End Stage Renal Disease and Uremia

Uremia

the biochemical and clinical syndrome characteristic of symptomatic renal disease

major signs (BRS): azotemia; acidosis (from accumulations of sulfates, phosphates, organic acids); hyperkalemia;

abnormal fluid volume control (initial inability to concentrate urine, later inability to dilute urine);

hypocalcemia (ß renal vit D metabolism); anemia from ß erythropoietin; HTN

occurs with GFR < 15 mL/min and results from decreased renal function leading to toxin retention, hormone abnormalities, and disturbances of ECF and ICFcomposition

Uremic Solute Retention – what is the toxin?

urea: toxic in very acute high dose, but even high conc. are not toxic if infusion is slow

not toxic, but urea level correlates well with symptoms, so it is a good indicator

guanidine: in vitro shown to inhibit NaK-ATPase, but little evidence for toxic properties in vitro

b₂ microglobulin, PTH, myoinostiol urofuranic acids, polyamines also sited Þ weak evidence

aluminum (from dialysis machine): microcytic anemia, bone disease, dialysis dementia

Alterations in Uremia

hormonal – ß erythropoietin Þ normochromic normocytic anemia

ß conversion of vit D₃ Þ secondary hyperparathyroidism Þ renal osteodystrophy

ß testosterone/estrogen Þ sexual dysfunction/infertility (etiology unknown)

ß insulin clearance Þ increased incidence of hypoglycemic incidents in DM patients (need to adjust insulin dosing)

ECF Composition – metabolic acidosis: due to ß titratable acid and ammonium Þ impaired pp and bone metabolism

hyperkalemia: when GFR < 5-10 mL/min (if GFR > 10, then need to look for other cause of hyperkalemia)

K rarely goes above 6 - 6.5 in uremic syndrome due to enhanced gut excretion and intracellular shift

hyperphosphatemia: when GFR < 30

ICF Composition: Ý intracellular Na and Ca (due to ß NaK-ATPase, ß Ca-ATPase)

Cardiovascular: the most important factor in uremic syndome

uremic pericarditis: accounted for 50% of deaths before dialysis Þ now rare due to dialysis

Symptoms: chest pain, pericardial rub, tamponade

dialysis associated pericarditis: almost always hemorrhagic, etiology unknown: inadequate dialysis?, infection?

Symptoms: leukocytosis, chest pain, fever
Treatment: intense dialysis

arrhythmias due to electrolyte imbalance, calcifications, CAD

hypertension: most common problem in CRF; Ý renin, Ý SNS, Ý pressors; Na/H₂O retention is most important

occurs in 80% of ESRD patients; 50% of ESRD HTN can be controlled by dialysis

atherosclerosis is accelerated Þ increased incidence of CAD

uremic cardiomyopathy: uremic serum is shown in animals to uncouple myocardial ox/phos

cardiac calcifications: mainly valves, conduction system (causes arrhythmias, heart block)

CHF: due to HTN, CAD, volume overload, anemia, hemodialysis vascular access can lead to high CO failure

Nervous

uremic encephalopathy: Symptoms - impaired memory, insomnia, apathy, irritability, lethargy, stupor, coma

signs: myoclonus, asterixis, tonic-clonic seizures, diffuse slowing of cerebral activity on EEG

pathogenesis unknown: ß cerbral blood flow?; ß cerebral oxygen utilization?

peripheral neuropathy: symmetrical, distal Þ proximal sensorimotor neuropathy

pathogenesis: segmental demyelination, axon loss, Wallerian degeneration

autonomic neuropathy: orthostatic hypotension (without tachycardic response); impaired sweating; abnormal response to valsalva maneuver

GI: may be first or only complications on presentation; anorexia with nausea and vomiting is suggestive of CRF

other symptoms: salty metalic taste, dry mouth, thirst, upper GI bleed, ammonia odor

pathology: GI mucosal changes, edema, capillary hyperemia, angiodysplasia, superficial ulcerations, hemorrhagic and necrotic lesions due to Ý ammonia production in gut

Hematologic: normochromic normocytic anemia due to ß erythropoietin, Ý erythropoietin inhibitors, ß RBC lifespan

crit is rarely below 30 in CRF, so if it is, look for other causes

uremic bleeding: due to platelet dysfunction; Ý NO/PGI₂; abnormal vWF structure

Metabolic – reduced tissue response to insulin Þ carbo intolerance and Ý insulin levels

ÝÝ TG, Ý cholesterol Þ similar to Type IV hyperlipoproteinemia

Ý protein catabolism, ß synthesis Þ negative nitrogen balance

Endocrine: dysfunction of hypothalamic-pituitary-adrenal axis Þ Ý LH, Ý FSH, Ý PL, Ý LHRH, ß test/prog

Symptoms: impotence, ß libido, testicular atrophy, ß sperm count, amenorrhea, infertility

Treatment

conservative: dietary restriction of Na, K, P, protein, water (1000 mL/d)

meds: high-dose loop diuretics; K-binding resins; alkali to combat acidosis; phosphate binders; erythropoietin, iron; DDAVP, cryoprecipitate, conjugated estrogens for bleeding

hemodialysis –indications: fluid overload; hyperkalemia; metabolic acidosis; uremic pericarditis; uremic symptomatology

vascular access: native AV fistula, synthetic AV graft; catheter
conventionally 3-4x/wk, 3-4 hrs

peritoneal dialysis – same indications as above; also KT/V_urea < 2.0 (a measure of urea clearance)

renal transplant: contraindicated in severe vascular disease