Renal Handling of Citrate in Chronic Renal Insufficiency

Abstract

Citrate is a relevant component of the inhibitory potential of the urine environment. Its excretion and renal handling have been widely studied in subjects with normal renal function, but little is known about changes induced by chronic renal insufficiency. We have investigated renal handling of citrate in 50 patients with different degrees of renal insufficiency as compared to 30 healthy subjects with normal renal function. Among patients 34 were defined as having mild renal insufficiency based on a GFR of 80 through 40 ml/min/1.73 m² BSA, while 16 had moderate-to-severe renal failure, defined by a GFR ranging from 40 to 20 ml/min/1.73 m² BSA. Serum citrate increased in mild renal insufficiency, while it tended to be restored to normal values at more advanced renal failure. There was a stepwise decrease in the filtered load of citrate as GFR decreased, while its renal clearance was significantly reduced only at higher degrees of renal failure. This behavior was due to an increase in the fractional excretion of citrate which was inversely related to the decrease in GFR (p = 0.015). These data suggest that serum citrate levels and excretion are governed by renal mechanisms at mild degrees of renal insufficiency; in these conditions citrate is shown to behave conformly to other poorly reabsorbable anions such as sulfate. At more advanced renal failure the ensuing metabolic acidosis plays a crucial role as a regulatory factor of both serum concentration and renal handling of citrate, by increasing cellular uptake and metabolism as well as tubular reabsorption of this anion. Thus, even the severely diseased kidney seems to respond to acid-base imbalance as efficiently as the normal kidney does.

Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients

“…Plasma concentrations of aspartate aminotransferase were increased in the noncirrhotic group, but there was no difference in alanine aminotransferase concentrations, blood gas analysis, acid-base state, electrolyte concentrations, and variables of renal function. In the control group, all but one baseline concentration of citrate were within the normal range (Ͻ0.17 mmol/L) (17). In contrast, all cirrhotic patients showed increased citrate concentrations at baseline (Table 3).…”

“…According to published literature, a stepwise decrease in the filtered load of citrate occurs with decreasing GFR, whereas renal clearance of citrate is significantly reduced only at higher degrees of renal failure (26). Urinary citrate clearance has been reported to be only 19 Ϯ 9 mL/min in healthy persons (17).…”

Efficacy of oral citrate administration in primary hyperoxaluria

“…Indeed, saturation was not normalized in all patients. Additional measures, notably a large fluid intake and early diagnosis, are crucial to prevent renal insufficiency which also depresses urinary citrate excretion [7,12]. Further experience in more patients is certainly needed in PHI, a disease carrying a prognosis that is difficult to predict.…”

Effect of Potassium Magnesium Citrate and Vitamin B-6 Prophylaxis for Recurrent and Multiple Calcium Oxalate and Phosphate Urolithiasis

“…Systemic acidosis, distal renal tubular acidosis, hypocalciuria, and hypomagnesemia are common acid-base disturbances that can cause calcium oxalate urolithiasis. Furthermore, electrolyte disorders [14], drugs [15,16], changes in diet [17], and other disorders can be associated with low urine citrate [18,19]. Genetic polymorphisms of VDR and NaDc-1 genes have also been linked with hypocitraturia [13].…”