Role of hypertension in progression of chronic kidney disease in children

Vidi, Smitha R.

doi:10.1097/mop.0000000000000595

Cited by 30 publications

(21 citation statements)

References 36 publications

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“…We observed that the body weight loss were reversed in both treated groups, indicating that hiPSCs and RPCs could minimize the impact of CKD on general symptoms, allowing animals to feed regularly, thereby avoiding weight loss, described in CKD [33]. Increased arterial blood pressure levels, another hallmark of CKD, was also partially improved by RPCs and hiPSCs treatment, suggesting that both cell types may have contributed to ameliorating some pathophysiological mechanisms underlying hypertension in CKD [34,35].…”

Section: Discussionmentioning

confidence: 72%

Therapeutic potential of human induced pluripotent stem cells and renal progenitor cells in experimental chronic kidney disease

Ribeiro

Lojudice

Fernandes-Charpiot

et al. 2020

Preprint

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Background: Chronic Kidney Disease (CKD) is a global public health problem. Cell therapy using pluripotent stem cells represents an attractive therapeutic approach for the treatment of CKD.Methods: We transplanted Mitomycin C (MMC)-treated human induced pluripotent stem cells (hiPSCs) and renal progenitor cells (RPCs) into a CKD rat model system. The RPCs and hiPSCs cells were characterized by immunofluorescence and qRT-PCR. Untreated 5/6 nephrectomized rats were compared to CKD animals receiving the same amount of MMC-treated hiPSCs or RPCs. Renal function, histology and immunohistochemistry were evaluated 45 days post-surgery.Results: We successfully generated hiPSCs from peripheral blood and differentiated them into RPCs expressing renal progenitor genes (PAX2, WT1, SIX2, and SALL1) and podocyte-related genes (SYNPO, NPHS1). RPCs also exhibited reduced OCT4 expression, confirming the loss of pluripotency. After cell transplantation into CKD rats, the body weight change was significantly increased in both hiPSC and RPC groups, in comparison with the control group. Creatinine clearance (CCr) was preserved only in the hiPSC group. Similarly, the number of macrophages in the kidneys of the hiPSC group reached a statistically significant reduction, when compared to control rats. Both treatments reduced positive staining for the marker α-smooth muscle actin. Histological features showed decreased tubulointerstitial damage (interstitial fibrosis and tubular atrophy) as well as a reduction in glomerulosclerosis in both iPSC and RPC groups.Conclusions: In conclusion, we describe that both MMC-treated hiPSCs and RPCs exert beneficial effects in attenuating CKD progression. Both cell types were equally efficient to reduce histological damage and weight loss caused by CKD. hiPSCs seems to be more efficient than RPCs, possibly due to a paracrine effect triggered by hiPSCs. These results demonstrate that the use of MMC-treated hiPSCs and RPCs improve clinical and histological CKD parameters, avoided tumor formation, and therefore may be a promising cell therapy strategy for CKD.

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Section: Discussionmentioning

confidence: 72%

Therapeutic potential of human induced pluripotent stem cells and renal progenitor cells in experimental chronic kidney disease

Ribeiro

Lojudice

Fernandes-Charpiot

et al. 2020

Preprint

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“…For example, systolic blood pressure (SBP) as low as 116 mm Hg could be hypertensive in a short 12‐year‐old boy, while 127 mm Hg would not be considered hypertensive in a taller male child of the same age. In turn, failure to recognize hypertensive crises in hospitalized children can result in end‐organ damage or progression of certain chronic diseases 1,11,16,17 . At our institution, we observed that PRN antihypertensive medications were often held without documented explanation, despite ordered administration parameters.…”

Section: Introductionmentioning

confidence: 81%

Identification of hypertension in hospitalized children prescribed as‐needed antihypertensive medication

Kocher¹,

Tumin

Lehmann

et al. 2020

J of Clinical Hypertension

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Imperfect measurement conditions, transient blood pressure (BP) elevation due to pain or anxiety, and heavy clinical demands complicate hypertension (HTN) diagnosis in hospitalized children, and may prevent recognition of hypertensive episodes for children prescribed as‐needed (PRN) antihypertensive medication. The authors sought to describe the incidence and predictors of missed BP elevation among hospitalized children prescribed PRN antihypertensive medication at our hospital. BP data were retrospectively audited for children age 2‐18 admitted in 2018 to the general ward, and prescribed PRN oral nifedipine, intravenous [IV] or oral hydralazine, or IV labetalol. Appropriate recognition of BP elevation (exceeding the parameters in the medication order) was defined as administering medication within the ordered dosing interval, administering the medication earlier than planned, or physician documentation of why HTN treatment was withheld. Mixed‐effects logistic regression was used to identify factors associated with recognition of BP elevation. Fifty‐six hospitalizations including 616 BP measurements were analyzed. BP elevation was appropriately recognized in 230 (37%) instances, in most of which (n = 190) the antihypertensive medication was given after excessive BP was noted. On multivariable analysis, higher systolic BP and BP elevation occurring at night were associated with increased likelihood of appropriate recognition. BP elevations are frequently missed in hospitalized children prescribed PRN antihypertensive medication. Particularly, there was low recognition of diastolic BP elevation and of systolic BP elevation close to but still exceeding the ordered threshold. Further staff education may be needed to raise awareness of lower BP thresholds for HTN in younger and smaller children.

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“…RPCs could minimize the impact of CKD on general symptoms, allowing animals to feed regularly, thereby avoiding weight loss, described in CKD [30]. Increased arterial blood pressure levels, another hallmark of CKD, was also partially improved by RPCs and hiPSCs treatment, suggesting that both cell types may have contributed to ameliorating some pathophysiological mechanisms underlying hypertension in CKD [31,32].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of Human Induced Pluripotent Stem Cells and Renal Progenitor Cells in Experimental Chronic Kidney Disease

Ribeiro

Lojudice

Fernandes-Charpiot

et al. 2020

Preprint

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BackgroundChronic Kidney Disease (CKD) is a global public health problem. Regenerative medicine using pluripotent stem cells represents an attractive therapeutic approach for the treatment of CKD.MethodsWe transplanted Mitomycin C (MMC)-treated human induced pluripotent stem cells (hiPSCs) and renal progenitors cells (RPCs) into a CKD rat model system. The RPCs and hiPSCs cells were characterized by immunofluorescence and qRT-PCR. Untreated 5/6 nephrectomized rats were compared to CKD animals receiving the same amount of MMC-treated hiPSCs or RPCs. Renal function, histology and immunohistochemistry were evaluated 45 days post-surgery. ResultsWe successfully generated hiPSCs from peripheral blood and differentiated them into RPCs expressing renal progenitor genes (PAX2, WT1, SIX2, and SALL1) and podocyte-related genes (SYNPO, NPHS1). RPCs also exhibited reduced OCT4 expression, confirming the loss of pluripotency. After cell transplantation into CKD rats, the body weight change was significantly increased in both hiPSC and RPC groups, in comparison with the control group. Creatinine clearance (CCr) was preserved only in the hiPSC group. Similarly, the number of macrophages in the kidneys of the hiPSC group reached a statistically significant reduction, when compared to control rats. Both treatments reduced positive staining for the marker α-smooth muscle actin. Histological features showed decreased tubulointerstitial damage (interstitial fibrosis and tubular atrophy) as well as a reduction in glomerulosclerosis in both iPSC and RPC groups.ConclusionsIn conclusion, we describe that both MMC-treated hiPSCs and RPCs exert beneficial effects in attenuating CKD progression. Both cell types were equally efficient to reduce histological damage and weight loss caused by CKD. hiPSCs seems to be more efficient than RPCs, possibly due to an anti-inflammatory mechanism triggered by hiPSCs. These results demonstrate that the use of MMC-treated hiPSCs and RPCs improve clinical and histological CKD parameters, avoided tumor formation, and therefore may be a promising cell therapy strategy for CKD.

show abstract

Role of hypertension in progression of chronic kidney disease in children

Cited by 30 publications

References 36 publications

Therapeutic potential of human induced pluripotent stem cells and renal progenitor cells in experimental chronic kidney disease

Therapeutic potential of human induced pluripotent stem cells and renal progenitor cells in experimental chronic kidney disease

Identification of hypertension in hospitalized children prescribed as‐needed antihypertensive medication

Therapeutic Potential of Human Induced Pluripotent Stem Cells and Renal Progenitor Cells in Experimental Chronic Kidney Disease

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