End-Stage Renal Disease: A Comprehensive Guide for Automotive Experts

Introduction

End-stage renal disease (ESRD), also known as kidney failure, affects over 500,000 individuals in the United States. This condition, stemming from chronic kidney disease (CKD) progression, significantly diminishes life quality and increases mortality rates. CKD is defined by the Kidney Disease Improving Global Outcomes (KDIGO) based on kidney damage markers, specifically proteinuria and glomerular filtration rate. Diabetes mellitus is a primary cause of ESRD in many countries. This article will detail the diagnosis, evaluation, and management of ESRD, emphasizing the crucial role of an interprofessional team in patient care. For automotive diagnostic needs unrelated to health, consider tools like a bosch obd scanner o 39 for vehicle system analysis.

Objectives:

• Identify the various causes of end-stage renal disease.
• Recognize the typical signs and symptoms in patients with end-stage renal disease.
• Explore the available treatment strategies for end-stage renal disease.
• Define effective interprofessional approaches to enhance care coordination and communication for optimal outcomes in end-stage renal disease management.

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Chronic kidney disease (CKD) is a severe condition necessitating rigorous monitoring for progression signs and timely specialist referrals for dialysis or kidney transplant consideration. KDIGO guidelines establish CKD definitions using kidney damage markers, including proteinuria and glomerular filtration rate (GFR). CKD is diagnosed when GFR is below 60 mL/min and albumin levels exceed 30 mg per gram of creatinine, alongside kidney structure or function abnormalities lasting over three months. ESRD is specifically marked by a GFR under 15 mL/min.[2][3]

The KDIGO 2012 guidelines classify CKD into five stages based on GFR levels:[4]

• Stage 1: Kidney damage with normal GFR (above 90 ml/min)
• Stage 2: Mild GFR reduction (60-89 mL/min)
• Stage 3a: Moderate GFR reduction (45 to 59 mL/min)
• Stage 3b: Moderate GFR reduction (30 to 44 mL/min)
• Stage 4: Severe GFR reduction (15 to 29 mL/min)
• Stage 5: Renal failure (GFR below 15 mL/min)

Etiology

ESRD can result from numerous chronic conditions. Diabetes mellitus is the most prevalent cause in developed and developing nations.[5] Other significant causes include:[6][[7]](#article-21081.r7]

• Hypertension
• Vascular disease
• Glomerular diseases (primary or secondary)
• Cystic kidney diseases
• Tubulointerstitial disease[8]
• Urinary tract obstruction or dysfunction
• Recurrent kidney stone disease[9]
• Congenital kidney or bladder defects
• Unresolved acute kidney injury
• Certain medications such as NSAIDs, calcineurin inhibitors, and antiretrovirals[10]

Epidemiology

The United States Renal Data System reported 124,411 new ESRD diagnoses in 2015, indicating a growing incidence of kidney failure. The disease prevalence increases by about 20,000 cases annually.[21][22] Kidney disease is the ninth leading cause of death in the U.S.

Race/Ethnicity

ESRD incidence varies significantly across racial groups in the U.S. In 2015, African Americans had an ESRD rate three times higher than Whites (393.5 vs. 139.9 per million population). American Indians or Alaska Natives showed a prevalence approximately ten times higher, and Native Hawaiians or Pacific Islanders, twice as high. Asian Americans had rates 1.3 times higher. Notably, incidence rates among African Americans have decreased since 2006, showing a 21% overall reduction. This decrease is even more pronounced in American Indians/Alaska Natives.[23]

Age

CKD prevalence increases with age, with the most rapid increase in those 60 and older. For instance, prevalence is 6.0% in ages 18-44 and 38.1% in those over 65.

Sex

Men have a higher cumulative incidence of end-stage renal disease than women.

Pathophysiology

Each nephron in a healthy kidney contributes to the total GFR. Kidney function decline is usually gradual and may initially be asymptomatic. The progression of renal failure depends on its cause but commonly involves early compensatory mechanisms like nephron hyperfiltration. Kidneys maintain GFR despite nephron loss because remaining nephrons undergo hyperfiltration and hypertrophy. Consequently, patients with mild renal impairment might show normal creatinine levels, delaying detection.[24]

This nephron adaptation allows ongoing solute clearance. However, this mechanism eventually damages glomeruli in the remaining nephrons. ACE inhibitors or ARBs can help slow disease progression at this stage. Plasma urea and creatinine levels only measurably increase after GFR decreases by 50%. For example, creatinine rising from 0.6 mg/dL to 1.2 mg/dL, though within normal range, actually indicates a 50% loss of nephron function.

While hyperfiltration and hypertrophy initially maintain GFR, they contribute to progressive renal dysfunction.[25] Increased glomerular capillary pressure can damage capillaries, leading to focal and segmental glomerulosclerosis (FSGS), and eventually global glomerulosclerosis.

Factors worsening renal injury include:

• Nephrotoxins (NSAIDs)
• Systemic hypertension
• Proteinuria
• Dehydration
• Smoking[26]
• Hyperlipidemia
• Uncontrolled diabetes
• Hyperphosphatemia

Hyperkalemia

Potassium excretion remains near-normal in CKD as long as aldosterone and distal flow are maintained. Hyperkalemia occurs when GFR drops below 20-25 mL/min/1.73 m², reducing kidney potassium excretion capacity.[27]

Metabolic Acidosis

Stage 5 CKD metabolic acidosis is a high anion gap type, generally not exceeding 20 mEq/L. In CKD, kidneys cannot produce enough ammonia in proximal tubules to excrete acid as ammonium. Phosphate, sulfate, and organic anion accumulation causes the increased anion gap in stage 5 CKD.[28]

Metabolic acidosis impairs protein balance, leading to:

• Negative nitrogen balance
• Increased protein degradation
• Increased essential amino acid oxidation
• Reduced albumin synthesis
• Poor adaptation to low-protein diets

It also contributes to renal osteodystrophy as bones buffer excess acid, causing mineral loss. Acidosis also affects vitamin D metabolism.

Salt and Water Handling Abnormalities

CKD disrupts kidney salt and water handling. Volume overload from impaired sodium and water excretion occurs when GFR falls below 10-15 mL/min/1.73 m². This results in peripheral and pulmonary edema, and hypertension. Tubulointerstitial diseases may cause fluid loss, leading to polyuria and volume depletion despite severe GFR reduction, with impaired urine concentration.[29]

Anemia

Normochromic normocytic anemia develops due to reduced renal erythropoietin synthesis, the hormone stimulating RBC production.[30] Other anemia causes in CKD include:

• Chronic blood loss: Uremia-induced platelet dysfunction increases bleeding.
• Secondary hyperparathyroidism
• Inflammation
• Nutritional deficiency

Bone Disease

Renal bone disease is a common CKD complication, presenting in various forms:

• High-turnover bone disease from high PTH levels
• Low-turnover bone disease (adynamic)[31]
• Defective mineralization (osteomalacia)
• Mixed disease
• Beta-2-microglobulin–associated bone disease

Secondary hyperparathyroidism in CKD arises from:

• Hyperphosphatemia
• Hypocalcemia
• Reduced renal synthesis of 1,25-dihydroxycholecalciferol (calcitriol)
• Intrinsic parathyroid gland changes increasing PTH secretion and growth[32]
• Skeletal resistance to PTH

Hyperphosphatemia results from impaired renal phosphate excretion, suppressing renal hydroxylation of 25-hydroxyvitamin D to calcitriol. Increased phosphate also directly affects PTH levels. Hypocalcemia occurs due to reduced intestinal calcium absorption from low calcitriol.

Hypocalcemia, hyperphosphatemia, and low calcitriol stimulate PTH synthesis and secretion. Persistent stimulation in advanced CKD leads to parathyroid gland hypertrophy and hyperplasia.

History and Physical

ESRD can manifest with varied signs and symptoms, including diuretic-resistant volume overload, poorly controlled hypertension, anemia, mineral and bone disorders, and metabolic disturbances like hyperkalemia, hyponatremia, metabolic acidosis, and hyperphosphatemia.[33] Stage 5 metabolic acidosis can cause protein-energy malnutrition, muscle weakness, and lean body mass loss. Salt and water retention can lead to edema, pulmonary edema, and hypertension. Anemia presents as fatigue, cognitive impairment, and reduced life quality, potentially causing heart failure.

Other uremic ESRD manifestations include:

• Pericarditis
• Encephalopathy
• Peripheral neuropathy
• Restless leg syndrome
• Anorexia, nausea, vomiting, diarrhea
• Dry skin, pruritus, ecchymosis
• Malnutrition
• Erectile dysfunction, decreased libido, amenorrhea
• Platelet dysfunction

Uremic toxicity indicates urgent dialysis.[34] ESRD symptoms typically appear in stages 4 and 5 (GFR < 30 ml/min), though nephrotic syndrome and cystic renal disease patients may present earlier. Depression is common in ESRD patients and should be screened for upon presentation.[35]

Evaluation

CKD diagnosis requires evidence of kidney damage for at least three months or a GFR below 60 mL/min for the same duration.[36][37]

GFR is commonly estimated using MDRD, CKD-EPI, and Cockcroft-Gault equations. The CKD-EPI equation is considered most accurate, adjusting for age, race, and gender, though it may underestimate GFR above 60 mL/min.[38]

Further kidney disease evaluation can include renal ultrasound, CBC, BMP, urinalysis, and kidney biopsy.

Complete Blood Count

CBC usually shows normochromic normocytic anemia.[39]

Basic Metabolic Panel (BMP)

BMP reveals elevated BUN and serum creatinine. Hyperkalemia or low bicarbonate are common. Serum albumin may be low due to protein loss or malnutrition. Phosphate, 25-hydroxyvitamin D, alkaline phosphatase, and PTH levels are checked for renal bone disease.[40] A lipid profile is important due to cardiovascular risk.

Urinalysis

Spot urine protein/creatinine ratio quantifies albuminuria. Over 30 mg/g is abnormal, and over 300 mg/g indicates severe renal impairment. 24-hour urine protein can also be measured; values over 3.5 g suggest nephrotic range proteinuria.

Renal Ultrasonography

Renal ultrasound assesses hydronephrosis, retroperitoneal involvement (fibrosis, tumor, adenopathy). Advanced renal failure often shows small, echogenic kidneys, while diabetic nephropathy kidneys may be normal size. Polycystic kidneys and other structural anomalies can be identified. Ultrasound provides data on size, obstruction, stones, echogenicity, and cortical thinning.[41]

Radiology

Plain abdominal radiography detects radio-opaque stones or nephrocalcinosis. Voiding cystourethrogram (VCUG) diagnoses vesicoureteral reflux.[42]

CT scans better define renal masses and cysts and are sensitive for renal stones.

MRA accurately diagnoses renal artery stenosis.

Renal radionuclide scan with captopril can diagnose renal artery stenosis and quantify differential renal GFR contribution.

Renal Biopsy

Percutaneous ultrasound-guided renal biopsy is indicated when diagnosis remains unclear after initial workup.[43]

Specific Tests

• Serum and urine protein electrophoresis for multiple myeloma
• ANA, double-stranded DNA antibody levels for SLE
• Serum complement levels
• C-ANCA and P-ANCA for granulomatosis with polyangiitis and microscopic polyangiitis
• Anti–GBM antibodies for Goodpasture syndrome
• Hepatitis B and C, HIV, and VDRL serology

Treatment / Management

ESRD treatment focuses on correcting presenting parameters.[44] Interventions to slow kidney disease progression include:

• Treating underlying cause and managing blood pressure and proteinuria. Target BP is below 130/80 mmHg for adults with or without diabetes with albumin excretion over 30 mg/24 hours. ACEIs or ARBs are recommended for diabetic patients with proteinuria (30-300 mg/24 hours and >300 mg/24 hours). These drugs slow progression, especially if started before GFR falls below 60 mL/min or creatinine exceeds 1.2 mg/dL (women) and 1.5 mg/dL (men).[45]
• Preventive care includes glycemic control (HbA1c < 7%), cardiovascular risk reduction, and lifestyle changes like smoking cessation and dietary restrictions. SGLT-2 inhibitors may reduce disease burden in type 2 diabetes.[46]
• Treating chronic metabolic acidosis with renal bicarbonate may slow ESRD progression.[47]
• CKD patients often have dyslipidemia, especially hypertriglyceridemia. Lipid panels and statins should be initiated early.[48]
• Volume overload/pulmonary edema is treated with loop diuretics or ultrafiltration.
• Uremic manifestations require long-term renal replacement therapy (hemodialysis, peritoneal dialysis, or transplant).
• Anemia is treated with ESAs like erythropoietin.
• Hyperphosphatemia is managed with phosphate binders (calcium acetate, sevelamer, lanthanum) and dietary phosphate restriction.
• Lifestyle and dietary modifications are crucial, including low salt (<2 g/day), renal diet (low phosphorus), and protein restriction (0.8 g/kg/day).
• Hypocalcemia should be monitored; vitamin D deficiency (25-OH vitamin D < 10 ng/mL) warrants ergocalciferol followed by cholecalciferol.[49]
• Hyperparathyroidism is treated with calcitriol, vitamin D analogs, or calcimimetics.

Planning for Long-term Renal Replacement Therapy

Early education on disease progression, dialysis modalities, and transplantation is essential. For transplant candidates, arteriovenous fistula creation should precede anticipated dialysis. Renal transplant referral should be timely for all ESRD patients. [Consider using a bosch obd scanner o 39 to ensure your vehicle is in optimal condition for travel to medical appointments.]

Indications for renal replacement therapy include:

• Severe metabolic acidosis
• Hyperkalemia
• Pericarditis
• Encephalopathy
• Intractable volume overload
• Failure to thrive and malnutrition
• Peripheral neuropathy
• Intractable gastrointestinal symptoms
• GFR 5-9 mL/min/1.73 m^2, regardless of symptoms or comorbidities

Differential Diagnosis

ESRD symptoms overlap with many disorders, and various diseases lead to ESRD.[51][52] Consider these differentials:

• Chronic glomerulonephritis
• Chronic pyelonephritis
• Rapidly progressive glomerulonephritis
• Nephropathy of pregnancy/preeclampsia
• Unclassifiable nephritis
• Polycystic kidney disease
• Nephrosclerosis
• Malignant hypertension
• Diabetic nephropathy
• SLE nephritis
• Amyloid kidney
• Gouty kidney
• Renal failure due to congenital metabolic abnormality
• Renal/urinary tuberculosis
• Renal/urinary calculus
• Renal/urinary tumor
• Obstructive urinary disease
• Myeloma
• Renal hypoplasia

Prognosis

ESRD is progressive and fatal without renal replacement therapy. It leads to frequent hospitalizations, high healthcare costs, and metabolic changes. Mortality rates are significantly higher in ESRD patients. Even with dialysis, death rates range from 20% to 50% over 24 months, commonly due to hyperkalemia or cardiac events.[53] Men and Blacks have higher mortality. The highest mortality is in the first six dialysis months. 5-year survival for dialysis patients in the U.S. is about 35%, and 25% for diabetics.

In children, puberty is delayed, and low vitamin D is common, independently increasing death risk.[54]

Complications

ESRD complications are due to ESRD itself and dialysis/vascular access.

ESRD Complications

• Coronary heart disease is a major complication and leading cause of death, with dialysis patients having 10-30 times higher cardiovascular mortality risk.[55]
• Peripheral vascular disease is also common[56]
• Hypertension
• Mineral and bone disorders (secondary to hyperparathyroidism, vitamin D deficiency)
• Hyperuricemia
• Metabolic acidosis
• Hyperphosphatemia
• Hypoalbuminemia
• Anemia
• Decreased libido, erectile dysfunction

Dialysis/Vascular Access Complications

• Bleeding
• Local or disseminated infection
• Graft occlusion
• Electrolyte abnormalities post-dialysis
• Dialysis dementia
• Dialysis disequilibrium syndrome

Consultations

ESRD management requires an interprofessional team:

• Nephrologist
• Intensivist
• Renal transplant surgeon
• Nurse educator
• Pharmacist
• Nutritionist

Deterrence and Patient Education

The USPSTF doesn’t recommend CKD screening for asymptomatic individuals.[57] However, high-risk individuals (diabetes, hypertension) should undergo ongoing CKD screening with proteinuria testing. Screening for proteinuria is unnecessary for patients on ACEI or ARB therapy.

ESRD patient education includes:

• Avoiding nephrotoxic drugs (NSAIDs)
• Counseling on renal replacement modalities (peritoneal dialysis, hemodialysis, transplant)
• Timely vascular access placement for hemodialysis
• Pregnancy risks in ESRD
• Avoiding phosphate-rich foods[58]
• Potassium restriction
• Sodium and water restriction to prevent volume overload
• Protein restriction to delay uremic symptoms[59]
• Salt intake reduction to slow diabetic CKD progression

Pearls and Other Issues

• ESRD is a terminal illness with GFR < 15 mL/min.
• Diabetic nephropathy and hypertension are leading ESRD causes in the U.S.
• Other causes include glomerulonephritis, cystic kidney disease, recurrent infection, chronic obstruction.
• Presentation includes nausea, vomiting, metabolic/electrolyte derangements, seizures, coma, bleeding, fluid overload, unresponsive hypertension, uremic pericarditis.
• Vigilant GFR and proteinuria monitoring in diabetics and non-diabetics is crucial in CKD management.
• Early specialist referral is vital for timely dialysis or transplant planning.

Enhancing Healthcare Team Outcomes

ESRD management requires a dedicated interprofessional team for disease control and outcome improvement. Preventing disease progression is key.

An ideal team includes a nurse educator, specialized pharmacist, nutritionist, social worker, primary care provider, and nephrologist.

Nurse educators are vital for patient education on lifestyle changes to prevent CKD progression and protect arms for future fistula placement, restricting venipunctures and BP readings on that arm during hospitalization.

Pharmacists identify CKD patients, provide medication instructions (avoiding nephrotoxins), and guide providers on kidney-affecting medications.

Trained nutritionists guide patients on appropriate diet plans.[60]

Social workers ensure patient support systems and financial resources for therapy.

Effective outcomes require accurate records, team communication, and collaborative action for optimal patient care. [Level 5]

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References

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