Effect of fluvastatin and dipyridamole on proteinuria and renal function in childhood IgA nephropathy with mild histological findings and moderate proteinuria

Kano, Kenichi; Nishikura, Kiyoshi; Yamada, Yoshihisa; Arisaka, Osamu

doi:10.5414/cnp60085

Cited by 39 publications

(16 citation statements)

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“…Ultimately, leukemic progenitor colony formation assays using patients with AML and healthy donor samples would have further evaluated the therapeutic efficacy and potential hemotoxic effects of the statin-dipyridamole combination, as these are long-term assays that more accurately recapitulate the microenvironment of the disease. However, clinical studies have been conducted that show that the statin-dipyridamole combination is safe and well tolerated in humans when assessed for effects on cardiovascular protection (41) and renal function (42). Therefore, we predict that a safe therapeutic window exists as this combination has been previously safely administered to humans.…”

Section: Discussionmentioning

confidence: 99%

Immediate Utility of Two Approved Agents to Target Both the Metabolic Mevalonate Pathway and Its Restorative Feedback Loop

et al. 2014

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New therapies are urgently needed for hematologic malignancies, especially in patients with relapsed acute myelogenous leukemia (AML) and multiple myeloma. We and others have previously shown that FDA-approved statins, which are used to control hypercholesterolemia and target the mevalonate pathway (MVA), can trigger tumor-selective apoptosis. Our goal was to identify other FDA-approved drugs that synergize with statins to further enhance the anticancer activity of statins in vivo. Using a screen composed of other FDA approved drugs, we identified dipyridamole, used for the prevention of cerebral ischemia, as a potentiator of statin anticancer activity. The statin-dipyridamole combination was synergistic and induced apoptosis in multiple myeloma and AML cell lines and primary patient samples, whereas normal peripheral blood mononuclear cells were not affected. This novel combination also decreased tumor growth in vivo. Statins block HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the MVA pathway. Dipyridamole blunted the feedback response, which upregulates HMGCR and HMG-CoA synthase 1 (HMGCS1) following statin treatment. We further show that dipyridamole inhibited the cleavage of the transcription factor required for this feedback regulation, sterol regulatory element-binding transcription factor 2 (SREBF2, SREBP2). Simultaneously targeting the MVA pathway and its restorative feedback loop is preclinically effective against hematologic malignancies. This work provides strong evidence for the immediate evaluation of this novel combination of FDA-approved drugs in clinical trials. Cancer Res; 74(17); 4772-82. Ó2014 AACR.

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Section: Discussionmentioning

confidence: 99%

Immediate Utility of Two Approved Agents to Target Both the Metabolic Mevalonate Pathway and Its Restorative Feedback Loop

et al. 2014

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“…In addition, the majority of subjects had diabetes and/or nephrotic syndrome, and although the degree of renal dysfunction was similar, the rate of renal decline observed was greater than that seen in hypertensive/dyslipidemic populations without a primary renal pathology. Among a cohort of 30 children with "early" IgA nephropathy, similar beneficial effects have been observed on proteinuria, hematuria, and serum creatinine after fluvastatin therapy for 12 mo (37).…”

Section: Statin Trials In Patients With Chronic Renal Diseasementioning

confidence: 55%

From Finland to Fatland

Afzali

Haydar

Vinen

et al. 2004

Journal of the American Society of Nephrology

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“…Kano et al 15 have also reported that 1 year treatment with fluvastatin combined with dipyridamole significantly decreased proteinuria, hematuria and BUN, and increased creatinine clearance and serum albumin. Although their results differed from ours with regard to the decline in proteinuria, the anti-inflammatory, antifibrogenic, antiproliferative, and proapoptotic effects of statins might ameliorate the renal function of IgAN, without decreasing proteinuria.…”

Section: Discussionmentioning

confidence: 98%

Statins stabilize the renal function of IgA nephropathy

et al. 2013

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Background: The renoprotective pleiotropic effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has recently been reported by several investigators. However, the effect of statins on IgA nephropathy (IgAN) is still unknown. Methods: We selected 24 IgAN patients who had newly started statin therapy and were not treated with steroids and immunosuppressive agents during the observation period. We analyzed and compared clinical findings 1 year before and after treatment. Results: Mean age was 50.5 AE 9.91 years and mean blood pressure was 90.9 AE 10.8 mmHg. Renal function was slightly deteriorated, serum creatinine was 1.03 (0.71-1.24) mg/dL and estimated glomerular filtration rate (eGFR) was 55.8 AE 22.8 mL/min. Lipid metabolism was poorly controlled [total cholesterol 247.7 AE 35.7 mg/dL, low-density lipoprotein cholesterol 151.5 (140.8-172.8

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Effect of fluvastatin and dipyridamole on proteinuria and renal function in childhood IgA nephropathy with mild histological findings and moderate proteinuria

Cited by 39 publications

References 0 publications

Immediate Utility of Two Approved Agents to Target Both the Metabolic Mevalonate Pathway and Its Restorative Feedback Loop

Immediate Utility of Two Approved Agents to Target Both the Metabolic Mevalonate Pathway and Its Restorative Feedback Loop

From Finland to Fatland

Statins stabilize the renal function of IgA nephropathy

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