Hematuria and proteinuria with nightsweats and weightloss


Hi. I’m a 46 year old man. Fit and healthy. Non-smoker who rarely drinks but has a stressful job with long days. I have felt very tired and down for the past 12-18 months. I also have a lot of pain in my upper abdomen and into my lower back (left hand side). I’ve lost 8-9 kg in the last 7 months. I am 188 cm tall but have been fairly constantly 82/83 kg since my early twenties. I eat like a horse and have never held back because I exercise a lot (long distance running, cross country skiing and gym). I have severe night sweats although this appears to come and go. I frequently drench the sheets and I find it embarrassing that the mattress on my side of the bed has terrible sweat stains. At my annual health checks I have had microscopic hematuria and some protein in the urine for the past 3 years. Eventually I was referred to a urologist who took biopsies and removed a “velvety red patch” from the bladder wall under GA. The histology results were uncertain describing it as possibly dysplasia but recommending «å følge nøye med denne pasienten med nye biopsier» due to various strong immunohistochemical markers. I’ve also had CT abdomen and full blood count. Nothing alarming in either and the only points of interes. I had a colonoscopy and gastroscopy - no Celiacs although I have the gene as I understood. Since I was continuing to feel fairly exhausted with no real explanation, I was referred to an indremedisiner. He took more tests and as I understand excluded diabetes. One test result which was abnormal was a high renin count. My blood pressure was also fairly high 156/85 - 145/75. I had a 4 month check today with the urologist who thought the renin test may be relevant to my bladder issues but said it was not in his field of expertise. My questions are (a) if the renin result should be followed up (heard nothing since my appointment), (b) if my blood pressure is normal for a man my age, and (c) if I should push for more investigation of my abdomen? Thank you!

Mann 46


Thank you for writing us and providing a very good longitudinal history of your symptoms, complete with a list of your more pressing and immediate questions or concerns. As you describe several symptoms and problems, there are a number of pertinent questions or historical features that would be helpful to know, and which I suspect have been delineated in your conversations and exams with your physicians. I will attempt to answer your more immediate questions, but will also offer several important things to consider or discuss with your physicians. I will also provide comments on issues you should consider prioritizing. 

Starting with your questions about the blood pressure and your renin level elevation, your blood pressure is elevated and, as defined by the 2017 American College of Cardiology/American Heart Association guidelines, is considered to be Stage 2 Hypertension. () Making the diagnosis of hypertension can sometimes be complex and requires the integration of measurements in and outside of your physicians office. Quantitatively, hypertension is the most important modifiable risk factor for premature cardiovascular disease (as it is so common) and you can impact on your future health by focusing on this with your physician. 

The renin level is difficult to interpret in isolation (by itself) without other information about the health of your kidneys (serum creatinine levels), your electrolytes, and (potentially) an aldosterone level which is often done concurrently with the renin. Some time ago, physicians used renin in isolation to make judgements about the status of your circulatory system to guide blood pressure management, but it is not often used in this isolated manner in today. It is nonetheless important as it is used to help us exclude a number of conditions of which primary aldosteronism is the most common and a relatively common cause of secondary hypertension (where the blood pressure is caused by a secondary  or another condition). You should inquire about the renin level in relation to aldosterone (a ratio between the two). Ask about the plasma renin activity (PRA) as it is a common first step in excluding primary aldosteronism. I think doing so will give you the answer you seek regarding the renin. 

With respect to the abdominal pain, I find it reassuring that you have had a gastroscopy and colonoscopy which I presume were normal. It is additionally reassuring that you have had a CT scan of the abdomen which I assume was normal or unremarkable. If you continue to have pain I would continue to discuss the abdominal pain with your indremedisiner but remember to discuss it broadly and also to discuss it in light of the concern about the recurrent and persistent microscopic hematuria and proteinuria. I again find the tests that you have had to be quite reassuring. 

I find it interesting that the microscopic hematuria and proteinuria have been present for three years. This suggests they are not from an isolated or self-limited event which means it is all that much more important to continue to work with your doctor on understanding why they are there. I suggest you start with an early morning repeat urinalysis (preferably from the urine of your first urinary void of the day). I also suggest you take a brief holiday (one week) from the frequent and vigorous exercise before the specimen is collected. Vigorous exercise can sometimes cause both.

Many conditions can cause hematuria or blood in the urine. Many conditions can cause proteinuria or protein in the urine. When they occur together it is important to remember that the amount of proteinuria found on a common urinary assay or dip-stick in the office cannot generally be explained by the blood itself (even if the blood is visible which I assume yours was not as you describe microscopic hematuria). That is important because if the protein and the blood have both occurred in the same time frame (clearly related temporally and one did not happen at a different time than the other or before the other) then we must always consider the possibility that they are both arising or coming from the renal (the kidney's) glomerulus (the filtering part of the kidney and not just the structural or supporting tissues or elements). The amount of the protein loss in the urine can be helpful in making this determination as large amounts suggest involvement at the renal glomerulus. There is a lot of variability though, and small amounts do not exclude glomerular proteinuria. Often the best way to ascertain if the glomerulus is involved is to examine the red blood cells in the urine under a microscpe as red blood cells that come from the glomerulus have a characteristic shape (crenated or dysmorphic are common pathology descriptions) or shapes (red blood cells organized in something called casts). Your physician could examine the urine with a pathologist if he or she is not sure if these findings are present (as they are sometimes hard to find or appreciate and are sometimes only on the periphery of the slide and easy to miss). I would suggest seeing a nephrologist (a kidney expert) is probably the better course of action. 

Excluding a glomerular source for the hematuria and proteinuria are important as many systemic (involving multiple organ systems or your body as a whole) diseases can result in inflammation in the glomerulus or protein loss from the glomerulus. As you have several symptoms, this is an important distinction and your doctors will know how to exclude glomerular diseases (or glomerular involvement from a multi-system disease), or they may consult with a nephrologist if this is not clear or if you need more advanced tests or procedures to make this distinction. 

If there is no suggestion of glomerular disease, the microscopic hematuria may be simply explained by the findings of the potentially dysplastic cells found on your cystoscopy. I cannot stress enough how important it is to follow this closely with your urologist as this is a clear finding in what has otherwise been a diagnostic conundrum and you do not want to ignore the possibility of progression of dysplastic cells. If you do nothing else, continue to follow closely with your urologist.

It is also important that the remainder of your urothelial tract be examined or imaged. I'm guessing that your urologist did what we call retrograde pyelograms at the time of the cystoscopy and that this has been done as it is very standard. A CT Urogram would offer the same information and is a common first strategy. Combining a kidney ultrasound with the cystoscopy is also a good strategy. Any of the three are acceptable and are better alternatives than the tests of just a few years ago.

Your weight loss and nightsweats are also important, and if your doctors are not aware of these, please make sure they know. 

It is important to also report to your doctors any travel you have done, any infectious diseases you might have, whether from exotic places, sexually transmitted or via drug use. These are questions your doctors probably already asked you, and are part of establishing a differential diagnosis (possible causes) of your symptoms. 

I would also ask about your family history of both autoimmune diseases, malignancies or other medical problems if I were seeing you. 

In short, I think you need proper evaluation for the microscopic hematuria, proteinuria, your weight-loss and nightsweats, and close follow-up of your bladder findings and your urinary tract from your kidneys to your bladder. 

Best of luck, and don’t hesitate to contact us again!

Nina Bryhn, MD