Primary systemic carnitine dehciency. II. Renal handling of carnitine

Abstract

Renal tubular reabsorption rates, reabsorptive maxima, and apparent renal plasma excretory thresholds for carnitine were determined in four children with primary systemic carnitine deficiency (SCD), in two of the mothers of these children, in one patient with muscle carnitine deficiency (MCD), and in seven controls. In SCD the observed values were well below those found in six of seven controls, but one control, a healthy 20-year-old woman with normal muscle carnitine level, also exhibited a renal carnitine leak. In the two mothers of patients with SCD and in the case of MCD some of the parameters of the renal handling of carnitine were slightly altered. Tubular secretion of short-chain acylcarnitines was noted in patients and controls at high plasma free carnitine levels. Augmented excretion of short-chain acylcarnitines occurred at lower plasma free carnitine levels in the patients with SCD than in the other subjects. Free and short-chain acyl-carnitines may compete for the same renal reabsorptive site. A renal defect cannot fully account for primary SCD but may contribute to the carnitine depletion in this disorder.

Renal Handling of Carnitine in Secondary Carnitine Deficiency Disorders

“…Because the normal mean fractional excretion of free carnitine is only 1-2%, the method tends to overestimate the threshold. This may partly account for fact that the value of 56 pmol/L found in the control child was considerably higher than the value of 35-40 pmol/L found in normal subjects by Engel et al (12) using carnitine loading. Moreover, as noted above, the effects of prior carnitine treatment had not disappeared completely in this child by the end of the study period.…”

“…The MCAD, IVA, and PA patients had estimated renal thresholds for free carnitine between 10 and 25 pmol/L, well below either that of the control child or the range found by the carnitine infusion method. In both of the LCAD patients, the estimated renal thresholds for free carnitine were lower than that of the control child but not below those reported by Engel et al (12). There was no evidence of other renal tubular dysfunction such as glucosuria or phosphate or bicarbonate wasting in any of the patients, and in vitro studies have shown that the carnitine transport system is normal in MCAD and LCAD (9).…”

“…Clearance rates were plotted against plasma concentrations and the intercept with a clearance rate of 5% estimated by linear interpolation. The normal renal threshold for free carnitine, based on a more precise method using short-term carnitine infusions, is similar to normal plasma concentrations of free carnitine (12). Table 1 shows the concentrations of plasma carnitine and rates of urinary carnitine excretion in 12 patients with five genetic defects in acyl-CoA oxidation obtained while they were not receiving carnitine treatment and compares them with values found in control children.…”

“…A second possible mechanism is that renal conservation of free carnitine is impaired, leading to carnitine deficiency in a manner similar to that seen in patients with a genetic defect in carnitine transport (9,10) or the renal Fanconi syndrome (I I). This mechanism is supported by observations that acylcarnitines inhibit the transport of free carnitine in cultured cells (10) and that the renal threshold for free carnitine is decreased in patients with MCAD (2,12,13). Previous studies of the initial stages in the development of carnitine deficiency in patients given pivalate and in patients with a genetic defect in carnitine transport have provided the clearest method of distinguishing between these two different mechanisms (6,9).…”

Is there a Role for Oral L-Carnitine Therapy in Anemia and Cardiac Dysfunction Management in Egyptian Patients on Maintenance Hemodialysis?

“…However, during the first month of hemodialysis therapy, plasma L-carnitine concentrations declined by approximately 30%, and after 12 months they had decreased by approximately 40%, with a pattern suggesting an ongoing decline (12 L-carnitine is not bound to plasma proteins and therefore is freely filtered at the Glomerulus (13). However, at plasma concentrations greater than approximately 60 mmol/L, fractional reabsorption begins to decrease because of partial saturation of the tubular transporter (14).…”