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.

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.

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.

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.

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.

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.

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.

Safety and adequacy of percutaneous kidney biopsy performed by nephrology trainees.

BACKGROUND: Recently there has been a progressive loss of specialty related skills for nephrologists. Among the skills we find the kidney biopsy that has a central role in diagnosis of renal parenchymal disease. One of the causes might be the belief that the kidney biopsy should be performed only in larger Centers which can rely on the presence of a renal pathologist and on nephrologists with a large experience. This trend may increase in the short term procedural safety but may limit the chance of in training nephrologists to become confident with the technique. METHODS: We evaluated renal biopsies performed from May 2002 to October 2016 in our Hospital, a mid-sized facility to determine whether the occurrence of complications would be comparable to those reported in literature and whether the increase in the number of biopsy performing physicians including nephrology fellows which took place since January 2012, after our Nephrology Unit became academic, would be associated to an increase of complications or a reduction of diagnostic power of renal biopsies. Three hundred thirty seven biopsies were evaluated. Patients underwent ultrasound guided percutaneous renal biopsy using a 14 G core needle loaded on a biopsy gun. Observation lasted for 24 h, we evaluated hemoglobin levels 6 and 24 h and kidney ultrasound 24 h after the biopsy. RESULTS: Complications occurred in 18.7% of patients, of these only 1,2% were major complications. Complications were more common in female (28%) compared to male patients (14,8%) (p = 0.004). We found no correlation between diagnosis, kidney function and complication rates; hypertension was not associated to a higher risk in complications. The increase of biopsy performing personnel was not associated to an increase in complication rates (18,7% both pre and post 2012) or with an increase of major complications (1.2% vs 1,2%). CONCLUSIONS: Kidney biopsy can be safely performed in mid-sized hospitals. Safety and adequacy are guaranteed even if the procedure is performed by a larger number of less experienced nephrologists as long as under tutor supervision, thus kidney biopsy should become an integral part of a nephrology fellow training allowing more widespread diffusion of this technique.

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.

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.