In the clinical settings, an abrupt decline of GFR is detected as an increase in sCr levels. Although a small creatinine increase will predict adverse outcomes, the limitations of serum creatinine for early detection and accurate estimation of renal injury in AKI are well known [24]. Recently, AKI biomarkers Pacritinib aml have been developed to facilitate early detection, differential diagnosis, and prognosis. Among them, novel biomarkers such as urinary L-type fatty acid-binding protein (L-FABP) or neutrophil gelatinase-associated lipocalin (NGAL) are considered to reflect tubular epithelial cell injury [25, 26]. Figure 2Acute kidney injury and progression to CKD [19]. (a) Conceptual model of acute kidney injury (AKI). (b) Natural history of AKI.

Patients who develop AKI may experience (1) complete recovery of renal function, (2) development of progressive chronic kidney …Table 3Staging of acute kidney injury [20].In patients with suspected MM, monoclonal heavy or light chains, known as Bence-Jones protein, should be analyzed in concentrated urine using electrophoresis with immunofixation of any identified protein bands in accordance with current myelomas guidelines [27]. Coincidence measurement of serum/urine albumin should be performed when the possibility of immunoglobulin light chain (AL) amyloid or monoclonal Ig deposition disease (MIDD) is suspected. The casts contain monoclonal free light chains (FLC) and Tamm-Horsfall glycoproteins and have been shown to acutely depress single nephron glomerular filtration rate [28].

The FLCs are freely filtered by the glomerulus and taken up by mesangial cells (toxicity to which may cause amyloidosis or light chain deposition disease) or tubular epithelial cells, where they can activate nuclear factor kappa beta (NF-kB) and cause apoptosis or epithelial-mesenchymal transition, leading to transcription of inflammatory cytokines. Recruitment of inflammatory cells to the interstitium ensues, promoting fibrosis [29]. Cast nephropathy is nearly always observed in advanced MM, when production of large amounts of LC overwhelms the capacity of catabolism in proximal tubules [8]. This nephropathy is usually triggered by several factors that increase urine FLC concentration. These factors include dehydration, hypercalcemia, infections, contrast medium usage, or use of nephrotoxic medications, including NSAIDs, diuretics, angiotensin-conversing enzyme inhibitors (ACEI), and angiotensin II receptor blockers (ARB).

Also, patients with high serum monoclonal FLC (>500mg/L) have a Carfilzomib risk of developing AKI [30]. Even in the setting of severe kidney dysfunction, the serum FLC assay is a sensitive and specific screening tool [31]. The lack of sensitivity of serum protein electrophoresis in the detection of monoclonal FLC [32], which causes cast nephropathy, makes this test inappropriate as a screening tool, particularly in the setting of AKI.