Antiproteinuric effect of oral paricalcitol in chronic kidney disease

Agarwal, Rajiv; Acharya, Muralidhar; Tian, Jinying; Hippensteel, Richard; Melnick, Joel Z.; Qiu, Ping; Williams, Laura A.; Batlle, Daniel

doi:10.1111/j.1523-1755.2005.00755.x

Cited by 336 publications

(227 citation statements)

References 26 publications

(26 reference statements)

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“…A delayed and less intense rise of albumin excretion was achieved with R-568 and calcitriol, consistent with previous findings in experimental studies (17,19) and clinical observations (2).…”

Section: Discussionsupporting

confidence: 81%

Calcimimetic R-568 or calcitriol: equally beneficial on progression of renal damage in subtotally nephrectomized rats

Piecha¹,

Kökény²,

Nakagawa³

et al. 2008

American Journal of Physiology-Renal Physiology

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Patients with renal insufficiency develop secondary hyperparathyroidism. Monotherapy with active vitamin D or calcimimetics ameliorates secondary hyperparathyroidism. We compared kidney damage in subtotally nephrectomized (SNX) rats treated with active vitamin D (calcitriol) or the calcimimetic R-568. Male Sprague-Dawley SNX and sham-operated (sham-op) rats were randomized into the following treatment groups: SNX ϩ R-568, SNX ϩ calcitriol, SNX ϩ vehicle, sham-op ϩ R-568, sham-op ϩ calcitriol, and sham-op ϩ vehicle. Albuminuria and blood pressure were monitored and kidneys were examined using morphometry, immunohistochemistry, quantitative RT-PCR, and in situ hybridization. Parathyroid hormone concentrations were lowered to the same extent by the two interventions, although phosphorus and the calcium-phosphorus product were reduced only by R-568 treatment. SNX rats developed marked albuminuria, which was significantly reduced in ad libitum-and pair-fed animals treated with R-568 and animals treated with calcitriol. Mean glomerular volume (6.05 Ϯ 1.46 vs. 2.70 Ϯ 0.91 mm 3 ), podocyte volume (831 Ϯ 127 vs. 397 Ϯ 67 m 3 ), the degree of foot process fusion (mean width of foot processes ϭ 958 Ϯ 364 vs. 272 Ϯ 35 nm), and glomerular basement membrane thickness (244 Ϯ 6 vs. 267 Ϯ 23 nm), as well as desmin staining, were significantly higher in vehicletreated SNX than sham-operated animals. These changes were ameliorated with R-568 and calcitriol. In SNX, as well as sham-operated, animals, expression of the calcium-sensing receptor (protein and mRNA) was upregulated by treatment with the calcimimetic, but not calcitriol. Calcitriol and R-568 were similarly effective in ameliorating kidney damage. secondary hyperparathyroidism; chronic renal failure; nephroprotection; calcimimetics; calcitriol SECONDARY HYPERPARATHYROIDISM (sHPT) is a common feature of chronic kidney disease. Parathyroid hormone (PTH) concentrations increase progressively with diminishing glomerular filtration rate, but it is unclear whether PTH per se modifies progression.Active metabolites of vitamin D are widely used to control sHPT. Moreover, beneficial effects of active vitamin D on progression of chronic kidney disease have been documented (13,19).A therapeutic alternative is the use of calcimimetics (R-568 and, in humans, cinacalcet HCl), allosteric activators of the calcium-sensing receptor (CaSR), which reduce PTH secretion and interfere with parathyroid hyperplasia (4,20,22). In addition, however, Ogata et al. (17) showed that short-term treatment with R-568 reduces albuminuria and attenuates glomerular and tubulointerstitial lesions in subtotally nephrectomized (SNX) rats.The present study was designed to compare the effect of the two interventions on albuminuria and morphological lesions of the kidney in the SNX rat. The readouts were morphology and ultrastructure of podocytes, glomerulosclerosis index (GSI), and tubulointerstitial damage index, as well as expression profile of TGF-␤1, endothelin-1 (ET-1), and VEGF using immunohistochemistry a...

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Section: Discussionsupporting

confidence: 81%

Calcimimetic R-568 or calcitriol: equally beneficial on progression of renal damage in subtotally nephrectomized rats

Piecha¹,

Kökény²,

Nakagawa³

et al. 2008

American Journal of Physiology-Renal Physiology

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“…However, four RCTs showed that a number of patients had a reduction in proteinuria. 25) provided the data on albuminuria before and after paricalcitol treatment. Therefore, we used a reduction in proteinuria .10% from baseline value as our study end point.…”

Section: Effects On Proteinuriamentioning

confidence: 99%

“…Four studies of nine RCTs were undertaken to prospectively test the effectiveness of paricalcitol in reducing of residual albuminuria in a total of 469 patients with CKD who were receiving stable treatment with an angiotensinconverting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) (9,(25)(26)(27). In these studies, 285 patients were assigned to the treatment groups and 184 patients received placebo.…”

Section: Effects On Proteinuriamentioning

confidence: 99%

“…After discarding a number of duplicates retrieved by individual searches and reviewing all titles and abstracts, many studies were excluded because they were not RCTs, did not investigate any of the outcomes of interest to this study, or were animal or basic research studies or review articles. Overall, this analysis included nine trials that enrolled a total of 832 patients (9,(19)(20)(21)(22)(23)(24)(25)(26)(27) (Figure 1). Of the 10 included articles, those by Coyne et al (19) and Agarwal et al (25) were from the same clinical trials.…”

Section: Trial Flow and Study Characteristicsmentioning

confidence: 99%

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Efficacy and Safety of Paricalcitol Therapy for Chronic Kidney Disease

Cheng

Zhang

et al. 2012

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Observational data indicate that newer vitamin D compounds such as paricalcitol can suppress serum intact parathyroid hormone (iPTH) and reduce proteinuria in patients with CKD. To systematically evaluate the efficacy and safety of paricalcitol for CKD, we conducted a meta-analysis of the published randomized controlled trials (RCTs).Design, setting, participants, & measurements MEDLINE, Embase, the Cochrane Library, and article reference lists were searched for RCTs that compared paricalcitol with placebo in the treatment of patients with stage 2-5 CKD. The quality of the studies was evaluated using the Jadad method. The results are summarized as risk ratios (RRs) for dichotomous outcomes or mean differences for continuous outcomes.Results Nine studies (832 patients) were included. Compared with placebo, paricalcitol suppressed serum iPTH (RR, 6.37; 95% confidence interval [95% CI], 4.64-8.74; P,0.001) and reduced proteinuria (RR, 1.68; 95% CI, 1.25-2.25; P,0.001). Compared with the control group, the RR for hypercalcemia associated with paricalcitol use was 2.25 (95% CI, 0.81-6.26; P=0.12). Patients receiving paricalcitol therapy did not have an increased risk of endocrine system and cardiovascular system adverse effects (RR, 1.07; 95% CI, 0.84-1.36; P=0.58).Conclusions We confirm that paricalcitol suppresses iPTH and lowers proteinuria in patients with stage 2-5 CKD without an increased risk of adverse events. A trend toward increased hypercalcemia did not reach statistical significance, but may be clinically relevant. A randomized trial is needed to determine if paricalcitol affects the development of ESRD or mortality.

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“…Evidence shows that pleitropic effects of vitamin D go beyond bone and mineral metabolism and the activity of parathyroid glands, thus being possibly related to other potential areas of CKD. It has been demonstrated that vitamin D supplementation has an antiproteinuric effect, 33 to regulate the reninangiotensin-aldosterone, 34 , to reduce histological changes found in glomerulosclerosis, 35 , and, finally, to reduce CKD progression. 4 To sum up even if our population with CKD is in a tropical environment, which leads to more exposure to the sun and, consequently, a higher production and serum levels of 25(OH)D, our study showed that most analyzed patients had serum levels of 25(OH)D below recommended values, especially lower among women and in patients with larger abdominal circumference.…”

Section: Discussionmentioning

confidence: 99%

Insuficiência e deficiência de vitamina D em pacientes portadores de doença renal crônica

et al. 2012

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ResumoIntrodução: Hipovitaminose D é bem documentada em pacientes portadores de doença renal crônica (DRC). Espera-se níveis inferiores em habitantes de regiões não tropicais em relação aos habitantes de regiões tropicais, pela inferição de uma maior exposição solar e maior produção de vitamina D. Objetivo: Analisar os níveis séricos de vitamina D, como 25-hidroxivitamina D -25(OH)D, de 125 pacientes brasileiros portadores de DRC em fase pré-dialítica. Métodos: Foram estudados 125 pacientes (57,4 ± 16,2 anos, 78 brancos e 55,2% homens), com creatinina de 2,67 ± 1,73 mg/dL e o clearance estimado 43,7 ± 34,5 mL/min. O índice de massa corporal era de 27,4 ± 4,7 kg/m² e a circunferência abdominal de 95,0 ± 14,0 cm. O cálcio era de 9,3 ± 0,6 mg/dL, o paratormônio intacto (PTHi) 212,6 ± 221,2 pg/mL e a albumina sérica 4,2 ± 0,6 g/dL. A média de 25(OH)D era de 23,9 ± 10,7 ng/mL. Resultados: Dos 125 pacientes, 92 (72,6%) apresentavam níveis de 25(OH)

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Antiproteinuric effect of oral paricalcitol in chronic kidney disease

Cited by 336 publications

References 26 publications

Calcimimetic R-568 or calcitriol: equally beneficial on progression of renal damage in subtotally nephrectomized rats

Calcimimetic R-568 or calcitriol: equally beneficial on progression of renal damage in subtotally nephrectomized rats

Efficacy and Safety of Paricalcitol Therapy for Chronic Kidney Disease

Insuficiência e deficiência de vitamina D em pacientes portadores de doença renal crônica

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