Kidneys

The kidneys are a pair of bean-shaped organs about the size of a fist each, sitting retroperitoneally against the back muscles at roughly the T12-L3 level. Together they contain about 2 million nephrons, filter about 180 liters of plasma ultrafiltrate per day, and carefully reabsorb almost all of it to produce 1-2 liters of urine. They also regulate blood pressure, acid-base balance, red cell production, vitamin D activation, and electrolyte composition. You cannot live without them.

At a glance

What it does

Filters blood and produces urine. Every functional unit — the nephron — has a glomerulus (a capillary tuft that filters plasma) and a tubule (which reabsorbs almost all the filtrate back into the blood while excreting what the body does not need). The net output is urine carrying wastes (urea, creatinine, ammonia), excess electrolytes, drug metabolites, and regulated amounts of water.

The kidneys also run endocrine functions that most people do not associate with them. They secrete erythropoietin in response to hypoxia, driving red cell production in bone marrow — which is why chronic kidney disease causes anemia. They activate vitamin D through the 1-alpha-hydroxylase step, which is why CKD causes mineral and bone disease. They release renin from juxtaglomerular cells, which kicks off the renin-angiotensin-aldosterone system and regulates blood pressure.

Acid-base regulation is another major job. The kidneys excrete hydrogen ions and reabsorb bicarbonate, providing the slow but high-capacity side of pH regulation (the lungs handle fast CO2-driven changes). When the kidneys fail, metabolic acidosis follows.

How it works

Blood enters via the renal artery, reaches the glomerulus, and is filtered across a three-layered barrier (fenestrated endothelium, glomerular basement membrane, podocyte foot processes with slit diaphragms) into Bowman's space. The filtrate is essentially plasma minus proteins and cells. Glomerular filtration rate is the central metric of kidney function, normally around 90-120 mL/min per 1.73 m² in healthy young adults, declining with age.

The tubule then gets to work. Proximal tubule reabsorbs about 65-70% of filtered sodium, glucose, amino acids, and water — bulk reabsorption without much regulatory control. Loop of Henle creates the medullary concentration gradient that lets the kidney concentrate urine; the thick ascending limb is the target of loop diuretics like furosemide. Distal convoluted tubule fine-tunes sodium reabsorption and is the target of thiazide diuretics. Collecting duct is where aldosterone (final sodium reabsorption, potassium excretion) and ADH (water reabsorption via aquaporin-2) do their work.

Blood pressure control via RAAS: low renal perfusion or low tubular sodium triggers renin release. Renin cleaves angiotensinogen to angiotensin I. ACE (mostly in the lungs) converts it to angiotensin II, which constricts vessels directly, stimulates aldosterone from the adrenal cortex, and increases thirst and ADH. ACE inhibitors, ARBs, and aldosterone antagonists all intervene at different points in this loop and collectively form the backbone of hypertension and heart failure therapy.

When it goes wrong

Chronic kidney disease is the slow catastrophe. Diabetes and hypertension account for the majority of cases globally. CKD is defined by sustained reduction in eGFR or evidence of kidney damage (albuminuria) for more than 3 months, and is staged 1-5 by eGFR. Progression drives anemia, bone disease, electrolyte disturbances, cardiovascular disease, and ultimately end-stage renal disease requiring dialysis or transplant.

Early CKD is silent. By the time creatinine rises meaningfully in a healthy-weight young adult, substantial nephron mass is already gone. This is why screening — especially in diabetic and hypertensive patients — uses urine albumin-to-creatinine ratio in addition to eGFR, because albuminuria is the earlier and more sensitive signal of glomerular damage.

Acute kidney injury is the fast disaster. Prerenal (volume depletion, shock), intrinsic (acute tubular necrosis from ischemia or toxins, glomerulonephritis), and postrenal (obstruction) are the classic categories. Most cases recover if the insult is treated, but severe or prolonged AKI can leave residual CKD.

Dialysis keeps people alive when kidneys fail. Hemodialysis three times a week replaces roughly 10-15% of normal kidney function — enough to survive, nowhere near a normal kidney. Peritoneal dialysis is the home alternative. Neither is a cure; both are holding patterns. Transplantation is the better option when feasible, with living donor grafts lasting a median of 15-20 years and deceased donor grafts somewhat less.

Kidney stones affect about 10% of adults at some point — calcium oxalate is most common. Prevention: hydrate aggressively (enough to produce 2+ liters of urine daily), moderate salt and animal protein, and for specific stone types targeted interventions.

Interactions

NSAIDs reduce prostaglandin-mediated renal blood flow and can precipitate AKI, especially in dehydrated patients or those on ACEi/ARBs and diuretics (the "triple whammy"). Contrast agents used in CT and cardiac catheterization can cause contrast-induced nephropathy, though the risk in modern practice is lower than earlier literature suggested.

SGLT2 inhibitors — dapagliflozin, empagliflozin — have reshaped CKD management. They slow progression of diabetic and non-diabetic kidney disease, reduce heart failure events, and work independently of glucose lowering. Alongside RAAS blockade and GLP-1 agonists, they are the modern nephroprotection stack.

Alcohol disrupts ADH and causes diuresis. Caffeine has a modest diuretic effect. High protein intake raises glomerular filtration and can accelerate CKD in the already-compromised kidney — not a reason for healthy people to avoid protein, but a genuine consideration in late-stage CKD.

Honest take

Sources

• KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD.
• Heerspink et al., NEJM (2020) — dapagliflozin in chronic kidney disease (DAPA-CKD).
• Perkovic et al., NEJM (2019) — canagliflozin and renal outcomes (CREDENCE).