Evidence for prevention of renal dysfunction associated with primary myelofibrosis by cytoreductive therapy

Fukuda, Yasutaka; Araki, Marito; Yamamoto, Keiji; Morishita, Soji; Inano, Tadaaki; Misawa, Kyohei; Ochiai, Tomonori; Edahiro, Yoko; Imai, Misa; Yasuda, Hajime; Gotoh, Akihiko; Ohsaka, Akimichi; Komatsu, Norio

doi:10.3324/haematol.2018.208876

Cited by 12 publications

(7 citation statements)

References 16 publications

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“…Some studies have often focused on the linear regression coefcient of eGFR as an observation item during the course [15][16][17]. A study reported that there was a rapid reduction in the kidney function in 20% of patients with MPNs, whereas an improvement in the kidney function was achieved in approximately 50% [15].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies found the association between cardiovascular risk factors and thrombosis in patients with MPNs [11,12], but few studies have examined the association between CKD and the onset of thrombosis or prognosis [13,14]. Furthermore, a study investigated serial changes in the estimated glomerular fltration rate (eGFR) during the observation period in patients with ET [15][16][17]. However, no study has examined the prognosis of patients who developed CKD during follow-up.…”

Section: Introductionmentioning

confidence: 99%

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Presence and Onset of Chronic Kidney Disease as a Factor Involved in the Poor Prognosis of Patients with Essential Thrombocythemia

Hashimoto,

Omura,

Tanaka

2024

Advances in Hematology

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Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease, thrombosis, and all-cause death. However, few studies have examined the association between CKD and the prognosis of patients with essential thrombocythemia (ET). We collected ET patients who met the WHO classification 2017 and performed a retrospective clinical study to clarify the association between the presence and onset of CKD and prognosis. Of 73 patients who met the diagnostic criteria, 21 (28.8%) had CKD at the time of ET diagnosis. The age of patients with CKD was significantly higher, and a high proportion of these patients had the JAK2V617F gene mutation. The presence of CKD was a risk factor for the prognosis (hazard ratio (HR): 3.750, 95% confidence interval (CI): 1.196–11.760, P=0.023), and the survival curve was significantly poorer. Furthermore, we analyzed patients without CKD at the time of ET diagnosis using the onset of CKD as a time-dependent variable and identified the onset of CKD as a risk factor for the prognosis (HR: 9.155, 95% CI: 1.542–54.370, P=0.005). In patients with renal hypofunction at the time of ET diagnosis or those with a reduction in the kidney function during follow-up, strict renal function monitoring at regular intervals is necessary.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Presence and Onset of Chronic Kidney Disease as a Factor Involved in the Poor Prognosis of Patients with Essential Thrombocythemia

Hashimoto,

Omura,

Tanaka

2024

Advances in Hematology

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“…In keeping with this hypothesis, patients with primary myelofibrosis (PMF) may experience improvement of kidney function when treated with the JAK inhibitor ruxolitinib (RUX) [28]. However, whether cytoreductive therapy for MPN improves renal dysfunction overall remains a matter of current debate: while one study showed an increase in the estimated glomerular filtration rate (eGFR) during hydroxyurea treatment (HU) in polycythemia vera (PV) patients [25], this was not seen in another study [29], where HU appeared to be beneficial in PMF, but it was not the case in PV or in essential thrombocythemia (ET) patients. A third study [24] found that HU treatment did not significantly affect progression of kidney dysfunction during the course of MPN disease.…”

Section: Introductionmentioning

confidence: 99%

Kidney Dysfunction Is Associated with Thrombosis and Disease Severity in Myeloproliferative Neoplasms: Implications from the German Study Group for MPN Bioregistry

Gecht

Tsoukakis

Kricheldorf

et al. 2021

Cancers

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Inflammation-induced thrombosis represents a severe complication in patients with myeloproliferative neoplasms (MPN) and in those with kidney dysfunction. Overlapping disease-specific attributes suggest common mechanisms involved in MPN pathogenesis, kidney dysfunction, and thrombosis. Data from 1420 patients with essential thrombocythemia (ET, 33.7%), polycythemia vera (PV, 38.5%), and myelofibrosis (MF, 27.9%) were extracted from the bioregistry of the German Study Group for MPN. The total cohort was subdivided according to the calculated estimated glomerular filtration rate (eGFR, (mL/min/1.73 m2)) into eGFR1 (≥90, 21%), eGFR2 (60–89, 56%), and eGFR3 (<60, 22%). A total of 29% of the patients had a history of thrombosis. A higher rate of thrombosis and longer MPN duration was observed in eGFR3 than in eGFR2 and eGFR1. Kidney dysfunction occurred earlier in ET than in PV or MF. Multiple logistic regression analysis identified arterial hypertension, MPN treatment, increased uric acid, and lactate dehydrogenase levels as risk factors for kidney dysfunction in MPN patients. Risk factors for thrombosis included arterial hypertension, non-excessive platelet counts, and antithrombotic therapy. The risk factors for kidney dysfunction and thrombosis varied between MPN subtypes. Physicians should be aware of the increased risk for kidney disease in MPN patients, which warrants closer monitoring and, possibly, early thromboprophylaxis.

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“…Hence, underlying mutation (particularly V617F mutation in the JAK2 gene) partially determines the incidence of arterial, venous, and microcirculatory complications of ET [6], and it is possible that it also may influence the susceptibility to renal complications of the disease. The putative explanation is that hematopoietic cells with mutations, such as JAK2 V617F, CALR exon 9, or MPL W515K/L, exhibit increased growth potential and production of various cytokines, promoting renal dysfunction associated with aging [7].…”

Section: Introductionmentioning

confidence: 99%

Treatment of Essential Thrombocythemia with Anagrelide Is Associated with an Increased Risk of Worsened Kidney Function

Kwiatkowski

Kuliszkiewicz‐Janus²,

Rymer

et al. 2021

Pharmacology

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Background and Purpose: When choosing a cytoreduction method for patients suffering from essential thrombocythemia (ET), it is important to know the safety profile of the medicine used. Few articles have been published about the effects of hydroxycarbamide (hydroxyurea, HU) and anagrelide (ANA) on renal function in ET patients. This study is the largest analysis of nephrotoxicity of cytoreductive drugs used in ET therapy so far, which additionally includes risk factors for the progression of kidney disease and coexisting genetic mutation. Experimental Approach: The retrospective study included 310 patients diagnosed with ET. Demographic data, comorbidities, Cr, and estimated glomerular filtration rate (eGFR) were all taken into account prior to diagnosis and after 6 months of HU and ANA treatment. Key Results: A statistically significant difference was found between Cr and eGFR levels at baseline and after 6 months of treatment (p < 0.001). The applied treatment (HU and ANA) had the greatest impact on kidney function. ANA significantly increased the risk of worsening renal function in contrary to hydroxycarbamide after 6 months of treatment (eGFR change: median +1 mL/min/1.73 m2 [interquartile range (IQR) (−4)–(+7)] in the HU group vss. median −13 mL/min/1.73 m2 [IQR (−18)–(−6)] in the ANA group, odds ratio [OR] 7.92 95% confidence interval [95% CI] [4.17–15.08], p < 0.001). Lowering of eGFR <60 mL/min/1.73 m2 occurred in 31 patients (31.0%) from the ANA group and 10 people (4.8%) treated with HU (p = 0.000). In 1 patient from the ANA group, >50% decrease in eGFR was observed. The chance for an increase in Cr levels was higher in people with pre-existing arterial hypertension (OR 1.92 CI = 95% [1.21–3.05], p = 0.006). Sex, type of mutation found (JAK2 V617F or CALR), and previous renal impairment did not affect renal function after 6 months of treatment. In addition, there was no difference in the efficacy of ET treatment between HU and ANA (p = 0.998). Conclusions and Implications: The observations indicate that ANA should be used in patients with ET with great caution and taking into account the risk of worsened kidney function.

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Evidence for prevention of renal dysfunction associated with primary myelofibrosis by cytoreductive therapy

Cited by 12 publications

References 16 publications

Presence and Onset of Chronic Kidney Disease as a Factor Involved in the Poor Prognosis of Patients with Essential Thrombocythemia

Presence and Onset of Chronic Kidney Disease as a Factor Involved in the Poor Prognosis of Patients with Essential Thrombocythemia

Kidney Dysfunction Is Associated with Thrombosis and Disease Severity in Myeloproliferative Neoplasms: Implications from the German Study Group for MPN Bioregistry

Treatment of Essential Thrombocythemia with Anagrelide Is Associated with an Increased Risk of Worsened Kidney Function

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