Crystals in the urine Quiz Flash cards

Topic Discussion: Stones: HEART of the MATTER

Last year, a prospective study was published in JAMA suggesting that having a history of kidney stones as an independent risk factor for cardiac disease (CHD). 

            In short, this was a prospective study of 45 748 men and 196 357 women in the United States without a history of CHD at baseline who were participants in the three study cohort registries. Coronary heart disease was defined as fatal or nonfatal myocardial infarction (MI) or coronary revascularization. The outcome was identified by biennial questionnaires and confirmed through review of medical records.

            Of a total of over 240,000 participants, over 19,000 reported a history of kidney stones. After up to 24 years of follow-up in men and 18 years in women, 16 838 incident cases of CHD occurred. After adjusting for all confounders, amongst the 2 cohorts of women, a history of kidney stones was associated with a modest but statistically significantly increased risk of CHD; there was no significant association in a separate cohort of men.

The knowledge of history of kidney stones was obtained via an independently validated survey.

When looking at the covariates, most risk variants of both formation of kidney stones and CHD were evaluated and controlled for.

Why this risk?

1.    CHD and stone formers share the same risk factors- obesity, metabolic syndrome, DMII, HTN, high lipids but when controlled for all this, the risk of getting CHD was independently associated with history of stones

2.    Perhaps common dietary factors- sugary drinks, low calcium diet, high protein diet, but dietary adjustments were also made in the study.

3.    One adjustment that was not made was renal disease. Stone formers can perhaps have CKD and CKD becomes then a CHD risk factor.  This was not analyzed per authors in the manuscript.

What is the mechanism?

1.    Perhaps there is a unknown metabolic state that is both a risk factor for stones and CHD

2.    The stone might increase some other factor that we don’t know that leads to CHD

3.    There might be some other confounding factor we haven’t found.

Why Women: - No clear explanation can be found, perhaps an unknown factor that is not clear yet.

Major limitations: Self reported questionnaire, stone analysis not clear, most patients were white and not many blacks, Asians or Hispanics.

Very fascinating study but leaves us with more questions than answers.  At this point, would not make any major statements based on this observational study re risk of cardiac disease and stones.

Primary hyperoxaluria and the Kidney

Coffee, tea, or soda: are they going to cause kidney stones?

Beverages and risk of kidney stones has been a recently studied topic.
Recently published studies and most recent being in CJASN by Curhan's group suggested the following:

1. Sugar sweetened sodas was associated with higher incidence of stones( as fructose increased urinary ca excretion and uric acid excretion).
2. Consumption of sugar sweet soda and punch was associated with highest risk of stone formation.
3. Coffee and tea drinking was associated with lower risk of stone formation( coffee and tea act as diuretics and diuresis via both proximal and distal tubules)- mainly due to caffeine related effect.
4. Interestingly, decaffeinated coffee was also associated with lower incidence of stones ( perhaps an anti oxidant effect suggested by the authors)
5. Wine and alcohol ingestion was associated with lower incidence of stones( diuretic effect)- interesting find but still needs to be studied further.
6. Orange juice intake was associated with lower incidence of stones( has K citrate and fructose in it). K citrate wins out! Some juices such as apple juice has more fructose than K citrate and hence there have been more stones in those drinkers.

Clinical Case 70: Answers and Summary

A 31 Y OLD MALE WAS FOUND TO HAVE 6MM KIDNEY STONE INCIDENTALLY ON RENAL SONOGRAM? WHAT DO YOU DO NEXT?

Urology referral

  10 (18%)

Observe with no further imaging

  20 (37%)

Stone workup

  14 (25%)

Start Potassium citrate

  1 (1%)

Observe with frequent imaging yearly

  9 (16%)

What do you do with a 6mm stone incident finding? Varied answers from majority saying do nothing and observe and second highest saying stone workup and then urology referral. One study of 107 such patients for a mean of 32 months. The likelihood of developing symptoms was approximately 32 percent at 2.5 years and 49 percent at 5 years; the risk was lowest in patients who had no history of previous stones.  Wait and watch approach may be a reasonable in asymptomatic patients with small, non-infected calculi, without evidence of obstruction. Based on stone experts, certain asymptomatic patients, depending upon their occupation (airline pilots, frequent business travelers) or having anatomic consideration( solitary kidney, diversions) should consider undergoing evaluation and treatment to reduce the risk of recurrent stone formation or growth of existing stones with perhaps options that we listed above. Tough question and practices might be varied depending on nephrology or urology. Not much data to support either way. 

Clinical Case 57: Answers and Summary

TRUE OR FALSE: LITHOTRIPSY CONCURS A HIGH RISK OF LIFETIME DEVELOPMENT OF HYPERTENSION AND DIABETES.

What is the data on this? Does Shock wave Lithotripsy cause high risk of HTN and Diabetes?

Human studies have shown that this therapy can leading to hemorrhaging and edema in the kidney.  As the dose increases, perhaps chronic scarring might ensue. Elve et al prospectively studied 228 patients with small calculi < 15nm and a control group. Followed for 2.2 years, found that there was no statistical significance in hypertension incidence. Another group found similar results. In a report of 578 patients who had undergone this, att a mean follow-up of 19 years, hypertension was significantly more prevalent in the lithotripsy group.Mayo Clinic researchers reported in the 2006  that patients who undergo this procedure are nearly four times more likely to develop diabetes and face a nearly 50 percent higher risk of high blood pressure over the following decades than those getting alternative treatment( retrospective study). In a more recent study, in a large, population-based cohort, the long-term risk of developing DM was not increased in persons who underwent this procedure to treat their kidney stones. Lithotripsy using the HM-3 was not associated with increased DM or hypertension in a Canadian study from 2011 as well.

Perhaps the jury is still out on this association. 

Here are a few references:

http://www.ncbi.nlm.nih.gov/pubmed/22088569
http://www.ncbi.nlm.nih.gov/pubmed/18387387

http://www.ncbi.nlm.nih.gov/pubmed/21635683

http://www.ncbi.nlm.nih.gov/pubmed/18952267

http://www.ncbi.nlm.nih.gov/pubmed/10458379

CLINICAL CASE 53: Answers and Summary

A 45 Y OLD CAUCASIAN MALE IS SEEN AND YOU DIAGNOSE IDIOPATHIC CALCIUM OXALATE STONE DISEASE. THE STONE FORMATION BEGINS AS SURFACES OF THE RENAL PAPILLAE START COLLECTING SUBUROTHELIAL PLAQUES CALLED RANDALL PLAQUES. WHERE DOES THIS PROCESS BEGIN?

Proximal Tubule  17%
Thin Loop of Henle 30%
Thick Loop of Henle 12%

Distal Collecting Duct 33%

Glomeruli 5%

The correct answer is Thin Loop of Henle.  

http://www.jci.org/articles/view/17038 is the article that made this point with a nice study of biopsies around the plaque sites. They performed intra operative biopsies of plaques in kidneys with calcium stone formers.  They showed this in their paper that the plaques originated in the basement membranes of thin loops of Henle and spread to the interstitum and then the urothelium.  In the patients with obesity related bypass procedures, the stones and plaques were different and instead had intratubular crystals in the collecting ducts.  

The figure 1 and figure 2 from an editorial nicely depicts it.

Medicine for residents: urinary calcium and renal stones

Medicine for residents: urinary calcium and renal stones: "Calcium oxalate stones are the most common type of renal stone.(around 75%). 3 types of stones can be caused by calcium- calcium oxalat..."