[IgA nephropathy: the beginning of a new therapeutic era]. / Néphropathie à IgA: le début d'une nouvelle ère thérapeutique.

Primary IgA nephropathy is a common glomerular disease, heterogeneous in its clinical presentation. Historically considered to assume a benign course, we actually know that up to 40% of the cases progress to end stage renal disease at 20-30 years. Clinical and basic research has now allowed to understand the pathophysiology of this disease, to predict its course and to treat progressive forms more aggressively. This article summarizes classical treatments and recent therapeutic additions (sparsentan and targeted-release budenoside), which demonstrated remarkable efficacy. Complement inhibitors and B cells or plasma cells inhibitors to target aberrant IgA production have already emerged as new potential treatments. Collectively these advances may open a new therapeutic era in the management of this disease.

La néphropathie à IgA primaire est une maladie glomérulaire fréquente, hétérogène dans sa présentation clinique. Longtemps considérée comme bénigne, nous savons aujourd'hui que jusqu'à 40 % des cas progressent vers l'insuffisance rénale terminale après 20 à 30 ans de progression. La recherche a maintenant permis de mieux comprendre la physiopathologie de cette maladie, d'en prédire le devenir et de traiter plus agressivement les formes évolutives. Cet article fait le point sur les traitements classiques et les additions récentes (sparsentan et budénoside à libération entérique) qui ont démontré une efficacité remarquable. Les inhibiteurs du complément, des lymphocytes B ou des plasmocytes, ciblant la production d'IgA pathogéniques, montrent des résultats prometteurs. Ces avancées ouvrent une ère thérapeutique nouvelle dans la prise en charge de cette maladie.

Hyperoxemia in postsurgical sepsis/septic shock patients is associated with reduced mortality.

BACKGROUND: Despite growing interest in treatment strategies that limit oxygen exposure in ICU patients, no studies have compared conservative oxygen with standard oxygen in postsurgical patients with sepsis/septic shock, although there are indications that it may improve outcomes. It has been proven that high partial pressure of oxygen in arterial blood (PaO2) reduces the rate of surgical-wound infections and mortality in patients under major surgery. The aim of this study is to examine whether PaO2 is associated with risk of death in adult patients with sepsis/septic shock after major surgery. METHODS: We performed a secondary analysis of a prospective observational study in 454 patients who underwent major surgery admitted into a single ICU. Patients were stratified in two groups whether they had hyperoxemia, defined as PaO2 > 100 mmHg (n = 216), or PaO2 ≤ 100 mmHg (n = 238) at the day of sepsis/septic shock onset according to SEPSIS-3 criteria maintained during 48 h. Primary end-point was 90-day mortality after diagnosis of sepsis. Secondary endpoints were ICU length of stay and time to extubation. RESULTS: In patients with PaO2 ≤ 100 mmHg, we found prolonged mechanical ventilation (2 [8] vs. 1 [4] days, p < 0.001), higher ICU stay (8 [13] vs. 5 [9] days, p < 0.001), higher organ dysfunction as assessed by SOFA score (9 [3] vs. 7 [5], p < 0.001), higher prevalence of septic shock (200/238, 84.0% vs 145/216) 67.1%, p < 0.001), and higher 90-day mortality (37.0% [88] vs. 25.5% [55], p = 0.008). Hyperoxemia was associated with higher probability of 90-day survival in a multivariate analysis (OR 0.61, 95%CI: 0.39-0.95, p = 0.029), independent of age, chronic renal failure, procalcitonin levels, and APACHE II score > 19. These findings were confirmed when patients with severe hypoxemia at the time of study inclusion were excluded. CONCLUSIONS: Oxygenation with a PaO2 above 100 mmHg was independently associated with lower 90-day mortality, shorter ICU stay and intubation time in critically ill postsurgical sepsis/septic shock patients. Our findings open a new venue for designing clinical trials to evaluate the boundaries of PaO2 in postsurgical patients with severe infections.

Children of a lesser god or miracles? An emotional and behavioural profile of children born to mothers on dialysis in Italy: a multicentre nationwide study 2000-12.

BACKGROUND: Pregnancy on dialysis is increasingly being reported. This study evaluates the behavioural profile of the children of mothers on dialysis and the parental stress their mothers undergo when compared with a group of mothers affected by a different chronic disease (microcythaemia) and a group of healthy control mothers. METHODS: Between 2000 and 2012, 23 on-dialysis mothers gave birth to 24 live-born children in Italy (23 pregnancies, 1 twin pregnancy, one of the twins deceased soon after delivery); of these, 16 mothers and 1 father (whose wife died before the inquiry) were included in the study (1 mother had died and the father was unavailable; 2 were not asked to participate because their children had died and 3 were unavailable; children: median age: 8.5, min-max: 2-13 years). Twenty-three mothers affected by transfusion-dependent microcythaemia or drepanocitosis (31 pregnancies, 32 children) and 35 healthy mothers (35 pregnancies, 35 children; median age of the children: 7, min-max: 1-13 years) were recruited as controls. All filled in the validated questionnaires: 'Child Behaviour Checklist' (CBCL) and the 'Parental Stress Index-Short Form' (PSI-SF). RESULTS: The results of the CBCL questionnaire were similar for mothers on dialysis and healthy controls except for pervasive developmental problems, which were significantly higher in the dialysis group, while microcythaemia mothers reported higher emotional and behavioural problems in their children in 8 CBCL sub-scales. Two/16 children in the dialysis and 3/32 in the microcythaemia group had pathological profiles, as assessed by T-scores (p: ns). PSI-SF indicated a normal degree of parental stress in microcythaemia subjects and healthy controls, while mothers on dialysis declared significantly lower stress, suggesting a defensive response in order to minimize problems, stress or negativity in their relationship with their child. CONCLUSIONS: According to the present analysis, the emotional and behavioural outcome is normal in most of the children from on-dialysis mothers. A 'positive defence' in the dialysis mothers should be kept in mind when tailoring psychological support for this medical miracle.

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.

The children of dialysis: live-born babies from on-dialysis mothers in Italy--an epidemiological perspective comparing dialysis, kidney transplantation and the overall population.

BACKGROUND: A successful pregnancy is an exceptional event on dialysis. Few data are available comparing pregnancy rates on dialysis, transplantation and the overall population. The aim of the study was to assess the incidence of live births from mothers on chronic dialysis compared with the overall population and with kidney transplant patients. METHODS: The setting of the study is in Italy between 2000-12. Data on dialysis was aquired by phone inquiries that were carried out between June and September, 2013, involving all the public dialysis centres in Italy; the result was a 100% response rate. The date included was end-stage renal disease, type of dialysis, residual glomerular filtration rate, changes in dialysis and therapy, hospitalization; week of birth, birth weight, centile; and outcome of mother and child. Information on transplantation was acquired by inquiry by the kidney and pregnancy study group who were contacted by phone or e-mail; the result was a 60% response rate. Data concerning prevalence of women in childbearing age (20-45) were obtained from the Italian Dialysis and Transplant Registries (2010-11 update). Official site of the Italian Ministry of Health. RESULTS: During the study period, 23 women on dialysis (three on peritoneal dialysis) delivered live-born babies and one woman delivered twins (24 babies). Three babies died in the first weeks-months of life (including one twin); 19 of 21 singletons with available data were pre-term (33.3% <34 weeks); the prevalence of children <10th gestational age-adjusted centile was 33.3%. Birth weight and gestational age were lower in children from on-dialysis mothers as compared with 110 pregnancies following kidney graft, (weight: 1200 versus 2500 g; gestational age: 30 versus 36 weeks; P < 0.001). Incidence of live-born babies was inferred as 0.7-1.1 per 1000 female dialysis patients aged 20-45 and 5.5-8.3 per 1000 grafted patients in the same age range (Italian live-birth rates: 72.5 per 1000 women aged 20-45 years). CONCLUSIONS: Having a baby while on dialysis is rare but not impossible, though early mortality remains high. There is a 'scale of probability' estimating that women on dialysis have a 10-fold lower probability of delivering a live-born baby than those who have undergone renal transplantation, who in turn have a 10-fold lower probability of delivering a live-born baby as compared with the overall population.

Case Report: A Rare Truncating Variant of the CFHR5 Gene in IgA Nephropathy.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Despite appropriate therapy, 20-40% of affected-patients evolve toward end-stage kidney disease (ESKD). Mesangial IgA deposits are the hallmark of IgAN, and complement deposition (C3) seems to differentiate latent IgA mesangial deposits from active IgAN. Atypical hemolytic uremic syndrome (aHUS), another disease in which complement plays an important role, is caused by inherited or acquired deregulation of the alternative pathway (AP) of complement. A subgroup of IgAN shows thrombotic microangiopathy (TMA) lesions in kidney biopsies, the histological characteristic of aHUS. Genetic variants of complement Factor H (CFH), known to be present in aHUS, have been associated with rapidly progressive forms of IgAN and a clinical pattern of aHUS. Genome-wide association studies (GWAS) have confirmed that the 1q32 region, encoding for CFH and its related proteins, is an IgAN susceptibility locus. A 30 year-old man was admitted for seizures and malignant hypertension. The kidney biopsy showed IgAN associated with features of TMA. Despite five plasma exchanges, the patient remained dialysis-dependent, and ESKD was diagnosed. Functional and genetic complement analysis were performed. A monoallelic protein-truncating, likely loss-of-function variant was identified in the CFHR5 gene. Eculizumab is the treatment of aHUS. As it has been successfully used in a few cases of rapidly progressive IgAN, it was decided to administer eculizumab over a period of 12 months in addition to the usual immunosuppression for renal transplantation. After a follow-up of 3 years, there was no clinical disease recurrence. Systematic biologic and genetic screening of complement in individuals with IgAN might be useful to better delineate the role of the AP of complement in renal disease progression, and this may have therapeutic implications.

Eculizumab as a New Treatment for Severe Acute Post-infectious Glomerulonephritis: Two Case Reports.

Acute post-infections glomerulonephritis (APIGN) is a frequent cause of glomerulonephritis and represents the most common cause of acute glomerulonephritis in children. It can evolve to severe acute renal failure and chronic kidney disease or even end-stage kidney disease. The precise pathophysiological mechanisms of APIGN are still incompletely understood. The implication of the alternative complement pathway and the potential benefits of C5 blockade have been recently highlighted, in particular in the presence of a C3 Nephritic Factor (C3Nef), anti-Factor B or H autoantibodies. We report two children with severe APIGN, successfully treated with eculizumab. The first patient presented a severe form of APIGN with advanced renal failure and anuria, associated with a decreased level of C3 and an increased level of soluble C5b-9, in the presence of a C3NeF autoantibody. The second case had a severe oliguric APIGN associated with low C3 level. Kidney biopsy confirmed the diagnosis of APIGN in both cases. Eculizumab allowed full renal function recovery and the avoidance of dialysis in both cases. In conclusion, the alternative and terminal complement pathways activation might be common in PIGN, and in severe cases, eculizumab might help.

Renal involvement in sarcoidosis: histological patterns and prognosis, an Italian survey.

BACKGROUND: Granulomatous interstitial nephritis in sarcoidosis (sGIN) is generally clinically silent, but in <1% causes acute kidney injury (AKI). METHODS: This Italian multicentric retrospective study included 39 sarcoidosis-patients with renal involvement at renal biopsy: 31 sGIN-AKI, 5 with other patterns (No-sGIN-AKI), 3 with nephrotic proteinuria. We investigate the predictive value of clinical features, laboratory, radiological parameters and histological patterns regarding steroid response. Primary endpoint: incident chronic kidney disease (CKD) beyond the 1°follow-up (FU) year; secondary endpoint: response at 1°line steroid therapy; combined endpoint: the association of initial steroid response and outcome at the end of FU. RESULTS: Complete recovery in all 5 No-sGIN-AKI-patients, only in 45% (13/29) sGIN-AKI-patients (p=0.046) (one lost in follow-up, for another not available renal function after steroids). Nobody had not response. Primary endpoint of 22 sGIN-AKI subjects: 65% (13/20) starting with normal renal function developed CKD (2/22 had basal CKD; median FU 77 months, 15-300). Combined endpoint: 29% (6/21) had complete recovery and final normal renal function (one with renal relapse), 48% (10/21) had partial recovery and final CKD (3 with renal relapse, of whom one with basal CKD) (p=0.024). Acute onset and hypercalcaemia were associated to milder AKI and better recovery than subacute onset and patients without hypercalcaemia, women had better endpoints than men. Giant cells, severe interstitial infiltrate and interstitial fibrosis seemed negative predictors in terms of endpoints. CONCLUSIONS: sGIN-AKI-patients with no complete recovery at 1°line steroid should be treated with other immunosuppressive to avoid CKD, in particular if males with subacute onset and III stage-not hypercalcaemic AKI.

The Inhibition of Complement System in Formal and Emerging Indications: Results from Parallel One-Stage Pairwise and Network Meta-Analyses of Clinical Trials and Real-Life Data Studies.

This manuscript presents quantitative findings on the actual effectiveness of terminal complement component 5 (C5) inhibitors and complement component 1 (C1) esterase inhibitors through their formal and common "off-label" (compassionate) indications. The results emanated from pairwise and network meta-analyses to present evidence until September 2019. Clinical trials (CT) and real-life non-randomized studies of the effects of interventions (NRSI) are consistent on the benefits of C5 inhibitors and of the absence of effects of C1 esterase inhibitors (n = 7484): Mathematically, eculizumab (surface under the cumulative ranking area (SUCRA) >0.6) and ravulizumab (SUCRA ≥ 0.7) were similar in terms of their protective effect on hemolysis in paroxysmal nocturnal hemoglobinuria (PNH), thrombotic microangiopathy (TMA) in atypical hemolytic uremic syndrome (aHUS), and acute kidney injury (AKI) in aHUS, in comparison to pre-/off-treatment state and/or placebo (SUCRA < 0.01), and eculizumab was efficacious on thrombotic events in PNH (odds ratio (OR)/95% confidence interval (95% CI) in CT and real-life NRSI, 0.07/0.03 to 0.19, 0.24/0.17 to 0.33) and chronic kidney disease (CKD) occurrence/progression in PNH (0.31/0.10 to 0.97, 0.66/0.44 to 0.98). In addition, meta-analysis on clinical trials shows that eculizumab mitigates a refractory generalized myasthenia gravis (rgMG) crisis (0.29/0.13 to 0.61) and prevents new acute antibody-mediated rejection (AMR) episodes in kidney transplant recipients (0.25/0.13 to 0.49). The update of findings from this meta-analysis will be useful to promote a better use of complement inhibitors, and to achieve personalization of treatments with this class of drugs.

The Friday evening case of acute kidney injury: a crystal dilemma.

We report a case of acute kidney injury (AKI) induced by amoxycillin crystalluria suggested by massive amounts of urinary crystals of unusual morphology. This hypothesis was further reinforced by a particular solubility pattern when the urine sample was exposed to various temperatures, alkali, acids and alcohol. We therefore suspended amoxycillin, which produced a rapid and complete recovery of kidney function. Infrared spectroscopy later confirmed the amoxycillin composition of the crystals. Since infrared spectroscopy is not easily available, we propose that these solubility tests of urinary crystals be used as a first-step investigation when amoxycillin crystalluria is suspected.

Long-Term Outcomes and Discard Rate of Kidneys by Decade of Extended Criteria Donor Age.

BACKGROUND AND OBJECTIVES: Extended criteria donors represent nowadays a main resource for kidney transplantation, and recovery criteria are becoming increasingly inclusive. However, the limits of this approach are not clear as well as the effects of extreme donor ages on long-term kidney transplantation outcomes. To address these issues, we performed a retrospective study on extended criteria donor kidney transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In total, 647 consecutive extended criteria donor kidney transplantations performed over 11 years (2003-2013) were included. Donor, recipient, and procedural variables were classified according to donor age decades (group A, 50-59 years old [n=91]; group B, 60-69 years old [n=264]; group C, 70-79 years old [n=265]; and group D, ≥80 years old [n=27]). Organs were allocated in single- or dual-kidney transplantation after a multistep evaluation including clinical and histologic criteria. Long-term outcomes and main adverse events were analyzed among age groups and in either single- or dual-kidney transplantation. Kidney discard rate incidence and causes were evaluated. RESULTS: Median follow-up was 4.9 years (25th; 75th percentiles: 2.7; 7.6 years); patient and graft survival were comparable among age groups (5-year patient survival: group A, 87.8%; group B, 88.1%; group C, 88.0%; and group D, 90.1%; P=0.77; graft survival: group A, 74.0%; group B, 74.2%; group C, 75.2%; and group D, 65.9%; P=0.62) and between dual-kidney transplantation and single-kidney transplantation except for group D, with a better survival for dual-kidney transplantation (P=0.04). No difference was found analyzing complications incidence or graft function over time. Kidney discard rate was similar in groups A, B, and C (15.4%, 17.7%, and 20.1%, respectively) and increased in group D (48.2%; odds ratio, 5.1 with A as the reference group; 95% confidence interval, 2.96 to 8.79). CONCLUSIONS: Discard rate and long-term outcomes are similar among extended criteria donor kidney transplantation from donors ages 50-79 years old. Conversely, discard rate was strikingly higher among kidneys from octogenarian donors, but appropriate selection provides comparable long-term outcomes, with better graft survival for dual-kidney transplantation.

Intensive weight loss combining flexible dialysis with a personalized, ad libitum, coach-assisted diet program. A "pilot" case series.

UNLABELLED: Obesity is a growing problem on dialysis. The best approach to weight loss has not been established. The risks of malnutrition may offset the advantages of weight loss. Personalized hemodialysis schedules, with an incremental approach, are gaining interest; to date, no studies have explored its potential in allowing weight loss. This case series reports on combining flexible, incremental hemodialysis, and intensive weight loss. SETTING: a small Dialysis Unit, following incremental personalized schedules (2-6 sessions/week, depending on residual function), tailored to an equivalent renal clearance >12 mL/min. Four obese and two overweigh patients (5 male, 1 female; age: 40-63 years; body mass index [BMI] 31.1 kg/m(2)) were enrolled in a coach-assisted weight loss program, with an "ad libitum" approach (3-6 foods/day chosen on the basis of their glycemic index and glycemic load). The diet consists of 8 weeks of rapid weight loss followed by 8-12 weeks of maintenance; both phases can be repeated. This study measures weight loss, side effects, and patients' opinions. Over 12-30 months, all patients lost weight (median -10.3 kg [5.7-20], median ΔBMI-3.2). Serum albumin (pre-diet 3.78; post-diet 3.83 g/dL), hemoglobin (pre-diet 11; post-diet 11.2 g/dL), and acid-base balance (HCO(3) pre-diet: 23.3; post-diet: 23.4 mmol/L) remained stable, with decreasing needs for erythropoietin and citrate or bicarbonate supplements. Calcium-phosphate-parathyroid hormone (PTH) balance improved (PTH-pre 576; post 286 pg/mL). Three out of 4 hypertensive patients discontinued, 1 decreased antihypertensives. None experienced severe side effects. Patient satisfaction was high (9 on a 0-10 analog scale). Personalized, incremental hemodialysis schedules allow patient enrollment in intensive personalized weight loss programs, with promising results.

Calcium-phosphate and parathyroid intradialytic profiles: A potential aid for tailoring the dialysate calcium content of patients on different hemodialysis schedules.

Severe hyperparathyroidism is a challenge on hemodialysis. The definition of dialysate calcium (Ca) is a pending issue with renewed importance in cases of individualized dialysis schedules and of portable home dialysis machines with low-flow dialysate. Direct measurement of calcium mass transfer is complex and is imprecisely reflected by differences in start-to-end of dialysis Ca levels. The study was performed in a dialysis unit dedicated to home hemodialysis and to critical patients with wide use of daily and tailored schedules. The Ca-phosphate (P)-parathyroid hormone (PTH) profile includes creatinine, urea, total and ionized Ca, albumin, sodium, potassium, P, PTH levels at start, mid, and end of dialysis. "Severe" secondary hyperparathyroidism was defined as PTH > 300 pg/mL for ≥3 months. Four schedules were tested: conventional dialysis (polysulfone dialyzer 1.8-2.1 m(2) ), with dialysate Ca 1.5 or 1.75 mmol/L, NxStage (Ca 1.5 mmol/L), and NxStage plus intradialytic Ca infusion. Dosages of vitamin D, calcium, phosphate binders, and Ca mimetic agents were adjusted monthly. Eighty Ca-P-PTH profiles were collected in 12 patients. Serum phosphate was efficiently reduced by all techniques. No differences in start-to-end PTH and Ca levels on dialysis were observed in patients with PTH levels < 300 pg/mL. Conversely, Ca levels in "severe" secondary hyperparathyroid patients significantly increased and PTH decreased during dialysis on all schedules except on Nxstage (P < 0.05). Our data support the need for tailored dialysate Ca content, even on "low-flow" daily home dialysis, in "severe" secondary hyperparathyroid patients in order to increase the therapeutic potentials of the new dialysis techniques.

[Intensive weight-loss in dialysis: a personalized approach]. / La sfida del dimagrimento nell'obeso in trattamento dialitico. Case report.

UNLABELLED: Obesity is increasingly encountered in dialysis patients, who have difficulty to lose weight. Several Transplant Centres require BMI <30-35 Kg/m2 at waiting-list. Thus, losing weight becomes a must for young obese patients, however the best policy to obtain it (if any) is not defined. The aim of the present case report is to suggest that tailored dialysis and intensive diets could be a successful combination, that should be tested on a larger scale. A 56-year-old obese male patient (BMI 37.7 kg/m²) on daily home hemodialysis since 10 months (ESRD due to focal segmental glomerulosclerosis) started a coach-assisted qualitative ad libitum diet. The diet, alternating 8 weeks of rapid weight loss and maintenance phases, was based on a combinations of different foods, chosen on the account of glycaemic index and biochemical properties. It was salt free and olive oil was permitted in liberal quantities. Dialysis duration was increased to allow weight loss, and dialysate Na was incremented to permit a strict low sodium diet. Over a period of 21 months, the patient attained a -18.5 Kg weight loss (50% overweight loss; BMI -6.3 Kg/m²), reaching the goal to be included in a kidney transplant waiting list. Main metabolic data remained stable (pre diet and end of the diet period: albumin 3.5-3.8 g/dL; HCO3 26.1-24.8 mmol/L discontinuing citrate) or improved (haemoglobin 11.4-12.1 g/dL, halving EPO dose; calcium 2.3-2.5 mmol/L; phosphate 1.5-1.5 mmol/L; PTHi 1718-251 pg/mL, reducing chelation). CONCLUSION: Daily dialysis may allow enrolling obese hemodialysis patients in intensive weight loss programs, under strict clinical control.

Tailoring dialysis and resuming low-protein diets may favor chronic dialysis discontinuation: report on three cases.

Renal function recovery (RFR), defined as the discontinuation of dialysis after 3 months of replacement therapy, is reported in about 1% of chronic dialysis patients. The role of personalized, intensive dialysis schedules and of resuming low-protein diets has not been studied to date. This report describes three patients with RFR who were recently treated at a new dialysis unit set up to offer intensive hemodialysis. All three patients were females, aged 73, 75, and 78 years. Kidney disease included vascular-cholesterol emboli, diabetic nephropathy and vascular and dysmetabolic disease. At time of RFR, the patients had been dialysis-dependent from 3 months to 1 year. Dialysis was started with different schedules and was progressively discontinued with a "decremental" policy, progressively decreasing number and duration of the sessions. A moderately restricted low-protein diet (proteins 0.6 g/kg/day) was started immediately after dialysis discontinuation. The most recent update showed that two patients are well off dialysis for 5 and 6 months; the diabetic patient died (sudden death) 3 months after dialysis discontinuation. Within the limits of small numbers, our case series may suggest a role for personalized dialysis treatments and for including low-protein diets in the therapy, in enhancing long-term RFR in elderly dialysis patients.

Chronic dialysis discontinuation: a systematic narrative review of the literature in the new millennium.

INTRODUCTION AND AIMS: Renal function recovery (RFR), defined as the discontinuation of dialysis after 3 months of replacement therapy, is an uncommon occurrence. At a time when the "too early" start of dialysis is in discussion, a systematic review of the literature for cases in which patients recovered renal function after starting dialysis with chronic indications, including single cases and large series, may lead to attention being focused on this interesting issue. METHODS: The search strategy was built in Medline on Pubmed, in EMBASE and in the Cochrane Collaboration (August 2013) combining Mesh, Emtree and free terms: dialysis or hemodialysis, kidney function, renal function and recovery (publication date 2000-2013). The following tasks were performed in duplicate: titles and abstracts were manually screened, the data were extracted: title, author, objective, year, journal, period of study, multi-center, country, type of study. RESULTS: The systematic review retrieved 1,894 titles; 58 full papers were retrieved and the final selection included 24 papers: 11 case series or Registry data (4 from ANZdata) and 13 case reports. In spite of the high heterogeneity of the studies, overall they suggest that RFR occurs in about 1% of patients, without differences between PD and HD. RFR appears to be more frequent in elderly patients with renal vascular disease (up to 10% RFR in cholesterol emboli or scleroderma), but is reported in all types of primary and secondary kidney diseases. CONCLUSIONS: RFR is a clinical event that should be looked for, particularly in elderly patients with vascular comorbidity.