I have copied my original replies (black) to your 1st post, your second lot of questions (blue), and my replies (in red and bold) to those 2nd set of questions below:
Thank you so much for your reply! You don’t know how much I appreciate it. I have a few comments from your reply as noted below (>>>>):
- “Central to your problem, I think, is the mantle cell lymphoma. This is a relatively rare presentation of non-Hodgkins lymphoma, and it can affect the kidneys in a variety of ways, but mainly either through direct lymphomatous cell infiltration, by causing an interstitial nephritis, or by inducing membranoproliferative glomerulonephritis.”
>>>>I had a biopsy performed at my diagnosis in February of this year. The biopsy showed a direct lymphomatous cell infiltration as you noted. Here is a link to that report: http://bit.ly/1lTsTf3. From my understanding the lymphoma infiltration no longer exists as I have been in remission since May. I was seen by an ONC doctor at the MD Anderson Cancer clinic, which is one of the top cancer centers in the world. He treated me for lymphoma and he also referred me to a nephrologist in their lymphoma section. That doctor seemed to think the direct effect of the lymphoma no longer existed when I saw him in June. That DX was from lab work, a PET scan and an MRI scan. He indicated that there was no atrophy of the kidney that he could determine from the scans. He did not perform another biopsy or ultrasound.
- “The first of these – interstitial nephritis - tends to swell the kidneys and jam them full of lymphocytes . This structurally and functionally damages the kidneys and can cause intra-renal (within the kidney) tubular obstruction … swamping the normal kidney architecture with an ‘imported’ cell population of lymphoma cells.
[B]Oops … there is a typo of mine there … it should have read “The first of these – infiltrative disease… ” and not “The first of these – interstital nephritis… ”
[/B]
The second, an acute inflammatory change in the interstitium of the kidney – the supportive tissues of the kidney that lie in between and around the nephrons – and this leads to an acute inflammatory response and acute kidney injury.”
>>>Yes, I agree 100%. That is what my local doctors have told me and that is what is reflected in the biopsy report. As noted above, I believe the lymphocytes no longer exist and that leaves only the initial damage (inflammation and swelling), which begs the big question; can the kidneys recover from this damage? Your thoughts?
My thoughts here are tending to another biopsy. This might quantify and document the degree of residual damage, the amount of remaining interstitial disease and the state of the glomeruli (ie: any newly developed changes) … etc. It might help with prognosis – especially re any late recovery of renal function. I guess we tend to be a little ‘freer’ with biopsies here than is usual in the US.
- “The third major possible effect is a mantle cell lymphoma-related glomerulonephritis with the typical features on biopsy of membranoproliferative (or mesangiocapillary) glomerulonephritis – a specific appearance on kidney biopsy where the glomerular basement membrane thickens and reduplicates with major disruption of the normal filtration capacity of the glomeruli.”
>>> From my review of the biopsy report, I do not think the condition you describe exists.
True … though this can develop over time and hence my comment re a repeat biopsy.
- “Then, you unfortunately had to add on top of this rather potent mix of problems the issues around chemotherapy. Chemotherapy is not a one-plan-fits-all treatment, either. There are a multitude of chemotherapeutic drugs, drug combinations, and ways in which the many and varied chemotherapy drugs work, combine, and interact. Some chemotherapy agents are, of themselves, directly toxic to the kidneys, some are not. In addition, some chemotherapy drugs can lead to – and this is especially in lymphoma treatments – a rapid lysis (or destruction) of the cancer cells such that there is the sudden release of a range of cellular toxins (like uric acid) from the destroyed cancer cells into the circulation. Inevitably, these toxins are carried through to the kidneys by the blood and can cause a further ‘hit’ on kidney function. This can result in superimposed conditions like acute urate nephropathy, though oncologists are now pretty good at anticipating this and pre-treating the chemotherapy with agents like allopurinol - or one of the stronger and more effective urate-protecting drugs.”
>>I am unsure of the impact you describe here. For the most part the chemo treatment drugs were: Rituxan, Vincristine, Adriamycin, Cytoxan and Prednisone. There were six treatments/infusions that began in March and ended in early July. The treatment was effective for the lymphoma (in remission since May). I certainly understand there would be a significant impact to the cells and by other toxins released into the system as a result of these drugs – both directly from the drugs and indirectly as you describe. Clearly, during treatment and for some period of time afterward (many weeks) this would be the case. I am now two months beyond the last treatment and assume that the direct impact at this point might be greatly reduced. That is my view – I have no medical opinion to confirm this. So, the big question is would the action you describe cause permanent damage? If not, then there is one less issue effecting recovery. Your thoughts?
[B][COLOR="#FF0000"][B]Of all of those on your list, the one that sticks out is Adriamycin, a drug that has been used as a model for chronic progressive glomerular disease (Kidney International (1986) 29, 502–510). There are a number of studies around the actual toxicity of Adriamycin - the main expressions of which are - primarily - its cardiac toxicity, but also its nephrotoxicity. It causes a primary glomerular lesion with capsular adhesions and subsequent scarring with a rather odd but recurring lesion at the glomerulo-tubular interface … that no-mans land where the glomerular urinary space blends into the first part of the proximal tubule. Whether the lesion is a primary glomerular one secondary tubular effects, or whether tubular injury per se is a part of the process, seems yet unresolved. However, and this is where I am coming from re a repeat biopsy, the lesion does lead to subsequent scarring that might be substantiated by another look at a new specimen for microscopy. That is not at all to say that Adriamycin was a bad choice for the treatment of your mantle cell lymphoma … not at all - and it may very well have been a life-saving drug for you… but there are always two sides to every coin, and the down side of Adriamycin is its potential to cause tissue toxicity … both for the heart and the kidneys - and this can express itself more in one organ than the other. While some of the other agents have been reported (sporadically) to have (sometimes debatable) nephrotoxic effects, it is the Adriamycin that is waving the red flag to me.
Again, a repeat biopsy might just give some prognostic clues.
I have to say I am feeling a little pessimistic re any meaningful recovery from, at the best, advanced dialysis-independent CKD4-5, but, while stranger things have happened, I would be getting ready for fixed, deep CKD5 and likely ongoing dialysis independence. Remember, I do NOT have any knowledge of your case, other than what you have told me, and even though that information has helped me get a sense of the problem, it is NOT the same as knowing the detail. As for recovery of renal function, while it can take a number of months to claw back to a stable level of recovered function, you are beginning to stretch that envelope at your current eGFR of ‘12’ … and even that ‘12’ is, as best I read it, a post dialysis or near-recent-dialysis ‘12’ and, in the context of your ongoing dialysis dependence, an eGFR says very, very little – if anything – about the true grunt left in your kidneys. In this context, any eGFR ‘number’ is not a number to put too much store by.[/B][/B][/COLOR]
- “I also have to say that the long period of time you have required dialysis – and the fact that you still appear to need dialysis – are not very encouraging signs for a meaningful recovery of renal function. I hear what you say about your fear that “dialysis may be working against the return of my kidneys” … and that’s a hard call for me to comment on from here … but the post dialysis numbers you quote do suggest to me that you are likely still dialysis-dependent. However, only those who care for you can make that call and advise you on that. For people who appear to have ‘potentially’ recovering function, we often try to slowly wind back the dialysis hours and/or frequency, and assess their post to pre dialysis rate of climb in easily measured wastes like urea and creatinine … but this is a very individual thing, and can only be judged, day by day, treatment by treatment, and is beyond my capacity to make any judgment on.”
>>>I would agree with your first sentence. However, my early condition and diagnosis (from the biopsy) certainly indicated there was a possible return of kidney function at the time of the biopsy. Subsequent to that biopsy I was in chemo for six months which would have impacted the return as you describe. I guess the big question is did that treatment simply delay the repair process or did it cause further permanent damage from which there can be no recovery. If the first (slow recovery), then now is the time to see progress since I am no longer on chemo and have not been for 60 days.
I am afraid I strongly suspect the second (further damage), not the first (slow recovery) … see all above.
I believe there are signs (baby steps). Although my current numbers call for dialysis, these numbers have been steadily improving since my diagnosis. My first GFR result in the clinic was 7. It has slowly increased to the current 12. While this is not a major move, it does show a trend. Also, over the last three or four weeks I have noticed a return of yellow color in my urine. It is not back to normal but from February until this recent change it was as clear as water. And, I continue to make a normal amount of urine.
The amount of urine you make - or its’ colour - is not always (even, not often) a useful sign. Urine volume and urine colour do NOT equate to glomerular or tubular function, and many patients who are utterly and long-term dependent on maintenance dialysis will still pass urine. The main advantage of a urine output in a dialysis-dependent patient is the freer fluid intake that is accorded by a useful urine volume, but solute clearance can still be totally inadequate … ‘colour’ notwithstanding. I am sorry to disappoint, here, but the fact you are passing urine is not necessarily something to place great hope in.
A second important question is this; is dialysis helping or hurting the possible recovery (if recovery is possible)? I believe the answer to that question is – it is not helping and it may be hindering the process (this is an opinion from my own research and not from a medical professional).
I doubt very much that dialysis is ‘hurting’ the recovery of renal function … though dialysis can delay (or mask) the small signs of functional recovery, I have to say that I doubt that ‘hurting’ or diminishing the chance of recovery is likely to be the case. Certainly, it will not be negatively impacting on any eventual recovery that might occur, though it may (as said) ‘delay’ or ‘mask’ – at least for a period.
A final and critically important question is assuming that all is not lost for a recovery as described above, is there any treatment that may help. From my own research, I’m afraid the answer to that question is a resounding NO – other than some adjustment of dialysis. This, of course, is a double edge sword. From all that I can tell any potential recovery treatment consists of removing the underlying cause. There is no proactive treatment that exists. Am I correct?
Sadly, no … I do not know of any treatment that can reverse any damage done or increase the chances of a recovery. As for the answer your research has returned … I have to say I agree with you. I am afraid that proactive treatment is not a likely option and that there simply isn’t anything out there to change your renal outcome, whatever that will be … and I would be preparing myself, if I were you, for dialysis dependence. While I maybe wrong - and I hope I am - I suspect I am not.
Again, thank you for taking the time to reply to my question. I am scheduled to see a nephrologist at UAB (http://bit.ly/1yKerqm) which is a teaching and research hospital that is ranked fairly high in nephrology at the end of the month to discuss these issues. They are local and if there is any hope and they are not able to come up with a possible solution I will plan on reaching out to one of the top one or two facilities in the nation. Otherwise, it is on to home dialysis.
Yes, your team is clearly a fine one. Trust in them.