👤 Cosetta Minelli

Chronic kidney disease (CKD) is a growing global health burden, strongly associated with cardiovascular disease, the leading cause of mortality in this population. Dyslipidemia is a key metabolic abnormality in CKD, but traditional lipid measures such as total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides often fail to capture the complexity of lipid disturbances in CKD and after kidney transplantation. Apolipoproteins have emerged as more reliable markers of cardiovascular and renal risk. Elevated apolipoprotein B (ApoB), reduced apolipoprotein A1 (ApoA1), and a higher ApoB/ApoA1 ratio are linked to CKD progression, cardiovascular events, and post-transplant complications, including post-transplant diabetes mellitus. Lipoprotein(a), a genetically determined atherogenic lipoprotein, accumulates in CKD due to impaired clearance and further increases cardiovascular risk. Other apolipoproteins, such as APOL1 and APOE, modulate CKD susceptibility through lipid-dependent and independent mechanisms. In addition, proprotein convertase subtilisin/kexin type 9 (PCSK9) has been identified as an important regulator of lipid metabolism, and PCSK9 inhibitors may represent a promising therapeutic option, though evidence in advanced CKD and transplant recipients is still limited, especially regarding their effects on apolipoproteins. This review summarizes current evidence on apolipoproteins and PCSK9 in CKD and transplantation, with attention to their potential as biomarkers and therapeutic targets. Show less

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD. Show less

Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m(2); n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide-significant loci (P < 5 x 10(-8)) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2 and SLC7A9) and 7 loci suspected to affect creatinine production and secretion (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72 and BCAS3). These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney. Show less