Purpose

Kidney stone prevention relies on the 24-hour urine collection to diagnose metabolic abnormalities and direct dietary and pharmacological therapy. While its use is guideline supported for high risk and interested patients, evidence that the test can accurately predict recurrence or treatment response is limited. We sought to critically reassess the role of the 24-hour urine collection in stone prevention.

Materials and methods

In addition to a MEDLINE® search to identify controlled studies of dietary and pharmacological interventions, evidence supporting the AUA (American Urological Association) and EAU (European Association of Urology) guidelines for metabolic stone prevention were evaluated. Additionally, the placebo arms of these studies were examined to assess the stone clinic effect, that is the impact of regular office visits without specific treatment on stone recurrence.

Results

The 24-hour urine test has several limitations, including the complexity of interpretation, the need for repeat collections, the inability to predict stone recurrence with individual parameters and supersaturation values, the unclear rationale of laboratory cutoff values and the difficulty of determining collection adequacy. Only 1 prospective trial has compared selective dietary recommendations based on 24-hour urine collection results vs general dietary instructions. While the trial supported the intervention arm, significant limitations to the study were found. Placebo arms of intervention trials have noted a 0% to 61% decrease in stone recurrence rate and a remission rate during the study of 20% to 86%.

Conclusions

Whether all recurrent stone formers benefit from 24-hour urine collection has not been established. Additional comparative effectiveness trials are needed to determine which stone former benefits from selective therapy, as guided by the 24-hour urine collection.

Objectives

To describe a new hypothesis for the initial events leading to urinary stones. A biomechanical perspective on Randall's plaque formation through form and function relationships is applied to functional units within the kidney, we have termed the 'medullo-papillary complex' - a dynamic relationship between intratubular and interstitial mineral aggregates.

Methods

A complete MEDLINE search was performed to examine the existing literature on the anatomical and physiological relationships in the renal medulla and papilla. Sectioned human renal medulla with papilla from radical nephrectomy specimens were imaged using a high resolution micro X-ray computed tomography. The location, distribution, and density of mineral aggregates within the medullo-papillary complex were identified.

Results

Mineral aggregates were seen proximally in all specimens within the outer medulla of the medullary complex and were intratubular. Distal interstitial mineralisation at the papillary tip corresponding to Randall's plaque was not seen until a threshold of proximal mineralisation was observed. Mineral density measurements suggest varied chemical compositions between the proximal intratubular (330 mg/cm³ ) and distal interstitial (270 mg/cm³ ) deposits. A review of the literature revealed distinct anatomical compartments and gradients across the medullo-papillary complex that supports the empirical observations that proximal mineralisation triggers distal Randall's plaque formation.

Conclusion

The early stone event is initiated by intratubular mineralisation of the renal medullary tissue leading to the interstitial mineralisation that is observed as Randall's plaque. We base this novel hypothesis on a multiscale biomechanics perspective involving form and function relationships, and empirical observations. Additional studies are needed to validate this hypothesis.

PURPOSE: We evaluated the relationship between dietary fiber, fruit and vegetable intake, and the risk of kidney stone formation. MATERIALS AND METHODS: Overall 83,922 postmenopausal women from the Womens Health Initiative observational study were included in the analysis and followed prospectively. Cox proportional hazards regression analyses were used to evaluate the associations between total dietary fiber, fruit and vegetable intake, and the risk of incident kidney stone formation, adjusting for nephrolithiasis risk factors (age, race/ethnicity, geographic region, diabetes mellitus, calcium supplementation, hormone therapy use, body mass index and calibrated caloric intake; and dietary water, sodium, animal protein and calcium intake). Women with a history of kidney stones (3,471) were analyzed separately. RESULTS: Mean age of the women was 64±7 years, 85% were white and 2,937 (3.5%) experienced a kidney stone in a median followup of 8 years. In women with no history of kidney stones higher total dietary fiber (6% to 26% decreased risk, p <0.001), greater fruit intake (12% to 25% decreased risk, p <0.001) and greater vegetable intake (9% to 22% decreased risk, p=0.002) were associated with a decreased risk of incident kidney stone formation in separate adjusted models. In women with a history of stones there were no significant protective effects of fiber, fruit or vegetable intake on the risk of kidney stone recurrence. CONCLUSIONS: Greater dietary intake of fiber, fruits and vegetables was associated with a reduced risk of incident kidney stones in postmenopausal women. The protective effects were independent of other known risk factors for kidney stones. In contrast, there was no reduction in risk in women with a history of stones.

INTRODUCTION:Cystinuria is a genetic disorder marked by elevated urinary cystine excretion and recurrent cystine nephrolithiasis. Interestingly, despite seemingly similar contralateral renal anatomy, a subset of cystinuric patients consistently form stones in only one kidney. The aim of this study is to evaluate clinical outcomes in unilateral vs bilateral cystine stone formers. PATIENTS AND METHODS:We performed a retrospective case-control study of cystinuric patients evaluated and treated at the University of California, San Francisco between 1994 and 2015 and categorized patients as either unilateral or bilateral stone formers. Clinical presentation, baseline patient demographics, stone procedures, medical therapy regimens, and long-term renal function were compared between the two groups. RESULTS:A total of 42 cystine stone patients (22 female, 20 male) were included in the analysis. The median age at first presentation was 18.5 years and median age at study conclusion was 45.5 years. Two-thirds of patients (n = 28) had a history of bilateral stones, whereas one-third (n = 14) had unilateral stones. Medical therapy regimens were similar between groups. Despite an increased average number of lifetime surgeries (7.5 sessions for bilateral vs 3.7 sessions for unilateral, p < 0.05), there was no significant difference in medians of the most recent glomerular filtration rate when compared with unilateral stone formers (81.5 vs 95 mL/min, respectively; p = 0.28). CONCLUSIONS:The majority of cystinuric patients within our cohort form stones bilaterally during their lifetime, and require more surgical interventions than unilateral stone formers. Despite this, overall renal function is well preserved in unilateral and bilateral cystinuric stone formers treated with minimally invasive stone extraction procedures.

Calcium-based renal calculi demonstrated significant heterogeneity in the structure, density, mineral composition, and material hardness not elucidated by routine clinical testing. Mineral density distributions within calcium oxalate stones revealed differential areas of low (590±80 mg/cc), medium (840±140 mg/cc), and high (1100±200 mg/cc) densities. Apatite stones also contained regions of low (700±200 mg/cc), medium (1100±200 mg/cc), and high (1400±140 mg/cc) densities within layers extending from single or multiple nucleation sites. Despite having lower average mineral density, calcium oxalate (CaOx) stones demonstrated higher material hardness compared to apatite stones, suggesting other chemical components might be involved in determining stone hardness properties. Carbon concentrated sites were identified between morphologic layers in CaOx stones and in stratified layers of apatite stones. Elemental analyses revealed numerous additional trace elements in both stone types. Despite the widespread assumption that stone mineral density is an indicator of susceptibility to lithotripsy, calcium stone mineral density estimates do not directly correlate with actual ex vivo stone hardness. Underlying stone heterogeneity in both structure and mineral density could explain why historical approaches have failed in accurately predicting response of stones to lithotripsy.

OBJECTIVES: Registry-based clinical research in nephrolithiasis is critical to advancing quality in urinary stone disease management and ultimately reducing stone recurrence. A need exists to develop Health Insurance Portability and Accountability Act (HIPAA)-compliant registries that comprise integrated electronic health record (EHR) data using prospectively defined variables. An EHR-based standardized patient database-the Registry for Stones of the Kidney and Ureter (ReSKU™)-was developed, and herein we describe our implementation outcomes. MATERIALS AND METHODS: Interviews with academic and community endourologists in the United States, Canada, China, and Japan identified demographic, intraoperative, and perioperative variables to populate our registry. Variables were incorporated into a HIPAA-compliant Research Electronic Data Capture database linked to text prompts and registration data within the Epic EHR platform. Specific data collection instruments supporting New patient, Surgery, Postoperative, and Follow-up clinical encounters were created within Epic to facilitate automated data extraction into ReSKU. RESULTS: The number of variables within each instrument includes the following: New patient-60, Surgery-80, Postoperative-64, and Follow-up-64. With manual data entry, the mean times to complete each of the clinic-based instruments were (minutes) as follows: New patient-12.06 ± 2.30, Postoperative-7.18 ± 1.02, and Follow-up-8.10 ± 0.58. These times were significantly reduced with the use of ReSKU structured clinic note templates to the following: New patient-4.09 ± 1.73, Postoperative-1.41 ± 0.41, and Follow-up-0.79 ± 0.38. With automated data extraction from Epic, manual entry is obviated. CONCLUSIONS: ReSKU is a longitudinal prospective nephrolithiasis registry that integrates EHR data, lowering the barriers to performing high quality clinical research and quality outcome assessments in urinary stone disease.