Kidney Injury and Repair Biomarkers in Marathon Runners.

BACKGROUND Investigation into strenuous activity and kidney function has gained interest given increasing marathon participation. STUDY DESIGN Prospective observational study. SETTING & PARTICIPANTS Runners participating in the 2015 Hartford Marathon. PREDICTOR Completing a marathon. OUTCOMES Acute kidney injury (AKI) as defined by AKI Network (AKIN) criteria. Stage 1 AKI was defined as 1.5- to 2-fold or 0.3-mg/dL increase in serum creatinine level within 48 hours of day 0 and stage 2 was defined as a more than 2- to 3-fold increase in creatinine level. Microscopy score was defined by the number of granular casts and renal tubular epithelial cells. MEASUREMENTS Samples were collected 24 hours premarathon (day 0), immediately postmarathon (day 1), and 24 hours postmarathon (day 2). Measurements of serum creatinine, creatine kinase, and urine albumin were completed, as well as urine microscopy analysis. 6 injury urine biomarkers (IL-6, IL-8, IL-18, kidney injury molecule 1, neutrophil gelatinase-associated lipocalin, and tumor necrosis factor α) and 2 repair urine biomarkers (YKL-40 and monocyte chemoattractant protein 1) were measured. RESULTS 22 marathon runners were included. Mean age was 44 years and 41% were men. 82% of runners developed an increase in creatinine level equivalent to AKIN-defined AKI stages 1 and 2. 73% had microscopy diagnoses of tubular injury. Serum creatinine, urine albumin, and injury and repair biomarker levels peaked on day 1 and were significantly elevated compared to day 0 and day 2. Serum creatine kinase levels continued to significantly increase from day 0 to day 2. LIMITATIONS Small sample size and limited clinical data available at all time points. CONCLUSIONS Marathon runners developed AKI and urine sediment diagnostic of tubular injury. An increase in injury and repair biomarker levels suggests structural damage to renal tubules occurring after marathon. The results of our study should be validated in larger cohorts with longer follow-up of kidney function.

[1]  E. Elsayed,et al.  Study of the role of tumor necrosis factor-α (–308 G/A) and interleukin-10 (–1082 G/A) polymorphisms as potential risk factors to acute kidney injury in patients with severe sepsis using high-resolution melting curve analysis , 2016, Renal failure.

[2]  Leo Stockfelt,et al.  Heat stress, dehydration, and kidney function in sugarcane cutters in El Salvador--A cross-shift study of workers at risk of Mesoamerican nephropathy. , 2015, Environmental research.

[3]  J. Kellum,et al.  Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial. , 2015, JAMA.

[4]  S. Florquin,et al.  Deficiency for the Chemokine Monocyte Chemoattractant Protein-1 Aggravates Tubular Damage after Renal Ischemia/Reperfusion Injury , 2015, PloS one.

[5]  A. Garg,et al.  Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery. , 2015, Journal of the American Society of Nephrology : JASN.

[6]  D. Zanetta,et al.  Burnt sugarcane harvesting is associated with acute renal dysfunction. , 2015, Kidney international.

[7]  G. Baumann,et al.  Cardiac and renal function in a large cohort of amateur marathon runners , 2015, Cardiovascular Ultrasound.

[8]  D. Weiner,et al.  Changes in kidney function among Nicaraguan sugarcane workers , 2015, International journal of occupational and environmental health.

[9]  M. Perazella,et al.  Kidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury , 2014, Hepatology.

[10]  Buqu Hu,et al.  Chitinase 3–Like 1 Suppresses Injury and Promotes Fibroproliferative Responses in Mammalian Lung Fibrosis , 2014, Science Translational Medicine.

[11]  Z. Ni,et al.  Diagnostic Value of Urinary Kidney Injury Molecule 1 for Acute Kidney Injury: A Meta-Analysis , 2014, PloS one.

[12]  K. Hultenby,et al.  Clinical and pathological characterization of Mesoamerican nephropathy: a new kidney disease in Central America. , 2013, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[13]  D. Weiner,et al.  The Central American epidemic of CKD. , 2013, Clinical journal of the American Society of Nephrology : CJASN.

[14]  L. Cantley,et al.  Chitinase-like protein Brp-39/YKL-40 modulates the renal response to ischemic injury and predicts delayed allograft function. , 2013, Journal of the American Society of Nephrology : JASN.

[15]  Hollis G. Potter,et al.  Author Manuscript , 2013 .

[16]  Véronique L. Billat,et al.  Cardiac Output and Performance during a Marathon Race in Middle-Aged Recreational Runners , 2012, TheScientificWorldJournal.

[17]  J. Bonventre,et al.  Cellular pathophysiology of ischemic acute kidney injury. , 2011, The Journal of clinical investigation.

[18]  B. Ma,et al.  Role of chitin and chitinase/chitinase-like proteins in inflammation, tissue remodeling, and injury. , 2011, Annual review of physiology.

[19]  K. Chinnaiyan,et al.  Changes in Renal Markers and Acute Kidney Injury After Marathon Running , 2011, Nephrology.

[20]  Vandana Saini,et al.  MCP-1: chemoattractant with a role beyond immunity: a review. , 2010, Clinica chimica acta; international journal of clinical chemistry.

[21]  M. Perazella,et al.  Urine microscopy is associated with severity and worsening of acute kidney injury in hospitalized patients. , 2010, Clinical journal of the American Society of Nephrology : CJASN.

[22]  Rinaldo Bellomo,et al.  Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis. , 2009, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[23]  J. Bonventre.  Kidney injury molecule-1 (KIM-1): a urinary biomarker and much more. , 2009, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[24]  B. Jaber,et al.  Interleukin-8 and Acute Kidney Injury following Cardiopulmonary Bypass: A Prospective Cohort Study , 2009, Nephron Clinical Practice.

[25]  E. Siew,et al.  Urine neutrophil gelatinase-associated lipocalin moderately predicts acute kidney injury in critically ill adults. , 2009, Journal of the American Society of Nephrology : JASN.

[26]  Kent Doi,et al.  Reduced production of creatinine limits its use as marker of kidney injury in sepsis. , 2009, Journal of the American Society of Nephrology : JASN.

[27]  J. Starkes,et al.  Explaining performance in elite middle-aged runners: contributions from age and from ongoing and past training factors. , 2008, Journal of sport & exercise psychology.

[28]  M. Perazella,et al.  Diagnostic value of urine microscopy for differential diagnosis of acute kidney injury in hospitalized patients. , 2008, Clinical journal of the American Society of Nephrology : CJASN.

[29]  D. Bolignano,et al.  Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. , 2008, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[30]  A. Garg,et al.  Acute kidney injury: Better biomarkers and beyond. , 2008, Kidney international.

[31]  C. Parikh,et al.  New biomarkers of acute kidney injury , 2008, Critical care medicine.

[32]  John A Kellum,et al.  Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury , 2007, Critical care.

[33]  P. Clarkson.  Exertional Rhabdomyolysis and Acute Renal Failure in Marathon Runners , 2007, Sports medicine.

[34]  Mihwa Kim,et al.  Association between Increases in Urinary Neutrophil Gelatinase–associated Lipocalin and Acute Renal Dysfunction after Adult Cardiac Surgery , 2006, Anesthesiology.

[35]  M. Mitsnefes,et al.  Kidney NGAL is a novel early marker of acute injury following transplantation , 2006, Pediatric Nephrology.

[36]  Marek Ancukiewicz,et al.  Urine IL-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the intensive care unit. , 2005, Journal of the American Society of Nephrology : JASN.

[37]  Qing Ma,et al.  Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery , 2005, The Lancet.

[38]  S. Paydaş,et al.  Glomerular Disease in Patients with Malignant Disease: Four Cases and Review of Literature , 2005, Renal failure.

[39]  J. Bonventre,et al.  Ischemic acute renal failure: an inflammatory disease? , 2004, Kidney international.

[40]  M. Mitsnefes,et al.  Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. , 2003, Journal of the American Society of Nephrology : JASN.

[41]  R. Kucherlapati,et al.  Differential gene expression following early renal ischemia/reperfusion. , 2003, Kidney international.

[42]  K. Ulm,et al.  DIFFERENTIAL REGULATION OF SYSTEMIC IL-18 AND IL-12 RELEASE DURING POSTOPERATIVE SEPSIS: HIGH SERUM IL-18 AS AN EARLY PREDICTIVE INDICATOR OF LETHAL OUTCOME , 2002, Shock.

[43]  J. Bonventre,et al.  Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. , 2002, Kidney international.

[44]  R. Fielding,et al.  Marathon running transiently increases c‐Jun NH2‐terminal kinase and p38γ activities in human skeletal muscle , 2000, The Journal of physiology.

[45]  Masato Suzuki.  Exercise and Renal Function , 1996 .

[46]  F. Brosius,et al.  Low fractional excretion of sodium in acute renal failure: role of timing of the test and ischemia. , 1986, American journal of nephrology.

[47]  W. C. Adams,et al.  Thermoregulation during marathon running in cool, moderate, and hot environments. , 1975, Journal of applied physiology.

[48]  D. Costill.  Physiology of marathon running. , 1972, JAMA.

[49]  M. Kew,et al.  Chronic interstitial nephritis as a consequence of heatstroke. , 1970, The Quarterly journal of medicine.

[50]  H. Husdan,et al.  Estimation of creatinine by the Jaffe reaction. A comparison of three methods. , 1968, Clinical chemistry.

[51]  L G Pugh,et al.  Rectal temperatures, weight losses, and sweat rates in marathon running. , 1967, Journal of applied physiology.

[52]  J. Knochel,et al.  Acute renal failure due to heat injury. An analysis of ten cases associated with a high incidence of myoglobinuria. , 1967, The American journal of medicine.

[53]  M. Kew,et al.  The effects of heatstroke on the function and structure of the kidney. , 1967, The Quarterly journal of medicine.

[54]  Kew Mc.  The effect of heat stroke on the function and structure of the kidney. , 1966 .

[55]  Craig Hofford,et al.  Annual Reports , 1952, Pennsylvania medical journal.