What Is Acute Kidney Injury? — A Tap That Suddenly Runs Dry, and Three Places to Look

Your Hospitalized Father's "Kidney Numbers Have Gone Up"

Your father, who is over seventy, was hospitalized for pneumonia. On the third day, the attending physician says, "A blood test shows your father's kidney numbers have gone up." Your father has never been told before admission that his kidneys are bad, and even now he does not say anything hurts. For a family caregiver, the very fact that the kidneys can turn bad in just a few days is unfamiliar.

The kidneys are a pair of kidney bean-shaped organs located in the lower back on either side above the waist, filtering the blood to send waste products and excess water out as urine. In Chinese characters, they are called sinjang. Acute kidney injury is a condition where, over the span of a few days, the kidneys suddenly start doing less of their job of filtering blood.

This event is not rare. In an analysis combining hospital studies from around the world, about one in five adults receiving inpatient treatment experienced this condition while in the hospital. This comes from 154 studies using the same criteria and data on approximately 3.59 million people, with the research coming mainly from high-income countries in North America, Northern Europe, and East Asia (PMID 23744003). This means it commonly visits while being treated for another illness in the hospital.

This article looks at three things in order: what it means for the kidneys to "suddenly" do less work, where we look for the cause, and what remains after recovery.

What the Kidneys Do, and How Sudden Is "Sudden"

Inside the kidneys are densely packed microscopic units that filter the blood. A nephron is the smallest filtering unit of the kidney that filters blood to make urine, consisting of a filtering component and a thin tubule through which the filtered water passes. The glomerulus is a tangle of thin capillaries at the very beginning of the nephron that filters water and small substances from the blood.

Tubes follow behind the glomerulus. The renal tubule is a thin tube through which the water filtered by the glomerulus passes, returning what the body needs to the blood and adding what is left over to make urine. How hard the kidneys are working is expressed by the amount they filter. The glomerular filtration rate (GFR) is the volume of water in the blood that the kidney's glomeruli filter out in one minute, serving as a representative number indicating how well the kidneys are working. Behind acute kidney injury lies a rapid drop in this glomerular filtration rate, and that event usually comes with a reduction in blood flow to the kidneys (PMID 23798302).

Because it is difficult to measure the filtered amount directly in a hospital room, doctors look at one waste product in the blood. Creatinine is a waste product mainly produced by muscles, and because the kidneys filter it out, its concentration in the blood is used to gauge kidney function. When the kidneys filter less, this waste product remains in the blood and its concentration rises. Your father's "kidney numbers" usually refer to this figure.

The Kidney Disease: Improving Global Outcomes (KDIGO) organization defines acute kidney injury by a rise in blood creatinine or a drop in urine output (PMID 24350317). What the criteria look at is how much the value has risen from the person's usual baseline over a matter of days. This guideline divides kidney function that drops suddenly over 7 days or less into acute kidney injury, and kidney disease that continues past 90 days into chronic (PMID 28239173). Chronic kidney disease is a condition where the kidneys are damaged or kidney function is reduced for three months or longer. The criterion separating the two names is speed and duration rather than the degree of badness.

Although creatinine and urine output are still used as the best indicators to find this condition, by the time these numbers move, the kidneys have often already been significantly damaged (PMID 24350317). Creatinine only tells you that the filtered amount has decreased; it cannot directly show whether the renal tubules are injured (PMID 33556265). How to read the creatinine numbers themselves is covered in "Reading Your Kidney Test Results — A Sieve You Cannot See, What Stays Behind and What Leaks Through".

A significant drop in urine output is one of two signals along with creatinine that alerts to this condition (PMID 24350317; PMID 22617274), and acute kidney injury is treated as an emergency (PMID 24350317). If it is not caught early and cared for, recovery is blocked and deaths increase (PMID 30135570). However, urine coming out as usual does not mean the filtered amount remains the same. Because forms where urine output does not decrease—such as when the kidneys are damaged by a hypersensitivity reaction to medication—are predominant, this condition often reveals itself through blood tests before symptoms appear (PMID 35830831).

When filtering drops suddenly, waste products accumulate, the balance of electrolytes such as body salts is disrupted, and the concentration of drugs that need to be eliminated through the kidneys changes. A body-wide reaction occurs, affecting even distant organs (PMID 30135570). The guidelines divide the injury into stages according to severity, and more severe injury carries a greater risk of progressing to chronic kidney disease (PMID 24350317).

Acute kidney injury is an event where the amount filtered by the kidneys drops suddenly within a few days, and creatinine, which signals this, moves later than the injury itself.

A Faucet That Has Stopped Flowing — Three Places to Look

If water suddenly stops coming out of a kitchen faucet, the person who comes to fix it looks in three places: whether the water coming into the house has been cut off, whether the faucet itself is broken, and whether the hose connected to the faucet is kinked. When acute kidney injury meets the criteria, the search begins with its causes (PMID 24350317), and those causes are divided into these three places.

Prerenal causes are cases where the blood coming into the kidney decreases, leaving the kidney with too little blood to filter. This happens when the body loses water due to severe diarrhea or vomiting, when a large amount of blood is lost, and when the heart fails to pump enough blood. In acute kidney injury occurring in patients with cirrhosis, where the liver has been damaged and hardened for a long time, the most common cause is a reduced amount of blood and water in the body, and this case responds when the lost volume is replenished (PMID 36075500).

The heart and kidneys are intertwined. Heart failure is a state where the heart fails to send as much blood as the body needs, or can send it only by raising the filling pressure. Heart failure and chronic kidney disease frequently coexist, and when they do, the risks of hospitalization, disease progression, and death increase (PMID 41791738). A rise in creatinine in the same setting does not always mean the kidneys have been injured. A conference held by KDIGO in 2024 concluded that a slight drop in kidney function after starting guideline-recommended heart failure treatment often stems from a change in blood flow and is not associated with bad outcomes, so it is usually not a reason to stop treatment (PMID 41791738). That judgment is made by the medical staff considering the individual's situation.

Prerenal causes are a side where once blood flow returns, the filtered volume also returns. However, a brief shortage of oxygen can progress to damage to the kidney itself. Because some sections of the renal tubules consume a lot of energy, they easily collapse if that energy falls short (PMID 23798302).

Intrinsic renal causes are cases where the kidney's tissue, especially the renal tubules, is directly injured and filtering decreases. Renal tubule cells are the cells at the center of injury in acute kidney injury (PMID 39178744). Shortages of blood and oxygen, medications, and toxic substances are representative causes (PMID 23798302).

Postrenal causes are cases where the urinary tract through which urine produced by the kidney descends is blocked, preventing urine from escaping and causing it to back up. An example is an enlarged prostate pressing against the outlet of the bladder so that urine cannot escape. For a stone to drop the entire filtering function, urine from both kidneys must be trapped, just as when both pathways are blocked together. The state where urine fills the bladder but cannot be expelled is covered by "Where Do Urinary Problems Come From? — A Narrowed Passage, an Alarm That Rings Too Early, a Tired Gatekeeper", and stones are covered by "What Is a Kidney Stone? — A Grain of Sand Caught in the Waterway".

In practice, acute kidney injury around surgery and in the intensive care unit is usually caused by multiple overlapping factors, and various processes such as changes in blood flow, tubular injury, and inflammation occur together or sequentially (PMID 29248138). The three-place framework is an order to find causes without missing them, and one person's causes may span multiple categories. Just the acute kidney injury that occurs before and after cardiac procedures is attributed to a combination of changes in blood flow, problems where the heart and kidneys worsen together, small debris detached from blood vessel walls, and the imaging contrast agents to be discussed later (PMID 37673499).

The faucet metaphor has limitations. The water in the metaphor is the amount filtered by the kidneys and differs from the visible volume of urine. Even when urine is produced, the filtered amount may be reduced (PMID 35830831). Also, while a faucet returns to its previous state once fixed, the kidneys may leave traces even after water flows again. This story is revisited at the end of the article.

The causes of acute kidney injury are identified by dividing them into three places: before the kidney (incoming blood), the kidney itself (tissue), and after the kidney (outgoing pathway).

The Most Common Trigger in the Intensive Care Unit — When the Body's Reaction Against Infection Backfires

About half of the cases of acute kidney injury that occur in the intensive care unit come from a single context (PMID 28364303). Sepsis is a state where the body's reaction against an infection backfires, causing organs to stop doing their jobs. The kidney is one of the organs that most commonly runs into trouble during sepsis (PMID 30626586; PMID 37401137).

There is a presumption that damage from sepsis may be a phenomenon where function stops before tissue breaks down, at least initially. This presumption comes from animal experiments and observations that there are few changes in human kidney tissue, and the mechanism is still not well understood (PMID 28364303).

The core of prevention is managing sepsis itself and early resuscitation treatment (PMID 28364303). Sepsis is caught early to administer drugs that control the infection, and blood flow is restored with intravenous fluids and drugs that support blood pressure (PMID 38892111). The type and amount of intravenous fluids are chosen carefully (PMID 28364303).

Even with these treatments, some people experience temporary or complete cessation of kidney function, and dialysis becomes necessary at that time (PMID 28364303). Dialysis is a treatment that filters out waste products in the blood and excess water outside the body using a machine or inside the body using a membrane, in place of the kidneys. What dialysis is and what life is like undergoing it for a long time are covered in "Dialysis and Kidney Transplantation — Three Sieves That Stand In, and the Path That Uses None".

When sepsis subsides, most people recover their kidney function. Even so, just a single episode of septic acute kidney injury is associated with an increased risk of developing chronic kidney disease later on (PMID 28364303).

The largest share of acute kidney injury in the intensive care unit is due to sepsis, and the core of its treatment is managing the infection and blood flow before the kidneys.

When a Drug Places a Load on Your Kidneys

There is a family of pain relievers commonly taken for headaches or knee pain. Nonsteroidal anti-inflammatory drugs are a family of pain relievers and anti-inflammatory drugs widely used to reduce pain, fever, and inflammation. They are used across the board for common symptoms like headaches, pain, and fever, and can be bought without a prescription (PMID 36947330).

Inside the kidneys, a substance works to widen blood vessels and protect the blood flowing to the kidneys. This drug blocks the pathway where that substance is made. Therefore, acute kidney injury caused by this drug mostly takes the form of reduced blood flow—analogous to a faucet where the incoming water pressure drops (PMID 30281062).

The risk varies greatly depending on the person and their conditions. The risk increases in older adults, people with dehydration, people taking high doses, and those taking a blood pressure medication family that blocks the hormone chain which raises blood pressure and retains salt (renin-angiotensin system blockers) or water pills (diuretics) together (PMID 36947330). In an analysis combining five case-control studies (involving just over 410,000 people) that examined the combination of all three—pain relievers, this blood pressure medication family, and diuretics—the likelihood of experiencing acute kidney injury within one year was about twice as high for people taking them together. However, the results varied greatly from study to study, so the certainty of the evidence was rated low, and deaths did not clearly increase (PMID 40876867).

There is also the flip side. One review summarizes that for people who have no kidney disease, are young, and have no other medical conditions, these drugs are not very harmful, and because the risk increases with dose, caution is needed when using them for a long time (PMID 30281062). In people with chronic kidney disease, these drugs are associated with acute injury and a further decline in filtering function. However, other pain relievers used instead to avoid these drugs carry well-known risks, so one review suggests weighing the risk factors for each person and using them cautiously (PMID 32479922). Which drug to continue taking is decided by medical staff by weighing the benefits and risks together (PMID 36947330).

Drugs can damage the kidneys in other ways, too. Acute interstitial nephritis is a condition where inflammation occurs in the tissue between the kidney's tubules, causing kidney function to drop suddenly. Drugs, infections, and autoimmune diseases are causes, and in many countries, drugs account for the largest share (PMID 35830831). When drugs are the cause, it is an allergic reaction of the body to the drug, appearing 7 to 10 days after taking the causative drug. Over 250 drugs have been named as causes, and it is summarized as the third most common cause of hospital-acquired acute kidney injury (PMID 28284381). Antibiotics, nonsteroidal anti-inflammatory drugs, and a family of stomach-acid-reducing drugs account for the majority of reported cases (PMID 35830831).

Symptoms are usually vague, such as fatigue, nausea, and vomiting, and the classic set of symptoms described in textbooks appears only rarely. A definitive diagnosis is made with a biopsy, which takes a tiny piece of kidney tissue (PMID 35830831). The core of treatment is stopping the drug suspected of being the cause, and failing to find and stop that drug in time can lead to irreversible scars and chronic kidney disease (PMID 28284381). Because this reaction repeats upon re-exposure to the same drug, medical staff inform patients of the causative drug (PMID 28284381).

The impact of drugs on the kidneys ranges widely, from functional changes like a slight rise in creatinine to actual tubule injury. Older adults commonly take multiple drugs together, and using several drugs that injure the tubules together generally increases the risk. On the other hand, combinations that only change function—such as when the aforementioned blood pressure medication family is used together with kidney-protecting diabetes drugs (SGLT2 inhibitors)—are generally well tolerated, as summarized (PMID 41535444).

The burden a drug places on the kidneys depends heavily on the person's age, physical condition, and the combination of drugs they take together, rather than on a single drug alone.

Contrast Agents — Re-measuring an Old Worry with Evidence

A contrast agent is a substance injected into blood vessels to make blood vessels and organs clearly visible in imaging tests such as CT scans. For a long time, contrast agents were feared as substances that damage the kidneys, and that fear frequently led people to delay or skip diagnostic tests that could have helped (PMID 37791729). The main reason the risk was exaggerated is that older studies lacked a comparison group capable of separating damage actually caused by the contrast agent from damage that simply happened to occur around that time (PMID 31961246).

Damage that happens after receiving a contrast agent is different from damage caused by a contrast agent. Higher-quality recent studies show that a large portion of the cases previously blamed on contrast agents were likely either damage caused by other causes around that time or simply natural fluctuations in kidney function mistakenly attributed to the contrast agent (PMID 37791729). That is why the term "contrast-associated acute kidney injury" is now widely used. This name captures only the fact that the timing overlapped, and does not judge the cause (PMID 37673493).

In an analysis pooling three studies (560 people) that compared critically ill patients who received a contrast agent with matched patients of similar condition who did not, there was no result showing that acute kidney injury increased in the group that received the contrast agent (PMID 28197679).

Questions remain. The actual risk caused by contrast agents in people with severe kidney disease is still uncertain. The 2020 consensus statement by the American College of Radiology (ACR) and the National Kidney Foundation (NKF), while viewing the risk of intravenous contrast agents as having been exaggerated, noted that prevention with intravenous fluids is appropriate for people who already have acute kidney injury or whose eGFR—the kidney function number estimated through blood tests—is below 30 and who are not on dialysis. For people with an eGFR of 30 to 44, it stated that prevention may be considered at the discretion of the physician ordering the test, limited to cases with high risk (PMID 31961246). How to read eGFR is covered in "Reading Your Kidney Test Results — A Sieve You Cannot See, What Stays Behind and What Leaks Through".

Cases where contrast agents are injected into arteries, such as procedures to widen coronary blood vessels, are studied separately. In such procedures, contrast-associated injury is particularly frequent in people who already have chronic kidney disease, are of advanced age, and have multiple other illnesses, so surgical techniques to reduce the amount of contrast agent are being studied (PMID 35790493). Although contrast-associated injury is associated with an increase in cardiovascular events and deaths, whether it is the cause of the poor outcome or a marker pointing to individuals with inherently high risk is still under debate (PMID 37673493).

A large portion of the damage that occurs after receiving a contrast agent is likely not caused by the agent itself, and the actual risk in people with substantially reduced kidney function remains uncertain.

Back to That Hospital Room — Tracing Three Places in Turn

Let us return to my father's case. This scene is a fictionalized example, and actual judgments are made by the medical staff through examinations and tests. My father had pneumonia, had frequently taken anti-inflammatory painkillers for knee pain before hospitalization, and had been taking blood pressure medication and a diuretic together. Let us assume the blood pressure medication belonged to the renin-angiotensin system blocker class. On the first day of admission, he had a CT scan using a contrast agent.

Tracing the three places one by one, it looks like this. On the incoming side, anti-inflammatory painkillers work to reduce blood flow going to the kidneys (PMID 30281062). The combination of using anti-inflammatory painkillers, this class of blood pressure medication, and diuretics together is associated with an increase in acute kidney injury, but the certainty of that evidence is low (PMID 40876867). If the body lacked water, the risk becomes greater (PMID 36947330).

Within the kidney itself, if it is a case where a newly started medication upon admission triggered a hypersensitivity reaction, how many days have passed since taking the medication becomes one of the clues (PMID 28284381). On the outgoing side, blockages are screened out using imaging tests such as ultrasound.

Sepsis and contrast agents do not fit neatly into a single box. If the body's reaction against pneumonia led instead to sepsis that harms organs, that is a trigger accounting for roughly half of acute kidney injuries occurring in the intensive care unit (PMID 28364303). Explanations suggest that both can affect blood flow and the tubules together (PMID 28364303; PMID 37673493). A contrast agent cannot be called the cause simply because the timing overlapped (PMID 37791729).

There are multiple suspects in this scene. What the medical staff does is find and treat the cause, reduce things that might place extra load on the kidneys, and prevent a second hit from coming to the kidneys (PMID 29248146; PMID 37673499).

In Many Cases It Comes Back, but What Remains After It Has Passed

There is still no miracle cure that fixes acute kidney injury itself. A 2016 review concluded that, aside from dialysis, there is no reliably proven treatment that increases survival, reduces damage, or accelerates recovery (PMID 26768243). Treatment involves managing the cause and supporting the body, and when problems arise that cannot be managed by other means, dialysis is started (PMID 24350317). When is the best time to start dialysis is still under debate (PMID 38892111; PMID 28364303).

In mild injury, surviving tubular cells can fill in the empty spaces so that kidney function returns completely. If the injury is severe or lasts a long time, this recovery goes awry, leading to scarring in the kidneys (PMID 39178744). Animal models have been used extensively to uncover this process, with the limitation that those models do not entirely mirror human disease (PMID 39298548).

Most people who experience this injury after being hospitalized for a serious illness get better without dialysis, but some need dialysis for days to months (PMID 34462285). A person who overcomes a serious illness generally recovers to the point of living without dialysis, provided they did not have chronic kidney disease beforehand (PMID 22617274). However, it is uncommon for kidney function to return completely, which leaves a lingering risk of disease and death (PMID 30135570). What should be considered "recovery" is still not clearly defined, other than coming off dialysis (PMID 29248147). The statement "function has been regained" and the statement "everything has gone back to the way it was" may not mean the same thing.

A name has even emerged for the period that continues past 7 days after the injury without full recovery. Acute kidney disease is a state in which abnormalities in kidney function or structure last for three months or less. It encompasses acute kidney injury, but also covers abnormalities that are milder or take longer than 7 days (PMID 34252450). This state is observed in about a quarter of people who survive acute kidney injury, but the data addressing it are still scarce (PMID 33752866). To sum up, something that happens suddenly over 7 days or less is acute kidney injury, an abnormality lasting up to three months is acute kidney disease, and past three months it is chronic kidney disease.

One analysis compiling long-term risks after acute kidney injury draws on data from 82 cohort studies following hospitalized adults for over a year, involving about 2 million people. Scaled to following 100 people for a year, instances of new or worsening chronic kidney disease were 17.8 versus 7.6, instances of kidneys losing function enough to require dialysis or a transplant were 0.47 versus 0.08, and deaths were 13.2 versus 7.3, comparing those who experienced acute kidney injury with those who did not. The risk was greater the more severe the injury stage (PMID 30473140). However, a significant number of these studies had missing outcome data or failed to adequately adjust for other factors. The authors concluded that these results demonstrate the poor long-term outcomes of acute kidney injury, and that the degree of injury and the context in which it occurred are important when gauging risk (PMID 30473140).

It has not all been sorted out whether acute kidney injury is the cause of these outcomes or merely a marker pointing to people who were already at high risk. There are observations suggesting that unadjusted, different differences may explain part of this result, yet evidence is growing that it is on the causal path leading to chronic kidney disease. The old idea that people who recover to their usual values or close to them are out of the woods has also been shaken by these studies (PMID 29248147).

Therefore, a 2021 expert consensus states that anyone who experiences acute kidney injury following major surgery other than cardiac surgery absolutely needs some form of follow-up kidney health check, with its format and setting determined by the nature and degree of the injury (PMID 33976395). For people who have experienced this injury after being hospitalized for a serious illness, checking the recovery of kidney function and following up both shortly and long-term are summarized as important for reducing readmissions and complications (PMID 34462285). For people who already have chronic kidney disease, avoiding acute injury is cited as one of the factors that slows down the progression of the disease (PMID 34576247).

A fixed faucet goes right back to how it was before. The kidneys are an organ that requires watching for a while after water starts flowing again to see if they are the same as before.

Acute kidney injury recovers in many cases when the cause is managed, but even after recovery, it is associated with a persistently high risk of chronic kidney disease and death.

Where to Look Next

New blood and urine markers that can tell us earlier than creatinine—and more directly whether the tubules are injured—are being studied, but limitations such as data skewed toward specific populations and unsettled reference values must first be resolved (PMID 33556265; PMID 35334515).

Kidney disease lasting three months or longer is taken up by "What Is Chronic Kidney Disease? — Lamps Going Out One by One, and the Load on Those Still Lit". How to read creatinine and urinalysis numbers is covered by "Reading Your Kidney Test Results — A Sieve You Cannot See, What Stays Behind and What Leaks Through", dialysis and transplantation by "Dialysis and Kidney Transplantation — Three Sieves That Stand In, and the Path That Uses None", and kidney stones and prostate problems involving blocked urinary tracts by "What Is A Kidney Stone? — A Grain of Sand Caught in the Waterway" and "Where Do Urinary Problems Come From? — A Narrowed Passage, An Alarm That Rings Too Early, A Tired Gatekeeper".

The path by which the heart and kidneys are connected through blood can be seen in "How the Heart Moves Blood — Four Chambers, Four Doors, Two Loops". The story of people with long-damaged livers like cirrhosis is handled by "What Does the Liver Do, and What Do Liver Tests Measure? — The Factory at the Gate, and the Signal That Leaks Through the Wall", and deep-seated infections like pneumonia by "How Do a Cold, the Flu, and Pneumonia Differ? — An Infection That Stays in the Entryway, and One That Reaches the Inner Room".

How to translate risk written in "multiples" into the stories of real people is found in "If the Risk Was Cut in Half, How Many Fewer People Got Sick? — Relative and Absolute Risk". How numbers inside the body getting better or worse, like creatinine, differ from the outcomes people actually experience is covered by "Better Numbers, Better Patients? — An Introduction to Surrogate Endpoints".

Source Papers

• "World incidence of AKI: a meta-analysis." (2013) — PMID 23744003 — 154 studies (3,585,911 individuals) using equivalent KDIGO definitions: 21.6% of hospitalized adults and 33.7% of children experienced acute kidney injury, with studies coming predominantly from high-income countries in North America, Northern Europe, and East Asia.
• "Pathophysiology of acute kidney injury." (2012) — PMID 23798302 — The main causes are ischemia, hypoxia, and nephrotoxicity; a rapid decline in the glomerular filtration rate usually occurs alongside reduced renal blood flow, and energy depletion in metabolically active tubular segments can turn transient hypoxia into intrinsic kidney damage.
• "Acute kidney injury." (2013) — PMID 24350317 — KDIGO defines AKI by a rise in serum creatinine or a drop in urine output; meeting these criteria prompts identifying the cause and staging severity, with greater severity raising the risk of CKD progression. Creatinine and urine output remain the best markers we have, but by the time they change, considerable damage has already occurred, and treatment consists of addressing the underlying cause, supportive care, and dialysis if complications arise.
• "AGA Clinical Practice Update on the Evaluation and Management of Acute Kidney Injury in Patients With Cirrhosis: Expert Review." (2022) — PMID 36075500 — Cirrhosis-related AKI is diagnosed using the rise within 48 hours, a rise of 50% or more over baseline, or urine output; the most common cause is hypovolemia (which responds to fluids), postrenal causes are rare, and workup to determine the type includes renal ultrasound.
• "Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup." (2017) — PMID 28239173 — KDIGO defines AKI as a sudden loss of function within 7 days or less, and CKD as kidney disease lasting longer than 90 days, proposing acute kidney disease for the window in between.
• "Current concepts and advances in biomarkers of acute kidney injury." (2021) — PMID 33556265 — AKI definitions rely on creatinine and urine output, which do not directly indicate tubular function or injury, prompting research into new biomarkers for specific tubular segments.
• "Global epidemiology and outcomes of acute kidney injury." (2018) — PMID 30135570 — AKI causes waste retention, electrolyte disturbances, and changes in drug concentrations, as well as systemic responses that affect remote organs, and complete recovery is uncommon; prevalence estimates range from under 1% to 66% depending on the criteria used.
• "Kidney disease and heart failure: recent advances and current challenges: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference." (2026) — PMID 41791738 — Heart failure and CKD frequently coexist and increase the risk of hospitalization, progression, and death; small drops in kidney function after starting heart failure treatment are usually hemodynamic and unrelated to bad outcomes, meaning treatment almost never needs to be stopped.
• "Renal tubular epithelial cells response to injury in acute kidney injury." (2024) — PMID 39178744 — Renal tubular epithelial cells are the primary target of injury in AKI; adaptive repair in cells that survive mild AKI leads to complete recovery, whereas severe or sustained injury leads to maladaptive repair and fibrosis.
• "Acute Kidney Injury Management Strategies Peri-Cardiovascular Interventions." (2023) — PMID 37673499 — Mechanisms of AKI around the time of cardiac procedures include contrast agent involvement, hemodynamic shifts, cardiorenal syndrome, and atheroembolism, and prevention involves limiting contrast volume, optimizing hemodynamics, and restricting other nephrotoxic exposures.
• "Acute kidney injury in sepsis." (2017) — PMID 28364303 — Roughly half of ICU cases of AKI are septic, which may initially be a functional phenomenon (suggested by animal models and a lack of tissue changes); prevention centers on treating sepsis and early resuscitation, careful use of fluids and vasoactive agents, and sometimes dialysis. Most patients recover once the sepsis resolves, but even a single episode is linked to an increased risk of CKD.
• "Sepsis associated acute kidney injury." (2019) — PMID 30626586 — Sepsis is organ dysfunction caused by a host's harmful response to infection, and the kidney is one of the most frequently involved organs.
• "Sepsis-associated acute kidney injury-treatment standard." (2023) — PMID 37401137 — Septic AKI is the most common form of organ dysfunction, accounting for about 50% of AKI in critically ill adults.
• "Acute Kidney Injury in Sepsis." (2024) — PMID 38892111 — The foundation of management is early recognition and prompt treatment of sepsis (appropriate antimicrobials, fluid resuscitation, and vasopressors when needed), and maladaptive repair carries the risk of progression to CKD.
• "Non-steroidal Anti-inflammatory Drugs: Clinical Implications, Renal Impairment Risks, and AKI." (2023) — PMID 36947330 — NSAIDs are commonly used for headaches, pain, and fever and are available without a prescription, and nephrotoxicity increases in older adults, those with low blood volume, those on high doses, or those combining them with RAAS inhibitors or diuretics, though clinician judgment of risks and benefits can reduce this.
• "Pathophysiological aspects of nephropathy caused by non-steroidal anti-inflammatory drugs." (2019) — PMID 30281062 — Renal prostaglandins widen blood vessels to maintain perfusion, which NSAIDs block, leading primarily to hemodynamic AKI, while the second type is acute interstitial nephritis; this is not particularly harmful in young people without comorbidities, but it is dose-dependent, so caution is warranted with long-term use.
• "Acute kidney injury and morbi-mortality associated with "triple whammy" combination: Systematic review and meta-analysis." (2025) — PMID 40876867 — Combining diuretics, RAAS inhibitors, and NSAIDs across 5 case-control studies involving 410,130 patients yielded an odds ratio for AKI within 12 months of 2.01 (with 90% heterogeneity and low certainty), and no increase in mortality was observed.
• "NSAIDs in CKD: Are They Safe?" (2020) — PMID 32479922 — Avoiding NSAIDs in CKD leads to increased use of alternative painkillers like opioids, the risks of which are also established, and recommendations are provided for carefully weighing risk factors on an individual basis.
• "Facing the Challenge of Drug-Induced Acute Interstitial Nephritis." (2023) — PMID 35830831 — AIN can be caused by drugs, infections, autoimmune conditions, or unknown factors, with drugs being the primary cause in many countries, mostly antibiotics, NSAIDs, and proton pump inhibitors; symptoms are nonspecific, the classic triad of signs is rare, confirmation requires a kidney biopsy, and stopping the culprit drug is the cornerstone of treatment.
• "Mechanisms of Drug-Induced Interstitial Nephritis." (2017) — PMID 28284381 — This presents as a drug hypersensitivity reaction 7 to 10 days after exposure, involves more than 250 drugs, and is the third most common cause of hospital-acquired AKI, leading to irreversible fibrosis and CKD if the causative drug is not identified and stopped in time.
• "[Polypharmacy and nephrotoxicity]." (2026) — PMID 41535444 — Polypharmacy is common in older adults, and renal effects range from a mild, functional rise in creatinine to structural tubular damage; combining structural tubular toxins increases risk, whereas functional mechanisms like combining an ACE inhibitor and an SGLT2 inhibitor are generally well tolerated.
• "Risk of Acute Kidney Injury Following IV Iodinated Contrast Media Exposure: 2023 Update, From the AJR Special Series on Contrast Media." (2024) — PMID 37791729 — Fear of nephrotoxicity prevents imaging studies and sacrifices diagnosis, and high-quality studies suggest that many cases considered contrast-induced were actually misattributed coincidences with other causes or normal fluctuations in kidney function.
• "Contrast-Associated Acute Kidney Injury: Definitions, Epidemiology, Pathophysiology, and Implications." (2023) — PMID 37673493 — Because causality cannot be confirmed in most cases, "contrast-associated AKI" is widely used, and while it is linked to cardiovascular events and death, whether it is a marker or a mediator is under debate.
• "Contrast-associated acute kidney injury in the critically ill: systematic review and Bayesian meta-analysis." (2017) — PMID 28197679 — An analysis of 3 studies (560 patients) in critically ill patients with matched unexposed controls showed that contrast agents did not increase AKI (odds ratio 0.95).
• "Use of Intravenous Iodinated Contrast Media in Patients with Kidney Disease: Consensus Statements from the American College of Radiology and the National Kidney Foundation." (2020) — PMID 31961246 — Risks have been exaggerated but remain uncertain in severe kidney disease, and prophylactic intravenous normal saline is used for patients with existing AKI, an eGFR below 30, or non-dialysis-dependent CKD, while for eGFR 30 to 44 it is left to physician discretion in high-risk situations.
• "Strategies for Renal Protection in Cardiovascular Interventions." (2022) — PMID 35790493 — Contrast-associated AKI during angiography and coronary procedures is especially frequent in individuals with preexisting CKD, older age, and comorbidities.
• "Renal recovery." (2017) — PMID 29248146 — Preventing a second hit of renal stress, treating underlying causes, preventing worsening, and promoting recovery during the acute kidney disease phase are central to AKI management.
• "Acute Kidney Injury." (2016) — PMID 26768243 — Aside from dialysis, there are no treatments that reliably improve survival, injury, or recovery, pointing to the limitations of animal models.
• "Transition from acute kidney injury to chronic kidney disease: mechanisms, models, and biomarkers." (2024) — PMID 39298548 — Mechanisms of the transition from AKI to CKD include maladaptive repair, persistent inflammation, and fibrosis, and animal models have limitations in replicating the complexity of human disease.
• "Recovery after Critical Illness and Acute Kidney Injury." (2021) — PMID 34462285 — Most early AKI improves with conservative management, though some patients require days to months of dialysis, and short- and long-term follow-up is important to reduce readmissions and complications.
• "Harmonizing acute and chronic kidney disease definition and classification: report of a Kidney Disease: Improving Global Outcomes (KDIGO) Consensus Conference." (2021) — PMID 34252450 — Acute kidney disease (AKD) refers to kidney function or structural abnormalities lasting 3 months or less, encompassing AKI as well as lesser abnormalities or those lasting longer than 7 days.
• "Acute Kidney Disease to Chronic Kidney Disease." (2021) — PMID 33752866 — AKD is a condition persisting 7 to 90 days after an AKI diagnosis, observed in about 25% of AKI survivors, though clinical data are limited.
• "Long-term risk of adverse outcomes after acute kidney injury: a systematic review and meta-analysis of cohort studies using consensus definitions of exposure." (2019) — PMID 30473140 — Across 82 cohorts totaling 2,017,437 hospitalized adults, the hazard ratios were 2.67 for CKD (17.76 versus 7.59 per 100 person-years), 4.81 for end-stage kidney disease (0.47 versus 0.08), and 1.80 for death (13.19 versus 7.26), showing a gradient by stage, with biases stemming from missing outcome data and inadequate adjustment for confounding.
• "Sequelae of AKI." (2017) — PMID 29248147 — AKI is followed by months to years of increased morbidity and mortality, with a possibility of residual confounding; while it may be a risk marker, there is growing evidence that it is part of the causal pathway to CKD, overturning the traditional view that survivors who recover near baseline have no long-term consequences.
• "Postoperative acute kidney injury in adult non-cardiac surgery: joint consensus report of the Acute Disease Quality Initiative and PeriOperative Quality Initiative." (2021) — PMID 33976395 — Postoperative AKI is strongly linked to long-term CKD, cardiovascular events, and death, and evaluating follow-up kidney health in any form is essential, with the format and setting depending on the nature and severity of the AKI.
• "Chronic Kidney Disease: Strategies to Retard Progression." (2021) — PMID 34576247 — Among factors involved in the onset and progression of CKD, avoiding AKI is heavily emphasized.
• "Acute Kidney Injury: Biomarker-Guided Diagnosis and Management." (2022) — PMID 35334515 — New biomarkers are more sensitive than creatinine and urine output in certain populations, but have limitations such as data skewed toward specific groups and a lack of established reference values.
• "Acute kidney injury." (2012) — PMID 22617274 — Diagnosed by a rapid loss of excretory function leading to urea and creatinine accumulation or reduced urine output, it is common in hospitalized and critically ill patients and usually stems from extrarenal events; managed with supportive care rather than specific treatments, survivors without prior CKD generally come off dialysis, but face an elevated subsequent risk of CKD.
• "Pathophysiology of AKI." (2017) — PMID 29248138 — Perioperative and critical care AKI is usually multifactorial (involving hemodynamic instability, sepsis, and drug toxicity), with multiple pathological processes occurring simultaneously and sequentially regardless of the cause.