Following glomerular ultrafiltration of ~180 L/day, the nephron selectively reabsorbs useful substances and secretes additional waste to produce final urine (~1.5 L/day). The proximal tubule reabsorbs ~65% of filtered water, sodium, glucose, amino acids, and other nutrients via active transport (Na-K-ATPase on the basolateral membrane) and aquaporin water channels. Tubular secretion actively pumps substances (H+, K+, ammonia, drugs, organic acids) into the tubule lumen from the blood, enhancing excretion beyond filtration. The proximal tubule epithelium is specialized for this selective reabsorption with abundant mitochondria, extensive brush border, and polarized transport proteins.
Study microperfusion of isolated tubule segments to observe specific transport processes. Compare plasma filtrate and final urine composition to determine what is reabsorbed and secreted. Use tracers to follow specific substances.
All filtered substances are not reabsorbed equally; glucose and amino acids are normally completely reabsorbed (threshold absorbed before excretion appears), while creatinine and inulin are normally not reabsorbed.
From your study of glomerular filtration and active transport, you know that the glomerulus produces a protein-free ultrafiltrate of plasma, and that cells can move substances against concentration gradients using energy-dependent carrier proteins. The nephron's task is then to sort through that filtrate — reclaiming valuable substances and discarding waste — using the selective properties of transport proteins along the tubule. The key insight is that selectivity is not all-or-nothing: different substances are handled with different efficiencies, and the transport maximum of each carrier determines whether and when a substance "spills" into the urine.
Consider glucose reabsorption as the clearest example. Under normal conditions, all filtered glucose is reabsorbed in the proximal tubule by SGLT2 and SGLT1 cotransporters — zero glucose appears in the urine. But these transporters have a finite number of binding sites. As plasma glucose rises (as in uncontrolled diabetes), the filtered load of glucose increases proportionally. At a plasma concentration of roughly 180 mg/dL, the filtered load exceeds the transport maximum (Tm) — all available carriers are saturated, and the excess glucose passes through unreabsorbed, appearing in the urine as glucosuria. This threshold concept applies to any substance reabsorbed by carrier-mediated transport: there is a plasma concentration below which the substance is completely recovered, and above which it spills into the urine. Amino acids, phosphate, and bicarbonate all have their own transport maxima.
Secretion follows a mirror-image logic. Substances like para-aminohippuric acid (PAH), organic acids, and many drugs are both filtered at the glomerulus and actively secreted by the proximal tubule from peritubular blood into the lumen. This double mechanism — filtration plus secretion — means the kidney can clear these substances from the blood much more efficiently than filtration alone would allow. PAH, in fact, is so efficiently secreted that at low plasma concentrations, nearly all PAH is removed from renal plasma in a single pass — which is why PAH clearance is used to estimate renal plasma flow. But secretory transporters also saturate at a Tm, so at high PAH concentrations, the extraction efficiency falls.
The selectivity of renal transport creates a spectrum of handling. At one extreme, glucose and amino acids are completely reabsorbed — none appears in normal urine. At the other extreme, inulin (a plant polysaccharide used experimentally) is freely filtered but neither reabsorbed nor secreted, so its clearance exactly equals the glomerular filtration rate. Creatinine, an endogenous muscle metabolite, is close to inulin — it is filtered and only minimally secreted, making it a practical clinical estimate of GFR. Urea is partially reabsorbed (about 50%), and its handling varies with hydration status. PAH and penicillin are filtered and aggressively secreted, giving them clearances that exceed GFR. By comparing a substance's clearance to the GFR (inulin clearance), you can determine whether the nephron is a net reabsorber or a net secretor of that substance — a principle that underlies much of renal physiology and pharmacology.