Do cysts continue to grow even after reaching end stage kidney failure?
This post was prompted by a question on a PKD Facebook page. Now, anecdotal evidence is often really useful, but after several responses warned that cysts continue to grow FOREVER, I began to wonder if there was any evidence that would pass scientific muster, one way or the other.
Finding any form of definitive answer proved elusive – most papers relate to either the physiology of cyst growth, the Tolvaptan or Sirolimus trials, that is looking at cyst growth that occurs as renal function is declining. Few papers comment on what to expect once the kidneys are non-functioning or after a transplant.
I found one reference from 1985 claiming a 1% reduction in renal size per month in patients on haemodyalysis (Thaysen,1985) and then a 27 year gap!
Some background pathology:
Cysts are formed by tubule epithelial cells that get confused about how they are meant to behave – they divide more than they should and get confused as to which way up they are (polarity) so eventually form small pockets separated from their original tubule. At this point they are about 2 cm in diameter, the size of a soya bean. The fluid inside the cyst is secreted from the lining epithelial cells, a process that probably utilises several physiological mechanisms. So far we know that this involves the chemical cyclic adenosine monophosphate (cAMP) and also calcium-dependent chloride channels. So the cysts grow by chloride secretion into the fluid and eventually they compress the surrounding kidney tissue, (parenchyma or interstitium) leading to scar tissue (fibrosis).
From that starting point one might wonder why they would stop growing after a transplant. But that seems to be what the papers suggest: native kidney volume decreases post transplant.
The main study on this in the last 2-3 years was by Yamamoto and colleagues, reported in 2012. Using CT scans pre- and post- transplant in 33 ADPKD patients, they demonstrated that native kidney volume decreased by an average 37% in the first year after transplant. In the subsequent years the proportions were smaller (40% at 3 years) but the trend in shrinking continued. This contrasted absolutely with the continued growth of cysts on the liver in those patients who had them. Liver cysts increased in size 8% in year 1 and 21% by year 3. The authors suggest the cause of the diminished renal cysts is anoxia from impaired blood supply – which could be due to compression of intra-renal vessels by huge cysts or just general reduction in blood supply along the renal artery. This makes sense in the face of continued growth of liver cysts, as they do not experience reduced circulation.
A review paper (Goldfarb, 2012) published later that year refers to the Yamamoto study but aside from this, there seem to have been few studies around this particular issue since that paper. Those that do mention cyst volumes have been mainly concerned with reducing extra massive native kidneys in order to place a transplant. Obviously native nephrectomy is one answer but some surgeons are using an embolisation process to effect volume reduction.
After this reading I am left with other questions:
1. If the chloride secretion into the cysts is driven by calcium-dependent channels in the epithelial cells, what effect would calcium channel blockers, one type of antihypertensive medication, have on cyst growth?
2. If the cysts shrink due to lack of oxygen or impaired blood supply, then why does the shrinking seem to tail off in later years, as was seen in the Yamamoto study?
3. Can this expectation of reduced cyst volume be used to predict which patients may need native nephrectomy after transplant or does it remain a seemingly random decision depending on where the patient has the transplant?
Those are for another day.
The bottom line, albeit supported by data from just one small study, is that after kidney transplantation the volume of native kidneys decreases – in other words, the cysts do not keep growing forever!
Note: Pierre Rayer (1793-1867) was a French physician of the early 19th century who published a 3-volume treatise on kidney diseases in 1841. His method of depicting pathological specimens in an atlas alongside the symptoms and urine findings was a novel approach at that time.
after renal transplantation. J Urol 2012;188:2268.
Thaysen JH et al. Volume changes in polycystic kidneys during
chronic dialysis and after renal transplantation. Ada Med Scand 1985; 217: 197-204
Yamamoto T, Watarai Y, Kobayashi T, et al. Kidney volume changes in patients with autosomal dominant
polycystic kidney disease after renal transplantation. Transplantation 2012;93:794-8.