scholarly journals The urea transporter UT-A1 plays a predominant role in a urea-dependent urine-concentrating mechanism

2020 ◽  
Vol 295 (29) ◽  
pp. 9893-9900 ◽  
Author(s):  
Xiaoqiang Geng ◽  
Shun Zhang ◽  
Jinzhao He ◽  
Ang Ma ◽  
Yingjie Li ◽  
...  

Urea transporters are a family of urea-selective channel proteins expressed in multiple tissues that play an important role in the urine-concentrating mechanism of the mammalian kidney. Previous studies have shown that knockout of urea transporter (UT)-B, UT-A1/A3, or all UTs leads to urea-selective diuresis, indicating that urea transporters have important roles in urine concentration. Here, we sought to determine the role of UT-A1 in the urine-concentrating mechanism in a newly developed UT-A1–knockout mouse model. Phenotypically, daily urine output in UT-A1–knockout mice was nearly 3-fold that of WT mice and 82% of all-UT–knockout mice, and the UT-A1–knockout mice had significantly lower urine osmolality than WT mice. After 24-h water restriction, acute urea loading, or high-protein (40%) intake, UT-A1–knockout mice were unable to increase urine-concentrating ability. Compared with all-UT–knockout mice, the UT-A1–knockout mice exhibited similarly elevated daily urine output and decreased urine osmolality, indicating impaired urea-selective urine concentration. Our experimental findings reveal that UT-A1 has a predominant role in urea-dependent urine-concentrating mechanisms, suggesting that UT-A1 represents a promising diuretic target.

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Tijana Azasevac ◽  
Violeta Knezevic ◽  
Sonja Golubović ◽  
Bojana Ljubiäiä‡ ◽  
Mira Markovic ◽  
...  

Abstract Background and Aims Most patients with end stage renal disease (ESRD) initiate maintenance dialysis in three times per week regime irrespectively of residual kidney function (RKF). Incremental haemodialysis (IHD) showed benefits of starting and maintaining patients on less than three times per week regime, most importantly preserving urine volume output (UVO) and RKF. The aim of this study was to assess the main differences between a group of patients initiating dialysis once-weekly (1xHD) and twice-weekly (2xHD), to evaluate time to dialysis regime change, UVO and patients volume status at the end of study period. Method Patients with ESRD who started haemodialysis through the planned IHD (once-weekly and twice-weekly) and were undergoing IHD for at least 4 months (M) were enrolled (n=44) in the study. Study was conducted from January 2016 to December 2019 at dialysis department of our hospital. Patients were divided into two groups: 1xHD (20 pts) and 2xHD (24 pts). They were excluded from the study at the end of study period or earlier if they transitioned to thrice-weekly haemodialysis or died. Patients fluid status and body composition was assessed using results derived from bioimpedance measurements performed using Body Composition Monitor device. Results The 1xHD pts were younger (66,8±11,6 versus 67,4±10 years: P>0.05) and weighed less (74,4±14,7 versus 75,5±11,9 kg, p>0,05) with lower BMI. In both groups there were more males (60% versus 62,5%: P>0,05). The most common cause of ESRD in both groups was nephrosclerosis (45% in 1xHD versus 47,1% in 2xHD, p>0,05), followed by diabetic nephropathy (30% versus 20,8%, p>0,05), obstructive nephropathy (10% versus 8,3%, p>0,05), multiple myeloma (10% versus 8,3%, p>0,05), glomerulonephritis (5% versus 8,3%, p>0,05) and others in 2xHD group (12,5%; polycystic kidney disease and chronic interstitial nephritis). The estimated glomerular filtration rate of all patients at the time of HD initiation was 7,5±2,2 ml/min/1.73m2 (8,2±2,8 in 1xHD group versus 6,9±1,48 ml/ min/1.73m2 in 2xHD group, p>0,05). Baseline daily urine output was similar, 1826,6±344,6 ml/day in 1xHD and 1772,2±343,8 ml/day in 2xHD group (p>0,05). Patients in 1xHD concluded the study after mean period of 13,4 M (min 4 M, max 35 M). At the end of study period only three patients (15%) continued receiving dialysis once-weekly (mean 14,5 M, min 7 M, max 19 M), 12 pts (60%) transitioned to twice-weekly dialysis regime after 2 to 6 M (mean 3,1 M) and continued to receive this dialysis regime until the end of study period. Four pts (20%) transitioned to full-dose dialysis (mean 18,2 M, 11-24 M). Most of the patients in 2xHD group (17; 70,8%) concluded study in the same dialysis regime (mean 20,4 M, 4-24 M), 7 pts (29%) transitioned to full-dose dialysis (mean 12,6 M, 5-21 M) and one patient transitioned to once-weekly HD (8M). At the end of study daily urine output was 1463,1±317,5 in 1xHD versus 1321,1±309,1 ml/day in 2xHD group (p>0,05). Results of assessment of fluid status and body composition at the end of study are in Table 1. We evaluated nutritional status at the end of study: total protein 57,4±8,9 g/l in 1xHD versus 62,8±5,3 g/l in 2xHD, albumin 36,9±10,6 versus 37,6±4,4 g/l, total cholesterol 4,1±1,6 versus 4,4±1,3 mmol/l, triglycerides 1,3±0,8 versus 1,7±0,7 mmol/l (p>0,05 for all parameters). At the end of the study 70% of patients treated with IHD maintained renal function that was sufficient to continue IHD regime with overall survival rate 90% in 1xHD group and 87,5% in 2xHD group. Conclusion IHD, in carefully selected patients with good compliance, provides preservation of UVO and RKF, thus delaying transition to full-dose dialysis and avoiding complications of dialysis, such as intradialytic hypotension and vascular access failure. This type of dialysis is individualized treatment that obtains easier adaptation to dialysis and better quality of life.


1955 ◽  
Vol 33 (1) ◽  
pp. 14-20 ◽  
Author(s):  
M. Špaček

Concentration of kynurenine in human urine shows variations of about 16% during the day and approximately as much (13%) from day to day. The variations are not clearly related to daily urine output, specific gravity, urinary creatinine, and the presence of indican or diazo-reaction.Elimination of tryptophan from the diet leads to gradual decrease of kynurenine excretion in persons who have excreted large amounts on mixed diet, but not in persons excreting only traces. Concentration of kynurenine in urine rises after administration of tryptophan. The response to tryptophan varies widely from subject to subject. Nicotinamide seems to decrease excretion of kynurenine. No consistent effect of pyridoxine has been observed.Older persons tend to excrete higher concentrations of kynurenine. Normal adults of 20 years average age present an average level of 0.1 mgm. kynurenine per 100 ml. of urine, much of which is not true kynurenine. The average level in older persons (47 years average age) without physical disease has been found to be 0.21 mgm. per 100 ml.


1955 ◽  
Vol 33 (1) ◽  
pp. 14-20
Author(s):  
M. Špaček

Concentration of kynurenine in human urine shows variations of about 16% during the day and approximately as much (13%) from day to day. The variations are not clearly related to daily urine output, specific gravity, urinary creatinine, and the presence of indican or diazo-reaction.Elimination of tryptophan from the diet leads to gradual decrease of kynurenine excretion in persons who have excreted large amounts on mixed diet, but not in persons excreting only traces. Concentration of kynurenine in urine rises after administration of tryptophan. The response to tryptophan varies widely from subject to subject. Nicotinamide seems to decrease excretion of kynurenine. No consistent effect of pyridoxine has been observed.Older persons tend to excrete higher concentrations of kynurenine. Normal adults of 20 years average age present an average level of 0.1 mgm. kynurenine per 100 ml. of urine, much of which is not true kynurenine. The average level in older persons (47 years average age) without physical disease has been found to be 0.21 mgm. per 100 ml.


2011 ◽  
Vol 301 (6) ◽  
pp. F1251-F1259 ◽  
Author(s):  
Tianluo Lei ◽  
Lei Zhou ◽  
Anita T. Layton ◽  
Hong Zhou ◽  
Xuejian Zhao ◽  
...  

Urea transporters UT-A2 and UT-B are expressed in epithelia of thin descending limb of Henle's loop and in descending vasa recta, respectively. To study their role and possible interaction in the context of the urine concentration mechanism, a UT-A2 and UT-B double knockout (UT-A2/B knockout) mouse model was generated by targeted deletion of the UT-A2 promoter in embryonic stem cells with UT-B gene knockout. The UT-A2/B knockout mice lacked detectable UT-A2 and UT-B transcripts and proteins and showed normal survival and growth. Daily urine output was significantly higher in UT-A2/B knockout mice than that in wild-type mice and lower than that in UT-B knockout mice. Urine osmolality in UT-A2/B knockout mice was intermediate between that in UT-B knockout and wild-type mice. The changes in urine osmolality and flow rate, plasma and urine urea concentration, as well as non-urea solute concentration after an acute urea load or chronic changes in protein intake suggested that UT-A2 plays a role in the progressive accumulation of urea in the inner medulla. These results suggest that in wild-type mice UT-A2 facilitates urea absorption by urea efflux from the thin descending limb of short loops of Henle. Moreover, UT-A2 deletion in UT-B knockout mice partially remedies the urine concentrating defect caused by UT-B deletion, by reducing urea loss from the descending limbs to the peripheral circulation; instead, urea is returned to the inner medulla through the loops of Henle and the collecting ducts.


2000 ◽  
Vol 279 (6) ◽  
pp. F1139-F1160 ◽  
Author(s):  
H. E. Layton ◽  
John M. Davies ◽  
Giovanni Casotti ◽  
Eldon J. Braun

A mathematical model was used to investigate how concentrated urine is produced within the medullary cones of the quail kidney. Model simulations were consistent with a concentrating mechanism based on single-solute countercurrent multiplication and on NaCl cycling from ascending to descending limbs of loops of Henle. The model predicted a urine-to-plasma (U/P) osmolality ratio of ∼2.26, a value consistent with maximum avian U/P osmolality ratios. Active NaCl transport from descending limb prebend thick segments contributed 70% of concentrating capability. NaCl entry and water extraction provided 80 and 20%, respectively, of the concentrating effect in descending limb flow. Parameter studies indicated that urine osmolality is sensitive to the rate of fluid entry into descending limbs and collecting ducts at the cone base. Parameter studies also indicated that the energetic cost of concentrating urine is sensitive to loop of Henle population as a function of medullary depth: as the fraction of loops reaching the cone tip increased above anatomic values, urine osmolality increased only marginally, and, ultimately, urine osmolality decreased.


2013 ◽  
Vol 118 (6) ◽  
pp. 909-916
Author(s):  
Chia Hsing Lu ◽  
Yi-Sheng Liu ◽  
Hong-Ming Tsai ◽  
Ming-Tsung Chuang ◽  
Chiung-Yu Chen ◽  
...  

2012 ◽  
Vol 6 (6) ◽  
pp. 448 ◽  
Author(s):  
Michael Moser ◽  
Michael Sharpe ◽  
Corinne Weernink ◽  
Harrison Brown ◽  
Thomas McGregor ◽  
...  

Background: Donation after cardiac death (DCD) has led to an increase of up to 40% in the number of kidney transplants in some programs. Unfortunately, the increase in warm ischemic time results in higher rates of delayed graft function (DGF). The purpose of our study was to examine our initial 5-year experience with DCD kidney transplantation and to determine the factors involved in early postoperative function and function at 1 year.Methods: This retrospective study included a review of the recipient and donor charts of 63 DCD kidneys retrieved and transplanted by the London Multi-Organ Transplant Program between July 2006 and October 2011. Comparisons were carried out between our early (n=31, July 2006 to January 2009) and our recent experience (n=32, March 2009 to October 2011). DGF and creatinine clearance at 3, 7 and 365 days were examined with regression analyses.Results: DGF was seen in 65% of transplanted kidneys. Mean creatinine clearance (CrCl) at 1 year was 66.7 mL/min. Low pre-transplant recipient daily urine output was the most statistically significant predictor of DGF in multivariate analysis (p < 0.001). In comparisons between our early and more recent results, improvements were noted in time from asystole to flush (16.0 vs. 12.0 minutes, p = 0.003), while cold ischemic time increased (464 vs.725 minutes, p = 0.006). Experience contributed to a significant reduction in hospital length of stay (16 vs. 13 days, p = 0.035) and improved early renal function (CrCl at 3 days 7.8 vs. 11.9 mL/min, p = 0.027). The use of machine cold perfusion and higher recipient preoperative daily urine output predicted improved early renal function, while increasing donor age predicted poorer funcion at 1 year.Discussion: Despite early DGF, our results justify the continued transplantation of kidneys from DCD donors.


2006 ◽  
Vol 291 (1) ◽  
pp. F186-F195 ◽  
Author(s):  
James Y. Yang ◽  
W. Y. Tam ◽  
Sidney Tam ◽  
Hong Guo ◽  
Xiaochun Wu ◽  
...  

To investigate the underlying causes for aldose reductase deficiency-induced diabetes insipidus, we carried out studies with three genotypic groups of mice. These included wild-type mice, knockout mice, and a newly created bitransgenic line that was homozygous for both the aldose reductase null mutation and an aldose reductase knockin transgene driven by the kidney-specific cadherin promoter to direct transgene expression in the collecting tubule epithelial cells. We found that from early renal developmental stages onward, urine osmolality did not exceed 1,000 mosmol/kgH2O in aldose reductase-deficient mice. The functional defects were correlated with significant renal cellular and structural abnormalities that included cell shrinkage, apoptosis, disorganized tubular and vascular structures, and segmental atrophy. In contrast, the transgenic aldose reductase expression in the bitransgenic mice largely but incompletely rescued urine concentrating capacity and significantly improved renal cell survival, cellular morphology, and renal structures. Together, these results suggest that aldose reductase not only plays important roles in osmoregulation and medullary cell survival but may also be essential for the full maturation of the urine concentrating mechanism.


1938 ◽  
Vol 34 (1) ◽  
pp. 80-87
Author(s):  
V. N. Smirnov

Of the drugs released in recent years by our Soviet pharmaceutical industry, merkuzal, an analogue of the German drug salirgan, attracts attention. According to its chemical composition, it is a complex compound of mercury acetic acid and sodium salt of allylamidosalicylic acid; soluble in water. This drug, released for sale in ampoules in the form of a 10% solution containing 0.036 grams of mercury in 1 cm3, belongs to the group of the strongest diuretics and is used intramuscularly, intravenously and intraperitoneally at intervals of 2-3 days. With intramuscular injections, according to our data, approximately 75% of daily urine output falls in the first 7-8 hours after injection.


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