Metabolomic profiles and pathogenesis of nephrolithiasis.

PURPOSE OF REVIEW: Kidney stone disease is caused by supersaturation of urine with certain metabolites and minerals. The urine composition of stone formers has been measured to prevent stone recurrence, specifically calcium, uric acid, oxalate, ammonia, citrate. However, these minerals and metabolites have proven to be unreliable in predicting stone recurrence. Metabolomics using high throughput technologies in well defined patient cohorts can identify metabolites that may provide insight into the pathogenesis of stones as well as offer possibilities in therapeutics. RECENT FINDINGS: Techniques including 1H-NMR, and liquid chromatography paired with tandem mass spectroscopy have identified multiple possible metabolites involved in stone formation. Compared to formers of calcium oxalate stones, healthy controls had higher levels of hippuric acid as well as metabolites involved in caffeine metabolism. Both the gut and urine microbiome may contribute to the altered metabolome of stone formers. SUMMARY: Although metabolomics has offered several potential metabolites that may be protective against or promote stone formation, the mechanisms behind these metabolomic profiles and their clinical significance requires further investigation.

Evidence for abnormal linkage between urine oxalate and citrate excretion in human kidney stone formers.

BACKGROUND: Animal models have demonstrated an interactive relationship between the epithelial anion exchanger SLC26A6 and transporter NaDC-1 that regulates citrate and oxalate homeostasis. This relationship is a potential mechanism to protect against kidney stones as higher urine oxalate is accompanied by higher urine citrate but it has not been explored in humans. METHODS: We examined 24-h urine data on 13,155 kidney stone forming patients (SF) from separate datasets at the University of Chicago and Litholink, a national laboratory, and 143 non-kidney stone forming participants (NSF) to examine this relationship in humans. We used multivariate linear regression models to examine the association between oxalate and citrate in all study participants and separately in SF and NSF. RESULTS: Higher urinary oxalate was associated with higher urinary citrate in both SF and NSF. In NSF, the multivariate adjusted urine citrate excretion was 3.0 (1.5-4.6) (mmol)/creatinine (mmol) per oxalate (mmol)/creatinine (mmol). In SF, the multivariate adjusted urine citrate excretion was 0.3 (0.2-0.4) (mmol)/creatinine (mmol) per oxalate (mmol)/creatinine (mmol). CONCLUSIONS: Higher urinary oxalate excretion was associated with higher urinary citrate excretion and this effect was larger in non-kidney stone forming participants compared with those who form kidney stones.

Insights Into Nephrolithiasis From the Nurses' Health Studies.

OBJECTIVES: To review the contributions of the Nurses' Health Study (NHS) I and NHS II to understanding the role of dietary factors, beverages, body size, and urinary factors in the development of kidney stones. METHODS: We conducted a review of kidney stone-related publications of NHS I and NHS II between 1976 and 2016. RESULTS: Studies using NHS I and NHS II data have demonstrated the importance of many factors in kidney stone formation and were the first to report that higher dietary calcium was associated with a lower risk of incident kidney stones in women. Data from these cohorts were instrumental in emphasizing that nephrolithiasis is a systemic disease and suggesting that a kidney stone or shared risk factors may lead to hypertension, diabetes, and cardiovascular disease. CONCLUSIONS: Findings from the NHSs have changed the scientific understanding and the clinical practice of stone prevention and have been incorporated into widely consulted textbooks and the American Urological Association Medical Management of Kidney Stones guidelines.

Outcomes for resident-identified high-risk patients and resident perspectives of year-end continuity clinic handoffs.

BACKGROUND: Many patients nationwide change their primary care physician (PCP) when internal medicine (IM) residents graduate. Few studies have examined this handoff. OBJECTIVE: To assess patient outcomes and resident perspectives after the year-end continuity clinic handoff DESIGN: Retrospective cohort PARTICIPANTS: Patients who underwent a year-end clinic handoff in July 2010 and a comparison group of all other resident clinic patients from 2009-2011. PGY2 IM residents surveyed from 2010-2011. MEASUREMENTS: Percent of high-risk patients after the clinic handoff scheduled for an appointment, who saw their assigned PCP, lost to follow-up, or had an acute visit (ED or hospitalization). Perceptions of PGY2 IM residents surveyed after receiving a clinic handoff. RESULTS: Thirty graduating residents identified 258 high-risk patients. While nearly all patients (97 %) were scheduled, 29 % missed or cancelled their first new PCP visit. Only 44 % of patients saw the correct PCP and six months later, one-fifth were lost to follow-up. Patients not seen by a new PCP after the handoff were less likely to have appropriate follow-up for pending tests (0 % vs. 63 %, P<0.001). A higher mean no show rate (NSR) was observed among patients who missed their first new PCP visit (22 % vs. 16 % NSR, p<0.001) and those lost to follow-up (21 % vs. 17 % NSR, p=0.019). While 47 % of residents worried about missing important data during the handoff, 47 % reported that they do not perceive patients as "theirs" until they are seen by them in clinic. CONCLUSIONS: While most patients were scheduled for appointments after a clinic handoff, many did not see the correct resident and one-fifth were lost to follow-up. Patients who miss appointments are especially at risk of poor clinic handoff outcomes. Future efforts should improve patient attendance to their first new PCP visit and increase PCP ownership.

Problems after discharge and understanding of communication with their primary care physicians among hospitalized seniors: a mixed methods study.

BACKGROUND: Communication and coordination with primary care physicians (PCPs) is recommended to ensure safe care transitions for hospitalized older patients. Understanding patient experiences of problems after discharge can help clinical teams design more patient-centered care transitions. OBJECTIVE: To report older patients' experiences with problems after hospital discharge and investigate whether PCPs were aware of their hospitalization. DESIGN: Prospective mixed methods study. SETTING: Single academic medical center. PATIENTS: Hospitalized patients and PCPs. MEASUREMENTS: Telephone interviews of frail, older general medical patients conducted 2 weeks after discharge to elicit patient problems after discharge, such as: (1) obtaining medications, or follow-up appointments; and (2) perceptions of hospital physician communication with their PCP. For each patient interviewed, their PCP was faxed a survey 2 weeks after discharge to assess awareness of hospitalization. RESULTS: Forty-two percent (27) of patients reported 42 different post-discharge problems. The most frequently reported problems were difficulty with follow-up appointments or tests (12). Other reported problems included readmission and return to the Emergency Department (10), problems with medications (8), not-prepared for discharge (8), and hospital complications or questions (4). Thirty percent of PCPs were unaware of patient hospitalization. Patients were twice as likely to report a problem if their PCP was unaware of the hospitalization (31% PCP aware, vs. 67% PCP not aware; P < 0.05). CONCLUSION: This study suggests that many frail, older patients reported problems after discharge and were twice as likely to do so when the patient's PCP was not aware of the hospitalization. Systematic interventions to improve communication with PCPs during patient hospitalization are needed.