Background: The kidney has a remarkable capacity to withstand insults for an extended period of time. In the past, the monitoring of patients in clinical trials was primarily based on serum creatinine, blood urea nitrogen, glomerular filtration rate (GFR) and the detection of urinary components and other waste products. However, the diagnostic value of all of these parameters is poor and sensitive and specific tests for early diagnosis of acute kidney injury (AKI) are extremely needed, particularly in patients affected by diseases commonly complicating with renal failure, such as type 2 diabetes and primary hyperparathyroidism (PHPT).
Aim: The primary end point of this study is to establish the potential role of AKI biomarkers in detecting subtle renal damage in diabetes and PHPT patients with normal renal function.
Methods: We will include 40 patients with diabetes, 40 patients with PHPT and 50 healthy age and sex-matched subjects. Exclusion criteria will be GFR
Expected results: The project will provide new and intriguing data on the presence of kidney disease in patients with diabetes and PHPT and no apparent reduction of renal function, as measured by creatinine and GFR. Data from the study will therefore open a "new" area of research through the early identification of diabetic and PHPT patients at risk of CKD and therefore provide a strong impact on the clinical outcome of these patients.
The project will provide new and intriguing data on the presence of kidney disease in patients with diabetes and PHPT and no apparent reduction of renal function, as measured by creatinine and GFR. To this end, the evaluation of a panel of different biomarkers of AKI will help us elucidating the role of any of them in detecting subtle renal damage. The panel of biomarkers was indeed chosen with the scope of detecting, monitoring, and determining the evolution of AKI. Also, they were chosen for the simplicity, repeatability and low costs of their detection (commercial ELISA assays) and the number of studies that exist in literature about them.
Data from the study will therefore open a "new" area of research in the evaluation of the renal complications of diseases that are frequently managed in the Internal Medicine setting. The evaluation of the specific and most sensitive AKI biomarkers will allow us to identify patients with renal disease, and therefore at risk of future reduced renal function, before the elevation of serum creatinine or other "classical" parameters of kidney function.
The early identification of diabetic and PHPT patients at risk of CKD will strongly impact the clinical outcome of these patients. Among the conditions that usually complicate renal failure, disorders of the cardiovascular and mineral metabolism system are indeed frequent and associated with high morbidity and mortality. In particular, vascular calcifications, stroke and myocardial infarction strongly influence the prognosis in patients with CKD. Hence, the early evaluation of any kidney damage in patients at high risk of CKD will strongly impact the clinical outcomes and help clinicians to identify patients who need treatment. In this context, the data will also influence the clinical and surgical management of these patients, as different treatment strategies are indicated in diabetic patients with incipient nephropathy and CKD represents one of the indications for parathyroidectomy in PHPT.
Finally, the use of the AKI biomarkers will give important information in order to elucidate specific mechanisms of renal damage in diabetic and, particularly in PHPT patients.
We suggest that the early evaluation of renal damage will also apply to many other conditions usually managed in the Internal Medicine setting and could be, in the future, one of the main parameters to assess in the clinical practice in order to better manage patients with diseases predisposing to CKD.