Effects of the environment on the evolution of the vertebrate urinary tract.

Evolution of the vertebrate urinary system occurs in response to numerous selective pressures, which have been incompletely characterized. Developing research into urinary evolution led to the occurrence of clinical applications and insights in paediatric urology, reproductive medicine, urolithiasis and other domains. Each nephron segment and urinary organ has functions that can be contextualized within an evolutionary framework. For example, the structure and function of the glomerulus and proximal tubule are highly conserved, enabling blood cells and proteins to be retained, and facilitating the elimination of oceanic Ca+ and Mg+. Urea emerged as an osmotic mediator during evolution, as cells of large organisms required increased precision in the internal regulation of salinity and solutes. As the first vertebrates moved from water to land, acid-base regulation was shifted from gills to skin and kidneys in amphibians. In reptiles and birds, solute regulation no longer occurred through the skin but through nasal salt glands and post-renally, within the cloaca and the rectum. In placental mammals, nasal salt glands are absent and the rectum and urinary tracts became separate, which limited post-renal urine concentration and led to the necessity of a kidney capable of high urine concentration. Considering the evolutionary and environmental selective pressures that have contributed to renal evolution can help to gain an increased understanding of renal physiology.

Identification of Clinically Insignificant Renal Calculi on Sonography.

OBJECTIVE: To determine factors predicting if a radiologists... report of a .. stone... on ultrasound (US) was not actually a clinically significant stone, based on subsequent computed tomogram (CT). US often overestimates stone size and various pathologic entities are also hyperechoic;.ßthus, a subsequent CT without a clinically significant stone may represent unnecessary radiation exposure. A decision-tree and nomogram were developed to predict when stones are unlikely on subsequent CT. METHODS: Retrospective analysis of patients, of any age, receiving CT within 24.ßhours of a sonographic report documenting a single renal stone, during 2019...2020, in any phase of care, at one institution. Novel stone-likelihood-systems for US and CT (US-SLS, CT-SLS) were devised and validated to classify stones as clinically significant or insignificant, with CT as the gold standard. Binomial logistic regression predicting clinically significant stones was performed with sonographic and patient characteristics. RESULTS: Eight hundred twenty patients had US followed by CT, 228 (27.8%) reported documented stones, 140 (17.1%) reported a single stone. Clinically significant stones were associated with larger stone size (P: .002), location (P: .002), hydronephrosis (P: .04), shadowing-artifact (P: .02) depth.ßto.ßstone (P: .008), and Body mass Index (BMI) (P: .01). US-SLS had higher sensitivity (95.4%) and negative-predictive-value (81.8%) compared to a multivariate model of significant variables. CONCLUSION: US-SLS appears to exclude clinically irrelevant .. stones... better than established criteria including twinkle or shadow in this retrospective analysis. A diagnostic algorithm and nomogram are presented. US-SLS and the associated decision tree can assist providers in avoiding unnecessary radiation when clinically significant stones are unlikely.

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

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.

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

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.

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

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.

Architecture-Guided Fluid Flow Directs Renal Biomineralization.

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.

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

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.

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

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.

A continuum of mineralization from human renal pyramid to stones on stems.

The development of new modalities for kidney stone prevention rests upon understanding the progression of mineralization within the renal pyramid. The progression from small foci of mineralized volumes within the renal pyramid to larger interstitial plaques that ultimately lead into clinically detectable calcium-based stones on calcium phosphate stems will be presented through correlative microscopy approach. High resolution X-ray computed tomography (micro-XCT), electron microscopy, and energy dispersive X-ray (EDX) compositional analyses of interstitial plaques, stems, and attached stones were performed. Increase in mineral density progressed with mineralization severity, with the highest mineral densities detected within mature Randall's plaque and stems to which kidney stones were attached. EDX analyses revealed variable elemental composition within interstitial plaque, stems, and stones. Micro-XCT reconstructions of stones with stems enabled visualization of unoccluded tubules within stems, with average tubule diameters corresponding to thin limbs of Henle, blood vessels, and collecting ducts. Correlative microscopy confirmed that the progression of mineralization leading to calcium-based nephrolithiasis occurs through a continuum involving four anatomically and structurally distinct biomineralization regions: 1) proximal intratubular mineralization within the renal pyramid; 2) interstitial Randall's plaque near the tip of the papilla; 3) emerging plaque (stems); and, 4) the body of heterogeneous stones. STATEMENT OF SIGNIFICANCE: Nephrolithiasis is a common condition affecting nearly 1 in 11 Americans. The most common type of stone, calcium oxalate is known to form on a calcium phosphate deposit on the renal papilla known as Randall's plaque. Novel imaging techniques have identified distinct regions of biomineralization not just at the tip, but throughout the renal papilla. The classic understanding of Randall's plaque formation is reformulated using correlative imaging techniques. This study establishes a stepwise progression of anatomically-specific biomineralization events including, 1) proximal intratubular mineralization within the renal pyramid; 2) interstitial Randall's plaque near the tip of the papilla; 3) emerging plaque (stems); and, 4) the body of heterogeneous stones, and provides insights into the need for plausible site-specific therapeutic intervention.

Effect of stone composition on operative time during ureteroscopic holmium:yttrium-aluminum-garnet laser lithotripsy with active fragment retrieval.

OBJECTIVE: To assess whether the stone composition affects the operative time of ureteroscopic holmium:yttrium-aluminum-garnet laser lithotripsy (ULL) with active fragment retrieval. The chemical composition of a calculus is known to affect the efficacy with which it is fragmented by a device, such as pneumatic, laser, or shock wave lithotripter. Previous studies examining the efficacy of holmium:yttrium-aluminum-garnet laser lithotripsy have been performed in vitro, but it is not known whether the operative time is significantly affected by the chemical composition of a patient's stone. METHODS: We selected all patients who had undergone ULL for stone disease from July 2008 to January 2011 for a retrospective chart review. We used a standardized operative technique of fragmentation and active retrieval of all fragments identified on full inspection of the entire collecting system using rigid and flexible endoscopes. The stone composition was defined as the presence of a single predominant (>51%) component. Statistical analysis was performed on a per-procedure basis relative to the stone burden, as measured in minutes of operative time per gram of stone. RESULTS: A total of 187 cases of unilateral ULL with active retrieval of stone fragments confirmed to have a single predominant chemical composition met the inclusion criteria. When accounting for the weight of the recovered stone, no difference was found in the operative time among the apatite, brushite, cystine, calcium oxalate monohydrate, calcium oxalate dihydrate, and uric acid stones. CONCLUSION: Although stone composition is widely recognized as an important procedural variable, especially for shock wave lithotripsy, it appears to have little effect on the overall operative time for holmium:yttrium-aluminum-garnet lithotripsy when using active fragment retrieval.