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Abstract Background The course of kidney function and outcomes of severe malaria infection in pregnant women is poorly understood. The indications for renal replacement therapy in pregnant patients with AKI are similar to the general population. This is the case of a pregnant patient with severe Plasmodium falciparum infection that caused cerebral malaria, acute kidney injury (AKI) who required renal replacement therapy and kidney biopsy during her hospitalization. Case presentation A 29-year-old pregnant woman from Equatorial Guinea was admitted to the hospital with haemolytic anaemia, hyperbilirubinaemia and thrombocytopenia. During hospitalization, a thick blood smear was performed where parasitaemia by P. falciparum were observed and confirmed by real-time PCR assay. The patient developed cerebral malaria secondary to an ischaemic-type cerebral vascular event, hypotension and severe. After confirming diagnosis of P. falciparum infection, artesunate, artemether/lumefantrine and primaquine were started. Kidney biopsy revealed an active tubulointerstitial nephritis with acute tubular lesion and pigment tubulopathy with negative immunofluorescence. After CVVHDF, the patient received intermittent haemodialysis until the recovery of kidney function. After discharge, follow-up was carried until the successful resolution of the pregnancy by cesarean delivery and not shown deterioration in kidney function or proteinuria. Conclusion In this case, intensive dialysis was started and dialysis intensity progressively reduced when kidney function improved. Due to the evolution of kidney function, a kidney biopsy was performed which showed tubulointerstitial nephritis as a manifestation of the infection. While the kidney biopsy was of interest for discriminating between tubular and glomerular involvement, the availability of placental biomarkers (sflt1-PlGF) would have been of help for ruling out preeclampsia and placental damage. The multidisciplinary approach to AKI during pregnancy should be the rule, with diligent care of maternal–fetal well-being during pregnancy and monitoring of kidney function after delivery.

The differential diagnosis between new occurrence or revelation of chronic kidney diseases in pregnancy and hypertensive disorders of pregnancy is not easy, and the presence of a hypertensive disorder superimposed on a glomerular disease is even more challenging, as this case exemplifies. A 29-year-old woman was referred with HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome at the end of her pregnancy. Immediately after cesarean delivery, she developed anuria, unexplained by blood loss or hypotension, and in the absence of known nephrotoxic drugs. While the laboratory features of HELLP rapidly resolved, AKI persisted, and the finding of high-level proteinuria was the hint leading to diagnosis of a glomerular disease (focal segmental glomerulosclerosis, FSGS), later proven by kidney biopsy. This case, reporting on the rare association between HELLP and FSGS, offers the opportunity to discuss the role of proteinuria, hypertension, and in the differential diagnosis of pregnancy-related acute kidney injury (pAKI).

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.

Abstract 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.

Abstract 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

IntroductionThe “Renal Risk Score” (RRS) and the histopathological classification have been proposed to predict the risk of end-stage kidney disease (ESKD) in ANCA-associated glomerulonephritis (ANCA-GN). Besides, factors associated with kidney function recovery after ANCA-GN onset remain to be more extensively studied. In the present study, we analyzed the value of the RRS and of the histopathological classification for ESKD prediction. Next, we analyzed factors associated with eGFR change within the first 2 years following ANCA-GN diagnosis.Materials and MethodsWe included patients from the Maine–Anjou ANCA-associated vasculitis registry with at least 6 months of follow-up. The values of ANCA-GN, histopathological classification, and RRS, and the factors associated with eGFR variations between ANCA-GN diagnosis and 2 years of follow-up were assessed.ResultsThe predictive values of the histopathological classification and RRS were analyzed in 123 patients. After a median follow-up of 42 months, 33.3% patients developed ESKD. The predictive value of RRS for ESKD was greater than that of the histopathological classification. Determinants of eGFR variation were assessed in 80/123 patients with complete eGFR measurement. The median eGFR increased from ANCA-GN diagnosis to month 6 and stabilized thereafter. The only factor associated with eGFR variation in our study was eGFR at ANCA-GN diagnosis, with higher eGFR at diagnosis being associated with eGFR loss (p

Abstract The present increase in life span has been accompanied by an even higher increase in the burden of comorbidity. The challenges to healthcare systems are enormous and performance measures have been introduced to make the provision of healthcare more cost-efficient. Performance of hospitalisation is basically defined by the relationship between hospital stay, use of hospital resources, and main diagnosis/diagnoses and complication(s), adjusted for case mix. These factors, combined in different indexes, are compared with the performance of similar hospitals in the same and other countries. The reasons why an approach like this is being employed are clear. Cutting costs cannot be the only criteria, in particular in elderly, high-comorbidity patients: in this population, although social issues are important determinants of hospital stay, they are rarely taken into account or quantified in evaluations. Quantifying the impact of the “social barriers” to care can serve as a marker of the overall quality of treatment a network provides, and point to specific out-of-hospital needs, necessary to improve in-hospital performance. We therefore propose a simple, empiric medico-social checklist that can be used in nephrology wards to assess the presence of social barriers to hospital discharge and quantify their weight. Using the checklist should allow: identifying patients with social frailty that could complicate hospitalisation and/or discharge; evaluating the social needs of patient and entourage at the beginning of hospitalisation, adopting timely procedures, within the partnership with out-of-hospital teams; facilitating prioritization of interventions by social workers. The following ten items were empirically identified: reason for hospitalisation; hospitalisation in relation to the caregiver’s problems; recurrent unplanned hospitalisations or early re-hospitalisation; social/family isolation; presence of a dependent relative in the patient’s household; lack of housing or unsuitable housing/accommodation; loss of autonomy; lack of economic resources; lack of a safe environment; evidence of physical or psychological abuse. The simple tool here described needs validation; the present proposal is aimed at raising attention on the importance of non-medical issues in medical organisation in our specialty, and is open to discussion, to allow its refinement.

Abstract Background Choice of dialysis is context sensitive, explored for PD and extracorporeal dialysis, but less studied for haemodialysis (HD) and hemodiafiltration (HDF), both widely employed in Italy and France; reasons of choice and differences in prescriptions may impact on dialysis-related variables, particularly relevant in elderly, high-comorbidity patients. Methods The study involved two high-comorbidity in-hospital cohorts, treated in Centers with similar characteristics, in Italy (Cagliari) and France (Le Mans). All patients (204) agreed to participate. Stable cases on thrice-weekly dialysis, with at least 2 months follow-up were selected (180 patients, Males 59.4%, median age 71 years, vintage 4.3 years, Charlson index 9). Univariate and multivariate correlations between baseline data, HD-HDF, dialysis efficiency and nutritional markers were assessed. Results In Le Mans HDF was mainly chosen to increase efficiency (large surface dialysers, high convective volume; 76.3% of the patients), in Cagliari to improve tolerance (smaller surfaces, lower convective volume; 59% of patients). Kt/V was similar in HD and HDF, and in both settings(median Kt/V Daugirdas 2: 1.6); in the setting of high efficiency no correlation was found between Kt/V, BMI, urea, creatinine, n-PCR and phosphate. The relationship between Kt/V and albumin was divergent: a weak consensual increase was present in Cagliari, a decrease in Le Mans, suggesting a role of albumin losses with high convective volumes. In the multivariate analysis, after adjustment for other covariates (including comorbidity and type of treatment) low albumin level = 7 (OR: 3.153 (1.311–7.582)), MIS index> = 7 (OR: 5.916 (2.457–14.241)). Conclusions The different prescriptions of HD and HDF may have similar effects on dialysis efficiency, but diverging effects on crucial nutritional markers, such as albumin levels, probably more evident in high-comorbidity populations.

Abstract Background Although fatigue is common in dialysis patients, polypharmacy is seldom listed among its causes. In this report, we describe a dialysis patient who developed severe fatigue due to pharmacological interaction between two commonly prescribed drugs, phosphate binders and levothyroxine. Case Presentation A 65-year old woman, on dialysis for 17 years, complained of fatigue (weight 54 Kg, height 1.55 m, BMI: 23 Kg/m2; malnutrition inflammation index: 10; Charlson index 9). She had been treated with lithium for about 20 years. A heavy smoker, she was obese and diabetic when young, but stopped treatment after weight loss. She had undergone thyroidectomy for papillary carcinoma, left hemicolectomy for colon adenocarcinoma, left quadrantectomy followed by radiotherapy for ductal mammary adenocarcinoma, subtotal parathyroidectomy for tertiary hyperparathyroidism. At the time of this report, she was on thrice-weekly hemodiafiltration (Daugirdas 2 Kt/V: 1.6–1.8). Her recent treatment included spironolactone, amlodipine, perindopril, valproate, lamotrigine, levothyroxine, vitamin D, calcium carbonate, sodium polystyrene and sevelamer. After she questioned her doctor about whether her fatigue might be the result of a drug interaction, levothyroxine interference was identified (TSH, previously normal, increased to 13.07 mU/L, after increasing sevelamer dose, and normalized after change of drug schedule). Literature review: only 5 relevant papers on levothyroxine and phosphate binders on dialysis were found on Pubmed and EMBASE (out of 351 titles retrieved). Information was therefore inferred from studies in normal volunteers or in other diseases. Discussion and conclusions Our case differs from other reports on lower TSH at diagnosis, underlining the need for awareness of the importance of early diagnosis. Integrating the scant literature on dialysis patients with data available in the general population, some working conclusions can be reached: while all phosphate binders potentially interfere with levothyroxine absorption, interference seems to be highest for sevelamer; interference is limited but not excluded by increasing the intervals between drugs; morning fast is usually indicated but, when clashing with the timing of other drugs, a bedtime dose and liquid preparations may be indicated. In the absence of an agreed control schedule, our case supports close monitoring of TSH (1–3 months if unstable, twice-yearly in stable patients).

Abstract Background Although the relationship between hyperparathyroidism and hypertension has been described for decades, the role of hyperparathyroidism in hypertension in dialysis is still unclear. Following the case of a severely hypertensive dialysis patient, in which parathyroidectomy (PTX) corrected the metabolic imbalance and normalized blood pressure (BP), we tried to contextualize our observation with a systematic review of the recent literature on the effect of PTX on BP. Case presentation A dialysis patient, aged 19 years at the time of this report, with chronic kidney disease (CKD) from childhood; he was an early-preterm baby with very low birth weight (910 g), and is affected by a so-far unidentified familial nephropathy. He started dialysis in emergency at the age of 17. Except for low-dose Bisoprolol, he refused all chronic medication; hypertension (165–200/90–130 mmHg) did not respond to attainment of dry weight (Kt/V > 1.7; BNP 70–200 pg/ml pre-dialysis). He underwent subtotal PTX 1 year after dialysis start; after PTX, his blood pressure stabilized in the 100–140/50–80 range, and is normal without treatment 5 months later. Conclusion Our patient has some peculiar features: he is young, has a non-immunologic disease, poor compliance to drug therapy, excellent dialysis efficiency. His lack of compliance allows observing the effect of PTX on BP without pharmacologic interference. The prompt, complete and long-lasting BP normalization led us to systematic review the current literature (Pubmed, Embase, Cochrane Collaboration 2000–2016) retrieving 8 case series (194 cases), and one case report (3 patients). The meta-analysis showed a significant, albeit moderate, improvement in BP after PTX (difference: systolic BP -8.49 (CI 2.21–14.58) mmHg; diastolic BP -4.14 (CI 1.45–6.84) mmHg); analysis is not fully conclusive due to lack of information on anti-hypertensive agents. The 3 cases reported displayed a sharp reduction in BP after PTX. In summary, PTX may have a positive influence on BP control, and may result in complete correction or even hypotension in some patients. The potential clinical relevance of this relationship warrants prospective large-scale studies.

Abstract Gabriel Richet was one of the great pioneers of European Nephrology. After a pivotal period of work with Jean Hamburger, whom we owe the name of our discipline, Nephrology, he contributed to all aspects of this specialty and was, in particular, a forerunner in dialysis and in the study of interstitial nephropathies. In this passionate and lucid interview, recorded in Paris in 2010, he describes himself as a “lucky man”, able to transform folly in happiness. He does not describe himself as an intellectual, but as a warrior, and closes a detailed history of the early days of European Nephrology with a strong statement of the moral stature a physician should have: he underlines, in line with his strong personality, that a physician is a man able to decide, to give orders and to assume their consequences. However, science and care of human beings cannot exist without a heart. “A doctor is someone who decides; when he writes a prescription, this means he prescribes and takes responsibility. Is it possible to give a prescription and decide regardless of compassion?”. In his interview, he commented that this last statement is probably not uniformly agreed, but that he’ll always defend it, adds freedom as a moral value that a physician should proudly defend: “Unfortunately I know that many do not share my idea, but that’s life... I am like the Queen of Holland, whose motto is: I will maintain!”.

Abstract Background Starting dialysis at an advanced age is a clinical challenge and an ethical dilemma. The advantages of starting dialysis at “extreme” ages are questionable as high dialysis-related morbidity induces a reflection on the cost- benefit ratio of this demanding and expensive treatment in a person that has a short life expectancy. Where clinical advantages are doubtful, ethical analysis can help us reach decisions and find adapted solutions. Case presentation Mr. H is a ninety-year-old patient with end-stage kidney disease that is no longer manageable with conservative care, in spite of optimal nutritional management, good blood pressure control and strict clinical and metabolic evaluations; dialysis is the next step, but its morbidity is challenging. The case is analysed according to principlism (beneficence, non-maleficence, justice and respect for autonomy). In the setting of care, dialysis is available without restriction; therefore the principle of justice only partially applied, in the absence of restraints on health-care expenditure. The final decision on whether or not to start dialysis rested with Mr. H (respect for autonomy). However, his choice depended on the balance between beneficence and non-maleficence. The advantages of dialysis in restoring metabolic equilibrium were clear, and the expected negative effects of dialysis were therefore decisive. Mr. H has a contraindication to peritoneal dialysis (severe arthritis impairing self-performance) and felt performing it with nursing help would be intrusive. Post dialysis fatigue, poor tolerance, hypotension and intrusiveness in daily life of haemodialysis patients are closely linked to the classic thrice-weekly, four-hour schedule. A personalized incremental dialysis approach, starting with one session per week, adapting the timing to the patient’s daily life, can limit side effects and “dialysis shock”. Conclusions An individualized approach to complex decisions such as dialysis start can alter the delicate benefit/side-effect balance, ultimately affecting the patient’s choice, and points to a narrative, tailor-made approach as an alternative to therapeutic nihilism, in very old and fragile patients.

Abstract Background No effective treatment is currently available and dialysis related amyloidosis continues to be invalidating in long-term dialysis patients. A recent case series reported reduction of osteoarticular pain on doxycycline treatment, extending the indications of this drug, used in other uncommon forms of amyloidosis, to dialysis patients. Explanations of the antalgic effect were the anti-inflammatory properties and anti-coiling effects of tetracycline. Case presentation Our report regards a 54-year-old woman, who was never transplanted and has been on hemodialysis and hemodiafiltration for overall 37 years, due to renal hypoplasia. In spite of high efficiency hemodiafiltration, she complained of increasing, invalidating osteoarticular pain; history and imaging suggested beta-2 microglobulin amyloid. Positron emission tomography (PET scan) identified metabolically active lesions in the involved settings. Low-dose doxycycline (100 mg/day) was started, leading to a considerable decrease in pain (over 6 months, from 7 to 8 to 4–5 on a 0–10 scale). At 6 months, a PET scan showed unmodified or increased uptake in the involved settings. Conclusions In summary, the previously described antalgic effect of doxycycline in dialysis related amyloidosis is confirmed in our case, the first studied using PET scan. The pattern at PET can suggests that the antalgic effect is independent from inflammation and points to other factors, such as interaction with fibril geometry or with bone structure.

In France, diphtheria tetanus and inactivated polio vaccine (DT-IPV) coverage and immunization are insufficient in the elderly and decrease with age. The principal objective of this study was to assess the impact of a strategy of catch-up DT-IPV vaccination during hospitalization in people over the age of 65 years in central France (the Sarthe region). We performed a prospective, single-center, cluster-randomized study (four hospital wards). We included patients aged ≥65 years, without mental impairment, contraindication and who accepted to participate, hospitalized in the internal medicine wards in Le Mans Hospital from 28 May 2018 to 27 May 2019. The DT-IPV vaccination status of the patients was determined at inclusion and the wards were randomized (intervention and control). In the intervention group, vaccination was up-dated during hospitalization. In case of temporary contraindication, vaccination was prescribed at hospital discharge. Patients hospitalized in the control wards received oral information only. Final immunization status was determined by calling the patient’s general practitioner two months after hospital discharge. One hundred and fifty seven patients were included: 73 in the intervention and 84 in the control arm. Baseline immunization coverage was 46.5%. Vaccination coverage increased from 56.2% to 80.8% in the intervention group and from 38.1% to 40.5% in the control group (p < 0.001). Having received sufficient information from the general practitioner was the only factor associated with vaccination being up-to-date in uni- and multivariate analysis: OR = 5.07 [2.45–10.51]. In a setting of low vaccination coverage DT-IPV vaccination during hospitalization is an effective catch-up strategy.

In the new millennium, few kidney diseases changed their perspectives as much as autosomal dominant polycystic kidney disease (ADPKD). New diagnostic approaches, including the evaluation of renal or liver volume by computerised tomography (CT) scan, the detection of cyst infections by positron emission tomography (PET) scan, and new therapeutic approaches (including vaptans, mTOR inhibitors, and somatostatin analogues) pose new clinical and ethical dilemmas. Therefore, the analysis of the recent advances offers an occasion for reviewing our counselling policy. The aim of this narrative review is to discuss a few crucial points concerning counselling in ADPKD: should all ADPKD patients undergo genetic testing for characterisation of the involved gene? What is the role of prenatal counselling and preimplantation selection? Should all ADPKD patients be followed in a nephrology clinic? Which imaging to use in which patients? Whom should we treat, when, and by which drugs, and how to communicate the treatment options? The working conclusions highlight the trends towards earlier referral of ADPKD patients, the importance of offering the diet options, including low-salt, high-water intake, difficult to follow, but devoid of side-effects, and the expectancy for the new therapeutic options, alone or in combination, aimed at reduction of cyst volume and/or control of cyst growth.

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La crisi economica globale, l'indicazione alla massima deospedalizzazione dei pazienti cronici e le innovazioni nel trattamento dell'uremia cronica sono alla base del rinnovato interesse per trattamenti dialitici “non convenzionali o intensivi”, spesso od obbligatoriamente domiciliari. Un primo punto evidenziato da questa revisione narrativa della letteratura è il superamento dell'antagonismo storico tra emodialisi domiciliare (HHD) e dialisi peritoneale (PD), all'insegna del motto “home dialysis first”: ascrivere il successo di una metodica domiciliare alla competizione con l'altra è riduttivo quanto il considerare che i pazienti ideali per l'HHD siano principalmente i soggetti che hanno dovuto interrompere la dialisi peritoneale. Ciò detto, è possibile scomporre il problema della dialisi domiciliare non solo secondo criteri clinici, ma anche secondo i quattro principi etici di beneficio, non maleficio, giustizia e autonomia. Se il beneficio non è facile da dimostrare, anche per la peculiare selezione dei pazienti, il non maleficio è evidente: in tutti gli studi analizzati, l'emodialisi domiciliare, sia essa standard o quotidiana o intensiva, non risulta mai significativamente inferiore ai trattamenti convenzionali. Il principio della giustizia, inteso in maniera un po' riduttiva come giustizia distributiva, può essere analizzato valutando i costi del trattamento, divisi tra costi diretti (disposable e macchine) e costo del personale medico e infermieristico; il vantaggio economico della riduzione del personale è ovvio, ma va anche ricordato che un sistema domiciliare necessita di una massa critica per essere favorevole dal punto di vista economico e che i costi “indiretti” (struttura ospedaliera in particolare) sono difficili da quantificare. Il quarto principio è l'autonomia dei pazienti: per questo sarebbe necessario offrire l'emodialisi domiciliare a tutti coloro che ne hanno le indicazioni, creando dei Centri di riferimento accessibili, dove i pazienti possano ascoltare il parere di medici, infermieri e pazienti con esperienza specifica.

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