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Andrew D. Rule - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of inactive matrix gla protein mgp as a biomarker for incident and recurrent kidney stones
    Journal of Nephrology, 2020
    Co-Authors: Vincent Castiglione, John C Lieske, Hans Pottel, Pierre Lukas, Etienne Cavalier, Pierre Delanaye, Andrew D. Rule
    Abstract:

    BACKGROUND Matrix-Gla-protein (MGP) is an inhibitor of vascular calcification. Its dephosphorylated and uncarboxylated inactive form, dpucMGP, is a marker of vitamin K status and of cardio-vascular outcomes in chronic kidney disease. We hypothesized that higher serum dpucMGP would be a biomarker of kidney stone disease. METHODS We measured serum dpucMGP in incident symptomatic kidney stone-formers and non-stone formers at a baseline visit. Symptomatic stone recurrence was assessed in the stones formers over a 5-year period. The association of dpucMGP with incident or recurrent kidney stones was assessed with and without adjustment for clinical, blood, and urine characteristics. RESULTS There was no significant difference in serum dpucMGP level between 498 stone formers and 395 non-stone former (510 vs 501 pmol/L; p = 0.66). In a multivariable model adjusting for clinical, blood and urine chemistries, higher MGP was associated with lower risk of stone formation (OR = 0.674, 95% CI 0.522-0.870), contrary to previous reports. Among 375 stone formers with 5 years of follow-up, 79 (21%) had symptomatic recurrence. No difference in serum dpucMGP was evident in recurrent versus non-recurrent stone-formers (482 vs 502 pmol/L; p = 0.26). Serum dpucMGP was correlated with cystatin C levels in non stone-formers, incident stone-formers and recurrent stone-formers (r > 0.3, p < 0.0001). CONCLUSION Elevated serum dpucMGP was not associated with incident or recurrent symptomatic kidney stone events. However, higher level of dpucMGP was associated with lower risk of kidney stone in a multivariable logistic regression model.

  • evaluation of inactive matrix gla protein mgp as a biomarker for incident and recurrent kidney stones
    Journal of Nephrology, 2020
    Co-Authors: Vincent Castiglione, John C Lieske, Hans Pottel, Pierre Lukas, Etienne Cavalier, Pierre Delanaye, Andrew D. Rule
    Abstract:

    Matrix-Gla-protein (MGP) is an inhibitor of vascular calcification. Its dephosphorylated and uncarboxylated inactive form, dpucMGP, is a marker of vitamin K status and of cardio-vascular outcomes in chronic kidney disease. We hypothesized that higher serum dpucMGP would be a biomarker of kidney stone disease. We measured serum dpucMGP in incident symptomatic kidney stone-formers and non-stone formers at a baseline visit. Symptomatic stone recurrence was assessed in the stones formers over a 5-year period. The association of dpucMGP with incident or recurrent kidney stones was assessed with and without adjustment for clinical, blood, and urine characteristics. There was no significant difference in serum dpucMGP level between 498 stone formers and 395 non-stone former (510 vs 501 pmol/L; p = 0.66). In a multivariable model adjusting for clinical, blood and urine chemistries, higher MGP was associated with lower risk of stone formation (OR = 0.674, 95% CI 0.522–0.870), contrary to previous reports. Among 375 stone formers with 5 years of follow-up, 79 (21%) had symptomatic recurrence. No difference in serum dpucMGP was evident in recurrent versus non-recurrent stone-formers (482 vs 502 pmol/L; p = 0.26). Serum dpucMGP was correlated with cystatin C levels in non stone-formers, incident stone-formers and recurrent stone-formers (r > 0.3, p < 0.0001). Elevated serum dpucMGP was not associated with incident or recurrent symptomatic kidney stone events. However, higher level of dpucMGP was associated with lower risk of kidney stone in a multivariable logistic regression model.

  • predictors of symptomatic kidney stone recurrence after the first and subsequent episodes
    Mayo Clinic proceedings, 2019
    Co-Authors: Lisa E Vaughan, Felicity Enders, John C Lieske, Vernon M Pais, Marcelino E Rivera, Ramila A Mehta, Terri J Vrtiska, Andrew D. Rule
    Abstract:

    Abstract Objective To predict symptomatic recurrence among community stone formers with one or more previous stone episodes. Patients and Methods A random sample of incident symptomatic kidney stone formers in Olmsted County, Minnesota, was followed for all symptomatic stone episodes resulting in clinical care from January 1, 1984, through January 31, 2017. Clinical and radiographic characteristics at each stone episode predictive of subsequent episodes were identified. Results There were 3364 incident kidney stone formers with 4951 episodes. The stone recurrence rates per 100 person-years were 3.4 (95% CI, 3.2-3.7) after the first episode, 7.1 (95% CI, 6.4-7.9) after the second episode, 12.1 (95% CI, 10.3-13.9) after the third episode, and 17.6 (95% CI, 15.1-20.0) after the fourth or higher episode (P Conclusion The revised Recurrence Of Kidney Stone tool predicts the risk of symptomatic recurrence by using readily available clinical characteristics of stone formers.

  • risk of esrd and mortality in kidney and bladder stone formers
    American Journal of Kidney Diseases, 2018
    Co-Authors: Tsering Dhondup, Lisa E Vaughan, Felicity Enders, John C Lieske, Ramila A Mehta, Wonngarm Kittanamongkolchai, Jasdeep K Chhina, La Tonya J Hickson, Andrew D. Rule
    Abstract:

    Rationale & Objectives Kidney stones have been associated with increased risk for end-stage renal disease (ESRD). However, it is unclear whether there is also an increased risk for mortality and if these risks are uniform across clinically distinct categories of stone formers. Study Design Historical matched-cohort study. Setting & Participants Stone formers in Olmsted County, MN, between 1984 and 2012 identified using International Classification of Diseases, Ninth Revision codes. Age- and sex-matched individuals who had no codes for stones were the comparison group. Predictor Stone formers were placed into 5 mutually exclusive categories after review of medical charts: incident symptomatic kidney, recurrent symptomatic kidney, asymptomatic kidney, bladder only, and miscoded (no stone). Outcomes ESRD, mortality, cardiovascular mortality, and cancer mortality. Analytical Approach Cox proportional hazards models with adjustment for baseline comorbid conditions. Results Overall, 65 of 6,984 (0.93%) stone formers and 102 of 28,044 (0.36%) non–stone formers developed ESRD over a mean follow-up of 12.0 years. After adjusting for baseline hypertension, diabetes mellitus, dyslipidemia, gout, obesity, and chronic kidney disease, risk for ESRD was higher in recurrent symptomatic kidney (HR, 2.34; 95% CI, 1.08-5.07), asymptomatic kidney (HR, 3.94; 95% CI, 1.65-9.43), and miscoded (HR, 6.18; 95% CI, 2.25-16.93) stone formers, but not in incident symptomatic kidney or bladder stone formers. The adjusted risk for all-cause mortality was higher in asymptomatic kidney (HR, 1.40; 95% CI, 1.18-1.67) and bladder (HR, 1.37; 95% CI, 1.12-1.69) stone formers. Chart review of asymptomatic and miscoded stone formers suggested increased risk for adverse outcomes related to diagnoses including urinary tract infection, cancer, and musculoskeletal or gastrointestinal pain. Conclusions The higher risk for ESRD in recurrent symptomatic compared with incident symptomatic kidney stone formers suggests that stone events are associated with kidney injury. The clinical indication for imaging in asymptomatic stone formers, the correct diagnosis in miscoded stone formers, and the cause of a bladder outlet obstruction in bladder stone formers may explain the higher risk for ESRD or death in these groups.

  • stone composition among first time symptomatic kidney stone formers in the community
    Mayo Clinic proceedings, 2015
    Co-Authors: Prince Singh, Amy E. Krambeck, Lisa E Vaughan, Felicity Enders, John C Lieske, Eric J Bergstralh, John J Knoedler, Andrew D. Rule
    Abstract:

    Abstract Objective To determine the variation in kidney stone composition and its association with risk factors and recurrence among first-time stone formers in the general population. Patients and Methods Medical records were manually reviewed and validated for symptomatic kidney stone episodes among Olmsted County, Minnesota, residents from January 1, 1984, through December 31, 2012. Clinical and laboratory characteristics and the risk of symptomatic recurrence were compared between stone compositions. Results There were 2961 validated first-time symptomatic kidney stone formers. Stone composition analysis was obtained in 1508 (51%) at the first episode. Stone formers were divided into the following mutually exclusive groups: any brushite (0.9%), any struvite (0.9%), any uric acid (4.8%), and majority calcium oxalate (76%) or majority hydroxyapatite (18%). Stone composition varied with clinical characteristics. A multivariable model had a 69% probability of correctly estimating stone composition but assuming calcium oxalate monohydrate stone was correct 65% of the time. Symptomatic recurrence at 10 years was approximately 50% for brushite, struvite, and uric acid but approximately 30% for calcium oxalate and hydroxyapatite stones ( P P for trend=.10). However, among calcium oxalate stones, 10-year recurrence rate ranged from 38% for 100% calcium oxalate dihydrate to 26% for 100% calcium oxalate monohydrate ( P for trend=.007). Conclusion Calcium stones are more common (93.5% of stone formers) than has been previously reported. Although clinical and laboratory factors associate with the stone composition, they are of limited utility for estimating stone composition. Rarer stone compositions are more likely to recur.

John C Lieske - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of inactive matrix gla protein mgp as a biomarker for incident and recurrent kidney stones
    Journal of Nephrology, 2020
    Co-Authors: Vincent Castiglione, John C Lieske, Hans Pottel, Pierre Lukas, Etienne Cavalier, Pierre Delanaye, Andrew D. Rule
    Abstract:

    BACKGROUND Matrix-Gla-protein (MGP) is an inhibitor of vascular calcification. Its dephosphorylated and uncarboxylated inactive form, dpucMGP, is a marker of vitamin K status and of cardio-vascular outcomes in chronic kidney disease. We hypothesized that higher serum dpucMGP would be a biomarker of kidney stone disease. METHODS We measured serum dpucMGP in incident symptomatic kidney stone-formers and non-stone formers at a baseline visit. Symptomatic stone recurrence was assessed in the stones formers over a 5-year period. The association of dpucMGP with incident or recurrent kidney stones was assessed with and without adjustment for clinical, blood, and urine characteristics. RESULTS There was no significant difference in serum dpucMGP level between 498 stone formers and 395 non-stone former (510 vs 501 pmol/L; p = 0.66). In a multivariable model adjusting for clinical, blood and urine chemistries, higher MGP was associated with lower risk of stone formation (OR = 0.674, 95% CI 0.522-0.870), contrary to previous reports. Among 375 stone formers with 5 years of follow-up, 79 (21%) had symptomatic recurrence. No difference in serum dpucMGP was evident in recurrent versus non-recurrent stone-formers (482 vs 502 pmol/L; p = 0.26). Serum dpucMGP was correlated with cystatin C levels in non stone-formers, incident stone-formers and recurrent stone-formers (r > 0.3, p < 0.0001). CONCLUSION Elevated serum dpucMGP was not associated with incident or recurrent symptomatic kidney stone events. However, higher level of dpucMGP was associated with lower risk of kidney stone in a multivariable logistic regression model.

  • evaluation of inactive matrix gla protein mgp as a biomarker for incident and recurrent kidney stones
    Journal of Nephrology, 2020
    Co-Authors: Vincent Castiglione, John C Lieske, Hans Pottel, Pierre Lukas, Etienne Cavalier, Pierre Delanaye, Andrew D. Rule
    Abstract:

    Matrix-Gla-protein (MGP) is an inhibitor of vascular calcification. Its dephosphorylated and uncarboxylated inactive form, dpucMGP, is a marker of vitamin K status and of cardio-vascular outcomes in chronic kidney disease. We hypothesized that higher serum dpucMGP would be a biomarker of kidney stone disease. We measured serum dpucMGP in incident symptomatic kidney stone-formers and non-stone formers at a baseline visit. Symptomatic stone recurrence was assessed in the stones formers over a 5-year period. The association of dpucMGP with incident or recurrent kidney stones was assessed with and without adjustment for clinical, blood, and urine characteristics. There was no significant difference in serum dpucMGP level between 498 stone formers and 395 non-stone former (510 vs 501 pmol/L; p = 0.66). In a multivariable model adjusting for clinical, blood and urine chemistries, higher MGP was associated with lower risk of stone formation (OR = 0.674, 95% CI 0.522–0.870), contrary to previous reports. Among 375 stone formers with 5 years of follow-up, 79 (21%) had symptomatic recurrence. No difference in serum dpucMGP was evident in recurrent versus non-recurrent stone-formers (482 vs 502 pmol/L; p = 0.26). Serum dpucMGP was correlated with cystatin C levels in non stone-formers, incident stone-formers and recurrent stone-formers (r > 0.3, p < 0.0001). Elevated serum dpucMGP was not associated with incident or recurrent symptomatic kidney stone events. However, higher level of dpucMGP was associated with lower risk of kidney stone in a multivariable logistic regression model.

  • predictors of symptomatic kidney stone recurrence after the first and subsequent episodes
    Mayo Clinic proceedings, 2019
    Co-Authors: Lisa E Vaughan, Felicity Enders, John C Lieske, Vernon M Pais, Marcelino E Rivera, Ramila A Mehta, Terri J Vrtiska, Andrew D. Rule
    Abstract:

    Abstract Objective To predict symptomatic recurrence among community stone formers with one or more previous stone episodes. Patients and Methods A random sample of incident symptomatic kidney stone formers in Olmsted County, Minnesota, was followed for all symptomatic stone episodes resulting in clinical care from January 1, 1984, through January 31, 2017. Clinical and radiographic characteristics at each stone episode predictive of subsequent episodes were identified. Results There were 3364 incident kidney stone formers with 4951 episodes. The stone recurrence rates per 100 person-years were 3.4 (95% CI, 3.2-3.7) after the first episode, 7.1 (95% CI, 6.4-7.9) after the second episode, 12.1 (95% CI, 10.3-13.9) after the third episode, and 17.6 (95% CI, 15.1-20.0) after the fourth or higher episode (P Conclusion The revised Recurrence Of Kidney Stone tool predicts the risk of symptomatic recurrence by using readily available clinical characteristics of stone formers.

  • risk of esrd and mortality in kidney and bladder stone formers
    American Journal of Kidney Diseases, 2018
    Co-Authors: Tsering Dhondup, Lisa E Vaughan, Felicity Enders, John C Lieske, Ramila A Mehta, Wonngarm Kittanamongkolchai, Jasdeep K Chhina, La Tonya J Hickson, Andrew D. Rule
    Abstract:

    Rationale & Objectives Kidney stones have been associated with increased risk for end-stage renal disease (ESRD). However, it is unclear whether there is also an increased risk for mortality and if these risks are uniform across clinically distinct categories of stone formers. Study Design Historical matched-cohort study. Setting & Participants Stone formers in Olmsted County, MN, between 1984 and 2012 identified using International Classification of Diseases, Ninth Revision codes. Age- and sex-matched individuals who had no codes for stones were the comparison group. Predictor Stone formers were placed into 5 mutually exclusive categories after review of medical charts: incident symptomatic kidney, recurrent symptomatic kidney, asymptomatic kidney, bladder only, and miscoded (no stone). Outcomes ESRD, mortality, cardiovascular mortality, and cancer mortality. Analytical Approach Cox proportional hazards models with adjustment for baseline comorbid conditions. Results Overall, 65 of 6,984 (0.93%) stone formers and 102 of 28,044 (0.36%) non–stone formers developed ESRD over a mean follow-up of 12.0 years. After adjusting for baseline hypertension, diabetes mellitus, dyslipidemia, gout, obesity, and chronic kidney disease, risk for ESRD was higher in recurrent symptomatic kidney (HR, 2.34; 95% CI, 1.08-5.07), asymptomatic kidney (HR, 3.94; 95% CI, 1.65-9.43), and miscoded (HR, 6.18; 95% CI, 2.25-16.93) stone formers, but not in incident symptomatic kidney or bladder stone formers. The adjusted risk for all-cause mortality was higher in asymptomatic kidney (HR, 1.40; 95% CI, 1.18-1.67) and bladder (HR, 1.37; 95% CI, 1.12-1.69) stone formers. Chart review of asymptomatic and miscoded stone formers suggested increased risk for adverse outcomes related to diagnoses including urinary tract infection, cancer, and musculoskeletal or gastrointestinal pain. Conclusions The higher risk for ESRD in recurrent symptomatic compared with incident symptomatic kidney stone formers suggests that stone events are associated with kidney injury. The clinical indication for imaging in asymptomatic stone formers, the correct diagnosis in miscoded stone formers, and the cause of a bladder outlet obstruction in bladder stone formers may explain the higher risk for ESRD or death in these groups.

  • stone composition among first time symptomatic kidney stone formers in the community
    Mayo Clinic proceedings, 2015
    Co-Authors: Prince Singh, Amy E. Krambeck, Lisa E Vaughan, Felicity Enders, John C Lieske, Eric J Bergstralh, John J Knoedler, Andrew D. Rule
    Abstract:

    Abstract Objective To determine the variation in kidney stone composition and its association with risk factors and recurrence among first-time stone formers in the general population. Patients and Methods Medical records were manually reviewed and validated for symptomatic kidney stone episodes among Olmsted County, Minnesota, residents from January 1, 1984, through December 31, 2012. Clinical and laboratory characteristics and the risk of symptomatic recurrence were compared between stone compositions. Results There were 2961 validated first-time symptomatic kidney stone formers. Stone composition analysis was obtained in 1508 (51%) at the first episode. Stone formers were divided into the following mutually exclusive groups: any brushite (0.9%), any struvite (0.9%), any uric acid (4.8%), and majority calcium oxalate (76%) or majority hydroxyapatite (18%). Stone composition varied with clinical characteristics. A multivariable model had a 69% probability of correctly estimating stone composition but assuming calcium oxalate monohydrate stone was correct 65% of the time. Symptomatic recurrence at 10 years was approximately 50% for brushite, struvite, and uric acid but approximately 30% for calcium oxalate and hydroxyapatite stones ( P P for trend=.10). However, among calcium oxalate stones, 10-year recurrence rate ranged from 38% for 100% calcium oxalate dihydrate to 26% for 100% calcium oxalate monohydrate ( P for trend=.007). Conclusion Calcium stones are more common (93.5% of stone formers) than has been previously reported. Although clinical and laboratory factors associate with the stone composition, they are of limited utility for estimating stone composition. Rarer stone compositions are more likely to recur.

James E Lingeman - One of the best experts on this subject based on the ideXlab platform.

  • Mechanisms of human kidney stone formation
    Urolithiasis, 2014
    Co-Authors: Andrew P. Evan, F. L. Coe, Elaine M. Worcester, James Williams, James E Lingeman
    Abstract:

    The precise mechanisms of kidney stone formation and growth are not completely known, even though human stone disease appears to be one of the oldest diseases known to medicine. With the advent of the new digital endoscope and detailed renal physiological studies performed on well phenotyped stone formers, substantial advances have been made in our knowledge of the pathogenesis of the most common type of stone former, the idiopathic calcium oxalate stone former as well as nine other stone forming groups. The observations from our group on human stone formers and those of others on model systems have suggested four entirely different pathways for kidney stone formation. Calcium oxalate stone growth over sites of Randall's plaque appear to be the primary mode of stone formation for those patients with hypercalciuria. Overgrowths off the ends of Bellini duct plugs have been noted in most stone phenotypes, do they result in a clinical stone? Micro-lith formation does occur within the lumens of dilated inner medullary collecting ducts of cystinuric stone formers and appear to be confined to this space. Lastly, cystinuric stone formers also have numerous small, oval, smooth yellow appearing calyceal stones suggestive of formation in free solution. The scientific basis for each of these four modes of stone formation are reviewed and used to explore novel research opportunities

  • contrasting histopathology and crystal deposits in kidneys of idiopathic stone formers who produce hydroxy apatite brushite or calcium oxalate stones
    PMC, 2014
    Co-Authors: Andrew P. Evan, Elaine M. Worcester, James E Lingeman, James C Williams, Andre J Sommer, Carrie L Phillips, Fredric L Coe
    Abstract:

    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.

  • Three pathways for human kidney stone formation
    Urological Research, 2010
    Co-Authors: Andrew P. Evan, Elaine M. Worcester, James E Lingeman
    Abstract:

    No single theory of pathogenesis can properly account for human kidney stones, they are too various and their formation is too complex for simple understanding. Using human tissue biopsies, intraoperative imaging and such physiology data from ten different stone forming groups, we have identified at least three pathways that lead to stones. The first pathway is overgrowth on interstitial apatite plaque as seen in idiopathic calcium oxalate stone formers, as well as stone formers with primary hyperparathyroidism, ileostomy, and small bowel resection, and in brushite stone formers. In the second pathway, there are crystal deposits in renal tubules that were seen in all stone forming groups except the idiopathic calcium oxalate stone formers. The third pathway is free solution crystallization. Clear examples of this pathway are those patient groups with cystinuria or hyperoxaluria associated with bypass surgery for obesity. Although the final products may be very similar, the ways of creation are so different that in attempting to create animal and cell models of the processes one needs to be careful that the details of the human condition are included.

  • renal intratubular crystals and hyaluronan staining occur in stone formers with bypass surgery but not with idiopathic calcium oxalate stones
    Anatomical Record-advances in Integrative Anatomy and Evolutionary Biology, 2008
    Co-Authors: Andrew P. Evan, James E Lingeman, Fredric L Coe, Sharon B Bledsoe, Daniel L Gillen, Elaine M. Worcester
    Abstract:

    Whether idiopathic calcium oxalate (CaOx) stone formers form inner medullary collecting duct (IMCD) crystal deposits bears on pathogenetic mechanisms of stone formation. In prior work, using light and transmission electron microscopy, we have found no IMCD crystal deposits. Here, we searched serial sections of papillary biopsies from a prior study of 15 idiopathic calcium oxalate stone formers, 4 intestinal bypass patients with CaOx stones, and 4 non-stone-forming subjects, and biopsies from an additional hitherto unreported 15 idiopathic calcium oxalate stone formers and 1 bypass patient using polarized light oil immersion optics, for deposits overlooked in our original study. We found no IMCD deposits in any of 1,500 serial sections from the 30 idiopathic calcium oxalate stone formers, nor in 87 additional sections from a frozen idiopathic calcium oxalate stone former biopsy sample processed without exposure to aqueous solutions. Among 4 of the 5 bypass patients but in none of the 30 idiopathic calcium oxalate stone formers or 4 normal stone formers, we found tiny birefringent thin crystalline overlays on scattered IMCD cell membranes. We also found IMCD lumen deposits in two bypass patients that contained mixed birefringent and nonbirefringent crystals, presumably CaOx and apatite. In the bypass patients, we observed focal apical IMCD cell hyaluronan staining, which was absent in idiopathic calcium oxalate stone formers. The absence of any IMCD deposits in 1,500 serial sections of biopsies from 30 idiopathic calcium oxalate stone formers allows us to place the upper limit on the probability of their occurrence at approximately 0.002 and place the lower limit of their size at the resolution of the optics (<0.2 mu). The tiny deposits in bypass patients may be the initial crystal lesion.

  • renal inter α trypsin inhibitor heavy chain 3 increases in calcium oxalate stone forming patients
    Kidney International, 2007
    Co-Authors: Andrew P. Evan, James E Lingeman, Sharon B Bledsoe, Elen Worcester, Frederic L Coe, Kristin J Bergsland
    Abstract:

    Inter-α-trypsin inhibitor heavy-chain proteins bind to the protease inhibitor bikunin and to hyaluronan, stabilizes extracellular matrix in various tissues, and also inhibits calcium oxalate crystallization in vitro . In both normal and stone-forming patients, we found heavy chain 3 and hyaluronan in the interstitial matrix of the kidney. Osteopontin was found in the collecting duct, thin loop of Henle, and urothelial cells. In stone formers, heavy chain 3 was also present in collecting duct, thin loop, and interstitial cells. Heavy chain 3 and osteopontin colocalized in plaque matrix and urothelial cells. Within individual plaque spherules, heavy chain 3 was found in the matrix layer while osteopontin was located along the crystal–matrix interface. Bikunin was present only in the collecting duct apical membranes and the loop cell cytoplasm of stone formers colocalizing with osteopontin and heavy chain 3. Widespread heavy chain 3 was only present in stone formers, whereas osteopontin was similarly expressed in normal and stone-forming subjects except for its localization in plaques of the stone formers. This is consistent with studies linking inter-α-trypsin inhibitor components to human stone disease, although their role is still unclear. Heavy chain 3 may also play a role in stabilizing hyaluronan in the renal interstitial matrix.

Andrew P. Evan - One of the best experts on this subject based on the ideXlab platform.

  • Mechanisms of human kidney stone formation
    Urolithiasis, 2014
    Co-Authors: Andrew P. Evan, F. L. Coe, Elaine M. Worcester, James Williams, James E Lingeman
    Abstract:

    The precise mechanisms of kidney stone formation and growth are not completely known, even though human stone disease appears to be one of the oldest diseases known to medicine. With the advent of the new digital endoscope and detailed renal physiological studies performed on well phenotyped stone formers, substantial advances have been made in our knowledge of the pathogenesis of the most common type of stone former, the idiopathic calcium oxalate stone former as well as nine other stone forming groups. The observations from our group on human stone formers and those of others on model systems have suggested four entirely different pathways for kidney stone formation. Calcium oxalate stone growth over sites of Randall's plaque appear to be the primary mode of stone formation for those patients with hypercalciuria. Overgrowths off the ends of Bellini duct plugs have been noted in most stone phenotypes, do they result in a clinical stone? Micro-lith formation does occur within the lumens of dilated inner medullary collecting ducts of cystinuric stone formers and appear to be confined to this space. Lastly, cystinuric stone formers also have numerous small, oval, smooth yellow appearing calyceal stones suggestive of formation in free solution. The scientific basis for each of these four modes of stone formation are reviewed and used to explore novel research opportunities

  • contrasting histopathology and crystal deposits in kidneys of idiopathic stone formers who produce hydroxy apatite brushite or calcium oxalate stones
    PMC, 2014
    Co-Authors: Andrew P. Evan, Elaine M. Worcester, James E Lingeman, James C Williams, Andre J Sommer, Carrie L Phillips, Fredric L Coe
    Abstract:

    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.

  • Three pathways for human kidney stone formation
    Urological Research, 2010
    Co-Authors: Andrew P. Evan, Elaine M. Worcester, James E Lingeman
    Abstract:

    No single theory of pathogenesis can properly account for human kidney stones, they are too various and their formation is too complex for simple understanding. Using human tissue biopsies, intraoperative imaging and such physiology data from ten different stone forming groups, we have identified at least three pathways that lead to stones. The first pathway is overgrowth on interstitial apatite plaque as seen in idiopathic calcium oxalate stone formers, as well as stone formers with primary hyperparathyroidism, ileostomy, and small bowel resection, and in brushite stone formers. In the second pathway, there are crystal deposits in renal tubules that were seen in all stone forming groups except the idiopathic calcium oxalate stone formers. The third pathway is free solution crystallization. Clear examples of this pathway are those patient groups with cystinuria or hyperoxaluria associated with bypass surgery for obesity. Although the final products may be very similar, the ways of creation are so different that in attempting to create animal and cell models of the processes one needs to be careful that the details of the human condition are included.

  • renal intratubular crystals and hyaluronan staining occur in stone formers with bypass surgery but not with idiopathic calcium oxalate stones
    Anatomical Record-advances in Integrative Anatomy and Evolutionary Biology, 2008
    Co-Authors: Andrew P. Evan, James E Lingeman, Fredric L Coe, Sharon B Bledsoe, Daniel L Gillen, Elaine M. Worcester
    Abstract:

    Whether idiopathic calcium oxalate (CaOx) stone formers form inner medullary collecting duct (IMCD) crystal deposits bears on pathogenetic mechanisms of stone formation. In prior work, using light and transmission electron microscopy, we have found no IMCD crystal deposits. Here, we searched serial sections of papillary biopsies from a prior study of 15 idiopathic calcium oxalate stone formers, 4 intestinal bypass patients with CaOx stones, and 4 non-stone-forming subjects, and biopsies from an additional hitherto unreported 15 idiopathic calcium oxalate stone formers and 1 bypass patient using polarized light oil immersion optics, for deposits overlooked in our original study. We found no IMCD deposits in any of 1,500 serial sections from the 30 idiopathic calcium oxalate stone formers, nor in 87 additional sections from a frozen idiopathic calcium oxalate stone former biopsy sample processed without exposure to aqueous solutions. Among 4 of the 5 bypass patients but in none of the 30 idiopathic calcium oxalate stone formers or 4 normal stone formers, we found tiny birefringent thin crystalline overlays on scattered IMCD cell membranes. We also found IMCD lumen deposits in two bypass patients that contained mixed birefringent and nonbirefringent crystals, presumably CaOx and apatite. In the bypass patients, we observed focal apical IMCD cell hyaluronan staining, which was absent in idiopathic calcium oxalate stone formers. The absence of any IMCD deposits in 1,500 serial sections of biopsies from 30 idiopathic calcium oxalate stone formers allows us to place the upper limit on the probability of their occurrence at approximately 0.002 and place the lower limit of their size at the resolution of the optics (<0.2 mu). The tiny deposits in bypass patients may be the initial crystal lesion.

  • renal inter α trypsin inhibitor heavy chain 3 increases in calcium oxalate stone forming patients
    Kidney International, 2007
    Co-Authors: Andrew P. Evan, James E Lingeman, Sharon B Bledsoe, Elen Worcester, Frederic L Coe, Kristin J Bergsland
    Abstract:

    Inter-α-trypsin inhibitor heavy-chain proteins bind to the protease inhibitor bikunin and to hyaluronan, stabilizes extracellular matrix in various tissues, and also inhibits calcium oxalate crystallization in vitro . In both normal and stone-forming patients, we found heavy chain 3 and hyaluronan in the interstitial matrix of the kidney. Osteopontin was found in the collecting duct, thin loop of Henle, and urothelial cells. In stone formers, heavy chain 3 was also present in collecting duct, thin loop, and interstitial cells. Heavy chain 3 and osteopontin colocalized in plaque matrix and urothelial cells. Within individual plaque spherules, heavy chain 3 was found in the matrix layer while osteopontin was located along the crystal–matrix interface. Bikunin was present only in the collecting duct apical membranes and the loop cell cytoplasm of stone formers colocalizing with osteopontin and heavy chain 3. Widespread heavy chain 3 was only present in stone formers, whereas osteopontin was similarly expressed in normal and stone-forming subjects except for its localization in plaques of the stone formers. This is consistent with studies linking inter-α-trypsin inhibitor components to human stone disease, although their role is still unclear. Heavy chain 3 may also play a role in stabilizing hyaluronan in the renal interstitial matrix.

Eric J Bergstralh - One of the best experts on this subject based on the ideXlab platform.

  • stone composition among first time symptomatic kidney stone formers in the community
    Mayo Clinic proceedings, 2015
    Co-Authors: Prince Singh, Amy E. Krambeck, Lisa E Vaughan, Felicity Enders, John C Lieske, Eric J Bergstralh, John J Knoedler, Andrew D. Rule
    Abstract:

    Abstract Objective To determine the variation in kidney stone composition and its association with risk factors and recurrence among first-time stone formers in the general population. Patients and Methods Medical records were manually reviewed and validated for symptomatic kidney stone episodes among Olmsted County, Minnesota, residents from January 1, 1984, through December 31, 2012. Clinical and laboratory characteristics and the risk of symptomatic recurrence were compared between stone compositions. Results There were 2961 validated first-time symptomatic kidney stone formers. Stone composition analysis was obtained in 1508 (51%) at the first episode. Stone formers were divided into the following mutually exclusive groups: any brushite (0.9%), any struvite (0.9%), any uric acid (4.8%), and majority calcium oxalate (76%) or majority hydroxyapatite (18%). Stone composition varied with clinical characteristics. A multivariable model had a 69% probability of correctly estimating stone composition but assuming calcium oxalate monohydrate stone was correct 65% of the time. Symptomatic recurrence at 10 years was approximately 50% for brushite, struvite, and uric acid but approximately 30% for calcium oxalate and hydroxyapatite stones ( P P for trend=.10). However, among calcium oxalate stones, 10-year recurrence rate ranged from 38% for 100% calcium oxalate dihydrate to 26% for 100% calcium oxalate monohydrate ( P for trend=.007). Conclusion Calcium stones are more common (93.5% of stone formers) than has been previously reported. Although clinical and laboratory factors associate with the stone composition, they are of limited utility for estimating stone composition. Rarer stone compositions are more likely to recur.

  • altered calcium and vitamin d homeostasis in first time calcium kidney stone formers
    PLOS ONE, 2015
    Co-Authors: Hemamalini Ketha, Andrew D. Rule, John C Lieske, Eric J Bergstralh, Ravinder J Singh, Stefan K G Grebe, Rajiv Kumar
    Abstract:

    Background Elevated serum 1,25-dihydroxyvitamin D (1,25(OH)2D) concentrations have been reported among cohorts of recurrent calcium (Ca) kidney stone-formers and implicated in the pathogenesis of hypercalciuria. Variations in Ca and vitamin D metabolism, and excretion of urinary solutes among first-time male and female Ca stone-formers in the community, however, have not been defined. Methods In a 4-year community-based study we measured serum Ca, phosphorus (P), 25-hydroxyvitamin D (25(OH)D), 1,25(OH)2D, 24,25-dihydroxyvitamin D (24,25(OH)2D), parathyroid hormone (PTH), and fibroblast growth factor-23 (FGF-23) concentrations in first-time Ca stone-formers and age- and gender frequency-matched controls. Results Serum Ca and 1,25(OH)2D were increased in Ca stone-formers compared to controls (P = 0.01 and P = 0.001). Stone-formers had a lower serum 24,25(OH)2D/25(OH)D ratio compared to controls (P = 0.008). Serum PTH and FGF-23 concentrations were similar in the groups. Urine Ca excretion was similar in the two groups (P = 0.82). In controls, positive associations between serum 25(OH)D and 24,25(OH)2D, FGF-23 and fractional phosphate excretion, and negative associations between serum Ca and PTH, and FGF-23 and 1,25(OH)2D were observed. In SF associations between FGF-23 and fractional phosphate excretion, and FGF-23 and 1,25(OH)2D, were not observed. 1,25(OH)2D concentrations associated more weakly with FGF-23 in SF compared with C (P <0.05). Conclusions Quantitative differences in serum Ca and 1,25(OH)2D and reductions in 24-hydroxylation of vitamin D metabolites are present in first-time SF and might contribute to first-time stone risk.

  • thiazide diuretic prophylaxis for kidney stones and the risk of diabetes mellitus
    The Journal of Urology, 2014
    Co-Authors: Prince Singh, Amy E. Krambeck, John C Lieske, Eric J Bergstralh, John J Knoedler, Andrew D. Rule
    Abstract:

    Purpose: Thiazide diuretics used to treat hypertension are associated with a modest risk of diabetes mellitus. It is unknown if there is a similar risk with kidney stone prevention.Materials and Methods: We identified and validated incident stone formers in Olmsted County, Minnesota from 1984 to 2011 with manual review of medical records using the Rochester Epidemiology Project. The risk of diabetes mellitus after thiazide therapy was evaluated with and without multivariate adjustment for hypertension, age, gender, race, family history of stones, body mass index and number of stone events.Results: Among 2,350 incident stone formers with a median followup of 10 years, 332 (14%) were treated with thiazide diuretics at some point after the first stone event and 84 (3.6%) received the thiazide diuretic only for kidney stone prevention. Stone formers who received thiazide diuretics were more likely to be older, have hypertension, have higher body mass index and have more stone events. The incidence of diabetes...

  • the roks nomogram for predicting a second symptomatic stone episode
    Journal of The American Society of Nephrology, 2014
    Co-Authors: Andrew D. Rule, Amy E. Krambeck, John C Lieske, Joseph L Melton, Eric J Bergstralh
    Abstract:

    Most patients with first-time kidney stones undergo limited evaluations, and few receive preventive therapy. A prediction tool for the risk of a second kidney stone episode is needed to optimize treatment strategies. We identified adult first-time symptomatic stone formers residing in Olmsted County, Minnesota, from 1984 to 2003 and manually reviewed their linked comprehensive medical records through the Rochester Epidemiology Project. Clinical characteristics in the medical record before or up to 90 days after the first stone episode were evaluated as predictors for symptomatic recurrence. A nomogram was developed from a multivariable model based on these characteristics. There were 2239 first-time adult kidney stone formers with evidence of a passed, obstructing, or infected stone causing pain or gross hematuria. Symptomatic recurrence occurred in 707 of these stone formers through 2012 (recurrence rates at 2, 5, 10, and 15 years were 11%, 20%, 31%, and 39%, respectively). A parsimonious model had the following risk factors for recurrence: younger age, male sex, white race, family history of stones, prior asymptomatic stone on imaging, prior suspected stone episode, gross hematuria, nonobstructing (asymptomatic) stone on imaging, symptomatic renal pelvic or lower-pole stone on imaging, no ureterovesicular junction stone on imaging, and uric acid stone composition. Ten-year recurrence rates varied from 12% to 56% between the first and fifth quintiles of nomogram score. The Recurrence of Kidney Stone nomogram identifies kidney stone formers at greatest risk for a second symptomatic episode. Such individuals may benefit from medical intervention and be good candidates for prevention trials.

  • phenotypic characterization of kidney stone formers by endoscopic and histological quantification of intrarenal calcification
    Kidney International, 2013
    Co-Authors: Michael P Linnes, Amy E. Krambeck, Andrew D. Rule, Terri J Vrtiska, Eric J Bergstralh, Lynn D Cornell, James C Williams, Mark Korinek, C Mccollough, John C Lieske
    Abstract:

    Interstitial Randall's plaques and collecting duct plugs are distinct forms of renal calcification thought to provide sites for stone retention within the kidney. Here we assessed kidney stone precursor lesions in a random cohort of stone formers undergoing percutaneous nephrolithotomy. Each accessible papilla was endoscopically mapped following stone removal. The percent papillary surface area covered by plaque and plug were digitally measured using image analysis software. Stone composition was determined by micro-computed tomography and infrared analysis. A representative papillary tip was biopsied. The 24-h urine collections were used to measure supersaturation and crystal growth inhibition. The vast majority (99%) of stone formers had Randall's plaque on at least 1 papilla, while significant tubular plugging (over 1% of surface area) was present in about one-fifth of patients. Among calcium oxalate stone formers the amount of Randall's plaque correlated with higher urinary citrate levels. Tubular plugging correlated positively with pH and brushite supersaturation but negatively with citrate excretion. Lower urinary crystal growth inhibition predicted the presence of tubular plugging but not plaque. Thus, tubular plugging may be more common than previously recognized among patients with all types of stones, including some with idiopathic calcium oxalate stones.