Research

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19 pages, 3816 KiB

Open AccessArticle

Phosphorylation of PACSIN2 at S313 Regulates Podocyte Architecture in Coordination with N-WASP

by Rim Bouslama, Vincent Dumont, Sonja Lindfors, Lassi Paavolainen, Jukka Tienari, Harry Nisen, Tuomas Mirtti, Moin A. Saleem, Daniel Gordin, Per-Henrik Groop, Shiro Suetsugu and Sanna Lehtonen

Cells 2023, 12(11), 1487; https://doi.org/10.3390/cells12111487 - 27 May 2023

Viewed by 1445

Abstract

Changes in the dynamic architecture of podocytes, the glomerular epithelial cells, lead to kidney dysfunction. Previous studies on protein kinase C and casein kinase 2 substrates in neurons 2 (PACSIN2), a known regulator of endocytosis and cytoskeletal organization, reveal a connection between PACSIN2 [...] Read more.

Changes in the dynamic architecture of podocytes, the glomerular epithelial cells, lead to kidney dysfunction. Previous studies on protein kinase C and casein kinase 2 substrates in neurons 2 (PACSIN2), a known regulator of endocytosis and cytoskeletal organization, reveal a connection between PACSIN2 and kidney pathogenesis. Here, we show that the phosphorylation of PACSIN2 at serine 313 (S313) is increased in the glomeruli of rats with diabetic kidney disease. We found that phosphorylation at S313 is associated with kidney dysfunction and increased free fatty acids rather than with high glucose and diabetes alone. Phosphorylation of PACSIN2 emerged as a dynamic process that fine-tunes cell morphology and cytoskeletal arrangement, in cooperation with the regulator of the actin cytoskeleton, Neural Wiskott–Aldrich syndrome protein (N-WASP). PACSIN2 phosphorylation decreased N-WASP degradation while N-WASP inhibition triggered PACSIN2 phosphorylation at S313. Functionally, pS313-PACSIN2 regulated actin cytoskeleton rearrangement depending on the type of cell injury and the signaling pathways involved. Collectively, this study indicates that N-WASP induces phosphorylation of PACSIN2 at S313, which serves as a mechanism whereby cells regulate active actin-related processes. The dynamic phosphorylation of S313 is needed to regulate cytoskeletal reorganization. Full article

(This article belongs to the Special Issue Recent Advances in Development and Progression of Kidney Diseases)

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14 pages, 2273 KiB

Open AccessArticle

Fyn Phosphorylates Transglutaminase 2 (Tgm2) and Modulates Autophagy and p53 Expression in the Development of Diabetic Kidney Disease

by Ryota Uehara, Eijiro Yamada, Shuichi Okada, Claire C. Bastie, Akito Maeshima, Hidekazu Ikeuchi, Kazuhiko Horiguchi and Masanobu Yamada

Cells 2023, 12(8), 1197; https://doi.org/10.3390/cells12081197 - 20 Apr 2023

Viewed by 1612

Abstract

Autophagy is involved in the development of diabetic kidney disease (DKD), the leading cause of end-stage renal disease. The Fyn tyrosine kinase (Fyn) suppresses autophagy in the muscle. However, its role in kidney autophagic processes is unclear. Here, we examined the role of [...] Read more.

Autophagy is involved in the development of diabetic kidney disease (DKD), the leading cause of end-stage renal disease. The Fyn tyrosine kinase (Fyn) suppresses autophagy in the muscle. However, its role in kidney autophagic processes is unclear. Here, we examined the role of Fyn kinase in autophagy in proximal renal tubules both in vivo and in vitro. Phospho-proteomic analysis revealed that transglutaminase 2 (Tgm2), a protein involved in the degradation of p53 in the autophagosome, is phosphorylated on tyrosine 369 (Y369) by Fyn. Interestingly, we found that Fyn-dependent phosphorylation of Tgm2 regulates autophagy in proximal renal tubules in vitro, and that p53 expression is decreased upon autophagy in Tgm2-knockdown proximal renal tubule cell models. Using streptozocin (STZ)-induced hyperglycemic mice, we confirmed that Fyn regulated autophagy and mediated p53 expression via Tgm2. Taken together, these data provide a molecular basis for the role of the Fyn–Tgm2–p53 axis in the development of DKD. Full article

(This article belongs to the Special Issue Recent Advances in Development and Progression of Kidney Diseases)

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12 pages, 2125 KiB

Open AccessCommunication

Tubule-Derived Follistatin Is Increased in the Urine of Rats with Renal Ischemia and Reflects the Severity of Acute Tubular Damage

by Izumi Nagayama, Kaori Takayanagi, Hajime Hasegawa and Akito Maeshima

Cells 2023, 12(5), 801; https://doi.org/10.3390/cells12050801 - 04 Mar 2023

Cited by 1 | Viewed by 1789

Abstract

Activin A, a member of the TGF-beta superfamily, is a negative regulator of tubular regeneration after renal ischemia. Activin action is controlled by an endogenous antagonist, follistatin. However, the role of follistatin in the kidney is not fully understood. In the present study, [...] Read more.

Activin A, a member of the TGF-beta superfamily, is a negative regulator of tubular regeneration after renal ischemia. Activin action is controlled by an endogenous antagonist, follistatin. However, the role of follistatin in the kidney is not fully understood. In the present study, we examined the expression and localization of follistatin in normal and ischemic rat kidneys and measured urinary follistatin in rats with renal ischemia to assess whether urinary follistatin could serve as a biomarker for acute kidney injury. Using vascular clamps, renal ischemia was induced for 45 min in 8-week-old male Wistar rats. In normal kidneys, follistatin was localized in distal tubules of the cortex. In contrast, in ischemic kidneys, follistatin was localized in distal tubules of both the cortex and outer medulla. Follistatin mRNA was mainly present in the descending limb of Henle of the outer medulla in normal kidneys but was upregulated in the descending limb of Henle of both the outer and inner medulla after renal ischemia. Urinary follistatin, which was undetectable in normal rats, was significantly increased in ischemic rats and peaked 24 h after reperfusion. There was no correlation between urinary follistatin and serum follistatin. Urinary follistatin levels were increased according to ischemic duration and were significantly correlated with the follistatin-positive area as well as the acute tubular damage area. These results suggest that follistatin normally produced by renal tubules increases and becomes detectable in urine after renal ischemia. Urinary follistatin might be useful to assess the severity of acute tubular damage. Full article

(This article belongs to the Special Issue Recent Advances in Development and Progression of Kidney Diseases)

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16 pages, 3303 KiB

Open AccessArticle

MK-2206 Alleviates Renal Fibrosis by Suppressing the Akt/mTOR Signaling Pathway In Vivo and In Vitro

by Meiling Chen, Yihang Yu, Tao Mi, Qitong Guo, Bin Xiang, Xiaomao Tian, Liming Jin, Chunlan Long, Lianju Shen, Xing Liu, Jianbo Pan, Yuanyuan Zhang, Tao Xu, Deying Zhang and Guanghui Wei

Cells 2022, 11(21), 3505; https://doi.org/10.3390/cells11213505 - 05 Nov 2022

Cited by 4 | Viewed by 2023

Abstract

Renal fibrosis is a common pathological feature of various kidney diseases, leading to irreversible renal failure and end-stage renal disease. However, there are still no effective treatments to reverse renal fibrosis. This study aimed to explore the potential mechanism of a targeted drug [...] Read more.

Renal fibrosis is a common pathological feature of various kidney diseases, leading to irreversible renal failure and end-stage renal disease. However, there are still no effective treatments to reverse renal fibrosis. This study aimed to explore the potential mechanism of a targeted drug for fibrosis. Here, unilateral ureteral obstruction (UUO)-treated mice and a TGF-β1-treated human renal tubular epithelial cell line (HK-2 cells) were used as models of renal fibrosis. Based on the changes of mRNA in UUO kidneys detected by transcriptome sequencing, MK-2206, an Akt inhibitor, was predicted as a potential drug to alleviate renal fibrosis through bioinformatics. We dissolved UUO mice with MK-2206 by gastric gavage and cultured TGF-β-induced HK-2 cells with MK-2206. Histopathological examinations were performed after MK-2206 intervention, and the degree of renal fibrosis, as well as the expression of Akt/mTOR pathway-related proteins, were evaluated by immunohistochemical staining, immunofluorescence staining, and Western blot. The results showed that MK-2206 significantly improved the pathological structure of the kidney. Furthermore, MK-2206 intervention effectively inhibited UUO- and TGF-β1-induced epithelial-mesenchymal transition, fibroblast activation, and extracellular matrix deposition. Mechanistically, MK-2206 treatment attenuated the activation of the Akt/mTOR signaling pathway. Taken together, our study revealed for the first time that MK-2206 is a promising drug for the improvement of renal fibrosis. Full article

(This article belongs to the Special Issue Recent Advances in Development and Progression of Kidney Diseases)

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20 pages, 3913 KiB

Open AccessArticle

Repeated Administration of Cisplatin Transforms Kidney Fibroblasts through G2/M Arrest and Cellular Senescence

by Jia-Bin Yu, Dong-Sun Lee, Babu J. Padanilam and Jinu Kim

Cells 2022, 11(21), 3472; https://doi.org/10.3390/cells11213472 - 02 Nov 2022

Cited by 5 | Viewed by 2470

Abstract

Cisplatin is a potent chemotherapeutic used for the treatment of many types of cancer, but it has nephrotoxic side effects leading to acute kidney injury and subsequently chronic kidney disease (CKD). Previous work has focused on acute kidney tubular injury induced by cisplatin, [...] Read more.

Cisplatin is a potent chemotherapeutic used for the treatment of many types of cancer, but it has nephrotoxic side effects leading to acute kidney injury and subsequently chronic kidney disease (CKD). Previous work has focused on acute kidney tubular injury induced by cisplatin, whereas the chronic sequelae post-injury has not been well-explored. In the present study, we established a kidney fibroblast model of CKD induced by repeated administration of cisplatin (RAC) as a clinically relevant model. In NRK-49F rat kidney fibroblasts, RAC upregulated α-smooth muscle actin (α-SMA) and fibronectin proteins, suggesting that RAC induces kidney fibroblast-to-myofibroblast transformation. RAC also enhanced cell size, including the cell attachment surface area, nuclear area, and cell volume. Furthermore, RAC induced p21 expression and senescence-associated β-galactosidase activity, suggesting that kidney fibroblasts exposed to RAC develop a senescent phenotype. Inhibition of p21 reduced cellular senescence, hypertrophy, and myofibroblast transformation induced by RAC. Intriguingly, after RAC, kidney fibroblasts were arrested at the G2/M phase. Repeated treatment with paclitaxel as an inducer of G2/M arrest upregulated p21, α-SMA, and fibronectin in the kidney fibroblasts. Taken together, these data suggest that RAC transforms kidney fibroblasts into myofibroblasts through G2/M arrest and cellular senescence. Full article

(This article belongs to the Special Issue Recent Advances in Development and Progression of Kidney Diseases)

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10 pages, 2826 KiB

Open AccessArticle

Blocking Periostin Prevented Development of Inflammation in Rhabdomyolysis-Induced Acute Kidney Injury Mice Model

by Jun Muratsu, Fumihiro Sanada, Nobutaka Koibuchi, Kana Shibata, Naruto Katsuragi, Shoji Ikebe, Yasuo Tsunetoshi, Hiromi Rakugi, Ryuichi Morishita and Yoshiaki Taniyama

Cells 2022, 11(21), 3388; https://doi.org/10.3390/cells11213388 - 27 Oct 2022

Viewed by 1958

Abstract

Background: Rhabdomyolysis is the collapse of damaged skeletal muscle and the leakage of muscle-cell contents, such as electrolytes, myoglobin, and other sarcoplasmic proteins, into the circulation. The glomeruli filtered these products, leading to acute kidney injury (AKI) through several mechanisms, such as intratubular [...] Read more.

Background: Rhabdomyolysis is the collapse of damaged skeletal muscle and the leakage of muscle-cell contents, such as electrolytes, myoglobin, and other sarcoplasmic proteins, into the circulation. The glomeruli filtered these products, leading to acute kidney injury (AKI) through several mechanisms, such as intratubular obstruction secondary to protein precipitation. The prognosis is highly mutable and depends on the underlying complications and etiologies. New therapeutic plans to reduce AKI are now needed. Up to now, several cellular pathways, with the nuclear factor kappa beta (NF-kB), as well as the proinflammatory effects on epithelial and tubular epithelial cells, have been recognized as the major pathway for the initiation of the matrix-producing cells in AKI. Recently, it has been mentioned that periostin (POSTN), an extracellular matrix protein, is involved in the development of inflammation through the modulation of the NF-kB pathway. However, how POSTN develops the inflammation protection in AKI by rhabdomyolysis is uncertain. This study aimed to investigate the role of POSTN in a rhabdomyolysis mice model of AKI induced by an intramuscular injection of 50% glycerol. Methods: In vivo, we performed an intramuscular injection of 50% glycerol (5 mg/kg body weight) to make rhabdomyolysis-induced AKI. We examined the expression level of POSTN through the progression of AKI after glycerol intramuscular injection for C57BL/6J wildtype (WT) mice. We sacrificed mice at 72 h after glycerol injection. We made periostin-null mice to examine the role of POSTN in acute renal failure. The role of periostin was further examined through in vitro methods. The development of renal inflammation is linked with the NF-kB pathway. To examine the POSTN function, we administrated hemin (100 μM) on NIH-3T3 fibroblast cells, and the following signaling pathways were examined. Results: The expression of periostin was highly increased, peaking at about 72 h after glycerol injection. The expression of inflammation-associated mRNAs such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-a) and IL-6, and tubular injury score in H-E staining were more reduced in POSTN-null mice than WT mice at 72 h after glycerol injection. Conclusion: POSTN was highly expressed in the kidney through rhabdomyolysis and was a positive regulator of AKI. Targeting POSTN might propose a new therapeutic strategy against the development of acute renal failure. Full article

(This article belongs to the Special Issue Recent Advances in Development and Progression of Kidney Diseases)

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16 pages, 3216 KiB

Open AccessArticle

Add-On Cyclic Angiotensin-(1-7) with Cyclophosphamide Arrests Progressive Kidney Disease in Rats with ANCA Associated Glomerulonephritis

by Domenico Cerullo, Daniela Rottoli, Daniela Corna, Mauro Abbate, Ariela Benigni, Giuseppe Remuzzi and Carlamaria Zoja

Cells 2022, 11(15), 2434; https://doi.org/10.3390/cells11152434 - 05 Aug 2022

Cited by 3 | Viewed by 1708

Abstract

Rapidly progressive crescentic glomerulonephritis associated with anti-neutrophil cytoplasmic antibodies (ANCA-GN) is a major cause of renal failure. Current immunosuppressive therapies are associated with severe side effects, intensifying the need for new therapeutic strategies. The activation of Mas receptor/Angiotensin-(1-7) axis exerted renoprotection in chronic [...] Read more.

Rapidly progressive crescentic glomerulonephritis associated with anti-neutrophil cytoplasmic antibodies (ANCA-GN) is a major cause of renal failure. Current immunosuppressive therapies are associated with severe side effects, intensifying the need for new therapeutic strategies. The activation of Mas receptor/Angiotensin-(1-7) axis exerted renoprotection in chronic kidney disease. Here, we investigated the effect of adding the lanthionine-stabilized cyclic form of angiotensin-1-7 [cAng-(1-7)] to cyclophosphamide in a rat model of ANCA-GN. At the onset of proteinuria, Wistar Kyoto rats with ANCA-GN received vehicle or a single bolus of cyclophosphamide, with or without daily cAng-(1-7). Treatment with cAng-(1-7) plus cyclophosphamide reduced proteinuria by 85% vs. vehicle, and by 60% vs. cyclophosphamide, and dramatically limited glomerular crescents to less than 10%. The addition of cAng-(1-7) to cyclophosphamide protected against glomerular inflammation and endothelial rarefaction and restored the normal distribution of parietal epithelial cells. Ultrastructural analysis revealed a preserved GBM, glomerular endothelium and podocyte structure, demonstrating that combination therapy provided an additional layer of renoprotection. This study demonstrates that adding cAng-(1-7) to a partially effective dose of cyclophosphamide arrests the progression of renal disease in rats with ANCA-GN, suggesting that cAng-(1-7) could be a novel clinical approach for sparing immunosuppressants. Full article

(This article belongs to the Special Issue Recent Advances in Development and Progression of Kidney Diseases)

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21 pages, 14170 KiB

Open AccessArticle

Enhanced Autophagic Flux, Suppressed Apoptosis and Reduced Macrophage Infiltration by Dasatinib in Kidneys of Obese Mice

by Hassan Reda Hassan Elsayed, Randa El-Gamal, Mohammed R. Rabei, Mona G. Elhadidy, Shereen Hamed, Basma H. Othman, Mohamed Mahmoud Abdelraheem Elshaer, Mostafa Khaled Sedky, Ahmed Tarek Abd Elbaset Hassan and Mohammad El-Nablaway

Cells 2022, 11(4), 746; https://doi.org/10.3390/cells11040746 - 21 Feb 2022

Cited by 4 | Viewed by 2775

Abstract

Obesity causes renal changes (ORC), characterized by defective renal autophagy, lipogenesis, enhanced macrophage infiltration and apoptosis. We hypothesize that Dasatinib, a tyrosine kinase inhibitor, may ameliorate changes associated with obesity. We the mice with either Obesogenic diet (OD) or a standard basal diet. [...] Read more.

Obesity causes renal changes (ORC), characterized by defective renal autophagy, lipogenesis, enhanced macrophage infiltration and apoptosis. We hypothesize that Dasatinib, a tyrosine kinase inhibitor, may ameliorate changes associated with obesity. We the mice with either Obesogenic diet (OD) or a standard basal diet. After 12 weeks, the mice received either vehicle or Dasatinib 4 mg/kg/d for an additional four weeks. We examined serum creatinine, urea, lipid profile and renal cortical mRNA expression for lipogenesis marker SREBP1, inflammatory macrophage marker iNOS and fibrosis markers; TGFβ and PDGFA genes; immunohistochemical (IHC) staining for CD68; inflammatory macrophage marker and ASMA; fibrosis marker, LC3 and SQSTM1/P62; autophagy markers and western blotting (WB) for caspase-3; and, as an apoptosis marker, LC3II/I and SQSTM1/P62 in addition to staining for H&E, PAS, Sirius red and histopathological scoring. Dasatinib attenuated renal cortical mRNA expression for SREBP1, iNOS, PDGFA and TGFβ and IHC staining for CD68, ASMA and SQSTM1/P62 and WB for caspase-3 and SQSTM1/P62, while elevating LC3 expression. Moreover, Dasatinib ameliorated ORC; glomerulosclerosis, glomerular expansion, tubular dilatation, vacuolation and casts; inflammatory cellular infiltration; and fibrosis. Dasatinib is a promising therapy for ORC by correcting autophagy impairment, attenuating lipogenesis, apoptosis and macrophage infiltration by inducing antifibrotic activity. Full article

(This article belongs to the Special Issue Recent Advances in Development and Progression of Kidney Diseases)

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15 pages, 3376 KiB

Open AccessArticle

p53 in Proximal Tubules Mediates Chronic Kidney Problems after Cisplatin Treatment

by Shuangshuang Fu, Xiaoru Hu, Zhengwei Ma, Qingqing Wei, Xiaohong Xiang, Siyao Li, Lu Wen, Yumei Liang and Zheng Dong

Cells 2022, 11(4), 712; https://doi.org/10.3390/cells11040712 - 17 Feb 2022

Cited by 10 | Viewed by 2515

Abstract

Nephrotoxicity is a major side-effect of cisplatin in chemotherapy, which can occur acutely or progress into chronic kidney disease (CKD). The protein p53 plays an important role in acute kidney injury induced by cisplatin, but its involvement in CKD following cisplatin exposure is [...] Read more.

Nephrotoxicity is a major side-effect of cisplatin in chemotherapy, which can occur acutely or progress into chronic kidney disease (CKD). The protein p53 plays an important role in acute kidney injury induced by cisplatin, but its involvement in CKD following cisplatin exposure is unclear. Here, we address this question by using experimental models of repeated low-dose cisplatin (RLDC) treatment. In mouse proximal tubular BUMPT cells, RLDC treatment induced p53 activation, apoptosis, and fibrotic changes, which were suppressed by pifithrin-α, a pharmacologic inhibitor of p53. In vivo, chronic kidney problems following RLDC treatment were ameliorated in proximal tubule-specific p53-knockout mice (PT-p53-KO mice). Compared with wild-type littermates, PT-p53-KO mice showed less renal damage (KIM-1 positive area: 0.97% vs. 2.5%), less tubular degeneration (LTL positive area: 15.97% vs. 10.54%), and increased proliferation (Ki67 positive area: 2.42% vs. 0.45%), resulting in better renal function after RLDC treatment. Together, these results indicate that p53 in proximal tubular cells contributes significantly to the development of chronic kidney problems following cisplatin chemotherapy. Full article

(This article belongs to the Special Issue Recent Advances in Development and Progression of Kidney Diseases)

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Review

Jump to: Research

15 pages, 681 KiB

Open AccessReview

Acute Kidney Injury in Cancer Immunotherapy Recipients

by Adrien Joseph, Antoine Lafarge, Elie Azoulay and Lara Zafrani

Cells 2022, 11(24), 3991; https://doi.org/10.3390/cells11243991 - 10 Dec 2022

Cited by 4 | Viewed by 2643

Abstract

Cancer immunotherapy has now entered clinical practice and has reshaped the standard of care for many cancer patients. With these new strategies, specific toxicities have emerged, and renal side effects have been described. In this review, we will describe the causes of acute [...] Read more.

Cancer immunotherapy has now entered clinical practice and has reshaped the standard of care for many cancer patients. With these new strategies, specific toxicities have emerged, and renal side effects have been described. In this review, we will describe the causes of acute kidney injury in CAR T cell, immune checkpoint inhibitors and other cancer immuno-therapy recipients. CAR T cell therapy and bispecific T cell engaging antibodies can lead to acute kidney injury as a consequence of cytokine release syndrome, tumor lysis syndrome, sepsis or specific CAR T cell infiltration. Immune checkpoint blockade most often results in acute tubular interstitial nephritis, but glomerular diseases have also been described. Although the pathophysiology remains mostly elusive, we will describe the mechanisms of renal damage in these contexts, its prognosis and treatment. As the place of immunotherapy in the anti-cancer armamentarium is exponentially increasing, close collaboration between nephrologists and oncologists is of utmost importance to provide the best standard of care for these patients. Full article

(This article belongs to the Special Issue Recent Advances in Development and Progression of Kidney Diseases)

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13 pages, 326 KiB

Open AccessReview

Gender and Renal Insufficiency: Opportunities for Their Therapeutic Management?

by Tiziana Ciarambino, Pietro Crispino and Mauro Giordano

Cells 2022, 11(23), 3820; https://doi.org/10.3390/cells11233820 - 29 Nov 2022

Cited by 9 | Viewed by 1523

Abstract

Acute kidney injury (AKI) is a major clinical problem associated with increased morbidity and mortality. Despite intensive research, the clinical outcome remains poor, and apart from supportive therapy, no other specific therapy exists. Furthermore, acute kidney injury increases the risk of developing chronic [...] Read more.

Acute kidney injury (AKI) is a major clinical problem associated with increased morbidity and mortality. Despite intensive research, the clinical outcome remains poor, and apart from supportive therapy, no other specific therapy exists. Furthermore, acute kidney injury increases the risk of developing chronic kidney disease (CKD) and end-stage renal disease. Acute tubular injury accounts for the most common intrinsic cause of AKI. The main site of injury is the proximal tubule due to its high workload and energy demand. Upon injury, an intratubular subpopulation of proximal epithelial cells proliferates and restores the tubular integrity. Nevertheless, despite its strong regenerative capacity, the kidney does not always achieve its former integrity and function and incomplete recovery leads to persistent and progressive CKD. Clinical and experimental data demonstrate sexual differences in renal anatomy, physiology, and susceptibility to renal diseases including but not limited to ischemia-reperfusion injury. Some data suggest the protective role of female sex hormones, whereas others highlight the detrimental effect of male hormones in renal ischemia-reperfusion injury. Although the important role of sex hormones is evident, the exact underlying mechanisms remain to be elucidated. This review focuses on collecting the current knowledge about sexual dimorphism in renal injury and opportunities for therapeutic manipulation, with a focus on resident renal progenitor stem cells as potential novel therapeutic strategies. Full article

(This article belongs to the Special Issue Recent Advances in Development and Progression of Kidney Diseases)

22 pages, 2509 KiB

Open AccessReview

Diabetic Proteinuria Revisited: Updated Physiologic Perspectives

by Samuel N. Heyman, Itamar Raz, Jamie P. Dwyer, Roni Weinberg Sibony, Julia B. Lewis and Zaid Abassi

Cells 2022, 11(18), 2917; https://doi.org/10.3390/cells11182917 - 18 Sep 2022

Cited by 12 | Viewed by 5374

Abstract

Albuminuria, a hallmark of diabetic nephropathy, reflects not only injury and dysfunction of the filtration apparatus, but is also affected by altered glomerular hemodynamics and hyperfiltration, as well as by the inability of renal tubular cells to fully retrieve filtered albumin. Albuminuria further [...] Read more.

Albuminuria, a hallmark of diabetic nephropathy, reflects not only injury and dysfunction of the filtration apparatus, but is also affected by altered glomerular hemodynamics and hyperfiltration, as well as by the inability of renal tubular cells to fully retrieve filtered albumin. Albuminuria further plays a role in the progression of diabetic nephropathy, and the suppression of glomerular albumin leak is a key factor in its prevention. Although microalbuminuria is a classic manifestation of diabetic nephropathy, often progressing to macroalbuminuria or overt proteinuria over time, it does not always precede renal function loss in diabetes. The various components leading to diabetic albuminuria and their associations are herein reviewed, and the physiologic rationale and efficacy of therapeutic interventions that reduce glomerular hyperfiltration and proteinuria are discussed. With these perspectives, we propose that these measures should be initiated early, before microalbuminuria develops, as substantial renal injury may already be present in the absence of proteinuria. We further advocate that the inhibition of the renin–angiotensin axis or of sodium–glucose co-transport likely permits the administration of a normal recommended or even high-protein diet, highly desirable for sarcopenic diabetic patients. Full article

(This article belongs to the Special Issue Recent Advances in Development and Progression of Kidney Diseases)

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20 pages, 1458 KiB

Open AccessReview

Going Micro in Leptospirosis Kidney Disease

by Wiwat Chancharoenthana, Asada Leelahavanichkul, Marcus J. Schultz and Arjen M. Dondorp

Cells 2022, 11(4), 698; https://doi.org/10.3390/cells11040698 - 16 Feb 2022

Cited by 9 | Viewed by 4513

Abstract

Leptospirosis is a zoonotic and waterborne disease worldwide. It is a neglected infectious disease caused by Leptospira spp., as well as a reemerging disease and global public health problem with respect to morbidity and mortality both in humans and animals. Leptospirosis emerges as [...] Read more.

Leptospirosis is a zoonotic and waterborne disease worldwide. It is a neglected infectious disease caused by Leptospira spp., as well as a reemerging disease and global public health problem with respect to morbidity and mortality both in humans and animals. Leptospirosis emerges as a leading cause of acute febrile illness along with hepatorenal injury in many countries, including Thailand. While most affected persons are symptomatic in acute disease, which is always difficult to differentiate from other tropical diseases, there is growing evidence of subtle manifestations that cause unrecognized chronic symptoms. The kidney is one of the common organs affected by Leptospires. Although acute kidney injury in the spectrum of interstitial nephritis is a well-described characteristic in severe leptospirosis, chronic kidney disease from leptospirosis is widely discussed. Early recognition of severe leptospirosis leads to reduce morbidity and mortality. Thus, in this review, we highlight the spectrum of characteristics involved in leptospirosis kidney disease and the use of serologic and molecular methods, as well as the treatments of severe leptospirosis. Full article

(This article belongs to the Special Issue Recent Advances in Development and Progression of Kidney Diseases)

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