How is uremia managed?

Management of Uremia

Uremia requires a systematic approach targeting both immediate life-threatening complications through dialysis and chronic manifestations through multisystem supportive care, with the primary goal of preventing mortality from cardiovascular events, encephalopathy, and bleeding complications. 1, 2

Immediate Indications for Dialysis Initiation

The following are absolute indications requiring urgent renal replacement therapy:

• Uremic pericarditis or pleuritis - these represent overt uremic symptoms that will not resolve with conservative management 1, 2, 3
• Uremic encephalopathy - manifesting as altered mental status, seizures, asterixis, or coma 2, 4
• Uremic neuropathy - a sign of advanced uremic toxicity requiring immediate dialysis initiation 3
• Volume overload refractory to diuretics - particularly when causing pulmonary edema 3
• Persistent hyperkalemia (>5.3 mEq/L) in the setting of uremic symptoms 3
• Severe metabolic acidosis (bicarbonate <18 mmol/L) with clinical implications 1
• Bleeding diathesis from platelet dysfunction 2

Timing of Dialysis Initiation

For patients without absolute indications, initiate dialysis when eGFR falls below 10-15 mL/min/1.73 m² AND uremic symptoms develop, rather than at a predetermined eGFR threshold alone. 1, 2

• Monitor for uremic symptoms at each consultation using standardized validated assessment tools 1
• Key symptoms include: reduced appetite, nausea, persistent fatigue/lethargy, hiccups, altered taste, and pruritus 2
• Earlier initiation (eGFR 10-14 mL/min) does not improve outcomes compared to later initiation (eGFR 5-7 mL/min) in asymptomatic patients 1
• Protein-energy malnutrition developing despite vigorous dietary optimization is an indication for dialysis initiation 1

Dialysis Prescription and Adequacy

Target a minimum delivered dose of total small-solute clearance (Kt/V urea) of at least 1.7 per week for hemodialysis patients. 1

• Measure total solute clearance within the first month after initiating dialysis and at least every 4 months thereafter 1
• For patients with residual kidney function >100 mL/day urine volume, measure 24-hour urine collection every 2 months 1
• Residual kidney function is more important for patient survival than peritoneal small-solute clearance 1
• Unscheduled measurements should be performed when urine volume changes abruptly or during hospitalization to avoid prolonged insufficient dialysis 1

Management of Metabolic Complications

Metabolic Acidosis

• Consider pharmacological treatment with or without dietary intervention when serum bicarbonate <18 mmol/L 1
• Monitor treatment to ensure bicarbonate does not exceed upper limit of normal and does not adversely affect blood pressure, potassium, or fluid status 1

Hyperkalemia

• Implement individualized approach combining dietary and pharmacologic interventions 1
• Limit intake of foods rich in bioavailable potassium (particularly processed foods) for CKD G3-G5 patients with history of hyperkalemia 1
• Assessment and education through renal dietitian is advised 1

Hyperuricemia

• Offer uric acid-lowering intervention only for symptomatic hyperuricemia (gout) 1
• Prescribe xanthine oxidase inhibitors (allopurinol) in preference to uricosuric agents 1
• For acute gout treatment, use low-dose colchicine or intra-articular/oral glucocorticoids rather than NSAIDs 1
• Do not use uric acid-lowering agents for asymptomatic hyperuricemia to delay CKD progression 1

Management of Anemia

Anemia in uremia results from both erythropoietin deficiency and uremic toxin accumulation impairing erythropoiesis. 5

• Erythropoiesis-stimulating agents (ESAs) are indicated but not effective for transfusion-dependent anemia 1
• Provide RBC transfusions for symptomatic anemia 1
• In transplant candidates, use leukocyte-reduced blood products to prevent HLA alloimmunization 1
• Consider iron chelation for patients receiving >20 transfusions and/or ferritin >2500 ng/mL in low/intermediate-1 risk patients, though the role remains unclear 1

Management of Bleeding Complications

• Provide platelet transfusions for thrombocytopenic bleeding or platelet count <10,000/mm³ 1
• Consider antifibrinolytic agents for bleeding refractory to transfusions 1
• Recognize that uremic patients have platelet dysfunction despite normal platelet counts 2

Cardiovascular Risk Management

Initiate statin therapy for all adults ≥50 years with eGFR <60 mL/min per 1.73 m² not on chronic dialysis. 1

• Use statin or statin/ezetimibe combination for CKD G3a-G5 1
• Counsel patients at baseline and throughout disease course regarding cardiovascular risk factors (smoking, diet, exercise) 1
• Monitor for and treat hypertension refractory to ≥4 antihypertensive agents as this warrants specialist referral 1

Nutritional Management

Screen patients with CKD G4-G5, age >65, or symptoms of involuntary weight loss twice annually for malnutrition using validated assessment tools. 1

• Enable medical nutrition therapy under supervision of renal dietitians for patients with signs of malnutrition 1
• Recognize that protein-energy wasting is a component of the "residual syndrome" that may require treatments independent of dialysis 1
• Monitor for heightened catabolism and insulin resistance 2

Infection Prevention

• Provide antibiotic prophylaxis for recurrent infections 1
• In splenectomized patients, give antibiotic prophylaxis per IDSA guidelines 1
• Consider G-CSF or GM-CSF for recurrent infections in neutropenic patients 1
• Administer appropriate vaccinations 1

Multidisciplinary Care and Referral

Enable access to patient-centered multidisciplinary care team including dietary counseling, medication management, education about KRT modalities, transplant options, and psychological/social care. 1

Refer to specialist kidney care when:

• eGFR <30 mL/min per 1.73 m² 1
• ≥5% 5-year risk of requiring KRT by validated risk equation 1
• Sustained fall in GFR >20-30% in those initiating hemodynamically active therapies 1
• Persistent abnormalities of potassium, acidosis, anemia, bone disease, or malnutrition 1

Critical Pitfalls to Avoid

• Do not rely solely on BUN or creatinine levels to diagnose uremia - the clinical syndrome is defined by signs and symptoms, not laboratory values alone 2
• Recognize that uremic symptoms are nonspecific and can have alternative causes, particularly in elderly patients on polypharmacy 2
• Do not delay dialysis when absolute indications are present - pericarditis, encephalopathy, and neuropathy require immediate intervention 2, 3
• Avoid NSAIDs in CKD patients - use alternative agents for pain and gout management 1
• Be alert to subtle symptoms indicating need for more dialysis than standard guidelines recommend, as individual toxin generation rates vary 1

Residual Syndrome Management

After controlling immediate life-threatening uremia with dialysis, address the "residual syndrome" with targeted therapies beyond dialysis adequacy. 1

This syndrome includes:

• Anemia requiring ESAs or transfusion 1
• Hyperparathyroidism requiring phosphate binders and vitamin D analogs 1
• Pruritus requiring specific antipruritic therapy 1
• Psychological depression requiring psychiatric intervention 1
• Protein-energy wasting requiring nutritional support 1

The underlying cause of kidney disease (diabetes, lupus) may continue contributing to symptoms and requires ongoing disease-specific management 1. Research suggests retention of protein-bound uremic toxins, gut microbiome products, and inflammatory mediators contribute to this syndrome beyond what standard dialysis can address 1, 6, 7.