The objective of this review is to draw people’s attention to the unexpected variation in non-renal drug clearance in patients with end-stage kidney disease (CKD stage V). As listed below, this review describes some cases of increase of bioavailability, decrease of hepatic clearance, and increase of non-renal clearance in patients with end-stage kidney disease:
1. Cases of increase of bioavailability: propranolol and pravastatin
2. Cases of inhibition of hepatic metabolism: losartan and warfarin
3. Cases of inhibition of hepatic uptake: erythromycin, fexofenadine, and digoxin
4. Cases of increase of non-renal clearance: CPT-11
5. Cases of disease-specific drug interaction: interaction between colchicine and clarithromycin, and digoxin and fexofenadine
The abovementioned cases show that we should be careful about not only the decrease in renal function but also the variation in non-renal function, such as increase of bioavailability, decrease of hepatic clearance, and increase of non-renal clearance in patients with end-stage renal failure. In addition, we should be cautious that patients with normal renal function do not suffer from unexpected drug interaction.

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Patients undergoing hemodialysis frequently develop a deficiency in water soluble vitamins, because they are restricted to a high potassium diet. In addition, water soluble vitamins are easily removed during hemodialysis, and it has been reported that the consumption of anti-oxidant vitamins by increased oxidative stress could induce a deficiency of certain types of vitamins in these patients. To address this problem, “Nephvitan KD (KD-MV)”, the multi-vitamin chewable tablet supplement for patients undergoing hemodialysis was developed and released for the first time in Japan. The efficacy and the safety of KD-MV were evaluated in the present study.
Eighty three maintenance hemodialysis patients participated in a double blind randomized placebo controlled crossover trial for one year. Crossover was carried out six months after the beginning of the trial. Patients in group A had taken KD-MV for the first six months of the trial, and then took a placebo for the last six months. Conversely, patients in group B were given a placebo for the first six months, and were then given KD-MV for the last six months. The quality of life for the patients with kidney disease were evaluated by means of a questionnaire, measurements of oxidative stress, and various laboratory data were used as a marker for the efficacy of KD-MV. Reports by the medical staff members and patients themselves were used to evaluate the safety of KD-MV. A statistical analysis was carried out for patients with a compliance rate of more than 75% and without a lack of the blood samples, the analysis objects were then 45 patients.
The results suggested that, based on the tendency for the symptoms and the influences of the daily life, the KDQOL items were as the result of taking KD-MV. It is particularly noteworthy that muscle cramps and numbness were improved. The values for alanine aminotransferase and alanine aminotransferase were significantly increased（⊿AST; 3.4±5.6 IU/L，p<0.001，⊿ALT; 4.2±6.5 IU/L，p<0.001）, but no significant differences were found in other laboratory tests or for the markers of oxidative stress. Indefinite complaints were observed in only three patients, but the relationship between the ingestion of KD-MV and adverse effects were not clarified. Although no change in major laboratory tests and markers of oxidative stress were observed, the quality of life for the hemodialysis patients tended to improve. Therefore, the ingestion of KD-MV may be useful for patients undergoing hemodialysis.

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Purpose: To examine the efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin in diabetic patients on hemodialysis. Subjects: 46 diabetic hemodialysis patients who were treated with vildagliptin for more than 3 months (initial treatment group, 3 patients treated with vildagliptin for the first time; changeover group, 18 patients were changed from drugs prescribed until then to vildagliptin; and supplement group, 25 patients were added vildagliptin to regimens prescribed until then). Methods: The initial dose of vildagliptin was 25 mg, and its maximum dose was 50 mg. The efficacy of vildagliptin was determined by the plasma glucose at the start of hemodialysis (PG) and glycated albumin (GA) levels 3 months after the administration of the drug. Results: The PG and GA levels significantly decreased 3 months after the administration of vildagliptin (from initial to 3 months later: PG, 185 ± 52 to 159 ± 45 mg/dL, p< 0.01; GA, 24.9 ± 5.6 to 22.8 ± 4.3%, p< 0.01; vildagliptin dose, 33.7 ± 12.0 mg). In the initial treatment group, the PG and GA levels decreased from 195 ± 25 to 155 ± 16 mg/dL, and from 22.3 ± 1.8 to 19.7 ± 1.6%, respectively. For the changeover group, the most common treatment before changeover was insulin regimen (11 ± 8 units), and the PG and GA levels did not increase after changeover. In the supplement group (before supplement: mitiglinide for 14 patients, α-glucosidase inhibitor (α-GI) for 2 patients, and mitiglinide + α-GI for 9 patients), the patients showed significant decreases in the PG and GA levels (PG, 200 ± 40 to 160 ± 41 mg/dL, p< ion: Vildagliptin is an effective and safe drug for hemodialysis patients if it is carefully administered at low doses.

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