It is an object of the present invention to provide methods and compositions for protection of subjects from acute kidney injury by treating the subject with compounds that modulate the cell cycle. Modulating the cell cycle can comprise inducing G.sub.0/G.sub.1 cell cycle arrest, and/or inducing cell cycle progression. As demonstrated below, even a single administration of a compound which induces G.sub.0/G.sub.1 cell cycle arrest can protect subjects from AKI, and may be used prophylactically in advance of, or as a treatment following, various treatments or conditions that are known to be injurious to the kidney, followed optionally by release of the arrest. Once AKI is established, cell cycle progression can be induced to increase replacement of lost and damaged cells.

It is an object of the present invention to provide methods and compositions for protection of subjects from acute kidney injury by treating the subject with compounds that modulate the cell cycle. Modulating the cell cycle can comprise inducing G.sub.0/G.sub.1 cell cycle arrest, and/or inducing cell cycle progression. As demonstrated below, even a single administration of a compound which induces G.sub.0/G.sub.1 cell cycle arrest can protect subjects from AKI, and may be used prophylactically in advance of, or as a treatment following, various treatments or conditions that are known to be injurious to the kidney, followed optionally by release of the arrest. Once AKI is established, cell cycle progression can be induced to increase replacement of lost and damaged cells.

The present invention relates to a method for assessing whether a subject has experienced one or more silent infarcts in a subject, said method comprising a) determining the amount of IGFBP7 in a sample from the subject, b) comparing the amount determined in step a) to a reference, and c) assessing whether a subject has experienced one or more silent infarcts. The present invention further relates to a method for predicting silent infarcts and/or cognitive decline, and methods for assessing and monitoring of the extent of silent small and large noncortical and cortical infarcts in a subject. Further encompassed by the present invention are the corresponding uses.

The present invention is concerned with a novel circulating biomarker of cardiac disease. The present invention provides assays, methods and test kits for detection of insulin-like growth factor binding protein 3 and to the utility of IGFBP-3 in clinically relevant diagnoses of acute coronary syndromes including, for example, unstable angina pectoris, alongside classical risk factors including history of angina and abnormal electrocardiogram. The present invention further provides assays, methods and test kits for identifying inducible cardiac ischaemia in a patient by measuring the levels of IGFBP-3 in conjunction with other risk factors such as an elevated levels of troponin, an abnormal electrocardiogram, a history of heart failure and/or a history of myocardial alongside interrogation of the IGFBP-3 or ΔIGFBP-3 levels in a sample obtained from the patient, and using this information to inform prophylactic or therapeutic treatment options for ischaemia.

Disclosed are methods for identifying a pregnant female who is susceptible to spontaneous preterm delivery. In particular, disclosed are methods for identifying a pregnant female who is susceptible to spontaneous preterm delivery based on ratios of steroids in samples obtained from the pregnant female. Further, the methods can include treating the pregnant female identified susceptible to spontaneous preterm delivery.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using assays that detect one or more of Insulin-like growth factor-binding protein 2, Insulin-like growth factor-binding protein 3, Insulinlike growth factor-binding protein 4, and Insulin like growth factor-binding protein 6 as diagnostic and prognostic biomarker assays in renal injuries.

The invention is a method for treating a heart failure patient with the steps of measuring the concentration of IGFBP2 in a blood, plasma or urine sample obtained from the heart failure patient and comparing the patient's IGFBP2 level to a threshold value derived from IGFBP2 measured in samples taken from a group of patients with heart failure selected from the group consisting of stage I, stage stage III and stage IV heart failure, according to New York Heart Association (NYHA) classification system. A patient with an IGFBP2 level that exceeds the threshold value is admitted or readmitted to a hospital and treated with at least one treatment selected from the group consisting of administration of a beta-blocker, an angiotensin-converting enzyme inhibitor, an angiotensin receptor blocker, an aldosterone antagonist, an implantable cardiac defibrillator, a cardiac resynchronization therapy, an implantable left ventricular assist device and a heart transplant.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using a measured urine concentration of one or more of TIMP2 and IGFBP7 in combination with one or more of a measured serum creatinine and a measured urine output, which results are correlated to the renal status of the subject, and can be used for diagnosis, prognosis, risk stratification, staging, monitoring, categorizing and determination of further diagnosis and treatment regimens in subjects suffering or at risk of suffering from an injury to renal function, reduced renal function, and/or acute renal failure.

The present invention relates to the role of the IGFBP3/TMEM219 axis in the onset of diabetes and the related use of IGFBP3/TMEM219 axis inhibitors for the treatment and/or prevention of diabetes. The invention also relates to a method to identify a subject at risk of developing Type 1 and/or Type 2 diabetes and relative kit.

The disclosure provides a pair of isolated biomarkers selected from the group consisting of IBP4/SHBG, IBP4/PSG3, IBP4/LYAM1, IBP4/IGF2, CLUS/IBP3, CLUS/IGF2, CLUS/LYAM1, INHBC/PSG3, INHBC/IGF2, PSG2/LYAM1, PSG2/IGF2, PSG2/LYAM1, PEDF/PSG3, PEDF/SHBG, PEDF/LYAM1, CD14/LYAM1, and APOC3/LYAM1, wherein the pair of biomarkers exhibits a change in reversal value between pregnant females at risk for pre-term birth and term controls. Also provided is a method of determining probability for preterm birth in a pregnant female, the method comprising measuring in a biological sample obtained from the pregnant female a reversal value for at least one pair of biomarkers selected from the group consisting of IBP4/SHBG, IBP4/PSG3, IBP4/LYAM1, IBP4/IGF2, CLUS/IBP3, CLUS/IGF2, CLUS/LYAM1, INHBC/PSG3, INHBC/IGF2, PSG2/LYAM1, PSG2/IGF2, PSG2/LYAM1, PEDF/PSG3, PEDF/SHBG, PEDF/LYAM1, CD14/LYAM1, and APOC3/LYAM1 to determine the probability for preterm birth in the pregnant female.