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Published in: Journal of Nephrology 1/2019

01-02-2019 | Original Article

Infusion of autologous bone marrow derived mononuclear stem cells potentially reduces urinary markers in diabetic nephropathy

Authors: Abduzhappar Gaipov, Zhannat Taubaldiyeva, Manarbek Askarov, Zaiyrkhan Turebekov, Larisa Kozina, Askhat Myngbay, Olga Ulyanova, Saltanat Tuganbekova

Published in: Journal of Nephrology | Issue 1/2019

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Abstract

Background

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Previous studies demonstrated safety and efficacy of autologous bone marrow-derived mononuclear cells (ABM-MNCs) in induced type-1 diabetes mellitus (T1DM) rats. However, the effect of ABM-MNCs on urinary markers of DN in humans is not well studied. We evaluated the therapeutic effect of ABM-MNCs on the urinary markers microalbuminuria (MAU), urinary type-IV collagen and urinary neutrophil gelatinase-associated lipocalin (uNGAL) in T1DM patients with and without nephropathy.

Methods

This prospective open-label pilot study included 15 patients with T1DM, who had completed 2 visits within 6 months. Patients were divided into two groups according to the presence (DN, n = 7) and absence of nephropathy (T1DM, n = 8). ABM-MNCs were injected at each visit as per study protocol. Routine laboratory data, diabetes tests (fasting serum C-peptide and insulin, glycated hemoglobin, fasting and postprandial glucose), 24-h MAU and urinary type-IV collagen were measured at each visit. uNGAL levels were studied before and after 3 days of ABM-MNCs infusion at each visit.

Results

Mean age of patients was 29.2 ± 10.4 years, 33% were male, and 27% of the overall group had hypertension. MAU was significantly reduced in the overall group (− 26.0%, p = 0.037), including in DN (− 83.2%, p = 0.021). A short-term significant reduction of uNGAL levels was observed 3 days after ABM-MNCs administration during the both the 1st visit (median 13.4 vs. 9.5 ng/ml, p = 0.027) and 2nd visit (median 8.8 vs. 6.4 ng/ml, p = 0.042) in both groups. However this reduction did not remain significant at the 6-month follow-up. Urinary type-IV collagen did not respond significantly to ABM-MNCs infusion.

Conclusion

Infusion of autologous bone marrow-derived mononuclear cells significantly reduced levels of MAU in DN patients. Further studies with larger sample size are needed to confirm these observations.
Literature
3.
go back to reference Hadjadj S, Cariou B, Fumeron F, Gand E, Charpentier G, Roussel R, Kasmi AA, Gautier JF, Mohammedi K, Gourdy P, Saulnier PJ, Feigerlova E, Marre M, French JDNCRI, Group Ss, Group Ds (2016) Death, end-stage renal disease and renal function decline in patients with diabetic nephropathy in French cohorts of type 1 and type 2 diabetes. Diabetologia 59(1):208–216. https://doi.org/10.1007/s00125-015-3785-3 CrossRefPubMed Hadjadj S, Cariou B, Fumeron F, Gand E, Charpentier G, Roussel R, Kasmi AA, Gautier JF, Mohammedi K, Gourdy P, Saulnier PJ, Feigerlova E, Marre M, French JDNCRI, Group Ss, Group Ds (2016) Death, end-stage renal disease and renal function decline in patients with diabetic nephropathy in French cohorts of type 1 and type 2 diabetes. Diabetologia 59(1):208–216. https://​doi.​org/​10.​1007/​s00125-015-3785-3 CrossRefPubMed
5.
go back to reference Araki S-i, Haneda M, Koya D, Isshiki K, Kume S, Sugimoto T, Kawai H, Nishio Y, Kashiwagi A, Uzu T (2010) Association between urinary type IV collagen level and deterioration of renal function in type 2 diabetic patients without overt proteinuria. Diabetes care 33(8):1805–1810CrossRefPubMedPubMedCentral Araki S-i, Haneda M, Koya D, Isshiki K, Kume S, Sugimoto T, Kawai H, Nishio Y, Kashiwagi A, Uzu T (2010) Association between urinary type IV collagen level and deterioration of renal function in type 2 diabetic patients without overt proteinuria. Diabetes care 33(8):1805–1810CrossRefPubMedPubMedCentral
6.
go back to reference Okonogi H, Nishimura M, Utsunomiya Y, Hamaguchi K, Tsuchida H, Miura Y, Suzuki S, Kawamura T, Hosoya T, Yamada K (2001) Urinary type IV collagen excretion reflects renal morphological alterations and type IV collagen expression in patients with type 2 diabetes mellitus. Clin Nephrol 55(5):357–364PubMed Okonogi H, Nishimura M, Utsunomiya Y, Hamaguchi K, Tsuchida H, Miura Y, Suzuki S, Kawamura T, Hosoya T, Yamada K (2001) Urinary type IV collagen excretion reflects renal morphological alterations and type IV collagen expression in patients with type 2 diabetes mellitus. Clin Nephrol 55(5):357–364PubMed
10.
go back to reference Taghizadeh-Ghehi M, Sarayani A, Ashouri A, Ataei S, Moslehi A, Hadjibabaie M (2015) Urine neutrophil gelatinase associated lipocalin as an early marker of acute kidney injury in hematopoietic stem cell transplantation patients. Renal failure 37(6):994–998CrossRefPubMed Taghizadeh-Ghehi M, Sarayani A, Ashouri A, Ataei S, Moslehi A, Hadjibabaie M (2015) Urine neutrophil gelatinase associated lipocalin as an early marker of acute kidney injury in hematopoietic stem cell transplantation patients. Renal failure 37(6):994–998CrossRefPubMed
11.
15.
go back to reference Couri CE, Oliveira MC, Stracieri AB, Moraes DA, Pieroni F, Barros GM, Madeira MI, Malmegrim KC, Foss-Freitas MC, Simoes BP, Martinez EZ, Foss MC, Burt RK, Voltarelli JC (2009) C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA 301(15):1573–1579. https://doi.org/10.1001/jama.2009.470 CrossRefPubMed Couri CE, Oliveira MC, Stracieri AB, Moraes DA, Pieroni F, Barros GM, Madeira MI, Malmegrim KC, Foss-Freitas MC, Simoes BP, Martinez EZ, Foss MC, Burt RK, Voltarelli JC (2009) C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA 301(15):1573–1579. https://​doi.​org/​10.​1001/​jama.​2009.​470 CrossRefPubMed
17.
21.
go back to reference Penaforte-Saboia JG, Montenegro RM Jr, Couri CE, Batista LA, Montenegro A, Fernandes VO, Akhtar H, Negrato CA, Malmegrim KCR, Moraes DA, Dias JBE, Simoes BP, Gomes MB, Oliveira MC (2017) Microvascular complications in type 1 diabetes: a comparative analysis of patients treated with autologous nonmyeloablative hematopoietic stem-cell transplantation and conventional medical therapy. Front Endocrinol (Lausanne) 8:331. https://doi.org/10.3389/fendo.2017.00331 CrossRef Penaforte-Saboia JG, Montenegro RM Jr, Couri CE, Batista LA, Montenegro A, Fernandes VO, Akhtar H, Negrato CA, Malmegrim KCR, Moraes DA, Dias JBE, Simoes BP, Gomes MB, Oliveira MC (2017) Microvascular complications in type 1 diabetes: a comparative analysis of patients treated with autologous nonmyeloablative hematopoietic stem-cell transplantation and conventional medical therapy. Front Endocrinol (Lausanne) 8:331. https://​doi.​org/​10.​3389/​fendo.​2017.​00331 CrossRef
23.
go back to reference Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, Ckd EPI (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612CrossRefPubMedPubMedCentral Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, Ckd EPI (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612CrossRefPubMedPubMedCentral
26.
go back to reference Dzholdasbekova A, Fedotovskikh G, Askarov M, Komsabakova B, Baigenzhina A, Kairatova A, Abylkassymova G (2015) Systemic administration of autologous mononuclear precultured bone marrow stem cells in heart failure. J Clin Med Kaz 3(37):14–18 Dzholdasbekova A, Fedotovskikh G, Askarov M, Komsabakova B, Baigenzhina A, Kairatova A, Abylkassymova G (2015) Systemic administration of autologous mononuclear precultured bone marrow stem cells in heart failure. J Clin Med Kaz 3(37):14–18
27.
go back to reference Rakhimbekova GA, Tuganbekova SK, Askarov MB, Zhusupova AS, Krivoruchko NA, Akshalova GA, Rahimberlina HA, Gaipov AE, Ponomarenko YN, Temirgalieva AM, Tokbergenova AB (2013) Autologous hematopoietic stem cell transplantation in systemic sclerosis. J Clin Med Kaz 3(29):7–10 Rakhimbekova GA, Tuganbekova SK, Askarov MB, Zhusupova AS, Krivoruchko NA, Akshalova GA, Rahimberlina HA, Gaipov AE, Ponomarenko YN, Temirgalieva AM, Tokbergenova AB (2013) Autologous hematopoietic stem cell transplantation in systemic sclerosis. J Clin Med Kaz 3(29):7–10
31.
go back to reference Ezquer M, Arango-Rodriguez M, Giraud-Billoud M, Ezquer F (2014) Mesenchymal stem cell therapy in type 1 diabetes mellitus and its main complications: from experimental findings to clinical practice. J Stem Cell Res Ther 4(227):2 Ezquer M, Arango-Rodriguez M, Giraud-Billoud M, Ezquer F (2014) Mesenchymal stem cell therapy in type 1 diabetes mellitus and its main complications: from experimental findings to clinical practice. J Stem Cell Res Ther 4(227):2
32.
go back to reference Xu Y-X, Chen L, Wang R, Hou W-K, Lin P, Sun L, Sun Y, Dong Q-Y (2008) Mesenchymal stem cell therapy for diabetes through paracrine mechanisms. Med Hypotheses 71(3):390–393CrossRefPubMed Xu Y-X, Chen L, Wang R, Hou W-K, Lin P, Sun L, Sun Y, Dong Q-Y (2008) Mesenchymal stem cell therapy for diabetes through paracrine mechanisms. Med Hypotheses 71(3):390–393CrossRefPubMed
Metadata
Title
Infusion of autologous bone marrow derived mononuclear stem cells potentially reduces urinary markers in diabetic nephropathy
Authors
Abduzhappar Gaipov
Zhannat Taubaldiyeva
Manarbek Askarov
Zaiyrkhan Turebekov
Larisa Kozina
Askhat Myngbay
Olga Ulyanova
Saltanat Tuganbekova
Publication date
01-02-2019
Publisher
Springer International Publishing
Published in
Journal of Nephrology / Issue 1/2019
Print ISSN: 1121-8428
Electronic ISSN: 1724-6059
DOI
https://doi.org/10.1007/s40620-018-0548-5

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