Thomas Chi

Impact of nutritional factors on incident kidney stone formation: A report from the WHI OS

PURPOSE Increased fluid intake, and decreased dietary sodium and animal protein intake are thought to reduce the risk of kidney stones but the role of calcium intake is controversial. We evaluated the relationship between dietary factors and incident kidney stone formation. MATERIALS AND METHODS Secondary analysis was done of 78,293 women from the prospective WHI OS (Womens Health Initiative Observational Study) with no history of nephrolithiasis who completed the validated food frequency questionnaire. Multivariate logistic regression was used to determine demographic and dietary factors, and supplement use independently associated with incident kidney stones. RESULTS Overall 1,952 women (2.5%) reported an incident kidney stone in 573,575 person-years of followup. The risk of incident kidney stones was decreased by 5% to 28% (p = 0.01) with higher dietary calcium intake and by 13% to 31% (p = 0.002) with higher water intake after adjusting for nephrolithiasis risk factors. Conversely higher dietary sodium intake increased the risk of nephrolithiasis by 11% to 61% (p <0.001) after adjustment with the most pronounced effect in women with the highest intake. Higher body mass index independently increased the risk of incident nephrolithiasis (adjusted OR 1.19-2.01, p <0.001). Animal protein intake was not associated with nephrolithiasis on multivariate analysis. CONCLUSIONS This study adds to the growing evidence underscoring the importance of maintaining adequate fluid and dietary calcium intake. Greater dietary calcium intake significantly decreased the risk of incident kidney stones. In contrast, excess sodium intake increased the risk of incident nephrolithiasis, especially in women with the highest intake. Animal protein intake was not independently associated with nephrolithiasis.

New insights into the pathogenesis of renal calculi.

The pathophysiology of the various forms of urinary stone disease remains a complex topic. Epidemiologic research and the study of urine and serum chemistries have created an abundance of data to help drive the formulation of pathophysiologic theories. This article addresses the associations of urinary stone disease with hypertension, cardiovascular disease, atherosclerosis, obesity, dyslipidemia, diabetes, and other disease states. Findings regarding the impact of dietary calcium and the formation of Randalls plaques are also explored and their implications discussed. Finally, further avenues of research are explored, including genetic analyses and the use of animal models of urinary stone disease.

A Drosophila Model Identifies a Critical Role for Zinc in Mineralization for Kidney Stone Disease

Ectopic calcification is a driving force for a variety of diseases, including kidney stones and atherosclerosis, but initiating factors remain largely unknown. Given its importance in seemingly divergent disease processes, identifying fundamental principal actors for ectopic calcification may have broad translational significance. Here we establish a Drosophila melanogaster model for ectopic calcification by inhibiting xanthine dehydrogenase whose deficiency leads to kidney stones in humans and dogs. Micro X-ray absorption near edge spectroscopy (μXANES) synchrotron analyses revealed high enrichment of zinc in the Drosophila equivalent of kidney stones, which was also observed in human kidney stones and Randall’s plaques (early calcifications seen in human kidneys thought to be the precursor for renal stones). To further test the role of zinc in driving mineralization, we inhibited zinc transporter genes in the ZnT family and observed suppression of Drosophila stone formation. Taken together, genetic, dietary, and pharmacologic interventions to lower zinc confirm a critical role for zinc in driving the process of heterogeneous nucleation that eventually leads to stone formation. Our findings open a novel perspective on the etiology of urinary stones and related diseases, which may lead to the identification of new preventive and therapeutic approaches.

Changes in Urinary Stone Risk Factors in Hypocitraturic Calcium Oxalate Stone Formers Treated With Dietary Sodium Supplementation

PURPOSE We investigated the effects of supplemental dietary sodium on risk factors for urinary stone disease in stone forming patients with hypocitraturia. MATERIALS AND METHODS Ten patients diagnosed with recurrent isolated hypocitraturic calcium urolithiasis were identified. Baseline 24-hour urinalysis was performed with patients on their regular diet, including citrate replacement with 20 mEq potassium citrate 3 times per day. Strict daily dietary logs were kept for a 7-day period, during which patients had normal oral intake and potassium citrate replacement. Patients then received supplemental sodium chloride for 1 week (1 gm orally 3 times per day), in addition to their regular diets and potassium citrate supplementation. Dietary logs were continued and 24-hour urinalysis was performed at the end of 1 week of supplemental sodium. Risk factors for urinary stone disease were compared using the Student t test and ANOVA. RESULTS Two patients were unable to comply with sodium supplementation based on 24-hour urinalysis and, therefore, they were excluded from study. The remaining 8 patients were analyzed. Patients on supplemental dietary sodium demonstrated significantly increased mean urinary voided volume (933 ml per day above baseline, p <0.05) and mean urinary sodium excretion (66 mEq per day above baseline, p <0.05). There was no statistically significant change in urinary calcium, oxalate or uric acid. The urinary supersaturation relative risk ratio decreased for calcium oxalate stones (0.93 vs 0.63, p <0.05), while those of brushite, struvite and uric acid were not different before vs after supplemental sodium. CONCLUSIONS Dietary sodium supplementation resulted in an increased voided urine volume and decreased the relative risk supersaturation ratio for calcium oxalate stones in patients with a history of hypocitraturic calcium oxalate nephrolithiasis. Urinary calcium excretion as well as other urine parameters that are risk factors for nephrolithiasis was not changed. Sodium restriction may be inappropriate in patients with hypocitraturia and recurrent urinary stones. Sodium supplementation may be beneficial in these patients because it results in voluntary increased fluid intake.

ORIGINAL RESEARCH—PEYRONIE'S DISEASE: Penile Sonographic and Clinical Characteristics in Men with Peyronie's Disease

INTRODUCTION Ultrasonography of the penis is readily available to the urologist and gives good anatomic detail of soft tissue structures. It has not been widely utilized in the assessment of Peyronies disease (PD). AIMS To describe the sonographic characteristics of the penis in PD and the relationship between clinical and sonographic features. METHODS This cross-sectional study enrolled patients from a single clinical practice. A PD-specific questionnaire was administered and sonographic evaluations were performed. MAIN OUTCOME MEASURES Sonographic characteristics of men with PD. RESULTS Tunical thickening, calcifications, septal fibrosis, and intracavernosal fibrosis, were observed at initial clinical evaluation in 50%, 31%, 20%, and 15% of men, respectively. Men aged 40-49 (OR 2.4, P = 0.02) and men aged 50-59 (OR 2.4, P = 0.004) were more likely to have sub-tunical calcifications relative to men under age 40. Men with septal fibrosis had fewer chronic medical conditions such as diabetes (OR 0.3, P = 0.04), hypertension (OR 0.5, P = 0.03), and coronary artery disease (OR 0.2, P = 0.05), and presented within 1 year of disease onset (OR 2.1, P = 0.001). Men with septal fibrosis were less likely to have lost penile length (OR 0.5, P = 0.04) and more likely to be able to have intercourse (OR 1.9, P = 0.05). Men with intracavernosal fibrosis were less likely to have penile pain (OR 0.5, P = 0.05), but more likely to have penetration difficulty during intercourse (OR 1.9, P = 0.008), an additional penile deformity (OR 1.8, P = 0.02), or rapid onset of disease (OR 1.7, P = 0.04). Tunical thickening was associated with a decreased ability to have intercourse (OR 2.3, P < 0.001). CONCLUSION PD is a clinically and sonographically heterogeneous condition. Sonography is a safe, low-cost, and rapid means of objectively characterizing lesions in this condition. This may help track the evolution of the condition in individual patients and in the future may be useful for tailoring treatment strategies.

Dietary Intake of Fiber, Fruit and Vegetables Decreases the Risk of Incident Kidney Stones in Women: A Women's Health Initiative Report

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.

Increased Echogenicity as a Predictor of Poor Renal Function in Children With Grade 3 to 4 Hydronephrosis

PURPOSE Prenatally diagnosed hydronephrosis is a common finding that often requires further radiological evaluation to determine whether it is associated with compromised renal function. We hypothesize that findings on postnatal renal sonography may help determine which patients require more extensive evaluation of renal function in the assessment for prenatal hydronephrosis. We show that increased renal parenchymal echogenicity on postnatal US is a strong predictor of compromised renal function. MATERIALS AND METHODS A total of 97 patients diagnosed with prenatal hydronephrosis presented to our institution for furosemide (99m)technetium MAG3 renogram evaluation of renal function between January 2000 and December 2001. All patients had SFU grade 3 to 4 hydronephrosis noted on postnatal US before age 6 months. For these 97 patients (178 renal units) we correlated the degree of renal parenchymal echogenicity and parenchymal thinning on the first postnatal sonogram with the differential renal function as determined by furosemide MAG3 renography. RESULTS Among 97 patients diagnosed with prenatal hydronephrosis 10 of 20 renal units (50%) with markedly increased echogenicity had severely decreased relative renal function of less than 10%, while 136 of 151 (90%) with normal echogenicity exhibited normal relative renal function of 40% or greater. Increased echogenicity on US yielded a sensitivity of 100% and specificity of 99% for predicting relative renal function of 20% or greater. In predicting relative renal function of 40% or less sensitivity and specificity were 48% and 100%, respectively. CONCLUSIONS Increased renal parenchymal echogenicity found on the first postnatal ultrasound can be used as a predictor of impaired relative renal function as measured on furosemide MAG3 renogram.

Microcomposition of human urinary calculi using advanced imaging techniques

PURPOSE Common methods of commercial urolithiasis analysis, such as light microscopy and Fourier transform infrared spectroscopy, provide limited or no information on the molecular composition of stones, which is vital when studying early stone pathogenesis. We used synchrotron radiation based microfocused x-ray fluorescence, x-ray absorption and x-ray diffraction advanced imaging techniques to identify and map the elemental composition, including trace elements, of urinary calculi on a μm (0.0001 cm) scale. MATERIALS AND METHODS Human stone samples were obtained during serial percutaneous nephrolithotomy and ureteroscopy procedures. A portion of each sample was sent for commercial stone analysis and a portion was retained for synchrotron radiation based advanced imaging analysis. RESULTS Synchrotron radiation based methods of stone analysis correctly identified stone composition and provided additional molecular detail on elemental components and spatial distribution in uroliths. Resolution was on the order of a few μm. CONCLUSIONS Knowledge of all elements present in lithogenesis at this detail allows for better understanding of early stone formation events, which may provide additional insight to prevent and treat stone formation.

Strontium substitution for calcium in lithogenesis

PURPOSE Strontium has chemical similarity to calcium, which enables the replacement of calcium by strontium in biomineralization processes. Incorporating strontium into human bone and teeth has been studied extensively but little research has been performed of the incorporation of strontium into urinary calculi. We used synchrotron based x-ray fluorescence and x-ray absorption techniques to examine the presence of strontium in different types of human kidney stones. MATERIALS AND METHODS Multiple unique human stone samples were obtained via consecutive percutaneous nephrolithotomies/ureteroscopies. A portion of each stone was sent for standard laboratory analysis and a portion was retained for x-ray fluorescence and x-ray absorption measurements. X-ray fluorescence and x-ray absorption measurements determined the presence, spatial distribution and speciation of strontium in each stone sample. RESULTS Traditional kidney stone analyses identified calcium oxalate, calcium phosphate, uric acid and cystine stones. X-ray fluorescence measurements identified strontium in all stone types except pure cystine. X-ray fluorescence elemental mapping of the samples revealed co-localization of calcium and strontium. X-ray absorption measurements of the calcium phosphate stone showed strontium predominately present as strontium apatite. CONCLUSIONS Advanced x-ray fluorescence imaging identified strontium in all calcium based stones, present as strontium apatite. This finding may be critical since apatite is thought to be the initial nidus for calcium stone formation. Strontium is not identified by standard laboratory stone analyses. Its substitution for calcium can be reliably identified in stones from multiple calcium based stone formers, which may offer opportunities to gain insight into early events in lithogenesis.

Ultrasound Guidance for Renal Tract Access and Dilation Reduces Radiation Exposure during Percutaneous Nephrolithotomy

Purposes. To present our series of 38 prone percutaneous nephrolithotomy procedures performed with renal access and tract dilation purely under ultrasound guidance and describe the benefits and challenges accompanying this approach. Methods. Thirty-eight consecutive patients presenting for percutaneous nephrolithotomy for renal stone removal were included in this prospective cohort study. Ultrasonographic imaging in the prone position was used to obtain percutaneous renal access and guide tract dilation. Fluoroscopic screening was used only for nephrostomy tube placement. Preoperative, intraoperative, and postoperative procedural and patient data were collected for analysis. Results. Mean age of patients was 52.7 ± 17.2 years. Forty-five percent of patients were male with mean BMI of 26.1 ± 7.3 and mean stone size of 27.2 ± 17.6 millimeters. Renal puncture was performed successfully with ultrasonographic guidance in all cases with mean puncture time of 135.4 ± 132.5 seconds. Mean dilation time was 11.5 ± 3.8 min and mean stone fragmentation time was 37.5 ± 29.0 min. Mean total operative time was 129.3 ± 41.1. No patients experienced any significant immediate postoperative complication. All patients were rendered stone-free and no additional secondary procedures were required. Conclusions. Ultrasound guidance for renal access and tract dilation in prone percutaneous nephrolithotomy is a feasible and effective technique. It can be performed safely with significantly reduced fluoroscopic radiation exposure to the patient, surgeon, and intraoperative personnel.