[Prevention of preeclampsia and its complications]. / Prévention de la prééclampsie et de ses complications.

Preeclampsia is a pregnancy-specific condition characterized by gestational hypertension associated with proteinuria or organ dysfunction after 20 weeks of gestation. It complicates 2 to 8 % of pregnancies worldwide and represents the leading cause of maternal and fetal mortality in developed countries. The only definitive treatment remains termination of pregnancy and delivery of the placenta. Prompt assessment of maternal and fetal status should be held in search of severity criteria and adequate management of this condition according to gestational age. Foremost concerns for pregnant patients are impending eclampsia or placental abruption, while fetal complications arise from placental insufficiency and risks associated with premature pregnancy termination. The sole efficient prophylaxis of preeclampsia in current state of evidence is aspirin at a dosage of 160 mg per day in high risk patients. Preeclampsia is now recognized as a high-risk factor for cardiovascular, renal, and neurological diseases and should therefore be considered as an opportunity for screening and prevention.

La prééclampsie (PE) est un syndrome unique à la grossesse défini par une hypertension artérielle gravidique, associée à une protéinurie ou une atteinte d'organe après 20 semaines d'aménorrhée. Elle complique 2 à 8 % des grossesses à l'échelle mondiale, et représente la première cause de mortalité maternelle et fœtale dans les pays industrialisés. Le seul traitement curatif demeure l'arrêt de la grossesse et la délivrance du placenta. Cette pathologie justifie une évaluation rapide de l'état maternel et fœtal, afin de juger des critères de sévérité et d'orienter la prise en charge selon le terme de la grossesse. La menace maternelle est dominée par le risque de survenue d'une éclampsie ou d'un hématome rétroplacentaire alors que les complications fœtales découlent de l'insuffisance placentaire et des risques inhérents à un arrêt prématuré de grossesse. Le seul traitement préventif actuellement validé en prévention secondaire chez les patientes à haut risque est l'aspirine à une dose de 160 mg par jour. La PE est désormais reconnue comme un facteur de risque cardiovasculaire, rénal et neurologique, et doit être considérée, de ce fait, comme une opportunité de dépistage et de prévention.

[Renal manifestations of syphilis]. / Manifestations rénales de la syphilis.

Syphilis is an acquired or congenital systemic pathology, currently on the rise in Europe. The clinical manifestations of syphilis are not very specific and variable over time. In this case report, we describe two renal presentations of syphilis in patients followed in a Pre-Exposure Prophylaxis (PrEP) program for the prevention of HIV infection. The specificity of the renal involvement of syphilis, the diagnostic and the therapeutic management will be discussed in this article.

La syphilis est une pathologie systémique acquise ou congénitale, actuellement en recrudescence en Europe. Les manifestations cliniques de la syphilis sont souvent peu spécifiques et variables au cours du temps. Nous décrivons ici deux présentations rénales de la syphilis survenues chez des patients suivis dans un programme de Pre-Exposure Prophylaxis (PrEP) de prévention contre l'infection VIH. La spécificité de l'atteinte rénale de la syphilis, la mise au point diagnostique et la prise en charge thérapeutique seront discutées dans cet article.

[Blood pressure variability : useful, trivial or potentially dangerous ?] / La variabilité tensionnelle : utile, futile ou potentiellement dangereuse ?

Usually, blood pressure variability is an adaptive physiological process allowing optimal perfusion of internal organs every time and in every clinical situation. This variability may nevertheless be excessive and then be associated with a poor cardiovascular and renal but also neurological prognosis. An excess in blood pressure variability may also be responsible for unpleasant symptoms in some patients. The different types of blood pressure variability, their causes and consequences as well as the mean to improve its control will be discussed in this article.

La variabilité tensionnelle est habituellement un processus physiologique adaptatif permettant une perfusion optimale des organes internes en tout temps et en toute situation clinique. Cette variabilité peut néanmoins être excessive, ce qui est associé à un mauvais pronostic cardiovasculaire et rénal, mais aussi neurologique. Une variabilité tensionnelle excessive peut également être responsable d'une symptomatologie gênante chez certains patients. Les différents types de variabilité tensionnelle, leurs causes et conséquences ainsi que la manière de mieux la contrôler seront discutés dans cet article.

[Delayed graft function : an ongoing clinical challenge]. / Reprise retardée de fonction du greffon après transplantation rénale : un challenge clinique toujours d'actualité.

Delayed Graft Function (DGF) is defined as the need for dialysis during the first week after transplantation. DGF is frequent and mostly derived from the ischemia/reperfusion cascade to which the graft is subjected throughout the transplantation process. A graft biopsy is recommended after 7 days of DGF to exclude an episode of acute rejection. Note that DGF per se is associated with an increased risk of acute graft rejection, as well as with a shorter long-term graft survival. Several strategies are being studied to mitigate the ischaemic damage, thereby improving graft quality. Among these, cellular therapy using mesenchymal stromal cells (MSC) is promising, in particular via the administration of MSC in the machine perfusion during the preservation of the graft. We will discuss here the different definitions of DGF and the main predictive factors of DGF, as well as the impact on the graft outcomes. The current strategies to prevent DGF will be briefly reviewed.

La reprise retardée de fonction du greffon rénal (DGF en anglais pour Delayed Graft Function), définie notamment par la nécessité de dialyse durant la 1ère semaine après transplantation, reste un événement fréquent. La DGF résulte principalement des phénomènes d'ischémie/reperfusion auxquels le greffon est soumis tout au long du processus de transplantation. Néanmoins, une biopsie du greffon est préconisée après 7 jours de DGF afin d'exclure une cause non ischémique telle qu'un rejet aigu. La DGF est per se associée à un risque accru de rejet du greffon, ainsi qu'à une moins bonne survie du greffon rénal au long cours. Plusieurs stratégies sont étudiées afin d'atténuer les dommages ischémiques et améliorer la qualité du greffon. Parmi celles-ci, la thérapie cellulaire par cellules stromales mésenchymateuses est prometteuse, notamment via l'administration de celles-ci dans la machine de perfusion lors de la préservation du greffon. Nous aborderons les différentes définitions de la DGF ainsi que ses principaux facteurs prédictifs, l'impact sur le devenir du greffon et, brièvement, les stratégies actuelles dans le cadre de la prévention de la DGF.

The prospective screening for SARS-CoV-2 S1/S2 antibodies delineates the factual incidence of COVID-19 and shows a sustained serological response post COVID-19 in kidney transplant recipients.

BACKGROUND: The impact of immunosuppression on the occurrence of Coronavirus Disease 2019 (COVID-19) remains unclear. METHODS: We conducted a prospective screening of anti-S1/S2 IgGs against SARS-CoV-2 Spike protein from March, 1 2020 to May, 15 2021 (prior to the vaccination campaign) in a cohort of 713 kidney transplant recipients (KTRs). In a first phase, the factual incidence and seroprevalence of COVID-19 was established in this cohort: cases diagnosed by serology were added to RT-PCR-based diagnoses to obtain the overall incidence of COVID-19 in both symptomatic and asymptomatic KTRs. In the second phase, the kinetics of the post-COVID-19 humoral response were studied, taking into account the severity of the disease defined by the need for oxygen therapy (group S, "severe") or not (group nS, "not severe"). RESULTS: The combined diagnostic approaches identified 138 COVID-19 cases (19.2%), with 37 diagnoses by serology (26.8%). The rate of asymptomatic KTRs reached 20.3% (28/138). Thirteen patients (9.4%) died from COVID-19. The seroconversion rate was 91.7% (99/108). The peak anti-S1/S2 IgG level was 85 [30-150] AU/ml and was similar between the S and nS groups (117 [38; 186] AU/ml versus 73 [23; 140] AU/ml). A high probability of persistence of anti-S1/S2 IgG post-COVID-19 was observed, with only 10.1% (7/69) of the patients having negated their serology during the 9-month follow-up. CONCLUSION: Our pragmatic serological screening combined with RT-PCR tests provides a better estimation of the real incidence of COVID-19 in KTRs. A significant proportion of KTRs develop humoral immunity post COVID-19, which most often persists beyond 9 months.

The uptake of [18F]-fluorodeoxyglucose by the renal allograft correlates with the acute Banff scores of cortex inflammation but not with the 1-year graft outcomes.

Introduction: [18F]FDG PET/CT noninvasively disproves acute kidney allograft rejection (AR) in kidney transplant recipients (KTRs) with suspected AR. However, the correlation of biopsy-based Banff vs. PET/CT-based scores of acute inflammation remains unknown, as does the prognostic performance of [18F]FDG PET/CT at one year post suspected AR. Methods: From 2012 to 2019, 114 [18F]FDG-PET/CTs were prospectively performed in 105 adult KTRs who underwent per cause transplant biopsies. Ordinal logistic regression assessed the correlation between the extent of histological inflammation and the mean standardized [18F]FDG uptake values (mSUVmean). Functional outcomes of kidney allografts were evaluated at one year post per cause biopsy and correlated to mSUVmean. Results: A significant correlation between mSUVmean and acute Banff score was found, with an adjusted R 2 of 0.25. The mSUVmean was significantly different between subgroups of "total i", with 2.30 ± 0.71 in score 3 vs. 1.68 ± 0.24 in score 0. Neither the function nor the survival of the graft at one year was statistically related to mSUVmean. Discussion: [18F]FDG-PET/CT may help noninvasively assess the severity of kidney allograft inflammation in KTRs with suspected AR, but it does not predict graft outcomes at one year.

Proteinuria in COVID-19: prevalence, characterization and prognostic role.

BACKGROUND: Proteinuria has been commonly reported in patients with COVID-19. However, only dipstick tests have been frequently used thus far. Here, the quantification and characterization of proteinuria were investigated and their association with mortality was assessed. METHODS: This retrospective, observational, single center study included 153 patients, hospitalized with COVID-19 between March 28th and April 30th, 2020, in whom total proteinuria and urinary α1-microglobulin (a marker of tubular injury) were measured. Association with mortality was evaluated, with a follow-up until May 7th, 2020. RESULTS: According to the Kidney Disease Improving Global Outcomes staging, 14% (n = 21) of the patients had category 1 proteinuria (< 150 mg/g of urine creatinine), 42% (n = 64) had category 2 (between 150 and 500 mg/g) and 44% (n = 68) had category 3 proteinuria (over 500 mg/g). Urine α1-microglobulin concentration was higher than 15 mg/g in 89% of patients. After a median follow-up of 27 [14;30] days, the mortality rate reached 18%. Total proteinuria and urinary α1-microglobulin were associated with mortality in unadjusted and adjusted models. This association was stronger in subgroups of patients with normal renal function and without a urinary catheter. CONCLUSIONS: Proteinuria is frequent in patients with COVID-19. Its characterization suggests a tubular origin, with increased urinary α1-microglobulin. Tubular proteinuria was associated with mortality in COVID-19 in our restropective, observational study.

COVID-19-associated Nephropathy Includes Tubular Necrosis and Capillary Congestion, with Evidence of SARS-CoV-2 in the Nephron.

Background: Kidney damage has been reported in patients with COVID-19. Despite numerous reports about COVID-19-associated nephropathy, the factual presence of the SARS-CoV-2 in the renal parenchyma remains controversial. Methods: We consecutively performed 16 immediate (≤3 hours) postmortem renal biopsies in patients diagnosed with COVID-19. Kidney samples from five patients who died from sepsis not related to COVID-19 were used as controls. Samples were methodically evaluated by three pathologists. Virus detection in the renal parenchyma was performed in all samples by bulk RNA RT-PCR (E and N1/N2 genes), immunostaining (2019-nCOV N-Protein), fluorescence in situ hybridization (nCoV2019-S), and electron microscopy. Results: The mean age of our COVID-19 cohort was 68.2±12.8 years, most of whom were male (69%). Proteinuria was observed in 53% of patients, whereas AKI occurred in 60% of patients. Acute tubular necrosis of variable severity was found in all patients, with no tubular or interstitial inflammation. There was no difference in acute tubular necrosis severity between the patients with COVID-19 versus controls. Congestion in glomerular and peritubular capillaries was respectively observed in 56% and 88% of patients with COVID-19, compared with 20% of controls, with no evidence of thrombi. The 2019-nCOV N-Protein was detected in proximal tubules and at the basolateral pole of scattered cells of the distal tubules in nine out of 16 patients. In situ hybridization confirmed these findings in six out of 16 patients. RT-PCR of kidney total RNA detected SARS-CoV-2 E and N1/N2 genes in one patient. Electron microscopy did not show typical viral inclusions. Conclusions: Our immediate postmortem kidney samples from patients with COVID-19 highlight a congestive pattern of AKI, with no significant glomerular or interstitial inflammation. Immunostaining and in situ hybridization suggest SARS-CoV-2 is present in various segments of the nephron.

Diagnostic yield of 18 F-FDG PET/CT imaging and urinary CXCL9/creatinine levels in kidney allograft subclinical rejection.

Subclinical kidney allograft acute rejection (SCR) corresponds to "the unexpected histological evidence of acute rejection in a stable patient." SCR detection relies on surveillance biopsy. Noninvasive approaches may help avoid biopsy-associated complications. From November 2015 to January 2018, we prospectively performed positron emission tomography/computed tomography (PET/CT) after injection of F18 -fluorodeoxyglucose (18 F-FDG) in adult kidney transplant recipients with surveillance biopsy at ~3 months posttransplantation. The Banff-2017 classification was used. The ratio of the mean standard uptake value (mSUVR) between kidney cortex and psoas muscle was measured. Urinary levels of CXCL-9 were concomitantly quantified. Our 92-patient cohort was categorized upon histology: normal (n = 70), borderline (n = 16), and SCR (n = 6). No clinical or biological difference was observed between groups. The mSUVR reached 1.87 ± 0.55, 1.94 ± 0.35, and 2.41 ± 0.54 in normal, borderline, and SCR groups, respectively. A significant difference in mSUVR was found among groups. Furthermore, mSUVR was significantly higher in the SCR vs normal group. The area under the receiver operating characteristic curve (AUC) was 0.79, with 83% sensitivity using an mSUVR threshold of 2.4. The AUC of urinary CXCL-9/creatinine ratios comparatively reached 0.79. The mSUVR positively correlated with ti and acute composite Banff scores. 18 F-FDG-PET/CT helps noninvasively exclude SCR, with a negative predictive value of 98%. External validations are required.

IgG4-related membranous glomerulonephritis and generalized lymphadenopathy without pancreatitis: a case report.

BACKGROUND: IgG4-related disease is a recently described pathologic entity. This is the case of a patient with nephrotic syndrome and lymphadenopathy due to IgG4-related disease. Such a kidney involvement is quite peculiar and has only been described a few times recently. Renal biopsy showed a glomerular involvement with membranous glomerulonephritis in association with a tubulo-interstitial nephropathy. Moreover, the patient was not suffering from pancreatitis. CASE PRESENTATION: The patient is a middle-aged man of Moroccan origin. He has developed recurrent episodes of diffuse lymphadenopathies, renal failure and nephrotic syndrome. Renal biopsies showed membranous glomerulonephritis. DISCUSSION AND CONCLUSION: The diagnostic approach of this atypical presentation is discussed in this case report as well as diagnostic criteria, therapeutic strategies, biomarkers and pathophysiology of IgG4-related disease. IgG4-related membranous glomerulonephritis is a well-established cause of membranous glomerulonephritis. It must be sought after in every patient with a previous diagnosis of IgG4-related disease and in every patient with this histological finding on renal biopsy. Corticoids are still the first-line treatment of IgG4-related disease. New therapeutic strategies are needed to avoid glucocorticoids long term side-effects. Interestingly, the patient was prescribed cyclophosphamide in addition to glucocorticoids for an immune thrombocytopenia. This treatment had a very good impact on his IgG4-related disease.

[Fibrillary nonamyloid glomerulonephritis: a rare etiology of nephrotic syndrome]. / La glomérulonéphrite fibrillaire non amyloïde: une cause rare de syndrome néphrotique.

The fibrillary nonamyloïd glomerulonephritis is a glomerulopathy with fibrillar, nonamyloid deposits of predominantly polyclonal immunoglobulin G. It is an idiopathic glomerulopathy responsible for heavy proteinuria, generally in the nephrotic range, and renal failure up to end stage in 40 % of the cases after five years. The histologic pattern is variable, correlating with renal prognosis. The Congo red-negativity of the deposits and the size of the fibrils on electron microscopy make the differential diagnosis with amyloid deposits. There is no specific efficient therapy. Recurrence in the transplant is frequent, but with better renal prognosis.

Polyomavirus in renal transplantation: a hot problem.

Polyomavirus BK has emerged as an important complication after kidney transplantation. Although, BK nephropathy develops in only 1% to 5% of renal transplant recipients, its prognosis when present is very poor. The most accepted risk factor is the level of immunosuppressive treatment, but the serostatus of donor and recipient and the absence of human leukocyte antigen C7 in donor and/or recipient influence the BK virus (BKV) reactivation. The gold standard in diagnosing BKV nephropathy (BKVN) continues to be biopsy with use of immunohistochemistry for large T antigens. Urinary decoy cells and blood BKV DNA polymerase chain reaction are used in the screening, but their positive predictive values are poor. However, their use as predictors of the evolution of BKVN is more valuable. The reduction of immunosuppressive therapy currently represents the first-line treatment for BKVN. Cidofovir and leflunomide can be used when BKVN continues to progress. In the event of graft loss, retransplantation is possible with a low risk of recurrence when the infection is no longer active.

Is cystatin C useful for the detection and the estimation of low glomerular filtration rate in heart transplant patients?

Although previously studied in patients with chronic kidney disease, there is less data for the use of cystatin C and cystatin C-based formulas in heart transplant recipients. The ability of creatinine and cystatin C to detect renal failure (glomerular filtration rate [GFR] below 60 mL/min/1.73 m(2)) in heart transplant patients has been compared. The accuracy and precision of a creatinine-based formula (Modification of Diet in Renal Disease [MDRD]) versus a cystatin C-based formula (Rule's formula) to estimate GFR have also been studied. GFR was measured using the (51)Cr-ethylenediamine tetraacetic acid tracer in 27 patients. There was no significant difference between GFR and the reciprocal of creatinine or cystatin C. Receiver operating characteristic curves for cystatin C and creatinine were similar. Both formulas were well correlated with the GFR. The bias of the cystatin C-based was significantly better than one of the MDRD formula, but the standard deviation appeared better for the MDRD formula (bias of +3.9 mL/min/1.73 m(2) versus +12 mL/min/1.73 m(2) and SD of 8.5 versus 11.6, respectively). Plasma cystatin C has no clear advantage over serum creatinine to detect renal failure in heart transplanted patients.

Creatinine-based formulae for the estimation of glomerular filtration rate in heart transplant recipients.

Chronic renal failure (CRF) is a common complication in heart transplant patients. Serum creatinine has clear limitations for the detection and estimation of glomerular filtration rate (GFR). Various creatinine-based formulae are classically used for GFR estimation, but little scientific evidence exists for such use in a heart transplant population. GFR was measured using the plasmatic clearance of the glomerular tracer (51)Cr-EDTA in 27 heart transplant patients with two measures for 22 of the patients. Forty-nine measures were thus available for analysis. The precision and accuracy (Bland and Altman analysis) of the Cockcroft, simplified Modified Diet in Renal Diseases (MDRD) and new Mayo Clinic formulae were compared. The mean GFR of the population was 39 +/- 15 mL/min/1.73 m(2). All formulae were well correlated with the GFR. With the Bland and Altman analysis, the accuracy of the MDRD formula appeared higher than that of the Cockcroft or the Mayo Clinic formulae (bias of +12 mL/min/1.73 m(2), vs. +19.9 mL/min/1.73 m(2), and +22.1 mL/min/1.73 m(2), respectively). The difference between the estimated and measured GFR was higher than 20 mL/min/1.73 m(2) in 51% and 55% cases when using the Cockcroft and the Mayo Clinic formulae respectively, whereas the difference was only noted in 14% cases when the MDRD was used. Among creatinine-based formulae, the MDRD appears the most precise and accurate for estimating the GFR in heart transplant patients. However, when the GFR must be measured with high accuracy, we recommend the use of a reference method like inulin or (51)Cr-EDTA plasma clearance techniques.