Comparing the Reliability of the Glomerular Filtration Rate Estimated with 99m-Technetium Diethylene-Triamine-Pentaacetate versus the Effective Renal Plasma Flow Obtained with 99m-Technetium Ethylene Dicysteine: A Prospective Observational Study.

The glomerular filtration rate (GFR) is important for assessing renal function and must be calculated reliably and reproducibly. This study aimed to compare the reliability and accuracy of GFR estimated with 99m-technetium diethylene-triamine-pentaacetate (99mTc-DTPA) versus that calculated from the effective renal plasma flow (ERPF) (GFR is 20% of ERPF) determined by the 99m-technetium ethylene dicysteine (99mTc-EC) technique. Forty-five patients suffering from cancer requiring platinum compound-based chemotherapy or from chronic renal failure were recruited. The patients were divided into two cohorts: (1) those with normal serum creatinine (SCr) levels (≤2 mg/dL) and (2) deranged SCr levels (>2 mg/dL). For all patients, the relative renal function was estimated by the 99mTc-DTPA and 99mTc-EC methods, 2-4 days apart. A 24-h urine sample for estimating 24-h creatinine clearance (CrCl) was obtained. GFR was also calculated using the Modification of Diet in Renal Disease (MDRD) formula. The GFR estimated via 24-h urine CrCl, 99mTc-DTPA, and ERPF obtained with 99mTc-EC were examined by quantile comparison plots, and all showed evidence of following a non-Gaussian distribution. For SCr values ≤2 mg/dL, the GFR estimated by the MDRD formula consistently shows significantly higher values than the GFR estimated with 99mTc-DTPA or 99mTc-EC. We found a high degree of correlation between the 99mTc-DTPA and 99mTc-EC radionuclide methods of estimating GFR. However, in patients with renal dysfunction, GFR estimated through Gates' method using a gamma camera overestimated the GFR; in these patients, calculating the GFR from the ERPF obtained with 99mTc-EC is more accurate.

Serum Uromodulin, a Potential Biomarker of Tubulointerstitial Damage, Correlates Well with Measured GFR and ERPF in Patients with Obstructive Nephropathy.

Background and Objectives: In chronic kidney obstruction, the severity of tubulointerstitial damage correlates best with the loss of kidney function and the risk for progression to end-stage kidney disease. The present study aimed to investigate the potential clinical significance of serum uromodulin (sUmod) as a marker of early kidney disfunction in patient with obstructive nephropathy (ON). Materials and Methods: Serum Umod level was measured by sensitive ELISA method in 57 adult patients with obstructive nephropathy and 25 healthy subjects in control group. Kidney function was precisely evaluated via measured glomerular filtration rate (mGFR) (renal clearance of 99 mTc-diethylenetriamine penta-acetic acid), effective renal plasma flow (ERPF) and Cystatin C level. Recruited patients were divided into subgroups based on the mGFR: group I­GFR ≤ 60 mL/min/1.73 m2 (N = 31), group II­GFR > 60 mL/min/1.73 m2 (N = 26). Results: A significantly lower level of serum uromodulin was measured in patients with ON (50.2 ± 26.3 ng/mL) compared to the control group (78.3 ± 24.5 ng/mL) (p < 0.001). The mean level of serum Umod was significantly different between group I (30.5 ng/mL ± 11.1) and group II (73.6 ng/mL ± 18.6) (p < 0.001), but not between group II (73.6 ng/mL ± 18.6) and control group (78.3 ± 24.5 ng/mL). There was a positive correlation between sUmod and mGFR (R = 0.757, p < 0.001) and ERPF (R = 0.572 p < 0.001), with lower sUmod levels in patients with impaired renal function. An inverse relationship was detected between sUmod and filtration markers­cystatin C (R = −0.625, p < 0.001), creatinine, urea and uric acid. ROC analysis of sUmod to differentiate between ON patients with GFR below 60 mL/min/1.73 m2 and above 60 mL/min/1.73 m2 resulted in AUC of 0.98 (p < 0.001, 95% CI 0.922 vs. 0.998) at a cut-off value of 46 ng/mL (specificity 96.8%, sensitivity 92.2%). Conclusions: The significant correlation of sUmod with kidney function parameters may imply potential clinical significance as a noninvasive biomarker of early kidney disfunction in obstructive nephropathy.

Plasma uric acid and renal haemodynamics in type 2 diabetes patients.

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.

Prognostic Value of Effective Renal Plasma Flow for First-year Renal Outcome in Kidney Allograft Recipients.

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.

Renal and Vascular Effects of Uric Acid Lowering in Normouricemic Patients With Uncomplicated Type 1 Diabetes.

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.

[Significance of renal filtration fraction evaluation of renal artery stenting for atherosclerotic renal artery stenosis treatment].

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.

Influence of sex on hyperfiltration in patients with uncomplicated type 1 diabetes.

The aim of this analysis was to examine sex-based differences in renal segmental resistances in healthy controls (HCs) and patients with type 1 diabetes (T1D). We hypothesized that hyperfiltration-an early hemodynamic abnormality associated with diabetic nephropathy-would disproportionately affect women with T1D, thereby attenuating protection against the development of renal complications. Glomerular hemodynamic parameters were evaluated in HC (n = 30) and in normotensive, normoalbuminuric patients with T1D and either baseline normofiltration [n = 36, T1D-N, glomerular filtration rate (GFR) 90-134 ml·min-1·1.73 m2] or hyperfiltration (n = 32, T1D-H, GFR ≥ 135 ml·min-1·1.73 m2) during euglycemic conditions (4-6 mmol/l). Gomez's equations were used to derive efferent (RE) and afferent (RA) arteriolar resistances, glomerular hydrostatic pressure (PGLO) from inulin (GFR) and paraaminohippurate [effective renal plasma flow (ERPF)] clearances, plasma protein and estimated ultrafiltration coefficients (KFG). Female patients with T1D with hyperfiltration (T1D-H) had higher RE (1,985 ± 487 vs. 1,381 ± 296 dyne·sec-1·cm-5, P < 0.001) and filtration fraction (FF, 0.20 ± 0.047 vs. 0.16 ± 0.03 P < 0.05) and lower ERPF (876 ± 245 vs. 1,111 ± 298 134 ml·min-1·1.73 m2P < 0.05) compared with male T1D-H patients. Overall, T1D-H patients had higher PGLO and lower RA vs. HC subjects, although there were no sex-based differences. In conclusion, female T1D-H patients had higher RE and FF and lower ERPF than their male counterparts with no associated sex differences in RA Prospective intervention studies should consider sex as a modifier of renal hemodynamic responses to renal protective therapies.

Split renal function of both kidneys after robot-assisted partial nephrectomy for renal tumor larger than 4 cm.

PURPOSE: Relative few studies reported the changes in split renal function using renal scintigraphy for robot-assisted partial nephrectomy (RaPN) for renal tumor >4 cm. This study aimed at demonstrating that RaPN is safe for renal tumor >4 cm without damaging the renal function of ipsilateral and contralateral kidney. METHODS: Patients who underwent RaPN for single renal tumor from December 2009 to December 2013 were identified from a prospectively collected database. We compared demographic, perioperative, and postoperative outcomes between patients with renal tumor >4 cm (case group) and patients with renal tumor ≦4 cm (control group). Renal function was assessed by serum creatinine, estimated glomerular filtration rate, and effective renal plasma flow (ERPF). RESULTS: One hundred and three consecutive patients (45 in case group and 58 in control group) were identified. Case group had significantly longer operative time (P = 0.011), longer warm ischemia time (P < 0.001), and more estimated blood loss (P = 0.010) than control group. Only one patient in the case group had conversion surgery. There was no significant difference regarding hospital stay, blood transfusion, complications rate, and positive surgical margin. The changes in ipsilateral ERPF and contralateral ERPF were not significantly different between groups (ipsilateral kidney: -10.5 vs. -12.5%, P = 0.989; contralateral kidney: -3.6 vs. -5.2%, P = 0.611). CONCLUSIONS: RaPN is a safe and feasible modality of nephron-sparing surgery for renal tumor >4 cm, as it is for renal tumor ≦4 cm.

Magnetic Resonance Imaging-Derived Renal Oxygenation and Perfusion During Continuous, Steady-State Angiotensin-II Infusion in Healthy Humans.

BACKGROUND: The role of kidney hypoxia is considered pivotal in the progression of chronic kidney disease. A widely used method to assess kidney oxygenation is blood oxygen level dependent (BOLD)-magnetic resonance imaging (MRI), but its interpretation remains problematic. The BOLD-MRI signal is the result of kidney oxygen consumption (a proxy of glomerular filtration) and supply (ie, glomerular perfusion). Therefore, we hypothesized that with pharmacological modulation of kidney blood flow, renal oxygenation, as assessed by BOLD-MRI, correlates to filtration fraction (ie, glomerular filtration rate/effective renal plasma flow) in healthy humans. METHODS AND RESULTS: Eight healthy volunteers were subjected to continuous angiotensin-II infusion at 0.3, 0.9, and 3.0 ng/kg per minute. At each dose, renal oxygenation and blood flow were assessed using BOLD and phase-contrast MRI. Subsequently, "gold standard" glomerular filtration rate/effective renal plasma flow measurements were performed under the same conditions. Renal plasma flow decreased dose dependently from 660±146 to 467±103 mL/min per 1.73 m(2) (F[3, 21]=33.3, P<0.001). Glomerular filtration rate decreased from 121±23 to 110±18 mL/min per 1.73 m(2) (F[1.8, 2.4]=6.4, P=0.013). Cortical transverse relaxation rate (R2*; increases in R2* represent decreases in oxygenation) increased by 7.2±3.8% (F[3, 21]=7.37, P=0.001); medullar R2* did not change. Cortical R2* related to filtration fraction (R(2) 0.46, P<0.001). CONCLUSIONS: By direct comparison between "gold standard" kidney function measurements and BOLD MRI, we showed that cortical oxygenation measured by BOLD MRI relates poorly to glomerular filtration rate but is associated with filtration fraction. For future studies, there may be a need to include renal plasma flow measurements when employing renal BOLD-MRI.

Plasma uric acid effects on glomerular haemodynamic profile of patients with uncomplicated Type 1 diabetes mellitus.

AIMS: Increased plasma uric acid (PUA) levels are associated with impaired renal function in patients with Type 1 diabetes, but the mechanisms are not well understood. Our aim was to evaluate whether higher PUA levels are associated with increased afferent arteriolar resistance in patients with Type 1 diabetes vs. healthy controls, thereby influencing renal function. METHODS: PUA, GFR (inulin) and effective renal plasma flow (ERPF; para-aminohippurate) were measured in 70 otherwise healthy patients with Type 1 diabetes and 60 healthy controls. Gomez's equations were used to estimate afferent (RA ) and efferent (RE ) arteriolar resistances, glomerular hydrostatic pressure (PGLO ) and filtration pressure (ΔPF ). The relationships between PUA and glomerular haemodynamic parameters were evaluated by univariable linear regression correlation coefficients. RESULTS: In patients with Type 1 diabetes, higher PUA correlated with lower PGLO (P = 0.002) and ΔPF (P = 0.0007), with higher RA (P = 0.001), but not with RE (P = 0.55). These associations were accompanied by correlations between higher PUA with lower GFR (P = 0.0007), ERPF (P = 0.008), RBF (P = 0.047) and higher RVR (P = 0.021). There were no significant correlations between PUA and renal haemodynamic parameters in the healthy controls. CONCLUSIONS: The association between higher PUA with lower GFR and lower ERPF in patients with Type 1 diabetes is driven by alterations in the estimated RA . PUA-mediated RA may be caused by increased tone or thickening of the afferent renal arteriole, which might potentiate renal injury by causing ischaemia to the renal microcirculation.

¿Cuál es el flujo de baño óptimo en la hemodiafiltración on-lineposdilucional? / What is the optimum dialysate flow in post-dilution online haemodiafiltration?

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)

Change in glomerular volume and its clinicopathological impact after kidney transplantation.

BACKGROUND: Both immunological and non-immunological etiologies affect graft function after kidney transplantation, including acute rejection, calcineurin inhibitor toxicity, and a recurrence of glomerulonephritis. Glomerular enlargement or glomerular sclerosis due to glomerular hyperfiltration related to increased renal blood flow is another cause. Although the glomerular volume in baseline biopsies predicts late allograft function, the relationship between allograft function and the annual changes in glomerular volume after kidney transplantation are unclear. AIM: We investigated changes in glomerular volume after kidney transplantation and their clinicopathological relationship. METHODS: We enrolled 23 patients with stable kidney function without an episode of rejection or any complication resulting in a functional decrease in the graft. We measured glomerular volume (GV) using the Weibel-Gomez method and glomerular density (GD) using 0,1 h biopsy samples as baseline controls and 1 yr biopsy samples and investigated the association between the changes in them and clinical parameters, including graft function, proteinuria, and renal hemodynamic markers, including effective renal plasma flow (ERPF) and filtration fraction (FF). The ERPF was calculated from a 99mTc-mercaptoacetyltriglycine (MAG3) renogram. RESULTS: The GV and ERPF increased significantly 1 yr after kidney transplantation. In contrast, proteinuria decreased significantly and Δproteinuria (1 yr - 1 month after transplantation) was correlated with ΔGV (P < 0.05, rs = -0.467). CONCLUSION: Glomerular enlargement 1 yr after transplantation may be related to improved proteinuria. It is possible that glomerular enlargement serves as a renal adaptation after kidney transplantation.

Plasma endothelin-1 level, measured glomerular filtration rate and effective renal plasma flow in diabetic nephropathy.

BACKGROUND: Endothelin-1 (ET-1) is potent vasoconstrictor peptide which is able to contribute to the functional and structural renal changes. The aim of this study was to investigate the relationship between plasma concentration of ET-1 and indices of renal function in patients with diabetic nephropathy. METHODS: We measured plasma ET-1 levels in 99 patients with type 2 diabetes, divided into two groups according to the values of their glomerular filtration rate (GFR): group I (GFR ≥ 60 mL/min/1.73 m(2); n = 50), group II (GFR ≥ 60 mL/min/1.73 m(2), n = 49), and the control group (n = 30) with clinically healthy subjects who were matched by age and sex. GFR and effective renal plasma flow (ERPF) were measured by the radioisotopic clearance. Other renal function parameters, such as serum concentrations of cystatin C, urea, creatinine, uric acid, 24-h albuminuria and proteinuria were additionally measured. RESULTS: There were significant differences in plasma concentration of ET-1 among groups I, II and the control group (1.45 vs. 2.40 vs. 0.80 pg/mL, p < 0.001). The correlation between ET-1 and mGFR (r = -0.52, p < 0.001), ERPF (r = -0.42, p < 0.001), albuminuria and proteinuria (r = 0.36, p < 0.001; r = 0.48, p < 0.001) and cystatin C (r = 0.42, p < 0.001) was significant. In multiple regression analyses, only plasma concentration of ET-1 (p < 0.001) and duration of hypertension (p < 0.05) were independently and significantly associated with mGFR. CONCLUSION: A higher plasma concentration of ET-1 is independently associated with a decreased value of GFR in patients with diabetic nephropathy.

Higher filtration fraction in formerly early-onset preeclamptic women without comorbidity.

Formerly preeclamptic women have an increased risk for developing end-stage renal disease, which has been attributed to altered renal hemodynamics and abnormalities in the renin-angiotensin-aldosterone system. Whether this is due to preeclampsia itself or to comorbid conditions is unknown. Renal hemodynamics and responsiveness to ANG II during low Na(+) intake (7 days, 50 mmol Na(+)/24 h) and high Na(+) (HS) intake (7 days, 200 mmol Na(+)/24 h) were studied in 18 healthy normotensive formerly early-onset preeclamptic women (fPE women) and 18 healthy control subjects (fHP women), all selected for absence of comorbidity. At the end of each diet, renal hemodynamics and blood pressure were measured before and during graded ANG II infusion. Both HS intake and former preeclampsia increased filtration fraction (FF) without an interaction between the two. FF was highest during HS intake in fPE women [0.31 ± 0.12 vs. 0.29 ± 0.11 in fHP women, generalized estimating equation analysis (body mass index corrected), P = 0.03]. The renal response to ANG II infusion was not different between groups. In conclusion, fPE women have a higher FF compared with fHP women. As this was observed in the absence of comorbidity, preeclampsia itself might exert long-term effects on renal hemodynamics. However, we cannot exclude the presence of prepregnancy alterations in renal function, which, in itself, lead to an increased risk for preeclampsia. In experimental studies, an elevated FF has been shown to play a pathogenic role in the development of hypertension and renal damage. Future studies, however, should evaluate whether the subtle differences in renal hemodynamics after preeclampsia contribute to the increased long-term renal risk after preeclampsia.

The effect of angiotensin converting enzyme inhibition on effective renal plasma flow in patients with diffuse renal parenchymal diseases and hypertension.

INTRODUCTION: Angiotensin converting enzyme inhibitors are commonly used to treat various hypertensive conditions and in addition to lowering blood pressure these drugs affect the local renal hemodynamic status, thereby influencing the glomerular filtration rate and effective renal plasma flow. The study was aimed at determining whether angiotensin converting enzyme inhibitors can produce significant changes in effective renal plasma flow in patients with parenchymal renal disease and to assess whether the changes depend on the pre-existing functional status of the kidney. MATERIAL AND METHODS: The study included 80 subjects, 40 subjects with hypertension associated with diffuse renal parenchymal disease and 40 subjects with essential hypertension. All study subjects underwent the baseline effective renal plasma flow measurement and the repeated effective renal plasma flow measurement after administration of captopril. Effective renal plasma flow was determined by 131 I-hippuran clearance in blood samples taken at 20 and 30 minutes. RESULTS: Angiotensin converting enzyme inhibitors caused significant effective renal plasma flow changes in 55% of subjects with diffuse renal parenchymal disease and in 75% of subjects with essential hypertension. The effective renal plasma flow changes were more significant in subjects with preserved renal function (normal baseline effective renal plasma flow) compared to subjects with reduced baseline effective renal plasma flow. CONCLUSION: The application of angiotensin converting enzyme inhibitors in patients with diffuse renal parenchymal disease and in individuals with essential hypertension may result in significant hemodynamic changes in the kidney, accompanied by changes in effective renal plasma flow. The extent of the changes caused by angiotensin converting enzyme inhibitors depends on the preexisting functional status of the kidney.

Clinical Significance of Urodynamic Study Parameters in Maintenance of Renal Function in Spinal Cord Injury Patients

OBJECTIVE: To analyze association between urodynamic study (UDS) parameters and renal function in spinal cord injured (SCI) patients with neurogenic detrusor overactivity. METHODS: Patients with a suprasacral SCI, who underwent UDS and radioisotope renogram at least twice between January 1, 2006 and January 31, 2013, were included. UDS (cystometric capacity, reflex volume, compliance, and maximal detrusor pressure) and radioisotope renogram (total effective renal plasma flow [ERPF] of both kidneys) data were collected. The following were conducted to reanalyze any association between reflex volume and ERPF: initial and follow-up results of consecutive evaluations were compared; a mixed-model regression analysis to account for clustered data was conducted to evaluate the association between UDS parameters and ERPF; and finally, a mixed-model analysis type 3 test with data pairs, of which the first evaluation showed involuntary detrusor contraction. RESULTS: A total of 150 patients underwent 390 evaluations which were arranged into 240 pairs of consecutive evaluations, of which 171 had first evaluations with observed involuntary detrusor contraction. The following results were obtained: cystometric capacity was significantly larger and maximal detrusor pressure was significantly lower on follow-up; on univariate analysis, reflex volume and maximal detrusor pressure were significant, and multivariate analysis using these two parameters showed that maximal detrusor pressure is significantly associated with total ERPF; and no significant differences were observed. CONCLUSION: Maximal detrusor pressure should be closely monitored in the urologic management of neurogenic detrusor overactivity in SCI patients. The results also may serve as a reference for regular UDS follow-up.

Short-term renal hemodynamic effects of tolvaptan in subjects with autosomal dominant polycystic kidney disease at various stages of chronic kidney disease.

Vasopressin V2-receptor antagonists may delay disease progression in ADPKD. Trials with V2-receptor antagonists have been performed predominantly in patients with an estimated creatinine clearance of 60 ml/min or more. Here we determined renal hemodynamic effects of the V2-receptor antagonist tolvaptan in 27 patients with ADPKD at various stages of chronic kidney disease: group A: >60, group B: 30-60, and group C: <30 ml/min per 1.73 m(2). Measurements were performed before, after 3 weeks of tolvaptan (up titration to 90/30 mg/day, split dose), and 3 weeks after the last dose of tolvaptan. With tolvaptan, a minor, reversible decrease in GFR ((125)I-iothalamate clearance) was found that reached significance in groups A and B: -7.8 (interquartile range -13.7 to -1.3) and -4.3 (-9.7 to -0.9) ml/min per 1.73 m(2), respectively, but not in group C (GFR decrease -0.7 (-1.1 to 1.5) ml/min/1.73 m(2)). The percentage change in GFR, ERPF ((131)I-hippuran clearance), and filtration fraction with tolvaptan did not differ between the three study groups. No differences between the three study groups were found in other main efficacy variables, besides smaller increases in urine volume in group C during tolvaptan treatment. Tolvaptan was well tolerated, with only two patients withdrawing. Thus, doses of tolvaptan typically used in patients with ADPKD do not produce a difference in renal hemodynamic profile in chronic kidney disease stages 1 through 4, but minor GFR drops may be observed in individual patients.

A comparison of single plasma sample methods to estimate renal clearance using 99mTc-ethylenedicysteine and 99mTc-mercaptoacetyltriglycine.

Several single sample methods for determination of (99m)Tc-mercaptoacetyltriglycine (MAG3) clearance are being used clinically. Kabasakal et al. proposed a similar formula for (99m)Tc-ethylenedicysteine (EC). This study was performed to compare his method with Bubeck et al. formula for (99m)Tc-MAG3 already in use. Twenty-eight subjects divided in two groups were registered which included 22 patients with various renal diseases (group-I) and six normal volunteers (group II). All subjects were studied twice using both the radiopharmaceuticals. The images and renogram parameters, that is TMAX and T1/2 of both the agents, were similar in all the subjects. The clearance of the (99m)Tc-EC was however considerably higher than (99m)Tc-MAG3 in both the groups (mean ± SEM =279 ± 14 ml min(-1)/1.73 m(2) versus 177 ± 15 ml min(-1)/1.73 m(2) in group-I and 377 ± 11.90 ml min(-1)/1.73 m(2) versus 238 ± 8.23 ml min(-1)/1.73 m(2) in group II). This difference was more pronounced in cases with reduced renal functions. Among the Effective Renal Plasma Flow (ERPF) values determined from EC and MAG3 clearances in six normal volunteers, four cases only in MAG3 had ERPF below the lower limit. This study has demonstrated superiority of single sample method for (99 m)Tc-EC clearance over its analogous method for (99m)Tc-MAG3.

Compensatory changes in the retained kidney after nephrectomy in a living related donor.

OBJECTIVE: Herein, we investigate the compensatory changes in morphology, function, and hemodynamic indices of the retained kidney after nephrectomy among living related donors. METHODS: The 136 living related kidney donors underwent assessments before surgery as well as at 1 and 12 months, postoperatively, including length, width, short diameter, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), peak systolic blood flow velocity (Vsmax), resistance index (RI), as well as pulsatility indices (PI) of main renal artery (MRA), segmental renal artery (SRA), and interlobar renal artery (IRA). RESULTS: All subjects were followed up for 12 to 62 months, with no observed hypertension or kidney failure. The length, width, and short diameters of the retained kidney increased significantly (P < .01) at 1 and 12 months postoperatively. The renal sizes were similar (P > .05). GFR and ERPF increased significantly compared with preoperative values (P < .01) with similar values at postoperative month 1 and 12 (P > .05). The Vsmax of MRA, SRA, and IRA in the retained kidney increased significantly (P < .01); the RI and PI also increased compared with the preoperative values (P < .05), albeit these indicators were similar at postoperative months 1 and 12 (P > .05). CONCLUSIONS: For all subjects studied after unilateral nephrectomy in a living related donor, the diameter of the retained kidney as well as the GFR and ERPF showed compensatory increases. Various arterial hemodynamic parameters also showed compensatory changes. Under strict donor inclusion criteria, living related kidney donor procedures should be safe.

Renal function after preeclampsia: a longitudinal pilot study.

BACKGROUND: Women with a history of preeclampsia are at increased risk to develop end-stage renal disease. In this longitudinal study, we evaluated renal function in women with a history of severe preeclampsia and parous controls over a period of 14 years. METHODS: Renal function was measured 1 and then 14 years postpartum by para-aminohippurate and inulin clearances in 20 women with a history of severe preeclampsia and 8 parous controls. RESULTS: The difference in glomerular filtration rate 1 year postpartum between women with a history of preeclampsia and parous controls (112 ± 10 and 125 ± 8 ml/min/1.73 m(2), p < 0.01) had disappeared 14 years postpartum (104 ± 10 and 109 ± 13 ml/min/1.73 m(2), p = 0.37). There was a consistent trend for a lower effective renal plasma flow both 1 and 14 years postpartum (477 ± 90 and 543 ± 92, p = 0.09 and 473 ± 85 and 543 ± 98 ml/min/1.73 m(2), p = 0.07). CONCLUSIONS: This explorative study suggests no accelerated renal function loss in the first decade after preeclampsia.