Kinetics of Serum Carnitine Fractions in Patients with Chronic Kidney Disease Not on Dialysis.

BACKGROUND: Carnitine plays a pivotal role in energy synthesis through ß-oxidation in mitochondria. Serum and tissue levels of free carnitine are significantly decreased in dialysis patients, whereas acylcarnitine levels are increased. However, the precise kinetics and fate of carnitine fractions in chronic kidney disease (CKD) patients who are not on dialysis have not been clarified. This study aims to determine the kinetics of serum carnitine fractions in patients who were not on dialysis. METHODS: Seventy-five CKD patients not on dialysis were recruited in this study. Serum and urinary carnitine fraction levels were measured to evaluate the kinetics and regulation of serum carnitine fractions. Carnitine fractions were measured by the enzymatic cycling method. RESULTS: Total and free serum carnitine levels did not change with progression of CKD, whereas acylcarnitine levels and the acyl/free carnitine ratio significantly increased. Serum acylcarnitine levels were inversely associated with estimated glomerular filtration rate (r2 = 0.239, p < 0.001), but free carnitine levels were not. Serum free carnitine levels were positively associated with urinary free carnitine excretion (r2 = 0.214, p < 0.001), but serum acylcarnitine levels were not. Multiple stepwise regression analysis revealed that urinary free carnitine excretion and blood urea nitrogen were independent determinants of serum free carnitine and acylcarnitine levels, respectively. CONCLUSIONS: The present study demonstrated that serum acylcarnitine levels increased with renal dysfunction independent of urinary excretion levels. Serum free carnitine was not affected by renal function in CKD patients who were not on dialysis.

Effect of tolvaptan on renal involvement in patients with autosomal dominant polycystic kidney disease according to different gene mutations.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder caused by mutations in the polycystic kidney disease (PKD) gene. Although tolvaptan has benefits for renal involvement, the different effects depending on the gene mutation type are unknown. Thus, we explore the different effects of tolvaptan on the annual changes in total kidney volume (%TKV) and estimated glomerular filtration rate (eGFR) according to the gene mutation type in ADPKD patients. METHODS: In total, 135 ADPKD patients were screened, and 22 patients taking tolvaptan for at least a year were retrospectively studied at the Kurume University Hospital. We examined the decline in renal function and %TKV by computed tomography and analyzed the gene mutation. Patients were classified into the following four groups according to gene mutation type: PKD1-truncated, PKD1-non-truncated, PKD2, and mutation not found. Patients were treated with tolvaptan, and the effects of tolvaptan were analyzed according to the gene mutation type. RESULTS: Patients (age: 52.3 ± 11.2 years) were administered tolvaptan at a dose of 45 or 60 mg. No variation was observed in the annual changes in eGFR (%eGFR) (before: - 10.5% ± 13.9%, after: - 14.4% ± 8.1%, P = 0.139), whereas %TKV was significantly improved after the tolvaptan treatment (before: 14.9% ± 8.0%, after: - 5.4% ± 7.6%, P < 0.001). Unlike %eGFR, tolvaptan treatment significantly improved %TKV, regardless of the type of gene mutation. CONCLUSIONS: A year treatment with tolvaptan significantly improved %TKV in patients with ADPKD, regardless of the gene mutation type.