[Italian nephrology and the progress of dialysis from its dawn to the present day].

In Italy, over the last 50 years, dialysis has been the driving force of research in nephrology. The work of many Italian nephrologists has fueled progress in dialytic techniques worldwide, improving dramatically the quality of dialytic therapy. Our foreign colleagues unanimously agree that we have been the first to look into the complexities of dialysis, into the many differences between dialytic patients and how to best address this diversity. This has allowed us to adopt a holistic approach, deeply connected to technological innovation, with the aim of putting the patient center stage and creating a "precision dialysis".

Prognostic value of inflammation-based prognostic scores on outcome in patients undergoing continuous ambulatory peritoneal dialysis.

BACKGROUND: Inflammation-based prognostic scores have been used as outcome predictors in patients with cancer or on hemodialysis. However, their role in patients on continuous ambulatory peritoneal dialysis (CAPD) remains unclear. This study aimed to examine the prognostic value of inflammation-based composite scores for mortality in CAPD patients. METHODS: This study was conducted in CAPD patients enrolled from January 1, 2006 to December 31, 2014 and followed until December 31, 2016. Three inflammation-based prognostic scores, including Glasgow prognostic score (GPS), prognostic nutritional index (PNI), and prognostic index (PI), were conducted in this study. The associations between these scores and all-cause or cardiovascular mortality were evaluated by Kaplan-Meier method and Cox proportional hazards models. The areas under the curve (AUC) of receiver-operating characteristic (ROC) analysis were used to determine the predictive values of mortality. RESULTS: A total of 1501 patients were included. During a median follow-up of 38.7 (range, 21.6-62.3) months, 346 (23.1%) patients died, of which 168 (48.6%) were due to cardiovascular diseases (CVD). After adjustment for confounders, the results showed that elevated GPS, PNI, and PI scores were all independently associated with all-cause [GPS: Score 1: hazard ratio(HR) 3.94, 95% confidence interval(CI) 2.90-5.35; Score 2: HR 7.56, 95% CI 5.35-10.67; PNI: HR 1.82, 95% CI 1.36-2.43; PI: Score 1: HR 2.08, 95% CI 1.63-2.65; Score 2: HR 3.03, 95% CI 2.00-4.60)] and CVD mortality(GPS: Score 1: HR 4.41, 95% CI 2.76-7.03; Score 2: HR 9.64, 95% CI 5.72-16.26; PNI: HR 1.63, 95% CI 1.06-2.51; PI: Score 1: HR 2.57, 95% CI 1.81-3.66, Score 2: HR 3.85, 95% CI 1.99-7.46).The AUC values of GPS score were 0.798 (95% CI0.770-0.826) for all-cause mortality and 0.781 (95% CI 0.744-0.817) for CVD mortality, both of which significantly higher than those of PNI and PI scores (P < 0.001, respectively). CONCLUSIONS: All elevated GPS, PNI, and PI scores were independently associated with all-cause and CVD mortality. The GPS score showed better predictive value than PNI and PI scores in CAPD patients.

Icodextrin-associated generalized exfoliative skin rash in a CAPD patient: a case-report.

BACKGROUND: Icodextrin is a starch-derived, water soluble glucose polymer, which is used as an alternative to glucose in order to enhance dialytic fluid removal in peritoneal dialysis patients. Although the safety and efficacy of icodextrin is well-established, its use in everyday clinical practice has been associated with the appearance of skin rashes and other related skin reactions. CASE PRESENTATION: Herein, we report the rare case of a 91-year-old woman with a history of severe congestive heart failure, who initiated continuous ambulatory peritoneal dialysis with icodextrin-based dialysate solutions and 15 days after the initial exposure to icodextrin developed a generalized maculopapular and exfoliative skin rash extending over the back, torso and extremities. Discontinuation of icodextrin and oral therapy with low-dose methyl-prednisolone with quick dose tapering improved the skin lesions within the following days. CONCLUSIONS: This case report highlights that skin hypersensitivity is a rare icodextrin-related adverse event that should be suspected in patients manifesting skin reactions typically within a few days or weeks after the initial exposure.

Current state of continuous ambulatory peritoneal dialysis in Egypt.

Patients with end-stage renal disease (ESRD) continue to increase in number worldwide, especially in developing countries. Although continuous ambulatory peritoneal dialysis (CAPD) has comparable survival advantages as hemodialysis (HD), it is greatly underutilized in many regions worldwide. The prevalence of use of CAPD in Egypt is 0.29/million population in 2017. The aim of this study is to describe the current state and practice of CAPD in Egypt and included 22 adult patients who were treated by CAPD. All the study patients were switched to CAPD after treatment with HD failed due to vascular access problems. Patients were mainly female (68.2 %) with the mean age of 49.77 ± 11.41 years. The average duration on CAPD was 1.76 ± 1.30 years. Hypertension was the main cause of end-stage renal disease (ESRD) constituting 36.4%, followed by diabetes (27.3 %), and toxic nephropathy (4.5%). Of importance is that about 31.8% of patients had ESRD of unknown etiology. The mean weekly Kt/V urea of patients on PD was 1.92 ± 0.18. The mean hemoglobin, serum calcium, phosphorus, parathormone, and albumin levels were 10.27 ± 1.98 g/dL, 8.36 ± 1.19 mg/dL, 5.70 ± 1.35 mg/dL, 541.18 ± 230.12 pg/mL, and 2.98 ± 0.73 g/dL, respectively. There was no significant difference between diabetic and nondiabetic CAPD patients regarding demographic and laboratory data. Our data indicate that there is continuing underutilization of CAPD in Egypt which may be related to nonavailability of CAPD fluid, patient factors (education and motivation), gradual decline of the efficiency of health-care professionals, and lack of a national program to start PD as the first modality for renal replacement therapy. It is advised to start an organized program to make CAPD widespread and encourage local production of PD fluids to reduce the cost of CAPD.

Association of baseline, longitudinal serum high-sensitive C-reactive protein and its change with mortality in peritoneal dialysis patients.

BACKGROUND: The prognostic values of baseline, longitudinal high-sensitivity C-reactive protein (hs-CRP) and its change over time on mortality in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) remain uncertain. METHODS: We retrospectively studied 1228 consecutive CAPD patients from 2007 to 2012, and followed up through December 2014. Cox regression models were performed to assess the association of hs-CRP on outcomes using serum hs-CRP levels as: (1) stratified by tertile of baseline or longitudinal hs-CRP levels; (2) baseline or longitudinal hs-CRP levels as continuous variables; and (3) categorized by tertile of slopes of hs-CRP change per year for each subject. RESULTS: Higher baseline hs-CRP levels were not associated with clinical outcomes after adjustment for potential confounders. However, patients with the upper tertile of longitudinal hs-CRP had a nearly twice-fold increased risk of both all-cause and cardiovascular mortality [adjusted hazard ratio (HR) 1.77; (95% CI 1.16-2.70) and 2.08 (1.17-3.71), respectively], as compared with those with lower tertile. Results were similar when baseline or longitudinal hs-CRP was assessed as continuous variable. Additionally, the risk of all-cause and cardiovascular mortality in patients with increased trend in serum hs-CRP levels over time (tertile 3) was significantly higher [adjusted HR 2.48 (1.58-3.87) and 1.99 (1.11-3.56), respectively] when compared to those with relatively stable hs-CRP levels during follow-up period. These associations persisted after excluding subjects with less than 1-year follow up. CONCLUSIONS: Higher longitudinal serum hs-CRP levels and its elevated trend over time, but not baseline levels were predictive of worse prognosis among CAPD patients.

Incremental start to PD as experienced in Italy: results of censuses carried out from 2005 to 2014.

BACKGROUND: It is not known how widely used in Italy an incremental start to in peritoneal dialysis (Incr-PD) is. METHODS: By analyzing the peritoneal dialysis (PD) censuses conducted by the PD Study Group (GSDP-SIN) for the years 2005, 2008, 2010, 2012 and 2014 in all the Centers performing PD in Italy, the use of Incr-PD, i.e. continuous ambulatory peritoneal dialysis (CAPD) with 1 or 2 exchanges/day or automated peritoneal dialysis (APD) with 3-4 sessions/week, was examined among incident PD patients. RESULTS: In 2014 PD was started in Italy by 1,652 patients, 455 (27.5%) of whom incrementally (Incr-CAPD 82.2% vs. Incr-APD 17.8%). Incr-PD was used in 53.5% of the 225 Centers. The number of patients and of Centers using Incr-DP increased constantly over the years up to 2012 (in 2005 Incr-PD was used in 33.4% of Centers, and in 11.9% of patients). The use of Incr-PD was greater in Centers with a more extensive PD program and greater use of PD in general. The most widely-used modality in Incr-PD was CAPD. CONCLUSIONS: Incr-PD is used in Italy in a large number of incident PD patients. The reasons for this increase need to be clarified, as current adequacy targets are based on full-dose studies with a very low glomerular filtration rate (GFR).

[Renal replacement therapies ­ Past, present and future]. / Nierenersatzverfahren - gestern, heute und morgen.

Extracorporeal renal replacement therapy is one of the most successful stories of artificial organ replacement. The current article describes the important steps in the evolution of renal replacement therapy towards modern state of the art peritoneal dialysis and hemodialysis. Open questions and possibilities for future developments are discussed. Today patients have a choice with respect to the method used to replace their failing kidney. However, in order to carefully plan and select the best possible method for a patient, he has to be seen and confronted with the various methods by a nephrologist at least six month before the necessity to start renal replacement therapy. Late referral increases mortality and the necessity for a temporary central venous access represents an additional thrombotic and infectious risk. A patient first seen by the nephrologist at the occasion of an emergeny dialysis will never have the possibility to profit from a preemptive living kidney donation. Furthermore, such patients usually stay in the center and are difficult to motivate for home or selfcare dialysis.

Where we come from and where we are going in terms of peritoneal dialysis: identifying barriers and strategies for the future.

Despite the 40 years history, the comparable survival of Hemodialysis and Peritoneal Dialysis (PD), and the improved PD technique survival, the percentage of patients performing PD is low. After a short history review and data description, we analyze the many non-medical factors (“the vicious circle”) that contribute to the underutilization of PD: inadequate medical training, lack of infrastructures, small PD units, inadequate patient education for choice of dialysis modality, lack of multidisciplinary end-stage renal disease units, the proliferation of hemodialysis centers, or the trends in government reimbursement. Several of these factors are modifiable, and we propose future strategies to increase the use of PD.

[Peritoneal dialysis from the beginnings up to today: which developments of the last decades were important?]. / Peritonealdialyse gestern und heute: welche Entwicklungen und Erkenntnisse waren in den letzten Jahrzehnten bedeutend?

During the past years new developments in peritoneal dialysis (PD) technique have resulted in continuous improvement of patient outcome. The importance of salt and fluid balance, residual renal function and peritoneal glucose load are of increasing interest, whereas small solute clearances have lost importance. In patients with high peritoneal transport rates automated PD (APD) is indicated. However, APD can also be chosen as initial PD treatment since recent studies show comparable or even better survival as compared to continuous ambulatory PD patients. Alternative PD solutions improve peritoneal ultrafiltration (icodextrin), reduce peritoneal glucose load (amino acid solution, icodextrin) and protect the peritoneal membrane (solutions with low concentration of glucose degradation products). Infection risk can be reduced when using antibiotic creams, but resistances should be considered. Ongoing studies will clarify if non-antibiotic agents, e.g. medihoney, are effective in preventing PD-associated infections. Due to these improvements PD and hemodialysis have become equivalent treatments.

Dynamic cardiac dyssynchrony is strongly associated with 2-year dialysis adequacy in continuous ambulatory peritoneal dialysis patients.

BACKGROUND: Left ventricular (LV) dyssynchrony is associated with increased risk of all-cause mortality in patients with end-stage renal disease. Our aim was to determine the associations of LV dynamic dyssynchrony with peritoneal solute clearance in continuous ambulatory peritoneal dialysis (CAPD) patients. Our primary objective was to determine the association between dynamic LV dyssynchrony and CAPD clearance at 2 years. Secondary objectives were to identify the factors influencing dynamic dyssynchrony, and to examine the association between dialysis adequacy and echocardiography-assessed LV outcomes. METHODS: Fifty CAPD patients and 13 healthy volunteers underwent three-dimensional (3D) dobutamine stress echocardiography (DSE). The main endpoint was systolic dyssynchrony index (SDI). Secondary endpoints, including NT-proBNP, troponin I, Kt/V, and biochemical parameters, were measured before stress echocardiography, and Kt/V was measured again 2 years later. All values are expressed as medians and interquartile ranges (IQR). RESULTS: NT-proBNP (3872 [808-11779] vs. 4.99 [4.99-36.83] pg/mL, P < 0.001), and log NT-proBNP (3.587 [2.896-4.071] vs. 0.698 [0.698-1.540], P < 0.001) levels were significantly higher in the CAPD group than in the control group. Real-time 3D DSE showed that the systolic dyssynchrony index was significantly different between the two groups at the peak dobutamine stage (1.11% [0.76-1.64%] vs. 0.66% [0.50-1.02%], P = 0.004), but not at resting (1.30% [0.89-1.74%] vs. 1.22 % [0.72-1.68%], P = 0.358).The subgroup of patients in the CAPD group with greater improvements in dialysis adequacy had lower baseline dynamic SDI and more favorable echocardiographic findings at 2 years. Dialysis adequacy decreased significantly at 2 year in patients with higher, but not in those with lower dynamic SDI at baseline. In multivariate linear regression analysis, log NT-proBNP and SDI at the peak dobutamine dose were significantly associated with Kt/V and weekly creatinine clearance at 2 years, while log NT-proBNP was significant associated with SDI at the peak dobutamine stage. Female CAPD patients group had more pronounced dynamic LV dyssynchrony compared with male patients. CONCLUSIONS: Dynamic systolic dyssynchrony was strongly associated with future dialysis adequacy in CAPD patients. Log NT-proBNP was the important predictor of dynamic dyssynchrony. Our study confirmed the concept that cardiac dysfunction has an impact on dialysis adequacy.

How automated peritoneal dialysis is applied and maintained in Japan.

According to a nationwide statistical survey in Japan, only 9,858 patients (3.3% of dialysis patients) were on maintenance peritoneal dialysis (PD) at the end of 2009. In this survey, 8,635 patients answered questions about the PD method, while 1,223 patients did not respond. In Japan, at the end of 2009, 5,143 patients (59.6%) on PD were treated with CAPD and 3,492 patients (40.4%) on PD were treated with automated PD (APD). It is well known that around 20% of Japanese PD patients choose to apply and maintain PD + HD combination therapy. The number of PD + HD patients (1,569) accounted for 20.7% of the PD-treated patients (7,591). In Japan, patients with fluid overloading preferably select PD + HD combination therapy with or without icodextrin use. Young patients select APD while patients on PD suffered from fluid overloading with high transporter membrane. What then are the factors that effect APD selection in Japan? The use of various forms of APD has increased considerably in the past few years. Important factors that contribute to APD selection are better adjustment of APD to the patient's lifestyle and the flexibility that APD offers to patients. In addition, patients with APD will be able to have good quality of life (QOL). Young patients on PD select APD because of good QOL. It is well known that almost all of children younger than 19 years with end-stage renal disease (ESRD) are undergoing APD. APD has a pivotal role in the management of pediatric patients with ESRD. Children on APD had a lower incidence of peritonitis compared with those with CAPD. The switch from CAPD to APD resulted in better ultrafiltration, less edema, lower mean arterial blood pressure, lower peritonitis rate and fewer hospital admissions. As in young patients, APD is also good method to select in elderly patients on PD. The need for the exchange to be performed by another person is increased in elderly and handicapped ESRD patients, however APD therapy is a good selection for them because of the smaller number of manipulations, resulting in a substantial reduction of help required. In the future, telemedicine systems with APD may be play an important role for young and elderly patients on PD.

Prognosis of patients on continuous ambulatory peritoneal dialysis (CAPD) for over 10 years.

BACKGROUND: Patients who have been on continuous ambulatory peritoneal dialysis (CAPD) for over 10 years are known to have a risk of developing encapsulating peritoneal sclerosis (EPS). However, the prognosis of patients on CAPD for over 10 years remains unclear. METHODS: To better understand the efficacy of a variety of treatments for EPS, we retrospectively reviewed 25 patients who started CAPD at Toranomon Hospital from 1981 to 1997 and continued it for longer than 10 years. RESULTS: The CAPD catheter was removed without peritoneal lavage in the initial 3 patients and they developed massive ascites. They all died of infection without resolution of the ascites. Accordingly, in the remaining 13 patients who did not undergo kidney transplantation, peritoneal lavage therapy was performed for 12 months before removing the CAPD catheter. As a result, 4 patients did not develop EPS. However, 9 patients had EPS with ascites, among whom 4 died of EPS-related diseases and 5 are alive. Five patients underwent cadaveric donor kidney transplantation. At the time of surgery, the CAPD catheter was removed without peritoneal lavage; 1 patient suffered from massive ascites immediately, although this subsided within 3 months after kidney transplantation, and 4 patients remain free from EPS-related symptoms and are doing well. CONCLUSION: Kidney transplantation may be an option for preventing EPS. This study showed that improvement of the uremic state as well as treatment with immunosuppressants including corticosteroids may contribute to preventing EPS.

Peritoneal dialysis, an expanding mode of renal replacement therapy in Qatar.

Qatar is one of the gulf countries with a current estimated population of 1.4 million. Diabetes mellitus, hypertension and chronic kidney diseases are major emerging epidemics, with an incidence of end-stage kidney disease (ESKD) of 202 patients per million population per year. Peritoneal dialysis (PD) was initiated in Qatar in 1997 with a rapid expansion in the number of patients. The study included all patients performing PD in Qatar, during the period from 1 January 2003 to 31 December 2007. Retrospective analysis of data included the records of 241 patients in terms of their demography, treatment, complications, and survival. During the study period, PD patients formed 23% of all the dialysis population in Qatar, with a mean annual expansion rate of 12%. Diabetic nephropathy was the commonest cause of ESKD seen in 43% of PD patients. All age groups were included in our program, with a mean age of 53 ± 13 years. Males represented 74%. Continuous ambulatory peritoneal dialysis remained the initial mode of PD, with significant numbers being changed to automated PD over the years. The 1- and 5-year survival rates were 91% and 26%, respectively, with cardiac causes being responsible for 86% of mortality. The rate of peritonitis was 0.24 ± 0.1 episodes per patient years, and technique survival at 1 and 5 year was 84% and 32%, respectively. We conclude that the components of the PD program in Qatar are comparable to that in other countries with a good outcome.

[Morbidity and mortality in diabetic patients on peritoneal dialysis. Twenty-five years of experience at a single centre]. / Morbimortalidad en pacientes diabéticos en diálisis peritoneal. Experiencia de 25 años en un solo centro.

AIMS: To describe PD outcomes over 25 years in a single centre, comparing hospitalisation rate, technique withdrawal, and survival between diabetic (DM) and non-diabetic (NonDM) patients. Differences between type 1 (DM1) and type 2 (DM2) diabetics were also analysed. PATIENTS AND METHODS: One hundred and eighteen DM patients (52 year old average, 74 men, 44 female) and 117 Non-DM (53 year old average, 64 men, 53 female), with at least 2 months on PD, 25±20 (2-109) and 29.4±27 (2-159) months respectively, were included. Diabetics were divided in 66 DM1 and 52 DM2. The survival and hospitalisation study was also analysed in two different time periods: before 1992 (1981-1992) and after 1992 (1993-2005). RESULTS: 93% Non-DM and 75% DM were self-sufficient to manage the PD technique (P<.001) as well as 65% of 44 blind patients. 28% of Non-DM and 15% of DM received a renal allograft (P<.001). There was no difference in transfer to haemodialysis. 18.6% of DM and 4.3% of Non-DM patients presented ≥4 comorbid factors on starting PD (P<.001). Hospitalisation (admissions/year) was higher in DM than in Non-DM (3.4 vs 1.8, P<.01) and also hospitalisation length (46 vs 22 days/year, P=.01), without differences between DM1 and DM2. Admissions due to cardiovascular events, infections, technical problems and peritonitis were more frequent in DM2 than in Non-DM and DM1 patients (P<.05). Mortality was 48% in DM and 22% in Non-DM (P<.001). Survival adjusted for comorbidity was higher in Non-DM (P<.001). Cerebrovascular disease was the highest risk factor for mortality in DM. Mortality was higher in DM2 than in DM1 and Non-DM (P<.001). Age (HR 1.052, P=.001), DM2 (HR 1.96, P<.01) and cerebrovascular disease (HR 4.01, P<.001) were the most important risk factors. In the post-1992 period, the hospitalisation rate and survival improved in DM1 and Non-DM patients. CONCLUSIONS: DM patients more often require outside assistance to perform PD and have more comorbidity, lower survival, and higher admissions than Non-DM, but there is no difference in HD discontinuation. Age and cardiovascular comorbidity are the factors involved in mortality. Technological advances and cumulative center experience may achieve dialysis outcome improvements in diabetic patients. 

Five decades of Indian nephrology: a personal journey.

Impressive accomplishments have been made in Indian nephrology during the last 5 decades. The first renal biopsy performed in 1956 ushered in a new era of modern nephrology practice in India and led to the recognition of nephrology as a distinct specialty. The first hemodialysis facility was established in 1961; presently, there are 950 nephrologists, 850 hospitals equipped with dialysis facilities, and 170 institutions recognized for kidney transplantation, with approximately 3,500 transplantations performed every year. The majority of dialysis units are small minimal-care facilities with fewer than 5 dialysis stations, and more than 85% are in the private sector. Government hospitals provide free treatment to poor patients with chronic kidney disease; however, inadequate funding and lack of health insurance schemes pose serious hurdles in providing renal replacement therapy. In contrast, private/corporate hospitals located in big cities have large units with state-of-the-art dialysis and transplantation facilities, similar to advanced centers of the world, but are accessible to only upper-income groups. Of the estimated 175,000 new patients who develop end-stage renal disease annually, less than 10% are able to gain access to renal replacement therapy. Research in the field of renal diseases has evolved slowly and is focused primarily on tropical conditions. The availability of structured nephrology training programs coupled with excellent diagnostic and therapeutic facilities in some academic institutions and tertiary-care private/corporate hospitals have diminished the need for foreign travel by students, patients, and consultants to a considerable extent. The expansion of therapeutic facilities in India is hampered by only economic constraints, not lack of expertise.