Kidney Disease

TL;DR. Your kidneys filter your entire blood volume roughly 30 times a day, producing about 180 litres of filtrate and reclaiming almost all of it, so that what leaves is about 1.5 litres of urine containing exactly the waste, salt, acid, and water you needed to lose. They also make the hormone that tells your marrow to produce red blood cells, activate vitamin D, and set your blood pressure. Chronic kidney disease is the slow loss of the million filtering units in each kidney, usually caused by diabetes or high blood pressure, and it is silent until roughly 80 to 90 percent of function is gone. Most people with it never reach dialysis, because they die of cardiovascular disease first, which the kidney disease itself accelerated.

Key takeaways

• More than 850 million people worldwide have some form of kidney disease, roughly one in ten adults, and most do not know.
• Diabetes and hypertension cause the majority of cases. Kidney disease is largely a complication of the two preceding chapters.
• It is graded by eGFR (how fast the kidneys filter) and albuminuria (how much protein leaks into urine). Both are needed; either alone misses people.
• Damage is a self-accelerating loop: lose nephrons, the survivors filter harder, overwork scars them too.
• Kidney disease is primarily a cardiovascular risk multiplier. A person with moderate CKD is far more likely to die of a heart attack than to reach dialysis.
• SGLT2 inhibitors changed the field, slowing progression substantially in people with and without diabetes, after two decades in which only blood pressure drugs helped.

What it is

In short: Two axes define it, filtration rate and protein leak, and using either alone misses people who are at high risk.

Each kidney contains about a million nephrons, and each nephron is a filter plus a long processing tube. Blood enters a tuft of capillaries called the glomerulus, where pressure forces water and small molecules through a three-layer barrier that holds back cells and proteins. The filtrate then travels down a tubule where the body reclaims what it wants: nearly all the water, all the glucose, most of the sodium, and adjusts acid and potassium precisely.

Beyond filtration, the kidney does four other jobs that explain most of the symptoms of kidney failure:

Chronic kidney disease (CKD) is abnormal kidney structure or function present for more than three months. It is staged on two axes.

Crossed with albuminuria: A1 (normal, under 30 mg albumin per gram creatinine), A2 (30 to 300), A3 (over 300). Someone at G1 A3 (normal filtration, heavy protein leak) can be at higher risk than someone at G3a A1, which is why both axes are needed.

Don't be confused: acute kidney injury and chronic kidney disease are different events. AKI is a sudden drop in function over hours to days, usually from dehydration, sepsis, severe blood loss, obstruction, or a nephrotoxic drug. It is often reversible if the cause is corrected fast. CKD is slow, structural, and mostly irreversible. They interact: an episode of AKI raises the long-term risk of CKD, and CKD makes AKI more likely and more damaging.

The history

In short: From Bright's 1827 description to a dialyser built from sausage casing and a washing machine, and the rationing committee that founded modern bioethics.

Richard Bright at Guy's Hospital in London established the field in 1827 by connecting three findings that had been seen separately: swelling of the body, protein in the urine (detected by heating it and watching it coagulate), and diseased kidneys at autopsy. Kidney disease was called Bright's disease for the next century.

Understanding did not translate into treatment until the twentieth century. In 1943, in occupied Holland, Willem Kolff built the first working dialysis machine from sausage casing, orange juice cans, and a washing machine drum. His first fifteen patients died; the sixteenth, in 1945, survived. Dialysis could only be used a few times per patient because each session required cutting into a new artery and vein, until Belding Scribner's Teflon shunt in 1960 made repeated access possible and turned dialysis into a long-term therapy.

That created the first modern rationing crisis. Seattle had far more eligible patients than machines, and an anonymous lay committee decided who received treatment, weighing occupation, family, and perceived social worth. A 1962 Life magazine article about the "God Committee" is widely regarded as a founding moment of modern bioethics.

The first successful kidney transplant was performed in 1954 by Joseph Murray between identical twins, which sidestepped rejection entirely. Effective immunosuppression, above all ciclosporin in the 1980s, made transplantation between unrelated people routine. Recombinant erythropoietin arrived in 1989 and largely ended the severe anaemia that had defined life on dialysis.

What actually goes wrong

In short: Diabetes and hypertension cause most of it, and the surviving filtering units then overwork themselves into scarring.

Causes, in rough global order:

1. Diabetes (about 30 to 40 percent of cases in most high-income countries). High glucose damages the glomerular capillaries, thickens the filtration barrier, and lets protein through.
2. Hypertension (about 25 percent). Pressure damages the small vessels feeding the nephrons.
3. Glomerulonephritis: a family of immune-mediated diseases attacking the glomerulus directly, including IgA nephropathy (the commonest worldwide), lupus nephritis, and membranous nephropathy.
4. Polycystic kidney disease: an inherited autosomal dominant condition in which fluid-filled cysts progressively replace working tissue. It affects roughly 1 in 1,000 people and is the commonest inherited cause of kidney failure.
5. Obstruction: prostate enlargement, stones, tumours.
6. Chronic kidney disease of unknown cause (CKDu): epidemics among agricultural workers in Central America, Sri Lanka, and India, discussed below.

The self-accelerating loop. Whatever the initial insult, once a meaningful number of nephrons are lost, the survivors increase their individual filtration rate to compensate (hyperfiltration). That maintains total function for a while, and it damages the overworked glomeruli, which scar (glomerulosclerosis), which increases the load on the remaining ones. Beyond a threshold, progression continues even if the original cause is removed.

Protein leak drives damage too. Albumin passing into the tubules is not an innocent marker; it provokes inflammation and scarring in the tubule cells. This is why reducing proteinuria, not just lowering blood pressure, is a treatment target in its own right, and why drugs that lower it slow progression.

What it does to the body

In short: Silent until late, then anaemia, bone disease, acidosis, fluid overload, and a large rise in cardiovascular risk.

Early CKD produces nothing at all. Symptoms appear late, and they are the accumulated failure of all five kidney jobs.

The most important single fact about CKD is one people rarely hear: it is a cardiovascular disease multiplier. Someone with stage 3 CKD is several times more likely to have a cardiovascular event than to progress to dialysis, and cardiovascular disease is the leading cause of death at every stage of CKD.

Is it deadly?

Yes, and increasingly so in global terms.

• More than 850 million people worldwide have some form of kidney disease, roughly double the number with diabetes.
• Around 4 million people are on dialysis or living with a transplant, while millions more who need kidney replacement therapy die without access to it, particularly in low-income countries where dialysis is unaffordable.
• CKD is projected to become the fifth leading cause of death globally by 2050, one of the largest projected rises of any condition.
• Mortality on dialysis is high: five-year survival is comparable to several common cancers, driven mostly by cardiovascular death. Transplantation roughly doubles life expectancy compared with remaining on dialysis.

Is it contagious?

No. Kidney disease itself does not spread.

Two related points. Some causes of kidney disease are infectious: hepatitis B and C and HIV can cause kidney damage, streptococcal infection can trigger post-infectious glomerulonephritis, malaria and schistosomiasis damage kidneys, and untreated urinary infections that reach the kidneys can scar them. Historically, hepatitis B and C spread within dialysis units through inadequate infection control, which is why dialysis units now have rigorous isolation and screening protocols.

Who gets it

In short: Mostly people with diabetes and high blood pressure, plus an ancestry-linked genetic risk and an occupational epidemic among heat-exposed farm workers.

Diabetes and hypertension account for most of it. Add age (filtration declines naturally with age, though how much is normal ageing is debated), obesity, smoking, cardiovascular disease, family history, recurrent kidney stones, prolonged NSAID use, and episodes of acute kidney injury.

Genetics: the APOL1 story. Two variants of the APOL1 gene, common in people of West African ancestry, substantially raise the risk of several kidney diseases, including hypertension-attributed kidney failure, HIV-associated nephropathy, and focal segmental glomerulosclerosis. Carrying two copies raises the lifetime risk of kidney failure several-fold. These variants persisted because they confer protection against the parasite causing African sleeping sickness, the same evolutionary bargain visible in sickle cell and malaria (Chapter 62). This explains a substantial part of the roughly threefold to fourfold higher rate of kidney failure among African Americans, though socioeconomic factors, access to care, and diabetes and hypertension prevalence contribute as well. It is one of the clearest examples in medicine of an ancestry-linked genetic risk that is specific, mechanistic, and now druggable, and it is worth contrasting with the many claims about "racial" differences that turn out to be about environment.

CKD of unknown cause (CKDu). Since the 1990s, epidemics of kidney failure have appeared among young agricultural workers, chiefly sugarcane cutters, in Central America (especially Nicaragua and El Salvador), Sri Lanka, and parts of India. These are men in their twenties to forties with no diabetes and no hypertension. The leading hypothesis is recurrent heat stress and dehydration during hard physical labour, possibly combined with agrochemical exposure. In some communities it has become the leading cause of death in working-age men. As global temperatures rise, this is one of the first clearly documented occupational disease epidemics attributable in part to heat.

Access is the other determinant. In high-income countries, kidney failure means dialysis or transplant. In much of the world it means death, because a year of dialysis costs more than most families earn. The gap between the number of people who need kidney replacement therapy and the number who receive it is one of the largest inequities in medicine.

Treatment, and how it works

In short: Nothing regrows nephrons, so treatment slows the loss, and SGLT2 inhibitors substantially changed how much can be slowed.

There is no way to regrow nephrons. Treatment slows loss, manages consequences, and eventually replaces function.

Slowing progression

The arrival of SGLT2 inhibitors is the most consequential change in nephrology in a generation. A drug developed to lower blood sugar turned out to slow kidney decline in people who do not have diabetes, and the effect is large.

Managing the consequences

Anaemia: erythropoiesis-stimulating agents plus iron, with a target haemoglobin deliberately below normal, because trials showed that correcting anaemia fully increased strokes and death. Bone and mineral disorder: phosphate binders taken with meals, vitamin D analogues. Acidosis: oral sodium bicarbonate. High potassium: dietary restriction and potassium-binding drugs, which increasingly allow patients to stay on the kidney-protective drugs that raise potassium. Fluid overload: loop diuretics and salt restriction.

Replacing function

Haemodialysis. Blood is pumped through a filter of thousands of hollow fibres, with dialysis fluid flowing the other way. Waste diffuses out down its concentration gradient and excess fluid is pulled off by pressure. Typically three sessions a week, four hours each, usually in a centre. It requires vascular access, ideally an arteriovenous fistula, a surgically joined artery and vein in the arm that enlarges over weeks into a vessel able to take large needles.

Peritoneal dialysis. Fluid is run into the abdominal cavity through a permanent catheter, and the peritoneal membrane acts as the filter. Done at home, often overnight by machine. It preserves independence and residual kidney function and carries a risk of peritonitis.

Transplantation is the best treatment for those eligible: better survival, better quality of life, and lower long-term cost than dialysis. A kidney from a living donor lasts longer on average (median around 15 to 20 years) than one from a deceased donor (around 10 to 15). Recipients take lifelong immunosuppression, which brings its own infection and cancer risks. The limiting factor everywhere is organ supply; waiting lists run to years, and many patients die waiting.

Conservative management is a legitimate choice, particularly for frail elderly patients in whom dialysis may extend life little while dominating what remains of it. Choosing not to dialyse, with good symptom control, is a decision an informed patient is entitled to make.

What treatment costs

• ACE inhibitors and ARBs cause an expected small rise in creatinine when started (up to about 30 percent is acceptable and reflects the intended change in glomerular pressure), plus raised potassium.
• SGLT2 inhibitors cause a similar initial dip in eGFR that reverses and predicts long-term benefit, plus genital yeast infections and rare euglycaemic ketoacidosis.
• Haemodialysis: fatigue and low blood pressure after sessions, cramps, access infections and clotting, and a very large time cost, roughly 12 to 15 hours a week before travel.
• Peritoneal dialysis: peritonitis, hernias, and eventual membrane failure after several years.
• Transplant immunosuppression: infections, higher rates of skin cancer and lymphoma, diabetes, kidney toxicity from the drugs themselves, and rejection if doses are missed.

What the person can do

In short: Control pressure and glucose, avoid regular NSAIDs, and learn the sick-day rules that stop a stomach bug becoming kidney failure.

• Control blood pressure and blood sugar. This is most of the disease.
• Avoid NSAIDs (ibuprofen, naproxen, diclofenac) for regular use. They reduce blood flow to the kidney and are a common contributor to both acute injury and chronic decline. Occasional use in someone with healthy kidneys is a different matter.
• Know your "sick day rules." During vomiting, diarrhoea, or fever, several drugs (ACE inhibitors, ARBs, diuretics, SGLT2 inhibitors, metformin, NSAIDs) should usually be paused, because dehydration plus these drugs is how a routine stomach bug becomes acute kidney injury. Ask for a written list.
• Salt reduction helps blood pressure and fluid retention.
• Protein: moderate rather than high intake in advanced CKD, individualised, because too little causes malnutrition, which is itself dangerous.
• Stop smoking, which accelerates kidney decline as well as everything else.
• Get tested if you are at risk. A blood creatinine and a urine albumin-to-creatinine ratio are cheap, and they are the only way to find this disease in time to slow it. Both are recommended annually for anyone with diabetes, hypertension, or cardiovascular disease.

Living with it

Dialysis restructures a life around a schedule. Three afternoons a week, plus recovery time, plus fluid restrictions that are among the hardest parts (often around 1 litre a day including everything), plus dietary limits on potassium and phosphate that exclude many ordinary foods. Employment rates fall sharply after starting dialysis. Depression is common and undertreated.

Transplantation removes most of that and substitutes a different regimen: strict medication timing, infection precautions, skin surveillance, and the knowledge that the graft has a finite life. Many patients need a second transplant eventually.

What's next

• Xenotransplantation. Genetically modified pig kidneys have been transplanted into human recipients from 2024 onward, with the longest survivals so far measured in months. If rejection and infection risk can be managed, the organ shortage becomes solvable in principle.
• APOL1 inhibitors. Inaxaplin, a drug targeting the specific mechanism of APOL1-mediated kidney disease, is in trials. Precision medicine for an ancestry-associated variant.
• Bioartificial and wearable kidneys, aiming to replace intermittent dialysis with continuous filtration.
• Earlier detection at scale, using routine albuminuria testing and risk equations, on the argument that the drugs now available make finding CKD early genuinely worthwhile.
• Heat and occupational protection, the main lever against CKDu: shade, rest, hydration protocols, and shorter shifts during heat, which have reduced kidney injury in intervention studies among sugarcane workers.

Sources and notes

Global prevalence (over 850 million with some form of kidney disease) is from the International Society of Nephrology's Global Kidney Health Atlas and related analyses; approximately 4 million receiving kidney replacement therapy, and the projection to the fifth leading cause of death by 2050, are from Global Burden of Disease modelling published in The Lancet (2025). Staging is KDIGO. Bright's original description: Reports of Medical Cases, 1827. Kolff's dialyser: 1943 to 1945. Scribner shunt: 1960. The Seattle committee: Life, 9 November 1962. Murray's twin transplant: 1954. SGLT2 inhibitor kidney outcomes: DAPA-CKD (NEJM, 2020) and EMPA-KIDNEY (NEJM, 2023). Finerenone: FIDELIO-DKD and FIGARO-DKD. Semaglutide: FLOW trial (NEJM, 2024). APOL1 variants: Genovese et al., Science, 2010. CKDu in Mesoamerica: reviewed in NEJM and American Journal of Kidney Diseases; causation remains under investigation.

Open questions. Whether CKDu is primarily heat stress, agrochemical exposure, or a combination is unresolved. How much decline in eGFR with age is disease rather than normal ageing is genuinely contested. Long-term outcomes of xenotransplantation are unknown.

Next: the disease that is not one disease, and the reason it is so hard to cure. 👉