Medullary cystic kidney disease

Nephronophthisis, which means “nephron wasting”, and medullary cystic kidney disease, which refers to fluid-filled sacs in the medulla, are two kidney diseases that share some similar features: they’re both genetic, they both affect the nephrons, and both can lead to kidney cysts and renal failure over time.

To help understand these diseases, let’s first take a zoomed-in look at a nephron and talk about how it works. Alright so the outer layer of the kidney is called the cortex, and this is where the glomeruli live, which is where blood is initially filtered into the nephron, as well as the proximal convoluted tubule, where some of the filtered substances are reabsorbed back into the body.

The filtered substances, or filtrate, that don’t get reabsorbed then moves down through the medulla via the descending and then ascending parts of the loop of Henle.

The filtrate then goes back to the cortex briefly in the distal convoluted tubule, and then returns back to the medulla in the collecting duct.

Zooming back out a bit, the collecting ducts in each region of the kidney - called a renal pyramid, converge on the renal papilla, which dumps fully formed urine into a minor calyx.

From there the urine goes into the major calyx, and soon after, it goes into the ureter and the bladder.

And finally, zooming back in, surrounding each nephron’s tubule is the tubular interstitium, a hypertonic environment optimized to help resorb water and other substances from the tubules.

Alright so in nephronophthisis, which presents in childhood, the tubules atrophy and the interstitium gets infiltrated by macrophages and becomes fibrotic.

Inflammation of the tubules and the interstitium qualifies nephronophthisis as a tubulointerstitial nephritis, but don’t confuse this with nephritic syndrome, which is where red blood cells and protein escape in the urine as a result of damage to the glomerulus.

In nephronophthisis, the affected tubules lose their ability to concentrate the urine by reabsorbing water and other substances back to the body, so urine ends up being more dilute than usual, which leads to polyuria, excessive urination, and therefore polydipsia, or excessive drinking.