The outcome of SARS-CoV2 infection in patients who have received a kidney allograft and are being treated with immunosuppression is unclear. We describe 20 kidney transplant recipients (median age 59 ...years inter quartile range 51-64 years, median age of transplant 13 years 9-20 years, baseline eGFR 36.5 23-47.5) with SARS-CoV2 induced pneumonia. At admission, all had immunosuppression withdrawn and were started on methylprednisolone 16 mg/day, all but one was commenced on antiviral therapy and hydroxychloroquine with doses adjusted for kidney function. At baseline, all patients presented fever but only one complained of difficulty in breathing. Half of patients showed chest radiographic evidence of bilateral infiltrates while the other half showed unilateral changes or no infiltrates. During a median follow-up of seven days, 87% experienced a radiological progression and among those 73% required escalation of oxygen therapy. Six patients developed acute kidney injury with one requiring hemodialysis. Six of 12 patients were treated with tocilizumab, a humanized monoclonal antibody to the IL-6 receptor. Overall, five kidney transplant recipients died after a median period of 15 days 15-19 from symptom onset. These preliminary findings describe a rapid clinical deterioration associated with chest radiographic deterioration and escalating oxygen requirement in renal transplant recipients with SARS-Cov2 pneumonia. Thus, in this limited cohort of long-term kidney transplant patients, SARS-CoV-2 induced pneumonia is characterized by high risk of progression and significant mortality.
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The SARS-CoV-2 epidemic is pressuring healthcare systems worldwide. Disease outcomes in certain subgroups of patients are still scarce, and data are needed. Therefore, we describe here the experience ...of four dialysis centers of the Brescia Renal COVID Task Force. During March 2020, within an overall population of 643 hemodialysis patients, SARS-CoV-2 RNA positivity was detected in 94 (15%). At disease diagnosis, 37 of the 94 (39%) patients (group 1) were managed on an outpatient basis, whereas the remaining 57 (61%) (group 2) required hospitalization. Choices regarding management strategy were made based on disease severity. In group 1, 41% received antivirals and 76% hydroxychloroquine. Eight percent died and 5% developed acute respiratory distress syndrome (ARDS). In group 2, 79% received antivirals and 77% hydroxychloroquine. Forty two percent died and 79% developed ARDS. Overall mortality rate for the entire cohort was 29%. History of ischemic cardiac disease, fever, older age (over age 70), and dyspnea at presentation were associated with the risk of developing ARDS, whereas fever, cough and a C-reactive protein higher than 50 mg/l at disease presentation were associated with the risk of death. Thus, in our population of hemodialysis patients with SARS-CoV-2 infection, we documented a wide range of disease severity. The risk of ARDS and death is significant for patients requiring hospital admission at disease diagnosis.
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The outcome of kidney transplant patients with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is still unclear. Here we describe the clinical characteristics, disease outcome, ...and risk factors for acute respiratory distress syndrome (ARDS) and death of a cohort of 53 kidney transplant patients with coronavirus disease 2019 (COVID‐19). Eight of 53 have been handled as outpatients because of mild disease, on average with immunosuppression reduction and the addition of hydroxychloroquine and azithromycin; no patients required admission, developed ARDS, or died. Because of severe symptoms, 45/53 required admission: this cohort has been managed with immunosuppression withdrawal, methylprednisolone 16 mg/d, hydroxychloroquine, and antiviral drugs. Dexamethasone and tocilizumab were considered in case of ARDS. About 33% of the patients developed acute kidney injury, 60% ARDS, and 33% died. In this group, thrombocytopenia was associated to ARDS whereas lymphopenia at the baseline, higher D‐dimer, and lack of C‐reactive protein reduction were associated with risk of death. In the overall population, dyspnea was associated with the risk of ARDS and age older than 60 years and dyspnea were associated with the risk of death with only a trend toward an increased risk of death for patients on tacrolimus. In conclusion, SARS‐CoV‐2 infection may have a variable outcome in renal transplant patients, with higher risk of ARDS and death in the ones requiring admission.
Findings from an Italian cohort of kidney transplant patients with COVID‐19 support heterogenous disease courses with higher risks of acute respiratory distress syndrome and death in the subgroup with severe disease.
Abstract
Background and Aims
Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis (PD). Its prevalence, ranging from 0.7 to 3.3%, and its reported ...mortality is 25-55%. Post-transplantation encapsulating peritoneal sclerosis (PT-EPS) usually occurs within two years from PD interruption due to kidney transplantation. Calcineurin inhibitors are thought to be involved in the pathogenesis of PT-EPS.
Method
This is a retrospective, single-center study: all the patients who received PD for 2 or more months before kidney transplantation between 1979 and 2018 in our unit were enrolled. All PD patients diagnosed with EPS after transplantation were identified, and their data were compared with those of non-transplanted PD patients (NT-PD).
Results
Data from a total of 1014 PD patients were examined; 215 underwent kidney transplantation and 799 remained on PD. PT-EPS occurred in 5/215 patients (2.3%), a prevalence not significantly different from that of NT-PD (21/799= 2.6%; P = 0.39) (Table 1). Calcineurin inhibitors were administered to 178/215 (83%) patients without EPS and all 5 patients with PT-EPS (P = 0.68). Calcineurin inhibitors were associated with corticosteroids (41%), mycophenolate mofetil (34%), or both (42%). Inhibitors of mammalian targets of rapamycin were used in association with calcineurin inhibitors in 25%, with calcineurin inhibitors and steroids in 24% and steroids alone in 7%. Mortality due to PT-EPS was 4.3% vs 1.2% in NT-PD (P = 0.38) (Figure 1).
Conclusion
The prevalence of PT-EPS was similar to that of EPS in NT-PD. Therapy with calcineurin inhibitors did not appear to be a crucial risk key in the development of PT-EPS.
Table 1.
Encapsulating peritoneal sclerosis (C-EPS) vs those with post-transplantation encapsulating Comparison of characteristics between the non-transplanted PD patients (NT-PD) vs those transplanted (KT-PD) and between the patients with classic peritoneal sclerosis (PT-EPS)
NT-PD
KT-PD
p
Number of patients (%)
799 (78.9)
215 (21.2)
--
Male/female
444/355
125/90
0.56
Total time on PD* (months) (median, IQR)
26 (10-44)
27 (16-46)
0.38
Deceased for all causes (%)
662 (82.8)
47 (21.9)
<0.001
Deceased for EPS (%)
8 (1.2)
2 (4.3)
0.38
C-EPS
PT-EPS
P
Cases of EPS (%)
21 (2.6)
5 (2.3)
0.39
Age at EPS diagnosis (M±SD)
64±12
55±7
0.08
Months spent on PD at diagnosis* (median, IQR)
103 (42-156)
79 (54-97)
0.33
Months from diagnosis to the end of observation# (median, IQR)
22 (5-75)
62 (46-114)
0.13
Deceased due to EPS (%)
8 (38.1)
2 (40.0)
0.94
*
For all treatments. #Dead or lost to follow-up
Figure 1.
Comparative cumulative survival from EPS in the 215 KT-PD patients (continuous line) vs the 799 NT-PD patients (dotted line) (log-rank test: p=0.38).
Abstract
Background and Aims
EDTA published data gathered between 2012 and 2016 showed greatly reduced survival in elderly prevalent dialysis patients as compared to similar aged individuals in the ...general population: a 70 year-old dialysis patient had a life expectancy of 5 years (instead of 16), an 80 year-old patient could expect to survive 3 years (instead of 9). This was due to the multiple comorbidities often present in elderly patients with advanced Chronic Kidney Disease (CKD). This burden of disease is further increased by dialysis itself, in particular by hemodynamic instability during treatment and by vascular access problems which often determine the need for central venous catheter insertion and for hospitalization. In 2007 the DODE study (a randomized, controlled, multicentric study in which our center took part) validated a conservative treatment of uremia based upon a Very Low Protein Diet supplemented with ketoanalogues (sVLPD): survival in patients on conservative management was similar to that of patients on chronic dialysis; also, no negative effect on nutritional status was observed. Our aim was to analyse clinical and epidemiologic data and outcomes of patients treated at our center with a sVLPD.
Method
We analized 222 selected from a group of approximately 300 patients with stage 5 CKD managed conservatively with a sVLPD (0.3 g/kg/day proteins). The inclusion criterion was active follow-up for at least six months; patients unable to maintain fluid and electrolyte balance with medical therapy were excluded. Except for one patient, all subjects were aged 75 years and older. Clinical and epidemiologic data were recorded at the beginning, during and at the end of follow-up.
Results
Mean age at the beginning of observation was 80 ± 7 years (51-96); 48% of patients were male (107), 52% were female (115). Median initial Renal Residual Function (RRF, ml/min) was 6,3 ± 2,1 ml/min, at the end of follow-up it was 5,3 ± 2,9 ml/min. The most common significant comorbidities were hypertension (84,5%), heart (61,4%) and vascular disease (48,6%); these and other significant comorbidities are illustrated in Fig. 1. Conservative management allowed to delay the initiation of dialysis by an average of one year; 24% of patients continued on the sVLPD for two year and some patients reached a duration of treatment of 7 years. Median duration of sVLPD is shown in Fig. 2. At the end of follow-up 40% of patients had begun chronic hemodialysis and 9% peritoneal dialysis, 8% were still on conservative management, 27% were deceased (Fig. 3).
Conclusion
The supplemented Very Low Protein Diet is an effective treatment which can delay the beginning of chronic dialysis in elderly stage 5 CKD patients with multiple comorbidities. It is a safe treatment and does not increase morbility and mortality. Current epidemiologic data (incident patients in dialysis: 170 pmp/year, 50% aged over 70 years old) support the use of this conservative strategy which can represent a valid alternative to dialysis in selected patients.
Fig. 1.
Patient comorbidities at the beginning of observation.
Fig. 2.
Median duration of sVLPD.
Fig. 3.
Status of patients at the end of follow-up.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease (COVID-19), is a major pandemic challenging health care systems around the world. The optimal ...management of patients infected with COVID-19 is still unclear, although the consensus is moving toward the need of a biphasic approach. During the first phase of the disease (from onset of the symptoms up to 7–10 days) viral-induced effects are prominent, with the opportunity to institute antiviral therapy. In the second inflammatory phase of the disease, immunosuppressive strategies (for example with glucocorticoids or anticytokine drugs) may be considered. This latter stage is characterized by the development of progressive lung involvement with increasing oxygen requirements and occasionally signs of the hemophagocytic syndrome. The management of the disease in patients with kidney disease is even more challenging, especially in those who are immunosuppressed or with severe comorbidities. Here we present the therapeutic approach used in Brescia (Italy) for managing patients infected with COVID-19 who underwent kidney transplantation and are receiving hemodialysis. Furthermore, we provide some clinical and physiopathological background, as well as preliminary outcome data of our cohort, to better clarify the pathogenesis of the disease and clinical management.
Figure:
Background and Aims
in Italy only a minority of uremic patients perform peritoneal dialysis (PD). In dialysis centers where PD is practiced and proposed the prevalence is no more than 23%. ...Proposed advantages of PD over HD are a more preserved Residual renal function (RRF), that has been associated with better survival, and better Quality of life (Qol) due to possible more preservation of previous lifestyle, independence, possibility of traveling, and flexibility. Incremental peritoneal dialysis is a promising way to further improve Qol and to preserve RRF. Lastly, PD is less expensive than HD. Aim of this study has been to retrospectively evaluate our ten-years experience of PD treatment on survival, dialysis adequacy, preservation of RRF and nutrition in uremic patients followed at our Dialysis Center.
Method
We retrospectively evaluated all the incident patients that started PD treatment due to uremia from 01-01-2008 to 31-12-2018 at the U.O. Nephrology ASST Spedali Civili of Brescia. The exclusion criteria were time of dialysis treatment less than 3 months and absence of previous dialytic treatment or kidney transplantation. For each patient anthropometric, clinical-anamnestic data and comorbidities at dialysis start were recorded.
Data on dialysis adequacy, nutrition, RRF and PD dialysis modality performed were also recorded.
Results
During the observation period 329 patients started PD. 60 were excluded due to follow-up of less than 3 months. Therefore, 269 patients (males 160, 59%) were studied. The average age was 65±16 years, BMI 24±4 kg/m2. Comorbidities were: hypertension (87%), diabetes mellitus (32%), cerebral vascular disease (26%) and ischemic heart disease (25%). The mean duration of dialysis treatment was 2.1±1.5 years. At the end of ten-years follow-up 24% of patients have had a kidney transplant, 18% were on PD treatment, 17% have had a shift towards HD, 39% had died. The main causes of death were: infection (39%) and cardiovascular disease (31%). The most common dialysis modality performed was APD (61%); CAPD was performed in 39% of pts. Dialysis modality (CAPD; APD), nutrition parameters (PNA; BMI), as well as RRF, expressed as an average value during follow-up, are shown in Figure 1. 81 patients (30%) were treated with incremental PD; 85% of them with manual exchanges. The comparison of dialysis parameters between incremental PD and standard PD are shown in Figure 2.
Multivariate analysis with survival as dependent variable (Figure 3), showed that age, diabetes mellitus, and low wKt/V were independently associated with an increased risk of mortality. Diuresis volume and male gender were protective factors. No independent influence on mortality of the dialysis treatment modality was found.
Conclusion
In this ten-years experience of patients undergoing PD at our Center, incremental PD seems to be a protective factor for the maintenance of a preserved diuresis and better dialysis adequacy, and these factors are associated with better survival of the patients.
Abstract
Background and Aims
Survival comparison between peritoneal dialysis (PD) and hemodialysis (HD) is still controversial. While some retrospective studies have shown better survival in PD, ...particularly in the first year, others have not identified this difference. The only RCT published so far showed a 3-year mortality rate similar between two groups. However, the number of patients was too small to provide sufficient statistical power to identify any survival differences between the two dialysis techniques. Aim of this study was to compare HD and PD in term of survival rate and factors possibly involved in a ten-years observational study.
Method
We retrospectively evaluated all the incident patients that started a dialytic treatment, either HD or PD, due to uremia from 01-01-2008 to 31-12-2018 at the U.O. Nephrology ASST Spedali Civili of Brescia. Exclusion criteria were: duration of dialysis treatment less than 3 months, and previous dialytic treatment or kidney transplantation. For each patient anthropometric, clinical-anamnestic data and comorbidities at dialysis start were recorded.
Results
One thousand and six patients were identified. 130 patients were excluded due to dialysis treatment less than 3 months. A total 876 patients were analyzed. 77% of patients started dialysis on HD while 23% chose PD. Age was significantly higher in HD patients (69±15 vs 65±16 years; p<0.05). No differences were found in the incidence of: ischemic heart disease (HD 24%, PD 25%, p=0.90), diabetes (32% vs 32%, p=0.83), cancer (20% vs 17%, p=0.37), cardiac arrhythmia (20% vs 25%, p=0.08) and peripheral vascular disease (25% vs 25%, p=0.89). An increased incidence of COPD (HD 17% vs PD 8%, p<0.05) and hypertension (73% vs 87%, p<0.05) was present in PD patients. During follow-up, 17% of patients treated with PD shifted to HD due to catheter malfunction, recurrent infections, insufficient dialytic adequacy or ultrafiltration failure. Kidney transplants were performed more frequently in PD patients (HD 12%; PD 24%, p<0.05). At an intention to treat analysis of the data, univariate analysis showed better survival in PD patients (p<0.05, Figure 1). This difference was not confirmed at multivariate analysis (Figure 2), where age, cardiac arrhythmia, cirrhosis, diabetes and peripheral vascular disease were independently associated with an increased risk of mortality. No independent influence on mortality of the dialysis treatment modality was found.
Conclusion
This ten years observational study shows that HD and PD are similar in term of patient survival. Age and comorbidities seem to play the most important role in patient survival.
Figure:
Abstract
Background and Aims
Steroid therapy is efficient in inducing remission of IgA nephropathy (IgAN) and preventing end stage renal disease (ESRD) but there are concerns about their safety. The ...TESTING trial in particular has been stopped early because of a higher incidence of side effects than conservative treatment thus inducing a conservative therapy with RAAS (renin angiotensin antagonist system) blockers. The aim of this analysis was to evaluate the incidence of adverse events (AE) in a retrospective observational trial on the real clinical practice.
Method
We evaluated 1209 patients (pz) with IgAN coming from 48 Italian centers: 285 pz in RAAS blockers alone, 732 treated for 6 months with steroid and 192 with a combination of steroid and other immunosuppressants (also with RAAS blockers). The analysis was limited to the 6 months of therapy.
Results
The basal characteristics of the 3 groups are shown in the table below.
The figure shows the frequencies of 69 adverse events related with immunosuppression: the most frequent were infections (23, 2.73% of all patients, 34.3% of all AE), impaired glycemic control (11, 0.91% of patients, 16% of all AE), severe hypertension (6, 8.7% of all AE) and leukopenia (9, 0.80% of patients, 13% of all AE). Infections were observed in 16 (2.19%) pz in steroid therapy and 7 (3.65%) pz in steroid+immunosoppressive treatment. Liver toxicity and and gastrointestinal AE were observed almost in pz receiving steroid+ immunosuppressants 1(0.14%) and 2 (1.04%) pz, respectively. 7 pz in steroid therapy (0.96%) and 2 in steroid+ immunosuppressants experienced an impaired glycemic control. All the 9 cases of leucopenia were registered in pz in steroid+ immunosuppressants (4.69%). A slightly higher incidence of allergies was observed in the RAAS blocker group (20 cases, 0.7%). The higher rates of infections and leucopenia were observed in pz above 70 years of age (6.12%,p<0.05), as higher incidence of infections and impaired glycemic control were registered in pz with an eGFR<30 ml/min/1.73 m2 (4.64 and 1.99%,p<0.05). Severe hypertension and leucopenia were observed respectively in 9 and 3 pz with an eGFR <60 ml/min/1.73m2. No significant relationships were found between AE, proteinuria and sex. Multivariate logistic regression showed an independent association of immunosuppressive treatment and age with any AE ODDS ratio: 3,35 (CI:2,18-5,14) and 1,02 (CI:1,01-1,04), respectively; p<0.05. Death occurred for sepsis in a 70 years old pz (eGFR=21.7 ml/min/m2, 24hproteinuria=16.1 g/day) after 3 months of treatment.
Conclusion
the incidence of EA in our observational study is lower than that observed in the TESTING and STOP trials (5.71% vs 14.7% and 40%, respectively). The most frequent AE were almost observed in oldest subjects with impaired renal function on steroid+other immunosuppressants. Though this trial is not randomized nor controlled (RC), it considers a large cohort of pz coming from the real clinical practice of the Italian Nephrology Units and demonstrates that the significantly lower incidence of steroid related AE than that observed in some RC trials doesn’t justify the abstention from steroids in IgAN at risk of progression. Much more attention should be paid in elderly pts with severe renal dysfunction with a closer follow-up, dose adjustments and antibiotic prophilaxis.
Figure:
The causes of intradialytic hypertension (IDHyper) are not well understood and this condition can complicate the clinical management of hemodialysis (HD) patients.
To evaluate the potential role of ...intradialytic sodium gradient (NaG) on blood pressure values and IDHyper during HD.
206 prevalent HD patients on 3 times weekly HD treatment for at least 6 months (dialytic vintage 6-240 months) followed at our institution were studied. Mean age was 68 ± 14 years, 129 were men. For 2 consecutive months (24 HD sessions) after the start of observation, the following variables were evaluated in predialysis after the long interdialysis interval: pre-HD plasma sodium (pNa, mmol/l) and potassium (pK, mmol/l) concentrations (mean value of 8 determinations), pre- and post-HD systolic (SBP, mm Hg) and diastolic (DBP, mm Hg) blood pressure, dry body weight (dBW, kg), interdialytic weight gain (IDWG, kg), ultrafiltration rate (UFR, ml/kg/h), dialysis dose (Kt/V), protein catabolic rate (PCRn, g/kg/day), hemoglobin (Hb, g/dl). SBP, DBP, IDWG, UFR are the mean values of the 24 HD sessions. 76% of patients were on antihypertensive therapy, 171 patients were on bicarbonate HD, and 35 on HDF. Dialysate Na concentration was set at 140 mmol/l in all patients. Duration of HD and the blood and dialysate flow rate were kept constant during observation.
Data are expressed as mean ± SD; linear and multiple regression analysis and t test for unpaired data were employed. Significant differences were defined as p < 0.05.
Pre-HD pNa was 138.1 ± 2.3 mmol/l, pK 5.0 ± 0.4 mmol/l, dBW 67 ± 14 kg, IDWG 2.9 ± 0.8 kg, UFR 11.2 ± 3.7 ml/kg/h, Kt/V 1.43 ± 0.18, PCRn 1.13 ± 0.17 g/kg/day, and Hb 11.2 ± 0.8 g/dl. Pre- and post-HD SBP values were 139 ± 13 and 134 ± 12 mm Hg (p < 0.0001); pre- and post-HD DBP did not change significantly. A dialysis Na gradient (NaG) (dialysate Na - pre-HD pNa) was calculated, as well as the delta of SBP (ΔSBP) (post-HD SBP - pre-HD SBP). IDHyper was defined as ΔSBP >0. A significant direct correlation was found between NaG and ΔSBP (p < 0.0001) and multiple regression analysis with ΔSBP as dependent variable confirmed the strong correlation with NaG (p < 0.00001). According to ΔSBP behavior, 171 patients (83%) had a decrease or no change in post-HD SBP (group 1; no IDHyper); 35 patients (17%) increased their post-HD SBP (group 2; IDHyper). NaG values were significantly greater in patients in group 2 (group 1: 1.5 ± 2.2 vs. group 2: 3.3 ± 2.5, p < 0.0001).
This study shows that the intradialytic ΔSBP is independently and strongly associated with the dialytic NaG. The more positive the NaG (net intradialytic Na gain), the more positive the ΔSBP and IDHyper.
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