In end-stage renal disease, the kidneys' functional capacity becomes severely compromised. Initially, in chronic kidney disease, the remaining functional nephrons adapt by compensating through hyperfiltration and hypertrophy to maintain the GFR. However, this compensatory mechanism ultimately leads to glomerular damage and sclerosis, contributing to further nephron loss. Factors such as nephrotoxins (e.g., non-steroidal anti-inflammatory drugs), systemic hypertension, uncontrolled diabetes, and proteinuria can accelerate kidney damage and progression to ESRD. As the disease advances, patients experience significant disruptions in the body’s ability to excrete potassium, leading to hyperkalemia, and in its ability to manage acid-base balance, resulting in metabolic acidosis.
One of the key complications of ESRD is metabolic acidosis, which arises when the kidneys are no longer able to produce enough ammonia to excrete endogenous acids in the form of ammonium. The accumulation of phosphate, sulfate, and organic acids in ESRD patients also leads to a high anion gap acidosis, which can contribute to negative nitrogen balance, muscle wasting, and reduced albumin synthesis. Furthermore, the acidic environment causes the bones to act as buffers, leading to demineralization and the development of renal osteodystrophy, a bone disease commonly seen in patients with advanced CKD and ESRD.
