The kidneys are remarkable organs, filtering approximately 200 quarts of blood daily to remove waste products, excess fluid, and toxins while retaining essential nutrients and maintaining electrolyte balance. Beyond filtration, kidneys regulate blood pressure, stimulate red blood cell production, activate vitamin D for bone health, and maintain acid-base balance. When kidney function declines progressively over time, the condition is called chronic kidney disease (CKD).

CKD affects approximately 37 million American adults—about 1 in 7—making it more common than diabetes. Yet an estimated 90% of people with CKD don’t know they have it because early stages are asymptomatic. Unlike acute kidney injury, which occurs suddenly from infection, medication toxicity, or blocked blood flow and may be reversible, CKD develops gradually over months or years and is usually irreversible. Damage accumulates silently until significant kidney function is lost.

The progression of CKD varies widely. Some people remain stable at mild or moderate kidney impairment for decades with appropriate management. Others progress to kidney failure (also called end-stage renal disease or ESRD) requiring dialysis or kidney transplant. Two primary factors—diabetes and high blood pressure—cause approximately two-thirds of CKD cases. These conditions damage the small blood vessels in the kidneys, impairing filtration.

What makes CKD particularly dangerous is its insidious nature and serious complications. Reduced kidney function causes waste product accumulation, fluid and electrolyte imbalances, anemia, bone disease, and dramatically increased cardiovascular disease risk. People with CKD are more likely to die from heart disease than to progress to kidney failure, making cardiovascular protection a critical component of CKD management.

Early detection through routine screening—particularly in people with diabetes, hypertension, or family history—enables interventions to slow progression. Blood pressure control, glucose management in diabetes, dietary modifications, medication adjustments, and treatment of complications can preserve remaining kidney function and improve outcomes. Understanding CKD—its causes, stages, symptoms, complications, and management strategies—empowers patients to partner with healthcare providers in protecting kidney health and preventing progression to kidney failure.

Quick Summary:

• Chronic kidney disease (CKD) is progressive loss of kidney function developing gradually over months or years, usually irreversible
• 37 million Americans have CKD—1 in 7 adults—with 90% unaware because early stages are asymptomatic
• CKD has 5 stages based on estimated glomerular filtration rate (eGFR), from mild (Stage 1, eGFR >90) to kidney failure (Stage 5, eGFR <15)
• Diabetes and hypertension cause 2/3 of CKD by damaging kidney blood vessels over time
• Early CKD is asymptomatic—symptoms appear only in advanced stages (4-5) with fatigue, swelling, nausea, confusion
• Diagnosis requires blood and urine tests: serum creatinine, eGFR calculation, and urine albumin-to-creatinine ratio (ACR)
• CKD dramatically increases cardiovascular disease risk—people with CKD are more likely to die from heart disease than progress to kidney failure
• Major complications include anemia, bone disease, electrolyte imbalances, fluid overload, metabolic acidosis, and malnutrition
• Blood pressure control is the most important intervention to slow CKD progression—target <130/80 mmHg
• ACE inhibitors or ARBs are preferred medications for people with CKD and proteinuria, providing kidney protection beyond blood pressure lowering
• Dietary modifications are essential: protein restriction in advanced CKD, sodium limitation, potassium and phosphorus management
• Stage 5 CKD (kidney failure) requires dialysis or transplant to sustain life when kidneys can no longer adequately filter waste

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What Are the Kidneys and What Do They Do?

The kidneys are two bean-shaped organs, each about the size of a fist, located on either side of the spine just below the rib cage. Despite their modest size, kidneys receive approximately 20% of the blood pumped by the heart—about 1.2 liters per minute—reflecting their critical role in blood filtration.

Kidney Structure

Each kidney contains approximately 1 million nephrons, the functional units responsible for filtering blood. A nephron consists of:

Glomerulus: A cluster of tiny blood vessels (capillaries) where blood filtration begins. Blood pressure forces water, waste products, and small molecules through the glomerular membrane into the nephron tubule, while blood cells and large proteins remain in the bloodstream.

Tubule: A long, winding tube where filtered fluid travels. As fluid moves through different tubule segments, essential substances (water, glucose, amino acids, electrolytes) are reabsorbed back into the bloodstream while waste products and excess substances remain in the tubule to become urine.

This filtration and reabsorption process concentrates waste products while conserving nutrients and maintaining fluid and electrolyte balance.

Essential Kidney Functions

Waste Removal:

Kidneys filter and excrete metabolic waste products including urea (from protein metabolism), creatinine (from muscle breakdown), uric acid, and various toxins. When kidney function declines, these waste products accumulate in the blood (uremia), causing symptoms and organ dysfunction.

Fluid Balance:

Kidneys regulate total body water by adjusting urine concentration and volume. They respond to dehydration by concentrating urine and conserving water, or respond to excess fluid by producing dilute urine. This regulation maintains proper hydration and prevents fluid overload.

Electrolyte Balance:

Kidneys precisely control blood levels of sodium, potassium, calcium, phosphorus, magnesium, and chloride by adjusting how much is excreted versus reabsorbed. Electrolyte imbalances from kidney disease can cause dangerous complications including cardiac arrhythmias.

Acid-Base Balance:

The body constantly produces acids through metabolism. Kidneys maintain blood pH in the narrow range necessary for life (7.35-7.45) by excreting acids and regenerating bicarbonate (a base). Kidney disease causes metabolic acidosis (excessive blood acidity) when this function fails.

Blood Pressure Regulation:

Kidneys regulate blood pressure through multiple mechanisms: controlling fluid volume (more fluid raises pressure), producing renin (an enzyme triggering hormones that constrict blood vessels and increase sodium retention), and producing vasodilators that lower pressure. Kidney disease disrupts these mechanisms, causing or worsening hypertension.

Red Blood Cell Production:

Kidneys produce erythropoietin (EPO), a hormone stimulating bone marrow to produce red blood cells. Kidney disease reduces EPO production, causing anemia that contributes to fatigue and cardiovascular complications.

Vitamin D Activation:

Kidneys convert inactive vitamin D from diet or sun exposure into active calcitriol, essential for calcium absorption, bone health, and immune function. Kidney disease impairs this activation, contributing to bone disease and other complications.

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What Is Chronic Kidney Disease?

Chronic kidney disease is defined as abnormalities in kidney structure or function lasting more than 3 months with health implications. CKD is diagnosed if either:

1. Estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73m² for at least 3 months, OR
2. Evidence of kidney damage (proteinuria, blood in urine, kidney cysts, scarring on imaging, kidney biopsy abnormalities) for at least 3 months, regardless of eGFR

The 3-month duration distinguishes chronic from acute kidney conditions. Acute kidney injury (AKI) occurs suddenly—from dehydration, infection, medication toxicity, or urinary obstruction—and often resolves with treatment. CKD develops gradually and is generally irreversible, though progression can be slowed or sometimes halted.

CKD vs. Acute Kidney Injury

Understanding the distinction is important:

Acute Kidney Injury (AKI):

• Sudden onset (hours to days)
• Often reversible if cause treated promptly
• Caused by specific events: severe dehydration, infection, medication toxicity, urinary blockage, major surgery, trauma
• Creatinine rises rapidly
• May cause no symptoms or sudden swelling, reduced urine output, confusion

Chronic Kidney Disease (CKD):

• Gradual onset (months to years)
• Usually irreversible, though progression can be slowed
• Caused by ongoing conditions: diabetes, hypertension, chronic inflammation
• Creatinine rises slowly over time
• Early stages asymptomatic; symptoms appear only in advanced stages

Some people experience AKI superimposed on pre-existing CKD—an acute deterioration in someone with chronic kidney impairment—which can accelerate CKD progression if kidney function doesn’t fully recover.

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The Five Stages of Chronic Kidney Disease

CKD is classified into five stages based on estimated glomerular filtration rate (eGFR), which reflects how well kidneys are filtering blood. Normal eGFR is approximately 90-120 mL/min/1.73m². As kidney disease progresses, eGFR declines. Staging guides treatment decisions and helps predict complications.

Stage 1: Kidney Damage with Normal or High GFR (eGFR ≥90)

Kidneys filter normally or even at higher-than-normal rate, but evidence of kidney damage exists—typically proteinuria (protein in urine), blood in urine, or structural abnormalities on imaging. Stage 1 CKD is often discovered incidentally during evaluation of other conditions, as it causes no symptoms.

Management Focus: Treat underlying cause, control blood pressure, manage diabetes if present, lifestyle modifications to prevent progression.

Stage 2: Mild Reduction in GFR (eGFR 60-89)

Kidney function is mildly reduced but still adequate for normal life. Like Stage 1, Stage 2 requires evidence of kidney damage (proteinuria or structural abnormalities) for CKD diagnosis—eGFR 60-89 alone without damage evidence may be normal, particularly in elderly people.

Management Focus: Same as Stage 1—aggressive management of underlying causes and risk factors to slow progression.

Stage 3: Moderate Reduction in GFR

Stage 3 is divided into 3A and 3B:

Stage 3A (eGFR 45-59): Mild-to-moderate reduction in kidney function. Many people remain asymptomatic, but complications begin emerging—mild anemia, early bone disease, slight electrolyte disturbances.

Stage 3B (eGFR 30-44): Moderate-to-severe reduction in kidney function. Complications become more common—noticeable anemia, worsening bone disease, fluid retention, and early uremic symptoms in some patients.

Stage 3 is when CKD typically comes to medical attention, either through routine testing revealing reduced eGFR or because complications develop. This stage is critical—aggressive management can slow or halt progression to more advanced disease.

Management Focus: All previous interventions plus monitoring and treating complications (anemia, bone disease, metabolic acidosis), medication adjustments for kidney function, dietary modifications, and nephrology referral.

Stage 4: Severe Reduction in GFR (eGFR 15-29)

Severe kidney impairment with multiple complications. Symptoms become noticeable—fatigue from anemia, fluid retention causing swelling, appetite loss, nausea, difficulty concentrating, sleep disturbance, restless legs. Quality of life declines.

Management Focus: Intensive management of complications, preparation for kidney replacement therapy (dialysis or transplant), dietary counseling, patient education about treatment options, consideration for transplant evaluation or dialysis access creation.

Stage 5: Kidney Failure (eGFR <15)

Also called end-stage renal disease (ESRD), kidneys have lost most or all ability to filter waste and maintain fluid, electrolyte, and acid-base balance. Without dialysis or kidney transplant, waste accumulation and metabolic derangements become life-threatening.

Symptoms are severe—profound fatigue, nausea and vomiting, loss of appetite, severe swelling, shortness of breath from fluid in lungs, confusion, seizures, coma in untreated cases. Uremic frost (urea crystals on skin), pericarditis (heart sac inflammation), and bleeding tendency can occur.

Management: Dialysis (hemodialysis or peritoneal dialysis) or kidney transplantation is required to sustain life. Some patients choose conservative management (comprehensive medical care without dialysis), particularly elderly patients with multiple comorbidities where dialysis burden may outweigh benefits.

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How Common Is Chronic Kidney Disease?

Chronic kidney disease affects approximately 37 million American adults—about 15% of the population or 1 in 7 adults. Prevalence increases with age, affecting 38% of adults over age 65. Globally, CKD affects approximately 9-10% of the population, with prevalence rising due to aging populations and increasing diabetes and hypertension rates.

Importantly, an estimated 90% of people with CKD don’t know they have it, particularly in early stages. Only about 48% of people with severely reduced kidney function (Stage 3B or worse) are aware of their condition. This lack of awareness delays interventions that could slow progression and prevent complications.

CKD Prevalence by Stage:

• Stage 1-2: Difficult to estimate due to asymptomatic nature and diagnostic requirement for evidence of kidney damage
• Stage 3: Approximately 7-8% of US adults (most common stage at diagnosis)
• Stage 4: Approximately 0.4% of US adults
• Stage 5 (kidney failure): Approximately 0.2% of US adults, or about 750,000 people

Groups at Higher Risk:

• People with diabetes (approximately 1 in 3 have CKD)
• People with hypertension (approximately 1 in 5 have CKD)
• People over age 65
• African Americans, Hispanic Americans, Native Americans, Asian Americans, Pacific Islanders
• People with family history of CKD
• People with history of acute kidney injury
• People with cardiovascular disease
• People with obesity

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Causes of Chronic Kidney Disease

Diabetes (Leading Cause)

Diabetes causes approximately 38% of CKD cases, making it the leading cause. Both type 1 and type 2 diabetes damage kidneys through multiple mechanisms. High blood glucose damages small blood vessels in glomeruli, impairing filtration. This diabetic kidney disease (diabetic nephropathy) typically develops after 10-20 years of poorly controlled diabetes, though some people develop it sooner.

Early signs include microalbuminuria (small amounts of albumin in urine), progressing to overt proteinuria as damage worsens. Without intervention, diabetic kidney disease can progress to kidney failure. Intensive glucose control significantly reduces diabetic kidney disease risk—every 1% reduction in HbA1c decreases CKD risk by approximately 25-30%.

Hypertension (Second Leading Cause)

High blood pressure causes approximately 28% of CKD cases. Chronic hypertension damages kidney blood vessels, reducing blood flow and impairing filtration. This creates a vicious cycle—hypertension causes kidney damage, and kidney damage worsens hypertension through fluid retention and activation of renin-angiotensin system (hormones that raise blood pressure).

Hypertensive kidney disease (hypertensive nephrosclerosis) typically develops over many years of uncontrolled or inadequately controlled hypertension. African Americans are particularly susceptible, developing hypertensive kidney disease more frequently and at younger ages than other ethnic groups.

Glomerulonephritis

A group of diseases causing inflammation of glomeruli (kidney filtering units). Glomerulonephritis can be primary (kidney-specific) or secondary (part of systemic disease like lupus). Types include:

IgA Nephropathy: Most common primary glomerular disease worldwide, caused by IgA antibody deposits in glomeruli, leading to inflammation and scarring.

Focal Segmental Glomerulosclerosis (FSGS): Scarring of some glomeruli, causing proteinuria and progressive kidney decline. Can be primary or secondary to conditions like obesity, sickle cell disease, or HIV.

Membranous Nephropathy: Thickening of glomerular membrane causing heavy proteinuria. Can be primary or secondary to infections, medications, or cancers.

Lupus Nephritis: Kidney inflammation in systemic lupus erythematosus, affecting up to 60% of lupus patients.

Polycystic Kidney Disease (PKD)

An inherited disorder causing fluid-filled cysts to grow in kidneys, gradually replacing normal kidney tissue and impairing function. Autosomal dominant PKD (ADPKD) is most common, affecting 1 in 400-1,000 people, typically presenting in adulthood. Cysts progressively enlarge, causing kidney enlargement (sometimes massive), pain, high blood pressure, and eventual kidney failure in 50% of patients by age 60.

Chronic Urinary Obstruction

Long-term blockage of urine flow damages kidneys through back-pressure. Causes include:

• Benign prostatic hyperplasia (enlarged prostate in men)
• Kidney stones
• Tumors blocking urinary tract
• Congenital abnormalities (birth defects affecting urinary tract)
• Neurogenic bladder (nerve damage impairing bladder emptying)

Recurrent Kidney Infections

Chronic or recurrent pyelonephritis (kidney infections) can scar kidneys and impair function, particularly in people with anatomical abnormalities causing reflux (backward flow of urine from bladder to kidneys).

Medications and Toxins

Long-term use of certain medications damages kidneys:

• Nonsteroidal anti-inflammatory drugs (NSAIDs): Chronic use (years) of ibuprofen, naproxen, and others can cause chronic interstitial nephritis
• Proton pump inhibitors: Long-term use associated with increased CKD risk through mechanisms not fully understood
• Lithium: Used for bipolar disorder, can cause chronic kidney damage with long-term use
• Heavy metals: Lead, cadmium, mercury exposure over time
• Herbal supplements: Some traditional Chinese herbal supplements cause kidney damage (aristolochic acid nephropathy)

Other Causes

• Chronic reflux nephropathy: Kidney damage from vesicoureteral reflux (urine flowing backward from bladder to kidneys)
• Renal artery stenosis: Narrowing of arteries supplying kidneys
• Multiple myeloma: Cancer producing abnormal proteins that damage kidneys
• Amyloidosis: Abnormal protein deposits in kidneys
• Chronic interstitial nephritis: Inflammation of kidney tissue between tubules

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Symptoms of Chronic Kidney Disease

Early CKD (Stages 1-2 and early Stage 3) is typically asymptomatic. Kidneys have tremendous reserve capacity—symptoms don’t appear until approximately 75% of kidney function is lost. This explains why CKD often goes undetected until advanced stages. As kidney function declines further (late Stage 3, Stage 4-5), symptoms emerge and progressively worsen.

Common Symptoms in Advanced CKD

Fatigue and Weakness:

The most common symptom, caused by anemia (reduced red blood cells), toxin accumulation, poor nutrition, and metabolic disturbances. Fatigue is often profound, limiting daily activities and work capacity.

Swelling (Edema):

Fluid retention causes swelling in feet, ankles, legs, hands, and face. In severe cases, fluid accumulates in lungs (pulmonary edema) causing shortness of breath, particularly when lying down.

Changes in Urination:

• More frequent urination, particularly at night (nocturia)
• Decreased urine output in some cases
• Foamy urine (indicates proteinuria)
• Blood in urine (hematuria)
• Difficulty urinating or weak urine stream

Nausea and Vomiting:

Waste product accumulation (uremia) causes gastrointestinal symptoms—nausea, vomiting, loss of appetite, early satiety (feeling full quickly), and metallic taste in mouth. These symptoms contribute to malnutrition common in advanced CKD.

Confusion and Difficulty Concentrating:

Toxin accumulation affects brain function, causing mental fog, difficulty concentrating, memory problems, confusion, and in severe cases, altered consciousness or seizures.

Sleep Problems:

Difficulty falling asleep, frequent nighttime awakenings, restless legs syndrome (uncomfortable leg sensations causing urge to move legs), sleep apnea, and daytime sleepiness despite spending time in bed.

Muscle Cramps and Twitching:

Electrolyte imbalances, particularly calcium, phosphorus, and magnesium disturbances, cause painful muscle cramps, especially at night, and muscle twitching.

Itching (Pruritus):

Severe, persistent itching affects 50-90% of dialysis patients and many people with advanced CKD not yet on dialysis. Caused by phosphorus retention, calcium-phosphorus deposits in skin, dry skin, and other uremic factors.

Shortness of Breath:

From fluid in lungs, anemia reducing oxygen-carrying capacity, and metabolic acidosis causing compensatory rapid breathing.

Chest Pain:

Can result from pericarditis (inflammation of heart sac), fluid around heart, or cardiovascular disease (more common with CKD).

High Blood Pressure:

Often worsens as CKD progresses due to fluid retention and hormonal changes.

Loss of Appetite and Weight Loss:

Nausea, altered taste, depression, and uremia suppress appetite, leading to inadequate nutrition and muscle wasting, particularly in advanced stages.

Bone Pain and Fractures:

CKD-related bone disease causes bone pain, particularly in spine, hips, and legs, and increases fracture risk.

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Diagnosis and Testing for Chronic Kidney Disease

CKD diagnosis requires laboratory testing—physical examination and symptoms alone cannot reliably detect kidney disease, particularly in early stages. Routine screening is recommended for people at risk: those with diabetes, hypertension, family history of CKD, age over 60, obesity, heart disease, or history of acute kidney injury.

Blood Tests

Serum Creatinine:

Creatinine is a waste product from normal muscle metabolism. Healthy kidneys filter creatinine from blood; as kidney function declines, creatinine accumulates, and blood levels rise. Serum creatinine is measured in mg/dL (U.S.) or µmol/L (internationally).

However, creatinine alone doesn’t define kidney function precisely because levels vary with muscle mass, age, sex, race, and diet. A muscular young man may have “normal” creatinine of 1.2 mg/dL while actually having normal kidney function, whereas a frail elderly woman with the same creatinine has significantly impaired kidney function. This is why eGFR calculation is essential.

Estimated Glomerular Filtration Rate (eGFR):

eGFR is calculated from serum creatinine using equations that account for age, sex, and race. It estimates how much blood the kidneys filter per minute, expressed as mL/min/1.73m². eGFR is the primary metric for CKD staging.

Normal eGFR: >90 mL/min/1.73m² Mild reduction: 60-89 (may be normal in elderly) Moderate reduction: 30-59 Severe reduction: 15-29 Kidney failure: <15

eGFR should be measured at least annually in people at risk and more frequently (every 3-6 months) in people with established CKD to monitor progression.

Blood Urea Nitrogen (BUN):

Urea is another waste product filtered by kidneys. BUN rises with kidney impairment but is less specific than creatinine—diet (high protein intake), dehydration, bleeding, medications, and liver disease all affect BUN independent of kidney function. BUN is typically used alongside creatinine; elevated BUN-to-creatinine ratio suggests dehydration or other issues rather than primary kidney disease.

Electrolytes:

Potassium: Normally kidneys excrete excess potassium. With kidney failure, potassium accumulates (hyperkalemia), which can cause dangerous cardiac arrhythmias.

Sodium: Usually normal until advanced CKD, then may be low due to fluid retention exceeding sodium retention.

Bicarbonate: Decreases with metabolic acidosis as kidneys fail to excrete acids and regenerate bicarbonate.

Calcium and Phosphorus: Calcium tends to decrease while phosphorus increases due to impaired vitamin D activation and parathyroid hormone dysregulation.

Hemoglobin and Hematocrit:

Measure red blood cell levels. Anemia develops progressively in CKD as kidneys produce less erythropoietin.

Albumin:

A protein made by liver; low albumin indicates malnutrition, inflammation, or heavy proteinuria (albumin lost in urine), all common in advanced CKD.

Parathyroid Hormone (PTH):

Rises in CKD as kidneys fail to activate vitamin D, causing secondary hyperparathyroidism contributing to bone disease.

Urine Tests

Urine Albumin-to-Creatinine Ratio (ACR):

The most important urine test for CKD. Measures albumin (a protein that shouldn’t be in urine) relative to creatinine in a spot urine sample. ACR is more reliable than 24-hour urine collection and doesn’t require timed collection.

Normal: <30 mg/g Moderately increased (microalbuminuria): 30-300 mg/g Severely increased: >300 mg/g

Albumin in urine (albuminuria or proteinuria) indicates kidney damage. Even small amounts (microalbuminuria) predict CKD progression and cardiovascular disease risk. Higher ACR correlates with faster kidney function decline and higher mortality risk.

Urinalysis:

Examines urine for blood (hematuria), protein, white blood cells (suggesting infection or inflammation), crystals, and cellular casts (indicating kidney damage). Urinalysis helps identify underlying causes—blood and protein suggest glomerular disease, white blood cells suggest infection or interstitial nephritis.

24-Hour Urine Collection:

Occasionally used to measure total protein excretion or assess kidney function through creatinine clearance, though spot urine ACR and eGFR have largely replaced 24-hour collections due to inconvenience and frequent collection errors.

Imaging Studies

Kidney Ultrasound:

Non-invasive imaging visualizing kidney size, structure, and detecting abnormalities:

• Small kidneys suggest chronic disease with scarring
• Large kidneys suggest acute swelling, polycystic kidney disease, or infiltrative disease
• Hydronephrosis (fluid-filled kidneys) indicates obstruction
• Kidney stones, cysts, tumors

Ultrasound is often the first imaging study in CKD evaluation.

CT Scan or MRI:

Provides detailed kidney and urinary tract images, identifying structural abnormalities, stones, masses, vascular abnormalities, and complications. CT is quicker and more available; MRI avoids radiation but is more expensive and time-consuming.

Nuclear Medicine Scans:

Assess individual kidney function using radioactive tracers. Useful before procedures affecting one kidney (surgery, donation) to determine how well each kidney functions independently.

Kidney Biopsy

Involves inserting a needle through skin into kidney to obtain tissue sample for microscopic examination. Biopsy is invasive with small bleeding risk but provides definitive diagnosis of kidney disease type—essential when cause is unclear, glomerulonephritis suspected, or treatment decisions require specific diagnosis.

Biopsy is typically performed when:

• Cause of CKD is uncertain
• Proteinuria and/or hematuria without clear cause
• Rapid kidney function decline
• Suspected glomerulonephritis requiring specific treatment
• Transplanted kidney function declining

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Complications of Chronic Kidney Disease

CKD affects multiple organ systems beyond the kidneys. Managing complications is crucial for quality of life and preventing further deterioration.

Cardiovascular Disease

The most important CKD complication—cardiovascular disease is the leading cause of death in people with CKD. CKD dramatically increases heart attack, stroke, heart failure, and peripheral artery disease risk through multiple mechanisms:

• Hypertension (difficult to control with kidney disease)
• Dyslipidemia (abnormal cholesterol)
• Fluid overload stressing the heart
• Anemia reducing oxygen delivery
• Inflammation and oxidative stress
• Calcification of arteries and heart valves from calcium-phosphorus imbalances
• Uremic toxin accumulation affecting vascular health

People with Stage 3-4 CKD have 2-4 times higher cardiovascular death risk than people without CKD. In Stage 5 (dialysis patients), cardiovascular death risk is 10-30 times higher. Importantly, most people with CKD die from cardiovascular disease before progressing to kidney failure, emphasizing the critical importance of cardiovascular risk management.

Anemia

Kidneys produce erythropoietin (EPO), stimulating red blood cell production. As kidney function declines, EPO production decreases, causing anemia. Additionally, uremic toxins, inflammation, iron deficiency, and shortened red blood cell lifespan contribute to anemia.

Anemia causes:

• Fatigue and weakness
• Shortness of breath
• Difficulty concentrating
• Dizziness
• Cold intolerance
• Worsening heart function (heart must work harder with fewer oxygen-carrying red blood cells)

Anemia typically develops when eGFR falls below 45 (Stage 3B) and worsens progressively. Treatment includes iron supplementation (oral or intravenous) and erythropoiesis-stimulating agents (ESAs) that mimic EPO.

Mineral and Bone Disorder (CKD-MBD)

A complex syndrome involving abnormalities in calcium, phosphorus, vitamin D, and parathyroid hormone metabolism, leading to bone disease, vascular calcification, and fractures.

Pathophysiology:

As kidney function declines, phosphorus excretion decreases, causing hyperphosphatemia. High phosphorus suppresses active vitamin D production, reducing calcium absorption and lowering blood calcium. Low calcium triggers parathyroid glands to produce excess PTH (secondary hyperparathyroidism). Elevated PTH pulls calcium from bones to restore blood calcium, weakening bones.

Consequences:

• Renal osteodystrophy: Abnormal bone remodeling causing bone pain, deformities, and fractures
• Vascular calcification: Calcium-phosphorus deposits in arteries and heart valves, increasing cardiovascular disease risk
• Calciphylaxis: Rare but severe complication where calcium deposits in small blood vessels cause skin ulcers and tissue death, with high mortality

Management:

• Dietary phosphorus restriction
• Phosphate binders (medications binding dietary phosphorus to prevent absorption)
• Active vitamin D supplements (calcitriol)
• Calcimimetics (medications reducing PTH secretion)

Fluid Overload

Impaired fluid excretion causes fluid accumulation, manifesting as:

• Peripheral edema (swelling in feet, ankles, legs)
• Pulmonary edema (fluid in lungs causing shortness of breath)
• Hypertension
• Heart failure
• Weight gain

Management includes sodium and fluid restriction, diuretics (medications increasing urine output), and in advanced cases, ultrafiltration (fluid removal during dialysis).

Electrolyte Imbalances

Hyperkalemia (High Potassium):

Potassium accumulates when kidneys can’t excrete it, particularly dangerous because elevated potassium disrupts heart electrical activity, causing arrhythmias and potentially cardiac arrest. Management includes dietary potassium restriction, potassium-binding medications, and dialysis in severe cases.

Hyponatremia (Low Sodium):

Dilutional hyponatremia occurs when fluid retention exceeds sodium retention. Severe hyponatremia causes confusion, seizures, and coma.

Hyperphosphatemia (High Phosphorus):

Discussed under CKD-MBD; contributes to bone disease and vascular calcification.

Metabolic Acidosis

Healthy kidneys excrete daily acid production from metabolism. With kidney failure, acids accumulate, lowering blood pH (metabolic acidosis). Chronic acidosis:

• Accelerates CKD progression
• Causes muscle breakdown and bone dissolution
• Worsens bone disease
• Increases mortality risk

Treatment includes sodium bicarbonate supplementation and addressing underlying causes.

Malnutrition and Muscle Wasting

Multiple factors cause malnutrition in CKD:

• Appetite loss from uremia
• Nausea and vomiting
• Dietary restrictions (low protein, low potassium, low phosphorus diets limiting food choices)
• Inflammation and metabolic acidosis causing muscle breakdown
• Depression

Protein-energy wasting (loss of muscle and fat mass) is common in advanced CKD and dialysis patients, associated with infections, hospitalizations, poor quality of life, and increased mortality. Nutritional counseling and adequate protein intake (within restrictions) are essential.

Uremic Syndrome

Accumulation of uremic toxins causes a constellation of symptoms and complications affecting multiple organ systems:

• Neurological: Confusion, difficulty concentrating, peripheral neuropathy, restless legs, seizures
• Gastrointestinal: Nausea, vomiting, loss of appetite, metallic taste, bleeding
• Hematological: Anemia, bleeding tendency from platelet dysfunction
• Dermatological: Severe itching, dry skin, uremic frost (urea crystals on skin)
• Pericarditis: Heart sac inflammation causing chest pain
• Immune dysfunction: Increased infection risk

Uremic syndrome indicates need for dialysis initiation.

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Treatment and Management of Chronic Kidney Disease

CKD management goals include slowing progression, managing complications, treating underlying causes, and preparing for kidney replacement therapy if needed. Treatment approaches vary by CKD stage.

Treating Underlying Causes

Diabetes Management:

Intensive glucose control slows diabetic kidney disease progression. Target HbA1c <7% for most people with diabetes, though individualized targets may be higher in elderly or those with frequent hypoglycemia. Use of SGLT2 inhibitors (a class of diabetes medications) in people with diabetic kidney disease provides kidney protection beyond glucose lowering—they slow eGFR decline and reduce proteinuria.

Blood Pressure Control:

The single most important intervention for slowing CKD progression regardless of cause. Target blood pressure <130/80 mmHg, and potentially <120/80 mmHg for people with heavy proteinuria. Blood pressure control reduces proteinuria, slows kidney function decline, and reduces cardiovascular risk.

Proteinuria Reduction:

Proteinuria is both a marker of kidney damage and a driver of progression—protein in tubules is toxic to kidney cells. Reducing proteinuria slows CKD progression and reduces cardiovascular risk.

Medications for Kidney Protection

ACE Inhibitors and ARBs:

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are preferred blood pressure medications for people with CKD and proteinuria. Beyond lowering blood pressure, they reduce proteinuria by dilating blood vessels exiting glomeruli, reducing pressure inside glomeruli and decreasing protein leakage.

Common ACE inhibitors: Lisinopril, enalapril, ramipril Common ARBs: Losartan, valsartan, irbesartan

These medications are proven to slow CKD progression and delay dialysis need, particularly in diabetic kidney disease. Side effects include cough (more common with ACE inhibitors), hyperkalemia (elevated potassium requiring monitoring), and rare angioedema (dangerous swelling).

SGLT2 Inhibitors:

Originally diabetes medications, SGLT2 inhibitors provide kidney protection in both diabetic and non-diabetic CKD with proteinuria. They reduce proteinuria, slow eGFR decline, reduce hospitalization for heart failure, and lower cardiovascular death risk. Examples include empagliflozin, dapagliflozin, canagliflozin.

Mineralocorticoid Receptor Antagonists:

Medications like finerenone reduce proteinuria and slow CKD progression, particularly in diabetic kidney disease, with additional cardiovascular benefits.

Managing Complications

Anemia Treatment:

• Iron supplementation (oral or intravenous) for iron deficiency
• Erythropoiesis-stimulating agents (ESAs): Epoetin alfa, darbepoetin alfa for severe anemia
• Target hemoglobin 10-11.5 g/dL (higher targets associated with increased cardiovascular risk)

CKD-MBD Management:

• Dietary phosphorus restriction
• Phosphate binders: Calcium acetate, sevelamer, lanthanum carbonate
• Active vitamin D: Calcitriol, paricalcitol
• Calcimimetics: Cinacalcet for secondary hyperparathyroidism
• Calcium supplementation if hypocalcemic (carefully, to avoid excess calcium)

Metabolic Acidosis Treatment:

• Sodium bicarbonate supplementation targeting serum bicarbonate >22 mEq/L
• May slow CKD progression and reduce muscle wasting

Fluid and Electrolyte Management:

• Sodium restriction (typically 2 grams daily)
• Fluid restriction if fluid overloaded
• Potassium restriction if hyperkalemic
• Diuretics (loop diuretics like furosemide) for fluid overload
• Potassium binders (sodium polystyrene sulfonate, patiromer) for hyperkalemia

Dietary Management

Diet is crucial for managing CKD complications and slowing progression. Specific recommendations vary by CKD stage and individual complications.

Protein:

In Stages 1-2, normal protein intake (0.8 g/kg/day) is appropriate. In Stages 3-5 (not on dialysis), moderate protein restriction (0.6-0.8 g/kg/day) may slow progression and reduce uremic symptoms, though maintaining adequate nutrition is critical—excessive restriction causes malnutrition. Once on dialysis, protein needs increase (1.0-1.2 g/kg/day) due to protein losses during dialysis.

Sodium:

Limit to 2 grams (2,000 mg) daily or less. Sodium restriction helps control blood pressure, reduces fluid retention, and may slow progression. Most dietary sodium comes from processed foods, restaurant meals, and added salt.

Potassium:

With normal kidney function, high potassium intake (from fruits, vegetables, beans, nuts) is healthy. In advanced CKD (Stage 4-5), kidneys can’t excrete potassium adequately, requiring restriction to 2-3 grams daily to prevent dangerous hyperkalemia. High-potassium foods to limit include bananas, oranges, potatoes, tomatoes, spinach, beans, nuts.

Phosphorus:

Limit to 800-1,000 mg daily in Stages 3-5. High-phosphorus foods include dairy products, meat, poultry, fish, nuts, beans, and cola beverages. Food additives in processed foods are highly absorbable phosphorus sources requiring particular avoidance.

Fluid:

In early CKD, adequate hydration is important. In advanced CKD with fluid retention, fluid restriction (typically 1-2 liters daily depending on urine output) prevents fluid overload.

Meal Planning:

CKD diet restrictions are complex, often requiring multiple simultaneous limitations (low protein, low sodium, low potassium, low phosphorus). Working with renal dietitian is essential for balanced meal planning meeting nutritional needs while managing restrictions.

Lifestyle Modifications

Smoking Cessation:

Smoking accelerates CKD progression and increases cardiovascular risk. Quitting is crucial.

Exercise:

Regular physical activity improves cardiovascular health, helps control blood pressure and glucose, reduces inflammation, and improves quality of life. Recommended: 150 minutes moderate-intensity exercise weekly.

Weight Management:

If overweight or obese, weight loss of 5-10% improves blood pressure, glucose control, and proteinuria.

Medication Management:

• Avoid nephrotoxic medications: NSAIDs (ibuprofen, naproxen), some antibiotics, contrast dyes when possible
• Adjust medication doses for kidney function—many medications require dose reduction in CKD
• Review all medications and supplements with healthcare providers

Preparing for Kidney Replacement Therapy

When CKD progresses to Stage 4-5, preparation for dialysis or transplant begins:

Transplant Evaluation:

Kidney transplant offers better quality of life and survival than dialysis. Evaluation for transplant eligibility should begin when eGFR falls to 20-30. Living donor transplant (from family member or friend) is ideal, as it can occur before dialysis is needed (preemptive transplant).

Dialysis Planning:

If transplant isn’t immediately available, dialysis preparation includes education about dialysis types (hemodialysis vs. peritoneal dialysis), dialysis access creation (arteriovenous fistula or catheter for hemodialysis, catheter placement for peritoneal dialysis), and training for home dialysis if chosen.

Conservative Management:

Some patients, particularly elderly with multiple comorbidities, choose comprehensive medical care without dialysis. This focuses on symptom management, quality of life, and palliative care when appropriate.

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Prevention of Chronic Kidney Disease

Screening High-Risk Individuals

Early detection allows interventions before significant damage occurs. Annual screening with serum creatinine (for eGFR calculation) and urine albumin-to-creatinine ratio is recommended for:

• People with diabetes
• People with hypertension
• People over age 60
• People with family history of CKD
• People with cardiovascular disease
• People with history of acute kidney injury
• African Americans, Hispanic Americans, Native Americans, Asian Americans, Pacific Islanders

Managing Risk Factors

Diabetes Prevention and Control:

Lifestyle interventions (diet, exercise, weight loss) reduce diabetes risk by 58%. For people with diabetes, intensive glucose control prevents or delays diabetic kidney disease.

Blood Pressure Control:

Target <130/80 mmHg through lifestyle modifications (sodium reduction, weight loss, exercise, moderate alcohol) and medications when needed.

Healthy Lifestyle:

• Maintain healthy weight
• Regular physical activity
• Heart-healthy diet (Mediterranean or DASH diet)
• Don’t smoke
• Moderate alcohol consumption
• Adequate hydration

Avoid Nephrotoxic Exposures:

• Limit NSAID use—don’t use chronically without medical supervision
• Use medications only as prescribed
• Avoid herbal supplements with nephrotoxic potential
• Minimize exposure to environmental toxins

Prompt Treatment of Acute Kidney Injury

AKI increases CKD risk—approximately 25% of AKI patients develop CKD. Prompt treatment of AKI causes (rehydration, stopping nephrotoxic medications, treating infections, relieving obstruction) optimizes recovery and reduces CKD risk.

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Living With Chronic Kidney Disease

CKD diagnosis can be overwhelming, particularly given complex dietary restrictions, multiple medications, frequent medical appointments, and potential progression to dialysis. However, many people with CKD maintain good quality of life through appropriate management, support, and coping strategies.

Medical Management

Regular follow-up with nephrologist (kidney specialist) is essential for Stages 3-5 CKD. Frequency depends on stage and rate of progression—typically every 3-6 months for Stage 3, every 2-3 months for Stage 4-5. Primary care providers manage early CKD with nephrology consultation as needed.

Medication adherence is crucial—CKD often requires multiple medications (blood pressure medications, phosphate binders, iron, vitamins, etc.). Use medication organizers, set reminders, and discuss barriers to adherence with healthcare team.

Diet and Nutrition

Working with renal dietitian helps navigate complex dietary restrictions while maintaining adequate nutrition. Meal planning, label reading, cooking techniques to reduce potassium and phosphorus, and recipe modifications make dietary management more manageable.

Emotional and Psychological Support

CKD commonly causes depression, anxiety, and stress. Mental health support—counseling, support groups, antidepressant medications when appropriate—improves quality of life and potentially improves medical outcomes, as depression impairs medication adherence and self-care.

Support groups (in-person or online) connect patients with others navigating similar challenges, providing practical advice, emotional support, and reduced isolation.

Work and Finances

Many people with CKD, even Stage 4-5, continue working. Fatigue may require schedule adjustments or reduced hours. Disability benefits may be available for those unable to work. Financial counseling helps navigate insurance coverage, medication costs, and dialysis or transplant expenses.

Quality of Life

Despite challenges, many CKD patients maintain good quality of life through:

• Staying physically active within capabilities
• Maintaining social connections
• Pursuing hobbies and interests
• Setting realistic goals
• Focusing on what can be controlled
• Finding meaning and purpose

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When to See a Healthcare Provider

Seek medical attention if:

• You have diabetes, hypertension, or other CKD risk factors and haven’t had kidney function testing
• You experience symptoms suggesting kidney problems (reduced urination, blood in urine, severe swelling, unexplained fatigue)
• You have known CKD and experience worsening symptoms
• You need help managing CKD dietary restrictions or medications

Don’t wait for symptoms—early CKD is asymptomatic but detectable through screening, and early intervention provides the best opportunity to slow progression.

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Early detection of chronic kidney disease through routine screening, particularly in people with diabetes, hypertension, or other risk factors, enables interventions to slow progression, manage complications, and delay or prevent kidney failure. Blood pressure control, diabetes management, dietary modifications, appropriate medications, and regular monitoring preserve kidney function and improve outcomes.