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.

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.

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.

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.

Outcomes in Living Donor Kidney Transplantation: The Role of Donor's Kidney Function.

INTRODUCTION: Living donor kidney transplant (LDKT) is one of the best therapeutic options for end-stage kidney disease (ESKD). Guidelines identify different estimated glomerular filtration rate (eGFR) thresholds to determine the eligibility of donors. The aim of our study was to evaluate whether pretransplant donor eGFR was associated with kidney function in the recipient. METHODS: We retrospectively studied LDKT recipients who received a kidney graft between September 1, 2005, and June 30, 2016 in the same transplant center in France and that had eGFR data available at 3, 12, 24, and 36 months posttransplant. RESULTS: We studied 90 donor-recipient pairs. The average age at time of transplant was 51.47 ± 10.95 for donors and 43.04 ± 13.52 years for recipients. Donors' average eGFR was 91.99 ± 15.37 mL/min/1.73 m2. Donor's age and eGFR were significantly correlated (p < 0.0001, r2 0.023). Donor's age and eGFR significantly correlated with recipient's eGFR at 3, 12, and 24 months posttransplant (age: p < 0.001 at all intervals; eGFR p = 0.001, 0.003, and 0.016, respectively); at 36 months, only donor's age significantly correlated with recipient's eGFR. BMI, gender match, and year of kidney transplant did not correlate with graft function. In the multivariable analyses, donor's eGFR and donor's age were found to be associated with graft function; correlation with eGFR was lost at 36 months; and donor's age retained a strong correlation with graft function at all intervals (p < 0.001). CONCLUSIONS: Donor's eGFR and age are strong predictors of recipient's kidney function at 3 years. We suggest that donor's eGFR should be clinically balanced with other determinants of kidney function and in particular with age.

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.

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.

Challenges in Managing Pregnancy in Underserved Women with Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is a global public health problem and is linked to adverse outcomes during pregnancy; the high prevalence of CKD (3-6%) in women of childbearing age is of particular relevance in emerging countries where CKD prevalence is higher and resources are limited. Although CKD is a public health problem in Mexico, there is scant information on outcomes in pregnant CKD women in this country. We report maternal-fetal outcomes in a prospective cohort of poor, CKD pregnant women, and compare results with those of pregnant women without CKD. METHODS: A prospective study of pregnant CKD women referred to a public obstetrics/nephrology clinic from July 2013 to December 2017; sociodemographic and clinical data, including complications and perinatal outcomes, were recorded. CKD was defined at referral as per KDIGO guidelines; preeclampsia and superimposed preeclampsia were defined as appearance or worsening of hypertension and proteinuria. Findings were compared to official data for -Mexico and to a historic control of pregnant women without CKD who delivered at our hospital. RESULTS: Sixty-two pregnancies in CKD patients, age 23.4 ± 5.8 years were observed; 46.8% of patients were primiparous. At referral, serum creatinine was 1.8 (1.1-3.0) mg/dL with an estimate glomerular filtration rate (eGFR) of 38.1 (21.9-68.0) mL/min/1.73 m2. In half of the cases, CKD was diagnosed during pregnancy. Forty-eight pregnant women without CKD, age 27 (22-34) years, who delivered during the study period were selected as controls: 33% were primiparous, serum creatinine was 0.50 (0.4-0.6) mg/dL, and estimate glomerular filtration rate was 135 (112-174) mL/min/1.73 m2. Twenty patients needed dialysis (HD-CKD): 2 were already on dialysis, and 18 began treatment during pregnancy; 42 CKD patients did not require dialysis (non-HD CKD). After delivery, 15 patients remained dialysis dependent while 5 did not. Preeclampsia was more frequent in CKD patients in comparison to controls. In total, 93% of CKD patients and 98% of controls delivered a live baby. Prematurity was more frequent in CKD patients than controls and was higher in HD-CKD than in non-HD CKD. Birth weight was lower in CKD when compared to controls. Logistic regression showed a higher risk of preeclampsia in CKD pregnancies than in controls, but it was not affected by age, parity, CKD stage, or need for dialysis during pregnancy. CONCLUSIONS: Underserved CKD Mexican women have a high rate of adverse maternal-fetal outcomes during pregnancy. The risk may be higher in patients needing dialysis during pregnancy, many of whom remained dialysis dependent after delivery.

Adipokines and Myokines as Markers of Malnutrition and Sarcopenia in Patients Receiving Kidney Replacement Therapy: An Observational, Cross-Sectional Study.

Chronic kidney disease (CKD) is linked to an elevated risk of malnutrition and sarcopenia, contributing to the intricate network of CKD-related metabolic disorders. Adipokines and myokines are markers and effectors of sarcopenia and nutritional status. The aim of this study was to assess whether the adipokine-myokine signature in patients on kidney replacement therapy could help identify malnutrition and sarcopenia. The study involved three groups: 84 hemodialysis (HD) patients, 44 peritoneal dialysis (PD) patients, and 52 kidney transplant recipients (KTR). Mean age was 56.1 ± 16.3 years. Malnutrition was defined using the 7-Point Subjective Global Assessment (SGA) and the Malnutrition-Inflammation Score (MIS). Sarcopenia was diagnosed based on reduced handgrip strength (HGS) and diminished muscle mass. Concentrations of adipokines and myokines were determined using the enzyme-linked immunosorbent assay (ELISA). 32.8% of all study participants were identified as malnourished and 20.6% had sarcopenia. For malnutrition, assessed using the 7-Point SGA, in ROC analysis albumin (area under the curve (AUC) 0.67 was the best single biomarker identified. In dialysis patients, myostatin (AUC 0.79) and IL-6 (AUC 0.67) had a high discrimination value for sarcopenia, and we were able to develop a prediction model for sarcopenia, including age, albumin, adiponectin, and myostatin levels, with an AUC of 0.806 (95% CI: 0.721-0.891). Adipokines and myokines appear to be useful laboratory markers for assessing malnutrition and sarcopenia. The formula we propose could contribute to a better understanding of sarcopenia and potentially lead to more effective interventions and management strategies for dialysis patients.

Analysis of the rate of force development reveals high neuromuscular fatigability in elderly patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) induces muscle wasting and a reduction in the maximum voluntary force (MVF). Little is known about the neuromuscular fatigability in CKD patients, defined as the reduction of muscle force capacities during exercise. Neuromuscular fatigability is a crucial physical parameter of the daily living. The quantification of explosive force has been shown to be a sensitive means to assess neuromuscular fatigability. Thus, our study used explosive force estimates to assess neuromuscular fatigability in elderly CKD patients. METHODS: Inclusion criteria for CKD patients were age ≥ 60 years old and glomerular filtration rate (GFR) < 45 mL/min/1.73 m2 not on dialysis, and those for controls were GFR > 60 mL/min/1.73 m2 , age and diabetes matched. The fatigability protocol focused on a handgrip task coupled with surface electromyography (sEMG). Scalars were extracted from the rate of force development (RFD): absolute and normalized time periods (50, 75, 100, 150 and 200 ms, RFD50 , RFD75 , RFD100 , RFD150 and RFD200 , respectively), peak RFD (RFDpeak in absolute; NRFDpeak normalized), time-to-peak RFD (t-RFDpeak ) and the relative force at RFDpeak (MVF-RFDpeak ). A statistical parametric mapping approach was performed on the force, impulse and RFD-time curves. The integrated sEMG with time at 0-30, 0-50, 0-100 and 0-200 ms time intervals relative to onset of sEMG activity was extracted and groups were compared separately for each sex. RESULTS: The cohort of 159 individuals had a median age of 69 (9IQR ) years and body mass index was 27.6 (6.2IQR ) kg/m2 . Propensity-score-matched groups balanced CKD patients and controls by gender with 66 males and 34 females. In scalar analysis, CKD patients manifested a higher decrement than controls in the early phase of contraction, regarding the NRFDpeak (P = 0.009; η2 p  = 0.034) and RFD75 and RFD100 (for both P < 0.001; η2 p  = 0.068 and 0.064). The one-dimensional analysis confirmed that CKD males manifest higher and delayed neuromuscular fatigability, especially before 100 ms from onset of contraction. sEMG was lower in CKD patients than controls in the 0-100 ms (at rest: P = 0.049, Cohen's d = 0.458) and 0-200 ms (at rest: P = 0.016, Cohen's d = 0.496; during exercise: P = 0.006, Cohen's d = 0.421) time windows. Controls showed greater decrease of sEMG than CKD patients in the 0-30 ms (P = 0.020, Cohen's d = 0.533) and 0-50 ms (P = 0.010, Cohen's d = 0.640) time windows. As opposite to females, males showed almost the same differences between groups. CONCLUSIONS: Our study is the first to show that CKD patients have higher fatigability than controls, which may be associated with an impaired motor-unit recruitment, highlighting a neural drive disturbance with CKD. Further studies are needed to confirm these findings.

Neural Drive Impairment in Chronic Kidney Disease Patients Is Associated with Neuromuscular Fatigability and Fatigue.

INTRODUCTION: Chronic kidney disease (CKD) patients have a high degree of fatigue relating to neuromuscular symptoms. There is a lack of evidence regarding the etiology of neuromuscular fatigability in elderly CKD patients. METHODS: Inclusion criteria are as follows: age ≥60 yr, glomerular filtration rate (GFR) <45 mL·min -1 per 1.73 m 2 in CKD patients, and GFR >60 mL·min -1 ·1.73 m -2 in controls. The fatigability protocol consisted in a submaximal handgrip task at 40% peak force. Fatigue was assessed using the Multidimensional Fatigue Inventory-20 items (MFI-20) and the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaires. Peak rate of force development (RFD peak , normalized: NRFD peak ) and rate of EMG rise (RER) were measured during explosive contractions; peak force and mean surface EMG were measured during maximum voluntary contractions. Multilevel models tested neuromuscular parameters adjusted for clinical and Multidimensional Fatigue Inventory-20 items subscales. Neuromuscular fatigability contribution to fatigue description was tested using model comparison. RESULTS: The study included 102 participants; 45 CKD patients and 57 controls. CKD mainly affected the mental and the reduced motivation subscales of fatigue. CKD was associated with greater neuromuscular fatigability assessed using NRFD peak (group-time interaction, -16.7 % MVF·s -1 , P = 0.024), which increased with fatigue severity ( P = 0.018) and with a higher rate of decrement in RER compared with controls (RER at 50 ms: ß = -121.2 µV·s -1 , P = 0.016, and ß = -48.5 µV·s -1 , P = 0.196, respectively). Furthermore, these patients show an association between the reduced motivation subscale and the RER (e.g., 30 ms: ß = -59.8% EMG peak ·s -1 , P < 0.001). Only peak force fatigability contributed to fatigue variance, whereas RFD peak did not. CONCLUSIONS: In CKD patients, the neuromuscular fatigability assessed using RFD peak is related to an impairment in motor-unit recruitment or discharge rates, whereas only peak force fatigability was related to fatigue. This suggests that targeting exercise interventions might lessen fatigue and improve quality of life in CKD patients.

Plant-Based Diets Improve Maternal-Fetal Outcomes in CKD Pregnancies.

Reducing protein intake in patients with chronic kidney disease (CKD) limits glomerular stress induced by hyperfiltration and can prevent the progression of kidney disease; data in pregnancy are limited. The aim of this study is to analyze the results obtained in CKD patients who followed a plant-based moderately protein-restricted diet during pregnancy in comparison with a propensity-score-matched cohort of CKD pregnancies on unrestricted diets. A total of 52 CKD pregnancies followed up with a protein-restricted plant-based diet (Torino, Italy) were matched with a propensity score based on kidney function and proteinuria with CKD pregnancies with unrestricted protein intake (Cagliari Italy). Outcomes included preterm (<37 weeks) and very preterm (<34 weeks) delivery and giving birth to a small-for-gestational-age baby. The median age in our cohort was 34 years, 63.46% of women were primiparous, and the median body mass index (BMI) was 23.15 kg/m2 with 13.46% of obese subjects. No statistical differences were found between women on a plant-based diet and women who were not in terms of age, parity, BMI, obesity, CKD stage, timing of referral, or cause of CKD. No differences were found between the two groups regarding the week of delivery. However, the combined negative outcome (birth before 37 completed gestational weeks or birth-weight centile <10) occurred less frequently in women following the diet than in women in the control group (61.54% versus 80.77%; p = 0.03). The lower risk was confirmed in a multivariable analysis adjusted for renal function and proteinuria (OR: 0.260 [Q1:0.093-Q3:0.724]; p = 0.010), in which the increase in proteinuria from the first to the last check-up before delivery was lower in patients on plant-based diets (median from 0.80 to 1.87 g/24 h; p: ns) than in controls (0.63 to 2.39 g/24 h p <0.0001). Plant-based, moderately protein-restricted diets in pregnancy in patients with CKD are associated with a lower risk of preterm delivery and small-for-gestational-age babies; the effect may be mediated by better stabilization of proteinuria.

Incremental and Personalized Hemodialysis Start: A New Standard of Care.

Introduction: Incremental hemodialysis (iHD) may attenuate "dialysis shock" and reduce costs, preserving quality of life. It is considered difficult to reconcile with HD wards' routine; fear of underdialysis and increasing mortality are additional concerns. The aim of this study was to evaluate mortality, morbidity, and costs in a large HD ward where iHD is the standard of HD start. Methods: This observational study included all incident HD patients in 2017 to 2021, stratified according to HD start: iHD (1-2 sessions/wk), decremental HD (dHD, 3 sessions/wk at start, later reduced), or standard (3 sessions/wk). Results were compared with data recorded in the same unit before the incremental program (2015-2017) and with a propensity score-matched cohort from the French Renal Epidemiology and Information Network (REIN) registry. Results: A total of 158 patients started HD in 2017 to 2021, 57.6% on iHD, 8.9% dHD, and 33.5% standard HD schedule. Patients on the standard schedule had lower initial estimated glomerular filtration rate (eGFR) (5 vs. 7 ml/min per 1.72 m2, P = 0.003). We found no survival differences according to period of start (same center) and propensity score matching (REIN). Patients intensively followed in the pre-HD period were more likely to start on iHD-dHD. Persistence on iHD-dHD was about 50% at 1 year and 35% at 2 years. Hospitalization rates and time to first hospitalization or death did not differ between the schedules. The iHD-dHD policy allowed a 16% cost saving, even accounting for supplemental biochemical tests. Conclusion: Our study reveals that iHD can be a new standard of care, as it is safe and feasible in up to two-thirds of patients on incident HD.

History of Preeclampsia in Patients Undergoing a Kidney Biopsy: A Biphasic, Multiple-Hit Pathogenic Hypothesis.

Introduction: It is not fully elucidated whether preeclampsia (PE) is a marker or a cause of chronic kidney disease (CKD). To test the hypothesis of a biphasic relationship between PE and CKD, we assessed PE prevalence in women who underwent a kidney biopsy. Methods: This retrospective, observational study recruited patients who underwent a kidney biopsy after delivery in 2014 to 2019 in 3 Italian Centers (Cagliari, Bari, Messina); low-risk pregnancies observed in Cagliari served as controls. A history of PE was assessed on the clinical charts and by phone interview. Results: In the biopsy cohort (379 pregnancies, 205 patients; 38 PE in 32 patients), kidney biopsy shows clustering in the first 5 years after PE (11 of 32). Pre-existing CKD was detected in 8 of 11 of these cases. Focal-segmental glomerulosclerosis (FSGS) and complex lesions were found in 12 of 32 biopsies. The odds ratio (OR) of having had a PE episode, compared with 561 low-risk pregnancies, was 10.071 (95% CI: 4.859-20.875; P < 0.001); multiparity maintained a protective effect (OR: 0.208). The delivery-to-biopsy time was significantly shorter in women with PE, both considering the first or the last PE versus the first or last delivery in patients with or without PE episodes. The characteristics of PE did not differ as compared with low-risk controls. Conclusion: Within the limitation of the retrospective design, our study, quantifying the association between needing a kidney biopsy and history of PE, suggests a biphasic pattern, with a peak in the first 5 years after delivery (probably due to pre-existing diseases) and a later increase, suggesting that PE may have later played as one hit in a multiple-hit pathogenesis.

Hypnosis in Treatment of Stomatodynia: Preliminary Retrospective Study of 12 Cases.

Stomatodynia is an oral dysesthesia with a psychosomatic component. Twelve consecutive patients with stomatodynia were offered hypnosis sessions. Measures of anxiety, depression, and pain were administered before the first and after the last hypnosis session. Pain severity was assessed with a Numeric Rating Scale (NRS). Anxiety and depression were assessed with the Hospital Anxiety and Depression Scale (HADS). The data were collected retrospectively from medical records on the 12 patients. The difference between NRS pain ratings and HADS scores before and after hypnosis was significant (p < .05). Six patients reported receiving treatment for stomatodynia before hypnotherapy; 3 of them stopped treatment for stomatodynia before completion of the hypnosis intervention. Results provide support for potential positive effects of hypnosis intervention for stomatodynia and point to the need for additional research on this issue.

Toward an individualized determination of dialysis adequacy: a narrative review with special emphasis on incremental hemodialysis.

INTRODUCTION: The search for the 'perfect' renal replacement therapy has been paralleled by the search for the perfect biomarkers for assessing dialysis adequacy. Three main families of markers have been assessed: small molecules (prototype: urea); middle molecules (prototype ß2-microglobulin); comprehensive and nutritional markers (prototype of the simplified assessment, albumin levels; composite indexes as malnutrition-inflammation score). After an era of standardization of dialysis treatment, personalized dialysis schedules are increasingly proposed, challenging the dogma of thrice-weekly hemodialysis. AREAS COVERED: In this review, we describe the advantages and limitations of the approaches mentioned above, focusing on the open questions regarding personalized schedules and incremental hemodialysis. EXPERT OPINION: In the era of personalized dialysis, the assessment of dialysis adequacy should be likewise personalized, due to the limits of 'one size fits all' approaches. We have tried to summarize some of the relevant issues regarding the determination of dialysis adequacy, attempting to adapt them to an elderly, highly comorbidity population, which would probably benefit from tailor-made dialysis prescriptions. While no single biomarker allows precisely tailoring the dialysis dose, we suggest using a combination of clinical and biological markers to prescribe dialysis according to comorbidity, life expectancy, residual kidney function, and small and medium-size molecule depuration.

Elderly Patients in a Large Nephrology Unit: Who Are Our Old, Old-Old and Oldest-Old Patients?

The world population is aging, and the prevalence of chronic kidney disease (CKD) is increasing. Whether this increase is also due to the methods currently being used to assess kidney function in the elderly is still a matter of discussion. We aimed to describe the actual referral pattern of CKD patients in a large nephrology unit and test whether the use of different formulae to estimate kidney function could affect the staging and the need for specialist care in the older subset of our population. In 2019, 1992 patients were referred to our center. Almost 28% of the patients were aged ≥80 and about 6% were ≥90 years old. Among the causes of kidney disease, glomerulonephritis displayed a higher prevalence in younger patients whereas hypertensive or diabetic kidney disease were more prevalent in older patients. The prevalence of referred patients in advanced CKD stages increased with age; estimated glomerular filtration rate (eGFR) decreased with age regardless of which equation was used (chronic kidney disease epidemiology collaboration (CKD-EPI), Lund-Malmö Revised (LMR), modification of diet in renal disease (MDRD), Full Age Spectrum (FAS), or Berlin Initiative Study 1 (BIS)). With CKD-EPI as a reference, MDRD and FAS underestimated the CKD stage while LMR overestimated it. The BIS showed the highest heterogeneity. Considering an eGFR threshold limit of 45 mL/min for defining "significant" CKD in patients over 65 years of age, the variability in CKD staging was 10% no matter which equation was used. Our study quantified the weight of "old" and "old-old" patients on follow-up in a large nephrology outpatient unit and suggested that with the current referral pattern, the type of formula used does not affect the need for CKD care within the context of a relatively late referral, particularly in elderly patients.

Quality of Life in CKD Patients on Low-Protein Diets in a Multiple-Choice Diet System. Comparison between a French and an Italian Experience.

Prescribing a low-protein diet (LPD) is part of the standard management of patients in advanced stages of chronic kidney disease (CKD). However, studies on the quality of life (QoL) of patients on LPDs are lacking, and the impact these diets have on their QoL is often given as a reason for not prescribing one. We, therefore, decided to assess the QoL in a cohort of CKD stage 3-5 patients followed up by a multiple-choice diet approach in an outpatient nephrology clinic in France. To do so, we used the short version of the World Health Organization's quality of life questionnaire and compared the results with a historical cohort of Italian patients. We enrolled 153 patients, managed with tailored protein restriction in Le Mans, and compared them with 128 patients on similar diets who had been followed in Turin (Italy). We found there were no significant differences in terms of age (median 73 vs. 74 years, respectively), gender, CKD stage, and comorbidities (Charlson's Comorbidity Index 7 vs. 6). French patients displayed a greater body mass index (29.0 vs. 25.4, p < 0.001) and prevalence of obesity (41.2 vs. 15.0%, p < 0.001). Baseline protein intake was over the target in France (1.2 g/kg of real body weight/day). In both cohorts, the burden of comorbidities was associated with poorer physical health perception while kidney function was inversely correlated to satisfaction with social life, independently of the type of diet. Our study suggests that the type of LPD they follow does not influence QoL in CKD patients and that a personalized approach towards protein restriction is feasible, even in elderly patients.

Spontaneously Low Protein Intake in Elderly CKD Patients: Myth or Reality? Analysis of Baseline Protein Intake in a Large Cohort of Patients with Advanced CKD.

The recent guidelines on nutritional management of chronic kidney disease (CKD) advise a reduction in protein intake as early as CKD stage 3, regardless of age, to slow kidney function impairment. However, since elderly patients are usually considered as having a spontaneously reduced protein intake, nutritional interventions to reduce protein intake are often considered futile. This study aimed to assess the baseline protein intake of elderly CKD patients referred for nephrology care, and explore the need for dietary evaluations, focusing on the current recommendations for protein restriction in CKD. This is an observational study of CKD patients followed in the unit dedicated to advanced CKD patients in Le Mans, France. Patients with stages 3 to 5 not on dialysis were included. All patients were evaluated by an expert dietician to assess their baseline protein intake, whenever possible on the basis of a 7-days diet journal; when this was not available, dietary recall or analysis of delivered meals was employed. Demographic characteristics, underlying kidney disease, Charlson Comorbidity Index (CCI), Malnutrition-Inflammation Score (MIS), Subjective Global Assessment (SGA) and clinical and laboratory data were recorded. Between 15 November 2017 and 31 December 2020, 436 patients were evaluated in the unit. Their age distribution was as follows: "young": <60 (n = 62), "young-old": 60-69 (n = 74), "old": 70-79 (n = 108), "old-old": 80-89 (n = 140) and "oldest-old": ≥90 (n = 54). The prevalence of vascular nephropathies was higher in patients older than 70 years compared to younger ones, as did CCI and MIS (p < 0.001). Moderate nutritional impairment (SGA: B) was higher in elderly patients, reaching 53.7% at ≥90, while less than 3% of patients in the overall cohort were classified as SGA C (p < 0.001). The median protein intake was higher than the recommended one of 0.8 g/kg/day in all age groups; it was 1.2 g/kg/day in younger patients and 1.0 thereafter (p < 0.001). Patient survival depended significantly on age (p < 0.001) but not on baseline protein intake (p = 0.63), and younger patients were more likely to start dialysis during follow-up (p < 0.001). Over half of the patients, including the old-old and oldest-old, were still on follow-up two years after referral and it was found that survival was only significantly associated with age and comorbidity and was not affected by baseline protein intake. Our study shows that most elderly patients, including old-old and extremely old CKD patients, are spontaneously on diets whose protein content is higher than recommended, and indicates there is a need for nutritional care for this population.

Unmet needs for CKD care: from the general population to the CKD clinics-how many patients are we missing?

INTRODUCTION: Prevalence of chronic kidney disease (CKD) varies around the world. Little is known about the discrepancy between the general population's needs and nephrology care offered. We aimed to contribute to filling this gap and propose a means to infer the number of patients needing follow-up. METHODS: All patients undergoing at least one nephrology consultation in 2019 were enrolled. We used the ratio between CKD Stages 3 and 4 reported in the literature, and considered that only 25-50% of CKD Stage 3 patients have progressive CKD, to hypothesize different scenarios to estimate the number of CKD Stage 3 patients still needing nephrology follow-up. RESULTS: The 1992 CKD patients were followed-up in our centre (56.93% males; age 66.71 ± 18.32 years; 16.82% Stage 1; 14.66% Stage 2; 39.46% Stage 3; 19.88% Stage 4; 7.68% Stage 5). The ratio between Stages 3 and 4 in population studies ranged from 7.72 to 51.29, being 1.98 in our centre. Hypothesizing that we followed-up 100, 70 or 50% of CKD Stage 4 patients, 528-2506 CKD Stage 3 patients in our area would need nephrology follow-up [1885-8946 per million population (p.m.p.)]. Three to 17 additional nephrologists p.m.p. would be necessary to fully cover the need for care. CONCLUSIONS: The number of patients with CKD Stage 3 who would benefit from nephrology care is high. Considering that one patient-year of delay of dialysis could cover a nephrologist's annual salary, interventions aimed to improve the care of advanced CKD may be economically sound.