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Nephron number

Carlos Menendez-Castro, Dörte Nitz, Nada Cordasic, Jutta Jordan, Tobias Bäuerle, Fabian B Fahlbusch, Wolfgang Rascher, Karl F Hilgers, Andrea Hartner
Neonatal nephron loss may follow hypoxic-ischemic events or nephrotoxic medications. Its long-term effects on the kidney are still unclear. Unlike term infants, preterm neonates less than 36 weeks gestational age show ongoing nephrogenesis. We hypothesized that nephron loss during nephrogenesis leads to more severe renal sequelae than nephron loss shortly after the completion of nephrogenesis. Rats show nephrogenesis until day 10 of life resembling the situation of preterm infants. Animals were uninephrectomized at day 1 (UNX d1) resulting in nephron reduction during nephrogenesis and at day 14 of life (UNX d14) inducing nephron loss after the completion of nephrogenesis...
March 14, 2018: Scientific Reports
Michelangelo Nigro, Davide Viggiano, Vincenzo Ragone, Tiziana Trabace, Annamaria di Palma, Michele Rossini, Giovambattista Capasso, Loreto Gesualdo, Giuseppe Gigliotti
BACKGROUND: The classical approach to the analysis of kidney biopsies is based on semi-quantitative scores of the amount of sclerosis, inflammatory infiltrate, fibrosis and vascular damage. However, advanced renal lesions may be accompanied by a paucity of clinical features and, conversely, important clinical abnormalities may be accompanied by minimal histopathological changes. The objective of this study is to correlate new, semiautomatic, quantitative features of kidney biopsies (e...
March 14, 2018: BMC Nephrology
Eva Nüsken, Jörg Dötsch, Lutz T Weber, Kai-Dietrich Nüsken
Chronic kidney disease affects more than 10% of the population. Programming studies have examined the interrelationship between environmental factors in early life and differences in morbidity and mortality between individuals. A number of important principles has been identified, namely permanent structural modifications of organs and cells, long-lasting adjustments of endocrine regulatory circuits, as well as altered gene transcription. Risk factors include intrauterine deficiencies by disturbed placental function or maternal malnutrition, prematurity, intrauterine and postnatal stress, intrauterine and postnatal overnutrition, as well as dietary dysbalances in postnatal life...
2018: Frontiers in Pediatrics
Karen L Price, Maria Kolatsi-Joannou, Chiara Mari, David A Long, Paul J D Winyard
Kidney function is directly linked to the number of nephrons which are generated until 32-36 weeks gestation in humans. Failure to make nephrons during development leads to congenital renal malformations, whilst nephron loss in adulthood occurs in progressive renal disease. Therefore, an understanding of the molecular processes which underlie human nephron development may help design new treatments for renal disease. Mesenchyme to epithelial transition (MET) is critical for forming nephrons, and molecular pathways which control rodent MET have been identified...
December 2018: Cell Death Discovery
José A Damasceno-Ferreira, Leonardo A S Abreu, Gustavo R Bechara, Waldemar S Costa, Marco A Pereira-Sampaio, Francisco J B Sampaio, Diogo B De Souza
BACKGROUND: Mannitol has been employed to ameliorate renal warm ischemia damage during partial nephrectomy, however, there is limited scientific evidence to support the use of mannitol during partial nephrectomy. The objective of the present study was to investigate the glomerular number after renal warm ischemia, with and without the use of mannitol in a Pig Model. METHODS: Twenty-four male pigs were assigned into three groups. Eight animals were allocated to the sham group that was subjected to laparoscopic dissection of the left renal hilum, without renal ischemia...
March 6, 2018: BMC Urology
S K Frees, R Mager, H Borgmann, W Jäger, C Thomas, A Haferkamp
BACKGROUND: Several new treatment strategies have emerged in the treatment of small renal masses (<4 cm in diameter). Active surveillance and ablative techniques have been introduced but it remains unclear which patients will benefit the most from these new treatment options. A surgical approach remains standard of care. In recent decades, radical nephrectomy has been replaced by nephron-sparing surgery for the management of small renal masses. RESULTS: In addition to the open partial nephrectomy, which is considered the standard approach, the number of surgeries performed using minimally invasive techniques is increasing...
March 2018: Der Urologe. Ausg. A
Martin W W Janssen, Johannes Linxweiler, Ines Philipps, Zentia Bütow, Stefan Siemer, Michael Stöckle, Carsten-Henning Ohlmann
BACKGROUND: Kidney autotransplantation (KAT) is the ultimate approach for nephron-sparing surgery. It is a rarely used method in renal tumor surgery today as minimal invasive and open techniques for nephron-sparing surgery improve constantly. In this publication, the complication rate and the long-term functional and oncological outcome at a single center are analyzed. METHODS: A prospectively constructed database of patients with renal tumors who underwent renal surgery was retrospectively analyzed to identify patients with KAT and describe surgical and oncological outcomes and to obtain long-term follow-up...
February 20, 2018: World Journal of Surgical Oncology
Nils O Lindström, Jill A McMahon, Jinjin Guo, Tracy Tran, Qiuyu Guo, Elisabeth Rutledge, Riana K Parvez, Gohar Saribekyan, Robert E Schuler, Christopher Liao, Albert D Kim, Ahmed Abdelhalim, Seth W Ruffins, Matthew E Thornton, Laurence Basking, Brendan Grubbs, Carl Kesselman, Andrew P McMahon
Human kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number is linked to disease. Human kidney development initiates around 4 weeks of gestation and ends around 34-37 weeks of gestation. Over this period, a reiterative inductive process establishes the nephron complement. Studies have provided insightful anatomic descriptions of human kidney development, but the limited histologic views are not readily accessible to a broad audience...
February 15, 2018: Journal of the American Society of Nephrology: JASN
Kee Hwan Yoo, Hyung Eun Yim, Eun Soo Bae, Young Sook Hong
Proper and timely assembly of the kidney vasculature with their respective nephrons is crucial during normal kidney development. In this study, we investigated the effects of enalapril (angiotensin-converting enzyme inhibitor) on angiogenesis-related gene expression and microvascular endothelium related to glomeular and tubular changes in the neonatal rat kidney. Enalapril-treated rats had higher tubular injury scores and lower glomerular maturity grades than those of untreated rats. In the enalapril-treated group, intrarenal angiopoietin-2, Tie-2, and thrombospondin-1 protein expression increased, whereas intrarenal angiopoietin-1 protein expression decreased...
February 13, 2018: Journal of Molecular Histology
Joshua Rowland, Artur Akbarov, Akhlaq Maan, James Eales, John Dormer, Maciej Tomaszewski
Ageing of the kidney is a multi-dimensional process that occurs simultaneously at the molecular, cellular, histological, anatomical and physiological level. Nephron number and renal cortical volume decline, renal tubules become atrophic and glomeruli become sclerotic with age. These structural changes are accompanied by a decline in glomerular filtration rate, decreased sodium reabsorption and potassium excretion, reduced urinary concentrating capacity and alterations in the endocrine activity of the kidney...
January 24, 2018: Kidney & Blood Pressure Research
Zhen Wang, Li-Min Guo, Hong-Kang Zhou, Hong-Ke Qu, Shu-Chao Wang, Feng-Xia Liu, Dan Chen, Ju-Fang Huang, Kun Xiong
Evolutionary medicine has proven helpful to understand the origin of human disease, e.g. in identifying causal roles of recent environmental changes impacting on human physiology (environment-phenotype mismatch). In contrast, diseases affecting only a limited number of members of a species often originate from evolutionary trade-offs for usually physiologic adaptations assuring reproductive success in the context of extrinsic threats. For example, the G1 and G2 variants of the APOL1 gene supporting control of Trypanosoma infection come with the trade-off that they promote the progression of kidney disease...
February 1, 2018: Histology and Histopathology
Kerstin Benz, Julia Schlote, Christoph Daniel, Christoph Kopp, Anke Dahlmann, Agnes Schröder, Nada Cordasic, Bernd Klanke, Karl Hilgers, Jens Titze, Kerstin Amann
BACKGROUND/AIMS: One potential pathomechanism how low nephron number leads to hypertension in later life is altered salt handling. We therefore evaluated changes in electrolyte and water content in wildtype (wt) and GDNF+/- mice with a 30% reduction of nephron number. METHODS: 32 GDNF+/- and 36 wt mice were fed with low salt (LSD, 0.03%, normal drinking water) or high salt (HSD, 4%, 0.9% drinking water) diet for 4 weeks. Blood pressure was continuously measured by telemetry in a subgroup...
January 23, 2018: Kidney & Blood Pressure Research
David T Selewski, Dylan M Hyatt, Kevin M Bennett, Jennifer R Charlton
PURPOSE OF REVIEW: Despite abundant evidence in adults, the relationship between acute kidney injury (AKI) and chronic kidney disease (CKD) remains unanswered in pediatrics. Obstacles to overcome include the challenges defining these entities and the lack of long-term follow-up studies. This review focuses on pediatric populations at high-risk for AKI, the evidence of the long-term effect of AKI on renal health, and biomarkers to detect renal disease. RECENT FINDINGS: AKI in critically ill children and neonates is common and independently associated with adverse outcomes...
April 2018: Current Opinion in Pediatrics
Lori L O'Brien, Qiuyu Guo, Emad Bahrami-Samani, Joo-Seop Park, Sean M Hasso, Young-Jin Lee, Alan Fang, Albert D Kim, Jinjin Guo, Trudy M Hong, Kevin A Peterson, Scott Lozanoff, Ramya Raviram, Bing Ren, Ben Fogelgren, Andrew D Smith, Anton Valouev, Andrew P McMahon
Nephron progenitor number determines nephron endowment; a reduced nephron count is linked to the onset of kidney disease. Several transcriptional regulators including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required for specification and/or maintenance of nephron progenitors. However, little is known about the regulatory intersection of these players. Here, we have mapped nephron progenitor-specific transcriptional networks of Six2, Hoxd11, Osr1, and Wt1. We identified 373 multi-factor associated 'regulatory hotspots' around genes closely associated with progenitor programs...
January 29, 2018: PLoS Genetics
Roxana Cleper
Solitary functioning kidney (SFK) occurs with unilateral renal agenesis (URA) in 1/2000 live births - or after uninephrectomy for tumor, trauma, uncontrolled infections or hypertension and post-kidney donation. URA-associated states include urological, cardiac, gastrointestinal and skeletal anomalies or it might be a component of a genetic syndrome. In 10% of cases of URA another family member is affected. In any case of SFK a compensatory process is triggered consisting of glomerular hypertension with hyperfiltration which achieves 75% of two kidneys' function...
January 2018: Harefuah
Anita T Layton, Volker Vallon
Sodium-glucose co-transporter 2 (SGLT2) inhibitors enhance urinary glucose, Na+ and fluid excretion and lower hyperglycemia in diabetes by targeting Na+ and glucose reabsorption along the proximal convoluted tubule. A goal of this study is to predict the effects of SGLT2 inhibitors in diabetic and non-diabetic patients with chronic kidney disease. To that end, we employed computational rat kidney models to explore how SGLT2 inhibition affects renal solute transport and metabolism when nephron populations are normal or reduced...
January 17, 2018: American Journal of Physiology. Renal Physiology
Anita T Layton, Aurélie Edwards, Volker Vallon
We sought to decipher the mechanisms underlying the kidney's response to changes in K+ load and intake, under physiological and pathophysiological conditions. To accomplish that goal, we applied a published computational model of epithelial transport along rat nephrons in a \Red{sham}, uninephrectomized (UNX), and 5/6-nephrectomized (5/6-NX) \Red{rats that also considers adaptations in GFR and tubular growth}. Model simulations \Red{of an acute K+ load} indicate that elevated expression levels and activities of Na+/K+-ATPase, epithelial sodium channels (ENaC), large conductance Ca2+-activated K+ channels (BK), and renal outer medullary K+ channels (ROMK), together with downregulation of sodium-chloride cotransporters (NCC), increase K+ secretion along the connecting tubule, resulting in a > 6-fold increase in urinary K+ excretion in \Red{sham rats}, which substantially exceeds the filtered K+ load...
December 13, 2017: American Journal of Physiology. Renal Physiology
Michael Hultström, Mediha Becirovic-Agic, Sofia Jönsson
Acute kidney injury (AKI) is a syndrome of reduced glomerular filtration rate and urine production caused by a number of different diseases. It is associated with renal tissue damage. This tissue damage can cause tubular atrophy and interstitial fibrosis that leads to nephron loss and progression of chronic kidney disease (CKD). This review describes the in-common mechanisms behind tissue damage in AKI caused by different underlying diseases. Comparing six high-quality microarray studies of renal gene expression after AKI in disease models (gram-negative sepsis, gram-positive sepsis, ischemia-reperfusion, malignant hypertension, rhabdomyolysis, and cisplatin toxicity) identified 5,254 differentially expressed genes in at least one of the AKI models; 66% of genes were found only in one model, showing that there are unique features to AKI depending on the underlying disease...
March 1, 2018: Physiological Genomics
Tawatchai Taweemonkongsap, Chalairat Suk-Ouichai, Ekkarin Chotikawanich, Siros Jitpraphai, Varat Woranisarakul, Patkawat Ramart, Kittipong Phinthusophon, Teerapon Amornvesukit, Sunai Leewansangtong, Sittiporn Srinualnad, Chaiyong Nualyong
INTRODUCTION: Robot-assisted partial nephrectomy (RAPN) with different arterial clamping techniques has increasingly been performed to avoid ischemic injury to nephron. However, postoperative renal function remains controversial. We determine the impact of each renal arterial clamping on surgical and renal outcomes after RAPN. MATERIALS AND METHODS: Patients who underwent RAPN at Siriraj Hospital from 2010 to 2016 were retrospectively reviewed and stratified into 3 cohorts: main-clamp (MAC), selective-clamp, and off-clamp...
January 16, 2018: Urologia Internationalis
Susan E Zimmerman, Chitkale Hiremath, Jun Tsunezumi, Zhufeng Yang, Bronwyn Finney, Denise K Marciano
A critical aspect of kidney function occurs at the glomerulus, the capillary network that filters the blood. The glomerular basement membrane (GBM) is a key component of filtration, yet our understanding of GBM interactions with mesangial cells, specialized pericytes that provide structural stability to glomeruli, is limited. We investigated the role of nephronectin ( Npnt ), a GBM component and known ligand of α 8 β 1 integrin. Immunolocalization and in situ hybridization studies in kidneys of adult mice revealed that nephronectin is produced by podocytes and deposited into the GBM...
January 15, 2018: Journal of the American Society of Nephrology: JASN
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