CONGENITAL RENAL ANOMALIES: CONGENITAL RENAL ANOMALIES Dr. PANKAJ GARG DEVELOPMENT OF KIDNEY: DEVELOPMENT OF KIDNEY A. The Pronephros Is the cranial most set of tubes, which mostly regress B. The mesonephros Is located along the midsection of the embryo and develops into mesonephric tubules and the mesonephric duct (Wolffian duct). These tubules carry out some kidney function at first, but then many of the tubules regress. C. The metanephros Gives rise to the definitive adult kidney. Develops from an outgrowth of the caudal mesonephric duct, the ureteric bud, and from a condensation of nearby renogenic intermediate mesoderm, the metanephric blastema. PowerPoint Presentation: Derivatives of the ureteric bud and metanephric blastema in the adult kidney A. Derivatives of the metanephric blastema: Podocytes covering glomerular capillaries Epithelial cells lining Bowman’s capsule Proximal convoluted tubules Descending thick limbs of the loops of Henle Thin limbs of the loops of Henle Ascending thick limbs of the loop of Henle Distal convoluted tubules B. Derivatives of the ureteric bud: Collecting tubules and ducts Minor and major calyces Ureters PowerPoint Presentation: Renal-Coloboma syndrome The Pax2 gene essential for metanephric mesenchyme to differentiate into epithelial tubules in response to inductive signals from ureteric bud, so mutations (even if HETEROZYGOUS) can produce renal defects. Patients typically exhibit the following symptoms: Renal hypoplasia - due to reduced proliferation of the mesenchyme derived epithelia during development. Vesicouretral Reflux - most likely due to improper connection of the ureter to the bladder or possibly due to inherent defects in epithelial cells of the mature ureter. Colobomas (ventral fissures in iris, retina, and/or optic nerve) - due to failure of the optic fissure to fuse (expression of Pax2 is observed in ventral part of the optic cup and optic stalk). Nephroblastoma (Wilms Tumor) found in infants from 0-24 months of age consists of blastemal, epithelial, and stromal cell types associated with mutations in genes related to kidney development (PAX2, WT1, etc.) essentially due to incomplete mesenchymal-to-epithelial transformation (i.e. the cells fail to fully differentiate and transform into cancerous cells). FETAL KIDNEY: FETAL KIDNEY The fetal kidneys have lobular surface. The lobulation usually disappears during the infancy as the nephrons increase & grow. POSITIONAL CHANGES OF THE KIDNEY: POSITIONAL CHANGES OF THE KIDNEY Initially the metanephric kidneys( primordial permanent kidney) lie close to each other in the pelvis ventral to the sacrum. As the abdomen & the pelvis grow, the kidneys gradually come to lie in the abdomen and move further apart. They attain their adult position by the 9th week. This relative ascent results mainly from the growth of the embryos body caudal to the kidneys. Defect at this level causes ECTOPIC KIDNEY . PowerPoint Presentation: During the fifth and sixth weeks of development, the mature kidneys lie in the pelvis with their hila pointed anteriorly. As the pelvis and abdomen grow, the kidneys slowly move upward. By the seventh week, the hilum points medially and the kidneys are located in the abdomen. As the embryo continues to grow in a caudal direction, the kidneys are left behind and eventually come to lie in a retroperitoneal position at the level of L1 by the ninth week of development The kidneys rotate completely and the hila face anteromedially CONGENITAL ANOMALIES OF KIDNEY: CONGENITAL ANOMALIES OF KIDNEY Agenesis of kidney Hypoplasia Ectopic Kidneys Horseshoe kidney Pancake kidney Malrotated kidney Polycystic kidney Double kidney AGENESIS: AGENESIS UNILATERAL BILATERAL UNILATERAL RENAL AGENESIS : UNILATERAL RENAL AGENESIS Occurs every 1/1000 new born infants. Males are affected more than female . Left kidney is the one usually absent. Unilateral agenesis often causes no symptoms during infancy owing to the compensatory hypertrophy of the other kidney. It is suspected in infants with a single umbilical artery. The opposite kidney is usually enlarged as a result of compensatory hypertrophy. Bilateral renal agenesis: Bilateral renal agenesis 1/3000 births. The condition is incompatible with postnatal life because of the associated pulmonary hypoplasia . The associated syndrome is known as POTTER’S SYNDROME. 1 . oligohydramnios , because little or no urine is excreted into the amniotic cavity. 2. characterstic facial appearance: Eyes- wide set, with epicanthic folds. Ears-low set. Nose-broad and flat. Chin-receding . 3. no limb defects. PowerPoint Presentation: Agenesis occurs when the metanephric diverticula fail to develop or the primodia of the ureters degenerate. Failure of the metanepric diverticula to penetrate the metanephrogenic blastema results in failure of kidney development because no nephrons are induced by the collecting tubules to develop from metanphrogenic blastema However, the etiology is multifactorial . HYPOPLASTIC KIDNEY: HYPOPLASTIC KIDNEY Usually unilateral. Bilateral may present with renal failure in early childhood. Differentiation between congenital & acquired hypoplastic kidney is difficult, but the following points go in favour of CONGENITAL. HYPOPLASTIC KIDNEY: No scars. Reduced number of renal lobes & pyramids. In one form of hypoplastic kidney, oligomeganephronia, the kidney is small but the nephrons are markedly hypertrophied. Pure hypoplasia is very uncommon, and is more commonly associated with vascular occlusion, long-standing urinary reflux, a chronic inflammatory process, or in conjunction with renal dysplasia. PowerPoint Presentation: Hypoplastic kidney with renal dysplasia MALROTATED KIDNEY: MALROTATED KIDNEY If a kidney fails to rotate the hilum faces anteriorly, that is, the fetal kidney retains its embryonic position. If the hilum faces posteriorly , rotation of the kidney proceeded too far. If faces laterally= abnormal rotation. Abnormal rotation is often associated with ectopic kidney . ECTOPIC KIDNEY: ECTOPIC KIDNEY One or both kidneys may be in an abnormal position. They result from failure of the kidneys to alter position during embryonic growth. Most ectopic kidneys lie in the pelvis. These PELVIC KIDNEY lie close to each other and may fuse to form a discoid (‘pancake’)kidney. Ectopic kidney receives its blood supply from blood vessels near them. They are often supplied by multiple vessels. Complications : Arise due to tortuosity of ureters owing to abnormal position. There may be urinary obstruction which further leads to bacterial infection. PowerPoint Presentation: Sometimes a kidney crosses to other side, resulting in CROSSED RENAL ECTOPIA with or without fusion. an unusual type of abnormal kidney is unilateral fused kidney. In such cases, the developing kidneys fuse while they are in the pelvis, and one kidney attains its normal position, carrying the other kidney with it. HORSESHOE KIDNEY: HORSESHOE KIDNEY In 0.2% of the population the poles are fused, usually the inferior ones (90% & 10% for the upper poles) & the fused renal structure lies continuous across the midline anterior to great vessels. POSITION: the large U shape lies in the hypogastrium, anterior to the inferior lumbar vertebra. Normal assent of these fused kidneys is prevented because they are caught by the root of the inferior mesenteric artery. Usually asymptomatic because its collecting system develops normally and the ureters enter the bladder. If urinary flow is impeded, signs and symptoms of obstruction and /or infection may appear. Approximately 7% of person with TURNER’s syndrome have horse shoe kidney. Lower poles usually lie fused at the level of L4. CYSTIC KIDNEY DISEASE: CYSTIC KIDNEY DISEASE It is of 2 types: Autosomal recessive PKD is a rare inherited form. Symptoms of autosomal recessive PKD begin in the earliest months of life, even in the womb. Autosomal dominant PKD is the most common inherited form. Symptoms usually develop between the ages of 30 and 40, but they can begin earlier, even in childhood. About 90 percent of all PKD cases are autosomal dominant PKD. AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE : AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE Diagnosis: at birth or in utero by ultrasound. The condition is usually bilateral & inherited in autosomal recessive pattern. Both kidneys contain many hundreds of small cysts which result in renal insufficiency. Death occurs shortly after birth. Kidney transplant is the answer. THE DEFECTIVE GENE IN PKD: THE DEFECTIVE GENE IN PKD PKHD1, that maps to chromosome region 6p21-23. The gene encodes for a large, membrane protein, fibrocystin. The function of this protein is thought to be acting as cell surface receptor with a role in collecting duct & biliary differentiation. Infantile polycystic disease: Infantile polycystic disease Clinical features : enlarged kidneys. renal insufficiency. radiographic medullary ductal ectasia. congenital hepatic fibrosis (seen in those surviving in infancy). ON BIOPSY: Grossly: Enlarged. Smooth external appearance. On cut section : Numerous small cysts in the cortex & medulla give the kidney a sponge like appearance. Dilated elongated channels are present a t right angles to the cortical surface. PowerPoint Presentation: Infantile polycystic kidney. These massively enlarged kidneys retain their reniform shape. Cysts are much smaller than adult polycystic kidney. PowerPoint Presentation: Microscopically 1. Cylindrical dilation of all collecting tubules. (less commonly it is of saccular type). 2. Lining epithelium of the cyst wall is uniform with cuboidal cells, indicating their origin from collecting tubules. 3. Liver is involved in almost all cases, Liver shows cysts with portal fibrosis Proliferation of portal bile ducts. Autosomal dominant (Adult) polycystic kidney disease: It is characterized by multiple expanding cysts of both kidneys that ultimately destroy the renal parenchyma & cause renal failure. The disease is universally bilateral. Origin of the cysts: these originate from only portions of nephrons , so renal function is retained until 4 th -5 th decade of life. Autosomal dominant (Adult) polycystic kidney disease Inheritance : Inheritance Autosomal dominant 85% cases showing mutation in 16p13.3 (PKD1) while, Rest 15% show mutated 4q21 (PKD2). PKD1 encodes for polycystin-1 which is localized to tubular epithelial cells, esp. distal nephrons. PKD1 is a tumor suppressor gene. Its loss leads to hyperplasia of epithelial cells. The PKD2 encodes for polycystin-2 which is localized to all segments of renal tubules & is also expressed in many extra renal tissues. PowerPoint Presentation: Clinical features 1. renal insufficiency. 2. pain & dragging sensation owing to hemorrhage or progressive dilation of cysts. 3. renal colic from excretion of blood clots. 4. may also begin with hematuria. 5. 40% have associated polycystic liver disease. Cysts are derived from biliary epithelium. Less frequently associated with cysts of spleen, lung & pancreas. 6. intracranial berry aneurysm are formed as a result of altered expression of polycystin in vascular smooth muscle. It may account to intracranial hemorrhages. 7. mitral valve prolapse. PowerPoint Presentation: GROSSLY: Bilaterally enlarged, weighing up to 4 kgs. External surface consists solely of mass of cysts, with no intervening parenchyma. Cysts are filled with fluid which is usually turbid. It may be clear, serous or hemorrhagic. MICROSCOPICALLY: Functioning nephrons are seen dispersed between the cysts. The cysts arise from tubules throughout the nephron. Hence variable lining epithelium is seen, depending upon the origin. The epithelial lining cells have high proliferation rate. Those cells that are non-proliferating exhibit an abnormally simplified structure with immature phenotype. PowerPoint Presentation: GROSSLY A number of cysts of varying size are present; some contain luminal protein. PowerPoint Presentation: 3 separate cysts lined with simple cuboidal epithelium. Individual cyst wall lined with flat hyperplastic epithelium. Papillary projections from cyst wall exhibiting polypoidal hyperplasia. The Phenomenon of cyst development & enlargement: The Phenomenon of cyst development & enlargement The cysts are frequently detached from adjacent tubule & enlarge by active fluid secretion from the lining epithelial cells. The cyst fluid harbours mediators, derived from epithelial cells, that enhance fluid secretion & induce inflammation. The extra cellular matrix produced by cyst lining is abnormal leading to intestitial fibrosis. Predictors of accelerated progress: Predictors of accelerated progress 1. earlier age of diagnosis. 2. male sex. 3. PKD1 phenotype. 4. hypertension. 5. blacks (sickle cell trait) 6.rapidly increasing kidney size. 7. gross hematuria.