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Background: Peripheral artery disease (PAD) in hemodialysis (HD) patients has a significant social impact due to its prevalence, poor response to standard therapy and dismal prognosis. Rheopheresis is indicated by guidelines for PAD treatment., Materials and Methods: Twenty-five HD patients affected by PAD stage IV Lerichè-Fontaine and ischemic ulcer 1C or 2C according to the University of Texas Wound Classification System (UTWCS), without amelioration after traditional medical therapy and/or revascularization, were selected and underwent 12 Rheopheresis sessions in 10 weeks. Improvements in pain symptoms using Numerical Rating Scale (NRS), healing ulcers and laboratory hemorheological parameters have been evaluated., Results: A clinically and statistically significant mean value reduction and of relative percentage differences between estimated marginal means (Δ), calculated at each visits, of NRS was observed, with a maximum value (-48.5%) between the first and last visit. At the end of the treatment period 14.3% of ulcers were completely healed, 46.4% downgraded, 53.6% were stable. Overall, no ulcers upgraded. A statistically significant reduction of the Δ, between the first and last visit, for fibrinogen (-16%) was also observed., Conclusion: Rheopheresis reduced overall painful symptoms; data suggest that it could heal or improve ulcers and hemorheological laboratory parameters in HD patients with PAD and ischemic ulcers resistant to standard therapies., (© 2024 The Author(s). Journal of Clinical Apheresis published by Wiley Periodicals LLC.)

The prevalence of central venous catheters (CVC) in hemodialysis patients is around 20-30%. In this scenario, complications related to the use of the CVC are commonly observed, requiring active management by nephrologists. These include infectious complications as well as those related to CVC malfunction. Among the latter, the formation of a fibrin sheath around the catheter linked to foreign body reaction could cause CVC malfunction in various ways. Even after the removal of the catheter, the fibrin sheath can remain inside the vascular lumen (ghost fibrin sheath) and rarely undergo calcification. We describe the clinical case of a hemodialysis patient who, following the removal of a malfunctioning, stuck CVC, presented a calcified tubular structure in the lumen of the superior vena cava, diagnosed as calcified fibrin sheath (CFS). This rare occurrence, described in the literature in 8 other cases, although rare, is certainly underdiagnosed and can lead to complications such as sepsis resulting from CFS, pulmonary embolisms, and vascular thrombosis. Therapeutic approaches should be considered only in symptomatic cases and involve an invasive surgical approach., (Copyright by Società Italiana di Nefrologia SIN, Rome,Italy.)

Fertility is known to be impaired more frequently in patients with chronic kidney disease than in the general population. A significant proportion of chronic kidney disease patients may therefore need Medically Assisted Reproduction. The paucity of information about medically assisted reproduction for chronic kidney disease patients complicates counselling for both nephrologists and gynaecologists, specifically for patients with advanced chronic kidney disease and those on dialysis or with a transplanted kidney. It is in this context that the Project Group on Kidney and Pregnancy of the Italian Society of Nephrology has drawn up these best practice guidelines, merging a literature review, nephrology expertise and the experience of obstetricians and gynaecologists involved in medically assisted reproduction. Although all medically assisted reproduction techniques can be used for chronic kidney disease patients, caution is warranted. Inducing a twin pregnancy should be avoided; the risk of bleeding, thrombosis and infection should be considered, especially in some categories of patients. In most cases, controlled ovarian stimulation is needed to obtain an adequate number of oocytes for medically assisted reproduction. Women with chronic kidney disease are at high risk of kidney damage in case of severe ovarian hyperstimulation syndrome, and great caution should be exercised so that it is avoided. The higher risks associated with the hypertensive disorders of pregnancy, and the consequent risk of chronic kidney disease progression, should likewise be considered if egg donation is chosen. Oocyte cryopreservation should be considered for patients with autoimmune diseases who need cytotoxic treatment. In summary, medically assisted reproduction is an option for chronic kidney disease patients, but the study group strongly advises extensive personalised counselling with a multidisciplinary healthcare team and close monitoring during the chosen medically assisted reproduction procedure and throughout the subsequent pregnancy., (© 2023. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Even though fertility is reduced, conception and delivery are possible in all stages of CKD. While successful planned pregnancies are increasing, an unwanted pregnancy may have long-lasting deleterious effects, hence the importance of birth control, an issue often disregarded in clinical practice. The evidence summarized in this position statement is mainly derived from the overall population, or other patient categories, in the lack of guidelines specifically addressed to CKD. Oestroprogestagents can be used in early, non-proteinuric CKD, excluding SLE and immunologic disorders, at high risk of thromboembolism and hypertension. Conversely, progestin only is generally safe and its main side effect is intramestrual spotting. Non-medicated intrauterine devices are a good alternative; their use needs to be carefully evaluated in patients at a high risk of pelvic infection, even though the degree of risk remains controversial. Barrier methods, relatively efficacious when correctly used, have few risks, and condoms are the only contraceptives that protect against sexually transmitted diseases. Surgical sterilization is rarely used also because of the risks surgery involves; it is not definitely contraindicated, and may be considered in selected cases. Emergency contraception with high-dose progestins or intrauterine devices is not contraindicated but should be avoided whenever possible, even if far preferable to abortion. Surgical abortion is invasive, but experience with medical abortion in CKD is still limited, especially in the late stages of the disease. In summary, personalized contraception is feasible, safe and should be offered to all CKD women of childbearing age who do not want to get pregnant.

Background : Hepatitis C Virus (HCV) disease, which is commonly underdiagnosed, in addition to the well-known effects on the liver is also a risk factor for Cronic Kidney Disease (CKD) and End Stage Renal Disease (ESRD). It worsens the outcome at every stage of CKD; around 400.000 people worldwide die from HCV-related causes each year. The KDIGO 2018 Guidelines recommend that all patients be evaluated for renal disease when HCV is diagnosed and be screened for HCV when CKD is diagnosed, as the prevalence may be higher than in the general population. Effective screening is therefore necessary in order to establish early treatment. Aims of the study : We ran a systematic program of screening and management of HCV in nephropathic outpatients in order to improve Sustained Virological Response 12 weeks after the end of treatment (SVR 12) and renal functions such as GFR and proteinuria. Materials and methods : We considered outpatients not in dialysis and older than 18. The systematic, prospective observational study of HCV infection run over a period of 18 months. Results : Of 2798 nephropathic outpatients that came to our attention during this period, we identified 108 HCV-positive patients (prevalence: 3.85%). The test for HCV-RNA resulted positive in 78 patients and, after hepatological evaluation and informed consent to treatment, 51 of them underwent therapy with the new direct-acting antivirals (DAAs). 34 patients concluded the treatment during the 18-month period, all of them with 100% SVR 12. The average pre-treatment GFR was 40.5 ml/m'; after treatment resulted equal to 45 ml/m' (p=0.01). The average value of pre-treatment proteinuria was 1.18 g/24 h; it was reduced to 0.79 g/24 (p=0.015). The remaining 17 patients were still under treatment/evaluation at the end of the 18 months. Conclusions : Treatment with the new DAAs has been confirmed safe and effective and is associated with an improvement of renal functions. Systematic screening of nephropathic patients may therefore contribute to achieving the WHO target of eliminating HCV by 2030., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Fatty acid oxidation disorders are inborn errors of metabolism. One of the possible alterations involves the failure of the carnitin-based transport of long-chain fatty acids into the mitochondria, necessary for muscle metabolism in case of prolonged physical exertion. Three kinds of Carnitin-Palmitoyl Transferase type 2 (CPT2) deficiency have been described: a myopathic form, a severe infantile form and a neonatal form. The clinical picture is characterized by recurrent attacks of rhabdomyolysis, muscular pains and fatigue, secondary to a prolonged physical exercise and sometimes aggravated by intercurrent events. Rhabdomyolysis episodes are associated with a significant increase in creatine phosphokinase and myoglobinuria and may result in acute renal failure. Patients are usually asymptomatic during intercurrent periods. When acute renal failure from rhabdomyolysis arises after intense physical activity, it is therefore necessary to also investigate the presence of metabolic myopathies due to enzymatic deficiency., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Kidney transplantation (KT) is often considered to be the method best able to restore fertility in a woman with chronic kidney disease (CKD). However, pregnancies in KT are not devoid of risks (in particular prematurity, small for gestational age babies, and the hypertensive disorders of pregnancy). An ideal profile of the potential KT mother includes "normal" or "good" kidney function (usually defined as glomerular filtration rate, GFR ≥ 60 ml/min), scant or no proteinuria (usually defined as below 500 mg/dl), normal or well controlled blood pressure (one drug only and no sign of end-organ damage), no recent acute rejection, good compliance and low-dose immunosuppression, without the use of potentially teratogen drugs (mycophenolic acid and m-Tor inhibitors) and an interval of at least 1-2 years after transplantation. In this setting, there is little if any risk of worsening of the kidney function. Less is known about how to manage "non-ideal" situations, such as a pregnancy a short time after KT, or one in the context of hypertension or a failing kidney. The aim of this position statement by the Kidney and Pregnancy Group of the Italian Society of Nephrology is to review the literature and discuss what is known about the clinical management of CKD after KT, with particular attention to women who start a pregnancy in non-ideal conditions. While the experience in such cases is limited, the risks of worsening the renal function are probably higher in cases with markedly reduced kidney function, and in the presence of proteinuria. Well-controlled hypertension alone seems less relevant for outcomes, even if its effect is probably multiplicative if combined with low GFR and proteinuria. As in other settings of kidney disease, superimposed preeclampsia (PE) is differently defined and this impairs calculating its real incidence. No specific difference between non-teratogen immunosuppressive drugs has been shown, but calcineurin inhibitors have been associated with foetal growth restriction and low birth weight. The clinical choices in cases at high risk for malformations or kidney function impairment (pregnancies under mycophenolic acid or with severe kidney-function impairment) require merging clinical and ethical approaches in which, beside the mother and child dyad, the grafted kidney is a crucial "third element".

In the original publication of the article, the first name and last name of the authors were interchanged.

Preeclampsia (PE) is a protean syndrome causing a transitory kidney disease, characterised by hypertension and proteinuria, ultimately reversible after delivery. Its prevalence is variously estimated, from 3 to 5% to 10% if all the related disorders, including also pregnancy-induced hypertension (PIH) and HELLP syndrome (haemolysis, increase in liver enzyme, low platelets) are included. Both nephrologists and obstetricians are involved in the management of the disease, according to different protocols, and the clinical management, as well as the role for each specialty, differs worldwide. The increased awareness of the role of chronic kidney disease in pregnancy, complicating up to 3% of pregnancies, and the knowledge that PE is associated with an increased risk for development of CKD later in life have recently increased the interest and redesigned the role of the nephrologists in this context. However, while the heterogeneous definitions of PE, its recent reclassification, an emerging role for biochemical biomarkers, the growing body of epidemiological data and the new potential therapeutic interventions lead to counsel long-term follow-up, the lack of resources for chronic patients and the increasing costs of care limit the potential for preventive actions, and suggest tailoring specific interventional strategies. The aim of the present position statement of the Kidney and Pregnancy Study Group of the Italian Society of Nephrology is to review the literature and to try to identify theoretical and pragmatic bases for an agreed management of PE in the nephrological setting, with particular attention to the prevention of the syndrome (recurrent PE, presence of baseline CKD) and to the organization of the postpartum follow-up.

Many of information on the safety of drugs during pregnancy were obtained many years ago, before the pregnant women were excluded from the study protocols for possible fetal risks. Because randomized trials in pregnancy are complex and considered unethical. For the same reasons, there are no randomized controlled trials in pregnant women on dialysis. Moreover Compared to the normal subject, the pharmacokinetics and pharmacodynamics in these patients are influenced or by pregnancy or from dialysis techniques or from chronic uremia. Protein energy wasting PEW- is largely present in dialysis subjects. Nausea and vomiting are present in over 85% of pregnancy and may aggravate PEW. Therefore, it is necessary to adopt specific measures to prevent the PEW as well as periodic inspections of weight gain during pregnancy.

Pregnancy is increasingly undertaken in patients with chronic kidney disease (CKD) and, conversely, CKD is increasingly diagnosed in pregnancy: up to 3 % of pregnancies are estimated to be complicated by CKD. The heterogeneity of CKD (accounting for stage, hypertension and proteinuria) and the rarity of several kidney diseases make risk assessment difficult and therapeutic strategies are often based upon scattered experiences and small series. In this setting, the aim of this position statement of the Kidney and Pregnancy Study Group of the Italian Society of Nephrology is to review the literature, and discuss the experience in the clinical management of CKD in pregnancy. CKD is associated with an increased risk for adverse pregnancy-related outcomes since its early stage, also in the absence of hypertension and proteinuria, thus supporting the need for a multidisciplinary follow-up in all CKD patients. CKD stage, hypertension and proteinuria are interrelated, but they are also independent risk factors for adverse pregnancy-related outcomes. Among the different kidney diseases, patients with glomerulonephritis and immunologic diseases are at higher risk of developing or increasing proteinuria and hypertension, a picture often difficult to differentiate from preeclampsia. The risk is higher in active immunologic diseases, and in those cases that are detected or flare up during pregnancy. Referral to tertiary care centres for multidisciplinary follow-up and tailored approaches are warranted. The risk of maternal death is, almost exclusively, reported in systemic lupus erythematosus and vasculitis, which share with diabetic nephropathy an increased risk for perinatal death of the babies. Conversely, patients with kidney malformation, autosomal-dominant polycystic kidney disease, stone disease, and previous upper urinary tract infections are at higher risk for urinary tract infections, in turn associated with prematurity. No risk for malformations other than those related to familiar urinary tract malformations is reported in CKD patients, with the possible exception of diabetic nephropathy. Risks of worsening of the renal function are differently reported, but are higher in advanced CKD. Strict follow-up is needed, also to identify the best balance between maternal and foetal risks. The need for further multicentre studies is underlined.

Background: Pregnancy during dialysis is increasingly being reported and represents a debated point in Nephrology. The small number of cases available in the literature makes evidence-based counselling difficult, also given the cultural sensitivity of this issue. Hence, the need for position statements to highlight the state of the art and propose the unresolved issues for general discussion., Methods: A systematic analysis of the literature (MESH, Emtree and free terms on pregnancy and dialysis) was conducted and expert opinions examined (Study Group on Kidney and Pregnancy; experts involved in the management of pregnancy in dialysis in Italy 2000-2013). Questions regarded: timing of dialysis start in pregnancy; mode of treatment, i.e. peritoneal dialysis (PD) versus haemodialysis (HD); treatment schedules (for both modes); obstetric surveillance; main support therapies (anaemia, calcium-phosphate parathormone; acidosis); counselling tips., Main Results: Timing of dialysis start is not clear, considering also the different support therapies; successful pregnancy is possible in both PD and HD; high efficiency and strict integration with residual kidney function are pivotal in both treatments, the blood urea nitrogen test being perhaps a useful marker in this context. To date, long-hour HD has provided the best results. Strict, personalized obstetric surveillance is warranted; therapies should be aimed at avoiding vitamin B12, folate and iron deficits, and at correcting anaemia; vitamin D and calcium administration is safe and recommended. Women on dialysis should be advised that pregnancy is possible, albeit rare, with both types of dialysis treatment, and that a success rate of over 75% may be achieved. High dialysis efficiency and frequent controls are needed to optimize outcomes.

A 55-years-old woman with end-stage renal disease presented on hemodialysis bloody ascitis after transfer from peritoneal dialysis. During the 8 years of peritoneal dialysis, she had exit-site infection and a culture-negative peritonitis. She was dropped-out of hemodialysis for ultrafiltration failure associated with "high" peritoneal transport. Clinic and radiologic findings was suggestive for the encapsulating peritoneal sclerosis, which was confirmed upon biopsy of the peritoneum. The patient was treated successfully with immunosuppressive. Our case is relevant, both because many clinical features that have been described must draw attention to the encapsulating peritoneal sclerosis, rare but life-threatening complication of peritoneal dialysis and because of its favorable outcome, unfortunately infrequent.

Background: In the last decade, significant improvements have been achieved in maternal-fetal and diabetic care which make pregnancy possible in an increasing number of type 1 diabetic women with end-organ damage. Optimal counseling is important to make the advancements available to the relevant patients and to ensure the safety of mother and child. A systematic review will help to provide a survey of the available methods and to promote optimal counseling., Objectives: To review the literature on diabetic nephropathy and pregnancy in type 1 diabetes., Methods: Medline, Embase, and the Cochrane Library were scanned in November 2012 (MESH, Emtree, and free terms on pregnancy and diabetic nephropathy). Studies were selected that report on pregnancy outcomes in type 1 diabetic patients with diabetic nephropathy in 1980-2012 (i.e. since the detection of microalbuminuria). Case reports with less than 5 cases and reports on kidney grafts were excluded. Paper selection and data extraction were performed in duplicate and matched for consistency. As the relevant reports were highly heterogeneous, we decided to perform a narrative review, with discussions oriented towards the period of publication., Results: Of the 1058 references considered, 34 fulfilled the selection criteria, and one was added from reference lists. The number of cases considered in the reports, which generally involved single-center studies, ranged from 5 to 311. The following issues were significant: (i) the evidence is scattered over many reports of differing format and involving small series (only 2 included over 100 patients), (ii) definitions are non-homogeneous, (iii) risks for pregnancy-related adverse events are increased (preterm delivery, caesarean section, perinatal death, and stillbirth) and do not substantially change over time, except for stillbirth (from over 10% to about 5%), (iv) the increase in risks with nephropathy progression needs confirmation in large homogeneous series, (v) the newly reported increase in malformations in diabetic nephropathy underlines the need for further studies., Conclusions: The heterogeneous evidence from studies on diabetic nephropathy in pregnancy emphasizes the need for further perspective studies on this issue.

Aim: The cholelithiasis (CL) has a 10-20% prevalence in the adult population. The end stage renal disease and dialysis would seem factors of risk since uremic patients show increased bile cholesterol, increased saturation indices and lithogenicity. Nevertheless the studies to confirm this hypothesis have furnished contradictory results. The aim of the study was to appraise prevalence of CL in dialysis-patients., Methods: The authors examined 127 patients (92 in hemodialysis and 35 in peritoneal dialysis) comparing them with a non-uremic control group (CNU) and the prevalence in the general population taking as champion the town of Castellana, near to ''S. Maria Degli Angeli'' Hospital, where, previously, an epidemiological study was performed. Sonographic examination was done with Esaote/Biomedica AU3 instrument with 3.5/5 mHz transducer. The evidence of gallstone(s) by ultrasonography or previously cholecystectomy have been considered diagnostics., Results: Gallstones were detected in 33 of the 127 dialysis-patients (25.9% prevalence). In the CNU the prevalence was 15% (P=0.046). Furthermore the comparison of prevalence of CL between dialysis-patients and the Castellana population was greater in dialysis-population considering the attended rate (13 vs 9.6) and had a greater attributable risk (35%). A global greater prevalence of CL in older patients (>60 years) showed a possible role of the increasing age as a correlated factor to the CL. Any other considered parameter has shown significant correlations., Conclusions: These results underline a greater risk of CL in the dialysis-patient.

We report a case of a healthy woman - whose previous pregnancy was uncomplicated - with early onset of hypertension, proteinuria and edema, during her second pregnancy. Ultrasound examination at 19th week of amenor rhea showed a fetus with growth retardation, corresponding to 17 weeks' gestation, ascites, cardiomegaly with serious multiple congenital anomalies. Amniocentesis for fetal karyotyping revealed 69, XXX. Because of continued elevated blood pressure, increasing proteinuria and severe lethal fetal anomalies, interruption of pregnancy was suggested. It was subsequently carried out by surgery. The patient underwent renal biopsy 10 days post-partum: histology showed the presence of the characteristic pathologic renal changes of preeclampsia. A year later, she became pregnant by the same partner. The third pregnancy was uneventful. The combination of fetal triploidy and preeclampsia may suggest a causative relationship. Clinically, most cases manifest as severe early-onset preeclampsia and must be differentiated from essential hypertension and a chronic glomerulonephritis (GN), which becomes symptomatic during pregnancy. When a fetus has triploidy, the counseling should stress the high incidence of preeclampsia; particularly when fetal anomaly is not compatible with life, it is well known that delivery of the fetus is curative in this syndrome. This information is important in counseling patients who are hesitant to terminate the pregnancy purely for a fetal abnormality, even if lethal.