Renalase Potential as a Marker and Therapeutic Target in Chronic Kidney Disease
Abstract
:1. Introduction
2. Renalase—A Brief Description
3. Renalase in Chronic Kidney Disease
Study, Year | Patients | Aim | Significant Results | Assay for Serum RNLS (Unit of Measure) | Formula for CKD Staging | Serum Levels of RNLS |
---|---|---|---|---|---|---|
Xu, 2005 [12] | 8 HD, 4 healthy | Identification of a new protein secreted by the kidney | RNLS almost undetectable in HD pts | Western blot | - | - |
Zbroch E, 2012 [43] | 62 transplanted 27 healthy controls | Associations between RNLS, BP, and kidney function | RNLS higher in transplanted pts than in controls, higher in hypertensives RNLS inverse correlation with eGFR. | ELISA* (µg/mL) | MDRD; CKD-EPI; Clcr | Transplanted: 6.72 ± 2.86; Controls: 3.86 ± 0.73 |
Zbroch E, 2012 [39] | 104 HD 27 healthy controls | RNLS levels in HD pts and relationship to BP control, type of antihypertensives, RRF | RNLS higher in HD than controls inverse relationship between RNLS and RRF No correlation between RNLS and BP, HR, HD vintage, or type of treatment. | ELISA* (µg/mL) | - | HD: 27.53 ± 7.18; Controls: 3.86 ± 0.73 |
Zbroch E, 2012 [40] | 26 PD 27 healthy controls | RNLS levels in PD pts and relationship to BP control, type of antihypertensives, RRF, PD parameters | RNLS higher in PD pts than in controls; RNLS directly correlated with dialysis vintage and inversely with RRF No relation between RNLS and BP, antihypertensive treatment type, dialysis dose, or PET. | ELISA* (µg/mL) | - | PD: 19.24 ± 4.50; Controls: 3.86 ± 0.73 |
Malyszko, 2012 [51] | 34 HD patients 22 healthy controls | Relation between RNLS, BP, stroke, and CV status | RNLS higher in HD than controls; In HD, RNLS lower in pts with history of stroke, lower in hypertensive than in normotensive, higher in glomerulonephritis vs. other etiologies. | ELISA* (µg/mL) | - | HD: 17.51 ± 6.73; Controls: 3.99 ± 1.73 |
Zbroch E, 2013 [36] | 76 HD 26 PD 27 healthy controls | Relation between RNLS and CA level, HR, BP, type of antihypertensives, and RRF | RNLS higher in HD vs. PD; No correlation between CA, RNLS, and BP; RNLS correlated directly with dialysis vintage and inversely with RRF; Higher RNLS levels in patients with cardiac death. | ELISA* (µg/mL) | - | Dialyzed: 25.37 ± 7.3; Healthy: 3.86 ± 0.74 |
Gluba-Brzózka, 2014 [35] | 139 CKD pts 45 subjects with normal kidney function | Describing markers of increased risk of CAD in CKD | Decreased levels of fetuin-A and increased concentration of osteocalcin, RNLS, MMP-2, and TIMP-2 in CKD pts with CAD RNLS correlated with serum calcium and phosphorus. | ELISA* (ng/mL) | MDRD | Controls: 251.0 ± 157.0; CKD stages 1 + 2: 354.5 ± 181.6; 3: 235.3 ± 152.3; 4: 279.4 ± 162.2; 5: 369.0 ± 110.5 |
Wang F, 2015 [30] | 87 CKD stages 1–5, including maintenance dialysis | Serum levels of RNLS and CA and their relationship with other renal function indicators | Serum levels of RNLS and RNLS/CA ratios higher in CKD 3–5 than CKD stage 1–2. RNLS no difference between CKD stage 1–2 and controls Serum RNLS highly correlated with CA and systolic BP. | ELISA* (ng/L) | MDRD | Controls: 167.8 ± 69.4; CKD 1: 169.4 ± 31.9 CKD 2: 159.0 ± 43.5 CKD 3: 226.6 ± 120.0 CKD 4: 286.9 ± 157.0 CKD 5:198.6 ± 76.2 CKD 5-ND: 242.2 ± 67.8 CKD 5-HD: 169.4 ± 58.8 CKD 5-PD: 232.9 ± 93.9 |
Malyszko J, 2015 [31] | 100 HD pts 17 HDF pts 24 healthy controls | RNLS concentration in serum, urine, and ultrafiltrate | Higher removal of RNLS in HDF vs. HD Direct correlation between residual urine and urine RNLS and inverse with serum RNLS Patients with bilateral nephrectomy had the highest serum RNLS. | ELISA* Western blot | - | - |
Cerqueira A, 2015 [62] | 64 pre-dialysis CKD pts | Association between plasma RNLS, renal function, and markers of endothelial dysfunction | Increased plasma RNLS correlated with the decrease of eGFR. | ELISA* | Not stipulated | Not available |
Stojanovic D, 2015 [56] | 73 renal transplant recipients 32 healthy controls | Relation between renal dysfunction, RNLS, and endothelial dysfunction parameters | RNLS was a strong predictor of decreased GFR Endothelial nitric oxide synthase was a strong protective factor for kidney function. | ELISA* (ng/mL) | Cockcroft-Gault | Transplant: 141.82 ± 36.47 Healthy: 16.36 ± 4.13 |
Oguz EG, 2016 [38] | 50 HD, 35 healthy controls | Relation between RNLS and LVH | There was no significant association of RNLS with LVMI; RNLS higher in HD than in healthy; positive correlation with creatinine and dialysis vintage. | ELISA* (ng/mL) | - | HD: 212 ± 127; Controls: 116 ± 67 |
Zbroch E, 2016 [63] | 211 CKD pts stages 1–5 with HT | Impact of age on RNLS and CA and relation to BP control and CVD | Higher RNLS and dopamine in pts >65 years; No relation between RNLS and echocardiographic abnormalities or type of treatment. | ELISA* (µg/mL) | Not stipulated | >65 years: 20.59 (1.9–62) <65 years: 13.14 (0.05–49.9) |
Gok Oguz E, 2017 [41] | 40 PD, 40 healthy controls | Serum level of RNLS and relation with EAT thickness. | RNLS higher in PD than in healthy; positive correlation with CRP, inverse correlation with RRF; no correlation with EAT. | ELISA* (ng/mL) | - | PD: 176.5 (100–278.3) Healthy: 122 (53.3–170.0) |
Dziedzic M, 2017 [50] | 50 HD | Relation between serum RNLS and AOPP | No significant correlations between CA and RNLS; positive correlation between RNLS and AOPP. | ELISA* (μg/mL) | - | 44.8 ± 6.5 |
Stojanovic D, 2017 [64] | 73 renal transplant recipients, 32 controls | Relationships between serum RNLS and parameters of endothelial dysfunction, lipids, and GFR | RNLS inversely correlated with GFR, Hb, and WBC; directly correlated with creatinine and cholesterol; no correlation with parameters of endothelial dysfunction and age. | ELISA* (ng/mL) | Cockcroft-Gault | Transplanted: 141.82 ± 36.47 Healthy: 16.36 ± 4.13 ng/mL |
Huang YS, 2018 [57] | 72 biopsies in pts with chronic nephropathies | Expression of RNL in renal tissue samples | Renal tubule injury index and tubular epithelial cell apoptosis index showed a negative linear correlation with RNLS. | Immunohistochemistry | - | - |
Skrzypczyk P, 2019 [49] | 38 CKD 38 healthy controls | RNLS levels in children with CKD, correlation with BP and markers of endothelial stiffness | RNLS correlated with CKD stage and pulse wave velocity, no correlation with BP or age. | ELISA* (μg/mL) | Schwarz formula | CKD: 59.45 ± 23.25 Healthy: 27.20 ± 5.15 |
Baek SH, 2019 [46] | 383 patients with CKD; follow-up 56 months | Whether plasma RNLS is a biomarker for CKD progression, MACCEs, or mortality | Each 10 μg/mL increase in serum RNLS was associated with significantly greater hazards of all-cause mortality and adverse renal outcomes; RNLS not associated with the rate of MACCEs | ELISA** (μg/mL) | Cockcroft-Gault | CKD 3: 67.7 ± 29.6 CKD 4: 79.7 ± 36.4 Controls: 28.2 ± 5.1 |
Li YH, 2018 [48] | 342 non-diabetic with CAD | Relation between serum RNLS, CKD, and ET-1 levels in patients with CAD | ET-1 levels positively correlated with serum RNLS and inversely correlated with the eGFR; In multivariate analysis, the combination of high serum RNLS with CKD was a significant risk factor for increased serum ET-1 levels. | ELISA* (ng/mL) | MDRD | CKD: 46.8 ± 17.1 Non-CKD: 33.9 ± 9.9 |
Al-Shamma ZAA, 2018 [44] | 68 non-diabetic CKD stages 2–5 50 healthy controls | Level of RNLS in different stages of CKD and relation with HT | Progressive increase of RNLS as GFR decreases and as Cystatin C increases; no difference between CKD stages 2–3 and controls; positive relation of RNLS with systolic BP in CKD 5. | ELISA*** (ng/mL) | CKD-EPI Cystatin C | CKD 2–3: 52.4 ± 11.8 CKD 5: 103.4 ± 36.3 Controls: 48.8 ± 5.7 |
Wiśniewska M, 2019 [65] | 155 CKD 30 healthy | Level of RNLS in serum, urine, and erythrocytes | Increased RNLS level in serum and decreased level in erythrocytes in CKD; no differences in the urine level No influence of primary renal disease. | ELISA* (ng/mL) | CKD-EPI | CKD: 103 (55.6–166) Healthy: 17.7 (16.3–21.8) |
Desir G, 2019 [42] | 267 CKD different stages | Association between renal function and plasma RNLS with a new developed ELISA method Association between plasma RNLS and mortality | Total RNLS correlated positively with GFR and negatively with CKD stages No correlation between GFR or CKD stages and free RNLS % free RNLS correlated negatively with GFR and positively with CKD stages % free RNLS independently predicted death at both 1 year and 5 years. | ELISA with monoclonal antibody m28-renalase (µg/mL) | CKD-EPI | Total RNLS: 4.1–49.4 Free RNLS: 0.13–2.6 |
Serwin NM, 2020 [66] | 62 pre-dialysis CKD 28 healthy | The balance between serum and urine RNLS in healthy and CKD | Serum RNLS and serum-to-urine ratio significantly higher in CKD No relation between serum RNLS and GFR or proteinuria Serum RNLS was the only significant positively associated with urinary RNLS. | ELISA**** (ng/mL) | MDRD | CKD 1: 34.73 (20.71–129.7) CKD 2: 41 (18.11–104) CKD 3: 32.29 (14.15–106.35) CKD 4: 37.67 (26.6–85.77) Healthy: 11.1 (2.5–26.5) |
Cerqueira A, 2021 [28] | 40 pre-dialysis CKD, mean follow-up 65 months | Relationship between RNLS and CV and renal outcomes | Significant higher RNLS in stages 4 + 5 vs. stages 1 + 2 RNLS predicted CKD progression, CVD, HT, diabetes, and dyslipidemia. | ELISA* (µg/mL) | CKD-EPI | Stages 1 + 2: 42.03 Stage 3: 71.35 Stages 4 + 5: 83.53 |
Wisniewska M, 2021 [37] | 77 HD, 30 healthy | RNLS levels in serum, erythrocytes, and urine | In HD, RNLS higher in serum and urine and lower in erythrocytes than in controls Plasma level of CA lower in HD vs. control. | ELISA* (ng/mL) | CKD-EPI | HD:185.5 ± 64.3 Controls: 19.6 ± 5.0 |
Knop W, 2021 [29] | 90 CKD stages 1–5 including HD 30 healthy Median follow-up 18 months | Relation between serum RNLS and occurrence of MACE, all-cause mortality, and the need for dialysis initiation | RNLS higher in HD vs. other stages or vs. controls; no difference between whole CKD and controls RNLS correlated only with mortality in HD RNLS correlated with MACE occurrence and all-cause deaths in all groups of CKD patients. | ELISA**** (µg/mL) | CKD-EPI | CKD: 22.5 (19.9–25.1) Controls: 23.9 (19.4–25.9) |
Wiśniewska M, 2021 [34] | 27 HD with bilateral nephrectomy (BN); 46 HD anuric without nephrectomy; 30 healthy with normal kidney function | The effect of bilateral nephrectomy on RNLS and CA levels in the serum and erythrocytes | In the post bilateral nephrectomy HD, serum RNLS was the lowest, and erythrocytes’ RNLS was the highest. In both HD groups, no correlation between serum and erythrocytes RNLS and BP; in controls, direct relationship between RNLS and BP | ELISA**** (ng/mL) | Serum creatinine | HD with BN: 101.1 ± 65.5 Healthy: 19.6 ± 5.0 HD anuric without nephrectomy: 177.2 ± 68.3 |
Yilmaz R, 2021 [25] | 20 kidney donors (with unilateral nephrectomy) 20 kidney recipients | The effect of kidney transplantation on RNLS and relation to BP | Before transplantation, RNLS lower in donors and higher in ESRD pts After transplantation, serum RNLS increased in donors and decreased in recipients RNLS associated with change in MAP and circadian rhythm of BP in donors and recipients. | ELISA***** (µg/mL) | Creatinine clearance | Kidney donors - Before KTx: 125.2 ± 35.0 - After Ktx: 140.2 ± 73.6 Kidney recipients - Before KTx: 242.4 ± 147.0 - After KtX: 162.3 ± 53.0 |
Gamal SG, 2021 [47] | 90 HD | Relation between plasma RNLS and LVMI | RNLS significantly increased with the moderately and severely abnormal LVMI. | ELISA (ng/mL) (assay kit not specified) | - | Cut-off for prediction abnormal LVMI > 57.9 (sensitivity 92.3%, specificity 84.0%) |
Kamel RA, 2022 [45] | 40 HD with LVH 30 HD without LVH | Relation between plasma RNLS, LVMI, and copeptin | A positive correlation between serum RNLS and all of systolic, diastolic BP, duration of HD, LVMI, and serum copeptin. | ELISA* (ng/mL) | - | Cut-off for prediction LVH > 115 (sensitivity 92.5%, specificity 86.7%) |
Authors, Year | Patients | Aim | Significant Results |
---|---|---|---|
Xu J, 2005 [12] | Rats | Effects of RNLS infusion | Decrease in cardiac contractility, HR, and BP and prevention of compensatory increase in peripheral vascular tone. |
Baraka A, 2012 [17] | Rats, 5/6 nephrectomized and controls | Effect of recombinant RNLS infusion on cardiac function in CKD | Partial reversal of LVH, significant reduction in BP; reduction in left ventricular hydroxyproline concentration. |
Lee HT, 2013 [60] | Wild-type mice with induced ischemic AKI | Whether administration of RNLS directly protects against ischemic AKI | RNLS ameliorated ischemic AKI by reducing renal tubular necrosis, apoptosis, and inflammation. |
Yin J, 2016 [54] | 5/6 nephrectomized rats | Role of RNLS in the progression of cardiorenal syndrome after subtotal nephrectomy. | Administration of RNLS reduced proteinuria, glomerular hypertrophy, and interstitial fibrosis after renal ablation. Systemic delivery of RNLS attenuated HT, cardiomyocyte hypertrophy, and cardiac interstitial fibrosis. |
Wu Y, 2017 [58] | Rats with unilateral ureteral obstruction Culture of human fibrotic renal interstitial tissue | Effects and mechanisms of RNLS in tubulointerstitial fibrosis | Experimental increased expression of RNLS attenuated renal interstitial fibrosis by suppression of tubular EMT through inhibition of the ERK pathway. |
Wu Y, 2018 [59] | Rats with unilateral ureteral obstruction Culture of human fibrotic renal interstitial tissue | Effects and mechanisms of RNLS in tubulointerstitial fibrosis | RNLS protects against tubulointerstitial fibrosis by reducing oxidative stress. |
Wang Y, 2022 [55] | RNLS knockout and wild-type mice with CKD | Relation between cardiac expression of RNLS and cardiac remodeling in CKD Effects of RNLS on cardiac remodeling in CKD | Knockout of RNLS aggravated cardiac remodeling in CKD, while RNLS cardiac-specific overexpression significantly reduced LVH and cardiac fibrosis induced by CKD. |
Guo X, 2022 [61] | Mice | Whether kidney-targeted delivery of RNLS might prevent cisplatin-induced CKD | RNLS agonist protects against cisplatin-induced CKD by decreasing cell death and improving the viability of the renal proximal tubule |
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Serban-Feier, L.F.; Cuiban, E.; Gogosoiu, E.B.; Stepan, E.; Radulescu, D. Renalase Potential as a Marker and Therapeutic Target in Chronic Kidney Disease. Biomedicines 2024, 12, 1715. https://doi.org/10.3390/biomedicines12081715
Serban-Feier LF, Cuiban E, Gogosoiu EB, Stepan E, Radulescu D. Renalase Potential as a Marker and Therapeutic Target in Chronic Kidney Disease. Biomedicines. 2024; 12(8):1715. https://doi.org/10.3390/biomedicines12081715
Chicago/Turabian StyleSerban-Feier, Larisa Florina, Elena Cuiban, Elena Bianca Gogosoiu, Elena Stepan, and Daniela Radulescu. 2024. "Renalase Potential as a Marker and Therapeutic Target in Chronic Kidney Disease" Biomedicines 12, no. 8: 1715. https://doi.org/10.3390/biomedicines12081715