About 5% of American women and 12% of men will develop a kidney stone at some time in their life, and prevalence has been rising in both sexes. Approximately 80% of stones are composed of calcium oxalate (CaOx) and calcium phosphate (CaP); 10% of struvite (magnesium ammonium phosphate produced during infection with bacteria that possess the enzyme urease), 9% of uric acid (UA); and the remaining 1% are composed of cystine or ammonium acid urate or are diagnosed as drug-related stones. Stones ultimately arise because of an unwanted phase change of these substances from liquid to solid state. Here we focus on the mechanisms of pathogenesis involved in CaOx, CaP, UA, and cystine stone formation, including recent developments in our understanding of related changes in human kidney tissue and of underlying genetic causes, in addition to current therapeutics.

There is a need to develop early biomarkers of acute kidney injury following cardiac surgery, where morbidity and mortality are increased by its presence. Plasma cystatin C (CyC) and plasma and urine Neutrophil Gelatinase Associated Lipocalin (NGAL) have been shown to detect kidney injury earlier than changes in plasma creatinine in critically ill patients. In order to determine the utility of urinary CyC levels as a measure of kidney injury, we prospectively collected plasma and urine from 72 adults undergoing elective cardiac surgery for analysis. Acute kidney injury was defined as a 25% or greater increase in plasma creatinine or renal replacement therapy within the first 72 hours following surgery. Plasma CyC and NGAL were not useful predictors of acute kidney injury within the first 6 hours following surgery. In contrast, both urinary CyC and NGAL were elevated in the 34 patients who later developed acute kidney injury, compared to those with no injury. The urinary NGAL at the time of ICU arrival and the urinary CyC level 6 hours after ICU admission were most useful for predicting acute kidney injury. A composite time point consisting of the maximum urinary CyC achieved in the first 6 hours following surgery outperformed all individual time points. Our study suggests that urinary CyC and NGAL are superior to conventional and novel plasma markers in the early diagnosis of acute kidney injury following adult cardiac surgery.

Background and objectives: Several novel urinary biomarkers have shown promise in the early detection and diagnostic evaluation of acute kidney injury (AKI). Clinicians have limited tools to determine which patients will progress to more severe forms of AKI at the time of serum creatinine increase. The diagnostic and prognostic utility of novel and traditional AKI biomarkers was evaluated during a prospective study of 123 adults undergoing cardiac surgery.Design, setting, participants, & measurements: Urinary neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CyC), kidney injury molecule-1 (KIM-1), hepatocyte growth factor (HGF), -glutathione-S-transferase (-GST), ␣-GST, and fractional excretions of sodium and urea were all measured at preoperative baseline, postoperatively, and at the time of the initial clinical diagnosis of AKI. Receiver operator characteristic curves were generated and the areas under the curve (AUCs) were compared.Results: Forty-six (37.4%) subjects developed AKI Network stage 1 AKI; 9 (7.3%) of whom progressed to stage 3. Preoperative KIM-1 and ␣-GST were able to predict the future development of stage 1 and stage 3 AKI. Urine CyC at intensive care unit (ICU) arrival best detected early stage 1 AKI (AUC ‫؍‬ 0.70, P < 0.001); the 6-hour ICU NGAL (AUC ‫؍‬ 0.88; P < 0.001) best detected early stage 3 AKI. -GST best predicted the progression to stage 3 AKI at the time of creatinine increase (AUC ‫؍‬ 0.86; P ‫؍‬ 0.002).Conclusion: Urinary biomarkers may improve the ability to detect early AKI and determine the clinical prognosis of AKI at the time of diagnosis.

Stone CaP% has risen for three decades. CaP SF, particularly with brushite stones, receive more ESWL treatments than CaOx SF, not explained by stone number or duration of stone disease. Urine supersaturations explain the high CaP%. High CaP% does not hamper medical stone prevention.

No abstract

No abstract

SYNOPSISKidney stones affect over 5% of adults in the United States, and the prevalence is rising. The fundamental cause for all stones is supersaturation of urine with respect to the stone components; factors affecting solubility include urine volume, pH, and total solute excretion. Calcium stones are the most common, in adults and children, and are associated with several metabolic disorders, the most common of which is idiopathic hypercalciuria. Therapy to prevent stones rests on lowering supersaturation, using both diet and medication. Effective treatment decreases stone recurrence and need for procedures for stone removal. Keywords kidney stones; calcium oxalate; kidney calculiNephrolithiasis is the most common chronic kidney condition, after hypertension, and also an ancient one: treatments for patients with stones have been described since the earliest medical texts. Stones are a preventable cause of morbidity, accounting for over 5 billion dollars in economic costs in the United States each year, both for hospitalization and procedures to remove symptomatic stones, as well as time lost from work 1 . EPIDEMIOLOGYStones are more common in men than in women, and stone types differ somewhat between the sexes (Table 1); in children, reported frequency of stone types differs modestly from those in adults, but the sexes are affected about equally 2 . Periodic studies of the United States population, called the National Health and Nutrition Examination Surveys, show that the prevalence of stones has been increasing over the past 30 years in both sexes 3 . The most recent survey found that by the seventh decade almost 12% of white men and 6% of white women reported having had a kidney stone; the prevalence in African Americans is less than half that in Caucasians, but has also been increasing. These surveys only include adults, so that prevalence rates in children are not as clear; however in the earliest cohort, ages 20-29, Correspondence to: Elaine M. Worcester. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The reasons for the increasing prevalence are not clear, but one factor may be increased rates of obesity, as risk of stones increases along with body mass index and waist circumference, especially in women 4 . Both inherited and environmental factors play a role in stone formation. The role of inheritance is clearest in monogenic diseases such as cystinuria, Dent's disease and primary hyperoxaluria 5 , but there is a clear familial tendency in idiopathic stone formation as well 6 , although the genes involved are currently unknown. Environmental factors, especially...

Although calcium oxalate (CaOx) renal stones are known to grow attached to renal papillae, and specifically to regions of papillae that contain Randall's plaque (interstitial apatite deposits), the mechanisms of stone overgrowth on plaque are not known. To investigate the problem, we have obtained biopsy specimens from two stone patients that included an attached stone along with its tissue base and have studied the ultrastructural features of the attachment point using light and transmission electron microscopy, Fourier transform infrared spectroscopy (m-FTIR), and immunohistochemical analysis. The epithelium is disrupted at the attachment site. The denuded plaque that borders on the urinary space attracts an envelope of ribbon-like laminates of crystal and organic matrix arising from urine ions and molecules. Into the matrix of this ribbon grow amorphous apatite crystals that merge with and give way to the usual small apatite crystals imbedded in stone matrix; eventually CaOx crystals admix with apatite and become the predominant solid phase. Over time, urine calcium and oxalate ions gradually overgrow on the large crystals forming the attached stone. Anat Rec, 290:1315Rec, 290: -1323Rec, 290: , 2007 2007 Wiley-Liss, Inc.