Wilkinson, S P; Arroyo, V A; Moodie, H; Blendis, L M; Williams, R
Renal function was evaluated in 40 patients with fulminant hepatic failure, They were divided into two groups on the basis of glomerular filtration rates greater than 40 ml/min or less than 25 ml/min. A number of patients in group 1 had markedly abnormal renal retention of sodium together with a reduced free water clearance and low potassium excretion which could be explained by increased proximal tubular reabsorption of sodium. The patients in group 2 had evidence that renal tubular integrity was maintained when the glomerular filtration rate was greater than or equal ml/min (functional renal failure), but evidence of tubular damage was present when this was less than 3 ml/min (acute tubular necrosis). PMID:964682
Samia, Barbouch; Hazgui, Faiçal; Abdelghani, Khaoula Ben; Hamida, Fethi Ben; Goucha, Rym; Hedri, Hafedh; Taarit, Chokri Ben; Maiz, Hedi Ben; Kheder, Adel
We will study the epidemiologic, clinical, biological, therapeutic, prognostic characteristics and predictive factors of development of nephropathy in ankylosing spondylitis patients. We retrospectively reviewed the medical record of 32 cases with renal involvement among 212 cases of ankylosing spondylitis followed in our service during the period spread out between 1978 and 2006. The renal involvement occurred in all patients a mean of 12 years after the clinical onset of the rheumatic disease. Thirty-two patients presented one or more signs of renal involvement: microscopic hematuria in 22 patients, proteinuria in 23 patients, nephrotic syndrome in 11 patients and decreased renal function in 24 patients (75%). Secondary renal amyloidosis (13 patients), which corresponds to a prevalence of 6,1% and tubulointerstitial nephropathy (7 patients) were the most common cause of renal involvement in ankylosing spondylitis followed by IgA nephropathy (4 patients). Seventeen patients evolved to the end stage renal disease after an average time of 29.8 ± 46 months. The average follow-up of the patients was 4,4 years. By comparing the 32 patients presenting a SPA and renal disease to 88 with SPA and without nephropathy, we detected the predictive factors of occurred of nephropathy: tobacco, intense inflammatory syndrome, sacroileite stage 3 or 4 and presence of column bamboo. The finding of 75% of the patients presented a renal failure at the time of the diagnosis of renal involvement suggests that evidence of renal abnormality involvement should be actively sought in this disease.
Ataga, K I; Orringer, E P
Sickle cell anemia and the related hemoglobinopathies are associated with a large spectrum of renal abnormalities. The patients have impaired urinary concentrating ability, defects in urinary acidification and potassium excretion, and supranormal proximal tubular function. The latter is manifest by increased secretion of creatinine and by reabsorption of phosphorus and beta(2)-microglobulin. Young patients with sickle cell disease (SCD) have supranormal renal hemodynamics with elevations in both effective renal plasma flow (ERPF) and glomerular filtration rate (GFR). These parameters decrease with age as well as following the administration of prostaglandin inhibitors. Proteinuria, a common finding in adults with sickle cell disease, may progress to the nephrotic syndrome. Proteinuria, hypertension, and increasing anemia predict end-stage renal disease (ESRD). While ESRD can be managed by dialysis and/or renal transplantation, there may be an increased rate of complications in renal transplant recipients with SCD. Hematuria is seen in individuals with all of the SCDs as well as with sickle cell trait. In most cases the etiology of the hematuria turns out to be benign. However, there does appear to be an increased association between SCD and renal medullary carcinoma. Therefore, those SCD patients who present with hematuria should initially undergo a thorough evaluation in order to exclude this aggressive neoplasm. Papillary necrosis may occur due to medullary ischemia and infarction. Erythropoietin levels are usually lower than expected for their degree of anemia and decrease further as renal function deteriorates. An abnormal balance of renal prostaglandins may be responsible for some of the changes in sickle cell nephropathy. Acute renal failure is a component of the acute multiorgan failure syndrome (MOFS). Finally, progression of sickle cell nephropathy to ESRD may be slowed by adequate control of hypertension and proteinuria. However, the prevention of the
Dias, Tiran; Sairam, Shanthi; Kumarasiri, Shanya
Development of the urogenital system in humans is a complex process; consequently, renal anomalies are among the most common congenital anomalies. The fetal urinary tract can be visualised ultrasonically from 11 weeks onwards, allowing recognition of megacystis at 11-14 weeks, which warrants comprehensive risk assessment of possible underlying chromosomal aneuploidy or obstructive uropathy. A mid-trimester anomaly scan enables detection of most renal anomalies with higher sensitivity. Bilateral renal agenesis can be confirmed ultrasonically, with empty renal fossae and absent bladder filling, along with severe oligohydramnios or anhydramnios. Dysplastic kidneys are recognised as they appear large, hyperechoic, and with or without cystic spaces, which occurs within the renal cortex. Presence of dilated ureters without obvious dilatation of the collecting system needs careful examination of the upper urinary tract to exclude duplex kidney system. Sonographically, it is also possible to differentiate between infantile type and adult type of polycystic kidney diseases, which are usually single gene disorders. Upper urinary tract dilatation is one of the most common abnormalities diagnosed prenatally. It is usually caused by transient urine flow impairment at the level of the pelvi-ureteric junction and vesico-ureteric junction, which improves with time in most cases. Fetal lower urinary tract obstruction is mainly caused by posterior urethral valves and urethral atresia. Thick bladder walls and a dilated posterior urethra (keyhole sign) are suggestive of posterior urethral valves. Prenatal ultrasounds cannot be used confidently to assess renal function. Liquor volume and echogenicity of renal parenchyma, however, can be used as a guide to indirectly assess the underlying renal reserve. Renal tract anomalies may be isolated but can also be associated with other congenital anomalies. Therefore, a thorough examination of the other systems is mandatory to exclude possible
Rubenfeld, Sheldon; Garber, Alan J.
To delineate the potential role of disordered glucose and glucose-precursor kinetics in the abnormal carbohydrate metabolism of chronic renal failure, alanine and glucose production and utilization and gluconeogenesis from alanine were studied in patients with chronic compensated renal insufficiency and in normal volunteers. With simultaneous primed injection-continuous infusions of radiolabeled alanine and glucose, rates of metabolite turnover and precursor-product interrelationships were calculated from the plateau portion of the appropriate specific activity curves. All subjects were studied in the postabsorption state. In 13 patients with chronic renal failure (creatinine = 10.7±1.2 mg/100 ml; mean±SEM), glucose turnover was found to be 1,035±99.3 μmol/min. This rate was increased 56% (P = 0.003) over that observed in control subjects (664±33.5 μmol/min). Alanine turnover was 474±96.0 μmol/min in azotemic patients. This rate was 191% greater (P = 0.007) than the rate determined in control subjects (163±19.4 μmol/min). Gluconeogenesis from alanine and the percent of glucose production contributed by gluconeogenesis from alanine were increased in patients with chronic renal failure (192% and 169%, respectively) as compared to controls (P < 0.05 for each). Alanine utilization for gluconeogenesis was increased from 40.2±3.86 μmol/min in control subjects to 143±39.0 μmol/min in azotemic patients (P < 0.05). The percent of alanine utilization accounted for by gluconeogenesis was not altered in chronic renal insufficiency. In nondiabetic azotemic subjects, mean fasting glucose and immunoreactive insulin levels were increased 24.3% (P = 0.005) and 130% (P = 0.046), respectively. These results in patients with chronic renal failure demonstrate (a) increased glucose production and utilization, (b) increased gluconeogenesis from alanine, (c) increased alanine production and utilization, and (d) a relative impairment to glucose disposal. We conclude that
Koepke, John P.; DiBona, Gerald F.
Discusses renal neuroanatomy, renal vasculature, renal tubules, renin secretion, renorenal reflexes, and hypertension as related to renal nerve functions. Indicates that high intensitites of renal nerve stimulation have produced alterations in several renal functions. (A chart with various stimulations and resultant renal functions and 10-item,…
Tieder, M; Levy, M; Gubler, M C; Gagnadoux, M F; Broyer, M
Four cases of BARDET-Biedl syndrome (BBS) are described which all suffer from renal abnormalities. Polyuria or polydipsia with impairment of renal concentration capacity were the earliest signs of renal dysfunction. Renal insufficiency developed in 3 cases and hypertension in two. Urographic abnormalities were demonstrated in all patients. The most remarkable features were cystic spaces communicating with the calices and lobulation of kidney. Caliceal clubbing and caliectasis surrounded by narrowed, unscarred parenchyma were frequent findings. Previous investigators reported various renal histological pictures in BBS. We found tubulo- interstitial lesions in all cases. Features of dysplasia and cystic formations were less frequent. Mesangial proliferation was not noted. Ultra-structural changes in the glomerular basement membrane were not observed in this study. Thirty-one of 32 recently reported cases of BBS included renal lesions which are the major cause of death. It is therefore suggested that renal abnormalities are accepted as the cardinal feature of this syndrome.
Zerin, J M; Ritchey, M L; Chang, A C
Postnatal imaging findings were reviewed in 130 neonates and young infants referred for imaging evaluation of antenatally detected renal abnormalities. All children underwent voiding cystourethrography and upper urinary tract imaging with sonography and/or renal scintigraphy. Vesicoureteral reflux was present in 49 patients (38%) and was bilateral in 24. All grades of reflux were observed. Reflux occurred in 41 of 98 neonates (42%) in whom postnatal imaging revealed persistent upper tract abnormalities (eg, hydronephrosis, cysts, renal agenesis) and in eight of 32 (25%) with normal findings at postnatal sonography and/or renal scintigraphy. Reflux was the single most common urologic diagnosis and was the only postnatal abnormality in 12 patients (9%). The authors conclude that neonates with antenatally detected hydronephrosis should be routinely screened for reflux with voiding cystography. Detection and aggressive management of reflux in the asymptomatic neonate in whom renal growth and function are unimpaired theoretically offer the best opportunity for preventing renal injury later in childhood.
Lam, B C; Wong, S N; Yeung, C Y; Tang, M H; Ghosh, A
Between January 1987 and December 1990, 60 fetuses were found to have renal abnormalities on antenatal ultrasonography. Six fetuses were aborted because of major renal abnormalities with or without associated chromosomal aberrations. Twelve babies with major renal abnormalities died in the immediate neonatal period. Forty-two babies were studied after birth and followed up. Babies who were found to have mild dilation of the renal pelvis of 6 to 10 mm during fetal life revealed either normal renal findings in the postnatal period or complete resolution of the abnormalities within the first year. Significant pelvic dilation of more than 10 mm occurred in 32 babies. A significant proportion (34%) had transitional hydronephrosis that resolved spontaneously during the follow-up period (mean, 2 1/2 years; range, 1 1/2 to 4 1/2 years). Extrarenal pelvis, another benign condition, accounted for 15.6%. Most babies with pelviureteral junction obstruction (15%) and vesicoureteral junction obstruction (6.2%) required early neonatal surgery. The technetium-99m diethylenetriamine renal scan with the diuretic renogram half-time was found to be a very useful tool to distinguish between obstructive and nonobstructive hydronephrosis. With early diagnosis and intervention, the prognosis for many of these renal abnormalities is much more favorable and such information is invaluable for antenatal counseling.
Sethi, N.; Trivedi, J.K.; Sethi, B.B.
SUMMARY Thirty patients of affective disorder who were on lithium for a year and thirty patients on antidepressant were studied in detail for renal functions. Our observation is that lithium therapy does not lead to any deterioration in kidney functions. The results are discussed. PMID:21927211
An investigation has been made into various parameters of renal function in patients with chronic bronchitis and in a group of hypoxic controls. Abnormalities of glomerular filtration rate and of water handling have been demostrated in chronic bronchitic patients but not in hypoxic controls. The abnormalities are related to the arterial Pco2. A hypothesis is presented as to the role of CO2 in causing abnormalities of renal function in chronic bronchitis. PMID:17853
Raman, Jay D; Jafri, Syed M; Qi, David
The diagnosis of small renal masses (SRMs) continues to increase likely attributable to widespread use of axial cross-sectional imaging. Many of these SRMs present in elderly patients with abnormal baseline renal function. Such patients are at risk for further decline following therapeutic intervention. Renal thermal ablation presents one approach for management of SRMs whereby tumors are treated in situ without need for global renal ischemia. These treatment characteristics contribute to favorable renal function outcomes following kidney tumor ablation particularly in patients with an anatomic or functional solitary renal unit. PMID:27152264
Gulleroglu, K; Baskin, E; Bayrakci, U S; Aydogan, M; Alehan, F; Kantar, A; Karakayali, F; Moray, G; Haberal, M
Neurocognitive dysfunction is one of the major complications of chronic renal failure (CRF). Uremic state during CRF encompasses a wide spectrum of neurobehavioral and neurological disturbances. Recent studies showed that the pathophysiology of neurocognitive dysfunction in CRF is related to plasma levels of uremic solutes. Successful renal transplantation improves renal, metabolic, and endocrine functions and the quality of life. The aim of our study was to determine the state of neurocognitive function in pediatric renal transplant recipients. We prospectively performed a neurological examination and neuropsychological test battery (Bender-Gestalt Test, Cancellation Test, and Visual and Auditory Number Assay Test) in 20 pediatric renal transplant recipients between 6 and 16 years of age. Twenty healthy children and 20 children with CRF were included in the study as the control groups. Mean age of the renal transplant recipients was 13.50 ± 3.40 years old. Mean evaluation time after transplantation was 2.0 ± 0.5 years. Bender-Gestalt Test result was abnormal in 40% of patients. The results of the Cancellation Test and the Visual and Auditory Number Assay Test showed significant decline in pediatric renal transplant patients when compared with the control. We found that neurocognitive dysfunction was frequent in pediatric renal transplantation patients. Awareness of this potential problem may be helpful for early recognition and treatment. Our findings suggest that periodic neurocognitive assessments may be indicated in transplant recipients.
Blum, R A; Kohli, R K; Harrison, N J; Schentag, J J
The single-dose pharmacokinetics of intravenously administered ampicillin (2.0 g) and sulbactam (1.0 g) were studied in normal subjects and in patients with various degrees of creatinine clearance (CLCR). Six normal subjects (CLCR, greater than 60 ml/min), six patients with mild renal failure (CLCR, 31 to 60 ml/min), four patients with severe renal failure (CLCR, 7 to 30 ml/min), and four patients requiring maintenance hemodialysis (CLCR, less than 7 ml/min) were studied. The terminal half-lives for ampicillin and sulbactam more than doubled in patients with severe renal failure compared with subjects with normal renal function and mild renal insufficiency. CLCR significantly correlated with ampicillin (r = 0.88) and sulbactam (r = 0.54) total body clearance. Mean steady-state volume of distribution and nonrenal clearance for ampicillin and sulbactam were not affected by renal function. Hemodialysis approximately doubled the ampicillin and sulbactam total body clearance. Mean totals of 34.8 +/- 4.0% of the ampicillin dose and 44.7 +/- 3.2% of the sulbactam dose were removed during a 4-h hemodialysis treatment. A slight rebound in concentrations in serum after hemodialysis was observed for both drugs in all four subjects. In hemodialysis patients, the ampicillin half-life was 17.4 +/- 8.0 h and the sulbactam half-life was 13.4 +/- 7.4 h. The ampicillin and sulbactam half-lives were appreciably altered during the hemodialysis period (means of 2.2 and 2.3 h, respectively). The nearly parallel decrease in total body clearance, with volume of distribution and nonrenal clearance remaining relatively constant, suggests that the same ratio of ampicillin to sulbactam is appropriate regardless of renal function. An adjustment of the ampicillin (2.0 g) and sulbactam (1.0 g) dose to twice daily would be appropriate in patients with a CLCR between 7 and 30 ml/min. Doses should be given every 24 h for those undergoing maintenance hemodialysis. On hemodialysis days, doses should
Rucker, Janet C
This chapter on lid function is comprised of two primary sections, the first on normal eyelid anatomy, neurological innervation, and physiology, and the second on abnormal eyelid function in disease states. The eyelids serve several important ocular functions, the primary objectives of which are protection of the anterior globe from injury and maintenance of the ocular tear film. Typical eyelid behaviors to perform these functions include blinking (voluntary, spontaneous, or reflexive), voluntary eye closure (gentle or forced), partial lid lowering during squinting, normal lid retraction during emotional states such as surprise or fear (startle reflex), and coordination of lid movements with vertical eye movements for maximal eye protection. Detailed description of the neurological innervation patterns and neurophysiology of each of these lid behaviors is provided. Abnormal lid function is divided by conditions resulting in excessive lid closure (cerebral ptosis, apraxia of lid opening, blepharospasm, oculomotor palsy, Horner's syndrome, myasthenia gravis, and mechanical) and those resulting in excessive lid opening (midbrain lid retraction, facial nerve palsy, and lid retraction due to orbital disease).
Bueschen, A J; Witten, D M
The renal scintillation camera study and the excretory urogram should be considered to be complementary studies. The renal scintillation camera study provides an accurate evaluation of changes in total, differential, and segmental renal function but affords only a gross assessment of anatomic changes. The excretory urogram provides superior information about renal anatomic changes but only inferior information about functional changes of the kidney. The advantages of a renal scintillation camera study with regard to the patient are that it is done in a state of normal hydration, it requires no bowel preparation, it is not associated with allergic reactions, it provides a low radiation exposure, and it is a noninvasive procedure for differential renal function which requires no ureteral catheters.
Dorshow, Richard B.; Bugaj, Joseph E.; Burleigh, B. Daniel; Johnson, Michael A.; Jones, William B.; Duncan, James R.
The feasibility of a new methodology for organ function determination, based on optical detection, is investigated. Differentiation between normal and abnormal organ function is demonstrated in an animal model for both the liver and the kidney. Two commercial dyes were employed in this initial study. Characteristic blood clearance curves associated with normal hepatic function and normal renal function are obtained. Upon ablation of a portion of the liver, the clearance curve ascribed to hepatic function is greatly extended as expected. Upon ligation of both kidneys, the clearance curve ascribed to renal function remains elevated and constant, indicating little if any clearance. The clearance curves are fit to standard physiological compartment models to yield quantitative information on decay times.
Lindell, A; Denneberg, T; Granerus, G
Total and separate renal functions were evaluated in 40 patients with cystinuria. The average duration of the renal stone disease was 26 years (range 1-53). The patients had been subjected to a stone-preventing regimen composed of increased fluid intake, urinary alkalinization and treatment with a sulphydryl compound, tiopronin or D-penicillamine, for an average of 11.7 years (range 1-24). Urinary cystine concentration was determined regularly to monitor the treatment. All patients were examined with gamma camera renography and an assessment of glomerular filtration rate (GFR), and early and late renographic results could be compared in 30 patients. The early renographic evaluation showed that 43% of binephric patients (13/30) had an abnormal relative renal function (RRF) before the start of the stone-preventing treatment. At the late evaluation, 50% of binephric patients (17/34) had an abnormal RRF, while 30% of all patients (12/40) had a GFR below the age-related normal range. Thirty percent of 74 evaluated kidneys (22/74) had a separate GFR below an estimated age-related normal range. At the late evaluation only 30% of the patients had functionally unaffected kidneys with both normal GFR and bilateral normal renography. There was, however, no case with terminal renal failure. The separate GFR of kidneys with a history of staghorn stones was significantly lower than for kidneys without that special type of stones, but otherwise there was no relationship between renal functional impairment and other estimates of the activity of the renal stone disease. In conclusion, impairment of renal function is common in patients with stone-forming cystinuria. Stone-preventive treatment appears to be effective in preserving renal function. The high frequency of renal functional impairment justifies close surveillance of this group of patients. By renographic examination, unilateral changes in renal function can be detected at an early stage and patients at risk for further
van 't Hoff, W.; Bicknell, E. J.
Renal tubular function was assessed in a group of patients with mild hyperparathyroidism before and after a mean period of 2.7 years conservative management. It was also assessed, before and after a mean of 3.3 years following surgery in a group of patients with initially higher plasma calcium concentration. Mean maximum urine osmolality was within the accepted range as was the maximum urine plasma hydrogen ion gradient in both groups at the time of diagnosis. No significant change in renal tubular function was observed in either group over the periods of this study. Although deterioration after a long period cannot be excluded, we do not consider that regular assessment of renal tubular function is necessary in the conservative management of primary hyperparathyroidism. PMID:2616415
Sica, Domenic A
Fibrates are a class of lipid-lowering medications primarily used as second-line agents behind statins. The adverse-effect profile of fibrates has been marked by a puzzling yet reversible rise in serum creatinine values with their use. It is not known whether this finding represents a true change in renal function. One proposed explanation for this phenomenon is that fibrates increase the production of creatinine, in which case a rise in serum creatinine values would not represent a true deterioration in renal function. An alternative theory is that fibrates reduce the production of vasodilatory prostaglandins, which would lead to a true change in renal function in patients who experience a rise in serum creatinine values. Routine serum creatinine monitoring is advisable in fibrate-treated patients, particularly in those with preexisting renal disease. A 30% increase in serum creatinine values in the absence of other causes of serum creatinine change warrants discontinuation of fibrate therapy. Serum creatinine values can take several weeks to return to their baseline values following discontinuation of a fibrate.
Morgan, E J; Hall, D R
Twenty subjects with symptoms of hay fever were studied to see whether abnormalities could be detected in the function of small airways. The investigations included dynamic compliance at varying respiratory frequencies, closing capacity, residual volume, transfer factor, and maximal expiratory flow-volume curves. The tests were repeated in the winter when symptoms had resolved. Frequency dependence of compliance was found in eight subjects with symptoms (40%), closing capacities being abnormal in only two instances. Conventional pulmonary function tests, including expiratory flow rates at mid vital capacity, were within the predicted range of all subjects. When tests were repeated in the winter, frequency dependence of compliance was no longer present in subjects whose symptoms had resolved. The study suggests that reversible small airway abnormalities are present in a significant proportion of subjects with symptoms of hay fever and that such abnormalities are best detected by the measurement of dynamic compliance at varying respiratory frequencies. PMID:769243
In patients with renal dystopia radionuclide urography in commonly used technique may yield inaccurate results concerning split renal function. In a case of unilateral pelvic kidney a simple strategy to avoid this methodical error is demonstrated.
Finkelstein, Julia B.; DeCastro, G. Joel; McKiernan, James M.
Historically, radical nephrectomy represented the gold standard for the treatment of small (≤ 4cm) as well as larger renal masses. Recently, for small renal masses, the risk of ensuing chronic kidney disease and end stage renal disease has largely favored nephron-sparing surgical techniques, mainly partial nephrectomy. In this review, we surveyed the literature on renal functional outcomes after partial nephrectomy for renal tumors. The largest randomized control trial comparing radical and partial nephrectomy failed to show a survival benefit for partial nephrectomy. With regards to overall survival, surgically induced chronic kidney disease (GFR < 60 ml/min/ 1.73m2) caused by nephrectomy might not be as deleterious as medically induced chronic kidney disease. In evaluating patients who underwent donor nephrectomy, transplant literature further validates that surgically induced reductions in GFR may not affect patient survival, unlike medically induced GFR declines. Yet, because patients who present with a renal mass tend to be elderly with multiple comorbidities, many develop a mixed picture of medically, and surgically-induced renal disease after extirpative renal surgery. In this population, we believe that nephron sparing surgery optimizes oncological control while protecting renal function.
Shih, W.J.; Domstad, P.A.; DeLand, F.H.
The authors observed extrarenal abnormalities during renal flow scintigraphy and retrospectively reviewed 90 patient studies to determine the types and frequencies of such abnormal findings. For each routine Tc-99m-DTPA renal flow study, they obtained nine 2-second sequential images, which included the heart, abdominal aorta, spleen and kidneys. Eighty abnormalities, observed in 62 patients, were divided into three categories: aortic, 37 cases; splenic, 40 cases; and miscellaneous, 3 cases. Other correlative studies including Tc-99m sulfur colloid-spleen scintigraphy, ultrasonography (US), CT, aortography, and surgical and/or autopsy findings were available for corroboration in 56 of 80 lesions.
Peterka, R. J.; Black, F. O.
The major motivation of this research is to understand the role the vestibular system plays in sensorimotor interactions which result in spatial disorientation and motion sickness. A second goal was to explore the range of abnormality as it is reflected in quantitative measures of vestibular reflex responses. The results of a study of vestibular reflex measurements in normal subjects and preliminary results in abnormal subjects are presented in this report. Statistical methods were used to define the range of normal responses, and determine age related changes in function.
Taylor, A. Jr.; Lallone, R.
An abnormal filtration fraction or a significant divergence between a kidney's ability to extract Tc-99m dimercaptosuccinic acid (DMSA) and other function parameters, such as the glomerular filtration rate (GFR) or the effective renal plasma flow (ERPF, could lead to different estimates of relative or absolute renal function, depending on the radiopharmaceutical administered. To evaluate this possible divergence, the authors measured the relative GFR (I-125 iothalamate), ERPF (I-131 hippurate), and Tc-99m DMSA accumulation in adult male Sprague-Dawley rats with unilateral ureteral obstruction or unilateral ischemia at various times after renal injury. The relative ERPF of the obstructed kidney was significantly greater than the relative GFR at all time periods studied; significant but less dramatic differences were noted comparing DMSA with GFR in obstruction and DMSA and ERPF with GRF in ischemia.
... term "renal" refers to the kidney. For example, renal failure means kidney failure. Related topics: Kidney disease Kidney disease - diet Kidney failure Kidney function tests Renal scan Kidney transplant
Renal osteodystrophy (ROD), a metabolic bone disease accompanying chronic renal failure (CRF), is a major clinical problem in pediatric nephrology. Growing and rapidly remodeling skeletal systems are particularly susceptible to the metabolic and endocrine disturbances in CRF. The pathogenesis of ROD is complex and multifactorial. Hypocalcemia, phosphate retention, and low levels of 1,25 dihydroxyvitamin D(3) related to CRF result in disturbances of bone metabolism and ROD. Delayed diagnosis and treatment of bone lesions might result in severe disability. Based on microscopic findings, renal bone disease is classified into two main categories: high- and low-turnover bone disease. High-turnover bone disease is associated with moderate and severe hyperparathyroidism. Low-turnover bone disease includes osteomalacia and adynamic bone disease. The treatment of ROD involves controlling serum calcium and phosphate levels, and preventing parathyroid gland hyperplasia and extraskeletal calcifications. Serum calcium and phosphorus levels should be kept within the normal range. The calcium-phosphorus product has to be <5 mmol(2)/L(2) (60 mg(2)/dL(2)). Parathyroid hormone (PTH) levels in children with CRF should be within the normal range, but in children with end-stage renal disease PTH levels should be two to three times the upper limit of the normal range. Drug treatment includes intestinal phosphate binding agents and active vitamin D metabolites. Phosphate binders should be administered with each meal. Calcium carbonate is the most widely used intestinal phosphate binder. In children with hypercalcemic episodes, sevelamer, a synthetic phosphate binder, should be introduced. In children with CRF, ergocalciferol (vitamin D(2)), colecalciferol (vitamin D(3)), and calcifediol (25-hydroxyvitamin D(3)) should be used as vitamin D analogs. In children undergoing dialysis, active vitamin D metabolites alfacalcidol (1alpha-hydroxy-vitamin D(3)) and calcitriol (1,25 dihydroxyvitamin
Park, Jeanie; Middlekauff, Holly R
Abnormal neurocirculatory control during exercise is one important mechanism leading to exercise intolerance in patients with both end-stage renal disease (ESRD) and earlier stages of chronic kidney disease (CKD). This review will provide an overview of mechanisms underlying abnormal neurocirculatory and hemodynamic responses to exercise in patients with kidney disease. Recent studies have shown that ESRD and CKD patients have an exaggerated increase in blood pressure (BP) during both isometric and rhythmic exercise. Subsequent studies examining the role of the exercise pressor reflex in the augmented pressor response revealed that muscle sympathetic nerve activity (MSNA) was not augmented during exercise in these patients, and metaboreflex-mediated increases in MSNA were blunted, while mechanoreflex-mediated increases were preserved under basal conditions. However, normalizing the augmented BP response during exercise via infusion of nitroprusside (NTP), and thereby equalizing baroreflex-mediated suppression of MSNA, an important modulator of the final hemodynamic response to exercise, revealed that CKD patients had an exaggerated increase in MSNA during isometric and rhythmic exercise. In addition, mechanoreflex-mediated control was augmented, and metaboreceptor blunting was no longer apparent in CKD patients with baroreflex normalization. Factors leading to mechanoreceptor sensitization, and other mechanisms underlying the exaggerated exercise pressor response, such as impaired functional sympatholysis, should be investigated in future studies.
Khazaei, Mahmood R; Mackie, Fiona; Rosenberg, Andrew R; Kainer, Gad
A renal length discrepancy (RLD) of more than 10 mm by ultrasound (US) is accepted as a potential indicator of an underlying renal pathology; however, there are few supporting data for this in children. Our objective was to determine a cutoff at which RLD on US is a reliable predictor of dimercaptosuccinate acid (DMSA) scan abnormality. We present data from 90 patients who had both renal US and a DMSA scan, as well as DMSA scan results compared with bipolar RLD by US. Positive (PPV) and negative (NPV) predictive values were calculated for renal RLD from 6 to >10 mm. The left kidney was longer in 56%, whereas the right kidney was longer in 37%; their lengths were equal in 8%. For children at all ages, a left kidney longer than the right by >or=10 mm or a right kidney longer than the left by >or=7 mm gave a PPV for DMSA abnormality of 79% and 100%, respectively. In children older than 4 years, if the right kidney was longer by >or=7 mm or if the left kidney was longer by >or=10 mm, the PPVs for DMSA abnormality were 100% and 63%, respectively. In children younger than 4 years, when the right kidney was longer by >or=6 mm or the left was kidney longer by >or=10 mm, the PPV were 86% and 100%, respectively. Thus, children with a right kidney longer than the left by even <10 mm is a reliable predictor of an abnormal DMSA scan.
Yasuda, Hidenori; Amakasu, Kohei; Tochigi, Yuki; Katayama, Kentaro; Suzuki, Hiroetsu
Renal hypoplasia due to a congenitally reduced number of nephrons progresses to chronic kidney disease and may cause renal anemia, given that the kidneys are a major source of erythropoietin in adults. Hypoplastic kidney (HPK) rats have only about 20% of the normal number of nephrons and develop CKD. This study assessed the renal function and hematologic changes in HPK rats from 70 to 210 d of age. HPK rats demonstrated deterioration of renal excretory function, slightly macrocytic erythropenia at all days examined, age-related increases in splenic hemosiderosis accompanied by a tendency toward increased hemolysis, normal plasma erythropoietin levels associated with increased hepatic and decreased renal erythropoietin production, and maintenance of the response for erythropoietin production to hypoxic conditions, with increased interstitial fibrosis at 140 d of age. These results indicate that increases in splenic hemosiderosis and the membrane fragility of RBC might be associated with erythropenia and that hepatic production of erythropoietin might contribute to maintaining the blood Hgb concentration in HPK rats.
Izzedine, Hassan; Méjean, Arnaud; Escudier, Bernard
Although radical nephrectomy is still practiced in many patients with large renal tumors, oncology and nephrology arguments for kidney-sparing approach for small renal masses has taken over this first. Indeed, partial nephrectomy provides equivalent oncologic results while preserving renal function and thereby limit morbidity and cardiovascular mortality related to chronic kidney disease. In addition, patients who develop kidney cancer often have medical comorbidities that may affect renal function, such as diabetes and hypertension. Histological examination of renal tissue adjacent to the tumor showed significant pathological changes in the majority of patients. For elderly patients or patients with comorbidities, active surveillance allows kidney-sparing approach with extremely low rates of progression and metastasis of cancer disease. Despite these significant advances in understanding for the treatment of small renal masses, partial nephrectomy remains underused. Better management must take into account the preservation of renal function in order to increase overall survival. A strategy for the systematic evaluation of renal function in patients with CR, with multidisciplinary staff (nephrologist urologist and oncologist), is therefore highly desirable.
Pérez Calvo, J I; Josa Laorden, C; Giménez López, I
Renal function is one of the most consistent prognostic determinants in heart failure. The prognostic information it provides is independent of the ejection fraction and functional status. This article reviews the various renal function assessment measures, with special emphasis on the fact that the patient's clinical situation and response to the heart failure treatment should be considered for the correct interpretation of the results. Finally, we review the literature on the performance of tubular damage biomarkers.
Vathsala, A; Weinberg, R B; Schoenberg, L; Grevel, J; Goldstein, R A; Van Buren, C T; Lewis, R M; Kahan, B D
Hyperlipidemia and hypertension, two major risk factors for accelerated atherosclerosis, undoubtedly contribute to the excessive cardiovascular morbidity and mortality experienced by renal transplant recipients. The present survey of posttransplant hyperlipidemia in 500 cyclosporine-treated patients documented a 37.6% incidence of hypercholesterolemia, which occurred within 6 months posttransplant in 82% of patients. An etiologic relation to corticosteroid therapy was suggested by the strong correlation between prednisone doses and cholesterol levels, by the reduced cholesterol levels in patients undergoing steroid withdrawal, and by the reduction in hypercholesterolemia to 13% by 3 years posttransplant when steroid doses were less than 10 mg daily. Hypertriglyceridemia, which was present in 14.7% of the patients, was more severe under CsA-prednisone compared with azathioprine-prednisone therapy. Hypertriglyceridemia, which occurred later in the posttransplant course than hypercholesterolemia, strongly correlated with an excessive percent relative weight and elevated serum creatinine but not with steroid or CsA doses. Increasing age, diabetes mellitus, beta-blockers and nephrotic syndrome contribute to posttransplant hyperlipidemia in the CsA-Pred era as they did in the azathioprine era of immunosuppression.
Sharma, Aashish; Mucino, Marìa Jimena; Ronco, Claudio
Renal functional reserve (RFR) represents the capacity of the kidney to increase glomerular filtration rate (GFR) in response to certain physiological or pathological stimuli or conditions. Once baseline GFR is determined, RFR can be assessed clinically after an oral protein load or intravenous amino acid infusion. In clinical practice, baseline GFR displays variable levels due to diet or other factors. RFR is the difference between peak 'stress' GFR induced by the test (p.o. or i.v.) and the baseline GFR. In clinical scenarios where hyperfiltration is present (high baseline GFR due to pregnancy, hypertension or diabetic nephropathy, in solitary kidney or kidney donors), RFR may be fully or partially used to achieve normal or supranormal renal function. Since commonly used renal function markers, such as GFR, may remain within normal ranges until 50% of nephrons are lost or in patients with a single remnant kidney, the RFR test may represent a sensitive and early way to assess the functional decline in the kidney. RFR assessment may become an important tool to evaluate the ability of the kidney to recover completely or partially after a kidney attack. In case of healing with a defect and progressive fibrosis, recovery may appear complete clinically, but a reduced RFR may be a sign of a maladaptive repair or subclinical loss of renal mass. Thus, a reduction in RFR may represent the equivalent of renal frailty or susceptibility to insults. The main aim of this article is to review the concept of RFR, its utility in different clinical scenarios, and future perspective for its use.
Stibolt, T.B. Jr.; Bacher, J.D.; Dunnick, N.R.; Lock, A.; Jones, A.E.; Bailey, J.J.
Renography using a gamma camera, a minicomputer, (/sup 123/I)orthoiodohippurate ((/sup 123/I)OIH), and a canine model was employed to evaluate computer-generated maps of regional renal function. Renograms were obtained before and after ligations of the right renal arterial branch in four dogs, with subsequent angiographic and histologic confirmation of the lesions. Postoperative time-activity curves were normal. Washout and persistence index in three of four right kidneys showed regional abnormality. Functional renal mapping may provide a clinical technique for evaluating human renal vascular hypertension.
Dabla, Pradeep Kumar
Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. Cardiovascular and renal complications share common risk factors such as blood pressure, blood lipids, and glycemic control. Thus, chronic kidney disease may predict cardiovascular disease in the general population. The impact of diabetes on renal impairment changes with increasing age. Serum markers of glomerular filtration rate and microalbuminuria identify renal impairment in different segments of the diabetic population, indicating that serum markers as well as microalbuminuria tests should be used in screening for nephropathy in diabetic older people. The American Diabetes Association and the National Institutes of Health recommend Estimated glomerular filtration rate (eGFR) calculated from serum creatinine at least once a year in all people with diabetes for detection of kidney dysfunction. eGFR remains an independent and significant predictor after adjustment for conventional risk factors including age, sex, duration of diabetes, smoking, obesity, blood pressure, and glycemic and lipid control, as well as presence of diabetic retinopathy. Cystatin-C (Cys C) may in future be the preferred marker of diabetic nephropathy due differences in measurements of serum creatinine by various methods. The appropriate reference limit for Cys C in geriatric clinical practice must be defined by further research. Various studies have shown the importance of measurement of albuminuria, eGFR, serum creatinine and hemoglobin level to further enhance the prediction of end stage renal disease. PMID:21537427
Lowenstein, Jerome; Grantham, Jared J
Residual renal function (RRF) in patients undergoing dialysis treatments is currently viewed as glomerular filtrate that has escaped tubular reabsorption. RRF has been quantified as a clearance of urea or creatinine, or urea + creatinine. A major paradigm shift has followed the recognition that a substantial number of organic anion retention solutes (possible "uremic toxins") are protein-bound and therefore are not readily filtered. These protein-bound aryl compounds are secreted by renal tubular organic anion transporters (OATs). This has led to the recognition that RRF in dialysis patients probably represents not only unreabsorbed glomerular filtrate but also a contribution of renal tubular transporters that secrete organic anions. Tubular secretion of hippurate, indoxyl sulfate, and p-cresol sulfate, protein-bound organic anions retained in the plasma of end-stage renal disease patients, can be quantified and used to evaluate the integrity of a function dependent on active solute transport. Here we propose a shift away from the exclusive "glomerulocentric" view of RRF as unreabsorbed glomerular filtrate and of the progression of renal disease as progressive glomerular loss. We expand the definition of RRF to include the combined renal and tubule functions remaining after a disease begins to destroy nephrons and proceeds to anuria. We propose renewed application of the first principles of renal physiology, articulated in the last century by Homer Smith, to the understanding and monitoring of RRF and progression of renal injury in patients during the sometimes long course of and at the end stage of chronic renal disease.
Raine, A E; Seymour, A M; Roberts, A F; Radda, G K; Ledingham, J G
Cardiac function and energetics in experimental renal failure in the rat (5/6 nephrectomy) have been investigated by means of an isolated perfused working heart preparation and an isometric Langendorff preparation using 31P nuclear magnetic resonance (31P NMR). 4 wk after nephrectomy cardiac output of isolated hearts perfused with Krebs-Henseleit buffer was significantly lower (P < 0.0001) at all levels of preload and afterload in the renal failure groups than in the pair-fed sham operated control group. In control hearts, cardiac output increased with increases in perfusate calcium from 0.73 to 5.61 mmol/liter whereas uremic hearts failed in high calcium perfusate. Collection of 31P NMR spectra from hearts of renal failure and control animals during 30 min normoxic Langendorff perfusion showed that basal phosphocreatine was reduced by 32% to 4.7 mumol/g wet wt (P < 0.01) and the phosphocreatine to ATP ratio was reduced by 32% (P < 0.01) in uremic hearts. During low flow ischemia, there was a substantial decrease in phosphocreatine in the uremic hearts and an accompanying marked increase in release of inosine into the coronary effluent (14.9 vs 6.1 microM, P < 0.01). We conclude that cardiac function is impaired in experimental renal failure, in association with abnormal cardiac energetics and increased susceptibility to ischemic damage. Disordered myocardial calcium utilization may contribute to these derangements. PMID:8254048
Burlet, A; Drukker, A; Guignard, J P
We performed renal function tests in 18 young patients, 1.8-14.6 years of age, with cyanotic congenital heart disease (CCHD). Glomerular filtration rate was normal (116 +/- 4.5 ml/min/1.73 m2), and renal plasma flow was decreased (410 +/- 25 ml/min/1.73 m2) with a rise in the filtration fraction (29 +/- 1.1%). The suggested pathophysiologic explanation of these findings is that the blood hyperviscosity seen in patients with CCHD causes an overall increase in renal vascular resistance with a rise in intraglomerular blood pressure. Despite a sluggish flow of blood in the glomerular capillary bed, the effective filtration pressure was adjusted to conserve the glomerular filtration rate. In addition to these renal hemodynamic parameters, we also studied renal acidification and tubular sodium and water handling during a forced water diuresis. Our data indicate that children with CCHD have a mild to moderate normal ion gap metabolic acidosis due to a low proximal tubular threshold for bicarbonate. Proximal tubular sodium and water reabsorption under these conditions were somewhat increased, though not significantly, probably due to intrarenal hydrostatic forces, in particular the rise in the oncotic pressure in the postglomerular capillaries in patients with high hematocrit values. The distal tubular functions such as sodium handling and acidification were not affected.
García Nieto, Víctor M; Luis Yanes, Maria Isabel; Arango Sancho, Pedro; Sotoca Fernandez, Jorge V
Basic renal function tests such as maximum urine osmolality and urinary elimination of albumin and N-acetyl-glucosaminidase often reveal abnormalities in clinical cases involving hyperpressure in the urinary tract or loss of renal parenchyma. However, in all the available algorithms dedicated to the study of children with urinary tract infection or dilation, the benefit of using these functional parameters is not mentioned. In this review, we provide information about the practical usefulness of assessing the basic renal function parameters. From these data, we propose an algorithm that combines morphological and functional parameters to make a reasoned case for voiding cystourethrography.
Damment, Stephen; Secker, Roger; Shen, Victor; Lorenzo, Victor; Rodriguez, Mariano
Background. Lanthanum carbonate (FOSRENOL®, Shire Pharmaceuticals) is an effective non-calcium, non-resin phosphate binder for the treatment of hyperphosphataemia in patients with chronic kidney disease (CKD). In this study, we used a rat model of chronic renal failure (CRF) to examine the long-term effects of controlling serum phosphorus with lanthanum carbonate treatment on the biochemical and bone abnormalities associated with CKD–mineral and bone disorder (CKD–MBD). Methods. Rats were fed a normal diet (normal renal function, NRF), or a diet containing 0.75% adenine for 3 weeks to induce CRF. NRF rats continued to receive normal diet plus vehicle or normal diet supplemented with 2% (w/w) lanthanum carbonate for 22 weeks. CRF rats received a diet containing 0.1% adenine, with or without 2% (w/w) lanthanum carbonate. Blood and urine biochemistry were assessed, and bone histomorphometry was performed at study completion. Results. Treatment with 0.75% adenine induced severe CRF, as demonstrated by elevated serum creatinine. Hyperphosphataemia, hypocalcaemia, elevated calcium × phosphorus product and secondary hyperparathyroidism were evident in CRF + vehicle animals. Treatment with lanthanum carbonate reduced hyperphosphataemia and secondary hyperparathyroidism in CRF animals (P < 0.05), and had little effect in NRF animals. Bone histomorphometry revealed a severe form of bone disease with fibrosis in CRF + vehicle animals; lanthanum carbonate treatment reduced the severity of the bone abnormalities observed, particularly woven bone formation and fibrosis. Conclusions. Long-term treatment with lanthanum carbonate reduced the biochemical and bone abnormalities of CKD–MBD in a rat model of CRF. PMID:21098011
Mitchell, Charles D.; Chernoff, Miriam C.; Seage, George R.; Purswani, Murli U.; Spiegel, Hans M.L.; Zilleruelo, Gaston; Abitbol, Carolyn; Heckman, Barbara; Ponce, Christopher B.; Oleske, James M.
Background Among HIV infected youth, the role of renal disease (RD) and its management has become more important as children/adolescents age into young adulthood. Identification of predictors of abnormal renal laboratory events (RLE) may be helpful in the management of their HIV infection and its associated renal complications.” Methods Data collected from HIV-infected children and youth followed for ≥48 months was analyzed to identify predictors of resolution versus persistence of RLE and determine the utility of RLE to predict the onset of RD. Analysis included descriptive and inferential methods using a multivariable extended Cox proportional hazards model. Results 428 of 1874 at risk children (23%) developed RLE, which persisted in 229 of 428(54%). CD4<25% (hazard ratio[HR] 0.63, p<0.002) and HIV viral load>100,000 copies/ml (HR 0.31, p<0.01) were associated with reduced rates of resolution. Exposure to HAART/nephrotoxic HAART prior to or subsequent to RLE in most cases were not. Persistence of RLE was 88% sensitive for identifying new RD. Negative predictive values for RD were >95% for both the at risk cohort and in those with RLE. Conclusions Advanced HIV disease predicted persistence of RLE in HIV-infected youth. Persistent RLE were useful for identifying RD. PMID:25149850
Balink, Hans; Hoogendoorn, Mels; Hemmelder, Marc
A 41-year-old woman with a Harrington spondylodesis presented with lower back pain. Bone scintigraphy showed diffusely increased parenchymal uptake in both kidneys. She reported 2 previous periods of dark, almost black, urine. Additional flow cytometric analysis confirmed the diagnosis of paroxysmal nocturnal hemoglobinuria. The increased renal parenchyma uptake is very probably due to paroxysmal nocturnal hemoglobinuria-related renal hemosiderosis. Remarkably, the patient did not develop any abnormality of renal function.
Chen, C F; Chien, C T; Wu, M S; Fu, T C
This study was designed to investigate the possible role of renal nerves in the regulation of renal function after the application of heat (BH), by means of an electric heating pad (42 +/- 1 degree C) to the skin of the back overlying the kidneys. Both renal efferent (RENA) and renal afferent nervous activity (RANA) were recorded in 7 anesthetized female Wistar rats. It was found that RENA reduced to less than 80% of the control level during 30 min of back heating, accompanied by an increase in excretion of urine, sodium and potassium, and enhanced the glomerular filtration rate. BH in 9 chronic bilateral renal denervated rats (RD) showed the same renal responses as in the renal nerve intact rats (RI) after back heating. It is concluded that renal nerves played only a partially role in the renal diuretic action of back heating.
Sica, Domenic A
Focused ultrasonography (US) with simultaneous administration of a US microbubble contrast agent was used to transiently increase the glomerular filtration rate while altering the sieving properties of glomeruli in normal rabbits. In its current form, this process has very limited application potential to states of abnormal renal function.
The majority of outpatients with heart failure (HF) have chronic kidney disease (CKD) as an important comorbidity. Both glomerular filtration rate and abnormal urinary albumin excretion are major predictors of outcome in HF patients. Despite this, patients with renal dysfunction have been systematically excluded from the large randomized HF trials. There is lack of evidence for optimal treatment in these cardiorenal patients and treatment nihilism may account in part for their bad prognosis. Identifying and monitoring the progression of renal disease and making an effort to preserve renal function should be an important task in the management of all patients with HF. In this review, the current understanding of the pathophysiology of renal dysfunction in outpatients with HF will be summarized. Furthermore, important principles of the identification and management of cardiorenal patients will be described in order to make the physician more capable of managing outpatients with HF and renal dysfunction.
Kipper, M.S.; Witztum, K.F.; Taylor, A. Jr.
Forty patients (43 studies) referred for determination of differential renal function were imaged 24 hours after intravenous administration of Tc-99m-2, 3 DMSA. Visual assessment of relative renal uptake was estimated independently by three observers at three different hospitals from analog images on standard x-ray film. The results were compared with the relative DMSA uptake obtained by summing counts in computer-assisted regions of interest placed over each kidney. There was excellent correlation between the visual estimates of each observer and the computer-generated values (r = 0.98, 0.96, and 0.98, respectively). If a computer is not available, good visual estimates of differential uptake still may be obtained when static imaging agents such as DMSA are administered.
Belis, J A; Morabito, R A; Kandzari, S J; Lai, J C; Gabriele, O F
Differential quantitative radionuclide renal scans have been used to confirm that early removal of staghorn calculi by anatrophic nephrolithotomy preserves renal parenchyma without significant renal damage by the surgical procedure. The 99mtechnetium diethylenetriaminepentaacetic acid scan was useful in predicting recovery of function in the involved kidney, while the 131iodine orthoiodohippurate scan provided a quantitative evaluation of the effect of the surgical procedure on individual kidney function. All of 13 consecutive patients evaluated by 131iodine orthoiodohippurate renal scans had stable or improved effective renal plasma flow to the involved kidney and an unchanged or improved total excretory index 6 months after nephrolithotomy.
Belis, J.A.; Morabito, R.A.; Kandzari, S.J.; Lai, J.C.; Gabriele, O.F.
Differential quantitative radionuclide renal scans have been used to confirm that early removal of staghorn calculi by anatrophic nephrolithotomy preserves renal parenchyma without significant renal damage by the surgical procedure. The /sup 99m/technetium diethylenetriaminepentaacetic acid scan was useful in predicting recovery of function in the involved kidney, while the /sup 131/iodine orthoiodohippurate scan provided a quantitative evaluation of the effect of the surgical procedure on individual kidney function. All of 13 consecutive patients evaluated by /sup 131/iodine orthoiodohippurate renal scans had stable or improved effective renal plasma flow to the involved kidney and an unchanged or improved total excretory index 6 months after nephrolithotomy.
Sakurai, M; Hioki, T; Okuno, T; Sugimura, Y; Yamakawa, K; Yanagawa, M; Tajima, K; Tochigi, H; Kawamura, J
99mTc-DMSA renal scintigraphy was carried out in 54 patients with unilateral renal stones before and after PNL. Four to 8 weeks after PNL the DMSA renal uptake significantly decreased to 17.2 +/- 6.0% from 18.2 +/- 6.7% before PNL. DMSA renal uptake did not change in the contralateral side. Since in some patients changes in the DMSA renal uptake of 5-7% were observed after PNL not only in the PNL side but also in the contralateral side, the renal function was assessed by the formula: DMSA renal uptake in the PNL side/DMSA renal uptake in the contralateral side, and the change of this ratio was evaluated in 44 patients, in whom the renal DMSA uptake in the PNL side was less than two times that in the contralateral side. The DMSA renal uptake ratio decreased to 95.6 +/- 8.7% from the base line 4-8 weeks after PNL. This change was statistically significant. Some functional risks such as massive bleeding with PNL, the fever after PNL and the number of nephrostomy tract did not affect the decrease in the renal function. In 29 patients in whom renal function was reevaluated one year after PNL, the DMSA renal uptake ratio significantly decreased to 94.2 +/- 9.6% from the base line 4-8 weeks after PNL. But the ratio significantly improved to 99.6 +/- 11.6% about one year after PNL. In two patients with a cold area on the renal image, the renal function of the operated side still remained at about 80% levels from the base line even one year after PNL.(ABSTRACT TRUNCATED AT 250 WORDS)
Tian, Junzhang; Dong, Jianwei; He, Jinlong; Zhan, Wenfeng; Xu, Lijuan; Xu, Yikai; Jiang, Guihua
Purpose To study whole-brain microstructural alterations in patients with end-stage renal disease (ESRD) and examine the relationship between brain microstructure and physiological indictors in the disease. Materials and Methods Diffusion tensor imaging data were collected from 35 patients with ESRD (28 men, 18–61 years) and 40 age- and gender-matched healthy controls (HCs, 32 men, 22–58 years). A voxel-wise analysis was then used to identify microstructural alterations over the whole brain in the ESRD patients compared with the HCs. Multiple biochemical measures of renal metabolin, vascular risk factors, general cognitive ability and dialysis duration were correlated with microstructural integrity for the patients. Results Compared to the HCs, the ESRD patients exhibited disrupted microstructural integrity in not only white matter (WM) but also gray matter (GM) regions, as characterized by decreased fractional anisotropy (FA) and increased mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). Further correlation analyses revealed that the in MD, AD and RD values showed significantly positive correlations with the blood urea nitrogen in the left superior temporal gyrus and significantly negative correlations with the calcium levels in the left superior frontal gyrus (orbital part) in the patients. Conclusion Our findings suggest that ESRD is associated with widespread diffusion abnormalities in both WM and GM regions in the brain, and microstructural integrity of several GM regions are related to biochemical alterations in the disease. PMID:27227649
Thompson, I.M. Jr.; Boineau, F.G.; Evans, B.B.; Schlegel, J.U.
The renal quantitative scintillation camera study assesses glomerular filtration rate and effective renal plasma flow based upon renal uptake of 99mtechnetium-iron ascorbate and 131iodine-hippuran, respectively. The method was compared to inulin, para-aminohippuric acid and creatinine clearance studies in 7 normal subjects and 9 patients with various degrees of reduced renal function. The reproducibility of the technique was determined in 15 randomly selected pediatric patients. The values of glomerular filtration rate and effective renal plasma flow were not significantly different from those of inulin and para-aminohippuric acid studies. The reproducibility of the technique was comparable to that of inulin and para-aminohippuric acid studies. Patient acceptance of the technique is excellent and the cost is minimal. Renal morphology and excretory dynamics also are demonstrated. The technique is advocated as a clinical measure of renal function.
He, Ping; Kerr, Doug; Marbury, Thomas; Ries, Daniel; Farwell, Wildon; Stecher, Scott; Dong, Yingwen; Wei, Dong; Rogge, Mark
This phase I, open-label, single-dose study evaluated the pharmacokinetics, safety, and tolerability of renally excreted drug dexpramipexole in subjects with normal and impaired renal function, i.e. mild, moderate, severe renal impairment, or end-stage renal disease (ESRD) requiring hemodialysis when matched by age and sex. Dexpramipexole area under the curves (AUCs), but not Cmax, were significantly increased with the severity of renal impairment after a single dose administration. The geometric mean ratio of dose-normalized AUC(0–72) was 1.4, 1.7, 2.7, and 4.5, respectively, in mild, moderate, severe renal impairment, and ESRD subjects when compared to healthy subjects. There was a strong association between renal function (eGFR) and dexpramipexole CLr. The slope (90% confidence interval(CI)) of eGFR and renal clearance (CLr) in the regression model was 3.1 (2.4, 3.7). Dexpramipexole elimination in ESRD subjects during both dialysis and non-dialysis (i.e., interval between dialysis) was insignificant. Single 75 mg and 150 mg doses of dexpramipexole were well tolerated, and the safety profile was comparable across renal function groups. Extensive drug accumulation may occur with repeated dosing in patients with significant renal impairment. It is recommended that dexpramipexole not to be given to patients with severe renal impairment or in those with ESRD. PMID:24965504
Loran, O B; Siniakova, L A; Bernikov, E V
The kidneys of the patients with purulent pyelonephritis (PP) undergo anatomic and functional alterations. The latter may be irreversible in some cases. The severity of the above alterations depends on PP form, choice and time of treatment. Our study included 84 patients who had PP at the age of 15 to 70 years. Primary PP was detected in 47 (56%) patients, secondary--in 37 (44%) patients. Open surgery was performed in 18 patients (group 1), transcutaneous drainage was used in 38 patients (group 2), conservative treatment was conducted in 28 patients (group 3). Comparison of dynamic nephroscintigraphic findings showed that recovery of renal function in groups 2 and 3 lasted 6-12 months versus 60-84 months in group 1. The degree of the renal function recovery depends on the PP form, age of the patient, duration of the disease, virulence of the causing agent, comorbid pathology, immune status, method of treatment. This was confirmed by the data of complex radionuclide examination. Long term complications, for instance, progress of arterial hypertension (41% cases) and chronic pyelonephritis (44% cases) were observed more frequently and earlier in patients after open operations.
Russell, C.D.; Thorstad, B.L.; Yester, M.V.; Stutzman, M.; Dubovsky, E.V.
The technetium-labeled hippuran analog (/sup 99m/Tc)MAG3 was compared with ( T I)hippuran in 50 patients using a quantitative renal function protocol that includes: (a) estimation of effective renal plasma flow by a single-injection, single-sample plasma clearance method, (b) determination of relative function of right and left kidney from the initial count rate over each kidney, and (c) comparison of recovered urine activity with plasma disappearance. This protocol is suitable for routine clinical use, and, in fact, has been used heavily at our clinic for a number of years. By slight modification of the formulas, the results obtained with (/sup 99m/Tc)MAG3 agreed well with those using ( T I)hippuran. We conclude that (/sup 99m/Tc)MAG3 can be substituted for ( T I)hippuran in the quantitative protocol, with the better image quality and lower radiation dose (in abnormals) of a technetium-labeled agent.
Although liver function test abnormality is frequently noted in children, there is no report about the distribution of the etiology and natural recovery time of the abnormal liver function. From March 2005 to February 2014, clinical information was retrospectively collected from 559 children who had abnormal liver function and were hospitalized or visited the outpatient clinic at the Jeju National University Hospital. The etiology of abnormal liver function was classified into groups and the natural recovery time of abnormal liver function was analyzed. The etiological groups of 559 patients included ‘nonspecific hepatitis’ in 42 (7.5%), ‘infection’ in 323 (57.8%), ‘rheumatologic and autoimmune’ in 66 (11.8%), ‘nonalcoholic fatty liver disease’ in 57 (10.2%), ‘anatomic’ in 12 (2.1%), ‘toxic’ in 13 (2.1%), ‘metabolic’ in 8 (1.4%), ‘hematologic’ in 7 (1.3%), ‘hemodynamic’ in 4 (0.7%), and ‘others’ in 27 (4.8%). Among the ‘infection’ group (57.8%), the ‘viral infection in the respiratory tract’ subgroup, which had 111 patients (19.8%), was the most common. The natural recovery time of the abnormal liver function was 27 days (median) in ‘nonspecific hepatitis’, 13 days (median) in ‘viral respiratory tract disease’, 16 days (median) in ‘viral gastroenteritis’, 42 days (median) in ‘viral febrile illness”, and 7 days (median) in “Kawasaki disease”. The information on the natural recovery time of abnormal liver function may help the physician to perform good clinical consultation for patients and their parents. PMID:27709857
Kleinhans, Natalia M.; Richards, Todd; Sterling, Lindsey; Stegbauer, Keith C.; Mahurin, Roderick; Johnson, L. Clark; Greenson, Jessica; Dawson, Geraldine; Aylward, Elizabeth
Abnormalities in the interactions between functionally linked brain regions have been suggested to be associated with the clinical impairments observed in autism spectrum disorders (ASD). We investigated functional connectivity within the limbic system during face identification; a primary component of social cognition, in 19 high-functioning…
Anderson, C B; Etheredge, E E
Renal allograft blood flow (RBF) was measured at operation by electromagnetic flow meter and probes in 45 patients (34 cadaver donors and 11 living related donors). Mean RBF in 26 patients without acute tubular necrosis (ATN), was 412 +/- 80 ml/min and in 19 patients with ATN, 270 +/- 100 ml/min (p less than .001). Only two of 24 transplants (8%) with RBF greater than 350 ml/min had ATN; whereas, 17 of 21 transplants (81 per cent) with RBF less than 350 ml/min had ATN (p less than .001). In cadaver donor transplants, RBF did not correlate with duration of ATN, warm ischemia time, total ischemia time, pulsatile perfusion time or renal vascular resistance during perfusion. Measurement of renal allograft blood flow can predict presence or absence of postoperative ATN in 87% of patients. PMID:335986
Sinkeler, Steef J; Damman, Kevin; van Veldhuisen, Dirk J; Hillege, Hans; Navis, Gerjan
The association between cardiac failure and renal function impairment has gained wide recognition over the last decade. Both structural damage in the form of systemic atherosclerosis and (patho) physiological hemodynamic changes may explain this association. As regards hemodynamic factors, renal impairment in chronic heart failure is traditionally assumed to be mainly due to a decrease in cardiac output and a subsequent decrease in renal perfusion. This will lead to a decrease in glomerular filtration rate and a compensatory increase in tubular sodium retention. The latter is a physiological renal response aimed at retaining fluids in order to increase cardiac filling pressure and thus renal perfusion. In heart failure, however, larger increases in cardiac filling pressure are needed to restore renal perfusion and thus more volume retention. In this concept, in chronic heart failure, an equilibrium exists where a certain degree of congestion is the price to be paid to maintain adequate renal perfusion and function. Recently, this hypothesis was challenged by new studies, wherein it was found that the association between right-sided cardiac filling pressures and renal function is bimodal, with worse renal function at the highest filling pressures, reflecting a severely congested state. Renal hemodynamic studies suggest that congestion negatively affects renal function in particular in patients in whom renal perfusion is also compromised. Thus, an interplay between cardiac forward failure and backward failure is involved in the renal function impairment in the congestive state, presumably along with other factors. Only few data are available on the impact of intervention in volume status on the cardio-renal interaction. Sparse data in cardiac patients as well as evidence from cohorts with primary renal disease suggest that specific targeting of volume overload may be beneficial for long-term outcome, in spite of a certain further decrease in renal function, at least
From 1984 to 1990, 99mTc-DMSA renal scintigraphy was performed before and after nephrolithotomy (15 cases), pyelolithotomy (15 cases), percutaneous nephrolithotripsy (PNL: 15 cases) and extracorporeal shock wave lithotripsy (ESWL: 16 cases, 17 kidneys) in order to evaluate of influences of renal stone surgeries on split renal function. DMSA renal uptake change ratio of treated kidneys of nephrolithotomy (-24.94 +/- 5.60%) was significantly lower than that of PNL (-0.06 +/- 3.92%), pyelolithotomy (-4.08 +/- 4.79%) (p less than 0.01) and ESWL (-7.72 +/- 3.87%) (p less than 0.05). The average change ratios of contralateral kidneys were as follows: PNL 4.80 +/- 4.21% nephrolithotomy 4.67 +/- 4.73%, pyelolithotomy -1.46 +/- 5.39% and ESWL -2.02 +/- 4.44%. One to 3 weeks after PNL, the cold area on the renal image was found in 10 (66.7%) of 15 cases. In cases of ESWL, DMSA renal uptake decreased even 4-10 weeks (mean 7 weeks) after treatment. In conclusion, possivility of deterioration of renal function after ESWL was suggested.
Lowenstein, Jerome; Grantham, Jared J
The measurement of glomerular filtration rate by the clearance of inulin or creatinine has evolved over the past 50 years into an estimated value based solely on plasma creatinine concentration. We have examined some of the misconceptions and misunderstandings of the classification of renal disease and its course, which have followed this evolution. Furthermore, renal plasma flow and tubular function, which in the past were estimated by the clearance of the exogenous aryl amine, para-aminohippurate, are no longer measured. Over the past decade, studies in experimental animals with reduced nephron mass and in patients with reduced renal function have identified small gut-derived, protein-bound uremic retention solutes ("uremic toxins") that are poorly filtered but are secreted into the lumen by organic anion transporters (OATs) in the proximal renal tubule. These are not effectively removed by conventional hemodialysis or peritoneal dialysis. Residual renal function, urine produced in patients with advanced renal failure or undergoing dialysis treatment, may represent, at least in part, secretion of fluid and uremic toxins, such as indoxyl sulfate, mediated by proximal tubule OATs and might serve as a useful survival function. In light of this new evidence of the physiological role of proximal tubule OATs, we suggest that measurement of renal tubular function and renal plasma flow may be of considerable value in understanding and managing chronic kidney disease. Data obtained in normal subjects indicate that renal plasma flow and renal tubular function might be measured by the clearance of the endogenous aryl amine, hippurate.
John, E G; Bhat, R; Assadi, F K; Vidyasagar, D; Fornell, L
Tolazoline is used in pulmonary hypertension and hypoperfusion syndrome during the neonatal period. Some of the side effects of tolazoline are hypotension, bleeding disorders and renal dysfunction. The present study was designed to investigate the effect of hypoxia and tolazoline on renal function in newborn puppies. The data in normal animals administered tolazoline alone did not reveal any statistically significant changes in blood pressure or in renal function. In the hypoxia group changes in renal function were noticed in spite of normal blood pressure. When tolazoline was administered to the hypoxic animals, a marked decrease in blood pressure resulted. Indeed, changes in renal function were more profound in the hypoxic animals receiving tolazoline than in hypoxic animals not receiving tolazoline, even though some of the renal functional values did not reach statistical significance.
Tian, Xiao Yu; Wong, Wing Tak; Lau, Chi Wai; Wang, Yi-Xiang; Cheang, Wai San; Liu, Jian; Lu, Ye; Huang, Huihui; Xia, Yin; Chen, Zhen Yu; Mok, Chuen-Shing; Lau, Chau-Ming; Huang, Yu
Melamine incident, linked to nephrotoxicity and kidney stone in infants previously exposed to melamine-contaminated milk products, was unprecedentedly grave in China in 2008 as little was known about the mechanistic process leading to renal dysfunction in affected children. This study investigates whether neonatal ingestion of melamine leads to renal and vascular dysfunction in adulthood; and whether ingestion of melamine in pregnant rats leads to renal dysfunction in their offspring. A combination of approaches employed includes functional studies in rat renal arteries, renal blood flow measurement by functional magnetic resonance imaging, assay for pro-inflammatory and fibrotic biomarkers, immunohistochemistry, and detection of plasma and renal melamine. We provide mechanistic evidence showing for the first time that melamine reduces renal blood flow and impairs renal and vascular function associated with overexpression of inflammatory markers, transforming growth factor-β1, bone morphogenic protein 4 and cyclooxygenase-2 in kidney and renal vasculature. Melamine also induces renal inflammation and fibrosis. More importantly, melamine causes nephropathies in offsprings from pregnant rat exposed to melamine during pregnancy, as well as in neonatal rat exposed to melamine afterbirth, thus supporting the clinical observations of kidney stone and acute renal failure in infants consuming melamine-contaminated milk products. PMID:27324576
Whaley-Connell, Adam; Sowers, James R.
Abstract Loss of redox homeostasis and formation of excessive free radicals play an important role in the pathogenesis of kidney disease and hypertension. Free radicals such as reactive oxygen species (ROS) are necessary in physiologic processes. However, loss of redox homeostasis contributes to proinflammatory and profibrotic pathways in the kidney, which in turn lead to reduced vascular compliance and proteinuria. The kidney is susceptible to the influence of various extracellular and intracellular cues, including the renin–angiotensin–aldosterone system (RAAS), hyperglycemia, lipid peroxidation, inflammatory cytokines, and growth factors. Redox control of kidney function is a dynamic process with reversible pro– and anti-free radical processes. The imbalance of redox homeostasis within the kidney is integral in hypertension and the progression of kidney disease. An emerging paradigm exists for renal redox contribution to hypertension. Antioxid. Redox Signal. 11, 2047–2089. PMID:18821850
Pazhayattil, George Sunny; Shirali, Anushree C
Pharmaceutical agents provide diagnostic and therapeutic utility that are central to patient care. However, all agents also carry adverse drug effect profiles. While most of these are clinically insignificant, some drugs may cause unacceptable toxicity that impacts negatively on patient morbidity and mortality. Recognizing adverse effects is important for administering appropriate drug doses, instituting preventive strategies, and withdrawing the offending agent due to toxicity. In the present article, we will review those drugs that are associated with impaired renal function. By focusing on pharmaceutical agents that are currently in clinical practice, we will provide an overview of nephrotoxic drugs that a treating physician is most likely to encounter. In doing so, we will summarize risk factors for nephrotoxicity, describe clinical manifestations, and address preventive and treatment strategies. PMID:25540591
Kahr, Walter H A; Lo, Richard W; Li, Ling; Pluthero, Fred G; Christensen, Hilary; Ni, Ran; Vaezzadeh, Nima; Hawkins, Cynthia E; Weyrich, Andrew S; Di Paola, Jorge; Landolt-Marticorena, Carolina; Gross, Peter L
Gray platelet syndrome (GPS) is an inherited bleeding disorder associated with macrothrombocytopenia and α-granule-deficient platelets. GPS has been linked to loss of function mutations in NEABL2 (neurobeachin-like 2), and we describe here a murine GPS model, the Nbeal2(-/-) mouse. As in GPS, Nbeal2(-/-) mice exhibit splenomegaly, macrothrombocytopenia, and a deficiency of platelet α-granules and their cargo, including von Willebrand factor (VWF), thrombospondin-1, and platelet factor 4. The platelet α-granule membrane protein P-selectin is expressed at 48% of wild-type levels and externalized upon platelet activation. The presence of P-selectin and normal levels of VPS33B and VPS16B in Nbeal2(-/-) platelets suggests that NBEAL2 acts independently of VPS33B/VPS16B at a later stage of α-granule biogenesis. Impaired Nbeal2(-/-) platelet function was shown by flow cytometry, platelet aggregometry, bleeding assays, and intravital imaging of laser-induced arterial thrombus formation. Microscopic analysis detected marked abnormalities in Nbeal2(-/-) bone marrow megakaryocytes, which when cultured showed delayed maturation, decreased survival, decreased ploidy, and developmental abnormalities, including abnormal extracellular distribution of VWF. Our results confirm that α-granule secretion plays a significant role in platelet function, and they also indicate that abnormal α-granule formation in Nbeal2(-/-) mice has deleterious effects on megakaryocyte survival, development, and platelet production.
Partovi, Sasan; Zeller, Thomas; Breidthardt, Tobias; Kaech, Max; Boeddinghaus, Jasper; Puelacher, Christian; Nestelberger, Thomas; Aschwanden, Markus; Mueller, Christian
Background Identifying patients likely to have improved renal function after percutaneous transluminal renal angioplasty and stenting (PTRA) for renal artery stenosis (RAS) is challenging. The purpose of this study was to use a comprehensive multimarker assessment to identify those patients who would benefit most from correction of RAS. Methods In 127 patients with RAS and decreased renal function and/or hypertension referred for PTRA, quantification of hemodynamic cardiac stress using B-type natriuretic peptide (BNP), renal function using estimated glomerular filtration rate (eGFR), parenchymal renal damage using resistance index (RI), and systemic inflammation using C-reactive protein (CRP) were performed before intervention. Results Predefined renal function improvement (increase in eGFR ≥10%) at 6 months occurred in 37% of patients. Prognostic accuracy as quantified by the area under the receiver-operating characteristics curve for the ability of BNP, eGFR, RI and CRP to predict renal function improvement were 0.59 (95% CI, 0.48–0.70), 0.71 (95% CI, 0.61–0.81), 0.52 (95% CI, 0.41–0.65), and 0.56 (95% CI, 0.44–0.68), respectively. None of the possible combinations increased the accuracy provided by eGFR (lower eGFR indicated a higher likelihood for eGFR improvement after PTRA, P=ns for all). In the subgroup of 56 patients with pre-interventional eGFR <60 mL/min/1.73 m2, similar findings were obtained. Conclusions Quantification of renal function, but not any other pathophysiologic signal, provides at least moderate accuracy in the identification of patients with RAS in whom PTRA will improve renal function. PMID:27280085
Stage, K H; Lewis, S
Differential quantitative renal scans using 99-technetium diethylene triaminepentaacetic acid (DTPA) or 131I Hippuran were obtained properatively on 12 patients with unilateral or bilateral staghorn calculi. Of the 14 renal units studied, 12 kidneys underwent anatrophic nephrolithotomy, pyelolithotomy, or a combination of both techniques; 2 patients underwent nephrectomy based on poor function of the affected side preoperatively. Postoperative follow-up scans were obtained on the 12 kidneys undergoing stone cleanout. Seven of 12 kidneys (58 per cent) studied pre- and postoperatively showed moderate to significant improvement in per cent contribution to total renal function. Seven of 10 kidneys (70 per cent) studied pre- and postoperatively showed improvement in glomerular filtration rate or effective renal plasma flow. The scans revelaed no dramatic difference in postoperative functional loss between pyelolithotomy and anatrophic nephrolithotomy. The computerizewd quantitative renal scan helps in selection of surgical technique and objective postoperative assessment of surgical results.
Poston, Kathleen L.; Eidelberg, David
Clinical manifestations of movement disorders, such as Parkinson’s disease (PD) and dystonia, arise from neurophysiological changes within the cortico-striato-pallidothalamocortical (CSPTC) and cerebello-thalamo-cortical (CbTC) circuits. Neuroimaging techniques that probe connectivity within these circuits can be used to understand how these disorders develop as well as identify potential targets for medical and surgical therapies. Indeed, network analysis of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has identified abnormal metabolic networks associated with the cardinal motor symptoms of PD, such as akinesia and tremor, as well as PD-related cognitive dysfunction. More recent task-based and resting state functional magnetic resonance imaging studies have reproduced several of the altered connectivity patterns identified in these abnormal PD-related networks. A similar network analysis approach in dystonia revealed abnormal disease related metabolic patterns in both manifesting and non-manifesting carriers of dystonia mutations. Other multimodal imaging approaches using magnetic resonance diffusion tensor imaging in patients with primary genetic dystonia suggest abnormal connectivity within the CbTC circuits mediate the clinical manifestations of this inherited neurodevelopmental disorder. Ongoing developments in functional imaging and future studies in early patients are likely to enhance our understanding of these movement disorders and guide novel targets for future therapies. PMID:22206967
Vivier, P-H; Dolores, M; Le Cloirec, J; Beurdeley, M; Liard, A; Elbaz, F; Roset, J-B; Dacher, J-N
The kidney performs multiple functions. Glomerular filtration is the most studied of these functions. In clinical practice, the surgical indication for patients with unilateral uropathy is frequently based on the split renal function as demonstrated by scintigraphy. MRI is not yet validated as a technique but nonetheless offers an interesting non-radiating alternative to achieve both morphological and functional renal evaluation. Recent pulse sequences such as diffusion, arterial spin labeling, and blood oxygenation dependent imaging may also provide additional information. CT and US remain of limited value for the evaluation of renal function.
Alcazar, Miguel Angel Alejandre; Boehler, Eva; Rother, Eva; Amann, Kerstin; Vohlen, Christina; von Hörsten, Stephan; Plank, Christian; Dötsch, Jörg
Early postnatal hyperalimentation has long-term implications for obesity and developing renal disease. Suppressor of cytokine signaling (SOCS) 3 inhibits phosphorylation of signal transducer and activator of transcription (STAT) 3 and ERK1/2 and thereby plays a pivotal role in mediating leptin resistance. In addition, SOCS-3 is induced by both leptin and inflammatory cytokines. However, little is known about the intrinsic-renal leptin synthesis and function. Therefore, this study aimed to elucidate the implications of early postnatal hyperalimentation on renal function and on the intrinsic-renal leptin signaling. Early postnatal hyperalimentation in Wistar rats during lactation was induced by litter size reduction at birth (LSR) either to LSR10 or LSR6, compared with home cage control male rats. Assessment of renal function at postnatal day 70 revealed decreased glomerular filtration rate and proteinuria after LSR6. In line with this impairment of renal function, renal inflammation and expression as well as deposition of extracellular matrix molecules, such as collagen I, were increased. Furthermore, renal expression of leptin and IL-6 was up-regulated subsequent to LSR6. Interestingly, the phosphorylation of Stat3 and ERK1/2 in the kidney, however, was decreased after LSR6, indicating postreceptor leptin resistance. In accordance, neuropeptide Y (NPY) gene expression was down-regulated; moreover, SOCS-3 protein expression, a mediator of postreceptor leptin resistance, was strongly elevated and colocalized with NPY. Thus, our findings not only demonstrate impaired renal function and profibrotic processes but also provide compelling evidence of a SOCS-3-mediated intrinsic renal leptin resistance and concomitant up-regulated NPY expression as an underlying mechanism.
Poeppl, Timm B; Eickhoff, Simon B; Fox, Peter T; Laird, Angela R; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo
Despite its 0.5-1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multimodal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia.
Taverner, D; Craig, K; Mackay, I; Watson, M L
The renal excretory and haemodynamic responses to sustained moderate exertion were investigated in normotensive humans with impaired renal function and normal volunteers. The heart rate increase with exercise was similar in each group. Subjects with impaired renal function showed a significant fall in glomerular filtration rate on exertion, while normals did not. In the presence of renal disease, urine osmolality did not rise with exertion, although it rose markedly in the normal group. Free water clearance became negative after exercise in the normal group only. The diseased kidney is unable to maintain glomerular filtration rate or conserve water under the stress of exertion as well as the normal kidney.
Yu, Lei; Lv, Ji-Cheng; Zhou, Xu-jie; Zhu, Li; Hou, Ping; Zhang, Hong
Familial renal glucosuria (FRG) is characterized by persistent glucosuria despite normal serum glucose and in the absence of overt tubular dysfunction. Mutation of sodium/glucose co-transporter 2 (SGLT2) has been identified and was recently reported to be involved in FRG. However, the functional and pathological consequences of such mutations remain unknown. In the current study, we collected four families with FRG. Sequencing of the SGLT2 coding region, intronic segments and cDNA revealed three missense mutations (294C>A: F98L; 1388T>G: L463R; 1435C>G: R479G) and two splice mutations (IVS 1-16 C>A: Del exon3; IVS 11+1 G>C: Del exon11). The probands were either heterozygous or compound heterozygous for SGLT2 mutations, and had glucosuria quantified at 6-27 g/day. Human 293 cells were transfected with the plasmid constructs to study the expression and function of SGLT2 mutants in vitro. Confocal microscopy using green fluorescent protein (GFP) revealed that the mutation results in a loss of punctate membrane pattern typical of the wild-type SGLT2 except in the 294C>A mutant. All mutants had significantly lower transport capacity in comparison to the wild-type control (26.49-71.48%). Renal biopsy in one consenting proband revealed significantly lower SGLT2 expression in the apical side of the proximal convoluted tubule in comparison to both healthy and disease controls (minimal change disease and diabetic nephropathy). The current study provides functional clues regarding the SGLT2 molecule from genotype to phenotype in FRG families.
Gilbert, Cameron; Cherney, David Z I; Parker, Andrea B; Mak, Susanna; Floras, John S; Al-Hesayen, Abdul; Parker, John D
Abnormal renal function is common in acute and chronic congestive heart failure (CHF) and is related to the severity of congestion. However, treatment of congestion often leads to worsening renal function. Our objective was to explore basal determinants of renal function and their response to hemodynamic interventions. Thirty-seven patients without CHF and 59 patients with chronic CHF (ejection fraction; 23 ± 8%) underwent right heart catheterization, measurements of glomerular filtration rate (GFR; inulin) and renal plasma flow (RPF; para-aminohippurate), and radiotracer estimates of renal sympathetic activity. A subset (26 without, 36 with CHF) underwent acute pharmacological intervention with dobutamine or nitroprusside. We explored the relationship between baseline and drug-induced hemodynamic changes and changes in renal function. In CHF, there was an inverse relationship among right atrial mean pressure (RAM) pressure, RPF, and GFR. By contrast, mean arterial pressure (MAP), cardiac index (CI), and measures of renal sympathetic activity were not significant predictors. In those with CHF there was also an inverse relationship among the drug-induced changes in RAM as well as pulmonary artery mean pressure and the change in GFR. Changes in MAP and CI did not predict the change in GFR in those with CHF. Baseline values and changes in RAM pressure did not correlate with GFR in those without CHF. In the CHF group there was a positive correlation between RAM pressure and renal sympathetic activity. There was also an inverse relationship among RAM pressure, GFR, and RPF in patients with chronic CHF. The observation that acute reductions in RAM pressure is associated with an increase in GFR in patients with CHF has important clinical implications.
Mukai, Takashi; Sato, Shuhei; Iguchi, Toshihiro; Mimura, Hidefumi; Yasui, Kotaro; Gobara, Hideo; Saika, Takashi; Nasu, Yasutomo; Kumon, Hiromi; Kanazawa, Susumu
We quantitatively evaluated total and individual renal function by technetium-99m mercaptoacetyltriglycine (Tc-99m MAG3) renal scintigraphy before and after radiofrequency ablation (RFA) of renal tumors. Eleven patients who underwent Tc-99m MAG3 renal scintigraphy 1 week before and after RFA were evaluated (7 men and 4 women; age range: 23-83 years; mean age: 60.6 years). Five patients had solitary kidneys, and five had normally or minimally functioning contralateral kidneys. One patient had a renal cell carcinoma in the contralateral kidney. One patient with a solitary kidney underwent RFA a second time for a residual tumor. In patients with a solitary kidney, MAG3 clearance decreased after 5 of 6 RFAs, and in patients with a normally functioning contralateral kidney, MAG3 clearance decreased after 4 of 5 RFAs, but no significant differences were observed between before and after treatments. In addition to the total MAG3 clearance, the split MAG3 clearance was evaluated in patients with a normally functioning contralateral kidney. MAG3 clearance decreased in 4 of 5 treated kidneys, while it adversely increased in the contralateral kidneys after 4 of 5 RFAs. No significant differences, however, were observed between before and after treatments. The results of our study revealed no significant differences in sCr, BUN, CCr, or MAG3 clearance between pre- and post-RFA values. These results support data regarding the functional impact and safety of renal RFA in published reports. We evaluated total and individual renal function quantitatively using Tc-99m MAG3 renal scintigraphy before and after treatment. This scintigraphy was very useful in assessing the effects of RFA on renal function.
Vayre, P; Chambraud, E; Fredj, G; Thuillier, A
The main pharmacokinetic parameters of pyrazinamide and pyrazinoïc acid (its major metabolite) were determined after oral administration of 1,500 mg/d in 10 patients with normal renal function and of 1,000 mg/d in 10 patients with impaired renal function (renal insufficiency). This study shows that, with these dosage regimens, almost all the pharmacokinetic parameters are identical for pyrazinamide and pyrazinoic acid in patients with normal renal function and patients with impaired renal function. Comparison of results between patients allows us to propose a dosage regimen of 1,000 mg/d as maintenance in patients with renal insufficiency.
Maddern, P J
Patients with renal disease are at risk of further deterioration of renal function and acute tubular necrosis when subjected to anaesthesia and surgery. Optimal fluid loading and careful selection of anaesthetic techniques and agents, appropriate monitoring and the use of mannitol and dopamine assist in the maintenance of renal blood flow and help preserve renal function in these patients. In association with renal failure, physiological changes in other systems result in reduced oxygen supply to the tissues, metabolic disturbances, impairment of the coagulation and immune defence mechanisms and an increased risk of cardiac and cerebrovascular catastrophe. Although many anaesthetic techniques including regional analgesia may be used successfully in these patients caution with most drugs, especially pethidine, phenoperidine, suxamethonium and all non-depolarising neuromuscular relaxants is recommended. Of the volatile anaesthetics currently available, halothane is the agent of choice. Oxygen therapy and close monitoring of cardiorespiratory function are necessary postoperatively.
Bovée, K C
Two previously published studies in dogs with reduced renal function are reviewed. In the first study, renal function and biochemical responses to dietary changes were studied in four dogs with stable chronic renal failure. The objective was to determine if dogs with moderate stable failure adjust to diets with varied protein and electrolyte content. These dogs were found to have the capacity to adapt to a wide range of dietary protein and electrolyte intake. The only exception was found in dogs fed a reduced-protein diet, which failed to appropriately adjust renal tubular excretion of sodium and phosphate. The only advantage of reduced dietary protein in this study was a reduction in blood urea nitrogen (BUN). Disadvantages of reduced-protein diets were reduced glomerular filtration rate (GFR) and renal plasma flow. In the second study, the hypothesis that large amounts of dietary protein sustain renal hyperfunction and produce progressive glomerulosclerosis in dogs as previously reported in rats was tested. Results failed to find a pattern of deterioration of renal function over 4 y. Light microscopic changes and electron microscopy also failed to find glomerular injury similar to that reported in rodents. These results do not support the hypothesis that feeding a high protein diet had a significant adverse effect on renal function or morphology.
Akulin, S M; Ianenko, E K; Demin, A I; Nikitinskaia, L P
Renal function in patients with stag-horn nephrolithiasis was assessed after two surgical treatments--percutaneous nephrolitholapaxy (PCN L) and pyelonephrolithotomy. The function of the operated and contralateral kidneys was studied early and late after operation by parameters of blood biochemistry, Doppler investigation of renal parenchyma, dynamic nephroscintigraphy. Stabilization or improvement of blood biochemical indices was observed in 58 (70%) patients. A secretory renal function late after surgery (from 6 months to 2 years) evidenced for improvement or stabilization of renal function (according to radionuclide test) in 71 (85.5%) patients. Integral parameters of renal blood flow were physiological or improved versus preoperative ones. PCNL was made in patients with deficient secretion less than 70%, 35 (87.5%) patients were diagnosed to have stabilization or functional improvement. After open intervention functional improvement took place in 11 (25.6%) patients, stabilization of renal function occurred in 25 (58.1%) patients. Tubular secretion deterioration was seen much more frequently in patients after open intervention. PCNL is less invasive surgical intervention than pyelonephrolithotomy as this technique produces milder surgical trauma and does not result in intraoperative renal ischemia. PCNL is the most effective surgical modality in stag-horn concrements of the kidneys and significantly expands potential of low-invasive treatment of such patients.
BACKGROUND Higher levels of baseline pulse wave velocity (PWV) have been associated with longitudinal decline in renal function in patients with kidney disease. We examined longitudinal decline in renal function in relation to levels of PWV. We hypothesized that longitudinal decline in renal function in a community-based, nonclinic sample would be associated with higher levels of PWV. METHODS We conducted a 4–5 year longitudinal study with 482 community-living individuals free from acute stroke, dementia, and end-stage renal disease (mean age = 60.9 years; 59% women; 93.2% white; 10% with diabetes mellitus; mean estimated glomerular filtration rate (eGFR) = 79.2ml/min/1.73 m2). Multiple linear regression analyses were used to examine the association between changes in renal function (eGFR and serum creatinine) from baseline to follow-up and PWV levels at follow-up, the outcome measure. Regression coefficients were adjusted for age, sex, education, race/ethnicity, weight, activity level, mean arterial pressure, treatment of hypertension, and cardiovascular risk factors. RESULTS With adjustment for covariables, decline in renal function was associated with higher levels of PWV over a mean follow-up of 4.68 years. CONCLUSIONS Decline in renal functioning from baseline levels measured 4–5 years before measurement of PWV is related to higher levels of PWV in a community sample. PMID:24080989
Anjum, Misbah; Moorani, Khemchand N; Sameen, Ifra; Mustufa, Muhammad Ayaz; Kulsoom, Shazia
Objectives: The association of malnutrition and systemic diseases like chronic kidney disease (CKD) is well known. Various urinary tract abnormalities may be associated with malnutrition. So objective of current study was to determine the frequency of functional and structural urinary tract abnormalities in severely malnourished children admitted in Nutritional Rehabilitation Unit (NRU) of a tertiary care facility, Karachi. Methods: This descriptive cases series of 78 children was conducted in NRU from October 2014 - March 2015. All newly admitted children aged 2-60 months, diagnosed as Severe Acute Malnutrition (SAM) were studied and children with known kidney and urinary tract disorders were excluded. Detailed history, examination and investigations like serum creatinine, ultrasound kidney and urinary tract in addition to routine tests for SAM, were done. A proforma was used to collect demographic data, clinical history, physical findings, and radio-imaging and biochemical investigations. Glomerular filtration rate (GFR) was calculated using Schwartz equation. Data was analyzed using descriptive statistics. Results: Among 78 children, male to female ratio was equal. Mean age was 18±15.53 months and majority (79.48%) of children were below 24 months. Majority (82%) of children with SAM had marasmus whereas 18% had edematous malnutrition. Out of 78, 57 (73%) children had either functional (80.7%) and or structural (19.3%) abnormalities whereas 21(36.84%) had normal functional and structural status. Most common functional abnormality was subnormal GFR (<90ml/min/1.73 m2) found in all 46 children. Functional abnormities were more common in children below 24 months. Other functional disorders were Bartter syndrome, renal tubular acidosis and urinary tract infection (UTI) found in two cases each. Common structural abnormalities were echogenic kidneys (n=4, 36%), hydronephrosis (n=3, 27%), hypoplastic kidneys (n=3, 27%) and calculi (n=1, 9%). Subnormal GFR was also
O'Connor, W J
The purpose here is to examine in relation to normal renal function three factors which might affect tubular reabsorption: (1) The reabsorption of SO4, PO4, K, Cl, HCO3 and water are all linked to the reabsorption of Na. This would amount to the reabsorption by the tubules of a net reabsorbate of a composition similar to Locke's fluid. Fixed linkage of the reabsorption of a substance to the reabsorption of Na would be a very effective way of maintaining its plasma concentration within a narrow range. The substance would be retained unless its plasma concentration exceeds a threshold value and then small increase in plasma concentration determines its excretion. (2) The rate of reabsorption of Na and substances linked to it is increased when the volume of the intraluminal fluid is increased. This would explain why there is only a small increase in the excretion of Na and other electrolytes when glomerular filtration rate is increased after a meal of meat. (3) Plasma protein concentration affects tubular reabsorption. This would explain why fall in plasma protein is a main agent determining Na excretion in normal animals. Trying to see 'how far the observed facts can be brought into accord with a theory' reveals the difficulty of applying critical tests. On the one hand, the theories are not stated quantitatively in reference to the small changes of normal life; rather the evidence is from experiments with large changes. On the other hand, the small changes within the range of normal function, while themselves statistically significant, are too small for effective investigation of circumstances which may modify them. In the examples discussed here, we cannot say more than that the theories could explain the facts and their participation cannot be excluded.
Zhang, Youxue; Xie, Bing; Chen, Heng; Li, Meiling; Liu, Feng; Chen, Huafu
Post-traumatic stress disorder (PTSD) is a psychiatric disorder that occurs in individuals who have experienced life-threatening mental traumas. Previous neuroimaging studies have indicated that the pathology of PTSD may be associated with the abnormal functional integration among brain regions. In the current study, we used functional connectivity density (FCD) mapping, a novel voxel-wise data-driven approach based on graph theory, to explore aberrant FC through the resting-state functional magnetic resonance imaging of the PTSD. We calculated both short- and long-range FCD in PTSD patients and healthy controls (HCs). Compared with HCs, PTSD patients showed significantly increased long-range FCD in the left dorsolateral prefrontal cortex (DLPFC), but no abnormal short-range FCD was found in PTSD. Furthermore, seed-based FC analysis of the left DLPFC showed increased connectivity in the left superior parietal lobe and visual cortex of PTSD patients. The results suggested that PTSD patients experienced a disruption of intrinsic long-range functional connections in the fronto-parietal network and visual cortex, which are associated with attention control and visual information processing.
Pan, Junmin; Seeger-Nukpezah, Tamina; Golemis, Erica A.
The primary cilium protrudes from the cell surface and acts as a sensor for chemical and mechanical growth cues, with receptors for a number of growth factors (PDGFα, Hedgehog, Wnt, Notch) concentrated within the ciliary membrane. In normal tissues, the cilium assembles after cells exit mitosis and is resorbed as part of cell cycle re-entry. Although regulation of the cilium by cell cycle transitions has been appreciated for over 100 years, only recently have data emerged to indicate the cilium also exerts influence on the cell cycle. The resorption/protrusion cycle, regulated by proteins including Aurora-A, VHL, and GSK-3β, influences cell responsiveness to growth cues involving cilia-linked receptors; further, resorption liberates the ciliary basal body to differentiate into the centrosome, which performs discrete functions in S-, G2-, and M-phase. Besides these roles, the cilium provides a positional cue that regulates polarity of cell division, and thus directs cells towards fates of differentiation versus proliferation. In this review, we summarize the specific mechanisms mediating the cilia-cell cycle dialog. We then emphasize the examples of polycystic kidney disease (PKD), nephronopthisis (NPHP), and VHL-linked renal cysts as cases in which defects of ciliary function influence disease pathology, and may also condition response to treatment. PMID:22782110
Pearson, R M; Breckenridge, A M
1 The effect of rapid (10s) injections of diazoxide was studied in ten hypertensive patients with varying degrees of impairment of renal function. 2 There was a significant correlation between the patient's plasma urea concentration and reduction in mean arterial blood pressure. Diazoxide was also shown to be less highly protein bound in patients with renal failure. 3 It is suggested that the explanation for the increased hypotensive effect of diazoxide observed in patients with reduced renal function is related to higher unbound drug concentrations. PMID:973937
Macleod, M A; Houston, A S
In a study of 100 patients referred for assessment of renal function a comparison is made between gamma camera computer assisted displays of 99mTc-DTPA(Sn) nephrograms, intra-venous urography (I.V.U.) and triple probe 131I-Hippuran renography. The computer processed data displays renal morphology and activity/time curves which are deconvolved enabling quantitative assessment of glomerular function to be made. Pattern recognition techniques for feature extraction are employed to facilitate classification of the curves. It is concluded that the computer processed data gives better results both in the recognition of morphological defects and in the indication and measurement of renal damage.
Weinstein, M J; Chute, L E; Schmitt, G W; Hamburger, R H; Bauer, K A; Troll, J H; Janson, P; Deykin, D
Factor VIII antigen (VIII:CAg) exhibits molecular weight heterogeneity in normal plasma. We have compared the relative quantities of VIII:CAg forms present in normal individuals (n = 22) with VIII:CAg forms in renal dysfunction patients (n = 19) and in patients with disseminated intravascular coagulation (DIC; n = 7). In normal plasma, the predominant VIII: CAg form, detectable by sodium dodecyl sulfate polyacrylamide gel electrophoresis, was of molecular weight 2.4 X 10(5), with minor forms ranging from 8 X 10(4) to 2.6 X 10(5) D. A high proportion of VIII:CAg in renal dysfunction patients, in contrast, was of 1 X 10(5) mol wt. The patients' high 1 X 10(5) mol wt VIII: CAg level correlated with increased concentrations of serum creatinine, F1+2 (a polypeptide released upon prothrombin activation), and with von Willebrand factor. Despite the high proportion of the 1 X 10(5) mol wt VIII:CAg form, which suggests VIII:CAg proteolysis, the ratio of Factor VIII coagulant activity to total VIII:CAg concentration was normal in renal dysfunction patients. These results could be simulated in vitro by thrombin treatment of normal plasma, which yielded similar VIII:CAg gel patterns and Factor VIII coagulant activity to antigen ratios. DIC patients with high F1+2 levels but no evidence of renal dysfunction had an VIII:CAg gel pattern distinct from renal dysfunction patients. DIC patients had elevated concentrations of both the 1 X 10(5) and 8 X 10(4) mol wt VIII:CAg forms. We conclude that an increase in a particular VIII:CAg form correlates with the severity of renal dysfunction. The antigen abnormality may be the result of VIII:CAg proteolysis by a thrombinlike enzyme and/or prolonged retention of proteolyzed VIII:CAg fragments. Images PMID:3932466
Chen, Shuo; Xing, Yishi; Kang, Jian
Autism spectrum disorder (ASD) is associated with disrupted brain networks. Neuroimaging techniques provide noninvasive methods of investigating abnormal connectivity patterns in ASD. In the present study, we compare functional connectivity networks in people with ASD with those in typical controls, using neuroimaging data from the Autism Brain Imaging Data Exchange (ABIDE) project. Specifically, we focus on the characteristics of intrinsic functional connectivity based on data collected by resting-state functional magnetic resonance imaging (rs-fMRI). Our aim was to identify disrupted brain connectivity patterns across all networks, instead of in individual edges, by using advanced statistical methods. Unlike many brain connectome studies, in which networks are prespecified before the edge connectivity in each network is compared between clinical groups, we detected the latent differentially expressed networks automatically. Our network-level analysis identified abnormal connectome networks that (i) included a high proportion of edges that were differentially expressed between people with ASD and typical controls; and (ii) showed highly-organized graph topology. These findings provide new insight into the study of the underlying neuropsychiatric mechanism of ASD. PMID:28377688
Doltra, Adelina; Hartmann, Arthur; Stawowy, Philipp; Goubergrits, Leonid; Kuehne, Titus; Wellnhofer, Ernst; Gebker, Rolf; Schneeweis, Christopher; Schnackenburg, Bernhard; Esler, Murray; Fleck, Eckart; Kelle, Sebastian
Aim To study the effects of RD on renal artery wall function non-invasively using magnetic resonance. Methods and Results 32 patients undergoing RD were included. A 3.0 Tesla magnetic resonance of the renal arteries was performed before RD and after 6-month. We quantified the vessel sharpness of both renal arteries using a quantitative analysis tool (Soap-Bubble®). In 17 patients we assessed the maximal and minimal cross-sectional area of both arteries, peak velocity, mean flow, and renal artery distensibility. In a subset of patients wall shear stress was assessed with computational flow dynamics. Neither renal artery sharpness nor renal artery distensibility differed significantly. A significant increase in minimal and maximal areas (by 25.3%, p = 0.008, and 24.6%, p = 0.007, respectively), peak velocity (by 16.9%, p = 0.021), and mean flow (by 22.4%, p = 0.007) was observed after RD. Wall shear stress significantly decreased (by 25%, p = 0.029). These effects were observed in blood pressure responders and non-responders. Conclusions RD is not associated with adverse effects at renal artery level, and leads to an increase in cross-sectional areas, velocity and flow and a decrease in wall shear stress. PMID:27003912
Ziessman, H.A.; Balseiro, J.; Fahey, F.H.; Le, T.V.; Dubiansky, V.
Differential renal function was calculated by using /sup 99m/Tc-glucoheptonate (Tc-GH) in 51 patients. Computer-acquired background-corrected individual renal function was calculated by using both the 1-3-min uptake counts and the 2-4-hr delayed static counts. The degree of correlation between the two was high (r = .96). An equally high correlation was noted in 16 children who were 12 years old or younger, in 15 patients with renal size disparity greater than 60/40%, and in six patients with abnormal creatinine clearances. Ten patients had a 30-min dynamic /sup 99m/Tc-DTPA study followed immediately by the injection of Tc-GH and acquisition of delayed static images 2-4 hr later. A high degree of correlation (r = .99) was seen between the 1-3-min differential function obtained by using Tc-DTPA and the 2-4-hr delayed differential function obtained by using Tc-GH. This study shows that Tc-GH is a clinically useful and valid tool for calculation of differential renal function and that Tc-GH combines many of the best aspects of Tc-DTPA and Tc-DMSA.
Georgatzakou, Hara T; Antonelou, Marianna H; Papassideri, Issidora S; Kriebardis, Anastasios G
Anemia is the most common hematologic complication in end-stage renal disease (ESRD). It is ascribed to decreased erythropoietin production, shortened red blood cell (RBC) lifespan, and inflammation. Uremic toxins severely affect RBC lifespan; however, the implicated molecular pathways are poorly understood. Moreover, current management of anemia in ESRD is controversial due to the "anemia paradox" phenomenon, which underlines the need for a more individualized approach to therapy. RBCs imprint the adverse effects of uremic, inflammatory, and oxidative stresses in a context of structural and functional deterioration that is associated with RBC removal signaling and morbidity risk. RBCs circulate in hostile plasma by raising elegant homeostatic defenses. Variability in primary defect, co-morbidity, and therapeutic approaches add complexity to the pathophysiological background of the anemic ESRD patient. Several blood components have been suggested as biomarkers of anemia-related morbidity and mortality risk in ESRD. However, a holistic view of blood cell and plasma modifications through integrated omics approaches and high-throughput studies might assist the development of new diagnostic tests and therapies that will target the underlying pathophysiologic processes of ESRD anemia.
Rutherford, Elaine; Talle, Mohammed A; Mangion, Kenneth; Bell, Elizabeth; Rauhalammi, Samuli M; Roditi, Giles; McComb, Christie; Radjenovic, Aleksandra; Welsh, Paul; Woodward, Rosemary; Struthers, Allan D; Jardine, Alan G; Patel, Rajan K; Berry, Colin; Mark, Patrick B
Noninvasive quantification of myocardial fibrosis in end-stage renal disease is challenging. Gadolinium contrast agents previously used for cardiac magnetic resonance imaging (MRI) are contraindicated because of an association with nephrogenic systemic fibrosis. In other populations, increased myocardial native T1 times on cardiac MRI have been shown to be a surrogate marker of myocardial fibrosis. We applied this method to 33 incident hemodialysis patients and 28 age- and sex-matched healthy volunteers who underwent MRI at 3.0T. Native T1 relaxation times and feature tracking-derived global longitudinal strain as potential markers of fibrosis were compared and associated with cardiac biomarkers. Left ventricular mass indices were higher in the hemodialysis than the control group. Global, Septal and midseptal T1 times were all significantly higher in the hemodialysis group (global T1 hemodialysis 1171 ± 27 ms vs. 1154 ± 32 ms; septal T1 hemodialysis 1184 ± 29 ms vs. 1163 ± 30 ms; and midseptal T1 hemodialysis 1184 ± 34 ms vs. 1161 ± 29 ms). In the hemodialysis group, T1 times correlated with left ventricular mass indices. Septal T1 times correlated with troponin and electrocardiogram-corrected QT interval. The peak global longitudinal strain was significantly reduced in the hemodialysis group (hemodialysis -17.7±5.3% vs. -21.8±6.2%). For hemodialysis patients, the peak global longitudinal strain significantly correlated with left ventricular mass indices (R = 0.426), and a trend was seen for correlation with galectin-3, a biomarker of cardiac fibrosis. Thus, cardiac tissue properties of hemodialysis patients consistent with myocardial fibrosis can be determined noninvasively and associated with multiple structural and functional abnormalities.
Messina, Irene; Bianco, Francesca; Cusinato, Maria; Calvo, Vincenzo; Sambin, Marco
Depression is widely seen as the result of difficulties in regulating emotions. Based on neuroimaging studies on voluntary emotion regulation, neurobiological models have focused on the concept of cognitive control, considering emotion regulation as a shift toward involving controlled processes associated with activation of the prefrontal and parietal executive areas, instead of responding automatically to emotional stimuli. According to such models, the weaker executive area activation observed in depressed patients is attributable to a lack of cognitive control over negative emotions. Going beyond the concept of cognitive control, psychodynamic models describe the development of individuals’ capacity to regulate their emotional states in mother-infant interactions during childhood, through the construction of the representation of the self, others, and relationships. In this mini-review, we link these psychodynamic models with recent findings regarding the abnormal functioning of the default system in depression. Consistently with psychodynamic models, psychological functions associated with the default system include self-related processing, semantic processes, and implicit forms of emotion regulation. The abnormal activation of the default system observed in depression may explain the dysfunctional aspects of emotion regulation typical of the condition, such as an exaggerated negative self-focus and rumination on self-esteem issues. We also discuss the clinical implications of these findings with reference to the therapeutic relationship as a key tool for revisiting impaired or distorted representations of the self and relational objects. PMID:27375536
Wood, Kyle; Keys, Tristan; Mufarrij, Patrick; Assimos, Dean G
Stone removal can improve renal function by eradicating obstruction and, in certain cases, an underlying infection. Stone-removing procedures, however, may negatively impact functional integrity. Many things may impact the latter, including the procedures used, the methods of assessing function, the time when these assessments are made, the occurrence of complications, the baseline condition of the kidney, and patient-related factors. In the majority of cases, little significant functional impairment occurs. However, there are gaps in our knowledge of this subject, including the cumulative effects of multiple procedures violating the renal parenchyma and long-term functional outcomes. PMID:21935339
Parajuli, Sandesh; Foley, David; Djamali, Arjang; Mandelbrot, Didier
Kidney injury is associated with increased morbidity and mortality in liver transplant recipients. Since the introduction of the model for end-stage liver disease for the allocation of organs for liver transplantation in 2002, the heavy weighting of serum creatinine in the model for end-stage liver disease score has significantly increased the incidence of renal dysfunction seen among patients undergoing liver transplantation. As a result, the frequency of simultaneous liver-kidney (SLK) transplantation compared to liver transplantation alone (LTA) has also increased. The decision to perform SLK rather than LTA is an important one because the benefits to the liver transplant recipient receiving a kidney transplant must be balanced with the benefits of using that organ for a patient with end-stage renal disease. However, predicting whether or not a patient with liver failure has reversible kidney disease, and therefore does not also need a kidney transplant, is difficult. The severity and duration of pretransplant renal dysfunction, hepatitis c, diabetes, and other risk factors for kidney disease are associated with an increased risk of posttransplant end-stage renal disease. However, there are currently no clinical findings that accurately predict renal recovery post liver transplant. As a result, the rate of SLK versus LTA differs significantly between transplant centers. To increase consistency across centers, multiple guidelines have been proposed to guide the decision between SLK and LTA, but their poor predictive value has limited their uniform adoption. Nevertheless, adoption of uniform rules for the allocation of kidneys would reduce the variability between centers in rates of SLK transplant.
Mapel, Douglas W; Marton, Jenõ P
Background The purpose of this study was to describe the prevalence of renal and hepatic disease, related laboratory abnormalities, and potentially hepatotoxic and nephrotoxic medication use in a population-based cohort of persons with chronic obstructive pulmonary disease (COPD). Methods This was a retrospective case-control cohort analysis of COPD patients enrolled in one regional health system for at least 12 months during a 36-month study period (n = 2284). Each COPD patient was matched by age and gender to up to three persons not diagnosed with COPD (n = 5959). Results The mean age for cases and controls was 70.3 years, and 52.5% were women. The COPD cohort had significantly higher prevalences (cases/100) of acute, chronic, and unspecified renal failure as compared with controls (1.40 versus 0.59, 2.89 versus 0.79, and 1.09 versus 0.44, respectively). Among the cases, 31.3% had at least one renal or urinary tract diagnosis during the study period, as compared with 21.1% of controls. COPD cases also had more gallbladder disease (2.76 versus 1.63) and pancreatic disease (1.40 versus 0.60), but not hepatic disease. COPD patients were more likely to have at least one serum creatinine level (5.1 versus 2.1) or liver aspartate aminotransferase level (4.5 versus 2.7) that was more than twice the upper limit of normal. COPD patients had prescription fills for an average of 17.6 potentially nephrotoxic and 27.4 hepatotoxic drugs during the study period, as compared with 13.6 and 19.9 for the controls (P value for all comparisons < 0.01). Conclusion COPD patients have a substantially increased prevalence of renal, gallbladder, and pancreatic diseases, as well as abnormal renal and hepatic laboratory values, but not diagnosed liver disease. COPD patients are also more likely to be prescribed medications with potentially toxic renal or hepatic side effects. PMID:23515180
Kumar, Kaushal; Ahmad, Ahsan; Kumar, Shailendra; Choudhry, Vijyanand; Tiwari, Rajesh Kumar; Singh, Mahendra; Muzaffar, Mohammad Ali
Background: Pyeloplasty is a widely accepted treatment for ureteropelvic junction obstruction (UPJO). However, the renal function recoverability after pyeloplasty is still a matter of debate. Different parameters have been used to predict renal functional recoverability after corrective surgery, with conflicting results. Objectives: In this study, renal biopsy was carried on a series of cases of UPJO, during pyeloplasty, to study the extent of histological alterations in renal parenchyma, as a result of obstruction, and its predictive value in renal function recoverability after pyeloplasty. Patients and Methods: We retrospectively analyzed the renal biopsy obtained during pyeloplasty in 53 adult patients. Histopathological changes were graded on a scale of 1 to 3, according to their severity, and compared with the differential renal function (DRF) revealed on the preoperative and postoperative follow up diethylene triamine pentaacetic acid (DTPA) renal scan. A Fischer’s t test was used to evaluate statistical differences between values. Results: This study showed a linear relationship between the severity of histological changes and renal function recovery, after pyeloplasty. Out of 24 obstructed renal units (ORU), with minimal histopathological changes (grade I), 21 ORU (87.5%), with > 35% DRF preoperatively, showed significant improvement in renal function after 12 months of pyeloplasty (P < 0.05). On the other hand, all kidneys (n = 29) with moderate to severe obstructive changes (grade II and III) had minimal improvement in DRF, after pyeloplasty, which was clinically insignificant (P > 0.05). Renal function deterioration after pyeloplasty was not observed in any of the cases. Conclusions: The severity of pathological changes in renal parenchyma, due to UPJO, is a good predictor of renal function recoverability, after pyeloplasty. The ORUs, with DRF > 35%, usually have normal (grade I) renal biopsy and might be expected to present better functional
Suehiro, K; Shimizu, J; Yi, G H; Gu, A; Wang, J; Keren, G; Burkhoff, D
Renal failure is common in heart failure due to renovascular constriction and hypotension. We tested whether selective pharmacological renal artery vasodilation and active renal artery perfusion (ARP) could improve renal function without adverse effects on systemic blood pressure in a canine model of acute heart failure (AHF). AHF was induced by coronary microembolization in 16 adult mongrel dogs. In five dogs, selective intrarenal (IR) papaverine (1, 2, and 4 mg/min) was administered into the left renal artery. In six dogs, ARP was performed in the left renal artery to normalize mean renal arterial pressure followed by administration of IR papaverine (2 mg/min). In five dogs, ARP plus intravenous furosemide was tested. Urine output (UO) and cortical renal blood flow decreased during AHF and were restored by 2 mg/min IR papaverine (UO: baseline 4.2 +/- 0.6, AHF 1.6 +/- 1.3, IR papaverine 5.8 +/- 1.1 ml/15 min; cortical blood flow: baseline 4.3 +/- 0.2, AHF 2.4 +/- 0.6, IR papaverine 4.2 +/- 1.2 ml/min/g) with no significant change in aortic pressure. ARP also increased urine output and cortical renal blood flow (UO: baseline 5.0 +/- 1.1, AHF 0.5 +/- 0.4, ARP 3.8 +/- 3.1 ml/15 min; cortical blood flow: baseline 4.0 +/- 0.5, AHF 2.0 +/- 0.8, ARP 3.52 +/- 1.1 ml/min/g). A combination of these methods in AHF further increased urine output to twice the normal baseline (10.5 +/- 7.5 ml/15 min). Addition of furosemide synergistically increased UO above that achieved with ARP alone (5.5 +/- 2.6 versus 40.3 +/- 24.7 ml/15 min, p = 0.03). In conclusion, ARP and selective renal vasodilation may effectively promote salt and water excretion in the setting of heart failure, particularly when systemic blood pressure is low.
Morris, R. Curtis; Schmidlin, Olga; Sebastian, Anthony; Tanaka, Masae; Kurtz, Theodore W.
Prevailing theory holds that abnormally large increases in renal salt retention and cardiac output are early pathophysiologic events mediating initiation of most instances of salt-induced hypertension. This theory has come under increasing scrutiny because it is based on studies that lack measurements of sodium balance and cardiac output obtained during initiation of salt-loading in proper normal controls, i.e., salt-resistant subjects with normal blood pressure. Here we make the case for a “vasodysfunction” theory for initiation of salt-induced hypertension: In response to an increase in salt intake, a subnormal decrease in total peripheral resistance that involves a subnormal decrease in renal vascular resistance, in the absence of abnormally large increases in sodium retention and cardiac output, is the hemodynamic abnormality that usually mediates initiation of salt-induced increases in blood pressure (BP). It is the failure to normally decrease vascular resistance in response to salt loading that enables a normal increase of cardiac output to initiate the salt-induced increase in blood pressure. This theory is based on the results of properly controlled studies which consistently demonstrate that in salt-sensitive subjects, salt-loading initiates increased BP through a hemodynamic mechanism that: 1) does not usually involve early increases in sodium retention and cardiac output greater than those which occur with salt-loading in normal controls, and 2) usually involves an early failure to decrease vascular resistance to the same extent as that observed during salt-loading in normal controls. Multiple mechanisms including disturbances in nitric oxide and sympathetic nervous system activity likely underlie this subnormal vasodilatory response to salt that usually precedes and initiates salt-induced hypertension. PMID:26927006
Chen, K.K.; Chang, L.S.; Chen, M.T.; Yeh, S.H. )
In an attempt to understand better the status of renal function after Kock pouch urinary diversion we conducted a prospective evaluation of renal function in 25 patients using the radionuclide 131iodine-hippurate. Studies were done before, and at 1 month and every 6 months for 30 months postoperatively. The radionuclide results were then compared to excretory urography and contrast study of the reservoir. Our renal function study included the determination of individual and total effective renal plasma flow (ml. per minute), the time to maximal radioactivity over the kidney (peak time in minutes) and a renogram. The mean total (both kidneys) effective renal plasma flow rates before (25 patients) and at month 1 (19), month 6 (14), month 12 (12), month 18 (6), month 24 (6) and month 30 (7) after operation were 385.5 +/- 112.2, 310.5 +/- 109.9, 362.7 +/- 69.2, 442.0 +/- 97.5, 468.2 +/- 82.5, 405.7 +/- 70.6 and 414.0 +/- 65.1, respectively. A comparison of individual and total effective renal plasma flow before and after operation revealed that only the change of the flow at each or both sides of the kidney before and at 1 month after the operation reached statistically significant differences, respectively (p less than 0.05, paired t test). Postoperatively 5 of 6 patients with hydronephrosis had abnormal peak time and a third segment on the renogram was performed on the corresponding side of the kidney. No reflux was noted on contrast study of the reservoir of any patient followed for up to 30 months. In conclusion, the radionuclide renal function evaluation showed a significant decrease of renal function 1 month after Kock pouch diversion, then it resumed and remained stable (neither improved nor deteriorated) for 30 months. Also the abnormal peak time and third segment on the renogram usually implicated a dilated upper urinary tract.
Bots, Michiel L; Blankestijn, Peter J
It is well established that the presence of impaired renal function is associated with an increased risk of end-stage renal disease, cardiovascular events and all-cause mortality. Irrespective of the starting level of renal function, a decline in renal function over two years is a relevant and strong risk factor for end-stage renal disease, cardiovascular death and all-cause mortality. Even a decline of 20 to 30 per cent is associated with to a considerable increased risk and requires further attention.
Kellerman, Gabriella R; Fan, Jin; Gorman, Jack M
Recently, findings on a wide range of auditory abnormalities among individuals with autism have been reported. To date, functional distinctions among these varied findings are poorly established. Such distinctions should be of interest to clinicians and researchers alike given their potential therapeutic and experimental applications. This review suggests three general trends among these findings as a starting point for future analyses. First, studies of auditory perception of linguistic and social auditory stimuli among individuals with autism generally have found impaired perception versus normal controls. Such findings may correlate with impaired language and communication skills and social isolation observed among individuals with autism. Second, studies of auditory perception of pitch and music among individuals with autism generally have found enhanced perception versus normal controls. These findings may correlate with the restrictive and highly focused behaviors observed among individuals with autism. Third, findings on the auditory perception of non-linguistic, non-musical stimuli among autism patients resist any generalized conclusions. Ultimately, as some researchers have already suggested, the distinction between impaired global processing and enhanced local processing may prove useful in making sense of apparently discordant findings on auditory abnormalities among individuals with autism.
Gupta, Pushpender Allen, Brian C. Chen, Michael Y. Childs, David D. Kota, Gopi Zagoria, Ronald J.
Purpose: To evaluate renal function changes related to radiofrequency ablation (RFA) for the treatment of multifocal renal neoplasms. Methods: This is an institutional review board-approved, Health Insurance Portability and Accountability Act compliant retrospective study of all patients treated with computed tomography guided RFA for multifocal renal neoplasms at one institution. Fifty-seven subjects, mean age 70 (range 37-88) years, underwent RFA of 169 renal neoplasms (average size 2.0 cm). Subjects had between 2 and 8 (mean 2.96) neoplasms ablated. Estimated glomerular filtration rate (eGFR) was measured before and after RFA. Complications related to RFA were recorded. Results: eGFR decreased on average of 4.4 % per tumor treated and 6.7 % per ablation session (average 1.76 tumors treated per session). For subjects with the largest neoplasm measuring >3 cm, eGFR decreased an average of 14.5 % during the course of their treatment. If the largest neoplasm measured 2-3 cm, eGFR decreased an average of 7.7 %, and if the largest neoplasm measured <2 cm, eGFR decreased an average of 3.8 %. Subjects with reduced baseline renal function were more likely to have a greater decline in eGFR after RFA. There was a minor complication rate of 6.3 % (6 of 96 sessions), none of which required treatment, and a major complication rate of 4.2 % (4 of 96 sessions). Conclusion: RFA for the treatment of multifocal renal neoplasms results in mild decline of renal function.
Shin, Sun; Lee, Yun Jung; Kim, Eun Ju; Lee, An Sook; Kang, Dae Gill; Lee, Ho Sub
The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.
Das, Nupur; Paria, Baishakhi; Sarkar, Sujoy
Introduction: Renal dysfunction is common in chronic liver disease. The cause of this renal dysfunction is either multi-organ involvement in acute conditions or secondary to advanced liver disease. Objectives: The study was undertaken to assess the renal function in chronic liver diseases and find out the association of alteration of renal function with gradation of liver disease. (assessed by child-pugh criteria) and to find out the association of alteration of renal function among the cases of chronic liver disease of different aetiology. Materials and Methods: This cross-sectional, observational study was undertaken in Department of General Medicine, Calcutta National Medical College & Hospital, Kolkata during March 2012 to July 2013 with 50 admitted patients of chronic liver disease after considering the exclusion criteria. The patients were interviewed with a pre-designed and pre-tested schedule, examined clinically, followed by some laboratory investigations relevant to diagnose the aetiology of chronic liver disease, and to assess the severity of liver and renal dysfunction. Data was analysed by standard statistical method. Results: Eighty six percent of the patients were male and the mean age of study population was 43.58 y, 68% patients suffered from alcoholic liver disease, followed by 14% patients had chronic Hepatitis-B, 10% patients developed acute kidney injury, 20% had hepato renal syndrome and 14% had IgA deposition. The distribution of serum urea and creatinine across the categories of Child Pugh classification tested by Mann-Whitney test and the distribution was statistically significant. Conclusion: The present study has found significant association between severity of liver dysfunction and certain parameters of renal dysfunction. PMID:25954647
Anderson, James W
Alterations in dietary protein intake have an important role in prevention and management of several forms of kidney disease. Using soy protein instead of animal protein reduces development of kidney disease in animals. Reducing protein intake preserves kidney function in persons with early diabetic kidney disease. Our clinical observations led us to the soy-protein hypothesis that "substitution of soy protein for animal protein results in less hyperfiltration and glomerular hypertension with resulting protection from diabetic nephropathy." These components of soy protein may lead to the benefits: specific peptides, amino acids, and isoflavones. Substituting soy protein for animal protein usually decreases hyperfiltration in diabetic subjects and may reduce urine albumin excretion. Limited data are available on effects of soy peptides, isoflavones, and other soy components on renal function on renal function in diabetes. Further studies are required to discern the specific benefits of soy protein and its components on renal function in diabetic subjects.
Mota, Ana Paula Lucas; Alpoim, Patrícia Nessralla; de Figueiredo, Roberta Carvalho; Simões e Silva, Ana Cristina; Braga Gomes, Karina; Dusse, Luci Maria SantAna
Kidney transplantation is the key for patients with end-stage renal disease, improving quality of life and longer survival. However, kidney transplant triggers an intense inflammatory response and alters the hemostatic system, but the pathophysiological mechanisms of these changes are not completely understood. The aim of this cross-sectional cohort study was to investigate hemostatic biomarkers in Brazilian renal transplanted patients according to renal function and time after transplantation. A total of 159 renal transplanted patients were enrolled and D-Dimer (D-Di), Thrombomodulin (TM), von Willebrand Factor (VWF), and ADAMTS13 plasma levels were assessed by ELISA. An increase of D-Di was observed in patients with higher levels of creatinine. ADAMTS13 levels were associated with creatinine plasma levels and D-Di levels with Glomerular Filtration Rate. These results suggested that D-Di and ADAMTS13 can be promising markers to estimate renal function. ADAMTS13 should be investigated throughout the posttransplant time to clarify the participation of this enzyme in glomerular filtration and acceptance or rejection of the graft in Brazilian transplanted patients. PMID:26229221
Eshima, D.; Fritzberg, A.R.; Taylor, A. Jr. )
Orthoiodohippuric (OIH) acid labeled with 131I is a widely used renal radiopharmaceutical agent and has been the standard radiopharmaceutical agent for the measurement of effective renal plasma flow (EPRF). Limitations to the routine clinical use of 131I OIH are related to the suboptimal imaging properties of the 131I radionuclide and its relatively high radiation dose. 123I has been substituted for 131I; however, its high cost and short shelf-life have limited its widespread use. Recent work has centered on the development of a new 99mTc renal tubular function agent, which would use the optimal radionuclidic properties and availability of 99mTc and combine the clinical information provided by OIH. The search for a suitable 99mTc renal tubular function agent has focused on the diamide dithiolate (N2S2), the paraaminohippuric iminodiacetic acid (PAHIDA), and the triamide mercaptide (N3S) donor ligand systems. To date, the most promising 99mTc tubular function agent is the N3S complex: 99mTc mercaptoacetyltriglycine (99mTc MAG3). Studies in animal models in diuresis, dehydration, acid or base imbalance, ischemia, and renal artery stenosis demonstrate that 99mTc MAG3 behaves similarly to 131I OIH. A simple kit formulation is available that yields the 99mTc MAG3 complex in high radiochemical purity. Studies in normal subjects and patients indicate that 99mTc MAG3 is an excellent 99mTc renal tubular agent, but its plasma clearance is only 50% to 60% that of OIH. In an effort to develop an improved 99mTc renal tubular function agent, changes have been made in the core N3S donor ligand system, but to date no agent has been synthesized that is clinically superior to 99mTc MAG3. 61 references.
Fontseré Baldellou, Néstor; Bonal I Bastons, Jordi; Romero González, Ramón
The chronic kidney disease represents one of the pathologies with greater incidence and prevalence in the present sanitary systems. The ambulatory application of different methods that allow a suitable detection, monitoring and stratification of the renal functionalism is of crucial importance. On the basis of the vagueness obtained by means of the application of the serum creatinine, a set of predictive equations for the estimation of the glomerular filtration rate have been developed. Nevertheless, it is essential for the physician to know its limitations, in situations of normal renal function and hyperfiltration, certain associate pathologies and extreme situations of nutritional status and age. In these cases, the application of the isotopic techniques for the calculation of the renal function is more recommendable.
Hong, C.D.; Hanenson, I.B.; Lerner, S.; Hammond, P.B.; Pesce, A.J.; Pollak, V.E.
Although nephrotoxicity is common following exposure to lead, the dose-response relationship in adults with occupational exposure is not well understood because information is lacking on early nephrotoxic effects. By the time serum urea nitrogen and creatinine levels are elevated, renal damage may be advanced and not fully reversible. Detailed investigations of renal glomerular and tubular function were performed in six adults with occupational exposure to lead. In all patients, the serum creatinine and urea nitrogen concentrations were within the normal range. GFR was decreased in all but two. Glucose reabsorptive capacity (TmG) was decreased in all, and this decrease was disproportionately greater than expected from the reduced GFR in all but one. Normal values for renal plasma flow (RFP) were observed in four of the six, and for rho-aminohippurate (PAH) secretory capacity (TmPAh) in all but one. Bicarbonate reabsorptive capacity (TmHCO3) and urinary excretion of beta2-microglobulin were normal in all. Routine clinical laboratory tests are insensitive for the detection of early renal effects of heavy metal exposure. Measurements of renal tubular reabsorptive capacity for glucose appears to be a sensitive method for the early detection of renal effect of lead.
Leduc, Martin; Hou, Xin; Hamel, David; Sanchez, Melanie; Quiniou, Christiane; Honoré, Jean-Claude; Roy, Olivier; Madaan, Ankush; Lubell, William; Varma, Daya R; Mancini, Joseph; Duhamel, François; Peri, Krishna G; Pichette, Vincent; Heveker, Nikolaus; Chemtob, Sylvain
Acute renal failure (ARF) is a serious medical complication characterized by an abrupt and sustained decline in renal function. Despite significant advances in supportive care, there is currently no effective treatment to restore renal function. PGE(2) is a lipid hormone mediator abundantly produced in the kidney, where it acts locally to regulate renal function; several studies suggest that modulating EP(4) receptor activity could improve renal function following kidney injury. An optimized peptidomimetic ligand of EP(4) receptor, THG213.29, was tested for its efficacy to improve renal function (glomerular filtration rate, renal plasma flow, and urine output) and histological changes in a model of ARF induced by either cisplatin or renal artery occlusion in Sprague-Dawley rats. THG213.29 modulated PGE(2)-binding dissociation kinetics, indicative of an allosteric binding mode. Consistently, THG213.29 antagonized EP(4)-mediated relaxation of piglet saphenous vein rings, partially inhibited EP(4)-mediated cAMP production, but did not affect Gα(i) activation or β-arrestin recruitment. In vivo, THG213.29 significantly improved renal function and histological changes in cisplatin- and renal artery occlusion-induced ARF models. THG213.29 increased mRNA expression of heme-oxygenase 1, Bcl2, and FGF-2 in renal cortex; correspondingly, in EP(4)-transfected HEK293 cells, THG213.29 augmented FGF-2 and abrogated EP(4)-dependent overexpression of inflammatory IL-6 and of apoptotic death domain-associated protein and BCL2-associated agonist of cell death. Our results demonstrate that THG213.29 represents a novel class of diuretic agent with noncompetitive allosteric modulator effects on EP(4) receptor, resulting in improved renal function and integrity following acute renal failure.
Manevska, Nevena; Stojanoski, Sinisa; Majstorov, Venjamin; Pop-Gjorcheva, Daniela; Zdraveska, Nikolina; Kuzmanovska, Dafina
BACKGROUND: Radionuclide techniques, as direct radionuclide cystography and 99mTc-DMSA scintigraphy, have been used in evaluation of vesicoureteral reflux (VUR) and reflux nephropathy (RN) in children. Dynamic 99mTc-DTPA scintigraphy is reserved for evaluation of differential renal function and obstruction in children, where hydronephrosis is detected by ultrasonography (US) pre- or postnatally. CASE REPORT: Six year old boy was prenatally diagnosed with bilateral hydronephrosis. Postnatal, severe bilateral VUR was detected by voiding urethrocytography. US and 99mTc-DTPA scintigraphy performed in the first month of life showed small left kidney that participated with 2% in the global renal function. Bilateral cutaneous ureterostomy has been performed in order to obtain good renal drainage and promote optimal renal growth. Twelve months later, classic antireflux procedure was done. Control 99mTc-DTPA scintigraphy, 5 ys after antireflux surgery, revealed persisting radioactivity during the diuretic phase, in the left kidney that indicated antireflux procedure failure with VUR reappearance. CONCLUSION: 99mTc-DTPA scintigraphy is the first method of choice for long-term monitoring of individual kidney function in children with VUR and other congenital urinary tract anomalies. Additionally, it can be used as indirect radionuclide cystography when rising of radioactivity in the kidney region, during the diuretic phase can indicate presence of VUR. PMID:27275347
Szafranska, Agnieszka; Pajak, Agata; Kilis-Pstrusinska, Katarzyna; Królak-Olejnik, Barbara
Abstract Renal vein thrombosis (RVT) in neonates is a rare condition of low mortality but significant morbidity due to renal impairment. We report the case of a male term newborn with left RVT and elevated serum factor VIII (FVIII). The main symptoms of the patient and the important clinical findings: prompt diagnosis of RVT was possible because the classic clinical presentation of macroscopic hematuria, thrombocytopenia, and palpable flank mass were present in this newborn infant. The main diagnoses: finally, the reason of RVT was established when the infant was 3 months of age: the increased level of FVIII was confirmed. We discuss the diagnosis, therapy, and outcome of the patient and compare with the literature. Therapeutics interventions: however, despite anticoagulant therapy the left kidney developed areas of scarring and then atrophy. Conclusions and outcomes: Prothrombotic defects should be considered in all patients with perinatal RVT. Elevated factor VIII as a reason of RVT in neonatal period is particularly rare. Given a poor renal outcome in children associated with elevated levels of factor VIII, consideration could be given to more aggressive antithrombotic therapy in such cases. PMID:26252276
Sag, Alan Alper; Inal, Ibrahim; Okcuoglu, John; Rossignol, Patrick; Ortiz, Alberto; Afsar, Baris; Sos, Thomas A; Kanbay, Mehmet
After three neutral trials in which renal artery stenting failed to improve renal function or reduce cardiovascular and renal events, the controversy surrounding diagnosis and treatment of atherosclerotic renal artery stenosis and renovascular hypertension has led to paradigm shifts in the diagnostic algorithm. Noninvasive determination of earlier events (cortex hypoxia and renal artery hemodynamic changes) will supersede late sequelae (calcific stenosis, renal cortical thinning). Therefore, this review proposes the concept of renal penumbra in defining at-risk ischemic renal parenchyma. The complex field of functional renal magnetic resonance imaging will be reviewed succinctly in a clinician-directed fashion.
Simeoni, Mariadelina; Cerantonio, Annamaria; Pastore, Ida; Liguori, Rossella; Greco, Marta; Foti, Daniela; Gulletta, Elio; Brunetti, Antonio; Fuiano, Giorgio
Thyroid dysfunction induces several renal derangements involving all nephron portions. Furthermore, dysthyroidism is a recognized risk factor associated with the development of chronic kidney disease. Current data, in fact, demonstrate that either subclinical or overt thyroid disease is associated with significant changes in creatinine, estimated glomerular filtration rate, measured glomerular filtration rate and Cystatin C. Herein, we systematically reviewed several relevant studies aiming at the identification of the most sensitive and specific parameter for the correct renal function evaluation in patients with thyroid dysfunction, that are usually treated as outpatients. Our systematic review indicates that estimated glomerular filtration rate, preferably with CKD-EPI equation, appears to be the most reliable and wieldy renal function parameter. Instead, Cystatin C should be better used in the grading of thyroid dysfunction severity.
A compartmental model is given for evaluating kidney function accurately and noninvasively. This model is cast into a parallel multi-compartment structure and each pixel region (picture element) of kidneys is considered as a single kidney compartment. The loss of radionuclide tracers from the blood to the kidney and from the kidney to the bladder are modelled in great detail. Both the uptake function and the excretion function of the kidneys can be evaluated pixel by pixel, and regional diagnostic information on renal function is obtained. Gamma Camera image data are required by this model and a screening test based renal function measurement is provided. The regional blood background is subtracted from the kidney region of interest (ROI) and the kidney regional rate constants are estimated analytically using the Kuhn-Pucker multiplier method in convex programming by considering the input/output behavior of the kidney compartments. The detailed physiological model of the peripheral compartments of the system, which is not available for most radionuclide tracers, is not required in the determination of the kidney regional rate constants and the regional blood background factors within the kidney ROI. Moreover, the statistical significance of measurements is considered to assure the improved statistical properties of the estimated kidney rate constants. The relations between various renal function parameters and the kidney rate constants are established. Multiple renal function measurements can be found from the renal compartmental model. The blood radioactivity curve and the regional (or total) radiorenogram determining the regional (or total) summed behavior of the kidneys are obtained analytically with the consideration of the statistical significance of measurements using convex programming methods for a single peripheral compartment system. In addition, a new technique for the determination of 'initial conditions' in both the blood compartment and the kidney
Gazel, Eymen; Biçer, Sait; Ölçücüoğlu, Erkan; Yığman, Metin; Taştemur, Sedat; Çamtosun, Ahmet; Ceylan, Cavit; Ateş, Can
Glomerular filtration rate (GFR) is directly proportionate to nephron reserves. In this respect, it is known that the patients who underwent radical nephrectomy due to renal tumor are under high risk of chronic kidney disease (CKD) in the long term. In this study, it was aimed to compare post-operative renal functions of patients who underwent radical nephrectomy due to renal malignancy and who underwent donor nephrectomy as renal donors, to observe whether renal failure process develops or not, and to determine the factors that affect post-operative renal functions. 70 patients who underwent donor nephrectomy as renal donors and 130 patients who underwent radical nephrectomy due to renal tumor were studied. When we divided the groups as those with a GFR of below 60 mL/min/1.73 m(2) and those with a GFR of above 60 mL/min/1.73 m(2), we observed that GFR values of patients who underwent radical nephrectomy had a significantly stronger tendency to stay below 60 mL/min/1.73 m(2) compared to patients who underwent donor nephrectomy (p < 0.001). When we divided the groups as those with a GFR of below 30 mL/min/1.73 m(2) and those with a GFR of above 30 mL/min/1.73 m(2), we observed that there were no patients in donor nephrectomy group whose GFR values dropped below 30 mL/min/1.73 m(2) and there was not a statistically significant difference between the groups (p = 0.099). If possible, nephron sparing methods should be preferred for patients to undergo nephrectomy because of the tumor without ignoring oncologic results and it should be remembered that patient's age and pre-operative renal functions may affect post-operative results in donor selection.
Dalal, K.B.; Ebbe, S.; Mazoyer, E.; Carpenter, D.; Yee, T. )
This study was designed to elucidate changes in rabbit platelet lipids induced by a cholesterol rich diet and to explore the possible correlation of these lipid changes with platelet abnormalities. Pronounced biochemical alterations were observed when serum cholesterol levels of 700-1000 mg% were reached. Hypercholesterolemic (HC) platelets contained 37% more neutral lipids and 16% less phospholipids than the controls. Lysolecithin, cholesterol esters and phosphatidylinositol (PI) levels were increased in HC platelets, and the levels of phosphatidylcholine (PC) were decreased. The cholesterol/phospholipid molar ratio of lipidemic platelets increased from 0.55 +/- 0.011 to 0.89 +/- 0.016 (P less than 0.01) in eight weeks. HC platelets had 90% more arachidonic acid (AA) in the PI than normal platelets. No significant changes in AA of PC were observed. Platelet function was monitored by the uptake and release of (14C)serotonin in platelet rich plasma (PRP), using varying concentrations of collagen as an aggregating agent. The uptake of (14C)serotonin in HC and normal platelets ranged from 78-94%. The percent of (14C)serotonin released from normal and HC platelets was proportional to the concentration of collagen. However, lipidemic platelets were hyperreactive to low concentrations of collagen. Incorporation of 50 microM acetylsalicylic acid into the aggregating medium suppressed the release of (14C)serotonin in normal PRP by more than 90%, but had only a partial effect on lipidemic PRP.
Carlini, R G; Rojas, E; Weisinger, J R; Lopez, M; Martinis, R; Arminio, A; Bellorin-Font, E
Renal osteodystrophy may persist during the early years after renal transplantation. However, information on bone status after a successful long-term renal transplantation is limited. We examined biochemical parameters, bone mineral density (BMD), and bone histomorphometry in 25 asymptomatic men with normal renal function after 7.5 +/- 5.7 years of a renal transplantation. Serum calcium, phosphorus, alkaline phosphatase, and 1,25(OH)(2)D(3) levels and urinary calcium level and cyclic andenosine monophosphate excretion were within normal range in all patients. Serum intact parathyroid hormone (PTH) level was elevated in 11 subjects (133.6 +/- 78 pg/mL) and normal in the other 14 subjects (47.9 +/- 13.6 pg/mL). Mean BMD at the lumbar spine and femoral neck was low in the entire group. However, it progressively increased as time after transplantation increased, approaching normal values after 10 years. Bone histomorphometric analysis showed bone resorption, osteoid volume, and osteoid surface greater than normal range in the majority of patients. Bone formation rate and mineralization surface were low, and mineralization time was delayed in most patients. These lesions were more severe in patients after 3 to 4 years of transplantation but improved with time and approached normal values after a period of 10 years. PTH values did not correlate with bone histological characteristics or BMD. These results show that the bone alterations observed after long-term renal transplantation consist of a mixed bone disease in which features of high bone turnover coexist with altered bone formation and delayed mineralization. These findings may result from the combined effect of preexisting bone disease and immunosuppressive therapy.
Bilo, H J; Schaap, G H; Blaak, E; Gans, R O; Oe, P L; Donker, A J
In 6 volunteers with normal renal function, we investigated the effects of various kinds of protein (soy, lactoprotein and beef) and various amounts of an intravenously administered amino acid solution on glomerular filtration (GFR) and effective renal plasma flow (ERPF). As for the protein-induced changes in renal function, rises in GFR and ERPF were lowest with soy protein, and highest with beef (baseline GFR, 110 +/- 5; soy, 122 +/- 5; beef, 131 +/- 5 ml/min/1.73 m2; mean +/- SEM). High doses of intravenous amino acids induced a rise in GFR comparable to that after beef (132 +/- 5 ml/min/1.73 m2). In a combined test a liquid mixed meal together with intravenously administered amino acids induced a comparable increase of the GFR (baseline 114 +/- 5 versus 129 +/- 5 ml/min/1.73 m2). When investigating 9 patients with chronic renal insufficiency after 4 weeks of low protein intake (LP) and after 4 weeks of high protein intake (HP), GFR and ERPF rose significantly under baseline conditions (GFR-LP41 +/- 9 versus GFR-HP 45 +/- 9 ml/min/1.73 m2, p less than 0.02; ERPF-LP 169 +/- 39 versus ERPF-HP 180 +/- 40 ml/min/1.73 m2, p less than 0.02; paired Wilcoxon). At the end of both dietary periods a comparable rise in renal function could be induced through acute stimulation (GFR-LP 20 +/- 5, GFR-HP 16 +/- 4; ERPF-LP 23 +/- 7, ERPF-HP 22 +/- 3%).(ABSTRACT TRUNCATED AT 250 WORDS)
Ma, Yilong; Tang, Chengke; Moeller, James R; Eidelberg, David
Normalization of regional measurements by the global mean is commonly employed to minimize inter-subject variability in functional imaging studies. This practice is based on the assumption that global values do not substantially differ between patient and control groups. In this issue of NeuroImage, Borghammer and colleagues challenge the validity of this assumption. They focus on Parkinson's disease (PD) and use computer simulations to show that lower global values can produce spurious increases in subcortical brain regions. The authors speculate that the increased signal observed in these areas in PD is artefactual and unrelated to localized changes in brain function. In this commentary, we summarize what is currently known of the relationship between regional and global metabolic activity in PD and experimental parkinsonism. We found that early stage PD patients exhibit global values that are virtually identical to those of age-matched healthy subjects. SPM analysis revealed increased normalized metabolic activity in a discrete set of biologically relevant subcortical brain regions. Because of their higher variability, the corresponding absolute regional measures did not differ across the two groups. Longitudinal imaging studies in this population showed that the subcortical elevations in normalized metabolism appeared earlier and progressed faster than did focal cortical or global metabolic reductions. The observed increases in subcortical activity, but not the global changes, correlated with independent clinical measures of disease progression. Multivariate analysis with SSM/PCA further confirmed that the abnormal spatial covariance structure of early PD is dominated by these subcortical increases as opposed to network-related reductions in cortical metabolic activity or global changes. Thus, increased subcortical activity in PD cannot be regarded as a simple artefact of global normalization. Moreover, stability of the normalized measurements, particularly at
Ko, Ji Hyun; Antonelli, Francesca; Monchi, Oury; Ray, Nicola; Rusjan, Pablo; Houle, Sylvain; Lang, Anthony E; Christopher, Leigh; Strafella, Antonio P
The main pattern of cognitive impairments seen in early to moderate stages of Parkinson's disease (PD) includes deficits of executive functions. These nonmotor complications have a significant impact on the quality of life and day-to-day activities of PD patients and are not effectively managed by current therapies, a problem which is almost certainly due to the fact that the disease extends beyond the nigrostriatal system. To investigate the role of extrastriatal dopamine in executive function in PD, PD patients and a control group were studied with positron-emission-tomography using a high-affinity dopamine D2/D3 receptor tracer, [(11) C]FLB-457. All participants were scanned twice while performing an executive task and a control task. Patients were off medication for at least 12 h. The imaging analysis revealed that parkinsonian patients had lower [(11) C]FLB-457 binding than control group independently of task conditions across different brain regions. Cognitive assessment measures were positively correlated with [(11) C]FLB-457 binding in the bilateral dorsolateral prefrontal cortex and anterior cingulate cortex only in control group, but not in PD patients. Within the control group, during the executive task (as compared to control task), there was evidence of reduced [(11) C]FLB-457 binding (indicative of increased dopamine release) in the right orbitofrontal cortex. In contrast, PD patients did not show any reduction in binding during the executive task (as compared with control task). These findings suggest that PD patients present significant abnormalities in extrastriatal dopamine associated with executive processing. These observations provide important insights on the pathophysiology of cognitive dysfunction in PD.
Girometti, Rossano; Stocca, Tiziano; Serena, Elena; Granata, Antonio; Bertolotto, Michele
AIM To investigate the role of contrast enhanced ultrasound (CEUS) in evaluating patients with renal function impairment (RFI) showing: (1) acute renal failure (ARF) of suspicious vascular origin; or (2) suspicious renal lesions. METHODS We retrospectively evaluated patients addressed to CEUS over an eight years period to rule-out vascular causes of ARF (first group of 50 subjects) or assess previously found suspicious renal lesions (second group of 41 subjects with acute or chronic RFI). After preliminary grey-scale and color Doppler investigation, each kidney was investigated individually with CEUS, using 1.2-2.4 mL of a sulfur hexafluoride-filled microbubble contrast agent. Image analysis was performed in consensus by two readers who reviewed digital clips of CEUS. We calculated the detection rate of vascular abnormalities in the first group and performed descriptive statistics of imaging findings for the second group. RESULTS In the first group, CEUS detected renal infarction or cortical ischemia in 18/50 patients (36%; 95%CI: 23.3-50.9) and 1/50 patients (2%; 95%CI: 0.1-12), respectively. The detection rate of infarction was significantly higher (P = 0.0002; McNemar test) compared to color Doppler ultrasonography (10%). No vascular causes of ARF were identified in the remaining 31/50 patients (62%). In the second group, CEUS detected 41 lesions on 39 patients, allowing differentiation between solid lesions (21/41; 51.2%) vs complex cysts (20/41; 48.8%), and properly addressing 15/39 patients to intervention when feasible based on clinical conditions (surgery and cryoablation in 13 and 2 cases, respectively). Cysts were categorized Bosniak II, IIF, III and IV in 8, 5, 4 and 3 cases, respectively. In the remaining two patients, CEUS found 1 pseudolesion and 1 subcapsular hematoma. CONCLUSION CEUS showed high detection rate of renal perfusion abnormalities in patients with ARF, influencing the management of patients with acute or chronic RFI and renal masses
van Welsem, M E; Lobatto, S
The case of a 41-year-old patient with end-stage renal failure and diabetes mellitus Type 1 who was being prepared for renal replacement therapy is described. After severe hypothyroidism was diagnosed, thyroid hormone substitution therapy was started. Subsequently, a substantial decline in serum creatinine was observed. Creatinine clearance rose from 19 to 40 ml/min and renal replacement therapy was no longer imminent. Several studies have described the pathophysiology of diminished renal function in hypothyroidism. Few studies or case reports have shown amelioration of end-stage renal failure as seen in our patient. The etiology is presumed to be multifactorial, in which hemodynamic effects and a direct effect of thyroid hormone on the kidney play an important role. Diagnosing signs of hypothyroidism and therapy with thyroid hormone in progressive renal failure could be very important in delaying the need for renal replacement therapy.
Lau, Yee Cheng; Xiong, Qinmei; Blann, Andrew D; Lip, Gregory Y H
Atrial fibrillation (AF) and chronic kidney disease are closely related, and any associated risk of stroke and thromboembolism due to AF is increased by concurrent renal dysfunction. The mechanism(s) for this include abnormalities in platelets and endothelial cells. We hypothesized relationships between levels of circulating platelet microparticles (PMPs, defined by CD42b), soluble P selectin (both reflecting platelet activation), soluble E-selectin (reflecting endothelial activation) and endothelial/platelet microparticles (EPMPs, defined by CD31) with progressive renal dysfunction. Blood samples were obtained from 160 anticoagulated AF patients. Microparticles were measured by flow cytometry, soluble E and P selectin levels by ELISA. Renal function was determined by estimated glomerular filtration rate (eGFR). EPMP levels demonstrated a linear increased trend across quartiles of eGFR (p = 0.034) and CKD stage (p < 0.001), and correlated with eGFR and serum creatinine (p < 0.01). PMPs, P-selectin and E-selectin levels were not significantly different across groupings of renal dysfunction, and no significant correlations with eGFR were evident (p = 0.186, p = 0.561, p = 0.746 respectively). Stepwise multivariable regression analysis demonstrated that worsening renal function was an independent predictor of EPMP levels (p < 0.001). In well-anticoagulated AF patients, there is potential relationship between endothelial function (as judged by elevated EPMP levels, with no change in PMPs) and renal function. Other markers of prothombotic state or cellular activation (PMP, P-selectin and E-selectin levels) were not significantly different across the various degree of renal dysfunction. Renal function must be addressed when measuring EPMP levels.
Udani, Suneel M; Koyner, Jay L
Summary Heart-kidney interactions have been increasingly recognized by clinicians and researchers involved in the study and treatment of heart failure and kidney disease. A classification system has been developed to categorize the different manifestations of cardiac and renal dysfunction. Recent work has highlighted the significant negative prognostic effect of worsening renal function on outcomes for individuals with heart failure. The etiology of the concomitant cardiac and renal dysfunction remains unclear; however, increasing evidence supports alternatives to the established theory of underfilling, including effects of venous congestion and changes in intra-abdominal pressure. Conventional therapy focuses on blockade of the renin-angiotensin-aldosterone system with expanding use of direct renin and aldosterone antagonists. Novel therapeutic interventions using extracorporeal therapy and antagonists of the adenosine pathway show promise and require further investigation. PMID:20621250
Löffler, Adrián Ignacio; Cappola, Thomas P; Fang, James; Hetzel, Scott J; Kadlec, Andrew; Astor, Brad; Sweitzer, Nancy K
Renal dysfunction (RD) is associated with increased mortality in heart failure (HF). The aim of this study was to identify whether worsened or improved renal function during mid-term follow-up is associated with worsened outcomes in patients with chronic HF. A total of 892 participants from a multicenter cohort study of chronic HF were followed over 3.1 ± 1.9 years of enrollment. Worsened and improved renal functions were tested with multivariate models as independent predictors of HF hospitalization and mortality. Although 12% of subjects experienced a ≥25% decrease in estimated glomerular filtration rate (eGFR), 17% experienced a ≥25% increase in eGFR, and there was stability of kidney function observed in the cohort as a whole. The quartile with the worst RD at any point in time had increased risk of HF hospitalization and mortality. Worsened eGFR was associated with HF outcomes in the unadjusted (hazard ratio = 1.71, 95% confidence interval 1.04 to 2.81, p = 0.035), but not the adjusted analysis. Improvement in eGFR was not associated with outcome (p = 0.453). In chronic HF, the severity of RD predicts risk of poor outcome better than changes in renal function during mid-term follow-up. This suggests that in patients with appropriately treated chronic HF, worsening renal function in itself does not yield useful prognostic information and may not reflect poor outcome.
Peerce, B E; Weaver, L; Clarke, R D
Hyperhosphatemia and secondary hyperparathyroidism are common and severe complications of chronic renal failure. Therapies to reduce serum phosphate have been shown to reduce serum parathyroid hormone (PTH) and slow the progression of renal failure. The effect of the inhibitor of intestinal phosphate absorption, 2'-phosphophloretin (2'-PP), on serum and urine chemistry, renal histology, and cardiac structure in the uremic rat model of renal failure, 5/6 nephrectomy (5/6 NX), was examined. The effect of 2'-PP on serum phosphate, serum PTH, serum total Ca(2+), and ionized Ca(2+), Ca(2+) x P(i) product, urine protein, urine osmolality, and creatinine clearance in 5/6 NX rats was examined. Uremic rats in chronic renal failure were gavaged daily with 25 microM 2'-PP. Over the course of a 5-wk experiment, serum chemistry in untreated uremic rats, 2'-PP-treated uremic rats, and age-matched control rats with normal renal function was determined twice a week. Urine creatinine, urine osmolality, urine phosphate, and urine protein were determined once a week from 24-h collections. 2'-PP reduced serum phosphate 40 +/- 3% compared with a 17% increase in untreated uremic control rats. 2'-PP did not alter total serum Ca(2+). During 5-wk experiments, serum PTH increased 65 +/- 25% in untreated uremic rats and decreased 70 +/- 7% in uremic rats treated with 25 microM 2'-PP. Creatinine clearance decreased 20% in untreated uremic rats compared with a 100% increase in 2'-PP-treated uremic rats. Urine protein decreased and urine osmolality increased in uremic rats treated with 2'-PP. The mechanism of the effect of 2'-PP on serum phosphate was inhibition of intestinal phosphate absorption. 2-PP inhibited intestinal phosphate absorption 50% without altering dietary protein absorption or intestinal Ca(2+) absorption. Over the course of the 5-wk treatment with 2'-PP, uremic animals treated with 2'-PP had a 2-4% weight gain/wk, similar to the weight gain seen in age-matched control rats
Durand, Emmanuel; Chaumet-Riffaud, Philippe; Grenier, Nicolas
The objective of this work is to compare the characteristics of various techniques for functional renal imaging, with a focus on nuclear medicine and magnetic resonance imaging. Even with low spatial resolution and rather poor signal-to-noise ratio, classical nuclear medicine has the advantage of linearity and good sensitivity. It remains the gold standard technique for renal relative functional assessment. Technetium-99m ((99m)Tc)-labeled diethylenetriamine penta-acetate remains the reference glomerular tracer. Tubular tracers have been improved: (123)I- or (131)I-hippuran, (99m)Tc-MAG3 and, recently, (99m)Tc-nitrilotriacetic acid. However, advancement in molecular imaging has not produced a groundbreaking tracer. Renal magnetic resonance imaging with classical gadolinated tracers probably has potential in this domain but has a lack of linearity and, therefore, its value still needs evaluation. Moreover, the advent of nephrogenic systemic fibrosis has delayed its expansion. Other developments, such as diffusion or blood oxygen level-dependent imaging, may have a role in the future. The other modalities have a limited role in clinical practice for functional renal imaging.
Shet, Arun S; Hoffmann, Thomas J; Jirouskova, Marketa; Janczak, Christin A; Stevens, Jacqueline R M; Adamson, Adewole; Mohandas, Narla; Manci, Elizabeth A; Cynober, Therese; Coller, Barry S
Berkeley sickle cell mice are used as animal models of human sickle cell disease but there are no reports of platelet studies in this model. Since humans with sickle cell disease have platelet abnormalities, we studied platelet morphology and function in Berkeley mice (SS). We observed elevated mean platelet forward angle light scatter (FSC) values (an indirect measure of platelet volume) in SS compared to wild type (WT) (37+/-3.2 vs. 27+/-1.4, mean+/-SD; p<0.001), in association with moderate thrombocytopenia (505+/-49 x 10(3)/microl vs. 1151+/-162 x 10(3)/microl; p<0.001). Despite having marked splenomegaly, SS mice had elevated levels of Howell-Jolly bodies and "pocked" erythrocytes (p<0.001 for both) suggesting splenic dysfunction. SS mice also had elevated numbers of thiazole orange positive platelets (5+/-1% vs. 1+/-1%; p<0.001), normal to low plasma thrombopoietin levels, normal plasma glycocalicin levels, normal levels of platelet recovery, and near normal platelet life spans. Platelets from SS mice bound more fibrinogen and antibody to P-selectin following activation with a threshold concentration of a protease activated receptor (PAR)-4 peptide compared to WT mice. Enlarged platelets are associated with a predisposition to arterial thrombosis in humans and some humans with SCD have been reported to have large platelets. Thus, additional studies are needed to assess whether large platelets contribute either to pulmonary hypertension or the large vessel arterial occlusion that produces stroke in some children with sickle cell disease.
Tanriover, Bekir; Fernandez, Sonalis; Campenot, Eric S.; Newhouse, Jeffrey H.; Oyfe, Irina; Mohan, Prince; Sandikci, Burhaneddin; Radhakrishnan, Jai; Wexler, Jennifer J.; Carroll, Maureen A.; Sharif, Sairah; Cohen, David J.; Ratner, Lloyd E.; Hardy, Mark A.
Background Relationship between live donor renal anatomic asymmetry and post-transplant recipient function has not been studied extensively. Methods We analyzed 96 live-kidney donors, who had anatomical asymmetry (>10% renal length and/or volume difference calculated from CT angiograms) and their matching recipients. Split function differences (SFD) were quantified with 99mTc-DMSA renography. Implantation biopsies at time-zero were semi-quantitatively scored. A comprehensive model utilizing donor renal volume adjusted to recipient weight (Vol/Wgt), SFD, and biopsy score was used to predict recipient estimated glomerular filtration rate (eGFR) at one-year. Primary analysis consisted of a logistic regression model of outcome (odds of developing eGFR>60ml/min/1.73 m2 at one-year), a linear regression model of outcome (predicting recipient eGFR at one-year, using the CKD-EPI formula), and a Monte Carlo simulation based on the linear regression model (N=10,000 iterations). Results In the study cohort, the mean Vol/Wgt and eGFR at one-year were 2.04 ml/kg and 60.4 ml/min/1.73m2, respectively. Volume and split ratios between two donor kidneys were strongly correlated (r=0.79, p-value<0.001). The biopsy scores among SFD categories (<5%, 5–10%, >10%) were not different (p=0.190). On multivariate models, only Vol/Wgt was significantly associated with higher odds of having eGFR>60ml/min/1.73 m2 (OR=8.94, 95% CI 2.47–32.25, p=0.001) and had a strong discriminatory power in predicting the risk of eGFR<60ml/min/1.73m2 at one-year (ROC curve=0.78, 95% CI 0.68–0.89). Conclusion In the presence of donor renal anatomic asymmetry, Vol/Wgt appears to be a major determinant of recipient renal function at one-year post-transplantation. Renography can be replaced with CT volume calculation in estimating split renal function. PMID:25719258
Merla, Ramanna; Martinez, Juan D; Martinez, Milagros A; Khalife, Wissam; Bionat, Susan; Bionat, Joanne; Barbagelata, Alejandro
The extent to which hypothyroidism affects renal function in patients with heart failure remains incompletely explored, despite the known adverse prognostic implications of renal dysfunction in these patients.In a pilot retrospective study, we evaluated 75 patients (age, >or=18 yr) with left ventricular ejection fractions <0.40. Forty-five patients had normal thyroid function (thyroid-stimulating hormone [TSH], 0.35-5.5 micro IU/mL) and 30 had hypothyroidism. The group with hypothyroidism was subdivided into 17 patients who had controlled hypothyroidism (TSH, 0.35-5.5 micro IU/mL) and 13 who had uncontrolled hypothyroidism (TSH, >5.5 micro IU/mL). Renal function, measured in terms of glomerular filtration rate, was analyzed once in each patient, and the populations were statistically compared, with P <0.05 conferring statistical significance.Baseline characteristics in all groups were similar. Mean glomerular filtration rate was better in patients with normal thyroid function than those with hypothyroidism (75.45 +/- 31.48 vs 63.95 +/- 21.43 mL/min/1.73 m2; P=0.032). There was no significant difference between patients with controlled hypothyroidism (66.89 +/- 24.18 mL/min/1.73 m2) and those with normal thyroid function (P=0.131). In patients with uncontrolled hypothyroidism, mean glomerular filtration rate (60.2 +/- 17.4 mL/min/1.73 m2) was significantly worse than in patients with normal thyroid function (P=0.015).We found that heart-failure patients with insufficiently treated hypothyroidism have worse renal function than do patients whose thyroid function is normal or whose hypothyroidism is effectively treated. Larger studies will be needed in order to evaluate this conclusion further. We recommend that hypothyroidism in heart-failure patients be strictly controlled, lest it affect prognosis adversely.
Choi, H.; Kirchner, P.T.
To assess the frequency and magnitude of errors caused by asymmetries in renal depth, when estimates of differential function are based only posterior projections (as in DTPA studies). The authors compared ratios of right-to-left (R/L) DMSA localization derived from posterior camera images with R/L ratios based on geometric mean of posterior and anterior counts of each kidney. The factor (X) required to convert the ratio of R/L posterior counts to the more accurate R/L geometric counts (Rp/Lp.X = Rg/Lg) was determined in 55 randomly selected patients referred for DMSA studies. Frequency distributions for X and l/X reveal that the use of posterior counts alone is likely to produce differential flow/function estimates with errors greater than 30% in 5% of patients, greater than 20% in 16 of patients. Lack of depth correction also widens the normal range derived from normal controls, thus reducing sensitivity and specificity of quantitative renal studies by two different mechanisms. The authors recommend routine application of depth correction by conjugate counting or ultrasound techniques for all quantitations of renal function.
Levine, Matthew H; Wang, Zhonglin; Xiao, Haiyan; Jiao, Jing; Wang, Liqing; Bhatti, Tricia R; Hancock, Wayne W; Beier, Ulf H
Current immunosuppressive medications used after transplantation have significant toxicities. Foxp3(+) T-regulatory cells can prevent allograft rejection without compromising protective host immunity. Interestingly, inhibiting the class III histone/protein deacetylase Sirtuin-1 can augment Foxp3(+) T-regulatory suppressive function through increasing Foxp3 acetylation. Here we determined whether Sirtuin-1 targeting can stabilize biological allograft function. BALB/c kidney allografts were transplanted into C57BL/6 recipients with a CD4-conditional deletion of Sirtuin-1 (Sirt1(fl/fl)CD4(cre)) or mice treated with a Sirtuin-1-specific inhibitor (EX-527), and the native kidneys removed. Blood chemistries and hematocrit were followed weekly. Sirt1(fl/fl)CD4(cre) recipients showed markedly longer survival and improved kidney function. Sirt1(fl/fl)CD4(cre) recipients exhibited donor-specific tolerance, accepted BALB/c, but rejected third-party C3H cardiac allografts. C57BL/6 recipients of BALB/c renal allografts that were treated with EX-527 showed improved survival and renal function at 1, but not 10 mg/kg/day. Pharmacologic inhibition of Sirtuin-1 also improved renal allograft survival and function with dosing effects having relevance to outcome. Thus, inhibiting Sirtuin-1 can be a useful asset in controlling T-cell-mediated rejection. However, effects on non-T cells that could adversely affect allograft survival and function merit consideration.
Kaude, J.V.; Williams, C.M.; Millner, M.R.; Scott, K.N.; Finlayson, B.
The acute effects of extracorporeal shock-wave lithotripsy (ESWL) on morphology and function of the kidney were evaluated by excretory urography, quantitative radionuclide renography (QRR), and magnetic resonance imaging (MRI) in 33 consecutive patients. Excretory urograms demonstrated an enlarged kidney in seven (18%) of 41 treatments and partial or complete obstruction of the ureter by stone fragments after 15 (37%) of 41 treatments. Total effective renal plasma flow (ERPF) was not changed after ESWL, but the percentage ERPF of the treated kidney was decreased by more than 5% in 10 (30%) of 33 cases. QRR images showed partial parenchymal obstruction in 10 (25%) of 41 teated kidneys and total parenchymal obstruction in 9 (22%). MRI disclosed one or more abnormalities in 24 (63%) of 38 treated kidneys. Treated kidneys were normal by all three imaging methods in 26% and abnormal by one or more tests in 74% of cases. The morphologic and functional changes are attributed to renal contusion resulting in edema and extravasation of urine and blood into the interstitial, subcapsular, and perirenal spaces.
Tucker, Bryan J.
This project was to examine the alterations in renal functions during skeletal muscle disuse in simulated microgravity. Although this area could cover a wide range of investigative efforts, the limited funding resulted in the selection of two projects. These projects would result in data contributing to an area of research deemed high priority by NASA and would address issues of the alterations in renal response to vasoactive stimuli during conditions of skeletal muscle disuse as well as investigate the contribution of skeletal muscle disuse, conditions normally found in long term human exposure to microgravity, to the balance of fluid and macromolecules within the vasculature versus the interstitium. These two projects selected are as follows: investigate the role of angiotensin 2 on renal function during periods of simulated microgravity and skeletal muscle disuse to determine if the renal response is altered to changes in circulating concentrations of angiotensin 2 compared to appropriate controls; and determine if the shift of fluid balance from vasculature to the interstitium, the two components of extracellular fluid volume, that occur during prolonged exposure to microgravity and skeletal muscle disuse is a result, in part, to alterations in the fluid and macromolecular balance in the peripheral capillary beds, of which the skeletal muscle contains the majority of recruitment capillaries. A recruitment capillary bed would be most sensitive to alterations in Starling forces and fluid and macromolecular permeability.
Belis, J A; Belis, T E; Lai, J C; Goodwin, C A; Gabriele, O F
Differential radionuclide renal scans can be useful in the management of patients with chronic partial obstruction of 1 kidney. The 99mtechnetium diethylenetriaminepentaacetic acid perfusion scan can be used to assess glomerular blood flow. The 131iodine orthoiodohippurate renal scan provides qualitative functional information from scintigrams and quantitative evaluation of effective renal plasma flow to each kidney, as well as a total excretory index. Sequential 99mtechnetium diethylenetriaminepentaacetic acid and 131iodine orthoiodohippurate renal scans were used to assess individual renal function before and after surgical correction of unilateral chronic renal obstruction in 31 patients. The preservation of cortical perfusion on 99mtechnetium diethylenetriaminepentaacetic acid scans indicated that potential existed for partial recovery of renal function. Effective renal plasma flow and excretory index determined in conjunction with the 131iodine orthoiodohippurate scans provided a quantitative assessment of preoperative renal function, an evaluation of the effect of surgery and a sensitive method for long-term evaluation of differential renal function. Correction of ureteropelvic junction obstruction usually resulted in improvement in unilateral renal function. Neither nephrolithotomy nor extended pyelolithotomy diminished renal function in the kidney subjected to an operation and often improved it. Patients with long-standing distal ureteral obstruction had the least improvement in renal function postoperatively.
Belis, J.A.; Belis, T.E.; Lai, J.C.; Goodwin, C.A.; Gabriele, O.F.
Differential radionuclide renal scans can be useful in the management of patients with chronic partial obstruction of 1 kidney. The /sup 99m/Tc diethylenetriaminepentaacetic acid perfusion scan can be used to assess glomerular blood flow. The /sup 131/I orthoiodohippurate renal scan provides qualitative functional information from scintigrams and quantitative evaluation of effective renal plasma flow to each kidney, as well as a total excretory index. Sequential /sup 99m/Tc diethylenetriaminepentaacetic acid and /sup 131/I orthoiodohippurate renal scans were used to assess individual renal function before and after surgical correction of unilateral chronic renal obstruction in 31 patients. The preservation of cortical perfusion on /supb 99m/Tc diethylenetriaminepentaacetic acid scans indicated that potential existed for partial recovery of renal function. Effective renal plasma flow and excretory index determined in conjunction with the /sup 131/I orthoiodohippurate scans provided a quantitative assessment of preoperative renal function, an evaluation of the effect of surgery and a sensitive method for long-term evaluation of differential renal function. Correction of ureteropelvic junction obstruction usually resulted in improvement in unilateral renal function. Neither nephrolithotomy nor extended pyelolithotomy diminished renal function in the kidney subjected to an operation and often improved it. Patients with long-standing distal ureteral obstruction had the least improvement in renal function postoperatively.
Fernandes, Paula Frassinetti Castelo Branco Camurça; Siqueira, Reed André; Girão, Evelyne Santana; Siqueira, Rainne André; Mota, Márcia Uchoa; Marques, Leyla Castelo Branco Fernandes; Andrade, Silvana Cristina Albuquerque; Barroso, Wilson Mendes; Silva, Sônia Leite; Rodrigues dos Santos, Bruno Gomes; de Oliveira, Claúdia Maria Costa
AIM To present clinical characteristics from renal transplant recipients with dengue fever and its impact on graft function. METHODS We retrospectively evaluated 11 renal transplant recipients (RTR) with dengue infection confirmed by laboratory test, between January 2007 and July 2012, transplanted in the Renal Transplant Center of Walter Cantídio University Hospital from Federal University of Ceará. RESULTS Positive dengue serology (IgM) was found in all patients. The mean time between transplant and dengue infection was 43 mo. Fever was presented in all patients. Nine patients presented with classical dengue and two (18%) with dengue hemorrhagic fever. All cases had satisfactory evolution with complete recovery of the symptoms. The time for symptom resolution varied from 2 to 20 d, with an average of 9 d. An increase of creatinine after the infection was observed in three (27.2%) patients with no clinically impact on the kidney graft function. CONCLUSION RTR with dengue infection seems to have a clinical presentation and evolution similar to those seen in the general population, with no long-term damage to patient and to the graft. PMID:28280696
Halgin, Richard P.
Describes three main types of therapeutic problems which college instructors of abnormal psychology courses may encounter with their students. Students may seek the instructor's assistance in helping a relative or acquaintance or for self-help. Often a student may not seek help but may display pathological behavior. (AM)
Maurer, Lukas; Schwarz, Franziska; Fischer-Rosinsky, Antje; Schlueter, Nina; Brachs, Sebastian; Möhlig, Matthias; Pfeiffer, Andreas; Mai, Knut; Bobbert, Thomas
Objective Betatrophin has been identified as a marker linking liver with beta cell function and lipid metabolism in murine models. Until now, the regulation of circulating betatrophin in humans is not entirely clear. We here analyzed the relation of betatrophin levels to phenotypes of the metabolic syndrome and speculated that renal function might influence circulating betatrophin levels and explain age-dependent changes of betatrophin. Subjects We analyzed blood samples from 535 individuals participating in the Metabolic Syndrome Berlin Potsdam study. Results In a crude analysis we found a positive correlation between betatrophin levels and HbA1c (r = 0.24; p < 0.001), fasting glucose (r = 0.20; p < 0.001) and triglycerides (r = 0.12; p = 0.007). Furthermore betatrophin was positively correlated with age (r = 0.47; p <0.001), systolic blood pressure (r = 0.17; p < 0.001), intima media thickness (r = 0.26; p < 0.001) and negatively correlated with CKD-EPI eGFR (r = -0.33; p < 0.001) as an estimate of renal function. Notably, eGFR remained highly associated with betatrophin after adjustment for age, waist circumference, gender, HbA1c and lipid parameters in a multivariate linear regression model (β = -0.197, p< 0.001). Conclusions Our data suggest that circulating levels of betatrophin depend on age, gender, waist circumference, total/HDL cholesterol ratio and renal function. Especially the association to eGFR highlights the importance for future studies to address renal function as possible influence on betatrophin regulation and consider eGFR as potential confounder when analyzing the role of betatrophin in humans. PMID:28257453
Kataria, Anglina; Trasande, Leonardo; Trachtman, Howard
The global incidence of chronic kidney disease (CKD) is increasing among individuals of all ages. Despite advances in proteomics, genomics and metabolomics, there remains a lack of safe and effective drugs to reverse or stabilize renal function in patients with glomerular or tubulointerstitial causes of CKD. Consequently, modifiable risk factors that are associated with a progressive decline in kidney function need to be identified. Numerous reports have documented the adverse effects that occur in response to graded exposure to a wide range of environmental chemicals. This Review summarizes the effects of such chemicals on four aspects of cardiorenal function: albuminuria, glomerular filtration rate, blood pressure and serum uric acid concentration. We focus on compounds that individuals are likely to be exposed to as a consequence of normal consumer activities or medical treatment, namely phthalates, bisphenol A, polyfluorinated alkyl acids, dioxins and furans, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. Environmental exposure to these chemicals during everyday life could have adverse consequences on renal function and might contribute to progressive cumulative renal injury over a lifetime. Regulatory efforts should be made to limit individual exposure to environmental chemicals in an attempt to reduce the incidence of cardiorenal disease.
Kataria, Anglina; Trasande, Leonardo; Trachtman, Howard
The global incidence of chronic kidney disease (CKD) is increasing among individuals of all ages. Despite advances in proteomics, genomics and metabolomics, there remains a lack of safe and effective drugs to reverse or stabilize renal function in patients with glomerular or tubulointerstitial causes of CKD. Consequently, modifiable risk factors that are associated with a progressive decline in kidney function need to be identified. Numerous reports have documented the adverse effects that occur in response to graded exposure to a wide range of environmental chemicals. This Review summarizes the effects of such chemicals on four aspects of cardiorenal function: albuminuria, glomerular filtration rate, blood pressure and serum uric acid concentration. We focus on compounds that individuals are likely to be exposed to as a consequence of normal consumer activities or medical treatment, namely phthalates, bisphenol A, polyfluorinated alkyl acids, dioxins and furans, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. Environmental exposure to these chemicals during everyday life could have adverse consequences on renal function and might contribute to progressive cumulative renal injury over a lifetime. Regulatory efforts should be made to limit individual exposure to environmental chemicals in an attempt to reduce the incidence of cardiorenal disease. PMID:26100504
Ragan, Harvey A.; Weller, Richard E.
Designed to aid the laboratory animal veterinarian, researcher, or toxicologist in the proper evaluation of organ function, this updated and revised edition provides the only comprehensive reference of the clinical chemistry of laboratory animals. With contributions from recognized experts in the field, new chapters are included that focus on the pig and the ferret, while many chapters have been rewritten. Expanded coverage was given to urine chemistry, hormones, including melatonin, and the control mechanisms of analytes. Reference values are given in both conventional and S.I. units.
Halberg, Kenneth A.; Terhzaz, Selim; Cabrero, Pablo; Davies, Shireen A.; Dow, Julian A. T.
Knowledge on neuropeptide receptor systems is integral to understanding animal physiology. Yet, obtaining general insight into neuropeptide signalling in a clade as biodiverse as the insects is problematic. Here we apply fluorescent analogues of three key insect neuropeptides to map renal tissue architecture across systematically chosen representatives of the major insect Orders, to provide an unprecedented overview of insect renal function and control. In endopterygote insects, such as Drosophila, two distinct transporting cell types receive separate neuropeptide signals, whereas in the ancestral exopterygotes, a single, general cell type mediates all signals. Intriguingly, the largest insect Order Coleoptera (beetles) has evolved a unique approach, in which only a small fraction of cells are targets for neuropeptide action. In addition to demonstrating a universal utility of this technology, our results reveal not only a generality of signalling by the evolutionarily ancient neuropeptide families but also a clear functional separation of the types of cells that mediate the signal. PMID:25896425
Halberg, Kenneth A; Terhzaz, Selim; Cabrero, Pablo; Davies, Shireen A; Dow, Julian A T
Knowledge on neuropeptide receptor systems is integral to understanding animal physiology. Yet, obtaining general insight into neuropeptide signalling in a clade as biodiverse as the insects is problematic. Here we apply fluorescent analogues of three key insect neuropeptides to map renal tissue architecture across systematically chosen representatives of the major insect Orders, to provide an unprecedented overview of insect renal function and control. In endopterygote insects, such as Drosophila, two distinct transporting cell types receive separate neuropeptide signals, whereas in the ancestral exopterygotes, a single, general cell type mediates all signals. Intriguingly, the largest insect Order Coleoptera (beetles) has evolved a unique approach, in which only a small fraction of cells are targets for neuropeptide action. In addition to demonstrating a universal utility of this technology, our results reveal not only a generality of signalling by the evolutionarily ancient neuropeptide families but also a clear functional separation of the types of cells that mediate the signal.
de Goeij, Moniek C M; Halbesma, Nynke; Dekker, Friedo W; Wijsman, Carolien A; van Heemst, Diana; Maier, Andrea B; Mooijaart, Simon P; Slagboom, P Eline; Westendorp, Rudi G J; de Craen, Anton J M
Studying renal function in subjects with a familial propensity for longevity may provide insight in (un)known mechanisms that determine the age-related decline in renal function of normal subjects. In the Leiden Longevity Study, middle-aged offspring of non-agenarian siblings and their partners as environmentally matched controls were included. Information was collected on lifestyle, medical history, medication use, and a non-fasting blood sample was drawn. Renal function (estimated glomerular filtration rate, eGFR) was assessed with the Chronic Kidney Disease epidemiology collaboration (CKD-EPI) formula. Linear mixed models were used to account for familial dependencies within the offspring and all analyses were stratified by sex. eGFR was similar between female offspring and female controls (0.44ml/min/1.73m(2) (SE 0.72) difference, p=0.54, age-adjusted). Male offspring had a higher eGFR compared to male controls (1.78ml/min/1.73m(2) (SE 0.78) difference, p=0.022, age-adjusted), and further adjustments for various characteristics did not materially change this difference. Among men with a history of hypertension, or myocardial infarction and/or stroke, offspring had a higher eGFR compared to controls (4.74ml/min/1.73m(2) (SE 1.53) difference, p=0.002, age-adjusted, and 6.21ml/min/1.73m(2) (SE 2.85) difference, p=0.033, age-adjusted, respectively). Middle-aged men, but not women, with a propensity for longevity have better renal function compared to environmentally matched controls, especially among those with a history of cardiovascular disease.
Schmieder, Roland E; Mitrovic, Veselin; Hengstenberg, Christian
Renal dysfunction is a frequent finding in patients with acute heart failure (AHF) and an important prognostic factor for adverse outcomes. Worsening of renal function occurs in 30-50% of patients hospitalised for AHF, and is associated with increased mortality, prolonged hospital stay and increased risk of readmission. Likely mechanisms involved in the decrease in renal function include impaired haemodynamics and activation of neurohormonal factors, such as the renin-angiotensin-aldosterone system, the sympathetic nervous system and the arginine-vasopressin system. Additionally, many drugs currently used to treat AHF have a detrimental effect on renal function. Therefore, pharmacotherapy for AHF should carefully take into account any potential complications related to renal function. Serelaxin, currently in clinical development for the treatment of AHF is a recombinant form of human relaxin-2, identical in structure to the naturally occurring human relaxin-2 peptide hormone that mediates cardiac and renal adaptations during pregnancy. Data from both pre-clinical and clinical studies indicate a potentially beneficial effect of serelaxin on kidney function. In this review, we discuss the mechanisms and impact of impairment of renal function in AHF, and the potential benefits of new therapies, such as serelaxin, in this context.
Wang, Jing; Kean, Laura; Yang, Jingli; Allan, Adrian K; Davies, Shireen A; Herzyk, Pawel; Dow, Julian AT
Background Comprehensive, tissue-specific, microarray analysis is a potent tool for the identification of tightly defined expression patterns that might be missed in whole-organism scans. We applied such an analysis to Drosophila melanogaster Malpighian (renal) tubule, a defined differentiated tissue. Results The transcriptome of the D. melanogaster Malpighian tubule is highly reproducible and significantly different from that obtained from whole-organism arrays. More than 200 genes are more than 10-fold enriched and over 1,000 are significantly enriched. Of the top 200 genes, only 18 have previously been named, and only 45% have even estimates of function. In addition, 30 transcription factors, not previously implicated in tubule development, are shown to be enriched in adult tubule, and their expression patterns respect precisely the domains and cell types previously identified by enhancer trapping. Of Drosophila genes with close human disease homologs, 50 are enriched threefold or more, and eight enriched 10-fold or more, in tubule. Intriguingly, several of these diseases have human renal phenotypes, implying close conservation of renal function across 400 million years of divergent evolution. Conclusions From those genes that are identifiable, a radically new view of the function of the tubule, emphasizing solute transport rather than fluid secretion, can be obtained. The results illustrate the phenotype gap: historically, the effort expended on a model organism has tended to concentrate on a relatively small set of processes, rather than on the spread of genes in the genome. PMID:15345053
Madkour, H; Gadallah, M; Riveline, B; Plante, G E; Massry, S G
The long-term effects of indapamide or hydrochlorothiazide on blood presssure and renal function were examined in patents with impaired renal function and moderate hypertension. Both drugs controlled hypertension and blood pressure remained normal during the 2 years of the study. Despite this comparable control of hypertension, indapamide therapy was associated with a 28.5 +/- 4.4% increase in creatinine clearance, whereas treatment with hydrochlorothiazide was associated with a 17.4 +/- 3.0% decrease in creatinine clearance. The results of the study indicate that indapamide is superior to hydrochlorothiazide in the treatment of patients with impaired renal function and moderate hypertension.
Seyam, Raouf; Firdous, Sadia
We determined the cause of renal deterioration after augmentation cystoplasty (AC). Twenty-nine adult patients with refractory bladder dysfunction and who underwent ileocystoplasty from 2004 to 2015 were studied. Patients with a decline in glomerular filtration rate (GFR) after augmentation were reviewed. The primary outcome was to determine the factors that might lead to deterioration of estimated GFR. Median follow-up was 7.0 ± 2.6 years. Significant bladder capacity, end filling pressure, and bladder compliance were achieved from median 114 ± 53.6 to 342.1 ± 68.3 ml (p = .0001), 68.5 ± 19.9 to 28.2 ± 6.9 cm H2O (p = .0001), and 3.0 ± 2.1 to 12.8 ± 3.9 (p = .0001), respectively. Renal function remained stable and improved in 22 (76%) patients from median eGFR 135 ± 81.98 to 142.82 ± 94.4 ml/min/1.73 m2 (p = .160). Significant deterioration was found in 7 (24%) patients from median eGFR 68.25 ± 42 to 36.57 ± 35.33 (p = .001). The causes of renal deterioration were noncompliance to self-catheterization (2 patients), posterior urethral valve/dysplastic kidneys (2 patients), and reflux/infection (2 patients). On multivariate analysis, recurrent pyelonephritis (OR 3.87, p = 0.0155) and noncompliance (OR 30.78, p = 0.0156) were significant. We concluded that AC is not the cause of progression to end-stage renal disease in patients with renal insufficiency. PMID:28367330
... Patients With Impaired Renal Function--Study Design, Data Analysis, and Impact on Dosing and Labeling... ``Pharmacokinetics in Patients With Impaired Renal Function--Study Design, Data Analysis, and Impact on Dosing and... influence of renal impairment on the pharmacokinetics of an investigational drug. It...
Barter, S.J.; Cunningham, D.A.; Lavender, J.P.; Gibellino, F.; Connellan, S.J.; Pride, N.B.
The uniformity of regional ventilation during tidal breathing has been assessed using continuous inhalation of krypton-81m in 43 male, lifelong nonsmokers and 46 male, current cigarette smokers (mean daily consumption 24.1 cigarettes/day) between 44 and 61 yr of age and with mild or no respiratory symptoms. All subjects had normal chest radiographs. The results of the ventilation scans were compared with tests of overall lung function (spirometry, maximal expiratory flow-volume curves, and single-breath N2 test). Diffuse abnormalities of the ventilation scan were found in 19 (41%) of the 46 smokers but in none of the nonsmokers. Focal abnormalities were found in 7 smokers and 3 nonsmokers. Smokers showed the expected abnormalities in overall lung function (reduced FEV1 and VC, increased single-breath N2 slope, and closing volume), but in individual smokers there was only a weak relation between the severity of abnormality of overall lung function and an abnormal ventilation scan. Abnormal scans could be found when overall lung function was normal and were not invariably found when significant abnormalities in FEV1/VC or N2 slope were present. There was no relation between the presence of chronic expectoration and an abnormal scan. The prognostic significance of an abnormal ventilation scan in such smokers remains to be established.
Pun, E; Dowling, R J; Mitchell, P J
Renal artery stenosis can present uncommonly in the acute state as flash pulmonary oedema and hypertensive encephalopathy. We present three such cases in patients with a solitary functioning kidney, with successful management via renal artery angioplasty and stent insertion.
de Souza, Livia Victorino; Oliveira, Vanessa; Laurindo, Aline Oliveira; Huarachı, DelmaRegına Gomes; Nogueira, Paulo Cesar Koch; Feltran, Luciana de Santis; Medina-Pestana, José Osmar
Endocan is an important biomarker of inflammation and endothelial dysfunction that increases in association with several chronic diseases. Few published data have described the role of endocan in pediatric renal transplant (RT) patients. We evaluated the endocan concentrations in 62 children who underwent renal transplantation and assessed their relationships with the patients' blood pressure and loss of renal function. The endocan levels were significantly elevated in the pediatric RT patients who had hypertension and a loss of renal function. We determined positive correlations between the endocan concentrations and the hemodynamic variables (systolic blood pressure: r = 0.416; P = 0.001; pulse pressure: r = 0.412; P = 0.003). The endocan levels were inversely correlated with the estimated glomerular filtration rate (r = −0.388; P = 0.003). An endocan cutoff concentration of 7.0 ng/mL identified pediatric RT patients who had hypertension and a loss of renal function with 100% sensitivity and 75% specificity. In conclusion, the endocan concentrations were significantly elevated in pediatric RT patients who had both hypertension and a loss of renal function. The correlations between the endocan levels and the hemodynamic variables and the markers of renal function strengthen the hypothesis that it is an important marker of cardiorenal risk. PMID:28083150
Quinine is widely used for the common symptom of leg cramps. Quinine tablets require a prescription, but quinine and the product from which it is derived, cinchona, are also available without prescription. They are components of over-the-counter remedies for many common symptoms, of nutrition products, and of beverages such as tonic water and bitter lemon. Although quinine has been used for centuries, initially as an extract from the bark of the cinchona tree, allergic reactions to quinine can be severe and can affect multiple organs. These allergic reactions can cause thrombocytopenia, neutropenia, anemia, disseminated intravascular coagulation, acute renal failure, liver toxicity, and neurological abnormalities. Because quinine use is often intermittent, defining quinine as a cause of an acute disorder may be difficult. Moreover, since quinine use is often self-regulated, patients may not mention it in response to direct questions about medication use, adding to diagnostic difficulty. The diversity and severity of quinine-associated disorders and the difficulties of diagnosis are illustrated by the presentation of 4 case histories. Awareness of the variety of potential quinine-associated reactions is important for accurate diagnosis and critical for prevention of recurrent illness. PMID:16278718
Yap, Desmond Y. H.; Lai, Kar N.
Lupus nephritis (LN) is a common and severe organ manifestation of systemic lupus erythematosus (SLE), and is associated with significant patient morbidity and mortality. Autoantibodies and aberrations in lymphocyte subsets have putative roles in the pathogenesis of SLE and LN, and might reflect disease activity and are amenable to immunosuppressive treatments. Anti-DNA is one of the well-studied autoantibodies, which correlates with disease activity and has direct nephritogenic effects on resident renal cells and various glomerular components. Other important autoantibodies in the pathogenesis of LN include anti-C1q, anti-α-actinin and anti-nucleosome antibodies. Changes in naive and memory B cells and plasma cells have been observed in SLE and LN patients. These B cell subsets exert diverse effects during pathogenesis of LN such as production of autoantibodies, secretion of proinflammatory and anti-inflammatory cytokines and presentation of auto-antigens to effector cells. Aberration of T lymphocytes, especially the T-helper subsets, is also highly pertinent in the development of LN. In this context, important T helper subsets include Th1, Th2, Th9, Th17, TReg and follicular T-helper cells. The growing knowledge on these autoantibodies and lymphocyte subset abnormalities will enhance our understanding of SLE and LN, and hence help devise better strategies for disease monitoring and treatment. PMID:25860947
Hu, L-H; Zhang, L-J; Jin, Z-T; Yang, W; Zhang, L-N; Lu, C-Y
ABSTRACT This study aimed to investigate the effect of chronic kidney dysfunction (CKD) on the clinical characteristics of patients with acute coronary syndrome (ACS) and the degree of coronary arterial stenosis. The study enrolled 368 patients with ACS who underwent coronary angiography. Blood glucose, glycated haemoglobin (HbA1c), total cholesterol, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), uric acid (UA), and serum creatinine were examined randomly, and the severity of coronary artery lesions was assessed using the Gensini score. Patients were divided into three groups according to estimated glomerular filtration rate: normal renal function (n = 102), mild renal insufficiency (n = 198), and moderate to severe renal dysfunction (n = 68). The characteristics of patients with coronary artery lesions in the three groups were analysed. Of all patients, 27.7% had normal renal function. In the moderate to severe renal dysfunction group, the majority of patients were women whose average age was older. The ratio of patients with history of hypertension and diabetes mellitus was higher, blood glucose, HbA1c, TG, UA and Gensini score were obviously increased, while HDL-C was significantly decreased; all differences had statistical significance (p < 0.05). Different degrees of CKD occur in patients with ACS. In patients with ACS and CKD, metabolism of glucose and fat are significantly abnormal, and coronary arterial lesions are more serious. PMID:26624587
Kaiser, B A; Lawless, S T; Palmer, J M; Dunn, S P; Polinsky, M S; Baluarte, H J
Although cyclosporine has improved allograft survival in renal transplant patients, problems with drug toxicity remain, raising the question whether cyclosporine should be stopped at some point post-transplant. However, the relative safety of converting from cyclosporine to another immunosuppressive agent, or simply stopping cyclosporine remains an issue of debate and has not been evaluated in children. We have developed a protocol to convert children, who are 6 months post-transplant and have stable kidney function, from cyclosporine and prednisone to azathioprine and prednisone. Eleven children have undergone conversion because of suspected/potential nephrotoxicity or because of other difficulties with cyclosporine (expense, hirsutism). These children were compared with a control group of 12 children who met all criteria for conversion at 6 months but remained on cyclosporine. Allograft survival was similar in both groups but the children converted from cyclosporine experienced an improvement in renal function as measured by calculated creatinine clearance. There were no episodes of rejection for a period of 4 months post-conversion and all rejection episodes that developed subsequently occurred during or after the change from daily to alternate-day prednisone. We believe that conversion from cyclosporine to azathioprine can be accomplished safely in children with stable allograft function but long-term risks and benefits need further evaluation.
Pacifico, Lucia; Bonci, Enea; Andreoli, Gian Marco; Di Martino, Michele; Gallozzi, Alessia; De Luca, Ester; Chiesa, Claudio
The association between nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease has attracted interest and attention over recent years. However, no data are available in children. We determined whether children with NAFLD show signs of renal functional alterations, as determined by estimated glomerular filtration rate (eGFR) and urinary albumin excretion. We studied 596 children with overweight/obesity, 268 with NAFLD (hepatic fat fraction ≥5% on magnetic resonance imaging) and 328 without NAFLD, and 130 healthy normal-weight controls. Decreased GFR was defined as eGFR < 90 mL/min/1.73 m2. Abnormal albuminuria was defined as urinary excretion of ≥30 mg/24 h of albumin. A greater prevalence of eGFR < 90 mL/min/1.73 m2 was observed in patients with NAFLD compared to those without liver involvement and healthy subjects (17.5% vs. 6.7% vs. 0.77%; p < 0.0001). The proportion of children with abnormal albuminuria was also higher in the NAFLD group compared to those without NAFLD, and controls (9.3% vs. 4.0% vs. 0; p < 0.0001). Multivariate logistic regression analysis revealed that NAFLD was associated with decreased eGFR and/or microalbuminuria (odds ratio, 2.54 (confidence interval, 1.16–5.57); p < 0.05) independently of anthropometric and clinical variables. Children with NAFLD are at risk for early renal dysfunction. Recognition of this abnormality in the young may help to prevent the ongoing development of the disease. PMID:27472326
Ulusoy, Suekrue Oezkan, Guelsuem; Dinc, Hasan; Kaynar, Kuebra; Oeztuerk, Mehmet Halil; Guel, Semih; Kaplan, Safiye Tuba
Recently, ultrasound-guided percutaneous renal biopsy has been used in the diagnosis of renal diseases. Development of an arteriovenous fistula (AVF), which is one of the post-biopsy complications, is not frequently encountered. AVFs are usually asymptomatic; however, they may lead to serious outcomes. We report a 21-year-old patient, who had been on dialysis for 5 years. Due to high blood pressure (230/160 mmHg) and a thrill in the lumbar area detected on physical examination, Doppler examination was performed and a renal AVF was detected. Because the patient had a history of renal biopsy 5 years previously, the fistula was thought to be secondary to the biopsy. After embolization of the AVF, renal functions improved enough to terminate dialysis treatment.
Marques da Silva, A; Narciso, L
Purpose: Commercial workstations usually have their own software to calculate dynamic renal functions. However, usually they have low flexibility and subjectivity on delimiting kidney and background areas. The aim of this paper is to present a public domain software, called RenalQuant, capable to semi-automatically draw regions of interest on dynamic renal scintigraphies, extracting data and generating renal function quantification parameters. Methods: The software was developed in Java and written as an ImageJ-based plugin. The preprocessing and segmentation steps include the user’s selection of one time frame with higher activity in kidney’s region, compared with background, and low activity in the liver. Next, the chosen time frame is smoothed using a Gaussian low pass spatial filter (σ = 3) for noise reduction and better delimitation of kidneys. The maximum entropy thresholding method is used for segmentation. A background area is automatically placed below each kidney, and the user confirms if these regions are correctly segmented and positioned. Quantitative data are extracted and each renogram and relative renal function (RRF) value is calculated and displayed. Results: RenalQuant plugin was validated using retrospective 20 patients’ 99mTc-DTPA exams, and compared with results produced by commercial workstation software, referred as reference. The renograms intraclass correlation coefficients (ICC) were calculated and false-negative and false-positive RRF values were analyzed. The results showed that ICC values between RenalQuant plugin and reference software for both kidneys’ renograms were higher than 0.75, showing excellent reliability. Conclusion: Our results indicated RenalQuant plugin can be trustingly used to generate renograms, using DICOM dynamic renal scintigraphy exams as input. It is user friendly and user’s interaction occurs at a minimum level. Further studies have to investigate how to increase RRF accuracy and explore how to solve
Valade, Elodie; Tréluyer, Jean-Marc; Dabis, François; Arrivé, Elise; Pannier, Emmanuelle; Benaboud, Sihem; Fauchet, Floris; Bouazza, Naïm; Foissac, Frantz; Urien, Saïk; Hirt, Déborah
Aims The aims were to describe emtricitabine (FTC) pharmacokinetics in a large population of pregnant women during the different trimesters of pregnancy, and to explain FTC pharmacokinetic variability during pregnancy. Methods FTC plasma concentrations were measured in 103 non-pregnant and 83 pregnant women, including women in the different trimesters of pregnancy and on the day of delivery. A total of 457 plasma concentrations were available for analysis. A population pharmacokinetic model was developed with Monolix 4.1.3. Results FTC pharmacokinetics was best described by a two compartment model. The effect of creatinine clearance on apparent elimination clearance (CL/F) was significant. CL/F in pregnant women was significantly higher compared with non-pregnant women (geometric mean 24.1 vs 20.5 l h−1, P < 0.001), reflecting a modified renal function. FTC daily exposures (AUC) during pregnancy were lower than AUC in non-pregnant women, regardless of the trimester of pregnancy. FTC AUC geometric means were 8.38 mg l−1 h in the second trimester of pregnancy, 8.16 mg l−1 h in the third trimester of pregnancy, 8.30 mg l−1 h on the day of delivery and 9.77 mg l−1 h in non-pregnant women. FTC concentrations 24 h after administration were lower in pregnant women compared with non-pregnant women (0.054 vs. 0.079 mg l−1, P < 0.001) but still above the inhibitory concentration 50%. Conclusions FTC CL/F was increased by 18% during pregnancy, reflecting a modified renal function with 50% increase in estimated glomerular filtration rate. However, the impact of this modified renal function on FTC pharmacokinetics was not sufficiently large to consider dose adjustments during pregnancy. PMID:24995851
Pluznick, Jennifer L.
In order to assess the status of the volume and composition of the body fluid compartment, the kidney monitors a wide variety of chemical and physical parameters. It has recently become clear that the kidney’s sensory capacity extends well beyond its ability to sense ion concentrations in the forming urine. The kidney also keeps track of organic metabolites derived from a surprising variety of sources and uses a complex interplay of physical and chemical sensing mechanisms to measure the rate of fluid flow in the nephron. Recent research has provided new insights into the nature of these sensory mechanisms and their relevance to renal function. PMID:25280495
Dorshow, Richard B.; Asmelash, Bethel; Chinen, Lori K.; Debreczeny, Martin P.; Fitch, Richard M.; Freskos, John N.; Galen, Karen P.; Gaston, Kimberly R.; Marzan, Timothy A.; Poreddy, Amruta R.; Rajagopalan, Raghavan; Shieh, Jeng-Jong; Neumann, William L.
The ability to continuously monitor renal function via the glomerular filtration rate (GFR) in the clinic is currently an unmet medical need. To address this need we have developed a new series of hydrophilic fluorescent probes designed to clear via glomerular filtration for use as real time optical monitoring agents at the bedside. The ideal molecule should be freely filtered via the glomerular filtration barrier and be neither reabsorbed nor secreted by the renal tubule. In addition, we have hypothesized that a low volume of distribution into the interstitial space could also be advantageous. Our primary molecular design strategy employs a very small pyrazine-based fluorophore as the core unit. Modular chemistry for functionalizing these systems for optimal pharmacokinetics (PK) and photophysical properties have been developed. Structure-activity relationship (SAR) and pharmacokinetic (PK) studies involving hydrophilic pyrazine analogues incorporating polyethylene glycol (PEG), carbohydrate, amino acid and peptide functionality have been a focus of this work. Secondary design strategies for minimizing distribution into the interstitium while maintaining glomerular filtration include enhancing molecular volume through PEG substitution. In vivo optical monitoring experiments with advanced candidates have been correlated with plasma PK for measurement of clearance and hence GFR.
Lauretani, Fulvio; Semba, Richard D.; Bandinelli, Stefania; Miller, Edgar R.; Ruggiero, Carmelinda; Cherubini, Antonio; Guralnik, Jack M.; Ferrucci, Luigi
Background Recent studies suggest an association between polyunsaturated fatty acids (PUFAs) and the development of chronic kidney disease. The aim of this study was to examine the relationship between PUFAs and renal function in older adults. Methods We performed a cross-sectional and prospective analysis of 931 adults, ≥65 years old, enrolled in the InCHIANTI study, a population-based cohort in Tuscany, Italy. Plasma PUFAs were measured at enrollment, and creatinine clearance was estimated by the Cockcroft-Gault equation at baseline and after 3-year follow-up. Results At enrollment, participants with higher creatinine clearance had higher concentrations of HDL cholesterol, total plasma PUFAs, plasma n-3 fatty acid (FA), and plasma n-6 FA and lower triglycerides. From enrollment to the 3-year follow-up visit, creatinine clearance declined by 7.8 (12.2) mL/min (P <0.0001). Baseline total plasma PUFAs, n-3 FA, n-6 FA, and linoleic, linolenic, and arachidonic acids were strong independent predictors of less steep decline in creatinine clearance from baseline to follow-up (P <0.0001, after adjusting for baseline creatinine clearance). After adjusting for baseline creatinine, baseline total plasma PUFAs, n-3 FA, and linoleic, linolenic, and arachidonic acids were negatively associated with creatinine at 3-year follow-up. Participants with higher plasma PUFAs at enrollment had a lower risk of developing renal insufficiency, defined by a creatinine clearance <60 mL/min, during 3-year follow-up. Conclusion High PUFA concentrations, both n-3 FA and n-6 FA, may attenuate the age-associated decline in renal function among older community-dwelling women and men. PMID:18202159
Wade, C E; Morey-Holton, E
Following spaceflight, changes in renal function of humans have been suggested. To assess the effects of readaptation on renal function, urine was collected from male rats ( approximately 245 g) over a 2-wk period following a 14-day spaceflight. Rats were assigned to three groups: flight animals (n = 6), flight controls (n = 6) housed in the flight cages on the ground, and vivarium controls (n = 5) housed in standard shoe box cages. Animals were placed into individual metabolic cages for urine collection. Urine output was significantly increased for 3 days following flight. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate. Creatinine excretion rate increased over the first two postflight days. Glomerular filtration rate increased immediately following spaceflight without changes in plasma creatinine, Na+, K+, or osmolality. Increased excretion of solute was thus the result of increased delivery and a decreased percent reabsorption of the filtered load. Osmolal clearance was increased immediately postflight while free water clearance was decreased. In growing rats, the diuresis after short-duration spaceflight is the result of an increase in solute excretion with an accompanying reduction in free water clearance.
Wade, C. E.; Morey-Holton, E.
Following spaceflight, changes in renal function of humans have been suggested. To assess the effects of readaptation on renal function, urine was collected from male rats ( approximately 245 g) over a 2-wk period following a 14-day spaceflight. Rats were assigned to three groups: flight animals (n = 6), flight controls (n = 6) housed in the flight cages on the ground, and vivarium controls (n = 5) housed in standard shoe box cages. Animals were placed into individual metabolic cages for urine collection. Urine output was significantly increased for 3 days following flight. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate. Creatinine excretion rate increased over the first two postflight days. Glomerular filtration rate increased immediately following spaceflight without changes in plasma creatinine, Na+, K+, or osmolality. Increased excretion of solute was thus the result of increased delivery and a decreased percent reabsorption of the filtered load. Osmolal clearance was increased immediately postflight while free water clearance was decreased. In growing rats, the diuresis after short-duration spaceflight is the result of an increase in solute excretion with an accompanying reduction in free water clearance.
Navalkissoor, Shaunak; Szyszko, Teresa; Gnanasegaran, Gopinath; Nunan, Thomas
In patients presenting with acute renal failure and known/suspected lymphoma, the diagnosis of diffuse renal involvement is important, as there is potential for rapid resolution with chemotherapy. Although FDG is excreted through the kidneys and focal renal disease may be difficult to identify, diffuse renal FDG is more easily recognized and is always abnormal. We report a patient presenting with acute renal failure and suspected lymphoma. F-18 FDG PET/CT study demonstrated diffuse increased FDG uptake in bilaterally enlarged kidneys. Following 1 cycle of chemotherapy, the renal function normalized. An interim F-18 FDG PET/CT demonstrated normal size and FDG uptake within both kidneys.
Stevens, Michael C; Lovejoy, David; Kim, Jinsuh; Oakes, Howard; Kureshi, Inam; Witt, Suzanne T
Several reports show that traumatic brain injury (TBI) results in abnormalities in the coordinated activation among brain regions. Because most previous studies examined moderate/severe TBI, the extensiveness of functional connectivity abnormalities and their relationship to postconcussive complaints or white matter microstructural damage are unclear in mild TBI. This study characterized widespread injury effects on multiple integrated neural networks typically observed during a task-unconstrained "resting state" in mild TBI patients. Whole brain functional connectivity for twelve separate networks was identified using independent component analysis (ICA) of fMRI data collected from thirty mild TBI patients mostly free of macroscopic intracerebral injury and thirty demographically-matched healthy control participants. Voxelwise group comparisons found abnormal mild TBI functional connectivity in every brain network identified by ICA, including visual processing, motor, limbic, and numerous circuits believed to underlie executive cognition. Abnormalities not only included functional connectivity deficits, but also enhancements possibly reflecting compensatory neural processes. Postconcussive symptom severity was linked to abnormal regional connectivity within nearly every brain network identified, particularly anterior cingulate. A recently developed multivariate technique that identifies links between whole brain profiles of functional and anatomical connectivity identified several novel mild TBI abnormalities, and represents a potentially important new tool in the study of the complex neurobiological sequelae of TBI.
Reichman, J; Cohen, S; Goldfarb, M; Shina, A; Rosen, S; Brezis, M; Karmeli, F; Heyman, S N
The constitutive cyclooxygenase (COX)-1 enzyme has been considered the physiologically important isoform for prostaglandin synthesis in the normal kidney. It has, therefore, been suggested that selective inhibitors of the 'inducible' isoform (COX-2) may be free from renal adverse effects. We studied the renal effects of the predominantly COX-2 antagonist nabumetone in isolated perfused kidneys. As compared with controls, kidneys removed after in vivo administration of oral nabumetone (15 mg/kg) disclosed altered renal function with reduced glomerular filtration rate, filtration fraction, and urine volume and enhanced hypoxic outer medullary tubular damage. By contrast, renal function and morphology were not affected in vivo by nabumetone or its active metabolite 6-methoxy-2-naphthylacetic acid. The latter agent (10-20 mg/kg i.v.) did not significantly alter renal microcirculation, as opposed to a selective substantial reduction in medullary blood flow noted with the nonselective COX inhibitor indomethacin (5 mg/kg i.v.). In a rat model of acute renal failure, induced by concomitant administration of radiocontrast, nitric oxide synthase, and COX inhibitors, the decline in kidney function and the extent of hypoxic medullary damage with oral nabumetone (80 mg/kg) were comparable to a control group, and significantly less than those induced by indomethacin. In rats subjected to daily oral nabumetone for 3 consecutive weeks, renal function and morphology were preserved as well. Both nabumetone and 6-methoxy-2-naphthylacetic acid reduced renal parenchymal prostaglandin E2 to the same extent as indomethacin. It is concluded that while nabumetone adversely affects renal function and may intensify hypoxic medullary damage ex vivo, rat kidneys are not affected by this agent in vivo, both in acute and chronic studies. COX selectivity may not explain the renal safety of nabumetone.
LeSouëf, P N; Myers, N A; Landau, L I
Recurrent respiratory illnesses are frequent in infants following repair of esophageal atresia and functional abnormalities of respiratory and esophageal function are often seen in older children. Recurrent aspiration is a potential cause of these respiratory abnormalities, but a relationship between abnormalities of gastrointestinal and respiratory mechanics has not been adequately investigated. We sought an association between lower esophageal sphincter (LES) incompetence, gastroesophageal reflux (GER), and respiratory function abnormalities in 18 subjects (age 12 to 21 years) following repair of esophageal atresia (Vogt type 111B). In each subject, measurements were made of spirometry, lung volumes assessed by plethysmography, esophageal manometry recorded using a constantly infused fluid-filled trilumen catheter to assess LES pressure and esophageal motility, and esophageal pH monitoring to detect GER. Subjects were grouped according to the presence or absence of a radiologically supported diagnosis of pneumonia in the first 4 years of life. Lung volumes were mildly but significantly decreased in the "pneumonia" group compared with the "nonpneumonia" group. There was no association between abnormalities of respiratory function and abnormal LES pressure or the presence of GER. These data suggest that pneumonia in esophageal atresia infants is associated with mild long-term lung damage. LES dysfunction and GER do not appear to play a major role in this process.
Spanos, Konstantinos; Rountas, Christos; Saleptsis, Vasileios; Athanasoulas, Athanasios; Fezoulidis, Ioannis; Giannoukas, Athanasios D
We validated the association of simple renal cysts with abdominal aortic aneurysm and other cardiovascular factors and assessed simple renal cysts' impact on renal function before and after endovascular abdominal aortic aneurysm repair. A retrospective analysis of prospectively collected data was conducted. Computed tomography angiograms of 100 consecutive male patients with abdominal aortic aneurysm who underwent endovascular abdominal aortic aneurysm repair (Group 1) were reviewed and compared with 100 computed tomography angiogram of aged-matched male patients without abdominal aortic aneurysm (Group 2). Patients' demographic data, risk factors, abdominal aortic aneurysm diameter, the presence of simple renal cyst and laboratory tests were recorded. No difference was observed between the two groups in respect to other cardiovascular risk factors except hyperlipidemia with higher prevalence in Group 1 (p < 0.05). Presence of simple renal cysts was independently associated with age (p < 0.05) and abdominal aortic aneurysm (p = 0.0157). There was no correlation between simple renal cysts and abdominal aortic aneurysm size or pre-operative creatinine and urea levels. No difference was observed in post-operative creatinine and urea levels either immediately after endovascular abdominal aortic aneurysm repair or in 12-month follow-up. In male patients, the presence of simple renal cysts is associated with abdominal aortic aneurysm and is increasing with age. However, their presence is neither associated with impaired renal function pre-endovascular abdominal aortic aneurysm repair and post-endovascular abdominal aortic aneurysm repair nor after 12-month follow-up.
Background: Cross hypersensitivity to inhalation anesthetics has not been studied. The aim of this study was to investigate it by comparing liver and renal function after repeated anesthesia with sevoflurane and isoflurane retrospectively. Materials and Methods: The adult patients who received general anesthesia twice within the interval of 14 days to 1 year were retrospectively analyzed. Those who received sevoflurane anesthesia twice (SS group, 53 cases), isoflurane anesthesia twice (II group, 31 cases), sevoflurane followed by isoflurane anesthesia (SI group, 29 cases), isoflurane followed by sevoflurane anesthesia (IS group, 35 cases), and propofol–fentanyl anesthesia twice (PP group, 58 cases) were enrolled. Serum concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (Bil), gamma-glutamyl transpeptidase (γ-GTP), blood urea nitrogen (BUN), and creatinine (Cr) measured 1-3, 5-8, and 12-16 days after surgery were investigated. Results: In the IS group, the number of the patients with abnormal values of ALT and γ-GTP 5–8 days after surgery were significantly smaller at second anesthesia compared to the first anesthesia. The number of the patients with abnormal values of AST, ALT, and γ-GTP were significantly larger in the II group than the SS and PP groups. The number of patients who had higher values in each parameter at second anesthesia compared to the first anesthesia was not different among the groups. Conclusions: Sevoflurane and isoflurane might have no cross hypersensitivity. Both anesthetics might not have any additional risks to increase liver and renal damage by second anesthesia. PMID:23493664
Franco, M C P; Nagasako, S S; Machado, P G; Nogueira, P C K; Pestana, J O M; Sesso, R
In clinical practice, the glomerular filtration rate (GFR) is often determined with serum creatinine. However, studies have shown cystatin C to be a better parameter for the diagnosis of impaired renal function. We compared GFR estimated by plasma cystatin C with GFR estimated by serum creatinine in a sample of 50 pediatric renal transplant recipients and 24 healthy children. The correlation between GFR estimated by serum creatinine and by cystatin C was significant (r = 0.75; P < 0.001, Person's correlation); however, in pediatric kidney transplant recipients, the GFR was 6.7 mL/min lower when determined using cystatin C rather than serum creatinine. Moreover, using GFR estimated by cystatin C we found that 42% of the pediatric kidney transplant recipients had an estimated GFR <60 mL.min-1.1.73 (m(2))-1, whereas when GFR was estimated by the serum creatinine formula only 16% of the children had values below this cutoff point indicative of chronic kidney disease (P < 0.001). We conclude that, in pediatric kidney transplant recipients, estimation of GFR yields lower values when cystatin C is used rather than serum creatinine.
Peti-Peterdi, János; Kishore, Bellamkonda K.; Pluznick, Jennifer L.
To maintain metabolic homeostasis, the body must be able to monitor the concentration of a large number of substances, including metabolites, in real time and to use that information to regulate the activities of different metabolic pathways. Such regulation is achieved by the presence of sensors, termed metabolite receptors, in various tissues and cells of the body, which in turn convey the information to appropriate regulatory or positive or negative feedback systems. In this review, we cover the unique roles of metabolite receptors in renal and vascular function. These receptors play a wide variety of important roles in maintaining various aspects of homeostasis—from salt and water balance to metabolism—by sensing metabolites from a wide variety of sources. We discuss the role of metabolite sensors in sensing metabolites generated locally, metabolites generated at distant tissues or organs, or even metabolites generated by resident microbes. Metabolite receptors are also involved in various pathophysiological conditions and are being recognized as potential targets for new drugs. By highlighting three receptor families—(a) citric acid cycle intermediate receptors, (b) purinergic receptors, and (c) short-chain fatty acid receptors—we emphasize the unique and important roles that these receptors play in renal and vascular physiology and pathophysiology. PMID:26667077
Morris, Laurel S; Baek, Kwangyeol; Tait, Roger; Elliott, Rebecca; Ersche, Karen D; Flechais, Remy; McGonigle, John; Murphy, Anna; Nestor, Liam J; Orban, Csaba; Passetti, Filippo; Paterson, Louise M; Rabiner, Ilan; Reed, Laurence; Smith, Dana; Suckling, John; Taylor, Eleanor M; Bullmore, Edward T; Lingford-Hughes, Anne R; Deakin, Bill; Nutt, David J; Sahakian, Barbara J; Robbins, Trevor W; Voon, Valerie
Naltrexone, an opioid receptor antagonist, is commonly used as a relapse prevention medication in alcohol and opiate addiction, but its efficacy and the mechanisms underpinning its clinical usefulness are not well characterized. In the current study, we examined the effects of 50-mg naltrexone compared with placebo on neural network changes associated with substance dependence in 21 alcohol and 36 poly-drug-dependent individuals compared with 36 healthy volunteers. Graph theoretic and network-based statistical analysis of resting-state functional magnetic resonance imaging (MRI) data revealed that alcohol-dependent subjects had reduced functional connectivity of a dispersed network compared with both poly-drug-dependent and healthy subjects. Higher local efficiency was observed in both patient groups, indicating clustered and segregated network topology and information processing. Naltrexone normalized heightened local efficiency of the neural network in alcohol-dependent individuals, to the same levels as healthy volunteers. Naltrexone failed to have an effect on the local efficiency in abstinent poly-substance-dependent individuals. Across groups, local efficiency was associated with substance, but no alcohol exposure implicating local efficiency as a potential premorbid risk factor in alcohol use disorders that can be ameliorated by naltrexone. These findings suggest one possible mechanism for the clinical effects of naltrexone, namely, the amelioration of disrupted network topology.
This study aimed to determine patients with T1b renal cell carcinoma (RCC) who could benefit from partial nephrectomy (PN) and method to identify them preoperatively using nephrometry score (NS). From a total of 483 radical nephrectomy (RN)-treated patients and 40 PN-treated patients who received treatment for T1b RCC between 1995 and 2010, 120 patients identified through 1:2 propensity-score matching were included for analysis. Probability of chronic kidney disease (CKD) until postoperative 5-years was calculated and regressed with respect to the surgical method and NS. Median follow-up was 106 months. CKD-probability at 5-years was 40.7% and 13.5% after radical and PN, respectively (P = 0.005). While PN was associated with lower risk of CKD regardless of age, comorbidity, preoperative estimated renal function, the effect was observed only among patients with NS ≤ 8 (P < 0.001) but not in patients with NS ≥ 9 (P = 0.746). Percent operated-kidney volume reduction and ischemia time were similar between the patients with NS ≥ 9 and ≤ 8. In the stratified Cox regression accounting for the interaction observed between the surgical method and the NS, PN reduced CKD-risk only in patients with NS ≤ 8 (hazard ratio [HR], 0.054; P = 0.005) but not in ≥ 9 (HR, 0.996; P = 0.994). In T1b RCC with NS ≥ 9, the risk of postoperative CKD was not reduced following PN compared to RN. Considering the potential complications of PN, minimally invasive RN could be considered with priority in this subgroup of patients. PMID:28145654
Cullen, Kathryn R.; Westlund, Melinda; Klimes-Dougan, Bonnie; Mueller, Bryon A.; Houri, Alaa; Eberly, Lynn E.; Lim, Kelvin O.
Importance Major depressive disorder (MDD) frequently emerges during adolescence and can lead to persistent illness, disability and suicide. The maturational changes that take place in the brain during adolescence underscore the importance of examining neurobiological mechanisms during this time period of early illness. However, neural mechanisms of depression in adolescents have been understudied. Prior research has implicated the amygdala in emotion processing in mood disorders, and adult depression studies have suggested amygdala-frontal connectivity deficits. Resting-state functional magnetic resonance imaging (rsfMRI) is an advanced tool that can be used to probe neural networks and identify brain-behavior relationships. Objective To examine amygdala resting-state functional connectivity (RSFC) in adolescents with and without MDD using rsfMRI, and to examine how amygdala RSFC relates to a broad range of symptom dimensions. Design Cross-sectional rsfMRI study. Setting Depression research program at an academic medical center. Participants 41 girls and boys aged 12–19 years with MDD and 29 healthy adolescents (frequency matched on age and sex) with no psychiatric diagnoses. Main Outcome Measure Using a whole-brain functional connectivity approach, we examined correlation of spontaneous fluctuation of blood-oxygen-level-dependent (BOLD) signal of each voxel in the whole brain with that of the amygdala. Results Adolescents with MDD showed lower positive RSFC between amygdala and hippocampus, parahippocampus and brain stem; this connectivity was inversely correlated with general depression, dysphoria, and lassitude, and positively correlated with well-being. Patients also showed greater (positive) amygdala-precuneus RSFC (in contrast to negative amygdala-precuneus RSFC in controls.) Conclusion Impaired amygdala-hippocampal/brainstem and amygdala-precuneus RSFC has not previously been highlighted in depression and may be unique to adolescent MDD. These circuits
Vesin, P.; Traverso, H.
The term ‘functional renal failure’ has been used to describe the renal failure developing in advanced cirrhosis in which tubular function and structure remain intact. It may develop spontaneously, in which case prognosis is poor, but may be secondary to gastro-intestinal haemorrhage or excessive use of diuretics, in which case correction of the precipitating factor leads to improvement in renal function. It is suggested that the renal failure is due to a reduction in effective circulating plasma volume. PMID:1234327
Taylor, Stephan F; Demeter, Elise; Phan, K Luan; Tso, Ivy F; Welsh, Robert C
Deficits in the γ-aminobutyric acid (GABA) system have been reported in postmortem studies of schizophrenia, and therapeutic interventions in schizophrenia often involve potentiation of GABA receptors (GABAR) to augment antipsychotic therapy and treat negative affect such as anxiety. To map GABAergic mechanisms associated with processing affect, we used a benzodiazepine challenge while subjects viewed salient visual stimuli. Fourteen stable, medicated schizophrenia/schizoaffective patients and 13 healthy comparison subjects underwent functional magnetic resonance imaging using the blood oxygenation level-dependent (BOLD) technique while they viewed salient emotional images. Subjects received intravenous lorazepam (LRZ; 0.01 mg/kg) or saline in a single-blinded, cross-over design (two sessions separated by 1-3 weeks). A predicted group by drug interaction was noted in the dorsal medial prefrontal cortex (dmPFC) as well as right superior frontal gyrus and left and right occipital regions, such that psychosis patients showed an increased BOLD signal to LRZ challenge, rather than the decreased signal exhibited by the comparison group. A main effect of reduced BOLD signal in bilateral occipital areas was noted across groups. Consistent with the role of the dmPFC in processing emotion, state negative affect positively correlated with the response to the LRZ challenge in the dmPFC for the patients and comparison subjects. The altered response to LRZ challenge is consistent with altered inhibition predicted by postmortem findings of altered GABAR in schizophrenia. These results also suggest that negative affect in schizophrenia/schizoaffective disorder is associated-directly or indirectly-with GABAergic function on a continuum with normal behavior.
Hamza, Rasha T; Shalaby, Mennatallah H; Hamed, Laith S; Abdulla, Dunya B A; Elfekky, Sahar M; Sultan, Omar M
Renal anomalies are present in up to 30% of patients with Turner syndrome (TS). Renal ultrasound (U/S) detects anatomical renal anomalies only while renal scintigraphy detects anomalies, detects early renal malfunction, and estimates glomerular filtration rate (GFR). Thus, we aimed to assess frequency of renal abnormalities detected by scintigraphy in comparison to renal U/S in TS patients. Ninety TS patients were subjected to auxological assessment, measurement of serum creatinine; and renal U/S and scintigraphy. Renal U/S detected renal anomalies in 22.22% of patients versus 17.78 % detected by scintigraphy (P = 0.035). Scintigraphy detected renal functional abnormalities in 44.44% of patients in the form of subnormal total GFR, abnormal renogram curve pattern, improper tracer handling and perfusion; and difference in split renal function >10% between both kidneys. Patients with a 45,X karyotype had more renal functional abnormalities (56%) than those with mosaic karyotype (33.33%), P = 0.04. In conclusion, renal scintigraphy is not superior to U/S in detection of renal anomalies but is a reliable method for early detection of renal malfunction in TS patients especially those with 45,X to ensure early management to offer a better quality of life.
Sheppard, M. C.; Ramsden, D. B.
Results of thyroid function tests were analysed in 199 clinically euthyroid inpatients with normal serum thyroid stimulating hormone values. Serum total triiodothyronine was less than 1.25 nmol/l in 61.8% of samples, free triiodothyronine less than 3.9 pmol/l in 57.8%, total thyroxine less than 63 nmol/l in 21.1% and free thyroxine less than 9.5 pmol/l in 17.6%. In contrast, thyroxine binding globulin ratio was below normal (less than 5) in only 5 samples. A significant positive correlation (P less than 0.001) of serum free thyroxine with total thyroxine, thyroxine/thyroxine binding globulin ratio and free triiodothyronine was present as well as a significant negative correlation (P less than 0.001) with serum thyroid stimulating hormone. There was no correlation of free thyroxine measurements with serum albumin or non-esterified fatty acid concentrations. Although serum free thyroxine is low in a number of patients with non-thyroidal illnesses, this does not appear to be due to a rise in non-esterified fatty acids or a fall in albumin as has been proposed. Serum thyroid stimulating hormone measurements are essential to confirm the diagnosis of hypothyroidism in such subjects. PMID:4070117
Dorshow, Richard B.; Bugaj, Joseph E.; Burleigh, B. D.; Duncan, James R.; Johnson, Michael A.; Jones, William B.
A noninvasive in vivo fluorescence detection scheme was employed to continuously monitor exogenous dye clearance from the vasculature. Differentiation between normal and impaired physiological function in a rat model was demonstrated for both liver and kidney. A fiber optic transmitted light from source to ear; a second fiber optic positioned near the ear transmitted the fluorescent light to a detector system. Two model dye systems were employed in this initial study. Indocyanine green, known to be exclusively cleared from the blood stream by the liver, was excited in vivo with laser light at 780 nm. The fluorescence signal was detected at 830 nm. A characteristic clearance curve of normal hepatic function was obtained. After a partial hepatectomy of the liver, the clearance curve was extended in time, as would be expected from reduced hepatic function. In addition, fluorescein labeled poly-D-lysine, a small polymer predominantly cleared from the blood stream by the kidney, was excited in vivo with laser light at 488 nm. The fluorescence signal was detected at 518 nm. A characteristic clearance curve of normal renal function was obtained. After a bilateral ligation of the kidneys, the clearance curve remained elevated and constant, indicating little if any clearance. Thus, the feasibility of a new noninvasive method for physiological function assessment was established.
Worcester, Elaine M.
Stone disease is a rare cause of renal failure, but a history of kidney stones is associated with an increased risk for chronic kidney disease, particularly in overweight patients. Loss of renal function seems especially notable for patients with stones associated with cystinuria, hyperoxaluria, and renal tubular acidosis, in whom the renal pathology shows deposits of mineral obstructing inner medullary collecting ducts, often diffusely. However, even idiopathic calcium oxalate stone formers have a mild but significant decrease in renal function, compared to age, sex and weight-matched normals, and appear to lose renal function with age at a slightly faster rate than non-stone formers. There is also an increased incidence of hypertension among stone formers, although women are more likely to be affected than men.
McGrath, Jane; Johnson, Katherine; O'Hanlon, Erik; Garavan, Hugh; Leemans, Alexander; Gallagher, Louise
Disruption of structural and functional neural connectivity has been widely reported in Autism Spectrum Disorder (ASD) but there is a striking lack of research attempting to integrate analysis of functional and structural connectivity in the same study population, an approach that may provide key insights into the specific neurobiological underpinnings of altered functional connectivity in autism. The aims of this study were (1) to determine whether functional connectivity abnormalities were associated with structural abnormalities of white matter (WM) in ASD and (2) to examine the relationships between aberrant neural connectivity and behavior in ASD. Twenty-two individuals with ASD and 22 age, IQ-matched controls completed a high-angular-resolution diffusion MRI scan. Structural connectivity was analysed using constrained spherical deconvolution (CSD) based tractography. Regions for tractography were generated from the results of a previous study, in which 10 pairs of brain regions showed abnormal functional connectivity during visuospatial processing in ASD. WM tracts directly connected 5 of the 10 region pairs that showed abnormal functional connectivity; linking a region in the left occipital lobe (left BA19) and five paired regions: left caudate head, left caudate body, left uncus, left thalamus, and left cuneus. Measures of WM microstructural organization were extracted from these tracts. Fractional anisotropy (FA) reductions in the ASD group relative to controls were significant for WM connecting left BA19 to left caudate head and left BA19 to left thalamus. Using a multimodal imaging approach, this study has revealed aberrant WM microstructure in tracts that directly connect brain regions that are abnormally functionally connected in ASD. These results provide novel evidence to suggest that structural brain pathology may contribute (1) to abnormal functional connectivity and (2) to atypical visuospatial processing in ASD. PMID:24133425
Olandoski, Karen Previdi; Koch, Vera; Trigo‐Rocha, Flavio Eduardo
AIMS: Preservation of renal function in children with congenital neurogenic bladder is an important goal of treatment for the disease. This study analyzed the evolution of renal function in patients with congenital neurogenic bladder. METHODS: We reviewed the records of 58 pediatric patients with respect to the following attributes: gender, age, etiology of neurogenic bladder, reason for referral, medical/surgical management, episodes of treated urinary tract infections, urodynamics, DMSA scintigraphy, weight, height, blood pressure, glomerular filtration rate, microalbuminuria and metabolic acidosis. Statistical analysis was performed, adopting the 5% significance level. RESULTS: The mean age at presentation was 4.2 ± 3.5 years. Myelomeningocele was the most frequent etiology (71.4%). Recurrent urinary tract infection was the reason for referral in 82.8% of the patients. Recurrent urinary tract infections were diagnosed in 84.5% of the patients initially; 83.7% of those patients experienced improvement during follow‐up. The initial mean glomerular filtration rate was 146.7 ± 70.1 mL/1.73 m2/min, and the final mean was 193.6 ± 93.6 mL/1.73 m2/min, p = 0.0004. Microalbuminuria was diagnosed in 54.1% of the patients initially and in 69% in the final evaluation. Metabolic acidosis was present in 19% of the patients initially and in 32.8% in the final assessment. CONCLUSIONS: Patient referral to a pediatric nephrologist was late. A reduction in the number of urinary tract infections was observed with adequate treatment, but microalbuminuria and metabolic acidosis occurred frequently despite adequate management. PMID:21484032
Gillen, Michael; Valdez, Shakti; Zhou, Dongmei; Kerr, Bradley; Lee, Caroline A; Shen, Zancong
Introduction Lesinurad is a selective uric acid reabsorption inhibitor approved for the treatment of gout in combination with a xanthine oxidase inhibitor (XOI) in patients who have not achieved target serum uric acid (sUA) levels with an XOI alone. Most people with gout have chronic kidney disease. The pharmacokinetics, pharmacodynamics, and safety of lesinurad were assessed in subjects with impaired renal function. Methods Two Phase I, multicenter, open-label, single-dose studies enrolled subjects with normal renal function (estimated creatinine clearance [eCrCl] >90 mL/min; N=12) or mild (eCrCl 60–89 mL/min; N=8), moderate (eCrCl 30–59 mL/min; N=16), or severe (eCrCl <30 mL/min; N=6) renal impairment. Subjects were given a single oral lesinurad dose of 200 mg (N=24) or 400 mg (N=18). Blood and urine samples were analyzed for plasma lesinurad concentrations and serum and urine uric acid concentrations. Safety was assessed by adverse events and laboratory data. Results Mild, moderate, and severe renal impairment increased lesinurad plasma area under the plasma concentration–time curve by 34%, 54%–65%, and 102%, respectively. Lesinurad plasma Cmax was unaffected by renal function status. Lower renal clearance and urinary excretion of lesinurad were associated with the degree of renal impairment. The sUA-lowering effect of a single dose of lesinurad was similar between mild renal impairment and normal function, reduced in moderate impairment, and greatly diminished in severe impairment. Lesinurad increased urinary urate excretion in normal function and mild renal impairment; the increase was less with moderate or severe renal impairment. Lesinurad was well tolerated by all subjects. Conclusion Lesinurad exposure increased with decreasing renal function; however, the effects of lesinurad on sUA were attenuated in moderate to severe renal impairment. PMID:27843295
Gruskin, A B; Baluarte, H J; Cote, M L; Elfenbein, I B
In those children with thoracic asphyxiant dystrophy, a genetically determined disorder, who survive infancy, the development of renal disease may be life-threatening. This report will present data obtained in six patients from three families which deals with the renal abnormalities in thoracic asphyxiant dystrophy. Both functional and anatomic abnormalities are described. Abnormalities in solute transport in the proximal tubule may be the earliest sign of renal dysfunction in this syndrome. Early glomerular changes may be more important than previously recognized. Finally, the various phenotypic expressions of this disorder are considered.
Sessa, Galina; Hjortshøj, Tina Duelund; Egfjord, Martin
Although many congenital diseases present disturbances of the central nervous system, eyes and renal function, only few of these have a defined genetic basis. The first clinical features of cerebro-oculo-renal diseases usually develop in early childhood and deterioration of kidney function and even end-stage kidney disease may occur in a young age. The syndromes should be considered in patients with retarded growth and development, central nervous system abnormalities, impaired vision or blindness and progressive renal failure.
Walker, R.D.; Reid, C.F.; Richard, G.A.; Talbert, J.L.; Rogers, B.M.
The objective of this study was to determine whether or not renal growth and function were adversely affected in the remaining kidneys of patients who had undergone nephrectomy for Wilms tumor. These patients received chemotherapy and some radiotherapy (tumoricidal agents which might affect the remaining kidney). Renal growth was compared between the treatment groups and normal renal growth. Hypertrophy did occur and did not appear to be affected by subsequent treatment. Renal function was minimally altered in all treatment groups irrespective of the type of treatment.
de Cataldo, F; Baudo, F; Redaelli, R; Corno, A R
The myelodysplastic syndromes (MDS) are neoplastic disorders of the hemopoietic system; multilineage involvement is also evidenced by specific cellular dysfunctions. The von Willebrand factor (vWF), synthesized and processed in the megakaryocytes (MK), is stored in the alpha granules of the platelets. The platelet vWF multimeric pattern was studied in 18 patients with MDS, and in 4 with pernicious anemia (PA), to investigate whether the processing of vWF is abnormal in the megakaryocytic dysplasia. An abnormal multimeric pattern was observed in 10/18 MDS and 4/4 PA patients. The abnormality of this specific protein is the discrete expression of the basic disorder, and is reversible when hemopoiesis is normalized. Although the data do not allow any conclusion, abnormal synthesis is the likely explantation of the abnormality.
Gholson, Georica K.; Mwendwa, Denée T.; Wright, Regina Sims; Callender, Clive O.; Campbell, Alfonso L.
Objective African Americans are disproportionately affected by chronic kidney disease (CKD). Recent research has documented that psychological factors have a significant influence on the progression and treatment of CKD. However, extant evidence exists that has examined the link between psychological factors and renal function in African Americans. The purpose of the study was to determine if psychological factors were associated with several biomarkers of renal functioning in this group. Participants 129 African American participants, with a mean age of 44.4 years (SD512.25). Design and Setting Data were analyzed from a cross-sectional study entitled Stress and Psychoneuroimmunological Factors in Renal Health and Disease. Main Predictor Measures Participants completed the Beck Depression Inventory-II, Cook Medley Scale, and Perceived Stress Scale-10. Main Outcome Measures Systolic blood pressure, as well as blood and urine samples, were collected and served as biomarkers of renal functioning. Results Our findings indicated that psychological factors were not associated with renal functioning. Age, sex, and systolic blood pressure emerged as significant predictors of renal functioning. Conclusions Depressive symptomatology, perceived stress, and hostility did not influence renal functioning in this sample. This unexpected finding may be attributed to the fact that this sample population was not elevated on depressive symptoms, perceived stress, or hostility. Elevated levels of these psychological factors, as well as other psychological factors associatd with the CKD, may be more influential on renal functioning in African Americans. PMID:26118136
Ivey, Kerry L.; Lewis, Joshua R.; Lim, Wai H.; Lim, Ee M.; Hodgson, Jonathan M.; Prince, Richard L.
Background Progression to chronic renal failure involves accelerated atherosclerosis and vascular calcification. Oxidative stress and endothelial dysfunction play a role in renal failure pathophysiology. In addition to improving vascular health and function, proanthocyanidins have been shown to exert renoprotective effects in animal models. Thus we hypothesize that proanthocyanidins may contribute to the maintenance of healthy renal function. Objective Determine the association of habitual proanthocyanidin intake with renal function and the risk of clinical renal outcomes in a population of elderly women. Design 948 women aged over 75 y, free of prevalent renal disease at baseline, were randomly selected from ambulant Caucasian women. Proanthocyanidin consumption was determined using a validated food frequency questionnaire and the United States Department of Agriculture proanthocyanidin food content database. Fasting serum cystatin C and creatinine were assessed at baseline. Renal failure hospitalisations and deaths were assessed over 5 years of follow-up through the Western Australia Data Linkage System. Results Compared to participants with low consumption, participants in the highest tertile of proanthocyanidin intake had a 9% lower cystatin C concentration (P<0.001). High proanthocyanidin consumers were at 50% lower risk of moderate chronic kidney insufficiency, and 65% lower risk of experiencing a 5-year renal disease event (P<0.05). These relationships remained significant following adjustment for renal disease risk factors and diet-related potential confounders. Conclusion Increased consumption of proanthocyanidins was associated with better renal function and substantially reduced renal associated events, which has been supported by mechanistic and animal model data. Proanthocyanidin intake should be further examined as a dietary contributor to better renal health. PMID:23940710
Lin, Chih-Kuang; Lin, Deng-Juin; Yen, Chi-Hwa; Chen, Shiuan-Chih; Chen, Chun-Chieh; Wang, Tsun-Yen; Chou, Ming-Chih; Chang, Horng-Rong; Lee, Meng-Chih
Renal disease is one of the top 10 leading causes of death, and the incidence of end-stage renal disease in Taiwan is the highest in the world. Many dietitians consider the diet of plant origin consumed by vegans to be 'lighter' and 'more healthful' than the diet of both plant and animal origin consumed by omnivores. Dietary protein has significant effects on renal functions. The study explored the effects of both the diets on renal functions. The study subjects included 102 Buddhist nun vegetarians and an equal number of matched control group (omnivores). A cross-sectional study was performed to investigate the effects of the diet of plant origin and the diet of both plant and animal origin on renal functions. There was no difference in the renal functions between the two groups. However, systolic blood pressure, blood urea nitrogen, serum sodium, glucose, cholesterol levels, and urinary specific gravity were lower in the vegetarian group. Although these results were compatible with general concepts regarding diet of plant origin, after adjusting for age, the duration of intake of this diet had no effect on the renal functions. Based on the findings, it is concluded that the renal functions, in terms of the estimated glomerular filtration rate, were not different between the vegetarians and the omnivores.
Nam, Jong Kil; Chung, Moon Kee
Purpose Diuretic 99mTc-diethylenetriaminepentaacetic acid (Tc-DTPA) renal scans may show false-negative or false-positive results in children with ureteropelvic junction obstruction (UPJO). We evaluated whether modified differential renal function (DRF) revised by the renal cross-sectional area on imaging study may be a more valuable predictor than conventional DRF on a renal scan for deciding on a proper interventional time. Materials and Methods Between September 2001 and January 2008, we reviewed the diuretic renal scan results of 29 pediatric patients who underwent pyeloplasty due to unilateral UPJO. Diuretic renal scans using the standard 99mTc-DTPA protocol and imaging studies for renal unit measurement area were done. Conventional DRF measurement and modified calculation of DRF per unit area were done. Conventional DRF was classified into group I (below 40%) and group II (above 40%). Results The mean age of all patients was 42.6±52.6 months (range, 3-198 months). The mean cross-sectional areas of the UPJO kidney and of the normal contralateral kidney were 62.1±29.2 cm2 and 41.3±22.5 cm2, respectively (p<0.01). The conventional and modified DRF of the UPJO kidney were 45.2±9.2% and 35.2±9.5%, respectively (p<0.01). Thirteen children (62%) in group II (n=21) were classified in group I by the modified DRF measurement. Conclusions The modified DRF measurement calculated according to cross-sectional area showed fewer false-negative results and may be a valuable method for deciding on pyeloplasty under equivocal circumstances. PMID:20428431
Slotkin, T.A.; Kavlock, R.J.; Cowdery, T.; Orband, L.; Bartolome, M.
The effects of prenatal exposure to methylmercury on the functional development of renal and hepatic response systems was examined in the developing rat. Methylmercury produced an elevation of basal activity of renal ornithine decarboxylase (ODC, an enzyme involved in regulation of cellular maturation) and an eventual relative hypertrophy; liver ODC was reduced and hypertrophy was not evident. In contrast, the reactivity of liver ODC to trophic stimulants (vasopressin, isoproterenol) was markedly enhanced by prenatal methylmercury exposure, whereas renal ODC responses were much less affected (vasopressin) or actually reduced (isoproterenol). Targeted actions of methylmercury on renal excretory function were also prominent, with increased fractional excretions urea and electrolytes and an eventual reduction in glomerular filtration as assessed by creatinine clearance. These studies show that doses of methylmercury ordinarily associated with selective actions on development of neurobehavioral patterns also influence the functional ontogeny of other organ systems; furthermore, the fact that the target tissues are different for prenatal vs postnatal methylmercury exposure, indicates that the functional teratology of methylmercury exhibits critical periods of sensitivity.
Wael, Mai; Ibrahim, El-Sayed H; Fahmy, Ahmed S
Purpose. To develop a method for identifying abnormal myocardial function based on studying the normalized wall motion pattern during the cardiac cycle. Methods. The temporal pattern of the normalized myocardial wall thickness is used as a feature vector to assess the cardiac wall motion abnormality. Principal component analysis is used to reduce the feature dimensionality and the maximum likelihood method is used to differentiate between normal and abnormal features. The proposed method was applied on a dataset of 27 cases from normal subjects and patients. Results. The developed method achieved 81.5%, 85%, and 88.5% accuracy for identifying abnormal contractility in the basal, midventricular, and apical slices, respectively. Conclusions. A novel feature vector, namely, the normalized wall thickness, has been introduced for detecting myocardial regional wall motion abnormality. The proposed method provides assessment of the regional myocardial contractility for each cardiac segment and slice; therefore, it could be a valuable tool for automatic and fast determination of regional wall motion abnormality from conventional cine MRI images.
Pipeleers, L; Wissing, K M; Pirson, Y; Cosyns, J P; Geers, C; Tielemans, C
Enteric hyperoxaluria causes tubular deposition calcium oxalate crystals and severe chronic interstitial nephritis. We describe a patient with pre-terminal renal failure due to oxalate nephropathy after ileal resection. Increased oral hydration, low oxalate diet, and oral calcium carbonate and potassium citrate supplements resulted in a significant improvement of renal function. During the three-year follow-up, urinary oxalate concentration was repeatedly reduced below the crystallization threshold and serum creatinine decreased from 4.5 to 1.7 mg/dL. This case illustrates the benefit of combining and optimizing dietary and medical management in enteric hyperoxaluria, even in patients with advanced chronic kidney disease.
Lilis, R; Valciukas, J A; Weber, J P; Malkin, J; Selikoff, I J
A medical cross-sectional examination of a copper smelter work force was undertaken after environmental contamination with lead, cadmium and arsenic had been documented. A total of 920 subjects was examined, including active smelter employees, retired workers and copper mine employees who had never worked in the smelter. Slight to moderate absorption of lead and cadmium was definitely present in the active copper smelter employees, who had significantly higher levels of Pb-B, ZPP and Cd-B than retired employees and miners. Cd-U levels were higher in retired workers, who were also older and had, as a group, longer duration of exposure in the smelter. Cd-U did not exceed 10 micrograms/g creatinine, the level considered critical for nephrotoxicity, in any of the subjects. Median Cd-B level for active workers was 2.75 micrograms/L. Lead absorption was characterized by a relatively small proportion (16.7%) of active employees with Pb-B levels 40 micrograms/dL or higher. We were particularly interested in exploring the possibility that simultaneous exposure to lead and cadmium, although at levels not associated with nephrotoxicity for each metal separately, could result in renal function impairment. Distribution patterns of BUN and serum creatinine levels were unremarkable. Urinary beta 2-microglobulin levels were less than 200 micrograms/g creatinine in 95% of copper smelter employees. There were no significant correlations between urinary beta 2-microglobulin levels and Cd-U, Cd-B, Pb-B and ZPP or between urinary beta 2-microglobulin excretion and serum creatinine or BUN levels. Urinary beta 2-microglobulin levels were significantly correlated with age in the copper smelter workers, but not in the miners. Nevertheless, in the absence of any significant correlations between urinary beta 2-microglobulin and Cd-U, Cd-B, a causal relationship with cadmium absorption cannot be affirmed. That kidney function could be impaired by long-term exposure in the smelter was only
Alexander, E.L.; Firestein, G.S.; Weiss, J.L.; Heuser, R.R.; Leitl, G.; Wagner, H.N. Jr.; Brinker, J.A.; Ciuffo, A.A.; Becker, L.C.
The effects of peripheral cold exposure on myocardial perfusion and function were studied in 13 patients with scleroderma without clinically evident myocardial disease. Ten patients had at least one transient, cold-induced, myocardial perfusion defect visualized by thallium-201 scintigraphy, and 12 had reversible, cold-induced, segmental left ventricular hypokinesis by two-dimensional echocardiography. The 10 patients with transient perfusion defects all had anatomically corresponding ventricular wall motion abnormalities. No one in either of two control groups (9 normal volunteers and 7 patients with chest pain and normal coronary arteriograms) had cold-induced abnormalities. This study is the first to show the simultaneous occurrence of cold-induced abnormalities in myocardial perfusion and function in patients with scleroderma. The results suggest that cold exposure in such patients may elicit transient reflex coronary vasoconstriction resulting in reversible myocardial ischemia and dysfunction. Chronic recurrent episodes of coronary spasm may lead to focal myocardial fibrosis.
Cooper, E H; Forbes, M A; Crockson, R A; MacLennan, I C
Proximal renal tubular function was studied in 522 consecutive patients entered into the Medical Research Council's fourth myelomatosis trial. Assessment was made at presentation after a 48 h period of hydration but before administration of chemotherapy. The most common abnormalities in the urine other than light chain proteinuria were raised concentrations of the low molecular weight proteins alpha 1-microglobulin and alpha 1-acid glycoprotein. These were usually accompanied by increases in urinary beta-N-acetyl-D-glucosaminidase concentrations. The concentration of these substances in the urine directly correlated with urinary free light chain output. This tubular proteinuria was seen whether or not patients had impaired glomerular function, as assessed by a rise in serum creatinine concentration. Urinary concentrations of retinol binding protein, however, were generally increased only when serum creatinine concentrations were raised. This applied even when there were high concentrations of light chains, alpha 1-microglobulin, alpha 1-acid glycoprotein, and beta-N-acetyl-D-glucosaminidase in the urine. There is therefore a selective tubular proteinuria in myelomatosis which is seen in almost all patients with urinary light chain values greater than 1 u/l. This proteinuria is generally reversible, when light chains no longer appear in the urine. Patients whose serum creatinine was greater than 200 mumol/l, however, had increased urinary output of retinol binding protein in addition to increased excretion of alpha 1-microglobulin, alpha 1-acid glycoprotein, and beta-N-acetyl-D-glucosaminidase. Tubular proteinuria in many of these patients presenting in renal failure persisted even when light chain output was reduced after chemotherapy. PMID:6206095
Park, Sung Kwang; Kang, Sung Kyew
Objectives To investigate the renal function and hemodynamic changes in obesity and hyperinsulinemia which are characteristics of type II diabetes. Methods Studies were carried out in two groups of female Zucker rats. Group 1 rats were obese Zucker rats with hereditary insulin resistance. Group 2 rats were lean Zucker rats and served as controls. In comparison with lean Zucker rats, obese Zucker rats exhibited hyperinsulinemia but normoglycemia. Micropuncture studies and morphologic studies were performed in these rats. Results Functional studies showed that obese Zucker rats exhibited increases in kidney weight and GFR(obese Zucker, 1.23±.07)ml/min; lean Zucker, 0.93±.03ml/min). Micropuncture studies revealed that the increase in GFR in obese Zucker rats was attributable to the increases in the single nephron plasma flow rate and glomerular transcapillary hydraulic pressure. The glomerular ultrafiltration coefficient was the same in both groups. Morphologic studies revealed that the increase in GFR in obese Zucker rats was associated with an increase in glomerular volume. Conclusions These results suggest that obesity and hyperinsulinemia, which are the characteristics of type II diabetes, can be associated with glomerular hyperfiltration and glomerular capillary hypertension. PMID:7626557
Lilis, R.; Valciukas, J.A.; Weber, J.P.; Malkin, J.; Selikoff, I.J.
A medical cross-sectional examination of a copper smelter work force was undertaken after environmental contamination with lead, cadmium and arsenic had been documented. A total of 920 subjects was examined, including active smelter employees, retired workers and copper mine employees who had never worked in the smelter. Slight to moderate absorption of lead and cadmium was definitely present in the active copper smelter employees, who had significantly higher levels of Pb-B, ZPP and Cd-B than retired employees and miners. Cd-U levels were higher in retired workers, who were also older and had, as a group, longer duration of exposure in the smelter. Cd-U did not exceed 10 ..mu..g/g creatinine, the level considered critical for nephrotoxicity, in any of the subjects. Median Cd-B level for active workers was 2.75 ..mu..g/L. Lead absorption was characterized by a relatively small proportion (16.7%) of active employees with Pb-B levels 40 ..mu..g/dL or higher. That kidney function could be impaired by long-term exposure in the smelter was only indirectly suggested. Effects on renal function at the low levels of cadmium and lead absorption that were observed in this smelter population are minimal. 21 references, 8 figures, 21 tables.
Sheerin, Noella J; Newton, Phillip J; Macdonald, Peter S; Leung, Dominic Y C; Sibbritt, David; Spicer, Stephen Timothy; Johnson, Kay; Krum, Henry; Davidson, Patricia M
Acute decompensated heart failure is a common cause of hospitalisation. This is a period of vulnerability both in altered pathophysiology and also the potential for iatrogenesis due to therapeutic interventions. Renal dysfunction is often associated with heart failure and portends adverse outcomes. Identifying heart failure patients at risk of renal dysfunction is important in preventing progression to chronic kidney disease or worsening renal function, informing adjustment to medication management and potentially preventing adverse events. However, there is no working or consensus definition in international heart failure management guidelines for worsening renal function. In addition, there appears to be no concordance or adaptation of chronic kidney disease guidelines by heart failure guideline development groups for the monitoring of chronic kidney disease in heart failure. Our aim is to encourage the debate for an agreed definition given the prognostic impact of worsening renal function in heart failure. We present the case for the uptake of the Acute Kidney Injury Network criteria for acute kidney injury with some minor alterations. This has the potential to inform study design and meta-analysis thereby building the knowledgebase for guideline development. Definition consensus supports data element, clinical registry and electronic algorithm innovation as instruments for quality improvement and clinical research for better patient outcomes. In addition, we recommend all community managed heart failure patients have their baseline renal function classified and routinely monitored in accordance with established renal guidelines to help identify those at increased risk for worsening renal function or progression to chronic kidney disease.
Mahieu, Stella T; Gionotti, Marisa; Millen, Néstor; Elías, María Mónica
The aim of the present work was to study the nephrotoxicity of aluminum lactate administered for 3 months (0.57 mg/100 g bodyweight aluminum, i.p., three times per week) to male Wistar rats. Renal function was studied after 6 weeks of treatment (urine was obtained from rats in metabolic cages) and at the end of the treatment using clearance techniques. Another group of rats was used as kidneys donors at the end of treatment. The renal cortex was separated and homogenized to determine glutathione (GSH) level, glutathione S-transferase (GST) activity and lipid peroxidation (LPO) level. Renal cortex slices were also used to study the p-aminohippuric acid (PAH) accumulation during steady-state conditions and the kinetics of uptake process. Clearance results, at the end of the treatment, indicated that renal functions in treated-rats were not different from those measured in control rats, although the renal concentration parameters differ when they were measured in treated rats after 24 h of food and water deprivation. Balances of water and sodium were also modified at both 1.5 and 3 months of treatment. The activity of alkaline phosphatase (AP) relative to inulin excreted in urine was significantly impaired: controls 2.2+/-0.6 IUI/mg, Al-treated 5.1+/-0.5 IU/mg, P<0.05. These data indicated that proximal tubular cells were loosing apical brush border membranes. Data obtained in cortex homogenates indicated that both GSH and GST activity were significantly decreased, and a significant increase of LPO was noted simultaneously in Al-treated rats. Renal accumulation of PAH, estimated as slice-to-medium ratio, decreased significantly in the Al-treated rats: control rats 3.06+/-0.02 ( n=12), Al-treated rats 2.26+/-0.04 ( n=12), P<0.0001. The maximal rate of uptake was also diminished in treated rats, while the apparent affinity remained unchanged. All these results indicate that aluminum accumulation in renal tissue affects cellular metabolism, promotes oxidative stress and
Shepard, Blythe D; Pluznick, Jennifer L
Olfactory receptors (ORs) are chemosensors that are responsible for one's sense of smell. In addition to this specialized role in the nose, recent evidence suggests that ORs are also found in a variety of additional tissues including the kidney. As this list of renal ORs continues to expand, it is becoming clear that they play important roles in renal and whole-body physiology, including a novel role in blood pressure regulation. In this review, we highlight important considerations that are crucial when studying ORs and present the current literature on renal ORs and their emerging relevance in maintaining renal function.
Wolf, Robert Christian; Sambataro, Fabio; Lohr, Christina; Steinbrink, Claudia; Martin, Claudia; Vasic, Nenad
Behavioral and functional neuroimaging studies indicate deficits in verbal working memory (WM) and frontoparietal dysfunction in individuals with dyslexia. Additionally, structural brain abnormalities in dyslexics suggest a dysconnectivity of brain regions associated with phonological processing. However, little is known about the functional…
Background Lateralization of brain structure and function occurs in typical development, and abnormal lateralization is present in various neuropsychiatric disorders. Autism is characterized by a lack of left lateralization in structure and function of regions involved in language, such as Broca and Wernicke areas. Methods Using functional connectivity magnetic resonance imaging from a large publicly available sample (n = 964), we tested whether abnormal functional lateralization in autism exists preferentially in language regions or in a more diffuse pattern across networks of lateralized brain regions. Results The autism group exhibited significantly reduced left lateralization in a few connections involving language regions and regions from the default mode network, but results were not significant throughout left- and right-lateralized networks. There is a trend that suggests the lack of left lateralization in a connection involving Wernicke area and the posterior cingulate cortex associates with more severe autism. Conclusions Abnormal language lateralization in autism may be due to abnormal language development rather than to a deficit in hemispheric specialization of the entire brain. PMID:24502324
Guan, Zhengrong; Inscho, Edward W.
Adenosine triphosphate (ATP) is an essential energy substrate for cellular metabolism but it can also influence many biological processes when released into the extracellular milieu. Research has established that extracellular ATP acts as an autocrine/paracrine factor that regulates many physiological functions. Alternatively, excessive extracellular ATP levels contribute to pathophysiological processes such as inflammation, cell proliferation and apoptosis, and atherosclerosis. Renal P2 receptors are widely distributed throughout glomeruli, vasculature and tubular segments, and participate in controlling renal vascular resistance, mediating renal autoregulation, and regulating tubular transport function. This review will focus on the role of ATP-P2 receptor signaling in regulating renal microvascular function and autoregulation, recent advances on the role of ATP-P2 signaling in hypertension-associated renal vascular injury, and emerging new directions. PMID:21768526
Narayanan, Karthikeyan; Schumacher, Karl M; Tasnim, Farah; Kandasamy, Karthikeyan; Schumacher, Annegret; Ni, Ming; Gao, Shujun; Gopalan, Began; Zink, Daniele; Ying, Jackie Y
Renal cells are used in basic research, disease models, tissue engineering, drug screening, and in vitro toxicology. In order to provide a reliable source of human renal cells, we developed a protocol for the differentiation of human embryonic stem cells into renal epithelial cells. The differentiated stem cells expressed markers characteristic of renal proximal tubular cells and their precursors, whereas markers of other renal cell types were not expressed or expressed at low levels. Marker expression patterns of these differentiated stem cells and in vitro cultivated primary human renal proximal tubular cells were comparable. The differentiated stem cells showed morphological and functional characteristics of renal proximal tubular cells, and generated tubular structures in vitro and in vivo. In addition, the differentiated stem cells contributed in organ cultures for the formation of simple epithelia in the kidney cortex. Bioreactor experiments showed that these cells retained their functional characteristics under conditions as applied in bioartificial kidneys. Thus, our results show that human embryonic stem cells can differentiate into renal proximal tubular-like cells. Our approach would provide a source for human renal proximal tubular cells that are not affected by problems associated with immortalized cell lines or primary cells.
Andro, M; Estivin, S; Comps, E; Gentric, A
Assessment of renal function is essential in the management of hospitalised patients, particularly in geriatric practice. Impairment of renal function is common in the elderly, aged of 80 years and over, and should be taken into account before prescribing drugs eliminated through the kidneys or performing investigations requiring iodine injection. Renal failure is also a predictor of mortality. In clinical practice, creatinine-based equations are recommended to assess kidney function. The most widely used equations are the Cockroft and Gault (CG) and the simplified Modification of diet in renal disease (MDRD) formulas. The former estimates the clearance of creatinine in millilitres per minute, the latter estimates the glomerular filtration rate in millilitres per minute per 1.73 m(2). In 2002, the French high authority for health recommended the use of the CG formula, but no recommendation was given for the elderly. In the literature, no study has compared CG and MDRD formulas with a reference method in this very old population. In the octogenarians, two studies have compared these formulas with the creatinine clearance calculated on the basis of a 24-hour urine collection and four studies have compared the formulas head to head. All these studies showed that the results obtained with the MDRD formula are higher from 10 to 30 mL/min/1.73 m(2) than the results obtained with the CG formula. Studies simulating drug prescription showed that the use of the MDRD formula would lead to a risk of drug over dosage in 20 to 36% of the elderly. Also, two studies have suggested that only creatinine clearance measured by the CG formula is a predictor of mortality in the very old population. In conclusion, in the octogenarian, none of these two formulas is ideal. However, based on the results of studies targeted to this elderly population, the best solution seems to be the use of the CG formula expecting new methods of evaluation of renal function.
Bellinghieri, G; Triolo, O; Stella, N C; Gemelli, M; Musolino, R; Monardo, P; Savica, V
Cat-eye syndrome is a rare congenital anomaly involving the kidney. It is rarely reported in literature, while renal function has never been studied up to now. Shown here are the morphofunctional renal alterations observed in a female patient affected by cat-eye syndrome.
Xu, Yixiao; Lin, Hongzhou; Zheng, Wenjie; Ye, Xiaohua; Yu, Lingfang; Zhuang, Jieqiu; Yang, Qing; Wang, Dexuan
Matrine (MAT) is an active alkaloid extracted from Radix Sophora flavescens. The present study was to investigate whether MAT could effectively treat Adriamycin-induced nephropathy (AIN). AIN was induced in rats using a single injection of Adriamycin (ADR). Renal interleukin-6 (IL-6), IL-10, IL-17 and transforming growth factor-β (TGF-β) levels, and the expression of forkhead box protein 3 (Foxp3) and retinoid-related orphan nuclear receptor γt (Rorγt) was measured. AIN rats developed severe albuminuria, hypoalbuminaemia, hyperlipidaemia and podocyte injury. Daily administration of MAT (100mg/kg or 200mg/kg) significantly prevented ADR-induced podocyte injury, decreased AIN symptoms and improved renal pathology manifestations. Of note, treatment with MAT (100mg/kg) plus prednisone (Pre, 5mg/kg) had equivalent efficacy to that of Pre alone (10mg/kg). Additional findings showed that ADR triggered a disordered cytokine network and abnormal expression of Foxp3 and Rorγt in rats, as reflected by increased levels of IL-6, IL-10, TGF-β, Rorγt and decreased levels of IL-10 and Foxp3. Interestingly, MAT weakened the disordered cytokine network and normalized the expression of Foxp3 and Rorγt. In addition, a significant negative correlation was observed between the values of Foxp3/Rorγt and renal pathology scores. Finally, MAT normalized regulatory T cells (Treg)/ T-helper17 cells (Th17) ratio in peripheral blood mononuclear cells of AIN rats. These data indicate MAT prevents AIN through the modification of disordered plasma lipids and recovery of renal function, and this bioactivity is at least partly attributed to the suppression of renal inflammation and the regulation of the Treg/Th17 imbalance.
Kang, Jung Julie; Toma, Ildiko; Sipos, Arnold; McCulloch, Fiona; Peti-Peterdi, Janos
Multiphoton fluorescence microscopy offers the advantages of deep optical sectioning of living tissue with minimal phototoxicity and high optical resolution. More importantly, dynamic processes and multiple functions of an intact organ can be visualized in real time using noninvasive methods, and quantified. These studies aimed to extend existing methods of multiphoton fluorescence imaging to directly observe and quantify basic physiological parameters of the kidney including glomerular filtration rate (GFR) and permeability, blood flow, urinary concentration/dilution, renin content and release, as well as more integrated and complex functions like the tubuloglomerular feedback (TGF)-mediated oscillations in glomerular filtration and tubular flow. Streptozotocin-induced diabetes significantly increased single-nephron GFR (SNGFR) from 32.4 +/- 0.4 to 59.5 +/- 2.5 nl/min and glomerular permeability to a 70-kDa fluorophore approximately eightfold. The loop diuretic furosemide 2-fold diluted and increased approximately 10-fold the volume of distal tubular fluid, while also causing the release of 20% of juxtaglomerular renin content. Significantly higher speeds of individual red blood cells were measured in intraglomerular capillaries (16.7 +/- 0.4 mm/s) compared with peritubular vessels (4.7 +/- 0.2 mm/s). Regular periods of glomerular contraction-relaxation were observed, resulting in oscillations of filtration and tubular flow rate. Oscillations in proximal and distal tubular flow showed similar cycle times ( approximately 45 s) to glomerular filtration, with a delay of approximately 5-10 and 25-30 s, respectively. These innovative technologies provide the most complex, immediate, and dynamic portrayal of renal function, clearly depicting the components and mechanisms involved in normal physiology and pathophysiology.
Khan, Sheraz; Michmizos, Konstantinos; Tommerdahl, Mark; Ganesan, Santosh; Kitzbichler, Manfred G.; Zetino, Manuel; Garel, Keri-Lee A.; Herbert, Martha R.; Hämäläinen, Matti S.
Functional connectivity is abnormal in autism, but the nature of these abnormalities remains elusive. Different studies, mostly using functional magnetic resonance imaging, have found increased, decreased, or even mixed pattern functional connectivity abnormalities in autism, but no unifying framework has emerged to date. We measured functional connectivity in individuals with autism and in controls using magnetoencephalography, which allowed us to resolve both the directionality (feedforward versus feedback) and spatial scale (local or long-range) of functional connectivity. Specifically, we measured the cortical response and functional connectivity during a passive 25-Hz vibrotactile stimulation in the somatosensory cortex of 20 typically developing individuals and 15 individuals with autism, all males and right-handed, aged 8–18, and the mu-rhythm during resting state in a subset of these participants (12 per group, same age range). Two major significant group differences emerged in the response to the vibrotactile stimulus. First, the 50-Hz phase locking component of the cortical response, generated locally in the primary (S1) and secondary (S2) somatosensory cortex, was reduced in the autism group (P < 0.003, corrected). Second, feedforward functional connectivity between S1 and S2 was increased in the autism group (P < 0.004, corrected). During resting state, there was no group difference in the mu-α rhythm. In contrast, the mu-β rhythm, which has been associated with feedback connectivity, was significantly reduced in the autism group (P < 0.04, corrected). Furthermore, the strength of the mu-β was correlated to the relative strength of 50 Hz component of the response to the vibrotactile stimulus (r = 0.78, P < 0.00005), indicating a shared aetiology for these seemingly unrelated abnormalities. These magnetoencephalography-derived measures were correlated with two different behavioural sensory processing scores (P < 0.01 and P < 0.02 for the autism
Delanaye, Pierre; Flamant, Martin; Cavalier, Étienne; Guerber, Fabrice; Vallotton, Thomas; Moranne, Olivier; Pottel, Hans; Boffa, Jean-Jacques; Mariat, Christophe
While the CKD-EPI (for Chronic Kidney Disease Epidemiology) equation is now implemented worldwide, utilization of the Cockcroft formula is still advocated by some physicians for drug dosage adjustment. Justifications for this recommendation are that the Cockcroft formula was preferentially used to determine dose adjustments according to renal function during the development of many drugs, better predicts drugs-related adverse events and decreases the risk of drug overexposure in the elderly. In this opinion paper, we discuss the weaknesses of the rationale supporting the Cockcroft formula and endorse the French HAS (Haute Autorité de santé) recommendation regarding the preferential use of the CKD-EPI equation. When glomerular filtration rate (GFR) is estimated in order to adjust drug dosage, the CKD-EPI value should be re-expressed for the individual body surface area (BSA). Given the difficulty to accurately estimate GFR in the elderly and in individuals with extra-normal BSA, we recommend to prescribe in priority monitorable drugs in those populations or to determine their "true" GFR using a direct measurement method.
Peti-Peterdi, János; Kishore, Bellamkonda K; Pluznick, Jennifer L
To maintain metabolic homeostasis, the body must be able to monitor the concentration of a large number of substances, including metabolites, in real time and to use that information to regulate the activities of different metabolic pathways. Such regulation is achieved by the presence of sensors, termed metabolite receptors, in various tissues and cells of the body, which in turn convey the information to appropriate regulatory or positive or negative feedback systems. In this review, we cover the unique roles of metabolite receptors in renal and vascular function. These receptors play a wide variety of important roles in maintaining various aspects of homeostasis-from salt and water balance to metabolism-by sensing metabolites from a wide variety of sources. We discuss the role of metabolite sensors in sensing metabolites generated locally, metabolites generated at distant tissues or organs, or even metabolites generated by resident microbes. Metabolite receptors are also involved in various pathophysiological conditions and are being recognized as potential targets for new drugs. By highlighting three receptor families-(a) citric acid cycle intermediate receptors, (b) purinergic receptors, and
Cheng, T.H.; Holman, B.L.
Twenty-four patients with increased skeletal:renal uptake ratios of /sup 99m/Tc-methylene diphosphonate were studied. Increased uptake was central in metastatic prostate carcinoma, peripheral in hematologic disorders, and heterogeneous in Paget disease and fibrous dysplasia. There was no discernible redistribution of skeletal uptake in patients with renal failure. Absence of both renal and bladder activity was not observed in patients with normal renal function. An increased ratio was always abnormal and frequently indicated diffuse bone disease.
Fritzberg, Alan; Kasina, Sudhaker; Johnson, Dennis L.
The present invention is directed to novel radiopharmaceutical imaging agents incorporating Tc-99m as a radiolabel. In particular, the novel imaging agents disclosed herein have relatively high renal extraction efficiencies, and hence are useful for conducting renal function imaging procedures. The novel Tc-99m compounds of a present invention have the following general formula: ##STR1## wherein X is S or N; and wherein Y is --H or wherein Y is ##STR2## and where R.sub.1 is --H, --CH.sub.3, or --CH.sub.2 CH.sub.3 ; R.sub.2 is --H, --CH.sub.2 CO.sub.2 H, --CH.sub.2 CONH.sub.2, --CH.sub.2 CH.sub.2 CO.sub.2 H, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.3, --CH.sub.2 CH.sub.3, CH.sub.2 C.sub.6 H.sub.5, or --CH.sub.2 OH; and Z is --H, --CO.sub.2 H, --CONH.sub.2, --SO.sub.3 H, --SO.sub.2 NH.sub.2, or --CONHCH.sub.2 CO.sub.2 H; and the Tc is Tc-99m; and water-soluble salts thereof. Of the foregoing, the presently preferred Tc-99m compound of the present invention is Tc-99m-mercaptoacetylglycylglycylglycine (Tc-99m-MAGGG). The present invention is also directed to novel chelating agents that may be reacted with Tc-99m to form the foregoing compounds. Such novel chelating agents have the following general formula. ##STR3## where X and Y have the same definitions as above, and wherein Y' is --H.sub.2 when X is N, or wherein Y' is --H, or a suitable protective group such as --COCH.sub.3, --COC.sub.6 H.sub.5, --CH.sub.2 NHCOCH.sub.3, --COCF.sub.3, or --COCH.sub.2 OH when X is S. The present invention also provides methods for preparing and using the novel Tc-99m compounds.
Fritzberg, Alan; Kasina, Sudhakar; Johnson, Dennis L.
The present invention is directed to novel radiopharmaceutical imaging agents incorporating Tc-99m as a radiolabel. In particular, the novel imaging agents disclosed herein have relatively high renal extraction efficiencies, and hence are useful for conducting renal function imaging procedures. The novel Tc-99m compounds of a present invention have the following general formula: ##STR1## wherein X is S or N; and wherein Y is--H or wherein Y is ##STR2## and where R.sub.1 is --H, --CH.sub.3, or --CH.sub.2 CH.sub.3 ; R.sub.2 is --H, --CH.sub.2 CO.sub.2 H, --CH.sub.2 CONH.sub.2, --CH.sub.2 CH.sub.2 CO.sub.2 H, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.3, --CH.sub.2 CH.sub.3, CH.sub.2 C.sub.6 H.sub.5, or --CH.sub.2 OH; and Z is --H, --CO.sub.2 H, --CONH.sub.2, --SO.sub.3 H, --SO.sub.2 NH.sub.2, or --CONHCH.sub.2 CO.sub.2 H; and the Tc is Tc-99m; and water-soluble salts thereof. Of the foregoing, the presently preferred Tc-99m compound of the present invention is Tc-99m-mercaptoacetylglycylglycylglycine (Tc-99m-MAGGG). The present invention is also directed to novel chelating agents that may be reacted with Tc-99m to form the foregoing compounds. Such novel chelating agents have the following general formula. ##STR3## where X and Y have the same definitions as above, and wherein Y' is --H.sub.2 when X is N, or wherein Y' is --H, or a suitable protective group such as --COCH.sub.3, --COC.sub.6 H.sub.5, --CH.sub.2 NHCOCH.sub.3, --COCF.sub.3, or --COCH.sub.2 OH when X is S. The present invention also provides methods for preparing and using the novel Tc-99m compounds.
D'Amico, G; Ferrario, F; Colasanti, G; Ragni, A; Bestetti Bosisio, M
End-stage renal failure requiring dialysis treatment developed within 5 years in 11 patients with IgA mesangial glomerulonephritis (out of 94 affected by this nephropathy) whose serum creatinine levels were less than 2 mg/100 ml at the time of biopsy. We compared these patients (Group 1) with 10 patients (Group 2) whose serum creatinine was comparable at the time of biopsy (1.2 +/- 0.3 vs 1.4 +/- 0.3 mg/100 ml) but remained unchanged (1.1 +/- 0.4 mg/100 ml) at the end of a minimum post-biopsy follow-up of 5 years. The analysis of clinical findings, at the time of biopsy, showed that the mean duration of disease, from apparent onset, was shorter in Group 1. Recurrent macroscopic hematuria, never reported in this group, was present in 40% of patients of Group 2, whereas minimal urinary abnormalities, discovered by chance, were the only findings in 73% of patients of Group 1 and in 30% of Group 2. No difference was present between the patients in the two groups in the amount of proteinuria and in the incidence of high IgA serum levels, whereas hypertension was more frequent (45% vs 20%) in Group 1. The analysis of histological lesions demonstrated that in Group 1 there was a greater incidence of diffuse mesangial proliferation (82% vs 30%), of extensive glomerular obsolescence (64% vs 0) and of severe interstitial fibrosis (54% vs 0). Immunofluorescence findings were similar in the two groups. Although no single clinical or morphological parameter was characteristic of the patients with subsequent rapid decline of renal function, some features were more commonly observed, or more severe, in these patients, and therefore should be considered reliable predictors of an unfavourable outcome.
Almueilo, Samir H
Renal dysfunction is encountered in 20-25% of patients with multiple myeloma (MM) at the time of diagnosis. There is often a precipitating event. Several biochemical and clinical correlations with renal failure in MM have been reported. Renal failure in MM is associated with worse outcome of the disease. We retrospectively analyzed the medical records of 64 patients with MM admitted to our institution during the period January 1992 to December 2012. Abnormal renal function was observed in 24 (37.5%) patients and 17 (26.6%) of them had renal failure; 14 of the 17 (82.4%) of patients with renal failure had Stage III MM. Urine Bence- Jones protein was positive in ten (58.8%) patients with renal failure versus ten (21.3%) patients without renal failure (P = 0.004). Potential precipitating factors of renal failure were determined in nine patients. Renal function normalized in 11 patients with simple measures, while six patients required hemodialysis; one remained dialysis dependent till time of death. Early mortality occurred in five (29.4%) patients with renal failure as compared with two (4.3%) patients in the group without renal failure (P = 0.005). In conclusion, renal failure is associated with a higher tumor burden and Bence-Jones proteinuria in patients with MM. It is reversible in the majority of patients; however, early mortality tends to be higher in patients with persistent renal failure.
cholinomimetic- induced diuresis , they do demonstrate a direct action of these compounds on renal cell electrolyte balance. Carter’s group did not examine the...Carrier. J. Friborg and 3. P. Onay, Vasodilators, intrarenal blood flow, and natriuresis in the dog. Amer. 3. Physiol., 221 (1971) 92- 98. 11. U.K...tylchol insestaraso activity. Diochem. Pharmacol., 7 (1961) 88-94. 19. 3.P. Hayslett, U. Kashgarian and F.H. Epstein, The diuresis of renal 17
Jesinkey, Sean R; Funk, Jason A; Stallons, L Jay; Wills, Lauren P; Megyesi, Judit K; Beeson, Craig C; Schnellmann, Rick G
Mitochondrial biogenesis may be an adaptive response necessary for meeting the increased metabolic and energy demands during organ recovery after acute injury, and renal mitochondrial dysfunction has been implicated in the pathogenesis of AKI. We proposed that stimulation of mitochondrial biogenesis 24 hours after ischemia/reperfusion (I/R)-induced AKI, when renal dysfunction is maximal, would accelerate recovery of mitochondrial and renal function in mice. We recently showed that formoterol, a potent, highly specific, and long-acting β2-adrenergic agonist, induces renal mitochondrial biogenesis in naive mice. Animals were subjected to sham or I/R-induced AKI, followed by once-daily intraperitoneal injection with vehicle or formoterol beginning 24 hours after surgery and continuing through 144 hours after surgery. Treatment with formoterol restored renal function, rescued renal tubules from injury, and diminished necrosis after I/R-induced AKI. Concomitantly, formoterol stimulated mitochondrial biogenesis and restored the expression and function of mitochondrial proteins. Taken together, these results provide proof of principle that a novel drug therapy to treat AKI, and potentially other acute organ failures, works by restoring mitochondrial function and accelerating the recovery of renal function after injury has occurred.
Kurtz, Ira; Zhu, Quansheng
NBCe1 belongs to the SLC4 family of base transporting membrane proteins that plays a significant role in renal, extrarenal, and systemic acid-base homeostasis. Recent progress has been made in characterizing the structure-function properties of NBCe1 (encoded by the SLC4A4 gene), and those factors that regulate its function. In the kidney, the NBCe1-A variant that is expressed on the basolateral membrane of proximal tubule is the key transporter responsible for overall transepithelial bicarbonate absorption in this nephron segment. NBCe1 mutations impair transepithelial bicarbonate absorption causing the syndrome of proximal renal tubular acidosis (pRTA). Studies of naturally occurring NBCe1 mutant proteins in heterologous expression systems have been very helpful in elucidation the structure-functional properties of the transporter. NBCe1 mutations are now known to cause pRTA by various mechanisms including the alteration of the transporter function (substrate ion interaction, electrogenicity), abnormal processing to the plasma membrane, and a perturbation in its structural properties. The elucidation of how NBCe1 mutations cause pRTA in addition to the recent studies which have provided further insight into the topology of the transporter have played an important role in uncovering its critically important structural-function properties. PMID:24391589
Li, Chao; Dong, Mengshi; Yin, Yi; Hua, Kelei; Fu, Shishun; Jiang, Guihua
The investigation of the mechanism of insomnia could provide the basis for improved understanding and treatment of insomnia. The aim of this study is to investigate the abnormal functional connectivity throughout the entire brain of insomnia patients, and analyze the global distribution of these abnormalities. Whole brains of 50 patients with insomnia and 40 healthy controls were divided into 116 regions and abnormal connectivities were identified by comparing the Pearson’s correlation coefficients of each pair using general linear model analyses with covariates of age, sex, and duration of education. In patients with insomnia, regions that relate to wakefulness, emotion, worry/rumination, saliency/attention, and sensory-motor showed increased positive connectivity with each other; however, regions that often restrain each other, such as regions in salience network with regions in default mode network, showed decreased positive connectivity. Correlation analysis indicated that some increased positive functional connectivity was associated with the Self-Rating Depression Scale, Insomnia Severity Index, and Pittsburgh Sleep Quality Index scores. According to our findings, increased and decreased positive connectivities suggest function strengthening and function disinhibition, respectively, which offers a parsimonious explanation for the hyperarousal hypothesis in the level of the whole-brain functional connectivity in patients with insomnia. PMID:28243094
Li, Chao; Dong, Mengshi; Yin, Yi; Hua, Kelei; Fu, Shishun; Jiang, Guihua
The investigation of the mechanism of insomnia could provide the basis for improved understanding and treatment of insomnia. The aim of this study is to investigate the abnormal functional connectivity throughout the entire brain of insomnia patients, and analyze the global distribution of these abnormalities. Whole brains of 50 patients with insomnia and 40 healthy controls were divided into 116 regions and abnormal connectivities were identified by comparing the Pearson's correlation coefficients of each pair using general linear model analyses with covariates of age, sex, and duration of education. In patients with insomnia, regions that relate to wakefulness, emotion, worry/rumination, saliency/attention, and sensory-motor showed increased positive connectivity with each other; however, regions that often restrain each other, such as regions in salience network with regions in default mode network, showed decreased positive connectivity. Correlation analysis indicated that some increased positive functional connectivity was associated with the Self-Rating Depression Scale, Insomnia Severity Index, and Pittsburgh Sleep Quality Index scores. According to our findings, increased and decreased positive connectivities suggest function strengthening and function disinhibition, respectively, which offers a parsimonious explanation for the hyperarousal hypothesis in the level of the whole-brain functional connectivity in patients with insomnia.
Bonarjee, V. V.; Omland, T.; Nilsen, D. W.; Caidahl, K.; Sundsfjord, J. A.; Dickstein, K.
OBJECTIVES--(a) To assess the relation between plasma concentrations of proatrial natriuretic factor (1-98) and non-invasively derived indices of left ventricular systolic and diastolic performance and (b) to assess the potential confounding effect of renal function and age on this relation in patients with acute myocardial infarction. DESIGN--Cross sectional comparison of biochemical and echocardiographic indices of cardiac function. SETTING--Norwegian central hospital. PATIENTS--Sixty four patients with acute myocardial infarction. MAIN OUTCOME MEASURES--Relation between plasma proatrial natriuretic factor (1-98) concentrations and echocardiographic indices of left ventricular systolic function as assessed by univariate and multivariate linear regression analysis. Sensitivity and specificity of plasma proatrial natriuretic factor (1-98) concentration as a measure of left ventricular systolic and diastolic dysfunction. RESULTS--Plasma proatrial natriuretic factor (1-98) concentrations were significantly related to left ventricular ejection fraction (r = -0.33; P = 0.008), age (r = 0.43; P < 0.001), and creatinine clearance (r = - 0.53; P < 0.001). In a multivariate model left ventricular ejection fraction and creatinine clearance were both independently related to plasma values. The mean concentration of proatrial natriuretic factor (1-98) was significantly higher in patients with an ejection fraction of < 40% than in those with an ejection fraction of > or = 40% (1876 (1151) v 1174 (530) pmol/l; P = 0.03) and in patients with an abnormal transmitral E/A ratio ( < 0.65 or > 1.65, where E/A is ratio of peak early filling velocity to peak atrial component) compared with those with a normal ratio (1572 (895) v 1137 (523) pmol/l, respectively; P = 0.02). When patients were subdivided according to the median concentration of proatrial natriuretic factor (1192 pmol/l) the sensitivity and specificity were 89% and 56% respectively for detecting a left ventricular ejection
Kelly, K J; Zhang, Jizhong; Han, Ling; Kamocka, Malgorzata; Miller, Caroline; Gattone, Vincent H; Dominguez, Jesus H
Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA.
Gruskin, A B; Root, A W; Duckett, G E; Baluarte, H J
Function of the parathyroid gland was evaluated in children with renal insufficiency prior to and after imitation of hemodialysis, and again following renal transplantation. Serum levels of immunoreactive parathyroid hormone responded appropriately to increases or decreases of serum calcium concentrations in the three groups. Functional and histologic studies in the children with renal insufficiency demonstrated the cause of their elevated circulating levels of iPTH to be diffuse parathyroid hyperplasia. During hemodialysis, the serum concentration of calcium rose and that of iPTH decreased, when the calcium gradient between the dialysate and the blood favored movement of calcium into the body. During treatment with prednisolone (20 mg/kg intravenously) for reversal of renal transplant rejection, the serum concentration of calcium decreased and that of iPTH increased. These observations suggest that autonomy of the parathyroid gland rarely occurs in children with renal insufficiency, and that hemodialysis using a dialysate with a high concentration of calcium might assist in retarding the progression of renal osteodystrophy. Furthermore, if hyperparathyroidism contributes in part to growth failure in children with chronic renal disease, steroid-induced changes in cirulating iPTH following renal transplantation may inhibit growth.
Ungar, Andrea; Iacomelli, Iacopo; Giordano, Antonella; Roberts, Anna Teresa; Rafanelli, Martina; Marchionni, Niccolò
In the elderly assessment of renal function by glomerular filtration rate estimation is crucial for diagnostic, therapeutic and prognostic purposes. Our aim is to illustrate the different formulas available and their respective advantages and disadvantages.
Gibbons, Christopher H.; Bonyhay, Istvan; Benson, Adam; Wang, Ningshan; Freeman, Roy
Objective To define the neuropathology, clinical phenotype, autonomic physiology and differentiating features in individuals with neuropathic and non-neuropathic postural tachycardia syndrome (POTS). Methods Twenty-four subjects with POTS and 10 healthy control subjects had skin biopsy analysis of intra-epidermal nerve fiber density (IENFD), quantitative sensory testing (QST) and autonomic testing. Subjects completed quality of life, fatigue and disability questionnaires. Subjects were divided into neuropathic and non-neuropathic POTS, defined by abnormal IENFD and abnormal small fiber and sudomotor function. Results Nine of 24 subjects had neuropathic POTS and had significantly lower resting and tilted heart rates; reduced parasympathetic function; and lower phase 4 valsalva maneuver overshoot compared with those with non-neuropathic POTS (P<0.05). Neuropathic POTS subjects also had less anxiety and depression and greater overall self-perceived health-related quality of life scores than non-neuropathic POTS subjects. A sub-group of POTS patients (cholinergic POTS) had abnormal proximal sudomotor function and symptoms that suggest gastrointestinal and genitourinary parasympathetic nervous system dysfunction. Conclusions and Relevance POTS subtypes may be distinguished using small fiber and autonomic structural and functional criteria. Patients with non-neuropathic POTS have greater anxiety, greater depression and lower health-related quality of life scores compared to those with neuropathic POTS. These findings suggest different pathophysiological processes underlie the postural tachycardia in neuropathic and non-neuropathic POTS patients. The findings have implications for the therapeutic interventions to treat this disorder. PMID:24386408
Jensen, Jens Dam; Peters, Christian Daugaard; Jespersen, Bente
It has been documented that preservation of residual renal function in dialysis patients improves quality of life as well as survival. Clinical trials on strategies to preserve residual renal function are clearly lacking. While waiting for more results from clinical trials, patients will benefit from clinicians being aware of available knowledge. The aim of this review was to offer an update on current evidence assisting doctors in clinical practice. PMID:25949486
Samoni, Sara; Nalesso, Federico; Meola, Mario; Villa, Gianluca; De Cal, Massimo; De Rosa, Silvia; Petrucci, Ilaria; Brendolan, Alessandra; Rosner, Mitchell H; Ronco, Claudio
An increase of glomerular filtration rate after protein load represents renal functional reserve (RFR) and is due to afferent arteriolar vasodilation. Lack of RFR may be a risk factor for acute kidney injury (AKI), but is cumbersome to measure. We sought to develop a non-invasive, bedside method that would indirectly measure RFR. Mechanical abdominal pressure, through compression of renal vessels, decreases blood flow and activates the auto-regulatory mechanism which can be measured by a fall in renal resistive index (RRI). The study aims at elucidating the relationship between intra-parenchymal renal resistive index variation (IRRIV) during abdominal pressure and RFR. In healthy volunteers, pressure was applied by a weight on the abdomen (fluid-bag 10% of subject's body weight) while RFR was measured through a protein loading test. We recorded RRI in an interlobular artery after application of pressure using ultrasound. The maximum percentage reduction of RRI from baseline was compared in the same subject to RFR. We enrolled 14 male and 16 female subjects (mean age 38 ± 14 years). Mean creatinine clearance was 106.2 ± 16.4 ml/min/1.73 m(2). RFR ranged between -1.9 and 59.7 with a mean value of 28.9 ± 13.1 ml/min/1.73 m(2). Mean baseline RRI was 0.61 ± 0.05, compared to 0.49 ± 0.06 during abdominal pressure; IRRIV was 19.6 ± 6.7%, ranging between 3.1% and 29.2%. Pearson's coefficient between RFR and IRRIV was 74.16% (p < 0.001). Our data show the correlation between IRRIV and RFR. Our results can lead to the development of a "stress test" for a rapid screen of RFR to establish renal susceptibility to different exposures and the consequent risk for AKI.
Bruder, Gerard E; Stewart, Jonathan W; Hellerstein, David; Alvarenga, Jorge E; Alschuler, Daniel; McGrath, Patrick J
Prior studies have found abnormalities of functional brain asymmetry in patients having a major depressive disorder (MDD). This study aimed to replicate findings of reduced right hemisphere advantage for perceiving dichotic complex tones in depressed patients, and to determine whether patients having "pure" dysthymia show the same abnormality of perceptual asymmetry as MDD. It also examined gender differences in lateralization, and the extent to which abnormalities of perceptual asymmetry in depressed patients are dependent on gender. Unmedicated patients having either a MDD (n=96) or "pure" dysthymic disorder (n=42) and healthy controls (n=114) were tested on dichotic fused-words and complex-tone tests. Patient and control groups differed in right hemisphere advantage for complex tones, but not left hemisphere advantage for words. Reduced right hemisphere advantage for tones was equally present in MDD and dysthymia, but was more evident among depressed men than depressed women. Also, healthy men had greater hemispheric asymmetry than healthy women for both words and tones, whereas this gender difference was not seen for depressed patients. Dysthymia and MDD share a common abnormality of hemispheric asymmetry for dichotic listening.
Wu, Chung-Kuan; Leu, Jyh-Gang; Wei, Cheng-Chun; Hsieh, Shih-Chung
Abstract Background: Acute thrombosis of a transplanted renal artery is a serious vascular complication following renal allograft transplantation, which usually occurs within the first month after transplantation and often results in graft loss. It rarely occurs beyond the first month, except in a rejected kidney or in a kidney with high-grade transplant renal artery stenosis. Result: A 65-year-old male with a history of type 2 diabetes mellitus, hypertension, pulmonary tuberculosis, and end-stage renal disease was previously treated with hemodialysis (HD). He received a kidney transplant and had a well-functioning graft for 2 years. He presented to our emergency department with gastric ulcer bleeding and received treatment involving an endoscopic submucosal epinephrine injection, a proton pump inhibitor, and blood transfusions. Nine days later, he complained of sudden lower abdominal pain and had acute anuric kidney failure. Renal ultrasonography revealed an absence of blood flow to the allograft kidney. Renal artery angiogram demonstrated complete occlusion of the transplanted renal artery. After thrombectomy and percutaneous transluminal angioplasty (PTA) with stent placement, 60% stenosis of the proximal renal artery with distal perfusion was noted. However, his graft function did not improve, and he received HD again. Histopathology of the transplanted kidney revealed ischemic tubular nephropathy with focal infarction without rejection. Conclusion: This is the first case of acute thrombosis of the transplanted renal artery following gastric ulcer bleeding in a patient with a long-term well-functioning graft kidney. PMID:27472705
Mehta, Rajendra H; Honeycutt, Emily; Patel, Uptal D; Lopes, Renato D; Shaw, Linda K; Glower, Donald D; Harrington, Robert A; Califf, Robert M; Sketch, Michael H
Whether prognosis differs in acute renal failure (ARF) after coronary artery bypass grafting (CABG) in patients with and without recovery of renal function is not known. We studied patients who had CABG at Duke University Medical Center (1995 to 2008). ARF was defined as an increase in peak creatinine ≥50% after CABG or ≥0.7 mg/dl above baseline or need for new dialysis. Patients were categorized into 3 groups: (1) no ARF after CABG, (2) ARF after CABG and completely recovered renal function at day 7 (return of creatinine to no higher than baseline and no dialysis), or (3) ARF after CABG with no recovery of renal function at day 7 (creatinine no higher than baseline or new dialysis). Main outcome measurement was risk-adjusted long-term mortality (excluding death ≤7 days). ARF after CABG occurred in 2,083 of 10,415 patients (20%) and completely recovered in 703 (33.7%). Risk-adjusted mortality was highest in patients with ARF without recovery of renal function (hazard ratios 1.47, 95% confidence interval 1.34 to 1.62) and intermediate in those with ARF but completely recovered renal function (hazard ratios 1.21, 95% confidence interval 1.07 to 1.37, referent no-ARF group). Mortality was lower in patients with ARF compared to those without complete recovery of renal function (p = 0.0083). In conclusion, in patients with ARF after CABG, complete recovery of renal function was associated with significantly lower long-term mortality compared to those without such recovery, although this was significantly higher than in those without ARF. Thus, major emphasis should be on prevention of ARF in patients undergoing CABG.
Gupta, Punkaj; Carlson, Jacob; Wells, Dennis; Selakovich, Patrick; Robertson, Michael J; Gossett, Jeffrey M; Fontenot, Eudice E; Steiner, Matthew B
The effects of extracorporeal membrane oxygenation (ECMO) support on renal function in children with critical illness are unknown. The objective of this study was to investigate the impact of ECMO on renal function among children in different age groups. We performed a single-center retrospective observational study in critically ill children ≤ 18 years supported on ECMO for refractory cardiac or pulmonary failure (2006-2012). The patient population was divided into four age groups for the purpose of comparisons. The Acute Kidney Injury Network's (AKIN's) validated, three-tiered staging system for acute kidney injury was used to categorize the degree of worsening renal function. Data on patient demographics, baseline characteristics, renal function parameters, dialysis, ultrafiltration, duration of mechanical cardiac support, and mortality were collected. Comparisons of baseline characteristics, duration of mechanical cardiac support, and renal function were made between the four age groups. During the study period, 311 patients qualified for inclusion, of whom 289 patients (94%) received venoarterial (VA) ECMO, 12 (4%) received venovenous (VV) ECMO, and 8 (3%) received both VV and VA ECMO. A total of 109 patients (36%) received ultrafiltration on ECMO, 58 (19%) received hemodialysis, and 51 (16%) received peritoneal dialysis. There was a steady and sustained improvement in renal function in all age groups during the ECMO run, with the maximum and longest-sustained improvement occurring in the oldest age group. Proportions of patients in different AKIN stages remained similar in the first 7 days after ECMO initiation. We demonstrate that renal dysfunction improves early after ECMO support. Irrespective of the underlying disease process or patient age, renal function improves in children with pulmonary or cardiac failure who are placed on ECMO.
Tinti, F; Umbro, I; Meçule, A; Rossi, M; Merli, M; Nofroni, I; Corradini, S Ginanni; Poli, L; Pugliese, F; Ruberto, F; Berloco, P B; Mitterhofer, A P
Renal dysfunction in cirrhotic patients is primary related to disturbances of circulatory function, triggered by portal hypertension with chronic intrarenal vasoconstriction and hypoperfusion. Pretransplant renal function is an important factor implicated in the development of acute renal failure (ARF) after liver transplantation (OLT), but other factors mostly related to liver function seem to influence the development of ARF. The Acute Dialysis Quality Initiative workgroup developed the RIFLE classification to define ARF. We sought to evaluate the incidence of ARF among patients undergoing OLT, to evaluate the association of ARF with pre-OLT renal and hepatic functions, and to evaluate the influence of ARF on chronic kidney disease (CKD) at 1 month post-OLT. Clinical, renal, hepatic function, and donor risk index data of 24 patients who underwent deceased donor OLT were collected before transplantation, in the perioperative period and in the first month post-OLT. ARF occurred in 37.5% of patients with 56% developing the R grade and 44% the I grade; no patient showed the F grade. An association was observed between ARF and a higher Model for End-Stage Liver Disease (MELD) score and between ARF and a reduced pre-OLT serum albumin. No association was noted between ARF and other pre-OLT parameters. In cirrhotic patients serum creatinine is a bias for renal function assessment and the Modification of Diet in Renal Disease formula overestimates GFR. Post-OLT CKD was present in 6.7% of patients without ARF and in 44.4% of patients with ARF. The R grade developed more frequently among patients with viral cirrhosis. The association of ARF with MELD and hypoalbuminemia may be the result of a close relationship between renal and hepatic functions among cirrhotic patients. Post-OLT CKD may be the result of unrecognized, preexisting CKD and/or the effects of not fully resolved acute damage to an injured kidney.
Gupta, Samir K.; Kitch, Douglas; Tierney, Camlin; Daar, Eric S.; Sax, Paul E.; Melbourne, Kathleen; Ha, Belinda; McComsey, Grace A.
Background. The effects of antiretrovirals on cystatin C-based renal function estimates are unknown. Methods. We analyzed changes in renal function using creatinine and cystatin C-based estimating equations in 269 patients in A5224s, a substudy of study A5202, in which treatment-naive patients were randomized to abacavir/lamivudine or tenofovir/emtricitabine with open-label atazanavir/ritonavir or efavirenz. Results. Changes in renal function significantly improved (or declined less) with abacavir/lamivudine treatment compared with tenofovir/emtricitabine using the Cockcroft-Gault formula (P = .016) and 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI; P = .030) and 2012 CKD-EPI cystatin C-creatinine (P = .025). Renal function changes significantly improved (or declined less) with efavirenz compared with atazanavir/ritonavir (P < .001 for all equations). Mean (95% confidence interval) renal function changes specifically for tenofovir/emtricitabine combined with atazanavir/ritonavir were −8.3 (−14.0, −2.6) mL/min with Cockcroft-Gault; −14.9 (−19.7, −10.1) mL/min per 1.732 with Modification of Diet in Renal Disease; −12.8 (−16.5, −9.0) mL/min per 1.732 with 2009 CKD-EPI; +8.9 (4.2, 13.7) mL/min per 1.732 with 2012 CKD-EPI cystatin C; and −1.2 (−5.1, 2.6) mL/min per 1.732 with 2012 CKD-EPI cystatin C-creatinine. Renal function changes for the other treatment arms were more favorable but similarly varied by estimating equation. Conclusions. Antiretroviral-associated changes in renal function vary in magnitude and direction based on the estimating equation used. PMID:25734077
van Veldhuisen, Dirk J; Ruilope, Luis M; Maisel, Alan S; Damman, Kevin
Heart failure guidelines suggest evaluating renal function as a routine work-up in every patient with heart failure. Specifically, it is advised to calculate glomerular filtration rate and determine blood urea nitrogen. The reason for this is that renal impairment and worsening renal function (WRF) are common in heart failure, and strongly associate with poor outcome. Renal function, however, consists of more than glomerular filtration alone, and includes tubulointerstitial damage and albuminuria. For each of these renal entities, different biomarkers exist that have been investigated in heart failure. Hypothetically, and in parallel to data in nephrology, these markers may aid in the diagnosis of renal dysfunction, or for risk stratification, or could help in therapeutic decision-making. However, as reviewed in the present manuscript, while these markers may carry prognostic information (although not always additive to established markers of renal function), their role in predicting WRF is limited at best. More importantly, none of these markers have been evaluated as a therapeutic target nor have their serial values been used to guide therapy. The evidence is most compelling for the oldest-serum creatinine (in combination with glomerular filtration rate)-but even for this biomarker, evidence to guide therapy to improve outcome is circumstantial at best. Although many new renal biomarkers have emerged at the horizon, they have only limited usefulness in clinical practice until thoroughly and prospectively studied. For now, routine measurement of (novel) renal biomarkers can help to determine cardiovascular risk, but there is no role for these biomarkers to change therapy to improve clinical outcome in heart failure.
Kawamura, J; Itoh, H; Okada, Y; Higashi, Y; Yoshida, O; Fujita, T; Torizuka, K
99mTechnetium dimercaptosuccinic acid renal scintigraphy, consisting of the cortical image and dimercaptosuccinic acid renal uptake rate, was used to assess preoperative and postoperative renal function in 55 patients with staghorn calculi. In 14 of 20 patients who had undergone extended pyelolithotomy and in 4 of 22 who had undergone nephrolithotomy there was an increase or no change in the postoperative dimercaptosuccinic acid renal uptake in the surgically treated kidney. However, there was no increase in the postoperative dimercaptosuccinic acid renal uptake in the patients who had undergone pyelolithotomy combined with nephrotomy or partial nephrectomy. Eight per cent of the preoperative dimercaptosuccinic acid renal uptake rate in the diseased kidney seems to be the absolute level for predicting the postoperative recovery of renal function. Dimercaptosuccinic acid renal images provide evidence of morphological changes in the cortex of the kidney with stones and the dimercaptosuccinic acid uptake rate is a useful adjunct for quantitative assessments of preoperative and postoperative residual cortical function.
Gross, R; Kirchheim, H; Ruffmann, K
We studied the effect of bilateral common carotid occlusion (implanted pneumatic cuffs) on renal blood flow (electromagnetic flowmeter) and renal function (implanted ureteral catheter) in nine chronically instrumented, conscious dogs on a high sodium diet (14 mmol/kg body weight per day). By means of suprarenal aortic constriction (pneumatic cuff) the influence of renal perfusion pressure was investigated. There was no change in renal blood flow or glomerular filtration rate (inulin clearance) with either reflexly increasing (+49.6%) or constant renal perfusion pressure. Carotid occlusion caused an increase of urine output by 80.5% and of sodium excretion by 85.3% due to a fall in fractional sodium reabsorption (-0.9%) when renal perfusion pressure was allowed to rise. Neither an increase of diuresis or sodium excretion nor an antinatriuresis was observed when renal perfusion pressure was kept constant during carotid occlusion. We conclude that, in conscious dogs at rest, the moderate sympathetic activation associated with carotid occlusion is too small to induce renal sympathetic vasoconstriction or antinatriuresis. The "carotid sinus polyuria" is a pressure-diuresis.
Park, Hyeon-Mi; Noh, Young; Yang, Ji Won; Shin, Dong Hoon; Lee, Yeong-Bae
Cefepime-induced encephalopathy including nonconvulsive status epilepticus has been known to develop in the patients with renal impairment. However, we report a 74-year-old woman with normal renal function who developed stuporous mental status during cefepime administration. Electroencephalogram (EEG) revealed 2 Hz rhythmic sharp-and-waves continuously, which suggested nonconvulsive status epilepticus (NCSE). After cefepime discontinuation, clinical symptoms recovered gradually and EEG findings showed only background slowing without epileptiform discharges. Cefepime-induced NCSE could be developed even in the patients with normal renal function, when they are elderly. Therefore, clinicians should be aware of the possibility of cefepime-induced NCSE when prescribing cefepime even to the patients with normal renal function. PMID:28101482
Omar, Ahmed; Ellen, Ruth; Sorisky, Alexander
We report a case of metformin-associated lactic acidosis (MALA) in the setting of normal renal function and review the relevant medical literature. A 77-year-old female diagnosed with type 2 diabetes mellitus previously treated with insulin and gliclazide MR was started on metformin. A few weeks later, she was found to have lactic acidosis. Renal function was normal, and no severe underlying illness was identified. Metformin was discontinued, and lactate levels normalized within 4 days, suggesting metformin was a reversible precipitant of the lactic acidosis. MALA can occur in the absence of renal impairment, systemic hypoperfusion or severe liver disease. A possible mechanism is a genetically determined alteration in metformin pharmacokinetics. Metformin is beneficial and safe in patients with normal renal function, but the development of MALA, although rare, should be kept in mind to prevent potentially life-threatening toxicity.
Peng, Yu-Hsuan; Sweet, Douglas H.; Lin, Shiuan-Pey; Yu, Chung-Ping; Lee Chao, Pei-Dawn; Hou, Yu-Chi
Chronic kidney disease (CKD) is a major health problem worldwide. Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are highly protein-bound nephro-cardiovascular toxins, which are not efficiently removed through hemodialysis. The renal excretions of IS and PCS were mediated by organic anion transporters (OATs) such as OAT1 and OAT3. Green tea (GT) is a popular beverage containing plenty of catechins. Previous pharmacokinetic studies of teas have shown that the major molecules present in the bloodstream are the glucuronides/sulfates of tea catechins, which are putative substrates of OATs. Here we demonstrated that GT ingestion significantly elevated the systemic exposures of endogenous IS and PCS in rats with chronic renal failure (CRF). More importantly, GT also significantly increased the levels of serum creatinine (Cr) and blood urea nitrogen (BUN) in CRF rats. Mechanism studies indicated that the serum metabolites of GT (GTM) inhibited the uptake transporting functions of OAT1 and OAT3. In conclusion, GT inhibited the elimination of nephro-cardiovascular toxins such as IS and PCS, and deteriorated the renal function in CRF rats. PMID:26552961
Taylor, A.; Lallone, R.
A significant divergence of GFR and ERPF within a single kidney could lead to different estimates of relative renal function depending on which radiopharmaceutical is administered. To address this question, the authors studied adult male Sprague-Dawley rats with unilateral ureteral obstruction by giving each animal an intravenous injection of 10 ..mu..Ci of I-125 iothalamate (GFR), I-131 hippurate (ERPF), and TC-99m DMSA and measuring the 30 minute clearance (renal uptake and urine excretion) of each agent. Normal control animals were sham operated; 25 experimental animals were subjected to permanent unilateral ureteral occlusion and studied at 6 hours, 1, 3, 7 and 14 days. Acute ureteral obstruction impaired the clearance of iothalamate to a much greater degree than OIH or DMSA at 6 hours and 1 day (rho<.005) and 3 days (rho<.05). The decline in DMSA clearance reflected ERPF more closely than GFR. In evaluating renal disease, one should consider the functional parameter reflected by the radiopharmaceutical as well as the underlying disease state.
Yajima, A; Ogawa, C; Yatabe, M; Kondo, N; Saito, S; Suzuki, Y; Uesawa, Y
Cisplatin, cis-Dichlorodiammine platinum (II) (CDDP) remains a major antineoplastic drug for the treatment of solid tumors. Its chief dose-limiting side effect is nephrotoxicity. To make a safe and effective dosing regimen of a drug excreted mainly by the renal route, evaluation of patients' renal function is essential. Creatinine clearance (CLcr) or glomerular filtration rate (GFR) is considered to be a standard renal-function test. Several equations have been used in clinical settings, to predict CLcr and GFR using serum creatinine concentration. We carried out a retrospective analysis of the correlation between 24-hour CLcr measured by a urine collection method; and the predicted CLcr and GFR estimated by various equations such as Jelliffe, Yasuda, Orita, Mawer, Mawer, MDRD and modified MDRD, and Cockcroft-Gault. This study used data from Japanese head-and-neck cancer patients, before and after chemotherapy with CDDP. Slopes of regression lines of scatter plots between measured CLcr and predicted renal function in post-CDDP patients were less compared to pre-CDDP patients. On the other hand, Y-intercepts were noted in the scatter plots on renal function from all equations. These results suggest that evaluation of renal function using predictive formulae may have been over-/under-estimated after CDDP administration.
De Stefano, V; Leone, G; Mastrangelo, S; Lane, D A; Girolami, A; de Moerloose, P; Sas, G; Abildgaard, U; Blajchman, M; Rodeghiero, F
Microheterogeneity of antithrombin III (AT-III) was investigated by crossed immunoelectrofocusing (CIEF) on eleven molecular variants. A normal pattern was found in five variants while two different abnormal CIEF patterns were found in the other four and two variants, respectively. Point mutations causing a major pI change (exceeding 4.0) of the amino acid substituted lead to alterations in the overall microheterogeneity. The variants thus substituted share a first type of abnormal CIEF pattern with alterations throughout the pH range, regardless of the location of the mutation (reactive site and adjacent regions or heparin binding region). Minor amino acid pI changes in these regions do not alter the AT-III overall microheterogeneity, whatever the resulting functional defect. However, if the mutation is placed in the region around positions 404 or 429, then even minor changes of the amino acid pI seem able to alter the overall charge, leading to a second type of abnormal CIEF pattern with the main alteration at pH 4.8-4.6. Neuraminidase treatment leads to disappearance of microheterogeneity except for the variants with the Arg393 to Cys substitution. Addition of thrombin induces CIEF modifications specifically related to the functional defect. A normal formation of thrombin-antithrombin complexes induces a shift towards the more acid pH range, whereas in the variants substituted at the reactive site the CIEF pattern is substantially unaffected by thrombin; variants substituted at positions 382-384 show a maximal thrombin-induced increase of the isoforms at pI 4.8-4.6. Therefore mutant antithrombins with different functional abnormalities but sharing a common CIEF pattern were well distinguished.(ABSTRACT TRUNCATED AT 250 WORDS)
The endogenous synthesis of arginine, a semiessential amino acid, relies on the production of citrulline by the gut and its conversion into arginine by the kidney in what has been called the "intestinal-renal axis" for arginine synthesis. Although the kidney is the main site for citrulline disposal,...
Besseling, René M. H.; Jansen, Jacobus F. A.; de Louw, Anton J. A.; Vlooswijk, Mariëlle C. G.; Hoeberigs, M. Christianne; Aldenkamp, Albert P.; Backes, Walter H.
Introduction Focal cortical dysplasia (FCD) is a congenital malformation of cortical development that often leads to medically refractory epilepsy. Focal resection can be an effective treatment, but is challenging as the surgically relevant abnormality may exceed the MR-visible lesion. The aim of the current study is to develop methodology to characterize the profile of functional connectivity around FCDs using resting-state functional MRI and in the individual patient. The detection of aberrant connectivity may provide a means to more completely delineate the clinically relevant lesion. Materials and Methods Fifteen FCD patients (age, mean±SD: 31±11 years; 11 males) and 16 matched healthy controls (35±9 years; 7 males) underwent structural and functional imaging at 3 Tesla. The cortical surface was reconstructed from the T1-weighted scan and the registered functional MRI data was spatially normalized to a common anatomical standard space employing the gyral pattern. Seed-based functional connectivity was determined in all subjects for all dysplasia locations. A single patient was excluded based on an aberrant FCD seed time series. Functional connectivity as a function of geodesic distance (along the cortical surface) was compared between the individual patients and the homotopic normative connectivity profiles derived from the controls. Results In 12/14 patients, aberrant profiles of functional connectivity were found, which demonstrated both hyper- and hypoconnectivity as well as combinations. Abnormal functional connectivity was typically found (also) beyond the lesion visible on structural MRI, while functional connectivity profiles not related to a lesion appeared normal in patients. Conclusion This novel functional MRI technique has potential for delineating functionally aberrant from normal cortex beyond the structural lesion in FCD, which remains to be confirmed in future research. PMID:27861502
Ali, Quaisar; Wu, Yonnie; Hussain, Tahir
Abnormal regulation of the renin angiotensin system such as enhanced renal AT1R function and reduced ACE2 activity contributes to obesity-related hypertension. Here we tested whether long-term AT2R activation affects renal function in obesity using lean and obese Zucker rats treated with the AT2R agonist CGP42112A for 2-weeks. This caused blood pressure to decrease by 13 mmHg which was associated with increased urinary sodium excretion in the obese rats. Cortical ACE2 expression and activity, the Mas receptor (MasR), and its ligand angiotensin-(1-7) were all increased in CGP-treated obese compared with control rats. Candesartan-induced natriuresis, a measure of AT1R function, was reduced but cortical AT1R expression and angiotensin II levels were similar in CGP-treated obese compared to control rats. Renin and AT2R expression in obese rats was not affected by CGP-treatment. In HK-2 cells in-vitro, CGP-treatment caused increased ACE2 activity and MasR levels but decreased AT1R levels and renin activity. Thus, long-term AT2R activation shifts the opposing arms of renin angiotensin system and contributes to natriuresis and blood pressure reduction in obese animals. Our study highlights the importance of AT2R as a target for treating obesity related hypertension. PMID:23823602
Shlipak, Michael G.; Katz, Ronit; Agarwal, Subhashish; Ix, Joachim H.; Hsu, Chi-yuan; Peralta, Carmen A.
Summary Background and objectives Clinical heart failure (HF) is associated with CKD and faster rates of kidney function decline. Whether subclinical abnormalities of cardiac structure are associated with faster kidney function decline is not known. The association between cardiac concentricity and kidney function decline was evaluated. Design, setting, participants, & measurements This is a longitudinal study of 3866 individuals from the Multi-Ethnic Study of Atherosclerosis (2000–2007) who were free of clinical cardiovascular disease, with an estimated GFR (eGFR) ≥60 ml/min per 1.73 m2 at baseline and 5 years of follow-up. Concentricity, a measurement of abnormal cardiac size, was assessed by magnetic resonance imaging and evaluated as a continuous measurement and in quartiles. GFR was estimated by creatinine (eGFRcr) and cystatin C (eGFRcys). The association of concentricity with annual eGFR decline, incident CKD, and rapid kidney function decline (>5% per year) was investigated using linear mixed models as well as Poisson and logistic regression, respectively. Analyses adjusted for demographics, BP, diabetes, and inflammatory markers. Results Median decline was −0.8 (interquartile range, −3.1, −0.5) by eGFRcr. Compared with the lowest quartile of concentricity, persons in the highest quartile had an additional 21% (9%–32%) decline in mean eGFRcr in fully adjusted models. Concentricity was also associated with incident CKD and with rapid kidney function decline after adjustment. Conclusions Subclinical abnormalities in cardiac structure are associated with longitudinal kidney function decline independent of diabetes and hypertension. Future studies should examine mechanisms to explain these associations. PMID:22580783
Bijarnia, Rakesh K.; Bachtler, Matthias; Chandak, Prakash G.; van Goor, Harry; Pasch, Andreas
Background Hyperoxaluria causes crystal deposition in the kidney, which leads to oxidative stress and to injury and damage of the renal epithelium. Sodium thiosulfate (STS, Na2S2O3) is an anti-oxidant, which has been used in human medicine for decades. The effect of STS on hyperoxaluria-induced renal damage is not known. Methods Hyperoxaluria and renal injury were induced in healthy male Wistar rats by chronic exposure to ethylene glycol (EG, 0.75%) in the drinking water for 4 weeks. The treatment effects of STS, NaCl or Na2SO4 were compared. Furthermore, the effects of STS on oxalate-induced oxidative stress were investigated in vitro in renal LLC-PK1 cells. Results Chronic EG exposure led to hyperoxaluria, oxidative stress, calcium oxalate crystalluria and crystal deposition in the kidneys. Whereas all tested compounds significantly reduced crystal load, only STS-treatment maintained tissue superoxide dismutase activity and urine 8-isoprostaglandin levels in vivo and preserved renal function. In in vitro studies, STS showed the ability to scavenge oxalate-induced ROS accumulation dose dependently, reduced cell-released hydrogen peroxide and preserved superoxide dismutase activity. As a mechanism explaining this finding, STS was able to directly inactivate hydrogen peroxide in cell-free experiments. Conclusions STS is an antioxidant, which preserves renal function in a chronic EG rat model. Its therapeutic use in oxidative-stress induced renal-failure should be considered. PMID:25928142
Holt, Daphne J.; Boeke, Emily A.; Coombs, Garth; DeCross, Stephanie N.; Cassidy, Brittany S.; Stufflebeam, Steven; Rauch, Scott L.; Tootell, Roger B.H.
Schizophrenia is associated with subtle abnormalities in day-to-day social behaviors, including a tendency in some patients to “keep their distance” from others in physical space. The neural basis of this abnormality, and related changes in social functioning, is unknown. Here we examined, in schizophrenic patients and healthy control subjects, the functioning of a parietal–frontal network involved in monitoring the space immediately surrounding the body (“personal space”). Using fMRI, we found that one region of this network, the dorsal intraparietal sulcus (DIPS), was hyper-responsive in schizophrenic patients to face stimuli appearing to move towards the subjects, intruding into personal space. This hyper-responsivity was predicted both by the size of personal space (which was abnormally elevated in the schizophrenia group) and the severity of negative symptoms. In contrast, in a second study, the activity of two lower-level visual areas that send information to DIPS (the fusiform face area and middle temporal area) was normal in schizophrenia. Together, these findings suggest that changes in parietal–frontal networks that support the sensory-guided initiation of behavior, including actions occurring in the space surrounding the body, contribute to social dysfunction and negative symptoms in schizophrenia. PMID:26484048
Holt, Daphne J; Boeke, Emily A; Coombs, Garth; DeCross, Stephanie N; Cassidy, Brittany S; Stufflebeam, Steven; Rauch, Scott L; Tootell, Roger B H
Schizophrenia is associated with subtle abnormalities in day-to-day social behaviors, including a tendency in some patients to "keep their distance" from others in physical space. The neural basis of this abnormality, and related changes in social functioning, is unknown. Here we examined, in schizophrenic patients and healthy control subjects, the functioning of a parietal-frontal network involved in monitoring the space immediately surrounding the body ("personal space"). Using fMRI, we found that one region of this network, the dorsal intraparietal sulcus (DIPS), was hyper-responsive in schizophrenic patients to face stimuli appearing to move towards the subjects, intruding into personal space. This hyper-responsivity was predicted both by the size of personal space (which was abnormally elevated in the schizophrenia group) and the severity of negative symptoms. In contrast, in a second study, the activity of two lower-level visual areas that send information to DIPS (the fusiform face area and middle temporal area) was normal in schizophrenia. Together, these findings suggest that changes in parietal-frontal networks that support the sensory-guided initiation of behavior, including actions occurring in the space surrounding the body, contribute to social dysfunction and negative symptoms in schizophrenia.
Recent studies of autism have identified functional abnormalities of the default network during a passive resting state. Since the default network is also typically engaged during social, emotional and introspective processing, dysfunction of this network may underlie some of the difficulties individuals with autism exhibit in these broad domains. In the present experiment, we attempted to further delineate the nature of default network abnormality in autism using experimentally constrained social and introspective tasks. Thirteen autism and 12 control participants were scanned while making true/false judgments for various statements about themselves (SELF condition) or a close other person (OTHER), and pertaining to either psychological personality traits (INTERNAL) or observable characteristics and behaviors (EXTERNAL). In the ventral medial prefrontal cortex/ventral anterior cingulate cortex, activity was reduced in the autism group across all judgment conditions and also during a resting condition, suggestive of task-independent dysfunction of this region. In other default network regions, overall levels of activity were not different between groups. Furthermore, in several of these regions, we found group by condition interactions only for INTERNAL/EXTERNAL judgments, and not SELF/OTHER judgments, suggestive of task-specific dysfunction. Overall, these results provide a more detailed view of default network functionality and abnormality in autism. PMID:19015108
Damman, Jeffrey; Hoeger, Simone; Boneschansker, Leo; Theruvath, Ashok; Waldherr, Ruediger; Leuvenink, Henri G; Ploeg, Rutger J; Yard, Benito A; Seelen, Marc A
Kidneys recovered from brain-dead donors have inferior outcomes after transplantation compared to kidneys from living donors. Since complement activation plays an important role in renal transplant related injury, targeting complement activation in brain-dead donors might improve renal function after transplantation. Brain death (BD) was induced in Fisher rats by inflation of an epidurally placed balloon catheter and ventilated for 6h. BD animals were treated with soluble complement receptor 1 (sCR1) 1h before or 1h after BD. Kidney transplantation was performed and 7 days after transplantation animals were sacrificed. Plasma creatinine and urea were measured at days 0, 1, 3, 5 and 7 after transplantation. Renal function was significantly better at day 1 after transplantation in recipients receiving a sCR1 pre-treated donor kidney compared to recipients of a non-treated donor graft. Also treatment with sCR1, 1h after the diagnosis of BD, resulted in a better renal function after transplantation. Gene expression of IL-6, IL-1beta and TGF-beta were significantly lower in renal allografts recovered from treated donors. This study shows that targeting complement activation, during BD in the donor, leads to an improved renal function after transplantation in the recipient.
Sommer, B.G.; Innes, J.T.; Whitehurst, R.M.; Sharma, H.M.; Ferguson, R.M.
Cyclosporine-associated arteriopathy was the cause of graft loss in 40 percent of all allografts that failed in a series of 200 consecutive cadaveric renal transplants. Arteriopathy was diagnosed by biopsy and renal uptake of indium 111m labeled platelets in the face of acute renal deterioration. A moderate thrombocytopenia and microangiopathic picture of hemolytic uremia was also present on peripheral blood smear. Immunofluorescence and histologic characteristics of the allograft biopsy specimens failed to show evidence for acute rejection: immunoglobulin M, immunoglobulin A, immunoglobulin G, C1q, C3, and C4 were not present, and there was no evidence of an interstitial or vascular mononuclear cellular infiltrate. Two clinical presentations have been described. In Group I (seven patients), anuria occurred rapidly within the first 2 weeks after transplantation. In Group II (nine patients) renal function gradually diminished 1 to 5 months after starting cyclosporine therapy. Fifteen of the 16 recipients had progressive and irreversible loss of renal function which was pathologically associated with fibrin deposition, intimal proliferation, and thrombotic occlusion of the cortical interlobular and arcuate arteries, with subsequent focal glomerular ischemia and cortical infarction. One recipient with rapid loss of renal function received an intraarterial allograft infusion of streptokinase and subsequent systemic heparinization, which resulted in return of normal allograft function. The syndrome of cyclosporine-associated arteriopathy has been linked to a lack of or reduced amounts of prostacyclin-stimulating factor or prostacyclin.
Background Chronic kidney disease (CKD) and coronary artery disease (CAD) are independently associated with increased vascular stiffness. We examined whether renal function contributes to vascular stiffness independently of CAD status. Methods We studied 160 patients with CAD and 169 subjects without CAD. The 4-variable MDRD formula was used to estimate glomerular filtration rate (eGFR); impaired renal function was defined as eGFR <60 mL/min. Carotid-femoral pulse wave velocity (PWV) was measured with the SphygmoCor® device. Circulating biomarkers were assessed in plasma using xMAP® multiplexing technology. Results Patients with CAD and impaired renal function had greater PWV compared to those with CAD and normal renal function (10.2 [9.1;11.2] vs 7.3 [6.9;7.7] m/s; P < 0.001). In all patients, PWV was a function of eGFR (β = −0.293; P < 0.001) even after adjustment for age, sex, systolic blood pressure, body mass index and presence or absence of CAD. Patients with CAD and impaired renal function had higher levels of adhesion and inflammatory molecules including E-selectin and osteopontin (all P < 0.05) compared to those with CAD alone, but had similar levels of markers of oxidative stress. Conclusions Renal function is a determinant of vascular stiffness even in patients with severe atherosclerotic disease. This was paralleled by differences in markers of cell adhesion and inflammation. Increased vascular stiffness may therefore be linked to inflammatory remodeling of the vasculature in people with impaired renal function, irrespective of concomitant atherosclerotic disease. PMID:23937620
Shin, Jung-Ho; Kwon, Hee Jin; Jang, Hye Ryoun; Lee, Jung Eun; Gwak, Geum-Youn; Huh, Wooseong; Jung, Sin-Ho; Lee, Joon Hyeok; Kim, Yoon-Goo; Kim, Dae Joong; Oh, Ha Young
Renal functional decline that is frequently seen during chronic hepatitis B (CHB) treatment can exert adverse effects on overall prognosis. It, however, is difficult to distinguish vulnerable patients who may experience renal dysfunction because most previous CHB studies were conducted in relatively healthy individuals. In this retrospective observational study, renal functional decline in CHB patients receiving oral antiviral agents for more than 6 months was analyzed and risk factors of chronic kidney disease (CKD) progression were determined. Renal functional decline was defined when the estimated glomerular filtration rate (eGFR) decreased by more than 25% from baseline and rapid CKD progression was defined as eGFR decreased by more than 5 mL/min/1.73 m2/y among patients who experienced renal functional decline. A total of 4178 patients were followed up for a median 23 months. Antiviral agents included lamivudine (17.0%), adefovir (3.7%), entecavir (70.4%), telbivudine (0.6%), tenofovir (4.0%), or clevudine (4.3%). Renal functional decline occurred in 706 (16.9%) patients. Based on multivariate Cox regression analysis, age, hypertension, diabetes, history of liver or kidney transplantation, underlying underlying CKD, and simultaneous administration of diuretics increased the hazard ratio for renal functional decline; however, clevudine reduced risk. The eGFR significantly increased over time in patients receiving telbivudine or clevudine compared with lamivudine. Among the 3175 patients followed up for more than 1 year, 407 (12.8%) patients experienced rapid CKD progression. Patients with rapid CKD progression showed lower serum albumin, higher total bilirubin, and prolonged prothrombin time compared with patients with stable renal function, but hepatitis B envelope antigen positivity and hepatitis B virus deoxyribonucleic acid level did not differ between the control and rapid CKD progression groups. Age, diabetes, kidney transplantation, underlying CKD, and
Jain, Tarun Kumar; Phulsunga, Rohit Kumar; Gupta, Nitin; Sood, Ashwani; Bhattacharya, Anish; Mittal, Bhagwant Rai
We present a case of 3-year-old boy who was incidentally diagnosed to have single left kidney on ultrasonography. Dynamic technetium-99m ethylenedicysteine renal scintigraphy was acquired for assessing the existing kidney function showed the tracer localization in bilateral renal fossae during the entire study. The single-photon emission computerized tomography/computerized tomography study revealed activity in the right renal fossa to be in the enlarged right lobe of the liver, which was mimicking as impaired functioning right kidney in planar images. The hybrid imaging helped in accurate delineation of tracer uptake by confirming it to be the false appearance of the right kidney in planar imaging. This case report also highlights the possible mechanism of renal tracer uptake in the liver parenchyma. PMID:26170576
Kraguljac, Nina Vanessa; White, David Matthew; Hadley, Jennifer Ann; Visscher, Kristina; Knight, David; ver Hoef, Lawrence; Falola, Blessing; Lahti, Adrienne Carol
Objective To describe abnormalities in large scale functional networks in unmedicated patients with schizophrenia and to examine effects of risperidone on networks. Material and methods 34 unmedicated patients with schizophrenia and 34 matched healthy controls were enrolled in this longitudinal study. We collected resting state functional MRI data with a 3T scanner at baseline and six weeks after they were started on risperidone. In addition, a group of 19 healthy controls were scanned twice six weeks apart. Four large scale networks, the dorsal attention network, executive control network, salience network, and default mode network were identified with seed based functional connectivity analyses. Group differences in connectivity, as well as changes in connectivity over time, were assessed on the group's participant level functional connectivity maps. Results In unmedicated patients with schizophrenia we found resting state connectivity to be increased in the dorsal attention network, executive control network, and salience network relative to control participants, but not the default mode network. Dysconnectivity was attenuated after six weeks of treatment only in the dorsal attention network. Baseline connectivity in this network was also related to clinical response at six weeks of treatment with risperidone. Conclusions Our results demonstrate abnormalities in large scale functional networks in patients with schizophrenia that are modulated by risperidone only to a certain extent, underscoring the dire need for development of novel antipsychotic medications that have the ability to alleviate symptoms through attenuation of dysconnectivity. PMID:26793436
Tucker, Bryan J.
This project has investigated mechanisms that influence alterations in compartmental fluid and electrolyte balance in microgravity and evaluates countermeasures to control renal fluid and electrolyte losses. Determining the alterations due to space flight in fluid compartments and renal function is an important component in understanding long term adaptation to spaceflight and the contribution to post-flight orthostatic intolerance. Four definition phase studies and two studies examining neuro-humoral and vascular mechanisms have been completed.
In this investigation, ultrasonic parameters of complex renal calculi and gall bladder stones, in vitro are measured using a double-probe contact by pulse-echo technique. Due to the variation in the chemical composition of the stones, a large variation in the value of ultrasonic parameters is found. A correlation between ultrasonic parameters and various renal calculi and gall bladder stone pathologies are also discussed. The ultrasonic parameters are found to vary as a function of density of the specimen used.
Mitchell, D Y; St Peter, J V; Eusebio, R A; Pallone, K A; Kelly, S C; Russell, D A; Nesbitt, J D; Thompson, G A; Powell, J H
Aims To determine the relationship between risedronate pharmacokinetics and renal function. Methods Risedronate was administered to adult men and women (n = 21) with various degrees of renal function (creatinine clearance 15–126 ml min−1) as a single oral dose of 30 mg. Serum samples were obtained for 72 h after dosing, and urine samples were collected for 72 h after dosing and then periodically for 6 weeks. Risedronate concentrations were determined using an enzyme-linked immunosorbent assay (ELISA). Risedronate serum concentration-time and urinary excretion rate-time profiles were analysed simultaneously using nonlinear regression. Results Renal clearance and volume of distribution were linearly related to creatinine clearance (r2 = 0.854, P < 0.001; and r2 = 0.317, P < 0.01, respectively). Decreases in predicted renal clearance and volume of distribution of 82 and 69%, respectively, were observed when creatinine clearance decreased from 120 to 20 ml min−1. A 64% decrease in predicted oral clearance was observed when creatinine clearance decreased from 120 to 20 ml min−1 (P = 0.064). Iohexol clearance, a predictor of renal function, produced similar results to those observed with creatinine clearance. Risedronate was well tolerated by the study population. Conclusions Risedronate renal clearance was significantly related to a decrease in renal function. There was a consistent reduction in oral clearance with a decrease in creatinine clearance. However, based on the regression analysis, generally no dosage adjustment appears to be necessary for most patients with mild or moderate renal impairment (creatinine clearance > 20 ml min−1). PMID:10718776
Cai, Qingqing; Peng, Guicheng; Zhang, Kun; Chen, Weiqing; Wang, Jingfeng; Huang, Hui
Elevated homocysteine (HCY) and smoking are both important risk factors for hypertensive patients. However, whether they have crossing effect on renal function deterioration of hypertensive patients and what is the underlying mechanism are unclear. In the present study, 3033 participants diagnosed as essential hypertension with estimated glomerular filtration rate (eGFR)> 30 ml/min/1.73 m2 from southern China were enrolled in this cross-sectional study. We collected the demographic and clinical data. In addition, the mediation effects were analyzed. The results showed that, comparing with non-smokers, smokers had significant higher levels of HCY (13.10 (11.20−16.87) vs. 11.00 (8.90−13.40) umol/L, P < 0.001) and lower eGFR (79.71 (66.83−91.05) vs. 82.89 (69.80−95.85) ml/min/1.73m2, P < 0.001). HCY levels and smoking were independently associated with decreased eGFR. Meanwhile, eGFR levels were significantly negatively correlated with HCY (P < 0.001), and this correlation might be stronger in current smokers. Current smoker consuming over 20 cigarettes per day would accelerate early renal function deterioration (OR = 1.859, P = 0.019). The mediation effects analysis further showed that the association between smoking and renal function deterioration was mediated by HCY. And elevated HCY was accounted for 56.94% of the estimated causal effect of smoking on renal function deterioration in hypertensive patients. Our findings indicated that cigarette smoking was associated with renal function deterioration in hypertensive patients, and the association between cigarette smoking and renal function deterioration was probably mediated by elevated HCY. Therefore, HCY-lowering therapy may be beneficial for renal function deterioration in hypertensive smoking patients. PMID:27852066
Peterson, Gail E; de Backer, Tine; Contreras, Gabriel; Wang, Xuelei; Kendrick, Cynthia; Greene, Tom; Appel, Lawrence J; Randall, Otelio S; Lea, Janice; Smogorzewski, Miroslaw; Vagaonescu, Tudor; Phillips, Robert A
African Americans with hypertension are at high risk for adverse outcomes from cardiovascular and renal disease. Patients with stage 3 or greater chronic kidney disease have a high prevalence of left ventricular (LV) hypertrophy and diastolic dysfunction. Our goal was to study prospectively the relationships of LV mass and diastolic function with subsequent cardiovascular and renal outcomes in the African American Study of Kidney Disease and Hypertension cohort study. Of 691 patients enrolled in the cohort, 578 had interpretable echocardiograms and complete relevant clinical data. Exposures were LV hypertrophy and diastolic parameters. Outcomes were cardiovascular events requiring hospitalization or causing death; a renal composite outcome of doubling of serum creatinine or end-stage renal disease (censoring death); and heart failure. We found strong independent relationships between LV hypertrophy and subsequent cardiovascular (hazard ratio, 1.16; 95% confidence interval, 1.05-1.27) events, but not renal outcomes. After adjustment for LV mass and clinical variables, lower systolic tissue Doppler velocities and diastolic parameters reflecting a less compliant LV (shorter deceleration time and abnormal E/A ratio) were significantly (P<0.05) associated with future heart failure events. This is the first study to show a strong relationship among LV hypertrophy, diastolic parameters, and adverse cardiac outcomes in African Americans with hypertension and chronic kidney disease. These echocardiographic risk factors may help identify high-risk patients with chronic kidney disease for aggressive therapeutic intervention.
Elinder, C G; Edling, C; Lindberg, E; Kågedal, B; Vesterberg, O
Cadmium induced renal effects were examined in 60 workers (58 men, 2 women) previously exposed to cadmium. Tubular damage in the form of beta 2-microglobulinuria was found in 40%, and urinary albumin and orosomucoid increased significantly with increasing urinary cadmium and increasing relative clearance of beta 2-microglobulin. It is suggested that increased albumin excretion is secondary to the tubular damage. In no case was typical glomerular proteinuria found that could be related to cadmium. Histories of renal stones were more common among the workers with high urinary cadmium concentrations. The glomerular filtration rate was measured in 17 of the workers who had pronounced tubular dysfunction. The average glomerular filtration rate for these men was less than the age adjusted predicted value (mean = 84%). Furthermore, there was a significant (p less than 0.05) correlation (r = -0.47) between tubular reabsorption loss and a decreased glomerular filtration rate. PMID:3904816
Morazo, Paloma; Fortepiani, Lourdes A; Clara Ortíz, M; Atucha, Noemí M; García-Estañ, Joaquín
Background The present study was designed to analyze the chronic renal response to omapatrilat, a new vasopeptidase inhibitor, in spontaneously hypertensive rats (SHR). To that end, the renal and blood pressure response to a 4-day salt loading protocol was analyzed and the respective chronic renal curves constructed. Results In non treated animals, and under normal sodium intake (around 2 mEq/day), mean arterial pressure (MAP), was significantly higher in the SHR as compared with the controls (WKY). After increasing salt intake (8 times normal), MAP did not change significantly in any group and the animals reached a normal sodium balance in four days. In a second group of animals, omapatrilat was given orally for 15 days at the dose of 40 mg/kg/day in the drinking water. In these omapatrilat-treated animals, and under normal sodium intake, MAP was significantly lower in both groups, although the antihypertensive effect was much greater in the SHR, so that the MAP of the SHR group was completely normalized and similar to the WKY-treated group. The subsequent elevation of sodium intake did not significantly elevate MAP in any group and the animals could manage the sodium excess as well as the non treated groups. Conclusions These results indicate that chronic treatment with omapatrilat normalizes blood pressure in SHR without affecting adversely the renal ability to eliminate a sodium load. Chronic treatment with omapatrilat resets the chronic pressure natriuresis relationship of the SHR to a normal level, thus without altering the normal salt-independence of this arterial hypertension model. PMID:11592920
Anticevic, Alan; Repovs, Grega; Krystal, John H.; Barch, Deanna M.
Characterizing working memory (WM) abnormalities represents a fundamental challenge in schizophrenia research given the impact of cognitive deficits on life outcome in patients. In prior work we demonstrated that dorsolateral prefrontal cortex (DLPFC) activation was related to successful distracter resistance during WM in healthy controls, but not in schizophrenia. Although understanding the impact of regional functional deficits is critical, functional connectivity abnormalities among nodes within WM networks may constitute a final common pathway for WM impairment. Therefore, this study tested the hypothesis that schizophrenia is associated with functional connectivity abnormalities within DLPFC networks during distraction conditions in WM. 28 patients and 24 controls completed a delayed non-verbal WM task that included transient visual distraction during the WM maintenance phase. We computed DLPFC whole-brain task-based functional connectivity (tb-fcMRI) specifically during the maintenance phase in the presence or absence of distraction. Results revealed that patients failed to modulate tb-fcMRI during distracter presentation in both cortical and sub-cortical regions. Specifically, controls demonstrated reductions in tb-fcMRI between DLPFC and the extended amygdala when distraction was present. Conversely, patients failed to demonstrate a change in coupling with the amygdala, but showed greater connectivity with medio-dorsal thalamus. While controls showed more positive coupling between DLPFC and other prefrontal cortical regions during distracter presentation, patients failed to exhibit such a modulation. Taken together, these findings support the notion that observed distracter resistance deficit involves a breakdown in coupling between DLPFC and distributed regions, encompassing both subcortical (thalamic/limbic) and control region connectivity. PMID:22863548
Heelmann, Volker; Lippert-Grüner, Marcela; Rommel, Thomas; Wedekind, Christoph
For the rehabilitation process, the treatment of patients surviving brain injury in a vegetative state is still a serious challenge. The aim of this study was to investigate patients exhibiting severely disturbed consciousness using functional magnetic resonance imaging. Five cases of posttraumatic vegetative state and one with minimal consciousness close to the vegetative state were studied clinically, electrophysiologically, and by means of functional magnetic resonance imaging. Visual, sensory, and acoustic paradigms were used for stimulation. In three patients examined less than 2 months after trauma, a consistent decrease in blood oxygen level dependent (BOLD) signal ('negative activation') was observed for visual stimulation; one case even showed a decrease in BOLD activation for all three activation paradigms. In the remaining three cases examined more than 6 months after trauma, visual stimulation yielded positive BOLD contrast or no activation. In all cases, sensory stimulation was followed by a decrease in BOLD signal or no activation, whereas auditory stimulation failed to elicit any activation with the exception of one case. Functional magnetic resonance imaging in the vegetative state indicates retained yet abnormal brain function; this abnormality can be attributed to the impairment of cerebral vascular autoregulation or an increase in the energy consumption of activated neocortex in severe traumatic brain injury.
Weaver, V; Lee, B; Ahn, K; Lee, G; Todd, A; Stewart, W; Wen, J; Simon, D; Parsons, P; Schwartz, B
Aims: To compare associations of lead biomarkers with renal function in current and former lead workers. Methods: Cross sectional analysis of first year results from a longitudinal study of 803 lead workers and 135 controls in South Korea. Clinical renal function was assessed by blood urea nitrogen (BUN), serum creatinine, and measured and calculated creatinine clearance. Urinary N-acetyl-ß-D-glucosaminidase (NAG) and retinol-binding protein were also measured. Results: Mean (SD) tibia lead, blood lead, and DMSA chelatable lead levels in lead workers were 37.2 (40.4) µg/g bone mineral, 32.0 (15.0) µg/dl, and 767.8 (862.1) µg/g creatinine, respectively. Higher lead measures were associated with worse renal function in 16/42 models. When influential outliers were removed, higher lead measures remained associated with worse renal function in nine models. An additional five associations were in the opposite direction. Effect modification by age was observed. In 3/16 models, associations between higher lead measures and worse clinical renal function in participants in the oldest age tertile were significantly different from associations in those in the youngest age tertile which were in the opposite direction. Mean urinary cadmium (CdU) was 1.1 µg/g creatinine (n = 191). Higher CdU levels were associated with higher NAG. Conclusions: These data suggest that lead has an adverse effect on renal function in the moderate dose range, particularly in older workers. Associations between higher lead measures and lower BUN and serum creatinine and higher creatinine clearances may represent lead induced hyperfiltration. Environmental cadmium may also have an adverse renal impact, at least on NAG. PMID:12883015
Levin, Mark D.; Zhang, Haixia; Uchida, Keita; Grange, Dorothy K.; Singh, Gautam K.; Nichols, Colin G.
Background Gain-of-function (GOF) mutations in the KATP channel subunits Kir6.1 and SUR2 cause Cantu syndrome (CS), a disease characterized by multiple cardiovascular abnormalities. Objective To better understand the electrophysiological consequences of such GOF mutations in the heart. Methods We generated transgenic mice (Kir6.1-GOF) expressing ATP-insensitive Kir6.1[G343D] subunits under α-myosin heavy chain (α-MHC) promoter control, to target gene expression specifically in cardiomyocytes, and carried out patch-clamp experiments on isolated ventricular myocytes, invasive electrophysiology on anesthetized mice. Results In Kir6.1-GOF ventricular myocytes, KATP channels show decreased ATP sensitivity, but there is no significant change in current density. Ambulatory ECG recordings on Kir6.1-GOF mice reveal AV nodal conduction abnormalities and junctional rhythm. Invasive electrophysiological analyses reveal slowing of conduction and conduction failure through the AV node, but no increase in susceptibility to atrial or ventricular ectopic activity. Surface electrocardiograms recorded from CS patients also demonstrate first degree AV block, and fascicular block. Conclusions The primary electrophysiological consequence of cardiac KATP GOF is on the conduction system, particularly the AV node, resulting in conduction abnormalities in CS patients, who carry KATP GOF mutations. PMID:26142302
Bjornstad, Petter; Škrtić, Marko; Lytvyn, Yuliya; Maahs, David M; Johnson, Richard J; Cherney, David Z I
Diabetic kidney disease (DKD) remains the leading cause of end-stage renal disease. A major challenge in preventing DKD is the difficulty in identifying high-risk patients at an early, pre-clinical stage. Albuminuria and eGFR as measures of renal function in DKD research and clinical practice are limited by regression of one-third of patients with microalbuminuria to normoalbuminuria and eGFR is biased and imprecise in the normal-elevated range. Moreover, existing methods that are used to assess renal function do not give detailed insight into the location of the renal hemodynamic effects of pharmacological agents at the segmental level. To gain additional information about the intrarenal circulation in-vivo in humans, mathematical equations were developed by Gomez et al in the 1950s. These equations used measurements of GFR, renal blood flow (RBF), effective renal plasma flow (ERPF), renal vascular resistance (RVR), hematocrit and serum protein to calculate afferent and efferent arteriolar resistances, glomerular hydrostatic pressure and filtration pressure. Although indirect and based on physiological assumptions, these techniques have the potential to improve researchers' ability to identify early pre-clinical changes in renal hemodynamic function in patients with a variety of conditions including DKD, thereby offering tremendous potential in mechanistic human research studies. In this review, we focus on the application of Gomez' equations and summarize the potential and limitations of this technique in DKD research. We also summarize illustrative data derived from Gomez' equations in patients with type 1 (T1D) and type 2 diabetes (T2D) and hypertension.
Chen, Li-Hao; Advani, Suzanne L; Thai, Kerri; Kabir, M Golam; Sood, Manish M; Gibson, Ian W; Yuen, Darren A; Connelly, Kim A; Marsden, Philip A; Kelly, Darren J; Gilbert, Richard E; Advani, Andrew
The progressive decline of renal function in chronic kidney disease (CKD) is characterized by both disruption of the microvascular architecture and the accumulation of fibrotic matrix. One angiogenic pathway recently identified as playing an essential role in renal vascular development is the stromal cell-derived factor-1α (SDF-1)/CXCR4 pathway. Because similar developmental processes may be recapitulated in the disease setting, we hypothesized that the SDF-1/CXCR4 system would regulate microvascular health in CKD. Expression of CXCR4 was observed to be increased in the kidneys of subtotally nephrectomized (SNx) rats and in biopsies from patients with secondary focal segmental glomerulosclerosis (FSGS), a rodent model and human correlate both characterized by aberration of the renal microvessels. A reno-protective role for local SDF-1/CXCR4 signaling was indicated by i) CXCR4-dependent glomerular eNOS activation following acute SDF-1 administration; and ii) acceleration of renal function decline, capillary loss and fibrosis in SNx rats treated with chronic CXCR4 blockade. In contrast to the upregulation of CXCR4, SDF-1 transcript levels were decreased in SNx rat kidneys as well as in renal fibroblasts exposed to the pro-fibrotic cytokine transforming growth factor β (TGF-β), the latter effect being attenuated by histone deacetylase inhibition. Increased renal SDF-1 expression was, however, observed following the treatment of SNx rats with the ACE inhibitor, perindopril. Collectively, these observations indicate that local SDF-1/CXCR4 signaling functions to preserve microvascular integrity and prevent renal fibrosis. Augmentation of this pathway, either purposefully or serendipitously with either novel or existing therapies, may attenuate renal decline in CKD.
Gajbhiye, Rahul; Kadam, Kaushiki; Khole, Aalok; Gaikwad, Avinash; Kadam, Seema; Shah, Rupin; Kumaraswamy, Rangaswamy; Khole, Vrinda
Background & objectives: The role of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in congenital bilateral absence of vas deferens and unilateral renal agenesis (CBAVD-URA) has been controversial. Here, we report the cases of five Indian males with CBAVD-URA. The objective was to evaluate the presence or absence of CFTR gene mutations and variants in CBAVD-URA. The female partners of these males were also screened for cystic fibrosis (CF) carrier status. Methods: Direct DNA sequencing of CFTR gene was carried out in five Indian infertile males having CBAVD-URA. Female partners (n=5) and healthy controls (n=32) were also screened. Results: Three potential regulatory CFTR gene variants (c.1540A>G, c.2694T>G and c.4521G>A) were detected along with IVS8-5T mutation in three infertile males with CBAVD-URA. Five novel CFTR gene variants (c.621+91A>G, c.2752+106A>T, c.2751+85_88delTA, c.3120+529InsC and c.4375-69C>T), four potential regulatory CFTR gene variants (M470V, T854T, P1290P, Q1463Q) and seven previously reported CFTR gene variants (c.196+12T>C, c.875+40A>G, c.3041-71G>C, c.3271+42A>T, c.3272-93T>C, c.3500-140A>C and c.3601-65C>A) were detected in infertile men having CBAVD and renal anomalies Interpretation & conclusions: Based on our findings, we speculate that CBAVD-URA may also be attributed to CFTR gene mutations and can be considered as CFTR-related disorder (CFTR-RD). The CFTR gene mutation screening may be offered to CBAVD-URA men and their female partners undergoing ICSI. Further studies need to be done in a large sample to confirm the findings. PMID:27488005
Adams, N R; Hearnshaw, H; Oldham, C M
Ewes with permanent phyto-estrogenic infertility show oestrus less regularly than normal ewes, and the present study examines the extent to which this results from abnormal ovarian function. Forty-nine affected ewes and 53 controls were run with rams fitted with marking crayons and harnesses, and crayon marks were recorded and laparoscopy performed at weekly intervals for 3 weeks. Fewer affected ewes showed oestrus accompanied by ovulation (28 v. 49, P less than 0.001), and four of these affected ewes had a second ovulation during the experiment. More of the ovulations observed in affected ewes were unaccompanied by behavioural oestrus than in controls (8 out of 38 v. 2 out of 50; P less than 0.05). Six affected ewes had no corpus luteum or oestrus, and five of these had adhesions over the genitalia. Hydrops uteri in five other affected ewes was accompanied by prolonged maintenance of the corpus luteum. Some other abnormalities were also observed. In a second study, plasma progesterone concentrations were measured twice daily in 12 affected ewes which were run with rams. Five ewes had oestrous cycles of abnormal duration (two of more than 23 days, two of 21 days, and one of 11 days), and these were accompanied by plasma progesterone patterns different from those of the ewes with an oestrous cycle duration of 16-18 days. It is concluded that the irregular oestrous cycles in affected ewes are due mainly to abnormal life span and progesterone secretion by the corpus luteum, which in turn largely result from changes in the uterus.
Pu, Weidan; Li, Li; Zhang, Huiran; Ouyang, Xuan; Liu, Haihong; Zhao, Jingping; Li, Lingjiang; Xue, Zhimin; Xu, Ke; Tang, Haibo; Shan, Baoci; Liu, Zhening; Wang, Fei
A salience network (SN), mainly composed of the anterior insula (AI) and anterior cingulate cortex (ACC), has been suggested to play an important role in salience attribution which has been proposed as central to the pathology of paranoid schizophrenia. The role of this SN in the pathophysiology of paranoid schizophrenia, however, still remains unclear. In the present study, voxel-based morphometry and resting-state functional connectivity analyses were combined to identify morphological and functional abnormalities in the proposed SN in the early-stage of paranoid schizophrenia (ESPS). Voxel-based morphometry and resting-state functional connectivity analyses were applied to 90 ESPS patients and 90 age- and sex-matched healthy controls (HC). Correlation analyses were performed to examine the relationships between various clinical variables and both gray matter morphology and functional connectivity within the SN in ESPS. Compared to the HC group, the ESPS group showed significantly reduced gray matter volume (GMV) in both bilateral AI and ACC. Moreover, significantly reduced functional connectivity within the SN sub-networks was identified in the ESPS group. These convergent morphological and functional deficits in SN were significantly associated with hallucinations. Additionally, illness duration correlated with reduced GMV in the left AI in ESPS. In conclusion, these findings provide convergent evidence for the morphological and functional abnormalities of the SN in ESPS. Moreover, the association of illness duration with the reduced GMV in the left AI suggests that the SN and the AI, in particular, may manifest progressive morphological changes that are especially important in the emergence of ESPS.
Tso, Ivy F; Fang, Yu; Phan, K Luan; Welsh, Robert C; Taylor, Stephan F
The involvement of the gamma-aminobutyric acid (GABA) system in schizophrenia is suggested by postmortem studies and the common use of GABA receptor-potentiating agents in treatment. In a recent study, we used a benzodiazepine challenge to demonstrate abnormal GABAergic function during processing of negative visual stimuli in schizophrenia. This study extended this investigation by mapping GABAergic mechanisms associated with face processing and social appraisal in schizophrenia using a benzodiazepine challenge. Fourteen stable, medicated schizophrenia/schizoaffective patients (SZ) and 13 healthy controls (HC) underwent functional MRI using the blood oxygenation level-dependent (BOLD) technique while they performed the Socio-emotional Preference Task (SePT) on emotional face stimuli ("Do you like this face?"). Participants received single-blinded intravenous saline and lorazepam (LRZ) in two separate sessions separated by 1-3weeks. Both SZ and HC recruited medial prefrontal cortex/anterior cingulate during the SePT, relative to gender identification. A significant drug by group interaction was observed in the medial occipital cortex, such that SZ showed increased BOLD signal to LRZ challenge, while HC showed an expected decrease of signal; the interaction did not vary by task. The altered BOLD response to LRZ challenge in SZ was significantly correlated with increased negative affect across multiple measures. The altered response to LRZ challenge suggests that abnormal face processing and negative affect in SZ are associated with altered GABAergic function in the visual cortex, underscoring the role of impaired visual processing in socio-emotional deficits in schizophrenia.
Jin, Seung-Hyun; Lin, Peter; Auh, Sungyoung; Hallett, Mark
The aim of the present study was to investigate functional connectivity in focal hand dystonia patients to understand the pathophysiology underlying their abnormality in movement. We recorded EEGs from 58 electrodes in 15 focal hand dystonia patients and 15 healthy volunteers during rest and a simple finger-tapping task that did not induce any dystonic symptoms. We investigated mutual information, which provides a quantitative measure of linear and nonlinear coupling, in the alpha, beta, and gamma bands. Mean mutual information of all 58 channels and mean of the channels of interest representative of regional functional connectivity over sensorimotor areas (C3, CP3, C4, CP4, FCz, and Cz) were evaluated. For both groups, we found enhanced mutual information during the task compared with the rest condition, specifically in the beta and gamma bands for mean mutual information of all channels, and in all bands for mean mutual information of channels of interest. Comparing the focal hand dystonia patients with the healthy volunteers for both rest and task, there was reduced mutual information in the beta band for both mean mutual information of all channels and mean mutual information of channels of interest. Regarding the properties of the connectivity in the beta band, we found that the majority of the mutual information differences were from linear connectivity. The abnormal beta-band functional connectivity in focal hand dystonia patients suggests deficient brain connectivity.
Chung, Doo Yong; Hong, Chang Hee; Im, Young Jae; Lee, Yong Seung; Kim, Sang Woon
Purpose To evaluate changes in differential renal function (DRF), as a functional outcome, in children who underwent redo pyeloplasty for management of failed pyeloplasty and to examine the factors that affect functional outcomes. Materials and Methods Between January 2002 and November 2010, a total of 18 patients who underwent redo pyeloplasty for persistent ureteropelvic junction obstruction after failed pyeloplasty were enrolled in this study. We assessed perioperative factors and evaluated changes in renal cortical thickness (RCT), renal function, and hydronephrosis by use of serial ultrasound and diuretic renography. Results The mean follow-up period was 44.83±28.86 months. After redo pyeloplasty, prevention of further functional deterioration was observed in only 12 of the 18 patients. After dividing the patients according to this observation, we discovered significant differences in both change in DRF (dDRF) and change in RCT (dRCT) (difference between before and after initial pyeloplasty) between the two groups (p<0.001). Additionally, we noted a significant positive correlation between dRCT and dDRF. All patients showed improvements in hydronephrosis grade and relief of symptoms compared with before redo pyeloplasty. Conclusions Redo pyeloplasty should be considered in cases of failed pyeloplasty to preserve renal function and obtain relief from symptoms. If patients show severe deterioration of DRF or a decrease in RCT after initial pyeloplasty, preservation of DRF in these patients after redo pyeloplasty could be difficult. Therefore, redo pyeloplasty should be performed before severe deterioration of DRF or decrease in RCT. PMID:25685304
Aburano, T.; Takayama, T.; Nakajima, K.; Tonami, N.; Hisada, K.; Yasuhara, S.; Miyamori, I.; Takeda, R.
The three different methods to evaluate the alterations of split renal function following continued captopril treatment were studied in patients with hypertension. Five patients had unilateral and 2 had bilateral renal artery stenosis, and 13 had normal renal arteries. The studies were performed the day prior to receiving captopril (baseline), and 6th or 7th day following continued captorpril treatment (37.5mg or 75mg/day): Split effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) after injections of I-131 iodohippuran and Tc-99m DTPA were measured respectively by the methods using kidney counting corrected for depth and dose, described by Schlegel and Gates. And Tc-99m DMSA uptake was also evaluated qualitatively. In most of patients with renal artery stenosis, split GFR and Tc-99m DMSA uptake in the affected kidney were markedly decreased 6th or 7th day following continued captorpril treatment. These findings suggest that the captopril induced alterations of split renal function may be of importance for the diagnosis of renovascular hypertension. For this purpose, split GFR determination and Tc-99m DMSA study are more useful than split ERPF determination.
Chung, Sang M; Lee, David J; Hand, Austin; Young, Philip; Vaidyanathan, Jayabharathi; Sahajwalla, Chandrahas
The study evaluated whether the renal function decline rate per year with age in adults varies based on two primary statistical analyses: cross-section (CS), using one observation per subject, and longitudinal (LT), using multiple observations per subject over time. A total of 16628 records (3946 subjects; age range 30-92 years) of creatinine clearance and relevant demographic data were used. On average, four samples per subject were collected for up to 2364 days (mean: 793 days). A simple linear regression and random coefficient models were selected for CS and LT analyses, respectively. The renal function decline rates per year were 1.33 and 0.95 ml/min/year for CS and LT analyses, respectively, and were slower when the repeated individual measurements were considered. The study confirms that rates are different based on statistical analyses, and that a statistically robust longitudinal model with a proper sampling design provides reliable individual as well as population estimates of the renal function decline rates per year with age in adults. In conclusion, our findings indicated that one should be cautious in interpreting the renal function decline rate with aging information because its estimation was highly dependent on the statistical analyses. From our analyses, a population longitudinal analysis (e.g. random coefficient model) is recommended if individualization is critical, such as a dose adjustment based on renal function during a chronic therapy.
Oliveira-Sales, Elizabeth B.; Maquigussa, Edgar; Semedo, Patricia; Pereira, Luciana G.; Ferreira, Vanessa M.; Câmara, Niels O.; Bergamaschi, Cassia T.; Campos, Ruy R.; Boim, Mirian A.
Renovascular hypertension induced by 2 Kidney-1 Clip (2K-1C) is a renin-angiotensin-system (RAS)-dependent model, leading to renal vascular rarefaction and renal failure. RAS inhibitors are not able to reduce arterial pressure (AP) and/or preserve the renal function, and thus, alternative therapies are needed. Three weeks after left renal artery occlusion, fluorescently tagged mesenchymal stem cells (MSC) (2×105 cells/animal) were injected weekly into the tail vein in 2K-1C hypertensive rats. Flow cytometry showed labeled MSC in the cortex and medulla of the clipped kidney. MSC prevented a further increase in the AP, significantly reduced proteinuria and decreased sympathetic hyperactivity in 2K-1C rats. Renal function parameters were unchanged, except for an increase in urinary volume observed in 2K-1C rats, which was not corrected by MSC. The treatment improved the morphology and decreased the fibrotic areas in the clipped kidney and also significantly reduced renal vascular rarefaction typical of 2K-1C model. Expression levels of IL-1β, TNF-α angiotensinogen, ACE, and Ang II receptor AT1 were elevated, whereas AT2 levels were decreased in the medulla of the clipped kidney. MSC normalized these expression levels. In conclusion, MSC therapy in the 2K-1C model (i) prevented the progressive increase of AP, (ii) improved renal morphology and microvascular rarefaction, (iii) reduced fibrosis, proteinuria and inflammatory cytokines, (iv) suppressed the intrarenal RAS, iv) decreased sympathetic hyperactivity in anesthetized animals and v) MSC were detected at the CNS suggesting that the cells crossed the blood-brain barrier. This therapy may be a promising strategy to treat renovascular hypertension and its renal consequences in the near future. PMID:24223811
Chugh, Gaurav; Lokhandwala, Mustafa F.
We tested the effects of inflammation on renal dopamine D1 receptor signaling cascade, a key pathway that maintains sodium homeostasis and blood pressure during increased salt intake. Inflammation was produced by administering lipopolysaccharide (LPS; 4 mg/kg ip) to rats provided without (normal salt) and with 1% NaCl in drinking water for 2 wk (high salt). Control rats had saline injection and received tap water. We found that LPS increased the levels of inflammatory cytokines, interleukin-6, and tumor necrosis factor-α in the rats given either normal- or high-salt intake. Also, these rats had higher levels of oxidative stress markers, malondialdehyde and nitrotyrosine, and lower levels of antioxidant enzyme superoxide dismutase in the renal proximal tubules (RPTs). The nuclear levels of transcription factors NF-κB increased and Nrf2 decreased in the RPTs in response to LPS in rats given normal and high salt. Furthermore, D1 receptor numbers, D1 receptor proteins, and D1 receptor agonist (SKF38393)-mediated 35S-GTPγS binding decreased in the RPTs in these rats. The basal activities of Na-K-ATPase in the RPTs were similar in control and LPS-treated rats given normal and high salt. SKF38393 caused inhibition of Na-K-ATPase activity in the primary cultures of RPTs treated with vehicle but not in the cultures treated with LPS. Furthermore, LPS caused an increase in blood pressure in the rats given high salt but not in the rats given normal salt. These results suggest that LPS differentially regulates NF-κB and Nrf2, produces inflammation, decreases antioxidant enzyme, increases oxidative stress, and causes D1 receptor dysfunction in the RPTs. The LPS-induced dysfunction of renal D1 receptors alters salt handling and causes hypertension in rats during salt overload. PMID:19794106
Lugon, J R; Boim, M A; Ramos, O L; Ajzen, H; Schor, N
The renal effects of a single intravenous dose of two different E. coli lipopolysaccharides (LPS 0111:B4 and LPS 0127:B8), at the same dose of 100 micrograms/kg, were evaluated in euvolemic Munich-Wistar (MW) rats by whole kidney clearance techniques and micropuncture studies. Following LPS infusion, a significant decrease (8%) in mean BP was observed only in the LPS 0127:B8 treated group. Inulin clearance fell 57% (LPS 0111:B4), P less than 0.01, and 38% (LPS 0127:B8), P less than 0.01. Para-aminohippuric (PAH) clearance decreased 31% (P less than 0.01) and total effective renal vascular resistance rose 70% (P less than 0.03) in response to LPS 0111:B4. No significant change in PAH clearance was noted in the LPS 0127:B8 group. Superficial single nephron glomerular filtration rate (SNGFR) was reduced 69% (LPS 0111:B4), P less than 0.03, and 33% (LPS 0127:B8), P less than 0.02. Superficial glomerular plasma flow fell 48% (LPS 0111:B4), P less than 0.03, and 24% (LPS 0127:B8), P less than 0.03. Both lipopolysaccharides were associated with an increase in afferent arteriolar resistance (RA) which accounted for a reduction in the glomerular capillary hydraulic pressure (PGC). There was no change in the proximal tubular pressure in either group and, therefore, the net transcapillary hydraulic pressures were reduced. No measurable change in the ultrafiltration coefficient. Kf, was observed in either group. In a second set of protocols, the effect of prior administration of indomethacin or captopril on LPS 0111:B4 action was investigated. A significant decrease in BP occurred when animals were pretreated with captopril. Both indomethacin and captopril prevented the renal effects of LPS 0111:B4.(ABSTRACT TRUNCATED AT 250 WORDS)
Lin, Hui; Liu, Wenyi; Zeng, Hui; Pu, Chaowen; Zhang, Renping; Qiu, Zhiqun; Chen, Ji-An; Wang, Lingqiao; Tan, Yao; Zheng, Chuanfen; Yang, Xiaohong; Tian, Yingqiao; Huang, Yujing; Luo, Jiaohua; Luo, Yang; Feng, Xiaobin; Xiao, Guosheng; Feng, Lei; Li, Heng; Wang, Feng; Yuan, Changyou; Wang, Jia; Zhou, Ziyuan; Wei, Tiantian; Zuo, Yonglin; Wu, Liping; He, Lixiong; Guo, Yaoping; Shu, Weiqun
Although the nephrotoxicity of microcystin and aflatoxin has been observed in animal and clinical cases, few population data are available. We conducted a cross-sectional study in Southwest China to investigate the association of renal function indicators (RFIs, including BUN, SCr, and eGFR) with exposure to microcystin and aflatoxin in 5493 members of the general population. Microcystin-LR levels in water and aquatic products and aflatoxin B1 levels in daily foods were measured by ELISA, and individual estimated daily intake (EDI) was assessed on the basis of the measurement and questionnaire. We found that participants with abnormal RFIs had a much higher mean level of microcystin-LR EDI than those with normal RFIs and that there was a significant increasing trend for abnormal rates and odds ratios of RFIs with increasing microcystin-LR EDI quartiles (p for trend = 0.000). Compared with the lowest quartile of microcystin-LR exposure, those in the highest quartile had significantly higher risks of abnormal BUN (OR = 1.80, 95% CI = 1.34-2.42), SCr (OR = 4.58, 95% CI = 2.92-7.21), and eGFR (OR = 4.41, 95% CI = 2.55-7.63), respectively, but no higher risk was found in subjects with higher AFB1 exposure. After adjustment for confounding factors, risk associations with microcystin-LR persisted. Consequently, our results suggest that microcystin, rather than aflatoxin, might be one important risk of renal-function impairment.
Steketee, Rebecca M.E.; Meijboom, Rozanna; Bron, Esther E.; Osse, Robert Jan; de Koning, Inge; Jiskoot, Lize C.; Klein, Stefan; de Jong, Frank Jan; van der Lugt, Aad; van Swieten, John C.; Smits, Marion
Purpose ‘Phenocopy’ frontotemporal dementia (phFTD) patients may clinically mimic the behavioral variant of FTD (bvFTD), but do not show functional decline or abnormalities upon visual inspection of routine neuroimaging. We aimed to identify abnormalities in gray matter (GM) volume and perfusion in phFTD and to assess whether phFTD belongs to the FTD spectrum. We compared phFTD patients with both healthy controls and bvFTD patients. Materials & methods Seven phFTD and 11 bvFTD patients, and 20 age-matched controls underwent structural T1-weighted magnetic resonance imaging (MRI) and 3D pseudo-continuous arterial spin labeling (pCASL) at 3T. Normalized GM (nGM) volumes and perfusion, corrected for partial volume effects, were quantified regionally as well as in the entire supratentorial cortex, and compared between groups taking into account potential confounding effects of gender and scanner. Results PhFTD patients showed cortical atrophy, most prominently in the right temporal lobe. Apart from this regional atrophy, GM volume was generally not different from either controls or from bvFTD. BvFTD however showed extensive frontotemporal atrophy. Perfusion was increased in the left prefrontal cortex compared to bvFTD and to a lesser extent to controls. Conclusion PhFTD and bvFTD show overlapping cortical structural abnormalities indicating a continuum of changes especially in the frontotemporal regions. Together with functional changes suggestive of a compensatory response to incipient pathology in the left prefrontal regions, these findings are the first to support a possible neuropathological etiology of phFTD and suggest that phFTD may be a neurodegenerative disease on the FTD spectrum. PMID:27222795
Martin, Caroline; Dubouchaud, Hervé; Mosoni, Laurent; Chardigny, Jean-Michel; Oudot, Alexandra; Fontaine, Eric; Vergely, Catherine; Keriel, Christiane; Rochette, Luc; Leverve, Xavier; Demaison, Luc
Aging triggers several abnormalities in muscle glycolytic fibers including increased proteolysis, reactive oxygen species (ROS) production and apoptosis. Since the mitochondria are the main site of substrate oxidation, ROS production and programmed cell death, we tried to know whether the cellular disorders encountered in sarcopenia are due to abnormal mitochondrial functioning. Gastrocnemius mitochondria were extracted from adult (6 months) and aged (21 months) male Wistar rats. Respiration parameters, opening of the permeability transition pore and ROS production, with either glutamate (amino acid metabolism) or pyruvate (glucose metabolism) as a respiration substrate, were evaluated at different matrix calcium concentrations. Pyruvate dehydrogenase and respiratory complex activities as well as their contents measured by Western blotting analysis were determined. Furthermore, the fatty acid profile of mitochondrial phospholipids was also measured. At physiological calcium concentration, state III respiration rate was lowered by aging in pyruvate conditions (-22%), but not with glutamate. The reduction of pyruvate oxidation resulted from a calcium-dependent inactivation of the pyruvate dehydrogenase system and could provide for the well-known proteolysis encountered during sarcopenia. Matrix calcium loading and aging increased ROS production. They also reduced the oxidative phosphorylation. This was associated with lower calcium retention capacities, suggesting that sarcopenic fibers are more prone to programmed cell death. Aging was also associated with a reduced mitochondrial superoxide dismutase activity, which does not intervene in toxic ROS overproduction but could explain the lower calcium retention capacities. Despite a lower content, cytochrome c oxidase displayed an increased activity associated with an increased n-6/n-3 polyunsaturated fatty acid ratio of mitochondrial phospholipids. In conclusion, we propose that mitochondria obtained from aged muscle
Clemente, C; Bosch, J; Rodés, J; Arroyo, V; Mas, A; Maragall, S
Forty-three patients with cirrhosis and ascites, 21 with normal renal function, 10 with a progressive functional renal failure (FRF), and 12 with a steady FRF, were investigated for the presence of endotoxaemia by the Limulus lysate test. Endotoxaemia was found in nine patients with FRF and in none of the 21 with normal renal function (P less than 0-01). A positive Limulus test was almost exclusively associated with a progressive FRF (eight of 10 patients) and all but one of them died. Renal function improved as endotoxaemia disappeared in the survivor. Endotoxaemia was also associated with haemorrhage due to acute erosions of the gastric mucosa, being present in six of the seven patients who had this complication. Intravascular coagulation was not found in any patient. The Limulus test was positive in the ascitic fluid in 18 of 21 patients tested, although only two of them had peritonitis. These results suggest that endotoxaemia may play a critical role in the development of progressive renal failure and haemorrhagic gastritis in cirrhosis, and emphasise the potential risk of procedures involving reinfusion of ascitic fluid. PMID:301485
Beck, Eugene A.; Shainoff, John R.; Vogel, Alfred; Jackson, Dudley P.
The rate of clotting and the rate of development and degree of turbidity after addition of thrombin to plasma or purified fibrinogen from a patient with fibrinogen Baltimore was delayed when compared with normal, especially in the presence of low concentrations of thrombin. Optimal coagulation and development of translucent, rather than opaque, clots occurred at a lower pH with the abnormal fibrinogen than with normal. Development of turbidity during clotting of the abnormal plasma or fibrinogen was less than normal at each pH tested, but was maximal in both at approximately pH 6.4. The physical quality of clots formed from fibrinogen Baltimore was abnormal, as demonstrated by a decreased amplitude on thromboelastography. The morphologic appearance of fibrin strands formed from fibrinogen Baltimore by thrombin at pH 7.4 was abnormal when examined by phase contrast or electron microscopy, but those formed by thrombin at pH 6.4 or by thrombin and calcium chloride were similar to, though less compact, than normal fibrin. The periodicity of fibrin formed from fibrinogen Baltimore was similar to normal and was 231-233 Å. A study of the release of the fibrinopeptides from the patient's fibrinogen and its chromatographic subfractions verified the existence of both a normally behaving and a defective form of fibrinogen in the patient's plasma. The defective form differed from normal in three functionally different ways: (a) the rate of release of fibrinopeptides A and AP was slower than normal; (b) no visible clot formation accompanied either partial or complete release of the fibrinopeptides from the defective form in 0.3 M NaCl at pH 7.4; and (c) the defective component possessed a high proportion of phosphorylated, relative to nonphosphorylated, fibrinopeptide A, while the coagulable component contained very little of the phosphorylated peptide (AP). The high phosphate content of the defective component did not appear to be the cause of the abnormality, but may be the
Dirks-Naylor, Amie J.
Renal transport is a central mechanism underlying electrolyte homeostasis, acid base balance and other essential functions of the kidneys in human physiology. Thus, knowledge of the anatomy and physiology of the nephron is essential for the understanding of kidney function in health and disease. However, students find this content difficult to…
D'Agati, Vivette D; Mengel, Michael
This review chronicles historical landmarks in the rise of renal pathology from the mid-20th century. Major technical advances followed the advent of percutaneous kidney biopsy in 1951, including applications of thin serial sections, special stains, immunofluorescence, and electron microscopy. Inspired by the 1961 Ciba Symposium, renal pathologists and nephrologists collaborated on detailed clinical-pathologic studies, and the publication of Robert Heptinstall's textbook in 1966 offered the first modern synthesis of these emerging entities. By 2000, refinements in morphology-based diagnosis had outstripped knowledge of pathogenesis. The last decade has witnessed an explosion of new insights into the cause of kidney disease fueled by advances in molecular diagnostics, such as genetic screening, transcriptomics, and proteomics. We are entering an era of personalized medicine in which more precise mechanism-based diagnosis is fostering the design of targeted therapies in the individual patient. Only the continued partnering of pathologists and nephrologists can meet the challenge of integrating molecular diagnostics into pathogenesis-based therapy.
Ritz, Eberhard; Amann, Kerstin; Koleganova, Nadezda; Benz, Kerstin
Impaired intrauterine nephrogenesis-most clearly illustrated by low nephron number-is frequently associated with low birthweight and has been recognized as a powerful risk factor for renal disease; it increases the risks of low glomerular filtration rate, of more rapid progression of primary kidney disease, and of increased incidence of chronic kidney disease or end-stage renal disease. Another important consequence of impaired nephrogenesis is hypertension, which further amplifies the risk of onset and progression of kidney disease. Hypertension is associated with low nephron numbers in white individuals, but the association is not universal and is not seen in individuals of African origin. The derangement of intrauterine kidney development is an example of a more general principle that illustrates the paradigm of plasticity during development-that is, that transcription of the genetic code is modified by epigenetic factors (as has increasingly been documented). This Review outlines the concept of prenatal programming and, in particular, describes its role in kidney disease and hypertension.
Iwai, Mina; Kimura, Michio; Yoshimura, Tomoaki; Yasuda, Tadashi
Although many analyses of S-1 side effects are reported, there are no reports where the analyses of side effects were performed in consideration of renal function, which is an important index of medication dose. Therefore, we investigated side effects in consideration of renal function. The subjects were 163 patients administered S-1 at the Department of Surgery of Ogaki Municipal Hospital, between October 2008 and December 2009. The frequency and severity of side effects were high and serious in the groupwhose creatinine clearance was low. A significant difference was observed among 3 groups with regard to thrombocytopenia and dehydration. In conclusion, we think that pharmacists must take renal function into consideration when administering medication, to keepclose medicinal guidance, and to actively observe progress.
Kemper, M J; Müller-Wiefel, D E
Congenital anomalies of the kidneys and urinary tract are a major cause of chronic and end-stage renal failure in children. The molecular mechanisms having been elaborated, there is now growing evidence that kidney function is to a large extent determined genetically at an early stage. Assessment of kidney function is an important tool in clinical medicine and is feasible in utero. Postnatally, determination of absolute glomerular filtration rate and also of split and excretory renal function play an important role in the determination of treatment and prognosis. This is supplemented by other biochemical, molecular and interventional prognostic factors, which are of help in preservation of kidney survival by minimizing modulating factors. If chronic or terminal renal failure ensues in childhood or even in early infancy, however, improved medical care has led to encouraging results, ultimately influencing the motivation in the care of children with congenital anomalies of the kidney and urinary tract.
van Beers, Eduard J; van der Plas, Mart N; Nur, Erfan; Bogaard, Harm-Jan; van Steenwijk, Reindert P; Biemond, Bart J; Bresser, Paul
Many patients with sickle cell disease (SCD) have a reduced exercise capacity and abnormal lung function. Cardiopulmonary exercise testing (CPET) can identify causes of exercise limitation. Forty-four consecutive SCD patients (27 HbSS, 11 HbSC, and 6 HbS-beta thalassemia) with a median age (interquartile range) of 26 (21-41) years underwent pulmonary function tests, CPET, chest x-ray, and echocardiography to further characterize exercise limitation in SCD. Peak oxygen uptake (V'O2 -peak), expressing maximum exercise capacity, was decreased in 83% of the studied patients. V'O2 -peak correlated with hemoglobin levels (R = 0.440, P = 0.005), forced vital capacity (FVC) (R = 0.717, P < 0.0001). Cardiothoracic ratio on chest x-ray inversely correlated with FVC (R = -0.637, P < 0.001). According to criteria for exercise limitation, the patients were limited in exercise capacity due to anemia (n = 17), cardiovascular dysfunction (n = 2), musculoskeletal function (n = 10), pulmonary ventilatory abnormalities (n = 1), pulmonary vascular exercise limitation (n = 1), and poor effort (n = 3). In the present study we demonstrate that anemia is the most important determinant of reduced exercise tolerance observed in SCD patients without signs of pulmonary hypertension. We found a strong correlation between various parameters of lung volume and cardiothoracic ratio and we hypothesize that cardiomegaly and relative small chest size may be important causes of the impairment in pulmonary function, that is, reduced long volumes and diffusion capacity, in SCD. Taking into account anthropomorphic differences between SCD patients and controls could help to interpret lung function studies in SCD better.
Faria, Leonardo C.
Partially isolated “undercut” neocortex with intact pial circulation is a well-established model of posttraumatic epileptogenesis. Results of previous experiments showed a decreased frequency of miniature inhibitory postsynaptic currents (mIPSCs) in layer V pyramidal (Pyr) neurons of undercuts. We further examined possible functional abnormalities in GABAergic inhibition in rat epileptogenic neocortical slices in vitro by recording whole cell monosynaptic IPSCs in layer V Pyr cells and fast-spiking (FS) GABAergic interneurons using a paired pulse paradigm. Compared with controls, IPSCs in Pyr neurons of injured slices showed increased threshold and decreased peak amplitude at threshold, decreased input/output slopes, increased failure rates, and a shift from paired pulse depression toward paired pulse facilitation (increased paired pulse ratio or PPR). Increasing [Ca2+]o from 2 to 4 mM partially reversed these abnormalities in Pyr cells of the epileptogenic tissue. IPSCs onto FS cells also had an increased PPR and failures. Blockade of GABAB receptors did not affect the paired results. These findings suggest that there are functional alterations in GABAergic presynaptic terminals onto both Pyr and FS cells in this model of posttraumatic epileptogenesis. PMID:20484536
Amagai, Yosuke; Matsuda, Hiroshi; Tanaka, Akane
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by dryness and itchy skin. Genetic factors as well as other factors, including abnormality in skin barrier function, hypersensitivity of itch sensory nerves, and dysfunction of the immune system, strongly affect the onset and exacerbation of AD. Recently, it has become clear that itch sensation is closely related to pain sensation. By using NC/Tnd mice, a unique spontaneous animal model for human AD, we found abnormalities in sensitivity against external stimuli as compared to two standard strains, BALB/c and B6 mice. Particularly, in conventional NC/Tnd mice with AD, stimulation against transient receptor potential (TRP) V1 reduced the scratching behavior, suggesting the possibility of a TRPV1 modulator in the treatment of atopic itch. The review outlines observations regarding itch sensation and skin barrier function in NC/Tnd mice by using a novel itch quantification system for the laboratory animals, which may bring great progress in the future study of itch.
Hüter, Lars; Simon, Tim-Philipp; Weinmann, Lenard; Schuerholz, Tobias; Reinhart, Konrad; Wolf, Gunter; Amann, Kerstin Ute; Marx, Gernot
Introduction The aim of the study was to evaluate some of the underlying pathomechanisms of hydroxyethylstarch (HES) induced adverse effects on renal function using 24 porcine kidneys in an isolated perfusion model over six hours. Methods Infusion of either 10% HES 200/0.5, 6% HES 130/0.42 or Ringer's lactate (RL) was performed to achieve an haematocrit of 20% in eight kidneys from four animals per group. Physiological and pathophysiological parameters were determined (including N-acetyl-beta-aminoglucosidase as a marker for lysosomal tubular damage). Histological investigations and immunohistological stainings of the kidneys were performed. Results Initially after haemodilution, HES 130/0.42 and HES 200/0.5 reduced urine output compared with RL (P < 0.01). After six hours, N-acetyl-beta-aminoglucosidase was significantly higher in HES 200/0.5 (81 ± 23 U/L) compared with HES 130/0.42 (38 ± 12 U/L) and RL (21 ± 13 U/L; P < 0.001). Osmotic nephrosis-like lesions (OL) of the tubuli were present in all groups showing a significantly lower number of OL in RL (1.1 ± 0.4; P = 0.002) compared with both HES groups (HES 200/0.5 = 2.1 ± 0.6; HES 130/0.42 = 2.0 ± 0.5). Macrophage infiltration was significantly higher in HES 200/0.5 compared with HES 130/0.42 (1.3 ± 1.0 vs. 0.2 ± 0.04; P = 0.044). There was a significant increase in interstitial cell proliferation in the HES 200/0.5 group vs. HES 130/0.42 (18.0 ± 6.9 vs. 6.5 ± 1.6; P = 0.006) with no significant difference in RL (13.5 ± 4.0). Conclusions We observed impaired diuresis and sodium excretion by HES and identified renal interstitial proliferation, macrophage infiltration and tubular damage as potential pathological mechanisms of HES-induced adverse effects on renal function using an isolated porcine renal perfusion model. Furthermore, we demonstrated that 10% HES 200/0.5 had more of a pro-inflammatory effect compared with 6% HES 130/0.42 and caused more pronounced tubular damage than 6% HES 130/0.42 and
Beasley, Jeannette M; Aragaki, Aaron K; LaCroix, Andrea Z; Neuhouser, Marian L; Tinker, Lesley F; Cauley, Jane A; Ensrud, Kristine E; Jackson, Rebecca D; Prentice, Ross L
With aging, renal function tends to decline, as evidenced by reduced glomerular filtration rate. High-protein intake may further stress the kidneys by causing sustained hyperfiltration. To investigate whether dietary protein is associated with impaired renal function, we used data from 2 nested case-control studies within the Women's Health Initiative Observational Study (n = 2419). We estimated protein intake using a FFQ and estimated glomerular filtration rate (eGFR) from cystatin C. To account for the original study designs, inverse probability weights were applied. Self-reported energy and protein were calibrated using biomarkers of energy and protein intake. Associations between protein intake and renal function were estimated by weighted linear and logistic regression models. Average calibrated protein intake (mean ± SD) was 1.1 ± 0.2 g/(kg body weight·d).Twelve percent (n = 292) of women had impaired renal function. The odds of impaired renal function, defined as eGFR <60 mL/(min·1.73m(2)), was not associated with calibrated protein intake. When eGFR was modeled continuously, there was no association with calibrated protein when protein was expressed in absolute (g/d) or relative to energy (protein % energy/d), but protein relative to body weight [g/(kg body weight·d)] was associated with higher eGFR. There was no evidence for effect modification by age, BMI, or general health status. These data suggest higher protein intake is not associated with impaired renal function among postmenopausal women without a diagnosis of chronic kidney disease.
Background To investigate functional aspects of silent ureteral stones with special focus on obstruction and its relationship to renal anatomy. The present study is the first investigation of renal excretory function in patients with silent ureteral stones. Methods Patients with primarily asymptomatic ureteral stones underwent a mercapto-acetyltriglycine (MAG-3) renal scintigraphy prior to treatment, in addition to anatomic evaluation of renal units and serum creatinine levels. The primary outcome measure was the presence or absence of obstruction. Secondary outcome measures were kidney anatomy, grade of hydronephrosis, location of stones, stone size, and serum creatinine levels. Results During a ten-year period, 14 patients (median age 52.6 years; range 37.3 to 80.7 years) were included in the study. The relative frequency of primarily asymptomatic ureteral stones among all patients treated for ureteral stones in the study period was 0.7%. Eleven renal units showed some degree of hydronephrosis while 3 kidneys were not dilated. On the MAG-3 scan, 7 patients had an obstruction of the ureter, 5 had no obstruction, and 2 had dysfunction of the kidney. A statistically significant correlation was established between the grade of obstruction and stone size (p = 0.02). Conclusions At the time of presentation, only 64.3% of the patients revealed an obstruction in the stone-bearing renal unit. The degree of hydronephrosis and renal function were very diverse in this subgroup of patients with ureteral stones. The onset of ureterolithiasis and the chronological sequence of obstruction remain unclear in patients who have never experienced symptoms due to their stones. PMID:24397735
Livi, R; Teghini, L; Pignone, A; Generini, S; Matucci-Cerinic, M; Cagnoni, M
Objective: To evaluate the functional response of the kidney to an amino acid challenge (the so called renal functional reserve (RFR)) in patients with systemic sclerosis (SSc) with no clinical sign of renal involvement. Methods: Before and after an intravenous amino acid load (Freamine III Baxter, 8.5% solution, 4.16 ml/min for two hours), glomerular filtration rate (GFR, as creatinine clearance), effective renal plasma flow (ERPF, as para-aminohyppurate clearance), and calculated total renal vascular resistance (TRVR) were measured in 21 patients with SSc with apparently normal renal function and 10 normal controls. Results: In basal conditions, patients had lower ERPF (403.5 (SD 43.8) v 496.4 (SD 71.3) ml/min, p<0.0002) and higher TRVR (10 822 (SD 2044) v 8874 (SD 1639) dyne/sxcm-5, p<0.014) than controls. The RFR, evaluated as the percentage increase of GFR after the amino acid load, was significantly reduced in patients with SSc (SSc +1.9 (SD18.6)%, controls +34.8 (SD 13.9)%; p<0.0002). However, the response of patients was not uniform. Multiple regression analysis showed that the RFR was inversely dependent on the patients' mean arterial pressure at admission and basal GFR (R2=65%, p<0.0001). Conclusions: Most patients with SSc cannot increase renal filtration under the challenge of a protein overload. This defective renal response to the amino acid load test sustains the concept of the prevalence of vasoconstrictor over vasodilating factors in the kidney of these patients. PMID:12117672
Chin, Anthony; O'Conner, Linh Nguyen; Radhakrishnan, Jayant; Fornell, Linda; John, Eunice
In this study, we observed the effects of moderate and high doses of dopamine on the renal functions of neonatal piglets during endotoxic shock. We found that fluid therapy alone was better at maintaining cardiac index and preventing elevation of systemic vascular resistance, than dopamine at 10 and at 20 microg/kg/min. Furthermore, urine output and glomerular filtration rate were reduced by dopamine. Following endotoxin administration dopamine decreased SVR and maintained a CI better than fluid alone. However, in spite of a better CI, greater deterioration in renal functions occurred in the dopamine groups as compared to the fluid group.
Hashimoto, Junichiro; Ito, Sadayoshi
Aortic stiffness determines the glomerular filtration rate (GFR) and predicts the progressive decline of the GFR. However, the underlying pathophysiological mechanism remains obscure. Recent evidence has shown a close link between aortic stiffness and the bidirectional (systolic forward and early diastolic reverse) flow characteristics. We hypothesized that the aortic stiffening-induced renal dysfunction is attributable to altered central flow dynamics. In 222 patients with hypertension, Doppler velocity waveforms were recorded at the proximal descending aorta to calculate the reverse/forward flow ratio. Tonometric waveforms were recorded to measure the carotid-femoral (aortic) and carotid-radial (peripheral) pulse wave velocities, to estimate the aortic pressure from the radial waveforms, and to compute the aortic characteristic impedance. In addition, renal hemodynamics was evaluated by duplex ultrasound. The estimated GFR was inversely correlated with the aortic pulse wave velocity, reverse/forward flow ratio, pulse pressure, and characteristic impedance, whereas it was not correlated with the peripheral pulse wave velocity or mean arterial pressure. The association between aortic pulse wave velocity and estimated GFR was independent of age, diabetes mellitus, hypercholesterolemia, and antihypertensive medication. However, further adjustment for the aortic reverse/forward flow ratio and pulse pressure substantially weakened this association, and instead, the reverse/forward flow ratio emerged as the strongest determinant of estimated GFR (P=0.001). A higher aortic reverse/forward flow ratio was also associated with lower intrarenal forward flow velocities. These results suggest that an increase in aortic flow reversal (ie, retrograde flow from the descending thoracic aorta toward the aortic arch), caused by aortic stiffening and impedance mismatch, reduces antegrade flow into the kidney and thereby deteriorates renal function.
Suzuki, Shinya; Murayama, Yuka; Sugiyama, Erika; Sekiyama, Masao; Sato, Hitoshi
We established dose estimation formulae for renal-excretion drugs using the glomerular filtration rate (GFR), tubular secretion clearance (Sc), and unbound fraction of drug in plasma (fp) as a renal function index of physiological development in neonates and infants not more than 2 years of age. A dose ratio of (DC/DA)=clearance ratio of (CLC/CLA) congruent with(fpC.GFRC)/(fpA.GFRA) for neonates and infants/adults was applied to drugs with fp.GFR>Sc, while DC/DA=CLC/CLA congruent with(beta.BSAC+fpC.GFRC)/(beta.BSAA+fpA.GFRA) was applied to drugs with Sc>fp.GFR using the coefficient of each drug (beta) and body surface area (BSA). Validity of the estimation formulae was investigated in drugs with fp.GFR>Sc such as vancomycin (VCM), arbekacin (ABK), fosfomycin (FOM) and norfloxacin (NFLX), and in drugs with Sc>fp.GFR such as digoxin (DGX) and amoxicillin (AMPC). First, we compared the clearance ratio (CLC/ CLA) of VCM, ABK, and DGX estimated by our method with those calculated using the Japanese population clearance values and those estimated allometrically (BSAC/BSAA). Next, we compared the established doses of all drugs investigated with the doses for neonates and infants calculated from the conventional dose estimation methods for children and our estimation formulae, and evaluated our method. As a result, favorable consistency was observed in the CL ratio for all drugs, and the doses of VCM, FOM, NFLX and AMPC calculated from our estimation formulae approximated the established doses. In conclusion, the validity of the dose estimation method using pharmacokinetic factors related to physiological development (i.e., GFR, fp, Sc) for renal-excretion drugs in neonates and infants was demonstrated.
Bergström, G; Herlitz, H; Himmelmann, A; Ljungman, S; Aurell, M
One hundred years ago, in 1898, Professor Robert Tigerstedt, Karolinska institutet, Sweden, discovered renin. The subsequent elaboration in 1960 of the renin-angiotensin-aldosterone system signalled the start of modern hypertension research. The kidney takes part in blood pressure regulation in a number of ways. Indications are that increased renovascular resistance due to increased renin-angiotensin activity is of importance for the barostatic function of the kidneys and for the pathogenesis of human hypertension. Several commonly used, efficacious and well tolerated antihypertensive agents act by blocking the renin-angiotensin system, thus normalising kidney function. A number of current large-scale trials--utilising ACE inhibitors and angiotensin receptor antagonists--will, it is hoped, elucidate the proper role of 'anti-renin therapy' in the treatment of hypertension. Thanks to effective modern management of hypertension, renal failure due to hypertensive kidney disease is rare in Sweden today.
Li, Ling; Zhi, Mengmeng; Hou, Zhenghua; Zhang, Yuqun; Yue, Yingying; Yuan, Yonggui
Patients with hyperthyroidism frequently have neuropsychiatric complaints such as lack of concentration, poor memory, depression, anxiety, nervousness, and irritability, suggesting brain dysfunction. However, the underlying process of these symptoms remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI), we depicted the altered graph theoretical metric degree centrality (DC) and seed-based resting-state functional connectivity (FC) in 33 hyperthyroid patients relative to 33 healthy controls. The peak points of significantly altered DC between the two groups were defined as the seed regions to calculate FC to the whole brain. Then, partial correlation analyses were performed between abnormal DC, FC and neuropsychological performances, as well as some clinical indexes. The decreased intrinsic functional connectivity in the posterior lobe of cerebellum (PLC) and medial frontal gyrus (MeFG), as well as the abnormal seed-based FC anchored in default mode network (DMN), attention network, visual network and cognitive network in this study, possibly constitutes the latent mechanism for emotional and cognitive changes in hyperthyroidism, including anxiety and impaired processing speed. PMID:28009983
Parreira, Ricardo Cambraia; Miguel, Renata Botelho; de Paula Rogerio, Alexandre; Oliveira, Carlo Jose Freire; Chica, Javier Emilio Lazo
Background Chagas disease is a neglected tropical disease caused by Trypanosoma cruzi. Despite the vast number of studies evaluating the pathophysiological mechanisms of the disease, the influence of parasite burden on kidney lesions remains unclear. Thus, the main goal of this work was to evaluate the effect of T. cruzi infection on renal function and determine whether there was a correlation between parasite load and renal injury using an acute experimental model of the disease. Methodology/Principal Findings Low, medium and high parasite loads were generated by infecting C57BL/6 mice with 300 (low), 3,000 (medium) or 30,000 (high) numbers of “Y” strain trypomastigotes. We found that mice infected with T. cruzi trypomastigotes show increased renal injury. The infection resulted in reduced urinary excretion and creatinine clearance. We also observed a marked elevation in the ratio of urine volume to kidney and body weight, blood urea nitrogen, chloride ion, nitric oxide, pro- and anti-inflammatory cytokines and the number of leukocytes in the blood and/or renal tissues of infected mice. Additionally, we observed the presence of the parasite in the cortical/medullary and peri-renal region, an increase of inflammatory infiltrate and of vascular permeability of the kidney. Overall, most renal changes occurred mainly in animals infected with high parasitic loads. Conclusions/Significance These data demonstrate that T. cruzi impairs kidney function, and this impairment is more evident in mice infected with high parasitic loads. Moreover, these data suggest that, in addition to the extensively studied cardiovascular effects, renal injury should be regarded as an important indicator for better understanding the pan-infectivity of the parasite and consequently for understanding the disease in experimental models. PMID:23951243
Faulhaber-Walter, Robert; Scholz, Sebastian; Haller, Herrmann; Kielstein, Jan T; Hafer, Carsten
Background Critically ill patients with acute kidney injury (AKI) in need of renal replacement therapy (RRT) may have a protracted and often incomplete rehabilitation. Their long-term outcome has rarely been investigated. Study design Survivors of the HANnover Dialysis OUTcome (HANDOUT) study were evaluated after 5 years for survival, health status, renal function, and quality of life (QoL). The HANDOUT study had examinded mortality and renal recovery of patients with AKI receiving either standard extendend or intensified dialysis after multi organ failure. Results One hundred fifty-six former HANDOUT participants were analyzed. In-hospital mortality was 56.4%. Five-year survival after AKI/RRT was 40.1% (86.5% if discharged from hospital). Main causes of death were cardiovascular complications and sepsis. A total of 19 survivors presented to the outpatient department of our clinic and had good renal recovery (mean estimated glomerular filtration rate 72.5±30 mL/min/1.73 m2; mean proteinuria 89±84 mg/d). One person required maintenance dialysis. Seventy-nine percent of the patients had a pathological kidney sonomorphology. The Charlson comorbidity score was 2.2±1.4 and adjusted for age 3.3±2.1 years. Numbers of comorbid conditions averaged 2.38±1.72 per patient (heart failure [52%] > chronic kidney disease/myocardial infarction [each 29%]). Median 36-item short form health survey (SF-36™) index was 0.657 (0.69 physical health/0.66 mental health). Quality-adjusted life-years after 5 years were 3.365. Conclusion Mortality after severe AKI is higher than short-term prospective studies show, and morbidity is significant. Kidney recovery as well as general health remains incomplete. Reduction of QoL is minor, and social rehabilitation is very good. Affectivity is heterogeneous, but most patients experience emotional well-being. In summary, AKI in critically ill patients leads to incomplete rehabilitation but acceptable QoL after 5 years. PMID:27284261
Mehmet, Necmettin Mercimek; Ender, Ozden
Urolithiasis is a common disease that affects urinary tract in all age groups. Both in adults and in children, stone size, location, renal anatomy, and other factors, can influence the success of treatment modalities. Recently, there has been a great advancement in technology for minimally invasive management of urinary stones. The epoch of open treatment modalities has passed and currently there are much less invasive treatment approaches, such as percutaneous nephrolithotomy, ureteroscopy, shockwave lithotripsy, and retrograde internal Surgery. Furthermore, advancement in imaging technics ensures substantial knowledge that permit physician to decide the most convenient treatment method for the patient. Thus, effective and rapid treatment of urinary tract stones is substantial for the preservation of the renal function. In this review, the effects of the treatment options for urinary stones on renal function have been reviewed. PMID:25949941
Kumar, Sachin; Taylor, David O
Over a million patients get hospitalized with the diagnosis of acute decompensated heart failure which poses an insurmountable financial burden on the health care system. Heart failure alone incurs over 30 billion dollars with half the cost spent towards acute hospitalizations. Majority of the treatment strategies have focused towards decongesting patients which often comes with the cost of worsening renal function. Renal dysfunction in the setting of acute decompensated heart failure portends worse morbidity and mortality. Recently, there has been a change in the focus with shift towards therapies attempting to conserve renal function. In the past decade, we have witnessed several large randomized controlled trials testing the established as well as emerging therapies in this subset of population with mixed results. This review intends to provide a comprehensive overview of the pharmacologic therapies commonly utilized in the management of acute decompensated heart failure and the body of evidence supporting these strategies.
Xinaris, Christodoulos; Benedetti, Valentina; Rizzo, Paola; Abbate, Mauro; Corna, Daniela; Azzollini, Nadia; Conti, Sara; Unbekandt, Mathieu; Davies, Jamie A; Morigi, Marina; Benigni, Ariela; Remuzzi, Giuseppe
The shortage of transplantable organs provides an impetus to develop tissue-engineered alternatives. Producing tissues similar to immature kidneys from simple suspensions of fully dissociated embryonic renal cells is possible in vitro, but glomeruli do not form in the avascular environment. Here, we constructed renal organoids from single-cell suspensions derived from E11.5 kidneys and then implanted these organoids below the kidney capsule of a living rat host. This implantation resulted in further maturation of kidney tissue, formation of vascularized glomeruli with fully differentiated capillary walls, including the slit diaphragm, and appearance of erythropoietin-producing cells. The implanted tissue exhibited physiologic functions, including tubular reabsorption of macromolecules, that gained access to the tubular lumen on glomerular filtration. The ability to generate vascularized nephrons from single-cell suspensions marks a significant step to the long-term goal of replacing renal function by a tissue-engineered kidney.
Benedetti, Valentina; Rizzo, Paola; Abbate, Mauro; Corna, Daniela; Azzollini, Nadia; Conti, Sara; Unbekandt, Mathieu; Davies, Jamie A.; Morigi, Marina; Benigni, Ariela; Remuzzi, Giuseppe
The shortage of transplantable organs provides an impetus to develop tissue-engineered alternatives. Producing tissues similar to immature kidneys from simple suspensions of fully dissociated embryonic renal cells is possible in vitro, but glomeruli do not form in the avascular environment. Here, we constructed renal organoids from single-cell suspensions derived from E11.5 kidneys and then implanted these organoids below the kidney capsule of a living rat host. This implantation resulted in further maturation of kidney tissue, formation of vascularized glomeruli with fully differentiated capillary walls, including the slit diaphragm, and appearance of erythropoietin-producing cells. The implanted tissue exhibited physiologic functions, including tubular reabsorption of macromolecules, that gained access to the tubular lumen on glomerular filtration. The ability to generate vascularized nephrons from single-cell suspensions marks a significant step to the long-term goal of replacing renal function by a tissue-engineered kidney. PMID:23085631
We compared postoperative renal function impairment between patients undergoing robot-assisted partial nephrectomy (RAPN) and those undergoing open partial nephrectomy (OPN) by using Tc-99m diethylenetriaminepentaacetic acid (DTPA) renal scintigraphy. Patients who underwent partial nephrectomy by a single surgeon between 2007 and 2013 were eligible and were matched by propensity score, based on age, tumor size, exophytic properties of tumor, and location relative to the polar lines. Of the 403 patients who underwent partial nephrectomy, 114 (28%) underwent RAPN and 289 (72%) underwent OPN. Mean follow-up duration was 35.2 months. Following propensity matching, there were no significant differences between the two groups in tumor exophytic properties (P = 0.818) or nephrometry score (P = 0.527). Renal ischemic time (24.4 minutes vs. 17.8 minutes, P < 0.001) was significantly longer in the RAPN group than in the OPN group, while the other characteristics were similar. Multivariate analysis showed that greater preoperative renal unit function (P = 0.011) and nephrometry score (P = 0.041) were independently correlated with a reduction in glomerular filtration rate. The operative method did not correlate with renal function impairment (P = 0.704). Postoperative renal function impairment was similar between patients who underwent OPN and those who underwent RAPN, despite RAPN having a longer ischemic time. PMID:27134496
Lee, Chanwoo; Kwon, Taekmin; Yoo, Sangjun; Jung, Jaeyoon; Lee, Chunwoo; You, Dalsan; Jeong, In Gab; Kim, Choung-Soo
We compared postoperative renal function impairment between patients undergoing robot-assisted partial nephrectomy (RAPN) and those undergoing open partial nephrectomy (OPN) by using Tc-99m diethylenetriaminepentaacetic acid (DTPA) renal scintigraphy. Patients who underwent partial nephrectomy by a single surgeon between 2007 and 2013 were eligible and were matched by propensity score, based on age, tumor size, exophytic properties of tumor, and location relative to the polar lines. Of the 403 patients who underwent partial nephrectomy, 114 (28%) underwent RAPN and 289 (72%) underwent OPN. Mean follow-up duration was 35.2 months. Following propensity matching, there were no significant differences between the two groups in tumor exophytic properties (P = 0.818) or nephrometry score (P = 0.527). Renal ischemic time (24.4 minutes vs. 17.8 minutes, P < 0.001) was significantly longer in the RAPN group than in the OPN group, while the other characteristics were similar. Multivariate analysis showed that greater preoperative renal unit function (P = 0.011) and nephrometry score (P = 0.041) were independently correlated with a reduction in glomerular filtration rate. The operative method did not correlate with renal function impairment (P = 0.704). Postoperative renal function impairment was similar between patients who underwent OPN and those who underwent RAPN, despite RAPN having a longer ischemic time.
Kiuchi, Márcio Galindo; Chen, Shaojie; Andrea, Bruno Rustum; Kiuchi, Tetsuaki; Carreira, Maria Angela Magalhães de Queiroz; Graciano, Miguel Luis; Lugon, Jocemir Ronaldo
Twenty-seven patients with resistant hypertension and chronic kidney disease were treated by renal sympathetic denervation (RSD) and followed for 12 months. Patients were retrospectively divided into controlled and uncontrolled blood pressure (BP) groups. Increases in mean estimated glomerular filtration rate (eGFR) were found at months 1, 3, 6, and 12 in the controlled group (P < .0001, for every time point). The mean change in eGFR after 12 months was 18.54 ± 8.15 mL/min/1.73 m(2) higher in the controlled group (P=.0318). In patients in the controlled group with baseline eGFR < 45 mL/min/1.73 m(2), responders (with an increase in eGFR > 6.2%) corresponded to 50% at 6 months and 83% at 12 months. In the patients with baseline eGFR ≥ 45 mL/min/1.73 m(2), all patients were labeled as responders at months 6 and 12. Median albumin:creatinine ratio after 12 months was lower than baseline only in the controlled group (P = .0003). Our results suggest that patients with this profile who reached BP control by RSD also experienced a significant improvement in renal function.
Kiehl, Kent A; Smith, Andra M; Mendrek, Adrianna; Forster, Bruce B; Hare, Robert D; Liddle, Peter F
We tested the hypothesis that psychopathy is associated with abnormalities in semantic processing of linguistic information. Functional magnetic resonance imaging (fMRI) was used to elucidate and characterize the neural architecture underlying lexico-semantic processes in criminal psychopathic individuals and in a group of matched control participants. Participants performed a lexical decision task in which blocks of linguistic stimuli alternated with a resting baseline condition. In each lexical decision block, the stimuli were either concrete words and pseudowords or abstract words and pseudowords. Consistent with our hypothesis, psychopathic individuals, relative to controls, showed poorer behavioral performance for processing abstract words. Analysis of the fMRI data for both groups indicated that processing of word stimuli, compared with the resting baseline condition, was associated with neural activation in bilateral fusiform gyrus, anterior cingulate, left middle temporal gyrus, right posterior superior temporal gyrus, and left and right inferior frontal gyrus. Analyses confirmed our prediction that psychopathic individuals would fail to show the appropriate neural differentiation between abstract and concrete stimuli in the right anterior temporal gyrus and surrounding cortex. The results are consistent with other studies of semantic processing in psychopathy and support the theory that psychopathy is associated with right hemisphere abnormalities for processing conceptually abstract material.
Kiehl, Kent A; Smith, Andra M; Mendrek, Adrianna; Forster, Bruce B; Hare, Robert D; Liddle, Peter F
We tested the hypothesis that psychopathy is associated with abnormalities in semantic processing of linguistic information. Functional magnetic resonance imaging (fMRI) was used to elucidate and characterize the neural architecture underlying lexico-semantic processes in criminal psychopathic individuals and in a group of matched control participants. Participants performed a lexical decision task in which blocks of linguistic stimuli alternated with a resting baseline condition. In each lexical decision block, the stimuli were either concrete words and pseudowords or abstract words and pseudowords. Consistent with our hypothesis, psychopathic individuals, relative to controls, showed poorer behavioral performance for processing abstract words. Analysis of the fMRI data for both groups indicated that processing of word stimuli, compared with the resting baseline condition, was associated with neural activation in bilateral fusiform gyrus, anterior cingulate, left middle temporal gyrus, right posterior superior temporal gyrus, and left and right inferior frontal gyrus. Analyses confirmed our prediction that psychopathic individuals would fail to show the appropriate neural differentiation between abstract and concrete stimuli in the right anterior temporal gyrus and surrounding cortex. The results are consistent with other studies of semantic processing in psychopathy and support the theory that psychopathy is associated with right hemisphere abnormalities for processing conceptually abstract material.
Kudo, Takashi; Matsuoka, Kiwamu; Yamamoto, Akihide; Takahashi, Masato; Nakagawara, Jyoji; Nagatsuka, Kazuyuki; Iida, Hidehiro; Kishimoto, Toshifumi
Background A significantly lower fractional anisotropy (FA) value has been shown in anterior parts of the corpus callosum in patients with bipolar disorder. Aims We investigated the association between abnormal corpus callosum integrity and interhemispheric functional connectivity (IFC) in patients with bipolar disorder. Methods We examined the association between FA values in the corpus callosum (CC-FA) and the IFC between homotopic regions in the anterior cortical structures of bipolar disorder (n=16) and major depressive disorder (n=22) patients with depressed or euthymic states. Results We found a positive correlation between the CC-FA and IFC values between homotopic regions of the ventral prefrontal cortex and insula cortex, and significantly lower IFC between these regions in bipolar disorder patients. Conclusions The abnormal corpus callosum integrity in bipolar disorder patients is relevant to the IFC between homotopic regions, possibly disturbing the exchange of emotional information between the cerebral hemispheres resulting in emotional dysregulation. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:27847590
Verghese, Joe; Allali, Gilles; Izzetoglu, Meltem; Wang, Cuiling; Mahoney, Jeannette R.
The posture first hypothesis suggests that under dual-task walking conditions older adults prioritize gait over cognitive task performance. Functional neural confirmation of this hypothesis, however, is lacking. Herein, we determined the functional neural correlates of the posture first hypothesis and hypothesized that the presence of neurological gait abnormalities (NGA) would moderate associations between brain activations, gait and cognitive performance. Using functional near-infrared spectroscopy we assessed changes in oxygenated hemoglobin levels in the pre-frontal cortex (PFC) during normal walk and walk while talk (WWT) conditions in a large cohort of non-demented older adults (n = 236; age = 75.5 ± 6.49 years; female = 51.7 %). NGA were defined as central (due to brain diseases) or peripheral (neuropathic gait) following a standardized neurological examination protocol. Double dissociations between brain activations and behavior emerged as a function of NGA. Higher oxygenation levels during WWT were related to better cognitive performance (estimate = 0.145; p < 0.001) but slower gait velocity (estimate = −6.336, p <0.05) among normals. In contrast, higher oxygenation levels during WWT among individuals with peripheral NGA were associated with worse cognitive performance (estimate = −0.355; p <0.001) but faster gait velocity (estimate = 14.855; p <0.05). Increased activation in the PFC during locomotion may have a compensatory function that is designed to support gait among individuals with peripheral NGA. PMID:26613725
Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang
Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM. PMID:27303259
Avery, Jason; Drevets, Wayne C.; Moseman, Scott; Bodurka, Jerzy; Barcalow, Joel; Simmons, W. Kyle
Background Somatic complaints and altered interoceptive awareness are common features in the clinical presentation of major depressive disorder (MDD). Recently, neurobiological evidence has accumulated demonstrating that the insula is one of the primary cortical structures underlying interoceptive awareness. Abnormal interoceptive representation within the insula may thus contribute to the pathophysiology and symptomatology of MDD. Methods We compared fMRI blood oxygenation level-dependent (BOLD) responses between twenty unmedicated adults with MDD and twenty healthy control participants during a task requiring attention to visceral interoceptive sensations and also assessed the relationship of this BOLD response to depression severity, as rated using the Hamilton Depression Rating Scale (HDRS). Additionally, we examined between-group differences in insula resting-state functional connectivity, and its relationship to HDRS ratings of depression severity. Results Relative to the healthy controls, unmedicated MDD subjects exhibited decreased activity bilaterally in the dorsal mid-insula cortex (dmIC) during interoception, as well as within a network of brain regions implicated previously in emotion and visceral control. Activity within the insula during the interoceptive attention task was negatively correlated with both depression severity and somatic symptom severity in depressed subjects. MDD also was associated with greater resting-state functional connectivity between the dmIC and limbic brain regions implicated previously in MDD, including the amygdala, subgenual prefrontal cortex, and orbitofrontal cortex. Moreover, functional connectivity between these regions and the dmIC was positively correlated with depression severity. Conclusions MDD and the somatic symptoms of depression are associated with abnormal interoceptive representation within the insula. PMID:24387823
Conway de Macario, Everly; Robb, Frank T.; Macario, Alberto J. L.
All archaea have a chaperonin of Group II (thermosome) in their cytoplasm and some have also a chaperonin of Group I (GroEL; Cpn60; Hsp60). Conversely, all bacteria have GroEL, some in various copies, but only a few have, in addition, a chaperonin (tentatively designated Group III chaperonin) very similar to that occurring in all archaea, i.e., the thermosome subunit, and in the cytosol of eukaryotic cells, named CCT. Thus, nature offers a range of prokaryotic organisms that are potentially useful as experimental models to study the human CCT and its abnormalities. This is important because many diseases, the chaperonopathies, have been identified in which abnormal chaperones, including mutant CCT, are determinant etiologic-pathogenic factors and, therefore, research is needed to elucidate their pathologic features at the molecular level. Such research should lead to the clarification of the molecular mechanisms underlying the pathologic lesions observed in the tissues and organs of patients with chaperonopathies. Information on these key issues is necessary to make progress in diagnosis and treatment. Some of the archaeal organisms as well as some of the bacterial models suitable for studying molecular aspects pertinent to human mutant chaperones are discussed here, focusing on CCT. Results obtained with the archaeon Pyrococcus furiosus model to investigate the impact of a pathogenic CCT5 mutation on molecular properties and chaperoning functions are reviewed. The pathogenic mutation examined weakens the ability of the chaperonin subunit to form stable hexadecamers and as a consequence, the chaperoning functions of the complex are impaired. The future prospect is to find means for stabilizing the hexadecamer, which should lead to a recovering of chaperone function and the improving of lesions and clinical condition. PMID:28119916
Jiang, Li; Tam, Beatrice M.; Ying, Guoxing; Wu, Sen; Hauswirth, William W.; Frederick, Jeanne M.; Moritz, Orson L.; Baehr, Wolfgang
In Caenorhabditis elegans, homodimeric [kinesin family (KIF) 17, osmotic avoidance abnormal-3 (OSM-3)] and heterotrimeric (KIF3) kinesin-2 motors are required to establish sensory cilia by intraflagellar transport (IFT) where KIF3 and KIF17 cooperate to build the axoneme core and KIF17 builds the distal segments. However, the function of KIF17 in vertebrates is unresolved. We expressed full-length and motorless KIF17 constructs in mouse rod photoreceptors using adeno-associated virus in Xenopus laevis rod photoreceptors using a transgene and in ciliated IMCD3 cells. We found that tagged KIF17 localized along the rod outer segment axoneme when expressed in mouse and X. laevis photoreceptors, whereas KIF3A was restricted to the proximal axoneme. Motorless KIF3A and KIF17 mutants caused photoreceptor degeneration, likely through dominant negative effects on IFT. KIF17 mutant lacking the motor domain translocated to nuclei after exposure of a C-terminal nuclear localization signal. Germ-line deletion of Kif17 in mouse did not affect photoreceptor function. A rod-specific Kif3/Kif17 double knockout mouse demonstrated that KIF17 and KIF3 do not act synergistically and did not prevent rhodopsin trafficking to rod outer segments. In summary, the nematode model of KIF3/KIF17 cooperation apparently does not apply to mouse photoreceptors in which the photosensory cilium is built exclusively by KIF3.—Jiang, L., Tam, B. M., Ying, G., Wu, S., Hauswirth, W. W., Frederick, J. M., Moritz, O. L., Baehr, W. Kinesin family 17 (osmotic avoidance abnormal-3) is dispensable for photoreceptor morphology and function. PMID:26229057
Maenhout, Annelies; Ham, Hamphrey; Ismaili, K; Hall, M; Dierckx, R A; Piepsz, A
The existence of supranormal differential renal function in unilateral hydronephrosis remains controversial. While some authors consider it as fact, others believe that it is just a technical artifact. Within our department, chromium-51 ethylene diamine tetra-acetic acid (Cr-EDTA) renal clearance is systematically performed in conjunction with technetium-99m mercaptoacetyltriglycine (MAG3) renograms to derive an absolute single kidney glomerular filtration rate (SKGFR). Our data allows us to ascertain whether supranormal differential renal function in unilateral hydronephrosis might be due to hypofunction of the contralateral kidney. Children with marked unilateral hydronephrosis were selected from a large database of MAG3 diuretic(s) renograms. We excluded patients with posterior urethral valves, duplex anomalies, neurogenic bladder, solitary kidney, and those who underwent any previous urological surgery. We also excluded children who had an early furosemide injection (F0 procedure), selecting only those having received furosemide at the end of the renogram (F+20 test). Seventy-three patients (92 renograms) fulfilled these criteria. Differential renal function was calculated using the integral method. Hydronephrotic kidney with a relative uptake > or =55% was defined as supranormal. Six renograms (four patients) demonstrated supranormal relative function on the hydronephrotic side. However, the SKGFR of these kidneys was in all cases within the range of normal values, while the contralateral side demonstrated borderline low SKGFR. Increased relative function on the side of the hydronephrotic kidney is relatively infrequent. When it occurs, it may be related to a borderline hypofunction of the contralateral kidney.
Makin, Stephen D.J.; Cook, F.A.B.; Dennis, Martin S.; Wardlaw, Joanna M.
Background The small vessel disease (SVD) that appears in the brain may be part of a multisystem disorder affecting other vascular beds such as the kidney and retina. Because renal failure is associated with both stroke and white matter hyperintensities we hypothesised that small vessel (lacunar) stroke would be more strongly associated with renal failure than cortical stroke. Therefore, we performed a systematic review and meta-analysis to establish first if lacunar stroke was associated with the renal function, and second, if cerebral small vessel disease seen on the MRI of patients without stroke was more common in patients with renal failure. Methods We searched Medline and EMBASE for studies in adults with cerebral SVD (lacunar stroke or white matter hyper intensities (WMH) on Magnetic Resonance Imaging (MRI)), in which renal function was assessed (estimated glomerular filtration rate (eGFR) or proteinuria). We extracted data on SVD diagnosis, renal function, demographics and comorbidities. We performed two meta-analyses: first, we calculated the odds of renal impairment in lacunar (small vessel) ischaemic stroke compared to other ischaemic stroke subtypes (non-small vessel disease); and second, we calculated the odds of renal impairment in non-stroke individuals with WMH on MRI compared to individuals without WMH. We then performed a sensitivity analysis by excluding studies with certain characteristics and repeating the meta-analysis calculation. Results After screening 11,001 potentially suitable titles, we included 37 papers reporting 32 studies of 20,379 subjects: 15 of stroke patients and 17 of SVD features in non-stroke patients. To diagnose lacunar stroke, 13/15 of the studies used risk factor-based classification (none used diffusion-weighted MRI). 394/1,119 (35%) of patients with lacunar stroke had renal impairment compared with 1,443/4,217 (34%) of patients with non-lacunar stroke, OR 0.88, (95% CI 0.6-1.30). In individuals without stroke the
Bernstein, Gail A.; Mueller, Bryon A.; Schreiner, Melinda Westlund; Campbell, Sarah M.; Regan, Emily K.; Nelson, Peter M.; Houri, Alaa K.; Lee, Susanne S.; Zagoloff, Alexandra D.; Lim, Kelvin O.; Yacoub, Essa S.; Cullen, Kathryn R.
Neuroimaging research has implicated abnormalities in cortico-striatal-thalamic-cortical (CSTC) circuitry in pediatric obsessive-compulsive disorder (OCD). In this study, resting-state functional magnetic resonance imaging (R-fMRI) was used to investigate functional connectivity in the CSTC in adolescents with OCD. Imaging was obtained with the Human Connectome Project (HCP) scanner using newly developed pulse sequences which allow for higher spatial and temporal resolution. Fifteen adolescents with OCD and 13 age- and gender-matched healthy controls (ages 12-19) underwent R-fMRI on the 3T HCP scanner. Twenty-four minutes of resting-state scans (two consecutive 12-minute scans) were acquired. We investigated functional connectivity of the striatum using a seed-based, whole brain approach with anatomically-defined seeds placed in the bilateral caudate, putamen, and nucleus accumbens. Adolescents with OCD compared with controls exhibited significantly lower functional connectivity between the left putamen and a single cluster of right-sided cortical areas including the orbitofrontal cortex, inferior frontal gyrus, insula, and operculum. Preliminary findings suggest that impaired striatal connectivity in adolescents with OCD in part falls within the predicted CSTC network, and also involves impaired connections between a key CSTC network region (i.e., putamen) and key regions in the salience network (i.e., insula/operculum). The relevance of impaired putamen-insula/operculum connectivity in OCD is discussed. PMID:26674413
Tomson, S.N.; Schreiner, M.; Narayan, M.; Rosser, Tena; Enrique, Nicole; Silva, Alcino J.; Allen, G.I.; Bookheimer, S.Y.; Bearden, C.E.
Neurofibromatosis type I (NF1) is a genetic disorder caused by mutations in the neurofibromin 1 gene at locus 17q11.2. Individuals with NF1 have an increased incidence of learning disabilities, attention deficits and autism spectrum disorders. As a single gene disorder, NF1 represents a valuable model for understanding gene-brain-behavior relationships. While mouse models have elucidated molecular and cellular mechanisms underlying learning deficits associated with this mutation, little is known about functional brain architecture in human subjects with NF1. To address this question, we used resting state functional connectivity MRI (rs-fcMRI) to elucidate the intrinsic network structure of 30 NF1 participants compared with 30 healthy demographically matched controls during an eyes-open rs-fcMRI scan. Novel statistical methods were employed to quantify differences in local connectivity (edge strength) and modularity structure, in combination with traditional global graph theory applications. Our findings suggest that individuals with NF1 have reduced anterior-posterior connectivity, weaker bilateral edges, and altered modularity clustering relative to healthy controls. Further, edge strength and modular clustering indices were correlated with IQ and internalizing symptoms. These findings suggest that Ras signaling disruption may lead to abnormal functional brain connectivity; further investigation into the functional consequences of these alterations in both humans and in animal models is warranted. PMID:26304096
Bu, Limei; Yu, Dahua; Su, Shaoping; Ma, Yao; von Deneen, Karen M.; Luo, Lin; Zhai, Jinquan; Liu, Bo; Cheng, Jiadong; Guan, Yanyan; Li, Yangding; Bi, Yanzhi; Xue, Ting; Lu, Xiaoqi; Yuan, Kai
Smoking is one of the most prevalent dependence disorders. Previous studies have detected structural and functional deficits in smokers. However, few studies focused on the changes of resting state functional connectivity (RSFC) of the brain regions with structural deficits in young adult smokers. Twenty-six young adult smokers and 26 well-matched healthy non-smokers participated in our study. Voxel-based morphometry (VBM) and RSFC were employed to investigate the structural and functional changes in young adult smokers. Compared with healthy non-smokers, young smokers showed increased gray matter (GM) volume in the left putamen and decreased GM volume in the left anterior cingulate cortex (ACC). Moreover, GM volume in the left ACC has a negative correlation trend with pack-years and GM volume in the left putamen was positively correlated with pack-years. The left ACC and putamen with abnormal volumes were chosen as the regions of interest (ROIs) for the RSFC analysis. We found that smokers showed increased RSFC between the left ACC and right amygdala and between the left putamen and right anterior insula. We revealed structural and functional deficits within the frontostriatal circuits in young smokers, which may shed new insights into the neural mechanisms of smoking. PMID:27757078
Piper, Brian J.; Acevedo, Summer F.; Kolchugina, Galena K.; Butler, Robert W.; Corbett, Selena M.; Honeycutt, Elizabeth B.; Craytor, Michael J.; Raber, Jacob
Methamphetamine/polysubstance abuse in women of childbearing age is a major concern because of the potential long-term detrimental effects on the brain function of the fetus following in utero exposure. A battery of established tests, including the Wechsler Abbreviated Scale of Intelligence, Conners’ Continuous Performance Test II, Behavioral Rating Inventory of Executive Function, the CMS Family Pictures and Dot Location tests, the Spatial Span test from the WISC-IV-Integrated, and a recently developed spatial learning and memory measure (Memory Island), was used to assess the effects of prenatal drug exposure on neurobehavioral performance. Participants were 7 to 9 year old children from similar socioeconomic backgrounds who either had (N = 31) or had not (N = 35) been exposed to methamphetamine/polysubstance during pregnancy. Compared to unexposed children, exposed children showed pronounced elevations (i.e. more problems) in parental ratings of executive function, including behavioral regulation and metacognition. Exposed children also exhibited subtle reductions in spatial performance in the Memory Island test. In contrast, IQ, Spatial Span, Family Pictures, Dot Location, and vigilance performance was unaffected by prenatal drug exposure history. Thus, children of women who reported using methamphetamine and other recreational drugs during pregnancy showed a selective profile of abnormalities in parentally rated executive function. PMID:21334365
Tomson, Steffie N; Schreiner, Matthew J; Narayan, Manjari; Rosser, Tena; Enrique, Nicole; Silva, Alcino J; Allen, Genevera I; Bookheimer, Susan Y; Bearden, Carrie E
Neurofibromatosis type I (NF1) is a genetic disorder caused by mutations in the neurofibromin 1 gene at locus 17q11.2. Individuals with NF1 have an increased incidence of learning disabilities, attention deficits, and autism spectrum disorders. As a single-gene disorder, NF1 represents a valuable model for understanding gene-brain-behavior relationships. While mouse models have elucidated molecular and cellular mechanisms underlying learning deficits associated with this mutation, little is known about functional brain architecture in human subjects with NF1. To address this question, we used resting state functional connectivity magnetic resonance imaging (rs-fcMRI) to elucidate the intrinsic network structure of 30 NF1 participants compared with 30 healthy demographically matched controls during an eyes-open rs-fcMRI scan. Novel statistical methods were employed to quantify differences in local connectivity (edge strength) and modularity structure, in combination with traditional global graph theory applications. Our findings suggest that individuals with NF1 have reduced anterior-posterior connectivity, weaker bilateral edges, and altered modularity clustering relative to healthy controls. Further, edge strength and modular clustering indices were correlated with IQ and internalizing symptoms. These findings suggest that Ras signaling disruption may lead to abnormal functional brain connectivity; further investigation into the functional consequences of these alterations in both humans and in animal models is warranted.
Bernstein, Gail A; Mueller, Bryon A; Schreiner, Melinda Westlund; Campbell, Sarah M; Regan, Emily K; Nelson, Peter M; Houri, Alaa K; Lee, Susanne S; Zagoloff, Alexandra D; Lim, Kelvin O; Yacoub, Essa S; Cullen, Kathryn R
Neuroimaging research has implicated abnormalities in cortico-striatal-thalamic-cortical (CSTC) circuitry in pediatric obsessive-compulsive disorder (OCD). In this study, resting-state functional magnetic resonance imaging (R-fMRI) was used to investigate functional connectivity in the CSTC circuitry in adolescents with OCD. Imaging was obtained with the Human Connectome Project (HCP) scanner using newly developed pulse sequences which allow for higher spatial and temporal resolution. Fifteen adolescents with OCD and 13 age- and gender-matched healthy controls (ages 12-19) underwent R-fMRI on the 3T HCP scanner. Twenty-four minutes of resting-state scans (two consecutive 12-min scans) were acquired. We investigated functional connectivity of the striatum using a seed-based, whole brain approach with anatomically-defined seeds placed in the bilateral caudate, putamen, and nucleus accumbens. Adolescents with OCD compared with controls exhibited significantly lower functional connectivity between the left putamen and a single cluster of right-sided cortical areas including parts of the orbitofrontal cortex, inferior frontal gyrus, insula, and operculum. Preliminary findings suggest that impaired striatal connectivity in adolescents with OCD in part falls within the predicted CSTC network, and also involves impaired connections between a key CSTC network region (i.e., putamen) and key regions in the salience network (i.e., insula/operculum). The relevance of impaired putamen-insula/operculum connectivity in OCD is discussed.
Montagna, P; Provini, F; Plazzi, G; Vetrugno, R; Gallassi, R; Pierangeli, G; Ragno, M; Cortelli, P; Perani, D
Methods: Patients underwent (18F)FDG PET scans and 24 hour polygraphic recordings of wake-sleep and t°. Results: PET showed bilateral thalamic hypometabolism in both patients with additional basal ganglia or mesiolateral frontal and cingular hypometabolism. Wake-sleep studies showed abnormal sleep organisation and in the case with frontal and limbic PET hypometabolism, pre-sleep behaviour associated with "subwakefulness" EEG activities, lack of EEG spindles and K complexes, and features of status dissociatus. The t° rhythms showed increased mesor in both (37.4°C and 37.75°C) and inverted rhythm in one patient. Conclusions: Paramedian thalamic structures and interconnected, especially frontal and cingular, areas play a part in the organisation of the wake-sleep cycle and attendant autonomic functions. PMID:12438490
Melcher, Tobias; Falkai, Peter; Gruber, Oliver
In the present article, we review functional neuroimaging studies on interference processing and performance monitoring in three groups of psychiatric disorders, (1) mood disorders, (2) schizophrenia, and (3) obsessive-compulsive disorder (OCD). Ad (1) Behavioral performance measures suggest an impaired interference resolution capability in symptomatic bipolar disorder patients. A series of neuroimaging analyses found alterations in the ACC-DLPFC system in mood disorder (unipolar depressed and bipolar) patients, putatively reflective of an abnormal interplay of monitoring and executive neurocognitive functions. Other studies of euthymic bipolar patients showed relatively decreased interference-related activation in rostroventral PFC which conceivably underlies defective inhibitory control. Ad (2) Behavioral Stroop studies revealed a specific performance pattern of schizophrenia patients (normal RT interference but increased error interference and RT facilitation) suggestive of a deficit in ignoring irrelevant (word) information. Moreover, reduced/absent behavioral post-error and post-conflict adaptation effects suggest alterations in performance monitoring and/or adjustment capability in these patients. Neuroimaging findings converge to suggest a disorder-related abnormal neurophysiology in ACC which consistently showed conflict- and error-related hypoactivation that, however, appeared to be modulated by different factors. Moreover, studies suggest a specific deficit in context processing in schizophrenia, evidently related to activation reduction in DLPFC. Ad (3) Behavioral findings provide evidence for impaired interference resolution in OCD. Neuroimaging results consistently showed conflict- and error-related ACC hyperactivation which--conforming OCD pathogenesis models--can be conclusively interpreted as reflecting overactive performance monitoring. Taken together, interference resolution and performance monitoring appeared to be fruitful concepts in the
Baller, Erica B.; Wei, Shau-Ming; Kohn, Philip D.; Rubinow, David R.; Alarcón, Gabriela; Schmidt, Peter J.; Berman, Karen F.
Objective To investigate the neural substrate of premenstrual dysphoric disorder (PMDD), the authors used [15O]H2O positron emission tomography (PET) regional cerebral blood flow (rCBF) and blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) signal measurements during working memory in conjunction with a 6-month hormone manipulation protocol. Method PET and fMRI scans were obtained from women with prospectively confirmed PMDD and asymptomatic comparison subjects while they completed the n-back task during three hormone conditions: ovarian suppression induced by the gonadotropin-releasing hormone agonist leuprolide acetate, leuprolide plus estradiol, and leuprolide plus progesterone. Fifteen patients and 15 matched comparison subjects underwent PET imaging. Fourteen patients and 14 comparison subjects underwent fMRI. For each hormone condition, rCBF was measured with [15O]H2O PET, and BOLD signal was measured with fMRI, both during an n-back working memory paradigm. Global Assessment of Functioning Scale (GAF) scores and clinical characteristics were obtained for each patient before hormone manipulation, and symptoms were measured before and during the protocol. Results In both the PET and fMRI studies, a main effect of diagnosis was observed, with PMDD patients showing greater prefrontal activation than comparison subjects. In the patient group, the degree to which dorsolateral prefrontal cortex activation was abnormally increased correlated with several dimensions of disease: disability as indicated by GAF scores, age at symptom onset, duration of PMDD, and differences in pre- and postmenses PMDD symptoms. Conclusions Abnormal working memory activation in PMDD, specifically in the dorsolateral prefrontal cortex, is related to PMDD severity, symptoms, age at onset, and disease burden. These results support the clinical relevance of the findings and the proposal that dorsolateral prefrontal cortex dysfunction represents a substrate of risk for PMDD. The
Lin, L C; Yang, S C; Lu, K W
Airway obstruction is a prominent feature in coal workers' pneumoconiosis (CWP). However, many patients with CWP have even demonstrated a normal forced vital capacity (FVC) and forced expiratory volume in 1s (FEV1). The purpose of this study was to evaluate the ventilatory defect by spirometry and search for parameters, other than FVC and FEV1, suitable for early detection of pulmonary impairment in CWP. A sample of 227 coal miners was selected from the medical clinics of two teaching hospitals. Maximal expiratory flow volume measurement and determination of functional residual capacity (FRC) and residual volume (RV) were carried out with an automated plethysmograph. The prevalence of airway obstruction (FEV1/FVC < 70%) in this sample of miners was 52.9% (120/227). There was a progression of functional impairment with the transition from category 0 to categories 2 and 3, no matter what the miners smoking habits. All of the 107 non-obstructed miners had a normal FVC and FEV1. However, the mean values for FEF25-75% (mean forced expiratory flow during the middle half of FVC) and Vmax50 (maximal expiratory flow rate at 50% FVC) were abnormally low, and RV was already elevated, in those non-obstructed subjects with category 1 simple pneumoconiosis. A borderline abnormally elevated FRC in the miners with radiological category 3 of CWP was also noted. We conclude that the Vmax50, FEF25-75%, and RV appeared to be the discriminative indices for detecting early ventilatory defect in non-obstructed patients with simple CWP. Further studies is still needed to clarify the cause of small airway dysfunction.
Jahn, Matheus Parmegiani; Gomes, Luana Ferreira; Jacob, Maria Helena Vianna Metello; da Rocha Janner, Daiane; Araújo, Alex Sander da Rosa; Belló-Klein, Adriane; Ribeiro, Maria Flávia Marques; Kucharski, Luiz Carlos
Dehydroepiandrosterone (DHEA) is an endogenous steroid hormone involved in a number of biological actions in humans and rodents, but its effects on renal tissue have not yet been fully understood. The aim of this study is to assess the effect of DHEA treatment on diabetic rats, mainly in relation to renal function and metabolism. Diabetic rats were treated with subcutaneous injections of a 10mg/kg dose of DHEA diluted in oil. Plasma glucose and creatinine, in addition to urine creatinine, were quantified espectophotometrically. Glucose uptake and oxidation were quantified using radioactive glucose, the urinary Transforming Growth Factor β(1) (TGF-β(1)) was assessed by enzyme immunoassay, and the total glutathione in the renal tissue was also measured. The diabetic rats displayed higher levels of glycemia, and DHEA treatment reduced hyperglycemia. Plasmatic creatinine levels were higher in the diabetic rats treated with DHEA, while creatinine clearance was lower. Glucose uptake and oxidation were lower in the renal medulla of the diabetic rats treated with DHEA, and urinary TGF-β(1), as well as total gluthatione levels, were higher in the diabetic rats treated with DHEA. DHEA treatment was not beneficial to renal tissue, since it reduced the glomerular filtration rate and renal medulla metabolism, while increasing the urinary excretion of TGF-β(1) and the compensatory response by the glutathione system, probably due to a mechanism involving a pro-oxidant action or a pro-fibrotic effect of this androgen or its derivatives. In conclusion, this study reports that DHEA treatment may be harmful to renal tissue, but the mechanisms of this action have not yet been fully understood.
Gupta, Punkaj; Rettiganti, Mallikarjuna; Gossett, Jeffrey M; Gardner, Megan; Bryant, Janet C; Noel, Tommy R; Knecht, Kenneth R
This study was initiated to assess the temporal trends of renal function, and define risk factors associated with worsening renal function in pediatric heart transplant recipients in the immediate post-operative period. We performed a single-center retrospective study in children ≤18 yr receiving OHT (1993-2012). The AKIN's validated, three-tiered AKI staging system was used to categorize the degree of WRF. One hundred sixty-four patients qualified for inclusion. Forty-seven patients (28%) were classified as having WRF after OHT. Nineteen patients (11%) required dialysis after heart transplantation. There was a sustained and steady improvement in renal function in children following heart transplantation in all age groups, irrespective of underlying disease process. The significant factors associated with risk of WRF included body surface area (OR: 1.89 for 0.5 unit increase, 95% CI: 1.29-2.76, p = 0.001) and use of ECMO prior to and/or after heart transplantation (OR: 3.50, 95% CI: 1.51-8.13, p = 0.004). Use of VAD prior to heart transplantation was not associated with WRF (OR: 0.50, 95% CI: 0.17-1.51, p = 0.22). On the basis of these data, we demonstrate that worsening renal function improves early after orthotopic heart transplantation.
Loggie, Jennifer M. H.; And Others
Included in the review are a description of the anatomic and functional development of the human kidney, a comparison of the renal physiology of the infant and adult, and a discussion of the pediatric clinical pharmacology of the most commonly used diuretic agents. (DB)
Wang, Tommy J.; Wade, Charles E.; Dalton, Bonnie P. (Technical Monitor)
Spaceflight induces changes in human renal function, suggesting similar changes may occur in rats. Since rats continue to be the prime mammalian model for study in space, the effects of chronic microgravity on rat renal function should be clarified. Acute studies in rats using the ground-based microgravity simulation model, head-down tilt (HDT), have shown increases in glomerular filtration rate (GFR), electrolyte excretion, and a diuresis. However, long term effects of HDT have not been studied extensively. This study was performed to elucidate rat renal function following long-term simulated microgravity. Chronic exposure to HDT will cause an increase in GFR and electrolyte excretion in rats, similar to acute exposures, and lead to a decrease in the fractional excretion of filtered electrolytes. Experimental animals (HDT, n=10) were tail-suspended for 37 days and renal function compared to ambulatory controls (AMB, n=10). On day 37 of HDT, GFR, osmolal clearance, and electrolyte excretion were decreased, while plasma osmolality and free water clearance were increased. Urine output remained similar between groups. The fractional excretion of the filtered electrolytes was unchanged except for a decrease in the percentage of filtered calcium excreted. Chronic exposure to HDT results in decreased GFR and electrolyte excretion, but the fractional excretion of filtered electrolytes remained primarily unaffected.
Hammad, Fayez T; Lubbad, Loay
Introduction: The aim of this study was to investigate the effect of thymoquinone, an antioxidant phytochemical compound found in the plant Nigella sativa, on the alterations in renal functional parameters following warm renal ischemia-reperfusion injury (IRI) in the rat. Methods: Wistar rats underwent left renal ischemia for 35 minutes. Group-TQ (n=15) received thymoquinone 10 mg/kg/day (dissolved in a vehicle (corn oil) orally by gavage starting 4 days prior to IRI and continued 6 days thereafter when the hemodynamic and tubular renal functions of the right and left kidneys were measured using clearance techniques. Group-Vx (n=15) underwent similar protocol but received only the vehicle. Results: IRI affected all hemodynamic and tubular parameters in the affected kidney. Thymoquinone attenuated the IRI-related alteration in renal functions so when the left ischemic kidney in Group-TQ and Group-Vx were compared, the left RBF and GFR were significantly higher in Group-TQ (2.02±0.39 vs. 1.27±0.21, P=0.04 and 0.33±0.08 vs. 0.18±0.03, P=0.03, respectively). Thymoquinone also improved left renal FENa (1.59±0.28 vs. 2.40±0.35, P=0.04). In addition, it decreased the gene expressions of KIM-1, NGAL, TNF-α, TGF-β1 and PAI-1 (143±20 vs. 358±49, 16±3 vs. 34±6, (1.1±0.2 vs. 2.8±0.4, 1.6±0.1 vs. 2.8±0.1, and 2.4±0.3 vs. 5.8±1.0, P<0.05 for all). Conclusion: Thymoquinone ameliorated the IRI effect on the hemodynamic and tubular renal functional parameters as well as the expression of some kidney injury markers and pro-inflammatory and pro-fibrotic cytokines indicating a renoprotective effect of this agent on the IRI-induced renal dysfunction with potential clinical implications. PMID:28078054
St Peter, J V; Borin, M T; Hughes, G S; Kelloway, J S; Shapiro, B E; Halstenson, C E
The disposition of cefpodoxime in 24 subjects with various degrees of renal function after administration of a single oral dose of 200 mg of cefpodoxime proxetil (equivalent to 200 mg of cefpodoxime activity) was studied. Subjects were assigned to one of four groups (six per group): group I, normal renal function (creatinine clearance [CLCR], greater than ml/min); group II, mild renal impairment (CLCR, 50 to 80 ml/min); group III, moderate renal impairment (CLCR, 30 to 49 ml/min); or group IV, severe renal impairment (CLCR, 5 to 29 ml/min). Although cefpodoxime terminal elimination half-life in group I (2.55 +/- 0.25 h [mean +/- standard deviation]) was not significantly different from that in group II (3.53 +/- 0.74 h), the half-life values for group III (5.90 +/- 1.67 h) and group IV (9.80 +/- 1.21 h) were significantly prolonged compared with those of group I. The mean absorption rate constant was similar among groups and ranged from 0.68 to 0.85 h-1. All groups exhibited absorption lag-times which were comparable (0.30 to 0.41 h), and the apparent volume of distribution was similar among groups. Cefpodoxime apparent total body clearance (CLP/F) values in groups II, III, and IV (132 +/- 29, 112 +/- 41, and 55.7 +/- 9.9 ml/min, respectively) were significantly lower than that in group I (238 +/- 44 ml/min). Cefpodoxime CLP/F was positively correlated with CLCR (r2 = 0.79; P less than 0.05): CLP/F = (1.9 CLCR) + 18.4. Renal clearance also declined with decreasing renal function. Adjustments in cefpodoxime organism and on the site and severity of infection. Simulated plasma concentration-time data from this study suggest that 200 mg of cefpodoxime proxetil administered every 12 to 24 h to subjects with CLcr between 30 and 49 ml/min and 200-mg dose taken every 24 h by subjects with CLcr between 5 and 29 ml/min will maintain cefpodoxime concentration in plasma similar to those in subjects with normal renal function who receive a standard dosage mg every 12 h. PMID
Rowe, D.M.; Becker, G.J.; Rabe, F.E.; Holden, R.W.; Richmond, B.D.; Wass, J.L.; Sequeira, F.W.
Five patients underwent preoperative embolization of osseous metastases from renal cell carcinoma. The group consisted of four men and one woman who ranged in age from 46 to 79 years. The lesions were located in the pubic ramus and acetabulum, proximal femur, femoral midshaft, proximal humerus, and proximal tibia. All embolizations were performed within 24 hours of surgery. The internal fixation and tumor curettage was accomplished with estimated perioperative blood loss ranging from 10 ml to 1,250 ml. All patients had significant restoration of function following surgery. The authors suggest that preoperative embolization is an important and efficacious adjunct in the management of hypervascular renal cell osseous metastases.
Woods, P R; Drost, W T; Clarke, C R; Rodebush, C J
Ten healthy horses were injected intravenously with 99mTc-MAG3 and the disappearance of radioactivity from the blood was measured. The total body clearance (Cl(B)) and elimination half-life (t1/2(beta)) were 7.9 +/- 1.5 ml/kg/minute and 32.8 +/- 4.1 minutes, respectively. The disappearance of 99mTc-MAG3 from the blood of 2 horses with compromised renal function was also measured. The data suggest that 99mTc-MAG3 is a useful and clinically applicable radiopharmaceutical for measurement of effective renal blood flow in the horse.
Meng, Hong-Zhou; Cao, Min; Xiang, Jian-Jian; Zhou, Xie-Lai; Yin, Hong-Ping; Jin, Bai-Ye; Chen, Zhao-Dian; Jin, Xiao-Dong
The aim of this study was to investigate the influence of the duration of bladder overdistention (DOBO) on kidney structure and function in rats. Bladder overdistention was induced in male Sprague-Dawley rats by an infusion of saline. Forty rats were divided into five groups: DOBO 1, 2, 4 or 8 h groups and the control. Renal function was evaluated using serum creatinine (SCr) and blood urea nitrogen (BUN). Apoptotic indices and morphologic changes of the kidney were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining and transmission electron microscopy (TEM). Compared with the control, rats undergoing 2, 4 or 8 h of overdistention showed significant, time-dependent increases in SCr (12.375 vs. 23.125, 34.375 and 51.500 μmol/l, respectively), BUN (6.980 vs. 18.689, 25.184 and 32.079 mmol/l, respectively), renal size (1.041 vs. 1.472, 1.484 and 1.634 cm(3), respectively) and renal pelvis separation (0.000 vs. 0.223, 0.320, 0.308 and 0.277 cm, respectively; P<0.01). In the rats, 2, 4 and 8 h of overdistention elicited time-dependent increases in the blood flow rate in the main renal artery (MRA; 44.827 vs. 49.082, 59.688 and 67.123 cm(3)/sec, control vs. DOBO 2, 4 and 8 h), the interlobar renal artery (IRA; 32.095 vs. 39.16 and 51.745 cm(3)/sec, control vs. DOBO 4 and 8 h) and the segmental renal artery (SRA; 21.171 vs. 24.355 and 25.358 cm(3)/sec, control vs. DOBO 4 and 8 h; P<0.01). TUNEL results showed that prolonged overdistention increased the apoptotic index of renal cells significantly (1.15, 1.77, 3.40, 5.34 and 13.91% for control and DOBO 1, 2, 4 and 8 h, respectively; P<0.01) and TEM indicated that prolonged overdistention resulted in ultrastructural injuries of increased severity. DOBO plays a significant role in the functional and structural impairment of the rat kidney. With increasing duration, the hemodynamic changes, cell apoptosis and ultrastructural injuries of the kidney are more evident, all of
Doucet, Gaelle E.; He, Xiaosong; Sperling, Michael; Sharan, Ashwini; Tracy, Joseph I.
Temporal lobe epilepsy (TLE) affects multiple brain regions through evidence from both structural (gray matter; GM) and functional connectivity (FC) studies. We tested whether these structural abnormalities were associated with FC abnormalities, and assessed the ability of these measures to explain episodic memory impairments in this population. A resting-state and T1 sequences were acquired on 94 (45 with mesial temporal pathology) TLE patients and 50 controls, using magnetic resonance imaging (MRI) technique. A voxel-based morphometry analysis was computed to determine the GM volume differences between groups (right, left TLE, controls). Resting-state FC between the abnormal GM volume regions was computed, and compared between groups. Finally, we investigated the relation between EM, GM and FC findings. Patients with and without temporal pathology were analyzed separately. The results revealed reduced GM volume in multiple regions in the patients relative to the controls. Using FC, we found the abnormal GM regions did not display abnormal functional connectivity. Lastly, we found in left TLE patients, verbal episodic memory was associated with abnormal left posterior hippocampus volume, while in right TLE, non-verbal episodic memory was better predicted by resting-state FC measures. This study investigated TLE abnormalities using a multi-modal approach combining GM, FC and neurocognitive measures. We did not find that the GM abnormalities were functionally or abnormally connected during an inter-ictal resting state, which may reflect a weak sensitivity of functional connectivity to the epileptic network. We provided evidence that verbal and non-verbal episodic memory in left and right TLE patients may have distinct relationships with structural and functional measures. Lastly, we provide data suggesting that in the setting of occult, non-lesional right TLE pathology, a coupling of structural and functional abnormalities in extra-temporal/non-ictal regions is
Mbarki, Houda; Tazi, Nada; Najdi, Adil; Tachfouti, Nabil; Arrayhani, Mohamed; Sqalli, Tarik
Fasting during Ramadan is prohibited when an individual's health is endangered. Little work has been published in this direction in patients with chronic kidney disease (CKD). We aimed to evaluate the impact of fasting during Ramadan on the renal function of patients with CKD, adjusting for the initial degree of renal impairment. We prospectively studied 60 patients with CKD (35 females; mean age 45.6 ± 15.8 years). All study patients were older than 15 years, being followed-up at the nephrology clinic for more than six months, having a stable CKD during the preceding six months and who had fasted during Ramadan the previous year. Patients who had a medical contra-indication for fasting were excluded from the study [severe or resistant arterial hypertension, insulin-requiring diabetes, acute renal failure (ARF), active renal disease, repetitive urolithiasis or terminal chronic renal failure]. Statistical analysis was performed in collaboration with the epidemiology lab at the Fez Medical School using the SPSS software version 17. Three of the study patients developed ARF in the first week and four of them at the end of the month of the study period. The risk of developing ARF was significantly higher for patients with baseline creatinine clearance of <60 mL/min/1.73 m 2 . However, the small sample size does not allow us to draw any firm conclusions on fasting during Ramadan in stable CKD patients. Studies on larger numbers of patients are recommended.
Platt, Mark; Kasprzyk, Joanna; Kuśnierz-Cabala, Beata; Gala-Błądzińska, Agnieszka; Woźnicka, Olga; Jany, Benedykt R.; Krok, Franciszek; Piekoszewski, Wojciech; Kuźniewski, Marek
The aim of this study was to check the relationship between the density of urinary EVs, their size distribution, and the progress of early renal damage in type 2 diabetic patients (DMt2). Patients were enrolled to this study, and glycated hemoglobin (HbA1c) below 7% was a threshold for properly controlled diabetic patients (CD) and poorly controlled diabetic patients (UD). Patients were further divided into two groups: diabetic patients without renal failure (NRF) and with renal failure (RF) according to the Glomerular Filtration Rate. Density and diameter of EVs were determined by Tunable Resistive Pulse Sensing. Additionally, EVs were visualized by means of Transmission and Environmental Scanning Electron Microscopy. Nano-liquid chromatography coupled offline with mass spectrometry (MALDI-TOF-MS/MS) was applied for proteomic analysis. RF had reduced density of EVs compared to NRF. The size distribution study showed that CD had larger EVs (mode) than UD (115 versus 109 nm; p < 0.05); nevertheless the mean EVs diameter was smaller in controls than in the CD group (123 versus 134 nm; p < 0.05). It was demonstrated that EVs are abundant in urine. Albumin, uromodulin, and number of unique proteins related to cell stress and secretion were detected in the EVs fraction. Density and size of urinary EVs reflect deteriorated renal function and can be considered as potential renal damage biomarkers. PMID:28105442
Higashihara, E.; Tokuda, H.; Kishi, H.; Niijima, T.; Okada, Y.; Nishikawa, J.; Iio, M.
We studied 23 long-term catheterized kidneys in 14 patients. The uptake of /sup 99m/Tc acid (/sup 99m/Tc-DMSA) was measured at one- and two-hour intervals after injection, and the uptake was corrected for variations in renal depth. These values were compared with inulin, creatinine, and para-amino hippurate (PAH) clearances which were measured in each kidney by collecting urine through long-term catheterization. Correlation coefficient was obtained between PAH clearance corrected for the body surface area and the two-hour uptake of /sup 99m/Tc-DMSA. The correlation coefficients between the two-hour uptake of /sup 99m/Tc-DMSA and the clearance values are not significantly different from those between the one-hour uptake and the clearance values. Corrections of the uptake for variations in renal depth did not improve the correlation coefficients. The results show that /sup 99m/Tc-DMSA is an excellent method to estimate the renal plasma flow and the one-hour uptake without correction for renal depth is clinically sufficient to evaluate the split renal function.
Epstein, M.; Shubrooks, S. J., Jr.; Fishman, L. M.; Duncan, D. C.
The effects of positive radial centrifugation (+Gz) on plasma resin activity (PRA) and renal function were assessed in 15 normal male subjects under carefully controlled conditions of Na, K, and water intake. Twenty minutes of +2.0 Gz resulted in significant decreases in the mean rate of sodium excretion and creatine clearance and in a doubling of PRA in seven sodium-depleted subjects (10 meq Na intake). In eight sodium-replete subjects (200 mq Na intake), 30 min of +2.0 Gz was also associated with a decrease in the mean rate of sodium excretion. As a consequence of a concurrent decrease in creatine clearance, the fractional excretion of sodium during centrifugation did not differ from control, suggesting that the changes in Na excretion were mediated primarily by renal hemodynamic factors, although enhanced renal tubular sodium reabsorption may also have played a role.
Ma, Zi-li; Gao, Yang; Ma, Hai-tian; Zheng, Liu-hai; Dai, Bin; Miao, Jin-feng; Zhang, Yuan-shu
This study investigated the putative protective effects of supplemental 2-aminoethane sulfonic acid (taurine) and reduced housing density on renal function in laying hens. We randomly assigned fifteen thousand green-shell laying hens into three groups: a free range group, a low-density caged group, and a high-density caged group. Each group was further divided equally into a control group (C) and a taurine treatment group (T). After 15 d, we analyzed histological changes in kidney cells, inflammatory mediator levels, oxidation and anti-oxidation levels. Experimental data revealed taurine supplementation, and rearing free range or in low-density housing can lessen morphological renal damage, inflammatory mediator levels, and oxidation levels and increase anti-oxidation levels. Our data demonstrate that taurine supplementation and a reduction in housing density can ameliorate renal impairment, increase productivity, enhance health, and promote welfare in laying hens. PMID:27921400
BLAZER-YOST, BONNIE L.; BANGA, AMIRAJ; AMOS, ADAM; CHERNOFF, ELLEN; LAI, XIANYIN; LI, CHENG; MITRA, SOMENATH; WITZMANN, FRANK A.
To assess effects of carbon nanoparticle (CNP) exposure on renal epithelial cells, fullerenes (C60), single-walled carbon nanotubes (SWNT), and multi-walled carbon nanotubes (MWNT) were incubated with a confluent renal epithelial line for 48 h. At low concentrations, CNP-treated cells exhibited significant decreases in transepithelial electrical resistance (TEER) but no changes in hormone-stimulated ion transport or CNP-induced toxicity or stress responses as measured by lactate dehydrogenase or cytokine release. The changes in TEER, manifested as an inverse relationship with CNP concentration, were mirrored by an inverse correlation between dose and changes in protein expression. Lower, more physiologically relevant, concentrations of CNP have the most profound effects on barrier cell function and protein expression. These results indicate an impact of CNPs on renal epithelial cells at concentrations lower than have been previously studied and suggest caution with regard to increasing CNP levels entering the food chain due to increasing environmental pollution. PMID:21067278
Ma, Zi-Li; Gao, Yang; Ma, Hai-Tian; Zheng, Liu-Hai; Dai, Bin; Miao, Jin-Feng; Zhang, Yuan-Shu
This study investigated the putative protective effects of supplemental 2-aminoethane sulfonic acid (taurine) and reduced housing density on renal function in laying hens. We randomly assigned fifteen thousand green-shell laying hens into three groups: a free range group, a low-density caged group, and a high-density caged group. Each group was further divided equally into a control group (C) and a taurine treatment group (T). After 15 d, we analyzed histological changes in kidney cells, inflammatory mediator levels, oxidation and anti-oxidation levels. Experimental data revealed taurine supplementation, and rearing free range or in low-density housing can lessen morphological renal damage, inflammatory mediator levels, and oxidation levels and increase anti-oxidation levels. Our data demonstrate that taurine supplementation and a reduction in housing density can ameliorate renal impairment, increase productivity, enhance health, and promote welfare in laying hens.
Hugdahl, Kenneth; Løberg, Else-Marie; Nygård, Merethe
In this article, we have reviewed recent findings from our laboratory, originally presented in Hugdahl et al. (2008). These findings reveal that auditory hallucinations in schizophrenia should best be conceptualized as internally generated speech mis-representations lateralized to the left superior temporal gyrus and sulcus, not cognitively suppressed due to enhanced attention to the ‘voices’ and failure of fronto-parietal executive control functions. An overview of diagnostic questionnaires for scoring of symptoms is presented together with a review of behavioral, structural, and functional MRI data. Functional imaging data have either shown increased or decreased activation depending on whether patients have been presented an external stimulus during scanning. Structural imaging data have shown reduction of grey matter density and volume in the same areas in the temporal lobe. We have proposed a model for the understanding of auditory hallucinations that trace the origin of auditory hallucinations to neuronal abnormality in the speech areas in the left temporal lobe, which is not suppressed by volitional cognitive control processes, due to dysfunctional fronto-parietal executive cortical networks. PMID:19753095
Azurmendi, Pablo J; Oddo, Elisabet M; Toledo, Jorge E; Martin, Rodolfo S; Ibarra, Fernando R; Arrizurieta, Elvira E
The role played by sexual hormones and vasoactive substances in the compensatory renal growth (CRG) that follows uninephrectomy (uNx) is still controversial. Intact and gonadectomized adult Wistar rats of both sexes, with and without uNx, performed at 90 days age, were studied at age 150 days. Daily urine volume, electrolyte excretion and kallikrein activity (UKa) were determined. Afterwards, glomerular filtration rate and blood pressure were measured, the kidneys weighed and DNA, protein and RNA studied to determine nuclei content and cell size. When the remnant kidney weight at age 150 days was compared with the weight of the kidney removed at the time of uNx, male uNx rats showed the greatest CRG (50%) while growth in the other uNx groups was 25%, 15% and 19% in orchidectomized, female and ovariectomized rats, respectively. The small CRG observed in the uNx female rats was accompanied by the lowest glomerular filtration value, 0.56 ± 0.02 ml/ min/g kwt compared, with the other uNx groups, p < 0.05. Cell size (protein or RNA/DNA) was similar for all the groups except for uNx orchidectomized rats. In this group the cytoplasmatic protein or RNA content was lower than in the other groups while DNA (nuclei content) was similar. Some degree of hyperplasia was determined by DNA content in the uNx groups. Male sexual hormones positively influenced CRG and its absence modulated cell size. Female sexual hormones, instead, did not appear to stimulate CRG. The kallikrein kinin system may not be involved in CRG.
Yamamura, Soichiro; Kawakami, Kazumori; Hirata, Hiroshi; Ueno, Koji; Saini, Sharanjot; Majid, Shahana; Dahiya, Rajvir
The secreted Frizzled-related proteins (sFRP) are modulators of the Wnt signaling pathway, which is involved in embryonic development and tumor progression. The functions of sFRP2 have not been studied in renal cancer. Transient transfection of sFRP2 promoted cell growth in renal carcinoma cells, whereby the largest effect was observed in A498 cells. To further study the functions of sFRP2 gene in renal carcinoma cells, we established A498 renal cancer cell lines, which stably expressed sFRP2. Stably expressed sFRP2 significantly promoted cell proliferation in vitro and in vivo tumor growth. The stably expressed sFRP2 cells were also found to have reduced UV-induced apoptosis and increased G(2) phase of the cell cycle. The phosphorylation level at Ser(33/37)/Thr(41) of beta-catenin was lower in the stable sFRP2 cell lines compared with the control cell line. sFRP2 significantly activated T-cell factor/lymphoid enhancer factor transcriptional activity. In the stable sFRP2 cell line, expression of c-Fos, Bcl2, Bcl-w, cyclin B2, and cyclin E2 genes was significantly increased and p53 expression was decreased. This is the first report documenting that sFRP2 activates the canonical Wnt pathway and promotes cell growth by evoking diverse signaling cascades in renal cancer cells. This study may provide better strategies for the management of renal cancer through regulation of sFRP2 pathways.
Hall, J E; Morse, C L; Smith, M J; Young, D B; Guyton, A C
This study was designed to investigate the long-term effects of glucocorticoids on the control of mean arterial pressure (MAP) and renal function. Infusion of 10 mg/day of methylprednisolone (MP), a glucocorticoid with minimal mineralocorticoid activity, for 10 days in six intact conscious dogs maintained on a sodium intake of 78 mEq/day resulted in a decrease in MAP from 98 +/- 1 to 89 +/- 2 mm Hg, a decrease in sodium iothalamate space to 89 +/- 2% of control, and a marked increase in glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and urinary sodium excretion. Chronic infusion of MP at doses of 2--800 mg/day in four dogs maintained on low (5 mEq/day) or high sodium intakes (160--223 mEq/day) also caused increases in GFR and ERPF, as well as natriuresis and decreased sodium iothalamate space, while causing either no change or a slight reduction in MAP. To determine whether glucocorticoids potentiate the chronic effects of angiotensin II (AII) on MAP and renal function, MP was infused in dogs undergoing AII infusion (5 ng/kg/min). During AII hypertension, chronic infusion of 5 or 10 mg/day of MP also resulted in a marked renal vasodilation, natriuresis, and reductions in sodium iothalamate space, while causing small reductions in MAP. Thus, we found no evidence that chronic glucocorticoid excess causes hypertension in dogs, or that glucocorticoids potentiate the blood pressure or renal effects of AII. Instead, glucocorticoids tended to reduce MAP, probably because of chronic renal vasodilation, increased excretion of sodium, and volume depletion.
Gupta, Samir K; Kitch, Douglas; Tierney, Camlin; Melbourne, Kathleen; Ha, Belinda; McComsey, Grace A
Objectives Both renal disease and systemic inflammation predict non-AIDS events and overall mortality in HIV-infected patients. Here we sought to determine the relationships between renal disease and circulating inflammation markers. Methods We performed a secondary analysis of AIDS Clinical Trials Group study A5224s to determine if markers of renal disease [urine protein/creatinine (uPCR); urine albumin/creatinine (uACR); estimated glomerular filtration rate, eGFR, using CKD-EPI creatinine and cystatin C-creatinine] were associated with markers of systemic inflammation [high sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, soluble receptors of TNF-α (sTNFRI and II), soluble vascular cellular and intercellular adhesion molecules]. We correlated these renal and inflammatory markers prior to antiretroviral initiation and at 96 weeks of therapy. Results We found that estimated eGFR (using CKD-EPI cystatin C-creatinine), uPCR, and uACR were significantly correlated with most assessed markers of systemic inflammation prior to antiretroviral initiation. uPCR and eGFR (using CKD-EPI cystatin C-creatinine), but not uACR, remained significantly correlated with most of the assessed inflammatory markers after 96 weeks of ART. Most of these correlations, although statistically significant, were under 0.50. eGFR using CKD-EPI creatinine was much less frequently associated with inflammation markers and only significantly correlated with sTNFR1 at Week 0 and with sTNFRI and II at Week 96. Conclusions Renal disease and function are associated with systemic inflammation in HIV both before and after ART. Systemic inflammation may partially explain the relationships between proteinuria, albuminuria, and reduced renal function and future adverse outcomes. PMID:25990642
Wang, Zewei; Yang, Qing; Chen, Li Min
The goals of this study are to characterize the temporal dynamics of inter-regional connectivity of the brain in chronic headache (CH) patients versus their age/gender matched controls (CONCH, n=28 pairs), and to determine whether dynamic measures reveal additional features to static functional connectivity and correlate with psychometric scores. Cortical thickness and inter-regional resting state fMRI connectivity were quantified and compared between CH and CONCH groups. Six cortical regions of interest (ROI) pairs that exhibited correlated cortical thickness and static functional connectivity abnormalities were selected for temporal dynamic analysis. Two methods were used: temporal sliding-window (SW) and wavelet transformation coherence (WTC). SW analyses using three temporal windows of 30, 60, 120s revealed that all six ROI pairs of CH exhibited higher percentage of strong connectivity (high r values), and smaller fast Fourier transform (FFT) amplitudes at a very low frequency range (i.e., 0.002-0.01Hz), compared to those of CONCH. These features were particularly prevalent in the 120s window analysis. Less variable dynamic fluctuation (i.e., smaller standard deviation of r values) was identified in two out of six ROI pairs in CH. WTC analysis revealed that time-averaged coherence was generally greater in CH than CONCH between wavelet decomposition scales 20 to 55 (0.018-0.05Hz), and was statistically significant in three out of six ROI pairs. Together, the most robust and significant differences in temporal dynamics between CH and CONCH were detected in two ROI pairs: left medial-orbitofrontal-left posterior-cingulate and left medial-orbitofrontal-left inferior-temporal. The high degrees of sleep disturbance (high PSQI score), depression (high HRSD score) and fatigue (low SF-36 score) were associated with high degree of inter-regional temporal coherence in CH. In summary, these dynamic functional connectivity (dFC) measures uncovered a temporal "lock
Souza, William Marciel; Heck, Thiago Gomes; Wronski, Evanio Castor; Ulbrich, Anderson Zampier; Boff, Everton
Creatine supplementation has been widely used by athletes and young physical exercise practioneers in order of increasing muscle mass and enhancing athletic performance, but their use/overuse may represent a health risk on hepatic and renal impaired function. In this study, we evaluated the effects of 40 days of oral creatine supplementation on hepatic and renal function biomarkers in a young animal model. Wistar rats (5 weeks old) were divided in five groups (n = 7): control (CONTR), oral creatine supplementation (CREAT), moderate exercise training (EXERC), moderate exercise training plus oral creatine supplementation (EXERC + CREAT) and pathological group (positive control for liver and kidney injury) by the administration of rifampicin (RIFAMPICIN). Exercise groups were submitted to 60 min/day of swimming exercise session with a 4% of body weight workload for six weeks. The EXERC + CREAT showed the higher body weight at the end of the training protocol. The CREAT and EXERC + CREAT group showed an increase in hepatic (Aspartate transaminase and gamma-glutamyl transpeptidase) and renal (urea and creatinine) biomarkers levels (p < 0.05). Our study showed that the oral creatine supplementation promoted hepatic and renal function challenge in young rats submitted to moderate exercise training.
Bernardi, M; Santini, C; Trevisani, F; Baraldini, M; Ligabue, A; Gasbarrini, G
The assumption of upright posture by patients with liver cirrhosis leads to striking activation of adrenergic and renin-angiotensin systems. The tilting-induced modifications in renal function of eight healthy controls and 14 untreated patients with liver cirrhosis and ascites were related to plasma concentrations of noradrenaline, renin activity and aldosterone. All patients had preserved renal blood perfusion. All parameters were evaluated during bed rest for two hours and in the sitting posture for one hour. Basal plasma renin activity (0.1 greater than p greater than 0.05), aldosterone and noradrenaline concentrations (p less than or equal to 0.01) were raised in cirrhotics. The renal function tests (creatinine clearance, filtered sodium, tubular rejection fraction, urinary sodium excretion) were significantly reduced in cirrhosis. Under basal conditions, in cirrhotic patients tubular rejection fraction and urinary sodium excretion were inversely related to both noradrenaline and aldosterone concentrations. After tilting, the noradrenaline and aldosterone integrated outputs (sigma delta) were significantly greater in cirrhosis. All renal function tests significantly decreased in cirrhotics, whereas creatinine clearance only significantly decreased in controls. Patient's tubular rejection fraction of sodium and sodium excretion were related to sigma delta aldosteronaemia (r = -0.72; p less than 0.01), but no longer to sigma delta plasma noradrenaline. PMID:3891534
Kawasaki, Takashi; Nakamura, Takeshi; Sasaki, Yusuke; Sakamoto, Keiko; Ito, Tomoyuki; Goto, Masaki; Shimomatsu, Tomoya; Tajima, Fumihiro
This study investigated the renal and endocrine responses to arm exercise in persons with spinal cord injury (SCI) under euhydration conditions (ad libitum drinking of water) and determined the physiological effects of exercise on renal function in these subjects. Eleven SCI (spinal lesions between T6 and L1, American Spinal Injury Association impairment scale A) and 14 able-bodied (AB) persons first rested for 1 h in a sitting position, before undergoing 2-h arm-crank ergometer exercise at 60% of maximum oxygen consumption followed by a 2-h recovery period. On another day, all subjects participated in a time control study (5 h of rest condition in sitting position). Urine and blood samples were collected hourly. There were no differences in mean blood pressure between the two groups. SCI patients showed attenuated increase in plasma adrenaline and increase in plasma aldosterone compared with AB controls, but similar changes in human atrial natriuretic polypeptide, plasma renin activity and plasma antidiuretic hormone following the exercise. Creatinine clearance, osmolal clearance, free water clearance and fractional excretion of Na(+) did not change during exercise in any of the subjects. These findings suggested that activated aldosterone and attenuated adrenaline responses during exercise in SCI could be due to adaptation to disordered sympathetic nervous system triggered to maintain renal function. The results showed no exercise-related adverse effects on renal function in hydrated subjects with SCI.
Raggi, Paolo; Su, Shaoyong; Karohl, Cristina; Veledar, Emir; Rojas-Campos, Enrique; Vaccarino, Viola
Background Loss of renal function is accompanied by a progressive increase in markers of inflammation; it is unknown whether they share common genetic pathways. Study Design We evaluated the shared heritability of estimated glomerular filtration rate (eGFR) and markers of inflammation and endothelial activation in 524 twin males from the Vietnam Era Twin Registry; 9 twins were excluded due to incomplete or incorrect data. Models were adjusted for age, race, body mass index, smoking, hypertension, diabetes mellitus, prior coronary artery disease and intercurrent medications. Results The mean eGFR was 89 ± 13 ml/min/1.73 m2 (range 35–146); eGFR, intracellular adhesion molecule (ICAM) and TNF-α receptor (TNF-αR) were moderately heritable (all ∼50%), while IL-6 receptor (IL-6R) and P-selectin were highly heritable (68 and 76%, respectively). IL-6R and TNF-αR showed a significant inverse association with eGFR (p = 0.04 and p < 0.0001) while the association with ICAM and P-selectin was direct (p = 0.001 and p = 0.06). Bivariate structural equation models showed that the association between eGFR and biomarkers was due to unique environmental factors and there were no shared genetic pathways. Conclusion We found no shared genetic pathways between renal function and inflammation. Thus, increased inflammation represents a response to declining renal function rather than being a mechanism contributing to renal deterioration. PMID:20720405
Liu, Qing; Li, Rui; Zhou, Renlai; Li, Juan; Gu, Quan
Objectives Premenstrual syndrome (PMS) refers to a series of cycling and relapsing physical, emotion and behavior syndromes that occur in the luteal phase and resolve soon after the onset of menses. Although PMS is widely recognized, its neural mechanism is still unclear. Design To address this question, we measured brain activity for women with PMS and women without PMS (control group) using resting-state functional magnetic resonance imaging (rs-fMRI). In addition, the participants should complete the emotion scales (Beck Anxiety Inventory, BAI; Beck Depression Inventory, BDI, before the scanning) as well as the stress perception scale (Visual analog scale for stress, VAS, before and after the scanning). Results The results showed that compared with the control group, the PMS group had decreased connectivity in the middle frontal gyrus (MFG) and theparahippocampalgyrus (PHG), as well as increased connectivity in the left medial/superior temporal gyri (MTG/STG) and precentralgyrus within the default mode network (DMN); in addition, the PMS group had higher anxiety and depression scale scores, together with lower stress perception scores. Finally, there were significantly positive correlations between the stress perception scores and functional connectivity in the MFG and cuneus. The BDI scores in the PMS group were correlated negatively with the functional connectivity in the MFG and precuneus and correlated positively with the functional connectivity in the MTG. Conclusion These findings suggest that compared with normal women, women with PMS displayed abnormal stress sensitivity, which was reflected in the decreased and increased functional connectivity within the DMN, blunted stress perception and higher depression. PMID:26325510
Tanna, Anisha; Randone, Olga; Tam, Frederick W. K.; Tarzi, Ruth M.; Levy, Jeremy B.; Griffith, Megan; Lightstone, Liz; Cook, H. Terence; Cairns, Tom; Pusey, Charles D.
Objective. Necrotizing and crescentic GN usually presents with rapidly declining renal function, often in association with multisystem autoimmune disease, with a poor outcome if left untreated. We aimed to describe the features of patients who have presented with these histopathological findings but minimal disturbance of renal function. Methods. We conducted a retrospective review (1995–2011) of all adult patients with native renal biopsy–proven necrotizing or crescentic GN and normal serum creatinine (<120 μmol/l) at our centre. Results. Thirty-eight patients were identified. The median creatinine at presentation was 84 μmol/l and the median proportion of glomeruli affected by necrosis or crescents was 32%. Clinicopathological diagnoses were ANCA-associated GN (74%), LN (18%), anti-GBM disease (5%) and HScP (3%). Only 18% of cases had pre-existing diagnoses of underlying multisystem autoimmune disease, although the majority (89%) had extra-renal manifestations accompanying the renal diagnosis. All patients received immunosuppression and most had good long-term renal outcomes (median duration of follow-up 50 months), although two progressed to end-stage renal disease within 3 years. We estimate that renal biopsy had an important influence on treatment decisions in 82% of cases. Conclusion. Necrotizing and crescentic GN may present in patients with no or only minor disturbance of renal function. This often occurs in patients with underlying systemic autoimmune disease; early referral for biopsy may affect management and improve long-term outcomes in these cases. PMID:25431483
Moon, Byung Sub; Kim, Jongho; Kim, Ji Hyun; Hyun, Young Youl; Park, Se Eun; Oh, Hyung-Geun; Park, Cheol-Young; Lee, Won-Young; Oh, Ki-Won; Lee, Kyu-Beck; Kim, Hyang; Park, Sung-Woo
Background The purpose of this study was to investigate the relationship between statin eligibility and the degree of renal dysfunction using the Adult Treatment Panel (ATP) III and the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines in Korean adults. Methods Renal function was assessed in 18,746 participants of the Kangbuk Samsung Health Study from January 2011 to December 2012. Subjects were divided into three groups according to estimated glomerular filtration rate (eGFR): stage 1, eGFR ≥90 mL/min/1.73 m2; stage 2, eGFR 60 to 89 mL/min/1.73 m2; and stages 3 to 5, eGFR <60 mL/min/1.73 m2. Statin eligibility in these groups was determined using the ATP III and ACC/AHA guidelines, and the risk for 10-year atherosclerotic cardiovascular disease (ASCVD) was calculated using the Framingham Risk Score (FRS) and Pooled Cohort Equation (PCE). Results There were 3,546 (18.9%) and 4,048 (21.5%) statin-eligible subjects according to ATP III and ACC/AHA guidelines, respectively. The proportion of statin-eligible subjects increased as renal function deteriorated. Statin eligibility by the ACC/AHA guidelines showed better agreement with the Kidney Disease Improving Global Outcomes (KDIGO) recommendations compared to the ATP III guidelines in subjects with stage 3 to 5 chronic kidney disease (CKD) (κ value, 0.689 vs. 0.531). When the 10-year ASCVD risk was assessed using the FRS and PCE, the mean risk calculated by both equations significantly increased as renal function declined. Conclusions The proportion of statin-eligible subjects significantly increased according to worsening renal function in this Korean cohort. ACC/AHA guideline showed better agreement for statin eligibility with that recommended by KDIGO guideline compared to ATP III in subjects with CKD. PMID:27586450
Yun, Bo Hyon; Chon, Seung Joo; Cho, Si Hyun; Choi, Young Sik; Lee, Byung Seok
Objectives Decreased renal function is associated with increased cardiovascular risk. Our study was planned to verify the association of decreased renal function and subclinical coronary atherosclerosis in postmenopausal women. Methods We performed a retrospective review of 251 Korean postmenopausal women who visited the health promotion center for a routine health checkup. Estimated glomerular filtration rate (eGFR) was used to show renal function, which was estimated by calculated using the Cockcroft-Gault (CG) and the modification of diet in renal disease (MDRD) formulas. Coronary atherosclerosis was assessed by 64-row multidetector computed tomography. Results Women with reduced eGFR (< 60 mL/minute/1.73 m2) had significantly higher brachial-ankle pulse wave velocity (baPWV) than women with normal eGFR (≥ 60 mL/minute/1.73 m2). The eGFR was negatively correlated with baPWV (r = -0.352, P < 0.001), significantly. The eGFR was lower in women with coronary atherosclerosis than in normal control women, markedly. Reduced eGFR was significantly associated with the presence of coronary atherosclerosis (odds ratio [OR] = 7.528, 95% confidence interval [CI] = 2.728-20.772, P < 0.001). Conclusions Decreased eGFR was closely associated with increased arterial stiffness and coronary atherosclerosis in postmenopausal women. Evaluating subclinical atherosclerosis by screening the renal function in postmenopausal women may be helpful screening high risk group and considering starting menopausal hormone therapy before atherosclerosis development. PMID:28119897
Xie, Chunming; Bai, Feng; Yu, Hui; Shi, Yongmei; Yuan, Yonggui; Chen, Gang; Li, Wenjun; Chen, Guangyu; Zhang, Zhijun; Li, Shi-Jiang
Abnormalities of functional connectivity in the default mode network (DMN) recently have been reported in patients with amnestic mild cognitive impairment (aMCI), Alzheimer's disease (AD) or other psychiatric diseases. As such, these abnormalities may be epiphenomena instead of playing a causal role in AD progression. To date, few studies have investigated specific brain networks, which extend beyond the DMN involved in the early AD stages, especially in aMCI. The insula is one site affected by early pathological changes in AD and is a crucial hub of the human brain networks. Currently, we explored the contribution of the insula networks to cognitive performance in aMCI patients. Thirty aMCI and 26 cognitively normal (CN) subjects participated in this study. Intrinsic connectivity of the insula networks was measured, using the resting-state functional connectivity fMRI approach. We examined the differential connectivity of insula networks between groups, and the neural correlation between the altered insula networks connectivity and the cognitive performance in aMCI patients and CN subjects, respectively. Insula subregional volumes were also investigated. AMCI subjects, when compared to CN subjects, showed significantly reduced right posterior insula volumes, cognitive deficits and disrupted intrinsic connectivity of the insula networks. Specifically, decreased intrinsic connectivity was primarily located in the frontal-parietal network and the cingulo-opercular network, including the anterior prefrontal cortex (aPFC), anterior cingulate cortex, operculum, inferior parietal cortex and precuneus. Increased intrinsic connectivity was primarily situated in the visual-auditory pathway, which included the posterior superior temporal gyrus and middle occipital gyrus. Conjunction analysis was performed; and significantly decreased intrinsic connectivity in the overlapping regions of the anterior and posterior insula networks, including the bilateral aPFC, left
Sandilands, Euan A; Dhaun, Neeraj; Dear, James W; Webb, David J
Chronic kidney disease affects millions of people worldwide and is associated with an increased morbidity and mortality as a result of kidney failure and cardiovascular disease. Accurate assessment of kidney function is important in the clinical setting as a screening tool and for monitoring disease progression and guiding prognosis. In clinical research, the development of new methods to measure kidney function accurately is important in the search for new therapeutic targets and the discovery of novel biomarkers to aid early identification of kidney injury. This review considers different methods for measuring kidney function and their contribution to the improvement of detection, monitoring and treatment of chronic kidney disease. PMID:23802624
Sandilands, Euan A; Dhaun, Neeraj; Dear, James W; Webb, David J
Chronic kidney disease affects millions of people worldwide and is associated with an increased morbidity and mortality as a result of kidney failure and cardiovascular disease. Accurate assessment of kidney function is important in the clinical setting as a screening tool and for monitoring disease progression and guiding prognosis. In clinical research, the development of new methods to measure kidney function accurately is important in the search for new therapeutic targets and the discovery of novel biomarkers to aid early identification of kidney injury. This review considers different methods for measuring kidney function and their contribution to the improvement of detection, monitoring and treatment of chronic kidney disease.
Bohon, Cara; Stice, Eric
Objective To test the hypothesis that women with full and subthreshold bulimia nervosa show abnormal neural activation in response to food intake and anticipated food intake relative to healthy control women. Method Females with and without full/subthreshold bulimia nervosa recruited from the community (N = 26) underwent functional magnetic resonance imaging (fMRI) during receipt and anticipated receipt of chocolate milkshake and a tasteless control solution. Results Women with bulimia nervosa showed trends for less activation than healthy controls in the right anterior insula in response to anticipated receipt of chocolate milkshake (versus tasteless solution) and in the left middle frontal gyrus, right posterior insula, right precentral gyrus, and right mid dorsal insula in response to consumptions of milkshake (versus tasteless solution). Discussion Bulimia nervosa may be related to potential hypo-functioning of the brain reward system, which may lead these individuals to binge eat to compensate for this reward deficit, though the hypo-responsivity might be a result of a history of binge eating highly palatable foods. PMID:21997421
Yokoi, Y; Nakamura, S; Muro, H; Baba, S
The purpose of this study was to determine the changes of hepatic sinusoidal endothelial cell (SEC) function in acute liver rejection with respect to receptor-mediated endocytosis. Orthotopic rat liver transplantation was performed in Lewis rats grafted with DA livers and in Lewis rats grafted with Lewis livers as rejectors and controls, respectively. Animals were killed at 1, 3, 5, 7, and 10 days after the operation. Fc receptors (FcRs) were histochemically stained on frozen liver sections by applying peroxidase-antiperoxidase IgG complex as a ligand, and the FcR activity, i.e., capacity of binding the ligands represented by the FcR staining intensity, was semiquantitatively analyzed as an indicator of SEC function. The serum level of hyaluronic acid, which is specifically cleared from the circulation by receptor-mediated SEC endocytosis, was also assayed, along with the total serum bilirubin. Three days after the operation, the SECs of rejectors showed a significantly weaker FcR staining intensity of about half the value of that seen in the controls (P < 0.05), and staining disappeared after 5 days (P < 0.01). The decrease of FcR staining intensity, i.e., FcR activity, showed a correlation with elevation of the serum hyaluronic acid level (r = -0.77; P < 0.001). Histological evidence of endothelialitis and a significant elevation of total serum bilirubin (P < 0.01) were also present at 3 and 5 days, respectively. These results suggest that impairment of the endocytic function of SECs occurs at an earlier phase of acute liver rejection when compared with development of abnormalities of traditional indicators. Determination of receptor-mediated SEC endocytic functions may thus provide useful information for the early diagnosis of acute rejection.
Aass, N.; Fosså, S. D.; Aas, M.; Lindegaard, M. W.
The renal function was evaluated with 131I-Hippuran clearance in 171 patients with malignant germ cell tumours. Assessments were performed before treatment and at three fixed times afterwards within 5 years. The patients were treated with surgery only (20 patients), infra-diaphragmatic radiotherapy only (median midplane dose 36 Gy) (48 patients), cisplatin-based chemotherapy (total cisplatin dose 500-850 mg) plus surgery (64 patients), cisplatin-based chemotherapy (total cisplatin dose greater than 850 mg) with or without surgery (23 patients) or cisplatin-based chemotherapy (total cisplatin dose 500-850 mg) plus infra-diaphragmatic radiotherapy (16 patients). No renal impairment was observed for patients treated with surgery only. In patients who received radiotherapy no change of the renal function occurred during the first year post-treatment. Three to five years after treatment discontinuation a statistically significant reduction within the normal range was observed in patients who were greater than 40 years at the time of irradiation. Cisplatin-based chemotherapy led to a statistically significant irreversible renal impairment for all the three groups. The greatest reduction was seen in patients who received the highest total cisplatin dose or who were treated with irradiation in addition to chemotherapy. The clinical significance of the observed nephrotoxicity is still unknown. PMID:2173944
de Resende, Marco A. C.; Pantoja, Alberto V.; Barcellos, Bruno M.; Reis, Eduardo P.; Consolo, Thays D.; Módolo, Renata P.; Domingues, Maria A. C.; Assad, Alexandra R.; Cavalcanti, Ismar L.; Castiglia, Yara M. M.; Módolo, Norma S. P.
Background. Ischemic postconditioning (IP) in renal Ischemia reperfusion injury (IRI) models improves renal function after IRI. Ketamine affords significant benefits against IRI-induced acute kidney injury (AKI). The present study investigated the effects of IP and IP associated with subanesthetic S(+)-ketamine in ischemia-reperfusion-induced AKI. Methods. Forty-one Wistar rats were randomized into four groups: CG (10), control; KG (10), S(+)-ketamine infusion; IPG (10), IP; and KIPG (11), S(+)-ketamine infusion + IP. All rats underwent right nephrectomy. IRI and IP were induced only in IPG and KIPG by left kidney arterial occlusion for 30 min followed by reperfusion for 24 h. Complete reperfusion was preceded by three cycles of 2 min of reocclusion followed by 2 min of reperfusion. Renal function was assessed by measuring serum neutrophil gelatinase-associated lipocalin (NGAL), creatinine, and blood urea nitrogen (BUN). Tubular damage was evaluated by renal histology. Results. Creatinine and BUN were significantly increased. Severe tubular injury was only observed in the groups with IRI (IPG and KIPG), whereas no injury was observed in CG or KG. No significant differences were detected between IPG and KIPG. Conclusions. No synergic effect of the use of subanesthetic S(+)-ketamine and IP on AKI was observed in this rat model. PMID:26413552
Karim, F; Poucher, S M; Summerill, R A
In chloralose-anaesthetized and artificially ventilated dogs, the carotid sinuses were vascularly isolated and perfused with arterial blood. Mean aortic pressure was held constant at 100 +/- 2 mmHg (mean +/- S.E. of mean, n = 19) by means of a pressure bottle connected to the aorta. Both vagus nerves were sectioned in the neck and propranolol hydrochloride (0.5 mg kg-1) was administered every 30 min. The left renal blood flow was measured by an electromagnetic flowmeter (wrap-round probe), glomerular filtration rate by creatinine clearance and urinary sodium by flame photometry. Decreasing pressure in the isolated carotid sinuses from 186 +/- 10 to 63 +/- 5 mmHg resulted in significant decreases in renal blood flow from 281 +/- 35 to 177 +/- 30 ml min-1 100 g-1 renal mass; glomerular filtration rate from 40.0 +/- 7.8 to 12.3 +/- 4.4 ml min-1 100 g-1; urine flow from 0.31 +/- 0.05 to 0.12 +/- 0.03 ml min-1 100 g-1 and sodium excretion from 21.7 +/- 7.2 to 8.2 +/- 3.0 mumol min-1 100 g-1. Increasing carotid sinus pressure back to 188 +/- 11 mmHg resulted in increases in all the variables to values not significantly different from their initial values. Tying renal sympathetic nerves at low carotid sinus pressure (73 +/- 11 mmHg) caused an increase in all of the variables. After denervation there was no response to changes in carotid sinus pressure. These results show that changes in carotid sinus pressure can result in significant reflex effects on renal function and that these effects are mediated by renal sympathetic nerves. PMID:6492002
Rosansky, S J; Hoover, D R; King, L; Gibson, J
We compared the changes in serum creatinine levels over time after a mean follow-up of 9.8 years in essential hypertensive (EH, n = 56) and control (n = 59) male veteran subjects. All subjects had normal serum creatinine levels (62 to 124 mumol/L) and "normal" urinalysis results on entry into the study. Subjects with comorbid renal diagnoses and diabetes mellitus were eliminated from the analysis. Although not statistically significant, the rate of change in the serum creatinine concentration over time was greater in the EH cohort compared with the control cohort (1.08 +/- 4.8 vs 0.027 +/- 3.5 mumol/L per year). The difference was especially marked in black EH subjects vs black control subjects (1.60 +/- 6.2 mumol/L per year vs -0.21 +/- 3.3 mumol/L per year). When age, race, body mass index, and a diagnosis of EH were entered into a logistic regression analysis, EH subjects had a statistically significantly greater rate of decline in renal function than did control subjects (1.5 +/- 8.3 mumol/L per year). When mean time-averaged systolic blood pressure for each subject was also included in the logistic regression analysis, only systolic time-averaged blood pressure was statistically significant (0.063 +/- 0.029 mumol/L per year). We conclude that in the absence of clinically detected parenchymal renal disease, EH subjects have a greater rate of decline in renal function than do nonhypertensive subjects. Time-averaged blood pressure is predictive of the change in serum creatinine concentration not only in EH subjects but also in nonhypertensive subjects. Thus, preservation of renal function may require a blood pressure lower than the currently accepted normotensive range.
Handa, Rajash K.; Willis, Lynn R.; Evan, Andrew P.; Connors, Bret A.; Ying, Jun; Fat-Anthony, William; Wind, Kelli R.; Johnson, Cynthia D.; Blomgren, Philip M.; Estrada, Mark C.; Paterson, Ryan F.; Kuo, Ramsay L.; Kim, Samuel C.; Matlaga, Brian R.; Miller, Nicole L.; Watkins, Stephanie L.; Handa, Shelly E.; Lingeman, James E.
Percutaneous nephrolithotomy (PCNL) involves gaining access into the urinary collecting system to remove kidney stones. Animal studies demonstrated that a reduction in renal filtration and perfusion in both kidneys, and a decline in tubular organic anion transport in the treated kidney characterizes the acute (hours) functional response to unilateral percutaneous access. The acute morphologic and histological changes in the treated kidney were consistent with blunt trauma and ischemia. Only tubular organic anion transport remained depressed during the late (3-day) response to the access procedure. Human studies revealed an acute decline in glomerular function and bilateral renal vasoconstriction following unilateral PCNL. Therefore, percutaneous access is not a benign procedure, but is associated with acute functional and structural derangements.
Page, L M; Girling, J C
Non-alcoholic fatty liver disease (NAFLD) is the commonest liver disease in the western world, but has never been reported in pregnancy before. We suggest that NAFLD should also be considered as a cause for abnormal liver function tests during pregnancy. As NAFLD is driven by insulin resistance, it is biologically plausible that pregnancy may reveal previously subclinical disease. Obstetricians have a vital role in optimising maternal health during and after pregnancy and therefore we need to include NAFLD in the differential diagnosis for abnormal liver function tests and recommend lifestyle modifications that may prevent progression to cirrhosis and hepatocellular carcinoma.
Mahieu, Stella; Millen, Néstor; González, Marcela; Contini, María del Carmen; Elías, María Mónica
Various indices of renal functions during the early stage of hepatic injury were studied in rats chronically treated with aluminum (Al) lactate. Tubular and hemodynamic parameters were analyzed four days after producing a 65% partial hepatectomy (PH). Water and sodium balances were also studied. Oxidative stress and the activity of Na-K-ATPase were determined in renal tissue. The rats were distributed in four groups: control, Al, PH, Al+PH. Al did not modify the hemodynamic renal functions and the PH-group reduced the glomerular filtrate rate (GFR). The Al + PH group presented a decrease in the renal blood flow and accentuated the GFR fall as compared with PH. The fractional excretion (FE) of water and sodium increased in the PH group. The rats chronically treated with Al and then submitted to the PH protocol developed a further increase in FE of water but a reduction in FE of sodium. Both PH and Al promoted an increase in the aldosterone. PH and Al induced a similar increase of the lipoperoxidation status with reduction of glutathione (GSH) and the activity of glutathione peroxidase (GSH-Px). The data indicated that Al is an inhibitor of catalase. The GSH and GSH-Px activity in the Al + PH group demonstrated a synergic effect of Al and PH. This work demonstrates that rats treated chronically with Al and submitted to another injury (such as hepatic damage) can aggravate renal functions, probably by increasing the oxidative state, at least in kidneys.
Leong, Khai Gene; Coombs, Peter
Abstract One of the principal roles of a nephrologist is to closely monitor renal transplant allograft function and promptly evaluate any dysfunction. Renal transplant sonography has a major role in this assessment process given its ability to easily define renal transplant anatomy and surrounding structures. Abnormalities can be extrarenal or involve vascular, parenchymal and urological components of the graft and these can acutely or chronically influence graft function and survival. Procedural guidance as is required during allograft biopsy, as well as routine surveillance and screening for post transplant complications such as malignancy are also important applications of ultrasound in the management of renal transplant recipients. This article outlines key ultrasound findings and applications in renal transplantation from the clinician's perspective. PMID:28191257
Benattia, Amira; Debeaumont, David; Guyader, Vincent; Tardif, Catherine; Peillon, Christophe; Cuvelier, Antoine
Background Impaired respiratory function may prevent curative surgery for patients with non-small cell lung cancer (NSCLC). Video-assisted thoracoscopic surgery (VATS) reduces postoperative morbility-mortality and could change preoperative assessment practices and therapeutic decisions. We evaluated the relation between preoperative pulmonary function tests and the occurrence of postoperative complications after VATS pulmonary resection in patients with abnormal pulmonary function. Methods We included 106 consecutive patients with ≤80% predicted value of presurgical expiratory volume in one second (FEV1) and/or diffusing capacity of carbon monoxide (DLCO) and who underwent VATS pulmonary resection for NSCLC from a prospective surgical database. Results Patients (64±9.5 years) had lobectomy (n=91), segmentectomy (n=7), bilobectomy (n=4), or pneumonectomy (n=4). FEV1 and DLCO preoperative averages were 68%±21% and 60%±18%. Operative mortality was 1.89%. Only FEV1 was predictive of postoperative complications [odds ratio (OR), 0.96; 95% confidence interval (CI), 0.926–0.991, P=0.016], but there was no determinable threshold. Twenty-five patients underwent incremental exercise testing. Desaturations during exercise (OR, 0.462; 95% CI, 0.191–0.878, P=0.039) and heart rate (HR) response (OR, 0.953; 95% CI, 0.895–0.993, P=0.05) were associated with postoperative complications. Conclusions FEV1 but not DLCO was a significant predictor of pulmonary complications after VATS pulmonary resection despite a low rate of severe morbidity. Incremental exercise testing seems more discriminating. Further investigation is required in a larger patient population to change current pre-operative threshold in a new era of minimally invasive surgery. PMID:27293834
Dunn, Kenneth W.; Sutton, Timothy A.; Sandoval, Ruben M.
Intravital microscopy, microscopy of living animals, is a powerful research technique that combines the resolution and sensitivity found in microscopic studies of cultured cells with the relevance and systemic influences of cells in the context of the intact animal. The power of intravital microscopy has recently been extended with the development of multiphoton fluorescence microscopy systems capable of collecting optical sections from deep within the kidney at subcellular resolution, supporting high-resolution characterizations of the structure and function of glomeruli, tubules, and vasculature in the living kidney. Fluorescent probes are administered to an anesthetized, surgically prepared animal, followed by image acquisition for up to 3 hr. Images are transferred via a high-speed network to specialized computer systems for digital image analysis. This general approach can be used with different combinations of fluorescent probes to evaluate processes such as glomerular permeability, proximal tubule endocytosis, microvascular flow, vascular permeability, mitochondrial function, and cellular apoptosis/necrosis. PMID:23042524
Kanagasegar, Sivalingam; Cimaz, Rolando; Kurien, Biji T; Brucato, Antonio; Scofield, R Hal
Neonatal lupus is characterized by typical clinical features and the presence of maternal autoantibodies. Mothers can have systemic lupus erythematosus (SLE) or Sjögren's syndrome, but are commonly not affected with any clinical disease. The major clinical manifestations in the infants are cardiac, dermatological and hepatic with rare instances of hemolytic anemia, thrombocytopenia or neutropenia. We describe an infant born to a mother with anti-Ro and anti-La, who had neutropenia and mildly abnormal liver functions without other major clinical features of neonatal lupus such as cardiac or dermatological manifestations. Neutropenia improved as maternal antibody was metabolized. Antibodies from both the infant and mother bound intact neutrophils, and this binding was inhibited by 60 kDa Ro. These data imply neutropenia may be an isolated manifestation of neonatal lupus. We studied the anti-Ro antibodies of 2 other mothers who gave birth to infants with complete congenital heart block and neutropenia. Their sera also bound neutrophils. Because healthy infants do not commonly undergo complete blood counts, the incidence of neutropenia among infants of anti-Ro-positive mothers may be much higher than previously recognized. Furthermore, although other factors may contribute, these data suggest that anti-60 kDa Ro is directly involved in the pathogenesis of neutropenia.
Margolis, Kara Gross; Li, Zhishan; Stevanovic, Korey; Saurman, Virginia; Anderson, George M.; Snyder, Isaac; Blakely, Randy D.; Gershon, Michael D.
Autism spectrum disorder (ASD) is an increasingly common behavioral condition that frequently presents with gastrointestinal (GI) disturbances. It is not clear, however, how gut dysfunction relates to core ASD features. Multiple, rare hyperfunctional coding variants of the serotonin (5-HT) transporter (SERT, encoded by SLC6A4) have been identified in ASD. Expression of the most common SERT variant (Ala56) in mice increases 5-HT clearance and causes ASD-like behaviors. Here, we demonstrated that Ala56-expressing mice display GI defects that resemble those seen in mice lacking neuronal 5-HT. These defects included enteric nervous system hypoplasia, slow GI transit, diminished peristaltic reflex activity, and proliferation of crypt epithelial cells. An opposite phenotype was seen in SERT-deficient mice and in progeny of WT dams given the SERT antagonist fluoxetine. The reciprocal phenotypes that resulted from increased or decreased SERT activity support the idea that 5-HT signaling regulates enteric neuronal development and can, when disturbed, cause long-lasting abnormalities of GI function. Administration of a 5-HT4 agonist to Ala56 mice during development prevented Ala56-associated GI perturbations, suggesting that excessive SERT activity leads to inadequate 5-HT4–mediated neurogenesis. We propose that deficient 5-HT signaling during development may contribute to GI and behavioral features of ASD. The consequences of therapies targeting SERT during pregnancy warrant further evaluation. PMID:27111230
Gabig, T G
Certain qualitative abnormalities in neutrophils and blood monocytes are associated with frequent, severe, and recurrent bacterial infections leading to fatal sepsis, while other qualitative defects demonstrated in vitro may have few or no clinical sequelae. These qualitative defects are discussed in terms of the specific functions of locomotion, phagocytosis, degranulation, and bacterial killing.
Madkour, H; Gadallah, M; Riveline, B; Plante, G E; Massry, S G
The long-term effects of indapamide or hydrochlorothiazide on blood pressure and renal function were examined in patients with impaired renal function and moderate hypertension. Both drugs controlled hypertension and blood pressure remained normal during the 2 years of the study. Despite this comparable control of hypertension, indapamide therapy was associated with a 28.5 +/- 4.4% increase in creatinine clearance while treatment with hydrochlorothiazide was associated with a 17.4 +/- 3.0% decrease in creatinine clearance. The results of the study indicate that indapamide is superior to hydrochlorothiazide in the treatment of patients with impaired renal function and moderate hypertension.
Zuber, Annie Mercier; Centeno, Gabriel; Pradervand, Sylvain; Nikolaeva, Svetlana; Maquelin, Lionel; Cardinaux, Léonard; Bonny, Olivier; Firsov, Dmitri
Renal excretion of water and major electrolytes exhibits a significant circadian rhythm. This functional periodicity is believed to result, at least in part, from circadian changes in secretion/reabsorption capacities of the distal nephron and collecting ducts. Here, we studied the molecular mechanisms underlying circadian rhythms in the distal nephron segments, i.e., distal convoluted tubule (DCT) and connecting tubule (CNT) and the cortical collecting duct (CCD). Temporal expression analysis performed on microdissected mouse DCT/CNT or CCD revealed a marked circadian rhythmicity in the expression of a large number of genes crucially involved in various homeostatic functions of the kidney. This analysis also revealed that both DCT/CNT and CCD possess an intrinsic circadian timing system characterized by robust oscillations in the expression of circadian core clock genes (clock, bma11, npas2, per, cry, nr1d1) and clock-controlled Par bZip transcriptional factors dbp, hlf, and tef. The clock knockout mice or mice devoid of dbp/hlf/tef (triple knockout) exhibit significant changes in renal expression of several key regulators of water or sodium balance (vasopressin V2 receptor, aquaporin-2, aquaporin-4, αENaC). Functionally, the loss of clock leads to a complex phenotype characterized by partial diabetes insipidus, dysregulation of sodium excretion rhythms, and a significant decrease in blood pressure. Collectively, this study uncovers a major role of molecular clock in renal function. PMID:19805330
Dynamic MR imaging with contrast media is increasingly used to provide a safe and noninvasive assessment of renal function. Following intravenous injection of a paramagnetic tracer such as Gd-DPTA, the time course of MR signal is measured in arterial blood and in the kidneys. We use mathematical modeling and Monte Carlo trials to evaluate errors in computed renal parameters such as mean transit time (sigma) m as a function of injected dose. The model assumes that tracer concentration in the renal compartments is the result of convolution of the arterial curve and unit response functions. Results indicate that (sigma) m is not a monotonic function of the dose: instead it reaches a minimum for 2.5 - 3.5 ml of 500 mmol/l solution of Gd-DPTA and it rapidly increases for doses lower than 1 ml. These results can help optimize MR protocol and establish the feasibility of MR measurements using reduced doses of Gd-DPTA.
Fernandes, Sheila Marques; Martins, Daniel Malisani; da Fonseca, Cassiane Dezoti; Watanabe, Mirian; Vattimo, Maria de Fátima Fernandes
Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI.
El-Kashef, Dalia H; El-Kenawi, Asmaa E; Abdel Rahim, Mona; Suddek, Ghada M; Salem, Hatem A
The present study was designed to explore the possible protective effects of agmatine, a known nitric oxide (NO) synthase inhibitor, against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of agmatine on gentamicin-induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was evaluated. Twenty-four male Wistar albino rats were randomly divided into 3 groups, namely control, gentamicin (100 mg/kg, i.p.), and gentamicin plus agmatine (40 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood and urine samples and kidneys were taken. Administration of agmatine significantly decreased kidney/body mass ratio, serum creatinine, lactate dehydrogenase (LDH), renal malondialdehyde (MDA), myeloperoxidase (MPO), NO, and tumor necrosis factor-alpha (TNF-α) while it significantly increased creatinine clearance and renal superoxide dismutase (SOD) activity when compared with the gentamicin-treated group. Additionally, agmatine ameliorated tissue morphology as evidenced by histological evaluation and reduced the responses of isolated bladder rings to ACh. Our study indicates that agmatine administration with gentamicin attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation, restoring NO level and inhibiting inflammatory mediators such as TNF-α.
Brown, E D; Chen, M Y; Wolfman, N T; Ott, D J; Watson, N E
Following renal transplantation, patients are often evaluated with ultrasonography (US) or radionuclide imaging to assess renal function and the presence of possible complications. Both modalities are inexpensive, noninvasive, and nonnephrotoxic. A basic understanding of the surgical techniques commonly used for renal transplantation is useful when imaging these patients in order to recognize complications and to direct further imaging or intervention. The most frequent complications of renal transplantation include perinephric fluid collections; decreased renal function; and abnormalities of the vasculature, collecting system, and renal parenchyma. Perinephric fluid collections are common following transplantation, and their clinical significance depends on the type, location, size, and growth of the fluid collection, features that are well-evaluated with US. Causes of diminished renal function include acute tubular necrosis, rejection, and toxicity from medications. Radionuclide imaging is the most useful modality for assessing renal function. Vascular complications of transplantation include occlusion or stenosis of the arterial or venous supply, arteriovenous fistulas, and pseudoaneurysms. Although the standard for evaluating these vascular complications is angiography, US is an excellent noninvasive method for screening. Other transplant complications such as abnormalities of the collecting system and renal parenchyma are well-evaluated with both radionuclide imaging and US.
Geisler, Daniel; Borchardt, Viola; Lord, Anton R.; Boehm, Ilka; Ritschel, Franziska; Zwipp, Johannes; Clas, Sabine; King, Joseph A.; Wolff-Stephan, Silvia; Roessner, Veit; Walter, Martin; Ehrlich, Stefan
Background Previous resting-state functional connectivity studies in patients with anorexia nervosa used independent component analysis or seed-based connectivity analysis to probe specific brain networks. Instead, modelling the entire brain as a complex network allows determination of graph-theoretical metrics, which describe global and local properties of how brain networks are organized and how they interact. Methods To determine differences in network properties between female patients with acute anorexia nervosa and pairwise matched healthy controls, we used resting-state fMRI and computed well-established global and local graph metrics across a range of network densities. Results Our analyses included 35 patients and 35 controls. We found that the global functional network structure in patients with anorexia nervosa is characterized by increases in both characteristic path length (longer average routes between nodes) and assortativity (more nodes with a similar connectedness link together). Accordingly, we found locally decreased connectivity strength and increased path length in the posterior insula and thalamus. Limitations The present results may be limited to the methods applied during preprocessing and network construction. Conclusion We demonstrated anorexia nervosa–related changes in the network configuration for, to our knowledge, the first time using resting-state fMRI and graph-theoretical measures. Our findings revealed an altered global brain network architecture accompanied by local degradations indicating wide-scale disturbance in information flow across brain networks in patients with acute anorexia nervosa. Reduced local network efficiency in the thalamus and posterior insula may reflect a mechanism that helps explain the impaired integration of visuospatial and homeostatic signals in patients with this disorder, which is thought to be linked to abnormal representations of body size and hunger. PMID:26252451
Sutton, S. Scott; Jumper, Mark; Cook, Sean; Edun, Babatunde; Wyatt, Michael D.
Drug-induced neurotoxicity is a rare adverse reaction associated with ertapenem. Encephalopathy is a type of neurotoxicity that is defined as a diffuse disease of the brain that alters brain function or structure. We report a patient with normal renal function who developed ertapenem-induced encephalopathy manifesting as altered mental status, hallucinations, and dystonic symptoms. The patient’s symptoms improved dramatically following ertapenem discontinuation, consistent with case reports describing ertapenem neurotoxicity in renal dysfunction. Since clinical evidence strongly suggested ertapenem causality, we utilized the Naranjo Scale to estimate the probability of an adverse drug reaction to ertapenem. Our patient received a Naranjo Scale score of 7, suggesting a probable adverse drug reaction, with a reasonable temporal sequence to support our conclusion. PMID:28203577
Tagle, Rodrigo; Acevedo, Monica; Xu, Meng; Pohl, Marc; Vidt, Donald
Atherosclerotic renal artery stenosis may result in hypertension and ischemic nephropathy. Renal artery endovascular stenting has emerged as current therapy; however, the percentage of patients who benefit from this procedure is still not well established. The authors studied 116 hypertensive patients with atherosclerotic renovascular stenosis who underwent successful renal artery stenting for the first time. At 1 year, there was a significant overall decrease in blood pressure in the group after stenting; however, there was no change in renal function. Also, no significant change in the number of antihypertensive drugs was noted. Blood pressure improved in 55% of the patients, worsened in 14%, and remained unchanged in 31%. Renal function improved in 16% of the patients, worsened in 30%, and remained stable in 54%. In relation to blood pressure control, patients with resistant or difficult-to-control hypertension showed the most improvement in blood pressure control after stenting.
Kastl, Justin T
The use of serum creatinine levels to estimate glomerular function in infants is admittedly fraught with inherent inaccuracies which are both physiological and methodological in nature. This characteristic can understandably reduce the neonatal clinician's confidence in the ability of serum creatinine levels to provide useful information relevant to their patients' medical care. The aim of this review is to provide further insight into the peculiarities of serum creatinine trends in both premature and term infants with special focus on the maturational and developmental changes occurring in the kidney during this crucial time-period. Though newer markers of glomerular function are gaining increasing traction in the clinical realm, the most prominent of which is currently cystatin C, creatinine nonetheless remains an important player in the scientific evolution of glomerular filtration rate (GFR) estimation. Not only do its limitations provide a level of distinction for newer markers of GFR, but its advantages persist in refining the precision of newer GFR formulae which incorporate multiple patient characteristics.
Takita, K; Goda, Y; Kawahigashi, H; Okuyama, A; Kubota, M; Kemmotsu, O
Pharmacodynamics of vecuronium were evaluated in seven kidney transplant recipients and compared with seven patients with normal renal function. Vecuronium 0.12 mg.kg-1 was used for the initial dose and 0.03 mg.kg-1 for the second dose for each patient under general anesthesia with either isoflurane, sevoflurane or halothane plus nitrous oxide after induction by thiamylal. The effect of vecuronium was evaluated by a muscle relaxation monitor. The time to the maximum blockade (onset time) and the time of 25% recovery of the first twitch height (duration time) were measured after each administration of vecuronium in patients of both groups. The onset times after the initial and second doses were similar in both groups (180.0 +/- 15.5 sec for recipients versus 185.7 +/- 14.9 sec for patients of normal renal function). However, duration was significantly longer in recipients than in patients of normal renal function. Durations after the initial and second doses were 130 +/- 19 min for the initial dose and 86 +/- 12 min for the second dose in recipients, whereas they were 51 +/- 5 min and 37 +/- 5 min in patients of normal renal function. The prolonged durations of vecuronium in the kidney transplant recipient were speculated to be mainly due to delayed elimination of the drug and effect of cyclosporin, an immunosuppressive agent in the recipients. These results suggest that the titrated administration of vecuronium by keen monitoring of muscle relaxation is needed in the kidney transplant recipient to avoid unnecessary prolongation in duration of action.
inulin . The change was more pronounced in the saline group, because the MCA + oil group had a somewhat diminished GFR. There were no significant effects...flow rate were not affected by MCA, VDC or the combined treatment. ftEMALES VDC decreased GFR, assessed as clearance of inulin , in both saline and MCA...apparently disparate, they are in agreement with the known relationship between renal function assessed by inulin clearance and lack of clearance of
Peters, Brandilyn A.; Hall, Megan N.; Liu, Xinhua; Slavkovich, Vesna; Ilievski, Vesna; Alam, Shafiul; Siddique, Abu B.; Islam, Tariqul; Graziano, Joseph H.; Gamble, Mary V.
Background Arsenic (As) methylation capacity in epidemiologic studies is typically indicated by the proportions of inorganic As (%InAs), monomethylarsonic acid (%MMA), and dimethylarsinic acid (%DMA) in urine as a fraction of total urinary As. The relationship between renal function and indicators of As methylation capacity has not been thoroughly investigated. Objectives Our two aims were to examine (1) associations between estimated glomerular filtration rate (eGFR) and %As metabolites in blood and urine, and (2) whether renal function modifies the relationship of blood %As metabolites with respective urinary %As metabolites. Methods: In a cross-sectional study of 375 As-exposed Bangladeshi adults, we measured blood and urinary As metabolites, and calculated eGFR from plasma cystatin C. Results In covariate-adjusted linear models, a one ml/min/1.73 m2 increase in eGFR was associated with a 0.39% increase in urinary %InAs (p<0.0001) and a mean decrease in urinary %DMA of 0.07 (p=0.0005). In the 292 participants with measurable blood As metabolites, the associations of eGFR with increased blood %InAs and decreased blood %DMA did not reach statistical significance. eGFR was not associated with urinary or blood %MMA in covariate-adjusted models. For a given increase in blood %InAs, the increase in urinary %InAs was smaller in those with reduced eGFR, compared to those with normal eGFR (p=0.06); this effect modification was not observed for %MMA or %DMA. Conclusions Urinary excretion of InAs may be impaired in individuals with reduced renal function. Alternatively, increased As methylation capacity (as indicated by decreased urinary %InAs) may be detrimental to renal function. PMID:26476787
Background Immediately after renal transplantation, patients experience rapid and significant improvement of their clinical conditions and undergo considerable systemic and cellular modifications. However, some patients present a slow recovery of the renal function commonly defined as delayed graft function (DGF). Although clinically well characterized, the molecular mechanisms underlying this condition are not totally defined, thus, we are currently missing specific clinical markers to predict and to make early diagnosis of this event. Methods We investigated, using a pathway analysis approach, the transcriptomic profile of peripheral blood mononuclear cells (PBMC) from renal transplant recipients with DGF and with early graft function (EGF), before (T0) and 24 hours (T24) after transplantation. Results Bioinformatics/statistical analysis showed that 15 pathways (8 up-regulated and 7 down-regulated) and 11 pathways (5 up-regulated and 6 down-regulated) were able to identify DGF patients at T0 and T24, respectively. Interestingly, the most up-regulated pathway at both time points was NLS-bearing substrate import into nucleus, which includes genes encoding for several subtypes of karyopherins, a group of proteins involved in nucleocytoplasmic transport. Signal transducers and activators of transcription (STAT) utilize karyopherins-alpha (KPNA) for their passage from cytoplasm into the nucleus. In vitro functional analysis demonstrated that in PBMCs of DGF patients, there was a significant KPNA-mediated nuclear translocation of the phosphorylated form of STAT3 (pSTAT3) after short-time stimulation (2 and 5 minutes) with interleukin-6. Conclusions Our study suggests the involvement, immediately before transplantation, of karyopherin-mediated nuclear transport in the onset and development of DGF. Additionally, it reveals that karyopherins could be good candidates as potential DGF predictive clinical biomarkers and targets for pharmacological interventions in renal
Xue, Dong; Zhou, Cuixing; Shi, Yunbo; Lu, Hao; He, Xiaozhou
BACKGROUND To explore the use of hepcidin as a marker of impaired renal function in a rat model for chronic allograft nephropathy (CAN). MATERIAL AND METHODS Twenty-four models were developed and 20 models were included in this study, using Fisher (F344) rats (donors) and Lewis rats (recipients). Renal function tests were performed preoperatively and postoperatively. Hepcidin, interleukin-6 (IL-6), and erythropoietin levels in serum and urine were measured by enzyme-linked immunosorbent assay (ELISA). To observe pathological changes in the kidneys, 10 rats each were sacrificed at 2 months and 4 months after surgery. RESULTS After transplantation, the serum hepcidin and IL-6 levels increased, while urine hepcidin levels decreased. Erythropoietin levels showed a similar trend; all P<0.05. Serum creatinine (SCr) and blood urea nitrogen significantly increased post-operatively, with SCr positively correlating with serum hepcidin. Serum hepcidin positively correlated with IL-6 and negatively correlated with EPO. Histopathological results were consistent with CAN, after transplantation. CONCLUSIONS Hepcidin may be considered as a potential marker of impaired renal function.
Roldán, Julián; Morillas, Pedro; Castillo, Jesús; Andrade, Helder; Guillén, Silvia; Núñez, Daniel; Quiles, Juan; Bertomeu, Vicente
There is increasing interest in the role of aldosterone in the pathophysiology of hypertension, cardiovascular disease and deteriorating renal function. The aim of this study was to investigate the relationship between aldosterone and the glomerular filtration rate (GFR) in hypertensive patients with preserved renal function. The study involved 186 consecutive hypertensive patients with a GFR >60 mL/min. The GFR was determined using the Modification of Diet in Renal Disease (MDRD) equation and the patients' plasma aldosterone levels were measured. Patients with a GFR between 60-89 mL/min had a significantly higher plasma aldosterone level than those with a GFR >90 mL/min (20.02 ng/dL vs. 15.3 ng/dL; P< .05). Multivariate analysis showed that the plasma aldosterone level was independently associated with the GFR (B=-7.36; P< .001). In hypertensive patients with preserved kidney function, the plasma aldosterone level was observed to increase as the GFR decreased.
Horster, Michael; Valtin, Heinz
Postnatal renal development was studied in dogs between 2 and 77 days. Single, superficial nephrons were evaluated by micropuncture, concurrently with measurements of total renal function and morphometric analyses in the same animals. Glomerular filtration rate for the entire kidney increased linearly from 0.13 ml/min per g kidney weight at 2 days to 0.91 at 77 days. Extraction of p-aminohippurate increased from about 20 to 80%, and renal plasma flow per g kidney weight, measured as Cpah/Epah, increased threefold during the same period. Filtration fraction increased to the mature value during the first half of the postnatal period studied. The clearance of urea per unit of renal mass increased with age, whereas the fraction of filtered urea reabsorbed declined during the early part of the postnatal period. The pattern of fractional urea reabsorption may be due mainly to increased medullary recycling of urea and to a rise in the reabsorption of water from the medullary collecting duct. Urine osmolality was higher than plasma from birth onward and rose with age. Osmolal equality of collecting duct fluid and medullary interstitium reflected mature vasopressin (ADH)-induced water permeability. The rise in urinary concentration was predominantly due to increasing medullary sequestration of urea. Glomerular filtration rate of the superficial nephron increased from 3.2 nl/min at 21 days, when subcapsular nephrons were uniformly patent, to 23.1 at 77 days. Despite this rise in filtered load, fractional reabsorption of sodium and water in superficial proximal tubules was constant and at the mature level from the onset of intratubular perfusion. Changes in arterial plasma protein concentration, in filtration fraction, and in the hydrostatic pressure gradient between proximal tubule and peritubular capillary may interact to maintain glomerulotubular balance. The data, together with results of an accompanying morphological study, demonstrate a sequence of coordinated changes
Wei, Guojun; Rosen, Seymour; Dantzler, William H.
The architecture of the inner stripe of the outer medulla of the human kidney has long been known to exhibit distinctive configurations; however, inner medullary architecture remains poorly defined. Using immunohistochemistry with segment-specific antibodies for membrane fluid and solute transporters and other proteins, we identified a number of distinctive functional features of human inner medulla. In the outer inner medulla, aquaporin-1 (AQP1)-positive long-loop descending thin limbs (DTLs) lie alongside descending and ascending vasa recta (DVR, AVR) within vascular bundles. These vascular bundles are continuations of outer medullary vascular bundles. Bundles containing DTLs and vasa recta lie at the margins of coalescing collecting duct (CD) clusters, thereby forming two regions, the vascular bundle region and the CD cluster region. Although AQP1 and urea transporter UT-B are abundantly expressed in long-loop DTLs and DVR, respectively, their expression declines with depth below the outer medulla. Transcellular water and urea fluxes likely decline in these segments at progressively deeper levels. Smooth muscle myosin heavy chain protein is also expressed in DVR of the inner stripe and the upper inner medulla, but is sparsely expressed at deeper inner medullary levels. In rodent inner medulla, fenestrated capillaries abut CDs along their entire length, paralleling ascending thin limbs (ATLs), forming distinct compartments (interstitial nodal spaces; INSs); however, in humans this architecture rarely occurs. Thus INSs are relatively infrequent in the human inner medulla, unlike in the rodent where they are abundant. UT-B is expressed within the papillary epithelium of the lower inner medulla, indicating a transcellular pathway for urea across this epithelium. PMID:26290371
Elias, Peter M.; Williams, Mary L.; Feingold, Kenneth R.
Ichthyoses, including inherited disorders of lipid metabolism, display a permeability barrier abnormality in which the severity of the clinical phenotype parallels the prominence of the barrier defect. The pathogenesis of the cutaneous phenotype represents the consequences of the mutation for epidermal function, coupled with a “best attempt” by affected epidermis to generate a competent barrier in a terrestrial environment. A compromised barrier in normal epidermis triggers a vigorous set of metabolic responses that rapidly normalizes function, but ichthyotic epidermis, which is inherently compromised, only partially succeeds in this effort. Unraveling mechanisms that account for barrier dysfunction in the ichthyoses has identified multiple, subcellular, and biochemical processes that contribute to the clinical phenotype. Current treatment of the ichthyoses remains largely symptomatic: directed toward reducing scale or corrective gene therapy. Reducing scale is often minimally effective. Gene therapy is impeded by multiple pitfalls, including difficulties in transcutaneous drug delivery, high costs, and discomfort of injections. We have begun to use information about disease pathogenesis to identify novel, pathogenesis-based therapeutic strategies for the ichthyoses. The clinical phenotype often reflects not only a deficiency of pathway end product due to reduced-function mutations in key synthetic enzymes but often also accumulation of proximal, potentially toxic metabolites. As a result, depending upon the identified pathomechanism(s) for each disorder, the accompanying ichthyosis can be treated by topical provision of pathway product (eg, cholesterol), with or without a proximal enzyme inhibitor (eg, simvastatin), to block metabolite production. Among the disorders of distal cholesterol metabolism, the cutaneous phenotype in Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects (CHILD syndrome) and X-linked ichthyosis reflect metabolite
Trzeciakowski, Jerome P.; Gardiner, Lesley; Parrish, Alan R.
A relationship between exposure to heavy metals, including lead and cadmium, and renal dysfunction has long been suggested. However, modeling of the potential additive, or synergistic, impact of metals on renal dysfunction has proven to be challenging. In these studies, we used structural equation modeling (SEM), to investigate the relationship between heavy metal burden (serum and urine levels of lead, cadmium and mercury) and renal function using data from the NHANES database. We were able to generate a model with goodness of fit indices consistent with a well-fitting model. This model demonstrated that lead and cadmium had a negative relationship with renal function, while mercury did not contribute to renal dysfunction. Interestingly, a linear relationship between lead and loss of renal function was observed, while the maximal impact of cadmium occurred at or above serum cadmium levels of 0.8 µg/L. The interaction of lead and cadmium in loss of renal function was also observed in the model. These data highlight the use of SEM to model interaction between environmental contaminants and pathophysiology, which has important implications in mechanistic and regulatory toxicology. PMID:24769258
Trzeciakowski, Jerome P; Gardiner, Lesley; Parrish, Alan R
A relationship between exposure to heavy metals, including lead and cadmium, and renal dysfunction has long been suggested. However, modeling of the potential additive, or synergistic, impact of metals on renal dysfunction has proven to be challenging. In these studies, we used structural equation modeling (SEM), to investigate the relationship between heavy metal burden (serum and urine levels of lead, cadmium and mercury) and renal function using data from the NHANES database. We were able to generate a model with goodness of fit indices consistent with a well-fitting model. This model demonstrated that lead and cadmium had a negative relationship with renal function, while mercury did not contribute to renal dysfunction. Interestingly, a linear relationship between lead and loss of renal function was observed, while the maximal impact of cadmium occurred at or above serum cadmium levels of 0.8 μg/L. The interaction of lead and cadmium in loss of renal function was also observed in the model. These data highlight the use of SEM to model interaction between environmental contaminants and pathophysiology, which has important implications in mechanistic and regulatory toxicology.
Rosen, P.R.; Kuruc, A.; Treves, S.T.
Three methods for evaluating relative renal function in a pediatric population were compared. The clinical and nuclear medicine data of 73 patients were reviewed. Pertinent data included patient age, serum creatinine and the referral diagnosis (reflux, hypertension, obstructive uropathy). Time activity curves for renal regions of interest (ROI) were obtained by renography with Tc-99m DTPA, and deconvolved by an externally detected blood pool curve Furosemide was then administered to evaluate the renal collecting system (if indicated). This was followed by DMSA administration. Relative function was determined in 3 ways: 1) Accumulated renal DTPA activity 60-120 sec. following injection. 2) Amplitude of the tubular phase of the deconvolved renal curve and, 3) Accumulated Tc-99m DMSA activity in renal ROI 4 or 24 hrs. post-injection. Regression analysis revealed: 1) The basic relationship of relative functional data obtained by all three methods was not affected by creatinine, age or other factors. 2) The relationship between the three methods is linear and highly correlated. 3) The DMSA values may be predicted from either method of analyzing the DTPA study using appropriate predictor equations. The authors conclude that Tc-99m DMSA, due to its higher cost and more radiation exposure should not be used for the routine evaluation of relative renal function.
Nakamura, T; Ghilardi, M F; Mentis, M; Dhawan, V; Fukuda, M; Hacking, A; Moeller, J R; Ghez, C; Eidelberg, D
activation compensating for abnormalities in basal ganglia function.
Ruiz, Marta; Perez-Garcia, Georgina; Ortiz-Virumbrales, Maitane; Méneret, Aurelie; Morant, Andrika; Kottwitz, Jessica; Fuchs, Tania; Bonet, Justine; Gonzalez-Alegre, Pedro; Hof, Patrick R.; Ozelius, Laurie J.; Ehrlich, Michelle E.
DYT6 dystonia is caused by mutations in THAP1 [Thanatos-associated (THAP) domain-containing apoptosis-associated protein] and is autosomal dominant and partially penetrant. Like other genetic primary dystonias, DYT6 patients have no characteristic neuropathology, and mechanisms by which mutations in THAP1 cause dystonia are unknown. Thap1 is a zinc-finger transcription factor, and most pathogenic THAP1 mutations are missense and are located in the DNA-binding domain. There are also nonsense mutations, which act as the equivalent of a null allele because they result in the generation of small mRNA species that are likely rapidly degraded via nonsense-mediated decay. The function of Thap1 in neurons is unknown, but there is a unique, neuronal 50-kDa Thap1 species, and Thap1 levels are auto-regulated on the mRNA level. Herein, we present the first characterization of two mouse models of DYT6, including a pathogenic knockin mutation, C54Y and a null mutation. Alterations in motor behaviors, transcription and brain structure are demonstrated. The projection neurons of the deep cerebellar nuclei are especially altered. Abnormalities vary according to genotype, sex, age and/or brain region, but importantly, overlap with those of other dystonia mouse models. These data highlight the similarities and differences in age- and cell-specific effects of a Thap1 mutation, indicating that the pathophysiology of THAP1 mutations should be assayed at multiple ages and neuronal types and support the notion of final common pathways in the pathophysiology of dystonia arising from disparate mutations. PMID:26376866
Goodenday, L S; Simon, G; Craig, H; Dalby, L
Wasted ventilatory volume (V(D)) and its ratio to tidal volume (V(D)/V(T)) were measured at rest and during exertion in 17 patients with aortic valve disease. We considered V(D)/V(T) to indicate abnormal ventilation: perfusion relations if it did not decrease on exertion, or if the exercising value was greater than 40 per cent. Plain chest radiographs were independently examined for evidence of diversion of pulmonary blood to the upper lobes. There was significant agreement (p<0.05) between radiographic and pulmonary function estimations of abnormality. This suggests that the raised pulmonary venous pressure associated with left ventricular failure creates an abnormal pattern of blood flow through the lung, which is responsible for causing inadequate perfusion with respect to ventilation.
... Listen Español Text Size Email Print Share Congenital Abnormalities Page Content Article Body About 3% to 4% ... of congenital abnormalities earlier. 5 Categories of Congenital Abnormalities Chromosome Abnormalities Chromosomes are structures that carry genetic ...
The history of observations and experimental work on compensatory changes following the loss of renal mass, and the historical reasons for the distinction between the concepts of compensatory adaptation (of renal functions) and of compensatory hypertrophy (of nephrons) are outlined. While the effector mechanisms of both types of compensatory changes are being elucidated at a rapid pace, many questions concerning the primary changes initiating these events, the control mechanisms implied and the interrelationship between functional adaptation and hypertrophy remain unanswered. PMID:366923
Shen, Chong; Meng, Qin; Zhang, Guoliang
Tissue engineering devices as in vitro cell culture systems in scaffolds has encountered the bottleneck due to their much lower cell functions than real tissues/organs in vivo. Such situation has been improved in some extent by mimicking the cell microenvironments in vivo from either chemical or physical ways. However, microenvironmental curvature, commonly seen in real tissues/organs, has never been manipulated to regulate the cell performance in vitro. In this regard, this paper fabricated polysulfone membranes with or without polyethylene glycol modification to investigate the impact of curvature on two renal tubular cells. Regardless the varying membrane curvatures among hollow fiber membranes of different diameters and flat membrane of zero curvature, both renal cells could well attach at 4 h of seeding and form similar confluent layers at 6 days on each membrane. Nevertheless, the renal cells on hollow fibers, though showing confluent morphology as those on flat membranes, expressed higher renal functions and, moreover, the renal functions significantly increased with the membrane curvature among hollow fibers. Such upregulation on functions was unassociated with mass transport barrier of hollow fibers, because the cultures on lengthwise cut hollow fibers without mass transfer barrier showed same curvature effect on renal functions as whole hollow fibers. It could be proposed that the curvature of hollow fiber membrane approaching to the large curvature in kidney tubules increased the mechanical stress in the renal cells and thus might up-regulate the renal cell functions. In conclusion, the increase of substrate curvature could up-regulate the cell functions without altering the confluent cell morphology and this finding will facilitate the design of functional tissue engineering devices.
Erdel, Blake L.; Juneja, Rattan; Evans-Molina, Carmella
Objective To present the case of a patient with a history of thyroid cancer, post-surgical hypoparathyroidism, chronic calcitriol use, and normal renal function who presented with painful skin lesions secondary to calciphylaxis. Methods We describe the history, biochemistry, histopathology, evaluation, and management of this patient. Results A 47 year-old female with hypoparathyroidism, chronically treated with calcitriol and calcium, presented with exquisitely painful skin ulcerations. Four months prior to the onset of symptoms, she had initiated warfarin therapy for atrial fibrillation. Review of laboratory data from the past year revealed elevated calcium and phosphorus levels. A diagnosis of calciphylaxis was made based upon pathologic evaluation of a skin biopsy. Management included titration of calcitriol and calcium to maintain serum calcium and phosphate levels in the low normal range. Sodium thiosulfate was administered at a dose of 25 mg IV three times a week with some resolution in the patient's pain. Unfortunately, the patient battled recurrent bacteremia and sepsis, presumably related to her calciphylaxis wounds, and ultimately succumbed to complications from sepsis. Conclusion While calciphylaxis is typically associated with renal insufficiency and secondary hyperparathyroidism, we highlight the case of a patient with normal renal function and hypoparathyroidism. Patients treated with chronic calcitriol should have serum calcium and phosphorus monitored closely and may benefit from non-calcium based phosphate binders if hyperphosphatemia becomes unavoidable. This is especially important in the presence of other risk factors for calciphylaxis including warfarin use. PMID:24518186
Somsak, Voravuth; Jaihan, Ubonwan; Srichairatanakool, Somdet; Uthaipibull, Chairat
Impairment of renal function from oxidative stress during malaria infection is one of the leading causes of death in endemic areas. Since blood urea nitrogen and creatinine levels in plasma can be used as markers for monitoring renal damage, this study investigated the effect of green tea extract on reduction of blood urea nitrogen and creatinine levels during malaria infection using Plasmodium berghei ANKA infected mice as in vivo model. For in vivo testing, ICR mice were infected with 1 × 10(7) parasitized erythrocytes and green tea extract was subsequently administered orally twice a day for 10 consecutive days. Parasitemia was estimated by standard microscopy, and blood urea nitrogen and creatinine levels in plasma were also measured. It was found that parasitemia kept increasing until animal death, and is strongly correlated with high blood urea nitrogen and creatinine. The highest levels of blood urea nitrogen and creatinine in plasma were found on day 10 after infection. However, blood urea nitrogen and creatinine levels in plasma were reduced and decreased significantly (p<0.01) in green tea extract treated mice, compared with untreated group. It can be concluded that green tea extract can protect and maintain renal function during malaria infection, and this extract can be developed for use as a supplement and combination therapy.
Ohkawa, M; Hirano, S; Tokunaga, S; Motoi, I; Shoda, R; Ikeda, A; Sugata, T; Sawaki, M; Shimamura, M; Okasho, A; Kuroda, K
The elimination kinetics of cefotetan (YM09330), a new parenteral semisynthetic cephamycin derivative, were studied in eight healthy volunteers and 41 patients with renal insufficiency after the administration of a single 500-mg dose intravenously. Concentrations of cefotetan in serum and urine were determined by both bioassay and high-pressure liquid chromatography. The pharmacokinetic parameters for cefotetan were calculated on the basis of a two-compartment open model. Serum concentrations of cefotetan immediately after administration were approximately 180 micrograms/ml in all subjects regardless of function; however, serum concentrations during the beta-phase increased directly with the degree of renal impairment. The mean serum half-life during the beta-phase was 3.0 h in normal subjects as compared with 13.1 h in hemodialysis patients. There was a linear correlation (P less than 0.0001) between the elimination rate constant of cefotetan and creatinine clearance. The mean cumulative urinary recovery of cefotetan in the 24-h urine was 83.3% of the administered dose in normal subjects and decreased with reduced renal function. PMID:6572490
Urt-Filho, Antônio; Oliveira, Rodrigo Juliano; Hermeto, Larissa Correa; Pesarini, João Renato; de David, Natan; Cantero, Wilson de Barros; Falcão, Gustavo; Marks, Guido; Antoniolli-Silva, Andréia Conceição Milan Brochado
Abstract Acute renal failure (ARF) is an extremely important public health issue in need of novel therapies. The present study aimed to evaluate the capacity of mesenchymal stem cell (MSC) therapy to promote the improvement and recovery of renal function in a preclinical model. Wistar rats were used as the experimental model, and our results show that cisplatin (5mg/kg) can efficiently induce ARF, as measured by changes in biochemical (urea and creatinine) and histological parameters. MSC therapy performed 24h after the administration of chemotherapy resulted in normalized plasma urea and creatinine levels 30 and 45d after the onset of kidney disease. Furthermore, MSC therapy significantly reduced histological changes (intratubular cast formation in protein overload nephropathy and tubular hydropic degeneration) in this ARF model. Thus, considering that current therapies for ARF are merely palliative and that MSC therapy can promote the improvement and recovery of renal function in this model system, we suggest that innovative/alternative therapies involving MSCs should be considered for clinical studies in humans to treat ARF. PMID:27275667
Freestone, S; McAuslane, J A; Prescott, L F
1. The effects of tenoxicam on renal function were studied in 10 patients with chronic renal failure (creatinine clearance 46.7 +/- 11.9 ml min-1 1.73 m-2) and eight healthy volunteers. A parallel treatment control group of eight healthy volunteers received placebo. Tenoxicam was given orally in a dose of 40 mg daily for 2 days followed by 20 mg daily for a further 8 days. Renal function was assessed by measurement of the renal clearances of inulin and p-aminohippurate (PAH) using the single injection technique before and during administration of tenoxicam. 2. In the healthy volunteers there were no changes in glomerular filtration rate, effective renal plasma flow, or the urinary excretion of N-acetylglucosaminidase and beta 2-microglobulin on the 3rd and 10th days of treatment with tenoxicam. The mean urinary excretion of prostaglandins E2 and 6-keto F1 alpha decreased during treatment but there was great individual variation and the differences were not statistically significant. Tenoxicam had no effect on the half-life, clearance, volume of distribution or urinary recovery of inulin and PAH. 3. There was no significant change in the clearance of inulin and creatinine after treatment with tenoxicam for 10 days in the patients with chronic renal failure. However, in this group there was a significant increase in plasma creatinine on the 3rd and 6th days with a return to pretreatment levels by the 10th day. The administration of tenoxicam for 10 days was associated with a small but significant increase in the plasma half-life and volume of distribution of inulin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1958445
Yang, Yan; Li, Hui-Yan; Zhou, Qian; Peng, Zhen-Wei; An, Xin; Li, Wei; Xiong, Li-Ping; Yu, Xue-Qing; Jiang, Wen-Qi; Mao, Hai-Ping
Renal dysfunction predicts all-cause mortality in general population. However, the prevalence of renal insufficiency and its relationship with mortality in cancer patients are unclear.We retrospectively studied 9465 patients with newly diagnosed cancer from January 2010 to December 2010. Renal insufficiency was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m using the Chronic Kidney Disease Epidemiology Collaboration equation. The hazard ratio (HR) of all-cause mortality associated with baseline eGFR was assessed by Cox regression.Three thousand sixty-nine patients (32.4%) exhibited eGFR <90 mL/min/1.73 m and 3% had abnormal serum creatinine levels at the time of diagnosis. Over a median follow-up of 40.5 months, 2705 patients (28.6%) died. Compared with the reference group (eGFR ≥ 60 mL/min/1.73 m), an elevated all-cause mortality was observed among patients with eGFR < 60 mL/min/1.73 m stratified by cancer stage in the entire cohort, the corresponding hazard ratios were 1.87 (95% CI, 1.41-2.47) and 1.28 (95% CI, 1.01-1.62) for stage I to III and stage IV, respectively. However, this relationship was not observed after multivariate adjustment. Subgroup analysis found that eGFR < 60 mL/min/1.73 m independently predicted death among patients with hematologic (adjusted HR 2.93, 95% CI [1.36-6.31]) and gynecological cancer (adjusted HR 2.82, 95% CI [1.19-6.70]), but not in those with other cancer. Five hundred fifty-seven patients (6%) had proteinuria. When controlled for potential confounding factors, proteinuria was a risk factor for all-cause mortality among patients in the entire cohort, regardless of cancer stage and eGFR values. When patients were categorized by specific cancer type, the risk of all-cause death was only significant in patients with digestive system cancer (adjusted HR, 1.85 [1.48-2.32]).The prevalence of renal dysfunction was common in patients with newly diagnosed cancer. Patients with eGFR < 60 m
Carreira, Vinicius S.; Fan, Yunxia; Kurita, Hisaka; Wang, Qin; Ko, Chia-I; Naticchioni, Mindi; Jiang, Min; Koch, Sheryl; Zhang, Xiang; Biesiada, Jacek; Medvedovic, Mario; Xia, Ying; Rubinstein, Jack; Puga, Alvaro
The Developmental Origins of Health and Disease (DOHaD) Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR), either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr-/- and in utero TCDD-exposed Ahr+/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr-/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease. PMID:26555816
Nogueira, António; Oliveira, Maria Manuel; Pires, Carlos André; Colaço, Bruno
Purpose. This study aimed to evaluate the effect of chronic treatment with chaetomellic acid A (CAA) on oxidative stress and renal function in a model of renal mass reduction. Methods. Male Wistar rats were subjected to 5/6 nephrectomy (RMR) or sham-operated (SO). One week after surgery, rats have been divided into four experimental groups: RMR: RMR rats without treatment (n = 14); RMR + CAA: RMR rats treated with CAA (n = 13); SO: SO rats without treatment (n = 13); and SO + CAA: SO rats treated with CAA (n = 13). CAA was intraperitoneally administered in a dose of 0.23 µg/Kg three times a week for six months. Results. RMR was accompanied by a significant reduction in catalase and glutathione reductase (GR) activity (p < 0.05) and a decrease in reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. CAA administration significantly increased catalase and GR activity (p < 0.05) and increased GSH/GSSG ratio, but no significant difference between the treated and nontreated groups was found in this ratio. No significant differences were found between the RMR groups in any of the parameters of renal function. However, CAA administration slightly improves some parameters of renal function. Conclusions. These data suggest that CAA could attenuate 5/6 RMR-induced oxidative stress. PMID:28326323
Morales, J; Fierro, A; Benavente, D; Zehnder, C; Ferrario, M; Contreras, L; Herzog, C; Buckel, E
New immunosuppressive agents are being actively researched to avoid complications of chronic allograft nephropathy (CAN), calcineurin inhibitor (CNI) nephrotoxicity, and posttransplantation cancer. The family of mTOR inhibitors offers a unique immunosuppressive opportunity to avoid CNI toxicity and reduce the incidence of malignancy. Nevertheless, increasing data have demonstrated that sirolimus (SRL), the first mTOR introduced in the treatment of solid organ transplant recipients, induces proteinuria, an adverse event that could produce deterioration of long-term renal function. In this short-term study of patients followed for 1 to 16 months, we examined changes in renal function and proteinuria among renal transplant recipients converted from a CNI-based regimen to an everolimus (EVL)-based one, a recently introduced mTOR inhibitor. Our data showed that renal function can be optimized after conversion to EVL by up to 42% in recipients showing CAN grade 1 or 2, or CNI nephrotoxicity. Importantly, patients who improved their creatinine clearance did not show increased proteinuria measured in a voided specimen as the ratio of urinary protein and creatinine concentration (P/C). These results, if confirmed with long-term follow-up and a larger number of patients, would allow us to consider EVL as a promising agent for maintenance immunosuppressive regimens in kidney transplantation.
Nookala, Ravi K; Langemeyer, Lars; Pacitto, Angela; Ochoa-Montaño, Bernardo; Donaldson, Jane C; Blaszczyk, Beata K; Chirgadze, Dimitri Y; Barr, Francis A; Bazan, J Fernando; Blundell, Tom L
Mutations in the renal tumour suppressor protein, folliculin, lead to proliferative skin lesions, lung complications and renal cell carcinoma. Folliculin has been reported to interact with AMP-activated kinase, a key component of the mammalian target of rapamycin pathway. Most cancer-causing mutations lead to a carboxy-terminal truncation of folliculin, pointing to a functional importance of this domain in tumour suppression. We present here the crystal structure of folliculin carboxy-terminal domain and demonstrate that it is distantly related to differentially expressed in normal cells and neoplasia (DENN) domain proteins, a family of Rab guanine nucleotide exchange factors (GEFs). Using biochemical analysis, we show that folliculin has GEF activity, indicating that folliculin is probably a distantly related member of this class of Rab GEFs.
Canga, Ana; Kislikova, Maria; Martínez-Gálvez, María; Arias, Mercedes; Fraga-Rivas, Patricia; Poyatos, Cecilio; de Francisco, Angel L M
Nephrogenic systemic fibrosis is a fibrosing disorder that affects patients with impaired renal function and is associated with the administration of gadolinium-based contrast media used in MRI. Despite being in a group of drugs that were considered safe, report about this potentially serious adverse reaction was a turning point in the administration guidelines of these contrast media. There has been an attempt to establish safety parameters to identify patients with risk factors of renal failure. The close pharmacovigilance and strict observation of current regulations, with special attention being paid to the value of glomerular filtration, have reduced the published cases involving the use of gadolinium-based contrast media. In a meeting between radiologists and nephrologists we reviewed the most relevant aspects currently and recommendations for its prevention.
Noskov, V B; Larina, I M; Pastushkova, L Kh; Dobrokhotov, I V; Valeeva, O A; Coupe, M; Custaud, M -A; Novoselova, A M
Renal function and body composition, including liquids, were investigated in 14 essentially healthy male subjects during simulation of some spaceflight effects by 5-d dry immersion (DI). Noninvasive measurement of water spaces of organism was performed with the methods of bio-impedance analysis (BIA). Increase of renal excretion of liquids and appearance of negative water balance were observed. BIA revealed reductions of total body and extracellular liquids and a decrease of circulating plasma volume. This means, that DI induced hypohydration of organism. In the post-DI period, the hydration status regained its baseline level fairly soon. Lean body mass slightly decreased; adipose mass, on the contrary, exceeded baseline values. Moreover, the experiment evidenced technical impossibility to obtain valid impedansimetry data in DI.
Chen, Yuqing; Mahata, Manjula; Rao, Fangwen; Khandrika, Srikrishna; Courel, Maite; Fung, Maple M.; Zhang, Kuixing; Stridsberg, Mats; Ziegler, Michael G.; Hamilton, Bruce A.; Lipkowitz, Michael S.; Taupenot, Laurent; Nievergelt, Caroline; Mahata, Sushil K.; O'Connor, Daniel T.
Chromogranin A (CHGA), a protein released from secretory granules of chromaffin cells and sympathetic nerves, triggers endothelin-1 release from endothelial cells. CHGA polymorphisms associate with an increased risk for ESRD, but whether altered CHGA–endothelium interactions may explain this association is unknown. Here, CHGA led to the release of endothelin-1 and Weibel–Palade body exocytosis in cultured human umbilical vein endothelial cells. In addition, CHGA triggered secretion of endothelin-1 from glomerular endothelial cells and TGF-β1 from mesangial cells cocultured with glomerular endothelial cells. In humans, plasma CHGA correlated positively with endothelin-1 and negatively with GFR. GFR was highly heritable in twin pairs, and common promoter haplotypes of CHGA predicted GFR. In patients with progressive hypertensive renal disease, a CHGA haplotype predicted rate of GFR decline. In conclusion, these data suggest that CHGA acts through the glomerular endothelium to regulate renal function. PMID:19520754
Vettoretti, Simone; Vavrinec, Peter; Ochodnicky, Peter; Deelman, Leo E; De Zeeuw, Dick; Henning, Rob H; Buikema, Hendrik
In healthy rats, the physiological variation of baseline endothelial function of intrarenal arteries correlates with the severity of renal damage in response to a subsequent specific renal injury. However, whether such a variation in endothelial function may also condition or predict the variable response to angiotensin-converting enzyme-inhibiting treatment in these individuals has not been addressed before. To study this, 5/6 nephrectomy was performed to induce renal injury and chronic kidney disease in a group of healthy Wistar rats. At the time of nephrectomy, interlobar arteries were obtained from the extirpated right kidney and studied in vitro for endothelium-dependent relaxation to acetylcholine. Six weeks thereafter, treatment with lisinopril was started (n = 11) and continued for 9 wk. Proteinuria (metabolic cages) and systolic blood pressure (SBP; tail cuff) were evaluated weekly, and these were analyzed in relation to renal endothelial function at baseline. 5/6 Nephrectomy induced an increase in SBP and progressive proteinuria. Treatment with lisinopril reduced SBP and slowed proteinuria, albeit to a variable degree among individuals. The acetylcholine-induced renal artery dilation at baseline negatively correlated with lisinopril-induced reduction of proteinuria (r(2) = 0.648, P = 0.003) and with the decrease in SBP (r(2) = 0.592, P = 0.006). Our data suggest that angiotensin-converting enzyme-inhibitor attenuates the progression of renal damage the most in those individuals with decreased basal renal endothelial-mediated vasodilation.
Brescia, Marília D’Elboux Guimarães; Massarollo, Paulo Celso Bosco; Imakuma, Ernesto Sasaki; Mies, Sérgio
Background This randomized prospective clinical trial compared the hepatic venous outflow drainage and renal function after conventional with venovenous bypass (n = 15) or piggyback (n = 17) liver transplantation. Methods Free hepatic vein pressure (FHVP) and central venous pressure (CVP) measurements were performed after graft reperfusion. Postoperative serum creatinine (Cr) was measured daily on the first week and on the 14th, 21st and 28th postoperative days (PO). The prevalence of acute renal failure (ARF) up to the 28th PO was analyzed by RIFLE-AKIN criteria. A Generalized Estimating Equation (GEE) approach was used for comparison of longitudinal measurements of renal function. Results FHVP-CVP gradient > 3 mm Hg was observed in 26.7% (4/15) of the patients in the conventional group and in 17.6% (3/17) in the piggyback group (p = 0.68). Median FHVP-CVP gradient was 2 mm Hg (0–8 mmHg) vs. 3 mm Hg (0–7 mm Hg) in conventional and piggyback groups, respectively (p = 0.73). There is no statistically significant difference between the conventional (1/15) and the piggyback (2/17) groups regarding massive ascites development (p = 1.00). GEE estimated marginal mean for Cr was significantly higher in conventional than in piggyback group (2.14 ± 0.26 vs. 1.47 ± 0.15 mg/dL; p = 0.02). The conventional method presented a higher prevalence of severe ARF during the first 28 PO days (OR = 3.207; 95% CI, 1.010 to 10.179; p = 0.048). Conclusion Patients submitted to liver transplantation using conventional or piggyback methods present similar results regarding venous outflow drainage of the graft. Conventional with venovenous bypass technique significantly increases the harm of postoperative renal dysfunction. Trial Registration ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01707810 PMID:26115520
Arjomandi, Mehrdad; Haight, Thaddeus; Redberg, Rita; Gold, Warren M
Objective To determine whether the flight attendants who were exposed to secondhand tobacco smoke (SHS) in the aircraft cabin have abnormal pulmonary function. Methods We administered questionnaires and performed pulmonary function testing in 61 never-smoking female flight attendants who worked in active air crews before the smoking ban on commercial aircraft (pre-ban). Results While the pre-ban flight attendants had normal FVC, FEV1, and FEV1/FVC ratio, they had significantly decreased flow at mid- and low-lung volumes, curvilinear flow-volume curves, and evidence of air trapping. Furthermore, the flight attendants had significantly decreased diffusing capacity (77.5±11.2 %predicted normal) with 51% having a diffusing capacity below their 95% normal prediction limit. Conclusions This cohort of healthy never-smoking flight attendants who were exposed to SHS in the aircraft cabin showed pulmonary function abnormalities suggestive of airway obstruction and impaired diffusion. PMID:19448573
Quante, Saskia; Fracassi, Federico; Gorgas, Daniela; Kircher, Patrick R; Boretti, Felicitas S; Ohlerth, Stefanie; Reusch, Claudia E
A 7-month-old male kitten was presented with chronic constipation and retarded growth. Clinical examination revealed disproportional dwarfism with mild skeletal abnormalities and a palpable thyroid gland. The presumptive diagnosis of congenital hypothyroidism was confirmed by low serum total thyroxine (tT(4)) concentration prior to and after the administration of thyroid stimulation hormone (TSH), increased endogenous TSH concentration and abnormal thyroid scintigraphic scan. The kitten had abnormal liver function tests and decreased insulin-like growth factor 1 (IGF-1) concentration, both of which returned to normal in correspondence with an improvement of the clinical signs after 6 weeks of thyroxine therapy. Congenital hypothyroidism is a rare disease that may present with considerable variation in clinical manifestation. In cases in which clinical signs are ambiguous, disorders such as portosystemic shunt and hyposomatotropism have to be taken into account as differential diagnosis. As hypothyroidism may be associated with abnormal liver function tests and low IGF-1 concentrations, test results have to be interpreted carefully.
Karim, F; Poucher, S M; Summerill, R A
1. Dogs were anaesthetized with chloralose and artificially ventilated. The carotid chemoreceptors were stimulated by changing the perfusion of vascularly isolated carotid sinus regions from arterial to venous blood. The mean carotid sinus pressure and the mean arterial blood pressure were held constant at 124 +/- 3 and 122 +/- 3 mmHg, respectively. Both vagosympathetic trunks were sectioned in the neck and propranolol (17 micrograms kg-1 min-1 I.V.) and gallamine triethiodide (0.2-2.0 mg kg-1 30 min-1 I.V.) were infused. Renal blood flow was measured by an electromagnetic flow probe, glomerular filtration rate by creatinine clearance, sodium excretion by flame photometry and solute excretion by osmometry. 2. In sixteen tests in thirteen dogs perfusion of the carotid sinus regions with venous blood resulted in significant decreases in renal blood flow from 271 +/- 24 to 198 +/- 21 ml min-1 100 g-1 renal mass; glomerular filtration rate from 41.0 +/- 4.8 to 22.1 +/- 3.1 ml min-1 100 g-1; filtration fraction from 0.25 +/- 0.02 to 0.19 +/- 0.02; urine flow from 0.48 +/- 1.0 to 0.21 +/- 0.03 ml min-1 100 g-1; sodium excretion from 18.1 +/- 4.1 to 12.9 +/- 4.2 mumol min-1 100 g-1; and osmolar excretion 327 +/- 42 to 171 +/- 26 mu osmol min-1 100 g-1. The right atrial pressure did not change significantly from 4.6 +/- 1.2 cmH2O. 3. In seven dogs, tying renal sympathetic nerves abolished all the responses except that of sodium excretion which was now reversed; sodium excretion increased from 68 +/- 19 to 116 +/- 38 mumol min-1 100 g-1 without significant change in right atrial pressure from 7.4 +/- 1.9 cmH2O. Crushing the carotid bodies, however, abolished all the responses. 4. The results show that carotid chemoreceptor stimulation can cause significant reflex effects on renal haemodynamics and function which are mediated via renal sympathetic nerves. They also show that the chemoreceptor stimulation can cause natriuresis in the absence of haemodynamic changes, in the
Madkour, Hosameldin; Ali, Kareim; Nosrati, Saeid; Massry, Shaul G
We examined the efficacy of low daily dose (1.25 mg/day) of indapamide in the treatment of high blood pressure in patients with diabetes mellitus with normal renal function and those with moderate renal insufficiency (serum creatinine <1.5 mg/dl). The study was an open label one of four months duration. Twenty-eight patients were enrolled in the study and only 15 completed it. Within 2 weeks of therapy, systolic blood pressure fell from 173 +/- 4.5 to 144 +/- 2.0 mm Hg and diastolic blood pressure from 96 +/- 2.1 to 80 +/- 1.8 mm Hg (p < 0.01) and blood pressure remained at these levels throughout the study. The results show that low dose indapamide is effective in the treatment of moderate hypertension in patients with diabetes mellitus who have normal renal function or moderate renal insufficiency. Therefore, this dose of 1.25 mg/day is recommended for the treatment of such patients.
Capitanio, Umberto; Larcher, Alessandro; Terrone, Carlo; Antonelli, Alessandro; Volpe, Alessandro; Fiori, Cristian; Furlan, Maria; Dehò, Federico; Minervini, Andrea; Serni, Sergio; Porpiglia, Francesco; Trevisani, Francesco; Salonia, Andrea; Carini, Marco; Simeone, Claudio; Montorsi, Francesco; Bertini, Roberto
Although nephron-sparing surgery (NSS) has demonstrated benefit in terms of renal function preservation, it is unclear whether NSS might also decrease the risk of end-stage renal disease (ESRD) relative to radical nephrectomy (RN). In the current paper, we aimed to report the rate and the predictors of ESRD after surgery, accounting for detailed individual baseline characteristics and comorbidities. A multi-institutional collaboration among five European tertiary care centers allowed study of 2027 patients with normal preoperative renal function and a clinically localized T1abN0M0 renal mass. Cox regression analyses were used to predict the risk of ESRD (defined as the onset of a postoperative estimated glomerular filtration rate <15ml/min per 1.73 m(2)) after adjusting for the individual baseline risk of developing chronic kidney disease. Univariable ESRD rates at 5 and 10 yr of follow-up were virtually equivalent for patients who underwent NSS (1.5% and 2.5%, respectively) versus RN (1.9% and 2.7%, respectively; hazard ratio [HR]: 0.8; 95% confidence interval [CI], 0.4-1.6). However, diabetes, smoking, uncontrolled hypertension, and other comorbidities were consistently more frequent in the NSS group relative to their RN counterparts. After adjusting for detailed baseline individual characteristics, NSS was shown to have an independent protective effect relative to RN (HR: 0.4; 95% CI, 0.2-0.8; p=0.02) at multivariable analyses.
Ali, Quaisar; Wu, Yonnie; Hussain, Tahir
Abnormal regulation of the renin angiotensin system such as enhanced renal AT1R function and reduced ACE2 activity contributes to obesity-related hypertension. Here, we tested whether long-term AT2R activation affects renal function in obesity using lean and obese Zucker rats treated with the AT2R agonist CGP42112A for 2 weeks. This caused blood pressure to decrease by 13 mm Hg, which was associated with increased urinary sodium excretion in the obese rats. Cortical ACE2 expression and activity, the Mas receptor (MasR), and its ligand angiotensin-(1-7) were all increased in CGP-treated obese compared with control rats. Candesartan-induced natriuresis, a measure of AT₁R function, was reduced but cortical AT₁R expression and angiotensin II levels were similar in CGP-treated obese compared with control rats. Renin and AT2R expression in obese rats was not affected by CGP treatment. In HK-2 cells in vitro, CGP treatment caused increased ACE2 activity and MasR levels but decreased AT₁R levels and renin activity. Thus, long-term AT2R activation shifts the opposing arms of renin angiotensin system and contributes to natriuresis and blood pressure reduction in obese animals. Our study highlights the importance of AT2R as a target for treating obesity-related hypertension.
Zou, Feng; Wu, Xinhuai; Zhai, Tianye; Lei, Yu; Shao, Yongcong; Jin, Xiao; Tan, Shuwen; Wu, Bing; Wang, Lubin; Yang, Zheng
Functional neuroimaging studies suggest that abnormal brain functional connectivity may be the neural underpinning of addiction to illicit drugs and of relapse after successful cessation therapy. Aberrant brain networks have been demonstrated in addicted patients and in newly abstinent addicts. However, it is not known whether abnormal brain connectivity patterns persist after prolonged abstinence. In this cross-sectional study, whole-brain resting-state functional magnetic resonance images (8 min) were collected from 30 heroin-addicted individuals after a long period of abstinence (more than 3 years) and from 30 healthy controls. We first examined the group differences in the resting-state functional connectivity of the nucleus accumbens (NAc), a brain region implicated in relapse-related processes, including craving and reactivity to stress following acute and protracted withdrawal from heroin. We then examined the relation between the duration of abstinence and the altered NAc functional connectivity in the heroin group. We found that, compared with controls, heroin-dependent participants exhibited significantly greater functional connectivity between the right ventromedial prefrontal cortex and the NAc and weaker functional connectivity between the NAc and the left putamen, left precuneus, and supplementary motor area. However, with longer abstinence time, the strength of NAc functional connectivity with the left putamen increased. These results indicate that dysfunction of the NAc functional network is still present in long-term-abstinent heroin-dependent individuals.
Poreddy, Amruta R.; Asmelash, Bethel; Debreczeny, Martin P.; Fitch, Richard M.; Freskos, John N.; Galen, Karen P.; Gaston, Kimberly R.; Kostelc, James G.; Kumar, Rana; Marzan, Tim A.; Neumann, William L.; Rajagopalan, Raghavan; Schoenstein, Tasha M.; Shieh, Jeng-Jong; Wilcox, J. Micah; Wojdyla, Jolette K.; Dorshow, Richard B.
Accurate measurement of glomerular filtration rate (GFR) at the bedside is highly desirable in order to assess renal function in real-time, which is currently an unmet clinical need. In our pursuit to develop exogenous fluorescent tracers as GFR markers, various hydrophilic derivatives of 3,6-diaminopyrazine-2,5-dicarboxylic acid with varying molecular weights and absorption/emission characteristics were synthesized. These include polyhydroxyalkyl based small molecules and poly(ethylene glycol) (PEG) substituted moderate molecular weight compounds, which were further sub-grouped into analogs having blue excitation with green emission, and relatively longer wavelength analogs having green excitation with orange emission. Lead compounds were identified in each of the four classes on the basis of structure- activity relationship studies, which included in vitro plasma protein binding, in vivo urine recovery of administered dose, and in vivo optical monitoring. The in vivo optical monitoring experiments with lead candidates have been correlated with plasma pharmacokinetic (PK) data for measurement of clearance and hence GFR. Renal clearance of these compounds, occurring exclusively via glomerular filtration, was established by probenecid blocking experiments. The renal clearance property of all these advanced candidates was superior to that of the iothalamate, which is currently an accepted standard for the measurement of GFR.
Smith, J H; Rush, G F; Hook, J B
A marked species difference exists in the induction of renal and hepatic mixed function oxidase (MFO) activity between rats and rabbits. However, little is known about MFO induction in these organs from other laboratory animals. Male Golden Syrian hamsters and male Hartley guinea pigs were administered phenobarbital (PB) or beta-napthoflavone (BNF) at 70 and 40 mg/kg, respectively, as daily i.p. injections for 4 days. Polybrominated biphenyl (PBB) (Firemaster BP-6) was given as a single i.p. injection (50 mg/kg). Hamster hepatic microsomal ethoxyresorufin-O-deethylase (EROD) and benzphetamine-N-demethylase (BPND) were selectively induced by BNF and PB, respectively. PBB administration induced both hamster hepatic EROD and BPND. In contrast, hepatic microsomal MFO activity from the guinea pig was inducible by PB, PBB and BNF. Renal microsomal MFO activity in both species was inducible by BNF and PBB as arylhydrocarbon hydroxylase and EROD were induced approximately 10-fold. On the other hand, hamster BPND was induced by PB whereas guinea pig MFO activity was unaffected. Total renal cytochrome P-450 content was not affected by any of these inducers in either species. These data demonstrate selective patterns of induction in both hamster and guinea pig liver and kidney suggesting the involvement of multiple forms of cytochrome P-450.
Yu, Sung-Hsun; Dubey, Navneet Kumar; Li, Wei-Shan; Liu, Ming-Che; Chiang, Han-Sun; Leu, Sy-Jye; Shieh, Ying-Hua; Tsai, Feng-Chou; Deng, Win-Ping
Diabetic nephropathy is derived from long-term effects of high blood glucose on kidney function in type 2 diabetic patients. Several antidiabetic drugs and herbal medications have failed to prevent episodes of DN. Hence, this study aimed to further investigate the renal injury-reducing effect of antidiabetic CmNo1, a novel combination of powders of fruiting bodies and mycelia of Cordyceps militaris. After being administered with streptozotocin-nicotinamide and high-fat-diet, the diabetic nephropathy mouse model displayed elevated blood glucose and renal dysfunction markers including serum creatinine and kidney-to-body weight ratio. These elevated markers were significantly mitigated following 8 weeks CmNo1 treatment. Moreover, the chronic hyperglycemia-induced pathological alteration in renal tissue were also ameliorated. Besides, immunohistochemical study demonstrated a substantial reduction in elevated levels