Publications by authors named "Marshall L Stoller"

195 Publications

Mineralized Peyronie's plaque has a phenotypic resemblance to bone.

Acta Biomater 2021 Nov 21. Epub 2021 Nov 21.

Division of Biomaterials and Bioengineering, Department of Preventative and Restorative Dental Sciences, School of Dentistry, University of California San Francisco, California, United States of America; Department of Urology, School of Medicine, University of California, San Francisco, California, United States of America. Electronic address:

Mineralized Peyronie's plaque (MPP) impairs penile function. The association, colocalization, and dynamic interplay between organic and inorganic constituents can provide insights into biomineralization of Peyronie's plaque. Human MPPs (n = 11) were surgically excised, and the organic and inorganic constituents were spatially mapped using multiple high-resolution imaging techniques. Multiscale image analyses resulted in spatial colocalization of elements within a highly porous material with heterogenous composition, lamellae, and osteocytic lacuna-like features with a morphological resemblance to bone. The lower (520 ±179 mg/cc) and higher (1024 ± 155 mg/cc) mineral density regions were associated with higher (11%) and lower (7%) porosities in MPP. Energy dispersive X-ray and micro-X-ray fluorescent spectroscopic maps in the higher mineral density regions of MPP revealed higher counts of calcium (Ca) and phosphorus (P), and a Ca/P ratio of 1.48 ± 0.06 similar to bone. More importantly, higher counts of zinc (Zn) were localized at the interface between softer (more organic to inorganic ratio) and harder (less organic to inorganic ratio) tissue regions of MPP and adjacent softer matrix, indicating the involvement of Zn-related proteins and/or pathways in the formation of MPP. In particular, dentin matrix protein-1 (DMP-1) was colocalized in a matrix rich in proteoglycans and collagen that contained osteocytic lacuna-like features. This combined materials science and biochemical with correlative microspectroscopic approach provided insights into the plausible cellular and biochemical pathways that incite mineralization of an existing fibrous Peyronie's plaque. STATEMENT OF SIGNIFICANCE: Aberrant human penile mineralization is known as mineralized Peyronie's plaque (MPP) and often results in a loss of form and function. This study focuses on investigating the spatial association of matrix proteins and elemental composition of MPP by colocalizing calcium, phosphorus, and trace metal zinc with dentin matrix protein 1 (DMP-1), acidic proteoglycans, and fibrillar collagen along with the cellular components using high resolution correlative microspectroscopic techniques. Spatial maps provided insights into cellular and biochemical pathways that incite mineralization of fibrous Peyronie's plaque in humans.
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http://dx.doi.org/10.1016/j.actbio.2021.11.025DOI Listing
November 2021

A large staghorn stone diagnosed and managed in an asymptomatic patient using the "Kidney Injury Test (Kit)" spot urine assay: A case report.

Urol Case Rep 2021 Nov 21;39:101854. Epub 2021 Sep 21.

Department of Urology, University of California, San Francisco, USA.

The Kidney Injury Test (KIT) Stone-Score provides an objective measure of stone burden. Unlike urinary supersaturation the KIT Stone-Scores assess underlying stone disease rather than urinary solute composition. We report a case of a 43-year-old woman with no history of nephrolithiasis who underwent an elective, voluntary KIT assay and was diagnosed with a large staghorn renal stone after an unanticipated markedly elevated score. This clinical scenario highlights the potential future use of the non-invasive urinary KIT assay as a reliable non-invasive tool to detect and monitor urinary stone disease.
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http://dx.doi.org/10.1016/j.eucr.2021.101854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479636PMC
November 2021

Corrigendum to "Physicochemical and biochemical spatiotemporal maps of a mouse penis". [J. Biomech. 101 (2020) 109637].

J Biomech 2021 Aug 25;125:110563. Epub 2021 Jun 25.

Division of Biomaterials and Bioengineering, Department of Preventive and Restorative Dental Sciences, School of Dentistry, University of California San Francisco, San Francisco, CA, United States; Department of Urology, School of Medicine, University of California San Francisco, San Francisco, CA, United States. Electronic address:

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http://dx.doi.org/10.1016/j.jbiomech.2021.110563DOI Listing
August 2021

Nedosiran Dramatically Reduces Serum Oxalate in Dialysis-Dependent Primary Hyperoxaluria 1: A Compassionate Use Case Report.

Urology 2021 Oct 25;156:e147-e149. Epub 2021 Mar 25.

Department of Urology, UCSF, San Francisco, CA. Electronic address:

Primary hyperoxaluria 1 (PH1) is a devastating condition involving recurrent urolithiasis, early end-stage renal disease and multisystemic deposition of calcium oxalate crystals. Treatment options for PH1 are limited, inevitably requiring transplantation, usually combined kidney and liver transplant. Here we report successful compassionate use of Nedosiran, an RNA interference targeting lactate dehydrogenase, in an index patient. Monthly Nedosiran injections led to dramatically decreased plasma oxalate levels, decreased frequency of weekly hemodialysis sessions from 6 to 3, and deferral of combined kidney and liver transplant. Nedosiran represents a novel and impactful potential therapeutic for PH1 patients with end-stage renal disease.
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http://dx.doi.org/10.1016/j.urology.2021.03.014DOI Listing
October 2021

Structure and elemental composition of Ceftriaxone induced pediatric nephrolithiasis.

Urolithiasis 2021 Aug 15;49(4):309-320. Epub 2021 Feb 15.

Department of Urology, Beijing Friendship Hospital, Capital Medical University, 95 Yong An Road, Xi Cheng District, Beijing, 100050, China.

Ceftriaxone is a widely used antibiotic because to its broad-spectrum gram-negative coverage, safety, and biological half life (5-9 h) permit dose once-daily administration. It is specifically used in pediatric patients in developing countries. Ceftriaxone forms insoluble sludge/stone when combined with calcium in the urinary system. In this study, Ceftriaxone induced sludge/stones from pediatric patients were collected to identify its microstructure and composition to gather insights into the mechanism of Ceftriaxone induced sludge/stone formation. The results illustrated that Ceftriaxone induced stones formed rapidly following antibiotic administration. Ceftriaxone calcium salt crystals could easily be broken with minimal intervention. However, Ceftriaxone combined with calcium phosphate formed an insoluble stone aggregate.
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http://dx.doi.org/10.1007/s00240-020-01231-5DOI Listing
August 2021

Structural and chemical heterogeneities of primary hyperoxaluria kidney stones from pediatric patients.

J Pediatr Urol 2021 04 20;17(2):214.e1-214.e11. Epub 2020 Nov 20.

Division of Preclinical Education, Biomaterials & Engineering, School of Dentistry, University of California San Francisco, San Francisco, CA, 94143, USA; Department of Urology, School of Medicine, University of California San Francisco, San Francisco, CA, 94143, USA. Electronic address:

Objective: Calcium oxalate stones are the most common type among stone-forming patients and in some cases result from predisposed genetic conditions. In this work, we examined the differences in structure and chemical composition between oxalate stones from patients from three groups: 1) pediatric patients that were genetically predisposed (primary hyperoxaluria) to form stones (PPH); 2) control pediatric patients that did not have such genetic predisposition (PN-PH); 3) adult patients that formed oxalate stones without the genetic predisposition (A-CaOx). A variety of instrumental analyses were conducted to identify physicochemical properties of stones characteristic of predisposed pediatric (PPH), pediatric hyperoxaluria (PN-PH), and adult (A-CaOx) patient populations.

Methods: Genetic variants of 16 stone-forming patients were determined using whole-exome gene sequencing. Components of stones from PPH (n = 6), PN-PH (n = 5), and A-CaOx (n = 5) groups were identified using Fourier transform infrared (FTIR) spectroscopy. Stone morphology and density were evaluated using high resolution X-ray computed tomography (micro-XCT). Stone microstructure and elemental composition were mapped with scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy, respectively.

Results: Calcium oxalate bipyramidal crystals were found on stones from all groups. Stones from PPH patients with PH types I and II were composed of calcium oxalate monohydrate (COM) with relatively uniform mineral density (1224 ± 277 mg/cc) and distinct smooth surfaces. By contrast, micro-spherical calcium phosphate particles were found only on PN-PH stones, which also showed a broader range of mineral densities (1266 ± 342 mg/cc). Stones from the PN-PH group also contained phosphorus (P), which was absent in NP-PH stones. A-CaOx stones were of significantly lower mineral density (645 ± 237 mg/cc) than pediatric stones and were more heterogeneous in their elemental composition.

Conclusion: Unique structural and compositional characteristics were identified in stones from pediatric patients with primary hyperoxaluria. These include the absence of phosphorus, a narrower mineral density distribution, and a uniform elemental composition compared to stones from pediatric patients without the genetic predisposition. Thus, characterization of stones at the macro- and micro-scales in combination with genetic testing of patients can provide insights and accurate diagnosis to develop a treatment plan for effective patient care.
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http://dx.doi.org/10.1016/j.jpurol.2020.11.023DOI Listing
April 2021

Ectopic biomineralization in kidney stone formers compared to non-stone formers.

Transl Androl Urol 2020 Oct;9(5):2129-2137

Department of Urology, University of California San Francisco, San Francisco, CA, USA.

Background: Kidney stone formers (SFs) are at increased risk of stroke, myocardial infarction, and atherosclerosis of the carotid and coronary arteries. These cardiovascular and urologic pathologies can result from ectopic biomineral deposition. The objectives of this study are: (I) to evaluate risk factors for ectopic biomineralization, and (II) to characterize the overall burden of ectopic minerals in known SFs compared to non-stone formers (NSFs) matched for these risk factors.

Methods: Presence and quantity of biominerals at eight anatomic locations (abdominal aorta, common iliac arteries, pelvic veins, prostate or uterus, mesentery, pancreas, and spleen) were determined in a case control study by retrospective analysis of clinical non-contrast computed tomography scans obtained from 190 SFs and 190 gender- and age-matched NSFs (renal transplant donors). Predictors of biomineralization were determined using negative binomial regression. A subgroup of 140 SFs and 140 NSFs were matched for risk factors for systemic biomineralization, and mineralization was compared between these matched SFs and NSFs using ordinal logistic regression.

Results: Hypertension, hyperlipidemia, diabetes mellitus, and smoking were more common amongst SFs. Risk factors for increased systemic biomineralization included history of nephrolithiasis, male gender, older age, and history of hyperlipidemia. When controlling for these comorbidities, SFs had significantly increased biomineralization systemically and at the abdominal aorta, iliac arteries, prostate, mesentery, pancreas, and spleen compared to NSFs.

Conclusions: The current study provides evidence that SFs are at increased risk of biomineralization systemically, independent of common risk factors of atherosclerosis.
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http://dx.doi.org/10.21037/tau-19-927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658123PMC
October 2020

Diagnostic Imaging for Kidney Stones.

JAMA 2020 10;324(14):1464-1465

Department of Radiology, University of California, San Francisco.

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http://dx.doi.org/10.1001/jama.2020.14865DOI Listing
October 2020

Consensus-based perioperative protocols during the COVID-19 pandemic.

J Neurosurg Spine 2020 Oct 2:1-9. Epub 2020 Oct 2.

Departments of1Neurological Surgery.

Objective: During the COVID-19 pandemic, quaternary-care facilities continue to provide care for patients in need of urgent and emergent invasive procedures. Perioperative protocols are needed to streamline care for these patients notwithstanding capacity and resource constraints.

Methods: A multidisciplinary panel was assembled at the University of California, San Francisco, with 26 leaders across 10 academic departments, including 7 department chairpersons, the chief medical officer, the chief operating officer, infection control officers, nursing leaders, and resident house staff champions. An epidemiologist, an ethicist, and a statistician were also consulted. A modified two-round, blinded Delphi method based on 18 agree/disagree statements was used to build consensus. Significant disagreement for each statement was tested using a one-sided exact binomial test against an expected outcome of 95% consensus using a significance threshold of p < 0.05. Final triage protocols were developed with unblinded group-level discussion.

Results: Overall, 15 of 18 statements achieved consensus in the first round of the Delphi method; the 3 statements with significant disagreement (p < 0.01) were modified and iteratively resubmitted to the expert panel to achieve consensus. Consensus-based protocols were developed using unblinded multidisciplinary panel discussions. The final algorithms 1) quantified outbreak level, 2) triaged patients based on acuity, 3) provided a checklist for urgent/emergent invasive procedures, and 4) created a novel scoring system for the allocation of personal protective equipment. In particular, the authors modified the American College of Surgeons three-tiered triage system to incorporate more urgent cases, as are often encountered in neurosurgery and spine surgery.

Conclusions: Urgent and emergent invasive procedures need to be performed during the COVID-19 pandemic. The consensus-based protocols in this study may assist healthcare providers to optimize perioperative care during the pandemic.
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http://dx.doi.org/10.3171/2020.6.SPINE20777DOI Listing
October 2020

Role of core body temperature in nephrolithiasis.

BJU Int 2020 11 26;126(5):620-624. Epub 2020 Aug 26.

Department of Urology, University of California, San Francisco, CA, USA.

Objectives: To assess the role of core body temperature in urinary stone formation using a large clinical dataset.

Patients And Methods: We retrospectively collected 14 519 039 individual temperature measurements from 580 416 patients with medical history, laboratory values and medication history between 2013 and 2018 at a single institution. After exclusions and matching 2:1 (controls:cases) to account for confounding variables, 7104 patients with a history of urinary stones were identified.

Results: Patients with a history of urinary stones (cases) had an elevated mean (SD) oral temperature compared to matched controls, at 36.666 (0.17) vs 36.659 (0.20)°C (P = 0.012). Logistic regression of matched samples showed that higher core body temperature was predictive of a history of nephrolithiasis (odds ratio 1.21, 95% confidence interval 1.04-1.4; P = 0.015).

Conclusion: Core body temperature was significantly higher in patients with a history of urinary stones compared to matched controls, contrary to the anticipated thermodynamic considerations leading to crystal aggregation. Given that the core body temperature is elevated, rather than decreased, thermodynamic process driving stone formation is unlikely.
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http://dx.doi.org/10.1111/bju.15185DOI Listing
November 2020

Underdiagnosis of Primary Hyperparathyroidism-The Need for a System-Level Fix.

JAMA Surg 2020 09;155(9):868-869

Department of Urology, University of California, San Francisco.

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http://dx.doi.org/10.1001/jamasurg.2020.2448DOI Listing
September 2020

Jean Oliver: Master of the Nephron.

Urology 2020 Oct 13;144:17-20. Epub 2020 Jun 13.

University of California, San Francisco, Department of Urology, San Francisco, CA.

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http://dx.doi.org/10.1016/j.urology.2020.06.002DOI Listing
October 2020

Fatty acid-binding protein 4 downregulation drives calcification in the development of kidney stone disease.

Kidney Int 2020 05 29;97(5):1042-1056. Epub 2020 Feb 29.

Department of Urology, University of California, San Francisco, California, USA. Electronic address:

Nephrolithiasis is a significant source of morbidity, and its incidence has increased significantly over the last decades. This rise has been attributed to concurrent increasing rates of obesity, associated with a 3-time risk of developing NL. To date, the mechanism by which obesity is linked to stone formation has not been elucidated. We aimed to utilize a transcriptomics approach to discover the missing link between these two epidemic diseases. We investigated gene expression profiling of nephrolithiasis patients by two RNA-sequencing approaches: comparison between renal papilla tissue with and without the presence of calcified Randall's plaques (RP), and comparison between the papilla, medulla, and cortex regions from within a single recurrent stone forming kidney. Results were overlaid between differently expressed genes found in the patient cohort and in the severely lithogenic kidney to identify common genes. Overlay of these two RNA-sequencing datasets demonstrated there is impairment of lipid metabolism in renal papilla tissue containing RP linked to downregulation of fatty acid binding protein (FABP) 4. Immunohistochemistry of human kidney specimens and microarray analysis of renal tissue from a nephrolithiasis mouse model confirmed that FABP4 downregulation is associated with renal stone formation. In a FABP4 knockout mouse model, FABP4 deficiency resulted in development of both renal and urinary crystals. Our study revealed that FABP4 plays an important, previously unrecognized role in kidney stone formation, providing a feasible mechanism to explain the link between nephrolithiasis and metabolic syndrome.
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http://dx.doi.org/10.1016/j.kint.2020.01.042DOI Listing
May 2020

Physicochemical and biochemical spatiotemporal maps of a mouse penis.

J Biomech 2020 03 16;101:109637. Epub 2020 Jan 16.

Division of Biomaterials and Bioengineering, Department of Preventive and Restorative Dental Sciences, School of Dentistry, University of California San Francisco, San Francisco, CA, United States; Department of Urology, School of Medicine, University of California San Francisco, San Francisco, CA, United States. Electronic address:

Spatiotemporal mechanobiology resulting in penile pathologies continues to be investigated using small scale animals models such as mice. However, species-dependent functional biomechanics of a mouse penis, is not known. In this study, spatial mapping of a mechanosensitive transcription factor, scleraxis (Scx), at ages 4, 5, 6 weeks, and 1 year were generated to identify mechanoactive regions within penile tissues. Reconstructed volumes of baculum collected using micro X-ray computed tomography illustrated significantly increased baculum length with decreased porosity, and increased mineral density (p < 0.05) with age. The bony-baculum was held centrally in the Scx positive corpus cavernosum glandis (CCG), indicating mechanoactivity within the struts in a 6 week old mouse. The struts also were stained positive for fibrillar proteins including collagen and elastin, and globular proteins including protein gene product 9.5, and α-smooth muscle actin. The corpus cavernosum penis (CCP) contained significantly (p < 0.05) more collagen than CCG within the same penis, and both regions contained blood vessels with equivalent innervation at any given age. Comparison of volumes of flaccid and erect penile forms revealed functional characteristics of the CCP. Results of this study provided insights into biomechanical function of the CCG; in that, it is a high-pressure chamber that stiffens the penis and is similar to the human corpus cavernosum.
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http://dx.doi.org/10.1016/j.jbiomech.2020.109637DOI Listing
March 2020

Techniques - Ultrasound-guided percutaneous nephrolithotomy: How we do it.

Can Urol Assoc J 2020 Mar 27;14(3):E104-E110. Epub 2019 Sep 27.

Department of Urology, University of California at San Francisco, San Francisco, CA, United States.

Ultrasonography has emerged as an alternative to fluoroscopy for image-guided percutaneous nephrolithotomy (PCNL) in many countries. Compared to fluoroscopy-guided PCNL (F-PCNL), ultrasound-guided PCNL (US-PCNL) is easier to learn and reduces radiation exposure to patients and providers. Despite these advantages, uptake of ultrasound-guided PCNL (US-PCNL) in Canada has been almost nonexistent, largely because it is not incorporated into urologists' training. In this article, we seek to familiarize Canadian urologists with this approach by describing our step-by-step technique for US-PCNL. Additionally, we provide keys to successful implementation of this technique.
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http://dx.doi.org/10.5489/cuaj.6076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053366PMC
March 2020

A conserved role of the insulin-like signaling pathway in diet-dependent uric acid pathologies in Drosophila melanogaster.

PLoS Genet 2019 08 15;15(8):e1008318. Epub 2019 Aug 15.

The Buck Institute for Research on Aging, Novato, California, United States of America.

Elevated uric acid (UA) is a key risk factor for many disorders, including metabolic syndrome, gout and kidney stones. Despite frequent occurrence of these disorders, the genetic pathways influencing UA metabolism and the association with disease remain poorly understood. In humans, elevated UA levels resulted from the loss of the of the urate oxidase (Uro) gene around 15 million years ago. Therefore, we established a Drosophila melanogaster model with reduced expression of the orthologous Uro gene to study the pathogenesis arising from elevated UA. Reduced Uro expression in Drosophila resulted in elevated UA levels, accumulation of concretions in the excretory system, and shortening of lifespan when reared on diets containing high levels of yeast extract. Furthermore, high levels of dietary purines, but not protein or sugar, were sufficient to produce the same effects of shortened lifespan and concretion formation in the Drosophila model. The insulin-like signaling (ILS) pathway has been shown to respond to changes in nutrient status in several species. We observed that genetic suppression of ILS genes reduced both UA levels and concretion load in flies fed high levels of yeast extract. Further support for the role of the ILS pathway in modulating UA metabolism stems from a human candidate gene study identifying SNPs in the ILS genes AKT2 and FOXO3 being associated with serum UA levels or gout. Additionally, inhibition of the NADPH oxidase (NOX) gene rescued the reduced lifespan and concretion phenotypes in Uro knockdown flies. Thus, components of the ILS pathway and the downstream protein NOX represent potential therapeutic targets for treating UA associated pathologies, including gout and kidney stones, as well as extending human healthspan.
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http://dx.doi.org/10.1371/journal.pgen.1008318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695094PMC
August 2019

Ultrasound-guided Access and Dilation for Percutaneous Nephrolithotomy in the Supine Position: A Step-by-Step Approach.

Urology 2019 Nov 31;133:245-246. Epub 2019 Jul 31.

Department of Urology, University of California San Francisco, San Francisco, CA.

Introduction: Ultrasound guidance for percutaneous nephrolithotomy (PCNL) has gained acceptance amongst urologists given its numerous advantages over fluoroscopy. While traditionally performed in the prone position, this video demonstrates a step-by-step approach to performing PCNL in the supine position, solely under ultrasound guidance.

Materials And Methods: Once in the modified supine (Galdakao-modified Valdivia) position, important anatomic landmarks are identified. It is important to first orient the ultrasound probe such that its cranial side corresponds to the left of the ultrasound screen. After optimizing a target calyx, keeping the needle in the imaging plane of the probe facilitates renal access. Tract dilation under ultrasound guidance is then achieved by keeping the wire and dilators in the same imaging plane.

Results: The 11th and 12th ribs, paraspinous muscle, iliac crest, midaxillary line, and costal margin are the anatomic landmarks that orient the probe to the location of the kidney. Placing the ultrasound probe in the midaxillary line, parallel to the 11th rib allows the operator to identify key renal landmarks: the renal cortex, peri-pelvic fat, collecting system, kidney stone with its associated postacoustic shadow, and the intended target calyx. Controlling the needle is easiest in the longitudinal view, as the needle can be visualized from skin to target. Dilation under ultrasound relies on keeping the wire in view. The tip of the 10-French dilator is based on the location where the wire image disappears as the dilator advances. The balloon dilator tip is visualized on ultrasound reaching the appropriate depth just inside the collecting system, at which time balloon inflation results in complete dilation of the tract.

Conclusions: This video provides a step-by-step approach demonstrating that PCNL can be performed in the supine position using only ultrasound-guidance. This approach facilitates renal access in this position and obviates the need for radiation exposure.
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http://dx.doi.org/10.1016/j.urology.2019.07.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021388PMC
November 2019

Nonrenal Systemic Arterial Calcification Predicts the Formation of Kidney Stones.

J Endourol 2019 12 25;33(12):1032-1034. Epub 2019 Jul 25.

Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio.

Recent data indicate that kidney stone formers (KSFs) may have increased biomineralization at anatomic sites throughout the body compared with nonstone formers (NSFs). The objective of this study is to compare the volume of nonrenal systemic calcifications between KSF and NSF by using a standardized system to analyze calcifications in the abdominal aorta (AA) and splenic artery (SA). The NSF cohort was obtained from a kidney donor's prospectively maintained database. One hundred ninety-seven NSF were matched to 197 KSF based on age, gender, and body mass index. Noncontrast CT scans were evaluated and semiautomated CT software was utilized to provide an AA and SA calcification Agatston score. Wilcoxon rank-sum test was used on continuous variables and chi-squared test or Fisher's exact test on categorical variables. Odds ratios (ORs) were given for a variable's influence on the formation of stones or calcifications. AA and SA calcifications were more prevalent in the KSF group ( = 0.011 and  = 0.027, respectively). KSFs were 1.9 times more likely to have intermediate or severe AA calcification than NSFs (OR = 1.9,  = 0.004). Severe AA calcifications had even a greater association (OR = 3.1,  = 0.019). KSFs were also more likely to have SA, but this did not reach statistical significance (OR = 3.7,  = 0.103). Patients with increased systemic calcifications, specifically aortic or splenic calcifications, may be at an increased risk for future kidney stone formation. Patients with these imaging findings and additional risk factors for stone disease may be counseled on the future risk of stones.
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http://dx.doi.org/10.1089/end.2019.0243DOI Listing
December 2019

Computed Tomography Radiation Exposure Among Referred Kidney Stone Patients: Results from the Registry for Stones of the Kidney and Ureter.

J Endourol 2019 07 29;33(7):619-624. Epub 2019 May 29.

1 Department of Urology, University of California, San Francisco, San Francisco, California.

Kidney stone patients routinely have CT scans during diagnostic work-up before being referred to a tertiary center. How often these patients exceed the recommended dose limits for occupational radiation exposure of >100 mSv for 5 years and >50 mSv in a single year from CT alone remains unknown. This study aimed to quantify radiation doses from CTs received by stone patients before their evaluation at a tertiary care stone clinic. From November 2015 to March 2017, consecutive new patients enrolled into the Registry for Stones of the Kidney and Ureter (ReSKU™) had the dose-length product of every available CT abdomen/pelvis within 5 years of their initial visit recorded, allowing for an effective dose (EDose) calculation. Multivariate logistic regression analysis identified factors associated with exceeding recommended dose limits. Models were created to test radiation reducing effects of low-dose and phase-reduction CT protocols. Of 343 noncontrast CTs performed, only 29 (8%) were low-dose CTs (calculated EDose <4 mSv). Among 389 total patients, 101 (26%) and 25 (6%) had an EDose >20 mSv and >50 mSv/year, respectively. Increased body mass index, number of scans, and multiphase scans were associated with exceeding exposure thresholds ( < 0.01). The implementation of a low-dose CT protocol decreased the estimated number of scans contributing to overexposure by >50%. Stone patients referred to a tertiary stone center may receive excessive radiation from CT scans alone. Unnecessary phases and underutilization of low-dose CT protocols continue to take place. Enacting new approaches to CT protocols may spare stone patients from exceeding recommended dose limits.
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http://dx.doi.org/10.1089/end.2019.0091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657296PMC
July 2019

Ultrasound guidance can be used safely for renal tract dilatation during percutaneous nephrolithotomy.

BJU Int 2020 02 3;125(2):284-291. Epub 2019 Oct 3.

Department of Urology, University of California, San Francisco, CA, USA.

Objectives: To compare clinical outcomes in patients who underwent percutaneous nephrolithotomy (PCNL) with renal tract dilatation performed under fluoroscopic guidance vs renal tract dilatation with ultrasound guidance.

Patients And Methods: We conducted a prospective observational cohort study, enrolling successive patients undergoing PCNL between July 2015 and March 2018. Included in this retrospective analysis were cases where the renal puncture was successfully obtained with ultrasound guidance. Cases were then grouped according to whether fluoroscopy was used to guide renal tract dilatation or not. All statistical analyses were performed using Stata version 15.1 including univariate (Fisher's exact test, Welch's t-test) and multivariate analyses (binomial logistic regression, ordinal logistic regression, and linear regression).

Results: A total of 176 patients underwent PCNL with successful ultrasonography-guided renal puncture, of whom 38 and 138 underwent renal tract dilatation with fluoroscopic vs ultrasound guidance, respectively. There were no statistically significant differences in patient age, gender, body mass index (BMI), preoperative hydronephrosis, stone burden, procedure laterality, number of dilated tracts, and calyceal puncture location between the two groups. Among ultrasound tract dilatations, a higher proportion of patients were placed in the modified dorsal lithotomy position as opposed to prone, and a significantly shorter operating time was observed. Only modified dorsal lithotomy position remained statistically significant after multivariate regression. There were no statistically significant differences in postoperative stone clearance, complication rate, or intra-operative estimated blood loss. A 5-unit increase in a patient's BMI was associated with 30% greater odds of increasingly severe Clavien-Dindo complications. A 5-mm decrease in the preoperative stone burden was associated with 20% greater odds of stone-free status. No variables predicted estimated blood loss with statistical significance.

Conclusions: Renal tract dilatation can be safely performed in the absence of fluoroscopic guidance. Compared to using fluoroscopy, the present study demonstrated that ultrasonography-guided dilatations can be safely performed without higher complication or bleeding rates. This can be done using a variety of surgical positions, and future studies centred on improving dilatation techniques could be of impactful clinical value.
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http://dx.doi.org/10.1111/bju.14737DOI Listing
February 2020

Factors Associated with Regional Adoption of Ureteroscopy in California from 2005 to 2016.

J Endourol 2019 01 31;33(1):9-15. Epub 2018 Dec 31.

1 Department of Urology, UCSF Medical Center, San Francisco, California.

Purpose: To explore regional adoption of ureteroscopy (URS) over extracorporeal shockwave lithotripsy (SWL) in the state of California (CA) and to identify factors associated with this adoption over time.

Materials And Methods: We used the California Office of Statewide Health Planning and Development (OSHPD) public data to identify URS and SWL procedures performed for renal and ureteral stones from 2005 to 2016. The level of analysis was the region wherein each procedure was performed, defined by the 19 CA labor market regions. OSHPD data were supplemented with the Area Health Resource File to provide information on regional characteristics. Generalized linear regression was used to determine procedural rates adjusted for age, gender and race. Choropleth time series maps were used to illustrate adoption of URS by region over time.

Results: A total of 328,795 URS and SWL procedures were identified from 2005 to 2016. The number of URS procedures surpassed the number of SWL procedures in 2011. Fourteen regions became URS predominant by 2016 and were characterized as having a higher per capita income, higher percentages with a college education and lower percentage of female heads-of-household (all p-values <0.05). A higher percentage of patients in these regions were male and had private or Medicare insurance (p = 0.03 for both).

Conclusions: From 2005 to 2016, most CA regions adopted URS as the primary renal and ureteral stone management strategy. These regions demonstrated characteristics of higher socioeconomic status compared to regions that remained SWL predominant. A better understanding of such differences in practice patterns will allow urologists to better negotiate for the capital expenditures required to conform to evolving standards of care and allow patients the ability to make more informed decisions on where they receive care.
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http://dx.doi.org/10.1089/end.2018.0776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352501PMC
January 2019

Re: Geobiology Reveals How Human Kidney Stones Dissolve In Vivo.

Eur Urol 2019 03 16;75(3):532. Epub 2018 Nov 16.

Department of Urology, School of Medicine, University of California San Francisco, San Francisco, CA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.eururo.2018.11.004DOI Listing
March 2019

Open versus robotic partial nephrectomy: Systematic review and meta-analysis of contemporary studies.

Int J Med Robot 2019 Feb 6;15(1):e1963. Epub 2018 Nov 6.

Department of Urology, University of California, San Francisco, San Francisco, California.

Objectives: To compare perioperative outcomes of robotic-assisted partial nephrectomy (RaPN) with open partial nephrectomy (OPN).

Methods: Systematically search through PubMed, Embase, ClinicalKey, Cochrane Library, ProQuest, ScienceDirect, Web of Science, and ClinicalTrials.gov for eligible studies was performed to April 11, 2018. A meta-analysis was conducted for studies comparing RaPN and OPN. Confounding variables were assessed by meta-regression or subgroup analysis.

Results: This study included 34 studies with 60 808 patients. Meta-analysis revealed less blood loss, less transfusion, longer operative time, less postoperative complications, lower readmission rate, shorter length of stay, and less estimated glomerular filtration rate (eGFR) decline in RaPN groups. The superiority of RaPN in blood loss was attenuated with highly complex renal masses. The superiority of RaPN in intraoperative complications was strengthened with renal hilar control. The advantage of RaPN in surgical margin was increased in patient with body mass index (BMI) < 28.

Conclusions: Compared with OPN, RaPN provided lower morbidities and better renal function preservation.
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http://dx.doi.org/10.1002/rcs.1963DOI Listing
February 2019

Architecture-Guided Fluid Flow Directs Renal Biomineralization.

Sci Rep 2018 09 21;8(1):14157. Epub 2018 Sep 21.

Department of Urology, School of Medicine, University of California San Francisco, San Francisco, CA, 94143, USA.

Nephrocalcinosis often begins on a calcium phosphate deposit, at the tip of the medullo-papillary complex (MPC) known as Randall's plaque (RP). Contextualizing proximally observed biominerals within the MPC has led us to postulate a mechanobiological switch that can trigger interstitial biomineralization at the MPC tip, remote from the intratubular biominerals. Micro X-ray computed tomography scans of human MPCs correlated with transmission and scanning electron micrographs, and X-ray energy dispersive spectrometry demonstrated novel findings about anatomically-specific biominerals. An abundance of proximal intratubular biominerals were associated with emergence of distal interstitial RP. The fundamental architecture of the MPC and mineral densities at the proximal and distal locations of the MPC differed markedly. A predominance of plate-like minerals or radially oriented plate-like crystallites within spheroidal minerals in the proximal intratubular locations, and core-shell type crystallites within spheroidal minerals in distal interstitial locations were observed. Based on the MPC anatomic location of structure-specific biominerals, a biological switch within the mineral-free zone occurring between the proximal and distal locations is postulated. The "on" and "off" switch is dependent on changes in the pressure differential resulting from changes in tubule diameters; the "Venturi effect" changes the "circumferential strain" and culminates in interstitial crystal deposits in the distal tubule wall in response to proximal tubular obstruction. These distal interstitial mineralizations can emerge into the collecting system of the kidney linking nephrocalcinosis with nephrolithiasis.
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http://dx.doi.org/10.1038/s41598-018-30717-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155006PMC
September 2018

Ultrasound-Guided Morcellation During Holmium Laser Enucleation of the Prostate.

J Endourol Case Rep 2018 1;4(1):133-135. Epub 2018 Aug 1.

Department of Urology, University of California, San Francisco, San Francisco, California.

Holmium laser enucleation of the prostate (HoLEP) has emerged as an accepted standard of care for the treatment of benign prostatic hyperplasia. This surgery relies on morcellation of the prostate adenoma once enucleation of the transition zone has been completed. Caution is required during this portion of the operation, as engaging bladder mucosa within the morcellator can result in bladder injury, a rare but potentially catastrophic complication of HoLEP. Morcellation of the prostatic tissue can be additionally challenging if visualization is poor from either equipment failure or increased bleeding from a highly vascularized prostate. We report the case of a 66-year-old Caucasian man with an estimated 158 g prostate who underwent HoLEP at our institution. Enucleation was uneventful; however, upon placement of the nephroscope to begin morcellation, it was immediately evident that the lens of the nephroscope was damaged as there was extremely poor visualization. Without a replacement nephroscope available, this would have normally resulted in aborting the case and returning another day to complete the morcellation. Concurrent bladder ultrasonography was performed and allowed for additional visual feedback to the operator, helping guide the morcellator to safely engage the enucleated adenoma and complete the operation. This case report demonstrates the ability of performing the morcellation portion of HoLEP mainly with the visualization provided by concurrent bladder ultrasonography. By providing additional imaging feedback to the operator, ultrasound can be a complementary tool to assist in safely performing morcellation in situations of suboptimal cystoscopic visualization during HoLEP.
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http://dx.doi.org/10.1089/cren.2018.0057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100697PMC
August 2018

Novel insights into renal mineralization and stone formation through advanced imaging modalities.

Connect Tissue Res 2018 12;59(sup1):102-110

a Department of Urology , University of California San Francisco , San Francisco , California , USA.

Purpose/Aim: The most common kidney stone composed of calcium oxalate forms on interstitial calcium phosphate mineral known as a Randall's plaque (RP). Due to limited information about events leading to the initial deposition of nanometer size interstitial calcium phosphate pre-clusters, there continues to be a debate on the initial site of calcium phosphate deposition and factors leading to stone formation.

Materials And Methods: High-resolution X-ray micro-computed tomography (CT), and light and electron microscopy techniques were used to characterize human renal pyramids and five representative kidney stones with identifiable stems. Mineral densities of mineralized aggregates within these specimens were correlated with micro- and ultra-structures as seen using light and electron microscopy techniques.

Results: The earliest detectable biominerals in the human renal papilla were proximal intratubular plate-like calcium phosphate deposits. Unoccluded tubules in stems connected to calcium phosphate stones were observed by electron microscope and X-ray micro-CT. These tubules were similar in diameter (30-100 μm) and shape to those observed in the distal regions of the renal papilla.

Conclusions: Observations were patterned through a novel and unified theory of stepwise-architecture guided biomineralization (a combination of smaller structures leading to a larger but similar structural framework). A plausible stepwise progression in renal biomineralization is proposed; proximal intratubular calcium phosphate deposits can lead to interstitial yet calcium phosphate rich RP and mature into a stem on which a calcium oxalate stone grows within the collecting system of a kidney.
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http://dx.doi.org/10.1080/03008207.2017.1409219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120852PMC
December 2018

Risk of Nephrolithiasis in Patients With Sleep Apnea: A Population-Based Cohort Study.

J Clin Sleep Med 2018 05 15;14(5):767-773. Epub 2018 May 15.

Faculty of Public Health, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan.

Study Objectives: To delineate the relationship between sleep apnea and subsequent risk of nephrolithiasis.

Methods: We conducted a retrospective cohort analysis of a general population sample from Taiwan National Health Insurance Research Database (NHIRD) from January 1, 2000 to December 31, 2012. Patients with sleep apnea without prior diagnosis of nephrolithiasis (n = 7,831) were identified and subsequent development of nephrolithiasis was compared to an age- and sex-matched control group (n = 31,293) without sleep apnea. The Cox proportional hazard regression models were used to evaluate the association between sleep apnea and subsequent nephrolithiasis development.

Results: After adjusting for age, sex, and comorbidities, the risk of nephrolithiasis remained significantly increased in the sleep apnea group (hazard ratio [HR] = 1.35; 95% confidence interval [CI] = 1.23-1.48; < .001). Compared to controls, elevated HRs of nephrolithiasis were observed for male patients (HR = 1.22; 95% CI 1.09-1.36; < .001) and those aged 20-39 years (HR = 1.28; 95% CI 1.09-1.49; < .01) and 40-59 years (HR = 1.17, 95% CI 1.03-1.34, < .05) in the sleep apnea cohort. Risk of nephrolithiasis in patients with sleep apnea increased significantly with concomitant metabolic-related comorbidities, gouty arthritis, and urinary tract infection.

Conclusions: Sleep apnea is associated with an increased subsequent risk of the development of nephrolithiasis. Young male patients with sleep apnea and concomitant comorbidities are at the greatest risk for nephrolithiasis formation.
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http://dx.doi.org/10.5664/jcsm.7102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940427PMC
May 2018

Beginnings of nephrolithiasis: insights into the past, present and future of Randall's plaque formation research.

Curr Opin Nephrol Hypertens 2018 07;27(4):236-242

Department of Urology, School of Medicine.

Purpose Of Review: Kidney stones form as a result of heterogeneous nucleation on a calcium phosphate lesion in the renal papilla known as Randall's plaque. Stone disease has plagued humans for millennia with relatively little progress made in the realm of prevention. An understanding of the historical aspects of research into Randall's plaque is necessary to interpret novel correlative imaging discoveries. Focus for the past several decades has been on the distal papillary tip, and the overlooked Anderson-Carr-Randall progression is revitalized with novel supporting evidence.

Recent Findings: Novel correlative techniques of three-dimensional micro-XCT imaging combined with electron and light microscopy techniques have revealed that the earliest mineralization event in the papilla is a distinct event that occurs proximal to the region where Randall's plaque has traditionally been identified.

Summary: The history of Randall's plaque research and the Anderson-Carr-Randall progression is reviewed. Proximal intratubular mineral deposits in normal and Randall's plaque affected papillae may be a target for future therapeutic interventions for nephrolithiasis. Further collaboration between nephrologists and urologists is necessary to cure this debilitating disease.
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http://dx.doi.org/10.1097/MNH.0000000000000414DOI Listing
July 2018

Laparoscopic Heminephrectomy of Chronically Obstructed Horseshoe Kidney Moiety with Staghorn Calculus, Massive Pyonephrosis, and Xanthogranulomatous Pyelonephritis.

J Endourol Case Rep 2018 1;4(1):39-41. Epub 2018 Mar 1.

Department of Urology, UCSF Medical Center, San Francisco, California.

Laparoscopic heminephrectomy was performed in a 64-year-old woman with a chronically obstructed horseshoe kidney moiety. More than 3000 cc of pyonephrosis was drained through two percutaneous nephrostomy tubes for infection control before left moiety laparoscopic resection. This case report attests to the feasibility of laparoscopic resection of a massively obstructed horseshoe kidney when performed in a staged manner after prolonged drainage. Since an incision was required for removal of the large specimen, ligation of the horseshoe isthmus was completed through the same incision after hilar control and laparoscopic mobilization of the moiety were completed.
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http://dx.doi.org/10.1089/cren.2017.0130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899298PMC
March 2018
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