Better Renal Resistive Index Profile in Subjects with Beta Thalassemia Minor.

OBJECTIVE: Beta thalassaemia minor is a common genetic disorder without any characteristic symptoms except mild anemia. It is found to be associated with some cardiovascular risk factors such as insulin resistance and diabetes mellitus. The renal resistive index (RRI) is a measure of renal arterial resistance to blood flow. The aim of this study was to evaluate the RRI in subjects with beta thalassemia minor (BTM). SUBJECTS AND METHODS: A total of 253 subjects were included in this cross-sectional study. The study group consisted of 148 subjects with BTM and the control group consisted of 105 healthy subjects. BTM was diagnosed by a complete blood count and hemoglobin electrophoresis. Blood pressure measurement and biochemical tests were performed. The RRI of all subjects was measured using renal Doppler ultrasonography. RESULTS: Subjects with BTM had lower renal resistive indices compared to healthy subjects (0.58 ± 0.04 vs. 0.60 ± 0.06, p = 0.0016). Additionally, the RRI levels of subjects with BTM were correlated with systolic blood pressure (p = 0.017, r = 0.194). CONCLUSION: In this study, lower RRI were found in subjects with BTM. This may be associated with a decreased vascular resistance and blood viscosity in these subjects.

Hemodiafiltración on-line con autosustitución: valoración de los cambios del flujo de sangre sobre el volumen convectivo y eficacia / On-line haemodiafiltration with auto-substitution: assessment of blood flow changes on convective volume and efficiency

Introducción: La hemodiafiltración on-line (HDF-OL) es actualmente la técnica más efectiva y varios estudios aleatorizados y metaanálisis han visto una reducción de la mortalidad, observándose una asociación en relación directa con el volumen convectivo. El flujo de sangre (Qb) limita el flujo de infusión al 25-33 % y constituye el principal factor limitante para alcanzar un volumen de sustitución óptimo. Con la reciente incorporación de monitores con sistema de autosustitución, el objetivo del estudio fue valorar el efecto de las variaciones del Qb sobre el volumen convectivo y la capacidad depurativa. Material y métodos: Se incluyeron 23 pacientes, 17 varones y 6 mujeres, con una edad media de 65,5 ± 10 años, tiempo de diálisis 292,2 ± 15 min, que se encontraban en programa de HDF-OL con monitor 5008 Cordiax con autosustitución. Cada paciente fue analizado en cinco sesiones en las que solo se varió el Qb (250, 300, 350, 400 y 450 ml/min). En cada sesión se determinaron el volumen de sustitución, el volumen convectivo total y los parámetros de diálisis. Se determinó la concentración de urea (60 Da), creatinina (113 Da), β2-microglobulina (11 800 Da), mioglobina (17 200 Da), prolactina (23 000 Da), α1-microglobulina (33 000 Da) y α1-glicoproteína ácida (40 000 Da) en plasma al inicio y al final de cada sesión para calcular el porcentaje de reducción de estos solutos. Resultados: La presión transmembrana fue inferior con Qb 250 ml/min. Se observó un aumento significativo del volumen convectivo con el incremento del Qb, 23,7, 26,9, 30,2, 32,8 y 35,2 l/sesión a 250, 300, 350, 400 y 450 ml/min, respectivamente (P < 0,001), representando un porcentaje de la sangre total depurada del 33,2, 31,2, 30,2, 28,7 y 27,3 %, respectivamente. Los porcentajes de reducción de urea y creatinina aumentaron progresivamente con el Qb, se observaron ligeras diferencias con la β2-microglobulina y la mioglobina, y no se observaron cambios en las grandes moléculas. Conclusión: Por cada 50 ml/min de aumento del Qb el volumen convectivo aumenta entre 8 y 12 ml/min. El sistema de autosustitución potencia los Qb más bajos en el porcentaje del volumen convectivo respecto a la sangre total depurada. El Qb aumenta la capacidad depurativa de las moléculas pequeñas, favorece la de la β2-microglobulina y la mioglobina, y no influye en moléculas de superior peso molecular (AU)

Introduction: On-line haemodiafiltration (OL-HDF) is currently the most effective technique and several randomised studies and meta-analyses have seen a reduction in mortality and an association directly related with convective volume is observed. Blood flow (Qb) limits the infusion rate to 25-33 % and is the main limiting factor for reaching an optimum substitution volume. With the recent incorporation of monitors with auto-substitution systems, the aim of the study was to assess the effect of Qb variations on convective volume and purifying capacity. Material and Methods: 23 patients, 17 men and 6 women, were included, with an average age of 65.5 ±10 years, time on dialysis 292.2 ± 15 minutes, which were in the OL-HDF programme with the 5008 Cordiax monitor with auto-substitution. Each patient was analysed over 5 sessions in which only the Qb was changed (250, 300, 350, 400 and 450 ml/min). In each session the substitution volume, total convective volume and parameters of dialysis were measured. The concentration of urea (60 Da), creatinine (113 Da), β2-microglobulin (11,800 Da), myoglobin (17,200 Da), prolactin (23,000 Da), α1-microglobulin (33,000 Da) and α1-acid glycoprotein (40,000 Da) in plasma was measured at the start and end of each session in order to calculate the percentage of reduction of these solutes. Results: The trans-membrane pressure was less, with Qb 250 ml/min. A significant increase in convective volume was observed with the increase in Qb, 23.7, 26.9, 30.2, 32.8 and 35.2 l/session to 250, 300, 350, 400 and 450 ml/min, respectively (P < 0.001), representing a percentage of total purified blood of 33.2, 31.2, 30.2, 28.7 and 27.3 % respectively. The percentages of reduction of urea and creatine progressively increased with Qb, slight differences were observed with β2-microglobulin and myoglobin, and no changes were observed in the larger molecules. Conclusion: For each 50 ml/min increase in Qb, the convective volume increased by between 8 and 12 ml/min. The auto-substitution system strengthens the lowest Qbs in the percentage of convective volume with regards to total purified blood. Qb increases the purifying capacity of small molecules, favouring that of β2-microglobulin and myoglobin, and does not influence molecules of a greater molecular weight (AU)

Associations of N-terminal pro-B-type natriuretic peptide with kidney function decline in persons without clinical heart failure in the Heart and Soul Study.

BACKGROUND: Subclinical volume overload in the absence of diagnosed heart failure (HF) may be an underrecognized contributor to kidney function decline in coronary artery disease (CAD) patients. We evaluated associations of circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP), a marker of ventricular stretch, with change in estimated glomerular filtration rate (eGFR). METHODS: We evaluated 535 patients with stable CAD and no history of HF, who were enrolled in the Heart and Soul Study and followed for 5 years. N-terminal pro-B-type natriuretic peptide was measured at baseline. We evaluated the associations of NT-proBNP with change in kidney function over 5 years: (a) annual percent change in eGFR, (b) rapid kidney function loss (> 3% per year for 5 years), and (c) incident eGFR < 60 mL/min per 1.73 m2. In multivariable models, we adjusted for demographics, comorbid conditions, echocardiographic parameters, medications, and baseline kidney function. RESULTS: Among 535 participants, median NT-proBNP was 130.6 (interquartile range 61.8-280.9) pg/mL, and median B-type natriuretic peptide (BNP) was 32.5 (14.4-75.9) pg/mL. Individuals with NT-proBNP levels in the highest quartile (> 280.9 pg/mL) had a greater odds of rapid kidney function loss after full adjustment (odds ratio 2.95; 95% CI 1-8.65; P = .0492). Associations with incident eGFR < 60 mL/min per 1.73 m2 were also significant (adjusted odds ratio 4.23; 95% CI 1.05-16.98; P = .0422). Results were similar when analyzed using BNP as the predictor. CONCLUSIONS: N-terminal pro-B-type natriuretic peptide and BNP are strongly and independently associated with accelerated kidney function loss, even in the absence of clinical HF. These findings suggest that subclinical cardiovascular dysfunction may contribute to elevated kidney disease risk in persons with CAD.

Relationship between serum TSH levels and intrarenal hemodynamic parameters in euthyroid subjects.

OBJECTIVE: Low thyroid function may be associated with a reduced glomerular filtration rate (GFR) calculated on the basis of creatinine metabolism. Thyroid hormone directly affects serum creatinine in muscle and low thyroid function might exert a similar direct effect in the kidney. The goal of the study was to evaluate this possibility by assessment of the inulin-based GFR and to examine the mechanism underlying the reduction of GFR. PATIENTS AND METHODS: Renal and glomerular hemodynamics were assessed by simultaneous measurements of plasma clearance of para-aminohippurate (CPAH) and inulin (Cin) in 26 patients with serum creatinine <1.00 mg/dl and without thyroid disease. All subjects were normotensive with or without antihypertensive treatment and were kept in a sodium-replete state. Renal and glomerular hemodynamics were calculated using Gomez's formulae. RESULTS: Serum TSH, including within the normal range (0.69-4.30 µIU/ml), was positively correlated with vascular resistance at the afferent arteriole (Ra) (r=0.609, P=0.0010), but not at the efferent arteriole (Re). Serum TSH was significantly and negatively correlated with renal plasma flow (RPF), renal blood flow (RBF), and GFR (r=-0.456, P=0.0192; r=-0.438, P=0.0252; r=-0.505, P=0.0086 respectively). In multiple regression analysis, serum TSH was significantly positively associated with Ra after adjustment for age and mean blood pressure. CONCLUSIONS: These findings suggest that low thyroid function, even within the normal range, is associated with reduced RPF, RBF, and GFR, which might be caused by a preferential increase in Ra.

[Comparison of different techniques of hemodialysis vascular access flow evaluation: blood temperature monitoring thermodilution and doppler debimetry]. / Comparaison des mesures des débits d'abords vasculaires pour hémodialyse obtenues par méthode de thermodilution utilisant le module Blood Temperature Monitoring et par débimétrie doppler.

BACKGROUND: Access blood flow measurements are considered useful indicators for thrombosis prevention. It was the purpose of this study to compare measurements of access blood flow by two different techniques: duplex doppler and BTM thermodilution. METHODS: Patients included must be on chronic hemodialysis on arterioveinous vascular access. They must be in a unit fit with hemodialysis generator equipped with BTM tool. The measurements of access blood flow were made during the first hour of the hemodialysis session. A measurement with each technique was performed for each patient. RESULTS: Fifteen patients were included: seven men and eight women, average age 60.8 ± 9.2 years, average weight 76 ± 16 kg, duration on hemodialysis therapy 6.6 ± 6.1 years. Access blood flow was native fistula (14 patients) and a prothetic access (one patient). Average access blood flow was 1088 ± 586 mL/mn (doppler) and 1094 ± 570 mL/mn (BTM). Comparison of access flows obtained by the BTM and doppler techniques showed a strong linear relationship. The average time to perform a measure was six minutes for the doppler technique and five minutes for the BTM technique. No adverse effect was observed in our study. CONCLUSION: Our study shows a strong correlation between the two techniques (doppler and BTM) for the measurement of hemodialysis access blood flow. The BTM access blood flow measurement technique is fast, economic and made during the hemodialysis session by the nurse.

Preparation of 99mTc(CO)3-Carboxymethylthioethyl iminodiacetic acid and evaluation as a potential renal imaging agent.

UNLABELLED: The ligand, carboxymethylthioethyl iminodiacetic acid (CMT-IDA) has a suitable array of donor atoms for coordination with [99mTc(CO)3]+ core, wherein the resultant complex is expected to possess free carboxylic residues contributing towards hydrophilicity of the complex. The aim of the studies was to study the renal clearance of 99mTc(CO)3- labeled CMT-IDA and determine the potential of the complex towards its use as a renal tubular imaging agent. METHODS: CMT-IDA was radiolabeled with the [99mTc(CO)3(H2O)3]+ precursor and was characterized by reverse phase HPLC gradient elution system. Stability, hydrophilicity and plasma protein binding studies were carried out for the complex. Biodistribution studies were carried out in normal male Swiss mice at 10 min.p.i. and 2 h.p.i. The clearance was estimated from the activity observed in the urinary bladder by tying the urethra prior to injection of the complexes under study. Imaging studies were performed with male Swiss mice administered with [99mTc(CO)3(CMT-IDA)]-2 at 30 min. p.i. and blocking studies were carried out by intraperitoneal injection of probenecid 10 min. prior to the injection of the radiotracer. RESULTS: [99mTc(CO)3(CMT-IDA)]-2 could be obtained in > 98% radiochemical purity. The complex showed renal clearance of 71.0� 5.9% ID at 10 min.p.i. which increased to 84.1� 10.6% ID at 2 h.p.i., with no major activity in blood, liver, heart, lungs, stomach and spleen. However, the intestinal uptake was high (10.3� 2.0% ID) at 2 h.p.i. Scintigraphic image of the animal injected with probenecid showed an increase in the activity in kidneys indicating excretion of the [99mTc(CO)3(CMT-IDA)]-2 complex via tubular pathway. CONCLUSION: The complex, [99mTc(CO)3(CMT-IDA)]-2 has shown excellent renal clearance and thereby can be explored further for potential use as an agent towards assessing effective renal plasma flow.

The effects of warm ischaemia time on renal function after laparoscopic partial nephrectomy in patients with normal contralateral kidney.

PURPOSE: To assess the effects of warm ischaemia time (WIT) on renal function after laparoscopic partial nephrectomy (LPN) for renal masses in patients with a normal contralateral kidney. METHODS: From October 2006 to December 2008, 53 patients treated with LPN were enrolled in this prospective study. Effective renal plasma flow (ERPF) was estimated with 99mTc-mercaptoacetyltriglycine renal scintigraphy before the intervention and after 3 and 12 months. Multiple linear regression analysis was used to assess the effects of demographic and operative variables on postoperative renal function. Logistic regression analysis was used to evaluate the associations between the same variables and a ≥20% reduction in postoperative ERPF compared with baseline (defined as significant loss of renal function-LRF). ROC curve analysis was used to identify potential ischaemia time cut-off points. RESULTS: Fifty-one patients were eligible. The mean lesion size was 30 mm, and the mean WIT was 21.9 min. Longer WIT was associated with lower postoperative ERPF values (P < 0.001). A logistic regression model confirmed that longer WITs were significantly associated with ERPF decreases ≥20% (OR 1.454 and 1.741, for each 1-min increase, respectively). ROC analysis identified 25 min as a 'safe' cut-off for WIT (AUC 0.874, P < 0.001). Postoperative ERPF differences between the two groups (WIT ≤25 and >25 min) were significant. CONCLUSIONS: Longer WIT was associated with LRF, as estimated with renal scintigraphy. LRF occurred within 3 months and remains stable until the 12th month after LPN. Every effort should be made to minimise warm ischaemic intervals during LPN, and the limit of 25 min should be not exceeded.

Effects of high blood flow and high pre-dilution replacement fluid rates on small solute clearances in hemofiltration.

BACKGROUND/AIMS: In pre-dilution hemofiltration (HF), solute clearance is less than the HF rate. While the amount of this loss is predictable, it has not been validated in high-volume HF associated with high blood flow rates. METHODS: Using isovolemic pre-dilution HF, we studied small solute clearances using combinations of blood flow (Q(B); 150, 250, 350, 450 ml/min) and replacement fluid (RF) flow (Q(RF); 2, 4, 6 l/h) to determine clearance losses we entitled 'measured efficiency' (E(M)). E(M) was compared to predicted efficiency (E(P)) = (Q(B)/Q(B) + Q(RF)). RESULTS: Pre-dilution produced E(M) values of 61-93%. Increases in Q(B) for any Q(RF) and decreases in Q(RF) for any Q(B) increased E(M) over a wide range of Q(B) and Q(RF). E(P) was equivalent to E(M). CONCLUSION: In high-volume pre-dilution HF, E(P) can be used to determine E(M) across a broad range of Q(B) and Q(RF) values. Higher Q(RF) requires higher Q(B) to minimize the attenuating effects of pre-dilution on clearance.

Cardio-renal syndrome: an entity cardiologists and nephrologists should be dealing with collegially.

Heart failure may lead to acute kidney injury and vice versa. Chronic kidney disease may affect the clinical outcome in terms of cardiovascular morbidity and mortality while chronic heart failure may cause CKD. All these disorders contribute to the composite definition of cardio-renal syndromes. Renal impairment in HF patients has been increasingly recognized as an independent risk factor for morbidity and mortality; however, the most important clinical trials in HF tend to exclude patients with significant renal dysfunction. The mechanisms whereby renal insufficiency worsens the outcome in HF are not known, and several pathways could contribute to the "vicious heart/kidney circle." Traditionally, renal impairment has been attributed to the renal hypoperfusion due to reduced cardiac output and decreased systemic pressure. The hypovolemia leads to sympathetic activity, increased renin-angiotensin-aldosterone pathways and arginine-vasopressin release. All these mechanisms cause fluid and sodium retention, peripheral vasoconstriction and an increased congestion as well as cardiac workload. Therapy addressed to improve renal dysfunction, reduce neurohormonal activation and ameliorate renal blood flow could lead to a reduction in mortality and hospitalization in patients with cardio-renal syndrome.

Cardio-renal syndromes: from foggy bottoms to sunny hills.

"Cardio-renal syndromes" (CRS) are disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The current definition has been expanded into five subtypes whose etymology reflects the primary and secondary pathology, the time-frame and simultaneous cardiac and renal co-dysfunction secondary to systemic disease: CRS type I: acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF-CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV: chronic kidney disease (CKD) leading to heart injury, disease and/or dysfunction. CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. These different subtypes may have a different pathophysiological mechanism and they may represent separate entities in terms of prevention and therapy.

Copeptin, a surrogate marker of vasopressin, is associated with disease severity in autosomal dominant polycystic kidney disease.

BACKGROUND AND OBJECTIVES: Experimental studies suggest a detrimental role for vasopressin in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). However, it is unknown whether endogenous vasopressin concentration is associated with disease severity in patients with ADPKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Plasma copeptin concentration (a marker of endogenous vasopressin levels) was measured in 102 ADPKD patients (diagnosis based on Ravine criteria) by an immunoassay. Plasma and urinary osmolarity were also measured. To assess disease severity, GFR and effective renal blood flow were measured by continuous infusion of 125I-iothalamate and 131I-hippuran, total renal volume by magnetic resonance imaging, and 24-hour urinary albumin excretion by nephelometry. RESULTS: In these ADPKD patients, copeptin was associated with the various markers of disease severity in ADPKD (positively with total renal volume [R=0.47] and albuminuria [R=0.39] and negatively with GFR [R=-0.58] and effective renal blood flow [R=-0.52], all P<0.001). These associations were independent of age, gender, and use of diuretics. Copeptin was furthermore associated with plasma osmolarity (P<0.001) but not with 24-hour urinary volume, 24-hour urinary osmolarity or fractional urea excretion (P=0.7, 0.9, and 0.3, respectively). CONCLUSIONS: On cross-sectional analysis, copeptin is associated with disease severity in ADPKD patients, supporting the results of experimental studies that suggest that vasopressin antagonists have a renoprotective effect in ADPKD and offering a good prospect for clinical studies with these agents.

Electrical forces determine glomerular permeability.

There is ongoing controversy about the mechanisms that determine the characteristics of the glomerular filter. Here, we tested whether flow across the glomerular filter generates extracellular electrical potential differences, which could be an important determinant of glomerular filtration. In micropuncture experiments in Necturus maculosus, we measured a potential difference across the glomerular filtration barrier that was proportional to filtration pressure (-0.045 mV/10 cm H2O). The filtration-dependent potential was generated without temporal delay and was negative within Bowman's space. Perfusion with the cationic polymer protamine abolished the potential difference. We propose a mathematical model that considers the relative contributions of diffusion, convection, and electrophoretic effects on the total flux of albumin across the filter. According to this model, potential differences of -0.02 to -0.05 mV can induce electrophoretic effects that significantly influence the glomerular sieving coefficient of albumin. This model of glomerular filtration has the potential to provide a mechanistic theory, based on experimental data, about the filtration characteristics of the glomerular filtration barrier. It provides a unique approach to the microanatomy of the glomerulus, renal autoregulation, and the pathogenesis of proteinuria.

Prenatal exposure to alcohol reduces nephron number and raises blood pressure in progeny.

Prenatal ethanol exposure is teratogenic, but the effects of ethanol on kidney development and the health of offspring are incompletely understood. Our objective was to investigate the effects of acute ethanol exposure during pregnancy on nephron endowment, mean arterial pressure, and renal function in offspring. We administered ethanol or saline by gavage to pregnant Sprague-Dawley rats on embryonic days 13.5 and 14.5. At 1 month of age, the nephron number was 15% lower and 10% lower in ethanol-exposed males and females, respectively, compared with controls. Mean arterial pressure, measured in conscious animals via indwelling tail-artery catheter, was 10% higher in both ethanol-exposed males and females compared with controls. GFR was 20% higher in ethanol-exposed males but 15% lower in ethanol-exposed females; moreover, males had increased proteinuria compared with controls. Furthermore, embryonic kidneys cultured in the presence of ethanol for 48 hours had 15% fewer ureteric branch points and tips than kidneys cultured in control media. Taken together, these data demonstrate that acute prenatal ethanol exposure reduces the number of nephrons, possibly as a result of inhibited ureteric branching morphogenesis, and that these changes affect adult cardiovascular and renal function.

Angiotensin II type 1 receptor gene polymorphism could influence renoprotective response to losartan treatment in type 1 diabetic patients with high urinary albumin excretion rate.

BACKGROUND/AIM: Diabetic nephropathy (DN) is a clinical syndrome characterized by persistent albuminuria, increasing arterial blood pressure and progressive decline in glomerular filtration rate (GFR). When persistent albuminuria is established, antihypertensive treatment becomes most important factor in slowing the progression of diabetic glomerulopathy. The aim of this study was to examine if renoprotective response to a short-term losartan therapy depends on 1166 A/C gene polymorphism for its target receptor. METHOD: The study included 35 patients with diabetes mellitus type 1 and persistently high urinary albumin excretion rate (UAE: > 30 mg/24 h), genotyped for the 1166 A/C gene polymorphism for the angiotensin II type 1 receptor (AT1R). The participants were segregated into 3 genotype groups according to combinations of A or C allele: AA (16%), AC (15%) and CC (11%). The patients received losartan 50 mg daily for 4 weeks, following 100 mg daily for another 8 weeks. At baseline and after 12 weeks of the treatment period UAE, blood pressure, GFR and filtration fraction (FF) were determined. RESULTS: After 12 weeks of the treatment with losartan, albuminuria was reduced from baseline by 9% [95% confidence interval (CI): 1-17, p = 0.039] in the AA genotype, and by 11% (95% CI: 6-17, p = 0.0001) in the AC genotype. Losartan treatment reduced albuminuria in the CC group by 5% (95% CI: -13-22, p = 0.47). Glomerular filtration rate remained unchanged in all genotype groups. Filtration fraction was significantly reduced from baseline by 0.018 +/- 0.024 (p = 0.012) only in the AC genotype. In the AA genotype, FF was reduced from baseline by 0.017 +/- 0.03 (p = 0.052), and in the CC genotype by 0.01 +/- 0.008 (p = 0.092). In the AA group, systolic blood pressure declined from 136 +/- 24 mmHg at baseline, to an average of 121 +/- 18 mmHg at the end of the study (p = 0.001). The AC group achived reduction from 131 +/- 10 mmHg at baseline to 115 +/- 7 mmHg (p = 0.001) during the investigation period. In the AA genotype group losartan reduced diastolic blood pressure from 86 +/- 13 mmHg at baseline to 78 +/- 8 mmHg (p = 0.004), and in the AC genotype from 88 +/- 5 mmHg at baseline to 11.7 +/- 5.6 mmHg during the investigation period (p = 0.001). In the CC genotype diastolic blood pressure reduction remained nonsignificant (p = 0.066). CONCLUSION: The results of our small sample size study provide the evidence that 1166 A/C AT1R polymorphism could be associated with the renoprotective response to losartan therapy.

Developmental effect of antenatal exposure to betamethasone on renal angiotensin II activity in the young adult sheep.

Antenatal corticosteroids may have long-term effects on renal development which have not been clearly defined. Our objective was to compare the responses to intrarenal infusions of ANG II in two groups of year-old, male sheep: one group exposed to a clinically relevant dose of betamethasone before birth and one not exposed. We wished to test the hypothesis that antenatal steroid exposure would enhance renal responses to ANG II in adult life. Six pairs of male sheep underwent unilateral nephrectomy and renal artery catheter placement. The sheep were infused for 24 h with ANG II or with ANG II accompanied by blockade of the angiotensin type 1 (AT(1)) or type 2 (AT(2)) receptor. Baseline mean arterial blood pressure among betamethasone-exposed sheep was higher than in control animals (85.8 +/- 2.2 and 78.3 +/- 1.0 mmHg, respectively, P = 0.003). Intrarenal infusion of ANG II did not increase systemic blood pressure (P >/= 0.05) but significantly decreased effective renal plasma flow and increased renal artery resistance (P < 0.05). The decrease in flow and increase in resistance were significantly greater in betamethasone- compared with vehicle-exposed sheep (betamethasone P < 0.05, vehicle P >/= 0.05). This effect appeared to be mediated by a heightened sensitivity to the AT(1) receptor among betamethasone-exposed sheep. Sodium excretion initially decreased in both groups during ANG II infusion; however, a rebound was observed after 24 h. AT(1) blockade was followed by a significant rebound after 24 h in both groups. AT(2) blockade blunted the 24-h rebound effect among the vehicle-exposed sheep compared with the betamethasone-exposed sheep. In conclusion, antenatal corticosteroid exposure appears to modify renal responsiveness to ANG II by increasing AT(1)- and decreasing AT(2) receptor-mediated actions particularly as related to renal blood flow and sodium excretion.

The impact of experimental hypoperfusion on subsequent kidney function.

OBJECTIVE: To investigate the short- and medium-term renal hemodynamic and functional responses to both short and sustained hypoperfusion. SUBJECTS: Eleven Merinos ewes. SETTING: Animal laboratory of the University Physiology Institute. DESIGN: Prospective observational study. INTERVENTIONS: Studies were performed in conscious sheep after unilateral nephrectomy with a vascular occluder and flow probe implanted on the remaining renal artery. In five sheep, renal blood flow (RBF) was reduced by 25, 50 and 75%, respectively, by acute vascular occlusion for 30 min at weekly intervals. In another six sheep, RBF was reduced by 80% for 2 h. MEASUREMENTS AND RESULTS: After 25, 50 or 75% renal hypoperfusion for 30 min, there was no associated extended loss of renal function. During 2 h of 80% hypoperfusion, urine output decreased from 80 to 17 ml, and creatinine clearance from 32 to 3 ml/min, whereas plasma creatinine increased from 103 to 132 mumol/l, and fractional excretion of sodium and urea increased. Release of occlusion induced brief hyperemia before all measured variables returned to normal within 8 h and remained normal for the following 72 h. At autopsy, the kidneys were histopathologically normal. CONCLUSIONS: Various degrees of renal hypoperfusion for 30 min did not induce prolonged changes in renal function or blood flow. Even with sustained severe hypoperfusion, there was rapid recovery to baseline function and flow. Unlike total ischemia, severe hypoperfusion alone is insufficient to induce subsequent persistent AKI.

Renal functional effects of simultaneous bilateral single-tract percutaneous access in pigs.

OBJECTIVE: To present our findings of simultaneous bilateral percutaneous nephrolithotomy (sbPCNL) on bilateral renal haemodynamic and excretory function in an in vivo pig model, as despite sbPCNL being a treatment strategy for patients with bilateral renal stones, the functional response of both kidneys to such a procedure is unknown. MATERIALS AND METHODS: Nine anaesthetized female pigs ( approximately 70 kg) had a single-tract PCNL procedure in the left kidney and then the right kidney in one session (sbPCNL). Percutaneous access was achieved by a 30 F balloon dilator system. Bilateral renal function was measured before, 1.5 and 4.5 h after sbPCNL and included glomerular filtration rate (GFR), effective renal plasma flow (RPF), renal extraction of para-aminohippurate (EPAH, a measure of the efficiency of tubular organic anion transport), urine flow (UV), absolute sodium excretion (UNaV) and fractional sodium excretion (FENa). RESULTS: Both kidneys had similar baseline haemodynamic and excretory function, and showed comparable changes after sbPCNL. Bilateral GFR and RPF decreased by approximately 35% at 1.5 and 4.5 h after sbPCNL; EPAH was reduced to a similar degree in both kidneys at 1.5 h after sbPCNL and remained depressed throughout the observation period; bilateral UV and UNaV progressively decreased by approximately 30% and approximately 60% at 1.5 and 4.5 h after sbPCNL, respectively; bilateral FENa did not significantly change at 1.5 h after sbPCNL but decreased significantly by approximately 50% at 4.5 h. CONCLUSIONS: Both kidneys responded in a similar fashion after sbPCNL, with declines in haemodynamic and excretory function. These bilateral functional responses were comparable to those previously reported after unilateral PCNL, and help to reduce concerns that PCNL of both kidneys in one session could lead to greater functional complications, at least acutely.