The normal glomerulus of the kidney at high power with periodic acid-Schiff (PAS) stain has thin, delicate capillary loops around the mesangial regions ( ), which are not prominent, containing two to four mesangial cells. Most glomerular filtration occurs through the capillary loops into Bowman space (♦). The mesangium accounts for about 16% of filtration and also serves a macrophage-like function and a reparative function. The visceral epithelial cells (podocytes) that surround the capillary loops (▼) are not easily recognized by light microscopy; parietal epithelial cells line the external surface of Bowman space. The afferent arteriole (▪) in autoregulation and JG apparatus (▲) in tubuloglomerular feedback aid in maintaining homeostasis.

Figure 10.7

Normal kidney, electron microscopy

A glomerular capillary loop at high magnification has a visceral epithelial cell (podocyte) with interdigitating foot processes (♦) embedded in and adherent to the lamina rara externa (◼) of the basement membrane. Adjacent foot processes (pedicels) are separated by 20–30-nm wide filtration slits (✚). The basement membrane is of uniform thickness, composed mainly of type IV collagen, and has thin endothelial cell cytoplasm with fenestrations (▲) on the opposite surface. The exclusion of molecules such as albumin from the glomerular filtrate is a function of anionic charges from polyanionic proteoglycans and the anatomic size of the slit pores.

Figure 10.8

Normal kidney, angiogram

The normal distribution of blood flow in the kidney is seen here, extending distally from the main renal artery and branches to arcuate branches at the corticomedullary junction. The kidneys receive about 25% of the cardiac output, and the renal cortex receives 90% of this renal blood flow. Decreasing renal blood flow triggers release of renin, which triggers generation of angiotensin I converted to angiotensin II, elevating blood pressure through vasoconstriction to increase peripheral vascular resistance and through stimulation of aldosterone secretion from adrenal cortical glomerulosa cells, which promotes distal tubular sodium reabsorption to increase blood volume.

Figure 10.9

Normal fetal kidney, microscopic

Beneath the capsule of the developing fetal kidney is a nephrogenic zone ( ) composed of primitive dark-blue cells from which development of glomeruli (▶) and tubules (♦) is taking place and from which the new cortex forms. At the time of birth, most of this formative process has occurred, with just a small remnant of the nephrogenic zone persisting for 3 months. At birth, the infant’s urine is quite dilute because the solute concentration of the medulla has not yet increased to the point that the countercurrent urine concentrating mechanism is fully operational.

Figure 10.10

Renal agenesis, gross

Agenesis refers to absence of formation of a body part during embryogenesis. Here the kidneys are absent from the retroperitoneum; no ureteric bud induced metanephros. This results in oligohydramnios in utero because amniotic fluid is mainly derived from fetal urine. Bilateral renal agenesis is rare, present in about 1 in 4500 births, and incompatible with life. At birth, there is severe pulmonary hypoplasia from the oligohydramnios sequence. Unilateral renal agenesis is still rare but survivable; the opposite kidney develops to nearly twice the size of a single normal kidney from compensatory hyperplasia.

Figures 10.11 and 10.12

Renal acquired hypoplasia, gross and CT image

In the CT image is one normal-sized right kidney (▶) but with a grossly granular surface and a few scattered, shallow cortical scars as a result of left renal arterial occlusion from severe atherosclerosis. The renal veins (▼) here are highlighted by contrast material. The increased renin secretion from the smaller, atrophic left kidney (◀) led to hypertension (Goldblatt kidney), which eventually damaged the opposite kidney. The atherosclerosis is marked by prominent aortic mural thrombus (▲) in the CT scan. True congenital hypoplasia is quite rare and without scars, with renal lobes and pyramids reduced in number and size.

Figure 10.13

Horseshoe kidney, gross

This congenital anomaly may occur in association with other anomalies or syndromes or with specific genetic defects, such as trisomy 18. Horseshoe kidney occurs as an isolated anomaly in about 1 in 500 people. Because the ureters take an abnormal course across the “bridge” (▲) of renal tissue, there is a potential for partial ureteral obstruction with resultant hydronephrosis. In many cases, this anomaly is just an incidental finding because renal filtration function and urine flow are not significantly affected, and the total mass of renal tissue is normal. Abnormal fusion usually occurs at the lower renal poles.

Figures 10.14 and 10.15

Simple renal cyst, gross and CT image

Note the large simple cyst of the right upper pole (◀). Other smaller clear fluid-filled cysts are scattered within the renal cortex in the left panel . Simple renal cysts are a common incidental finding in adults. A large renal cyst (♦) can be seen in this CT scan, but it can be distinguished from a neoplasm by its fluid density and thin wall. In the CT scan, a smaller simple cyst (▲) has the characteristic features of low fluid attenuation and discrete, round borders. There is sufficient remaining functional renal cortex to provide adequate renal function in nearly all individuals with simple renal cysts. An uncommon complication is cyst hemorrhage with pain.

Figures 10.16 and 10.17

Autosomal-dominant polycystic kidney disease (ADPKD), gross and CT image

The right kidney shown here grossly weighed 3 kg, as did the left kidney. ADPKD is a bilateral process. Mutations in the PKD1 gene encoding polycystin-1 account for 85% of cases, and mutations in PKD2 encoding polycystin-2 most of the rest; these proteins are part of ciliated tubular epithelium regulating intracellular calcium. The cysts (♦) are not typically present at birth but develop slowly over time, so that onset of renal failure occurs in middle age to later adult life from reduction in functional parenchyma. An initial laboratory finding is often hematuria from cyst hemorrhage, followed by proteinuria (rarely >2 g/day). Patients often have polyuria and hypertension. Cysts may appear in other organs, such as liver, pancreas, and spleen. About 4%–10% of patients with ADPKD have an intracranial berry aneurysm.

Figures 10.18 and 10.19

Normal fetal kidney and autosomal-recessive polycystic kidney disease (ARPKD), gross

The normal term infant kidneys in the left panel reveal typical fetal lobulations and smooth cortical surfaces with some attached adipose tissue. Note the well-defined corticomedullary junctions on cut section. In the right panel , note the bilaterally massively enlarged kidneys (♦) that nearly fill the abdomen below the liver, consistent with ARPKD in this fetus at 23 weeks’ gestation that died from pulmonary hypoplasia as a result of oligohydramnios. There are perinatal, neonatal, infantile, and juvenile subcategories depending on the nature of the PKHD1 gene mutation (encoding a large novel protein, fibrocystin that is part of tubular cell cilia ), the time of presentation, and the presence of associated hepatic lesions. The first two are the most common; serious manifestations are usually present, typically with renal failure from birth. The latter two are compatible with longer survival, but patients often develop congenital hepatic fibrosis leading to complications from portal hypertension. With different PKHD1 mutations, compound heterozygotes can occur.

Figure 10.20

Autosomal-recessive polycystic kidney disease (ARPKD), gross

A bilaterally and symmetrically enlarged kidney with ARPKD is shown here on cut surface. The numerous glistening cysts are small, about 1–2 mm in diameter, but uniformly distributed throughout the parenchyma to produce a spongy appearance, and there is no distinguishable cortex or medulla. This condition is most often present from birth (hence the synonym, infantile polycystic kidney disease). In utero, this condition results in reduced production of fetal urine, which forms amniotic fluid. Fetal ultrasound shows oligohydramnios, or anhydramnios if severe.

Figure 10.21

Autosomal-recessive polycystic kidney disease (ARPKD), microscopic

ARPKD is characterized by many cysts (♦) involving the collecting ducts, often elongated and radially arranged or saccular. A few scattered glomeruli are within the residual intervening renal cortex. The cysts have a uniform lining of cuboidal cells. Consequent oligohydramnios in utero leads to a deformation sequence from constriction of the fetus. In addition to pulmonary hypoplasia, there can be varus deformities of the lower extremities, glove-like redundant skin on hands, and flattened (Potter) facies.

Figure 10.22

Autosomal-recessive polycystic kidney disease (ARPKD), microscopic

Characteristic of ARPKD is the appearance of congenital hepatic fibrosis, a ductal plate malformation, seen as expanded portal regions with collagenous fibrosis and a surrounding proliferation of radially arranged portal bile ducts (◀). The adjacent normal hepatic parenchyma contains islands of extramedullary hematopoiesis, mainly clusters erythroid precursors, typical for second-trimester and third-trimester fetal liver. In cases where survival into childhood occurs, portal hypertension with splenomegaly may result.

Figure 10.23

Multicystic renal dysplasia, gross

The fetal kidneys (left panel) are composed of cysts and are asymmetric in size. The cut surface (right panel) of one kidney shows irregularly sized cysts separated by dense stroma. Multicystic renal dysplasia (or multicystic dysplastic kidney) is more common than autosomal-recessive polycystic kidney disease, has larger cysts, and occurs sporadically without a defined inheritance pattern. It may be part of a malformation complex, such as Meckel-Gruber syndrome. Many cases are associated with additional urinary tract anomalies, such as ureteropelvic obstruction, ureteral agenesis, or atresia. Often, multicystic dysplastic kidney is unilateral. If bilateral, it is often asymmetric, as seen here, and oligohydramnios and its complications can ensue.

Figure 10.24

Multicystic renal dysplasia, microscopic

Dysplasia in pediatric terms implies disordered organ development (not an epithelial precursor to neoplasia). The dysplasia is evident here in the renal parenchyma composed of irregular vascular channels, islands of cartilage (♦), undifferentiated mesenchyme, and scattered immature collecting ductules (◀) in a fibrous stroma with cysts. There is abnormal lobar organization. If the process is unilateral, or involves just a part of a kidney, there is enough renal reserve capacity with compensatory hyperplasia of the remaining renal tissue for adequate renal function to live a normal life. A person may survive with just half of one normal kidney.

Figure 10.25

Congenital urinary obstruction with cystic change, gross

Urinary tract obstruction in utero can lead to renal parenchymal cystic change in addition to hydronephrosis. Obstruction below the bladder (▲) in this case (either urethral atresia or posterior urethral valves may be suspected) has led to bladder dilation and hypertrophy, bilateral hydroureter (▼), and numerous small cysts (▶) in the renal cortices. Oligohydramnios in utero also accompanies this obstruction to urine flow.

Figure 10.26

Congenital urinary obstruction with cystic change, microscopic

The renal cortical microcysts (♦) appear near the nephrogenic zone (◀) because the developing glomeruli are most sensitive to the increased pressure. Causes of congenital urinary tract obstruction include posterior urethral valves (in males) or urethral atresia (in both sexes). Obstruction below the bladder is detected by bladder enlargement on fetal ultrasound scans; diminished (or absent) fetal urine production leads to oligohydramnios (or anhydramnios) with a diminished amniotic fluid index.

Figure 10.27

Pulmonary hypoplasia, gross

Congenital renal diseases or urinary tract outflow anomalies lead to the oligohydramnios sequence, which constricts lung development in utero, causing pulmonary hypoplasia. A fetal ultrasound scan shows marked oligohydramnios because fetal urine that forms the bulk of the amniotic fluid volume is reduced. The chest cavity opened here at autopsy reveals a normal-sized heart but very small lungs (▲), which become the rate-limiting step for survival after birth. Additional features of oligohydramnios sequence include Potter facies with flattened nose and prominent infraorbital creases. Deformations of the extremities are common, with talipes equinovarus and joint contractures.

Figure 10.28

Medullary sponge kidney (MSK), gross

Note the 1–7-mm cysts (◀) involving the medulla, but not the overlying pale brown cortex of this kidney, that resulted from congenital nonprogressive dilation of the distal portion of the collecting ducts and tubules in the renal papillae. Most cases are bilateral and are discovered incidentally with radiologic imaging studies. Renal function is usually normal because the cortex with glomeruli is not involved. In 20% of cases of MSK, there may be formation of renal calculi, which predisposes to obstruction and infection (pyelonephritis) and hematuria in middle-aged individuals. Some cases appear in conjunction with Marfan syndrome, Ehlers-Danlos syndrome, and Caroli disease.

Figure 10.29

Nephronophthisis, CT image

Note medullary cysts (▶), which may be up to 2 cm, concentrated at the corticomedullary junctions seen in this abdominal CT with contrast. There is ongoing tubulointerstitial injury from tubular basement membrane disruption. Glomeruli are usually spared. Cases can occur sporadically, associated with retinal lesions, and most commonly as an autosomal recessive familial form with onset in childhood or adolescence, with multiple possible mutations, including NPHP genes encoding for primary ciliary protein. Patients have polyuria from lack of concentrating ability, sodium wasting, and tubular acidosis. There is progression to end-stage renal disease.

Figure 10.30

Acquired renal cystic disease, gross

Patients with chronic renal failure who undergo hemodialysis for many years may develop multiple cortical cysts (▲). This is probably the result of obstruction with progressive interstitial fibrosis and/or oxalate crystal deposition in end-stage renal disease. When such cysts develop, they are more numerous than the common simple renal cysts, but usually less numerous than the cysts with autosomal-dominant polycystic kidney disease (ADPKD), and the size of the kidneys with dialysis-induced cystic disease is usually not markedly increased, as it is with ADPKD, because it is superimposed on chronic kidney disease. There may be hemorrhage into the cysts. There is an increased risk for development of renal cell carcinoma.

Figure 10.31

Postinfectious glomerulonephritis, microscopic

This glomerulus is hypercellular with increased inflammatory cells, and capillary loops are poorly defined. This type of acute proliferative glomerulonephritis (GN) is termed postinfectious GN, but historically known as poststreptococcal GN when most diagnosed cases followed streptococcal pharyngitis (a different bacterial strain than that producing acute rheumatic fever). Other predisposing infections include staphylococcal endocarditis, pneumococcal pneumonia, hepatitis B or C, HIV, or malaria. The infectious agent induces a humoral immune response with antibodies that cross-react with glomerular antigens or lead to antigen-antibody complex formation with glomerular deposition and activation of the alternate complement pathway.

Figure 10.32

Postinfectious glomerulonephritis (PIGN), microscopic

At higher magnification, the hypercellularity of PIGN is due to increased numbers of epithelial, endothelial, and mesangial cells and neutrophils (▲) infiltrating in and around the capillary loops. This disease may occur 1–4 weeks after recovery from infection, classically with certain (nephritogenic) strains of group A β-hemolytic streptococci that involve the pharynx (“strep throat”) or skin (impetigo). These patients typically have elevated antistreptolysin O, anti-DNase B, or antihyaluronidase titers. Patients may have microscopic hematuria, mild proteinuria, and mild to moderate hypertension.

Figure 10.33

Postinfectious glomerulonephritis (PIGN), electron microscopy

The immune deposits that appear in a bumpy granular pattern consist mainly of IgG, IgM, and C3, as shown by immunofluorescence, and seen here by electron microscopy to be predominantly subepithelial. There are electron-dense subepithelial “humps” ( ) above the basement membrane and below the epithelial cell (podocyte) foot processes (▲). The capillary lumen is filled with a leukocyte having multiple cytoplasmic granules (♦). PIGN is usually self-limited and more than 95% of children with this disease recover, but a few may evolve to rapidly progressive glomerulonephritis. About 40% of adults with this condition may go on to develop chronic renal disease.

Figure 10.34

Rapidly progressive glomerulonephritis (RPGN), microscopic

Seen here within three glomeruli are crescents ( ) composed of proliferating visceral epithelial cells (podocytes). Crescentic glomerulonephritis (GN) is known as RPGN because this disease has a fulminant course. RPGN may be idiopathic or result from immune complex deposition with diseases such as systemic lupus erythematosus or postinfectious GN; from various types of vasculitis, often “pauci-immune” forms; and less commonly but distinctively from anti–glomerular basement membrane antibody disease, such as Goodpasture syndrome. In the lower left glomerulus, the capillary loops (▶) are markedly thickened (the so-called wire-loop lesion of lupus nephritis).

Figure 10.35

Rapidly progressive glomerulonephritis (RPGN), immunofluorescence

This glomerulus shows crescentic bright green immunofluorescence (◀) with antibody to fibrinogen. With RPGN, glomerular damage is so severe that fibrinogen leaks into the Bowman space, leading to proliferation of the visceral epithelial cells and formation of a crescent. Patients typically develop RPGN over a few days, but up to 3 months. Manifestations include hematuria, moderate to severe proteinuria with edema, and hypertension. Hemoptysis characterizes patients with Goodpasture syndrome, who also have detectable circulating anti–glomerular basement membrane antibody. Patients with systemic vasculitis, such as microscopic polyangiitis, may have circulating antineutrophil cytoplasmic antibody.

Figure 10.36

Rapidly progressive glomerulonephritis (RPGN), immunofluorescence

There is bright green positivity with antibody to IgG with a smooth, diffuse, linear (▼) pattern that is characteristic of RPGN caused by circulating anti–glomerular basement membrane antibody with Goodpasture syndrome. The antibody is directed at the noncollagenous domain of the α 3 chain of type IV collagen. This leads to a form of type II hypersensitivity reaction. Patients with RPGN have rapidly increasing serum urea nitrogen and creatinine, decreasing urine output, and urinary sediment that may contain red blood cells (RBCs) and RBC casts. The presence of the urinary dysmorphic RBCs and RBC casts along with oliguria and hypertension characterizes a nephritic syndrome.

Figure 10.37

Microscopic polyangiitis (MPA), microscopic

Note the focal segmental necrotizing glomerulonephritis (♦) in the right panel and a glomerular crescent (♦) in the left panel in this case of an antineutrophil cytoplasmic antibody–associated glomerulonephritis. Tubular atrophy is also present. This is a pauci-immune form of rapidly progressive glomerulonephritis, and immunofluorescence will show minimal deposition of immunoglobulins or complement in the glomeruli and small renal vessels. MPA typically has an onset in the sixth decade, with fever or weight loss accompanying renal disease with nephrosis in mild cases to nephritis with severe involvement, as well as systemic small vessel vasculitis leading to findings such as fever, skin rash, myalgias, and arthralgias. Lung involvement may occur.

Figure 10.38

Membranous nephropathy microscopic

These capillary loops (▲) are diffusely thickened and prominent, but the overall glomerular cellularity is not increased. Membranous nephropathy is the most common cause of nephrotic syndrome in adults. Nephrotic syndrome is defined as more than 3.5 g of urine protein (mainly albumin) per day per 1.62 m 2 body surface area. With pure nephrotic syndrome, red blood cells are typically absent in the urine. About 25% of cases are secondary to an underlying condition, such as a chronic infection (e.g., hepatitis B or C), a carcinoma, drugs (NSAIDs), or systemic lupus erythematosus. Most cases are idiopathic. Autoantibodies to M-type phospholipase A2 receptor (PLA 2 R) are present in about 75% of idiopathic cases but not in those with secondary membranous nephropathy or other renal diseases.

Figure 10.39

Membranous nephropathy, microscopic

A Jones silver stain of this glomerulus highlights the proteinaceous basement membranes of capillary loops in black. These are characteristic “spikes” (◀) involving the capillary loops with membranous nephropathy, seen here with black basement membrane material appearing as small projections distributed within the capillary loops. The immune complexes, not highlighted by the Jones stain, lie between the black spikes. Loss of anticoagulant proteins with nephrosis predisposes to thrombosis, including renal vein thrombosis. Urinalysis with nephrotic syndrome may show lipiduria and proteinuria, whereas blood lipids (cholesterol and triglyceride) are increased.

Figure 10.40

Membranous nephropathy, electron microscopy

The immunofluorescence pattern here has a “bumpy” or granular staining pattern as a result of irregular deposition of immune complexes within the basement membranes of the glomerular capillary loops. Various fluorescein-labeled antibodies can be employed, such as those directed against immunoglobulins or complement components, which commonly compose the immune complexes. The onset of membranous nephropathy is often gradual, with nephrotic syndrome a likely presenting finding. Some patients may have hypertension; hematuria is less common. About 10% of patients go on to develop chronic renal failure within 10 years.

Figure 10.41

Membranous nephropathy, electron microscopy

By electron microscopy, the darker electron-dense immune deposits ( ) appear scattered within the thickened capillary basement membrane. The “spikes” seen with the silver stain are the lighter areas (♦) representing the intervening increased matrix of basement membrane between the darker immune deposits. The loss of basement membrane function leads to proteinuria, which is often “selective” because mostly lower molecular weight proteins such as albumin are lost. Besides PLA 2 R, a small subset of patients has antibodies to thrombospondin type-1 domain–containing 7A (THSD7A).

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Dec 29, 2020 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on The Kidneys

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