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Renal/urol- stones

Primary Care Corner with Geoffrey Modest MD: alpha blockers help with ureteral stone passage

7 Dec, 16 | by EBM

By Dr. Geoffrey Modest

A recent meta-analysis/systematic review confirmed that a-blockers are efficacious in the treatment of patients with ureteral stones (see doi.org/10.1136/bmj.i6112 ).

Details:

  • 55 unique RCTs, with 5990 randomized patients, mostly in European and Asian subjects. Mean stone size 5.7 mm, tamsulosin was the a-blocker in 40 studies, mean follow-up of 28 days
  • Primary outcome: proportion of patients who passed their stone
  • Secondary outcomes: time to passage of stone, number of pain episodes, and proportion of patients who had surgery/were admitted to hospital/experienced adverse events

Results:

  • a-blockers facilitated the passage of stone, with risk ratio (RR)=1.49 (1.39-1.61), a 49% higher likelihood of stone passage (moderate qualityevidence)
    • The pooled risk difference was 0.27, meaning that 4 patients needed treatment for 1 to get benefit
    • The pooled % for stone passage was 75.8% in the a-blocker group vs 48.4% in the control group. this was basically independent of the type of a-blocker used or if imaging was done to assess stone passage
  • Subgroup analysis
    • No benefit for those with small stones, RR=1.19 (1.00-1.48), though on the cusp of being significant
      • Review of their figure of stone size:
        • Small trend to benefit if <5mm, increasing trend if <6mm
        • Reasonably clear benefit if >6mm, and esp if >8mm
      • In those with larger stones, RR=1.57 (1.39-1.61), a 57% higher likelihood of stone passage
      • No difference based on where the stone was located (upper or middle ureteral stones)
    • Secondary analyses, benefit of a-blocker:
      • Shorter time to stone passage, mean decrease of 3.79 days (3.14 to 4.45 days), moderate quality evidence
      • Fewer episodes of pain, mean decrease of 0.74 (0.21 to 1.28), low quality evidence
      • Lower risk of surgical intervention, RR 0.44 (0.37-0.52), moderate quality evidence
      • Lower risk of hospital admission, RR 0.37 (0.22-0.64), moderate quality evidence
      • Similar risk of adverse events, low quality evidence

Commentary:

  • This meta-analysis/systematic review follows on the tail of a recent RCT (see Pickard R. Lancet 2015; 386: 341), finding that neither tamsulsin4 mg nor nifedipine 30mg decreased the need for further intervention for stone clearance within 4 weeks of randomization. I am often concerned that we all tend to give disproportionate weight to the newest study. In fact this Pickard study, though a large one with 1136 patients, had 75% of them with stone size <5mm (which pass pretty easily on their own, and the above meta-analysis did not find much benefit to the a-blocker), and though the remaining 25% were >5mm, they do not indicate whether this was mostly 5.5mm or 9.8mm. And, likely because of the small size of the stones overall, 80% of the patients did not need any further urologic intervention in the ensuing month in either the intervention or control groups.
  • I should also reiterate the caveat that meta-analyses and systematic reviews are not the be-all and end-all, but are fraught with their own limitations, and are not considered very high on the evidence-based medicine hierarchy (and not even included in the pyramid of the most thoughtful pyramids, to my thinking. See http://blogs.bmj.com/ebm/2016/11/21/primary-care-with-geoffrey-modest-md-lessons-ive-learned-from-looking-at-the-medical-literature/ )

So, bottom line is that this review does support the use of a-blockers in those with ureteral stones, especially if >5-6mm in size. There are also studies showing that calcium-channel blockers help (most studied being nifedipine), and the data are mixed as to whether the a-blockers or calcium channel blockers are better.

Primary Care Corner with Geoffrey Modest MD: Interventions to prevent recurrent kidney stones

30 Jan, 15 | by EBM

By: Dr. Geoffrey Modest

The Am College of Physicians released a clinical practice guideline on interventions to prevent recurrent kidney stones (see doi:10.7326/M13-2908​).

Background:

–13% of men and 7% of women get kidney stones, and 35-50% have recurrence within 5 years without treatment
–80% are calcium oxalate or calcium phosphate or both
–Dietary efforts include increasing water intake, reducing dietary oxalate, reducing dietary animal protein and other purines, and maintaining normal calcium intake

Results of this systematic review:

–1 good quality and 28 fair-quality trials found insufficient evidence that assessing stone composition, or blood/urine chemistries reduces recurrences
–80 fair-quality trials of dietary interventions have found that:
–Increased fluid intake, reduced soft drink intake (esp. soda acidified by phosphoric acid, eg colas), and a high-calcium, low-protein, low-sodium diet reduce stone recurrences, though these studies were typically of low-quality and often with mixed results.
–One trial also found that low sodium intake (50 mmol/d) helped in patients with calcium oxalate stones.
–No trial specifically assessed low oxalate diet, though there was a trial finding benefit of high calcium (1200 mg/d) vs. low calcium diets (400 mg/d) — which has been attributed to dietary calcium binding oxalate in the gut and decreasing oxalate absorption.

Pharmacologic therapy:

–Thiazides — moderate-quality evidence from 6 fair-quality trials of 24.9% vs. 48.5% incidence of recurrent stones. no difference in type of thiazide. Though 8% vs. 1% withdrew for adverse reactions. ​ (In terms of dose — they note that these studies were done with higher dose thiazides. none with lower doses which have fewer adverse effects — it is evident that even low doses of thiazides increase serum calcium levels, though I could find no good data on dose-dependent calcium excretion. and I have prescribed lower dose thiazides with apparent good effect)
​–Citrates (which interfere with stone formation) — moderate-quality evidence in 5 trials of calcium stones with lower recurrence (11.1% vs. 52.3%). though 15% vs. 2% withdrew for adverse reactions.
–Allopurinol — moderate-quality evidence in 4 trials in patients with calcium oxalate stones of decreased recurrence (33.3% vs. 55.4%). no increase in adverse effects found.

So, their recommendations:

–Increase fluid intake spread throughout the day to achieve at least 2 L of urine/d (weak recommendation, low-quality evidence). They suggest avoiding colas (acidified by phosphoric acid) but not drinks acidified by citric acid (eg fruit-flavored sodas)
–Use drug monotherapy with thiazides, citrate or allopurinol in patients where increased fluid intake fails to reduce recurrent stones (weak recommendation, moderate-quality evidence)

So, a couple of comments:

1. Although I do give patients lists of high oxalate foods to avoid when they have calcium oxalate stones (and I do check stone chemistry analysis), my guess is that a more acceptable diet is the high calcium one, which I also recommend.
2. The issue of allopurinol. unclear what the mechanism is. 2 RCTs have found that patients who had hyperuricosuria put on allopurinol had fewer calcium oxalate stones, but an observational study found no difference in uric acid excretion in people with or without stones (observational study. controlled for some risk factors. but who knows?). Uric acid as nidus for stone formation (unclear). As most of you know by now, I am very concerned about food additives, and one of the obvious targets is high-fructose corn syrup, which is associated with dramatic increases in fructose consumption (currently about 25% of calories in the US, mostly from sodas, with increase from about 15 gm/d when fructose was consumed naturally from fruits to 73 gm/day now), has a different metabolism from glucose (which is converted into glycogen in the liver, vs. fructose, which is converted to fructose-1-phosphate and depletes the liver of phosphates, increases uric acid levels, increases small dense and more atherogenic LDL particles, and may increase insulin resistance). I have had some patients completely stop soda intake and have found pretty dramatic decreases in uric acid levels. So, this is now one of my dietary recommendations for those with kidney stones.

Primary Care Corner with Geoffrey Modest MD: Kidney Stone Predictive Model

21 May, 14 | by EBM

a recent study developed a clinical prediction rule for uncomplicated ureteral stones (see doi: 10.1136/bmj.g2191).  there were 2 components to the study. first was a retrospective observational study to develop the screening tool, a random selection of 1040 adults (derivation cohort) who underwent non-contrast CT for suspected uncomplicated kidney stone from 2005 to 2010. their data was used to derive the top five factors associated with stones analysis and ascribe points reflecting their importance (see STONE score below). the second study was the validation study, 491 patients where the ER physicians felt that the patient presentation was consistent with ureteral stone.

–for the observational component: the five key factors were — male sex, short duration of pain, non-black race, presence of nausea or vomiting, and microsopic hematuria.
–in the derivation and the validation cohorts (respectively)
–STONE score of 0-5: 8.3% and 9.2% had stones (this reflected 19.8% and 15.5% of patients)
–STONE score of 6-9: 51.6% and 51.3% had stones (this reflected 49.6% and 46.8% of patients)
–STONE score of 10-13: 89.6% and 88.6% had stones (this reflected 30.6% and 37.7% of patients)
— of note, in this high probability group, acutely important alternative findings were present in 0.3% and 1.6% (mostly diverticulitis, appendicitis, cholecystitis and a spattering of other diagnoses)

STONE score:

male sex =2

duration of pain: >24 hours =0, 6-24 hours =1, <6 hrs =3

race: nonblack=3

nausea alone=1, vomiting  alone=2

erythrocytes in urine: present =3

max total = 13

so, interesting study in that it could decrease the use of CT scans and the attendant ionizing radiation (average of 11.2 mSv), especially in the 1/3 of patients who are high risk. CT scans are the diagnostic procedure of choice in the US, though ultrasounds are preferred in Europe. the authors comment that “despite a 10-fold increase in the utilization of CT scanning for diagnosis of kidney stones from 1996-2007, the proportion of patients with a diagnosis of kidney stone, findings of significant alternative diagnoses, or hospital admission has not changed”. one potential plus for CT in those in the high probability STONE score is to find the 20% or so with large stones who likely need an intervention. they offer the possibility of a substantially reduced dose CT scan (which could miss some important alternative findings, though present in <2% of their groups), or ultrasound (which sometimes cannot see the stone well). or possibly limiting the reduced dose CT to younger patients who are even less likely to have an important alternative finding.

but a few caveats: this is one study done in 2 centers at Yale, so needs to be repeated. 85% of patients were white (more common for stones in whites, but interestingly also more common in men and 46% of the patients were women). so not sure about generalizability to other regions, ethnicities. however, i am always concerned about the amount of ionizing radiation we subject patients to. the thought of low-dose CT is appealing, though ultrasound makes a lot of sense to me for initial imaging

geoff

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