The effect of some medications given to CKD patients on vitamin D levels.

BACKGROUND: Vitamin D deficiency and polypharmacy is a common problem over chronic kidney disease (CKD) population. OBJECTIVES: To assess the clinical and analytical characteristics of CKD patients with 25-OH-D3 deficiency (<15 ng/mL), including the possible role of associated drugs. METHODS: A single center observational review of 137 incident patients referred to our outpatient clinic with different stages of CKD and 25-OH-D3<15ng/mL (male gender 53.3%, mean age 70.8 [±16.1] years, mean GFR (MDRD-4) 43.6 [±25.5] ml/min/1.73 m²). 25-OH-D3 levels were collected in spring. Clinical and biochemical data and associated medications were recorded. RESULTS: Mean 25-OH-D3 levels were 8.23 [±4.03] ng/ml. Eighty-eight patients (64.7%) had 3 or more concomitant drugs. Only 7 patients (5.1%) were not receiving any medication. Patients were divided in three groups according the therapies into none (n=26), RAS inhibitors or allopurinol (n=81), and RAS inhibitors plus allopurinol (n=30); with the aim to study the influence of statin therapy. Patients under renin angiotensin (RAS) inhibitors or Allopurinol treatment presented significantly higher 25-OH-D3 levels (p=0.001 and p=0.01 respectively), however patients with Statins treatment had lower 25-OH-D3 level (p=0.039). Personal history of diabetes, cardiovascular events or other therapies did not modify 25-OH-D3 levels, adjusted by age and eGFR. CONCLUSIONS: CKD patients with vitamin D deficiency who received RAS inhibitors or Allopurinol treatment had higher 25-OH-D3 levels, however those with statins treatment had lower vitamin D levels. Randomized controlled trials are required to confirm these findings.

The effect of some medications given to CKD patients on vitamin D levels / Efectos de algunos fármacos administrados a los pacientes de ERC sobre los niveles de vitamina D

Background: Vitamin D deficiency and polypharmacy is a common problem over chronic kidney disease (CKD) population. Objectives: To assess the clinical and analytical characteristics of CKD patients with 25-OH-D3 deficiency (<15 ng/mL), including the possible role of associated drugs. Methods: A single center observational review of 137 incident patients referred to our outpatient clinic with different stages of CKD and 25-OH-D3<15ng/mL (male gender 53.3%, mean age 70.8 [±16.1] years, mean GFR (MDRD-4) 43.6 [±25.5] ml/min/1.73 m2). 25-OH-D3 levels were collected in spring. Clinical and biochemical data and associated medications were recorded. Results: Mean 25-OH-D3 levels were 8.23 [±4.03] ng/ml. Eighty-eight patients (64.7%) had 3 or more concomitant drugs. Only 7 patients (5.1%) were not receiving any medication. Patients were divided in three groups according the therapies into none (n=26), RAS inhibitors or allopurinol (n=81), and RAS inhibitors plus allopurinol (n=30); with the aim to study the influence of statin therapy. Patients under renin angiotensin (RAS) inhibitors or Allopurinol treatment presented significantly higher 25-OH-D3 levels (p=0.001 and p=0.01 respectively), however patients with Statins treatment had lower 25-OH-D3 level (p=0.039). Personal history of diabetes, cardiovascular events or other therapies did not modify 25-OH-D3 levels, adjusted by age and eGFR. Conclusions: CKD patients with vitamin D deficiency who received RAS inhibitors or Allopurinol treatment had higher 25-OH-D3 levels, however those with statins treatment had lower vitamin D levels. Randomized controlled trials are required to confirm these findings (AU)

Antecedentes: La deficiencia de vitamina D y la polifarmacia constituyen un problema común en la población con enfermedad renal crónica (ERC). Objetivos: Evaluar las características clínicas y analíticas de los pacientes de ERC con deficiencia de 25-OH-D3 (<15 ng/mL), incluyendo la función posible de los fármacos asociados. Métodos: Se realizó una revisión observacional en un único centro, de 137 pacientes incidentes remitidos a nuestra clínica ambulatoria con diferentes estadios de ERC y 25-OH-D3<15 ng/mL (varones 53,3%, edad media 70,8 [±16,1] año, GFR medio (MDRD-4) 43,6 [±25,5] ml/min/1,73 m2). Los valores de 25-OH-D3 se recolectaron en primavera. Se registraron los datos bioquímicos y los fármacos asociados. Resultados: Los niveles medios de 25-OH-D3 fueron de 8,23 [±4,03] ng/ml. Ochenta y ocho pacientes (64,7%) tomaban tres o más fármacos concomitantes. Únicamente siete pacientes (5,1%) no recibían medicación alguna. Los pacientes fueron divididos en tres grupos, conforme a las terapias: ninguna (n = 26), inhibidores RAS o Alopurinol (n = 81), e inhibidores RAS más alopurinol (n = 30), a fin de estudiar la influencia de la terapia de estatinas. Los pacientes sometidos a tratamiento de inhibidores de la renina-angiotensina (RAS) o Alopurinol presentaron unos niveles considerablemente superiores de 25-OH-D3 (p = 0,001 y p = 0,01 respectivamente), y sin embargo los pacientes con tratamiento de estatinas presentaron unos menores niveles de 25-OH-D3 (p = 0,039). La presencia de diabetes, episodios cardiovasculares u otras terapias no modificaron los niveles de 25-OH-D3, ajustados por edad y eGFR. Conclusiones: Los pacientes de ERC con deficiencia de vitamina D, sometidos a tratamiento de inhibidores RAS o Alopurinol reflejaron unos niveles superiores de 25-OH-D3, y sin embargo aquellos sometidos a tratamiento de estatinas reflejaron unos menores niveles de vitamina D. Se precisan ensayos aleatorizados controlados para confirmar estos hallazgos (AU)

Effects of dual blockade of the renin-angiotensin system in primary proteinuric nephropathies.

BACKGROUND: Blockade of the renin-angiotensin system (RAS) with angiotensin converting enzyme (ACE) inhibitors or with angiotensin II type 1 (AT1) receptor blockers has been shown to reduce proteinuria and to slow down the progression of renal disease in diabetic and non-diabetic primary proteinuric nephropathies. Additionally, this beneficial effect is not dependent on blood pressure control. METHODS: To assess and compare the effects of lisinopril (up to 40 mg/day), candesartan (up to 32 mg/day) and combination therapy (lisinopril up to 20 mg/day plus candesartan up to 16 mg/day) on urinary protein excretion, 45 patients with primary proteinuric nephropathies (urinary protein/creatinine ratio 3.8+/-2.4 g/g) and normal or slightly reduced renal function (CCr 95+/-33 mL/min) were enrolled in a six month multicenter, prospective, open, randomized, active-controlled and parallel-group trial with 1:1:1 allocation. Blood pressure goal was set at or below 125/75 mm Hg for all patients, with additional antihypertensive medication prescribed if required. RESULTS: Renal function, estimated by creatinine clearance, remained stable throughout the study. Hyperkalemia (K>5.5 mmol/L) was detected in 3.1% of all measurements in follow-up, and was more frequent in patients treated with lisinopril alone or lisinopril plus candesartan (P<0.001) than in those on candesartan alone. No other relevant adverse event was recorded. The blood pressure goal (<125/75 mm Hg) was achieved by week 4 in all treatment groups (P<0.005 when compared to baseline), and afterwards the mean systolic and diastolic blood pressure remained below these values until the end of the trial with no statistically significant differences between groups. Urinary protein/creatinine ratio (percentage reduction 95% confidence intervals CI) decreased in patients treated with lisinopril alone to -33% (CI -12-56) to -31% (CI 0-68) and to -50% (CI -9-90), in patients treated with candesartan to -28% (CI -12-45), to -41% (CI -30-52) and to -48% (CI -32-63), in patients treated with the combination of both to -60% (CI -44-77) to -54% (CI -38-69) and to -70% (CI -57-83) at two, three, and six months, respectively. All comparisons with baseline achieved statistical significance and treatment with combination therapy was statistically more effective in proteinuria reduction than treatment with candesartan alone at two and six months (P=0.004 and P=0.023, respectively) and than treatment with lisinopril only at two months (P=0.03). CONCLUSION: Dual blockade of the renin-angiotensin system with ACE inhibitors and AT1 receptor blockers produces a beneficial antiproteinuric effect that could not be explained only by the systemic blood pressure reduction. All treatments were well tolerated.