Increased Filtration in Unaffected Glomeruli and Progressive Kidney Function Loss

Pathophysiology of Glomerular Hyperfiltration in CKD

Surviving glomeruli develop increased single-nephron filtration rates to maintain overall kidney function, a phenomenon known as glomerular hyperfiltration, which occurs through efferent arteriolar vasoconstriction coupled with afferent arteriolar dilation, increasing intraglomerular pressure 1, 3
The local renin-angiotensin system is activated, causing preferential constriction of the efferent arteriole over the afferent arteriole, further raising intraglomerular pressure 3
These hemodynamic changes initially help maintain global GFR despite fewer functioning nephrons 3

Sustained increased intraglomerular pressure damages the glomerular filtration barrier 1, 3
The increased hemodynamic stress on surviving glomeruli accelerates glomerulosclerosis 2

Long-standing type 2 diabetes has caused initial nephron loss 3
The biopsy showing segmental sclerosis indicates ongoing glomerular damage 1
Rising creatinine and increasing albuminuria reflect the consequences of hyperfiltration 3
Despite good blood pressure control, kidney function continues to decline due to this maladaptive hyperfiltration 2

ACE inhibitors and ARBs reduce intraglomerular pressure by preferentially dilating the efferent arteriole, reducing hyperfiltration, as recommended by the American Heart Association 4

Decreased plasma creatinine would indicate improving kidney function, not progression, according to the National Kidney Foundation 5
Decreased urine protein would suggest improvement in glomerular barrier function 3
Increased formation of new bone mineral is not directly related to kidney disease progression, as stated by the American Society of Nephrology 6