Decreased Renal Gluconeogenesis Is a Hallmark of Chronic Kidney Disease.

INTRODUCTION: CKD is associated with alterations of tubular function. Renal gluconeogenesis is responsible for 40% of systemic gluconeogenesis during fasting, but how and why CKD affects this process and the repercussions of such regulation are unknown. METHODS: We used data on the renal gluconeogenic pathway from more than 200 renal biopsies performed on CKD patients and from 43 kidney allograft patients, and studied three mouse models, of proteinuric CKD (POD-ATTAC), of ischemic CKD, and of unilateral urinary tract obstruction. We analyzed a cohort of patients who benefitted from renal catheterization and a retrospective cohort of patients hospitalized in the intensive care unit. RESULTS: Renal biopsies of CKD and kidney allograft patients revealed a stage-dependent decrease in the renal gluconeogenic pathway. Two animal models of CKD and one model of kidney fibrosis confirm gluconeogenic downregulation in injured proximal tubule cells. This shift resulted in an alteration of renal glucose production and lactate clearance during an exogenous lactate load. The isolated perfused kidney technique in animal models and renal venous catheterization in CKD patients confirmed decreased renal glucose production and lactate clearance. In CKD patients hospitalized in the intensive care unit, systemic alterations of glucose and lactate levels were more prevalent and associated with increased mortality and a worse renal prognosis at follow-up. Decreased expression of the gluconeogenesis pathway and its regulators predicted faster histologic progression of kidney disease in kidney allograft biopsies. CONCLUSION: Renal gluconeogenic function is impaired in CKD. Altered renal gluconeogenesis leads to systemic metabolic changes with a decrease in glucose and increase in lactate level, and is associated with a worse renal prognosis.

[Nephrology: what's new in 2022]. / Néphrologie : ce qui a changé en 2022.

Severe cases of IGA nephropathy might benefit from corticosteroid therapy. Inflimidase may be a promising treatment of Goodpasture disease. SGLT2 inhibitors and acetazolamide act synergistically with loop diuretics in the treatment of acute cardiac failure. In hemodialysis, use of lung ultrasound to determine the ultrafiltration seems to decrease hospitalizations due to acute heart failure but does not reduce patient-centered outcomes. Icodextrin may mitigate the loss of ultrafiltration in PD patients who are carriers of the Aquaporin I promotor TT genotype. MICA-antibodies have an impact on the risk of graft rejection. Xenotransplantation may become a reality.

Une corticothérapie peut être proposée dans les formes sévères de néphropathie à IgA. L'inflimidase est une molécule prometteuse dans le traitement de la maladie de Goodpasture. Les inhibiteurs du SGLT2 et l'acétazolamide sont des diurétiques d'appoint aux diurétiques de l'anse dans le traitement de l'insuffisance cardiaque aiguë. En hémodialyse, l'ultrason pulmonaire pour déterminer le volume d'ultrafiltration diminue les hospitalisations pour insuffisance cardiaque mais pas la morbimortalité globale. L'hémodialyse incrémentale gagne en popularité. L'icodextrine permet de pallier la baisse de l'ultrafiltration chez les patients en dialyse péritonéale porteurs du génotype TT du promoteur de l'aquaporine-1. Les anticorps anti-MICA dirigés spécifiquement contre le greffon rénal ont un impact sur le risque de rejet du greffon. La xénotransplantation devient une réalité.

Diffusion-magnetic resonance imaging predicts decline of kidney function in chronic kidney disease and in patients with a kidney allograft.

Kidney cortical interstitial fibrosis is highly predictive of kidney prognosis and is currently assessed by evaluation of a biopsy. Diffusion-weighted magnetic resonance imaging is a promising non-invasive tool to evaluate kidney fibrosis. We recently adapted diffusion-weighted imaging sequence for discrimination between the kidney cortex and medulla and found that the cortico-medullary difference in apparent diffusion coefficient (ΔADC) correlated with histological interstitial fibrosis. Here, we assessed whether ΔADC as measured with diffusion-weighted magnetic resonance imaging is predictive of kidney function decline and dialysis initiation in chronic kidney disease (CKD) and patients with a kidney allograft in a prospective study encompassing 197 patients. We measured ΔADC in 43 patients with CKD (estimated GFR (eGFR) 55ml/min/1.73m2) and 154 patients with a kidney allograft (eGFR 53ml/min/1.73m2). Patients underwent a kidney biopsy and diffusion-weighted magnetic resonance imaging within one week of biopsy; median follow-up of 2.2 years with measured laboratory parameters. The primary outcome was a rapid decline of kidney function (eGFR decline over 30% or dialysis initiation) during follow up. Significantly, patients with a negative ΔADC had 5.4 times more risk of rapid decline of kidney function or dialysis (95% confidence interval: 2.29-12.58). After correction for kidney function at baseline and proteinuria, low ADC still predicted significant kidney function loss with a hazard ratio of 4.62 (95% confidence interval 1.56-13.67) independent of baseline age, sex, eGFR and proteinuria. Thus, low ΔADC can be a predictor of kidney function decline and dialysis initiation in patients with native kidney disease or kidney allograft, independent of baseline kidney function and proteinuria.

[Acute interstitial nephritis: clinical presentation and diagnosis]. / Néphrite interstitielle aiguë : quand la suspecter et quelle prise en charge ?

Acute interstitial nephritis is characterized by renal inflammation and interstitial edema. The clinical presentation is pauci-symptomatic and often non-specific. Acute interstitial nephritis typically presents with acute renal failure, alone or with fever, eosinophilia, hematuria, sterile pyuria and small range proteinuria. An early diagnosis is crucial to prevent the morbidity and mortality associated with renal function decline. The most frequent etiology of this disease is drug-induced. A kidney biopsy is not systematically required to establish the diagnosis. It should be considered in the absence of renal function improvement 5 to 7 days after withdrawal of the causal agent. Although the benefits of glucocorticoid treatment have not been proven to date, its use may be associated with a better kidney function recovery.

La néphrite interstitielle aiguë est caractérisée par une inflammation dans le compartiment interstitiel rénal. La présentation clinique est paucisymptomatique. Elle se présente généralement par une insuffisance rénale aiguë qui peut être accompagnée de fièvre, d'éosinophilie, d'hématurie, de leucocyturie stérile et de protéinurie non néphrotique. Son diagnostic précoce est crucial pour prévenir la morbi-mortalité liée au déclin de la fonction rénale. L'étiologie la plus fréquente est médicamenteuse. Le diagnostic par la ponction-biopsie rénale n'est pas systématique, mais doit être considéré en l'absence d'amélioration de la fonction rénale 5 à 7 jours après l'arrêt de la substance incriminée. Le principal traitement consiste en l'interruption du médicament incriminé et à l'administration de corticostéroïdes.

HLA-D and PLA2R1 risk alleles associate with recurrent primary membranous nephropathy in kidney transplant recipients.

Recurrence of primary membranous nephropathy after transplantation occurs in up to 44% of patients and is driven by PLA2R antibody. Here, we asked whether genetic determinants could improve risk prediction. First, we sequenced PLA2R1 and HLA-D loci in 248 patients with primary membranous nephropathy and identified two independent single nucleotide polymorphisms (SNPs) at risk for primary membranous nephropathy at each locus. These were rs9271188 (intergenic between HLA-DRB1 and HLA-DQA1,) and rs9275086 (intergenic between HLA-DQB1 and HLA-DQA2) at the HLA-D locus along with rs6726925 and rs13018963 at the PLA2R1 locus. Then we investigated whether primary membranous nephropathy at-risk variants were associated with recurrence in a retrospective cohort of 105 donor-recipient pairs and a replication cohort of 40 pairs. Seven SNPs located between HLA-DRB1 and HLA-DQA1 in linkage disequilibrium with rs9271188, and three SNPs in the PLA2R1 region predicted recurrence when presented by the donor, but not when presented by the recipient. The two SNPs in the HLA-D region most strongly associated with recurrence (rs9271705 and rs9271550) were confirmed in the replication cohort. A genetic risk score based on the two best predictors at each locus (rs9271705, rs9271550, rs17830558, and rs3828323) identified a group of patients with high risk of recurrence. Thus, our results suggest that the graft contributes to recurrence of primary membranous nephropathy through the disease susceptibility HLA-D and PLA2R1 SNPs in an autoimmune milieu. Further studies are needed before implementation of genetic testing for these in donor selection.

Thiamine, Ascorbic Acid, and Hydrocortisone As a Metabolic Resuscitation Cocktail in Sepsis: A Meta-Analysis of Randomized Controlled Trials With Trial Sequential Analysis.

OBJECTIVES: Sepsis is a common condition in the ICU. Despite much research, its prognosis remains poor. In 2017, a retrospective before/after study reported promising results using a combination of thiamine, ascorbic acid, and hydrocortisone called "metabolic resuscitation cocktail" and several randomized controlled trials assessing its effectiveness were performed. DESIGN: We conducted a systematic review and meta-analysis of randomized controlled trials in septic ICU patients to assess the effects of this combination therapy. SETTING: PubMed, Embase, and the Cochrane library databases were searched from inception to March of 2021. Data were extracted independently by two authors. The main outcome was the change in Sequential Organ Failure Assessment score within 72 hours. Secondary outcomes included renal composite endpoints (acute kidney injury) Kidney Disease - Improving Global Outcome organization stage 3 or need for renal replacement therapy, vasopressor duration, and 28-day mortality. SUBJECTS: We included randomized controlled trials with patients admitted to the ICU with sepsis or septic shock. INTERVENTION: The trials compared a combination of thiamine, ascorbic acid, and hydrocortisone to standard care or placebo in patients admitted to ICU with sepsis or septic shock. MEASUREMENTS AND MAIN RESULTS: We included eight randomized controlled trials (n = 1,335 patients). Within 72 hours, the median of mean improvement was -1.8 and -3.2 in the control and intervention groups, respectively (eight randomized controlled trials, n = 1,253 patients); weighted mean difference -0.82 (95% CI, -1.15 to -0.48). Data were homogeneous and the funnel plot did not suggest any publication bias. Duration of vasopressor requirement was significantly reduced in the intervention group (six randomized controlled trials). There was no evidence of a difference regarding the ICU mortality and the renal composite outcome (acute kidney injury KDIGO 3 or need for renal replacement therapy, seven randomized controlled trials). CONCLUSIONS: Metabolic resuscitation cocktail administrated in ICU septic patients improves change in Sequential Organ Failure Assessment score within 72 hours. However, this improvement is modest and its clinical relevance is questionable. The impact on renal failure and mortality remains unclear.

Validation of the corticomedullary difference in magnetic resonance imaging-derived apparent diffusion coefficient for kidney fibrosis detection: a cross-sectional study.

BACKGROUND: Kidney cortical interstitial fibrosis (IF) is highly predictive of renal prognosis and is currently assessed by the evaluation of a biopsy. Diffusion magnetic resonance imaging (MRI) is a promising tool to evaluate kidney fibrosis via the apparent diffusion coefficient (ADC), but suffers from inter-individual variability. We recently applied a novel MRI protocol to allow calculation of the corticomedullary ADC difference (ΔADC). We here present the validation of ΔADC for fibrosis assessment in a cohort of 164 patients undergoing biopsy and compare it with estimated glomerular filtration rate (eGFR) and other plasmatic parameters for the detection of fibrosis. METHODS: This monocentric cross-sectional study included 164 patients undergoing renal biopsy at the Nephrology Department of the University Hospital of Geneva between October 2014 and May 2018. Patients underwent diffusion-weighted imaging, and T1 and T2 mappings, within 1 week after biopsy. MRI results were compared with gold standard histology for fibrosis assessment. RESULTS: Absolute cortical ADC or cortical T1 values correlated poorly to IF assessed by the biopsy, whereas ΔADC was highly correlated to IF (r=-0.52, P < 0.001) and eGFR (r = 0.37, P < 0.01), in both native and allograft patients. ΔT1 displayed a lower, but significant, correlation to IF and eGFR, whereas T2 did not correlate to IF nor to eGFR. ΔADC, ΔT1 and eGFR were independently associated with kidney fibrosis, and their combination allowed detection of extensive fibrosis with good specificity. CONCLUSION: ΔADC is better correlated to IF than absolute cortical or medullary ADC values. ΔADC, ΔT1 and eGFR are independently associated to IF and allow the identification of patients with extensive IF.

Impact of superimposed nephrological care to guidelines-directed management by primary care physicians of patients with stable chronic kidney disease: a randomized controlled trial.

BACKGROUND: Optimal clinical care of patients with chronic kidney disease (CKD) requires collaboration between primary care physicians (PCPs) and nephrologists. We undertook a randomised trial to determine the impact of superimposed nephrologist care compared to guidelines-directed management by PCPs in CKD patients after hospital discharge. METHODS: Stage 3b-4 CKD patients were enrolled during a hospitalization and randomised in two arms: Co-management by PCPs and nephrologists (interventional arm) versus management by PCPs with written instructions and consultations by nephrologists on demand (standard care). Our primary outcome was death or rehospitalisation within the 2 years post-randomisation. Secondary outcomes were: urgent renal replacement therapy (RRT), decline of renal function and decrease of quality of life at 2 years. RESULTS: From November 2009 to the end of June 2013, we randomised 242 patients. Mean follow-up was 51 + 20 months. Survival without rehospitalisation, GFR decline and elective dialysis initiation did not differ between the two arms. Quality of life was also similar in both groups. Compared to randomised patients, those who either declined to participate in the study or were previously known by nephrologists had a worse survival. CONCLUSION: These results do not demonstrate a benefit of a regular renal care compared to guided PCPs care in terms of survival or dialysis initiation in CKD patients. Increased awareness of renal disease management among PCPs may be as effective as a co-management by PCPs and nephrologists in order to improve the prognosis of moderate-to-severe CKD. TRIAL REGISTRATION: This study was registered on June 29, 2009 in clinicaltrials.gov (NCT00929760) and adheres to CONSORT 2010 guidelines.

Comparison of readout-segmented and conventional single-shot for echo-planar diffusion-weighted imaging in the assessment of kidney interstitial fibrosis.

PURPOSE: To compare readout-segmented echo-planar imaging (EPI) (RESOLVE) to single-shot EPI (ss-EPI) diffusion-weighted imaging (DWI) for the assessment of renal interstitial fibrosis. MATERIALS AND METHODS: A phantom, eight healthy volunteers (under 30 years to avoid age-fibrosis related) and 27 chronic kidney disease (CKD) patients (scheduled for kidney biopsy) were scanned (at 3T) with ss-EPI and 5-shot RESOLVE DWI (resolution: 2 × 2 × 5 mm3 , 10 b-values). The cortico-medullary difference for each DW parameter from a monoexponential fit (ΔADC) or, segmented biexponential fit (ΔD, ΔD*, ΔFp ) were compared between both sequences. A fibrosis threshold of 40% was defined to separate all 35 subjects into low and high fibrosis groups. The linear relationship between DW parameters and percentage fibrosis (up to 80%) from Masson trichrome was assessed with the Pearson product-moment correlation coefficient. Fisher Z-transform was used for R2 correlation comparison. RESULTS: A coefficient of variation between ADCs of 3% was measured between both sequences in the phantom. In healthy volunteers, no significant difference was measured for all DW parameters. Both sequences separated low to high level of fibrosis with a significant decrease of ΔADC (RESOLVE P = 3.1 × 10-6 , ss-EPI P = 0.003) and ΔD (RESOLVE P = 8.2 × 10-5 , ss-EPI P = 0.02) in the high level of fibrosis. However, RESOLVE ΔADC had a stronger negative correlation (P = 0.04 for R2 comparison) with fibrosis than ss-EPI ΔADC (RESOLVE R2 = 0.65, P = 5.9 × 10-9 , ss-EPI R2 = 0.29, P = 8.9 × 10-4 ). ΔD (RESOLVE) was correlated (moderately) with fibrosis (R2 = 0.29, P = 9.2 × 10-4 ); however, ΔD* and ΔFp did not show, in our population, a significant correlation with interstitial fibrosis (0.01 < R2 < 0.08). CONCLUSION: ΔADC derived from both sequences correlated with fibrosis. ΔADC from RESOLVE showed better correlation with fibrosis than ΔADC from ss-EPI and therefore has potential to monitor CKD. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1631-1640.

Increased Synthesis of Liver Erythropoietin with CKD.

Anemia of CKD seems to be related to impaired production of renal erythropoietin (Epo). The glycosylation pattern of Epo depends on the synthesizing cell and thus, can indicate its origin. We hypothesized that synthesis of Epo from nonkidney cells increases to compensate for insufficient renal Epo production during CKD. We determined plasma Epo levels and Epo glycosylation patterns in 33 patients with CKD before undergoing dialysis and nine patients with CKD undergoing dialysis. We compared these values with values obtained in healthy volunteers and other controls. Although patients with CKD before undergoing dialysis had median (interquartile range) Epo levels higher than those of healthy controls (13.8 IU/L; interquartile range, 10.0-20.7 IU/L versus 8.4 IU/L; interquartile range, 7.6-9.0 IU/L; P<0.01), these patients were moderately anemic (mean±SD; hemoglobin =118±17 g/L). Detected as the percentage of migrated isoforms (PMI), Epo glycosylation in patients with CKD before undergoing dialysis (PMI=36.1±11.7%) differed from that in healthy controls (PMI=9.2±3.8%; P<0.01) but not from that in umbilical cord plasma (PMI=53.9±10.6%; P>0.05), which contains mainly liver-derived Epo. Furthermore, glycosylation modification correlated with eGFR loss. These results suggest that patients with CKD maintain persistent Epo synthesis despite declining renal function, and this maintenance may result in part from increased liver Epo synthesis.

Living kidney donation does not adversely affect serum calcification propensity and markers of vascular stiffness.

Living kidney donors (LKDs) experience a decline in glomerular filtration rate (GFR) after donation. Calcification propensity (T50 ) can be determined by a blood test predicting all-cause mortality in patients with chronic kidney disease. We studied the impact of kidney donation on T50 and markers of arterial stiffness. We analyzed T50 prospectively before and 1 year after kidney donation in 21 LKDs along with fetuin-A, mineral metabolism markers, kidney length, pulse wave velocity (PWV), augmentation index (AI), and renal resistive index (RRI) as markers of arterial stiffness. We studied the impact of kidney donation on these parameters. LKDs were 54 ± 10 years old and had a GFR of 101 ± 18 ml/min/1.73 m(2) before donation, decreasing to 67 ± 8 ml/min/1.73 m(2) after donation (P < 0.001). Despite this, T50 improved after donation (290 ± 53 to 312 ± 38 min, P = 0.049). This change was inversely related to plasma phosphate (P = 0.03), which declined after donation (P = 0.002). Fetuin-A levels increased after donation (P = 0.01). Upon donation, the length of the remaining kidney increased (P < 0.001) while PWV, AI, and RRI remained unchanged. Calcification propensity was not adversely affected by kidney donation. This indicates that T50 is independent from GFR in LKDs and that kidney donation does neither worsen calcification propensity nor markers of vascular stiffness at 1 year.

Validation of automatically measured T1 map cortico-medullary difference (ΔT1) for eGFR and fibrosis assessment in allograft kidneys.

MRI T1-mapping is an important non-invasive tool for renal diagnosis. Previous work shows that ΔT1 (cortex-medullary difference in T1) has significant correlation with interstitial fibrosis in chronic kidney disease (CKD) allograft patients. However, measuring cortico-medullary values by manually drawing ROIs over cortex and medulla (a gold standard method) is challenging, time-consuming, subjective and requires human training. Moreover, such subjective ROI placement may also affect the work reproducibility. This work proposes a deep learning-based 2D U-Net (RCM U-Net) to auto-segment the renal cortex and medulla of CKD allograft kidney T1 maps. Furthermore, this study presents a correlation of automatically measured ΔT1 values with eGFR and percentage fibrosis in allograft kidneys. Also, the RCM U-Net correlation results are compared with the manual ROI correlation analysis. The RCM U-Net has been trained and validated on T1 maps from 40 patients (n = 2400 augmented images) and tested on 10 patients (n = 600 augmented images). The RCM U-Net segmentation results are compared with the standard VGG16, VGG19, ResNet34 and ResNet50 networks with U-Net as backbone. For clinical validation of the RCM U-Net segmentation, another set of 114 allograft kidneys patient's cortex and medulla were automatically segmented to measure the ΔT1 values and correlated with eGFR and fibrosis. Overall, the RCM U-Net showed 50% less Mean Absolute Error (MAE), 16% better Dice Coefficient (DC) score and 12% improved results in terms of Sensitivity (SE) over conventional CNNs (i.e. VGG16, VGG19, ResNet34 and ResNet50) while the Specificity (SP) and Accuracy (ACC) did not show significant improvement (i.e. 0.5% improvement) for both cortex and medulla segmentation. For eGFR and fibrosis assessment, the proposed RCM U-Net correlation coefficient (r) and R-square (R2) was better correlated (r = -0.2, R2 = 0.041 with p = 0.039) to eGFR than manual ROI values (r = -0.19, R2 = 0.037 with p = 0.051). Similarly, the proposed RCM U-Net had noticeably better r and R2 values (r = 0.25, R2 = 0.065 with p = 0.007) for the correlation with the renal percentage fibrosis than the Manual ROI results (r = 0.3, R2 = 0.091 and p = 0.0013). Using a linear mixed model, T1 was significantly higher in the medulla than in the cortex (p<0.0001) and significantly lower in patients with cellular rejection when compared to both patients without rejection and those with humoral rejection (p<0.001). There was no significant difference in T1 between patients with and without humoral rejection (p = 0.43), nor between the types of T1 measurements (Gold standard manual versus automated RCM U-Net) (p = 0.7). The cortico-medullary area ratio measured by the RCM U-Net was significantly increased in case of cellular rejection by comparison to humoral rejection (1.6 +/- 0.39 versus 0.99 +/- 0.32, p = 0.019). In conclusion, the proposed RCM U-Net provides more robust auto-segmented cortex and medulla than the other standard CNNs allowing a good correlation of ΔT1 with eGFR and fibrosis as reported in literature as well as the differentiation of cellular and humoral transplant rejection. Therefore, the proposed approach is a promising alternative to the gold standard manual ROI method to measure T1 values without user interaction, which helps to reduce analysis time and improves reproducibility.

Calcification Propensity (T50) Predicts a Rapid Decline of Renal Function in Kidney Transplant Recipients.

BACKGROUND: Serum creatinine level, proteinuria, and interstitial fibrosis are predictive of renal prognosis. Fractional excretion of phosphate (FEP)/FGF23 ratio, tubular reabsorption of phosphate (TRP), serum calcification propensity (T50), and Klotho's serum level are emerging as determinants of poor kidney outcomes in CKD patients. We aimed at analysing the use of FGF23, FEP/FGF23, TRP, T50, and Klotho in predicting the rapid decline of renal function in kidney allograft recipients. METHODS: We included 103 kidney allograft recipients in a retrospective study with a prospective follow-up of 4 years. We analysed the predictive values of FGF23, FEP/FGF23, TRP, T50, and Klotho for a rapid decline of renal function defined as a drop of eGFR > 30%. RESULTS: During a follow-up of 4 years, 23 patients displayed a rapid decline of renal function. Tertile of FGF23 (p value = 0.17), FEP/FGF23 (p value = 0.78), TRP (p value = 0.62) and Klotho (p value = 0.31) were not associated with an increased risk of rapid decline of renal function in kidney transplant recipients. The lower tertile of T50 was significantly associated with eGFR decline >30% with a hazard ratio of 3.86 (p = 0.048) and remained significant in multivariable analysis. CONCLUSION: T50 showed a strong association with a rapid decline of renal function in kidney allograft patients. This study underlines its role as an independent biomarker of loss of kidney function. We found no association between other phosphocalcic markers, such as FGF23, FEP/FGF23, TRP and Klotho, with a rapid decline of renal function in kidney allograft recipients.

Diffusion-Weighted MRI in the Genitourinary System.

Diffusion weighted imaging (DWI) constitutes a major functional parameter performed in Magnetic Resonance Imaging (MRI). The DW sequence is performed by acquiring a set of native images described by their b-values, each b-value representing the strength of the diffusion MR gradients specific to that sequence. By fitting the data with models describing the motion of water in tissue, an apparent diffusion coefficient (ADC) map is built and allows the assessment of water mobility inside the tissue. The high cellularity of tumors restricts the water diffusion and decreases the value of ADC within tumors, which makes them appear hypointense on ADC maps. The role of this sequence now largely exceeds its first clinical apparitions in neuroimaging, whereby the method helped diagnose the early phases of cerebral ischemic stroke. The applications extend to whole-body imaging for both neoplastic and non-neoplastic diseases. This review emphasizes the integration of DWI in the genitourinary system imaging by outlining the sequence's usage in female pelvis, prostate, bladder, penis, testis and kidney MRI. In gynecologic imaging, DWI is an essential sequence for the characterization of cervix tumors and endometrial carcinomas, as well as to differentiate between leiomyosarcoma and benign leiomyoma of the uterus. In ovarian epithelial neoplasms, DWI provides key information for the characterization of solid components in heterogeneous complex ovarian masses. In prostate imaging, DWI became an essential part of multi-parametric Magnetic Resonance Imaging (mpMRI) to detect prostate cancer. The Prostate Imaging-Reporting and Data System (PI-RADS) scoring the probability of significant prostate tumors has significantly contributed to this success. Its contribution has established mpMRI as a mandatory examination for the planning of prostate biopsies and radical prostatectomy. Following a similar approach, DWI was included in multiparametric protocols for the bladder and the testis. In renal imaging, DWI is not able to robustly differentiate between malignant and benign renal tumors but may be helpful to characterize tumor subtypes, including clear-cell and non-clear-cell renal carcinomas or low-fat angiomyolipomas. One of the most promising developments of renal DWI is the estimation of renal fibrosis in chronic kidney disease (CKD) patients. In conclusion, DWI constitutes a major advancement in genitourinary imaging with a central role in decision algorithms in the female pelvis and prostate cancer, now allowing promising applications in renal imaging or in the bladder and testicular mpMRI.

Impact of Hyponatremia after Renal Transplantation on Decline of Renal Function, Graft Loss and Patient Survival: A Prospective Cohort Study.

BACKGROUND: Hyponatremia is one of the most common electrolyte disorders observed in hospitalized and ambulatory patients. Hyponatremia is associated with increased falls, fractures, prolonged hospitalisation and mortality. The clinical importance of hyponatremia in the renal transplant field is not well established, so the aim of this study was to determine the relationships between hyponatremia and mortality as main outcome and renal function decline and graft loss as secondary outcome among a prospective cohort of renal transplant recipients. METHODS: This prospective cohort study included 1315 patients between 1 May 2008 and 31 December 2014. Hyponatremia was defined as sodium concentration below 136 mmol/L at 6 months after transplantation. The main endpoint was mortality. A secondary composite endpoint was also defined as: rapid decline in renal function (≥5 mL/min/1.73 m2 drop of the eGFR/year), graft loss or mortality. RESULTS: Mean sodium was 140 ± 3.08 mmol/L. 97 patients displayed hyponatremia with a mean of 132.9 ± 3.05 mmol/L. Hyponatremia at 6 months after transplantation was associated neither with mortality (HR: 1.02; p = 0.97, 95% CI: 0.47-2.19), nor with the composite outcome defined as rapid decline in renal function, graft loss or mortality (logrank test p = 0.9). CONCLUSIONS: Hyponatremia 6 months after transplantation is not associated with mortality in kidney allograft patients.

Kinetic GFR Outperforms CKD-EPI for Slow Graft Function Prediction in the Immediate Postoperative Period Following Kidney Transplantation.

BACKGROUND: Rapid identification of patients at high risk for slow graft function (SGF) is of major importance in the immediate period following renal graft transplantation, both for early therapeutic decisions and long-term prognosis. Due to the high variability of serum creatinine levels after surgery, glomerular filtration rate (GFR) estimation is challenging. In this situation, kinetic estimated GFR (KeGFR) equations are interesting tools but have never been assessed for the identification of SGF patients. METHODS: We conducted a single-center retrospective cohort study, including all consecutive kidney allograft recipients in the University Hospitals of Geneva from 2008 to 2016. GFR was estimated using both CKD-EPI and KeGFR formulae. Their accuracies for SGF prediction were compared. Patients were followed up for one year after transplantation. RESULTS: A total of 326 kidney recipients were analyzed. SGF occurred in 76 (23%) patients. KeGFR estimation stabilized from the day following kidney transplantation, more rapidly than CKD-EPI. Discrimination ability for SGF prediction was better for KeGFR than CKD-EPI (AUC 0.82 and 0.66, p < 0.001, respectively). CONCLUSION: KeGFR computed from the first day after renal transplantation was able to predict SGF with good discrimination, outperforming CKD-EPI estimation. SGF patients had lower renal graft function overall at the one-year follow up.

Author Correction: Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.