Single-kidney Glomerular Filtration Rate Research Articles

#5661 EARLY COMPENSATORY INCREASE IN SINGLE-KIDNEY EGFR AFTER UNILATERAL NEPHRECTOMY IS ASSOCIATED WITH A LOWER LONG-TERM RISK OF EGFR DECLINE

Abstract Background and Aims The healthy kidney has reserve capacity, allowing for an increase in single-kidney GFR (ΔskGFR) in the remaining kidney after nephrectomy. We evaluated whether higher ΔskGFR, as a reflection of renal resilience, is associated with a lower long-term risk of eGFR decline in individuals undergoing unilateral nephrectomy. Method We included 1777 participants from the observational SCREAM project who underwent radical unilateral nephrectomy in Stockholm during 2006–2021. We calculated the ΔskGFR using the eGFR (CKD-EPI 2009) at 3 months post-nephrectomy eGFR minus 50% of the pre-nephrectomy eGFR and evaluated its pre-nephrectomy determinants (age, sex, eGFR, comorbidities) with multivariable linear regression. Follow-up started at 3-months post-nephrectomy, and Cox regression was used to explore the association between Δsk-GFR and the subsequent risk of CKD progression (defined as composite of a decline >30% relative to three months post-nephrectomy eGFR or initiation of kidney replacement therapy), adjusting for age, sex and pre-nephrectomy eGFR. Results Mean (SD) age was 68 ± 11 years, 40% of patients were female, 92% had a kidney cancer diagnosis and mean (SD) pre-nephrectomy eGFR was 75 ± 19 mL/min/1.73m2. Median (IQR) Δsk-GFR was 11 (7–20) mL/min/1.73m2. Pre-nephrectomy determinants of Δsk-GFR were age (St.Β = −0.20, P≪0.001) and pre-nephrectomy eGFR (St.Β = 0.14, P<0.001). During a median follow-up of 4 years (maximum 15 years), 178 participants developed CKD progression. The group with a Δsk-GFR above the median value (11 mL/min/1.73m2) had a 42% lower risk of CKD progression (adjusted HR: 0.58, 95% CI: 0.42 – 0.80), compared to those with a lower Δsk-GFR (Figure). Conclusion A larger compensatory increase in single-kidney eGFR early after unilateral nephrectomy, suggesting better renal resilience, was associated with a lower risk of CKD progression during long-term follow-up. Evaluation of Δsk-GFR could help identify patients at higher risk of progressive kidney function decline.

Mapping single-nephron filtration in the isolated, perfused rat kidney using magnetic resonance imaging.

The kidney has an extraordinary ability to maintain glomerular filtration despite natural fluctuations in blood pressure and nephron loss. This is partly due to local coordination between single-nephron filtration and vascular perfusion. An improved understanding of the three-dimensional (3-D) functional coordination between nephrons and the vasculature may provide a new perspective of the heterogeneity of kidney function and could inform targeted therapies and timed interventions to slow or prevent the progression of kidney disease. Here, we developed magnetic resonance imaging (MRI) tools to visualize single-nephron function in 3-D throughout the isolated perfused rat kidney. We used an intravenous slow perfusion of a glomerulus-targeted imaging tracer [cationized ferritin (CF)] to map macromolecular dynamics and to identify glomeruli in 3-D, followed by a bolus of a freely filtered tracer (gadolinium diethylenetriamine penta-acetic acid) to map filtration kinetics. There was a wide intrakidney distribution of CF binding rates and estimated single-nephron glomerular filtration rate (eSNGFR) between nephrons. eSNGFR and CF uptake rates did not vary significantly by distance from the kidney surface. eSNGFR varied from ∼10 to ∼100 nL/min throughout the kidney. Whole single-kidney GFR was similar across all kidneys, despite differences in the distributions eSNGFR of and glomerular number, indicating a robust adaptive regulation of individual nephrons to maintain constant single-kidney GFR in the presence of a natural variation in nephron number. This work provides a framework for future studies of single-nephron function in the whole isolated perfused kidney and experiments of single-nephron function in vivo using MRI.NEW & NOTEWORTHY We report MRI tools to measure and map single-nephron function in the isolated, perfused rat kidney. We used imaging tracers to identify nephrons throughout the kidney and to measure the delivery and filtration of the tracers at the location of the glomeruli. With this technique, we directly measured physiological parameters including estimated single-nephron glomerular filtration rate throughout the kidney. This work provides a foundation for new studies to simultaneously map the function of large numbers of nephrons.

Dosing Limitation for Intra-Renal Arterial Infusion of Mesenchymal Stromal Cells.

The immunomodulatory and regenerative properties of mesenchymal stromal cells (MSCs) make MSC therapy a promising therapeutic strategy in kidney disease. A targeted MSC administration via the renal artery offers an efficient delivery method with limited spillover to other organs. Although local administration alleviates safety issues with MSCs in systemic circulation, it introduces new safety concerns in the kidneys. In a porcine model, we employed intra-renal arterial infusion of ten million allogenic adipose tissue-derived MSCs. In order to trigger any potential adverse events, a higher dose (hundred million MSCs) was also included. The kidney function was studied by magnetic resonance imaging after the MSC infusion and again at two weeks post-treatment. The kidneys were assessed by single kidney glomerular filtration rate (skGFR) measurements, histology and inflammation, and fibrosis-related gene expression. None of the measured parameters were affected immediately after the administration of ten million MSCs, but the administration of one hundred million MSCs induced severe adverse events. Renal perfusion was reduced immediately after MSC administration which coincided with the presence of microthrombi in the glomeruli and signs of an instant blood-mediated inflammatory reaction. At two weeks post-treatment, the kidneys that were treated with one hundred million MSCs showed reduced skGFR, signs of tissue inflammation, and glomerular and tubular damage. In conclusions, the intra-renal administration of ten million MSCs is well-tolerated by the porcine kidney. However, higher concentrations (one hundred million MSCs) caused severe kidney damage, implying that very high doses of intra-renally administered MSCs should be undertaken with caution.

Prediction of Renal Function in Living Kidney Donors and Recipients of Living Donor Kidneys Using Quantitative Histology.

Living kidney donors (LKDs) are at increased risk of chronic kidney disease, whereas transplant recipients experience progressive reduction of graft function. We examined the predictive value of quantitative stereology on renal function in LKDs and recipients of living donor kidneys, based on perioperative biopsies from the donated kidney. Cortex volume of both donor kidneys was determined by contrast-enhanced computed tomography and single-kidney glomerular filtration rate (GFR) by 51 chrome-EDTA clearance together with renography. Glomerular density was used to estimate total glomeruli number in addition to glomerular volume, glomerular sclerosis, kidney fibrosis, and arteriole dimensions. GFR measurements were repeated 1 y after transplantation in both LKDs and recipients. Associations between GFR at follow-up and cortex volume and histomorphometric parameters after adjustment of age, gender, body mass index, smoking status, 24-h blood pressure, and single-kidney GFR were examined. We included 49 LKDs (age, 51 ± 12 y) and 51 recipients (age, 44 ± 13 y). At follow-up, GFR was 71 ± 16 mL/min in LKDs and 61 ± 18 mL/min in recipients with hyperfiltration being more prominent in LKDs (30.4%) as compared to recipients (16.4%; P < 0.05). One-year GFR in donors correlated to cortex volume ( P < 0.001) but not to any histological parameters, whereas GFR in recipients correlated to the amount of interstitial fibrosis ( P < 0.01) but not to other histological parameters or cortex volume. Kidney cortex volume, but not renal histology parameters, predicts 1-y renal outcome in LKDs. In contrast, the amount of interstitial fibrosis, but not cortex volume, predicts 1-y graft function in recipients.

Protective effect of sacubitril/valsartan (Entresto) on kidney function and filtration barrier injury in a porcine model of partial nephrectomy.

Kidney surgery often includes organ ischaemia with a risk of acute kidney injury. The present study tested if treatment with the combined angiotensin II-angiotensin II receptor type 1 and neprilysin blocker Entresto (LCZ696, sacubitril/valsartan) protects filtration barrier and kidney function after ischaemia and partial nephrectomy (PN) in pigs. Single kidney glomerular filtration rate (GFR) by technetium-99m diethylene-triamine-pentaacetate clearance was validated (n=6). Next, four groups of pigs were followed for 15 days (n=24) after PN (one-third right kidney, 60min ischaemia) + Entresto (49/51mg/day; n=8), PN+vehicle (n=8), sham+Entresto (49/51mg/day; n=4) and sham+vehicle (n=4). GFR, diuresis and urinary albumin were measured at baseline and from each kidney after 15 days. The sum of single-kidney GFR (right 25± 6mL/min, left 31± 7mL/min) accounted for the total GFR (56± 14mL/min). Entresto had no effect on baseline blood pressure, p-creatinine, mid-regional pro-atrial natriuretic peptide (MR-proANP), heart rate and diuresis. After 15 days, Entresto increased GFR in the uninjured kidney (+23± 6mL/min, P<.05)and reduced albuminuria from both kidneys. In the sham group, plasma MR-proANP was not altered by Entresto; it increased to similar levels 2 h after surgery with and without Entresto. Fractional sodium excretion increased with Entresto. Kidney histology and kidney injury molecule-1 in cortex tissue were not different. In conclusion, Entresto protects the filtration barrier and increases the functional adaptive response of the uninjured kidney.

The Application Value of the Renal Region of Interest Corrected by Computed Tomography in Single-Kidney Glomerular Filtration Rate for the Evaluation of Patients With Moderate or Severe Hydronephrosis.

Objective: This study aimed to investigate the application value of the renal region of interest (ROI) corrected by computed tomography (CT) in single-kidney glomerular filtration rate (GFR) in patients with hydronephrosis. Methods: A total of 46 patients with hydronephrosis were divided into four groups based on their degree of unilateral hydronephrosis: a normal group (left kidney and right kidney) and three abnormal groups (mild, moderate, and severe hydronephrosis). GFR was measured using the two-sample method (tGFR). The single-kidney GFR of each patient was derived from differential renal function values in dynamic renal imaging multiplied by GFR. The single-kidney GFRs, including GFR from the Gates method (gGFRsingle) and CT area-corrected GFR (aGFRsingle), were compared with tGFRsingle. A paired-sample t-test and Pearson’s test were used for data analysis. p < 0.05 was considered statistically significant. Results: There were no significant differences between aGFRsingle and tGFRsingle in patients in the normal, mild hydronephrosis, and moderate hydronephrosis groups (t = –0.604∼1.982, all p > 0.05), but there was a significant difference between them in the severe hydronephrosis group (t = 2.302, p < 0.05). There were no significant differences between gGFRsingle and tGFRsingle in the normal and mild hydronephrosis groups (t = 0.194∼0.962, all p > 0.05), but there was a significant difference between them in the moderate and severe hydronephrosis groups (t = 3.321, 3.494, p < 0.05). Both gGFRsingle and aGFRsingle were correlated with tGFRsingle, with aGFRsingle being more strongly correlated (r = 0.890, p < 0.001). Conclusion: In patients with moderate hydronephrosis, aGFRsingle is more strongly correlated with tGFRsingle than gGFRsingle. However, in patients with severe hydronephrosis and accompanying renal morphological changes, the aGFRsingle measured by the renal ROI area-correction method using CT has higher accuracy and better clinical application value than the conventional gGFRsingle.

Early increase in single-kidney glomerular filtration rate after living kidney donation predicts long-term kidney function

Single-kidney glomerular filtration rate (GFR) increases after living kidney donation due to compensatory hyperfiltration and structural changes. The implications of inter-individual variability in this increase in single-kidney GFR are unknown. Here, we aimed to identify determinants of the increase in single-kidney GFR at three-month postdonation, and to investigate its relationship with long-term kidney function. In a cohort study in 1024 donors, we found considerable inter-individual variability of the early increase in remaining single-kidney estimated GFR (eGFR) (median [25th-75th percentile]) 12 [8-18] mL/min/1.73m2. Predonation eGFR, age, and cortical kidney volume measured by CT were the main determinants of the early postdonation increase in single-kidney eGFR. Individuals with a stronger early increase in single-kidney eGFR had a significantly higher five-year postdonation eGFR, independent of predonation eGFR and age. Addition of the postdonation increase in single-kidney eGFR to a model including predonation eGFR and age significantly improved prediction of a five-year postdonation eGFR under 50 mL/min/1.73m2. Results at ten-year follow-up were comparable, while accounting for left-right differences in kidney volume did not materially change the results. Internal validation using 125I-iothalamate-based measured GFR in 529 donors and external validation using eGFR data in 647 donors yielded highly similar results. Thus, individuals with a more pronounced increase in single-kidney GFR had better long-term kidney function, independent of predonation GFR and age. Hence, the early postdonation increase in single-kidney GFR, considered indicative for kidney reserve capacity, may have additional value to eGFR and age to personalize follow-up intensity after living kidney donation.

Differential GFR estimation of the double moiety kidneys by modified GATE’S formula

Aim: This retrospective analysis of the GFR values of the individual moieties obtained by using a novel software with modified GATE’S formula in the in house software created at SSSIHL, compared and evaluated with the value derived by the combined GFR value of the single kidney GFR as obtained from the Icon software loaded in the gamma camera. Materials and Method: This retrospective study of 10patients diagnosed with unilateral double moiety and 5 patients with bilateral duplication was undertaken to validate the modified GATE’S formula in house software created at SSSIHL. This group had 12 males in the age range of 03-66 years with the mean age of 26.5 ± 2 years and 3 females in the age range of 29 – 31 years with mean age of 31 ± 2 years. Renal scans were done using Siemens dual head gamma camera (E.CAM). The radiopharmaceutical 99mTc-DTPA 5 mCi was injected as a bolus intravenously for the adult patients and 3 mCi was injected for the children. The images were obtained and processed by using GFR/Renal differential processing protocol in icon software. Later the raw data of the scan study transferred to the workstation loaded with the in house software created at SSSIHL with modified GATE’S formula created by us. The individual moiety GFR values were calculated using the software with modified Gate’s formula developed in MATLAB GUI algorithm and tabulated. Then the combined value of individual moiety GFR values compared with that of the individual whole kidney GFR value obtained by the Icon software protocol. Result: The T test evaluation done in the online statistical calculator of Maths Portal org revealed that the mean values of the two groups showed no significant difference at p &lt; 0.05. The calculated t value is smaller than the critical value (0.0217 &lt; 2.024), so the means are not significantly different. Pearson Correlation performed between the above two samples using statistical online calculators also showed the correlation coefficient of r = 0.9247 and a mean difference of 0.09 indicating that the high correlation between them. The observed significance p value &lt; 0.0001 at t value of 10.27, showed no significant difference detected between the two samples. Conclusion: It can be concluded that the in house software created at SSSIHL with modified GATE’S formula method of GFR calculating software showed identical values with that of the GFR calculated with the original Gate’s formula. This was found to be useful in calculating the GFR of individual moieties separately in the cases of Double moieties in both Unilateral and Bilateral involvement effectively. The utility and usefulness of the separate estimation of individual moieties GFR needed for Nephron Sparing Surgery.

Noninvasive Assessment of Fibrosis Following Ischemia/Reperfusion Injury in Rodents Utilizing Na Magnetic Resonance Imaging.

Fibrosis is often heterogeneously distributed, and classical biopsies do not reflect this. Noninvasive methods for renal fibrosis have been developed to follow chronic kidney diseases (CKD) and to monitor anti-fibrotic therapy. In this study, we combined two approaches to assess fibrosis regression following renal ischemia-reperfusion injury (IRI): magnetic resonance imaging (MRI) and noninvasive extracellular matrix (ECM) biomarkers. MRI was used to evaluate fibrosis in bilateral IRI in rats after reperfusion at 7, 14, and 21 days. This was performed with 1HT1 and T2* mapping, dynamic contrast-enhanced (DCE)-MRI, and chemical shift imaging (CSI)-23Na. The degradation of laminin gamma-1 chain (LG1M) and type III collagen (C3M) was measured in urine and plasma. Fibrosis was analyzed in tissue using fibronectin (FN) and alpha-smooth muscle actin (α-SMA) using quantitative polymerase chain reaction qPCR and western blotting. We found increased fibrosis 7 days after reperfusion, which dropped to sham levels after 21 days. Single kidney glomerular filtration rate (skGFR), perfusion (DCE-MRI), and total 23Na kidney content correlated positively with fibrotic markers FN and α-SMA as well as noninvasive LG1M and C3M. We showed that novel MRI protocols and ECM markers could track fibrogenic development. This could give rise to a multi-parametric practice to diagnose and assess fibrosis whilst treating kidney disease without using invasive methods.

P1620PROGNOSTIC VALUE OF RENAL BIOPSY QUANTITATIVE HISTOLOGY IN LIVING KIDNEY DONORS AND RECIPIENTS OF KIDNEYS FROM LIVING DONORS

Abstract Background and Aims Living kidney donors (LKD) have an increased risk of chronic kidney disease. Likewise, renal transplant recipients may experience early or unexplained loss of graft function. We examined the predictive value of stereology based on a CT-scan and a biopsy from the transplanted kidney in relation to renal function outcome in both LKD and recipients of kidneys from living donors. Method A pre-transplantation contrast-enhanced CT-scan was used to obtain cortical volume of both kidneys using the Cavalieri estimator. Glomerular number density in a baseline biopsy from the transplanted kidney (taken at the time of transplantation) was estimated by a model-based method and multiplied with cortex volume to estimate the total number of glomeruli in the donated kidney. Glomerular volume was estimated by the 2D nucleator (1). In addition, kidney fibrosis (point-counting), glomerular sclerosis, and arteriole dimensions (2D nucleator) were also calculated. Pre-donation single kidney glomerular filtration rate (GFR) was determined using 51chrome EDTA clearance together with a renography and the GFR measurement was repeated one year after transplantation in both donors and recipients. We examined the association between GFR at one-year follow-up and cortex volume and various histology parameters from the baseline biopsy after adjustment of age, sex, body mass index, smoking status, 24-hour mean blood pressure and single-kidney GFR before transplantation. Results CT-scans, GFR measurements and kidney histology from 49 LKD and 38 recipients of kidneys from living donors were available for analysis. Mean age of donors was 50±12 years (55% women) and of recipients 46±13 years (26% women). In donors, GFR decreased from 113±24 to 71±16 ml/min while in recipients GFR was 61±18 ml/min at one-year follow-up (all with a functioning graft). In donors, GFR at follow-up of the remaining kidney had increased by 28% as compared to baseline. Follow-up GFR correlated to cortex volume (P&amp;lt;0.001), but not to any of the histological parameters (total glomerular number, glomerular volume, % sclerosed glomeruli, % kidney fibrosis or arteriolar dimensions). In recipients, GFR at follow-up had increased by 8% as compared to single-kidney GFR before donation. Follow-up GFR correlated to % kidney fibrosis (P=0.02) and % sclerosed glomeruli (P=0.05), but not any of the other histological parameters or cortex volume. Conclusion When adjusted for relevant clinical confounders the estimation of cortex volume had predictive value for renal function outcome in LKD while % kidney fibrosis and % sclerosed glomeruli had predictive value in recipients of kidneys from living donors.

Hyperpolarized [1-13 C] alanine production: A novel imaging biomarker of renal fibrosis.

Renal tubulointerstitial fibrosis is strongly linked to the progressive decline of renal function seen in chronic kidney disease. State-of-the-art noninvasive diagnostic modalities are currently unable to detect the earliest changes associated with the onset of fibrosis. This study was undertaken to evaluate the potential for detecting the earliest alterations in fibrogenesis using a biofluid-based method and metabolic hyperpolarized [1-13 C]pyruvate imaging. We evaluated renal fibrosis in a combined ischemia reperfusion-induced and streptozotocin-induced diabetic nephropathy rodent model by hyperpolarized [1-13 C]pyruvate MRI and correlated the metabolic MRI parameters with biomarkers of fibrosis measured on renal tissue and plasma/urine. The hyperglycemic rats experienced maladaptive injury repair after the ischemic insults, as shown by the elevation in the injury markers kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. Renal function was significantly impaired in the ischemic hyperglycemic kidney, as seen in the reduced perfusion and single-kidney glomerular filtration rate. A deranged energy metabolism was detected in the ischemic hyperglycemic kidney, as seen in the reduced fractional perfusion of lactate. Renal fibrosis biomarkers correlated significantly with the alanine production. Hyperpolarized carbon-13 MRI provides a promising approach to assess renal fibrosis in an animal model of fibrotic chronic kidney disease. In particular, the metabolic supply of amino acids for fibrogenesis (alanine production) correlates well with biomarkers of fibrosis. Thus, [1-13 C]pyruvate-to-[1-13 C]alanine conversion might be a candidate for noninvasive assessment of renal fibrogenesis.

Multiparametric Renal MRI: An Intrasubject Test-Retest Repeatability Study.

BackgroundRenal multiparametric magnetic resonance imaging (MRI) is a promising tool for diagnosis, prognosis, and treatment monitoring in kidney disease.PurposeTo determine intrasubject test–retest repeatability of renal MRI measurements.Study TypeProspective.PopulationNineteen healthy subjects aged over 40 years.Field Strength/SequencesT1 and T2 mapping, R2* mapping or blood oxygenation level‐dependent (BOLD) MRI, diffusion tensor imaging (DTI), and intravoxel incoherent motion (IVIM) diffusion‐weighted imaging (DWI), 2D phase contrast, arterial spin labelling (ASL), dynamic contrast enhanced (DCE) MRI, and quantitative Dixon for fat quantification at 3T.AssessmentSubjects were scanned twice with ~1 week between visits. Total scan time was ~1 hour. Postprocessing included motion correction, semiautomated segmentation of cortex and medulla, and fitting of the appropriate signal model.Statistical TestTo assess the repeatability, a Bland–Altman analysis was performed and coefficients of variation (CoVs), repeatability coefficients, and intraclass correlation coefficients were calculated.ResultsCoVs for relaxometry (T1, T2, R2*/BOLD) were below 6.1%, with the lowest CoVs for T2 maps and highest for R2*/BOLD. CoVs for all diffusion analyses were below 7.2%, except for perfusion fraction (FP), with CoVs ranging from 18–24%. The CoV for renal sinus fat volume and percentage were both around 9%. Perfusion measurements were most repeatable with ASL (cortical perfusion only) and 2D phase contrast with CoVs of 10% and 13%, respectively. DCE perfusion had a CoV of 16%, while single kidney glomerular filtration rate (GFR) had a CoV of 13%. Repeatability coefficients (RCs) ranged from 7.7–87% (lowest/highest values for medullary mean diffusivity and cortical FP, respectively) and intraclass correlation coefficients (ICCs) ranged from −0.01 to 0.98 (lowest/highest values for cortical FP and renal sinus fat volume, respectively).Data ConclusionCoVs of most MRI measures of renal function and structure (with the exception of FP and perfusion as measured by DCE) were below 13%, which is comparable to standard clinical tests in nephrology.Level of Evidence2Technical EfficacyStage 1

Assessment of Split Renal Function Using a Combination of Contrast-Enhanced CT and Serum Creatinine Values for Glomerular Filtration Rate Estimation.

OBJECTIVE. The objective of our study was to develop a novel method to estimate single-kidney glomerular filtration rate (GFR) using a combination of contrast-enhanced CT and serum creatinine (SCr) values and to validate the resulting estimated glomerular filtration rates (eGFRs) by comparing them with the single-kidney Gates GFR, which is based on renal dynamic imaging. MATERIALS AND METHODS. Sixty-two patients with asymmetric renal disease who underwent unenhanced and triphasic contrast-enhanced CT of the kidneys, 99mTc-diethylenetriamine pentaacetic acid renal dynamic imaging, and SCr testing within 1 week were retrospectively included. The eGFR was split into single-kidney GFRs of the left and right kidneys by a proportionality factor derived from the products of renal volume and CT number increments of the multiphasic CT images, which produced unenhanced phase (yielded by the renal volume proportional factor alone), arterial phase, venous phase, and nephrographic phase CT split eGFRs. The four CT split eGFRs were compared with the Gates GFR using the paired-sample t test, Pearson correlation analysis, and Bland-Altman analysis. RESULTS. Correlation coefficients and 95% CIs between the four CT split eGFRs and Gates GFR were as follows: unenhanced phase, 0.729 (95% CI, 0.626-0.805); arterial phase, 0.781 (95% CI, 0.685-0.849); venous phase, 0.788 (95% CI, 0.690-0.839); and nephrographic phase, 0.842 (95% CI, 0.758-0.902) (all, p < 0.001). The paired differences between the CT split eGFRs and Gates GFR were as follows: unenhanced phase, 2.04 ± 10.85 (95% CI, 0.01-4.07) mL/min/1.73 m2; arterial phase, 2.04 ± 10.56 (95% CI, 0.06-4.02) mL/min/1.73 m2; venous phase, 2.04 ± 10.04 (95% CI, 0.16-3.92) mL/min/1.73 m2; and nephrographic phase, 2.04 ± 8.92 (95% CI, 0.37-3.71) mL/min/1.73 m2. These results suggest a maximum deviation from the Gates GFR of ± 44.9% for the unenhanced phase eGFR, ± 43.7% for the arterial phase eGFR, ± 41.6% for the venous phase eGFR, and ± 36.9% for nephrographic phase eGFR. CONCLUSION. Split renal function can be estimated using a combination of contrast-enhanced CT and SCr values to calculate eGFR. The CT images of the nephrographic phase may be the optimal choice to use in this proposed method.

Predonation Single Kidney Glomerular Filtration Rate in Living Kidney Transplantation to Predict Graft Function and Donor Functional Gain

BackgroundThe 2 main objectives regarding living kidney transplant are to provide optimal graft function and to ensure the safety of donation. Our study hypothesized that the glomerular filtration rate of a single kidney (skGFR), when transplanted, might predict graft function and that the skGFR of the remaining kidney could predict donor functional gain. MethodsA prospective monocentric study was conducted at Grenoble-Alpes University Hospital. Twenty couples of donors and recipients were included. Dimercaptosuccinic acid renal scintigraphy and 51Cr-ethylene-diamine tetra-acetic acid clearance were evaluated predonation to calculate skGFR. All patients had renal function according to 51Cr-ethylene-diamine tetra-acetic acid clearance at 1 year post transplant to assess graft function and donor functional gain. All donors had normal renal function predonation. ResultsAt 1 year post transplant, median glomerular filtration rate of the graft was 50 mL/min/1.73 m2 (range, 46-56 mL/min/1.73 m2) and donor median glomerular filtration rate was 59 mL/min/1.73 m2 (range, 55-74 mL/min/1.73 m2). Median functional gain was 20 mL/min/1.73 m2 (range, 12-22 mL/min/1.73 m2). No statistical correlation was found between skGFR of the transplanted kidney and graft function at 1 year (R2 = 0.096, P = .7). For the donor, functional gain was not associated with predonation skGFR of the remaining kidney (R2 = 0.17, P = .5). A statistical difference was found between donor functional gain (18 [SD, 10] mL/min) and recipient gain (delta between skGFR before and after transplant, 7 [SD, 16] mL/min; P = .02). ConclusionPredonation skGFR of the transplanted kidney had no influence on renal allograft function at 1 year post transplant. Similarly, there was no association between measured skGFR of the remaining kidney and donor functional gain at 1 year.

Postnatal management of bilateral Grade 3-4 ureteropelvic junction obstruction.

Introduction:Bilateral hydronephrosis on prenatal ultrasound can be managed expectantly or with surgical intervention. The treatment strategies and outcomes are not clearly defined.Methods:We conducted a retrospectively audit of outcomes of management of prenatally detected severe bilateral ureteropelvic junction obstruction (UPJO) in our institution.Patients with bilateral Grade 3–4 hydronephrosis were included. Those with complications like rupture, underwent bilateral intervention within 4 weeks; in the remaining, unilateral pyeloplasty was performed at 4–12 weeks. The contralateral renal unit was re-evaluated at a later date for further improvement or deterioration. All the patients were followed up with ultrasonography and renogram at 3 months, 6 months, and 1-year post operatively. The case records were analyzed for the resolution of antero-posterior diameter (APD) or the improvement in single-kidney glomerular filtration rate (s-GFR) in the operated units.Results:Over 15 years, 28 patients (56 renal units) had bilateral UPJO (male-to-female ratio = 13:1). Twelve units underwent neonatal intervention to tackle the complications (6 bilateral pyeloplasty), 17 units underwent early pyeloplasty, and 15 underwent late pyeloplasty. Twelve of the twenty-two (54%) contralateral units, which were stented/observed, resolved spontaneously. Receiver operating characteristics analysis revealed that those with initial APD <25 mm and initial s-GFR >35 ml/m were more likely to improve during the observation. Ten of the forty-four operated units (22%) failed to show an improvement. Units with initial s-GFR <10 ml/m had poor chance of postoperative functional recovery.Conclusions:In neonates with bilateral UPJO, the worse affected kidney is operated first, as it still has the potential to recover. The contralateral milder UPJO unit is known to recover spontaneously following unilateral pyeloplasty. In those with bilateral Grade 4 UPJO and mass, bilateral pyeloplasty is feasible. Alternatively, unilateral pyeloplasty + contralateral cystoscopic retrograde stenting may prevent rupture or functional deterioration in the opposite kidney.

Coexisting renal artery stenosis and metabolic syndrome magnifies mitochondrial damage, aggravating poststenotic kidney injury in pigs.

Renovascular disease (RVD) produces chronic underperfusion of the renal parenchyma and progressive ischemic injury. Metabolic abnormalities often accompany renal ischemia, and are linked to poorer renal outcomes. However, the mechanisms of injury in kidneys exposed to the ischemic and metabolic components of RVD are incompletely understood. We hypothesized that coexisting renal artery stenosis (RAS) and metabolic syndrome (MetS) would exacerbate mitochondrial damage, aggravating poststenotic kidney injury in swine. Domestic pigs were studied after 16 weeks of either standard diet (Lean) or high-fat/high-fructose (MetS) with or without superimposed RAS (n = 6 each). Single-kidney renal blood flow (RBF) and glomerular filtration rate (GFR) were assessed in vivo with multidetector-CT, and renal tubular mitochondrial structure, homeostasis and function and renal injury ex vivo. Both RAS groups achieved significant stenosis. Single-kidney RBF and GFR were higher in MetS compared with Lean, but decreased in Lean+RAS and MetS+RAS vs. their respective controls. MetS and RAS further induced changes in mitochondrial structure, dynamics, and function, and their interaction (diet × ischemia) decreased matrix density, mitophagy, and ATP production, and lead to greater renal fibrosis. Coexisting RAS and MetS synergistically aggravate mitochondrial structural damage and dysfunction, which may contribute to structural injury and dysfunction in the poststenotic kidney. These observations suggest that mitochondrial damage precedes loss of renal function in experimental RVD, and position mitochondria as novel therapeutic targets in these patients.

A modified two-compartment model for measurement of renal function using dynamic contrast-enhanced computed tomography.

ObjectivesTo validate and adapt a modified two-compartment model, originally developed for magnetic resonance imaging, for measuring human single-kidney glomerular filtration rate (GFR) and perfusion using dynamic contrast-enhanced computed tomography (DCE-CT).MethodsThis prospective study was approved by the institutional review board, and written informed consent was obtained from all patients. Thirty-eight patients with essential hypertension (EH, n = 13) or atherosclerotic renal artery stenosis (ARAS, n = 25) underwent renal DCE-CT for GFR and perfusion measurement using a modified two-compartment model. Iothalamate clearance was used to measure reference total GFR, which was apportioned into single-kidney GFR by renal blood flow. Renal perfusion was also calculated using a conventional deconvolution algorithm. Validation of GFR and perfusion and inter-observer reproducibility, were conducted by using the Pearson correlation and Bland-Altman analysis.ResultsBoth the two-compartment model and iothalamate clearance detected in ARAS patients lower GFR in the stenotic compared to the contralateral and EH kidneys. GFRs measured by DCE-CT and iothalamate clearance showed a close match (r = 0.94, P<0.001, and mean difference 2.5±12.2mL/min). Inter-observer bias and variation in model-derived GFR (r = 0.97, P<0.001; mean difference, 0.3±7.7mL/min) were minimal. Renal perfusion by deconvolution agreed well with that by the compartment model when the blood transit delay from abdominal aorta to kidney was negligible.ConclusionThe proposed two-compartment model faithfully depicts contrast dynamics using DCE-CT and may provide a reliable tool for measuring human single-kidney GFR and perfusion.

Clinical research of CT urography in quantitative assessment of single-kidney glomerular filtration rate in renal tumors and hydronephrosis patients

Objective To evaluate the clinical value of CT urography (CTU) in quantitative analysis of single-kidney renal glomerular filtration rate (GFR) in patients with renal tumor and hydronephrosis. Methods A total of 49 patients with renal tumor or hydronephrosis from January 2018 to September 2018 in the Second Hospital of Tianjin Medical University were prospectively collected. In all cases, the CT urography and 99mTc-DTPA renal dynamic imaging data and related clinical data were collected. All patients were divided into two groups: the experimental group (39 patients with a total of 78 kidneys) and the validation group (10 patients with a total of 20 kidneys). According to the presence or absence of renal diseases, the kidneys of the experimental group and the validation group were further divided into four groups, namely, the single kidney group, the tumor group, the stagnant water group and the healthy group. The CT urography protocol consisted of noncontrast, arterial phase, nephrographic, and excretory phase imaging. The total renal GFR was determined by CT measurement of renal clearance of contrast media (CM), and the total CT-GFR was then split into single-kidney CT-GFR by a left and right kidney proportionality factor. Differences between CT-GFR and SPECT-GFR measurements in each group of the experimental group was compared by paired-sample t test. Correlations between CT-GFR and SPECT-GFR in the experimental group and their correlations with RPV was analyzed by Pearson method. The Bland-Altman mapping method was used to evaluate the consistency between CT-GFR and SPECT-GFR in the experimental group. Results Paired difference between single-kidney CT-GFR (48.76±18.50) ml·min-1·1.73 m-2 and single-kidney SPECT-GFR (45.68±17.95) ml·min-1·1.73 m-2 in the experimental group, P 0.05).Pearson Correlation analysis showed that the correlations between CT-GFR and RPV in all experimental groups were better than the correlation between Gates-GFR and RPV (P<0.05). Conclusions This study demonstrated the feasibility of using CT urography to measure single-kidney GFR, verifying its application value in diseases such as kidney tumors and obstructive hydronephrosis, and proved that the proposed single-kidney CT-GFR correlates better than the SPECT-GFR with RPV. Key words: Kidney neoplasms; CT urography; Glomerular filtration rate; Comparative study

Analytical validation of single-kidney glomerular filtration rate and split renal function as measured with magnetic resonance renography

Analytical validation of single-kidney glomerular filtration rate and split renal function as measured with magnetic resonance renography

Measurement of single kidney glomerular filtration rate in dogs using dynamic contrast-enhanced magnetic resonance imaging and the Rutland-Patlak plot technique

BackgroundNephropathies are among the most common diseases in dogs. Regular examination of the kidney function plays an important role for an adequate treatment scheme. The determination of the glomerular filtration rate (GFR) is seen as the gold standard in assessing the kidney status. Most of the tests have the disadvantage that only the complete glomerular filtration rate of both kidneys can be assessed and not the single kidney glomerular filtration rate. Imaging examination techniques like dynamic contrast-enhanced magnetic resonance imaging have the potential to evaluate the single kidney GFR. There are studies in human medicine describing the determination of the single kidney GFR using this technique. To our knowledge there are no such studies for dogs.ResultsAn exponential fit was found to describe the functional interrelation between signal intensity and contrast medium concentrations. The changes of contrast medium concentrations during the contrast medium bolus propagation were calculated. The extreme values of contrast medium concentrations in the kidneys were reached at nearly the same time in every individual dog (1st maximum aorta 8.5 s, 1st maximum in both kidneys after about 14.5 s; maximum concentration values varied between 17 and 125 µmol/mL in the aorta and between 4 and 15 µmol/mL in the kidneys). The glomerular filtration rate was calculated from the concentration changes of the contrast medium using a modified Rutland-Patlak plot technique. The GFR was 12.7 ± 2.9 mL/min m2 BS for the left kidney and 12.0 ± 2.2 mL/min/m2 BS for the right kidney. The mean values of the coefficient of determination of the regression lines were averagely 0.91 ± 0.08.ConclusionsThe propagation of contrast medium bolus could be depicted well. The contrast medium proceeded in a similar manner for every individual dog. Additionally, the evaluation of the single kidney function of the individual dogs is possible with this method. A standardized examination procedure would be recommended in order to minimize influencing parameters.