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Effects of Exercise on Acute Kidney Injury Biomarkers and the Potential Influence of Fluid Intake.
Juett, LA, James, LJ, Mears, SA
Annals of nutrition & metabolism. 2020;:53-59
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Abstract
Acute kidney injury (AKI) incidence (diagnosed by changes in serum creatinine [Cr]) following prolonged endurance events has been reported to be anywhere from 4 to 85%, and hypohydration may contribute to this. Whilst an increase in serum Cr indicates impaired kidney function, this might be influenced by muscle damage. Therefore, the use of other AKI biomarkers which can detect renal tubular injury may be more appropriate. The long-term consequences of AKI are not well understood, but there are some potential concerns of an increased subsequent risk of chronic kidney disease (CKD). Therefore, this brief review explores the effects of exercise training/competition on novel AKI biomarkers and the potential influence of fluid intake. The increase in novel AKI biomarkers following prolonged endurance events suggests renal tubular injury. This is likely due to the long duration and relatively high exercise intensity, producing increased sympathetic tone, body temperature, hypohydration, and muscle damage. Whilst muscle damage appears to be an important factor in the pathophysiology of exercise-associated AKI, it may require coexisting hypohydration. Fluid intake seems to play a role in exercise-associated AKI, as maintaining euhydration with water ingestion during simulated physical work in the heat appears to attenuate rises in AKI biomarkers. The composition of fluid intake may also be important, as high-fructose drinks have been shown to exacerbate AKI biomarkers. However, it is yet to be seen if these findings are applicable to athletes performing strenuous exercise in a temperate environment. Additionally, further work should examine the effects of repeated bouts of strenuous exercise on novel AKI biomarkers.
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Systematic review and meta-analysis of randomised controlled trials on the effects of potassium supplements on serum potassium and creatinine.
Cappuccio, FP, Buchanan, LA, Ji, C, Siani, A, Miller, MA
BMJ open. 2016;(8):e011716
Abstract
OBJECTIVES High potassium intake could prevent stroke, but supplementation is considered hazardous. We assessed the effect of oral potassium supplementation on serum or plasma potassium levels and renal function. SETTING We updated a systematic review of the effects of potassium supplementation in randomised clinical trials carried out worldwide, published in 2013, extending it to July 2015. We followed the PRISMA guidelines. PARTICIPANTS Any individual taking part in a potassium supplementation randomised clinical trial. Studies included met the following criteria: randomised clinical trials, potassium supplement given and circulating potassium levels reported. INTERVENTION Oral potassium supplementation. PRIMARY OUTCOME MEASURES Serum or plasma potassium and serum or plasma creatinine. RESULTS A total of 20 trials (21 independent groups) were included (1216 participants from 12 different countries). All but 2 were controlled (placebo n=16, control n=2). Of these trials, 15 were crossover, 4 had a parallel group and 1 was sequential. The duration of supplementation varied from 2 to 24 weeks and the amount of potassium given from 22 to 140 mmol/day. In the pooled analysis, potassium supplementation caused a small but significant increase in circulating potassium levels (weighted mean difference (WMD) 0.14 mmol/L, 95% CI 0.09 to 0.19, p<1×10(-5)), not associated with dose or duration of treatment. The average increase in urinary potassium excretion was 45.75 mmol/24 hours, 95% CI 38.81 to 53.69, p<1×10(-5). Potassium supplementation did not cause any change in circulating creatinine levels (WMD 0.30 µmol/L, 95% CI -1.19 to 1.78, p=0.70). CONCLUSIONS In short-term studies of relatively healthy persons, a moderate oral potassium supplement resulted in a small increase in circulating potassium levels and no change in renal function.
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Accuracy and Usefulness of Select Methods for Assessing Complete Collection of 24-Hour Urine: A Systematic Review.
John, KA, Cogswell, ME, Campbell, NR, Nowson, CA, Legetic, B, Hennis, AJ, Patel, SM
Journal of clinical hypertension (Greenwich, Conn.). 2016;(5):456-67
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Twenty-four-hour urine collection is the recommended method for estimating sodium intake. To investigate the strengths and limitations of methods used to assess completion of 24-hour urine collection, the authors systematically reviewed the literature on the accuracy and usefulness of methods vs para-aminobenzoic acid (PABA) recovery (referent). The percentage of incomplete collections, based on PABA, was 6% to 47% (n=8 studies). The sensitivity and specificity for identifying incomplete collection using creatinine criteria (n=4 studies) was 6% to 63% and 57% to 99.7%, respectively. The most sensitive method for removing incomplete collections was a creatinine index <0.7. In pooled analysis (≥2 studies), mean urine creatinine excretion and volume were higher among participants with complete collection (P<.05); whereas, self-reported collection time did not differ by completion status. Compared with participants with incomplete collection, mean 24-hour sodium excretion was 19.6 mmol higher (n=1781 specimens, 5 studies) in patients with complete collection. Sodium excretion may be underestimated by inclusion of incomplete 24-hour urine collections. None of the current approaches reliably assess completion of 24-hour urine collection.
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Glomerular filtration rate and albuminuria for detection and staging of acute and chronic kidney disease in adults: a systematic review.
Levey, AS, Becker, C, Inker, LA
JAMA. 2015;(8):837-46
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IMPORTANCE Because early-stage kidney disease is asymptomatic and is associated with both morbidity and mortality, laboratory measurements are required for its detection. OBJECTIVE To summarize evidence supporting the use of laboratory tests for glomerular filtration rate (GFR) and albuminuria to detect and stage acute kidney injury, acute kidney diseases and disorders, and chronic kidney disease in adults. EVIDENCE REVIEW We reviewed recent guidelines from various professional groups identified via the National Guideline Clearing House and author knowledge, and systematically searched MEDLINE for other sources of evidence for selected topics. FINDINGS The KDIGO (Kidney Disease Improving Global Outcomes) guidelines define and stage acute and chronic kidney diseases by GFR and albuminuria. For initial assessment of GFR, measuring serum creatinine and reporting estimated GFR based on serum creatinine (eGFRcr) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation is recommended. If confirmation of GFR is required because of conditions that affect serum creatinine independent of GFR (eg, extremes of muscle mass or diet), or interference with the assay, cystatin C should be measured and estimated GFR should be calculated and reported using cystatin C (eGFRcys) and serum creatinine (eGFRcr-cys) or GFR should be measured directly using a clearance procedure. Initial assessment of albuminuria includes measuring urine albumin and creatinine in an untimed spot urine collection and reporting albumin-to-creatinine ratio. If confirmation of albuminuria is required because of diurnal variation or conditions affecting creatinine excretion, such as extremes of muscle mass or diet, the albumin excretion rate should be measured from a timed urine collection. CONCLUSIONS AND RELEVANCE Detection and staging of acute and chronic kidney diseases can be relatively simple. Because of the morbidity and mortality associated with kidney disease, early diagnosis is important and should be pursued in at-risk populations.
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Finding the cause of acute kidney injury: which index of fractional excretion is better?
Gotfried, J, Wiesen, J, Raina, R, Nally, JV
Cleveland Clinic journal of medicine. 2012;(2):121-6
Abstract
The fractional excretion of urea (FEU) is a useful index for differentiating the main categories of causes of acute kidney injury, ie, prerenal causes and intrinsic causes. It may be used in preference to the more widely used fractional excretion of sodium (FENa) in situations in which the validity of the latter is limited, such as in patients taking a diuretic.
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Fasting and postprandial spot urine calcium-to-creatinine ratios do not detect hypercalciuria.
Jones, AN, Shafer, MM, Keuler, NS, Crone, EM, Hansen, KE
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2012;(2):553-62
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SUMMARY Clinicians can diagnose high urine calcium by asking patients to collect urine for 24 h or to provide a random urine specimen. In this study, random urine calcium levels were not as accurate as those from the 24-h collection. Clinicians should only use 24-h collections to diagnose high urine calcium. INTRODUCTION Clinicians diagnose hypercalciuria using a 24-h urine calcium (24HUC) or a spot urine-calcium-to-creatinine ratio (SUCCR) specimen. The SUCCR is reportedly interchangeable with the 24HUC. However, studies to date show mixed results when comparing SUCCR and 24HUC values. We systematically compared fasting and postprandial SUCCR measurements to 24HUC measurements using Bland-Altman analysis. METHODS Twenty-one postmenopausal women aged 58 ± 7 years came to the research ward for three 24-h inpatient stays. At each study visit, research nurses collected fasting morning (n = 62) and postprandial (n = 62) spot urine specimens along with carefully timed and complete 24-h urine specimens (n = 63) from each woman. RESULTS Hypercalciuria was present in 13 24HUC samples (21%) using an upper limit of 250 mg/24-h. The fasting SUCCR underestimated the 24HUC (Bland-Altman bias -71 mg/24-h), with a sensitivity and specificity for diagnosing hypercalciuria of 0% and 98%, respectively. The postprandial SUCCR overestimated the 24HUC (Bland-Altman bias +61 mg/24-h), with a sensitivity and specificity of 77% and 61%, respectively. The average of fasting and postprandial SUCCR measurements had a lower Bland-Altman bias of -3 mg/24-h but demonstrated a sensitivity and specificity of only 42% and 78%, respectively. CONCLUSIONS The SUCCR is not interchangeable with the 24HUC. The fasting SUCCR systematically underestimates, and the postprandial SUCCR systematically overestimates, 24HUC. The average SUCCR demonstrates low sensitivity and specificity for hypercalciuria. Clinicians must use the 24HUC to diagnose hypercalciuria in postmenopausal women.
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Diagnostic value of urinary sodium, chloride, urea, and flow.
Schrier, RW
Journal of the American Society of Nephrology : JASN. 2011;(9):1610-3
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Up to 30% of hospitalized critically ill patients may have a rise in serum creatinine concentration. In addition to history and physical examination, there is diagnostic value in assessing urinary electrolytes, solute excretion, and urine flow in these patients. The correct interpretation of these urinary parameters can avoid unnecessary volume overload and mechanical ventilation, risk factors for increased mortality in patients with rising serum creatinine. The present article also discusses the role of arterial underfilling in causing prerenal azotemia in the presence of an increase in total body sodium and extracellular fluid expansion. As with extracellular fluid volume depletion, arterial underfilling secondary to impaired cardiac function or primary arterial vasodilation can delay or prevent recovery from ischemic or toxic acute tubular necrosis. The present brief review discusses the various aspects of the correct interpretation of urinary electrolytes, solute excretion, and urine flow in the setting of a rising serum creatinine concentration.
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Is doubling of serum creatinine a valid clinical 'hard' endpoint in clinical nephrology trials?
Lambers Heerspink, HJ, Perkovic, V, de Zeeuw, D
Nephron. Clinical practice. 2011;(3):c195-9; discussion c199
Abstract
The composite of end stage renal disease (ESRD), doubling of serum creatinine and (renal) death, is a frequently used endpoint in randomized clinical trials in nephrology. Doubling of serum creatinine is a well-accepted part of this endpoint because a doubling of serum creatinine reflects a large sustained change in glomerular filtration rate (GFR) and predicts the development of ESRD. Although doubling of serum creatinine is frequently used, the validity of using this outcome as part of a composite endpoint is hampered by various factors. Firstly, serum creatinine may reflect changes in muscle mass unrelated to true GFR changes. Secondly, changes in serum creatinine may reflect hemodynamic changes in renal perfusion and not a structural effect on renal function. Finally, doubling of serum creatinine is an arbitrary choice and different proportional changes may represent a better indicator for ESRD. In this minireview, each of these factors will be discussed and recommendations are made for interpretation of clinical trials using doubling of serum creatinine as a composite endpoint in nephrology trials.
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Assessing kidney function in Asia.
Ho, E, Teo, BW
Singapore medical journal. 2010;(11):888-93
Abstract
An equation for accurate estimation of the glomerular filtration rate (GFR) is vital for staging and directing the treatment of chronic kidney disease (CKD), which is a source of considerable morbidity and mortality around the world. The Modification of Diet for Renal Disease (MDRD) equation, which includes a racial coefficient, is commonly used. The MDRD equation has been validated in Caucasian populations, but modifying the racial coefficient for Asian countries has resulted in substantially different values that may not be due to race alone. Moreover, it is sometimes difficult to define race, particularly in multi-ethnic populations and among offspring of inter-ethnic marriages. Furthermore, the precision of the MDRD equation is poorer at the early stages of CKD. New markers, such as cystatin C, and new equations may be needed to accurately assess wider ranges of GFR in multi-ethnic countries. We review the development of GFR-estimating equations from an Asian perspective.