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.

Pregnancy in dialysis patients in the new millennium: a systematic review and meta-regression analysis correlating dialysis schedules and pregnancy outcomes.

BACKGROUND: Advances have been made in the management of pregnancies in women receiving dialysis; however, single-centre studies and small numbers of cases have so far precluded a clear definition of the relationship between dialysis schedules and pregnancy outcomes. The aim of the present systematic review was to analyse the relationship between dialysis schedule and pregnancy outcomes in pregnancies in chronic dialysis in the new millennium. METHODS: Medline-PubMed, Embase and the Cochrane library were searched (1 January 2000-31 December 2014: MESH, Emtree, free terms on pregnancy and dialysis). A separate analysis was performed for case series (more than five cases) and case reports. Meta-regression was performed in case series dealing with the larger subset of haemodialysis (HD) patients; case reports were analysed separately [according to peritoneal dialysis (PD) versus HD; conception before or during dialysis]. RESULTS: We obtained 190 full texts and 25 congress abstracts from 2048 references. We selected 101 full papers and 25 abstracts (36 series; 90 case reports), for a total of 681 pregnancies in 647 patients. In the case series (574 pregnancies in 543 patients), preterm delivery was extremely frequent (83%). Meta-regression analysis showed a relationship between hours of dialysis per week in HD and preterm delivery, and was significant for preterm deliveries (<37 gestational weeks: P = 0.044; r2 = 0.22) and for small for gestational age (SGA) (P = 0.017; r2 = 0.54). SGA was closely associated with the number of dialysis sessions per week (P = 0.003; r2 = 0.84). Case report analysis suggests a lower incidence of SGA on HD versus PD (31 versus 66.7%; P = 0.015). No evidence of an increased risk of congenital abnormality was found in the retrieved papers. CONCLUSIONS: Data on pregnancy on dialysis are heterogeneous but rapidly accumulating; the main determinant of outcomes on HD is the dialysis schedule. The differences between PD and HD should be further analysed.

Revisiting nephrocalcinosis: A single-centre perspective. A northern Italian experience.

AIM: Nephrocalcinosis is a clinical-pathological entity characterized by the deposition of calcium salts within the kidney parenchyma. Both the protean presentation and multiple causes may explain the lack of data regarding its prevalence. The aim of this study is to report the prevalence and main clinical features of nephrocalcinosis diagnosed in a newly opened nephrology outpatient unit. METHODS: Analysis on the data we prospectively gathered from the start of activity (2007-2013) was carried out. Clinical and laboratory data were collected from the medical records and from the general laboratory; diagnosis was based upon imaging data reviewed by the same radiologists. RESULTS: Sixty-five of 2695 patients referred to our unit were diagnosed with nephrocalcinosis (2.4%). The affected patients were younger than the overall out-patient population (median: 37.7 (min-max: 8-82) vs 63 years (2-102) P < 0.001), with higher female prevalence (68% vs 51.4%: P < 0.05) and better preserved kidney function (CKD-EPI 103 (23-165) vs 60 mL/min (3.2-169) P < 0.001). Kidney stones were the main reason for referral (35.4%), followed by electrolyte disturbances (22.7%), acute pyelonephritis (4.6%), AKI or CKD (4.6%). Nephrocalcinosis was associated with autoimmune diseases in 29% and with microcythaemia in 23%, while positive family history was present in 23% of patients. Various electrolyte disturbances were observed, with hypercalciuria being the hallmark of beta thalassaemic patients. CONCLUSIONS: Nephrocalcinosis is a rare, but not exceptional disease in nephrology. In Mediterranean countries, microcythaemia would appear to be a major cause of this disease. Greater awareness of nephrocalcinosis is needed for an integrated approach involving various branches of internal medicine and radiology.

Diet as a system: an observational study investigating a multi-choice system of moderately restricted low-protein diets.

BACKGROUND: There is no single, gold-standard, low-protein diet (LPD) for CKD patients; the best compliance is probably obtained by personalization. This study tests the hypothesis that a multiple choice diet network allows patients to attain a good compliance level, and that, in an open-choice system, overall results are not dependent upon the specific diet, but upon the clinical characteristics of the patients. METHODS: Observational study: Three LPD options were offered to all patients with severe or rapidly progressive CKD: vegan diets supplemented with alpha-ketoacids and essential aminoacids; protein-free food in substitution of normal bread and pasta; other (traditional, vegan non supplemented and tailored). Dialysis-free follow-up and survival were analyzed by Kaplan Meier curves according to diet, comorbidity and age. Compliance and metabolic control were estimated in 147 subjects on diet at March 2015, with recent complete data, prescribed protein intake 0.6 g/Kg/day. Protein intake was assessed by Maroni Mitch formula. RESULTS: Four hundreds and forty nine patients followed a LPD in December, 2007- March, 2015 (90% moderately restricted LPDs, 0.6 g/Kg/day of protein, 10% at lower targets); age (median 70 (19-97)) and comorbidity (Charlson index: 7) characterized our population as being in line with the usual CKD European population. Median e-GFR at start of the diet was 20 mL/min, 33.2% of the patients were diabetics. Baseline data differ significantly across diets: protein-free schemas are preferred by older, high-comorbidity patients (median age 76 years, Charlson index 8, GFR 20.5 mL/min, Proteinuria: 0.3 g/day), supplemented vegan diets by younger patients with lower GFR and higher proteinuria (median age 65 years, Charlson index 6, GFR 18.9 mL/min; Proteinuria: 1.2 g/day); other diets are chosen by an intermediate population (median age 71 years, Charlson index 6; GFR 22.5 mL/min; Proteinuria: 0.9 g/day); (p <0.001 for age, Charlson index, proteinuria, GFR). Adherence was good, only 1.1% of the patients were lost to follow-up and protein intake was at target in most of the cases with no differences among LPDs (protein intake: 0.47 (0.26-0.86) g/Kg/day). After adjustment for confounders, and/or selection of similar populations, no difference in mortality or dialysis start was observed on the different LPDs. Below the threshold of e-GFR 15 mL/min, 50% of the patients remain dialysis free for at least two years. CONCLUSION: A multiple choice LPD system may allow reaching good adherence, without competition among diets, and with promising results in terms of dialysis-free follow-up. The advantages with respect to a non-customized approach deserve confirmation in further comparative studies or RCTs.

Low protein diets in patients with chronic kidney disease: a bridge between mainstream and complementary-alternative medicines?

Dietary therapy represents an important tool in the management of chronic kidney disease (CKD), mainly through a balanced reduction of protein intake aimed at giving the remnant nephrons in damaged kidneys a "functional rest". While dialysis, transplantation, and pharmacological therapies are usually seen as "high tech" medicine, non pharmacological interventions, including diets, are frequently considered lifestyle-complementary treatments. Diet is one of the oldest CKD treatments, and it is usually considered a part of "mainstream" management. In this narrative review we discuss how the lessons of complementary alternative medicines (CAMs) can be useful for the implementation and study of low-protein diets in CKD. While high tech medicine is mainly prescriptive, prescribing a "good" life-style change is usually not enough and comprehensive counselling is required; the empathic educational approach, on which CAMs are mainly, though not exclusively based, may support a successful personalized nutritional intervention.There is no gold-standard, low-protein diet for all CKD patients: from among a relatively vast choice, the best compliance is probably obtained by personalization. This approach interferes with the traditional RCT-based analyses which are grounded upon an assumption of equal preference of treatments (ideally blinded). Whole system approaches and narrative medicine, that are widely used in the study of CAMs, may offer ways to integrate EBM and personalised medicine in the search for innovative solutions respecting individualization, but gaining sound data, such as with partially-randomised patient preference trials.

Risk of Adverse Pregnancy Outcomes in Women with CKD.

CKD is increasingly prevalent in pregnancy. In the Torino-Cagliari Observational Study (TOCOS), we assessed whether the risk for adverse pregnancy outcomes is associated with CKD by comparing pregnancy outcomes of 504 pregnancies in women with CKD to outcomes of 836 low-risk pregnancies in women without CKD. The presence of hypertension, proteinuria (>1 g/d), systemic disease, and CKD stage (at referral) were assessed at baseline. The following outcomes were studied: cesarean section, preterm delivery, and early preterm delivery; small for gestational age (SGA); need for neonatal intensive care unit (NICU); new onset of hypertension; new onset/doubling of proteinuria; CKD stage shift; "general" combined outcome (preterm delivery, NICU, SGA); and "severe" combined outcome (early preterm delivery, NICU, SGA). The risk for adverse outcomes increased across stages (for stage 1 versus stages 4-5: "general" combined outcome, 34.1% versus 90.0%; "severe" combined outcome, 21.4% versus 80.0%; P<0.001). In women with stage 1 CKD, preterm delivery was associated with baseline hypertension (odds ratio [OR], 3.42; 95% confidence interval [95% CI], 1.87 to 6.21), systemic disease (OR, 3.13; 95% CI, 1.51 to 6.50), and proteinuria (OR, 3.69; 95% CI, 1.63 to 8.36). However, stage 1 CKD remained associated with adverse pregnancy outcomes (general combined outcome) in women without baseline hypertension, proteinuria, or systemic disease (OR, 1.88; 95% CI, 1.27 to 2.79). The risk of intrauterine death did not differ between patients and controls. Findings from this prospective study suggest a "baseline risk" for adverse pregnancy-related outcomes linked to CKD.

Eco-dialysis: the financial and ecological costs of dialysis waste products: is a 'cradle-to-cradle' model feasible for planet-friendly haemodialysis waste management?

BACKGROUND: Approximately 2 million chronic haemodialysis patients produce over 2,000,000 tons of waste per year that includes about 600,000 tons of potentially hazardous waste. The aim of the present study was to analyse the characteristics of the waste that is produced through chronic haemodialysis in an effort to identify strategies to reduce its environmental and financial impact. METHODS: The study included three dialysis machines and disposables for bicarbonate dialysis, haemodiafiltration (HFR) and lactate dialysis. Hazardous waste is defined as waste that comes into contact with bodily fluids. The weight and cost of waste management was evaluated by various policies of differentiation, ranging from a careful-optimal differentiation to a careless one. The amount of time needed for optimal management was recorded in 30 dialysis sessions. Non-hazardous materials were assessed for potential recycling. RESULTS: The amount of plastic waste that is produced per dialysis session ranges from 1.5 to 8 kg (from 1.1 to 8 kg of potentially hazardous waste), depending upon the type of dialysis machine and supplies, differentiation and emptying policies. The financial cost of waste disposal is high, and is mainly related to hazardous waste disposal, with costs ranging from 2.2 to 16 Euro per session (2.7-21 USD) depending on the waste management policy. The average amount of time needed for careful, optimal differentiation disposal is approximately 1 minute for a haemodialysis session and 2 minutes for HFR. The ecological cost is likewise high: less than one-third of non-hazardous waste (23-28%) is potentially recyclable, while the use of different types of plastic, glues, inks and labels prevents the remaining materials from being recycled. CONCLUSION: Acknowledging the problem of waste management in dialysis could lead to savings of hundreds of millions of Dollars and to the reuse and recycling of hundreds of tons of plastic waste per year on a world-wide scale with considerable financial and ecological savings.

Is renal hyperfiltration protective in chronic kidney disease-stage 1 pregnancies? A step forward unravelling the mystery of the effect of stage 1 chronic kidney disease on pregnancy outcomes.

BACKGROUND: The correlation between advanced or proteinuric chronic kidney disease (CKD) and adverse pregnancy outcomes is intuitive, although how early CKD affects pregnancy remains unknown. Glomerular hyperfiltration is a physiological response to pregnancy, correlated with outcomes in hypertension or collagen diseases. The aim of the study was to correlate first trimester hyperfiltration with pregnancy outcomes in stage 1 CKD patients. METHODS: A historical prospective study was conducted on the database of our Unit, gathering all pregnant CKD patients referred since 1 January 2000. From 383 pregnancies referred in 2000-2013, 75 patients were selected (stage 1 CKD, referred within the 14th gestational week, singleton deliveries, absence of diabetes, hypertension or nephrotic proteinuria at referral, body mass index [BMI] < 30); 267 'low-risk' pregnancies, followed in the same setting, served as controls. Glomerular filtration rate (GFR) was assessed by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and dichotomized at 120 mL/min. The odds for Caesarean section, prematurity, need for Neonatal Intensive Care Unit (NICU) were assessed by univariate analysis and logistic regression. RESULTS: Risk for adverse pregnancy outcomes was not affected by hyperfiltration (univariate OR GFR ≥ 120 mL/min: Caesarean section 1.30 (0.46-3.65); preterm delivery: 0.84 (0.25-2.80)). In contrast, even in these cases with normal kidney function, stage 1 CKD was associated with prematurity (17.3% vs 4.9% P = 0.001), lower birth weight (3027 ± 586 versus 3268 ± 500 P < 0.001) need for NICU (12% vs 1.1% P < 0.001). In the multivariate analysis, the risks were significantly increased by proteinuria and maternal age but not by GFR. CONCLUSIONS: In pregnant Stage 1 CKD patients, hyperfiltration was not associated with maternal-foetal outcomes, thus suggesting a need to focus attention on qualitative factors, eventually enhanced by age, as vascular stiffness, endothelial damage or oxidative stress.

Renal infarction versus pyelonephritis in a woman presenting with fever and flank pain.

Patients with fever, flank pain, and dysuria frequently are encountered in the emergency department. Acute pyelonephritis is the most likely diagnosis; however, its clinical and radiologic presentation consistently overlap with that of acute renal infarction. Ultrasound is unable to distinguish early infarction from nonabscessed acute pyelonephritis. Hence, computed tomography or magnetic resonance imaging are needed. We report the case of a 68-year-old woman who presented with fever, flank pain, and dysuria, along with respiratory distress and tachycardia. Elevated values for inflammatory indexes suggested a diagnosis of acute pyelonephritis, and subsequent contrast-enhanced computed tomography showed hypodense wedge-shaped areas in both kidneys. However, the presence of a thin rim of capsular enhancement (cortical rim sign), the absence of perirenal inflammatory changes, and the location of the lesions apart from defined calyces suggested the alternative diagnosis of renal infarction. The underlying cause was not identified until an episode of acute dyspnea revealed paroxysmal arrhythmia. Our case demonstrates that a thorough knowledge of the imaging findings of renal infarction and acute pyelonephritis is essential to correctly making the diagnosis.

Interferon beta-related nephropathy and interstitial lung disease: a new association and a long-term warning.

We report on a so-far never described association between glomerulonephritis and sarcoid-like lung disease after long-term interferon beta (IFNb) treatment for relapsing-remitting multiple sclerosis. The interest in this case resides in the documented remission after IFNb discontinuation. The history of IFNb-related adverse events is probably not yet completely written. The rapid reversal of the pathological signs in our patient underlines the importance of careful clinical and laboratory surveillance, including kidney functional parameters, for an early diagnosis of IFNb-related diseases.

Vegetarian low-protein diets supplemented with keto analogues: a niche for the few or an option for many?

BACKGROUND: Low-protein diets are often mentioned but seldom used to slow chronic kidney disease (CKD) progression. The aim of the study was to investigate the potential for implementation of a simplified low-protein diet supplemented with alpha-keto analogues (LPD-KA) as part of the routine work-up in CKD patients. METHODS: In an implementation study (December 2007-November 2011), all patients with CKD Stages IV-V not on dialysis, rapidly progressive Stage III and/or refractory proteinuria, were offered either a simplified LPD-KA, or commercially available low-protein food. LPD-KA consisted of proteins 0.6 g/kg/day, supplementation with Ketosteril 1 pill/10 Kg, 1-3 free-choice meals/week and a simplified schema based on 'allowed' and 'forbidden' foods. 'Success' was defined as at least 6 months on LPD-KA. Progression was defined as reduction in glomerular filtration rate (GFR)[(Chronic Kidney Disease Epidemiology Collaboration) formula CKD-EPI] in patients with at least 6 months of follow-up. RESULTS: Of about 2500 patients referred (8% CKD Stages IV-V), 139 started LPD-KA; median age (70 years) and prevalence of comorbidity (79%) were in line with the dialysis population. Start of dialysis was the main reason for discontinuation (40 cases, unplanned in 7); clinical reasons were recorded in 7, personal preference in 14 and improvement and death in 8 each. The low gross mortality (4% per year) and the progression rate (from -8 to 0 mL/min/year at 6 months) are reassuring concerning safety. None of the baseline conditions, including age, educational level, comorbidity or kidney function, discriminated the patients who followed the diet for at least 6 months. CONCLUSIONS: Our data suggest a wider offer of LPD-KA to patients with severe and progressive CKD. The promising results in terms of mortality and progression need confirmation with different study designs.

Excessive urinary tract dilatation and proteinuria in pregnancy: a common and overlooked association?

BACKGROUND: Proteinuria and dilatation of the urinary tract are both relatively common in pregnancy, the latter with a spectrum of symptoms, from none to severe pain and infection. Proteinuria is a rare occurrence in acute obstructive nephropathy; it has been reported in pregnancy, where it may pose a challenging differential diagnosis with pre-eclampsia.The aim of the present study is to report on the incidence of proteinuria (≥ 0.3; ≥ 0.5 g/day) in association with symptomatic-severe urinary tract dilatation in pregnancy. METHODS: Case series. SETTING: Nephrological-Obstetric Unit dedicated to pregnancy and kidney diseases (January 2000-April 2011). SOURCE: database prospectively updated since the start of the Unit. Retrospective review of clinical charts identified as relevant on the database, by a nephrologist and an obstetrician. RESULTS: From January 2000 to April 2011, 262 pregnancies were referred. Urinary tract dilatation with or without infection was the main cause of referral in 26 cases (predominantly monolateral in 19 cases): 23 singletons, 1 lost to follow-up, 1 twin and 1 triplet. Patients were referred for urinary tract infection (15 cases) and/or renal pain (10 cases); 6 patients were treated by urologic interventions ("JJ" stenting). Among them, 11 singletons and 1 triple pregnancy developed proteinuria ≥ 0.3 g/day (46.1%). Proteinuria was ≥ 0.5 g/day in 6 singletons (23.1%). Proteinuria resolved after delivery in all cases. No patient developed hypertension; in none was an alternative cause of proteinuria evident. No significant demographic difference was observed in patients with renal dilatation who developed proteinuria versus those who did not. An association with the presence of "JJ" stenting was present (5/6 cases with proteinuria ≥ 0.5 g/day), which may reflect both severer obstruction and a role for vescico-ureteral reflux, induced by the stent. CONCLUSIONS: Symptomatic urinary tract dilatation may be associated with proteinuria in pregnancy. This association should be kept in mind in the differential diagnosis with other causes of proteinuria in pregnancy, including pre-eclampsia.

Lung ultrasonography performed by nephrologist: COVID-19 as an opportunity to reveal ultrasound's full potential and usefulness in the dialysis room.

Background: Interest in point-of-care ultrasound (POCUS) and lung ultrasound (LUS) is growing in the nephrology and dialysis field, and the number of nephrologists skilled in what is proving to be the "5th pillar of bedside physical examination" is increasing. Patients on hemodialysis (HD) are at high risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) and developing coronavirus disease 2019 (COVID-19) serious complications. Despite this, to our knowledge there are no studies to date that show the role of LUS in this setting, while there are many in the emergency room, where LUS proved to be an important tool, providing risk stratification and guiding management strategies and resource allocation. Therefore, it is not clear whether the usefulness and cut-offs of LUS highlighted in studies in the general population are reliable in dialysis, or whether variations, precautions and adjustments to this specific situation are necessary. Methods: This was a 1-year monocentric prospective observational cohort study of 56 HD patients with COVID-19. Patients underwent a monitoring protocol that included at first evaluation bedside LUS, using a 12-scan scoring system, by the same nephrologist. All data were prospectively and systematically collected. Outcomes. hospitalization rate, combined outcome [non-invasive ventilation (NIV + death)], mortality. Descriptive variables are presented as medians (interquartile range), or percentage. Univariate and multivariate analysis, as well as Kaplan-Meier (K-M) survival curves, were carried out. P was fixed at .05. Results: Median age was 78 years, 90% had at least one comorbidity (46% diabetics), 55% were hospitalized and 23% deaths. Median duration of disease was 23 days (14-34). A LUS score ≥11 represented a 13-fold risk of hospitalization, a 16.5-fold risk of combined outcome (NIV + death) vs risk factors such as age [odds ratio (OR) 1.6], diabetes (OR 1.2), male sex (OR 1.3) and obesity (OR 1.25), and a 7.7-fold risk of mortality. In the logistic regression, LUS score ≥11 is associated with the combined outcome with a hazard ratio (HR) of 6.1 vs inflammations indices such as CRP ≥9 mg/dL (HR 5.5) and interleukin-6 (IL-6) ≥62 pg/mL (HR 5.4). In K-M curves, survival drops significantly with LUS score above 11. Conclusions: In our experience of COVID-19 HD patients, LUS appeared to be an effective and easy tool, predicting the need for NIV and mortality better than "classic" known COVID-19 risk factors such as age, diabetes, male sex and obesity, and even better than inflammations indices such as CRP and IL-6. These results are consistent with those of the studies in the emergency room setting, but with a lower LUS score cut-off (11 vs 16-18). This is probably due to the higher global frailty and peculiarity of HD population, and emphasizes how nephrologists should themselves use LUS and POCUS as a part of their everyday clinical practice, adapting it to the peculiarity of the HD ward.

Protean presentation and multiple challenges of nephrocalcinosis in pregnancy (six pregnancies in four patients).

BACKGROUND: Nephrocalcinosis is an umbrella term covering increased content of calcium salts in the renal parenchyma, interstitial damage and potential evolution towards renal failure. Pregnancy is often the first occasion for biochemical or imaging tests in young women and may allow early diagnosis. Conversely, even mild kidney disease may represent a challenge in pregnancy. AIM: The aim of this study was to report on four patients in whom nephrocalcinosis was first diagnosed during pregnancy, exemplifying the protean presentation and multiple challenges of nephrocalcinosis in pregnancy. METHODS: This is a case series study including data on all pregnancies prospectively gathered in the Nephrological-Obstetric Unit dedicated to pregnancy and kidney diseases (2000-11). RESULTS: Six pregnancies were observed in four patients (31-35 years; one twin pregnancy, one ongoing, one patient with three pregnancies). Symptoms were oedema in two (later developed in a further patient), renal functional impairment and electrolyte imbalance in two each. Two patients developed hypertension late in pregnancy. Electrolyte imbalance was life-threatening in one patient (severe acidosis, severe hyperkalaemia: 7.5 mEq/L). Delivery was by Caesarean section in three patients, preterm in one. Multiple or long hospitalizations for metabolic reasons were needed in three patients, the fourth was hospitalized for obstetric reasons. In all patients, diagnosis of nephrocalcinosis was made at ultrasounds during basic nephrological evaluation, confirmed at computerized tomography scan in three. The pathogenesis was linked to diuretic abuse in one case and to collagen disease, inborn errors and prematurity, possibly associated with diuretic misuse, in the others. CONCLUSION: Nephrocalcinosis may have protean presentations in pregnancy. The risk of severe electrolyte derangements, oedema and hypertension warrants strict clinical surveillance.

Chronic kidney disease, severe arterial and arteriolar sclerosis and kidney neoplasia: on the spectrum of kidney involvement in MELAS syndrome.

BACKGROUND: MELAS syndrome (MIM ID#540000), an acronym for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes, is a genetically heterogeneous mitochondrial disorder with protean manifestations and occasional kidney involvement. Interest in the latter is rising due to the identification of cases with predominant kidney involvement and to the hypothesis of a link between mitochondrial DNA and kidney neoplasia. CASE PRESENTATION: We report the case of a 41-year-old male with full blown MELAS syndrome, with lactic acidosis and neurological impairment, affected by the "classic" 3243A > G mutation of mitochondrial DNA, with kidney cancer. After unilateral nephrectomy, he rapidly developed severe kidney functional impairment, with nephrotic proteinuria. Analysis of the kidney tissue at a distance from the two tumor lesions, sampled at the time of nephrectomy was performed in the context of normal blood pressure, recent onset of diabetes and before the appearance of proteinuria. The morphological examination revealed a widespread interstitial fibrosis with dense inflammatory infiltrate and tubular atrophy, mostly with thyroidization pattern. Vascular lesions were prominent: large vessels displayed marked intimal fibrosis and arterioles had hyaline deposits typical of hyaline arteriolosclerosis. These severe vascular lesions explained the different glomerular alterations including ischemic and obsolescent glomeruli, as is commonly observed in the so-called "benign" arteriolonephrosclerosis. Some rare glomeruli showed focal segmental glomerulosclerosis; as the patient subsequently developed nephrotic syndrome, these lesions suggest that silent ischemic changes may result in the development of focal segmental glomerulosclerosis secondary to nephron loss. CONCLUSIONS: Nephron loss may trigger glomerular sclerosis, at least in some cases of MELAS-related nephropathy. Thus the incidence of kidney disease in the "survivors" of MELAS syndrome may increase as the support therapy of these patients improves.

[COVID-19 recurrence due to reinfection with SARS-CoV-2 in a hemodialysis patient: there and back again].

The COVID-19 pandemic has caused millions of infections and deaths so far. After recovery, the possibility of reinfection has been reported. Patients on hemodialysis are at high risk of contracting SARS-CoV-2 and developing serious complications. Furthermore, they are a relatively hypo-anergic population, in which the development and duration of the immune and antibody response is still partially unknown. This may play a role in the possible susceptibility to reinfection. To date, only 3 cases of SARS-CoV-2 reinfection from strains prior to the Omicron variant in patients on chronic hemodialysis have been reported in literature. In all of them, the first infection was detected by screening in the absence of symptoms, potentially indicating a poor immune response, and there are no data about the antibody titre developed. We report a case of recurrence of COVID-19 in 2020 - first infection likely from Wuhan strain; reinfection likely from English variant (Alpha) after 7 months - in a hemodialysis patient with clinical symptoms and pulmonary ultrasound abnormalities. Swabs were negative in the interval between episodes (therefore excluding any persistence of positivity) and the lack of antibody protection after the first infection was documented by the serological test. The role of the potential lack - or rapid loss - of immune protection following exposure to SARS-CoV-2 in hemodialysis patients needs to be better defined, also in consideration of the anti-COVID vaccination campaign and the arrival of the Omicron variant, which appears to elude the immunity induced by vaccines and by previous variants. For this purpose, prospective multicenter studies are in progress in several European countries. This case also highlights the need for a careful screening with nasopharyngeal swabs in dialysis rooms, even after patients overcome infection and/or are vaccinated.

[Severe lactic acidosis requiring continuos haemodiafiltration in a young patient with unrecognized metabolic abnormality. Case report].

BACKGROUND: Lactic acidosis (LA) is the most common form of metabolic acidosis, defined by lactate values greater than 5 mmol/L and pH<7.34. The pathogenesis of LA involves hypoxic causes (type A) and non-hypoxic (type B), often coexisting. Identification and removal of the trigger are mandatory in the therapeutic management of LA. The case: A 38 years-old male patient entered the Emergency Ward for dyspnea, fever, vomiting and hyporexia. An important respiratory distress with hyperventilation due to severe LA was found, together with severe hypoglicemia, without renal impairment. Past medical history unremarkable, except for reported episodic hypoglicemia in the childhood, with fructose "intolerance", without any other data. No evidence of intoxications, septic shock or significant cytolysis. No drugs causing LA. The patient underwent orotracheal intubation, glucose infusion, and continuous haemodiafiltration for 36-hrs. A rapid general improvement was obtained with stabilization of acid-base balance. A diagnosis of fructose-1,6-diphosphatase deficiency was made. It is an autosomical recessive gluconeogenesis abnormality, with recurrent episodes of hypoglicemia and lactic acidosis after fasting, potentially lethal. The therapy is based on avoiding prolonged fasts, glucose infusion, and a specific diet, rich in glucose without fructose intake. CONCLUSIONS: The presence of not-otherwise-explained lactic acidosis in young patients has to place the suspect of an underlying and unknown metabolic derangement; in these cases, the involvement of the nephrologist appears to be pivotal for the differential diagnosis of the abnormalities of the acid-base balance, and for setting the best treatment.