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.

Baseline proteinuria level and adverse outcomes in pregnant women with chronic kidney disease: new evidence and a note of caution.

About 3% of all pregnancies occur in patients with some degree of chronic kidney disease (CKD) and, in turn, CKD is a risk factor for developing hypertensive disorders of pregnancies (HDP) and unfavorable pregnancy outcomes, at both the maternal and fetal level. CKD is often characterized by proteinuria and proteinuria is a risk factor for HDP. However, even if the positive correlation between proteinuria and unfavorable pregnancy outcomes is well acknowledged, the degree of proteinuria associated with adverse outcomes is still a matter of debate. In this issue of the Journal, Li et al. present a retrospective study that shows that >1 g of proteinuria/day is associated with worse maternal outcomes while >2 g/day with worse fetal ones. This study gives proteinuria thresholds for unfavorable outcomes in pregnant CKD patients, but it should be kept in mind that there is a linear correlation between proteinuria and worse pregnancy outcomes, thus a strict surveillance during the entire gestation should be advised independently of the proteinuria level.

Personalized Low-Protein Diet Prescription in CKD Population: Merging Evidence From Randomized Trials With Observational Data.

Nutritional therapy is a cornerstone of the clinical management of chronic kidney disease (CKD). Nevertheless, randomized controlled trials often have failed to show a relevant benefit of low-protein diets in nonselected CKD populations in terms of slowing the progression of kidney disease and need for dialysis. The more the target population is selected, the less the results can be generalizable to implement in clinical practice. On the contrary, observational studies, especially if performed with patient-centered, flexible approaches, point toward an extensive implementation of dietary protein restriction in different and unselected CKD populations. The observational evidence cannot be disregarded anymore. The most recent guidelines advise implementing low-protein diets or even very-low-protein diets in all CKD patients as early as stage 3. However, the lack of data from large randomized controlled trials on unselected CKD populations as well as on specific subpopulations, such as diabetic or obese patients, which nowadays comprise the majority of CKD subjects, reduces the generalizability of the recommendations. For some patient populations, such as those encompassing very old, nephrotic, or pregnant patients, the literature is even more limited because of the lower prevalence of these conditions and diffused prejudices against reducing protein intake. This pragmatic review discusses the need for integrating information derived from randomized trials with evidence derived from observational studies to guide feasible strategies for more successful implementation of low-protein diets in the treatment of all segments of the CKD population.

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.

Chronic kidney disease, female infertility, and medically assisted reproduction: a best practice position statement by the Kidney and Pregnancy Group of the Italian Society of Nephrology.

Fertility is known to be impaired more frequently in patients with chronic kidney disease than in the general population. A significant proportion of chronic kidney disease patients may therefore need Medically Assisted Reproduction. The paucity of information about medically assisted reproduction for chronic kidney disease patients complicates counselling for both nephrologists and gynaecologists, specifically for patients with advanced chronic kidney disease and those on dialysis or with a transplanted kidney. It is in this context that the Project Group on Kidney and Pregnancy of the Italian Society of Nephrology has drawn up these best practice guidelines, merging a literature review, nephrology expertise and the experience of obstetricians and gynaecologists involved in medically assisted reproduction. Although all medically assisted reproduction techniques can be used for chronic kidney disease patients, caution is warranted. Inducing a twin pregnancy should be avoided; the risk of bleeding, thrombosis and infection should be considered, especially in some categories of patients. In most cases, controlled ovarian stimulation is needed to obtain an adequate number of oocytes for medically assisted reproduction. Women with chronic kidney disease are at high risk of kidney damage in case of severe ovarian hyperstimulation syndrome, and great caution should be exercised so that it is avoided. The higher risks associated with the hypertensive disorders of pregnancy, and the consequent risk of chronic kidney disease progression, should likewise be considered if egg donation is chosen. Oocyte cryopreservation should be considered for patients with autoimmune diseases who need cytotoxic treatment. In summary, medically assisted reproduction is an option for chronic kidney disease patients, but the study group strongly advises extensive personalised counselling with a multidisciplinary healthcare team and close monitoring during the chosen medically assisted reproduction procedure and throughout the subsequent pregnancy.

Choice of the Dialysis Modality: Practical Considerations.

Chronic kidney disease and the need for kidney replacement therapy have increased dramatically in recent decades. Forecasts for the coming years predict an even greater increase, especially in low- and middle-income countries, due to the rise in metabolic and cardiovascular diseases and the aging population. Access to kidney replacement treatments may not be available to all patients, making it especially strategic to set up therapy programs that can ensure the best possible treatment for the greatest number of patients. The choice of the "ideal" kidney replacement therapy often conflicts with medical availability and the patient's tolerance. This paper discusses the pros and cons of various kidney replacement therapy options and their real-world applicability limits.

Plant-based diets for CKD patients: fascinating, trendy, but feasible? A green nephrology perspective.

Climate change is inducing us to rethink our way of life. There is widespread awareness that we need to adopt environmentally friendly approaches and reduce the amount of waste we generate. In medicine, nephrology was one of the first specialties to adopt a green approach. Plant-based or vegan-vegetarian diets, which are planet-friendly and associated with a reduced carbon footprint, were rapidly acknowledged as a valid method for reducing protein intake in the conservative management of chronic kidney disease (CKD). However, how the transition from an omnivorous to a plant-based diet should be managed is not universally agreed; there is little data in the literature and indications based on randomized trials fail to consider feasibility and patients' preferences. Nonetheless, in some conditions the use of plant-based diets has proved safe and effective. For example, in CKD pregnancies, it has reduced unfavorable maternal and fetal outcomes. This review will present the available evidence on the benefits of plant-based diets in CKD, as well as old and new criticisms of their use, including emerging issues, such as contaminants, additives and pesticides, from a green nephrology perspective.

Nutritional status and the risk of malnutrition in older adults with chronic kidney disease - implications for low protein intake and nutritional care: A critical review endorsed by ERN-ERA and ESPEN.

Increased life expectancy is posing unprecedented challenges to healthcare systems worldwide. These include a sharp increase in the prevalence of chronic kidney disease (CKD) and of impaired nutritional status with malnutrition-protein-energy wasting (PEW) that portends worse clinical outcomes, including reduced survival. In older adults with CKD, a nutritional dilemma occurs when indications from geriatric nutritional guidelines to maintain the protein intake above 1.0 g/kg/day to prevent malnutrition need to be adapted to the indications from nephrology guidelines, to reduce protein intake in order to prevent or slow CKD progression and improve metabolic abnormalities. To address these issues, the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Renal Nutrition group of the European Renal Association (ERN-ERA) have prepared this conjoint critical review paper, whose objective is to summarize key concepts related to prevention and treatment of both CKD progression and impaired nutritional status using dietary approaches, and to provide guidance on how to define optimal protein and energy intake in older adults with differing severity of CKD. Overall, the authors support careful assessment to identify the most urgent clinical challenge and the consequent treatment priority. The presence of malnutrition-protein-energy wasting (PEW) suggests the need to avoid or postpone protein restriction, particularly in the presence of stable kidney function and considering the patient's preferences and quality of life. CKD progression and advanced CKD stage support prioritization of protein restriction in the presence of a good nutritional status. Individual risk-benefit assessment and appropriate nutritional monitoring should guide the decision-making process. Higher awareness of the challenges of nutritional care in older adult patients with CKD is needed to improve care and outcomes. Research is advocated to support evidence-based recommendations, which we still lack for this increasingly large patient subgroup.

Ogilvie Syndrome and Acute Kidney Injury: A Rare Complication of Cesarean Section and Preeclampsia.

Ogilvie syndrome, or acute colonic pseudo-obstruction (ACPS) is a rare occurrence, usually following surgery. It consists of a massive dilatation of the cecum, whose diameter becomes greater than 10 cm; its severity is variable, but, if not promptly recognized, it may be life-threatening. Acute kidney injury (AKI) is reported in this context due to both septic complications and to effective hypovolemia. ACPS most commonly affects males and individuals older than 60. In women, the median age at diagnosis is lower due to a strong association with Caesarean sections. The differential diagnosis after delivery may be challenging, due to a potential overlap of symptoms with preeclampsia or hemolysis low platelet elevated liver enzymes (HELLP) syndrome, both associated with AKI. The case herein discussed, regarding a 35-year-old woman, who developed AKI and Ogilvie syndrome after a Caesarean section for preeclampsia, may exemplify these diagnostic and therapeutic challenges, and is intended to raise awareness on this unusual complication of Caesarean delivery.

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.

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.

The ABCs of personalized incremental dialysis start, Le Mans style.

Thrice weekly hemodialysis (HD) is considered the standard of care for patients with end-stage chronic kidney disease (CKD) on extracorporeal renal replacement therapy. However, recent evidence has shown that up to one third of patients start dialysis with a residual kidney function that could allow a reduced frequency/dialysis dose. Interest towards HD schedules other than thrice weekly and the lessons learned from peritoneal dialysis, in addition to growing attention to patients' quality of life, have promoted renewed attention towards incremental HD (iHD). iHD comprises once and twice weekly schedules, makes it possible to soften the "dialysis shock" at the inception of therapy and is patient-friendly. Moreover, it might contribute to preserving residual kidney function longer. Nevertheless, iHD is performed differently in different settings and no guidelines exist on this subject. Taking advantage of the experience accrued with regard to the treatment of advanced CKD both in the outpatient clinic and in the dialysis unit in Le Mans, where two thirds of incident HD patients start in an incremental way, we aimed to present the practical aspects of iHD and discuss its advantages and drawbacks.

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.

The Hypertensive Disorders of Pregnancy: A Focus on Definitions for Clinical Nephrologists.

About 5-10% of pregnancies are complicated by one of the hypertensive disorders of pregnancy. The women who experience these disorders have a greater risk of having or developing kidney diseases than women with normotensive pregnancies. While international guidelines do not provide clear indications for a nephrology work-up after pregnancy, this is increasingly being advised by nephrology societies. The definitions of the hypertensive disorders of pregnancy have changed greatly in recent years. The objective of this short review is to gather and comment upon the main definitions of the hypertensive disorders of pregnancy as a support for nephrologists, who are increasingly involved in the short- and long-term management of women with these disorders.