Randall's plaque: Pathogenesis and role in calcium oxalate nephrolithiasis

The purpose of these studies was to test the hypothesis that Randall's plaque develops in unique anatomical sites of the kidney and their formation is conditioned by specific stone-forming pathophysiologies. We performed intraoperative papillary biopsies from kidneys of idiopathic-calcium oxalate (CaOx), intestinal bypass for obesity, brushite (BR) and cystine stone formers (SF) during percutaneous nephrolithotomy. Tissues were examined by infrared analysis and light and electron microscopy. Our analysis revealed a distinct pattern of mineral deposition and papillary pathology for each type of SF. CaOx SF had interstitial apatite crystals beginning at thin loops of Henle. These deposits termed Randall's plaque are thought to serve as sites for stone attachment. No tubular injury was noted. Intestinal bypass patients possessed intraluminal apatite deposits in inner medullary collecting ducts (IMCD) with associated cell injury. BR SF showed the most severe form of cortical and medullary changes with sites of Randall's plaque, and yellowish intraluminal deposits of apatite in IMCD. Cystine SF had plugging of ducts of Bellini with cystine crystals and apatite deposits in IMCD and loops of Henle. Intratubular sites of crystalline deposits were always associated to adjacent regions of interstitial fibrosis. The metabolic, anatomic, and surgical pathologic findings in four distinct groups of SF clearly show that ‘the histology of the renal papilla from a stone former, is particular to the clinical setting’. We believe our approach to studying stone disease will provide insights into the pathogenesis of stone formation for each type of SF that will lead to improved clinical treatment

Determination of Flavonoids and Resveratrol in Wine by Turbulent-Flow Chromatography-LC-MS

Turbulent-flow chromatography (TFC) on-line coupled to liquid chromatography mass spectrometry (LC-MS) is used to determine flavonoids and resveratrol in different types of wines. A fully automated system was developed in which 10 mL of sample (diluted wine) was passed over a TFC column, after which the retained analytes were separated by reversed-phase LC and detected by negative ion mode atmospheric-pressure chemical ionization (APCI) MS. The method proved to be fast, non-laborious, robust and sensitive. The feasibility of the method was tested on several red, white and rose wines. Quantitation of resveratrol was possible using the standard addition procedure. Red wine showed the highest amount of resveratrol (4 mg

Transgluteal CT-Guided Percutaneous Renal Access for Percutaneous Nephrolithotomy in a Pelvic Horseshoe Kidney

CT-guided percutaneous renal access has been described as a safe and effective access technique in patients with complex anatomy, including ectopic kidney, retrorenal colon, spinal dysraphism, hepatomegaly, and splenomegaly. In comparison to conventional intraoperative fluoroscopic-guided access, CT imaging allows for delineation of surrounding structures that are at risk for injury during percutaneous access. However, previous reports indicate that pelvic kidneys might be inaccessible percutaneously without laparoscopic assistance. Herein, we present a novel transgluteal route to renal access for percutaneous nephrolithotomy (PCNL) in a patient with a pelvic horseshoe kidney and severe spinal deformity

Predictors of Enucleation and Morcellation Time During Holmium Laser Enucleation of the Prostate.

Objective To examine predictors of enucleation and morcellation times within a large cohort of men undergoing holmium laser enucleation of the prostate (HoLEP) for benign prostatic hypertrophy. Materials and Methods Preoperative, perioperative, and postoperative clinical characteristics were available from men treated with HoLEP between 1998 and 2013 at Indiana University Health Methodist Hospital. Stepwise linear regression was performed to determine clinical variables which are associated with enucleation and morcellation times. Results We identified 960 patients who underwent HoLEP. Average (range) enucleation time was 65.7 (11-245) minutes and morcellation time was 19.7 (3-260) minutes. History of anticoagulation was associated with a small decrease in enucleation time (P = .013) whereas increasing HoLEP specimen weight was associated with increasing enucleation time (P <.001). History of intermittent catheterization, urinary tract infections (UTI), presence of dense prostatic tissue (colloquially referred to as “beach balls”), and increasing specimen weight were associated with increasing morcellation time (P <.05 each). Having HoLEP performed by a less experienced urologist was associated with longer enucleation and morcellation times. Conclusion Prostate volume is significantly associated with increased enucleation and morcellation times during HoLEP. Additionally, history of UTI and clean intermittent catheterization (CIC) is associated with modest increases in enucleation and morcellation times. Dense enucleated prostate tissue significantly impacts the ability to morcellate effectively. Increasing surgeon experience can significantly improve both enucleation and morcellation efficiency

Contrasting histopathology and crystal deposits in kidneys of idiopathic stone formers who produce hydroxy apatite, brushite, or calcium oxalate stones

Our previous work has shown that stone formers who form calcium phosphate (CaP) stones that contain any brushite (BRSF) have a distinctive renal histopathology and surgical anatomy when compared with idiopathic calcium oxalate stone formers (ICSF). Here we report on another group of idiopathic CaP stone formers, those forming stone containing primarily hydroxyapatite, in order to clarify in what ways their pathology differs from BRSF and ICSF. Eleven hydroxyapatite stone formers (HASF) (2 males, 9 females) were studied using intra-operative digital photography and biopsy of papillary and cortical regions to measure tissue changes associated with stone formation. Our main finding is that HASF and BRSF differ significantly from each other and that both differ greatly from ICSF. Both BRSF and ICSF patients have significant levels of Randall's plaque compared with HASF. Intra-tubular deposit number is greater in HASF than BRSF and nonexistent in ICSF while deposit size is smaller in HASF than BRSF. Cortical pathology is distinctly greater in BRSF than HASF. Four attached stones were observed in HASF, three in 25 BRSF and 5-10 per ICSF patient. HASF and BRSF differ clinically in that both have higher average urine pH, supersaturation of CaP, and calcium excretion than ICSF. Our work suggests that HASF and BRSF are two distinct and separate diseases and both differ greatly from ICSF

Biopsy proven medullary sponge kidney: clinical findings, histopathology, and role of osteogenesis in stone and plaque formation

Medullary sponge kidney (MSK) is associated with recurrent stone formation, but the clinical phenotype is unclear because patients with other disorders may be incorrectly labeled MSK. We studied 12 patients with histologic findings pathognomonic of MSK. All patients had an endoscopically recognizable pattern of papillary malformation, which may be segmental or diffuse. Affected papillae are enlarged and billowy, due to markedly enlarged inner medullary collecting ducts (IMCD), which contain small, mobile ductal stones. Patients had frequent dilation of Bellini ducts, with occasional mineral plugs. Stones may form over white (Randall's) plaque, but most renal pelvic stones are not attached, and have a similar morphology as ductal stones, which are a mixture of calcium oxalate and apatite. Patients had no abnormalities of urinary acidification or acid excretion; the most frequent metabolic abnormality was idiopathic hypercalciuria. Although both Runx2 and Osterix are expressed in papillae of MSK patients, no mineral deposition was seen at the sites of gene expression, arguing against a role of these genes in this process. Similar studies in idiopathic calcium stone formers showed no expression of these genes at sites of Randall's plaque. The most likely mechanism for stone formation in MSK appears to be crystallization due to urinary stasis in dilated IMCD with subsequent passage of ductal stones into the renal pelvis where they may serve as nuclei for stone formation

Treatment of painful caliceal stones

Nonmobile caliceal stones cause pain more often than previously appreciated. The character and intensity of the pain differs from typical renal colic. Twenty-six patients with caliceal stones and pain underwent attempted treatment for pain control via stone removal or disintegration: 15 were treated with percutaneous stone extraction (PSE), 10 with extracorporeal shock-wave lithotripsy (ESWL), and 1 required open surgery after failing PSE. One patient had persistent pain after ESWL and subsequently underwent PSE; 25 of 26 patients had complete relief of pain. Morbidity was minimal. Patients with painful caliceal stones should be offered ESWL, followed by PSE if pain persists.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27186/1/0000189.pd

LC determination of propylene glycol in human plasma after pre-column derivatization with benzoyl chloride

A simple high-performance liquid chromatographic method, using photodiode array detection was developed for the determination of propylene glycol in human plasma and in the fluid retreived after continuous veno-venous hemofiltration. The method entailed alkaline derivatization with benzoyl chloride and ethylene glycol as internal standard. The separation of the compounds, after extraction with pentane, was carried out on a Pursuit C8 column with UV-detection at 230 nm. Validation samples were analyzed with an accuracy between 95 and 105%, and intra- and inter-day coefficients of variation of less than 8%. The calibration curve was linear over a concentration range of 5-100 mg

Endoscopic Evidence That Randall's Plaque is Associated with Surface Erosion of the Renal Papilla

OBJECTIVE: This study was conducted to assess the reliability and precision of an endoscopic grading scale to identify renal papillary abnormalities across a spectrum of equipment, locations, graders, and patients. MATERIALS AND METHODS: Intra- and interobserver reliability of the papillary grading system was assessed using weighted kappa scoring among 4 graders reviewing a single renal papilla from 50 separate patients on 2 occasions. Grading was then applied to a cohort of patients undergoing endoscopic stone removal procedures at two centers. Patient factors were compared with papillary scores on the level of the papilla, kidney, and patient. RESULTS: Graders achieved substantial (kappa >0.6) intra- and inter-rater reliability in scored domains of ductal plugging, surface pitting, and loss of contour. Agreement for Randall's Plaque (RP) was moderate. Papillary scoring was then performed for 76 patients (89 kidneys, 533 papillae). A significant association was discovered between pitting and RP that held both within and across institutions. A general linear model was then created to further assess this association and it was found that RP score was a highly significant independent correlate of pitting score (F = 7.1; p < 0.001). Mean pitting scores increased smoothly and progressively with increasing RP scores. Sums of the scored domains were then calculated as a reflection of gross papillary abnormality. When analyzed in this way, a history of stone recurrence and shockwave lithotripsy were strongly predictive of higher sums. CONCLUSIONS: Renal papillary pathology can be reliably assessed between different providers using a newly described endoscopic grading scale. Application of this scale to stone-forming patients suggests that the degree of RP appreciated in the papilla is strongly associated with the presence of pitting. It also suggests that patients with a history of recurrent stones and lithotripsy have greater burdens of gross papillary disease

P62-positive aggregates are homogenously distributed in the myocardium and associated with the type of mutation in genetic cardiomyopathy

© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd Genetic cardiomyopathy is caused by mutations in various genes. The accumulation of potentially proteotoxic mutant protein aggregates due to insufficient autophagy is a possible mechanism of disease development. The objective of this study was to investigate the distribution in the myocardium of such aggregates in relation to specific pathogenic genetic mutations in cardiomyopathy hearts. Hearts from 32 genetic cardiomyopathy patients, 4 non-genetic cardiomyopathy patients and 5 controls were studied. Microscopic slices from an entire midventricular heart slice were stained for p62 (sequestosome-1, marker for aggregated proteins destined for autophagy). The percentage of cardiomyocytes with p62 accumulation was higher in cardiomyopathy hearts (median 3.3%) than in healthy controls (0.3%; P <.0001). p62 accumulation was highest in the desmin (15.6%) and phospholamban (7.2%) groups. P62 accumulation was homogeneously distributed in the myocardium. Fibrosis was not associated with p62 accumulation in subgroup analysis of phospholamban hearts. In conclusion, accumulation of p62-positive protein aggregates is homogeneously distributed in the myocardium independently of fibrosis distribution and associated with desmin and phospholamban cardiomyopathy. Proteotoxic protein accumulation is a diffuse process in the myocardium while a more localized second hit, such as local strain during exercise, might determine whether this leads to regional myocyte decay