Recurrent Nephrolithiasis in Adults: Comparative Effectiveness of Preventive Medical Strategies

1
Recurrent Nephrolithiasis in Adults Comparative
Effectiveness ofPreventive Medical Strategies

• Prepared for
• Agency for Healthcare Research and Quality (AHRQ)
• www.ahrq.gov

2
Outline of Material

• An introduction to recurrent kidney stones
  (recurrent nephrolithiasis) and to the various
  dietary and pharmacological interventions
  available for preventing the recurrence of kidney
  stones
• Systematic review methods
• The clinical questions addressed by the
  comparative effectiveness review
• Results of studies and evidence-based conclusions
  about the relative benefits and adverse effects
  of currently available interventions to prevent
  kidney stone recurrence
• Gaps in knowledge and future research needs
• What to discuss with patients and their
  caregivers

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

3
BackgroundFormation and Incidence of Kidney
Stones

• Nephrolithiasis is a condition in which hard
  masses (kidney stones) form within the urinary
  tract.
• Formation of kidney stones may occur when
• The urinary concentration of crystal-forming
  substances (e.g., calcium, oxalate, uric acid) is
  high
• The urinary concentration of substances that
  inhibit stone formation (e.g., citrate) is low
• The lifetime incidence of kidney stones is
  approximately 13 percent for men and 7 percent
  for women.
• Among adults with kidney stones, approximately 80
  percent consist predominately of calcium oxalate
  and/or calcium phosphate stones.

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

4
BackgroundClinical Presentation of Kidney Stones

• Stones may be asymptomatic or may present with
• Abdominal and flank pain
• Nausea and vomiting
• Urinary tract obstruction
• Infection

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

5
Background Risk Factors for Kidney Stones

• Genetic factors are thought to account for about
  half the risk of developing kidney stones.
• Environmental risk factors include low fluid
  intake, low calcium intake, and high fructose
  intake.
• The evidence for a role for increased animal
  protein intake, high sodium intake, increased
  sucrose intake, and low magnesium intake as risk
  factors for kidney stones is mixed.
• Risk of kidney stones may be increased by medical
  conditions such as obesity, diabetes, primary
  hyperparathyroidism, gout, and anatomic
  abnormalities of the kidney.

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

6
Background Recurrence of Kidney Stones

• Following an initial stone event, the 5-year
  recurrence rate in the absence of specific
  treatment is 35 to 50 percent.
• Recurrence can be diagnosed by radiographic
  studies, by symptomatic recurrence, or by a
  composite definition that is a combination of
  symptomatic recurrence or radiographically
  detected recurrence.
• Kidney stone recurrence increases the risk of
  developing chronic kidney disease.

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

7
Background Interventions for Preventing Kidney
Stone Recurrence

• Dietary interventions that are suggested to
  prevent stone recurrence by altering
  concentrations of crystal-forming or
  crystal-inhibiting substances in urine include
• Increasing water intake, reducing dietary
  oxalate, reducing dietary animal protein and
  other purines, and maintaining normal dietary
  calcium
• Pharmacological interventions that are suggested
  to prevent stone recurrence include
• Thiazide diuretics, citrate, indapamide (a
  thiazide-like diuretic), allopurinol, magnesium
  hydroxide, and acetohydroxamic acid

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

8
Background Uncertainties Related to
Interventions for Preventing Kidney Stone
Recurrence

• Clinical uncertainty exists about the comparative
  effectiveness and adverse effects of
  pharmacological and dietary preventive
  treatments.
• Current guidelines recommend pretreatment
  biochemical analysis of blood and urine.
• However, it is unclear if using the results of
  these analyses to tailor treatment leads to
  better outcomes than empiric therapy.
• The authors of this systematic review examined
  the evidence around these uncertainties.

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

9
Agency for Healthcare Research and Quality (AHRQ)
Comparative Effectiveness Review (CER) Development

• Topics are nominated through a public process,
  which includes submissions from health care
  professionals, professional organizations, the
  private sector, policymakers, members of the
  public, and others.
• A systematic review of all relevant clinical
  studies is conducted by independent researchers,
  funded by AHRQ, to synthesize the evidence in a
  report summarizing what is known and not known
  about the select clinical issue. The research
  questions and the results of the report are
  subject to expert input, peer review, and public
  comment.
• The results of these reviews are summarized into
  Clinician Research Summaries and Consumer
  Research Summaries for use in decisionmaking and
  in discussions with patients. The Research
  Summaries and the full report, with references
  for included and excluded studies, are available
  at www.effectivehealthcare.ahrq.gov/kidney-stones.
  cfm.

Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
Comparative Effectiveness Review No.
61. Available at http//www.effectivehealthcare.ah
rq.gov/kidney-stones.cfm.
10
Clinical Questions Addressed by This Comparative
Effectiveness Review (1 of 3)

• Key Question 1. In adults with a history of
  nephrolithiasis, do results of baseline stone
  composition and blood and urine chemistries
  predict the effectiveness of diet and/or
  pharmacological treatment on final health
  outcomes and intermediate stone outcomes and
  reduce treatment adverse effects?
• Key Question 2. In adults with a history of
  nephrolithiasis, what is the effectiveness and
  comparative effectiveness of different dietary
  therapies on final health outcomes and
  intermediate stone outcomes?

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

11
Clinical Questions Addressed by This Comparative
Effectiveness Review (2 of 3)

• Key Question 3. In adults with a history of
  nephrolithiasis, what is the evidence that
  dietary therapies to reduce risk of recurrent
  stone episodes are associated with adverse
  effects?
• Key Question 4. In adults with a history of
  nephrolithiasis, what are the effectiveness and
  comparative effectiveness of different
  pharmacological therapies on final health
  outcomes and intermediate stone outcomes?

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

12
Clinical Questions Addressed by This Comparative
Effectiveness Review (3 of 3)

• Key Question 5. In adults with a history of
  nephrolithiasis, what is the evidence that
  pharmacological therapies reduce risk of
  recurrent stone episodes and are associated with
  adverse effects?
• Key Question 6. In adults with a history of
  nephrolithiasis being treated to prevent stone
  recurrence, do results of followup blood and
  urine biochemistry measures predict final health
  outcomes and intermediate stone outcomes?

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

13
Rating the Strength of Evidence From the
Comparative Effectiveness Review

• The strength of evidence was classified into four
  broad categories

High Further research is very unlikely to change the confidence in the estimate of effect.
Moderate Further research may change the confidence in the estimate of effect and may change the estimate.
Low Further research is likely to change the confidence in the estimate of effect and is likely to change the estimate.
Insufficient Evidence either is unavailable or does not permit estimation of an effect.

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

14
Dietary Interventions for Reducing the Risk of
Kidney Stone Recurrence Benefits (1 of 2)

• A limited body of evidence suggests that the risk
  of stone recurrence is reduced by the following
  dietary interventions (please see Table 1 in
  slides 16 and 17 for details)
• Increased fluid intake to maintain daily urine
  output of gt 2 L/day
• Advice to reduce soft drink intake, particularly
  in subjects with high baseline intake of soft
  drinks acidified solely by phosphoric acid but
  not by citric acid
• Low-protein, low-sodium, decreased-oxalate,
  increased-water, and normal-calcium diet when
  compared with a low-calcium, decreased-oxalate,
  and increased-water diet
• Tailored diet (based on a metabolic evaluation)
  when compared with an empiric diet
• Strength of Evidence Low for these dietary
  interventions

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

15
Dietary Interventions for Reducing the Risk of
Kidney Stone Recurrence Benefits (2 of 2)

• High-fiber, reduced-animal protein diets and
  increased oligomineral water intake as isolated
  interventions did not have a statistically
  significant effect on stone recurrence.
• Strength of Evidence Low

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

16
Table 1. Effects of Dietary Interventions on Risk
of Urinary Stone Recurrence (1 of 2)
Intervention Comparator Mode of Detection ARR, NNT, RR (95 CI) SOE
Increasing fluids to maintain urine output gt 2 L per day (for individuals with a single prior calcium stone episode) No increase in fluids Composite ARR 15, NNT 7, RR 0.45 (0.24 to 0.84) Low
Eliminating soft drinks (based on a single study in men) No advice to reduce soft drink intake Symptomatic ARR 7, NNT 14, RR 0.83 (0.71 to 0.98) Low
Eliminating soft drinks (based on a single study in men) No advice to reduce soft drink intake Symptomatic ARR 16, NNT 6, RR 0.65 (0.49 to 0.87) Low
Eliminating soft drinks acidified solely with phosphoric acid subgroup analysis of participants who were frequent consumers of such soft drinks No advice to reduce soft drink intake Symptomatic ARR 16, NNT 6, RR 0.65 (0.49 to 0.87) Low
Composite detection refers to stones detected by either symptoms or scheduled radiographs. ARR absolute risk reduction the difference in risk between the control group and the treatment group NNT number needed to treat the number of patients to be treated to find the benefit in one patient more than in the control group RR relative risk SOE strength of evidence 95 CI 95-percent confidence interval Composite detection refers to stones detected by either symptoms or scheduled radiographs. ARR absolute risk reduction the difference in risk between the control group and the treatment group NNT number needed to treat the number of patients to be treated to find the benefit in one patient more than in the control group RR relative risk SOE strength of evidence 95 CI 95-percent confidence interval Composite detection refers to stones detected by either symptoms or scheduled radiographs. ARR absolute risk reduction the difference in risk between the control group and the treatment group NNT number needed to treat the number of patients to be treated to find the benefit in one patient more than in the control group RR relative risk SOE strength of evidence 95 CI 95-percent confidence interval Composite detection refers to stones detected by either symptoms or scheduled radiographs. ARR absolute risk reduction the difference in risk between the control group and the treatment group NNT number needed to treat the number of patients to be treated to find the benefit in one patient more than in the control group RR relative risk SOE strength of evidence 95 CI 95-percent confidence interval Composite detection refers to stones detected by either symptoms or scheduled radiographs. ARR absolute risk reduction the difference in risk between the control group and the treatment group NNT number needed to treat the number of patients to be treated to find the benefit in one patient more than in the control group RR relative risk SOE strength of evidence 95 CI 95-percent confidence interval

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

17
Table 1 Effects of Dietary Interventions on Risk
of Urinary Stone Recurrence (2 of 2)
Intervention Comparator Mode of Detection ARR, NNT, RR (95 CI) SOE
Low-animal protein, low-sodium, decreased-oxalate, increased-water, and normal-calcium diet Low-calcium, decreased-oxalate, and increased-water diet Composite ARR 18, NNT 6, RR 0.52 (0.29 to 0.95) Low
Tailored diet based on a metabolic evaluation Empirical dietary recommendation Composite ARR 13, NNT 8 RR 0.32 (0.14 to 0.74) Low
Low-animal protein, high-fiber, increased-bran, low-purine, increased-fluid, and adequate calcium diet Increased fluid intake and adequate calcium Composite ARR -20, NNT 5 RR 5.88 (1.39 to 24.92) Low
The recommended level of dietary calcium intake in this study was 1,200 mg per day. Composite detection refers to stones detected by either symptoms or scheduled radiographs. Changes in risk according to the specific metabolic abnormality and dietary recommendation were not reported. ARR absolute risk reduction the difference in risk between the control group and the treatment group NNT number needed to treat the number of patients to be treated to find the benefit in one patient more than in the control group RR relative risk SOE strength of evidence 95 CI 95-percent confidence interval The recommended level of dietary calcium intake in this study was 1,200 mg per day. Composite detection refers to stones detected by either symptoms or scheduled radiographs. Changes in risk according to the specific metabolic abnormality and dietary recommendation were not reported. ARR absolute risk reduction the difference in risk between the control group and the treatment group NNT number needed to treat the number of patients to be treated to find the benefit in one patient more than in the control group RR relative risk SOE strength of evidence 95 CI 95-percent confidence interval The recommended level of dietary calcium intake in this study was 1,200 mg per day. Composite detection refers to stones detected by either symptoms or scheduled radiographs. Changes in risk according to the specific metabolic abnormality and dietary recommendation were not reported. ARR absolute risk reduction the difference in risk between the control group and the treatment group NNT number needed to treat the number of patients to be treated to find the benefit in one patient more than in the control group RR relative risk SOE strength of evidence 95 CI 95-percent confidence interval The recommended level of dietary calcium intake in this study was 1,200 mg per day. Composite detection refers to stones detected by either symptoms or scheduled radiographs. Changes in risk according to the specific metabolic abnormality and dietary recommendation were not reported. ARR absolute risk reduction the difference in risk between the control group and the treatment group NNT number needed to treat the number of patients to be treated to find the benefit in one patient more than in the control group RR relative risk SOE strength of evidence 95 CI 95-percent confidence interval The recommended level of dietary calcium intake in this study was 1,200 mg per day. Composite detection refers to stones detected by either symptoms or scheduled radiographs. Changes in risk according to the specific metabolic abnormality and dietary recommendation were not reported. ARR absolute risk reduction the difference in risk between the control group and the treatment group NNT number needed to treat the number of patients to be treated to find the benefit in one patient more than in the control group RR relative risk SOE strength of evidence 95 CI 95-percent confidence interval

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

18
Dietary Interventions for Reducing the Risk of
Kidney Stone Recurrence Adverse Effects

• Adverse effects, reported in terms of withdrawals
  for any cause, were low in trials evaluating
  increased fluid intake but high in long-term
  trials evaluating low-soft drink, high-fiber,
  low-animal protein, and multicomponent dietary
  interventions.
• However, no significant differences in
  withdrawals between intervention and control
  groups were reported in these trials.
• Other adverse events reporting was poor.

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

19
Pharmacological Interventions for Reducing the
Risk of Kidney Stone Recurrence Benefits (1 of 3)

• Thiazide diuretics reduce the risk of calcium
  stone recurrence (composite endpoint) absolute
  risk reduction (ARR) 29 percent number needed
  to treat (NNT) 3 (relative risk RR 0.53
  95-percent confidence interval (95 CI), 0.41 to
  0.68).
• Hydrochlorothiazide, chlorthalidone, and
  indapamide each reduce the risk of recurrent
  stones, but no trial directly compared thiazide
  agents to each other.
• No trial directly compared different dosages of
  agents, and no trial assessed the lower thiazide
  doses often used to treat hypertension.
• Strength of Evidence Moderate
• Composite endpoint stones detected either by
  symptoms or scheduled radiographs

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

20
Pharmacological Interventions for Reducing the
Risk of Kidney Stone Recurrence Benefits (2 of 3)

• Citrate reduces the risk of calcium stone
  recurrence (composite) ARR 41 percent NNT 3
  (RR 0.25 95 CI, 0.14 to 0.44).
• Strength of Evidence Moderate
• Allopurinol reduces the risk of calcium stone
  recurrence in patients with elevated blood and
  urine uric acid levels (composite) ARR 22
  percent NNT 5 (RR 0.59 95 CI, 0.42 to
  0.84).
• Strength of Evidence Moderate
• There is no additional benefit from adding
  citrate to thiazide in patients (composite), 35
  percent of whom had hypercalciuria and 15 percent
  of whom had hypocitraturia.
• Strength of Evidence Low

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

21
Pharmacological Interventions for Reducing the
Risk of Kidney Stone Recurrence Benefits (3 of 3)

• Treatment with magnesium did not reduce the risk
  (composite endpoint) of stone recurrence when
  compared with placebo. ???No statistically
  significant difference in the risk of stone
  recurrence was observed.
• Strength of Evidence Low
• The evidence about acetohydroxamic acid treatment
  for preventing stone recurrence (detected
  radiographically) in patients with chronic
  urinary tract infections and struvite stones is
  insufficient to permit conclusions however, this
  does not exclude the possibility that the drug
  does not work.
• Strength of Evidence Insufficient

Composite endpoint stones detected either by
symptoms or scheduled radiographs

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

22
Pharmacological Interventions for Reducing the
Risk of Kidney Stone Recurrence Adverse Effects

• When compared with participants given placebo or
  control treatments, patients given thiazide,
  citrate, or acetohydroxamic acid were more likely
  to withdraw from trials and to withdraw due to
  adverse effects.??
• Participants treated with allopurinol were not
  more likely than control group participants to
  withdraw from trials overall or to withdraw due
  to adverse effects.
• Patients given high-dose magnesium were more
  likely to withdraw due to adverse effects (all
  due to diarrhea) when compared with placebo
  groups.??
• Specific adverse effects were poorly reported.
  U.S. Food and Drug Administration labels should
  be consulted when using these agents.

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

23
Baseline Blood and Urine Biochemical Evaluations
To Predict Stone Recurrence (1 of 2)

• Almost no randomized controlled trials (RCTs)
  reported stone recurrence outcomes between
  treatments for subgroups stratified by baseline
  biochemistry levels.
• In two RCTs limited to patients with calcium
  stones and hyperuricosuria or hyperuricemia,
  those randomized to allopurinol versus a control
  had a significantly lower risk of recurrent
  stones using composite endpoints (33.3 vs.
  55.4 relative risk 0.59 95-percent
  confidence interval, 0.42 to 0.84).

The strength of evidence for these findings
was not rated. Composite endpoint stones
detected either by symptoms or scheduled
radiographs.

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

24
Baseline Blood and Urine Biochemical Evaluations
To Predict Stone Recurrence (2 of 2)

• Limited evidence suggests that baseline calcium,
  oxalate, and citrate do not appear to predict
  efficacy of diet and pharmacological
  interventions on recurrent stone outcomes.
• Otherwise, the evidence is limited to determine
  the effect of baseline values of urine magnesium,
  phosphate, potassium, pH, or supersaturation of
  calcium oxalate, uric acid, or calcium phosphate
  on predicting treatment efficacy.

The strength of evidence for these findings was
not rated.

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

25
Followup Blood and Urine Biochemical Evaluations
To Predict Stone Recurrence

• No randomized controlled trials (RCTs)
  prospectively compared subsequent stone
  recurrence outcomes between treatments stratified
  by followup biochemistry levels or by changes in
  these measures from pretreatment baseline.
• No eligible pharmacological RCT reported followup
  urine supersaturation levels and their role in
  predicting reduced risk of recurrent stones with
  drug treatment.
• Followup measurement of the urine calcium level
  after dietary treatment is unlikely to be a
  reliable predictor of treatment efficacy for
  reducing the risk of stone recurrence.
• Followup measurement of the urine calcium level
  after thiazide treatment may not be a reliable
  predictor of treatment efficacy for reducing risk
  of stone recurrence.

The strength of evidence for these findings was
not rated.

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

26
Conclusions (1 of 3)

• The published evidence regarding the
  effectiveness of dietary interventions to reduce
  the risk of recurrence of calcium stones is
  limited. There is low-strength evidence that
• Fluid intake to maintain urine excretion of gt 2
  liters per day may provide a clinically
  significant reduction in risk of stone
  recurrence.
• Abstaining from soft drinks or eliminating soft
  drinks acidified solely with phosphoric acid but
  not by citric acid (based on a single study in
  men) reduces risk of stone recurrence in frequent
  consumers.
• A normal-calcium, low-sodium, low-animal protein
  diet may reduce the risk for stone recurrence,
  but the independent effect of increasing dietary
  calcium has not been determined.
• High-fiber and reduced-animal protein diets may
  not help prevent stone recurrence.
• The effectiveness of other dietary interventions
  is not clear.

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

27
Conclusions (2 of 3)

• Among the pharmacological interventions, thiazide
  diuretics, citrate, and allopurinoleach combined
  with increased fluidreduce the risk of calcium
  stone recurrence more than increased fluid intake
  alone.
• Allopurinol treatment reduced the rate of stone
  recurrence for patients with elevated blood or
  urine levels of uric acid.
• Thiazides or citrates may be the preferred
  initial therapy over allopurinol in patients with
  calcium stones and no hyperuricosuria or
  hyperuricemia.
• Patients receiving pharmacological interventions
  may experience adverse effects that lead to
  withdrawal from treatment.

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

28
Conclusions (3 of 3)

• Clinical studies have not clearly established the
  general utility of baseline or followup blood and
  24-hour urine biochemical evaluations in
  predicting stone recurrence.
• Regarding applicability, nearly all trials
• Were limited to patients with a history of
  calcium stones
• Were conducted primarily in young to middle-aged
  men
• Excluded participants with biochemical
  abnormalities
• Excluded individuals with specific conditions
  that could predispose them to stone formation
• Were limited by the absence of reported data on
  patient characteristics

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

29
Gaps In Knowledge (1 of 2)

• A review of randomized controlled trials (RCTs)
  to assess benefits and of RCTs and observational
  studies to assess adverse effects revealed a
  number of gaps in knowledge seen in these types
  of studies.
• There is no direct evidence from RCTs about
  whether diets that increase calcium or lower
  sodium, oxalate, or purine (independent of other
  dietary components) reduce the risk of recurrent
  stones.
• It is unknown whether the efficacy of dietary
  interventions differs as a function of
  participant characteristics.
• Direct comparisons of dietary interventions to
  each other, of pharmacological interventions to
  each other, and between these two types of
  interventions are rare or absent.??

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

30
Gaps In Knowledge (2 of 2)

• The effect of dietary and pharmacological
  interventions on stone types other than calcium
  stonesand of acetohydroxamic acid for other than
  struvite stonesis unexamined in randomized
  controlled trials that report the effects of
  these treatments on the risk of stone recurrence.
• No trial assessed the effectiveness of lower
  thiazide doses, often used to treat hypertension,
  for reducing the risk of recurrent stones.
• Studies are needed to formally test whether the
  risk for stone recurrence after either dietary or
  pharmacological treatment can be stratified based
  on blood and urine biochemical measures, either
  at baseline or at followup.

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.

31
What To Discuss With Your Patients andTheir
Caregivers

• That kidney stones have a high chance of
  recurring if not managed properly
• The importance of maintaining daily fluid intake
  to achieve urine output of gt 2 L per day
• The benefits and adverse effects of medicines for
  preventing kidney stone recurrence
• Dietary changes that may be beneficial in
  preventing kidney stone recurrence (eliminating
  soft drinks acidified solely with phosphoric
  acid, increasing calcium-rich foods, and limiting
  oxalate-containing foods)

• Fink HA, Wilt TJ, Eidman KE, et al. AHRQ
  Comparative Effectiveness Review No. 61.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/kidney-stones.cfm.