Weatherly's Woes - Congenital

RENAL AGENESIS

No kidney disease

Renal Agenesis is when the kidney(s) doesn’t form. The mechanism is that the ureteric bud doesn’t “interact properly” with the mesonephric mesenchyme. No clue what that means. Sorry y'all, I dislike embryology. Unilateral renal agenesis is not a huge problem. You only have one kidney. No big deal right? It’s common knowledge that you only need one kidney to survive. The lone kidney becomes hypertrophic, and adequately compensates. This is an asymptomatic condition. But later on in life, as the kidneys fade into senescence as the number of nephrons naturally declines, patients are at a higher risk for kidney disease. Bilateral renal agenesis is incompatible with life. The fetus will die. It’s noteworthy because it highlights the importance of Amniotic Fluid. The fetus’s ultimate problem here is a lack of amniotic fluid, or oligohydramnios. Amniotic fluid is essentially just baby pee. Without it the fetus develops some unusual, but predictable, symptoms called the Potter Sequence. It’s easily remembered if you know the two functions of amniotic fluid

Cushioning - the fluid acts like a protective bubble. Without it, the baby’s body is squashed and develops a flat face and deformed limbs.

Breathing Training - fetal lungs “breathe” amniotic fluid into their lungs as a training mechanism (they lack surfactant, so they can’t handle air yet). This training drives the extensive branching of the airways. So in the Potter Sequence, the fetus will have lung hypoplasia. This causes ARDS at birth, and is a common cause of death.

POLYCYSTIC KIDNEY DISEASE

Big cystic kidney disease

Polycystic Kidney Disease (PKD) is a genetic disorder that causes the kidneys to balloon up with cysts, and eventually fail. The cysts form because a critical protein on cilia is lost. The polycystin (ADPKD) and fibrocystin (ARPKD) proteins are found on primary cilia, which are sensory organs found apically on tubular epithelium. When tubular fluid (urine) flows across the cilia, the physical force activates calcium channels, which in turn tells the cell “hey don’t proliferate.” Without polycystin, the cell doesn’t hear that signal, and it continuously replicates. The surplus of tubular epithelial cells somehow results in cysts. Although this is Polycystic KIDNEY Disease, cystic structures can form in a variety of locations throughout the body, wherever primary cilia are found. Bile ducts in the liver turn into cysts, the colon becomes studded with diverticula and the mitral valve grows redundant tissue which results in MVP. Now I omitted one important cyst found in PKD, which is berry aneurysms in the Circle of Willis, because they’re believed to be caused by a different mechanism, hypertension, which I’ll address in a moment.

Why do cysts cause renal failure? Cysts can hurt the kidney by compressing surrounding blood vessels, which starves nearby nephrons. The starved nephrons desperately release renin, which causes severe, treatment-resistant hypertension. Hypertension is theorized to be responsible for the aforementioned berry aneurysms of the brain (prevalence of 8% in PKD patients). Berry cyst rupture causes a subarachnoid hemorrhage, and is one of the most common causes of death in PKD. Shifting our attention back to the kidneys, the cysts are responsible for causing some localized symptoms. The most common symptoms of PKD are flank pain from capsule stretching and hematuria from distorted circulation patterns. The kidney growth is often dramatic, which can be physically appreciated by palpating bilateral flank masses.

There are two different genetic patterns of PKD. One is autosomal recessive (ARPKD) and the other is autosomal dominant (ADPKD). The recessive form strictly affects neonates, while the dominant form onsets in adulthood. If an adult fought a baby, the adult would be dominant.

Autosomal Recessive PKD (ARPKD) begins in utero. The cyst timeline is greatly accelerated compared to ADPKD. Look for renal failure, Potter’s sequence and hypertension at the time of birth. Often fatal.

Autosomal Dominant PKD (ADPKD) becomes symptomatic in adulthood (roughly age 30). Although the disease process began in utero, the pace of cyst formation takes decades to complete. Treatment is initially aimed at controlling their hypertension with a RAAS inhibitor like Lisinopril, but once ESRD is reached the emphasis turns to dialysis and transplantation.

Cysts in the kidneys, cysts in the brain, cysts in the liver, cysts in the gut

Gross

Ultrasound

LOW YIELD KIDNEY CYST DISEASES

Dysplastic Kidney is a congenital malformation of the kidney, where the organ is replaced by a useless cluster of cysts. Uniquely, there will be “unusual” tissue types too (eg, cartilage). It’s usually unilateral. Although it’s congenital, it ISN’T inherited. The resources are vague on the cause. It seems to have the same MOA as Renal Agenesis -- ureteric bud fails to induce the metanephric mesenchyme.

Medullary Cystic Kidney Disease (AD) is pretty self-explanatory. There are cysts in the collecting ducts as they course through the medulla. It results in fibrosis of the interstitium around the nephron that ultimately progresses to renal failure and shrunken kidneys in adulthood.

Simple Cysts are completely asymptomatic and benign. They are found incidentally. Very common. They will be small and unloculated. Essentially just a little balloon. They don’t warrant any additional testing or treatment.

Complex Cysts are large and heterogenous. They can have loculations, thick walls, asymmetry or different tissues. Large ones are able to obstruct a ureter (hydronephrosis), compress a nerve (flank pain), bleed (hematuria) or get infected (pyelonephritis). Biopsy it to rule out cancer or abscess.

GU ARCHITECTURAL ANOMALIES

Vesicoureteral Reflux (VUR) is a congenital genitourinary anomaly that allows urine to flow backwards up the ureters. The ureterovesicular junction is supposed to be a one way valve, maintained by its oblique opening and contraction of the trigone muscle. You don’t have to know exactly why VUR occurs, just that it’s a congenital problem. Children with VUR are usually asymptomatic, until they get a UTI. Every time they get cystitis, the infection always progresses into pyelonephritis. Repeated bouts of pyelonephritis should prompt a urological investigation. A fluoroscopic voiding cystourethrogram is the preferred diagnostic tool. VUR can be corrected with surgery.

Posterior Urethral Valves (PUV) is a congenital anomaly that blocks the urethra. It is due to the persistence of a little membrane near the prostate (only occurs in males). It’s kind of like BPH in a baby. The flow of urine becomes obstructed, resulting in bilateral hydronephrosis that can be detected with a prenatal ultrasound exam, and may result in Potter sequence if not corrected.

Ureteropelvic Junction Obstruction (UPJO) is a congenital blockage at the top of the ureter, where it feeds into the renal pelvis. It’s one of the most common structural GU disorders. The UPJ is the last segment of the fetal ureter to canalize. It results in unilateral hydronephrosis.

HORSESHOE KIDNEY

Congenital and conjoined

A Horseshoe Kidney is a relatively common congenital, asymptomatic finding where the kidneys are conjoined at the lower poles. It’s shaped like a horseshoe lol. The unusual shape doesn’t impact function. But the odd architecture predisposes to hydronephrosis, stones, infections and cancers. It has little-to-no impact on mortality :). It’s strongly associated with chromosomal aneuploidy, especially with Turner’s Syndrome (XO).

What’s weird is that the horseshoe is found lowerer in the abdomen than expected. That’s because during embryology the kidneys originate down low, then ascend upwards. But the horseshoe snags on the IMA, and can go no higher. Embryo tie in!