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Aim: To determine the effect of the dipeptidyl peptidase-4 inhibitor linagliptin on postprandial glomerular hyperfiltration compared with the sulphonylurea glimepiride in adults with type 2 diabetes (T2D). Materials and Methods: In this predefined substudy within a randomized, double-blind, parallel-group, intervention trial, overweight people with T2D without renal impairment were treated with once-daily linagliptin 5 mg (N = 10) or glimepiride 1 mg (N = 13) as an add-on to metformin for 8 weeks. After a standardized liquid protein-rich meal, the glomerular filtration rate (GFR) and effective renal plasma flow were determined by inulin and para-aminohippuric acid clearance, respectively, based on timed urine sampling. Intrarenal haemodynamics were estimated using the Gomez equations. Glucoregulatory/vasoactive hormones, urinary pH and fractional excretions (FE) of sodium, potassium and urea were measured. Results: Compared with glimepiride, linagliptin increased the postprandial filtration fraction (FF; mean difference 2.1%-point; P =.016) and estimated glomerular hydraulic pressure (mean difference 3.0 mmHg; P =.050), and tended to increase GFR (P =.08) and estimated efferent renal arteriolar resistance (RE; P =.08) from baseline to week 8. No differences in FE were noted. Glimepiride reduced HbA1c more than linagliptin (mean difference −0.40%; P =.004), without between-group differences in time-averaged postprandial glucose levels. In the linagliptin group, change in FF correlated with change in mean arterial pressure (R = 0.807; P =.009) and time-averaged mean glucagon (R = 0.782; P =.008), but not with changes in glucose, insulin, intact glucagon-like peptide-1, renin or FENa. Change in glucagon was associated with change in RE (R = 0.830; P =.003). Conclusions: In contrast to our hypothesis, compared with glimepiride, linagliptin does not reduce postprandial hyperfiltration, yet appears to increase FF after meal ingestion by increasing blood pressure or RE.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve hard renal outcomes in type 2 diabetes. This is possibly explained by the fact that SGLT2i normalize the measured glomerular filtration rate (mGFR) by increasing renal vascular resistance, as was shown in young people with type 1 diabetes and glomerular hyperfiltration. Therefore, we compared the renal hemodynamic effects of dapagliflozin with gliclazide in type 2 diabetes. The mGFR and effective renal plasma flow were assessed using inulin and para-aminohippurate clearances in the fasted state, during clamped euglycemia (5 mmol/L) and during clamped hyperglycemia (15 mmol/L). Filtration fraction and renal vascular resistance were calculated. Additionally, factors known to modulate renal hemodynamics were measured. In 44 people with type 2 diabetes on metformin monotherapy (Hemoglobin A1c 7.4%, mGFR 113 mL/min), dapagliflozin versus gliclazide reduced mGFR by 5, 10, and 12 mL/min in the consecutive phases while both agents similarly improved Hemoglobin A1c (-0.48% vs -0.65%). Dapagliflozin also reduced filtration fraction without increasing renal vascular resistance, and increased urinary adenosine and prostaglandin concentrations. Gliclazide did not consistently alter renal hemodynamic parameters. Thus, beyond glucose control, SGLT2i reduce mGFR and filtration fraction in type 2 diabetes. The fact that renal vascular resistance was not increased by dapagliflozin suggests that this is due to post-glomerular vasodilation rather than pre-glomerular vasoconstriction.

Although ureteroplasty with buccal mucosa graft for long-segmental ureteral stenosis has been developed long ago, evidence was still restricted to case series in published literature. This study aims to validate ureteroplasty with buccal mucosa graft (BMG) in long-segment stricture at the proximal and middle ureters under designed comparative methods. From April 2015 to January 2019, we performed robotic-assisted ureteroplasty with BMG with a two-phase design and compared ureteroplasty and BMG (phase 2 surgery) with endoscopic stenting (phase 1 surgery). Paired data of effective renal plasma flow (ERPF), glomerular filtration rate (GFR), hydronephrosis grade, and physical and psychological domains of the World Health Organization Quality of Life (WHOQOL)-BREF were compared. A total of 29 patients were enrolled, and only three (10%) patients had hydronephrosis resolution after treatment with endoscopic stenting (p = 0.250 to baseline). Compared to endoscopic ureteral stent, Hedges’ g of ureteroplasty with BMG was 0.56 (95% CI: 0.43-0.69), 0.63 (95% CI: 0.46-0.80), 0.80 (95% CI: 0.56-1.04), and 1.06 (95% CI: 0.69-1.43) in EGFR, GFR, physical domain of WHOQOL-BREF, and psychological domain of WHOQOL-BREF, respectively (All significance; p

Objective: Diabetic kidney disease is a microvascular complication of diabetes. Here, we assessed the association between skin microvascular function and renal hemodynamic function in a cohort of well-phenotyped adults with type 2 diabetes (T2D). Methods: We included 81 overweight/obese adults (age: 62 ± 8 years; BMI: 32 ± 4 kg/m2) with well-controlled T2D and no renal impairment. Skin microvascular function was assessed by nailfold capillary density in rest and after arterial occlusion (ie, peak capillary density). Renal hemodynamic functions (ie, measured glomerular filtration rate [mGFR], effective renal blood flow [ERBF], filtration fraction [FF], and effective renal vascular resistance [ERVR]) were assessed by combined inulin and para-aminohippurate clearances and blood pressure measurements. Results: Skin capillary density was 45 ± 10 capillaries/mm2 at baseline and 57 ± 11 capillaries/mm2 during post-occlusive peak; mGFR averaged 108 ± 20 ml/min. In multivariable regression analyses, positive associations between capillary density during post-occlusive peak and mGFR (β = 0.224; p = 0.022) and ERBF (β = 0.203; p = 0.020) and a positive trend for hyperemia and mGFR (β = 0.391; p = 0.053) were observed, while a negative association for post-occlusive capillary density with ERVR (β = −0.196; p = 0.027) was found. Conclusion: These findings indicate that microvascular dysfunction in overweight adults with T2D is associated with lower mGFR and ERPF and higher ERVR. We hypothesize that increased renal vascular resistance may contribute to glomerular dysfunction due to impaired renal perfusion.

Background: Blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) has been widely used to assess renal oxygenation changes in different kidney diseases in recent years. This study was designed to evaluate and compare renal tissue oxygenation using 2 BOLD-MRI analysis methods, namely, the regional and whole-kidney region of interest (ROI) selection methods. Methods: The study ended up with 10 healthy controls and 40 chronic kidney disease (CKD) patients without dialysis. Their renal BOLD-MRI data were analyzed using whole-kidney ROI selection method and compared with regional ROI selection method. Results: We found the cortical, medullary, and whole-kidney R2* values were significantly higher in CKD patients than those in controls. Compared with the regional ROI selection method, the whole-kidney ROI selection method yielded higher cortical R2* values in both controls and CKD patients. The whole-kidney R2* values of deteriorating renal function group were significantly higher than those in stable renal function group. Conclusions: Cortical and medullary oxygenation was decreased significantly in CKD patients compared with the healthy controls, particularly in the medulla. The whole-kidney R2* values were positively correlated with kidney function and inversely correlated with the estimated glomerular filtration rate and effective renal plasma flow. Whole-Kidney R2* value might effectively predict the progression of renal function in patients with CKD.

Purpose To evaluate the effect of renal stent-graft placement on kidney function and size alternation in chronic aortic dissection. Materials and Methods Twenty-five consecutive patients with chronic aortic dissection after thoracic endovascular aortic repair who underwent renal stent-graft placement between January 2015 and December 2016 were retrospectively reviewed. Forty-three patients with chronic aortic dissection who received thoracic endovascular aortic repair in the same period were reviewed as a control group for kidney volume comparison. Results Twenty-five stent-grafts were deployed over 25 renal arteries. Overall renal function was assessed by the slope of the regression line constructed from the plots of creatinine clearance versus time within 2 years after the procedure (–0.2810 vs –0.3146 mL/min–1/mo–1, P = .868), kidney volume at 12 months (129.4 ± 40.9 vs 137.0 ± 44.2 cm2, P = .193) and effective renal plasma flow at 6 months (106.3 ± 46.9 vs 124.4 ± 55.5 mL/min, P = .050) and was not significantly deteriorated. Seven treated patients (87.5%) with a renal artery supplied by a false lumen had a decrease in kidney volume, as did 14 patients (56%) in the control group (P = .206). Three patients with a dissected renal artery (75%) in the stent-graft group had an increase in kidney volume compared with 1 patient (11.1%) in the control group (P = .052). Conclusions Occlusion of the re-entry tear by a stent-graft in the renal artery remains a safe strategy to promote false lumen thrombosis. The stent-graft poses a potential risk of reducing the kidney volume in kidneys supplied by the false lumen but may provide a positive effect in kidney volume with a concomitant dissected renal artery in chronic aortic dissection.

AIMS To examine the relationship between normal plasma uric acid (PUA) levels, renal haemodynamic function, arterial stiffness and plasma renin and aldosterone over a wide range of type 1 diabetes (T1D) durations in adolescents, young adults and older adults. MATERIALS AND METHODS PUA, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), vascular stiffness parameters (aortic augmentation index [AIx], carotid AIx, carotid femoral pulse wave velocity [cfPWV]), and plasma renin and aldosterone were measured during a euglycaemic clamp in people with T1D: 27 adolescents (mean ± SD age 16.8 ± 1.9 years), 52 young adults (mean ± SD age 25.6 ± 5.5 years) and 66 older adults (mean ± SD age 65.7 ± 7.5 years). RESULTS PUA was highest in patients with the longest T1D duration: 197 ± 44 μmol/L in adolescents versus 264 ± 82 μmol/L in older adults (P

Background and objectives The neonatal and juvenile human kidney can be exposed to a variety of potentially toxic drugs ( e.g. , nonsteroidal anti-inflammatory drugs, antibiotics, antivirals, diuretics), many of which are substrates of the kidney organic anion transporters, OAT1 (SLC22A6, originally NKT) and OAT3 (SLC22A8). Despite the immense concern about the consequences of drug toxicity in this vulnerable population, the developmental regulation of OATs in the immature postnatal kidney is poorly understood. Design, setting, participants, & measurements Recognizing that today it is difficult to obtain rich data on neonatal kidney handling of OAT probes due to technical, logistic, and ethical considerations, multiple older physiologic studies that used the prototypical organic anion substrate para-aminohippurate (PAH) were reanalyzed in order to provide a quantitative description of OAT-mediated tubular secretion across the pediatric age continuum. Parametric and semiparametric models were evaluated for kidney function outcome variables of interest (maximum tubular secretory capacity of PAH [Tm PAH ], effective renal plasma flow [ERPF], and GFR). Results Data from 119 neonates, infants, and children ranging in age from 1 day to 11.8 years were used to fit Tm PAH , ERPF, and GFR as functions of postnatal age. Tm PAH is low in the immediate postnatal period and increases markedly after birth, reaching 50% of the adult value (80 mg/min) at 8.3 years of age. During the first 2 years of life, Tm PAH is lower than that of GFR when viewed as the fraction of the adult value. Conclusions During postnatal human kidney development, proximal tubule secretory function—as measured using PAH, a surrogate for OAT-mediated secretion of organic anion drugs, metabolites, and toxins—is low initially but increases rapidly. Despite developmental differences between species, this overall pattern is roughly consistent with animal studies. The human data raise the possibility that the acquisition of tubular secretory function may not closely parallel glomerular filtration.

Diabetic kidney disease remains the leading cause of end‐stage kidney disease and a major risk factor for cardiovascular disease. Large cardiovascular outcome trials and dedicated kidney trials have shown that sodium‐glucose cotransporter (SGLT)2 inhibitors reduce cardiovascular morbidity and mortality and attenuate hard renal outcomes in patients with type 2 diabetes (T2D). Underlying mechanisms explaining these renal benefits may be mediated by decreased glomerular hypertension, possibly by vasodilation of the post‐glomerular arteriole. People with T2D often receive several different drugs, some of which could also impact the renal vasculature, and could therefore modify both renal efficacy and safety of SGLT2 inhibition. The most commonly prescribed drugs that could interact with SGLT2 inhibitors on renal haemodynamic function include renin‐angiotensin system inhibitors, calcium channel blockers and diuretics. Herein, we review the effects of these drugs on renal haemodynamic function in people with T2D and focus on studies that measured glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) with gold‐standard techniques. In addition, we posit, based on these observations, potential interactions with SGLT2 inhibitors with an emphasis on efficacy and safety., SUMMARY AT A GLANCE This invited review describes the renal haemodynamic and protective effects of commonly prescribed drugs in people with type 2 diabetes and their interaction with SGLT2 inhibitors.

Objective Understanding cardiorenal pathophysiology in heart failure (HF) is of clinical importance. We sought to characterize the renal hemodynamic function and the transrenal gradient of the renin-angiotensin-aldosterone system (RAAS) markers in patients with HF and in controls without HF. Methods In this post hoc analysis, the glomerular filtration rate (GFRinulin), effective renal plasma flow (ERPFPAH) and transrenal gradients (arterial-renal vein) of angiotensin converting enzyme (ACE), aldosterone, and plasma renin activity (PRA) were measured in 47 patients with HF and in 24 controls. Gomez equations were used to derive afferent (RA) and efferent (RE) arteriolar resistances. Transrenal RAAS gradients were also collected in patients treated with intravenous dobutamine (HF, n = 11; non-HF, n = 11) or nitroprusside (HF, n = 18; non-HF, n = 5). Results The concentrations of PRA, aldosterone and ACE were higher in the renal vein vs the artery in patients with HF vs patients without HF (P Conclusions A larger transrenal RAAS marker gradient in patients with HF suggests a renal origin for neurohormonal activation associated with a vasoconstrictive renal profile.

Three-dimensional virtual models (3DVMs) are nowadays under scrutiny to improve partial nephrectomy (PN) outcomes. This report aims to analyze their impact on renal function preservation after minimally invasive PN. A total of 100 patients treated with minimally invasive PN with contrast-enhanced computed tomography from which a 3DVM was obtained, and having undergone baseline and 3rd month postoperative renal scans were prospectively enrolled and compared with a control group of 251 patients without 3DVMs. Weighted differential of pre- and postoperative renal scan-based effective renal plasmatic flow (b-WD ERPF) was calculated, according to the availability of 3DVMs and PADUA risk category. Multivariable logistic regression (MLR) models predicting a significant loss of renal function (LORF; ERPF drop >20%) were performed, overall and according to PADUA risk categories. The b-WD ERPF of the 3DVM group showed significantly lower LORF (–10%) than that of the control group (–19.6%, p = 0.02). In MLR, the availability of a 3DVM was found to be the only protective factor against a significant LORF (odds ratio [OR] = 0.3, p = 0.002). Moreover, after stratification as per tumor surgical complexity, this protective role was observed in both PADUA 8–9 and ≥10 category risk patients (OR = 0.3, p = 0.03 and OR = 0.1, p = 0.01). Patient summary The drop in operated kidney function was significantly lower in surgeries assisted by three-dimensional virtual models (3VDMs), indicating that the availability of a 3VDM is the only protective factor against a significant functional damage.

Objective Arginine vasopressin (AVP) and its surrogate, copeptin, have been implicated in diabetic kidney disease (DKD) pathogenesis, which develops in a subset of people with longstanding type 1 diabetes, but not in others (DKD Resistors). We hypothesized that patients with DKD would exhibit higher copeptin concentrations vs. DKD Resistors. Methods Participants with type 1 diabetes (n = 62, duration ≥50 years) were stratified into 42 DKD Resistors and 20 with DKD (eGFR ≤60 mL/min/1.73m2 or ≥30 mg/day urine albumin), and age/sex-matched controls (HC, n = 74) were included. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were calculated by inulin and p-aminohippurate clearance before and after angiotensin II (ang II) infusion. Renal vascular resistance (RVR) was calculated as mean arterial pressure/renal blood flow. Plasma copeptin, renin, aldosterone, neutrophil gelatinase-associated lipocalin (NGAL), and urea concentrations were measured, along with 24-h urine volume. Results DKD resistors had lower copeptin (95% CI: 4.0 [3.4–4.8] pmol/l) compared to DKD (5.8 [4.5–7.6] pmol/l, p = 0.02) and HC (4.8 [4.1–5.5] pmol/l, p = 0.01) adjusting for age, sex and HbA1c. In type 1 diabetes, higher copeptin correlated with lower GFR (r: −0.32, p = 0.01) and higher renin concentration (r: 0.40, p = 0.002) after multivariable adjustments. These relationships were not evident in HC. Copeptin inversely associated with RVR change following exogenous ang II only in participants with type 1 diabetes (β ± SE: −6.9 ± 3.4, p = 0.04). Conclusions In longstanding type 1 diabetes, copeptin was associated with intrarenal renin–angiotensin–aldosterone system (RAAS) activation and renal hemodynamic function, suggesting interplay between AVP and RAAS in DKD pathogenesis.

Over recent years, pigs have been promoted as potential animal model due to their anatomical and physiological similarities with humans. However, information about the contribution of distinct renal elimination processes [glomerular filtration rate (GFR), effective renal plasma flow (ERPF), tubular secretion, and reabsorption] in pigs is currently limited. Therefore, a cocktail of renal markers, consisting of iohexol (GFR), para-aminohippuric acid (ERPF and net tubular anion secretion), pindolol (net tubular cation secretion), and fluconazole (net tubular reabsorption) was administered intravenously to 7-week-old male conventional pigs. Plasma and urinary concentrations were determined using validated analytical methods. The clearance of iohexol (GFR) was 97.87 +/- 16.05 ml/min/m(2) (mean +/- SD). The ERPF, calculated as the renal clearance of PAH, was 226.77 +/- 62.45 ml/min/m(2), whereas the net tubular secretion of PAH was 130.28 +/- 52.62 ml/min/m(2). The net tubular secretion of R-pindolol and S-pindolol was 13.53 +/- 12.97 and 18.01 +/- 39.23 ml/min/m(2), respectively. The net tubular reabsorption of fluconazole was 78.32 +/- 13.52 ml/min/m(2). Overall, this cocktail of renal markers was considered to be safe for use in pigs since no adverse effects were observed. Iohexol, PAH and fluconazole were considered suitable renal marker to assess the porcine renal function. Pindolol seems less appropriate due to the high degree of nonrenal clearance in pigs. The values of GFR, ERPF, and anion secretion are within the same range for both human and pig. Regarding the tubular reabsorption of fluconazole, slightly higher values were obtained for pigs. Nevertheless, these results indicate the conventional pig could be an appropriate animal model to study renal drug elimination processes in humans.

The relationship between renal function and neuropathy is not well established in T1D. Our objective was to determine the relationship between renal hemodynamic function and neuropathy in adults with a ≥50-year history of T1D compared to nondiabetic controls. GFR (inulin), effective renal plasma flow (ERPF, p-aminohippurate) and modified Toronto Clinical Neuropathy Score (mTCNS) were measured in 66 patients with T1D for ≥50-years and in 73 patients without diabetes matched for age and sex. Afferent (RA), efferent (RE) arteriolar resistances and glomerular hydrostatic pressure (PGLO) were estimated using Gomez’s equations. Presence of DKD was defined as eGFRMDRD30mg/day at the screening visit. Linear regressions were applied to examine the relationships between renal function (dependent variable) and measures of neuropathy (independent variable), adjusted for age, sex and HbA1c in participants with T1D and for age and sex in nondiabetic controls. Greater mTCNS, a measure of neuropathy signs and symptoms, was associated with lower renal blood flow (β=-9.57±4.15, p=0.024) and greater RE (β=32.79±15.13, p=0.034) in adults with T1D after adjusting for age, sex and HbA1c. Participants with T1D and DKD had a greater mTCNS compared to those without DKD (6.3±5.2 vs. 3.8±3.6, p=0.016). In contrast, renal hemodynamic parameters did not associate with measures of neuropathy in nondiabetic controls in multivariable models. Neuropathy score was associated with lower renal perfusion in adults with longstanding T1D. Neurological dysfunction in the presence of diabetes may contribute to impaired renal perfusion resulting in ischemic injury in patients with T1D. Further work is required to understand factors - including the autonomic nervous system - that contribute to maintaining normal renal perfusion in longstanding T1D. Disclosure Y. Lytvyn: None. P. Bjornstad: Advisory Panel; Self; XORTX Therapeutics Inc. Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Novo Nordisk Foundation. Research Support; Self; Horizon Pharma. L. Lovblom: None. H. Liu: None. J.A. Lovshin: Consultant; Self; AstraZeneca. Consultant; Spouse/Partner; Bayer Inc. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk Inc. Research Support; Self; Novo Nordisk Inc. G. Boulet: Advisory Panel; Self; Medtronic. M. Farooqi: None. A. Weisman: None. H.A. Keenan: None. M.H. Brent: Advisory Panel; Self; Bayer AG, Novartis Pharmaceuticals Canada Inc., Roche Canada. N. Paul: None. V. Bril: Advisory Panel; Self; Alexion Pharmaceuticals, Inc., Alnylam Pharmaceuticals, Takeda Canada. Consultant; Self; Akcea Therapeutics, CSL Behring, Sanofi. Research Support; Self; Biogen, Grifols, Momenta Pharmaceuticals. B.A. Perkins: Consultant; Self; Abbott, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Other Relationship; Self; Medtronic. D. Cherney: Research Support; Self; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. Other Relationship; Self; from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS and Novo-Nordisk.

Aim: To evaluate the association of tubular markers and diabetic retinopathy (DR) in 2-DM patients with normal creatinine(Cr) and urinary microalbumin/Cr(ACR). Methods: In this study, we selected 1164 patients with 2-DM to integrate the clinical biochemical indexes and urinary alpha-1 microglobulin/Cr(A1CR), urinary immunoglobulin G/Cr(IGUCR), urinary transferrin/Cr(TRUCR), ACR and fundus examination. 274 patients underwent nuclear medicine 99mTc-EC to measure renal effective plasma flow (ERPF) and 99mTc-DTPA to measure glomerular filtration rate (GFR). They were divided into 2 groups: 52 cases with DR and 222 cases non-DR. Renal parameters were compared between 2 groups. Results: In this cross-sectional study, we fund the tubular markers: A1CR, IGUCR, and TRUCR in the DR group were higher (P < 0.001) than non-DR group, while ERPF decreased (P < 0.001). The glomerular parameters: ACR was slightly higher in the DR group, GFR had no significant difference between 2 groups (P > 0.05). Pearson correlation analysis showed A1CR had a better correlation with GFR and ERPF (P < 0.001) than ACR (P > 0.05). In a binary logistic analysis, after adjusting sex, age, course of DM, and other factors, A1CR, IGUCR, and ERPF were still independently associated with DR. Conclusion: In 2-DM patients, tubular indexes and DR were the sensitive and noninvasive biomarkers for early prediction of diabetic kidney disease. Disclosure L. Zhang: None. J. Lu: None.

Glomerular filtration rate (GFR) is a major determinant of renal energy expenditure. Animal models support a mismatch between renal oxygenation (RO2) and energy expenditure in diabetic kidney disease (DKD). The objective of this study was to compare the ratio of RO2 to GFR (RO2:GFR) in adolescents with and without type 1 diabetes (T1D) and correlate the ratio with albuminuria, effective renal plasma flow (ERPF), blood pressure, trunk mass and renal oxygen consumption. RO2 was measured by blood oxygenation level dependent (BOLD) MRI before and after 20 mg of I.V. furosemide, trunk mass by DXA, GFR by iohexol clearance, ERPF by p-aminohippurate clearance and albuminuria by urine albumin-to-creatinine ratio (UACR) in 50 adolescents with T1D (mean age 16.1±3.0 yrs, trunk mass 44.8±2.2%, HbA1c 8.6±1.2%, GFR 189±40 ml/min) and 20 non-obese controls (mean age 16.1±2.9 yrs, trunk mass 44.9±2.2%, HbA1c 5.2±0.2%, GFR 136±22 ml/min). The RO2:GFR (s/ml/min*1000) was calculated as renal oxygenation (T2*, s) divided by GFR (ml/min), and furosemide-suppressible oxygenation (FSOC) as change in RO2 in responses to furosemide. Relationships were evaluated by correlation and multivariable generalized linear regression models. RO2:GFR was 25% lower in adolescents with T1D vs. controls (mean±SD: 0.24±0.04 vs. 0.32±0.04, p Disclosure C.L. Vinovskis: None. K.J. Nadeau: None. K.L. Tommerdahl: None. P.V. Prasad: None. L. Li: None. L. Pyle: None. M. Rewers: None. M. Pragnell: None. F.H. Mahmud: Advisory Panel; Self; Eli Lilly and Company, Insulet Corporation. D.H. van Raalte: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Sanofi. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Sanofi. D. Cherney: Research Support; Self; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. Other Relationship; Self; from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS and Novo-Nordisk. R. Nelson: None. P. Bjornstad: Advisory Panel; Self; XORTX Therapeutics Inc. Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Novo Nordisk Foundation. Research Support; Self; Horizon Pharma. Funding JDRF (2-SRA-2018-627-M-B); National Institute of Diabetes and Digestive and Kidney Diseases (K23DK116720)

OBJECTIVE To compare effects of the dipeptidyl peptidase 4 (DPP-4) inhibitor linagliptin with those of a sulfonylurea on renal physiology in metformin-treated patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS In this double-blind randomized trial, 46 overweight T2DM patients without renal impairment received once-daily linagliptin (5 mg) or glimepiride (1 mg) for 8 weeks. Fasting glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippuric acid clearances. Fractional excretions, urinary damage markers, and circulating DPP-4 substrates (among others, glucagon-like peptide 1 and stromal cell–derived factor-1α [SDF-1α]) were measured. RESULTS HbA1c reductions were similar with linagliptin (–0.45 ± 0.09%) and glimepiride (–0.65 ± 0.10%) after 8 weeks (P = 0.101). Linagliptin versus glimepiride did not affect GFR, ERPF, estimated intrarenal hemodynamics, or damage markers. Only linagliptin increased fractional excretion (FE) of sodium (FENa) and potassium, without affecting FE of lithium. Linagliptin-induced change in FENa correlated with SDF-1α (R = 0.660) but not with other DPP-4 substrates. CONCLUSIONS Linagliptin does not affect fasting renal hemodynamics compared with glimepiride in T2DM patients. DPP-4 inhibition promotes modest natriuresis, possibly mediated by SDF-1α, likely distal to the macula densa.

OBJECTIVE. The purpose of this study was to compare the volume alteration and effective renal plasma flow of kidneys supplied by false lumens (FLs) with those of kidneys supplied by true lumens (TLs), to show the discrepancy in perfusion between the two lumens. We sought to corroborate malperfusion of FL-supplied kidneys with imaging characteristics observed on CT angiography. MATERIALS AND METHODS. A retrospective analysis was conducted using prospectively collected data for 87 patients with a diagnosis of residual chronic aortic dissection between 2005 and 2013 who had one kidney perfused by a TL and the other kidney perfused by a FL. RESULTS. Overall, at follow-up, FL-supplied kidneys had a mean (± SD) effective renal plasma flow (117.5 ± 42.6 vs 146.6 ± 41.0 mL/min; p = 0.004) and volume (131.1 ± 37.1 vs 146.5 ± 33.3 cm3; p = 0.004) that were lower than those of TL-supplied kidneys. Multivariate analysis revealed the presence of a proximal major inlet (odds ratio, 0.306; 95% CI, 0.103-0.910; p = 0.033) and large FL area (odds ratio, 0.104; CI, 0.012-0.880; p = 0.038) as factors protecting against malperfusion of FL-supplied kidneys. In patients with dissected renal arteries, the FL-supplied kidney had low effective renal plasma flow (mean, 88.5 ± 26.8 vs 149.6 ± 43.5 mL/min; p = 0.004) and diminished volume (mean, 120.4 ± 30.4 vs 152.3 ± 24.6 cm3; p = 0.001). CONCLUSION. In the present study, kidneys perfused by FLs showed decreased volume and reduced effective renal plasma flow during follow-up, particularly those kidneys with dissected renal arteries, a small FL area at the renal level, and lack of a proximal major inlet. Further studies are warranted to identify the clinical relevance of malperfusion in FL-supplied kidneys.

Measuring the therapeutic effects of drugs on the kidney has been dealt with elsewhere in this book, and this chapter will concentrate on the methods available for detecting their adverse effects. Space does not permit a detailed critique of each analytical method, but reference has been made to recent reviews.

Measurement of the concentration of hippurate in the inferior vena cava and renal blood samples performed in 13 subjects with normal or near‐normal serum creatinine concentrations confirmed the prediction that endogenous hippurate was cleared on a single pass through the kidney with the same avidity as that reported for infused para‐amino hippurate. This suggests that a timed urine collection without infusion would provide a measure of effective renal plasma flow. Comparison of the arteriovenous concentration differences for a panel of protein‐bound solutes identified solutes that were secreted by the renal tubule and solutes that were subjected to tubular reabsorption., The renal extraction of hippurate suggests that it can serve for the estimation of effective renal plasma flow without the need for infusion. The free (unbound) fraction of protein‐bound solutes are filtered at the glomerulus. Bound solutes are transported across the renal vascular bed, by organic anion transporters.

Objectives Increased renal sinus fat (RSF) is associated with hypertension and chronic kidney disease, but underlying mechanisms are incompletely understood. We evaluated relations between RSF and gold-standard measures of renal hemodynamics in type 2 diabetes (T2D) patients. Methods Fifty-one T2D patients [age 63 ± 7 years; BMI 31 (28–34) kg/m2; GFR 83 ± 16 mL/min/1.73 m2] underwent MRI-scanning to quantify RSF volume, and subcutaneous and visceral adipose tissue compartments (SAT and VAT, respectively). GFR and effective renal plasma flow (ERPF) were determined by inulin and PAH clearances, respectively. Effective renal vascular resistance (ERVR) was calculated. Results RSF correlated negatively with GFR (r = − 0.38; p = 0.006) and ERPF (r = − 0.38; p = 0.006) and positively with mean arterial pressure (MAP) (r = 0.29; p = 0.039) and ERVR (r = 0.45, p = 0.001), which persisted after adjustment for VAT, MAP, sex, and BMI. After correction for age, ERVR remained significantly related to RSF. Conclusions In T2D patients, higher RSF volume was negatively associated to GFR. In addition, RSF volume was positively associated with increased renal vascular resistance, which may mediate hypertension and CKD development. Further research is needed to investigate how RSF may alter the (afferent) vascular resistance of the renal vasculature. Electronic supplementary material The online version of this article (10.1007/s10334-019-00773-z) contains supplementary material, which is available to authorized users.

OBJECTIVE Our aim was to define the relationships between plasma biomarkers of kidney injury and intrarenal haemodynamic function (glomerular filtration rate [GFR], effective renal plasma flow [ERPF], renal vascular resistance [RVR]) in adults with type 1 diabetes (T1D). METHODS The study sample comprised patients with longstanding T1D (duration ≥50 years), among whom 44 were diabetic kidney disease (DKD) resistors (eGFR >60 mL/min/1.73 m2 and

AIMS: Copeptin, a surrogate of vasopressin, is elevated in type 1 diabetes (T1D) and predicts kidney disease and cardiovascular mortality. Given the cardiorenal protective effects of SGLT2 inhibition (SGLT2i), our aim was to examine: 1) the relationship between serum copeptin, metabolic, renal and systemic hemodynamic parameters in adults with T1D; and 2) serum copeptin after SGLT2i with empagliflozin. MATERIALS AND METHODS: In this post-hoc, exploratory analysis, serum copeptin, glomerular filtration rate (GFR(Inulin)), effective renal plasma flow (ERPF(PAH)), plasma renin angiotensin aldosterone system markers, HbA1c, 24-hour urine volume and sodium excretion were measured in 40 participants with T1D (24.3±5.1 years) during eu- and hyperglycemia before and after 8 weeks of 25 mg of daily empagliflozin. RESULTS: Higher baseline copeptin correlated with higher HbA1c, lower 24-hour urine volume and sodium excretion, after correcting for age, sex, systolic blood pressure, and HbA1c. Copeptin concentrations increased in response to empagliflozin under euglycemia (4.1±2.1 to 5.1±2.8 pmol/L, p=0.0053) and hyperglycemia (3.3±1.4 to 5.6±2.8 pmol/L, p

AIM Elevated fractional excretion of magnesium (FEMg) is a noninvasive biomarker of kidney damage, but its association with kidney functional parameters in nondiabetic chronic kidney disease (CKD) patients has not been sufficiently explored thus far. METHODS We enrolled 111 adult patients with nondiabetic CKD and 30 controls. To precisely investigate kidney function, the following parameters were assessed measured glomerular filtration rate (mGFR), effective renal plasma flow (ERPF), Cystatin C, albuminuria, and fractional excretion of magnesium (FEMg). All the CKD patients were divided into two groups according to the values of mGFR (mL/min/1.73m2): the first group consisted of those with GFR≥ 60 mL/min/1.73m2, whereas the second group included those with GFR< 60 mL/min/1.73m2. RESULTS FEMg (%) was significantly higher in the group of nondiabetic patients with CKD compared to the healthy subjects [6.3 vs. 5.3 %, P=0.013]. There was also significant difference in the value of FEMg between the first and second groups of CKD patients. Increased FEMg was significantly correlated with all the investigated kidney function parameters, mGFR, ERPF, Cystatin C and albuminuria (r=-0.62; r=-0.60; r=0.77; r=0.39; p

The aim was to assess the effect of standard fixed-dose protocol of 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in patients with borderline low renal function of one parameter (glomerular filtration rate [GFR], effective renal plasma flow [ERPF] or serum creatinine), that was discordant with the remaining parameters and determine the feasibility of this procedure in this group of patients. Renal toxicity of PRRT is a routine issue or concern for such cases. We compared different renal parameters used for pretherapy assessment in patients with borderline low single parameter at baseline and their potential significance with regards to deterioration of renal function subsequently. A retrospective analysis was performed in patients of metastatic neuroendocrine tumors who received therapeutic 177Lu-DOTATATE (using standard fixed-dose protocol) and had borderline compromised renal parameter values (either of GFR/ERPF/serum creatinine). Filtration fraction (FF) was also estimated in each case and all renal parameters were correlated using kappa statistics. The characteristics of cases showing progressive worsening of renal function in the follow-ups were also studied. A total of 15 patients (11 males, 4 females; age range: 32–75 years) were selected among a population of 450 patients. The follow-up duration ranged from 10 to 48 months and administered cumulative activity ranged 9.9–31.3 GBq (2–5 cycles). Based on the parameter characteristics, the study population was divided into following four groups: (a) patients with reduced GFR and maintained ERPF and normal serum creatinine (n = 3); (b) patients with reduced ERPF with maintained GFR and borderline elevated/normal serum creatinine (n = 3); (c) patients with both reduced GFR and ERPF and maintained serum creatinine (n = 1); (d) patients with compromised single kidney function (n = 5). A total of four patients were found who had normal baseline renal function values but showed progressive worsening in the subsequent period. There was no significant change in renal parameters during the follow-up in both Groups a and c. Two patients of Group b demonstrated well-maintained other renal parameters, whereas in 1 patient, there was the evidence of renal toxicity with gradual fall of GFR and ERPF and progressive increase in serum creatinine level. In patients with compromised single kidney function at baseline (Group d), there was overall maintained normal renal parameters, whereas 3 of 5 (60%) showed the increase of FF of the affected kidney. Interestingly, a compensatory hyperfunction was noted in the contralateral kidney. PRRT with 177Lu-DOTATATE is feasible and can be considered in patients with reduced GFR and with maintained ERPF and normal serum creatinine and also in the presence of single compromised parameter if the other two are normal; however, these patients need critical monitoring.

Burst Wave Lithotripsy (BWL) is a new stone treatment that utilizes ultrasound to fracture renal calculi. However, it is not known if BWL alters renal function, so we tested if a clinical dose of BWL impacts glomerular filtration rate (GFR) or kidney blood flow. Treatment consisted of placing each pig (32–42 kg) on its side, locating the lower pole of the right kidney, and treating that kidney with a BWL dose of 18,000 ultrasound pulses at 10Hz, 20 cycles/pulse and a peak negative pressure of −7 MPa (n = 6). Six additional pigs were used as sham controls. Inulin and para-aminohippuric acid (PAH) were infused into the pigs with blood and urine samples being collected both before and 1-h after BWL treatment. The concentrations of inulin and PAH were determined in the samples and used to calculate GFR and effective renal plasma flow (eRPF). For the BWL treated group, GFR and eRPF did not change after BWL exposure (−6.7 ± 7.2% for GFR, −10.9 ± 5.5% for eRPF), and this response was like the sham control group ( P = 0.23 for GFR, P = 0.08 for eRPF). A typical clinical dose of BWL caused no change in renal function. [Work supported by NIH, Grant P01 DK43881.]

The literature review examines the historical aspects and key issues of the clinical application of new radiopharmaceuticals (RF) for positron emission tomography (PET). The gold standard for measuring effective renal plasma flow is p-[18F] fluorohippurate ([18F] PFH) due to its structure close to p-aminoimpurate one. [18F] FDS is a new potential tracer for the diagnosis of acute renal failure. PET tracers Re (CO) 3 ([18F] FEDA) and [18F] PFH are effective as surrogate markers for the selection of patients for endoradiotherapy with a potential nephrotoxic profile, in patients with hematopoietic malignant tumours and prostate cancer. PET imaging of the kidneys and urinary system can be of additional importance in difficult clinical situations and provide effective support in making diagnostic decisions, in particular in paediatric patients. Further scientific diagnostic research should focus on the synthesis of new radiopharmaceuticals that will have ideal properties for renal functional imaging, low binding to plasma proteins, high metabolic stability and low hepatobiliary clearance., В статье рассмотрены исторические аспекты и ключевые вопросы клинического применения новых радиофармпрепаратов (РФП) для позитронно-эмиссионной томографии (ПЭТ). Золотым стандартом для измерения эффективного ренального плазмотока является p-[18F] фторгиппурат ([18F] PFH) благодаря структуре, схожей с р-аминоимпуратом. [18F] FDS — новый потенциальный трейсер для диагностики острой почечной недостаточности. ПЭТ-трейсеры Re (CO) 3 ([18F] FEDA) и [18F] PFH являются эффективными суррогатными маркерами с целью отбора пациентов для эндорадиотерапии с потенциальным нефротоксическим профилем, у больных с гемопоэтическими злокачественными опухолями, раком предстательной железы. ПЭТ-визуализация почек и мочевыделительной системы может иметь дополнительное значение в сложных клинических ситуациях и обеспечивать эффективную поддержку в принятии диагностических решений, в частности у педиатрических пациентов. Дальнейший научный диагностический поиск должен быть направлен на синтезирование новых РФП, которые будут иметь идеальные свойства для почечной функциональной визуализации, низкое связывание с белками плазмы, высокую метаболическую стабильность и низкий гепатобилиарный клиренс., У статті розглянуто історичні аспекти та ключові питання клінічного застосування нових радіофармпрепаратів (РФП) для позитронно-емісійної томографії (ПЕТ). Золотим стандартом для вимірювання ефективного ренального плазмотоку є p-[18F] фторгіпурат ([18F] PFH) завдяки структурі, що подібна до р-аміноімпурату. [18F] FDS — новий потенціальний трейсер для діагностики гострої ниркової недостатності. ПЕТ-трейсери Re (CO) 3 ([18F] FEDA) і [18F] PFH є ефективними сурогатними маркерами з метою відбору пацієнтів для ендорадіотерапії з потенційним нефротоксичним профілем, у хворих на гемопоетичні злоякісні пухлини, рак передміхурової залози. ПЕТ-візуалізація нирок і сечовидільної системи може мати додаткове значення у складних клінічних ситуаціях і забезпечувати ефективну підтримку у прийнятті діагностичних рішень, зокрема у педіатричних пацієнтів. Подальший науковий діагностичний пошук повинен бути спрямований на синтезування нових РФП, які матимуть ідеальні властивості для ренальної функціональної візуалізації, низьке зв’язування з білками плазми, високу метаболічну стабільність та низький гепатобіліарний кліренс.

Background Functional outcome is an important issue in nephron-sparing surgery. Various nephrometries have been developed to predict renal function preservation. The aim of this study was to examine the applicability of R.E.N.A.L., PADUA, C-index, and mathematical tumor contact surface area (CSA) in predicting ipsilateral renal function after partial nephrectomy using radio-isotope scans. Methods We performed this retrospective study in patients who underwent partial nephrectomy between May 2013 and April 2017, and used abdominopelvic computerized tomography or magnetic resonance imaging to obtain R.E.N.A.L., C-index, and CSA. Renal function was measured by 99mTc mercaptoacetyltriglycine (MAG3). We evaluated correlations between nephrometries and perioperative parameters, and comparatively analyzed different nephrometries to determine the predictive ability in the percent change of effective renal plasma flow of the affected kidney. Results Three, two, and 35 patients received partial nephrectomy in open, laparoscopic, and robotic approaches, respectively. The median (IQR) tumor size was 3.13 (2.4) cm. The median (IQR) R.E.N.A.L., PADUA, C-index, and CSA scores were 7 (3), 8 (2), 2.01 (1.87), and 14.14 (19.25) cm2, respectively. Spearman correlation analysis showed that four nephrometries were correlated with each other. The strongest correlations were between CSA and C-index (coefficient: − 0.885, p

Introduction: The kidney’s capacity to increase its glomerular filtration rate (GFR) in response to a higher functional demand is known as the renal functional reserve (RFR). Good short-term outcomes after living kidney donation have led to more acceptance of borderline donors (with hypertension, obesity, older age) due the ongoing shortage of donor organs. Given recent concerns about increased long-term risk in some donor subgroups, better donor stratification is needed. Measurement of RFR could inform assessment of donor risk. Methods: A systematic literature review of studies that assessed RFR in donors pre- and/or post-donation was performed. Given study heterogeneity, descriptive analysis and narrative synthesis was conducted. Results: Sixteen of 3250 identified studies published between 1956 and 2019 met inclusion criteria. Most studies were cross-sectional and conducted before (n = 8) and/or after (n = 16) kidney donation. Methods for measurement of GFR, effective renal plasma flow (ERPF) and RFR were not standardized. Changes in filtration fraction (FF) and ERPF relative to GFR observed after donation varied depending on stimulus used to induce RFR. Overall, RFR fell after donation; however, over the shorter term, RFR was largely preserved in young healthy donors. RFR was more significantly reduced in donors with hypertension, obesity, or older age. Conclusion: Existing data suggest possible blunting of RFR post-donation in older, obese, and hypertensive donors, which may represent increased single-nephron GFR at baseline. The long-term implications of these changes deserve further study to determine utility in informing selection of borderline kidney donors. Keywords: borderline kidney donors, glomerular filtration rate, kidney function, living kidney donation, nephron, renal functional reserve

Elevated copeptin, a stable surrogate of vasopressin, is recognized to be higher in T1D and predicts diabetic kidney disease and cardiovascular (CV) mortality. Vasopressin increases renal oxygen consumption through enhanced sodium reabsorption and may result in renal hypoxia. Given the natriuretic and cardiorenal protective effects of SGLT2 inhibition (SGLT2i) in clinical trials, our aim was to: 1) examine serum copeptin in adults with T1D after SGLT2i with empagliflozin (EMPA) for 8-weeks; and 2) determine the relationship between copeptin and metabolic, renal and system hemodynamic parameters. In this post hoc, exploratory analysis, serum copeptin concentration, glomerular filtration rate (GFR) by inulin clearance, effective renal plasma flow (ERPF) by PAH clearance, vascular stiffness parameters, plasma RAAS markers, HbA1c, 24-hour urine volume and sodium and glucose excretion were measured in 40 participants with T1D (24.1±5.0 years, HbA1c 8.0±0.9%) during eu- and hyperglycemia at baseline and after 25 mg of daily EMPA. Copeptin concentrations increased under both eu- and hyperglycemic conditions (4.0±2.1 to 5.1±6.0 pmol/L, p=0.005 and p SGLT2i increased serum copeptin concentrations, which positively correlated with HbA1c and inversely with urine output and natriuresis, but not with renal or system hemodynamic parameters. Further work is required to evaluate the clinical implications of elevated copeptin with SGLT2i; whether it is simply a marker of diuresis or may contribute to CV disease long-term. Disclosure Y. Lytvyn: None. P. Bjornstad: Advisory Panel; Self; Horizon, XORTX. Consultant; Self; Bayer US, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company. A. Katz: None. S.K. Singh: None. L.C. Godoy: None. L.T. Chung: None. C.L. Vinovskis: None. B.A. Perkins: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk Inc., Sanofi. D. Cherney: Other Relationship; Self; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Prometic Life Sciences Inc., Sanofi.

Objective: To determine the ability of renal contrast-enhanced ultrasonography (CEUS) to detect acute drug-induced changes in renal perfusion (using the glucagon-like peptide (GLP)-1 receptor agonist exenatide and nitric oxide [NO]-synthase inhibitor L-NG-monomethyl arginine [l-NMMA]), and assess its correlation with gold standard-measured effective renal plasma flow in humans. Methods: In this prespecified exploratory analysis of a placebo-controlled cross-over study, renal hemodynamics was assessed in 10 healthy overweight males (aged 20-27 years; BMI 26-31 kg/m2) over two separate testing days; during placebo (isotonic saline) and subsequent exenatide infusion (Day-A), and during l-NMMA, and subsequent exenatide plus l-NMMA infusion (Day-B). Renal cortical microvascular blood flow was estimated following microbubble infusion and CEUS destruction-refilling-sequences. Renal cortical microvascular blood flow was compared with simultaneously measured effective renal plasma flow in humans, derived from para-aminohippuric acid-clearance methodology. Results: On Day-A, effective renal plasma flow increased by 68 [26-197] mL/min/1.73 m2 during exenatide vs placebo infusion (+17%; P =.015). In parallel, exenatide increased renal cortical microvascular blood flow, from 2.42 × 10−4 [6.54 × 10−5-4.66 × 10−4] AU to 4.65 × 10−4 [2.96 × 10−4-7.74 × 10−4] AU (+92%; P =.027). On Day-B, effective renal plasma flow and renal cortical microvascular blood flow were reduced by l-NMMA, with no significant effect of concomitant exenatide on renal hemodynamic-indices assessed by either technique. Effective renal plasma flow correlated with renal cortical microvascular blood flow on Day-A (r =.533; P =.027); no correlation was found on Day-B. Conclusions: Contrast-enhanced ultrasonography can detect acute drug-induced changes human renal hemodynamics. CEUS-assessed renal cortical microvascular blood flow moderately associates with effective renal plasma flow, particularly when perfusion is in normal-to-high range. Renal CEUS cannot replace effective renal plasma flow measurements, but may be a complementary tool to characterize regional kidney perfusion.

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., SUMMARY AT A GLANCE This paper, which explored the relationship between plasma uric acid (UA) and renal haemodynamics in patients with type 2 diabetes without overt kidney disease showed that higher plasma UA is associated with lower glomerular filtration rate and effective renal plasma flow but higher effective renal vascular resistance, which may contribute to glomerular dysfunction due to impairment in kidney perfusion.

The preterm-born adult population is ever increasing following improved survival rates of premature births. We conducted a meta-analysis to investigate long-term effects of preterm birth on renal function in preterm-born survivors. We searched PubMed and EMBASE to identify studies that compared renal function in preterm-born survivors and full-term-born controls, published until 2 February 2019. A random effects model with standardized mean difference (SMD) was used for meta-analyses. Heterogeneity of the studies was evaluated using Higgin’s I2 statistics. Risk of bias was assessed using the Newcastle–Ottawa quality assessment scale. Of a total of 24,388 articles screened, 27 articles were finally included. Compared to full-term-born controls, glomerular filtration rate and effective renal plasma flow were significantly decreased in preterm survivors (SMD −0.54, 95% confidence interval (CI), −0.85 to −0.22, p = 0.0008, SMD −0.39, 95% CI, −0.74 to −0.04, p = 0.03, respectively). Length and volume of the kidneys were significantly decreased in the preterm group compared to the full-term controls (SMD −0.73, 95% CI, −1.04 to −0.41, p &lt, 0.001, SMD −0.82, 95% CI, −1.05 to −0.60, p &lt, 0.001, respectively). However, serum levels of blood urea nitrogen, creatinine, and cystatin C showed no significant difference. The urine microalbumin to creatinine ratio was significantly increased in the preterm group. Both systolic and diastolic blood pressures were also significantly elevated in the preterm group, although the plasma renin level did not differ. This meta-analysis demonstrates that preterm-born survivors may be subject to decreased glomerular filtration, increased albuminuria, decreased kidney size and volume, and hypertension even though their laboratory results may not yet deteriorate.

Diabetic kidney disease (DKD) remains the leading cause of end-stage renal disease. A major challenge in preventing DKD is the difficulty in identifying high-risk patients at a preclinical stage. Existing methods that are used to assess renal function, including albuminuria and eGFR, do not give detailed insight into the location of the renal hemodynamic effects of pharmacological agents at the segmental level. To gain additional information about the intrarenal circulation in vivo in humans, equations were developed by Gomez et al. in the 1950s. These equations used measurements of glomerular filtration rate, renal blood flow, effective renal plasma flow, renal vascular resistance, hematocrit, and serum protein to calculate afferent and efferent arteriolar resistances, glomerular hydrostatic pressure, and filtration pressure. The Gomez equations are, however, indirect and based on physiological assumptions derived from animal models, which may not hold true in human pathophysiology, including the assumption of a normal gross filtration coefficient and not considering changes in intratubular pressure that may affect the pressure gradient across the glomerular capillaries. Nevertheless, the equations have the potential to improve researchers' ability to identify early preclinical changes in renal hemodynamic function in patients with a variety of conditions, including DKD, thereby offering potential in mechanistic human research studies. In this review, we focus on the application of Gomez' equations and summarize the potential and limitations of these techniques in DKD research. We also summarize illustrative data derived from Gomez' equations in patients with type 1 and type 2 diabetes and hypertension.

Purpose: Urinary biomarkers of renal injury urinary may identify loss of renal function following nephron-sparing surgery (NSS). This study was designed to evaluate whether urinary l-type fatty acid-binding protein (l-FABP) is an early biomarker of loss of renal function after NSS. Specifically, the kinetics of urinary l-FABP level after NSS and its correlation with factors related to ischemic renal injury were analyzed. Methods: This study prospectively evaluated 18 patients who underwent NSS between July and December 2014, including 12 who underwent laparoscopic and six who underwent robot-assisted partial nephrectomy. Urinary l-FABP concentrations were measured preoperatively and 1, 2, 3, 6, 12, 24, 48, and 72 h after renal artery declamping. Loss of renal function loss was calculated by comparing the effective renal plasma flow, as determined by 99mTc-mercaptoacetyltriglycine (MAG3) clearance, on the operated and normal sides. The decrease in estimated glomerular filtration rate from before surgery to six months after surgery was also measured. Results: Urinary l-FABP concentration peaked within 2 h of declamping, which may quantify nephron damage caused by ischemia. The decrease in MAG3 reduction ratio correlated with both the ischemia time and peak urinary l-FABP concentration. Peak urinary l-FABP concentration showed a significant correlation with MAG3 reduction ratio. Conclusions: l-FABP is a suitable urinary biomarker for predicting the extent of ischemic renal injury.

Many patients with hepatorenal syndrome (HRS) end up receiving a combined liver and kidney transplant (CKLT) with preservation of native kidneys, specially type 1 HRS since is characterizes by a very rapid deterioration of renal function. Eventually, most of the patients regain renal function, but it is unknown if this is due to the transplanted kidney, the recovery of native renal function, or both. The aim of this study is to evaluate if there is recovery of native renal function in patients with HRS following CKLT. 22 patients (16 men; 6 women) with history of HRS and status post CKLT were studied. Mercapto-acetyltriglycine-3 renograms in the anterior and posterior views with the three kidneys in the field of view were simultaneously acquired. The renograms were analyzed by creating regions of interest around the transplanted and native kidneys. Relative contribution to the renal function, clearance, and effective renal plasma flow for the transplanted and native kidneys were obtained. 1/22 (4.5%) patients presented with a very poor functioning transplanted kidney, in 15/22 (68%) cases the combined native renal function was markedly poorer than the transplanted renal function and in 6/22 (27%) native kidneys showed a contribution to the renal function similar to the transplanted kidney. In conclusion, our series show that around 32% of the HRS patients recovered their native renal function after CKLT. Identification of common factors that affect recovery of native renal function may help to avoid unnecessary renal transplants, significantly reducing morbidity and cost, while facilitating a reallocation of scarce donor resources.

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 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 60 group (P 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 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.

Background: Delayed graft function (DGF) could worsen early and long-term outcomes of kidney transplantation (KT). DGF is caused by several pre-transplantation and perioperative factors in both donors and recipients. At present, there are no biomarkers or tests during the immediate post-KT period that can accurately predict the development of DGF. Materials and methods: This prospective study was conducted in deceased donor KT (DDKT) at King Chulalongkorn Memorial Hospital, Thailand. All recipients underwent furosemide stress test (FST) by receiving a single dose of intravenous furosemide, 1.5 mg/kg at 3 h after allograft reperfusion. We determined the correlations between DGF (requiring dialysis within the first week after transplantation) and the values of urine volume recorded hourly after FST until 6 h, the parameters of postoperative dynamic tests, including resistive index (RI) of renal arteries and effective renal plasma flow (ERPF), and urine neutrophil gelatinase-associated lipocalin (NGAL). Results: Of the 59 total DDKT recipients enrolled, 24 developed DGF. The FST is a more accurate biomarker than urine NGAL, RI of renal arteries, and ERPF in the prediction of DGF. The 4-h urine volume less than 350 mL (FST non-responsive) was the best cut-off value in predicting DGF with 87.5% sensitivity, 82.9% specificity, and 82.5% accuracy. Multiple logistic regression analyses showed an odds ratio of 0.993 (0.986–0.999, p = 0.035) for the 4-h urine volume to predict DGF. Conclusions: The FST is a simple and accurate biomarker for predicting DGF in early post-KT period. Close monitoring and well prepared dialysis are suggested in patients with urine volume < 350 mL after 4 h of FST. The FST non-responsive patients could be the target for further DGF preventive intervention. ClinicalTrials.gov identifier: NCT03071536.

Objectives The tyrosine kinase inhibitor crizotinib may affect renal function. The mechanism of this effect is not understood. We aimed to get more insight by measuring renal hemodynamics in patients treated with crizotinib. Materials and methods Renal hemodynamics (i.e. glomerular filtration rate and effective renal plasma flow) were measured with radioactive tracers in three patients with stage IV non small-cell lung cancer during treatment with crizotinib. The results were compared with simultaneous creatinine based renal function measurements in the same patients. Results Patients had been treated with crizotinib between 155 and 320 days at the first measurement. In one patient the measurement was repeated after a total of one year and two months of treatment. All patients had been treated with chemotherapy containing cisplatin before. In these patients true glomerular filtration rate was 64–83% higher than estimated by creatinine based measurements. Filtration fraction, a measure of glomerular pressure, was increased in all three patients. The glomerular pressure was even further increased in a follow-up measurement. Conclusion Creatinine-based estimates of GFR on crizotinib may underestimate the true GFR. However, evidence of increased glomerular pressure may increase risk of long term true nephrotoxicity.

OBJECTIVE Central adiposity is considered to be an important cardiorenal risk factor in the general population and in type 1 diabetes. We sought to determine the relationship between central adiposity and intrarenal hemodynamic function in adults with long-standing type 1 diabetes with and without diabetic nephropathy (DN). RESEARCH DESIGN AND METHODS Patients with type 1 diabetes (n = 66, duration ≥50 years) and age-/sex-matched control subjects (n = 73) were studied. The cohort was stratified into 44 DN Resistors (estimated glomerular filtration rate [eGFR] >60 mL/min/1.73 m2 and RESULTS Whereas measures of adiposity did not associate with GFRINULIN or ERPFPAH in healthy control subjects, trunk fat mass inversely correlated with GFRINULIN (r = −0.46, P < 0.0001) and ERPFPAH (r = −0.31, P = 0.01) and positively correlated with RVR (r = 0.53, P = 0.0003) in type 1 diabetes. In analyses stratified by DN status, greater central adiposity related to lower GFRINULIN values in DN and DN Resistors, but the relationships between central adiposity and ERPFPAH and RVR were attenuated and/or reversed in patients with DN compared with DN Resistors. CONCLUSIONS The adiposity-intrarenal hemodynamic function relationship may be modified by the presence of type 1 diabetes and DN, requiring further study of the mechanisms by which adiposity influences renal hemodynamic function.

Aldosterone blockade confers substantial cardiovascular and renal protection. The effects of aldosterone on mineralocorticoid receptors (MR) expressed in endothelial cells (EC) within the renal vasculature have not been delineated. We hypothesized that lack of MR in EC may be protective in renal vasculature and examined this by ablating the Nr3c2 gene in endothelial cells (EC-MR) in mice. Blood pressure, heart rate and PAH clearance were measured using indwelling catheters in conscious mice. The role of the MR in EC on contraction and relaxation was investigated in the renal artery and in perfused afferent arterioles. Urinary sodium excretion was determined by use of metabolic cages. EC-MR transgenics had markedly decreased MR expression in isolated aortic endothelial cells as compared to littermates (WT). Blood pressure and effective renal plasma flow at baseline and following AngII infusion was similar between groups. No differences in contraction and relaxation were observed between WT and EC-MR KO in isolated renal arteries during baseline or following 2 or 4 weeks of AngII infusion. The constriction or dilatations of afferent arterioles between genotypes were not different. No changes were found between the groups with respect to urinary excretion of sodium after 4 weeks of AngII infusion, or in urinary albumin excretion and kidney morphology. In conclusion, deletion of the EC-MR does not confer protection towards the development of hypertension, endothelial dysfunction of renal arteries or renal function following prolonged AngII-infusion.

BackgroundHyperglycaemia impairs tubulo-glomerular feedback. We tested whether variable tubulo-glomerular feedback during hyperglycaemia contributes to renal risk heterogeneity seen in Type 1 diabetes.MethodsDuring the period 1990–92, we studied the tubulo-glomerular feedback in Type 1 diabetic patients at high or low renal risk [21 of 54 with glomerular hyperfiltration and/or microalbuminuria against 11 of 55 with normal glomerular filtration rate (GFR) and urinary albumin despite uncontrolled diabetes]. The GFR, effective renal plasma flow, mean arterial pressure and fractional reabsorptions of glucose, osmols, sodium and lithium were measured sequentially during normo- and hyperglycaemia. All patients were followed up until 2016 for incident proteinuria, estimated GFR ResultsGlycaemia increased from 6.1 ± 1.3 to 15.1 ± 1.9 mmol/L in both high-risk and low-risk patients. Glycosuria was lower in the high- versus low-risk patients: 0.34 ± 0.25 versus 0.64 ± 0.44 mmol/min (P = 0.03). Both groups displayed similar kidney function during normoglycaemia. Hyperglycaemia increased more importantly GFR and fractional reabsorptions, and pre-glomerular vasodilatation in the high- than in the low-risk patients (all P ConclusionsReduced tubulo-glomerular feedback and glycosuria during hyperglycaemia indicate high renal risk for Type 1 diabetic patients. Inter-individual variability in tubulo-glomerular feedback activity determines renal risk in Type 1 diabetes.

Aim: To determine whether lixisenatide, a prandial short-acting glucagon-like peptide receptor agonist (GLP-1RA), ameliorates postprandial glomerular hyperfiltration in patients with type 2 diabetes mellitus (T2DM) compared with insulin-glulisine (iGlu). Methods: Postprandial renal haemodynamic effects of 8-week treatment with lixisenatide 20 µg vs once-daily titrated iGlu were measured in 35 overweight patients with T2DM inadequately controlled on insulin-glargine, with or without metformin [mean ± SD age 62 ± 7 years, HbA1c 8.0% ± 0.9%, estimated glomerular filtration rate (GFR) 85 ± 12 mL/min/1.73 m2, median (IQR) urinary albumin/creatinine ratio 1.5 (0.9-3.0) mg/mmol]. After a standardised breakfast, GFR (primary endpoint) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippuric acid renal clearance, respectively, based on timed urine sampling. Intrarenal haemodynamic functions were estimated using Gomez equations. Results: Compared with iGlu, lixisenatide did not affect GFR [+0.1 mL/min/1.73 m2 (95% CI −9 to 9)], ERPF [−17 mL/min/1.73 m2 (−61 to 26)], other (intra-)renal haemodynamics or renal damage markers, but increased fractional sodium excretion [+0.25% (0.09-0.41)] and urinary pH [+0.7 (0.3-1.2)]. Plasma renin, angiotensin-II and aldosterone were unchanged. Lixisenatide and iGlu reduced HbA1c similarly, by 0.8% ± 0.1% and 0.6% ± 0.1%, respectively, while postprandial glucose was lower with lixisenatide (P =.002). Compared with iGlu, lixisenatide reduced bodyweight [−1.4 kg (−2.5 to −0.2)] and increased postprandial mean arterial pressure [+9 mm Hg (4-14)]. Conclusion: Eight-week lixisenatide treatment does not affect postprandial (intra-)renal haemodynamics compared with iGlu when added to insulin-glargine in patients with T2DM without overt nephropathy. Prolonged lixisenatide treatment has a sustained natriuretic effect, which is in contrast to previous reports on long-acting GLP-1RA, reduces body weight and increases postprandial blood pressure compared with iGlu. Trial registration: ClinicalTrials.gov identifier NCT02276196.

Obstructive sleep apnea (OSA) and nocturnal hypoxemia are associated with chronic kidney disease and up-regulation of the renin-angiotensin system (RAS), which is deleterious to renal function. The extent to which the magnitude of RAS activation is influenced by the severity of nocturnal hypoxemia and comorbid obesity has not been determined.To determine the association between the severity of nocturnal hypoxemia and RAS activity and whether this is independent of obesity in patients with OSA.Effective renal plasma flow (ERPF) response to angiotensin II (AngII) challenge, a marker of renal RAS activity, was measured by paraaminohippurate clearance technique in 31 OSA subjects (respiratory disturbance index, 51 ± 25 h(-1)), stratified according to nocturnal hypoxemia status (mean nocturnal SaO2, ≥90% [moderate hypoxemia] or90% [severe hypoxemia]) and 13 obese control subjects.Compared with control subjects, OSA subjects demonstrated decreased renovascular sensitivity (ERPF, -153 ± 79 vs. -283 ± 31 ml/min; P = 0.004) (filtration fraction, 5.4 ± 3.8 vs. 7.1 ± 2.6%; P = 0.0025) in response to 60 minutes of AngII challenge (mean ± SD; all P values OSA vs. control). The fall in ERPF in response to AngII was less in patients with severe hypoxemia compared with those with moderate hypoxemia (P = 0.001) and obese control subjects after 30 minutes (P 0.001) and 60 minutes (P 0.001) of AngII challenge, reflecting more augmented renal RAS activity. Severity of hypoxemia was not associated with the blood pressure or the systemic circulating RAS component response to AngII.The severity of nocturnal hypoxemia influences the magnitude of renal, but not the systemic, RAS activation independently of obesity in patients with OSA.

BACKGROUND: Animal studies suggest that progression of chronic kidney disease (CKD) is related to renal hypoxia. With renal blood supply determining oxygen delivery and sodium absorption being the main contributor to oxygen consumption, we describe the relationship between renal oxygenation, renal artery blood flow, and sodium absorption in patients with CKD and healthy controls.STUDY DESIGN: Cross-sectional study.SETTING & PARTICIPANTS: 62 stable patients with CKD stages 3 to 4 (mean age, 61±13 [SD] years) and 24 age- and sex-matched controls.PREDICTORS: CKD versus control status.OUTCOMES: Renal artery blood flow, tissue oxygenation (relative changes in deoxyhemoglobin concentration of the renal medulla [MR2*] and cortex [CR2*]), and sodium absorption.MEASUREMENTS: Renal artery blood flow was determined by phase-contrast magnetic resonance imaging (MRI); MR2* and CR2* were determined by blood oxygen level-dependent MRI. Ultrafiltered and reabsorbed sodium were determined from measured glomerular filtration rate (mGFR) and 24-hour urine collections.RESULTS: mGFR in patients was 37% that of controls (36±15 vs 97±23mL/min/1.73m(2); P < 0.001), and reabsorbed sodium was 37% that of controls (6.9 vs 19.1mol/24 h; P < 0.001). Single-kidney patient renal artery blood flow was 72% that of controls (319 vs 443mL/min; P < 0.001). Glomerular filtration fraction was 9% in patients and 18% in controls (P < 0.001). Patients and controls had similar CR2* (13.4 vs 13.3s(-1)) and medullary MR2* (26.4 vs 26.5s(-1)) values. Linear regression analysis demonstrated no associations between R2* and renal artery blood flow or sodium absorption. Increasing arterial blood oxygen tension by breathing 100% oxygen had very small effects on CR2*, but reduced MR2* in both groups.LIMITATIONS: Only renal artery blood flow was determined and thus regional perfusion could not be related to CR2* or MR2*.CONCLUSIONS: In CKD, reductions of mGFR and reabsorbed sodium are more than double that of renal artery blood flow, whereas cortical and medullary oxygenation are within the range of healthy persons. Reduction in glomerular filtration fraction may prevent renal hypoxia in CKD.

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

The human kidney provides essential regulatory and excretory functions. Body water content, plasma electrolyte composition and plasma pH are all under the regulatory control of the kidney. In addition, the kidney provides a path of excretion for blood-borne, water-soluble, low-molecular-weight compounds. These include the end-products of protein metabolism, such as urea and creatinine, as well as foreign compounds with similar physicochemical characteristics and their metabolites. Endocrine activity of the human kidney includes the secretion of the hormones erythropoietin and renin and the activation of vitamin D by hydroxylation to its 1,25-dihydroxycholecalciferol form. The renal blood flow is immense, constituting 20–25% of resting cardiac output. The glomeruli form 170–200 litres of ultrafiltrate per day and the selective reabsorption of water and solutes results in the final formation of approximately 1.5 litres of urine. Here, commonly used laboratory tests of renal function are discussed, including glomerular filtration rate (GFR), creatinine clearance, serum creatinine concentration estimation of GFR, serum urea concentration, novel measures of renal function, emerging biomarkers for acute kidney injury, urinalysis, free water clearance and endocrine changes in renal disease. It must be noted, however, that these tests require a clinical assessment of the patient to allow meaningful interpretation.

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.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.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.A higher plasma concentration of ET-1 is independently associated with a decreased value of GFR in patients with diabetic nephropathy.

Renal plasma flow (RPF) (derived from renal blood flow, RBF) and glomerular filtration rate (GFR) allow the determination of the filtration fraction (FF), which may have a role as a non-invasive renal biomarker. This is a hypothesis-generating pilot study assessing the effect of nephrectomy on renal function in healthy kidney donors.Eight living kidney donors underwent arterial spin labelling (ASL) magnetic resonance imaging (MRI) and GFR measurement prior to and 1 year after nephrectomy. Chromium-51 labelled ethylenediamine tetraacetic acid ((51)Cr-EDTA) with multi-blood sampling was undertaken and GFR calculated. The RBF and GFR obtained were used to calculate FF.All donors showed an increase in single kidney GFR of 24 - 75 %, and all but two showed an increase in FF (-7 to +52 %) after nephrectomy. The increase in RBF, and hence RPF, post-nephrectomy was not as great as the increase in GFR in seven out of eight donors. As with any pilot study, the small number of donors and their relatively narrow age range are potential limiting factors.The ability to measure RBF, and hence RPF, non-invasively, coupled with GFR measurement, allows calculation of FF, a biomarker that might provide a sensitive indicator of loss of renal reserve in potential donors.• Non-invasive MRI measured renal blood flow and calculated renal plasma flow. • Effect of nephrectomy on blood flow and filtration in donors is presented. • Calculated filtration fraction may be a useful new kidney biomarker.