Any reduction in maternal kidney mass makes a difference during pregnancy in gestational and fetal outcome.

Little is known about the effect tubulointerstitial nephropathies have in modulating maternal-fetal outcomes in pregnancy. Therefore, we analyzed the main outcomes of pregnancy in these women to gain a better understanding of the role of a reduction in maternal kidney mass. From the Torino Cagliari Observational Study (TOCOS) cohort, we selected 529 patients with a diagnosis of tubulointerstitial disease and focused on 421 patients with chronic kidney disease (CKD) stage 1, without hypertension but with proteinuria less than 0.5 g/day at referral. From a cohort of 2969 singleton deliveries from low-risk pregnancies followed in the same settings we selected a propensity score matched control cohort of 842 pregnancies match 2:1 for age, parity, body mass index, ethnicity, and origin. Time to delivery was significantly shorter in the study cohort 38.0 (Quartile 1-Quartile 3: 37.0-39.0) versus 39.0 (Q1-Q3 38.0-40.0) weeks, with respect to controls. Incidence of delivery of less than 37 gestational weeks significantly increased from controls (7.4%) to women with previous acute pyelonephritis (10.8%), other tubulointerstitial diseases (9.7%) and was the highest in patients with a single kidney (31.1%). Similarly, neonatal birthweight significantly and progressively decreased from controls (3260 g [Q1-Q3: 2980-3530]), previous acute pyelonephritis (3090 g [Q1-Q3: 2868-3405], other tubulointerstitial diseases (3110 g [Q1-Q3: 2840-3417]), and to solitary kidney (2910 g [Q1-Q3: 2480-3240]). Risk of developing preeclampsia was significantly higher in the CKD cohort (3.6% vs 1.7% in low-risk controls). Thus, even a small reduction in functional kidney mass, such as a pyelonephritic scar, is associated with a shorter duration of pregnancy and an increased risk of preterm delivery. The risk is proportional to the extent of parenchymal reduction and is highest in cases with a solitary kidney.

Genome-wide analysis identifies MYH11 compound heterozygous variants leading to visceral myopathy corresponding to late-onset form of megacystis-microcolon-intestinal hypoperistalsis syndrome.

Megacystis-microcolon-hypoperistalsis-syndrome (MMIHS) is a rare and early-onset congenital disease characterized by massive abdominal distension due to a large non-obstructive bladder, a microcolon and decreased or absent intestinal peristalsis. While in most cases inheritance is autosomal dominant and associated with heterozygous variant in ACTG2 gene, an autosomal recessive transmission has also been described including pathogenic bialellic loss-of-function variants in MYH11. We report here a novel family with visceral myopathy related to MYH11 gene, confirmed by whole genome sequencing (WGS). WGS was performed in two siblings with unusual presentation of MMIHS and their two healthy parents. The 38 years-old brother had severe bladder dysfunction and intestinal obstruction, whereas the 30 years-old sister suffered from end-stage kidney disease with neurogenic bladder and recurrent sigmoid volvulus. WGS was completed by retrospective digestive pathological analyses. Compound heterozygous variants of MYH11 gene were identified, associating a deletion of 1.2 Mb encompassing MYH11 inherited from the father and an in-frame variant c.2578_2580del, p.Glu860del inherited from the mother. Pathology analyses of the colon and the rectum revealed structural changes which significance of which is discussed. Cardiac and vascular assessment of the mother was normal. This is the second report of a visceral myopathy corresponding to late-onset form of MMIHS related to compound heterozygosity in MYH11; with complete gene deletion and a hypomorphic allele in trans. The hypomorphic allele harbored by the mother raised the question of the risk of aortic disease in adults. This case shows the interest of WGS in deciphering complex phenotypes, allowing adapted diagnosis and genetic counselling.

Roadmaps to green nephrology: a mediterranean point of view.

PURPOSE OF REVIEW: Green nephrology is a movement whose aim is to find ways to reduce the environmental impact of kidney care. The question is of particular concern in this field since haemodialysis is one of the major contributors to waste generation, energy use and water consumption in healthcare. Although several ways for improving sustainability have been advocated, they are all context sensitive. This review aims to analyse the interventions that have been proposed to improve the ecologic sustainability and reduce the carbon footprint of nephrology care adapting to specific settings, and taking advantage of local expertise. RECENT FINDINGS: Green hospitals are becoming a reality in several high-income settings, thanks to new building guidelines, with greater awareness of climate change and users' demands. Water saving is feasible, and is increasingly done, in different ways (improving hardware, reducing and adapting dialysate flows). Recycling noncontaminated plastic waste is feasible, but is still rarely performed. However, ecological transition has been slow even in high-income countries, while in low and middle-income countries lack of resources limit the ability to cope with the planet's urgent needs. Conversely, where man-power cost is low, some time-consuming tasks, such as separation of various components for recycling may be affordable. Theoretically, implementation of all clinical tasks aiming to avoid or retard dialysis, should be a priority. SUMMARY: There is no single roadmap for achieving green nephrology. Each setting should start from those feasible interventions most in line with its specific needs and priorities.

A predictive mortality score in ANCA-associated renal vasculitis.

BACKGROUND: Several scores have been developed to predict mortality at ANCA-Associated Vasculitis (AAV) diagnosis. Their prognostic value in Caucasian patients with kidney involvement (AAV-GN) remains uncertain as none have been developed in this specific population. We aimed to propose a novel and more accurate score specific for them. METHODS: This multicentric study included patients diagnosed with AAV-GN since January 2000 in 4 nephrology Centers (recorded in the Maine-Anjou AAV-GN Registry). Existing scores and baseline characteristics were assessed at diagnosis before any therapeutic intervention. A multivariable analysis was performed to build a new predictive score for death. Its prognosis performance (AUROC and C-index) and accuracy (Brier score) was compared to existing scores. 185 patients with AAV-GN from the RENVAS registry were used as a validation cohort. RESULTS: 228 patients with AAV-GN from the Maine-Anjou registry were included to build the new score. It included the 4 components most associated with death: age, history of hypertension or cardiac disease, creatinine, and hemoglobin levels at diagnosis. 194 patients had all the data available to determine the performance of the new score and existing scores. The new score performed better than the previous ones in the development and in the validation cohort. Among the scores tested, only FFS (Five-Factor Score) and JVAS (Japanese Vasculitis Activity Score) had good performance in predicting death in AAV-GN. CONCLUSIONS: This original score, named DANGER (Death in ANCA Glomerulonephritis -Estimating the Risk), may be useful to predict the risk of death in AAV-GN patients. Validation in different populations is needed to clarify its role in assisting clinical decisions.

Water implications in dialysis therapy, threats and opportunities to reduce water consumption: a call for the planet.

Water is a dwindling natural resource, and potable water is wrongly considered an unlimited resource. Dialysis, particularly hemodialysis, is a water-hungry treatment that impacts the environment. The global annual water use of hemodialysis is approximately 265 million m3/yr. In this reference estimate, two-thirds of this water is represented by reverse osmosis reject water discharged into the drain. In this review, we would like to draw attention to the complexity and importance of water saving in hemodialysis. We propose that circular water management may comply with the "3R" concept: reduce (reduce dialysis need, reduce dialysate flow, and optimize reverse osmosis performance), reuse (reuse wastewater as potable water), and recycle (dialysis effluents for agriculture and aquaponic use). Awareness and sustainability should be integrated to create positive behaviors. Effective communication is crucial for water savings because local perspectives may lead to global opportunities. Besides the positive environmental impacts, planet-friendly alternatives may have significant financial returns. Innovative policies based on the transition from linear to circular water management may lead to a paradigm shift and establish a sustainable water management model. This review seeks to support policymakers in making informed decisions about water use, avoiding wasting, and finding solutions that may be planet friendly and patient friendly in dialysis, especially in hemodialysis treatments.

Glomerular diseases in pregnancy: pragmatic recommendations for clinical management.

Our understanding of the various aspects of pregnancy in women with kidney diseases has significantly improved in the last decades. Nevertheless, little is known about specific kidney diseases. Glomerular diseases are not only a frequent cause of chronic kidney disease in young women, but combine many challenges in pregnancy: immunologic diseases, hypertension, proteinuria, and kidney tissue damage. An international working group undertook the review of available current literature and elicited expert opinions on glomerular diseases in pregnancy with the aim to provide pragmatic information for nephrologists according to the present state-of-the-art knowledge. This work also highlights areas of clinical uncertainty and emphasizes the need for further collaborative studies to improve maternal and fetal health.

Adding creatinine to routine pregnancy tests: a decision tree for calculating the cost of identifying patients with CKD in pregnancy.

BACKGROUND: Even in its early stages, chronic kidney disease (CKD) is associated with adverse pregnancy outcomes. The current guidelines for pregnancy management suggest identifying risk factors for adverse outcomes but do not mention kidney diseases. Since CKD is often asymptomatic, pregnancy offers a valuable opportunity for diagnosis. The present analysis attempts to quantify the cost of adding serum creatinine to prenatal screening and monitoring tests. METHODS: The decision tree we built takes several screening scenarios (before, during and after pregnancy) into consideration, following the hypothesis that while 1:750 pregnant women are affected by stage 4-5 CKD and 1:375 by stage 3B, only 50% of CKD cases are known. Prevalence of abortions/miscarriages was calculated at 30%; compliance with tests was hypothesized at 50% pre- and post-pregnancy and 90% during pregnancy (30% for miscarriages); the cost of serum creatinine (production cost) was set at 0.20 euros. A downloadable calculator, which makes it possible to adapt these figures to other settings, is available. RESULTS: The cost per detected CKD case ranged from 111 euros (one test during pregnancy, diagnostic yield 64.8%) to 281.90 euros (one test per trimester, plus one post-pregnancy or miscarriage, diagnostic yield 87.7%). The best policy is identified as one test pre-, one during and one post-pregnancy (191.80 euros, diagnostic yield 89.4%). CONCLUSIONS: This study suggests the feasibility of early CKD diagnosis in pregnancy by adding serum creatinine to routinely performed prenatal tests and offers cost estimates for further discussion.

Association between kinetic of anti-neutrophil cytoplasmic antibody (ANCA), renal survival and relapse risk in ANCA glomerulonephritis.

BACKGROUND: Anti-neutrophil cytoplasmic antibody (ANCA) kinetic in ANCA-associated vasculitis with glomerulonephritis (AAV-GN) has been suggested to be associated with AAV relapse. Few studies have focused on its association with renal prognosis. Thus we aimed to investigate the relationship between ANCA specificity and the evolutive profile and renal outcomes. METHODS: This multicentric retrospective study included patients diagnosed with ANCA-GN since 1 January 2000. Patients without ANCA at diagnosis and with fewer than three ANCA determinations during follow-up were excluded. We analysed estimated glomerular filtration rate (eGFR) variation, renal-free survival and relapse-free survival according to three ANCA profiles (negative, recurrent and persistent) and to ANCA specificity [myeloperoxidase (MPO) or proteinase 3 (PR3)]. RESULTS: Over a follow-up of 56 months [interquartile range (IQR) 34-101], a median of 19 (IQR 13-25) ANCA determinations were performed for the 134 included patients. Patients with a recurrent/persistent ANCA profile had a lower relapse-free survival (P = .019) and tended to have a lower renal survival (P = .053) compared with those with a negative ANCA profile. Patients with a recurrent/persistent MPO-ANCA profile had the shortest renal survival (P = .015) and those with a recurrent/persistent PR3-ANCA profile had the worst relapse-free survival (P = .013) compared with other profiles. The negative ANCA profile was associated with a greater eGFR recovery. In multivariate regression analysis, it was an independent predictor of a 2-fold increase in eGFR at 2 years [odds ratio 6.79 (95% confidence interval 1.78-31.4), P = .008]). CONCLUSION: ANCA kinetic after an ANCA-GN diagnosis is associated with outcomes. MPO-ANCA recurrence/persistence identifies patients with a lower potential of renal recovery and a higher risk of kidney failure, while PR3-ANCA recurrence/persistence identifies patients with a greater relapse risk. Thus ANCA kinetics may help identify patients with a smouldering disease.

Nutritional and Dietary Management of Chronic Kidney Disease Under Conservative and Preservative Kidney Care Without Dialysis.

While dialysis has been the prevailing treatment paradigm for patients with advanced chronic kidney disease (CKD), emphasis on conservative and preservative management in which dietary interventions are a major cornerstone have emerged. Based on high-quality evidence, international guidelines support the utilization of low-protein diets as an intervention to reduce CKD progression and mortality risk, although the precise thresholds (if any) for dietary protein intake vary across recommendations. There is also increasing evidence demonstrating that plant-dominant low-protein diets reduce the risk of developing incident CKD, CKD progression, and its related complications including cardiometabolic disease, metabolic acidosis, mineral and bone disorders, and uremic toxin generation. In this review, we discuss the premise for conservative and preservative dietary interventions, specific dietary approaches used in conservative and preservative care, potential benefits of a plant-dominant low-protein diet, and practical implementation of these nutritional strategies without dialysis.

Pregnancy outcomes after kidney transplantation: the challenges of success.

Pregnancy after kidney transplantation is highly successful, though not without risk. A new national Dutch study of a large series of pregnancies in transplanted women highlights the complexities of pregnancy in this cohort and notes a move toward pregnancies in women with "less-than-perfect" graft function. We discuss these new data defining pregnancy outcomes and the ethical and clinical challenges that may arise in these mothers.

Contactin 1, a Potential New Antigen Target in Membranous Nephropathy: A Case Report.

Several novel antigens have recently been characterized in membranous nephropathy (MN), but those involved in the rare cases of MN associated with inflammatory neuropathies remain elusive. Although several antibodies have been identified in the serum, there is no evidence so far for their deposition in glomeruli. We report the case of a 73-year-old woman who was referred because of subacute onset of proximal asymmetric lower limb weakness together with ataxic gait. She was diagnosed with inflammatory neuropathy. Testing showed an estimated glomerular filtration rate of 73mL/min/1.73m2, hypoalbuminemia (2.89g/dL), and proteinuria (3.6g/d). Autoantibodies (antinuclear antibody, anti-extractable nuclear antigen antibody, anti-double stranded DNA antibody, lupus anticoagulant, anticardiolipin antibody, antineutrophil cytoplasmic antibody) were undetectable. Serum immunoglobulin and complement levels were normal. A kidney biopsy with electron microscopy examination showed a classical picture of MN. Testing for antibodies to phospholipase A2 receptor (PLA2R) gave negative results in the serum, and PLA2R and THSD7A antigens were not detected in kidney tissue. Anti-contactin 1 (CNTN1) antibody was detected by enzyme-linked immunosorbent assay at a 1:100 dilution of serum and shown to be mostly of IgG4 subclass by Western blot. CNTN1 antigen was colocalized with IgG4 within immune deposits by confocal microscopy. This observation suggests a pathophysiological link between inflammatory neuropathies and MN. CNTN1 should be considered as a potential candidate antigen involved in MN and tested in PLA2R-negative forms associated with inflammatory neuropathies.

Pre-eclampsia is a valuable opportunity to diagnose chronic kidney disease: a multicentre study.

BACKGROUND: Pre-eclampsia (PE) and chronic kidney disease (CKD) are known to be associated. Our objective was to assess the prevalence of CKD in a large multicentre cohort of women without acknowledged CKD who experienced a PE episode. METHODS: The setting for the study was France (Le Mans, Central France) and Italy (Cagliari, Sardinia). The study participants were patients who experienced PE in 2018-19, identified from the obstetric charts. Patients with known-acknowledged CKD were excluded. Only singletons were considered. Persistent (micro)albuminuria was defined as present and confirmed at least 3 months after delivery. CKD was defined according to the Kidney Disease Outcomes Quality Initiative guidelines; urinary alterations or low eGFR confirmed at a distance of at least 3 months, or morphologic changes. Patients were divided into four groups: evidence of CKD; no evidence of CKD; unclear diagnosis-ongoing work-up; or persistent microalbuminuria. The outcome 'diagnosis of CKD' was analysed by simple and multiple logistic regressions. Temporal series (week of delivery) were analysed with Kaplan-Meier curves and Cox analysis. RESULTS: Two hundred and eighty-two PE pregnancies were analysed (Le Mans: 162; Cagliari: 120). The incidence of CKD diagnosis was identical (Le Mans: 19.1%; Cagliari: 19.2%); no significant difference was found in unclear-ongoing diagnosis (6.2%; 5.8%) and microalbuminuria (10.5%; 5.8%). Glomerulonephritis and diabetic nephropathy were more frequent in Cagliari (higher age and diabetes prevalence), and interstitial diseases in Le Mans. In the multivariate logistic regression, CKD diagnosis was associated with preterm delivery (adjusted P = 0.035). Gestation was 1 week shorter in patients diagnosed with CKD (Kaplan-Meier P = 0.007). In Cox analysis, CKD remained associated with shorter gestation after adjustment for age and parity. CONCLUSIONS: The prevalence of newly diagnosed CKD is high after PE (19% versus expected 3% in women of childbearing age), supporting a systematic nephrology work-up after PE.

What a paediatric nephrologist should know about preeclampsia and why it matters.

Preeclampsia is a protean syndrome causing a kidney disease characterised by hypertension and proteinuria, usually considered transitory and reversible after delivery. Its prevalence ranges from 3-5 to 10% if all the related disorders are considered. This narrative review, on behalf of the Kidney and Pregnancy Study Group of the Italian Society of Nephrology, focuses on three reasons why preeclampsia should concern paediatric nephrologists and how they can play an important role in its prevention, as well as in the prevention of future kidney and cardiovascular diseases. Firstly, all diseases of the kidney and urinary tract diagnosed in paediatric age are associated with a higher risk of adverse pregnancy-related outcomes, including preeclampsia. Secondly, babies with low birth weights (small for gestational age, born preterm, or both) have an increased risk of developing the full panoply of metabolic diseases (obesity, hypertension, early-onset cardiopathy and chronic kidney disease) and girls are at higher risk of developing preeclampsia when pregnant. The risk may be particularly high in cases of maternal preeclampsia, highlighting a familial aggregation of this condition. Thirdly, pregnant teenagers have a higher risk of developing preeclampsia and the hypertensive disorders of pregnancy, and should be followed up as high risk pregnancies. In summary, preeclampsia has come to be seen as a window on the future health of both mother and baby. Identification of subjects at risk, early counselling and careful follow-up can contribute to reducing the high morbidity linked with this disorder.

Pedobarographic Statistical Parametric Mapping may identify specific plantar pressure patterns in patients with diabetes mellitus among different degrees of peripheral neuropathy: A pilot study.

AIMS: Peripheral neuropathy (PN) in patients with diabetes can lead to changes in the distribution of plantar pressure during walking, which can be recorded with pedobarography. Compared to traditional spatial data reduction analysis, the pedobarographic Statistical Parametric Mapping (pSPM) allows comparison of the footprints with the advantage that sub-regions do not need to be defined a priori. Aim of the study was to test the potential of pSPM in identifying specific distribution of spatial pressure in different stages of PN. METHODS: PN was defined according to usual tools (i.e., tendon reflexes and sensory tests). Four groups were compared: patients with diabetes without PN (n = 24; 239 steps); with signs of mild PN (n = 12; 117 steps); with signs of severe PN (n = 6; 52 steps) and a control group without diabetes (n = 12; 124 steps). Traditional spatial data reduction and pSPM were performed to compare plantar pressures in the different groups. RESULTS: In patients with PN, traditional spatial data reduction analysis showed lower plantar pressures with PN severity. pSPM analysis is able to better define the initial changes: mild PN patients presents higher pressures on the anterior side of the metatarsal heads compared to patients without neuropathy. Patients with severe PN are characterised by higher pressures under the medial foot arch compared to other groups. CONCLUSIONS: pSPM may identify specific features of plantar pressure distribution during walking in patients with mild PN and may become a useful screening tool for a timely identification of this complication.

Kidney Biopsy in Type 2 Diabetic Patients: Critical Reflections on Present Indications and Diagnostic Alternatives.

Roughly 3% of patients worldwide with a new diagnosis of type 2 diabetes mellitus (T2DM) already have an overt nephropathy at diagnosis and about 20-30% of the remaining ones develop a complication of this kind later in life. The early identification of kidney disease in diabetic patients is important as it slows its progression, which is important not only because this reduces the need for renal replacement therapy, but also because it decreases the high rate of mortality and morbidity associated with a reduction in kidney function. The increasing prevalence of type 2 diabetes and the consequent greater probability of finding different types of kidney diseases in diabetic patients frequently gives rise to overlapping diagnoses, a definition encompassing the differential diagnosis between diabetic and non-diabetic kidney disease. The issue is made more complex by the acknowledgement of the increasing frequency of presentations of what is termed "diabetic kidney disease" without relevant proteinuria, in particular in T2DM patients. Distinguishing between diabetes related and non-diabetes related forms of kidney disease in diabetic patients is not only a semantic question, as different diseases require different clinical management. However, while the urologic and macrovascular complications of diabetes, as well as overlapping parenchymal damage, can be diagnosed by means of imaging studies, often only a kidney biopsy will make a differential diagnosis possible. In fact, the coexistence of typical diabetic lesions, such as nodular glomerulopathy or glomerulosclerosis, with different glomerular, vascular and tubulo-interstitial alterations has been extensively described, and an analysis of the dominant histological pattern can contribute to determining what therapeutic approach should be adopted. However, due to the high frequency of kidney diseases, and to the fact that T2DM patients are often affected by multiple comorbidities, a kidney biopsy is not generally performed in T2DM patients. What follows is a review aiming to discuss the diagnostic work-up, on the base of clinical, laboratory and imaging criteria, and evaluate the present indications and alternatives to renal biopsy.

Dietary satisfaction and quality of life in chronic kidney disease patients on low-protein diets: a multicentre study with long-term outcome data (TOrino-Pisa study).

BACKGROUND: Concerns about adherence and quality of life (QoL) limit the diffusion of low-protein diets (LPDs) as a way to slow chronic kidney disease (CKD) progression and postpone dialysis. The aim of this multicentre study is to assess dietary satisfaction in stable CKD patients. METHODS: This was a multicentre cross-sectional study with long-term follow-up data. Prevalent patients on LPD for at least 6 months were selected in four Italian centres. QoL was assessed using the World Health Organization Quality of Life questionnaire, and diet satisfaction with the Modification of Diet in Renal Disease satisfaction questionnaire. Comorbidity was assessed by Charlson Comorbidity Index, estimated glomerular filtration rate (eGFR) was calculated by the CKD Epidemiology Collaboration equation and protein intake by Maroni-Mitch formula. Survival was analysed with Kaplan-Meier curves and Cox Proportional Hazard Model. RESULTS: Four hundred and twenty-two CKD Stages 3-5 patients were enrolled. Over 95% were on moderately restricted diets (0.6 g/kg/day). Compliance was good (protein intake: 0.59 g/kg/day at baseline, 0.72 at the end of follow-up). Median dietary satisfaction was 4 on a 1-5 scale. QoL was not affected by the type of diet, but was influenced by age, comorbidity and setting of care. Two years later, at the end of follow-up, 66.6% of the patients were still on a diet; the main causes of discontinuation were dialysis and death. The dropout rate was low (5.5%); in Cox analysis, patient and renal survival were influenced by age and eGFR, but not by QoL, setting of care or type of diet. CONCLUSIONS: LPDs are compatible with high dietary satisfaction and minimal dropout, at least in patients who are able to follow such a diet for at least 6 months.

Who should be responsible for the care of advanced chronic kidney disease? Do the guidelines point to the end of nephrology follow-up of advanced CKD or are they the starting point for a new approach?

The editorial comments on a recently published study in which 242 patients, with "stable" chronic kidney disease, recruited during a hospital stay, were randomised either to receiving support from nephrologists (co-management by primary care physicians and nephrologists), or to be managed by primary care physicians with written instructions and nephrology consultations on demand. After a mean follow-up of 4 years, the results in terms of dialysis start, hospitalisation and death were similar for both groups.This study gave the possibility to discuss about the options of follow-up of CKD patients, including on one side the advantage of a greater involvement of primary care physicians, who could oversee care by applying a common set of simplified guidelines, and on the other one the importance of a direct and deep involvement of the specialists that seems necessary in particular if personalised approaches have to be pursuit. The data of the present study are somehow in disagreement with the literature, usually suggesting better outcomes in intensive treatment, in which specialists are directly involved. The literature is heterogeneous, the goals vary and the populations are differently selected. The compliance issue is probably one of the missing pieces of the puzzle, and specific interventions should also be tailored to "reluctant" patients. Guidelines should probably be staring points for improvement, and not the standard of care; the study herein discussed may suggest that primary care physicians may be of great help in granting a good standard of care, hopefully as a baseline for further improvement, and personalised care.

PhysIOpathology of NEuromuscular function rElated to fatigue in chronic Renal disease in the elderly (PIONEER): study protocol.

BACKGROUND: Chronic Kidney Disease (CKD) is associated with reduced muscular strength resulting in profound fatigue. The physiopathology of these changes, their prevalence and evolution are still debated. Moreover, we have little data on elderly CKD patients. The present study protocol aims to 1) quantify the prevalence of low muscle strength (dynapenia) in a cohort of elderly patients with advanced CKD and to 2) characterize their force production coupled with electromyographic features and the symptoms of fatigue compared to a matched control group. METHODS: This is a case-control, prospective, interventional study. INCLUSION CRITERIA: age ≥ 60 years; CKD Stage 3b-5; clinical stability (i.e. no hospitalization and ≤ 25% in creatinine increase in the previous 3 months). Controls with normal kidney function will be matched in terms of age, gender and diabetes mellitus (requisite: estimated glomerular filtration rate ≥ 60 ml/min/1.73m2 available in the last 6 months). Exclusion criteria for cases and controls: neuromuscular disease, life expectancy < 3 months. The handgrip strength protocol is an intermittent test consisting in 6 series of 9 repetitions of 3-s sub-maximum contractions at 40% of the maximum voluntary contraction (MVC) and 2 s of resting time between contractions. Each series is separated by one fast sub-maximum contraction and one MVC. Strength is assessed with a high-frequency handgrip dynamometer paired with surface electromyography. Symptoms of fatigue are assessed using MFI-20 and FACIT-F questionnaires. In order to reach a statistical power of 96%, we plan to enroll 110 subjects in each group. DISCUSSION: The novelty of this study resides in the application of an already validated set of tests in a population in which this combination (dynamometer, electromyography and questionnaires) has not previously been explored. We expect a high prevalence of dynapenia and a higher fatigability in CKD patients. A positive correlation is expected between reported fatigue and fatigability. Better appreciation of the prevalence and the relationship between fatigability and a sensation of fatigue can help us target interventions in CKD patients to improve quality of life and survival. TRIAL REGISTRATION: The study was approved by Ethical Committee EST III n°20.03.01 and was recorded as a Clinical Trial (NCT04330807) on April 2, 2020.

A systematic review and meta-analysis indicates long-term risk of chronic and end-stage kidney disease after preeclampsia.

Preeclampsia is a pregnancy-related syndrome of variable severity, classically characterized by acute kidney involvement, with hypertension and/or proteinuria and reduced kidney function. Once considered a self-limited disease healed by delivery, it is now acknowledged that preeclampsia can affect cardiovascular and kidney health in the long term. The entity of risk has not been established and consequently follow-up policies have not been defined. Here we undertook a systematic review to gain better insights into the need for post-preeclampsia follow-up. Articles published between January 2000 and March 2018 were selected, dealing with at least 20 preeclampsia patients, with follow-up of 4 years or more (MEDLINE, Embase, and Cochrane Library). No quality selection or language restriction was performed. Of the 10,510 titles and abstracts originally considered, 21 papers were selected, providing information on 110,803 cases with and 2,680,929 controls without preeclampsia, with partial overlap between studies on the same databases. Heterogeneity was high, and a random meta-analytic model selected. The increase in risk of end stage renal disease after preeclampsia was significant (meta-analytic risk ratios (95% confidence interval) 6.35 (2.73-14.79)); the risk of albuminuria and chronic kidney disease increased but statistical significance was not reached (4.31 (0.95-19.58) and 2.03 (0.58-7.32), respectively). Translating meta-analytic risk into the number of patients who need follow-up to detect one adverse event, 310 patients with preeclampsia are needed to identify one woman with end stage renal disease or four to identify one woman with albuminuria. Heterogeneity in definitions, insufficient follow-up and incomplete recruitment may account for discrepancies. Thus, preeclampsia significantly increases the risk of end stage renal disease. However, there is lack of sufficient data to show a relationship between preeclampsia, albuminuria and chronic kidney disease, underlining the need for further prospective studies.