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1.
Nephrology (Carlton) ; 25(4): 290-297, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31429150

ABSTRACT

AIM: Increased plasma uric acid (PUA) concentrations are associated with chronic kidney disease in type 2 diabetes (T2D) patients. The mechanisms involved remain unclear. We investigated the relation between PUA and (intra)renal haemodynamics in T2D patients without overt kidney disease. METHODS: Eighty-eight white men and women with T2D were included (age 64 (58-68) years; body mass index 30.9 (28.3-33.6) kg/m2 ; glycated haemoglobin 7.1 (6.8-7.6)%). Plasma UA and fractional excretion of UA were measured, while glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were assessed by inulin and PAH-clearance techniques, respectively. Effective renal vascular resistance was calculated (ERVR). Renal afferent and efferent arteriolar resistances and glomerular hydrostatic pressure were estimated. Relationships between PUA and fractional excretion of UA and (intra)renal haemodynamic parameters were evaluated by multivariable linear regression analyses. RESULTS: Plasma UA concentrations were at the higher end of the normal range in most participants: 342 ± 68 µmol/L or 5.7 ± 1.1 mg/dL (mean ± SD). In multivariable analyses, PUA concentrations were negatively associated with GFR (r = -0.471; P = 0.001), ERPF (r = -0.436; P = 0.003) and glomerular hydrostatic pressure (r = -0.427; P = 0.003). In contrast, PUA concentrations had a positive correlation with ERVR (r = 0.474; P = 0.001), but not with efferent vascular resistance. Fractional excretion of UA was not related to renal haemodynamics. CONCLUSION: Plasma UA was negatively associated to GFR, ERPF but positively related to ERVR in T2D patients without overt renal impairment. Plasma UA-related increase in ERVR may be related to increased arterial afferent tone, which may put the kidney at risk for renal damage through ischaemia.


Subject(s)
Diabetes Mellitus, Type 2/blood , Glomerular Filtration Rate/physiology , Kidney/blood supply , Renal Insufficiency, Chronic/blood , Renal Plasma Flow, Effective/physiology , Uric Acid/blood , Vascular Resistance , Aged , Biomarkers/blood , Body Mass Index , Cross-Sectional Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/physiopathology , Female , Humans , Male , Middle Aged , Renal Insufficiency, Chronic/etiology , Renal Insufficiency, Chronic/physiopathology
2.
Transplant Proc ; 51(5): 1353-1356, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31056247

ABSTRACT

INTRODUCTION: Many studies have suggested that post-transplantation renal allograft function is associated with long-term allograft outcomes. However, accurate examination through non-invasive methods remains rare. The aim of the present study is to assess the association between 99mTc mercaptoacetyltriglycine (MAG3) effective renal plasma flow (ERPF) and first-year post-transplantation renal allograft function. METHODS: We conducted a retrospective cohort study at our center between January 2011 and December 2016. Kidney transplant recipients without an ERPF examination within 14 days post-transplantation, or those with less than 1 year of follow-up were excluded. Eligible cases were divided into 3 groups according to first-year eGFR <45, 45 < eGFR <60, eGFR >60. The Kruskal-Wallis test and χ2 were used for comparisons between continuous and categorical variables. RESULTS: A total of 123 patients were analyzed. Each group received 41 patients. The baseline characteristics were comparable in the 3 groups, except for repeated transplantation and delayed graft function. The results of the ERPF median (interquartile range) for the 3 groups were 193 (140.0-244.5) in the eGFR < 45 group, 236 (182.5-301.0) in the 45 < eGFR < 60 group, and 294 (202.5-384.5) in the eGFR > 60 group (P < .001). The receiver operating characteristic analysis showed that a cutoff ERPF value of >276 exhibited the best sensitivity (65.85%) and specificity (75.61%) for predicting first-year eGFR > 60 mL/min/1.73 m2, with an area under the receiver operating characteristic curve of .712, P < .0001. CONCLUSION: Our findings suggest that an ERPF value of more than 276 is likely to be associated with a favorable first-year renal graft outcome after transplantation. The 99mTc MAG3 ERPF may be a non-invasive alternative to sequential protocol biopsies.


Subject(s)
Graft Survival/physiology , Kidney Transplantation , Renal Plasma Flow, Effective/physiology , Technetium Tc 99m Mertiatide/blood , Adult , Allografts , Cohort Studies , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Transplantation, Homologous
3.
Diabetes ; 66(7): 1939-1949, 2017 07.
Article in English | MEDLINE | ID: mdl-28408434

ABSTRACT

Higher plasma uric acid (PUA) levels are associated with lower glomerular filtration rate (GFR) and higher blood pressure (BP) in patients with type 1 diabetes (T1D). Our aim was to determine the impact of PUA lowering on renal and vascular function in patients with uncomplicated T1D. T1D patients (n = 49) were studied under euglycemic and hyperglycemic conditions at baseline and after PUA lowering with febuxostat (FBX) for 8 weeks. Healthy control subjects were studied under normoglycemic conditions (n = 24). PUA, GFR (inulin), effective renal plasma flow (para-aminohippurate), BP, and hemodynamic responses to an infusion of angiotensin II (assessment of intrarenal renin-angiotensin-aldosterone system [RAAS]) were measured before and after FBX treatment. Arterial stiffness, flow-mediated dilation (FMD), nitroglycerin-mediated dilation (GMD), urinary nitric oxide (NO), and inflammatory markers were measured before and after FBX treatment. Gomez equations were used to estimate arteriolar afferent resistance, efferent resistance (RE), and glomerular hydrostatic pressure (PGLO). FBX had a modest systolic BP-lowering effect in T1D patients (112 ± 10 to 109 ± 9 mmHg, P = 0.049) without impacting arterial stiffness, FMD, GMD, or NO. FBX enhanced the filtration fraction response to hyperglycemia in T1D patients through larger increases in RE, PGLO, and interleukin-18 but without impacting the RAAS. FBX lowered systolic BP and modulated the renal RE responses to hyperglycemia but without impacting the RAAS or NO levels, suggesting that PUA may augment other hemodynamic or inflammatory mechanisms that control the renal response to hyperglycemia at the efferent arteriole. Ongoing outcome trials will determine cardiorenal outcomes of PUA lowering in patients with T1D.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Febuxostat/therapeutic use , Glomerular Filtration Rate/physiology , Gout Suppressants/therapeutic use , Hyperglycemia/metabolism , Renal Plasma Flow, Effective/physiology , Uric Acid/blood , Adult , Angiotensin II/pharmacology , Blood Pressure , Case-Control Studies , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 1/physiopathology , Female , Glomerular Filtration Rate/drug effects , Humans , Hyperglycemia/physiopathology , Interleukin-18/metabolism , Linear Models , Male , Nitric Oxide/urine , Nitroglycerin/pharmacology , Renal Plasma Flow, Effective/drug effects , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/physiology , Vascular Stiffness , Vasoconstrictor Agents/pharmacology , Vasodilation/drug effects , Vasodilation/physiology , Vasodilator Agents/pharmacology , Young Adult
4.
Beijing Da Xue Xue Bao Yi Xue Ban ; 49(1): 158-63, 2017 02 18.
Article in Chinese | MEDLINE | ID: mdl-28203024

ABSTRACT

OBJECTIVE: To investigate the significance of filtration fraction (FF) and renal artery stenting in the treatment of atherosclerotic renal artery stenosis. METHODS: In the study, 42 cases of renal artery stenosis were treated with 52 renal artery stent implantation. Percutaneous transluminal renal angioplasty and stent (PTRAS) of the patients' health side kidney, ipsilateral kidney (renal) glomerular filtration rate (GFR), renal effective renal plasma flow effective renal plasma flow (ERPF), kidney filtration fraction changes of preoperative and postoperative serum creatinine (SCR) and the changes in the patients with blood pressure (SBP) and the changes after taking antihypertensive drugs were observed and analyzed. RESULTS: The 52 cases of renal artery stent implantation were all successful. Preoperative ipsilateral GFR was significantly lower than that of normal side (t=-3.989, P=0.000); preoperative ipsilateral ERPF was significantly lower than the contralateral side (t=-4.926, P=0.000). On both sides, the overall FF values were equal (t=1.273, P=0.207). Postoperative ipsilateral renal GFR was increased, but there was no statistical difference (t=-1.411, P=0.164). Postoperative ipsilateral renal ERPF was increased significantly (t=-4.954, P=0.000), and FF lower (closer to the normal value (t=3.274, P=0.002). Postoperative side GFR was significantly reduced (t=2.569, P=0.000), the contralateral ERPF was significantly reduced (t=3.889, P=0.001), and FF had no significant change (t=-0.758, P=0.454). Postoperative side GFR was lower than that of the contralateral (t=-3.283, P=0.002) and postoperative side ERPF was still lower than that of the contralateral (t=-3.351, P=0.001), but on both sides, the FF values were equal (t=-0.361, P=0.719). Preoperative FF was relatively normal in the patients with kidney, and the postoperative FF value change was small (t=0.799, P=0.430); preoperative FF was significantly higher in the patients with kidney, and the postoperative FF value was lower than the preoperative (normal value, t=5.299, P=0.000). Postoperative overall serum creatinine was significantly decreased (t=2.505, P=0.016); but for the patients with unilateral renal artery stenosis, the changes in serum creatinine had no statistical difference (t=1.228, P=0.299); and for the patients with bilateral renal artery stenosis and serum creatinine compared with the preoperative, the changes were decreased significantly (t=2.518, P=0.030); postoperative blood pressure (SBP) was significantly decreased compared with that before operation (t=8.945, P=0.000); antihypertensive drugs taken were decreased significantly compared with the preoperative (t=5.280, P=0.000). CONCLUSION: For the patients with renal artery stenosis, FF is a useful index to understand the pathophysiological process of renal ischemia. Whether preoperative FF is significantly increased or FF is relatively normal, should be regarded as the indications of renal artery stent implantation.


Subject(s)
Atherosclerosis/surgery , Glomerular Filtration Rate/physiology , Hypertension, Renovascular/surgery , Recovery of Function/physiology , Renal Artery Obstruction/surgery , Renal Artery/surgery , Renal Plasma Flow, Effective/physiology , Angioplasty/statistics & numerical data , Antihypertensive Agents/therapeutic use , Biomarkers/blood , Blood Vessel Prosthesis Implantation/statistics & numerical data , Creatinine/blood , Creatinine/metabolism , Female , Humans , Hypertension, Renovascular/drug therapy , Hypertension, Renovascular/etiology , Ischemia/etiology , Ischemia/physiopathology , Ischemia/surgery , Kidney/blood supply , Kidney/physiopathology , Male , Reference Values , Renal Artery Obstruction/complications , Stents/statistics & numerical data
5.
Nefrología (Madr.) ; 35(6): 533-538, nov.-dic. 2015. tab
Article in Spanish | IBECS | ID: ibc-145697

ABSTRACT

Introducción: En la hemodiafiltración en línea posdilucional (HDFOL) la única recomendación acerca del líquido de diálisis (LD) hace referencia a su pureza. No se ha definido si usar flujos de baño (Qd) elevados tiene alguna utilidad para aumentar el Kt o el volumen de ultrafiltración-infusión (VI). Objetivo: Estudiar cómo influye el Qd en el Kt y en el VI en la HDFOL. Material y métodos: Estudio cruzado prospectivo. Se incluyó a 37 pacientes a los que se les realizaron 6 sesiones de HDFOL con cada Qd: 500, 600 y 700ml/min. Veintiún pacientes se dializaron en monitor 5008® y 17 con AK-200®. Los dializadores utilizados fueron: 20 con FX800® y 17 con Polyflux-210®. El resto de los parámetros se mantuvieron constantes. Se recogieron del monitor: flujo efectivo de sangre, tiempo efectivo de diálisis, Kt final y VI. Resultados: Encontramos que usando un Qd=600 o 700ml/min, el Kt aumentó un 1,7% respecto al uso de Qd=500ml/min. Las diferencias de VI no fueron significativas. Aumentar el Qd de 500ml/min a 600 y 700ml/min aumenta el consumo de LD un 20 y un 40%, respectivamente. Conclusiones: En la HDFOL con los monitores y dializadores utilizados no son útiles los Qd superiores a 500ml/min para aumentar la eficacia del Kt ni el VI, por lo que su utilización implica un despilfarro de un recurso como el agua, tan importante tanto desde el punto de vista ecológico como económico (AU)


Introduction: In post-dilution online hemodiafiltration (OL-HDF), the only recommendation concerning the dialysate, or dialysis fluid, refers to its purity. No study has yet determined whether using a high dialysate flow (Qd) is useful for increasing Kt or ultrafiltration-infusion volume. Objective: Study the influence of Qd on Kt and on infusion volume in OL-HDF. Material and methods: This was a prospective crossover study. There were 37 patients to whom 6 sessions of OL-HDF were administered at 3 different Qds: 500, 600 and 700ml/min. A 5008® monitor was used for the dialysis in 21 patients, while an AK-200® was used in 17. The dialysers used were: 20 with FX 800® and 17 with Polyflux-210®. The rest of the parameters were kept constant. Monitor data collected were effective blood flow, effective dialysis time, final Kt and infused volume. Results: We found that using a Qd of 600 or 700ml/min increased Kt by 1.7% compared to using a Qd of 500ml/min. Differences in infusion volume were not significant. Increasing Qd from 500ml/min to 600 and 700ml/min increased dialysate consumption by 20% and 40%, respectively. Conclusions: With the monitors and dialysers currently used in OL-HDF, a Qd higher than 500ml/min is unhelpful for increasing the efficacy of Kt or infusion volume. Consequently, using a high Qd wastes water, a truly important resource both from the ecological and economic points of view (AU)


Subject(s)
Humans , Hemodiafiltration/methods , Ultrafiltration/methods , Hemodialysis Solutions/pharmacology , Renal Insufficiency, Chronic/therapy , Prospective Studies , Renal Plasma Flow, Effective/physiology
7.
Nephrol Dial Transplant ; 22(6): 1738-42, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17384415

ABSTRACT

BACKGROUND: There is increasing evidence that paediatric kidneys transplanted to adults have good graft function and satisfactory graft survival. The relationship between size increment and functional potential of paediatric kidneys following transplantation is not defined in detail. We therefore initiated a prospective single centre study, comprising detailed and repeated measurements of size and function of paediatric kidneys transplanted to adults. METHODS: Nineteen adults receiving a first kidney transplant from a paediatric donor (<10 years of age) were included in the study. All patients were followed for 12 months post-transplant. Increment in size and function of the transplanted kidneys were assessed by ultrasound, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). All tests were performed during the first week, post-transplant and subsequently repeated at 1, 3, 6 and 12 months. RESULTS: Kidney volume increased 2.6-fold at 12 months (P < 0.001). GFR and ERPF showed a slightly more moderate increase, 1.8-fold and 1.6-fold, respectively. Patient and graft survival at 1 year were 100% and serum creatinine was 91 micromol/l (66-169). CONCLUSION: The study indicates that paediatric kidneys for transplantation may be considered as excellent rather than being referred to as suboptimal for adult recipients, at least the first year after transplantation.


Subject(s)
Kidney Transplantation/physiology , Kidney/anatomy & histology , Kidney/physiology , Adult , Aged , Child , Child, Preschool , Female , Glomerular Filtration Rate/physiology , Graft Survival/physiology , Humans , Infant , Kidney/diagnostic imaging , Kidney/growth & development , Kidney Transplantation/diagnostic imaging , Male , Middle Aged , Organ Size/physiology , Prospective Studies , Renal Plasma Flow, Effective/physiology , Ultrasonography
8.
Eur Heart J ; 28(2): 166-71, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17158825

ABSTRACT

AIMS: Anaemia is prevalent in the chronic heart failure (CHF) population, but its cause is often unknown. The present study aims to investigate the relation between anaemia, renal perfusion, erythropoietin production, and fluid retention in CHF patients. METHODS AND RESULTS: We studied 97 patients with CHF, of which 15 had anaemia (Hb<13.0 g/dL in men and Hb<12.0 g/dL in women), without haematinic deficiencies. Glomerular filtration rate (GFR) and extracellular volume (ECV) were measured as the clearance and the distribution volume of constantly infused 125I-iothalamate, respectively. Effective renal plasma flow (ERPF) was determined as the clearance of 131I-hippuran. Anaemic CHF patients displayed significantly reduced GFR (P=0.002), ERPF (P=0.005) and EPO production (P=0.001), and an elevated ECV (P=0.015). Multivariable analysis demonstrated that lower GFR (P=0.003), lower ERPF (P=0.004), lower EPO production (P=0.006), and a higher ECV (P=0.001) were significant independent predictors of lower haemoglobin levels. CONCLUSION: Anaemia in CHF is not only independently associated with impaired renal perfusion and blunted EPO production, but to fluid retention as well.


Subject(s)
Anemia/etiology , Erythropoietin/metabolism , Heart Failure/complications , Kidney Diseases/complications , Water-Electrolyte Imbalance/complications , Adolescent , Adult , Aged , Aged, 80 and over , Cell Size , Chronic Disease , Female , Heart Failure/metabolism , Hemoglobins/metabolism , Humans , Kidney Diseases/metabolism , Male , Middle Aged , Renal Circulation/physiology , Renal Plasma Flow, Effective/physiology
9.
Clin Hemorheol Microcirc ; 34(3): 391-9, 2006.
Article in English | MEDLINE | ID: mdl-16614463

ABSTRACT

The present study was designed to investigate whether L-ascorbic acid (AA) supplementation could prevent changes in renal hemodynamics in diabetic rats or not. The experiments were carried out in 48 male Sprague-Dawley rats. Diabetes mellitus was induced in rats by intravenous injection with streptozotocin (STZ) (55 mg/kg.bw), while the control rats were received citrate buffer alone. The renal hemodynamics was examined after the supplementation of AA (1 mg/l) for 8 and 16 weeks. The results demonstrated that AA could retard the increase (p<0.05) in renal vascular resistance (RVR) significantly compared with diabetic rats (STZ). Besides, at week 16, the effective renal plasma flow (ERPF) and the glomerular filtration rate (GFR) of STZ-AA were significantly higher than those of STZ (p<0.05). In conclusion, supplementation of AA was able to ameliorate the renal dysfunction in STZ-induced diabetic rats by decrease in RVR concomitant with an increase in both ERPF and GFR.


Subject(s)
Ascorbic Acid/pharmacology , Diabetes Mellitus, Experimental/physiopathology , Diabetes Mellitus, Type 1/physiopathology , Glomerular Filtration Rate/drug effects , Renal Plasma Flow, Effective/drug effects , Vascular Resistance/drug effects , Animals , Diabetes Mellitus, Type 1/chemically induced , Glomerular Filtration Rate/physiology , Male , Rats , Rats, Sprague-Dawley , Renal Plasma Flow, Effective/physiology , Streptozocin , Vascular Resistance/physiology
10.
J Chromatogr B Analyt Technol Biomed Life Sci ; 826(1-2): 267-72, 2005 Nov 05.
Article in English | MEDLINE | ID: mdl-16169291

ABSTRACT

A simple high-performance liquid chromatographic (HPLC) method was developed for the simultaneous determination of iohexol, iothalamate, p-aminohippuric acid (PAH) and n-acetyl-p-aminohippuric acid (n-acetyl-PAH) in human plasma and urine. A C(18) column at a flow rate of 1 ml/min with an aqueous mobile phase of trifluoroacetic acid (0.1% TFA in deionized water (pH 2.2), v/v) and methanol gradient was used for component separation. The plasma and urine assay demonstrated linearity from 10 to 50 microg/ml for iohexol and iothalamate, 5 to 40 microg/ml for PAH and 2.5 to 40 microg/ml for n-acetyl-PAH. The HPLC plasma and urine results obtained for PAH were used to calculate the subject kidney effective renal plasma flow (ERPF) and the iohexol results were used to calculate the subject kidney glomerular filtration rate (GFR). The HPLC results for PAH were then compared to an alternative colorimetric method for analyzing PAH to determine if subject metabolism (acetylation) of PAH affected the ERPF results obtained using the colorimetric method, the subsequent ERPF/GFR ratio and clinical impression of subject patient kidney function. The method was utilized in several different clinical studies evaluating the effect of kidney function from medications (phase IV evaluations) marketed for patients with cardiovascular disease.


Subject(s)
Aminohippuric Acids/analysis , Glomerular Filtration Rate/physiology , Iohexol/analysis , Iothalamic Acid/analysis , Renal Plasma Flow, Effective/physiology , p-Aminohippuric Acid/analysis , Aminohippuric Acids/blood , Aminohippuric Acids/urine , Chromatography, High Pressure Liquid/methods , Colorimetry/methods , Humans , Reproducibility of Results , Sensitivity and Specificity , Ultraviolet Rays , p-Aminohippuric Acid/blood , p-Aminohippuric Acid/urine
11.
Pediatr Nephrol ; 20(1): 46-51, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15503170

ABSTRACT

We evaluated the renal hemodynamics and the urine protein excretion rates of 73 children with Henoch-Schonlein nephritis (HSN). In 40 children we also performed a renal biopsy. The glomerular filtration rate (GFR) and effective renal plasma flow were determined by the clearances of inulin and para-aminohippurate during water diuresis. Urine albumin and IgG excretion were assessed in short-term timed samples. The mean GFR at the first examination was reduced in the HSN patients and most reduced in those with nephrotic proteinuria. There was an inverse correlation between the GFR at the first examination and the amount of albuminuria and urinary IgG excretion. Among the 40 patients with some degree of proteinuria who underwent a renal biopsy, 9 of 13 patients with mild to moderate proteinuria had severe morphological changes. GFR correlated inversely and fractional albumin and IgG excretion directly with the severity of the pathological findings on the biopsy, and with segmental and global sclerosis, the grade of mesangial proliferation, and interstitial inflammation. In conclusion, GFR is moderately reduced early in HSN and more reduced in patients with more proteinuria and in those with more advanced morphological changes. Moreover, even mild to moderate proteinuria may indicate severe morphological changes, which increase the indications for early renal biopsy in these patients.


Subject(s)
IgA Vasculitis/physiopathology , Kidney/pathology , Adolescent , Biopsy , Child , Child, Preschool , Female , Glomerular Filtration Rate/physiology , Humans , IgA Vasculitis/complications , IgA Vasculitis/pathology , Male , Proteinuria/etiology , Proteinuria/physiopathology , Renal Plasma Flow, Effective/physiology , Urodynamics/physiology
12.
J Cardiovasc Pharmacol ; 44(5): 571-6, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15505494

ABSTRACT

BACKGROUND: We previously showed that the renal vasodilator response to a D1-like receptor agonist is blunted in conscious SHR compared with WKY rats. The mechanism of this impaired dopaminergic responsiveness in SHR is unclear. An altered balance between the renin-angiotensin-aldosterone system (RAAS) and the dopaminergic system may be involved. To determine the interaction between the RAAS and the dopaminergic system in the blunted D1-like responsiveness in SHR, we studied the renal vasodilator response to the D1-like receptor agonist fenoldopam before and after 7 days of pretreatment with the AT1-receptor antagonist (AT1-A) L158,809 in conscious SHR and WKY rats. METHODS: Effective renal plasma flow (ERPF) was measured by the clearance of I-hippuran. Mean arterial pressure (MAP) was measured via an intraarterial catheter. RESULTS: Without pretreatment, MAP was reduced to comparable degrees by fenoldopam in WKY (-7 +/- 4%, ns) and SHR (-6 +/- 1%, P < 0.05). However, ERPF was significantly more increased (P < 0.006) by fenoldopam in WKY (+26 +/- 2%, P < 0.0001) than in SHR (+2 +/- 2%, ns). AT1-A treatment reduced MAP and increased ERPF and glomerular filtration rate significantly in both strains. Pretreatment with AT1-A significantly potentiated the fenoldopam-induced rise in ERPF in SHR, but not in WKY, without affecting the blood pressure responses in either strain. As a result, during pretreatment with an AT1-A, the rise in ERPF by fenoldopam was similar in both strains (SHR +25 +/- 2%, P < 0.0001; WKY +33 +/- 2%, P < 0.0001). CONCLUSIONS: These results suggest that the RAAS accounts for the blunted renal vasodilator response to a D1-like receptor agonist in SHR. A dysbalance between the dopaminergic system and the RAAS may be involved in the abnormal renal hemodynamic regulation in SHR.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/pharmacology , Kidney/blood supply , Kidney/physiopathology , Receptors, Dopamine D1/drug effects , Vasodilation/drug effects , Animals , Blood Pressure/drug effects , Fenoldopam/pharmacology , Glomerular Filtration Rate/drug effects , Glomerular Filtration Rate/physiology , Imidazoles/pharmacology , Kidney/drug effects , Kidney Function Tests , Male , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Renal Plasma Flow, Effective/drug effects , Renal Plasma Flow, Effective/physiology , Species Specificity , Tetrazoles/pharmacology , Time Factors , Vascular Resistance/drug effects , Vascular Resistance/physiology
13.
J Am Soc Nephrol ; 14(4): 881-7, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12660322

ABSTRACT

In the general population, renal function linearly declines with age; hypertension may accelerate this decline. Because concentric left ventricular (LV) hypertrophy is a strong marker of the severity of hypertension, the influence of LV geometry on the age-associated decline in renal function was assessed in 195 normotensive subjects and 645 patients with never-treated essential hypertension with an average duration of 30 mo. According to LV mass and relative wall thickness, hypertensive patients were divided into normal LV (NL, 48%), concentric remodeling (CR, 19%), and concentric (CH, 22%) and eccentric (EH, 11%) hypertrophy. GFR and effective renal plasma flow (ERPF) were estimated by isotopic clearance technique. GFR and ERPF were inversely correlated with age in normotensive and hypertensive subjects, and no marked influence of the BP level or the presence of LV hypertrophy was detected. However, the slope of the regression line of GFR versus age was accentuated (P < 0.01) in patients with CH or CR (slope values of -0.95 +/- 0.11, -0.86 +/- 0.14 ml/min per yr, respectively) when compared with patients with EH or NL (slope values of -0.58 +/- 0.16 and -0.58 +/- 0.08 ml/min per yr, respectively). No such results were obtained when creatinine clearance was considered. Urinary albumin excretion was higher in patients with concentric or eccentric LV hypertrophy than in patients with concentric LV remodeling or normal LV. These results demonstrate that in never-treated essential hypertension, the age-associated decline in GFR is markedly influenced by the concentric pattern of LV response to hypertension rather than the level of BP and/or the presence of LV hypertrophy.


Subject(s)
Hypertension/physiopathology , Hypertrophy, Left Ventricular/physiopathology , Kidney Diseases/physiopathology , Kidney/physiology , Ventricular Remodeling/physiology , Adolescent , Adult , Aged , Aging/physiology , Anatomy, Cross-Sectional , Echocardiography , Female , Glomerular Filtration Rate/physiology , Humans , Hypertension/complications , Hypertrophy, Left Ventricular/diagnostic imaging , Hypertrophy, Left Ventricular/etiology , Kidney Diseases/etiology , Male , Middle Aged , Renal Plasma Flow, Effective/physiology , Severity of Illness Index
14.
Scand J Gastroenterol ; 37(11): 1321-7, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12465732

ABSTRACT

BACKGROUND: Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in healthy humans can be induced by amino acid stimulation. The rise in GFR from baseline to maximum is referred to as the renal functional reserve (RFR). Recently, we showed that the RFR is preserved in patients with compensated cirrhosis despite impaired renal function. In the present study, we evaluated RFR in decompensated cirrhotics with ascites. METHODS: Steady-state inulin- and para-aminohippurate (PAH) clearances were performed at rest and during amino acid infusion in 22 patients with decompensated liver cirrhosis and ascites. RESULTS: Baseline GFR and ERPF (means +95% confidence intervals) were: GFR 25.2 (21.1-29.2) ml min(-1), ERPF 266.6 (229.7-303.5). Amino acid infusion significantly increased GFR by 67% (38.3-95.8) to 34.6 (29.2-40.0) ml min(-1) (means + (95% confidence intervals), P < 0.001) and ERPF by 29% (11.9-46.3) to 326.3 (274.1-378.5) ml min(-1) (P = 0.002). Renal vascular resistance dropped by 13.4% (3.3-23.5) from 29.4 (24.8-33.9) mmHg ml(-1) min(-1) to 26.4 (22.0-30.7) mmHg ml(-1) min(-1) (P = 0.036). The improved kidney function was accompanied by a decrease in systemic aldosterone levels (P < 0.05). CONCLUSION: In patients with liver cirrhosis and ascites, amino acid infusion improves kidney function. Trials are warranted to test the long-term effects of amino acid infusions in patients with hepatorenal syndrome.


Subject(s)
Ascites/physiopathology , Glomerular Filtration Rate/physiology , Liver Cirrhosis/physiopathology , Renal Plasma Flow, Effective/physiology , Aldosterone/blood , Amino Acids/administration & dosage , Ascites/complications , Endothelins/blood , Female , Hemodynamics , Humans , Inulin , Liver Cirrhosis/complications , Male , Middle Aged , Nitric Oxide/blood , Nitric Oxide/urine , Renal Circulation , Renin/blood , p-Aminohippuric Acid
15.
Br J Clin Pharmacol ; 54(6): 675-7, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12492618

ABSTRACT

AIMS: This study examined the 131I-hippuran extraction fraction during baseline renal blood flow rates and at high flow rates induced by dopamine. METHODS: In 12 healthy subjects, arterial and renal venous sampling was used to measure the renal extraction of 131I-hippuran. Effective renal plasma flow values determined by the urinary clearance of 131I-hippuran were compared with renal plasma flow values corrected for incomplete extraction of 131I-hippuran. RESULTS: Dopamine (3 micro g kg-1 min-1) decreased 131I-hippuran extraction from 75 +/- 4% at baseline to 62 +/- 6% (means +/- 95% confidence intervals, P < 0.001). Hence, the increase in renal plasma flow (85 +/- 23%) greatly exceeded the rise in effective renal plasma flow (51 +/- 15%, P < 0.002). CONCLUSIONS: Dopamine induced increases in renal blood flow are largely under-estimated when measurements are not corrected for incomplete extraction of 131I-hippuran.


Subject(s)
Dopamine/pharmacology , Iodohippuric Acid/pharmacokinetics , Kidney/metabolism , Renal Plasma Flow, Effective/physiology , Adult , Humans , Iodine Radioisotopes/pharmacokinetics , Male , Metabolic Clearance Rate
16.
Ann Rheum Dis ; 61(8): 682-6, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12117672

ABSTRACT

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 (R(2)=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.


Subject(s)
Glomerular Filtration Rate/physiology , Scleroderma, Systemic/physiopathology , Amino Acids/pharmacology , Blood Pressure/physiology , Electrolytes , Female , Glucose , Humans , Male , Middle Aged , Parenteral Nutrition Solutions , Regression Analysis , Renal Plasma Flow, Effective/physiology , Solutions
17.
Scand J Urol Nephrol ; 36(6): 464-72, 2002.
Article in English | MEDLINE | ID: mdl-12623513

ABSTRACT

OBJECTIVE: Increased physical activity is followed by a stimulation of the sympathetic nervous system and this effect is probably more pronounced in patients with chronic renal failure and hypertension than in healthy controls. The role of sustained exercise in hypertensive patients with chronic renal failure, with and without antihypertensive therapy, is unclear, as is hormonal regulation of the renal hemodynamics. We hypothesized that prolonged low-intensity bicycle exercise would have a greater effect in patients with chronic renal failure than in controls, and that antihypertensive treatment would ameliorate these effects. MATERIAL AND METHODS: Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), mean arterial blood pressure (MAP), norepinephrine (NE) and atrial natriuretic peptide (ANP) were measured in the upright position before and during low-intensity exercise for 2 h in healthy controls (n = 8) and in hypertensive patients with moderately reduced renal function who were not taking antihypertensives (n = 7) or who were receiving treatment with captopril (n = 10), enalapril (n = 6) or verapamil (n = 9). RESULTS: GFR tended to decrease and ERPF decreased significantly in healthy individuals when exercise duration was prolonged from 1 to 2 h. An earlier decline in GFR and ERPF was seen in the renal failure patients compared with the controls. Filtration fraction (FF) increased during exercise in all groups except the group taking enalapril. MAP increased in the captopril group during exercise but was unchanged in the other groups. Treatment with captopril produced a more pronounced and earlier fall in exercise-induced GFR than in untreated controls, while verapamil treatment completely blunted the decline in GFR, with a concomitant increase in plasma ANP. No significant changes were seen in plasma NE levels, but urinary NE excretion increased in controls and captopril-treated patients during exercise. CONCLUSIONS: The results suggest that prolonged low-intensity exercise has a substantially greater effect on renal hemodynamics in hypertensive renal failure patients than in healthy controls, with negligible changes in plasma NE levels. Verapamil treatment seems to ameliorate the renal effects of exercise on GFR in these patients, and this may in part be mediated via a stimulatory effect on ANP.


Subject(s)
Exercise , Hemodynamics/physiology , Hypertension/therapy , Kidney Failure, Chronic/therapy , Renal Circulation/physiology , Adult , Antihypertensive Agents/therapeutic use , Atrial Natriuretic Factor/blood , Blood Pressure/physiology , Captopril/therapeutic use , Enalapril/therapeutic use , Female , Glomerular Filtration Rate/physiology , Humans , Hypertension/drug therapy , Hypertension/physiopathology , Kidney Failure, Chronic/physiopathology , Male , Middle Aged , Norepinephrine/blood , Renal Plasma Flow, Effective/physiology , Verapamil/therapeutic use
18.
J Nucl Med Technol ; 28(3): 156-8, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11001496

ABSTRACT

OBJECTIVE: The relationship between age and effective renal plasma flow (ERPF) results, as measured in nuclear medicine, is well known. This paper explores the relationships among gender, age, and ERPF measurements. After reading this paper, the nuclear medicine technologist should be able to: (a) discuss the importance of establishing normal range values for ERPF that include age and gender variables; (b) state how age affects ERPF results; and (c) state how gender affects ERPF results.


Subject(s)
Iodine Radioisotopes/pharmacokinetics , Iodohippuric Acid/pharmacokinetics , Kidney/metabolism , Radiopharmaceuticals/pharmacokinetics , Technetium Tc 99m Mertiatide/pharmacokinetics , Adult , Age Factors , Aged , Algorithms , Body Surface Area , Female , Glomerular Filtration Rate/physiology , Humans , Kidney/diagnostic imaging , Linear Models , Male , Metabolic Clearance Rate , Middle Aged , Radionuclide Imaging , Renal Plasma Flow, Effective/physiology , Sex Factors , Time Factors
19.
Vet Radiol Ultrasound ; 40(6): 572-87, 1999.
Article in English | MEDLINE | ID: mdl-10608684

ABSTRACT

Renal nuclear medicine is used to evaluate renal function and morphology. Renal scintigraphy is the best imaging modality for evaluation of functional parameters such as glomerular filtration rate and effective renal plasma flow. The commonly used renal radiopharmaceuticals are reviewed. Both imaging and non-imaging techniques are presented. Specific applications of renal nuclear medicine are discussed.


Subject(s)
Kidney/diagnostic imaging , Animals , Glomerular Filtration Rate/physiology , Image Enhancement , Kidney/physiology , Radionuclide Imaging , Radiopharmaceuticals/administration & dosage , Renal Circulation/physiology , Renal Plasma Flow, Effective/physiology , Technetium Tc 99m Dimercaptosuccinic Acid , Technetium Tc 99m Mertiatide , Technetium Tc 99m Pentetate
20.
J Pharmacol Toxicol Methods ; 41(1): 17-25, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10507754

ABSTRACT

The objective of this study was to validate a kinetic approach for the simultaneous measurement of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in the dog. Six healthy male Beagle dogs were randomly assigned in a three-period cross-over study of intravenous bolus administration of iohexol (64.7 mg/kg), PAH (10 mg/kg), and an iohexol/PAH mixture. PAH and iohexol were determined simultaneously by a validated high-performance liquid chromatographic method. The iohexol and PAH data obtained after intravenous administration were analyzed using noncompartmental and bicompartmental approaches. A simplified iohexol plasma clearance was also calculated from the terminal elimination phase of the plasma iohexol concentrations versus time profile. The total plasma clearance values for PAH and exo-iohexol were 13+/-2.3 mL/kg/min and 2.9+/-0.3 mL/kg/min, respectively. No significant (or biologically relevant) effect of coadministration of PAH and iohexol was observed on the pharmacokinetic parameters of either drug. The calculation of simplified plasma clearance led to an overestimation of the true plasma clearance. In conclusion, GFR and ERPF can easily and rapidly be measured in the dog by this approach which is relatively noninvasive.


Subject(s)
Glomerular Filtration Rate/physiology , Iohexol/pharmacokinetics , Kidney Glomerulus/metabolism , Renal Plasma Flow, Effective/physiology , p-Aminohippuric Acid/pharmacokinetics , Animals , Area Under Curve , Chromatography, High Pressure Liquid , Consciousness , Dogs , Drug Therapy, Combination , Half-Life , Injections, Intravenous , Male
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