Introduction 1 2 3 Systemic and glomerular hypertension Systemic hypertension often accompanies renal disease and may both result from, and contribute to, CKD. Progression of CKD is accelerated by hypertension, and control of blood pressure is key in the treatment of CKD. In addition, the glomerulus has a unique structure, with both an afferent and an efferent arteriole, which permits modulation of glomerular perfusion and pressure without corresponding systemic blood pressure change. 4 4 6 7 3 8 9 10 11 Renin–angiotensin–aldosterone system 1 12 13 16 17 20 21 22 23 24 25 26 27 28 29 30 31 16 32 33 34 35 36 37 39 40 41 40 40 42 43 44 45 48 25 49 51 52 53 Specific cytokines/growth factors and progression of CKD 10 54 56 57 58 59 25 38 51 60 61 59 59 37 62 63 64 65 66 67 68 69 70 71 72 56 73 Podocyte loss 74 74 75 76 77 77 78 79 80 81 82 82 Podocyte genes and CKD 83 84 85 86 85 87 88 89 90 91 92 93 94 95 96 97 Dyslipidemia 98 99 102 102 98 101 Proteinuria 74 103 104 105 101 106 107 107 Mechanisms of tubulointerstitial fibrosis 108 109 110 61 111 112 113 114 114 114 114 Anatomic and genetic risks for CKD: nephron number and gene polymorphisms 115 116 117 118 119 120 121 122 10 123 124 125 127 128 133 134 135 These observations suggest that complex genetic traits can modulate the response of glomerular cells to pathogenic stimuli in experimental models. Whether ethnic differences in development of renal disease in humans reflect contributions of genetic and/or environmental influences remains to be definitively determined. FSGS due to mutation of podocin Minimal-change disease FSGS, usual type Diffuse mesangial sclerosis Collapsing glomerulopathy Diuretics Spironolactone ACEIs Beta blockers ACEIs and ARBs Edema White blood cell (WBC) count Blood pressure Proteinuria Podocyte loss Proteinuria Glomerular hypertension Infiltrating macrophages All of the above podocyte loss proteinuria dyslipidemia glomerular hypertension (b) and (c)