I'd be interested in hearing anyone's experiences with thiazides, or with citrates. My neph thinks it's best to wait and not take these until the symptoms get worse, and I see her point. But I'm wondering if anyone else works on a different philosophy.

Hi, my son is diagnosed as Dent's and we have been struggling with finding any remedies effective on this disease for more than 15 years. We have been seeing many doctors at one of the biggest university hospitals in Japan. I found that there are far wider variety of symptoms in Dent's, also there still is not a medicine clearly effective to this disease. we tried thiazide plus some citrates but years of that medication was not effective to my son and had some trouble in his health, shortage of potassium. Now the doctor prescribes just some potassium, and we are trying a high citrate diet, which was not suggested by the doctor but I read a thesis about rat testing showing the high citrate diet could delay the progress of the symptom (of rats...). In short, 1L orange juice a day. Our doctor is also curiously watching how the situation goes. If you or anyone else knows about any insights or examples on high citrate diet, please let us know...

Hi, Mune, we have been doing citrates for about a year, and my son's nephrologist seems to think it's helping. It's a prescription liquid that we mix with juice. We are also about to start on thiazides, although I'm a little nervous about that. But we are just hoping he won't have a lot of the side effects. We did a couple of years on prednisone before the Dents was diagnosed and the side effects were awful! Is your son an adult now? What kinds of kidney damage are you seeing?

Hi juuliedowns, My son is 17 years old, with high creatinine. When he was taking thiazides plus potassium citrate, he was not in a good shape for some years, and eventually fell down in hot Summer with low potassium and high creatinine plus numbed feeling in his hands and others. He does not have those symptoms now. Now he is fine.

Hi, my son was diagnosed with Dent's disease when he was 6 and he is now 14. He did take thiazides with potassium supplements. The thiazides made an enormous difference in his urine calcium output, but at the expense of extreme muscle weakness and pain and some osteoperosis. His nephro has opted to take him off the thiazides to relieve the side effects. Since diagnosis, he has tended to respond to mediations quite severly so we are trying to minimize usage as much as we can. His calcium and creat., while higher than normal have been consistent through the start of his teens. There does not seem to be any change in calcification in his kidneys according to annual ultrasounds. It seems that he has the milder form given that he is within the norm on the growth chart and has yet to have a stone. We do all that we can to stress the importance of hydration, particularly when he plays sports in warm weather. Not sure what the future has in store, but we are thankful for where we are at now!

MY SON WAS DIAGNOSED WITH DENTS AT THE AGE OF 3 HE IS NOW 15. WE HAVE TRIED EVERY MED IMAGINABLE BUT DO RECALL THE THIAZIDES MAKING HIM SICK AND REALLY DIDN'T HELP AT ALL. HE STRUGGLES EVERY DAY AND IS STILL THE SIZE OF A 7YR OLD. LOOKING FORWARD TO A BREAKTHROUGH

I have a 24 year old son with Dents. We knew he had kidney disease at age 9 months, but it wasn't diagnosed as Dents until he was 13, when they discovered the DNA code. It turns out that my father had Dents too, though at the time (1970's) they didn't have a name for what he had. He lived until age 43 and didn't get any treatment until he was in his late 30's. My son's creatinine has been pretty consistently 1.7. He's been on citrates and a low dose ACE inhibitor for as long as I can remember. He has never been on thiazides. He's a normal male adult size, and even with stones were showing up in his kidney ultrasounds since childhood, he never passed one until age 20. He's recently had a number of procedures to rupture the stones so they wouldn't cause any problems passing. I'd say that he's in excellent health.

While my son was taking thiazides, his health had been getting worth, creatinine as well. He eventually fell down at the corner of the street and brought by an ambulance. I found Johns Hopkins' "high citrate diet" paper of rat testing, and I started doing it on human... giving much orange juice and citrate supplement to my son since 1.5 years ago. Now our med doctor prescribes citrate, calcium and vitamin-D partly because his thyroid hormone is higher than before. He is fine now. Though once raised creatinine could never get better but up trend has slowed down.

Unfortunatelly, Thiazides seem to be difficult to tolerate in children who have normal blood pressure. Hydration is very important but there is often a problem with low potassium, also and children are taken off these medications. We know that thiazides lower calcium in the urine and can potentially reduce forming of calcium stones but we don't even now if they protect the kidney long term from kidney failure. Hydration is still the most important and safe factor to prevent the kidney stones. We don't know if citrates work because we don't have clinical studies on humans. Dent boys tend to have lower height but that's not universal. There is no published data on Dent adults, interestingly, all information is from kids and families report grandfathers who usually already died. It would be so important to collect information on adults who have Dent. We have to do a better job diagnosing Dent disease in adults. Lada

I have a question for all. How many of your children are on ACE inhibitors and has that controlled the amount of protein in the urine or is the protein still increasing on ACE inhibitor? Dent has two important components. One is increased calcium in the urine which causes calcifications and stones and the other is protein in the urine, which is possibly, even more improtant for kidney failure. We don't know. Lada

Lada -- Mason has been on thiazides for about 2 months now, and seems to be doing fine. I'm so thankful that we are "beating the odds" in that we seem to not be having a lot of bad side effects. So many other meds had been so bad for him!. He's been tested for potassium and is fine, his bp (which is normally on the low end) isn't dropping, and he seems to be taking it well. He never had stones, but is taking thiazides to reduce or at least slow progress of nephrocalcinosis. The thiazides havn't had any effect on his proteinuria. He's on an ACE inhibitor, but it hasn't helped the proteinuria, which seems to be pretty unaffected by anything. It bounces around all over the place all the time. He's also on an ARB.

Julie, Thiazides have no effect on proteinuria but they reduce calcium in the urine. I'm glad Mason is able to tolerate them with no problem. Be aware of the hot, summer months when he needs to make sure to drink enough fluid. What is the range of his proteinuria? Has it been progressing at all, or it stays in that range? I remeber you said he was initially treated with prednisone, so I'm assuming his proteinuria was quite significant to begin with. Even if ACE inh/ARB is not significantly improving proteinuria, it would be a good sign if it's not progressing. Is his creatinine stable? We need controlled clinical trials to evaluate long term effect of ACE-inhibitors and ARB's in Dent patients. Lada

Lada -- Thanks for your discussions. I'm interested to have some conversation on these subjects, because my intellectual curiosity is always high, and especially when it's on a topic that affects me as personally as this! His proteinuria, as measured by a P/C ratio, has been pretty dependably between about 200 and 400. It jumps around some, with no apparent correlation to the prednisone or the CellCept, or that other C-drug that he was on for a while and caused all the hair to grow all over his body. I've just figured it was because those drugs affect primarily albumin and not the low-molecular weight proteins which are also what the P/C ratio measures. I've been assuming the jumps in the p/c ratio were probably correlated to some other function which we weren't measuring. Especially since he never had any of the other symptoms of high P/C such as hypoalbuminemia or edema or the big BP swings. All the other numbers have been mostly stable and within acceptable ranges. He's ALWAYS thirsty, which was a problem when he was young since we have Type I diabetes in the family (his older brother has it, as well as one aunt on each side!) and he got a LOT of blood sugar pokes before we started realizing that the thirst was connected to the kidney problems instead. Also, the biopsies haven't shown a lot of progress in his FSGS (or rather FGGS) but indicate that the damage hasn't spread much, if at all. No one has any idea what this means, at least as far as I can find out. Do you know much about the connection between glomerular damage and Dent disease? Thanks for your replies. I really enjoy these kinds of talks and discussions. juulie

Juulie, You probably mean p/cr ratio 0.2-0.3 which is equivalent to 200-400 mg proteins/24 h, am I right? If yes, that is pretty good. Dent patients can have p/cr up to 2-2.5, which equivalents 2000-2500 mg/24h. Dent disease's primary abnormality is reabsorption of protein in the tubules. Low molecular proteins normaly get filtered thgrough glomerulus and get reabsorbed in the tubules. Because the reabsorption system does not work well in Dent, these low molecular proteins get spilled in the urine. As Dent diseases progresses, damagae develops on the glomerulus and it becomes sclerotic, causing spillage of albumin, which then shows up in the urine, too, but always less than low molecular weight proteins. The spillage of albumin in Dent is usually not significant enough to cause edema or hypoalbuminemia becuase most of the protiens in Dent patients are low molecular weight proteins. Why the glomerular damage happens, we don't know, because the gene that is mutated in Dent encodes a channel that cannot be found in the glomerulus. There must be some "back talk" between tubules and glomerulus but we are yet to find the signals. ACE inhibitors are known to reduce pressure in the glomerulus and glomerular proteinuria, however they do have some other positive effects and there was a study that showed that on diabetic pateints they work on tubular proteinuria, too. The mechanism of tubular proteinuria is differen in diabetes. We don't know how useful are ACE in Dent. Our first step would be to gather all the patients we can with Dent and then analyze which ones were on which medications and who did best. The next step would be to divide them in two groups and assign them for different medications and see who does better. That is called a randomized controlled trial and is considered to be the best scientific medical evidence. Such trials do not exist at all for Dent because it's such a rare disease, but they do for many other diseases. In the meantime, different scientists are trying to do lab experiments related to Dent. I hope this helped. Lada

Juulie, You probably mean p/cr ratio 0.2-0.3 which is equivalent to 200-400 mg proteins/24 h, am I right? If yes, that is pretty good. Dent patients can have p/cr up to 2-2.5, which equivalents 2000-2500 mg/24h. Dent disease's primary abnormality is reabsorption of protein in the tubules. Low molecular proteins normaly get filtered thgrough glomerulus and get reabsorbed in the tubules. Because the reabsorption system does not work well in Dent, these low molecular proteins get spilled in the urine. As Dent diseases progresses, damagae develops on the glomerulus and it becomes sclerotic, causing spillage of albumin, which then shows up in the urine, too, but always less than low molecular weight proteins. The spillage of albumin in Dent is usually not significant enough to cause edema or hypoalbuminemia becuase most of the protiens in Dent patients are low molecular weight proteins. Why the glomerular damage happens, we don't know, because the gene that is mutated in Dent encodes a channel that cannot be found in the glomerulus. There must be some "back talk" between tubules and glomerulus but we are yet to find the signals. ACE inhibitors are known to reduce pressure in the glomerulus and glomerular proteinuria, however they do have some other positive effects and there was a study that showed that on diabetic pateints they work on tubular proteinuria, too. The mechanism of tubular proteinuria is differen in diabetes. We don't know how useful are ACE in Dent. Our first step would be to gather all the patients we can with Dent and then analyze which ones were on which medications and who did best. The next step would be to divide them in two groups and assign them for different medications and see who does better. That is called a randomized controlled trial and is considered to be the best scientific medical evidence. Such trials do not exist at all for Dent because it's such a rare disease, but they do for many other diseases. In the meantime, different scientists are trying to do lab experiments related to Dent. I hope this helped. Lada

Lada, I came to the right forum. I have been struggling to get some help on the treatment options for this disease. My Son is 5 years old now. He is diagnosed with dents when he is 2 years. since then he is on Hydro chloro thiazide. And after 1 year his potacium was low so docotor prescribed KCAL Potacium supplement. We have not seen any side effects so far. Acts and plays well. His symptoms are protien creatine ratio around 4. calcium creatine ratio 0.5 with out the medications. After the treatment ca/creatine is 0.15 since the protien loss is low molecular protien loss, the ace inhibitors are not effective so we used it for couple of months and stopped it. What is your best advise from the patients you have seen with this. Also, parents who did go through this what is ur suggestion. Am i taking my son in the right direction. Please advise. Is there any better treatment options..

Dear vistaonly, I am really sorry to have to tell you that we don't have a real answer which are the medications that patients should be on for Dent. HCTZ works for your son's hypercalciuria and that is great. That will likelly reduce the likelyhood of his getting stones and worsening kidney calcifications. ACE inhibitors are not expected to have a major effect on low lolecular weight proteinuria, however, we do know that Dent patients develop focal global and focal segmental glomerular sclerosis. The question is, would ACE inhibitors delay progression of kidney disease to end stage kidney failure in Dent? Since all the doctors have 1-10 patients, nobody ever looked at that. The number of patients is too small. We have the unique opportunity that NIH decided to sponsor research of rare diseases and Dent is one of them. We have money allocated for the 5 years, we are almost at the end of the first year. We made the registry, it is running and we have, so far 16 patients. We have, so far, contacted physicians all over the US and Italy, Germany, Netherlands, Macedonia, Monte Negro, Korea and Israel. We are still trying to get in touch with as many physicians as we can. The problem is that physicians are always very busy and if they want to enter the information themselves, they have to go through all kinds of administrative problems. Each one we contacted said they would like to contribute and work with us but we are waiting for them to do the work. Patients, themselves, on the other hand, can do the work themselves. Our first step is to collect as much information from as many available patients, so that we can see, looking back, how did the disease behave. Did the kidneys of patients on ACE inhibitors last longer is one of the questions? Did patients on thiazides have less stones or nephrocalcinosis? These are called observational studies. They don't require anything but just collecting information. We can then decide to assign patients to different treatments and see how they do. That is a better medical evidence. Then we could tell you, your son should be on these medications. Now we are guessing. Next step is collecting genetic material and analyzing any other genes that can influence the course of the disease. I'm sorry we have no answers yet, but if we have the ability to get them and that is good. I'm confident that we will. Dent gene is being passed to younger generations, we should. Lada

Dr.Lada, Thanks for the info. I will get my sons reports to your registry over this weekend. Thanks,

Hi Lada and everyone. It is so great to finally be able to discuss with other people these topics that I have never ever been able to discuss with anybody else, except the nephrologist. I participated in a nephrology support group at the children's hospital here but never contributed or got much out of it because nobody else had Dent's. My son is now 19 and has been taking ACE (fosinopril or monopril) since he is 10 1/2 years old. I don"t think it has reduced the protein in his urine, which I believe is around 2 g. You would probably be better than me in reading his charts, Lada, which I don't know if the Mayo Clinic already requested from his nephrologist. So maybe you could contact Julie. The doctor prescribed the ACE inhibitor saying it would make his kidneys work less, be less stressed. He also warned us that his kidney function might seem lower because of taking the ACE. One question: I feel the measurements in the US are different than in Canada. Here we talk about the GFR whereas I feel people in the US always talk about creatinine and don't understand when I talk about GFR (kidney function). My son's creatinine is tested twice a year, but the kind of numbers I see are far off the ones mentioned in the US. To compare, when someone says their creatinine is 1.7, is this in urine , mmol or mmol/L.? I just don't see any number in my son's charts that resembles that. For example, my son's mmol/L creatinine, urine is around 5.7 and his creatinine, serum is around 270. This last number has been going up more rapidly in the last couple of years. The doctor does mention that my son is all muscle, no fat, and grew mainly in the last few years (late teens), so I don't know if that contributes to higher creatinine too. He has taken thiazides since the age of 4 but we never noticed any side effect. It did lower his calcium, as long as he doesn't consume excessive sodium in his diet. And the low potassium that other people mention amazes me because, if they are taking potassium citrate, shouldn't their potassium levels be OK or even high? My son's potassium has always been OK. Besides my question of how you measure creatinine, I also wonder if taking Orange Juice regularly is OK because of its high potassium content. But, from what I gather from other people in this forum, it's the opposite: orange juice is great because it has both potassium and citrates? Would orange juice be like taking a potassium citrate pill? Thanks, Lada (So many questions!)

My 25 year old son's potassium is extremely low, and his nephrologist told him not to do anything to increase it via vitamins or food. I'll try to find out why. In regard to hy son's creatinine being 1.9 recently, it was read in his blood, not urine. I was told that that number can fluctuate from day to day depending on how much water he may have drunk in the past day. Also, I was told that the 1.9 number means his has about 60% of his kidney function. Jeanne

Thanks Jeanne. I will ask about the creatinine reading in blood. I just looked at some of his previous blood work reports, and I don't see creatinine measured by itself, but I do see the ratio of calcium/creatinine at around 1.3. His kidney function is supposed to be around 35% if not lower, but until now he looks and acts like any other active 19 year old and hardly ever is sick and has never passed a stone that we know of. According to the kidney biopsy they did when he was 3 years old, he was already down to 55% at that early age.

One thing I notice is that nobody mentions allopurinol or novopurinol, which is used to reduce uric acid and is typically taken by gout patients. When diagnosed at 3 in Montreal, he was put on alllopurinol and potassium citrate, so, of the 4 meds, he takes, it's the one he has been taking the longest together with pot. citrate. His doctor did take him off it a couple of years ago saying it was not necessary, but that year his kidney function went down quickly, so I requested for him to start taking it again. So is my son the only one taking allopurinol?

I was away for a week and I'm glad to see so much activity on the site! Minu, the blood cr value in the US is in mg/dl, so it is very different from Canada where it is expressed in μmol/L. You would have to convert it. 1 mg/dL of creatinine is 88.4 μmol/L. To convert from mg/dl to μmol/L, you would have to multiply by 88.4. To convert from μmol/L to mg/dl, you would have to divide by 88.4. GFR (glomerular filtration rate) reflects kidney function. It can be calculated from creatinine (there are several formulas), or can be calculated from 24 hour urine measurements. Both are estimates of kidney function. Higher muscular mass will increase the creatinine.

Bleujeanne, I did talk to and actualy meet your son's nephrologist. He was very receptive and came to two of our Dent meetings held as a part of the large national nephrology meetings. I know he is seeing several Dent patients, however, none of them registered yet. I do keep asking him to remind your son and I am never sure if he has not reminded him or that your son was reluctant. I can see that this can be a difficult issue for the young adult and it's very possible that it's easier to be in a bit of denial. It seems that the mothers and fathers are more likely to be proactive.

Thanks for the conversion info., Lada. My son was doing the 24 hour urine until last year. I think his new adult doctor does not ask for it. Knowing the pediatric nephrologist who saw my son for 16 years, I am confident he would also be very willing to discuss my son's records with you (long distance), if you so desire. His name is Dr. Julian Midgley at Southern Alberta Children's Hospital. And I could ask my cousin's son in Israel, also afflicted by Dent's, to e-mail you his doctor's info. And your last paragraph just described my 19 year old son's attitude (a bit in denial; I am the proactive one). I was the one that actually did the registration process with the Mayo clinic, obviously with his awareness, permission and signature.