Renal Embryology, Anatomy & Congenital Anomalies

Building the kidney: three generations, two tissues

Three nephric systems. Intermediate mesoderm produces three kidneys in a head-to-tail wave. The pronephros (week 4) never functions and regresses. The mesonephros (late week 4) filters as an interim kidney through much of the first trimester and leaves behind the mesonephric (Wolffian) duct. The metanephros appears around week 5 and becomes the permanent kidney.

Wolffian duct. In males it becomes the epididymis, ductus deferens, seminal vesicle and ejaculatory duct; in females it regresses, occasionally leaving a Gartner duct cyst. In both sexes its caudal end first gives off the ureteric bud, so renal and genital duct anomalies often travel together.

Reciprocal induction. The ureteric bud grows into the metanephric mesenchyme (blastema). Mesenchymal GDNF binds RET on the bud and drives branching; the branch tips in turn induce the mesenchyme to form epithelial nephrons. WT1, the tumor suppressor lost in some Wilms tumors, is expressed in this responding mesenchyme. No bud, or no contact, means agenesis; faulty crosstalk means dysplasia.

Timing and ascent. The kidney makes urine by the late first trimester, and from the second trimester fetal urine is the main source of amniotic fluid. Nephrons form until about 34–36 weeks; none are added after birth. The placenta, not the fetal kidney, clears wastes, so a fetus without kidneys can still reach term. The metanephros ascends from the pelvis to the lumbar region by about week 9 while its hilum rotates medially; failure to ascend leaves a pelvic kidney, and persisting lower arterial branches become accessory renal arteries.

Potter sequence: when the fetus makes no urine

Mechanism. If neither kidney makes urine, or urine cannot leave the bladder, oligohydramnios follows. The uterine wall compresses the fetus, and without fluid moving through the airways the lungs fail to grow. It is a sequence because one upstream defect generates the whole picture.

Causes. Bilateral renal agenesis (the ureteric bud fails to form or to induce the mesenchyme), ARPKD, posterior urethral valves and bilateral MCDK. Prolonged rupture of membranes can produce the same deformities with normal kidneys. Unilateral lesions do not cause Potter sequence because the other kidney maintains fluid volume.

Unilateral renal agenesis. Usually silent, with compensatory hypertrophy of the solitary kidney; look for ipsilateral genital duct anomalies (uterine malformations in women, absent vas deferens or seminal vesicle in men).

Pulmonary hypoplasia, not renal failure, is what kills the newborn with Potter sequence.

Anomalies of fusion and differentiation

Horseshoe kidney. The most common fusion anomaly. The lower poles fuse into an isthmus lying anterior to the aorta, and during ascent the isthmus catches under the root of the inferior mesenteric artery (about L3). The kidney stays low and malrotated but usually functions normally.

Associations and complications. Turner syndrome (45,X) is the classic association; trisomies 13, 18 and 21 are also linked. High-inserting ureters that cross the isthmus drain poorly, causing UPJ obstruction with hydronephrosis, stones and infection, and Wilms tumor risk is increased.

Multicystic dysplastic kidney (MCDK). Faulty bud–mesenchyme interaction replaces the kidney with noncommunicating cysts separated by dysplastic stroma (primitive ducts, sometimes cartilage), usually with an atretic ureter and no function. It is sporadic and usually unilateral, found prenatally or as a neonatal flank mass. The other kidney hypertrophies but may itself reflux or obstruct, so it is imaged; the dysplastic kidney often involutes. Bilateral MCDK is lethal through Potter sequence.

Ureter, bladder outlet and urachus

UPJ obstruction. The UPJ canalizes last, making obstruction there the most common pathologic cause of fetal hydronephrosis: dilated pelvis and calyces with a normal ureter and bladder. In older children and adults a crossing lower-pole vessel can cause intermittent flank pain after a large fluid load.

Duplex collecting system. A bud that splits early gives a bifid ureter with one orifice; two separate buds give complete duplication with two orifices. By the Weigert–Meyer rule, the upper-pole ureter opens lower and more medially and tends to obstruct (ureterocele, ectopic opening), while the lower-pole ureter opens higher and more laterally with a short tunnel and tends to reflux. In a girl, an ectopic ureter opening below the external sphincter (urethra, vestibule, vagina) causes constant dribbling despite normal voiding; in boys ectopic ureters open above the sphincter and present with infection or epididymitis instead.

Vesicoureteral reflux (VUR). The ureter normally tunnels obliquely through the bladder wall, so bladder contraction presses it shut. In primary VUR the submucosal tunnel is too short; secondary VUR follows high bladder pressure (posterior urethral valves, neurogenic bladder). Refluxed infected urine causes recurrent pyelonephritis and reflux nephropathy (scarring, hypertension, CKD). VCUG demonstrates and grades reflux (I–V), and DMSA scanning shows scars. Primary VUR is familial, and low grades often resolve as the tunnel lengthens with growth.

Posterior urethral valves (PUV). Obstructing folds in the prostatic urethra are the most common cause of congenital bladder outlet obstruction in boys. Expect a thick trabeculated bladder, bilateral hydroureteronephrosis, secondary reflux and, when severe, oligohydramnios with Potter sequence. Prenatal ultrasound shows the keyhole sign; VCUG shows a dilated posterior urethra. Many survivors develop CKD.

Urachal remnants. The urachus, the intra-abdominal allantois, links the bladder dome to the umbilicus and normally fibroses into the median umbilical ligament (the medial umbilical ligaments are the umbilical arteries; the ligamentum teres is the umbilical vein). Urachal remnants are the classic source of adenocarcinoma of the bladder dome, a glandular, often mucin-producing tumor unlike ordinary urothelial carcinoma; bladder exstrophy and chronic irritation (cystitis glandularis) also predispose to bladder adenocarcinoma.

Clinical anatomy: kidneys, renal veins and ureters

Position. The kidneys are retroperitoneal (about T12–L3) in perirenal fat within Gerota fascia; the liver pushes the right kidney lower. At the hilum, from anterior to posterior: renal vein, renal artery, pelvis. Segmental arteries are end arteries, so ligating an accessory artery infarcts its territory.

Left renal vein. To reach the IVC it crosses anterior to the aorta just below the SMA origin, so it is much longer than the right, and the left kidney is preferred for living donation because the extra length eases the anastomosis. The right renal artery, passing behind the IVC, is the longer artery. The left gonadal and left adrenal veins drain into the left renal vein, whereas the right gonadal vein enters the IVC directly, one reason varicoceles favor the left. Nutcracker compression between SMA and aorta produces hematuria, left flank pain and a left varicocele (pelvic congestion in women).

A new left varicocele in an older man that does not decompress when supine calls for renal imaging: a left renal cell carcinoma can invade the renal vein.

Course of the ureter. The ureter descends on the psoas, crosses anterior to the iliac vessels at the pelvic brim, and passes beneath the uterine artery about 2 cm lateral to the cervix (beneath the ductus deferens in men): water under the bridge.

At hysterectomy the ureter can be clamped, tied or cut while the uterine artery or the ovarian vessels in the infundibulopelvic ligament are secured; postoperative flank pain or a rising creatinine warrants imaging.

Where stones stop. Stones lodge at the UPJ, at the pelvic brim where the ureter crosses the iliac vessels, and at the UVJ, the narrowest point and commonest impaction site; pain migrates from flank to groin as a stone descends.