Autosomal Dominant Polycystic Kidney Disease: Extrarenal Involvement.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder, but kidneys are not the only organs involved in this systemic disorder. Individuals with the condition may display additional manifestations beyond the renal system, involving the liver, pancreas, and brain in the context of cystic manifestations, while involving the vascular system, gastrointestinal tract, bones, and cardiac valves in the context of non-cystic manifestations. Despite kidney involvement remaining the main feature of the disease, thanks to longer survival, early diagnosis, and better management of kidney-related problems, a new wave of complications must be faced by clinicians who treated patients with ADPKD. Involvement of the liver represents the most prevalent extrarenal manifestation and has growing importance in the symptom burden and quality of life. Vascular abnormalities are a key factor for patients' life expectancy and there is still debate whether to screen or not to screen all patients. Arterial hypertension is often the earliest onset symptom among ADPKD patients, leading to frequent cardiovascular complications. Although cardiac valvular abnormalities are a frequent complication, they rarely lead to relevant problems in the clinical history of polycystic patients. One of the newest relevant aspects concerns bone disorders that can exert a considerable influence on the clinical course of these patients. This review aims to provide the "state of the art" among the extrarenal manifestation of ADPKD.

[Polytrauma and Acute Kidney Injury: A Multidisciplinary Approach].

The development of acute kidney injury (AKI) in polytrauma patients is a common and serious complication, with an incidence ranging from 6% to 50%. Polytrauma is a complex pathological condition that involves the collaboration of various specialists. On one hand, hemodynamic stabilization through fluid therapy and aminic support, with specific attack protocols, managed by anesthetists. On the other hand, if necessary, the initiation of renal replacement therapy such as Continuous Renal Replacement Therapy (CRRT), managed by nephrologists. CRRT is chosen both for managing fluid balance and ensuring the removal of toxic substances, as well as for proper control of electrolytes and acid-base balance.

[Acute kidney injury in severely burned patient: prevention and treatment].

Acute Kidney Injury (AKI) is associated with a great increase in morbidity and mortality in severely burned patients and occurs as a complication in more than 25% of these cases. The onset of ARF may be early or late. Early AKI depends mainly on reduced cardiac output resulting from fluid loss, rhabdomyolysis, or hemolysis. Late AKI, instead, is usually a consequence of sepsis and is often associated with multiorgan failure (MOF). The first sign of AKI is the contraction of diuresis despite adequate volemic filling, which is followed by elevation of serum urea and creatinine. Fluid therapy is the main treatment in the burned victim: in the first few hours after injury, it aims to avoid hypovolemic shock and the possible related MOF, while later it becomes the cornerstone of treatment, besides antibiotic therapy in the case of sepsis onset. Particular care must also be taken in the choice of administered drugs in order to avoid possible nephrotoxic damage in addition to burning injury. Hemodialytic renal replacement therapy is used both for water balance management in patients requiring massive fluid infusions and for blood purification purposes to control the metabolic state, acid-base balance, and electrolytes abnormality. Our team has been collaborating for over 25 years in the management of severely burned patients admitted to the Centro Grandi Ustionati at the Bufalini Hospital in Cesena.

[New Perspectives in Post-Surgical Acute Kidney Injury During Sepsis].

Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. Sepsis is a common complication in patients undergoing surgery and is a major risk factor for the development of acute kidney injury (SA-AKI). Prevention of AKI in surgery patients is largely based on identification of high baseline risk, monitoring, and reduction of nephrotoxic insults. Early identification of patients at risk of AKI, or at risk of progressing to severe and/or persistent AKI, is crucial to the timely initiation of adequate supportive measures, including limiting further insults to the kidney. Although specific therapeutic options are limited, several clinical trials have evaluated the use of care bundles and extracorporeal techniques as potential therapeutic approaches.

Primary membranous nephropathy in the Italian region of Emilia Romagna: results of a multicenter study with extended follow-up.

BACKGROUND: Since primary membranous nephropathy is a heterogeneous disease with variable outcomes and multiple possible therapeutic approaches, all 13 Nephrology Units of the Italian region Emilia Romagna decided to analyze their experience in the management of this challenging glomerular disease. METHODS: We retrospectively studied 205 consecutive adult patients affected by biopsy-proven primary membranous nephropathy, recruited from January 2010 through December 2017. The primary outcome was patient and renal survival. The secondary outcome was the rate of complete remission and partial remission of proteinuria. Relapse incidence, treatment patterns and adverse events were also assessed. RESULTS: Median (IQR) follow-up was 36 (24-60) months. Overall patient and renal survival were 87.4% after 5 years. At the end of follow-up, 83 patients (40%) had complete remission and 72 patients (35%) had partial remission. Among responders, less than a quarter (23%) relapsed. Most patients (83%) underwent immunosuppressive therapy within 6 months of biopsy. A cyclic regimen of corticosteroid and cytotoxic agents was the most commonly used treatment schedule (63%), followed by rituximab (28%). Multivariable analysis showed that the cyclic regimen significantly correlates with complete remission (odds ratio 0.26; 95% CI 0.08-0.79) when compared to rituximab (p < 0.05). CONCLUSIONS: In our large study, both short- and long-term outcomes were positive and consistent with those published in the literature. Our data suggest that the use of immunosuppressive therapy within the first 6 months after biopsy appears to be a winning strategy, and that the cyclic regimen also warrants a prominent role in primary membranous nephropathy treatment, since definitive proof of rituximab superiority is lacking.

Efficacy of SARS-CoV-2 Vaccination in Dialysis Patients: Epidemiological Analysis and Evaluation of the Clinical Progress.

This study investigated the impact of the fourth COVID-19 pandemic wave on dialysis patients of Romagna territory, assessing the associations of vaccination status with infection risk, clinical severity and mortality. From November 2021 to February 2022, an epidemiological search was conducted on 829 patients under dialysis treatment for at least one month. The data were then analyzed with reference to the general population of the same area. A temporal comparison was also carried out with the previous pandemic waves (from March 2020 to October 2021). The epidemiological evolution over time in the dialysis population and in Romagna citizens replicated the global trend, as the peak of the fourth wave corresponded to the time of maximum diffusion of omicron variant (B.1.1.529). Of 771 prevalent dialysis patients at the beginning of the study, 109 (14.1%) contracted SARS-CoV-2 infection during the 4-month observation period. Vaccine adherence in the dialysis population of the reference area was above 95%. Compared to fully or partially vaccinated subjects, the unvaccinated ones showed a significantly higher proportion of infections (12.5% vs. 27.0% p = 0.0341), a more frequent need for hospitalization (22.2% vs. 50.0%) and a 3.3-fold increased mortality risk. These findings confirm the effectiveness of COVID-19 vaccines in keeping infectious risk under control and ameliorating clinical outcomes in immunocompromised patients.

COVID-19 incidence and mortality in non-dialysis chronic kidney disease patients.

Many studies reported a higher risk of COVID-19 disease among patients on dialysis or with kidney transplantation, and the poor outcome of COVID-19 in these patients. Patients in conservative management for chronic kidney disease (CKD) have received attention only recently, therefore less is known about how COVID-19 affects this population. The aim of this study was to provide evidence on COVID-19 incidence and mortality in CKD patients followed up in an integrated healthcare program and in the population living in the same catchment area. The study population included CKD patients recruited in the Emilia-Romagna Prevention of Progressive Renal Insufficiency (PIRP) project, followed up in the 4 nephrology units (Ravenna, Forlì, Cesena and Rimini) of the Romagna Local Health Authority (Italy) and alive at 1.01.2020. We estimated the incidence of COVID-19, its related mortality and the excess mortality within this PIRP cohort as of 31.07.2020. COVID-19 incidence in CKD patients was 4.09% (193/4,716 patients), while in the general population it was 0.46% (5,195/1,125,574). The crude mortality rate among CKD patients with COVID-19 was 44.6% (86/193), compared to 4.7% (215/4,523) in CKD patients without COVID-19. The excess mortality of March-April 2020 was +69.8% than the average mortality of March-April 2015-19 in the PIRP cohort. In a cohort mostly including regularly followed up CKD patients, the incidence of COVID-19 among CKD patients was strongly related to the spread of the infection in the community, while its lethality is associated with the underlying kidney condition and comorbidities. COVID-19 related mortality was about ten times higher than that of CKD patients without COVID. For this reason, it is urgent to offer a direct protection to CKD patients by prioritizing their vaccination.

Persistence of Antibody Responses to the SARS-CoV-2 in Dialysis Patients and Renal Transplant Recipients Recovered from COVID-19.

Nephropathic subjects with impaired immune responses show dramatically high infection rates of coronavirus disease 2019 (COVID-19). This work evaluated the ability to acquire and maintain protective antibodies over time in 26 hemodialysis patients and 21 kidney transplant recipients. The subjects were followed-up through quantitative determination of circulating SARS-CoV-2 S1/S2 IgG and neutralizing antibodies in the 6-month period after clinical and laboratory recovery. A group of 143 healthcare workers with no underlying chronic pathologies or renal diseases recovered from COVID was also evaluated. In both dialysis and transplanted patients, antibody titers reached a zenith around the 3rd month, and then a decline occurred on average between the 270th and 300th day. Immunocompromised patients who lost antibodies around the 6th month were more common than non-renal subjects, although the difference was not significant (38.5% vs. 26.6%). Considering the decay of antibody levels below the positivity threshold (15 AU/mL) as "failure", a progressive loss of immunisation was found in the overall population starting 6 months after recovery. A longer overall antibody persistence was observed in severe forms of COVID-19 (p = 0.0183), but within each group, given the small number of patients, the difference was not significant (dialysis: p = 0.0702; transplant: p = 0.1899). These data suggest that immunocompromised renal patients recovered from COVID-19 have weakened and heterogeneous humoral responses that tend to decay over time. Despite interindividual variability, an association emerged between antibody persistence and clinical severity, similar to the subjects with preserved immune function.

COVID-19 Infection: Viral Clearance and Antibody Response in Dialysis Patients and Renal Transplant Recipients.

BACKGROUND/AIMS: The coronavirus disease 2019 (CO-VID-19) pandemic is the major current health emergency worldwide, adding a significant burden also to the community of nephrologists for the management of their patients. Here, we analyzed the impact of COVID-19 infection in renal patients to assess the time to viral clearance, together with the production and persistence of IgG and IgM antibody response, in consideration of the altered immune capacity of this fragile population. METHODS: Viral clearance and antibody kinetics were investigated in 49 renal patients recovered from COVID-19 infection: 7 of them with chronic decompensated renal failure, 31 under dialysis treatment, and 11 kidney transplant recipients. RESULTS: The time span between the diagnosis of infection and recovery based on laboratory testing (2 negative nasopharyngeal swabs in consecutive days) was 31.7 ± 13.3 days. Three new positive cases were detected from 8 to 13 days following recovery. At the first serological determination after swab negativization, all the patients developed IgG and IgM antibodies. The semiquantitative analysis showed a progressive increase in IgG and a slow reduction in IgM. DISCUSSION/CONCLUSION: In subjects with decompensated chronic kidney disease, under dialysis and in transplant recipients, viral clearance is lengthened compared to the general population. However, in spite of their common status of immunodepression, all of them were able to produce specific antibodies. These data might provide useful insights for monitoring and planning health-care activities in the weak category of patients with compromised renal function recovered from COVID-19.

[Minimal change disease during lithium therapy: case report].

Lithium is a largely used and effective therapy in the treatment of bipolar disorder. Its toxic effects on kidneys are mostly diabetes insipidus, hyperchloremic metabolic acidosis and tubulointerstitial nephritis. Also, a correlation between lithium and minimal change disease has sometimes been described. We report here the case of a patient with severe bipolar disorder on lithium therapy who, without any pre-existing nephropathy, developed nephrotic syndrome and AKI with histopathologic findings pointing to minimal change disease. The patient was treated with symptomatic therapy; the discontinuation of lithium therapy resulted in the remission of AKI and of the nephrotic syndrome, thus suggesting a close relationship between lithium and minimal change disease.

The PIRP project (Prevenzione Insufficienza Renale Progressiva): how to integrate hospital and community maintenance treatment for chronic kidney disease.

Chronic kidney disease (CKD) represents a global health burden with great economic impact on healthcare and therefore it requires appropriate interventions by Health Care Systems. The PIRP (Prevenzione Insufficienza Renale Progressiva) project is endorsed and funded by the Emilia-Romagna Regional Health Board and involves all the Nephrology Units of the Emilia-Romagna Region (Italy). The project has a predominantly clinical purpose and is expected to bring about a continuous quality improvement in the treatment of patients with CKD. Its aims are to intercept patients in an early phase of CKD, to delay their illness progression and to prevent cardiovascular complications. An integrated care pathway involving nephrologists, general practitioners (GPs) and other specialists has been created to identify patients to whom ambulatory care targeted on effective, efficient pharmaceutical and dietary treatment as well as on lifestyle modifications is subsequently provided. With the cooperation of GPs, in its 13 years of activity the project identified and followed up more than 25,000 CKD patients, who attended the Nephrology units with more than 100,000 visits. The effects of a closer and joint monitoring of CKD patients by GPs and nephrologists can be quantified by the reduction of the mean annual GFR decline (average annual CKD-EPI change: - 0.34 ml/min), and by the decrease in the overall incidence of patients who annually started dialysis in the Emilia-Romagna Region, that dropped from 218.6 (× million) in 2006 to 197.5 (× million) in 2016, corresponding to about 100 cases.

[Minimal Change Relapse During Pregnancy].

The appearance of nephrotic syndrome during pregnancy is considered an exceptional event, whose incidence is around 0.012-0.025% of all pregnancies, and it is even more rare when the cause is represented by minimal lesions glomerulonephritis. In this article we will describe the case of a patient with a histological diagnosis of glomerulonephritis with minimal lesions, tending to frequent relapses. She was in complete remission since 2013 after treatment with cyclosporine. suspended in May 2017. After few weeks she become pregnant, and the pregnancy was regular until the 23rd week. when a recurrence of nephrotic syndrome appears. She was treated with steroids bolus followed by oral steroid, and afterwards gave birth to a live fetus with spontaneous delivery at 37 weeks The few data in the literature confirm that recurrence of glomerulonephritis due to minimal lesions in pregnancy should be treated rapidly with steroids, that can induce rapid remission and protect both the pregnant than the fetus from even serious damage.

[Challenges and results of the PIRP project (Prevenzione della Insufficienza Renale Progressiva) of the Emilia-Romagna Region].

The PIRP project was conceived in 2004; with the aim to face the increased prevalence of chronic kidney disease (CKD) associated with the aging and increased survival of the population. The first phase of the project consisted of training primary care physicians to identify people at risk of CKD and to implement intervention strategies that proved to be effective in preventing CKD it or delaying its progression once it is established. In the second phase of the project, dedicated ambulatories were opened in the nephrology units of Emilia-Romagna hospitals to provide an in-depth assessment and personalized care to CKD patients, following them up until renal failure or death or referring them back to general practitioners, according to the study protocol. A web-based registry was implemented to collect demographic and clinical data on PIRP patients. As of 30 June 2018, the registry included 26.211 CKD patients, with a median follow-up of 24.5 months. Over the 14 years of the PIRP the mean age of incident patients increased from 71.0 years to 74.2 years and the mean eGFR increased from 30.56 to 36.52 mL/min/1.73 m ², proving that the project was successful in recruiting older patients with a better renal function. At 5 years, the percentage of patients still active in the project was =45%.The implementation of the project has seen a reduction in the number of patients arriving every year to the dialysis treatment in E-R (about 100 units less from 2006 to 2016). The PIRP cohort is the largest in Italy and in Europe, which makes it ideal for research based on international comparisons and as a model for national registries.

Renal function replacement by hemodialysis: forty-year anniversary and a glimpse into the future at hand.

From its introduction in 1943 and until the late 1970s, hemodialysis (HD) has been a lengthy and cumbersome treatment administered by a few skilled physicians and technicians to a very limited number of terminal kidney patients. The technological innovations introduced over the years made HD a treatment administered and supervised by nursing personnel to a very large numbers of kidney patients, hopefully until recovery of kidney functions or kidney transplantation. In 2013, it is estimated that 2.250.00 kidney patients were treated worldwide, and their number is steadily increasing. Shortage of transplant kidneys and quality of current treatments has contributed to increasing the survival of HD patients. Today, it is not unusual to find patients who have been on HD for longer than twenty years. All this generated the feeling that performance of membranes and dialysis technology has reached its limit. Recently, the increasing economic burden of healthcare caused by people ageing and the increasing incidence of degenerative diseases (e.g. diabetes and cardiovascular diseases), and the economic crisis has pushed many governments and health insurances to cut resources for healthcare. The main consequence is that investments in research and development in HD have been significantly reduced. The question is whether there is indeed no need for innovation in HD.In this paper, it is discussed how the paradigm of HD has changed and what possibly are now the drivers for innovation in HD. A few ideas are proposed that could be developed by adapting existing technologies to the future needs of HD.

[Atypical hemolytic uremic syndrome related to Oxalyplatin Cancer Chemotherapy responsive to Eculizumab]. / Sindrome emolitico uremica atipica secondaria a chemioterapia con Oxaliplatino responsiva a Eculizumab.

We describe the case of a patient with adenocarcinoma of the colon treated with FOLFOX-4 (5-Fluorouracil, Folinic acid, Oxalyplatin), with subsequent appearance of atypical hemolytic uremic syndrome (aHUS). From 1999 to 2009, 13 cases of atypical HUS receiving chemotherapy with oxaliplatin have been described, as well as some sporadic cases. None of these cases has been treated with eculizumab. This is the first report of a patient with aHUS secondary to Oxalyplatin treated with Eculizumab. This treatment induced a complete remission of the syndrome and, later on, it has been discontinued with clinical and laboratory permanent remission. We identified some genetic mutations in this patient that might have a pathogenic role in the determining aHUS when associated with exposure to Oxalyplatin. Oxalyplatin withdrawal and its replacement to Irinotecan allowed the patient to receive first line chemotherapy continuation (FOLFIRI) with the same life expectancy and the same symptoms free period.

Improving donor identification with the Donor Action programme.

The increasing demand for organs for transplantation entails a consensual need for enhancement of organ procurement activity. As organ donors reside mainly in hospital intensive care units (ICUs), the Donor Action programme is aimed at identifying critical areas in ICUs, in order to improve the first step of organ donation. The purpose of this paper is to analyse the problem of identification of potential donors by means of a chart revision of patients who died in 14 ICUs in the Emilia-Romagna region between 1 July 1998 and 31 December 2000. All deaths and patients with severe brain insult (score on Glasgow Coma Scale (GCS) = 3/15) were assessed by the local transplant coordinators together with a professional at the Transplant Reference Centre. Brain death diagnoses and potential donor referrals were therefore assessed in the study period, which was subdivided into five semesters. Of the 3,056 deaths reported in 30 months, 1,248 were due to severe brain damage (GCS score = 3). Brain death diagnosis (BD) was performed in 509 patients (40.8%). Although we applied the same parameters over the whole length of the study, we observed a significant increase in BDs (from 87 in the first semester to 125 in the last, 30.5% to 53.0% of the patients with GCS 3 ( P=0.003, chi(2) for trend=16.072), in spite of a slight decrease in the total number of deaths and in the total number of patients with GCS score = 3 (from 649 to 587, and from 44% to 41%, respectively). Study population characteristics could have contrasted with rather than facilitated our results: age and gender did not change significantly, whilst cause of death showed a significant reduction in trauma and an increase in cerebrovascular incidents over the whole length of the study. We can conclude that the more careful assessment of patients dying in ICUs, by the Donor Action programme, significantly contributed to the improvement of BDs observed in the study period. Therefore, Donor Action seems to be an efficient quality control programme to improve identification of potential donors, the first stage of organ procurement.