To ensure adequate solute, water, and acid-base balance, the surviving nephrons in the diseased kidney must adjust by increasing their filtration and excretion rates.
Without such adjustments, patients with chronic renal failure are vulnerable to edema formation and severe volume overload, hyperkalemia, hyponatremia, and azotemia. Thus, during progressive renal disease, sodium balance is maintained by increasing fractional excretion of sodium by the nephrons.
Acid excretion is usually maintained until the late stages of chronic renal failure, when the GFR falls to less than 15 mL/min Initially, increased tubular ammonia synthesis provides an adequate buffer for hydrogen in the distal nephron Later, a significant decrease in distal bicarbonate regeneration results in hyperchloremic metabolic acidosis. Further loss of nephronal mass leads to retention of organic ions such as sulfates and results in anion gap metabolic acidosis and titration of bone stores. Once renal insufficiency is established, the tendency is for renal disease to progress regardless of the initial insult. Glomerular sclerosis ensues, most likely the result glomerular hyperfiltration and/or hypertension. Compensatory glomerular hypertrophy is invariably associated with tubular hypertrophy in the remaining nephrons. Tubular hypertrophy is associated with increased energy expenditure, a metabolic event related to generation of reactive oxygen metabolites. Reactive oxygen metabolites have been proposed as a mechanism of tubulointerstitial damage in animal models. In addition, hyperlipidemia is believed to play a role in progressive renal insufficiency through mesangial proliferation and sclerosis.
Although this adaptive mechanism can be beneficial in maintaining fluid, electrolyte, and acid-base balance, the long-term consequence is perpetuation of tubulointerstitial damage. Interventions that reduce intraglomerular pressure such as protein restriction and the use of angiotensin-converting enzyme inhibitors have been shown to help attenuate progression of renal disease.
this subject illustrates different pathways through which these maladaptive mechanisms can result in progression of renal insufficiency and, ultimately, ESRD.