Elisa Persici

Restless legs syndrome enhances cardiovascular risk and mortality in patients with end-stage kidney disease undergoing long-term haemodialysis treatment

BACKGROUND Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterized by paraesthesia, dysaesthesia and the irresistible urge to move the legs especially at night. Its prevalence is much higher among dialysis patients at 12 to 62% compared to 3 to 9% in the general population. Here, we investigated the association between RLS and cardiovascular events risk and laboratory parameters in end-stage kidney disease (ESKD) patients on dialysis. METHODS One hundred ESKD patients undergoing haemodialysis were enrolled in an 18-month prospective observational study. The main outcomes were the associations of RLS with new cardiovascular events and cardiovascular mortality. RESULTS RLS affected 31% of the study population. It was associated with female gender, gradual reduction in residual diuresis, lower albumin (P = 0.039) and inflammation, but not the dialysis parameters Kt/V and URR. During observation, 47% of patients experienced new cardiovascular events (64.5% with and 39.1% without RLS; P = 0.019). New cardiovascular events increased with severity of RLS [intermittent (I-RLS) vs continuous (C-RLS)]. Mortality was 20.0% in all patients, 32.3% in those with and 14.5% in patients without RLS (P = 0.04). In patients with I-RLS, mortality was 23.8% compared to 55.6% in patients with C-RLS (P = 0.014). Multivariate analysis confirmed the relationship between RLS and mortality. CONCLUSIONS This study confirmed the high prevalence of RLS among dialysis patients and the associations between the severity of RLS and the risk of new cardiovascular events and higher short-term mortality.

5-Methyltetrahydrofolate Administration Is Associated with Prolonged Survival and Reduced Inflammation in ESRD Patients

BACKGROUND Hemodialysis (HD) patients have a greatly increased risk of cardiovascular morbidity and mortality. For this reason, attempts are often made to normalize hyperhomocysteinemia. This randomized prospective study sought to determine which risk factors are predictors of mortality and whether high doses of folates or 5-methyltetrahydrofolate (5-MTHF) could improve hyperhomocysteinemia and survival in HD patients. METHODS 341 patients were divided into two groups: group A was treated with 50 mg i.v. 5-MTHF, and group B was treated with 5 mg/day oral folic acid. Both groups received i.v. vitamin B(6) and B(12). By dividing patients into C-reactive protein (CRP) quartiles, group A had the highest survival for CRP <12 mg/l, whereas no survival difference was found for group B. CRP was the only predictive risk factor for death (RR 1.17, range 1.04-1.30, p = 0.02). Dialysis age, hyperhomocysteinemia, methylenetetrahydrofolate reductase polymorphism, albumin, lipoprotein (a) and folate did not influence mortality risk. Survival in group A was higher than that in group B, namely 36.2 +/- 20.9 vs. 26.1 +/- 22.2 months (p = 0.003). RESULTS Our results suggest that CRP, but not hyperhomocysteinemia, is the main risk factor for mortality in HD patients receiving vitamin supplements. Intravenous 5-MTHF seems to improve survival in HD patients independent from homocysteine lowering.

Coronary Calcifications in End-Stage Renal Disease Patients: A New Link between Osteoprotegerin, Diabetes and Body Mass Index?

The aim of the study was to assess the factors potentially involved in coronary artery calcifications (CAC) in end-stage renal disease patients. 253 hemodialysis (HD) patients (92 females, 161 males), aged 62.5 ± 13.5, who had been on HD treatment for at least 6 months, were enrolled in a cross-sectional study. Calcium-phosphate product (Ca × P), body mass index (BMI), fetuin-A, osteoprotegerin (OPG), osteopontin, transforming growth factor-β1 (TGF-β1), fibroblast growth factor-23 (FGF-23) and matrix Gla protein (MGP) were considered. CAC was assessed using multislice spiral computed tomography and calcium score was quantified by means of the Agatston score. The median calcium score was 364 Agatston (range 0–7,336). CAC was detected in 228/253 patients (90.1%). Multivariate regression analysis, adjusted for age and for dialysis vintage, showed that TGF-β1, OPG and days with Ca × P >55 mg/dl are independent predictors of CAC, while MGP was shown to be a protective factor. Surprisingly, results showed that BMI was a protective factor too: the interpolation with cubic spline function revealed a significant reduction in calcium score in patients with a high BMI (>28). However, when diabetes was considered in the regression analysis, only OPG emerged as a predictor of a high CAC score. The interpolation with spline function continued to show a significant reduction in CAC score in nondiabetic and in diabetic patients with the highest BMI quartile. The protective effect of a high BMI on CAC might represent another example of inverse biology in dialysis patients but it needs to be further addressed in larger longitudinal studies.

Family recurrence and oligo-anuria predict uremic restless legs syndrome

Pizza F, Persici E, La Manna G, Campieri C, Plazzi G, Carretta E, Cappuccilli ML, Ferri B, Stefoni S, Montagna P. Family recurrence and oligo‐anuria predict uremic restless legs syndrome. 
Acta Neurol Scand: 2012: 125: 403–409. 
© 2011 John Wiley & Sons A/S.

Renal transplant in patients with polycystic disease: the Italian experience.

We analyzed the results of kidney transplantation in autosomal dominent polycystic kidney disease (ADPKD) patients in Italy, including 14,305 transplantations performed from January 2002 to December 2010, including: 12,859 first single or double kidneys from cadaveric donors (13% polycystic), 172 combined liver-kidney cases (22% polycystic), and 1,303 living-donor organs (7% polycystic). Among the first transplantations (12,008 single, 851 double), with follow-ups ranging from 16 to 120 months, polycystic patients demonstrated better graft survival compared with other kidney diseases (86% vs 82% at 5 years; P < .01); mortality was not different (92% vs 79% at 1 year). A better trend was obtained also among combined liver-kidney transplantations in ADPKD. Regarding pretransplantation management of polycystic patients, we noticed a conservative attitude in 32/35 transplant centers. The main indication for nephrectomy was for the lack of abdominal space. Regarding instrumental studies, 86% of centers asked for second-level investigations computerized tomography for kidney dimensions. Radiologic investigations for vasculocerebral malformations were required in 97% of the centers: 74% as a routine and 23% in the presence of familial history of cerebral hemorrhage. Polycystic patients are good candidates for kidney transplantation with correct management before transplantation.

Incidence of Cancer in Kidney Transplantation Waiting List Patients: A Single Center Experience

INTRODUCTION It is widely accepted that the risk of malignancies is significantly increased among patients with end-stage kidney disease (ESKD) and after kidney transplantation compared with the general population. Only a few data are available on kidney transplantation waiting list patients. The aim of this study was to investigate solid organ cancer incidence among subjects on the waiting list at a single center. MATERIALS AND METHODS We retrospectively reviewed the records of all patients enrolled on our kidney transplantation waiting list between August 1, 2008 and July 31, 2010, seeking to evaluate the causes of withdrawal from the list, incidence of cancer, type of neoplasm, and its correlation with clinical features. We estimated the ratio of observed to expected numbers of cancers, the standardized incidence ratio (SIR). RESULTS Among 1184 patients, we excluded 569 patients from the waiting list including 26 (4.56%) who displayed malignancies. The overall incidence of cancer was 0.11 events/person-months and the overall prevalence of cancer was 2.2%. In 97% of patients, the malignant disease was confined to the primitive organ of origin without secondary dissemination. We observed a prevalence of cancers related to ESKD (17; 65.38%). The SIR for all cancer types in our population compared with the general population was 2.22. The SIR for native kidney and thyroid cancers among our population compared with the general population was >10. CONCLUSION The incidence of cancer was significantly increased among kidney transplantation waiting list patients compared with the general population. Our study highlighted the importance of a careful, targeted neoplastic screening. It could be particularly important for ESKD-related malignancies like native kidney tumors or thyroid cancers.

Native Kidney Function After Renal Transplantation Combined With Other Solid Organs in Preemptive Patients

Kidney transplantations combined with other solid organs are progressively increasing in number. There are no guidelines regarding the nephrologic indications for combined transplantations, namely liver-kidney (LKT), or heart-kidney (HKT), in preemptive patients with chronic kidney failure who are not on regular dialysis therapy. The objective of this study was to assess the functional contribution of the native kidneys after preemptive kidney transplantation combined with other solid organs. From 2004, 9 patients (aged 50.3 +/- 8.5 years) with chronic kidney failure (creatinine 2.5 +/- 1.0 mg/dL) caused by polycystic kidney disease (n = 4), vascular nephropathy (n = 2), interstitial nephropathy (n = 1), glomerulonephritis (n = 1), or end-stage kidney disease (n = 1), underwent combined transplantations (8 LKT, 1 HKT). A scintigraphic functional study (Tc-99DMSA or Tc-99mMAG3), was performed at 4 +/- 3 months after transplantation to evaluate the functional contribution of both the native kidneys and the graft. All patients were given immunosuppressive drugs, including a calcineurin inhibitor (tacrolimus/or cyclosporine). At the time of scintigraphy, renal function in all patients was 1.3 +/- 0.3 mg/dL. The functional contribution of the transplanted kidneys was on average 77 +/- 18%. Only in 1 patient was the contribution of the graft <50%. At follow-up after 36 months, patient and kidney survivals were 100%. The study confirmed a high risk of loss of native kidney function in the presence of organic nephropathy. In light of our experience, a creatinine clearance <30 mL/min in an appropriate cutoff for a combined transplantation. Close clinical and instrumental assessment pretransplant is essential before proceeding with a combined transplant program to exclude functional forms and to optimize the use of organs.

Incidence and prevalence of cancer in kidney transplantation waiting list patients: An italian experience

Introduction Evaluation of kidney transplant candidates is based on strict exclusion of major pathologies, such as neoplastic disease. The aim of this study is to evaluate epidemiological and clinical impact of tumor disease in an Italian renal transplant waiting list and to propose a screening schedule for neoplastic detection. Materials and methods We retrospectively observed data of patients enrolled on the Emilia-Romagna kidney transplant waiting list between 1st August 2008 and 31st December 2010, evaluating the different causes of getting out from the list, the histologic type and incidence of cancer and the correlation between cancer onset and clinical features. The ratio of observed to expected cancer numbers (standardized incidence ratio, SIR), was estimated. Results We observed 2345 patients; 1297 got out from the waiting list; 57 of them (4,4%) got out because the onset of tumor. The overall incidence rate of cancer was 1354.8 (x 100000 person-year) (1045.9 person-year in patients awaiting for first transplant(FT), 1851.5 person-year in patients awaiting for second transplant(ST)). The overall prevalence of cancer was 2,43% (2.2% in FT, 3.4% in ST) with a SIR of 1.8; In our population the prevalence of cancers related to ESKD was 52.6% with a SIR of 15.8. Conclusion Kidney transplant waiting list patients present a higher incidence and prevalence of cancer compared to general population; it could be important to evaluate them for ESKD related malignancies because of their high incidence.

A case of Paget's disease in hemodialysis.

Pagets disease is the second most common bone disease after osteoporosis and causes an excessive bone turnover. Moreover, chronic kidney failure causes an impairment of bone mineral metabolism and electrolytes and PTH homeostasis. As far as we know, this is the first reported case of Pagets disease in a hemodialysis patient: the patient was also affected by secondary hyperparathyroidism and was successfully treated with clodronate, cinacalcet and paracalcitol. The safety and efficacy of this combined therapy was periodically revised in a 12-month follow-up considering the common markers of bone turnover as well as the dosage of OPG, RANKL, IL-6 and MCSF, involved in the pathophysiology of Pagets disease.

Trapianto di rene in pazienti con patologia policistica: valutazione pre-trapianto e risultati. Esperienza italiana

aneurismatiche (intracraniche, aortiche, polmonari, spleniche, pancreatiche), a difetti valvolari cardiaci, a diverticolosi del colon, a ernie addominali o inguinali, ad ectasia biliare. I pazienti con rene policistico, nonostante le manifestazioni extrarenali correlate, hanno una sopravvivenza in dialisi maggiore rispetto ai pazienti affetti da insufficienza renale terminale da altre cause (6, 7). Anche relativamente a programmi di trapianto i risultati riportati in letteratura risultano mediamente superiori a quelli che si riscontrano in altre patologie renali (nefropatie glomerulari o vascolari). Il potenziale coinvolgimento di altri organi richiede una particolare attenzione nella fase di studio per programmi di trapianto. Spesso si registrano atteggiamenti diversi tra i vari Centri Trapianto per quanto riguarda gli aspetti chirurgici (indicazione alla nefrectomia) e la tipologia di indagini strumentali aggiuntive (per esempio, studio vascolare cerebrale); la proposta di percorsi differenziati per l’inserimento operativo in lista può ingenerare difficoltà di gestione da parte dei Centri Dialisi che hanno in carico i pazienti. Anche in letteratura, peraltro, si evince un’ampia eterogeneità di comportamenti. Al fine di individuare alcuni punti di riferimento lo studio si è proposto di verificare l’atteggiamento dei diversi Centri Trapianto Italiani relativamente alla gestione dei pazienti policistici candidati al trapianto sia dal punto di vista chirurgico (nefrectomia) che diagnostico/ strumentale (indagini al momento dell’inserimento in lista e nel successivo follow-up). È stato inoltre verificato, in collaborazione con il Centro Nazionale Trapianti, l’impatto della patologia policistica sui programmi di trapianto e i relativi risultati a breve, medio e lungo termine. Introduzione