We retrospectively analyzed the clinical records of 45 patients with CKD who had maintained dosing with an extended release formulation of fixed low-dose (500 mg) niacin (Niaspanor; Merck KGaA, Darmstadt, Germany) at Dong-A University Hospital between January 2009 and June 2011. We excluded eight patients with CKD stage 1 and 5. We also excluded three patients who had additional prescriptions such as 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statin) or omega-3 fatty acid (FA) during the investigational period. Among the 34 enrolled patients, we additionally excluded three patients who had quit taking niacin due to adverse drug reactions. Finally, we enrolled 31 patients with CKD who had taken niacin at a fixed dose of 500 mg/day for 6 months and analyzed 34 patients for adverse effects. Niacin was prescribed for reducing triglyceride and increasing HDL levels in the enrolled 31 patients with CKD. There were no patients who were hospitalized during the investigational period in the niacin group. We randomly selected 60 patients with CKD who had been taking a statin for 9 months or more as a control group. We defined baseline point of control group as the point after using statin for 3 months because the control group should be having controlling levels of cholesterol similar to the niacin group. We excluded 14 patients with CKD stage 1 and 5. We also excluded five patients whose baseline HDL level was >40 mg/dL in men, and >50 mg/dL in women so as to match with the niacin group. We excluded three more patients who were hospitalized and seven who had prescription changes such as addition of omega-3 FA during the investigational period. Finally, we enrolled 30 patients with CKD who had been taking a statin for 9 months or more as the control group.

We defined baseline as the first prescription point of niacin in the niacin group and as the point after receiving a 3-month statin prescription in the control group. The following demographic characteristics and comorbidities were collected: age, gender, smoking history, body mass index, and underlying comorbidities including diabetes mellitus, coronary artery disease, peripheral arterial disease, and cerebrovascular disease. We defined coronary artery disease as those with previous diagnosis by coronary angiography, echocardiography, electrocardiography changes, elevated levels of troponin I, or myocardial single-photon emission computed tomography scans. We defined cerebrovascular disease as those with previous ischemic stroke and brain hemorrhages diagnosed by clinical manifestation and magnetic resonance imaging. We defined peripheral arterial disease as those with previous amputation of extremities or diagnosis by Doppler ultrasonography of extremities.

We investigated systolic and diastolic blood pressures at baseline and after 12 and 24 weeks. We analyzed the following laboratory findings at the same intervals: hemoglobin, platelet count, calcium, phosphorus, blood urea nitrogen, creatinine, glomerular filtration rate (GFR), albumin, uric acid, aspartate aminotransferases, alanine aminotransferase, alkaline phosphatase (ALP), total cholesterol, triglyceride, HDL, LDL, C-reactive protein, HbA1c, random urine protein-to-creatinine ratio, and random urine microalbumin-to-creatinine ratio. We could not investigate serum parathyroid hormone, urine sodium, and urine phosphorus levels because these data were missing in most of the enrolled patients. GFR was estimated using the modification of diet in a renal disease study formula. The patients who were taking calcium-channel blockers, beta blockers, nitrates, furosemide, spironolactone, digoxin, low-dose aspirin, clopidogrel, allopurinol, omega-3 FA (Omacor; Pronova, Sandefjord, Norway), statins, angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin II receptor blockers (ARBs) during the follow-up period were noted.

Descriptive statistics that used means and standard deviations are presented as continuous variables, with the exceptions of the urine albumin-to-creatinine ratio and urine protein-to-creatinine ratio, which used means and standard error. The nonparametric Mann–Whitney U test was used to compare baseline data between the control and the niacin groups. The Fisher exact test was used to compare categorical data between the two groups. The nonparametric Wilcoxon rank-sum test was applied to compare baseline data with 12- and 24-week data. A P value ≤0.05 was considered to be statistically significant for all the tests. Statistical analyses were performed using SPSS 19.0 (SPSS Inc., Chicago, IL, USA).

The baseline characteristics were similar between the two groups (Table 1, Table 2). The mean age, lipid profiles, phosphorous levels, creatinine, and GFR were not significantly different between the niacin group and the control group.

In the niacin group, the percentage of patients already treated with a statin, omega-3 FA, both niacin and omega-3 FA, and neither of the medications was 67.7%, 48.8%, 38.7%, and 19.6%, respectively. The percentage of patient taking omega-3 FA was 36.7% in the control group. The percentage of patient taking ACEI in the niacin group was significantly lower than that in the control group, but administration of ARB medication was similar between the two groups. The percentage of patients taking both an ACEI and an ARB in the niacin group was significantly lower than that in the control group (6.5% vs. 26.7%, P=0.043).

Among the 34 patients with CKD who were prescribed niacin, five patients (14%) complained of adverse effects of niacin and three patients (8%) discontinued niacin. Three patients (8%) experienced flushing, one had flushing with itching, and another had anorexia. Two patients (5%) who experienced mild flushing found the side effect tolerable and continued to take niacin throughout the 24-week period without cessation. The mean platelet counts were significantly decreased at 12 and 24 weeks in the niacin group, but the counts remained within normal ranges.

There were no changes in statin dose, ACEI, or ARB medications during the investigational period in either the niacin group or the control group. There were no significant changes in blood pressure, creatinine, LDL cholesterol, C-reactive protein, random urine protein-to-creatinine ratio, and random urine microalbumin-to-creatinine ratio in both groups (Table 3).

HDL cholesterol was significantly increased at 12 (P=0.003) and 24 weeks (P<0.001) compared with baseline in the niacin group, but HDL cholesterol was significantly increased at only 24 weeks (P=0.001) compared with baseline in the control group (Fig. 1A). Triglyceride level was significantly decreased at 12 (P=0.016) and 24 weeks (P=0.001) compared with baseline in the niacin group, but was significantly decreased at only 24 weeks (P=0.007) compared with baseline in the control group (Fig. 1B).

Serum phosphorus levels (P=0.006) and calcium–phosphorus product (P=0.001) were significantly decreased at 24 weeks compared with baseline in the niacin group, but there was no change in serum phosphorus levels (Fig. 1C) and calcium–phosphorus product at 24 weeks compared with baseline in the control group. GFR (P=0.016) was significantly increased at 24 weeks compared with baseline in the niacin group, although serum creatinine was not significantly changed in the niacin group (Fig. 1D). GFR was significantly increased (55.4±24.5 mL/min/1.73 m² vs. 62.8±28.3 mL/min/1.73 m², P=0.016) and serum creatinine was significantly decreased (1.5±0.8 mg/dL vs. 1.3±0.7 mg/dL, P=0.021) at 24 weeks compared with baseline in the niacin subgroup without statin medication. There were no significant changes in GFR and serum creatinine at 24 weeks compared with baseline in the niacin subgroup taking statin. Uric acid level was significantly decreased (P=0.033) and ALP level was significantly increased (P=0.019) at 24 weeks compared with baseline in the niacin group.